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Biomedical subjects

R H Williams

Publications and source records attributed to R H Williams.

At least 91 records · Page 5Linked to original sources

Levels of the glutamic oxaloacetic transaminase of erythrocytes of pregnant women and of cord bloods of newborn infants.

The mean basal specific activity (S.A.) of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) for a group of 64 pregnant women was lower (p less than 0.001) than the value for the cord bloods of newborn infants, and lower (p less than 0.001) than the value for adults who had a top limit of S.A. of EGOT. In establishing the top limit of the S.A., it is important that the mean basal S.A. of the cord bloods from 49 newborn infants was identical to the mean basal S.A. of adults who had an adequate supplement of pyridoxine. There were no differences in the mean basal S.A.'s of the cord bloods between asymptomatic mothers and mothers who had anemia, edema, hypertension, proteinuria and glucosuria. An infant may be born with a top limit of S.A. which is non-deficient in pyridoxal 5'-phosphate, but a mother can have a low level of the transaminase, and which is deficient in the coenzyme.

Aspartate Aminotransferases↗

Immunocytochemical localization of a gastric imhibitory polypeptide-like material within A-cells of the endocrine pancreas.

In rat pancreatic islets, the glucagon-producing A-cells also contain a GIP-like material as revealed by the peroxidase-antiperoxidase immunocytochemical technique. Control studies showed that this dual staining was not due to the cross-reactivity of anti-GIP with glucagon. It is concluded either that the A-cells synthesize a GIP-like peptide or that it is taken up from the circulation.

Animals↗

Foam elastomer dressing in the management of open granulating wounds: experience with 250 patients.

Our experience in the use of a silicone foam elastomer in the dressing of granulating wounds is described in a series of 250 patients. Among the types of wound treated were a pilonidal sinus, abdominal, perianal and perineal wounds, bed sores and diabetic gangrene of the foot. The technique has marked advantages over conventional packing of wounds in relation to patient comfort and saving of nursing time in hospital, and can eliminate the need for district nursing care in the domiciliary situation. Details of preparation, application and surgical management are given.

Adult↗

Fibroblast monolayer cultures in scintillation counting vials: metabolic and growth experiments using radioisotopes and a microfluoremetric DNA assay.

We have developed a simple technique for the investigation of cellular metabolism and growth in cultured human fibroblasts which facilitates experiments using up to 3 x 10(5) cells in each of 100 or more culture vessels. The method has been used to study cell growth, glucose utilization and oxidation, and protein, RNA and DNA sysnthesis. The use of radiolabeled substrates in tracer experiments is simplified since transfer of cell material is not required. Methods for measuring both total cellular protein and DNA have been adapted to this culture system. Although we have used this tecnique for fibroblast cultures, it also can be easily applied to experiments on any other type of cell that can be grown in a monolayer.

Carbon Radioisotopes↗

Differences in growth response to hydrocortisone and ascorbic acid by human diploid fibroblasts.

The effects of hydrocortisone and ascorbic acid on growth parameters were measured in human diploid skin fibroblasts from fetal and adult donors. In the presence of culture medium containing 10% fetal bovine serum, 0.3 micrometer hydrocortisone produced a 20% increase in the population growth rate and a 50 to 70% increase in the confluent density of fibroblasts from adult donors. Daily addition of 28 micrometer ascorbic acid also stimulated the population growth rate and cell density at confluency. The effects of hydrocortisone and ascorbic acid on the final cell density were additive. The action of hydrocortisone was restricted to cells in log-phase growth, whereas ascorbic acid affected cells in both the log and the post-confluent phases of the growth cycle. In fibroblasts from fetal donors, ascorbic acid was stimulative but hydrocortisone was not. The data suggest that whereas both compounds stimulate cell growth in an additive manner, they do so by different cellular mechanisms.

Adult↗

Acute folate deficiency associated with intravenous nutrition with aminoacid-sorbitol-ethanol: prophylaxis with intravenous folic acid.

Preoperative folate levels were initially normal in 30 patients with gastrointestinal tract disease but fell within 48 h by 60-95% in 20 patients who received intravenous nutrition for 6-12 d with aminoacid-sorbitol-ethanol (ASE). This depression persisted in patients not given folate supplements. Folate levels in 10 control patients not given ASE showed only minimal decline. Haematological changes were reduced to a minimum in 10 patients given 0.5 mg i.v. folic acid daily whilst eight unsupplemented patients showed evidence of megaloblastic haemopoiesis. Three of these eight patients developed thrombocytopenia and/or leukopenia which was fatal in one patient.

Aged↗

Autoregulation of nephron filtration rate in the dog assessed by indicator-dilution technique.

Micropuncture studies were conducted in anesthetized dogs to evaluate single nephron glomerular filtrate rate (SNGFR) and SNGFR autoregulation when assessed by means of an indicator-dilution technique (SNGFRID), which does not require interruption of distal volume delivery. In 18 dogs, control renal arterial pressure was 124 +/- 11 mmHg (SD), renal blood flow (RBF) was 185 +/- 58 ml/min, and whole kidney GRF was 37 +/- 7 ml/min. SNGFRID averaged 57 +/- 15 nl/min and was significantly lower than SNGFR determined on the basis of total collections (SNGFRTC) from proximal tubules (75 +/- 17 nl/min). However, SNGFRID was not significantly different from the overall average SNGFR of 62 +/- 12 nl/min estimated from whole kidney GFR and the total number of glomeruli (613,000 +/- 74,000). In 10 animals, renal arterial pressure was reduced to an average of 94 +/- 8 mmHg; whole kidney autoregulation was highly efficient and average RBF and GRF remained within 1 and 3% of their control values. Likewise, SNGFRID was not significantly altered at 52 +/- 17 and 52 +/- 16 nl/min. In contrast, SNGFRTC decreased significantly from 72 +/- 17 to 51 +/- 13 nl/min. These results indicate that the indicator-dilution technique provides a reliable assessment of SNGFR and allows the manifestation of single nephron autoregulatory behavior. They provide further support for the hypothesis that maintenance of distal volume delivery may be a necessary aspect of the autoregulation phenomenon.

Animals↗

Plasma norepinephrine responses of man in cold water.

The hypothermic stress of immersion in cold water stimulates release of norepinephrine from the sympathetic nervous system. The speed and pattern of this response was studied in six healthy men by serial measurements of plasma norepinephrine concentrations before, during, and after 60 min of immersion in 10 degrees C water. After immersion for 2 min, the mean norepinephrine concentration was increased from 359+/-32 (basal) to 642+/-138 pg/ml and rose gradually to a maximum of 1.171+/-226 pg/ml after 45 min of immersion. Metabolic rate increased approximately threefold during the immersion period. After rewarming in warm water (40 degrees C), the subjects showed a transient peak in plasma norepinephrine followed by a rapid decrease to basal levels after 30 min. The fall in plasma norepinephrine after approximately 8 min of rewarming occurred despite persistent depression of the core temperature and coincided with a sudden decrease in metabolic rate and cessation of body shivering. These results suggest that the sympathetic nervous response to cold can be activated or suppressed very quickly and is dependent on the skin temperature.

Adult↗

Abnormalities in proliferation and protein synthesis in skin fibroblast cultures from patients with diabetes mellitus.

Several aspects of in-vitro cell growth and protein synthesis were assessed in cultures of skin fibroblasts from subjects with juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM) and from age-matched nondiabetic controls (C). There was an inverse correlation between increasing age and both the log-phase doubling rate and saturation density at confluence in C fibroblasts. JODM and AODM cells had a reduction in both indices of cell population growth in comparison with age-matched C fibroblasts. Fibroblasts grown in the presence of 0.3 micronM hydrocortisone were stimulated to grow more rapidly and to a greater saturation density. Stimulation of cell division by hydrocortisone accentuated the abnormalities in growth of JODM and AODM fibroblasts. Total protein and collagen synthesis was measured whtn the fibroblasts had grown to confluency in medium with or without hydrocorticone. Hydrocorticone did not produce a significant change in total protein and collagen synthesis per cell by C fibroblasts. Fibroblasts from AODM had a 180 per cent increase in total protein and collagen synthesis in the presence of hydrocortisone. In contrast, total protein and collagen synthesis decreased 40 per cent in fibroblasts from JODM when grown in the hydrocortisone medium. These studies indicate that skin fibroblast cultures from patients with diabetes exhibit abnormalities in cell proliferation. Furthermore, hydrocortisone appears to unmask diffeerences in protein synthesis that distinguish JODM and AODM fibroblasts in culture.

Adult↗

Deficiency of vitamin B6 in women taking contraceptive formulations.

The specific activities (S.A.) of the glutamic oxaloacetic transaminase from erythrocytes (EGOT) of 75 women taking 16 diversified contraceptive formulations were determined by the principle (CAS) of unsaturation and saturation of receptors of the Coenzyme-Apoenzyme-System with the coenzyme, pyridoxal 5'-phosphate. 52 women were not taking pyridoxine; 20 were taking 1-5 mg; 3 were taking 25-100 mg. The mean basal S.A. of the 52 women without pyridoxine was lower (p less than 0.01) than for the 20 on 1-5 mg. The mean basal S.A. for the women on 25-100 mg was higher (p less than 0.01) than for the women without pyridoxine. The mean % deficiency for the women on 25-100 mg was negligible and lower (p less than 0.01) than 18+/-8 for the 52 women, and 14+/-6 for the 20 women. These data indicate that 1-5 mg of pyridoxine is inadequate for women on contraceptives. The requisite daily dosage is projected at 50-100 mg. Other data indicate that 5-12 weeks of supplementation with pyridoxine can be required to reach a stable "ceiling" of S.A. of EGOT. This period indicates some regulatory mechanism by diminished levels of the apoenzyme upon gene expression to bring about normal levels of the transaminase.

Adolescent↗

Hormonal regulation of pancreatic islet adenyl cyclase.

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.

Adenylyl Cyclases↗

Inhibition of insulin rlease by scorpion toxin in rat pancreatic islets.

Toxin purified from venom of the scorpion Leiurus quinquestriatus was used to release the norepinephrine from adrenergic nerve terminals in isolated pancreatic islets perifused in vitro. Addition of toxin (10 mug./ml) to the perifusion medium caused a sixfold increase in release of norepinephrine in the presence or absence of 3 X 10(-5) M phenoxybenzamine. During 20 minutes of stimulation with toxin, the pancreatic islets released an average of 15 pg. of norepinephrine per islet, which represented 20 per cent of the normal content of norepinephrine in islets. Insulin secretory rates in response to either 1.0 or 3.0 mg./ml. glucose were inhibited similarly by scorpion toxin. Addition of phenoxybenzamine abolished the inhibition of insulin release caused by scorpion toxin. Phenoxybenzamine alone did not affect release of insulin. Neither the enhanced release of norepinephrine nor the decreased release of insulin was reversed by a 20-minute wash-out period after infusion of toxin. These results indicate that the sympathetic nerve terminals in the rat pancreatic islet contain considerable amounts of norepinephrine that can be released by scorpion toxin. The norepinephrine released from sympathetic nerve endings in the pancreatic islet can inhibit release of insulin through an alpha-adrenergic action that is blocked by phenoxybenzamine.

Animals↗