Deviant TATA-box binding protein.
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Animals↗
Biomedical subjects
M Read
Publications and source records attributed to M Read.
Tramadol: pain relief by an opioid without depression of respiration.
Two independent clinical trials were conducted simultaneously. In one, tramadol and pethidine were compared in 30 patients by patient-controlled analgesia during the first 24 h following abdominal surgery. The mean 24 h consumption of tramadol and pethidine was 642 mg and 606 mg respectively, giving a potency estimate of tramadol relative to pethidine of 0.94 (95% confidence interval 0.72-1.17). In the second trial, the effect on respiration of three doses of tramadol (0.5, 1.0, and 2.0 mg.kg-1) was compared with that of morphine sulphate (0.143 mg.kg-1) by intravenous injection during stable halothane anaesthesia. At approximately 1.5 times the equipotent dose, as estimated from the first trial, tramadol transiently depressed the rate of respiration but had no effect on end-tidal carbon dioxide tension. Morphine caused apnoea or considerable depression of ventilation. The results suggest that mechanisms other than opioid receptor activity play a significant role in the analgesia produced by tramadol.
Abdomen↗
Low thyroxine levels in female psychiatric inpatients with riboflavin deficiency: implications for folate-dependent methylation.
Intermediates in the folate-dependent methylation pathways may play a role in the etiology and treatment of such mental disorders as major depression. These pathways include a step dependent on a riboflavin (B2)-derived coenzyme, flavin adenine dinucleotide (FAD), which is reportedly sensitive to thyroid status and to phenothiazine and tricyclic drug exposure. In a sample of 52 male and female acute psychiatric inpatients, 17% (n = 9) showed B2 deficiency (i.e., insufficient FAD activity) on a functional red blood cell enzyme assay, but only one B2-deficient individual showed deficiency in another B-complex vitamin (folate). All patients with B2 deficiency were women, who were also significantly younger than the rest of the sample. The B2-deficient women had significantly lower thyroxine levels, even when controlling for sex and covarying for age. B2-deficient patients exhibited a nonsignificant trend toward more unipolar depression (44% vs 14%), but not toward bipolar or schizophrenic disorders. As in a previous study, drug exposure did not show a relationship to riboflavin deficiency in this sample. The findings suggest that B2 (FAD) activity may serve as a sensitive marker of thyroxine status in certain female psychiatric inpatients and that B2 deficiency may play an etiological role in defects of the methylation pathways in a subset of mentally ill individuals.
Adult↗
Glycolytic pathway of the human malaria parasite Plasmodium falciparum: primary sequence analysis of the gene encoding 3-phosphoglycerate kinase and chromosomal mapping studies.
We have isolated and characterised the gene (PGK) encoding the glycolytic enzyme 3-phosphoglycerate kinase (PGK) from the human malaria parasite Plasmodium falciparum. This was achieved using the polymerase chain reaction (PCR) to amplify genomic DNA with primers constructed on the basis of conserved regions identified within PGK molecules of other organisms, and using the PCR product to isolate genomic clones. The gene is present in a single copy, encoding a protein of 416 amino acids (aa). The predicted aa sequence (45.5 kDa) displays approx. 60% identity to both human and yeast PGK molecules, and of the three P. falciparum glycolytic enzymes reported to date, has the greatest sequence identity to the host homologue. All aa residues implicated in substrate and cofactor binding and catalysis are conserved in the malarial PGK molecule, but there are major differences in overall composition, with implications for enzyme stability. In asexual blood-stage parasites, a single mRNA transcript of approx. 2.1 kb is observed. We have mapped the PGK gene to chromosome 9 of the parasite, and a further gene encoding a glycolytic enzyme, aldolase, to chromosome 14.
Amino Acid Sequence↗
The effect of chronic alcohol ingestion on whole body and muscle protein synthesis--a stable isotope study.
The cause of the proximal myopathy associated with chronic alcohol ingestion has yet to be established. The clinical feature of muscle wasting implies either inhibited skeletal muscle protein synthesis, stimulated breakdown or a combination of both. Previous data suggest that breakdown is reduced, rather than promoted. This provides evidence, albeit indirect, that the myopathy is the result of inhibited muscle protein synthesis, which has been demonstrated recently in the rat model. We have examined the influence of chronic alcohol intake on post-absorptive fractional skeletal muscle protein synthesis in man using a primed continuous (1 mg/kg/hr) infusion of L-[1-13C]leucine for 8 hr. Percutaneous quadriceps muscle biopsies (200 mg) were taken after 2 and 8 hr of the infusion for measurement of the incorporation of 13C leucine into muscle protein. Plasma 13C enrichment of alpha-ketoisocaproic acid, the deaminated product of leucine, was used to represent that of the precursor pool. We studied 6 fully ambulant alcoholics, who exhibited no overt evidence of skeletal muscle disease and who had consumed at least 100 g alcohol daily for a minimum of 10 years. Mean (+/- S.D.) fractional muscle protein synthesis was 0.0274 +/- 0.0087 (95% confidence intervals 0.0204-0.0344%/hr). This value is significantly lower than recently published control values obtained using identical protocols which range from 0.046 to 0.055%/hr. In addition, whole body leucine oxidation was lower (P less than 0.05) in the chronic alcoholics than in healthy controls, whereas neither whole body protein synthesis nor breakdown was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Regulation of somatostatin secretion by gastrin- and acid-dependent mechanisms.
The regulation of gastric somatostatin is linked to changes in gastric acidity, with a number of studies showing a good correlation between somatostatin secretion and gastrin-stimulated luminal acidity. However, gastrin may also have direct effects on somatostatin secretion independent of the concurrent acid status. We have examined the relative contribution of gastrin itself vs. gastric acid on the increase in somatostatin secretion observed after gastrin administration. Pentagastrin administered to conscious sheep for 2 h caused a 10- to 12-fold increase in both portal venous and peripheral jugular venous plasma somatostatin levels. This was associated with a decrease in gastric pH from 3.5 to 1.7. When the sheep were pretreated with the proton pump inhibitor omeprazole to prevent any change in gastric acidity, pentagastrin caused a similar increase in plasma somatostatin. The increase in somatostatin could also be produced by gastrin-17 infusions. Thus, these studies demonstrate that in the conscious animal gastrin can stimulate somatostatin independent of changes in gastric acidity. It is proposed that there is a negative feedback between somatostatin and gastrin, which may modulate the acid secretory response to gastrin.
Animals↗
Long-term supplement users and dosages among adult westerners.
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Diet Surveys↗
Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support.
1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism. 2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy. 3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery. 4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P less than 0.05) and returned towards pre-operative levels thereafter. 5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P less than 0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P less than 0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered. 6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P less than 0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of general anaesthesia on whole body protein turnover in patients undergoing elective surgery.
To determine if general anaesthesia alone or in conjunction with surgery alters body protein turnover, we studied six healthy, unpremedicated females undergoing elective total abdominal hysterectomy. Changes in protein metabolism, synthesis and breakdown were estimated by an isotope dilution technique using a continuous infusion of the stable isotope tracer, L-[1-13C]leucine, before anaesthesia (4 h), during anaesthesia alone (1 h), during anaesthesia and surgery (1 h) and in the recovery period (2 h). General anaesthesia comprised thiopentone, pancuronium, enflurane (1 MAC) and oxygen-enriched air. An isotopic steady state in plasma 13C-alpha-ketoisocaproate (13C alpha-KIC) and expired 13C-carbon dioxide were obtained during the four periods. Collections of plasma and expired air were made during the steady state periods and plasma alpha-KIC enrichment measured to indicate precursor pool labelling from which leucine flux (equal to protein breakdown in the post-absorptive state) and oxidation were calculated, and whole body protein synthesis was derived. Whole body protein breakdown did not change with anaesthesia, but decreased with both surgery and during the acute recovery period (P less than 0.05). Protein synthesis did not change with anaesthesia and surgery, but decreased significantly after surgery (P less than 0.05).
Adult↗
Influence of insulin on albumin and non-albumin protein fractional synthetic rates in post-absorptive type I diabetic patients.
Two 8-h primed continuous infusions of L-[1-13C] leucine were used to determine fractional synthesis rates of albumin and non-albumin plasma protein in post-absorptive Type I diabetic patients during insulin infusion and its withdrawal. Fractional protein synthetic rates were calculated from the rate of incorporation of 13C-label into protein and employing plasma 13C-alpha-ketoisocaproic acid enrichment to represent the precursor pools label. Incorporation of 13C into albumin and non-albumin plasma protein was linear over the latter 6 h of the 8-h L-[1-13C] leucine infusion. Fractional synthetic rates of plasma albumin and non-albumin proteins were similar during insulin withdrawal and its infusion. The increased whole-body protein synthesis observed during insulin withdrawal in Type I diabetic patients appears unrelated to events in albumin and non-albumin plasma protein fractions. These data are further evidence that insulin per se does not stimulate protein synthesis in man.
Adult↗
Cytoplasmic interaction between pp60c-src and a truncated polyoma virus middle T antigen.
We have investigated the subcellular localization, transforming capacity and cellular protein binding properties of a mutant middle T antigen, 82JF3. This mutant lacks the carboxyterminal 86 amino acids of middle T and, as expected, failed to associate with cellular membranes. Like other cytoplasmic mutants, it also failed to transform. Nevertheless, 82JF3 middle T antigen associated with pp60c-src and increased its tyrosine kinase activity. The associated pp60c-src was also cytoplasmic, raising interesting questions about the nature and formation of the complex. This soluble complex also contained very reduced levels both of the p81 protein and of associated phosphatidylinositol (PI) kinase activity. These results are consistent with the hypothesis that p81 is a component of PI kinase.
Animals↗
Targeting messages to supplement users.
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Adult↗
Vitamin and mineral supplementation practices of adults in seven western states.
Seven western states (Arizona, California, Idaho, Nevada, New Mexico, Oregon, and Wyoming) were surveyed in 1986 to determine the extent of vitamin/mineral supplementation and dosage levels of single supplements. Questionnaires were mailed to 3,500 individuals. A 57.8% response rate was obtained from the deliverable surveys, with a sample size of 1,730. The sample consisted of 54% women and 46% men and was predominantly white (88.9%). Fifty-four percent of the sample consumed some type of supplement; multiple vitamin/minerals were consumed with the greatest frequency. For single supplements, vitamin C was reported with the greatest frequency (23.1%), followed by some type of calcium supplement (22.5%) and vitamin E (11.1%). More than 80% of the vitamin C users indicated a dosage of 250 mg/day. Most respondents consumed calcium dosages of less than 1,000 mg/day. For vitamin E, 75% of the users consumed more than 200 IU/day. The data suggest that the potential for toxicity due to excess supplementation levels exists in the western states studied.
Adolescent↗
White clot syndrome.
Heparin therapy is currently a vital component in the medical management of thromboembolic events. Despite its widespread use, it is associated with relatively few complications, and these are usually minor and quickly reversible. Recently a much more dramatic and serious complication of heparin therapy has been identified. In heparin-induced thrombocytopenia with associated thrombosis or "white clot syndrome," patients have paradoxic thromboembolic events while receiving heparin. These events are of acute onset and of major consequence, often resulting in limb loss or death. This paper describes our own experience with ten patients in whom the white clot syndrome occurred during heparin therapy for thrombotic or embolic events. Both porcine and bovine heparin preparations were being given through various routes. In the three cases in which platelet aggregation testing was completed, results were positive. Our ten patients ultimately had a 20% major limb amputation rate and an overall 50% mortality.
Aged↗
The structure and function of the integrated polyoma virus DNA in 82-rat and 53-rat transformed cells.
Integrated viral sequences and adjacent cellular sequences from the polyoma virus (Py)-transformed 53-Rat and 82-Rat cell lines which contain two and three partial early regions respectively, each in a single viral insert, have been molecularly cloned. Each of the cloned partial early regions have been subcloned and assessed with regard to their transcription, translation products (T antigens, T Ags) and biological activity including their transforming ability. The 53-Rat 5.3 kb EcoRI fragment is an intact Py EcoRI linear genome (derived from within the tandem duplicated sequences) which transforms rat cells with high efficiency and produces infectious virus when circularized and transfected into mouse cells. The 82-Rat cell line expresses three novel T Ag species of 63K, 40K and 32K in addition to the Py middle and small T Ags. The 63K protein was found to be a truncated form of large T Ag produced as the result of an addition/deletion in early region B sequences unique to large T Ag. The 40K and 32K proteins are hybrid viral-cellular middle and large T Ags respectively, which are expressed from early region A that has been truncated by recombination with rat cellular DNA. Differences in the nuclear and cytoplasmic location of the different 82-Rat early region RNAs are due to RNA stability and/or transport from the nucleus to the cytoplasm most likely as a result of different cellular sequences at their 3' ends. Finally no common structural feature or sequence specificity was observed at the virus-host DNA joins of the two cell lines.
Animals↗
The use of human plasmas and plasma-depleted blood fractions in the in vitro cultivation of the malaria parasite Plasmodium falciparum.
The decreasing availability of whole blood and serum from blood banks led us to investigate the suitability of untreated and heat-treated human plasma, as well as of plasma-depleted blood fractions, for routine culturing of P. falciparum. The practical problems of using plasma instead of serum were addressed and the effect of storage conditions tested. We conclude that plasma is a convenient and effective substitute for serum, and that plasma-depleted blood fractions are as receptive to parasite infection as unprocessed blood.
Animals↗