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Biomedical subjects

R Wiggins

Publications and source records attributed to R Wiggins.

At least 37 records · Page 2Linked to original sources
PubMed1991

Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit.

The purpose of this study was to assay for the presence of collagen synthesis stimulatory activity in the kidney during immune-induced renal injury that results in severe fibrosis in both glomerular and interstitial compartments. A model of antiglomerular basement (anti-GBM) disease in the rabbit was induced on day 0 by the injection of anti-GBM antibody and renal cortex tissues were then sampled at various time points. Only conditioned media prepared from diseased renal cortical samples showed collagen synthesis stimulatory activity when tested on rabbit mesangial cells. The activity had an estimated molecular weight range of 16 to 25 kd and was neutralized by antibody to transforming growth factor-beta (TGF-beta). A standard assay for TGF-beta using a mink lung epithelial cell line confirmed the increase in TGF-beta activity in conditioned media of diseased cortex from day 7 and day 14 animals, which was not significantly activated by previous acidification. This suggests that most of the TGF-beta present in renal conditioned media was in the active form. The increase in renal cortical secretion of active TGF-beta was accompanied by increases in renal cortical TGF-beta mRNA content on days 4 and 7 after induction, with subsequent return to control levels. A similar increase in TGF-beta activity was present in nonacidified conditioned media of purified glomeruli from diseased days 7 and 14 animals, which was also accompanied by significant increases in TGF-beta mRNA. However with acidification no significant differences were noted between control and diseased samples, suggesting the presence of substantial latent TGF-beta activity in control glomerular conditioned media. These same control-conditioned media contained inhibitor activity for added exogenous TGF-beta. These results support the conclusion that the association between increased TGF-beta secretion and increased renal cortical collagen synthesis in this model is consistent with a role for this cytokine in directing fibrogenesis in the kidney.

Animals↗
PubMed1989

Monocyte chemotactic protein gene expression by cytokine-treated human fibroblasts and endothelial cells.

A number of cytokines are active during the evolution of an inflammatory response, including tumor necrosis factor-alpha, interleukin-1, and novel chemotactic cytokines. This latter group of mediators belong to supergene families of inflammatory signals that play a key role in the selective recruitment of immune cells. In this presentation, we present data demonstrating, for the first time, endothelial cell expression of monocyte chemotactic protein (MCP) mRNA induced by LPS, interleukin-1 or tumor necrosis factor. Human fibroblasts were also found to express monocyte chemotactic factor mRNA in response to interleukin-1 or tumor necrosis factor, but LPS was not effective. In addition, neither primary cultures expressed MCP in response to interleukin-6. These studies demonstrate that non-immune "bystander" cells can play an active role in the recruitment of inflammatory cells via the production of novel chemotactic cytokines.

Cells, Cultured↗
PubMed1989

Demonstration by iodine-131-hippurate renography of a marked sensitivity of some transplanted kidneys to volume contraction.

Incidental observations made in a canine renal transplant model in which both native and transplanted kidneys were present revealed that abnormal I-131-iodohippurate renograms were derived from some of the transplanted kidneys in the presence of mild dehydration. In these cases, the renogram normalized with fluid administration. In contrast, the renograms derived from the native kidneys were unaffected by the mild dehydration of the animals. These findings demonstrate a greater sensitivity to dehydration of some transplanted kidneys when compared to normal kidneys.

Animals↗
PubMed1989

Comparative ability of human monocytes and neutrophils to degrade glomerular basement membrane in vitro.

We have compared the ability of human peripheral blood monocytes and neutrophils to degrade glomerular basement membrane (GBM) in vitro. When isolated cells were incubated with GBM containing anti-GBM immune complexes, both neutrophils and monocytes adhered and spread on the surface of the GBM, underwent a respiratory burst and released lysosomal enzymes into the medium. With neutrophils, this resulted in rapid degradation of the GBM, measured both as solubilization of collagenous and noncollagenous protein. In contrast, monocytes degraded GBM very slowly, with a slight increase in the rate of hydroxyproline solubilization after approximately 24 hours incubation. Degradation of GBM by neutrophils was predominantly due to the action of serine proteinases, whereas inhibition of monocyte-mediated hydroxyproline release required both phenylmethylsulfonyl fluoride and o-phenanthroline, suggesting some synergy between serine and metalloproteinases. The results indicate that neutrophils are more able to degrade GBM components than are monocytes, and suggest that they may be capable of greater damage to the GBM in vivo, mostly due to their higher proteolytic capacity.

Antigen-Antibody Complex↗
PubMed1989

Glomerular basement membrane-containing immune complexes stimulate tumor necrosis factor and interleukin-1 production by human monocytes.

The ability of human peripheral blood monocytes to produce tumor necrosis factor (TNF) and interleukin-1 (IL-1) in an in vitro model of immune complex-mediated glomerulonephritis was investigated. When isolated monocytes were incubated with human glomerular basement membrane (GBM) containing anti-GBM immune complexes, both TNF and IL-1 were produced and secreted into the medium. The time course of secretion differed, with IL-1 production being maximal after approximately 8 hours, whereas TNF levels continued to rise for 30 hours. The activities of the monocyte-derived TNF and IL-1 were inhibitable by specific antibodies. No effect was seen when monocytes were incubated separately with either GBM alone or anti-GBM IgG. The levels of TNF and IL-1 released were comparable with those induced by high concentrations of LPS, indicating that production was close to the maximal levels reported for these cells. High levels of TNF and IL-1 also were produced in response to soluble immune complexes. The results show that monocytes can produce significant levels of TNF and IL-1 in response to both surface-bound and soluble immune complexes and provide support for the participation of these monokines in glomerulonephritis.

Antigen-Antibody Complex↗
PubMed1987

Lipid microvesicles and their association with procoagulant activity in urine and glomeruli of rabbits with nephrotoxic nephritis.

The procoagulant activity (PCA) in urine of rabbits with nephrotoxic nephritis was characterized. Most of the PCA in urine was pelleted by centrifugation at 50,000 X g but was not pelleted together with cells and casts at 1,000 X g. PCA appeared in the void volume of a Sepharose 4B column but would not pass through a 0.2-micron filter. Ultrastructural studies using both transmission and scanning electron microscopy showed that urine PCA was associated with lipid vesicles 0.1 to 1-micron in diameter. These vesicular structures were shown to promote fibrin formation from recalcified plasma on a 0.2-micron filter surface. This microvesicular PCA was mostly Factor VII-like as judged by clotting assay using human factor-deficient plasmas. Aggregates of vesicles were present in urine as granular casts. Ultrastructural studies of rabbit kidney showed similar vesicular structures in the proximal tubular lumen and budding from glomerular epithelial cells. Fibrin was seen adjacent to both glomerular endothelial cells and epithelial cells in association with vesicular structures. We conclude that microvesicles in urine carry a procoagulant signal which is tissue factor/Factor VII-like. We speculate that these vesicles may come from the glomerulus by budding off from glomerular epithelial cells, or macrophages.

Animals↗
PubMed1986

Dietary supplementation of undernourished rats with soy or safflower oil: effects on myelin polyunsaturated fatty acids.

Undernourished suckling rats were administered, by gastric intubation, either soy oil (which is rich in both linoleic and linolenic acids) or safflower oil (which is rich in linoleic acid but deficient in linolenic acid) to determine (1) if dietary supplementation would offset the hypomyelination characteristic of the undernourished, developing brain and (2) to compare myelin fatty acids in normal, undernourished, and oil-supplemented rats. Myelin recovery was not increased by supplementation with either oil. The proportions of C22:4 and C22:6 fatty acids were reduced in myelin of the undernourished rats. Undernourished rats supplemented with either soy or safflower oil had higher than normal proportions of polyunsaturated fatty acids (C20:4 and C22:6). The triene-tetraene ratio in the oil-supplemented rats was lower than in normal controls, indicating that the oil-supplemented rats were not deficient in essential fatty acids. No significant differences were observed between the oil-supplemented groups.

Animals↗
PubMed1984

Cortical indices of impaired ocular accommodation and associated convergence mechanisms.

The accommodative and fusional vergence mechanisms were examined electrophysiologically in a juvenile suffering from a severe reduction in focusing ability. We used the visually evoked response (VER) to diagnose the accommodation-vergence insufficiency. The procedure is shown to be effective for monitoring longitudinally the ability of simple orthoptic techniques to restore normal accommodative function.

Accommodation, Ocular↗
PubMed1984

Constant intrarenal infusion of PGE1 into a canine renal transplant using a totally implantable pump.

A method was devised whereby PGE1 could be administered to a canine renal transplant recipient on a chronic basis. PGE1 was stored in the reservoir of an implantable pump and delivered continuously in high doses directly into the renal transplant artery. In the model studied a contralateral untreated transplant from the same donor served as a control. Sequential renal scans were used to study the effect of intraarterial PGE1 on the rejection process. Continuous delivery of PGE1 into the renal transplant artery did not prevent allograft failure under these conditions; blood flow diminished similarly in both PGE1-treated and untreated transplants. There were, however, striking differences in the histologic appearance of treated and untreated transplants. PGE1 perfusion resulted in the appearance of large numbers of polymorphonuclear leukocytes but few lymphocytes. In the untreated control allograft, however, the findings were typical of lymphocyte-mediated acute rejection. The distinctive differences noted histologically suggested that the local administration of PGE1 influenced the mechanism by which graft failure occurred. The ability to manipulate cell populations infiltrating an allograft represents a potentially important means for modifying the immune response.

Alprostadil↗
PubMed1984

Early undernutrition and [3H]gamma-aminobutyric acid binding in rat brain.

The effect of early undernutrition and dietary rehabilitation on [3H]gamma-aminobutyric acid ([3H]GABA) binding in rat brain cerebral cortex and hippocampus was examined. Undernourished animals were obtained by exposing their mothers to a protein-deficient diet during both gestation and lactation. Saturation analysis of [3H]GABA binding in the cerebral cortex and hippocampus revealed high- and low-affinity components in the undernourished group, whereas control animals possessed only a low-affinity site. The concentration of low-affinity binding sites was greater in the undernourished animals. Rehabilitation of undernourished animals completely abolished the binding site differences. Treatment of brain membranes with Triton X-100 yielded two binding components in both the undernourished and control animals, although the concentration of lower affinity sites was still greater in the undernourished group. Neither the efficacy nor the potency of GABA to activate benzodiazepine binding in cerebral cortex was modified by undernutrition. These data suggest that early undernourishment modifies the characteristics of [3H]GABA binding, perhaps by reducing the brain content of endogenous inhibitors of the higher affinity binding site. The lack of effect on GABA-activated benzodiazepine binding suggests the possibility that neither the high- nor the low-affinity GABA binding sites are coupled to this receptor component.

Aging↗
PubMed1982

Doctor diagnosis and maternal recall of lower respiratory illness.

Epidemiological studies of respiratory illness in childhood have used the mother's recall of her child's respiratory illness experience as a measure of the frequency with which these illnesses occur. This paper explores the relationship between the diagnosis by the doctor of lower respiratory illnesses and the recall by the mother of the occurrence of these illnesses in a cohort of children in the first year of life. While there is a poor relationship between doctor diagnosis and maternal recall of these illnesses, the group of children reported by their mothers to have had bronchitis or pneumonia in the first year of life appear to suffer more respiratory illness than those children whose mothers recall no such illnesses.

Bronchitis↗
PubMed1981

Estimating the prevalence of disability in the community: the influence of sample design and response bias.

An estimate of the prevalence of physical disability in the community based upon a sample survey may be influenced by the sample design and the response to the method of data collection employed. In this paper we describe a postal survey of a sample of households in the London borough of Lambeth and the procedures used for calculating the influence of these factors on the estimate produced. These procedures can be used to adjust the estimate to take account of the relative chance of households falling into the sample and to correct for non-response bias.

Adolescent↗
PubMed1981

Ossifying fibroma of the head and neck: involvement of the temporal bone- and unusual and challenging site.

Ossifying fibroma of the head and neck is most commonly described in the mandible and maxilla. A few isolated reports in the literature exhibit the rare existence of this lesion in the nasal bones, orbit, ethmoid sinus, sphenoid sinus, occiput, and in only two well-documented cases, the temporal bone. We present the case of an extensive ossifying fibroma of the temporal bone that presented as a suspected case of hyperostosis of the external auditory canal and conductive hearing loss, without any cosmetic deformity. A review of the recent literature concerning the sites, radiologic presentation, difficulty of pathologic differentiation, and modality of therapy is discussed.

Adult↗
PubMed1978

The inhibiton of adrenergically provoked renin release by salbutamol in man.

1 The beta-adrenoceptor agonist salbutamol is shown to have antagonist properties by its effect on adrenergically provoked renin release in normal people. 2 It significantly reduces the rate of renin secretion provoked by either endogenous (85 dregrees head-up tilt) or exogenous (isoprenaline infusion) adrenergic stimulation. 3 Because renin is relatively simple to measure, and because in acute studies its release is relatively uninfluenced by the vagaries of direct and reflex cardiovascular effects, we suggest that, in the characterization of drugs which act on adrenergic beta-receptors, an assessment of their effects on renin release would be useful.

Adult↗