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Biomedical subjects

R H Williams

Publications and source records attributed to R H Williams.

At least 73 records · Page 4Linked to original sources
PubMed1980

Incorporation of l-[3H]fucose and d-[3H]glucosamine into cell-surface-associated glycoconjugates in epidermis of cultured pig skin slices.

1. Electron microscope autoradiography indicated that L-[3H]fucose and D-[3H]glucosamine were both incorporated into cell-surface-associated glycoconjugates in the epidermis of cultured pig skin slices. 2. Acid hydrolysis and paper chromatography of skin homogenates confirmed that there was little metabolic conversion of the labeled precursors to other sugars. 3. Epidermis was separated from dermis using CaCl2, and was extracted with 8 M-urea/5% (w/v) sodium dodecyl sulphate and was then analysed by gel electrophoresis. The major component labelled with D-[3H]glucosamine had an apparent molecular weight in excess of 200 000. This material was not labelled with L-[3H]fucose. Lower molecular-weight components were labelled to a similar extent with both L-[3H]fucose and D-[3H]glucosamine. 4. The high molecular-weight material labelled with D-[3H]glucosamine was released into the medium when the epidermal cells were dispersed with trypsin, indicating that it was either surface-associated or was extracellular. It was also labelled with D-[14C]glucuronic acid, 35SO4(2-) and to a small extent with 14C-labelled amino acids indicating that it contained glycosaminoglycans derived from epidermal proteoglycans. This was confirmed by the fact that it was degraded by testicular hyaluronoglucosidase. It was not present in isolated membranes but was recovered in the soluble fraction from epidermal homogenates. It is therefore only very loosely bound at the cell surface or is present in the extracellular spaces. 5. Membrane-bound [3H]glycoproteins were identified after differential centrifugation of epidermal homogenates. The radioactivity profiles of membrane glycoproteins were similar whether L-[3H]fucose or D-[3H]glucosamine were used and both consisted of a major heterogeneous peak in the apparent mol.wt. range 70 000--150 000. [3H]Glycoproteins in this molecular-weight range were also major components of a plasma-membrane-enriched fraction. These glycoproteins were probably bound to the membrane by hydrophobic interactions, since they were only solubilized by treatment with detergent or organic solvent. They contained terminal sialic acid residues, since they were degraded by neuraminidase.

Animals↗
PubMed1980

Isolation of human intestinal neurotensin.

The biologically active peptide neurotensin (NT) has been isolated from fresh postmortem human small intestine and its identity with bovine hypothalamic and intestinal neurotensin has been established. Purification was achieved by gel filtration and two ion exchange chromatography steps; material was detected by radioimmunoassay (RIA). A substance was obtained that had integral molar ratios of amino acids and eluted in a single peak during reverse-phase high pressure liquid chromatography (HPLC). This material had an amino acid composition and COOH-terminal sequence identical with those of bovine NT. Human and bovine neurotensin gave rise to the same fragments when treated with papain; they were indistinguishable in RIAs using three different region-specific antisera and in their hypotensive effect on anesthetized rats. Using mucosal scrapings obtained immediately post-mortem from four subjects, the concentration of immunoreactive neurotensin was found to increase from duodenum to distal ileum, in agreement with results obtained in other mammalian species.

Amino Acids↗
PubMed1980

Distribution of glycoproteins containing fucose in normal and psoriatic keratinocytes.

Electron microscope autoradiography has been used to compare the fucose-containing glycoproteins of normal and psoriatic epidermis. Normal keratinocytes and uninvolved psoriatic cells have most of their fucose on the plasma membrane, whereas involved psoriatic cells retain more within the cytoplasm. The fucose distribution in other epidermal cell types is also described.

Autoradiography↗
PubMed1980

Coxsackie B virus antibody responses in juvenile-onset diabetes mellitus.

A prospective serological study of patients with recently diagnosed juvenile-onset diabetes mellitus was carried out to determine neutralizing antibody responses to Coxsackie B viruses. The sera were tested with and without staphylococcal protein A absorption, to selectively ascertain whether specific IgM or IgG antibody predominated. Of eleven patients studied, ten had reciprocal antibody titres of sixteen or greater to at least one serotype. Three patients showed no reduction in titre in at least one serum sample after protein A absorption, suggesting a predominant IgM-specific primary response to a recent infection by a Coxsackie B virus. The findings support the possibility that at least some cases of juvenile-onset diabetes mellitus are closely related to Coxsackie B virus infections.

Adolescent↗
PubMed1980

Studies on the natural history of the norepinephrine model of acute renal failure in the dog.

Studies on the natural history of the norepinephrine (NE) model of acute renal failure (ARF) in the dog. Group I (n = 6) was infused with NE into the renal artery (0.75 microgram/kg/min x 80 min) and glomerular filtration rate (GFR) determined sequentially. 21 days post-NE infusion (I) the GFR of the I kidneys (20 + or - (SE) 5ml/min) remained less (p less than 0.001) than the pre-I control value (44 plus or minus 2.9). Group II (n = 7) was treated in an identical fashion except that a contralateral nephrectomy (CN) was done on day 7 and the animals were prepared for micropuncture on day 16. In the animals with residual nephron function at CN, the GFR increased (p less than 0.02) from 26 plus or minus 6.4 ml/min on day 7 to 38 plus or minus 6.6 ml/min on day 14. Considerable interanimal heterogeneity of single nephron GFR (SNGFR) was demonstrated and morphologic studies revealed a very patchy lesion. Therefore, the model is reversible, heterogeneity of SNGFR is present, and the residual functioning nephrons have the capacity to undergo an increase in GFR after CN.

Acute Kidney Injury↗
PubMed1979

Pre-operative intravenous feeding--a controlled trial.

Seventy-four patients with a pre-operative diagnosis of stomach or oesophageal cancer were entered into a randomized, controlled clinical trial to assess the value of a short course of pre-operative intravenous nutrition. The effectiveness of this treatment was assessed by the clinical course and monitored by means of immune and biochemical profiles. Pre-operative parenteral nutrition given over a 7-10-day period resulted in a significant reduction in the incidence of postoperative wound infections. Clinical benefit was confined to those patients who had a low serum albumin on admission to hospital. It is doubtful whether this limited benefit justifies the routine use of intravenous feeding, with its attendant hazards, in the pre-operative preparation of patients with upper gastrointestinal cancer.

Aged↗
PubMed1978

N epsilonB29-(+)-biotinylinsulin and its complexes with avidin. Synthesis and biological activity.

Insulin was modified with d-biotin-N-hydroxysuccinimide ester in dimethylformamide. Mono-, di-, and triacylated insulins were separated by preparative isoelectric focusing. Monoacylated derivatives (isoelectric point 5.1) were fractionated twice on DEAE-cellulose to yield pure N epsilonB29-biotinylinsulin. The structure of the product was established by amino acid analysis before and after deamination. N epsilonB29-biotinylinsulin had biological activity indistinguishable from insulin on glucose oxidation and lipid synthesis assays using isolated rat epididymal fat cells. Complexes of N epsilonB29-biotinylinsulin with avidin, having essentially all but one binding site filled with biotin, were prepared in order to obtain a 1:1 insulin:avidin ration. The elicited identical maximal biological responses, but showed a potency decreased to 5% of that of insulin. Such complexes conjugated with ferritin will provide a useful tool in the development of electron microscopic stains of insulin receptors.

Adipose Tissue↗
PubMed1978

Epinephrine and dopamine beta-hydroxylase secretion from bovine adrenal.

The perfusate of the isolated, acetylcholine-stimulated bovine adrenal was studied for epinephrine (E) concentration and dopamine beta-hydroxylase (DBH) activity. Analysis of single stimuli showed that DBH disappeared from the perfusate with a t1/2 of 19.1-29.0 min. whereas E disappeared with a t1/2 of 0.78-1.0 min. Stimulation every 5 min over 105 min caused a gradual decline in E concentration to 36% of its initial value, whereas DBH activity reached a plateau after the second stimulus and thereafter remained unchanged. The decline in E was not influenced by addition of catecholamine precursors and biosynthetic cofactors to the medium and was not accompanied by a shift in the ratios of E and norepinephrine (NE) in the perfusate. Inhibitors of DBH activity were not detected in the perfusate and nonexocytotic leakage of DBH into the perfusate did not occur. These results document the temporal dissociation of the appearance and disappearance of DBH and E after a single stimulus and the progressive dissociation of DBH and E secretion under conditions of prolonged perfusion with rapid and repetitive stimulation. Possible explanations of these observations are offered.

Acetylcholine↗
PubMed1978

Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog.

Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.

Animals↗
PubMed1978

Characterization of proinsulin-insulin intermediates in human plasma.

This work addressed the problem of heterogeneity of immunoreactive insulin (IRI) in human plasma. Subjects with normal glucose tolerance were given 75g of an oral glucose solution, followed in 30 min by an intravenous infusion of 30g of arginine over 30 min. At the end of the infusion blood was withdrawn for analysis. IRI was extracted from plasma of individual subject by immunosorbent columns and was fractionated by gel filtration, disc gel electrophoresis and isoelectric focusing. Human IRI components were identified by molecular size, immunoreactivity with a human proinsulin antibody, sensitivity to trypsin, and by comparison of electrophoretic mobility and isoelectric point with porcine pancreatic products, after suitable correction for electric charge and molecular weight differences. The pattern of IRI heterogeneity was the same among six healthy subjects. Heterogeneity of proinsulin-size IRI in circulation was more marked than that of insulin-size material. Proinsulin and desdipeptide proinsulin were present in approximately equal amounts accompanied by minor amounts of split proinsulin and monodesamido-desdipeptide proinsulin. Insulin-size IRI contained over 80% insulin. Minor amounts of monodesamidoinsulin and diarginylinsulin were observed in some cases. The types of IRI components observed in plasma are evidence in support of a physiologic role of trypsin-and carboxypeptidase B-like enzymes in the conversion of proinsulin to insulin. Moreover, this study provides a base line for investigation of abnormalities in proinsulin-to-insulin conversion that may be associated with certain pathologic states.

Humans↗