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Biomedical subjects

P E Phillips

Publications and source records attributed to P E Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Vasculitis in the antiphospholipid syndrome. A cause of ischemia responding to corticosteroids.

A 63-year-old woman with atherosclerotic peripheral vascular disease and the lupus anticoagulant developed ischemia of the right lower extremity, requiring progressive amputations. Pathologic specimens revealed inflammatory vasculitis in multiple arteries. Her serum showed anticardiolipin antibodies in high titer. Treatment with high-dose corticosteroids reversed the ischemic process. In patients with antiphospholipid antibodies, thrombosis is the most common pathologic finding associated with cutaneous lesions and/or gangrene. Vasculitis, although uncommon, is known to occur and may respond to corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1992

Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus.

Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

OBJECTIVE: To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates. DESIGN: In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS: Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study. RESULTS: Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001). CONCLUSIONS: The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.

Adolescent↗
PubMed1991

Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat.

We investigated whether platelet-derived growth factor (PDGF), or its receptor (PDGF-R), was upregulated in a rat model of mesangial proliferative glomerulonephritis. A marked increase in both PDGF A- and B-chain mRNA could be demonstrated in glomerular RNA by Northern blot analysis 3 and 5 days after disease induction, corresponding to the time of mesangial cell proliferation. PDGF-R beta-subunit mRNA and protein were also increased in glomeruli in mesangial proliferative nephritis, being maximal at day 5. The principal cells expressing PDGF B-chain appeared by immunostaining to be a subpopulation of mesangial cells; in contrast, the majority of the mesangial cells expressed the PDGF-R beta-subunit protein. Both complement depletion and platelet depletion significantly reduced cell proliferation and expression of both PDGF and PDGF-R. Thus, in mesangial proliferative nephritis there is a platelet- and complement-mediated induction of PDGF A and B chain and PDGF-R beta-subunit gene transcription and protein synthesis. The finding that the majority of PDGF is produced by the mesangial cell supports the role of PDGF as an autocrine growth factor in glomerulonephritis.

Animals↗
PubMed1990

Receptor kinetics differ for endothelin-1 and endothelin-2 binding to Swiss 3T3 fibroblasts.

The equilibrium binding, kinetics of ligand-receptor interactions, and biological activity of endothelin-1 and -2 have been studied in Swiss 3T3 fibroblasts. Scatchard analyses of saturation binding data for ET-1 and -2, performed at 4 degrees C to prevent internalization of the occupied receptor, revealed similar affinity constants and numbers of binding sites for endothelin-1 and -2. Experiments designed to determine ligand-induced effects on 45Ca efflux demonstrated no qualitative or quantitative differences between the two endothelin isoforms. In contrast, kinetic studies resulted in different rates of dissociation for the two isoforms and different extents of dissociation. Specifically, only 40% of the bound [125I]endothelin-1 was dissociated at 4 h following the addition of excess unlabeled ligand, whereas 85-90% of the bound [125I]endothelin-2 was dissociated under the same conditions. Endothelin-1 and -2 also differed in the percent of specific cell-associated ligand bound after a 2 h incubation at 37 degrees C following an initial equilibration at 4 degrees C. The differences in dissociation rates and association or internalization rates at 37 degrees C are the first data that differentiate between the two isoforms. It is suggested that isoform-specific differences in the rate of dissociation from cell surface endothelin receptors influence the level of cell-associated endothelin and may be important in determining physiologic responses in vivo.

Animals↗
PubMed1989

Two different subunits associate to create isoform-specific platelet-derived growth factor receptors.

Recent evidence has demonstrated that there is more than one form of platelet-derived growth factor (PDGF) receptor and that these receptors differ in their specificity for the multiple isoforms of PDGF. We present evidence that high affinity binding of PDGF requires association of two different receptor subunits: an alpha-subunit that can bind either a B- or an A-chain of PDGF, and a beta-subunit that can bind only a B-chain. The alpha- and beta-subunits appear to be similar in size but can be distinguished by binding specificity and by an antireceptor monoclonal antibody, PR7212, which recognizes only the beta-subunit. In the absence of PDGF, these subunits either exist separately or form rapidly reversible complexes. In the presence of PDGF, receptor subunits of appropriate specificity interact with a PDGF molecule to form a high affinity complex. Both the absolute and relative numbers of these two PDGF receptor subunits vary on different cell types and correspond to differences in the mitogenic sensitivity of cells to the different PDGF isoforms.

Adult↗
PubMed1988

Enhancement of insulin binding to rat white adipocytes at 15 degrees C by 5,5'-dithiobis-(2-nitrobenzoic acid). Independence of the reagent's sulfhydryl group reactivity.

Insulin binding to isolated rat white adipocytes at 15 degrees C, a temperature at which cellular degradation of insulin is negligible, has been found to be described by the Two-step Binding Model: R + I in equilibrium RI in equilibrium R'I (Lipkin, E. W., Teller, D. C., and de Haën, C. (1986) J. Biol. Chem. 261, 1702-1711). RI is the initially formed complex between the receptor, R, and insulin, I, and R'I is the complex in an altered state or cellular location. Here the possibility was examined that R'I results from disulfide exchange between the receptor and insulin, an exchange proposed by Clark and Harrison (Clarke, S., and Harrison, L. C. (1986) J. Biol. Chem. 257, 12239-12244) to occur at 37 degrees C. A number of sulfhydryl reagents representing various chemical reactivities did not affect insulin binding. The exception was 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), which enhanced the number of insulin-binding sites up to 2-fold with no effect on the equilibrium constant. The data suggested that this enhancement was due to activation of cryptic binding sites pre-existing on the cell surface, possibly by increasing the valency of the receptor from 1 to 2. Insulin binding was also enhanced by structural congeners of DTNB devoid of sulfhydryl reactivity, the simplest one being benzoic acid. It was concluded that the effects were not related to modification of sulfhydryl groups, that modification of sulfhydryl groups on the receptor either did not take place or was without effect on binding, and finally, that disulfide exchange between insulin and the receptor was an unlikely explanation for the formation of R'I. Also, since it is possible to show insulin action at 15 degrees C, contrary to the proposal by Clark and Harrison (Clark, S., and Harrison, L. C. (1983) J. Biol. Chem. 258, 11434-11437), disulfide exchange does not appear to be necessary for signal transmission by the occupied receptor.

Adipose Tissue↗
PubMed1988

The role of infectious agents in the spondylarthropathies.

The clinical similarities of the spondylarthropathies and their frequent association with both HLA B27 and microbial infections suggest common pathogenetic mechanisms. The latter may include deposition of immune complexes containing bacterial antigens. or cross-reactivity of such antigens with host target tissue or responding cell antigens. Enteric bacteria, chlamydia and mycoplasma are all candidate etiologic agents, but proof is difficult because they are often found as normal flora, although only genetically susceptible individuals may acquire disease, and many patients have been treated with antibiotics before they can be studied. Nonetheless, a role for endogenous bacteria in reactive arthritis at least seems certain, and should stimulate further investigation into similar pathogenetic mechanisms in other chronic arthritides.

Arthritis↗
PubMed1986

High IgM antibody to human T-lymphotropic virus type I in systemic lupus erythematosus.

Twenty-six percent of 53 systemic lupus erythematosus sera had high levels of IgM antibody to human T-lymphotropic virus Type I, significantly more than the 5% of normal controls. Neither IgG antibodies to Type I virus nor IgM or IgG antibodies to Type II virus were increased in lupus. Further analysis using competition immunoassay and Western blot techniques also suggested that the IgM Type I antibodies in lupus sera were directed against viral antigens but did not completely exclude a nonviral reaction. Other studies also have not found IgG antibodies to the Type I virus but have not tested for IgM antibodies. Our study suggests that human T-lymphotropic virus Type I or a related virus may be involved in the pathogenesis of some cases of systemic lupus erythematosus.

Adolescent↗
PubMed1979

Increased toxoplasma antibodies in idiopathic inflammatory muscle disease. A case-controlled study.

Antibodies to Toxoplasma gondii were measured in sera from 69 patients with polymyositis, dermatomyositis, and myositis associated with other connective tissue diseases and compared to 69 age-, race-, and sex-matched controls with unrelated diseases. Complement fixation toxoplasma antibodies were significantly more frequent in polymyositis and correlated with high IgM levels. Other distinguishing clinical or laboratory features of these patients were not found. The high toxoplasma antibodies were not associated with generally hyperactive humoral immunity. The serologic data suggested that inflammatory muscle disease was associated with recent active toxoplasma infection in certain patients. The pathogenetic role of the microorganism remains uncertain.

Adolescent↗
PubMed1978

Platelet aggregation. Adult-onset diabetes mellitus and coronary artery disease.

Using a turbidimetric technique, we determined 1.7 micrometer adenosine diphosphate--induced platelet aggregation and disaggregation at 37 degrees C in the platelet-rich plasmas of two groups of men with coronary artery disease. Eleven men were nondiabetic and 11 had adult-onset diabetes mellitus without retinopathy. There were no significant differences (P greater than .05) between diabetics and nondiabetics of the following variables: age, platelet count in platelet-rich plasma, first and second phases of platelet aggregation, maximum extent of aggregation, and percent disaggregation at three minutes after maximum aggregation occurred. Although the mean adenosine diphosphate--induced platelet aggregation in the platelet-rich plasmas of adult-onset diabetic men with coronary artery disease and no retinopathy was not enhanced, and the mean rate of disaggregation was not reduced, when compared with nondiabetic men with coronary artery disease or with healthy men; a slow rate of platelet disaggregation (less than 10%) occurred more frequently in the platelet-rich plasmas of men with coronary artery disease.

Adenosine Diphosphate↗
PubMed1978

Immunopathologic studies of rheumatoid arthritis. I. Absence of complement-dependent cytotoxicity of rheumatoid sera for rheumatoid synovial cell cultures.

A sensitive complement-dependent chromium release cytotoxicity assay was used to determine whether sera from rheumatoid arthritis (RA) patients contain antibody specific for an antigen on rheumatoid synovial cell cultures. Two hundred eight RA sera-RA synovial culture combinations were studied employing 21 sera and 16 synovial membranes; control combinations were derived from 5 normal sera and 10 degenerative joint disease synovial membranes. Anticomplementary activity of some rheumatoid sera was overcome using an increased complement concentration. The percent cytotoxicity of RA serum-RA culture combinations, both homologous and autologous, was not significantly greater than that of RA serum-control culture combinations. No correlation between duration of disease or duration of cell culture and percent cytotoxicity was found. Thus a unique antigen on cultured rheumatoid synovial cells was not recognized by rheumatoid serum antibody by use of this cytotoxicity assay.

Adolescent↗
PubMed1978

Type C oncornavirus studies in systemic lupus erythematosus.

The following paper critically reviews published evidence that concerns the occurence of viruses in patients with systemic lupus erythematosus. Special emphasis is placed on the recent studies that implicate type C oncornaviruses. Evidence from our laboratory regarding the occurence of type C viruses in these patients is predominantly negative. It is concluded that the pathogenesis of systemic lupus erythematosus is almost certainly multifactorial and that the part that viruses play remains hypothetical.

Antibodies, Viral↗
PubMed1978

Effect of aspirin on exercise-induced angina.

Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we did a random-order, double-blind, crossover study of the effect of the platelet aggregation inhibitor, aspirin, on treadmill exercise-induced angina in 13 men with coronary artery disease. Although collagen-induced platelet aggregation and the second phase of adenosine diphosphate (ADP)-induced platelet aggregation were significantly decreased and the rate of disaggregation of ADP-induced platelet aggregates was significantly increased after 650 mg aspirin in buffered solution, there was no delay in onset of exercise-induced angina, change in heart rate-blood pressure product at onset of angina, or change in S-T segment depression at onset of angina. Regardless of whether the patients had received placebo or aspirin on the preceding day, treadmill exercise until angina was followed by no changes in platelet aggregation or disaggregation, platelet count in blood or platelet-rich plasma, or of the plasma concentration of nonesterified fatty acids.

Adult↗