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Biomedical subjects

R E Lewis

Publications and source records attributed to R E Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1987

Phospholipid environment alters hormone-sensitivity of the purified insulin receptor kinase.

Insulin receptor kinase, affinity-purified by adsorption and elution from immobilized insulin, is stimulated 2-3-fold by insulin in detergent solution. Reconstitution of the receptor kinase into leaky vesicles containing phosphatidylcholine and phosphatidylethanolamine (1:1, w/w) by detergent removal on Sephadex G-50 results in the complete loss of receptor kinase sensitivity to activation by insulin. Insulin receptors in these vesicles also exhibit an increase in their apparent affinity for 125I-insulin (Kd = 0.12 nM versus 0.76 nM). Inclusion of 8.3-16.7% phosphatidylserine into the reconstituted vesicles restores 40-50% of the insulin-sensitivity to the receptor kinase. An elevated apparent affinity for 125I-insulin of insulin receptors in vesicles containing phosphatidylcholine and phosphatidylethanolamine is also restored to the value observed in detergent solution by the inclusion of phosphatidylserine in the reconstituted system. The effect of phosphatidylserine on insulin receptor kinase appears specific, because cholesterol, phosphatidylinositol and phosphatidic acid are all unable to restore insulin-sensitivity to the receptor kinase. Autophosphorylation sites on the insulin receptor as analysed by h.p.l.c. of tryptic 32P-labelled receptor phosphopeptides are not different for insulin receptors autophosphorylated in detergent solution or for the reconstituted vesicles in the presence or absence of phosphatidylserine. These data indicate that the phospholipid environment of insulin receptors can modulate its binding and kinase activity, and phosphatidylserine acts to restore insulin-sensitivity to the receptor kinase incorporated into phosphatidylcholine/phosphatidylethanolamine vesicles.

Chromatography, Gel↗
PubMed1986

Neutrophil-dependent mediation of microvascular permeability.

Macromolecular extravasation induced by the chemoattractants N-formyl-methionylleucylphenylalanine (FMLP), complement fragment C5a, and leukotriene B4 (LTB4) has been reported to be neutrophil dependent. A review of experimental evidence argues against mechanical disruption of the endothelial barrier as a likely mechanism for enhanced microvascular permeability. Other proposed mechanisms attribute macromolecular efflux to extracellular liberation of granule constituents or granule-independent neutrophil release products (e.g., oxygen radicals) that can undermine vascular integrity by direct or indirect actions on endothelial cells or other components of vascular walls (glycocalyx, basement membrane). The cytotoxic potential of neutrophil-release products on endothelial cells prompts consideration of a transcellular pathway for macromolecular transport. Further studies are needed to clarify the precise nature of endothelial injury and its resolution to better understand the physiology behind the transient effects of these mediators on vascular permeability.

Animals↗
PubMed1985

[125I]Tyr-bradykinin binding in primary rat brain cultures.

Kinins bind to specific, high affinity recognition sites in rat brain cell culture. Studies in these cultures minimize non-specific binding and degradation of the ligand. Binding of [125I]Tyr-bradykinin to intact cultured brain cells from neonatal rats was time- and pH-dependent. Scatchard analysis of saturation experiments yielded two affinity components with dissociation constant and maximum binding site concentration averaging 1 nM and 100 fmol/mg protein, and 16 nM and 1000 fmol/mg protein, respectively. The binding sites were specific for kinins and kinin analogues, and the order of potency in competing for [125I]Tyr-bradykinin binding was Lys-bradykinin greater than bradykinin greater than Tyr-bradykinin greater than Tyr8-bradykinin much much greater than Des-Arg9-bradykinin. Monovalent and divalent cations inhibited kinin binding. Comparison of competition curves performed in glial-enriched vs neuron-enriched cultures suggested that the kinin binding sites resided primarily on neurons. These data enhance the existing evidence suggesting kinins as neurotransmitters or neuromodulators.

Animals↗
PubMed1985

Auto-antibody to kidney tubular cells during retrograde chronic pyelonephritis in rats.

Retrograde pyelonephritis was induced in inbred Fischer rat kidneys with Proteus mirabilis (1 X 10(8) organisms/ml). Sera from pyelonephritic animals sacrificed at 4 and 6 weeks contained cytotoxic antibodies to cultured syngeneic 51Cr-labeled kidney tubular cells (p less than 0.02 and p less than 0.05, respectively) which could be absorbed with plasma membranes. Immune sera from 4- and 6-week pyelonephritic animals also displayed a granular fluorescent pattern along the surface of cultured kidney tubular cells. Quick-frozen syngeneic rat kidney sections stained positively with fluorescent antibody on the intraluminal side of kidney tubular cells. The results suggest that during chronic phases of pyelonephritis, auto-antibodies to kidney tubular cells are induced.

Animals↗
PubMed1984

Serial monitoring of T-cell subset ratios with monoclonal antibodies in steroid- and antithymocyte globulin-treated patients with renal allotransplants.

Sequential changes in T-cell subsets or their ratios were employed to predict severity of rejection crises and to identify those patients who might require future antirejection therapy. Forty-two percent of the transplant recipients had a pretransplant OKT4:8 ratio in the range of 1.3 +/- 0.5. By contrast, only 11% had a OKT4:8 ratio of 2.9 or greater. Examination of the entire study group demonstrated that the mean OKT4:8 ratios fell (P less than 0.01) in the first week following the transplant procedure. All patients had at least one episode of acute rejection. There was a marked increase (P less than 0.05) in the OKT4:8 ratio between the first week value and the value immediately preceding (within 3 days) the start of the rejection episode which was 2.64 +/- 0.27. The mean OKT4:8 ratio in the 15 patients leaving the hospital with a functioning transplant was 1.18 +/- 0.35. Three months post-transplant, the OKT4:8 ratio was 1.98 +/- 0.39 in the 12 patients with functioning allografts. This value was not different from those patients' initial pretransplant values. Clinically, the rejection episodes could be divided into two groups based on their response to intravenous methylprednisolone therapy. The first group (n = 9) had milder rejection crises which responded rapidly to administration of one course of methylprednisolone. The second group of patients (n = 9) were also treated initially with methylprednisolone, to which they did not respond, and subsequently received antithymocyte globulin in an attempt to control their ongoing rejection crises. Following the transplant procedure, the OKT4:8 ratio decreased in patients who were destined to have steroid-responsive rejection episodes (P less than 0.01). The OKT4:8 ratio however, failed to fall in those who required ATG for control of their transplant rejection episodes. The onset of rejection episodes was associated with an increase in OKT4:8 ratio in both groups. Following steroid administration, two patterns of OKT4:8 cell responses were observed. Those in whom renal function improved demonstrated a decline in OKT4:8 ratio from 2.4 +/- 0.4 to 1.4 +/- 0.4 (P less than 0.05). However, no change occurred in the OKT4:8 ratios with steroid therapy (2.6 to 2.4 +/- 0.33, P greater than 0.05) in individuals in whom the serum creatinine concentration failed to decline. The patients who failed to respond to steroid therapy were treated with antithymocyte globulin (ATG).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1984

Localization of the central pressor action of bradykinin to the cerebral third ventricle.

Bradykinin injected into the lateral ventricle produces a rise in blood pressure. Cream plugs selectively localized to discrete regions of the ventricular system were used to block drug access to periventricular sites. Third ventricular plugs blocked the pressor response to lateral ventricular injections of 5 micrograms bradykinin (27 +/- 5 before vs. 5 +/- 5 mmHg after plug, n = 7) and 100 ng angiotensin II (22 +/- 3 before vs. 4 +/- 2 mmHg after plug, n = 5). Third ventricular plugs also suppressed the drinking response to angiotensin II (3.7 +/- 0.6 before vs. 0.9 +/- 0.6 ml after plug, n = 5). However, plugs that occluded the fourth ventricle failed to suppress the central bradykinin pressor response (27 +/- 8 before vs. 35 +/- 9 mmHg after plug, n = 5). The data suggest that the central bradykinin pressor response has a site of action similar to that of angiotensin II in the ventral third ventricle.

Angiotensin II↗
PubMed1983

Aspirin and prednisolone modification of radiographic changes caused by adulticide treatment in dogs with heartworm infection.

The effects of aspirin and prednisolone in modifying the radiographic changes following adulticide treatment were studied in 3 groups of 6 dogs each. The dogs were radiographed and then 9 Dirofilaria immitis adults were surgically transplanted in each dog. All dogs were treated with thiacetarsamide 4 weeks later. One group received no additional treatment, the 2nd group received aspirin (10 mg/kg, daily for 4 weeks), and the 3rd group received prednisolone (1 mg/kg, daily for 4 weeks). Radiographs were taken at 1, 2, and 3 weeks after adulticide treatment, and the dogs were euthanatized at 4 weeks. The most consistent radiographic sign of pulmonary disease was a perivascular alveolar pattern in the caudal and accessory lung lobes. The right caudal lobe was the one most frequently affected. These parenchymal lesions were more frequent and more severe in the dogs given only adulticide treatment than in those given aspirin after adulticide treatment; the latter group in turn was more severely affected than the dogs given prednisolone after adulticide treatment. The radiographic evidence of pulmonary disease was resolving in most dogs at 3 weeks. The alveolar pattern on radiographs was distributed similarly to that observed at necropsy, using parenchymal uptake of Evan's blue as an indication of increased vascular permeability. Dissection of the perfusion-fixed lungs revealed that heartworms in 3 of the 6 dogs given prednisolone appeared to survive adulticide treatment.

Animals↗