Search PubMed⌕ Search

Biomedical subjects

D B Corry

Publications and source records attributed to D B Corry.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytokine production by peripheral blood mononuclear cells in human coccidioidomycosis.

The production and mRNA expression of the cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-4, -10, and -12 by peripheral blood mononuclear cells (PBMC) after incubation with the coccidioidal antigen toluene spherule lysate (TSL) from various subjects were measured. The IFN-gamma concentration in PBMC supernatants incubated for 72 h from 8 subjects with disseminated coccidioidomycosis was significantly less than that from 7 healthy, coccidioidal-immune subjects (P = .015). No differences were seen among the subject groups in the concentrations of IL-4, -10, or -12. By use of competitive polymerase chain reaction, PBMC from subjects with disseminated coccidioidomycosis also expressed less mRNA for IFN-gamma and IL-12 than did cells from healthy, immune subjects. These data suggest that patients with disseminated coccidioidomycosis have a diminished T helper lymphocyte type 1 response.

Base Sequence↗
PubMed1996

Glucose and insulin metabolism in hypertension.

Individuals with abnormal glucose and insulin metabolism have a higher incidence of hypertension, and recent interest has focused on the fact that patients with untreated essential hypertension have higher than normal plasma insulin concentrations, are resistant to insulin-stimulated glucose uptake and often have accompanying lipid disorders. The pathophysiological significance of these observations lies in the findings that insulin has mitogenic properties and can potentiate vascular smooth muscle growth, thus promoting structural changes in vessels and atherosclerosis. Insulin could also promote high blood pressure via its effect in increasing sodium reabsorption and sympathetic nervous system activity. A variety of therapies is available for treatment of hypertension in patients with metabolic complications. Lifestyle modification is considered to be the initial approach, with weight management the most important component. Although diuretics and beta-blockers have a proven record in reducing morbidity and mortality, they may have adverse effects on glucose, insulin and lipids and should be used with caution in hypertensive subjects with metabolic risks. alpha-adrenergic blockers have favorable effects on lipids and glucose. Calcium antagonists have no adverse effect on glucose or insulin in patients with essential hypertension or diabetic patients with hypertension. ACE inhibitors, on the other hand, have neutral or beneficial effects on glucose, insulin and lipid metabolism, improving insulin sensitivity, insulin secretion, potassium balance and intermediary metabolism. Finally, oral hypoglycemic agents, which improve glucose metabolism and insulin sensitivity, can reduce blood pressure in obese, hypertensive subjects.

Animals↗
PubMed1995

The development of effector T cell subsets in murine Leishmania major infection.

Leishmania major infection has proven an exceptional model for CD4+ subset development in inbred mice. Most strains contain infection coincident with the appearance of T helper 1 (Th1) cells that produce gamma-interferon (IFN-gamma) required for macrophage activation. In contrast, mice on the BALB background are unable to control infection due to the development of Th2 cells that produce counter-regulatory cytokines, particularly interleukin 4 (IL-4), capable of abrogating the effects of IFN-gamma. Selective gene disruption studies in mice have illustrated critical components of the host response to L. major. Mice deficient in beta 2 microglobulin, which have no major histocompatibility complex (MHC) class I or CD8+ T cells, control infection as well as wild-type mice, whereas mice deficient in MHC class II (and CD4+ T cells) suffer fatal infection. Mice with disruption of the gene coding IFN-gamma are also incapable of containing infection, reflecting absolute requirements for this cytokine. A number of interventions have been demonstrated to abrogate Th2 cell development in BALB mice, enabling these mice to control infection. Each of these--IL-12, anti-IL-4, anti-IL-2, anti-CD4 and CTLA4-Ig--has in common the capacity to make IL-4 rate limiting at the time of CD4+ cell priming.

Animals↗
PubMed1995

Secondary aldosteronism.

Conditions of secondary aldosteronism are common in clinical medicine, occurring in normotensive and hypertensive settings. In some conditions such as edema disorders, this represents a partially beneficial response to restore volume and Na at the expense of hypokalemia. In RVH and malignant hypertension, the aldosteronism may be beneficial, but most evidence shows a detrimental impact. In both situations, aldosterone does not compensate fully for Na degradation and facilitates K loss. In pregnancy, aldosterone's effects is more successful for volume conservation, and the action on K is almost completely overridden by other K-sparing factors. Chronic renal failure seems to best benefit from hyperaldosteronism, but the response is limited because aldosterone must act on extrarenal targets. In iatrogenic causes of secondary aldosteronism, the effects of aldosterone are mostly detrimental. The overall conclusion supports the hypothesis that aldosterone functions best in physiologic situations, but in pathophysiologic settings it does not perfectly compensate for the basic defect. This implies that in these complex conditions, successful therapy should address the disorder in aldosterone and also the other underlying pathophysiologic mechanisms.

Aldosterone↗
PubMed1994

Interferon gamma-independent effects of interleukin 12 administered during acute or established infection due to Leishmania major.

Interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells, their generation of interferon gamma (IFN-gamma), and the differentiation of T helper type 1 (Th1) effector cells from naive precursors in vitro. These activities are consistent with the capacity of exogenous IL-12 to heal otherwise susceptible BALB/c mice infected with the intramacrophage parasite Leishmania major. Using this characterized model of CD4 cell subset differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection, when naive T cells are primed, or after 14 days of infection, by which time CD4+ subset differentiation has occurred. Given with the inoculation of parasites, IL-12 induced IFN-gamma and IL-10 and markedly suppressed IL-4. Effects on IL-10 and IL-4 were comparable in mice with homozygous disruption of the IFN-gamma gene (IFN-gamma 0/0), and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10 antibody. Induction of IFN-gamma and IL-10 mRNA by IL-12 also occurred in infected SCID mice. Given after day 14 of infection, however, IL-12 not only induced IFN-gamma and IL-10 but also induced IL-4 in normal and IFN-gamma 0/0 mice. These data demonstrate direct effects of IL-12 independent of IFN-gamma, IL-10, and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with L. major correlates with resistance of differentiated Th2 cells to the IL-4-suppressing activity of IL-12.

Animals↗
PubMed1994

Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis.

Infection of inbred strains of mice with Leishmania major is a well-characterized model for analysis of the development of effector CD4+ subsets of the Th1 and Th2 types in vivo. We co-administered a fusion protein, CTLA4Ig, that blocks the CD28-B7 costimulatory pathway important for optimal T cell activation, to assess the relative role for this pathway during maturation of Th1 and Th2 cells in vivo. Surprisingly, CTLA4Ig administered within the first week of infection completely abrogated progressive disease in susceptible BALB/c mice while having no effect on the protective immune response developed by resistant C57BL/6 mice. The protective effect in BALB/c mice was increasingly lost if administration of CTLA4Ig was delayed longer than 1 wk after infection. As in other protective interventions used in this model, control of infection was associated with down-regulation of IL-4 mRNA transcripts in lymph node cells recovered 5 wk after infection together with abrogation of IgE production and enhanced parasite-specific IgG2a relative to IgG1. Although a single dose of CTLA4Ig was protective, sustained delivery abolished the capacity of BALB/c mice to contain infection, suggesting that costimulation through this pathway is required at later stages of the immune response. Taken together, the data demonstrate that the priming of Th2 cells is more dependent upon the CD28-B7 pathway than the priming of Th1 cells, and suggest that the development of Th subsets in vivo may be influenced by limiting CD28-B7 costimulation.

Abatacept↗
PubMed1993

Constructing polycompetitor cDNAs for quantitative PCR.

Analysis of mRNA levels using reverse transcription coupled with the polymerase chain reaction provides a powerful tool for studying cytokine regulation in cellular immunology. We report a novel method for cloning competitor cDNAs that is rapid, efficient and inexpensive. By linking multiple competitor cDNAs in tandem, polycompetitor constructs can be created that allow the use of a single reagent for individual PCR assays. Assays can be performed on minute samples of cell culture or tissue and can be reliably quantitated after routine gel electrophoresis without the use of densitometry or labeled nucleotides. The utility of this technique lies in the ability to produce a relatively inexpensive customized reagent that is simple to use and that allows for sensitive determinations of gene expression in a rapid and convenient manner. This method should allow investigators in many areas of biology to easily quantitate a broad range of important regulatory molecules.

Animals↗
PubMed1993

Increased Na/H antiport activity and abundance in uremic red blood cells.

Alterations in red blood cell sodium (Na) transport have been described in chronic renal failure. This study examines the possible impact of uremia on two ouabain-insensitive pathways, the Na/H antiporter and the Cl-/NaCO3- anion exchanger. The Vmax of Na/H antiporter measured as Na influx driven by outward H gradient in acid loaded red blood cells was significantly higher in uremic red blood cells versus controls (60.5 +/- 16.5 vs. 24.5 +/- 5.4 mmol/liter cells/hr, P < 0.025). This increase in activity was associated with an increased abundance of the Na/H antiporter as determined by immunologic analysis using an affinity purified polyclonal antibody to the human NHE-1 isoform of the antiporter. By contrast, the activity of the anion exchanger measured as the DIDS-sensitive lithium (Li) influx was similar in uremic versus control red blood cells (2.10 +/- 0.18 vs. 2.14 +/- 0.20 mmol/liter cells/hr). These experiments, when considered in conjunction with prior studies showing normal Na/Li countertransport in uremia indicate that there is a selective increase in the number of functional Na/H antiporters in uremic red blood cells and that Na/Li countertransport measurements may not be a valid marker for Na/H antiporter activity in red blood cells in patients requiring dialysis for end-stage renal failure.

Aged↗
PubMed1991

Pathophysiology and management of hypertension in diabetes.

Arterial hypertension is more common in diabetes mellitus than in nondiabetic subjects, and many metabolic and hemodynamic features of diabetes mellitus contribute to the etiology of hypertension. Control of hypertension in diabetes mellitus is extremely important as high blood pressure accelerates both macrovascular and microvascular complications of this disease. Most classes of antihypertensive agents are effective in blood pressure control in diabetes mellitus, so the choice of antihypertensive therapy is based on the differences in adverse effects of these agents on metabolic control and other cardiovascular risks.

Antihypertensive Agents↗
PubMed1989

Stimulation by uraemic plasma of frusemide-sensitive sodium efflux in erythrocytes from normal women.

1. Reduced Na+,K+ pump activity has been reported in uraemic erythrocytes, and this has been attributed to the presence of a circulating ouabain-like inhibitor. Since we have previously reported marked suppression of Na+,K+ co-transport activity in erythrocytes from dialysis patients, we have now examined the effect of incubation with uraemic plasma on Na+ efflux through the Na+,K+ pump and the co-transport pathway in normal erythrocytes from both men and women. 2. The results show that Na+ efflux via the Na+,K+ pump is not different between men and women (3.14 +/- 0.14 vs 3.68 +/- 0.18 mmol h-1 litre-1 of cells) and is not inhibited by incubation with uraemic plasma. 3. In contrast, co-transport-mediated Na+ efflux is lower in erythrocytes from normal women when compared with normal men (0.17 +/- 0.02 vs 0.25 +/- 0.05 mmol h-1 litre-1 of cells, P less than 0.001). 4. Moreover, incubation with uraemic plasma causes stimulation of Na+ efflux through the co-transport pathway in erythrocytes of healthy women (0.17 +/- 0.02 vs 0.27 +/- 0.03 mmol h-1 litre-1 of cells, P less than 0.005), but not in erythrocytes of healthy men (0.27 +/- 0.03 vs 0.25 +/- 0.05 mmol h-1 litre-1 of cells). 5. Our data do not support the presence of either a Na+,K+ pump or a co-transport inhibitor in plasma from dialysed uraemic patients. Thus, the suppressed co-transport activity demonstrated in uraemic erythrocytes cannot be attributed to a circulating inhibitor, and may reflect an acquired membrane or transport defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

A kinetic study of cation transport in erythrocytes from uremic patients.

We previously described in red blood cells (RBCs) from uremic patients on dialysis a reduction in sodium (Na) efflux through the Na, potassium (K) cotransport system (Na,K CoT) while Na efflux through the Na,K pump was normal. We then examined Na efflux in fresh cells and in cells loaded to obtain one level of intracellular sodium (Nai) concentration at about 25 mmol/liter cell. In the present study we used similar cation flux methodology to examine the kinetics of cation efflux through the Na,K pump and Na,K CoT in uremic patients on dialysis. RBCs were Na-loaded to attain five different levels of Nai concentration over a range of 5 to 50 mmol/liter cells using the ionophore nystatin. At each level of Na-loading, the Nai achieved was similar in RBCs from controls and patients. Ouabain-sensitive Na efflux through the Na,K pump showed no difference in rate between normals and dialysis patients. When the kinetic parameters of this transport pathway were considered, the apparent affinity (K0.5) for sodium was not significantly different between controls and patients (18.4 +/- 2.3 vs. 20.0 +/- 2.6 mmol/liter cell) and the maximal velocity of efflux (Vmax) was also not different between controls and patients (9.6 +/- 0.7 vs. 8.5 +/- 1.2 mmol/liter cell/hr). Comparison of Nai-activated Na versus K efflux rates through the Na,K CoT in normal subjects demonstrated similar saturation kinetics, (K0.5 15.8 +/- 3.3 vs. 12.2 +/- 2.8 mmol/liter cell, Vmax 0.81 +/- 0.1 vs. 0.78 +/- 0.1 mmol/liter cell/hr) consistent with the known stoichiometric ratio of 1 Na:1 K:2 Cl described for this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension.

Alterations in red blood cell (RBC) Na+-K+ pump and Na+-K+ cotransport have been described in essential hypertension. We evaluated Na+-K+ pump and cotransport in 30 hypertensive and 26 normotensive subjects subdivided by race and family history of hypertension using an improved method to examine the kinetics of Na and K effluxes. RBCs were Na-loaded by the nystatin method to five different levels of internal Na with pump determined as ouabain-sensitive Na efflux and cotransport as furosemide-sensitive Na and K efflux. Two kinetic parameters were determined for both transport systems: the apparent affinity for Na (K0.5) and the velocity of efflux at saturating internal Na concentration (Vmax). Mean intracellular Na content in fresh RBCs (mmol/L cells) was higher in black hypertensive (12.6 +/- 1.8 mmol/L cells) and normotensive subjects (10.9 +/- 1.2 mmol/L cells) than in white hypertensive (8.7 +/- 1.0 mmol/L cells) or normotensive subjects (8.5 +/- 0.8 mmol/L cells). The Vmax and K0.5 for pump were not significantly different between study groups. The Vmax for cotransport was elevated in white hypertensive compared with normotensive subjects, but the K0.5 values were similar. Black normotensive and hypertensive subjects displayed a lower Vmax and increased K0.5 for cotransport compared with the white groups. A family history of hypertension had no influence on cotransport kinetics in blacks but did predict white normotensive and hypertensive subjects with low cotransport. The reduction in intracellular Na affinity for cotransport in black subjects may explain their higher intracellular Na in fresh RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Sodium transport in red blood cells from dialyzed uremic patients.

Studies on red blood cell (RBC) sodium (Na) transport in chronic renal failure have described abnormalities in the ouabain-sensitive Na, K pump. We now report Na transport in RBC using cation flux methodology, measuring both the ouabain-sensitive Na, K pump and the ouabain-insensitive Na, K cotransport (CoT) and Na, lithium (Li) countertransport (CTT) in 28 subjects on hemodialysis, eight subjects on chronic ambulatory peritoneal dialysis (CAPD) and 29 control subjects. Intracellular cation content and passive permeability of Na were also examined. Mean Na efflux through the ouabain-sensitive Na, K pump was not reduced in dialysis patients when compared to normal subjects, whether measured in fresh cells (1.41 +/- 0.05 vs. 1.30 +/- 0.03 mmole/liter RBC/hr; P less than 0.05) or in Na-loaded cells (7.10 +/- 0.24 vs. 6.90 +/- 0.22; NS). There was, however, a marked and uniform suppression of the CoT pathway in Na-loaded cells from dialysis patients versus controls (0.14 +/- 0.02 vs. 0.41 +/- 0.05 mmole/liter RBC/hr; P less than 0.001). Mean CTT activity, as measured by Li efflux, was not different between dialysis and normal subjects. Uremic and normal RBC had similar intracellular Na or K content as well as passive permeability for either ion. This indicates that intracellular cationic homeostasis is maintained, perhaps secondary to balanced changes in cationic flux activity through these transport pathways.

Adult↗
PubMed1986

Phosphate transport across rat jejunum: influence of sodium, pH, and 1,25-dihydroxyvitamin D3.

Inorganic phosphate (Pi) transport in intact, rat jejunal epithelium was measured in vitro under short-circuited conditions. Transepithelial net absorptive Pi flux increased linearly with increases in extracellular sodium concentration ([Na]) up to 144 mM. Transmucosal border Pi influx, in contrast, displayed a biphasic Na dependency. Pi influx increased as [Na] was raised from 0 to 100 mM. A further increase in [Na] to 144 mM caused unanticipated reduction in Pi influx. The reason for this dissociation between transmucosal border influx and transepithelial absorptive flux is not clear. We then examined the effect of changes in extracellular pH on Pi influx. Reduction in pH from 7.4 to 6.0 was associated with 150% increase in Pi influx, an observation consistent with the reported reciprocal relation between intestinal brush-border membrane vesicles (BBMV) Pi uptake and extravesicular pH. In contrast to BBMV data, however, a smaller increase (50%) in mucosal Pi influx was noted in intact epithelium when pH was increased from 7.4 to 8.5. Under optimized conditions for Pi influx, i.e., [Na] = 90 mM and pH 6.0, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Pi influx was measured. The total influx could be resolved into a saturable, Na-dependent and a nonsaturable, Na-independent component. 1,25(OH)2D3 stimulated the saturable component of Pi influx.

Animals↗