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<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Studies of the effect of dietary cholesterol on hepatic protein synthesis, reduced glutathione levels and serine dehydratase activity in the rat.? [/INST] A basal diet or a basal diet plus 1% of cholesterol and 0.33% cholic acid was fed to rats for varying lengths of time and (1) the activities of liver phosphoenolpyruvate-carboxykinase (PEP-CK), tyrosine transaminase (TT), and serine dehydratase (SD); (2) the rate of total hepatic protein synthesis and (3) the concentration of hepatic reduced glutathione (GSH) were quantitated. The specific activity of PEP-CK was significantly depressed by cholesterol plus cholic acid feeding, while the specific activity of TT was unchanged. No significant effect of dietary cholesterol plus cholic acid was found on the total liver activities. In contrast, SD specific activity was increased 3-fold. The rate of (U-14C)-L-leucine incorporation into total TCA precipitable protein following ingestion of cholesterol plus acid was significantly reduced when the data were expressed as dpm (U-14C)-L-leucine/mg protein. After correcting this expression for specific radioactivity of the liver tissue free leucine pool, no significant effect of dietary cholesterol plus cholic acid on hepatic protein synthesis existed. In fact, the amount of 14C-leucine incorporated into protein on a total liver basis was 50% greater for the cholesterol group. On a per gram of liver basis, the concentration of GSH in the liver of rats fed a cholesterol plus cholic acid diet was significantly decreased. Considering the liver enlargement in rats fed cholesterol plus cholic acid, total organ GSH was found to be significantly greater than for rats fed a basal diet. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Thiamine triphosphatase activity of myosin and accelerating effect of thiamine di- and tri-phosphates on superprecipitation of actomyosin.? [/INST] TTP accelerated ATP-induced superprecipitation of actomyosin in as low a concentration as 30 muM and decreased light scattering by actomyosin. These effects could also be observed in the same way, but to a lesser degree, by addition to TDP. Myosin was able to hydrolyze TTP to TDP, but some important differences were confirmed between myosin TTPase and ATPase. Myosin TTPase was inhibited by actin and showed a much larger Km than that of ATPase. TTP significantly inhibited myosin B ATPase and ATP greatly inhibited myosin B TTPase. These findings suggest that the accelerating effect of TDP and TTP may be due to the binding of thiamine phosphate to the regulatory site of myosin followed by a change in its physical chemical property, rather than due to the competitive binding of thiamine phosphate to the catalytically activity site of myosin. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The meaning of the Leydig cell in relation to the etiology of cryptorchidism: An experimental electron-microscopic study.? [/INST] In our electron-microscopic studies of testicular biopsies, both normal and cryptorchid, we found a simple atrophy of the Leydig cell in the cryptorchid testis. Based on experiments by Raynaud1,2 and Jean3 on pregnant mice, we tried to find the reason for changes in the Leydig cell relating to the etiology of cryptorchidism. We found on electron microscopic study of testes in the offspring of pregnant mice treated with estrogen the same atrophy of the Leydig cell as we see in human cryptorchidism. These changes are not evident when estrogen and HCG are given together. We can conclude from this experiment that lack of gonadotropin stimulation leads to the atrophy of Leydig cells. This atrophy then produces a lack of androgen which could be responsible for cryptorchidism. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The in vitro adsorption of drugs from horse serum onto carbon coated with an acrylic hydrogel.? [/INST] In vitro studies have shown that uncoated carbon and carbon coated with an acrylic hydrogel are capable of adsorbing drugs from horse serum at 37 degrees. Increase in the coating weight from 2 to 4% decreased the rate of adsorption but not the total capacity. In vivo data supports the concept of carbon haemoperfusion for use in the treatment of drug overdose. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The interaction of antihistamines with lecithin monolayers.? [/INST] The interaction of a series of antihistamines with monolayers of L-alpha-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6-8. It was not clear whether this effect was caused by the buffer components or was a pH effect. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effect of surfactant monomers on chloramphenicol association to an albumin-lecithin complex: a model for modified drug absorption.? [/INST] The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The effect of blending on the rheological properties of gelatin solutions and gels.? [/INST] The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1-0-3-5% w/v at 25 degrees), resulted in a decrease in gel rigidity whereas in the stronger gels (5-50% w/v at 25 degrees) and solutions (18% and 30% w/v at 35 degrees), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Amphetamine tachyphylaxis in the pithed guinea-pig.? [/INST] A single dose of (+)-amphetamine (8 mg kg-1, i.p.) administered 4 h before experimentation, reduced the pressor and positive chronotropic effects elicited by this drug (0-6 mg kg-1, i.v.) and augmented the rate of the development of tachyphylaxis to these responses in the pithed guinea-pig preparation. Amphetamine pretreatment reduced the pressor and positive chronotropic effects of phenylephrine (0-1 mg kg-1, i.v.) and the positive chronotropic effects of angiotensin (30 mug kg-1, i.v.). The rate of the development of tachyphylaxis to the cardiovascular responses elicited by phenylephrine and angiotensin was augmented by amphetamine pretreatment. The results suggest that an indirect mechanism (noradrenaline) may in part mediate the cardiovascular effects of these 3 drugs and/or that amphetamine may act as a competitive antagonist at adrenoceptor sites. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Phenylbutazone-warfarin interaction in the dog.? [/INST] The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2-6 to 8-0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18-4 h in control animals to 9-6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg-1 (orally) it was given with phenylbutazone (50 mg kg-1, orally). The unbound fraction of warfarin in canine plasma ranged from 1-7 to 4-3% indicating individual differences in the extent of the plasma binding of warfarin in the dog. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The effect of pancuronium on myocardial contraction and catecholamine metabolism.? [/INST] The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to "rebound" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate "rebound." </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Metabolism of delta1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism.? [/INST] The metabolism of (-)-delta1-tetrahydrocannabinol (delta1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-delta1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC was also present together with small amounts of 6alpha-hydroxy-delta1-THC and 6beta-hydroxy-delta1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6beta-hydroxy-delta1-THC and 6alpha-hydroxy-delta1-THC. 7-Hydroxy-delta1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3'-hydroxy-delta1-THC and 4'-hydroxy-delta1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of delta1-THC. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Determination of low cencentrations of the quaternary ammonium compound thiazinamium methylsulphate in plasma and urine.? [/INST] A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine-compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml-1 with a recovery of 88-0 +/- 6-2% from plasma, 91-4 +/- 4-6% from urine. The described method can also be applied to other quaternary ammonium compounds. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Kinetics and mechanisms of drug action on microorganisms XXII: Effects of aminosidine with and without organism pretreatment with bacteriostatic agents.? [/INST] Escherichia coli generation in the logarithmic growth phase was inhibited in peptone broth USP at pH 7.0 without kill below 3.0 mug/ml of aminosidine. Above this value, the logarithms of the number of viables of the drug-treated culture ultimately decreased linearly with time and the slopes of these plots were independent of concentration. A concentration-dependent lag in the time of attainment of the cidal action was observed, and the extent of this lag was related to the ease of emergence of resistant organisms. The minimal concentration for cidal action increased with increasing concentrations of nutrients and with decreasing pH. Pretreatment of the cultures with novobiocin and tetracycline lessened the minimum bactericidal concentration of aminosidine whereas chloramphenicol pretreatment increased it. Tetracycline pretreatment inhibited the emergence of aminosidine-resistant organisms. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Elementary osmotic pump.? [/INST] The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about New and expedient determination of atenolol in biological samples.? [/INST] A method is described for the GLC determination of atenolol BP in plasma and urine. Extraction is accomplished under dehydrating conditions, and interfering impurities are removed by using an acidified cyclohexane-isopropanol mixture (2:1) and charcoal-treated paper disks. The drug thus isolated appears to react more efficiently with heptafluorobutyric anhydride, increasing the sensitivity of GLC electron-capture analysis. Concentrations as low as 0.02 mug/ml were measured using 0.5-ml aliquots of plasma or 0.1 ml of urine. Amino alcohols such as atenolol may form hydrates or alcoholates, precluding complete derivatization with heptafluorobutyric anhydride. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Time course and dose dependence of antacid effect on urine pH.? [/INST] Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Quantitative analysis of tribromsalan in blood and urine.? [/INST] Tribromsalan can be quantitatively measured in whole blood and urine by a technique involving extraction with ethyl acetate, treatment with silica gel, separation by TLC, and quantitative measurement by fluorescent spectrophotometry. This method has a sensitivity down to 125 ng (25 ppb in 5.0 ml of sample) of free tribromsalan and shows an average 90% recovery of tribromsalan in blood and urine with standard deviations of 9.7 and 7.4%, respectively. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about pH-dependent secretion of procainamide into saliva.? [/INST] The relationship between serum and stimulated, mixed saliva concentrations of procainamide was determined in 12 chronically medicated patients. Samples were obtained at times chosen to approximate the maximum and minimum serum concentrations of the drug during a dosing interval. Marked intersubject variability was found in the ratio of saliva to serum concentration of the drug (0.27-8.93). There was no correlation between the dose (milligrams per kilogram per day) and the minimum serum or saliva concentration of procainamide. Saliva pH ranged from 6.3 to 8.0 in eight subjects. The ratio of saliva to serum concentration of procainamide increased with decreasing pH. This result can be largely explained by the pH-dependent ionization and distribution of procainamide, a weak base. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum.? [/INST] 1. Electrical and mechanical activities of the longtitudinal muscle of the dog antrum were recorded with the double sucrose-gap technique. 2. The muscle exhibited spontaneous action potentials which consisted of a spike-like potential which, after a brief and partial repolarization, was followed by a negative-going, plateau-type potential. In 97% of the preparations, no tension changes were produced by spontaneous action potentials. 3. Tetrodotoxin, atropine, alpha- and beta-adrenoceptor antagonists, and H1 and H2 receptor blocking agents had no effect on the action potential. It was concluded that the action potential was myogenic in origin. 4. The mean frequency of the action potential at 37+/- 0.5 degrees C was 1.0/min+/-0.06 (s.e. of mean, n=92) and the mean duration 7.1+/-0.2 sec (s.e. of mean, n=11). 5. Steady depolarizing current increased whereas hyperpolarizing current decreased the frequency of the action potential. 6. Length-tension relations were studied. In twelve strips, the average resting, passive, tension at LO was 570 mg. The active force of isometric contraction produced by acetylcholine increased with strip length up to a maximum, then decreased wtih further increased in length. There were no mechanical responses to pentagastrin. 7. Pentagastrin had two sites of action. On smooth muscle, it increased the frequency of the action potential in a dose dependent fashion. Threshold concentraions ranged from 2X10-14 to 10-11M. The ED50 was 2X10-10M. The maximum response, 5.4/min, was reached at 10-8M. Pentagastrin also released acetylcholine from intramural cholinergic nerves. 8. Pentagastrin reduced the amplitude and duration of the action potential. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about An alkyl etherase in rat liver.? [/INST] 1. Diethyl ether, which is known to be partly metabolized in vivo, has been found to show an O2 uptake with the rat liver microsomal membranes; a similar reaction is given with other short chain aliphatic ethers, isoproply and n-butyl ether. 2. The "etherase" reaction is optimal at pH 7.2-7.4 and is not accompanied by an increased formation of malondialdehyde. 3. When CoA is added to the microsomes together with a source of oxaloacetate and the consensing enzyme synthase, the etherase present forms citrate from diethyl ether, indicating an acetylation of CoA, which then enters the citric acid cycle. 4. Similarly to 3, fluorocitrate is formed from methyl fluoroethyl ether. 5. Differing from plasmalogens, a tetrahydropteridine does not have to be added as a co-factor. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Micro-electrode measurement of the internal pH of crab muscle fibres.? [/INST] The internal pH of crab muscle fibres was measured using recessed-tip pH-sensitive micro-electrodes. Immediately following electrode penetration the mean internal pH was 7-21 +/- 0-02 (S.E. of mean) and the mean membrane potential was -64-9 +/- 0-6 mV (S.E. of mean). If H+ ions were passively distributed across the fibre membrane the internal pH would have been 6-39. 2. The internal pH tended to rise before stabilizing at a mean value of 7-27 +/- 0-02 (S.E. of mean). The difference between immediate and stabilized values is highly significant and suggests acid injury on electrode penetration. 3. Changing the membrane potential or external pH had only small, slow effects on internal pH. 4. External CO2 caused a large and rapid decrease in internal pH. With low concentrations of CO2, the effect was dependent on the initial pH as predicted by the Law of Mass Action. During a long exposure to 2-65% CO2 at pH 7-5, the internal pH returned slowly to its previous value, suggesting active transport of H+ (or OH- or HCO3-) ions across the fibre membrane. 5. The internal buffering power calculated from the response to 2-65% CO2 was 47-3 +/- 2-8 slykes (m-equiv H+/pH unit per l.) (S.E. of mean). </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Proteins in the luminal fluid from the bovine oviduct.? [/INST] Oviducal fluid was collected by cannulation from four cows and by irrigation from fifteen slaughtered cows. The proteins in the fluid were examined by polyacrylamide gel electrophoresis at pH 4-5 and pH 8-9, isoelectric focusing on polyacrylamide, immunodiffusion, immunoelectrophoresis, affinity chromatography and gel filtration. The macromolecular components found were mainly serum proteins but small amounts of other proteins were detected in oestrous and dioestrous samples by electrophoresis at pH 8-9 following fractionation of the fluid by gel filtration or affinity chromatography. Small amounts of cathodically migrating proteins were detected directly by electrophoresis at pH 4-5 in dioestrous samples but not in oestrous samples. Determination of glycosidase activities revealed that the levels at oestrus were similar to the levels detected in serum. At dioestrus, the activities of B-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase were elevated. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Boar seminal zinc-precipitable protein and the haemagglutinin.? [/INST] About 30% of boar seminal plasma nitrogen is maximally precipitated at room temperature by 6 to 10 mM zinc in citrate solution at pH 8. A rise in the total nitrogen precipitated by 1 to 6 mM zinc is accompanied by a fall in the haemagglutinin titre of the supernatant fluid. At 6 mM zinc addition, 95% of the haemagglutinin is precipitated, but much of this is recoverable by re-solution of the zinc precipitate. Protein profile studies by gel-filtration chromatography of the zinc precipitate solution reveals a mixture of proteins, some of which are not by themselves zinc-precipitable. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Importance of the aromatic ring in adrenergic amines. 2. Synthesis and adrenergic activity of some nonaromatic six- and eight-membered ring analogs of beta-phenylethanolamine.? [/INST] The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Conformationally restricted analogs of histamine H1 receptor antagonists: trans and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine.? [/INST] The syntheses of trans- and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine (1 and 2) are described. Compounds 1 and 2 were found to be inhibitors to histamine, acetylcholine, and barium chloride induced contractions of the isolated guinea pig ileum. Compounds 1 and 2 do not exhibit appreciable stereoselectivity in their ability to inhibit smooth muscle contractions. The cis compound 2 is a more effective inhibitor of histamine N-methyltransferase than the trans isomer 1. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine.? [/INST] Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Prebiotic peptide-formation in the solid state. II. Reaction of glycine with adenosine 5'-triphosphate and P1,P2-diadenosine-pyrophosphate.? [/INST] When a solution containing gly-N-pa and imidazole is evaporated to dryness and then maintained at a temperature between 65 degrees C and 100 degrees C, high yields of AppA and obligoglycines are obtained. We believe that ImpA is formed first, and then activates the carboxyl group of glycine or gly-A-pA. If glycine, ATP or AppA, and imidazole are heated together in the solid state, ImpA is formed and ATP , or indirectly from imidazole and gly-N-pA. Next the carboxyl group or glycine is activated by the ImpA formed in situ. The subsequent reactions of activated glycine leads to the formation of oligoglycines and the 2' (3')-glycylester of pA. Under plausible prebiobic conditions, good yields of oligoglycines up to the octamer can be obtained from glycine, ATP and imidazole. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Prebiotic peptide-formation in the solid state. III. Condensation reactions of glycine in solid state mixtures containing inorganic polyphosphates.? [/INST] The reactions of glycine with inorganic polyphosphates in the solid state have been studied. The formation of peptides up to the decamer occurs at moderate temperatures(r.t.-100 degrees C) in the presence of imidazole and magnesium chloride. If adenosine 5' -monophosphate is added to the reaction mixture, 2'(3') -o-glycyl adenosine 5'-monophosphate is also obtained. These reactions could have occurred on the primitive earth. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The prebiotic synthesis of deoxthymidine oligonucleotides. II. Comparison of condensing agents.? [/INST] A reaction which oligomerizes nucleotides under possible prebiotic conditions has been characterized. Nucleoside monophosphate in the presence of cyanamide at acid pH condenses to form dithymideine pyrophosphate and phosphodiester bonded compounds. Imidazole compounds and activated precursors such as nucleoside triphosphate are not necessary for this ologomerization reaction which produces primarily cyclic ologonucleotides. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Formation of nucleoside 5'-polyphosphates from nucleotides and trimetaphosphate.? [/INST] When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about On the possible role of organic melanoidin polymers as matrices for prebiotic activity.? [/INST] One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an "organic soup". Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions. We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Hemoglobin function in the vertebrates: an evolutionary model.? [/INST] Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Aminoacyl transfer from an adenylate anhydride to polyribonucleotides.? [/INST] Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly(U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly(U). At pH 7.1, transfer to poly(U) was five times as great as to poly(A) and transfer to a poly(A) poly(U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly(U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2' hydroxyl groups throughout poly(U) and the 2' (3') hydroxyl groups at the terminus of poly(U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Hybrid-versus-parental strain reaction. I. Comparative mortality in allogenetic and parental strain male and female mice.? [/INST] Lethally irradiated male and female hybrids, parental strains, and the third party strain A mice were inoculated with reciprocal hybrid marrow from donors of the same sex. A graft-versus-host reaction was produced against H-Y antigens of reciprocal hybrids. Although the late mortality in inbred strain males was generally greater than that of females, without further tests this difference was not automatically attributable to an X or a Y chromosome disparity. Hybrids did not recognize the qualitative difference in antigenicity of their reciprocals, but they were able to recognize the quantitatively greater antigenicity of their parental strains, and a hybrid-versus-parental strain reaction occurred. The graft-versus-host reaction in the third party strain A mice was significantly more severe than that produced by hybrid marrow in their reciprocal hybrid recipients, but significantly less severe than that produced in the parental strains. The relationship between antigenicity and responsiveness was such that the severity of the graft-versus-host reactions masked the maternal influences observed with other reciprocal hybrids. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Graft versus leukemia. VI. Adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia-lymphoma in AKR mice.? [/INST] A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To "rescue" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about A study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction.? [/INST] The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Metabolic characteristics of cells infected with a herpesvirus of turkeys.? [/INST] Chicken embryo fibroblasts infected with the nononcogenic herpesvirus of turkeys (HVT) displayed an increased rate of glucose uptake, a pronounced alteration of the pH of the medium, and an increased production of lactic acid when compared to mock-infected cultures. Objective estimates of cytopathology (quantifiable neutral red uptake and cell protein determination) showed that cell deterioration was a slow process in HVT-infected cells when compared to infection by herpes simplex virus. Experiments with irradiated host cells demonstrated that HVT required functional cell DNA for replication. The inactivation of the necessary host cell function displayed multihit kinetics. In agreement with data on other herpesviruses, HVT damaged by UV light could be photoreactivated in chick cells. The results indicate that HVT shares biologic properties in common with other herpes and transforming viruses. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Control of mercury pollution.? [/INST] When a 203Ng(NO3)2 solution was kept at 25 degrees C in glass or polypropylene containers, 50 and 80% of original radioactivity was adsorbed to the containers' walls after 1 and 4 days, respectively. However, no loss in radioactivity was observed if the solution was supplemented with HgCl as carrier (100 mug Hg2+/ml) and stored in either container for 13 days. When 203Hg2+ was dissolved in glucose basal salt broth with added carrier, levels of 203Hg2+ in solution (kept in glass) decreased to 80 and 70% of original after 1 and 5 days and decreased even more if stored in polypropylene (60 and 40% of original activity after 1 and 4 days, respectively). In the absence of carrier, decreases of 203Hg2+ activities in media stored in either container were more pronounced due to chemisorption (but) not diffusion. The following factors affecting the removal of mercurials from aqueous solution stored in glass were examined: type and concentration of adsorbent (fiber glass and rubber powder); pH; pretreatment of the rubber; and the form of mercury used. Rubber was equally effective in the adsorption of organic and inorganic mercury. The pH of the aqueous 203Hg2+ solution was not a critical factor in the rate of adsorption of mercury by the rubber. In addition, the effect of soaking the rubber in water for 18 hr did not show any statistical difference when compared with nontreated rubber. It can be concluded that rubber is a very effective adsorbent of mercury and, thus, can be used as a simple method for control of mercury pollution. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species.? [/INST] The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Renal chromium accumulation and its relationship to chromium-induced nephrotoxicity.? [/INST] This report is an attempt to study the renal handling of chromium under in vitro conditions and to relate this to the actions of the ion in the production of nephrotoxicity. Renal slice techniques were employed in these studies and were used to examine the effects of chromium on various renal transport processes. In addition, the accumulation of chromium by the renal tissue has also been studied. Marked accumulation by renal cortical slices of the rat was observed when 51Cr-labeled chromate or dichromate was added to the bathing solution. Some metabolic inhibitors interfered with this uptake process; in addition, some substrates metabolized by renal tissue reduced the accumulation of 51Cr. The use of [51Cr] dichromate and [51Cr]-chromate, as well as alterations in the bathing solution pH, indicated that in the rat chromium can interfere with renal transport processes, but that the oxidation state of this metal is not important. On the other hand, in the rabbit a greater interference with 51Cr uptake was noted at lower bathing solution pHs. This is interpreted to mean that chromate is the effective inhibitor in this species. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Sarcotubular anomalous rectification of frog sartorius muscle.? [/INST] The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Properties of sarcolemmal delayed rectification in glycerol-treated fibers of frog sartorius muscle.? [/INST] Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Sarcolemmal slow conductance increase of frog sartorius fibers during hyperpolarization.? [/INST] The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of antidepressant drugs on amygdaloid after-discharge in rats.? [/INST] Effects of antidepressant drugs on the amygdaloid after-discharge induced by stimulating the amygdala in rats implanted with chronic electrodes, were investigated in correlation with anti-muricidal effects as well as neurotoxicity. Tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline markedly depressed both after-discharge and muricide at doses smaller than neurotoxic doses. The effect of PF-257 was also the same as tricyclic antidepressants. On the other hand, methamphetamine and pipradrol blocked the muricide at doses smaller than neurotoxic doses without depressing the amygdaloid after-discharge. Major tranquilizers, chlorpromazine and clozapine depressed both after-discharge and muricide only at doses larger than those which impaired rotarod performance. Haloperidol, on the contrary, depressed the after-discharge without selectively blocking the muricide. Minor tranquilizers, diazepam and chlordiazepoxide did not block the muricide at doses smaller than neurotoxic doses, although they showed a marked depression of the after-discharge. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of several beta-blockers on blood pressure in the rat.? [/INST] Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Renal response to short-term hypocapnia in man.? [/INST] This study examines the renal response to moderate hyperventilation in healthy man. Eight men hyperventilated for 26 hr (PaCO2 approximately 30 to 32 mm Hg) in normoxia (barometric pressure, PB approximately 740 mm Hg) and hypobaric hypoxia (PB approximately530 mm Hg). Anaerobic samples of arterial blood and urine were studied at two-hour intervals. Plasma [HCO3-] fell with time during sustained hypocapnia and after 26 hr was reduced 2.5 mEq/liter, with plasma pH compensated approximately 60%. Statistically significant changes in renal H+ handling were observed within the initial 2 hr of hyperventilation and were evident over the first 12 hr. Over 26 hr, mean total HCO3-excretion in hypocapnia was 10.2 mEq above control and mean total acid excretion (UVTA + UVNH4+) was 17.5 mEq below control. An increased urinary excretion of cations, especially sodium, accompanied the decrease in acid excretion. Plasma lactic acid accumulation was negligible. We conclude that renal mechanisms contribute significantly and relatively quickly to plasma pH compensation during the early phase of adaptation to hypocapnia in man. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about [Stress incontinence in the woman (author's transl)].? [/INST] The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis.? [/INST] The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower "energy pressure" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Studies in vitro of lipogenesis in rat testicular tissue.? [/INST] Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Fatty acid synthesis from 2-14C-acetate in rat testis mitochondrial and cytosol fractions in vitro.? [/INST] An in vitro system for acetate incorporation into fatty acids by the mitochondrial and the cytosol fractions of rat testis is described. The rate of incorporation of acetate into fatty acids was twice as fast with the mitochondrial as with the cytosol fraction; both systems were stimulated in the presence of adenosine triphosphate, reduced nicotinamide adenine dinucleotide phosphate, coenzyme A, and MgC1(2). The optimum pH was between 7.0-7.5 for the mitochondrial fraction and between 6.5-8.0 for the cytosol fraction. Radio gas chromatography showed that palmitic acid was the most highly labeled acid, followed by stearic acid, in the mitochondrial fraction in accord with the pathway of de novo fatty acid synthesis. Some of the labeled acetate was also incorporated into the 16:1 and 18:1 fatty acids of this fraction. Distribution of radioactivity among the mitochondrial lipid classes was highest in the phospholipids and monoglycerides, followed by diglycerides and cholesterol; little radioactivity was present in the triglyceride fraction. These observations are in accord with studies of the incorporation of labeled metabolites into testicular lipids following intratesticular injection and indicate the validity of the in vitro system for studies of specific reactions occurring in vivo. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Fat metabolism in higher plants: metabolism of medium chain fatty acids.? [/INST] Cell free preparations of avocado mesocarp and spinach leaf tissue rapidly convert lauryl CoA to DL-3-hydroxyl lauric acid as well as 2-, and 3-dodecanoic acids. The conversion does not occur under anaerobic conditions unless a suitable redox carrier such as ferredoxin is present. H2 18O is incorporated into the 3-hydroxyl function, but O2(18) is not. The characteristics of this system are presented and a possible function of this system is proposed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Stearoyl-CoA desaturase activity in mammary adenocarcinomas carried by C3H mice.? [/INST] Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Vasculitis with hepatitis B antigenemia: long-term observation in nine patients.? [/INST] The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Polyarthritis, polyarteritis and hepatitis B.? [/INST] An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Some evidence for aldosterone action on 2,3-diphosphoglycerate level in human red cells.? [/INST] In healthy male subjects aldosterone excretion and plasma renin activity were reduced by a 4-6 hr head-out immersion in thermoindifferent water baths (35.5 +/- 0.1 degrees C). The red cell 2,3-diphosphoglycerate (DPG) concentration before and throughout immersion period was positively correlated both with aldosterone excretion in 2 hr pooled urine (r = +0.69; 2 p less than 0.001) and with renin activity (r = + 0.54; 2p less than 0.001) despite a concomitant increase of cubital venous pH and inorganic phosphate concentration. These findings furnish evidence for a regulatory role of aldosterone in DPG metabolism, possibily by a direct influence on red cell glycolysis. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism.? [/INST] We studied the relative importance of hyperkalemia and mineralocorticoid deficiency in the metabolic acidosis of a patient with proved isolated hyporeninemic hypoaldosteronism and moderate kidney failure. The hyperkalemia and acidosis were severe in relation to the slight azotemia. Despite the systemic acidosis and urinary pH of 4.9, urinary ammonium excretion was distinctly blunted. Correction of the hyperkalemia by potassium-sodium exchange resin alone resolved the acidosis and restored the previously diminished urinary ammonium excretion to normal. Administration of mineralocorticoids only partially corrected the hyperkalemia and the acidosis. Hyperkalemia by itself, rather than hypoaldosteronism per se, caused the acidosis in this patient. Hyperkalemia apparently suppresses urinary ammonium excretion and thus interferes with urinary acidification. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Isolation of Penicillium corylophium Dierckx from acid mine water and its optimal growth on hydrocarbons at acid pH.? [/INST] Penicillium corylophilium Dieckx was isolated from sludge collected at the interface of an aqueous, copper-bearing leachate and an organic, kerosene based, ion exchange solvent. The organism assimilated kerosene and various straight chain and cyclic hydrocarbons including dodecane, hexadecane, octadecane, toluene, benzene, and cyclohexane. Assimilation of kerosene and hexadecane was optimal at pH 2 and was stimulated by yeast extract. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The effect of microbial mycolytic agents on Trichophyton rubrum.? [/INST] Chitinolytic microorganisms isolated from forest soil and from healthy gypsy moth larvae (Porthetria dispar (L.) were screened for their ability to lyse Trichophyton rubrum mycelia. A few of these isolates were mycolytic on both autoclaved and on actively growing, intact, T. rubrum mycelia. Supernatants from these isolates, utilizing live T. rubrum as the sole carbon source, showed the same mycolytic ability. Assays of the supernatants for enzymatic activity revealed exocellular, stable enzymes that releases reducing substances including N-acetylglucosamine from the mycelia. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Models for metal ion function in carbonic anhydrase.? [/INST] A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about [Regulation of lipid synthesis in animal organs].? [/INST] Studies were made of the mechanisms regulating the quantity and catalytic efficiency of hepatic acetyl coenzyme A carboxylase, which plays a critical role in the control of fatty acid biosynthesis. The microsomal enzyme system responsible for the formation of phosphatidic acid, the initial step in glycerolipid biosynthesis, was resolved into two component enzymes. The acyl-donor specificities of these and other acyltransferases account for the asymmetric fatty acid distribution in naturally occurring glycerolipids. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Studies on the mechanism of the action of morphine on the peristalsis of guinea pig ileum in situ.? [/INST] The influence of some drugs on the effect of morphine on the threshold pressure required to elicit peristalsis in the guinea pig ileum in situ was studied, in order to test the hypothesis that this effect of morphine is mediated by catecholamine release. Tachyphylaxis to this effect of morphine was confirmed. Pretreatemnt with two 8 mg/kg doses of reserpine, 24 and 48 hrs before the experiment, significantly reduced the effect of morphine on the pressure threshold. The i.v. administration of 10 mg/kg dl-Dopa re-established the effect of morphine in reserpinized animals to the level of the untreated controls. Pretreatment with guanethidine (15 mg/kg) decreased and even prevented this effect of morphine. Phentolamine pretreatment (10 mg/kg) also significantly inhibited the effect of morphine. Neither DCI nor propranolol influenced this morphine effect. Pretreatment with reserpine, guanethidine or phentolamine reduced the basic pressure threshold needed to elicit peristalsis. The possibility that the decrease of local circulation induced by hypotenison would reduce the local concentration of morphine was rejected because the same doses of guanethidine or phentolamine did not modify the effect of hexamethonium given i.v. in this preparation. All these results support the idea that the effect of morphine on intestinal peristalsis is mediated by a catecholamine acting on alpha-receptors, e.g. norepinephrine. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets.? [/INST] In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-keto-isovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to l-leucine, l-norleucine or l-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Changes in hypothalamic neurotransmitter uptake following pinealectomy, superior cervical ganglionectomy or melatonin administration to rats.? [/INST] Rats subjected to pinealectomy or to pinealectomy plus bilateral superior cervical ganglionectomy exhibited depressed serotonin uptake by hypothalamic synaptosomes; norepinephrine, dopamine or glutamate uptake was not affected by any of the surgical procedures. Treatment with melatonin resulted in inhibition of hypothalamic serotonin accumulation but it did not modify the uptake of norepinephrine, dopamine or glutamate. These data suggest a relationship between the pineal gland and the serotoninergic nerve endings of the hypothalamus. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about High pH ammonia toxicity, and the search for life on the Jovian planets.? [/INST] Jovian plants have enviroments apparently suitable for the evolution of life, but nevertheless, present severe challenges to organisms. One such challenge arises from the presence of ammonia. Ammonia is an efficient biocide, its effect being dependent on pH as well as on concentration. The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural enviornments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, survival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is, nevertheless, two to three orders of magnitude longer than for E. coli. Our data support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt.? [/INST] Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cardiovascular effects of electrical stimulation of the forebrain in the fetal lamb.? [/INST] Modified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115-135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of alpha-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to beta-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome.? [/INST] Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about pH and bicarbonate excretion in the rat parotid gland as a function of salivary rate.? [/INST] The bicarbonate concentration in rat parotid saliva increases with increasing flow rates and approximates plasma values at highest salivation. At lowest flow rates the bicarbonate concentration in the secretory fluid markedly exceeds the plasma levels. Intravenous administration of acetazolamide has no influence on the bicarbonate excretion of the parotid gland. Following retrograde application of acetazolamide into the gland duct the concentrations of both bicarbonate and sodium are elevated. The potassium concentrations in final saliva exceed 70 mEq/l at flow rates below 5 mul/min g gland weight. With increasing flow rates a precipitous decrease in potassium concentration below 10 mEq/l occurs. With further increase in flow rate the potassium concentration remains unchanged. The sodium concentrations increased with augmented salivation rate. At lowest flow rates the sodium concentrations showed an increase of modest degree. Our findings can best be explained by the existence of two independent ductular mechanism: a) bicarbonate reabsorption probably in the striated ducts of the parotid gland; b) secretion of potassium with concomitand secretion of bicarbonate in the main excretory duct. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about H+ transport and membrane-bound HCO - 3 ATPase in salivary duct epithelium.? [/INST] An ATPase stimulated by HCO - ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO - 3 ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO - 3. The HCO - 3 ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'-nucleotidase. The activities of the HCO - 3 ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO - 3 and K+ ions by the duct epithelium. These findings provide further evidence that the membrane-bound HCO - 3 ATPase is involved in active H+/HCO - 3 transport. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of cyanide and doxapram during hypothermia.? [/INST] The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and at two levels of hypothermia. In the normothermic animal, KCN evoked significant elevations of minute and alveolar ventilations. For the mildly hypothermic (32-33 degrees C) dog, minute and alveolar ventilations were proportionally greater than for normothermia. Bolus infusions of KCN to deeply hypothermic dogs (28-29 degrees C) elicited larger and nearly similar increases of minute and alveolar ventilations as compared, respectively, with normothermia and mild hypothermia. Compared to their controls, injections of doxapram during normothermia, mild and deep hypothermia augmented VE 43.3%, 63.6% and 31.5%, respectively. With doxapram there was a feeble increase in alveolar ventilation. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to respond to stimuli given acutely while lowering core temperature and in some circumstances this capacity is even enhanced as compared to normothermia. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of cyanide and doxapram during panting.? [/INST] The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic animal, KCN evoked elevation of VE (154.7%), VT (70.1%), f (48.3%, PaO2 (12.1%) and pH (0.098 units), while PaCO2 diminished by 9.7 mm Hg. During panting, KCN infusions resulted in increases of VE (24.5%), VT (46.6%), PaO2 (3.9%) and pH (0.034 units), while f decreased (10.1%). Bolus injections of doxapram during normothermia increased VE (32.6%), VT (18.8%) and f (17.1%). During panting VE, VT and f increased by 18.0%, 18.2% and 1.5%, respectively. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to react to acute chemical stimuli in animals in which the thermal stimuli override the normal chemical control of respiration in order to control body temperature, and that this reaction contributes to the integrated respiratory drive. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Combating diabetic ketoacidosis and other hyperglycemic-ketoacidotic syndromes.? [/INST] Diabetic ketoacidosis is an acute medical emergency that requires immediate diagnosis and treatment. Diagnosis may be established rapidly by measurement of urinary glucose and ketones, arterial blood pH and blood gases, and serum ketones. Rapid infusion of large volumes of fluids and electrolytes, together with continuous infusion of low doses of insulin, provides effective restoration of fluid and electrolyte balance and correction of metabolic derangements. Hyperosmolar nonketotic coma is characterized by marked hyperglycemia in the absence of ketoacidosis and occurs usually in patients with mild adult-onset diabetes. Symptoms develop more slowly than in diabetic ketoacidosis. Treatment is the same for both conditions. In alcoholic ketoacidosis, hyperketonemia is present without hyperglycemia. The syndrome differs from diabetic ketoacidosis in that blood glucose levels are lower and glycosuria is absent. Treatment consists of intravenous administration of dextrose in water and, if necessary, of sodium bicarbonate. Insulin administration usually is not necessary. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Regulation of synthesis of glutamine synthetase by adenylylated glutamine synthetase.? [/INST] We have examined three mutants of Klebsiella aerogenes whose genetic lesions (glnB, glnD, and glnE) are in loci unlinked to the structural gene for glutamine sythetase (glnA) and in which the control of both the level and state of adenylylation of glutamine synthetase is altered. Each mutation alters a different component of the adenylylation system of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. Inability of the cell to deadenylylate glutamine synthetase (glnB and glnD) greatly decreases its production, while inability to adenylylate glutamine sythetase (glnE) results in its constitutively high production. These results together with our previous results indicate that adenylylated glutamine synthetase inhibits the transcription of glnA. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Neuronal properties of hybrid neuroblastoma X sympathetic ganglion cells.? [/INST] Clonal mouse neuroblastoma cells without tyrosine 3-monooxygenase [EC 1.14.16.2; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating)] activity were fused with normal cells from embryonic mouse sympathetic ganglia. One of the 37 hybrid cell lines obtained possesses high tyrosine 3-monooxygenase activity and synthesizes dopamine. These cells also have excitable membranes and generate action potentials in response to electrical stimuli. Thus hybrid cells, generated by fusion of neuroblastoma cells with normal cells from the nervous system, can acquire neural properties not found with the parental neuroblastoma cells. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Regulation of ferredoxin-catalyzed photosynthetic phosphorylations.? [/INST] Under aerobic conditions that are likely to prevail in chloroplasts in vivo, the optimal concentration of ferredoxin for cyclic photophosphorylation was found to be equal to that required for NADP reduction and about one-tenth of that needed for cyclic photophosphorylation under anaerobic conditions. In the presence of ferredoxin and NADP, cyclic photophosphorylation operated concurrently with noncyclic photophosphorylation, producing an ATP: NADPH ratio of about 1.5. The effective operation of ferredoxin-catalyzed cyclic photophosphorylation by itself required a curtailment of the electron flow from water which was accomplished experimentally by the use of either an inhibitor or far-red monochromatic light. An unexpected discovery was that the operation of cyclic photophosphorylation by itself was also regulated by a back reaction of NADPH and ferredoxin with two components of chloroplast membranes, component C550 and cytochrome b559. The significance of these findings to photosynthesis in vivo is discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about High resolution 31P nuclear magnetic resonance studies of intact yeast cells.? [/INST] High resolution 31P nuclear magnetic resonance (NMR) spectra at 145.7 MHZ are presented for intact yeast cells. Several peaks are resolved and assigned. They include the middle phosphate peaks from long chain or cyclic polyphosphates. Our results are consistent with the suggestion that these polyphosphates act as a phosphate store in the cell. We have also been able to measure cytoplasmic pH using the orthophosphate peak inside the cell, as compared with outside the cell. The results show that yeast cells maintain their cytoplasmic pH around 6.3. This value is considerably higher than the acidic extracellular pH at which they normally live. These preliminary results indicate that 31P NMR at 145.7 MHZ can be a rapid, informative, and non-invasive method for probing biochemical events within living cells. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Reversal of UDP-galactose 4-epimerase deficiency of human leukocytes in culture.? [/INST] Stimulation with phytohemagglutinin of the leukocytes from six of the seven known individuals with UDP-galactose 4-epimerase (= UDP-glucose 4-epimerase; EC 5.1.3.2) deficiency consistently resulted in the appearance of epimerase activity in the cultured cells. A long-term lymphoblast culture derived from one proband also contained an active epimerase enzyme. A comparison of the properties of this enzyme with those of epimerase produced by control lymphoblast lines revealed comparable Km values for UDP-galactose and NAD and identical behavior on polyacrylamide electrophoresis. However, a difference in the NAD requirement for heat stability at 40 degree provided some evidence for a structural defect in this enzyme. Possible explanations for the appearance of UDP-galactose 4-epimerase activity in stimulated lymphocytes include an increased rate of synthesis of a mutant enzyme and a derepression of an epimerase locus during lymphocyte transformation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity.? [/INST] beta-Bungarotoxin, a pre-synaptic neurotoxin isolated from the venom of the snake Bungarus multicinctus, has been shown to modify release of neurotransmitter at the neuromuscular junction. In this communication, we demonstrate that beta-bungarotoxin is a potent phospholipase A2 (phosphatide 2-acyl hydrolase, EC 3.1.1.4), comparable in activity with purified phospholipase enzymes from Naja naja and Vipera russellii. The phospholipase activity of beta-bungarotoxin requires calcium and is stimulated by deoxycholate. When strontium replaces calcium, no phospholipase activity is detected. Since neuromuscular transmission is not blocked when calcium is replaced by strontium, it was possible to examine the effects of the toxin on neuromuscular transmission in the presence of strontium. Under these conditions, when the phospholipase activity should be inhibited, the toxin has little or no effect on neuromuscular transmission. If beta-bungarotoxin owes its toxicity in part to its enzymatic activity, then it must be placed in a different class from those toxins which produce their effect by binding passively to an appropriate receptor. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Isolation and characterization of an unsaturated fatty acid-requiring mutant of cultured mammalian cells.? [/INST] An unsaturated fatty acid-requiring mutant derived from Chinese hamster ovary (CHO) cells has been isolated and characterized. This mutant grows normally when oleate or other unsaturated fatty acids are supplemented in the growth medium. Unlike the wild-type CHO cells, growth stops when medium is deprived of unsaturated fatty acid. Whole cell pulse experiments with [14C]acetate or [14C]stearate indicate that the mutant is defective in unsaturated fatty acid synthesis. Enzyme assays in vitro show that the enzymatic defect of the mutant is localized to the microsomal stearoyl-CoA desaturase. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about DNA single-strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum.? [/INST] The method of DNA alkaline elution was applied to a study of the formation and resealing of DNA single-strand breaks after irradiation of human fibroblasts with ultraviolet light (UV). The general features of the results were consistent with current concepts of DNA excision repair, in that breaks appeared rapidly after UV, and resealed slowly in normal fibroblasts, whereas breaks did not appear in those cells of patients with xeroderma pigmentosum (XP) that are known to have defects in DNA repair synthesis. The appearance of breaks required a short post-UV incubation, consistent with the expected action of an endonuclease. Cells of the variant form of XP characterized by normal DNA repair synthesis exhibited normal production of breaks after UV, but were slower than normal cells in resealing these breaks. This difference was enhanced by caffeine. A model is proposed to relate this finding with a previously described defect in post-replication repair in these XP variant cells. DNA crosslinking appears to cause an underestimate in the measurement of DNA breakage after UV. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Modifications of purified glucose-6-phosphate dehydrogenase and other enzymes by a factor of low molecular weight abundant in some leukemic cells.? [/INST] Highly purified platelet glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49) can be modified in its isoelectric point and its molecular specific activity by extracts of some leukemic granulocytes. The "G6PD modifying factors" are relatively small molecules (molecular weight slightly under 5000), thermostable, dialyzable, and ultrafilterable. These molecules are destroyed by various endo- and exopeptidases and by serine enzymes present in crude extracts of leukocytes and commercial preparations of ribonuclease. The alterations of platelet G6PD due to the "G6PD modifying factors" are stable and not reversible by dialysis or further chromatography. The leukemic extracts which are able to modify G6PD also can modify the electrophoretic mobility and (or) the enzymatic activity of purified leukocyte pyruvate kinase, 6-phosphogluconate dehydrogenase, and glucosephosphate isomerase. The chemical nature of such modifications and their relationships with post-translational modifications which occur in leukemic or normal cells are discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Copper-induced activation of aortic lysyl oxidase in vivo.? [/INST] Raising day-old chicks on diets lacking copper severely depressed the activity of lysyl oxidase, a copper metalloenzyme in connective tissue. Administration of CuSO4 either through the diet or through intraperitoneal injections restored the lysyl oxidase activity in aortic tissue. Two hours after the chicks received CuSO4 (1 mg/kg) the activity of lysyl oxidase rose rapidly to attain, within 4-6 hr, a new steady-state level which was five to 20 times higher than the basal (saline-injected) activity. Twenty hours after copper administration, activity was still higher, in some experiments double that achieved at 6 hr. Very low amounts of cycloheximide injected intraperitoneally 45 min before and 3 hr after copper suppressed the activation response by two-thirds. Cycloheximide given 2 or 4 hr after the copper was only one-half as effective. Actinomycin D caused only a 10-15% inhibition of the copper-induced activation. The data suggest that copper is a key regulator of lysyl oxidase activity in aorta and may in fact be a major determinant of the steady-state levels of the enzyme in that tissue. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Evidence that acyl coenzyme A synthetase activity is required for repression of yeast acetyl coenzyme A carboxylase by exogenous fatty acids.? [/INST] The cellular content of acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] in Saccharomyces cerevisiae is reduced by the addition of long-chain fatty acids to the culture medium. Mutant strains of S. cerevisiae defective in acyl-CoA synthetase [acid:CoA ligase (AMP-forming), EC 6.2.1.3] were isolated and used to determine whether fatty acid itself or a metabolite of fatty acid is more directly responsible for the repression of acetyl-CoA carboxylase. Cells of the mutant strains were capable of incorporating fatty acid to an extent comparable to that observed with the wild-type strain, but they accumulated markedly more of the incorporated fatty acid in the nonesterified form than did the wild-type cells. The level of acetyl-CoA carboxylase activity in the mutants, in contrast to that in the wild-type strain, was hardly affected by the addition of fatty acids to the medium. These results indicate that the activation of exogenous fatty acid is required for the repression of acetyl-CoA carboxylase, supporting the view that the repressive effect is mediated by some compound metabolically derived from fatty acid. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa.? [/INST] Villus tip cells and crypt cells of rat jejunal mucosa were separated by the planning procedure of Imondi et al. and were studied with respect to their activities of the enzymes of the gamma-glutamyl cycle and glutathione content. The villus tip cells exhibit much higher gamma-glutamyl transpeptidase activities than do the crypt cells: thus, gamma-glutamyl trnaspeptidase appears to be a villus-specific enzyme. gamma-Glutamyl cyclotransferase and the enzymes required for glutathione synthesis are not specifically localized to either the crypt or villus tip cells but are present in both. The crypt cells have a high concentration of glutathione (4-5 mM) comparable to the levels found in liver and kidney; in contrast, the villus tip cells have much lower concentrations. On fasting, the glutathione concentration decreased markedly in both villus tip and crypt cells; feeding of protein, but not of sucrose, led to increased glutathione concentrations. The migration of cells from the undifferentiated crypt cell region to the villus tip is associated with structural and biochemical changes that equip the cell for its mature functional activities, which include transport. The present findings indicate that such cellular differentiation and migration is associated with a marked increase in gamma-glutamyl transpeptidase activity and in the utilization of glutathione. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Maturation of neuroblastoma cells in the presence of dimethylsulfoxide.? [/INST] Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Properties of a toxin from the sea anemone Stoichacis helianthus, including specific binding to sphingomyelin.? [/INST] Stoichactis helianthus toxin, a protein derived presumably from the nematocysts, was purified to homogeneity. It has a molecular weight of about 16,000, an isoelectric pH of 9.8, and it contains approximately 3.7% carbohydrate. It is powerfully hemolytic for erythrocytes derived from a variety of animal species, those of the cat being the most sensitive and those of the guinea pig the most resistant. The toxin is lytic also for rabbit blood platelets, and it destroys cultured fibroblasts but is inactive for several kinds of bacterial protoplasts and spheroplasts. The hemolytic activity is specifically inhibited by sphingomyelin, and it is proposed that this phospholipid is the constituent of the membrane which functions as receptor for the toxin. Supporting evidence includes the findings that enzymes known to destroy sphingomyelin (a) prevent erythrocyte membranes from inhibiting hemolysis, and (b) render erythrocytes resistant to lysis by the toxin. The mechanism underlying hemolysis may involve translocation of membrane sphingomyelin by virtue of a specific affinity of the coelenterate protein for this phospholipid. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Mechanistic studies of glutamine synthetase from Escherichia coli: kinetic evidence for two reaction intermediates in biosynthetic reaction.? [/INST] Fast reaction techniques were used to study the kinetics of protein fluorescence intensity changes that are associated with the reactions of unadenylylated Escherichia coli glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.2] with its substrates. It was established that the synthesis of glutamine occurs by a stepwise mechanism. During the catalytic process two fluorometrically distinct intermediates were observed. Both forward and reverse rate constants which lead to the formation and consumption of these intermediates were evaluated. The catalytic rate constant, kc, which was calculated from these rate constants agrees well with the values of kc which were determined by direct measurement of the overall biosynthetic activities by means of stopped-flow technique or the steady-state assay method. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Molecular mechanism of inhibition of firefly luminescence by local anesthetics.? [/INST] The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause of the inhibition, but hydrophilic interaction also contributes to the inhibition to a lesser degree. A molecular theory of anesthesia is outlined which postulates that release of electrostricted water molecules from the hydrophilic parts of the enzyme due to the protein conformational changes induced by anesthetics is the cause of the decreased luminescence. A similar mechanism is expected to occur at the cell membrane, which probably dehydrates the sodium channel and suppresses the conductance of this ion across the membrane. These events lead to a volume expansion of the total system, and the system becomes reactive to a pressure which reverses the anesthesia by shifting the equilibrium to the nonanesthetized original volume. The pressure antagonism of anesthesia can be explained by this overall volume expansion and not by a mere swelling of the cell membrane. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cyclic nucleotide metabolism in compensatory renal hypertrophy and neonatal kidney growth.? [/INST] Cyclic nucleotide metabolism was investigated in growing kidneys of rats during compensatory hypertrophy and during neonatal development. After unilateral nephrectomy a mild and short-lasting decrease in cyclic 3':5" adenosine monophosphate (cAMP) was observed in the hypertrophying kidney. In contrast, cyclic 3':5' guanosine monophosphate (cGMP) showed a sharp decline to 20% of control at 15 min and a rapid rise to 200-300% above base-line at 1-72 hr. The alterations in renal tissue levels of cGMP were associated with parallel changes in the soluble, 100,000 X g supernatant guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing): EC 4.6.1.2]. No change was observed in total cGMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase; EC 3.1.4.17). In the rapidly growing kidney of newborn rats cAMP levels were 983 +/- 65 and 833 +/- 42 pmol/g of kidney at 4 and 7 days after birth, and increased to adult levels (1518 +/- 57 pmol/g) at 21 days whereas cGMP levels were 59.8 +/- 6.8 and 92.5 +/- 13.9 pmol/g at 4 and 7 days and decreased to adult levels (36 +/- 1.5) at 21 days. The results indicate that compensatory renal hypertrophy and neonatal kidney growth are associated with changes in cAMP and cGMP metabolism. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of denaturants on the sweet-tasting protein monellin.? [/INST] Effects of the denaturants urea and guanidine-HCl on the sweet-tasting protein monellin have been studied. The pH at which monellin is initially treated with denaturant is an important factor in retention of sweetness, but the pH maintained during subsequent removal of denaturant by dialysis has no effect on activity. Recovery of sweetness of denaturant-treated monellin is favored when denaturation occurs at acid pH. Monellin treated with either 6 M guanidine-HCl or 8 M urea at acid pH retains all of its sweetness following removal of denaturant, but urea treatment at neutral pH leads to some irreversible loss of sweetness. Monellin precipitates from solution under some conditions during removal of denaturant by dialysis, and the precipitated protein is no longer sweet. Precipitation is least under acid conditions. Aggregated protein was demonstrated by gel filtration chromatography. The single sulfhydryl group of monellin was not demonstrable in the precipitated protein, having apparently become oxidized during denaturation and formation of the aggregated protein. The data support the hypothesis that the tertiary structure is important in the ability of monellin to elicit a sweet sensation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Thyroxine deiodination associated with NADPH-dependent lipid peroxidation in a submicrosomal system.? [/INST] A lipoprotein present in trypsin-treated microsomes can be oxidized with formation of malondialdehyde in a system which contains NADPH, ferric ion-ADP complex, NADPH-cytochrome c reductase and a factor. This factor, a mixture of peptides, can be isolated from hepatic microsomes by trypsin digestion and successive gel filtration through Sephadex G-100 and G-25 columns. Lipid peroxidation in this system catalyzes the deiodination of thyroxine, as does NADPH-dependent lipid peroxidation in fresh hepatic microsomes. Thyroxine inhibits lipid peroxidation as it is deiodinated in this system. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effect of environmental pH on adenovirus-associated virus.? [/INST] The influence of environmental pH on AAV was studied in infectious virus titrations, induction of CF antigens production of infectious virus, induction of immunofluorescent stainable antigen, and aggregation of the viral particles. The pH of the medium was found to influence the titer of virus stocks in that less virus was registered at acid pH's, giving differences of up to 105 TCID50 in HEK and HEp-2 cells. Less infectious virus was produced in KB cells, and decreased amounts of CF antigen appeared at acid pH's. However, increased levels of detectable intracellular FA antigen appeared at acid pH's. Electron microscopic examination of AAV particles negatively stained at various pH's showed increasingly large aggregates of particles as the pH was lowered. Under the acid conditions studied, the adenovirus helper and cell activities were only slightly suppressed, with the greatest effect due to aggregation of the virus particles. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The effect of dexamethasone on urinary acidification.? [/INST] Although it is well recognized that mineralocorticoids enhance renal acid excretion, the effect of glucocorticoids on renal acidification is unclear. Oral administration of dexamethasone to six healthy volunteers for 1 week at a daily dose of 4.5 mg was associated with mild respiratory alkalosis and a small but statistically significant increase in baseline urine pH. However, neither the ability to lower urine pH nor to excrete titratable acid and ammonium after NH4Cl acid-loading was altered. Administration of a single intravenous dose of dexamethasone sodium phosphate (7.5 mg) was associated with a significant rise in urine pH and potassium excretion and decreased titratable acid, ammonium , and phosphorus excretion in the absence of changes in blood acid-base status, creatinine clearance, or urine flow. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about A rapid method for measuring guanylate cyclase activity in mammary tissue.? [/INST] A simple and rapid method for measuring guanylate cyclase activity in broken cell preparations of biological tissues is described. This method employs the rate of conversion of [32P]GTP to [32P]cyclic-GMP. The product of this reaction is isolated by ion-exchange chromatography and by a ZnSO4-Ba(OH)2 precipitation at pH 5.7. Using this method, about 30-50 samples can be assayed for guanylate cyclase activity during a 5-6 hr period. The characteristics of this enzyme in the mammary gland were found to be similar to those described for other tissues using different methods for measuring guanylate cyclase activity. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Guanylate cyclase and cyclic-GMP phosphodiesterase activities in mammary glands of mice during pregnancy and lactation.? [/INST] Guanylate cyclase and cyclic-GMP phosphodiesterase activities were measured in homogenates of mammary glands from virgin, pregnant, and lactating mice. Guanylate cyclase activities increased 35% in mammary tissues during pregnancy, and a further 40% increase was observed during lactation. Cyclic-GMP phosphodiesterase activity also increased during pregnancy but activities were not different in glands from lactating mice vs glands from pregnant mice. These results are discussed with regard to a possible role of cyclic-GMP in regulating lactational processes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cyclic-AMP and pancreatic bicarbonate secretion in response to secretin in dogs.? [/INST] In anesthetized dogs given secretin intravenously in doses doubling every 60 min and ranging from 0.5 to 8 units per kg body weight per hr, cyclic-AMP levels in pancreatic tissue rose continuously, whereas DNA concentrations were slightly decreased. Bicarbonate concentrations and bicarbonate outputs, cyclic-AMP tissue concentrations and bicarbonate outputs, as well as cyclic-AMP tissue concentrations and juice outputs, were significantly correlated. In conscious pancreatic fistula dogs, there was also a significant correlation between cyclic-AMP and bicarbonate concentrations and outputs in the pancreatic juice after stimulation by exogenous secretin. Accordingly, enhanced release of endogenous secretin achieved by intraduodenal acidification led to a dose-dependent increase in bicarbonate and cyclic-AMP outputs in both conscious and anesthetized dogs. Phosphodiesterase inhibitors (aminophylline, caffeine, and papaverine) given alone to the conscious dogs did not initiate pancreatic bicarbonate secretion, but they potentiated bicarbonate responses to exogenous secretin. These data suggest that cyclic-AMP plays a part in secretin-stimulated pancreatic secretion. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects in the rat of intradermal injection of purified proteinases from streptococcus and Serratia marcescens.? [/INST] Purified streptococcal proteinase and Serratia proteinase are potent permeability factors in rat skin and initiate histopathological evidence of an acute inflammatory response. These effects appear to be largely independent of terminal components of complement, histamine, and polymorphonuclear leukocytes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Comparison of beta-adrenoceptor blocking properties of sotalol, oxprenolol, propranolol and pindolol on rabbit intestinal smooth muscle.? [/INST] Adrenergic agonists produced a characteristic and definite decrease in the amplitude of spontaneous contractions and tone of the isolated rabbit jejunum. Effect of phenylephrine was abolished either by phenoxybenzamine or phentolamine. Relaxation induced by epinephrine and by norepinephrine was inhibited after combined treatment with phentolamine and propranolol. Phentolamine alone diminished the response to epinephrine and to norepinephrine, but the diminution for epinephrine was greater, indicating that epinephrine has a greater affinity for alpha- than for beta-receptors in the rabbit jejunum. Stimulation of the beta-receptors by isoproterenol was inhibited by propranolol, oxprenolol, sotalol and pindolol, but the block was incomplete. The activity of these four beta-blockers in preventing the inhibitory response to isoproterenol was as follows: inidolol greater than or equal to oxprenolol greater than propranolol greater than sotalol. This demonstrates the fact that not all beta-adrenergic blocking agents possess an identical pharmacologic spectrum of activity. Also it can be suggested that the beta-receptors of jejunum differ in specificity from those of other organs. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effect of recurrent stress on postnatal increase of tyrosine hydroxylase.? [/INST] Tyrosine hydroxylase is present at birth and reaches adult levels in the hypothalamus usually during the second month. Recurrent stimulation of intrahypothalamic noradrenergic structures shortened this period of maturation in a statistically significant manner. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The antinicotinic effects of drugs with clinically useful sedative-antianxiety properties.? [/INST] Mice were given a drug per os and 2 h later were challenged with an intravenous LD95 of nicotine. Amitriptyline, imipramine, doxepin, meprobamate, chlordiazepoxide, diazepam, trifluoroperazine, haloperidol, thioridazine, chlorpromazine, phenobarbital, propranolol and diphenylhydantoin were all active in protecting mice from extensor convulsions and lethality. Iproniazid, tranylcypromine, atropine, benztropine and trimethadione were inactive. There appears to be a relationship between blockage of nicotine-induced extensor convulsions and lethality in mice and sedative-antianxiety effects in man. This relationship is especially good for drugs designated antidepressant, antianxiety and antipsychotic. </s>