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Biomedical subjects

R P Day

Publications and source records attributed to R P Day.

At least 19 recordsLinked to original sources
PubMed1988

Ocular renin-angiotensin: immunohistochemical evidence for the presence of prorenin in eye tissue.

Angiotensin II (A2) is a vasoconstrictor generated by the renin-angiotensin system. A2 appears to act also as an angiogenic factor. Recent evidence suggests that renin is synthesized at many tissue sites and may generate A2 locally. Local A2 may have important functions in the normal and diseased eye. We examined eight human eyes by immunostaining with an antibody to prorenin, the biosynthetic precursor of renin. In all eyes, prorenin staining was extensive in the pars plicata of the ciliary body suggesting that the ciliary body synthesizes renin and this renin may be part of an ocular A2 generating system.

Ciliary Body↗
PubMed1986

A monoclonal antibody specific for the amino terminal sequence of human prorenin identifies a common epitope on renal and amniotic fluid inactive renins.

A synthetic nonapeptide corresponding to the predicted amino terminus of human prorenin was synthesized and used as an antigen in the production of mouse hybridomas. Forty-seven clones producing antibody to this peptide were identified and screened for ability to bind to partially purified amniotic fluid inactive renin in a soluble phase assay. None showed activity. One purified antibody, 4D3-3C4, was found to bind by Western blotting to renal and amniotic fluid inactive renins, molecular size 52 kDa, after gel electrophoresis in sodium dodecyl sulphate (SDS) following reduction with mercaptoethanol. In contrast, the anti-renin monoclonal antibody, R3-27-6, recognizes active renin, molecular size 38 kDa, and two inactive renin species, 42 kDa and 52 kDa, in the same renin preparations. Kidney and amniotic fluid apparently contain an inactive renin that possesses the complete prorenin sequence. These data indicate that high molecular weight inactive renin from both kidney and amniotic fluid contain an epitope, accessible to antibody only after denaturation, which represents the amino-terminal octapeptide sequence of prorenin. The inactive renin preparations tested also contain smaller fragments which either possess this epitope or do not, while still reacting with antibodies to active renin. It is likely that all these smaller inactive renin species are the result of proteolysis, either post-synthetic or in vitro.

Amniotic Fluid↗
PubMed1985

Characterization of prostaglandin E2 binding to isolated human adipocytes.

Prostaglandin (PG) E2 binding to fat cells and its consequent antilipolytic effect have been studied in experiments using laboratory animals, but no binding studies have yet been reported using adipocytes from humans. Consequently, we have characterized PGE2 binding to human isolated fat cells to compare the apparent binding constant to the IC50 for the antilipolytic effect of PGE2. Our data indicate that human fat cells contain binding sites that specifically recognize prostaglandins of the E series and demonstrate stereospecific recognition of the more potent of two 15-methyl-PGE2 analogues. There was no evidence for rapid metabolism of PGE2 by isolated adipocytes such as occurs in lung and liver tissue. A double-reciprocal plot of binding data obtained at saturation using [3H]PGE2 and increasing concentrations of PGE2 indicated a single class of binding sites with an apparent binding constant (0.54 nM) that agreed well with the IC50 (0.26 nM) for the antilipolytic effect of PGE2 we observed in human fat cells. The findings from these binding and lipolysis studies are in general agreement with published observations using adipocytes from rodents and provide evidence that the conclusions reached from previous studies of laboratory animals are relevant to adipocyte physiology in humans.

Adipose Tissue↗
PubMed1985

Prostaglandin E2 metabolite levels during diabetic ketoacidosis.

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.

Adult↗
PubMed1976

Big renin and biosynthetic defect of aldosterone in diabetes mellitus.

To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of "big renin," a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis.

Adrenal Cortex↗
PubMed1976

Big renin: identification, chemical properties and clinical implications.

Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy.

Adult↗
PubMed1976

An approach to immunotherapy using antibody to IgE in mast cell leukemia.

Passive immunotherapy was attempted in a patient with mast cell leukemia using antibody against IgE. The results of both in vitro and in vivo studies indicate that although receptor sites for IgE were retained by the malignant mast cell, a secretory defect was present characterized by the spontaneous release of histamine and an impaired secretory response to anti-IgE antibody. Anti-IgE antibody selectively and reproducibly reduced the number of circulating mast cells probably by facilitating their permanent uptake by the reticuloendothelial system. Tolerance was not achieved with high dose deaggregated sheep IgG, nor were we able to confirm the effectivity of immunochemotherapy based on linking chlorambucil to antibody directed against the tumor-associated "antigen" IgE.

Animals↗
PubMed1976

Inhibition by prednisone of late cutaneous allergic responses induced by antiserum to human IgE.

Dual cutaneous allergic responses can be induced in human subjects by the intracutaneous injection of antiserum to human IgE (AHIGE). Adrenocortical steroid fails to inhibit the AHIGE-induced early wheal-and-flare response but does inhibit the late allergic response. This pattern of inhibition by adrenocortical steroid resembles that known to pertain to allergen-induced dual cutaneous allergic responses.

Humans↗
PubMed1976

Renin activity in dog brain: enzymological similarity to cathepsin D.

The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.

Animals↗
PubMed1976

Basophil-sensitizing antibody response to herpes simplex viruses in rabbits.

Antibodies to herpes simplex virus type 1 and type 2 were detected in the sera of rabbits by release of histamine from basophils sensitized in vitro with the sera. The time course of the appearance of the antibodies, the dose-response curve of the release of histamine in relation to antigen concentration, the sedimentation characteristics of the antibodies in sucrose gradients, and the ability to destroy the sensitizing capacity of the sera with heat suggest that the antibodies being assessed were of the IgE class. These antibodies were induced in animals injected intradermally, intramuscularly, and i.p. with live virus. The antibodies were detected 1 week after primary injection and a similar time course of antibody appearance was observed after a second or third injection. The same cross-reactivity between type 1 and type 2 virus observed with IgG antibody was also observed with IgE antibody.

Animals↗
PubMed1975

Occurrence of big renin in human plasma, amniotic fluid and kidney extracts.

Big renin, a relatively inactive renin which possesses a molecular weight larger than that of normal plasma or renal renin, has been demonstrated by gel filtration in certain human plasma, tumor extracts, and amniotic fluid. Big renin was not present in normal plasma or kidney extracts. Plasma from 3 hypertensive patients with nephropathy contained chiefly big renin. Varying proportions of both big and normal renin activity were present in plasma of other patients with hypertension and proteinuria. The renin present in amniotic fluid, which increased in activity following exposure to acid pH, was shown to be big renin in two patients. Large amounts of circulating big renin apparently can cause hypertension in patients with Wilms' tumors. Furthermore, the relatively inactive big renin may replace normal plasma renin in some patients, resulting in low plasma renin activity.

Adult↗
PubMed1975

Biochemical properties of big renin extracted from human plasma.

The properties of big renin, a relatively inactive form of renin isolated from human plasma, were examined following partial purification by gel filtration. Exposure of big renin to pH 3.0-3.6, or brief incubation with trypsin or pepsin, resulted in a ten-fold increase in enzymatic activity. Activation was not effected by 4M NaCl, 6M urea, or incubation with neuraminidase. Both before and after inactivation, big renin eluted from Sephadex gel more rapidly than normal plasma renin. During polyacrylamide gel disc electrophoresis, inactive big renin migrated more slowly than either normal renin or big renin previously activated. Using sheep substrate, the enzyme kinetics of normal renin and previously activated big renin were identical, while inactive big renin possessed a higher Michaelis constant. These data indicate that big renin is closely related biochemically to normal plasma renin. As the activation of big renin results in the formation of the substance even more similar to normal renin, the possibility exists that big renin may prove to be a precursor form of normal renin.

Chromatography, Gel↗
PubMed1975

Repopulation with IgA-containing cells of bronchial and intestinal lamina propria after transfer of homologous Peyer's patch and bronchial lymphocytes.

Transfer of 50 million rabbit allogeneic lymphocytes from either bronchus-associated lymphoid tissue (BALT) or Peyer's patches into 1000 R x-irradiated recipients results, 6 days later, in predominant repopulation of gut and bronchial lamina propria, as well as spleen with IgA-containing cells. After repopulation with BALT or Peyer's patch cells, lymphoid follicles in both gut and lung showed peripheral cellular membrane type of fluorescence with fluorescein-conjugated anti-IgA antisera only. Six days after x-irradiation alone, little evidence of repopulation was seen and immunofluorescent qualitative observations of gut and lung, and quantitative data in the spleen, confirmed these findings. After transfer of 50 million lymph node cells, very few immunoglobulin-containing cells were seen in the gut or bronchial lamina propria. These results suggest that there may be a common mucosal immunologic system, and that repopulation of gut and lung lamina propria may be through the organized lymphoid tissue therein.

Animals↗
PubMed1975

Presence of thymic antigen on rabbit basophils.

A goat heteroantiserum specific for a rabbit thymus lymphocyte antigen (RTLA) reacted with rabbit basophils resulting in the release of histamine. This activity was equally absorbed out by thymocytes or basophils. Absorption with either of these cell types also resulted in equal loss of thymocytotoxicity. No effect in either system occurred after absorption with either granulocytes or rabbit fibroblasts. These results could not be explained by the presence of immune complexes or aggregated globulin present in the RTLA antiserum. Further, the RTLA anti-serum had no anti-IgE activity, as demonstrated by its lack of reactivity with mast cells that were otherwise capable of releasing histamine normally after challenge with antigen. We have thus shown a basic difference between mast cells and basophils. We conclude that the rabbit basophil may bear a thymic marker.

Absorption↗