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Biomedical subjects

Z Brown

Publications and source records attributed to Z Brown.

At least 19 recordsLinked to original sources
PubMed1992

The Diabetes in Early Pregnancy Study: changes in cholesterol, triglycerides, body weight, and blood pressure. The National Institute of Child Health and Human Development--the Diabetes in Early Pregnancy Study.

This study examined changes in cholesterol, triglycerides, body weight, and blood pressure during pregnancy in 312 diabetic and 356 control women recruited within 21 days after conception. Cholesterol values rose in both groups but were significantly lower in diabetic women at each time point (166 vs 178 mg/dl at week 12, p = 0.0004). Triglyceride values also rose in both groups. Triglyceride levels did not differ between groups up to week 8 of gestation, but by weeks 10 to 12 they were significantly lower in diabetic women than in controls (75 vs 89 mg/dl at week 12, p = 0.0004). Although they were no heavier at entry, diabetic women gained significantly more weight between weeks 6 and 8 (p less than 0.001), resulting in a mean difference between groups of 1 kg. Systolic blood pressure increased steadily and significantly in the diabetic but not the control women (115.8 +/- 16.2 SD vs 109.3 +/- 11.8 mm Hg, p = 0.0006 at term). Diastolic blood pressure was higher in diabetic women on entry (70.7 vs 67.3 mm Hg, p = 0.0006) and throughout gestation. Significant correlations were found in the diabetic group between maternal blood pressure and lipids and infant birth weight. These newly found differences in cholesterol and triglyceride levels, weight gain, and blood pressure between type I diabetic and control women during gestation may have long-term cardiovascular implications.

Adult↗
PubMed1992

IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells.

The elicitation of neutrophils and monocytes from the circulation into the inflamed glomerulus is a key process in the pathogenesis of proliferative glomerulonephritis. The aim of this study was to determine the factors which regulate the expression and synthesis of the monocyte specific chemotaxin, monocyte chemotactic peptide 1 (MCP-1). Mesangial cells in culture did not constitutively express MCP-1, but could be induced to express both MCP-1 mRNA and antigenic MCP-1 by either stimulation with IL-1 alpha or TNF alpha, which are also stimuli for interleukin 8 (IL-8/NAP-1) expression and release. Pre-treatment of mesangial cells with the IL-1 receptor antagonist (IL-1ra) induced dose-dependent inhibition of both the expression of MCP-1 and IL-8 mRNA as well as the release of both chemotactic peptides in response to IL-1 alpha, while the receptor antagonist had no significant effect on TNF alpha induced MCP-1 and IL-8 generation. This study demonstrates that the IL-1 receptor antagonist was four times more effective at inhibiting the IL-1 induced expression and release of IL-8 compared to that of MCP-1. These results suggest that mesangial cell-derived MCP-1 may play an important role in the recruitment of monocytes in glomerular inflammation and that an IL-1 receptor antagonist may have therapeutic potential for the treatment of glomerulonephritis.

Base Sequence↗
PubMed1992

Herpes simplex virus-2 (HSV-2) type-specific antibody correlates of protection in infants exposed to HSV-2 at birth.

Western blot analysis was used to compare the herpes simplex virus (HSV)-2 antibody profiles of 40 infants less than 2 wk of age who had been exposed to maternal genital HSV-2 at birth. 4 mothers were HSV seronegative at delivery and seroconverted to HSV-2 ("primary infection"), 9 had HSV-1 antibodies and seroconverted to HSV-2 ("nonprimary first episode infection"), and 27 were HSV-2 seropositive ("recurrent infection"). Neonatal herpes infections developed in 1 of 4 infants of women with primary infection, in 3 of 9 infants of women with nonprimary first episode infection, and in none of the 27 infants of women with recurrent HSV-2. Antibodies to HSV-2 proteins gG-2, VP5, and ICP35 were detected in 83, 89, and 72% of the 36 uninfected infants, respectively. None of the four infected infants had detectable antibodies to gG-2 and only one (25%) had antibodies to VP5 or ICP35. The more limited profiles of the 13 infants born to mothers with first episodes of HSV-2 were then analyzed separately; these profiles were similar among infected and uninfected infants except for gG-2, which elicits antibodies that are type specific for HSV-2. None of the infected infants versus seven of nine (78%) uninfected infants were gG-2 seropositive. These comparisons suggest that maternal type-specific antibodies may play a role in preventing neonatal infection after exposure to HSV-2.

Antibodies, Viral↗
PubMed1991

Endothelium and glomerular growth.

The role of glomerular endothelium has been barely considered, let alone investigated, but this is in large part due to the extreme difficulty in isolating and growing it in culture. The glomerular capillary is part of the arterial system and is better perceived as a "hemiarteriole." The mesangium and its response to hemodynamic events in the glomerular capillary is equivalent to the smooth muscle cell wall of an arteriole. The capability of cytokines, derived from the endothelium, to act in an autocrine and paracrine manner is clearly demonstrated by angiogenesis. The glomerular endothelial cell is likely to play a crucial role in the glomerulus in health and disease.

Animals↗
PubMed1991

Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8.

Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibition of the release of extracellular IL-8, while cell-associated IL-8 and IL-8 mRNA were not significantly altered. We propose that the mesangial cell has a direct role in the initiation and propagation of inflammatory events within the glomerulus via the generation of the chemotactic cytokine IL-8.

Cells, Cultured↗
PubMed1990

Inhibition of prostacyclin formation by cyclosporin is not due to reduced availability of arachidonic acid in membrane phospholipids of cultured human endothelial cells.

Our studies have shown that CS inhibits PGI2 production in HUVEC, that this inhibition is not overcome when exogenous AA is supplied, that the inhibitory action of CS is proximal to PGI2 synthetase and finally that there is abundant free AA available in membrane phospholipids of CS treated HUVEC [4,5]. In conclusion, CS does not appear to inhibit PGI2 synthesis by reducing the availability of free AA in the endothelial cell membrane. Although CS appears to inhibit cyclo-oxygenase, we can not exclude an additional effect on acyltransferase.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Drug ingestion during pregnancy: infrequent exposure in a contemporary United States sample. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group.

Drug ingestion in a cohort of United States women proved consistently lower than in prior United States populations. Participating were 342 insulin-dependent diabetic and 387 control subjects who were enrolled before conception (76%) or no later than 21 days after conception (24%). Drug exposures were then recorded at entry and periodically throughout organogenesis (gestational weeks 6, 8, 10). During gestational weeks 1 to 10, approximately two thirds of the subjects were exposed to no agent other than oral iron, oral vitamins, or insulin (diabetic subjects). The mean exposures in gestational weeks 1 to 10 were 0.72 +/- 1.05 (SD) for diabetic women and 0.54 +/- 0.96 for control subjects; throughout pregnancy, the mean exposures were 1.26 +/- 1.66 and 1.58 +/- 1.78, respectively. The low exposure frequency in this contemporary United States population is highly encouraging. However, it follows that collaborative cohort efforts may be necessary in order to assess teratogenicity of drugs because relatively few women are now exposed.

Abnormalities, Drug-Induced↗
PubMed1988

Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis.

To determine how much insulin-dependent diabetes increases a woman's risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception.

Blood Glucose↗
PubMed1986

Prostacyclin deficiency in a young woman with recurrent thrombosis.

A young woman with recurrent deep venous thromboses and spontaneous abortions was studied. She suffered an ovarian infarction followed by aortic thrombosis and renal failure. Evidence for deficient prostacyclin production was found and she responded to treatment with a prostacyclin infusion. This syndrome is identical with that seen in women with the lupus anticoagulant, but the lupus anticoagulant was not detected and no other cause was identified.

Abortion, Habitual↗
PubMed1986

Increased factor VIII as an index of vascular injury in cyclosporine nephrotoxicity.

Very high plasma concentrations of factor-VIII-related antigen (RAG) (VIII-RAG) were found in renal allograft recipients during periods of nephrotoxicity induced by cyclosporine. In eight recipients, who were investigated at weekly intervals, levels of factor-VIII-RAG fell toward normal as the dose of cyclosporine was reduced. Plasma levels of C-reactive protein, an acute phase reactant protein, were never raised in these recipients. These findings are further evidence that toxic doses of cyclosporine are associated with vascular injury.

Antigens↗
PubMed1984

Impaired lymphocyte and suppressor cell function in minimal change nephropathy, membranous nephropathy and focal glomerulosclerosis.

The response of lymphocytes to Concanavalin A (Con A) was measured in patients with the nephrotic syndrome due to minimal change nephropathy (11 patients), focal glomerulosclerosis (15 patients) and membranous nephropathy (21 patients); autologous serum was not used in these studies. There was a significant reduction in lymphocyte transformation in each group of patients compared to normal controls (p less than 0.01 for each group), but there was no significant difference between the individual groups of patients. Impaired lymphocyte transformation to Con A appears therefore to be a general feature of the nephrotic syndrome and is not exclusive to minimal change nephropathy. Measurements of suppressor cell function in 4 patients with minimal change nephropathy, 9 patients with focal glomerulosclerosis and 12 patients with membranous nephropathy were performed at the same time as the above studies. In each group suppressor cell function was decreased, indicating that the impaired lymphocyte response to Con A is not due to increased suppressor cell activity. These findings do not support the hypothesis that an abnormality of lymphocyte function peculiar to minimal change nephropathy is pathogenetic in that disease and not in other causes of the nephrotic syndrome; it seems more likely that the abnormalities described are secondary to the nephrotic state.

Adolescent↗
PubMed1983

Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue.

NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.

Animals↗