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<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Glucosamine-labelled envelope proteins of Escherichia coli K-12. I. Electrophoretic studies and partial fractionation of phenol-soluble proteins.? [/INST] Hydrophobic envelope proteins were extracted by phenol from a glucosamine- and leucine-requiring mutant of Escherichia coli K-12 (E-110). Three protein fractions labelled with D-[1-14C]glucosamine and L-[4,5-3H]leucine were obtained by electrophoretic separation. Envelopes were isolated from cells labelled with D-[1-14C]glucosamine--HCL and acid hydrolyzed. At least 68% of the radioactivity was recovered as glucosamine and glucose with no random distribution of label. Fingerprinting of pronase digests of glucosamine-labelled proteins showed four radioactive spots associated with peptides. The glycoproteins were pronase- and trypsin-sensitive and had apparent molecular weights of 11 000 (fast mobility), 35 000 (intermediate mobility) and 62 000 (slow mobility) as estimated by sodium dodecyl sulfate-polyacrylamide disc electrophoresis. The two heavier fractions were labelled with meso-diamino[1,7-14C2]pimelic acid, while orth[32P]phosphate was not incorporated into any fraction. The glucosamine radioactivity of the fast fraction underwent rapid changes upon a chase with non-radioactive glucosamine. Using a Sephadex LH-20 column, the radioactive proteins were separated from the phenol and subsequently fractionated on a DEAE-cellulose column. The DEAE-cellulose fractions were distinct from each other in the number and composition of protein bands, when analyzed by sodium dodecyl sulfate-polyacrylamide disc electrophoresis. Radioactive bands with intermediate and fast electrophoretic mobilities were found in separate DEAE-cellulose fractions. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Glucosamine-labelled envelope proteins of Escherichia coli K-12. II. Location in inner and outer membranes.? [/INST] Outer and inner membranes were prepared from a culture of a glucosamine- and leucine-requiring mutant of Escherichia coli K-12, which was grown on L-[4,5-(3)H2]leucine and D-[1-(14)C]glucosamine and "chased" with unlabelled medium. Phenol-soluble glycoproteins were obtained from these membranes after phospholipid extraction. Sodium dodecyl sulfate-disc electrophoresis of the outer-membrane glycoproteins separated two components which were labelled with both isotopes and had a fast (F) and intermediate (I) migration. Dodecyl sulfate electrophoresis of the inner-membrane glycoproteins showed that only the F band incorporated both 14C and 3H labels. The 3H to 14C ratio in the F band from the outer membrane was completely different from the isotopic ratio in the F band from the inner membrane, indicating that these components were not identical despite their similar molecular weights. The F bands from both membranes lost their label during the chase with unlabelled medium, while the I band remained relatively stable. Chloroform-soluble 14C label extracted from the outer membrane decreased during the chase. In contrast, the chloroform-soluble 14C from the inner membrane, accumulated during the chase. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effect of activated nitrofurans on DNA.? [/INST] Enzymically activated nitrofurazone reacts with co-valently closed circular DNA (derived from Escherichia coli minicells carrying lambdadv) to give at least two kinds of damage: breaks which are detected on neutral sucrose gradients and alkali-labile lesions in DNA which are converted to breaks when the DNA is subsequently Treated with alkali. DNA, isolated from nimicells exposed to the drug, also contains lesions which are converted to breaks upon treatment with endonuclease preparations obtained from Micrococcus luteus. Minicells repaired both breaks and nuclease-susceptible lesions within 2 h but did not repair alkali labile lesions within that time. Experiments with three other nitrofurans show that there are considerable differences in the degree to which DNA is damaged by activated metabolites of various derivatives and that the potency of the compounds as mutagens and carcinogens is correlated with the amount of damage caused to minicell DNA. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Temperature and salt effects on the formation of preinitiation complexes between RNA polymerase and phage DNA.? [/INST] The influence of temperature and KCl concentration on the formation of rifampicin-resistant preinitiation complexes by holo RNA polymerase has been compared for T4 DNA and Azotobacter phage A21 DNA. The sharp transition with respect to temperature between an inactive complex of polymerase and DNA and a preinitiation complex reflects an equilibrium between the two complexes, the position of which depends on the temperature and the salt concentration. The transition is shifted to higher temperatures by increasing the KCl concentration. The position of this transition is characteristically different for T4 and A21 DNA. The midpoint for A21 DNA is about 15 degrees C above that for T4 at 0.006 M KCl. At 0.15 M KCl the transition for A21 DNA cannot be observed below 37 degrees C. This difference is responsible for the apparent inhibition of a21 dna transcription by KCl and for the low template activity of A21 DNA under the conditions of the standard assay. Both holo and core RNA polymerases are able to form complexes with A21 DNA that are resistant to attack by rifampicin. The second-order rate constant for the inactivation of the complex with the core enxyme is three times greater than that for the complex with the holoenzyme. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Ribosome run through of the termination codon in the absence of the ribosome releasing factor.? [/INST] The ribosome releasing factor (RR factor) which releases ribosomes from mRNA at the termination codon has been examined for its effects on the amino acid incorporation programmed by wild type R17 Phage RNA and amB2 R17 RNA. When RR factor was added at the beginning of the incorporation, there was no effect on the initial rate of incorporation but it reduced the final level of incorporation. The reduction of the final level of incorporation was more pronounced for histidine incorporation than for valine incorporation suggesting that the translation of the RNA polymerase cistron was more influenced by RR factor. These experiments were carried out under conditions where no reinitiation of protein synthesis occurred. In the presence of RR factor, suppressor tRNA functioned better for the incorporation of amino acids into proteins with amB2 R17 RNA than did wild type tRNA. No such differential effect of suppressor tRNA was observed in the absence of RR factor. This suggests that the ribosome has to be released from mRNA by RR factor in order for the amber mutation to be effective. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about DNA synthesis in vitro in lysates of Escherichia coli.? [/INST] A system using crude lysates of Escherichia coli PolA- for in vitro synthesis of DNA has properties similar to those described previously for washed DNA - membrane complexes, i.e. short-lived synthesis of DNA, 2-3-fold stimulation by ATP, semiconservative form of synthesis, and most of the product in the size distribution of Okazaki fragments. The proximate substrate is shown to be the deoxynucleoside triphosphate. The lysate system can be fractionated into a particular membrane - DNA complex and a soluble portion, each of which is inactive by itself, but which upon mixing restores activity. The particulate fraction provides template as well as essential protein(s). The soluble fraction contains DNA polymerases II and III both of which are capable of the necessary polymerase function, and a factor that is required for the stimulation of DNA synthesis by ATP. The stimulatory activity can also be assayed by restoration of activity to an aged lysate, which has lost the ATP-dependent synthesis; the activity is not a kinase, and is not an ATP-dependent nuclease, at least of the type currently known. The ATP-dependent stimulatory factor has been partially purified but further purification or characterization of it has been limited by its extreme instability. Both the stimulatory factor and ATP are required for semiconservative synthesis in the lysate, and for synthesis of the short fragments. Similar to results in vivo and in permeable cells the new DNA appears to contain RNA, as judged by the evidence for RNA - DNA junctions from modified nearest neighbor experiments. However, the nucleotides at the RNA - DNA junctions in the lysate system are not specific, in contrast to results in permeabilized Escherichia coli. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Wall mannan of Saccharomyces cerevisiae. Metabolic stability and release into growth medium.? [/INST] Selective labelling of cell wall mannan with radioactive precursors in growing Saccharomyces cerevisiae showed that this polysaccharide is metabolically stable during exponential growth. Mannan once inserted into the wall is not subject to turnover or release into the growth medium. However, about 10% of the amount of mannan incorporated into the cell wall fraction can be recovered in the non-dialyzable material isolated from the growth medium. Therefore, the mannan escaping from the cell must be either a mannan de novo synthesized, not trapped in the growing wall structure, or a mannan with a non-structural role. Radioactivity was also retained in the wall fraction of cells pre-labelled with [14C] glucose which pointed to metabolic stability of all cell wall polysaccharides in growing S. cerevisiae. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Levels and turnover of the proteinase B inhibitors in yeast.? [/INST] The ratio of the proteinase B inhibitors IB1 and IB2 from baker's yeast was shown to depend on the yeast strain by specific immunoprecipitation from boiled yeast extract and subsequent electrophoresis of the heat-dissociated precipitates on polyacrylamide gels. Bothe IB1 and IB2 were found, IB2 being by far predominant. Saccharomyces carlsbergensis NCYC 74 contained IB1, whereas in Saccharomyces cerevisiae X 2180 only IB2 was present. When cells of the latter strain were labelled with [14C] leucine from the beginning of growth and pulsed with [3H] leucine during the stationary phase, no short-lived IB1 could be detected. However, the peak of IB2 resolved on the gel showed an increased 3H/14C ratio in comparison to the majority of the other cellular proteins. The increased 3H/14C ratio was found to be the result of catabolite repression of inhibitor synthesis during exponential growth: cells growing on glucose as carbon source contain high inhibitor levels only during the stationary phase of growth, whereas during growth on acetate high amounts of inhibitor are present even in exponentially growing cells. During the stationary phase of growth the inhibitor is degraded with the same half-life as the total cellular proteins (about 50 h). </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The use of computed activity coefficients in Raoult's reference system, for n-alcohol/water mixtures, and their application to the study of proteins.? [/INST] Activity coefficients of alcohols in Raoult's reference system have been calculated. Using data from papers dealing with transition temperatures in the presence of n-alcohols, lipase deactivation and competitive inhibition by n-alcohols of pepsin and alpha-chymotrypsin, it is shown that the conversion of concentrations into activities (using Pierotti's equation) profoundly affects the original data. Within experimental error, if inhibition constants by alcohols keep the same value, lupase deactivation becomes independent of the length of the alcohol chain, and except for butanol, transition temperature is no longer dependent on the number of methylene groups. Interpretations which take into account the thermodynamic reference system and final environment are related to the fact that alcohol molecules bind to some inner parts of the proteins. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about A novel electrophoretic fractionation of Escherichia coli envelopes.? [/INST] Particulate fractions of Escherichia coli have been submitted to electrophoretic fractionation in a buffer stabilized by sucrose gradient. Inner membrane and outer membrane were readily resolved. A combination of electrophoresis, fractional centrifugation and gel filtration can remove remaining contamination by ribosomes and cytoplasm. The presence of particles containing no phospholipids was detected after differential centrifugation. The nature of this fraction is unknown. The inner membrane exhibited heterogeneity on electrophoresis. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Inducible gluconate permease in a gluconate kinase-deficient mutant of Escherichia coli.? [/INST] Gluconate-resistant mutants were isolated from Escherichia coli strain DF 1070 deficient in phosphogluconate dehydrogenase (EC 1.1.1.44) and in phosphogluconate dehydrogenase (EC 4.2.1.12) which is inhibited by gluconate. Among the resistant mutants, AR 13 has been identified as a gluconate kinase (EC 2.7.1.12)-deficient strain. This mutant exhibits an inducible gluconate transport system capable of concentrating gluconate in the cytoplasm against a concentration gradient. The accumulated gluconate is subject to permanent turnover, and is not chemically modified. The kinetics of induction and deinduction indicate a single inducible component, rate limiting for the transport function, and the distribution of transport capacity among non-induced progeny of induced parents indicates that the inducible protein is membrane bound. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Adrenergic mechanisms in the rabbit ear artery. A review.? [/INST] A number of factors which have been implicated in the response of the rabbit ear artery to adrenergic agents and stionstriction in the arterial smooth muscle; (b) the interrelationship between the intramural distribution of sympathetic nerves and muscle, and the influence of uptake and enzymic inactivation on the response to norepinephrine, and (c) the influence of presynaptic adrenergic and cholinergic receptors on the rwsponse to sympathetic nerve stimulation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The NBT test: Erratic behaviour in acute leukaemia.? [/INST] Non-stimulated and stimulated nitroblue tetrazolium (NBT) dye test was studied in sixteen adult patients with acute leukaemia in sequence, viz. at the time of diagnosis, during and after treatment. It was found that the capacity of the neutrophilic granulocytes to reduce NBT (non-stimulated) was below, within or above the range for the normal group. Two of the patients had a constant negative non-stimulated NBT test. The stimulated NBT test was below the normal range. Generally, there was no correlation between the percentage of NBT positive cells and fever of bacterial origin. All sixteen patients but four were found to be within the normal range concerning phagocytic ability. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effect on platelet counts and fever of platelet transfusion in leukemia.? [/INST] The efficacy of platelet transfusions in pretransfused HL-1 sensitized patients has been doubtful, particularly where repeated platelet transfusions were required. The efficacy of one hundred and nine ABO-compatible, cross match negative platelet transfusions in 26 adult patients with acute leukemia was therefore studied. Although most of the patientswere old and pretransfused and although no HL-A typing could be made, a statistically significant average increase of about 11 000 platelets/mul was seen not only after the first but also after subsequent (up to 8) platelet transfusions. Moreover, significant reduction in temperature followed platelet transfusions. However, platelet recoveries were worse in severely infected patients. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Depolarizing effects of the ionophores X-537A and A23187 and their relevance to secretion.? [/INST] The ionophore X-537A depolarized frog skeletal muscle fibres about 10 mV in 10 min and a further 30 mV or so over the next 50 minutes. With A23187, depolarization was relatively feeble and delayed in onset but was hastened when calcium was removed from the bathing medium. The results support conjecture that some functional responses to these ionophores are attributable, in part, to depolarization. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Studies on the hypotensive action of alpha-methyldopamine.? [/INST] 1. Intraventricular alpha-methyldopamine (50-200 mug) produced a dose-related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of alpha-methyldopamine. 2. The hypotensive effect of alpha-methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol. 3. Pretreatment with U-14,624, a selective central dopamine-beta-hydroxylase inhibitor, prevented the hypotensive effect of alpha-methyldopamine. 4. Alpha-methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and alpha-methylnoradrenaline were found to be equipotent. 5. Alpha-methyldopamine (1-5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the midbrain reticular formation in cats anaesthetized with chloralose. 6. It is concluded that the hypotensive action of alpha-methyldopamine in conscious animals involves intact central alpha-adrenergic neurones and a central adrenergic uptake mechanism for the formation of alpha-methylnoradrenaline. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Bile salts and gallstone disease.? [/INST] Bile salts play an important role in maintaining cholesterol in aqueous solution in bile. There is evidence that in some patients at least gallstones arise as a result of bile salt deficiency. The evidence to date suggests that although oral bile salts may be of use in treating some gallstone patients they are unlikely to replace cholecystectomy in the foreseeable future. The instillation of bile salts via an indwelling T-tube may well be of great use in the management of stones retained in the common duct after choledocholithotomy. There is no doubt that in this branch of medicine as in all others prevention is better than cure and our aim should be to perfect our technique so that we do not leave stones behind. However, should the situation occur we may soon have safe effective physiological solvents to dissolve our mistakes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Orthotopic liver transplantation: an experimental study on the prevention of infections with Gram-negative organisms.? [/INST] Infection with Gram-negative bacteria is frequently the cause of death in human liver transplantation. In experimental liver transplantation in mongrel dogs we detected Gram-negative septicaemia in 73% of our first 15 cases; maximal survival was 26 days. In a second series of 27 orthotopic liver transplantations in tissue-typed littermate dogs and littermate pigs the standard surgical technique and aftercare were changed with regard to four factors: an end-to-end common bile duct anastomosis was made instead of a gallbladder to duodenum anastomosis; the continuous postoperative bacteriostatic antibiotic therapy was changed to a single 2-day course of bactericidal antibiotics; preoperative selective bowel decontamination combined with postoperative protective isolation was introduced; the dosage of azathioprine used for immunosuppression was reduced.. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Gastric acid secretion following renal transplantation.? [/INST] Gastric acid secretion studies were performed in 10 patients on regular dialysis and again following transplantation. While on dialysis, the acid output was high, with mean peak values after pentagastrin of 37-2 mEq/h in males and 26-3 mEq/h in females. These compared with values in normal subjects of 21-6 mEq/h in males and 12-3 mEq/h in females. Following transplantation continuous steroid therapy was given. Repear gastric acid secretion studies showed no significant change, with values of 37-1 mEq/h in males and 24-6 mEq/h in females. The high incidence of gastro-intestinal haemorrhage and perforation following transplantation is probably due mainly to steroid therapy, but the ulcerogenic effect of steroids would not seem to be mediated by increased gastric acid secretion. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Analysis of treatment in childhood leukaemia. I. Predisposition to methotrexate-induced neutropenia after craniospinal irradiation. Report to the Medical Research Council of the Working Party on Leukaemia in Childhood.? [/INST] The degree of drug-induced neutropenia resulting from a controlled trial (UKALL I) of treatment in acute lymphoblastic leukaemia was analysed. The main agent associated with severe neutropenia was methotrexate, and methotrexate-induced neutropenia was significantly greater in patients who had received craniospinal irradiation. The synergistic toxic effect of irradiation followed by methotrexate treatment seems to have contributed to three of the five deaths which occurred in complete remission in this trial; all deaths in remission occurred in patients who had received central nervous system prophylaxis. Analysis of patients who subsequently relapsed compared with those still in remission after 18 months of treatment indicated that the former, on average, had slightly lower neutrophil counts. This suggests that the children who relapsed did not receive any less aggressive treatment than those who remained in remission. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Serum digoxin in patients with thyroid disease.? [/INST] Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Use of bacteriological investigations by general practitioners.? [/INST] The numbers of vaginal swabs, faecal specimens, throat swabs, and urine specimens submitted by 104 city general practitioners to the bacteriology laboratory at Aberdeen differed widely. The doctors who made most use of the laboratory service rarely did so equally for all four investigations but usually for only one or two. Similarly, those who used the service least often made frequent use of one particular investigation. Further studies are needed to identify and evaluate the reasons for the apparently substantial disagreement among general practitioners concerning the value of these diffferent bacteriological investigations in general practice. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Agonal phase, ischaemic times, and renal vascular abnormalities and outcome of cadaver kidney transplants.? [/INST] A retrospective study of 250 cadaver kidney transplants was carried out to determine the effects of the agonal period, the warm and cold ischaemic times, and the use of kidneys with vascular anomalies on the primary success and failure and the subsequent level of function of the transplants. Kidneys with vascular anomalies or from non-ventilated donors had a primary failure rate of over 30%, whereas those with normal vasculature or from ventilated donors had a rate of 17%. An initial warm ischaemic time of more than 60 minutes was associated with a primary failure rate of 57% and a cold ischaemic time of over 550 minutes with a primary failure rate of 47%. The interrelationship between the warm and cold ischaemic times in the primary success or failure of the transplants was examined and criteria defined for selecting potentially viable cadaver kidneys for transplantation, as follows: (1) The donor should be (a) ventilated, (b) aged 6-50 years, and (c) have normal ante-mortem renal function and have secreted more than 1-5 1 of urine in the 24 hours before death (or an equivalent volume if the urinary output was recorded for less than 24 hours before death); (2) the kidney should have normal renal vasculature enabling single arterial and venous anastomoses to be performed; (3) kidneys with I.W.I.T.s of longer than 60 minutes should not be used; (4) for kidneys with I.W.I.T.s of less than 20 minutes the C.I.T. is not critical but should not exceed 12 hours; (5) for kidneys with I.W.I.T.s of 20-60 minutes the C.I.T. should not exceed 450 minutes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Hyperparathyroidism after renal transplantation.? [/INST] Renal transplantation reduced circulating parathyroid hormone in recipients of renal allografts. Nevertheless, biochemical and histological evidence of mild hyperparathyroidism persisted up to eight years after renal transplantation despite good graft function. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Closure of abdominal wounds by adhesive strips: a clinical trial.? [/INST] In a randomized trial of wound closure in 512 abdominal wounds, wounds were closed with either reinforced Steristrip skin closures or interrupted silk sutures. Comparisons were made of wound pain and discomfort, wound infection, discharge, redness, width, and skin reaction. The causes of peeling of the tapes were assessed. The results showed that tapes were significantly more comfortable and that patients preferred them to sutures (P less than 0.01), but wide scars occurred more often. There was no difference in rates of wound infection and no case of allergy to the tapes was seen. Closure of abdominal wounds by these tapes is a satisfactory procedure that could be used more extensively. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Reticuloendothelial function in renal allograft recipients.? [/INST] The phagocytic capacity of the reticuloendothelial system (R.E.S.) was assessed in patients with chronic renal failure and in renal transplant recipients. R.E.S. phagocytosis was increased in the former group. Soon after transplantation R.E.S. phagocytosis was moderately reduced (through levels were comparable with those of normal controls) but was particularly reduced after high-dose corticosteroid treatment for rejection. In long-term allograft recipients R.E.S. phagocytosis was also depressed though steroid maintenance doses were small. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Survival of infants with unoperated myeloceles.? [/INST] Of the infants with spina bifida referred to a neonatal surgical unit over three years and denied early closure of the myelocele, a significant proportion survived long enough for procedures to drain hydrocephalus to be needed. The key decision in the management of this condition is not whether myeloceles should be closed but whether hydrocephalus should be treated. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Ultrastructural localization of luteinizing hormone-releasing hormone in the median eminence of the rat.? [/INST] The nature of cells in the hypothalamus that produce hypothalamic hypophysiotropic hormones remains unsettled. To investigate this problem electron microscopic immunocytochemistry was performed on thin sections of the median eminence of proestrous rats using antibodies to synthetic luteinizing hormone-releasing hormone (LHRH) and the peroxidase-antiperoxidase (PAP) technique. PAP complexes indicating the presence of LHRH were found over small, homogeneously dense neurosecretory granules 75-90 nm in diameter that occurred in clusters within neurons. Positive staining was more prevalent in the palisade zone in the anterior median eminence than at more posterior levels. LHRH positive granules were not obsereved in neuronal processes in the neurohemal contact zone, but appeared closer to the pericapillary space in the posterior median eminence than at more anterior levels. Occasional groups of LHRH positive granules were also found in the internal layer and hypendymal zone. No staining was observed in tanycytes or glial elements. These results support the hypothesis that hypothalamic hypophysiotropic hormones are produced by neurons and are stored in granules of homogeneous size and density in nerve processes located in the median eminence in the proximity of the hypophysial portal plexus. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Metabolism of [2-14C]prostaglandin E1 on passage through the pulmonary circulation.? [/INST] A multiple indicator dilution technique was used to study inactivation of [14C]prostaglandin E1 (PGE1) by isolated cat lungs. A bolus containing [2-14C]PGE1, indocyanine green dye and 3HOH was rapidly introduced into the blood entering the pulmonary artery. Sequential samples of the venous effluent were collected and analyzed for 3H, dye, and 14C. The 14C-labelled compounds were separated by thin-layer chromatography, and the quantity of PGE1 and its metabolites contained in each sample was determined (radiochromatogram scanning). Recovery of the dye and 3H was complete within the sampling period. However, only 79% of the injected 14C emerged from the lung within this period, 36% as [14C]PGE1, and 43% as two less polar metabolites. The mean transit times (including connecting tubing) for the unmetabolized [14C]PGE1 and the dye were 9.1 and 8.7 s, respectively. The apparent mean transit times for 14C in the metabolites were considerably longer, 12.4 and 14.3 s. The 3HOH mean transit time was 10.7 s. These data are compatible with an extraluminal site for PGE1 metabolism. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effective selection of Proteus mirabilis clones producing mirabilicin D-52.? [/INST] From a defective-lysogenic Proteus mirabilis strain we isolated several clones differing in the pattern of their growth on agar plates. Using electron microscopy we have shown some of the selected clones to be efficient in producing mirabilicin D-52 after UV induction, while other clones produced defective mirabilicin polysheaths and polycores. Clones producing polysheaths and polycores can be detected electron microscopically only, since these defective particles are biologically inactive. </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 a bacteriophage infective for a UDP-galactose-4-epimeraseless mutant of Escherichia coli.? [/INST] A DNA bacteriophage, designated CP13, was isolated against Escherichia coli J5, a UDP-galactose-4-epimeraseless mutant of E. coli 0111:B4. Bacteriophage CP13 appears to be specific for rough bacterial strains. Adsorption studies with E. coli J5 grown with galactose show that the bacteriophage will not adsorb when complete lipopolysaccharide is present in the cell membrane. This indicates that lipopolysaccharide may be directly or indirectly involved with the receptor site for bacteriophage CP13. The bacteriophage DNA has a G + C content of 52%. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Purification and properties of a nuclear polyhedrosis virus from Choristoneura fumiferana.? [/INST] The polyhedral inclusion bodies of a nuclear polyhedrosis virus from the spruce budworm Choristoneura fumiferana were purified by fluorocarbon treatment, sucrose columns, sucrose density gradients, and equilibrium centrifugation. The preparation yields a single and homogeneous band in potassium tartrate gradients at a density of 1.193 g/ml. The virions were released from the polyhedra by alkali treatment and purified by either rate zonal or equilibrium centrifugation in sucrose gradients. The purified virions, which band at a density of 1.265-1.300 g/ml in sucrose, were infectious to the spruce budworm larvae and their mean LD50 was 1.09 +/- 0.1 mug of virus. However, viral nucleocapsids, released by a nonionic detergent, Nonidet P-40, had a density of 1.315 g/ml and were noninfectious by either per os inoculation or intrahemocoelic injection. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Repair of heat injury in thymine auxotrophs of Escherichia coli.? [/INST] Heat-induced damage in four strains of bacteria has been studied. It has been shown that the damage is repairable on incubation at 37 degrees C in a medium not supporting growth. The extent of repair is dependent upon the strain of bacterium chosen. Recovery from the damage is prominent in the case of filament-forming bacteria, and in non-filament formers, recovery is not totally absent. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Alpha methyldopahydrazine as an adjunct to levodopa therapy in Parkinson's disease.? [/INST] A double-blind, double-observer study was carried out in twenty-five patients with Parkinson's disease. Alpha methyldopahydrazine in combination with L-dopa was compared to placebo with L-dopa. Combination therapy resulted in a reduction in L-dopa dosage to 1/3 of the amount required during the baseline. There were no side effects attributed directly to the alpha methyldopahydrazine. The overall incidence of side effects in the two groups was similar but the combination therapy significantly reduced the incidence of nausea and vomiting. The limiting factor in the combination therapy was the presence of L-dopa induced dyskinesias. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cucumber shaped and 35 nm particles in Creutzfeldt-Jakob disease.? [/INST] A 63 year old female with the ataxic form of Creutzfeldt-Jakob disease (CJD) is presented. In addition to amyloid plaques which were not associated with Alzheimer's neurofibrillary tangles, rare profiles similar to those reported in Scrapie were also seen. To our knowledge, these profiles have never been observed in CJD and their presence in this condition adds a further morphologic similarity between the human and animal forms of subacute spongiform "viral" encephalopathies. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Combined cyclophosphamide vincristine, procarbazine, and prednisone (COPP) therapy of malignant lymphoma. Evaluation of 190 patients.? [/INST] One hundred ninety patients who had advanced active Hodgkin's disease, lymphosarcoma, or reticulum cell sarcoma were treated with a combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) given in a cyclical fashion every month. Complete remission was produced in 91 of 138 (66%) patients with Hodgkin's disease and in 39 of 52 (75%) patients with non-Hodgkin's lymphoma (lymphosarcoma and reticulum cell sarcoma). The response rate was higher in patients who completed six cycles of therapy compared to those who completed only three to five cycles: 77% vs. 45%, respectively, in Hodgkin's disease, and 85% vs. 46%, respectively, in non-Hodgkin's lymphoma. The median duration of remission was longer for Hodgkin's disease patients who completed six cycles (30 months vs. 10 months). The median duration of complete remission of non-Hodgkin's lymphoma was 14 months. The response to treatment correlated positively with survival. The median survival time start of COPP treatment for patients with Hodgkin's disease was 7 months for nonresponders, 14 months for those who attained partial remission, and more than 48 months for those who attained complete remission. For patients with non-Hodgkin's lymphoma, the median survival time from start of COPP treatment was 24 months for nonresponders and those who had partial remission, and more than 32 months for those who attained complete remission. Of complete remission responders with Hodgkin's disease, 70% are still alive 84 months after diagnosis, and 63% of the patients witn non-Hodgkin's lymphoma are still alive 48 months after diagnosis. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Clinical comparison of the nitrosoureas.? [/INST] The nitrosourea group of antitumor agents was developed by the Division of Cancer Treatment of the National Cancer Institute. Three nitrosoureas (BCNU, CCNU, MeCCNU) have undergone extensive clinical trials, and two of them (BCNU, CCNU) will soon become commercially available. This paper briefly considers the preclinical development of the nitrosoureas and provides an overview and comparison of the extensive clinical data. Information is given regarding any clinical differences. We discuss general conclusions drawn from the nitrosourea development. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about In vitro determination of tritiated thymidine labeling index (LI). Evaluation of a method utilizing hyperbaric oxygen and observations on the LI of human mammary carcinoma.? [/INST] A simple method for incubation of tissue specimens with tritiated thymidine under 3 atm oxygen tension gave an in vitro labeling index (LI) that corresponded closely with LI's determined by injection of tritiated thymidine in vivo. The LI of tumors was not affected by storage at room temperature for up to 135 minutes. The mean LI for 39 human mammary carcinomas was 3.8, but the distribution was skewed to the right, and the most frequently observed LI's were between 2 and 3. Larger carcinomas had significantly larger LI's than smaller tumors, which suggests that the larger tumors were faster-growing at the time of observation than the smaller tumors. The capacity of the larger tumors to maintain a relatively rapid growth rate may account for their large size. The data suggested, but did not prove, that a high LI was associated with more frequent metastasis to axillary lymph nodes. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Acquired hypertrichosis languiginosa. Report of two new cases and a review of the literature.? [/INST] Hypertrichosis lanuginosa is a pathologic state characterized by an excessive, new growth of fine, fetal hair. Two cases of hypertrichosis languinosa with malignancy (lymphoma and uterine cancer) are presented and added to the 9 in the literature. Lymphoma and uterine cancer are previously unreported as associated with hypertrichosis osis lanuginosa. Review of the 11 cases of hypertrichosis lanuginosa revealed the following characteristics: females were predominant; none was below the 4th decade; all had advanced neoplastic disease; all malignancies except one were of epithelial origin; and there were no demonstrable endocrine abnormalities. Despite an attempt to find etiologic factors in our patients and in the literature, none could be elicited. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Immunohistochemical detection of growth hormone-release inhibiting hormone (somatostatin) in the guinea-pig brain.? [/INST] Utilizing the unlabeled antibody peroxidase-antiperoxidase method, we have studied the distribution of somatostatin (growth hormone release-inhibiting hormone) in the guinea pig brain. An immunohistochemical reaction was found in both internal and external zone of the caudal and median portions of the median eminence. Reaction products were also present in the arcuate nucleus in proximity of the third ventricule. The immunostained elements resembled nerve processes. No cell bodies were stained. A positive reaction was also present in the whole organum vasculosum of the lamina terminalis. In the subfornical and subcommissural organs, somatostatin was observed in the ependymal and subependymal layers and the perivascular areas. In the pineal gland, a positive reaction was also found mainly in the perivascular areas. All the other brain areas were completely negative. These results establish that, in the hypothalamus, somatostatin is mainly concentrated in the median eminence and suggest that periventricular organs can play a role in the regulation of growth hormone secretion. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The ratio of smooth muscle cell volume to cell surface area measured by electron microscopy with corrections for shrinkage.? [/INST] The ratio of cell volume to cell surface area (V/A) has been measured by electron microscopy, for smooth muscle cells of the guinea-pig taenia coli. The extent of shrinkage which occurs during processing for electron microscopy has been estimated using Archimedes' principle. The corrected ratio of V/A is 0.8 mum which is lower than previously published estimates for this tissue. The contribution of the surface vesicles to V/A was not included in the present estimate, but the extra surface area contributed by these organelles would lower V/A even more. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Intracellular localization of actin with fluorescently labelled heavy meromyosin.? [/INST] An improved technique for fluorescent labelling of heavy meromyosin has made it possible to detect on a light microscopic level the cellular sites of actin localization. Rabbit heavy meromyosin (HMM) was labelled with fluorescein isothiocyanate so that the actin binding site was protected during the reaction. The specificity of fluorescent HMM binding to cellular actin was tested by using glycerinated myofibrils. Staining was most intense in the I-Bands, and decreased at the edges of the A-Band, where actin filaments overlap with myosin. No staining occurred in the H-Zones or in the Z-Bands. The fluorescent HMM could be removed by washing with a relaxing solution. Similar sarcomeric patterns were obtained when embryonic chick skeletal and cardiac muscle cells were stained with fluorescent HMM. Localized fluorescent staining was also observed in smooth muscle fibers, axons and growth cones of nerves, acrosomal caps of sperm, cleavage furrows of dividing cells and pseudopods of various motile cells, all of which are known to contain actin. In sessile cells, the actin was found predominantly in fibrous bundles. This pattern of actin localization was altered when the cells underwent cleavage or became motile. The relationship between the intracellular distribution of actin and its function in the cell is discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Interaction of water with egg lecithin in benzene solution.? [/INST] Benzene solutions of purified egg lecithin, with small amounts of water added, have been examined by 60 MGz and 100 MHz NMR spectroscopy, infrared spectrophotometry and phase contrast microscopy. The transverse relaxation times of the water, N-methyl and O--H protons are dependent on water concentration. This dependence changes sharply for the water proton at a level of one water molecule per lecithin monohydrate molecule. These results do not fully agree with those reported by other workers. Four mathematical models are examined which could account for the behaviour of the water protons. Models which assume a constant transverse relaxation time for water protons above a level of one water molecule per lecithin molecule cannot predict the behaviour observed. It is sufficient to assume that water protons above this concentration have a single relaxation time which is a linear function of water concentration. The added water associates primarily with the phosphate in the lecithin head group. Above nine water molecules per lecithin monohydrate molecule free water is present in the system. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Tissue vitamin B-12 assay by a radioisotope dilution technique.? [/INST] A method is described for the measurement of vitamin B-12 (B-12) in solid tissues by radioisotope dilution (RID) assay. The method is a modivication using double extraction of a serum B-12 RID assay which uses chicken serum as the B-12 binder. The method was developed and tested using human and bat liver specimens. Double extraction was shown to be more efficient than single extraction, and resulted in complete release of endogenous liver [57Co] B-12 administered to bats. Results using the RID assay in 16 humans and 17 bat liver specimens were compared with those obtained using the Lactobacillus leichmannii microbiological assay. Correlation was good, but the RID assay gave higher results using the microbiological assay appear to be due to inadequate extraction of B-12 from tissues. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Gonadotrophin hormone releasing tests in women receiving hormonal contraception.? [/INST] Gonadotrophin secretion by the pituitary was tested by i.v. injections of synthetic LH and FSH releasing hormone (LHRH) in five normal women between day 21 and day 25 of the luteal phase of the cycle, in twelve women receiving contraception with i.m. injection of medroxyprogesterone acetate and in eight women taking combined oral contraceptives of different varieties. Treatment with oral contraceptives led to a decrease or even to complete suppression of the response and possibly the reserve capacity of both LH and FSH secretions. Treatment with medroxyprogesterone acetate for several years lowered basal serum LH and FSH as did oral contraceptives but had much less effect on the responses to LRH. In long-term steroid contraception, progestogens alone seem to exert much less deleterious effect on gonadotrophin function than when used in combination with an oestrogen. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The effect of progesterone and FSH and LH response to LHRH in normal women.? [/INST] An LHRH test was performed on twenty-eight regularly menstruating females during follicular phase of their cycles. Twenty-four were then given an intramuscular injection of progesterone in oil and retested with LHRH 20 or 44 h later, the remaining four received no pretreatment and acted as controls. The twelve subjects retested 20 h after the progesterone injection showed marked changes in response. The greatest increase in gonadotrophin release after LHRH was seen when subjects were tested between days 8 and 10 of the menstrual cycle. In contrast, the twelve studied 44 h after receiving the steroid showed no change in release. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about A field with a liver measles-mumps-rubella vaccine.? [/INST] Three lots of Lirutrin (measles-mumps-rubella live, attenuated virus vaccine) were evaluated in a double-blind, placebo-controlled clinical study involoving 273 children. The vaccine consisted of a combination of Schwarz strain measles, Jeryl Lynn strain mumps, and Cendehill strain rubella vaccine viruses. The frequency of positive clinical findings was essentially the same in susceptiable vaccinees, immune vaccinees, and placebo recipients; indicating that the observed symptoms were not caused by the vaccine. Antibody assay of paired serum samples revealed that measles, mumps, and rubella seroconverison rates in triple susceptible vaccinees were excellent, ranging from 96 to 98 per cent with all three lots combined. Results of this study show that Lirutrin trivalent vaccine is well tolerated and highly effective. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cephalexin in the management of bacteriuria.? [/INST] This report evaluates the effectiveness of cephalexin in the treatment of bacteriuria in 93 children. Cephalexin therapy eradicated sensitive organisms in 97 per cent of the cases regardless of recurrence, structural abnormality, or status of renal function. Nevertheless, recurrences with a new, resistant organism occurred significantly in certain patients, expecially those with major anatomic abnormalities, during a six-week follow-up period. The incidence of drug reactions was low. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Comparison of cardiac effects of timolol and propranolol.? [/INST] The cardiac effects of the beta-adrenergic blocking agent, timolol, were compared to those of propranolol after intravenous administration in 6 healthy male subjects. The effects of timolol and propranolol on maximal exercise-induced tachycardia were measured. Timolol was about ten times as potent as propranolol in antagonizing exercise-induced tachycardia. Dose-response curves to intravenous infusions of isoproterenol were obtained after three doses of each beta-antagonist. Changes in myocardial contractility were assessed by cardiac systolic time intervals and were compared to the simultaneous changes in heart rate elicited by isoproterenol. For the 6 subjects, the mean potency ratios of timolol to propranolol as an antagonist of the chronotropic and inotropic effects of isoproterenol were 13.8 (+/-0.8) and 12.7 (+/-1.0), respectively. Neither timolol nor propranolol acted more selectively on beta-receptors affecting heart rate than on those influencing contractility. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of marihuana combined with secobarbital.? [/INST] Twelve male volunteers smoked a marihuana cigarette prepared to deliver 0 or 25 mug/kg tetrahydrocannabinol (THC) 50 min after ingesting a capsule containing either placebo or 150 mg/70 kg sodium secobarbital. Drugs were administered in a double-blind manner, and all treatments were assigned to each subject in a randomized complete block design. Objective and subjective tests designed to measure mental and motor performance indicated that marihuana impaired stability, hand-eye coordination, and mental performance. Secobarbital affected motor performance, manual coordination, and mental performance. In combination, marihuana and secobarbital had an additive effect on subjective responses and impairment in certain psychomotor performance tests. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Triazolam in insomniac family practice patients.? [/INST] Triazolam, 0.5 mg, a benzodiazepine with hypnotic properties, was compared to secobarbital, 100 mg, and placebo in a 1-wk study conducted with 100 insomniac family practice patients. Considerable sensitivity to differential treatment effects was demonstrated for these family practice patients as well as for a research methodology that combines a crossover design, permitting preference ratings, with a between-patient design. In almost all sleep parameters, assessed with a variety of subjective techniques, triazolam and secobarbital were shown to be significantly more effective than placebo. Triazolam was consistently and often significantly indicated to be a more effective hypnotic, particularly for reducing nocturnal awakening, than secobarbital. Analysis of self-report emotional distress data revealed that present insomniac patients were slightly more emotionally symptomatic than other nonpsychiatric populations. Triazolam was followed by the greatest and secobarbital the least relief of emotional symptoms and triazolam emerged as an especially effective hypnotic for initially more depressed insomniac patients. Present findings suggest that type and degree of emotional symptomatology may affect the response of insomniac patients to hypnotics. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Penfluridol steady-state kinetics in psychiatric patients.? [/INST] Twenty-two hospitalized schizophrenic patients, participating in a large-scale phase II double-blind dose-effect study (30, 60, and 120 mg weekly) of penfluridol, a new diphenylbutylpiperidine neuroleptic, were maintained on a regular dosage regimen for 13 wk. Several blood samples were taken during the last dosage interval. Results show that the peak concentration develops within 12 hr after the last dose. A rapid decline, probably due to tissue re-equilibration, then occurs and is followed by a much slower falloff. Detectable concentrations 168 hr after administration are consistent with the long duration of action of penfluridol. Statistically significant differences between doses were found in the analysis of variance of plasma concentrations at all sampling times and in mean steady-state plasm concentrations. Wide differences in plasma concentrations were noted in patients receiving the same absolute dose, but a good relationship was defined between mean steady-state concentration and the dose expressed as mg per either kg of body weight or square meter of body surface area. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Bioavailability of dexamethasone. II. Dexamethasone phosphate.? [/INST] Plasma levels of dexamethasone phosphate (DP) and dexamethasone free alcohol (DA) were determined by a modification of existing radioimmunoassay methodology following intravenous administration of DP in man. Areas under DA plasma profiles were a linear function of DP dosage over the 40-fold range 0.05 to 2.0 mg/kg, and, by comparison with values obtained after DA was intravenously administered, indicated an overall conversion of DP to DA of 90%. The first-order rate constant for the conversion, 4.03 hr-1, was approximately 25 times that for hydrolysis in whole blood incubated in vitro. This relationship as well as disposition kinetics suggested that the major component of DP hydrolysis occurs within highly perfused organ(s) comprising the central kinetic compartment. Eighteen subjects were studied in a crossover experiment, and no significant differences were observed in best-fit parameters for the 4 mg/ml parenteral solution of DP in current use and an experimental high potency preparation of 24 mg/ml. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Suppression of cortisol by a progestational steroid, melengestrol.? [/INST] Melengestrol, a steroid with progestational activity but with a structure that does not resemble that of cortisol, suppresses plasma cortisol in humans with a potency 1/40th that of dexamethasone. The 6alpha-methyl and 17alpha-acetoxy substituents and the 6,7 double bond of melengestrol acetate are known to slow the metabolism of similar steroids. Insertion of a 6alpha-methyl group markedly increases the glucocorticoid activity of 17alpha-OH-progesterone. The glucocorticoid activity of melengestrol is presumably attributable to the large dose administered in our study, its slow metabolism and limitations of the specificity of glucocorticoid tissue receptors. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Correlation of plateau serum salicylate level with rate of salicylate metabolism.? [/INST] The range of plateau serum salicylate concentrations was 4.4 to 33 mg/100 ml in patients with rheumatoid arthritis after they were treated with 50 mg/kg of aspirin daily for 5 days. Individual plateau serum levels correlated better with urinary excretion rates of the metabolite, salicylurate (whose maximum production is capacity-limited), than with total urinary excretion of salicylates. These observations suggest that large intersubject variations in plateau serum salicylate levels are determined, at least in part, by similar differences in the maximum rates of capacity-limited metabolic reactions. For optimal therapeutic responses, individualization of aspirin dosage by following serum salicylate levels is recommended. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Pharmacokinetics of indomethacin.? [/INST] Plasma concentrations of indomethacin have been studied in 5 healthy volunteers after single and multiple doses (25 mg intravenously [iv], 25, 50, and 100 mg orally, 100 mg rectally, and 25 mg three times daily [tid]. In 8 other normal subjects and in 5 patients a 50-mg oral dose of indomethacin was given and the indomethacin concentration was followed from 8 to 32 hr after dosing. All analyses were carried out using a new mass fragmentographic method. After oral and rectal doses the plasma decay of indomethacin was biphasic, and the data were interpreted according to a 2-compartment open model. The half-life of the beta-phase varied between 2.6 and 11.2 hr. The volume of distribution ranged from 0.34 to 1.57 L/kg and the plasma clearance from 0.044 to 0.109 L/kg/hr. There was no evidence of dose-dependent elimination. Indomethacin was rapidly and well absorbed after oral dosing with peak plasma concentrations within 2 hr. Comparison with the area under the curve (AUC) after iv dosing indicated complete bioavailability. The AUC after rectal dosing indicated complete bioavailability, but the rate of absorption was slower than after oral administration. Indomethacin, 25 mg three times daily, was also given for 9 days to the same normal subjects; equilibrium concentrations obtained did not differ significantly (p greater than 0.1) from those predicted from single-dose data in the 5 subjects. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Relative potency of prorenoate and spironolactone in normal man.? [/INST] The potency of single doses of a new aldosterone antagonist, prorenoate, in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone was compared to that of spironolactone in a double-blind balanced crossover study in 12 healthy subjects. The potency of prorenoate potassium as related to elevation of the urinary log 10 10 Na/K ratio (2.69:1) and as related to potassium retention (3.75:1) was significantly higher than that of spironolactone. Prorenoate produced greater natriuresis (1.64:1) but the difference was not significant. There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion. The simple methodology described is based on standard bioassay principles, yielded a valid and sensitive comparison of the two drugs, and should prove useful in the evaluation of other aldosterone antagonists. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Temporal variations in acetaminophen and phenacetin half-life in man.? [/INST] Acetaminophen (APAP) and phenacetin mean plasma half-lives were approximately 15% longer in normal male volunteers at 6 A.M. than at 2 P.M. as determined after oral administration of each drug at 6 A.M. and 2 P.M. Concentrations of plasma 11-hydroxycorticoids (11-OHCS) in these volunteers were approximately 42% higher at 6 A.M. than at 2 P.M. The mean apparent volume of distribution (aVd) of APAP decreased by approximately 13% from 6 A.M. to 2 P.M., whereas the mean metabolic clearance rate (MCR) of APAP did not change significantly. Neither the mean aVd nor the mean MCR of phenacetin changed significantly from 6 A.M. to 2 P.M. Measurement of urinary metabolites showed no alteration in APAP glucuronidation in the 8-hr period following APAP administration at 6 A.M. or 2 P.M., but indicated that after phenacetin administration 10% more of the dose was oxidatively metabolized to APAP during a 24-hr period beginning at 2 P.M. than at 6 A.M. Within each subject, plasma acetaminophen or phenacetin half-life at 2 P.M. or 6 A.M. was highly reproducible, but large interindividual variations occurred in the extent of temporal variation during this period. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Bioavailability and single-dose pharmacokinetics of intramuscular phenytoin.? [/INST] Comparison of phenytoin plasma concentrations in an intravenous and intramuscular crossover study in 12 healthy ambulant, male subjects indicates that phenytoin administered intramuscularly is absorbed over a period of approximately five days. A model simulating precipitation and redissolution of the drug at the injection site has been shown to satisfactorily fit observed plasma concentration data following intramuscular administration. It is proposed that this model will be useful in the selection of an appropriate dosing regimen in situations in which intramuscular administration of phenytoin is indicated. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Combination 6-mercaptopurine-adriamycin in refractory adult acute leukemia.? [/INST] Remission induction therapy with 6MP and adriamycin in combination was administered to 19 adult leukemic patients refractory to previous therapy. Eight patients also received vincristine and prednisone. Thirteen patients had acute myelogenous leukemia, 3 undifferentiated leukemia, and 3 blastic transformation of chronic myelogenous leukemia. Four patients achieved remission but in only 2 were the remissions complete. Eleven patients failed to respond. Ten of the 19 patients developed unexpected severe liver toxicity manifested by a clinical picture of cholestasis (in the majority) or ascending cholangitis (in 2 patients). In the postmortem examination of 8 patients there was cholestasis and mild to severe hepatocellular damage in all. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Effects of ticlopidine, a new platelet aggregation inhibitor in man.? [/INST] Ticlopidine is a new platelet aggregation inhibitor. The effect of this drug was studied on 55 subjects, healthy volunteers and hospitalized patients. The action requires 24 to 48 hr to appear, and lasts more than 3 days. A dose-effect relationship was studied with oral daily doses ranging from 250 to 1,000 mg during 1 wk; it showed a 50% inhibition on adenosine diphosphate (ADP)-induced aggregation at 2 muM concentration on an oral daily dose of 450 mg. No action was found on collagen-induced aggregation, and a mild effect was observed on platelet adhesiveness. Clinical tolerance was assessed in patients given ticlopidine in oral doses up to 500 mg/day during several weeks, showing no overt side effects and no change in the safety parameters. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Idiopathic pulmonary hemosiderosis. Electron microscopic, immunofluorescent, and iron kinetic studies.? [/INST] The clinical course of a 37-year-old white man with idiopathic pulmonary hemosiderosis is presented. This patient is unusual in that he has had repeated exacerbations and remissions over a period of seven years and remains currently in spontaneous remission with no therapy. Routine sections of the lung biopsy revealed characteristec findings. Immunofluorescence staining of the lung was negative, and electron microscopic studies showed only nonspecific findings. While in remission, 51chromium-labelled red-blood-cell survival studies and 59iron kinetic studies were performed; the results were normal. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about [Fungal infections after renal transplantation (author's transl)].? [/INST] 21 of 41 patients developed clinically manifest or systemic Candida albicans infection 1-36 months after renal transplantation. Asymptomatic candiduria was diagnosed in all patients even before the onset of clinical symptoms. Fungal stomatitis was the most frequent clinical sign, followed by mycotic changes in the respiratory, genito-urinary (vaginitis) and gastro-intestinal tract. In five cases intrahepatic biliary stasis was diagnosed in the course of a Candida albicans septicaemia. In 12 patients with renal transplants it was possible, by treatment with nystatin, clotrimazole, flucytosine, miconazole and amphotericine B to control a generalized or clinically manifest Candida albicans infection. Three died of the septicaemia or meningoencephalitis, six as the result of bacterial superinfections. Inspection of the mouth is an important means of early diagnosing fungal infections. Antimycotic treatment should be started if fungal cultures from urine are repeatedly positive even if the clinical findings are still negative. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about [Indirect immunofluorescence in the serological diagnosis of chronic pyelonephritis (comparison with indirect haemagglutination and the Widal reaction (author's transl)].? [/INST] Using indirect immunofluorescence, o-antibodies against the homologous causative organism were determined in 119 adults with chronic pyelonephritis, during a one to two-and-a-half year period. Humoral antibodies were determined in the same group of patients with the Widal reaction and indirect haemagglutination. The results were compared with those in a group of adults without renal disease, using the same serological reactions. In adults with chronic pyelonephritis the antibody titre (by immunofluorescence) was above normal limits (as obtained in the healthy group) in 63.1%. The corresponding results for the Widal reaction and indirect haemagglutination reaction were 16.5% and 12, respectively. Indirect immunofluorescence is thus clearly better than the other two serological methods in the diagnosis of chronic pyelonephritis. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Antibacterial drugs today. I.? [/INST] Since the development of the sulphonamides in the 1930s and the subsequent development of antibiotics from the 1940s onwards, there have now been many drugs developed which are capable of chemotherapeutic activity in a patient infected by a susceptible micro-organism. This review is concerned with precise descriptions of important groups of antimicrobial drugs, with emphasis being placed on the more recently developed drugs. With each group of drugs the pharmacology, major therapeutic indications, dosages and adverse reactions are discussed. Part I of the article discusses the sulphonamides, the natural and semi-synthetic penicillins, cotrimoxazole, chloramphenicol, tetracyclines, the macrolides, lincomycin and clindamycin, fusidic acid, and the urinary antiseptics. The place of each in therapy is defined. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Age-related changes in pituitary responsiveness to LHRH in the female rat.? [/INST] Serum LH changes in response to LH-releasing hormone (LHRH) injection were measured in young (4-6 month-old) proestrous, estrous, and second-day-diestrous rats and in aged(23-30-month-old) constant estrous and irregular pseudopregnant (prolonged diestrus) female Long-Evans rats. Serum LH was measured by radioimmunoassay in serial blood samples taken before and at 15, 30 and 60 min after injection of 0, 5, 50 or 500 ng of LHRH. Serum LH also was assayed in similar groups of rats acutely pretreated with either 20 mug of estradiol benzoate (EB) or 5 mg of progesterone. Aged rats showed a smaller increase in serum LH following LHRH injection than the young groups. Within the young groups, the magnitude of response was greater in proestrous and estrous rats than in the diestrous animals. Pretreatment with EB resulted in increased serum LH after LHRH injection in young estrous and diestrous rats and in aged constant estrous rats, but did not alter serum LH levels in the aged pseudopregnant rats. Although the inccrease in serum LH after LHRH injection was greater in all young groups given progesterone pretreatment, progesterone pretreatment did not affect LHRH responsiveness in either of the aged groups. These results suggest that with aging, the pituitary becomes less capable of relasing LH in response to acute LHRH stimulation, and that the pituitaries of aged rats are less responsive to gonadal steroid sensitization to LHRH stimulation. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Immunoreactive gonadotropin-releasing hormone (Gn-RH) during maturation in the rat: Ontogeny of regional hypothalamic differences.? [/INST] The developmental appearance of immunoreactive gonandotropin releasing hormone (Gn-RH) was measured by radioimmunoassay in male and female rats from the 12th day of gestation to adulthood. Gn-RH content of the whole hypothalamus of both sexes increased from birth to 21 days of age. By the 28th day, Gn-RH content in females had approximately reached adult levels, while that in males continued to increase. Adult male rats exhibited significantly higher levels than adult females. The ontogeny of the regional differences previously observed in cycling female rats (4) was also studied. Regional analysis of Gn-RH development was characterized in the anterior hypothalamus by the rapid attainment of adult levels by day 7. In striking contrast, in the mid-hypothalamic region, Gn-RH content increased gradually, rising dramatically just prior to vaginal opening. The developmental pattern of Gn-RH content is consistent with the maturation of those hypothalamic structures concerned with synthesis, transport and storage of Gn-RH. The regional patterns observed may thus represent sequential maturation of the neural pathways involved. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Radioimmunoassay for luteinizing hormone releasing hormone in plasma.? [/INST] A sensitive and specific double antibody radioimmunoassay has been developed capable of measuring LH-RH in extracted human plasma. Thyrotropin releasing hormone, lysine vasopressin and most of LH-RH analogues did not appear to affect the assay. Hypothalamic extract and some of the LH-RH analogues produced displacement curves which were parallel to that obtained with the synthetic LH-RH. Sensitivity of the radioimmunoassay was about 3 pg per assay tube. The coefficient of variation of intraassay was 6.4%, while that of interassay was 9.6%. Exogenous LH-RH could be quantitatively extracted by acidic ethanol when varying amounts of synthetic LH-RH were added to plasma. Immunoreactivity of LH-RH was preserved in plasma until 2 hr in the cold and gradually reduced thereafter. The plasma levels in LH-RH were 20 pg/ml or less in normal adults and not detectable in children. The aged males over 60 yr and postmenopausal women showed a tendency to have higher levels of plasma LH-RH. Plasma LH-RH level was significantly higher in midcycle than in follicular and luteal stages. The disappearance rate of LH-RH from the circulation after intravenous injection could be represented as half times of 4-6 min. Between 0.2-0.4% of the injected dose was excreted into urine within 1 hr. These results indicate that the determination of LH-RH might be a useful tool for elucidating hypothalamic-pituitary-gonad interactions. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Fluorescence studies on the interaction between yeast seryl-tRNA synthetase and its substrates.? [/INST] Substrate-induced variations in the native fluorescence of seryl-tRNA synthetase from yeast have been used to evaluate the binding equilibria with its ligands. Binding of L-serine to the enzyme can be detected by equilibrium dialysis but not by fluorescence quenching. Hence, in contrast to ATP and tRNA(Ser), L-serine does not induce any fluorescence-sensitive conformational change of the synthetase. A comparison of the binding constants for ATP (2 X10(4) M-1) and seryl adenylate (1 x10(6) M-1) indicates that the activation reaction is mainly driven by the higher affinity of seryl adenylate to the enzyme. tRNA(Ser) and seryl-tRNA(Ser) though causing rather different maximal fluorescence quenching are bound to the enzyme with similar stoichiometry and association constant. The implications of this result are discussed with respect to the mechanism of the aminoacylation reaction. It is also shown that the enzyme clearly is capable of discriminating L-serine from other amino acids, ATP from other nucleotidetriphosphates and AMP, and tRNA(SER) from other tRNA species in the binding processes. The spectral properties, the effects of outside quenchers and the fluorescence decay times of the free enzyme and the enzyme-substrate complexes are discussed with respect to the intercalation hypothesis of Hélène. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about A study of codon-dependent binding of aminoacyl-tRNA with the ribosomal 30-S subparticle of Escherichia coli. Determination of the active-particle fraction and binding constants in different media.? [/INST] Titration of isolated Escherichia coli ribosomal 30-S particles with [14C]phenylalanyl-tRNA in the presence of poly(uridylic acid) was used for a quantitative assay of codon-dependent binding of aminoacyl-tRNA with the small ribosomal subparticle. The technique has allowed the estimation both of the fraction of "active" 30-S subparticles capable of forming the 30-S - poly(U) - phenylalanyl-tRNA complexes and the equilibrium constants of phenylalanyl-tRNA binding in different media. Heterogeneity of the ternary complexes formed has been revealed: at least two classes of complexes differing in stability have been observed. The stability of the 30-S - poly(U) - phenylalanyl-tRNA complexes has been shown to decrease with the lowering of the Mg2+ concentration, the increase of K+ concentration and the addition of urea. The stability of the complexes increases with the increase of Mg2+ concentration, with the addition of ethanol and decrease of temperature. It is demonstrated that the fraction of actively binding 30-S particles also varies in different medium conditions; it decreases with the increase of ionic strength (K+) and with the addition of urea, and increases with the increase of Mg2+ concentration and addition of ethanol. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The mode of action of pleuromutilin derivatives. Location and properties of the pleuromutilin binding site on Escherichia coli ribosomes.? [/INST] Using equilibrium dialysis techniques it could be demonstrated that (a) the pleuromutilin derivative 14-deoxy-14[(2-diethylaminoethyl)-mercaptoacetoxy] dihydromutilin HCl binds to one site per ribosome specifically, (b) the binding constant is 1.3 times 10(7) M(-1) and (c) chloramphenicol and puromycin compete with binding of the pleuromutilin derivative. Similarly the nucleotides CpA and CpCpA also displace the unsaturated derivative of the above-mentioned pleuromutilin compound. These findings suggest that the ribosomal binding site for pleuromutilin overlaps with that for chloramphenicol and analogs of the 3'-terminus of a tRNA, like puromycin or the nucleotides CpA and CpCpA. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The mechanism of template activation by exonuclease V.? [/INST] In crude extracts from Escherichia coli cells the ATP-dependent exonuclease V was found to be most active in converting double-stranded DNA into a suitable template for DNA polymerase. This phenomenon was studied in some detail with isolated exonuclease V and T7 DNA polymerase. We found that, at ATP concentrations arount 1 mM, the exonuclease produces a broad spectrum of DNA fragments. One class of fragments is largely single stranded with hydrogen-bonded small primer sequences. These structures allow the synthesis of remarkably homogeneous polynucleotide strands by T7 DNA polymerase. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Molecular morphology of ribosomes. Iodination of Escherichia coli ribosomal proteins with solid-state lactoperoxidase.? [/INST] Using either soluble or solid-state lactoperoxidase, a comparison was made between the enzymic iodination of ribosomal proteins iodinated as 30-S and 50-S subunits or as 70-S monosomes. Proteins S7, S11 and S12 of the 30-S subunit and proteins L2, L11, L26 and L28 of the 50-S subunit were labelled to a greater extent in isolated particles than in the 70-S ribosome. In contrast, proteins S4, S19 and S20 were labelled to a lesser extent in the isolated subunit. No significant differences were observed in the iodination patterns of ribosomes iodinated in the presence of soluble lactoperoxidase and those iodinated in the presence of lactoperoxidase bound to Sepharose 4B. It is suggested that the 30-S subunit undergoes a conformational change during its association with the 50-S subunit to form a 70-S monosome. Implications from results obtained with solid-state lactoperoxidase-catalyzed iodination of ribosomal proteins are also discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Covalent attachment of DNA to agarose. Improved synthesis and use in affinity chromatography.? [/INST] DNA has been covalently linked to insoluble matrices of agarose (Sepharose) in high yield using cyanogen bromide activation. Both double-stranded and single-stranded DNA have been coupled with yields up to 225 nmol/mg dry weight Sepharose or 3-8 mumol nucleotide phosphate/ml bed volume. The DNA-Sepharose has been used for (a) the affinity chromatography of various enzymes (Escherichia coli DNA polymerase I and RNA polymerase) from crude extracts or after initial purification steps, resulting in high yields and degrees of purification, and for (b) nucleic acid hybridization. The DNA-Sepharose is stable to high temperature, prolonged storage, and in the case of single-stranded DNA, can be washed with NaOH to destroy nuclease activity and to release any digested oligonucleotides or mononucleotides. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Sterol biosynthesis in yeast. 3-Hydorxy-3-methylglutaryl-Coenzyme A reductase as a regulatory enzyme.? [/INST] Anaerobically and aerobically grown yeast contains 3-hydroxy-3-methylglutaryl-CoA reductase, which is located in the mitochondrial fraction of the cell. Anaerobically grown yeast has a low specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase and a low sterol content. Aeration of this yeast in buffer, without growth, results in an increase in the specific activity of the enzyme, which is paralleled by an increase in the sterol content. This induction has an oscillatory profile with yeast grown anaerobically for 24 h and a linear pattern with cells grown anaerobically for 72 h. With the latter type of yeast, glucose is necessary for an induction, whereas with the other yeast an induction occurs with and without glucose. By an anaerobic incubation in buffer of the yeast grown anaerobically for 24 h, the oscillatory profile can be transformed into a linear one. The extent of induction of the reductase is strictly dependent on the concentration of glucose present. Sterols increase in whole cells, but they do not increase in the mitochondrial fraction. The induction of 3-hydroxy-3-methylglutaryl-CoA reductase is strongly inhibited by cycloheximide, but is not affected by chloramphenicol. The induction of the enzyme is closely connected with the glucose metabolism of the cell; fructose, mannose, and ethanol can also induce the reductase. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Mechanism of 2-deoxy-D-glucose inhibition of cell-wall polysaccharide and glycoprotein biosyntheses in Saccharomyces cerevisiae.? [/INST] The mechanism of inhibition by 2-deoxy-D-glucose of the synthesis of yeast wall polysaccharides and glycoproteins was investigated in Saccharomyces cerevisiae cells and protoplasts. The extent of the inhibition of mannan and glucan synthesis was found to be dependent on whether glucose or mannose was used as the carbon source in the medium. During growth on glucose, 2-deoxy-D-glucose inhibited more intensively mannan than glucan formation. Biosynthesis of wall glucan was strongly suppressed in mannose medium. Selective incorporation of 2-deoxy-D-glucose occurred into that polysaccharide, synthesis of which was more inhibited under given conditions. Suggestive evidence has been obtained that the decisive factor for the proportion of glucan and mannan in the walls is the direction of glucose 6-phosphate/mannose 6-phosphate interconversion dependent on the exogeneous hexose. No close correlation was found between the inhibition of mannan synthesis and the appearance of the mannan-protein enzymes invertase and acid phosphatase. Effect of 2-deoxy-D-glucose was therefore investigated on the parallel synthesis of protein, mannan and several extracellular and intracellular enzymes in protoplasts grown on glucose and mannose. The results obtained pointed out that the hindrance of the secretion of mannan-protein enzymes is of a complex nature and related more to the inhibition of synthesis of the protein moiety than to the inhibition of glycosylation. Synthesis of several enzymes was found to be a subject of a metabolic control by 2-deoxy-D-glucose or its metabolites. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Quantitative binding of antibiotics to ribosomes from a yeast mutant altered on the peptidyl-transferase center.? [/INST] Quantitative binding studies of [G-3H]anisomycin and [acetyl-14C]trichodermin to sensitive and resistant 80-S ribosomes from yeasts are described in this work. A single mutation, most probably affecting the ribosome peptidyl transferase centre, appears to have pleiotropic effects on the ribosome leading to resistance to trichodermin and anisomycin and to an increased sensitivity to sparsomycin. Resistance to trichodermin is due to a reduced affinity of ribosomes from the mutant for the antibiotic. Ribosomes from the sensitive strain (Y 1661 bind [acetyl-14C]trichodermin with a dissociation constant of 0.99 muM while those from the resistant one (TR1) bind [acetyl-14C]trichodermin with a dissociation constant of 15.4 muM. Similar results are obtained when the binding of [acetyl-14C]trichodermin to Y 166 and TR1 60-S subunits is studied. The mutant TR1 is also resistant to anisomycin. Although trichodermin and anisomycin bind to the ribosome at mutually exclusive sites, the higher affinity binding of [G-3H]anisomycin that is responsible for the inhibition of the peptidyl transferase center is practically identical for Y 166 and TR1 ribosomes. Therefore, the mutation in the ribosome leading to resistance to trichodermin and anisomycin decreases the affinity for trichodermin but not for anisomycin. Trichodermin, trichothecin and fusarenon X inhibit the binding of [G-3H]anisomycin to TR1 ribosomes to a lower extent than to Y 166 ribosomes, suggesting that the resistance of TR1 ribosomes to the effects of trichothecin and fusarenon X is caused by a decrease in the affinity of the ribosomes for these drugs, as was seen with trichodermin. On the other hand, verrucarin A inhibits [G-3H]anisomycin binding to Y 166 and TR1 ribosomes to a similar extent and therefore its affinity for the ribosome does not appear to be affected by the mutation leading to resistance. Trichothecin, trichodermin and fusarenon X appear to have a common binding site on the 60-S ribosomal subunits, which overlaps or is closely linked to the binding sites of anisomycin and verrucarin A. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Electrodialysis of lipopolysaccharides and their conversion to uniform salt forms.? [/INST] Ions of low molecular weight like metal cations and basic amines are present in lipopolysaccharides regardless of the isolation procedure employed. They are present in salt form with the acidic groups of the molecule and, partly, bound by chelation. Electrodialysis which removed a large proportion of these basic materials led to acidic lipopolysaccharides often with reduced solubility. Electrodialyzed lopopolysaccharides could be rendered soluble by neutralizing with alkali or with a basic amine. Depending on the base employed for neutralization preparations were obtained which showed in water distinct differences in solubility, viscosity and opalescence. These differences were related to differences in the sedimentation coefficients of the various salt forms. Neutralization with triethylamine led in all cases to highly soluble preparations with low sedimentation coefficients, while, on the other hand, neutralization with Mg(OH)2 led in most cases to insoluble preparations. The acidic lipopolysaccharides obtained by electrodialysis deteriorate on storing in a freeze-dried form. On heating in distilled water autohydrolysis occurs and free lipid A is liberated. The lipid A which is so far known as a water-insoluble material showed increased solubility when prepared from electrodialyzed lipopolysaccharides. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Regulation of protein secretion and metabolism in rat salivary glands. Effects of norepinephrine and carbachol on the glycogenolysis in submaxillary glands.? [/INST] Carbachol and norepinephrine induce glycogen breakdown in rat submaxillary glands incubated in vitro. These effects are suppressed by specific inhibitors of cholinergic receptors (atropine, a muscarinic blocker) and of adrenergic receptors (propranolol, a beta-blocker and phentolamine, an alpha-blocker). The beta-adrenergic effect seems to be mediated through the adenosine 3':5'-monophosphate system, whereas the alpha-adrenergic and cholinergic effects are dependent of Ca2+ influx into cell. In the two latter systems, it is suggested that a direct activation of phosphorylase b kinase by calcium takes place. These data clearly indicate that glycogenolysis in rat submaxillary glands in vitro can be independently affected by sympathetic and parasympathetic agents via specific receptors. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about tRNA conformation and magnesium binding. A study of a yeast phenylalanine-specific tRNA by a fluorescent indicator and differential melting curves.? [/INST] The binding of Mg2+ to tRNAPhe (yeast) in three conformational states was studied at 10, 30, 45, and 70 degrees C by the fluorescence indicator 8-hydroxyquinoline 5-sulphonic acid in the presence of 0.032 M monovalent cations (Na+). At temperatures below those characteristic for early melting (completely folded tRNA) the Scatchard plots are biphasic. They were well fitted by two classes of noninteracting binding sites with stability constants independent of temperature (KA = 9X10(4), KB = 6X10(3) M-1). In partially unfolded tRNA the strong binding process is co-operative. A single class of weak sites was found in the statistically coiled conformation at 70 degrees C (KB = 3.3X103 M-1). The total number of binding sites is 23 +/- 5; differences for the folded and unfolded conformations are smaller than 1. The influence of Mg2+ on the stability of the conformational elements of tRNAPhe (yeast) and its CCA-half (i.e. nucleotides 38--76) was determined by differential ultraviolet absorbance and depolarisation melting curves using the fluorescence of the Y base. Tertiary structure corresponding to early melting is stabilized by strongly bound Mg2+, whereas all other melting transitions are only influenced by Mg2+ bound at weak sites. The stability constants of tertiary structure obtained from the melting experiments can quantitatively be described by assuming that 5 +/- 1 non-interacting strong sites as characterized by the fluorescence titrations are converted to weak sites upon unfolding of the tertiary structure. Co-operative interaction of Mg2+ with the 5 strong sites in the folded conformation of tRNA can be ruled out. Strong binding of Mg2+ to completely folded tRNA does not produce a conformational transition changing ultraviolet absorbance, circular dichroism and sedimentation coefficient. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Isolation and partial characterisation of the relaxation protein from nuclei of cultured mouse and human cells.? [/INST] A protein, called relaxation protein because of its ability to remove superhelical turns in closed-circular DNA, has been isolated and partially characterized from the nuclei of LA9 mouse and HeLa cells. The purification was facilitated by an assay method, with PM2 DNA, which used the fluorescence enhancement of the intercalating dye ethidium bromide upon binding to the closed-circular DNA. The amount of dye bound depends upon the degree of the superhelix density of the DNA. The relaxation products were analysed by the buoyant separation method in CsCl containing ethidium bromide and were shown to be completely relaxed. The purification resulted in a single band in a dodecylsulfate gel electrophoresis with an apparent molecular weight of 37000. The pH optimum is 7.0 and the optimal salt concentration is 0.2 M NaCl. The relaxation protein removes negative as well as positive supercoils, the latter generated by the interaction of ethidium bromide with closed-circular DNA. Relaxation of positive supercoils results, after removal of the dye, in the formation of molecules with superhelix densities exceeding that of native PM2 DNA (0.054). The highest negative superhelix density observed was -0.098 +/- 0.001. The corresponding positive superhelix density has been calculated to be + 0.023. A nicking--swivelling--closing mechanism is postulated, but nicked intermediates have so far not been demonstrated. The relaxation protein is not inhibited by known mammalian endonuclease I inhibitors, except for denatured DNA, and does not possess a conventional polynucleotide ligase activity. The relaxation activity was found to be predominantly in the nuclei, with only small amounts present in the cytoplasm and mitochondria. The biological function of transient swivels induced by the relaxation protein is not known. However, transient swivels are considered necessary or useful in the replication of closed-circular DNA or long linear DNA, respectively. Relaxation protein could replace the combined action of an endonuclease and a ligase ahead of the replication fork. Alternatively, transient swivels could be involved in the transcription process. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Equivalent and non-equivalent binding sites for tRNA on aminoacyl-tRNA synthetases.? [/INST] Complexes between tRNAPhe (yeast), tRNASer (yeast) and tRNATyr (Escherichia coli) and their cognate aminoacyl-tRNA synthetases have been studied by sedimentation velocity runs in an analytical ultracentrifuge. The amount of complex formation was determined by the absorption and the sedimentation coefficients of the fast-moving boundary in the presence of excess tRNA or excess synthetase respectively. The same method has been applied to unspecific combinations of tRNAs and synthetases. Inactive material of tRNA or synthetase does not influence the results. 1. Two moles of tRNAPhe can be bound to one mole of phenylalanyl-tRNA synthetase with a binding constant greater than 10(6) M-1. The binding constants for both tRNAs are very similar; the binding sites are independent of each other. Omission of Mg2+ does not prevent binding. 2. Two moles of tRNASer can be bound to one mole of Seryl-tRNA synthetase; the binding of the first and second tRNA is non-equivalent, K1 greater than 10(6) M-1, K2 is determined to be 1.3 X 10(5) M-1 at pH 7.2. Omission of Mg2+ prevents complex formation. 3. Tyrosyl-tRNA synthetase behaves very similarly to seryl-tRNA synthetase. The binding constant for the weakly bound tRNA is 2.3 X 10(5) M-1 at pH 7.2, and 2.5 X 10(6) M-1 at pH 6.0. No complexes are observed in the absence of Mg2+. 4. Unspecific binding was only obtained with phenylalanyl-tRNA synthetase. It binds tRNASer (yeast), tRNAAla (yeast) and tRNATyr (E. coli) with a binding constant about 100 times lower compared to its cognate tRNA. The binding data are discussed with respect to the tertiary structure of the tRNAs, the subunit structure of the synthetases and the possible physical basis for the non-equivalence of binding sites. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about [Mechanism for the condensation reaction of fatty-acid biosynthesis (author's transl)].? [/INST] The spontaneous hydrogen-deuterium exchange of the methylene group of malonyl-thioesters was investigated by nuclear-magnetic-resonance (NMR) spectroscopy using the model compound S-malonyl-N-acetylcysteamine. The half life of the methylene proteins is 12 to 16 min in 0.1 M K-phosphate buffer at pH 6.5 to 7.0 at 25 degrees C, the conditions of maximal activity of fatty acid synthetase from yeast. Proton catalysis was used for the quick preparation of deuterium- and tritium-labeled malonylthioesters. Compared with malonyl-CoA, dideutero-malonyl-CoA had no primary isotope effect on the reaction velocity of the yeast enzyme catalysed fatty acid synthesis, in which the rate limiting step is the condensation reaction. Although deuterium oxide had a solvent isotope effect, there was no difference in reaction velocities between malonyl CoA and dideuteromalonyl CoA in deuterium oxide. The condensation reaction was investiaged separately from the overall fatty acid synthesis using beta-ketoacyl-acyl-carrier-protein (ACP) synthetase (condensing enzyme) of Escherichia coli. The condensation reaction with deuteromalonyl-ACP had no kinetic isotope effect, in agreement with the observations on the overall reaction. However, in this case no solvent isotope effect was observed with 2H2O. When the condensation reaction was carried out in the presence of tritiated water, there was no incorporation of label into the reaction product acetoacetyl-thioester, excluding proton exchange with the solvent. The results exclude a mechanism for the condensation reaction involving a malonyl carbanion and its acylation as intermediates in the sense of an organic-chemical malonic ester synthesis, and they indicate that the condensation reaction follows a concerted mechanism: The formation of the new carbon-carbon bond is coupled with the cleavage of the carboxyl bond of the malonyl group. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Quaternary structure of polynucleotide phosphorylase from Escherichia coli: evidence of a complex between two types of polypeptide chains.? [/INST] A new form of polynucleotide phosphorylase containing alpha and beta subunits was isolated (form B) by purification without preparative electrophoresis; this form was compared to the enzyme obtained by preparative electrophoresis purification (form A). The Stokes radius of these two forms are very different: 6.4 nm for form A and 8.7 - 9.0 nm for form B; on the other hand the sedimentation coefficients are close: 8.9 S and 9.9 S respectively. Such a result suggests that form B is very asymmetric. The apparent molecular weights, calculated from the Stokes radii and from the sedimentation coefficients, are approximately 365000 for form B and 252000 for form A. The latter is homogeneous on polyacrylamide gel, whereas the former yields two components, one of which behaves similarly to form A. Finally, whereas form A is composed of only one type of subunit, alpha, form B contains two types of chains: alpha (Mr 86000 +/- 5000) and beta (Mr 48000 +/- 2000) in stoichiometric proportions. From these results we believe that one should assume for form B the existence of a complex between form A and beta chains; the role of the latter still remains to be specified. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The modification of DNA-dependent RNA polymerase from Escherichia coli by an alkylating derivative of rifamycin SV.? [/INST] 3-(2-Bromo[1-14C]acetamidoethyl)-thio-rifamycin SV, abbreviated BrAcNEtS-Rif, and alkylating derivative of rifamycin SV was synthesized. A four-fold excess of BrAcNEtS-Rif inhibited the enzymic activity of RNA polymerase from Escherichia coli to 97%. Incubation of RNA polymerase with Br[14C]AcNEtS-Rif led to covalent substitution. The reaction of Br[14C]AcNEtS-Rif with enzyme at a ratio of 1.4:1 and a concentration of 63 nM was found to proceed with a half life of 1 h at 37 degrees C. The enzyme could be protected from reaction with BrAcNEtS-Rif by either rifampicin or the hybrid [poly(dT)]-[r(Ap)5a]. The modification of holoenzyme by Br[14C]AcNEtS-Rif in the presence of p-hydroxymercuribenzene sulfonic acid (pOH-HgBzSO3H) or 4 M LiCl occurred with faster kinetics and led to a higher degree of substitution. Reaction of Br[14C]AcNEtS-Rif with RNA polymerase core enzyme caused predominant substitution of subunit beta. In the case of RNA polymerase holenzyme the radioactive substituents were evenly distributed between subunits beta and sigma. Apparently the topology of the rifamycin binding site of holoenzyme, similarly to core enzyme, precludes attacks of nucleophilic functions from beta' and alpha, but it allows nucleophilic functions from subunits beta and sigma to react with equal probability on BrAcNEtS-Rif. In the presence of a 20-fold excess of pOH-HgBzSO3H, the modification of holoenzyme was drastically altered. Virtually all substitution took place on subunit beta', very little on beta and none on subunits sigma and alpha. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Role of ribosomal protein S1 in portein synthesis: effects of its addition to Bacillus stearothermophilus cell-free system.? [/INST] Products of the f2 phage RNA-directed protein synthesizing systems in vitro, derived from Escherichia coli and Bacillus stearothermophilus, were analyzed. In contrast to other reports, it was found that B. stearothermophilus ribosomes synthesized phage coat protein when the high-speed (100 000 X g) supernatant (S100) and ribosomal wash (crude initiation factors) of homologous origin were used. Furthermore, a marked stimulation of coat protein synthesis was observed with B. stearothermophilus ribosomes when either S100 or ribosomal wash or both from E. coli cells were used instead of the respective homologous components. The principle responsible for this stimulation was identified as the 30-S ribosomal protein S1 present in S100 and ribosomal wash. Purified S1 from E. coli at roughly one-to-one molar ratio to ribosomes resulted in about 10-fold stimulation of the incorporation of [14C]valine when added to the B. stearothermophilus system. This stimulation was observed mainly in the synthesis of coat protein and replicase. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Nucleotide sequences of Escherichia coli 16-S RNA associated with ribosomal proteins S7, S9, S10, S14 and S19.? [/INST] 1. A ribonucleoprotein fragment containing proteins S7, S9, S10, S14, and S19 was isolated in high yield from Escherichia coli 30-S ribosomal sub-particles. The same fragment was obtained whether ribosomes from E. coli strain A19 or MRE 600 were used, despite the fact that protein S7 differs widely between the two strains. RNA was extracted from this fragment and fractionated on gels containing 7 M urea, to reveal "hidden breaks". A well-defined and reporducible pattern of RNA fragments was obtained, with the main components being approximately 300, 240, 130, 115 and 75 nucleotides in length, respectively. The pattern of RNA fragments obtained was also independent of the strain of E. coli used. 2. Two-dimensional fingerprints were made from ribonuclease T1 hydrolysates of these RNA fragments, labelled with 32P, and the oligonucleotides were further analysed by digestion with either ribonuclease A or U2. The data obtained were fitted in detail to the new 16-S RNA sequence map of Ehresmann et al. (1975). Again no significant differences were observed between the RNA from E. coli A19 or MRE 600. The RNA sequences found lay in the region O'-D-E'-K-P-P'-E-A of the 16-S RNA, with a clear excision of several nucleotides in section E'-K. The total sequence length covered was approximately 430 nucleotides. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Cell-wall lipopolysaccharide from Escherichia coli B.? [/INST] The lipopolysaccharide of Escherichia coli BB and a number of R-phage selected (e.g. T3, T4) cell-wall-defective mutants were analyzed. From their lipopolysaccharides the respective core oligosaccharides were obtained. Following dephosphorylation, the oligosaccharides were methylated and analyzed by gas chromatography/mass spectrometry. This revealed the sugar sequence in the hexose-heptose region of the core. The linkage of heptose (Hep) to 2-keto-3-deoxyoctonate (KDO) was established as ... Hep 1,5 leads to KDO ... by methylation analysis. The substituted derivative of KDO was identified by gas chromatography and mass spectrometry. The KDO region contains three KDO units. Its structure was elaborated by (a) selective removal and identification of 7-phosphoryl ethanolamine-KDO (KDO-PN), (b) periodate oxidation and thiobarbituric acid reaction in conjunction with mild hydrolysis, (c) a modified methylation analysis. Phosphate substitution of E. coli BB core was studied by beta-elimination and using the information obtained with KDO-PN. The structures of the cell wall lipopolysaccharides from E. coli BB and cell-wall-defective mutants are given. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Malonyl and palmityl transferase-less mutants of the yeast fatty-acid-synthetase complex.? [/INST] 146 independently isolated mutants of the fatty acid synthetase gene locus fas 1 were subdivided into six different complementation groups. Three of these groups, Va, Vb and Vd, have not been described before. The mutant fatty acid synthetases isolated from representatives of complementation group Vb were specifically deficient in two component enzymes at the same time, the malonyl and palmityl transferases. Among more than 180 fas 1 and fas 2 mutants systematically screened for malonyl and palmityl transferase activities no mutant was found affected in only one of these two fatty acid synthetase component enzymes. From this it is concluded that both transfer reactions are catalyzed by the same enzyme. In any malonyl transferase-less fatty acid synthetase, neither of the two known malonyl binding sites, i.e. enzyme-bound pantetheine and the non-thiol binding site, accepts malonate. This indicates that malonate is transferred to both groups by the same enzyme. So far, no acetyl transferase-less fas mutants have been characterized. On the other hand, the mutants of two fas 1 complementation groups, Va and Vd, though negative in overall fatty acid synthetase activity had no deficiency in any of the known component enzymes which can be tested in vitro. A possible interrelationship between both findings is discussed. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Histidyl-tRNA synthetase from Salmonella typhimurium: specificity in the binding of histidine analogues.? [/INST] The topography of the active site of histidyl-tRNA synthetase has been investigated by determining Ki values for a variety of structural analogues of histidine, using the ATP-PPi exchange and tRNA aminoacylation reactions. Using these kinetic constants it has been possible to have a measure of the relative binding affinity of the enzyme for the histidine analogues. The following conclusions have been drawn: (a) the enzyme is stereospecific in the formation of aminoacyl-tRNA complexes, since the D-isomer of histidine does not influence the two reactions; (b) the carboxyl group is not required for binding; (c) bulky derivatives of the carboxyl group prevent the molecules from binding to the enzyme; (d) the amino group permits a good binding affinity; (e) the length of the ring side chain plays a very important role as point of attachment to the enzyme; (f) the kinds of heteroatoms on the ring determine the inhibitory properties of the analogues. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Biosynthesis of sterols by a yeast homogenate. Incorporation of mevalonic acid into cholesta-5,7,24-trien-3beta-ol and 5alpha-cholesta-7,24-dien-3beta-ol.? [/INST] Incubation of (3RS,2R)-[2-14C,2-3H]mevalonic acid and (3RS, 2S)-[2-14C,2-3H]mevalonic acid with mechanically disrupted yeast cells resulted in C27-metabolites. Two (14C5, 3H4)-metabolites, cholesta-5,7,24-trien-3beta-ol and 5 alpha-cholesta-7,24-dien-3beta-ol, were isolated and characterized. The impairment of the 24-methyl transferase system was confirmed by the lack of incorporation of 14C into the sterol fraction on incubation of S-adenosyl-L-[methyl-14C]methionine with the yeast homogenate. The results indicate that interference with the (C-24)-alkylating system did not prevent the transformation of lanosterol to the cholesta-5,7,24-trien-3beta-ol and to 5 alpha-cholesta-7,24-dien-3beta-ol. It can therefore be inferred that transformations of the nucleus and of the side chain can function independently. However our results do not provide a definition of the actual sequence of the metabolic events between lanosterol and ergosterol. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Determination of the complete amino-acid sequence of protein S4 from Escherichia coli ribosomes.? [/INST] After digestion of protein S4 with trypsin, all 32 tryptic peptides were isolated. Their amino acid compositions were analyzed and the sequence of the amino acids within the tryptic peptides was determined by means of a solid-phase peptide sequenator and by exopeptidases. Alignment of the tryptic peptides was established by analyzing and partially sequencing peptides isolated after digestion of the S4 protein with chymotrypsin, thermolysin and a glutamic-acid-specific protease. Further information about the alignment of peptides came from treatment of S4 with CNBr and with a lysine-modifying reagent. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The primary structure of tRNAIIArg from brewers' yeast. 1. Complete digestions with pancreatic and T1 ribonucleases.? [/INST] tRNAIIArg purified from bulk brewers' yeast tRNA by countercurrent distribution followed by two column-chromatographic steps was completely digested with pancreatic and T1 ribonucleases. Isolations of the products have been carried out either by column chromatography or by high-voltage electrophoresis. Analyses of the isolated nucleotides and olignoucleotides were in good agreement and indicate that this tRNA is composed of 76 nucltotide residues including 13 minor nucleotides. Overlaps resulting from the end-products of the two complementary digests led to a sequence of 25 residues. The primary structure of tRNAIIArg has been determined after partial digestion with T1 ribonuclease as described in the following paper. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Isolation and properties of a thymidylate-less mutant in Saccharomyces cerevisiae.? [/INST] A mutant, tmp3, has been isolated in Saccharomyces cerevisiae. Genetic and physiological analysis show that a single mendelian gene controls the multiple requirements for thymidylate, methionine, adenine and histidine and a neutral cytoplasmic petite character. Crude extracts of this mutant present a 60% decrease of serine transhydroxymethylase specific activity as compared to a wild-type strain. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Purification and properties of phosphoglucomutase from Fleischmann's yeast.? [/INST] 1. A procedure has been described for the purification of the major isozyme of yeast phosphoglucomutase of highest known specific activity. 2. The native enzyme has a molecular weight of about 65400 and was found to be homogeneous as judged by sucrose density gradient centrifugation, gel filtration, electrophoresis on acrylamide gel and ultracentrifugal analysis. In the presence of denaturing agents such as guanidine hydrochloride or sodium dodecyl sulfate, the enzyme dissociated into 32000-molecular-weight subunits. 3. As isolated, the enzyme has one mole of phosphate bound per mole of enzyme. Preparations incubated with 1.0 mM EDTA in 10 mM citrate buffer, pH 5.5 and dialysed against 10 mM metal-free citrate buffer, pH 5.5, contain no intrinsically bound Zn2+ and were enzymically inactive but fully active in the presence of 5 mM Mg2+ and 84% as active with 0.5 mM Zn2+. Simultaneous presence of both ions at these concentrations did not enhance activity. Enzyme was completely and irreversibly inactivated by preincubation with Be2+. Inactive enzyme had one mole of Be2+ bound per mole of enzyme. 4. Enzyme exhibited "ping-pong" kinetics rather than "random sequential". Km values for glucose 1-phosphate and for glucose 1,6-bisphosphate were calculated to be 2.34 times 10(-5) M and 2.24 times 10(-6) M, respectively. Rate of enzyme phosphate turnover was studied with rapid-mixing technique. The rates of 32P release from 32P-labeled enzyme and its appearance as glucose 6-[32P]phosphate were comparable and remained unaffected by addition of glucose 1,6-bisphosphate. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The thermodynamics and kinetics of conformational changes in 5-S RNA from Escherichia coli.? [/INST] Solutions of native, renatured and denatured 5-S RNA from Escherichia coli were each found to revert to a mixture of the denatured and renatured forms when incubated at elevated temperatures in the absence of divalent cations. The equilibrium and rate constants for the renaturation and denaturation reactions were studied as a function of temperature and concentration of added NaCl. The enthalpy and entropy of denaturation and the activation energies were determined. The activation energies for the renaturation reaction were found to be almost independent of the salt concentration, whereas the other parameters increased with the salt concentration. The results are interpreted in terms of a partially unfolded intermediate whose concentration is suppressed by the addition of salt. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about An inhibitory effect of thymidine on its own conversion to nucleotide in Escherichia coli.? [/INST] The cellular levels of thymidine nucleotide pool in thymine-requiring mutants of Escherichia coli were followed. The pool levels of dTDP, dTTP and compound-X reached maximal values in much lower concentration of thymidine than those in thymine. In higher concentrations of thymidine, an inhibitory effect on its own conversion to nucleotide was observed. The inhibited step was suggested to be the conversion of dTMP to dTDP. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about The regulation of arginine biosynthesis in Saccharomyces cerevisiae. The specificity of argR- mutations and the general control of amino-acid biosynthesis.? [/INST] The regulation of arginine biosynthetic enzymes in yeast is subjected to a double control. One level of arginine enzyme synthesis is under the control of an apo-repressor, called ARGR. ARGR molecules control specifically the arginine pathway. A second level of control of arginine biosynthesis has been disclosed. It also controls tryptophan, histidine, lysine, isoleucine-valine and probably many more biosyntheses. The general mechanism is turned on in leaky mutants in any of the amino acid pathways mentioned above. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Pools of ribosomal proteins in Escherichia coli. Studies on the exchange of proteins between pools and ribosomes.? [/INST] A labelling technique in vivo has been introduced which allows the tritiation of cell components with high specific activity during growth in rich medium. By this technique the pool size of each protein can be measured directly in the supernatant from centrifugation at 150000 times g. A measurable pool was found for the proteins S1, S2, S10, L1, L4, L7, L8/9, L10, L12, L21, and L25. Experiments on migration of ribosomal proteins from the supernatant to ribosomes (i.e. association) and vice versa (dissociation) demonstrate a remarkable constancy in the composition of the ribosome. There is no significant difference between ribosomes engaged or not engaged in poly-(Phe) synthesis. </s>

<s>[INST] <<SYS>> You are a very helpful assistant who provides accurate and concise responses. <</SYS>> can you explain about Fluorescent labelling of Escherichia coli ribosomal sulfhydryl groups.? [/INST] The reactivity of the sulfhydryl groups of Escherichia coli ribosome has been investigated using a fluorescent label. Under denaturing conditions, all the --SH groups can be titrated. In the native form of the ribosome, six and less than one labels can be respectively conjugated to the 30-S and 50-S subparticles without loss of activity for poly(U)-dependent polyphenylalanine synthesis. The most reactive thiol groups belong to proteins S1, S12, S18, S21. The binding of mRNA plus tRNA to the 70-S ribosomes affects the spectroscopic properties of the labels showing that conformational changes are induced by these interactions. Furthermore, the treatment of these complexes by the labelling agent demonstrates that the --SH group belonging to protein S1 is partially protected whereas other thiol groups located on the 50-S subparticle become reactive. </s>