[Blood vessel wall cells of the human in culture].
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Biomedical subjects
Publications and source records attributed to D Roth.
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Endoxin is an endogenous substance known to participate in the regulation of the sodium balance and hypertension. Its chemical nature remains elusive. Based on its capacity to specifically bind to Na-K ATPase receptors we describe a receptor assay for its measurement in human urine. The endoxin was extracted by methanol and desalted on a silicagel column with a mixture of chloroform-ethanol. Calibration curves have been established by the transformation of the weight of crude extract in actual content of active material expressed in nmol/l as calculated from Scatchard plots analysis. Normal values are given for subjects on regular salt diet. Changes in endoxin urinary elimination after an oral salt load are outlined.
In a series of extensive studies on gastric carcinogenesis, we have used Sprague-Dawley rats to examine the morphologic, histochemical, and biochemical effects of risk and protective factors on N-methyl-N'-nitro-N-nitroso guanidine (MNNG)-induced tumors in an attempt to link early observations with the end-point lesion, gastric cancer. We have observed that the putative risk factors sodium chloride (NaCl); a mixture of bile acids; aspirin; alcohol; and nitrite enhance MNNG-induced neoplasia of the gastric mucosa. On the other hand butylated hydroxyanisol (BHA), Se and difluromethylornithine (DFMO) were protective and inhibited the induction of gastric mucosal neoplasia. In most cases, early changes detected by a number of criteria correlated with the end-point, gastric neoplasia. This model appears to be useful in screening and evaluating chemicals for risk for or protection against gastric cancer.
The histopathology and incidence of AIDS-related glomerulopathy was evaluated by renal biopsy (N = 24) or at autopsy in 159 patients, including 131 adults and 28 infants and children with AIDS. Thirty-five patients had overt clinical manifestations of renal disease characterized by a nephrotic syndrome with focal and segmental glomerular sclerosis (FSS). Fifteen patients had diffuse glomerular mesangial hyperplasia (MH) without or with minimal clinical renal disease and 109 had intact or minimally involved glomeruli. Whereas 15 of 30 (50%) i.v. drug users with AIDS had evidence of renal disease, only one of 53 (2%) homosexuals had clinical renal disease and only 6 (11%) had histologic evidence of glomerular pathology. The study confirms the important risk of i.v. drug use as a pathogenic factor of renal disease and shows a rarity of renal disease in homosexual or bisexual men with AIDS. On the other hand, 30% of adult Haitians with AIDS had FSS or diffuse MH, although i.v. drug use is not an important risk factor in this population. Moreover, eight of 28 (29%) children with perinatal AIDS had evidence of renal involvement, including four with a nephrotic syndrome and FSS. The data provide strong evidence for the existence of an AIDS-related glomerulopathy independent of i.v. drug use, but suggest that unrecognized co-factors may be important in the development of renal disease.
Canine renal cortical cells were obtained by collagenase extraction from allogeneic haploidentical, donor-recipient beagle littermate pairs and from unrelated mongrels. Peripheral blood lymphocytes (PBL) of the mongrels, as well as of one member of the beagle pair that exhibited high mixed lymphocyte culture (MLC) reactivity against the other were also stimulated by renal cortical cells derived from both normal and rejected transplanted kidneys in mixed lymphocyte kidney cell culture (MLKC). A moderate autologous MLKC reactivity occurred in response to normal renal cortical cells. However, rejected kidney cortical cells were markedly more stimulatory than normal renal cortical cells in both allogeneic and autologous MLKC reactions. Lymphocytes from donor animals responded more strongly to autologous cortical cells isolated during rejection of the transplant than to cortical cells from normal allogeneic kidneys. Recipient infiltrating lymphocytes and propagated T cell lines extracted from the rejected kidney also responded more strongly than PBL to cortical cells from this kidney. Gradient purification of the stimulating cortical cells resulted in one virtually pure preparation of distal tubular epithelial cells, as demonstrated by immunohistochemical stains and electron microscopy, which caused enhanced stimulation in MLKC. Class II marker analysis of the canine renal cells from rejected kidneys revealed the presence of these molecules on tubular cells that were absent on normal kidney cells. A 16-hr coculture of normal renal cortical cells not exhibiting class II surface markers in the presence of allogeneic or autologous lymphocytes induced the expression of these molecules, associated with an increased stimulatory capacity. This also occurred to a lesser extent with MLC (and MLKC) cell culture media supernatants. However, the low level of class II expression by all the various gradient-purified fractions in the absence of rejection or coculture, and the increased but equivalent expression on all fractions after coculture did not correlate with the preferential stimulatory capacity of the purified distal tubular cell layer. We conclude that two signals are necessary for the MLKC reaction, one involving tissue (kidney)-associated epitopes (the nominal antigen demonstrated in this study to be present in normal distal tubular cells), the other involving class II molecules as costimulatory (amplification) moieties.
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A retrospective analysis of 15 renal transplant patients with end-stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) was performed. Overall actuarial patient and graft survival at 6 years was 93 and 84%, respectively. Recipients of HLA-identical kidneys did not appear to be at increased risk of allograft failure due to rejection or recurrent disease. Two biopsy-proven cases of recurrent lupus involving the allograft were observed and are discussed. Those patients currently experiencing excellent graft function (creatinine less than 2 mg/dl) had a significantly longer pretransplantation dialytic interval than the group whose most recent serum creatinine exceeds 2 mg/dl (or returned to dialysis). Posttransplantation monitoring of antinuclear antibody, antidouble-stranded DNA, C3, C4, and circulating immune complexes was not predictive of renal or extrarenal disease activity. Renal transplantation should be considered an excellent therapeutic modality for the lupus patient with ESRD, although an interim period on dialysis of at least 1 year seems warranted.
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Gradual narrowing and occlusion of a coronary artery in patients with atherosclerotic heart disease frequently causes enlargement of the collateral circulation. Although these vessels may protect from development of myocardial infarction, they frequently do not supply sufficient blood flow to prevent ischemia during periods of augmented myocardial oxygen demand. The purpose of this study was to develop a model of the collateral circulation in pigs, a species that previously has been shown to develop sparse collateral vessels. Eighteen pigs were instrumented with an Ameroid constrictor around the proximal left circumflex artery and left atrial and aortic catheters. In four animals the constrictor was placed just distal to a large proximal obtuse marginal vessel. Seven of the pigs were treated daily with oral aspirin (325 mg) and disopyramide (200 mg) throughout the study; the other 11 served as controls. After an average of 24 days postoperatively, radioactive microspheres were injected at rest, during exercise (mean heart rate = 245 beats/min), and during intravenous infusion of dypridamole (700 micrograms/kg). At autopsy the extent of necrosis was assessed by a point counting technique in the bed at risk. We found that 75-83% of the bed at risk remained viable. Although aspirin and disopyramide did not significantly alter the extent of infarction (37 +/- 36% untreated vs 17 +/- 6% treated), there was less variability of infarction in the treated group, and subendocardial blood flow during exercise was higher in the treated group compared to controls. The majority of infarction occurred in the subendocardial region. Animals with a large obtuse marginal branch developed significantly smaller infarcts (8 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)
It is now accepted that there is an endogenous digitalis-like substance (EDLS), previously called natriuretic factor, present in different mammalian species which participates to the regulation of the sodium balance and at least in some situations, to the genesis of hypertension. The physiological and pathophysiological role of this substance is well recognized. However, its chemical nature remains elusive. Our purpose was to define a receptor assay for this EDLS in order to be able to measure its concentration in urine and blood. To do so, we first prepared a pool of lyophylised urine from salt loaded men. The active material was isolated by Sephadex G25 chromatography. Using the same active fraction, we investigated its biological effects. Series of experiments have demonstrated the various properties of the EDLS: inducing natriuresis when injected into a rat, diminishing short circuit current in toad's bladder and colonic mucosa of rat in in vitro preparations, inhibiting Na-K ATPase activity in isolated toad's bladder cells, binding to ouabain receptors and cross-reacting with different antibodies directed against digoxin. Among these properties, the binding to ouabain receptors offers the unique opportunity to progress in our knowledges of the substance, making possible the calculation of its constant of affinity and the estimation of the molality of the active material contained in a gram of crude extract. Knowing the constant of affinity of the EDLS for its receptor would provide the best identification of the substance as long as we do not know its exact chemical nature.(ABSTRACT TRUNCATED AT 250 WORDS)
Previous research has reported prevalence rates of mental health problems among homeless individuals that range from 20% to 90%. Attempting to validly verify prevalence rates is important because of the implications concerning both deinstitutionalization and developing an appropriate mental health policy over the next decade. In the present research, which used as its sample the largest homeless sample assessed to date, prevalence was found to fall at the lower range of previously cited data. Despite the fact that the prevalence of mental health problems among the homeless population was found to be relatively low, it was found that homeless people with mental health problems are, at best, only marginally served by the mental health system. Implications for community mental health policymakers and program designers are discussed.
The social problem of homelessness is of increasing concern to mental health professionals. In a large-scale study of homelessness in Ohio, data were collected in face-to-face interviews with 979 homeless people in 19 counties. The median length of homelessness was 60 days. Almost half the respondents cited economic factors, such as unemployment or problems paying rent, as the major reason for their homelessness. Thirty percent had been hospitalized at least once for mental health reasons, and 31 percent showed symptoms serious enough to require mental health services. Findings are also presented in relation to a typology of the homeless--street people, shelter people, and resource people--and urban and rural respondents are compared. These and other findings support the principal conclusions that homelessness is clearly a multidimensional problem and that service strategies must reflect the multiple needs and varying characteristics of homeless people.