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Biomedical subjects

J Passwell

Publications and source records attributed to J Passwell.

At least 19 recordsLinked to original sources
PubMed1997

Engraftment of human kidney tissue in rat radiation chimera: I. A new model of human kidney allograft rejection.

BACKGROUND: We have recently shown that lethally irradiated normal strains of mice and rats, reconstituted with bone marrow from severe combined immune deficiency (SCID) mice, can be engrafted with human peripheral blood mononuclear cells (PBMC). METHODS: The feasibility of transplanting human renal tissue under the kidney capsule of the SCID/Lewis and SCID/nude radiation chimera and the effects of intraperitoneal infusion of allogeneic human PBMC on the human renal implants were investigated by histology, electron microscopy, immunohistochemistry, and fluorescence-activated cell sorter analysis. RESULTS: Sequential evaluation of the human renal implants from 10 days to 2 months after transplantation showed that human parenchymal elements survive in the implants up to 2 months after transplantation. The overall architecture of the transplanted kidney tissue and the normal structure of individual cells in the glomeruli and tubuli were preserved. Infusion of allogeneic human PBMC after kidney implantation resulted in patchy cellular infiltrates, composed mainly of activated human T cells, and led to prompt rejection of the human renal tissue, whereas no signs of inflammation were observed in human renal implants of chimeric rats that did not receive human PBMC. Treatment with OKT3 antibody, anti-human CD25 antibody, or CTLA4Ig fusion protein in vivo ameliorated the rejection process. CONCLUSIONS: Human adult kidney fragments transplanted into SCID-like rats transiently retain competent parenchymal structures. When these grafts are combined with allogeneic human PBMC, acute cellular rejection develops. We suggest that this chimeric model might be useful for the investigation of the effects of experimental manipulation on the kinetics of the inflammatory response during human renal allograft rejection.

Abatacept↗
PubMed1997

Differential cytokine regulation of complement proteins in human glomerular epithelial cells.

We have previously shown in inbred strains of mice which naturally develop systemic lupus erythematosus that kidney C3, C2, C4 and factor B gene expression increases coincidently with the occurrence of glomerulonephritis, suggesting that local tissue complement gene expression could contribute to the pathogenesis of immune complex injury. In this study, we investigated the synthesis of complement proteins in glomerular epithelial cells (GECs) and its regulation. Using biosynthetic labelling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we demonstrated that GECs synthesized C1r, C1s, C1 inhibitor, C3, C2 and factor B. Interferon-gamma induced increases in the synthesis of all these proteins. Both factor B and C3 proteins were increased following addition of either IL-1beta, IL-6 or TNF-alpha to GEC cultures; however, these cytokines did not increase either C2, C1r, C1s or C1-inhibitor biosynthesis. Lipopolysaccharide affected the biosynthesis of these proteins in a similar way. A semiquantitative analysis of the mRNA expression of some of these proteins by reverse-transcriptase polymerase chain reaction showed that these cytokine effects were pretranslational as there was enhancement of factor B mRNA expression by IL-1, TNF-alpha, IFN-gamma, IL-6 and endotoxin, but only IFN-gamma enhanced C1-inhibitor and C4 mRNA expression. These results may be of significance in the immunopathogenesis of glomerulonephritis, where it is likely that local complement production in GECs is independently regulated by cytokines, derived from resident glomerular mesangial cells or infiltrating monocyte/macrophages and T cells.

Animals↗
PubMed1994

Predictors of outcome of stroke in infants and children based on clinical data and radiologic correlates.

Outcome predictors were analyzed in 45 infants and children with cerebrovascular disorders (CVD), based on clinical features and radiological correlates. The clinical features at presentation could be categorized into three major groups: (1) generalized: alteration of consciousness with or without seizures--24 patients (54%); (2) focal: acute hemiplegia or monoplegia with or without focal seizures--18 patients (40%); (3) cerebellar disturbances--3 patients (6%). The underlying etiology was detected in 80% of children. Thirty-seven patients (82%) survived the initial debilitating event, of whom 11 (29.7%) recovered completely and the rest had either motor or cognitive handicaps during an average follow-up period of 4.2 years (range 1.5-11 years). A head CT performed in all children revealed ischemic infarction in 29 patients (64.4%), while the others had hemorrhagic infarction. Of those with an initial generalized neurological presentation, as many as 50% had multi-focal lesions on CT. All children with focal neurological findings had a solitary localized lesion on CT, mainly in the distribution of the middle cerebral artery. Statistical analysis for outcome prediction showed that the following variables were associated with increased risk of immediate death: (1) hemorrhagic infarction demonstrated by brain CT (p = 0.031); (2) patients who presented with a generalized neurological disorder, namely alteration of consciousness, with or without seizures (p = 0.036). No other clinical or laboratory variables were predictive of imminent death, motor or cognitive handicaps. These may therefore serve as outcome predictors of stroke in the pediatric age group.

Cerebellar Diseases↗
PubMed1989

Tissue-specific initiation of murine complement factor B mRNA transcription.

Factor B (Bf) gene expression is regulated independently in hepatic and extrahepatic tissues. In studying murine factor B expression, we found two mature mRNA species for Bf in kidney and intestine (2.7 and 2.4 kb) but in other tissues, including liver, lung, spleen, heart, brain, and skeletal muscle, only a single Bf transcript (2.4 kb) was observed. These two Bf transcripts in kidney or intestine are identical in structure except for a 300 bp 5' extension found in the 2.7-kb mRNA. The long Bf transcript originates from a tissue-specific alternative site of transcriptional initiation upstream of the initiation site for the 2.4-kb mRNA, as determined by primer extension and nuclease protection assays. The upstream initiation site lacks a typical promoter motif and is only 80 bp downstream from the terminus of the murine C2 gene. After stimulation in vivo with endotoxin, only the 2.4-kb mRNA increases in kidney indicating independent regulation of the two Bf transcripts. The differences in 5' untranslated region generated in these two Bf mRNA species may affect local concentrations of factor B protein in kidney and intestine by mechanisms depending on differential translation rates or stability of mRNA.

Acute-Phase Reaction↗
PubMed1988

Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is associated with the presence of complement proteins and immune complexes in affected organs. Since complement proteins are synthesized in hepatic and extrahepatic sites, we studied a murine model of SLE to ascertain the relative importance of local and humoral (liver) synthesis of complement. C3, C4, and C2 mRNA increase in kidney coincident with the development of nephritis in the MRL lpr/lpr mouse, a strain that spontaneously develops SLE. Two factor B messenger RNA transcripts are expressed in kidney and intestine; SLE nephritis is associated with decrease in the long factor B mRNA and increase in the short form. Increased local synthesis of C3 and B protein and a concomitant glomerular and renal interstitial macrophage infiltrate paralleled the increase in mRNA content in the (lpr/lpr) mice. In addition to kidney, an increase in C3, C4, C2 and factor B mRNA was noted in the lung, heart and intestine and to a lesser extent in liver of (lpr/lpr) in comparison to the MRL (+/+) animals. These results suggest that in SLE local expression of complement genes plays a role in the pathogenesis of chronic glomerulonephritis and in the autoimmune arteritis of other organs.

Animals↗
PubMed1987

The varied clinical and laboratory manifestations of type II Gaucher's disease.

An infant of Arab extraction with the Type II form of Gaucher's disease is described. His clinical presentation was unusual because in addition to the extensive neurological involvement and marked hepatosplenomegaly a severe congestive cardiomyopathy and renal tubular dysfunction were present. In addition, marked hypergammaglobulinemia and raised serum angiotensin converting enzyme levels were found. It is suggested that these varied manifestations may be ascribed to the consequences of glucocerebroside deposition within the macrophages of the reticuloendothelial system.

Cardiomyopathy, Dilated↗
PubMed1987

Effects of the components of breast milk on mucosal enzyme activity of the newborn small intestine.

The effects of the aqueous phase of human breast milk on the disaccharidase activity of newborn rabbit small intestinal mucosal explants were studied in vitro culture. These explants continuously synthesized protein and normal morphology was maintained for the duration of the cultures. Addition of the aqueous phase resulted in significant increase of lactase (p less than 0.001) and maltase (p less than 0.01) concentrations in these organ cultures. This effect was dose dependent and was observed whether the organ biopsies were derived from fed or starved newborn rabbits. Further purification of the aqueous phase showed that the active ingredient exerting these effects was lactose. These studies suggest that lactose may have an important function in stabilization of newborn intestinal disaccharidase enzymes.

Animals↗
PubMed1985

Human monocytes infected with Leishmania amastigotes enhance lymphocyte proliferation.

Human monocytes were infected in vitro with Leishmania tropica major (L. major) promastigotes which transformed to intracellular amastigotes. A spontaneous increase in lymphocyte proliferation occurred in mononuclear cell cultures where the monocytes had been infected with L. major organisms. In addition, an apparent additive effect of lymphocyte proliferation was seen in cultures infected with L. major following phytohaemagglutinin stimulation. This effect was apparent after 3 days in culture and the amount of increase in response was dependent on the number of monocytes in the culture. The effect was also dependent on the number of parasites ingested by the monocytes. The presence of monocytes was essential for this effect, as no enhancement was observed with supernatants from infected cells. This enhanced effect of lymphocyte proliferation was observed predominantly in the B lymphocyte subpopulation. These findings may be of relevance in the immunopathogenesis of Leishmania infections.

B-Lymphocytes↗
PubMed1984

Transient renovascular hypertension in childhood.

Two children aged 18 and 30 months presented with severe renovascular hypertension. Initially, surgical intervention was postponed because of the patients' young age. Adequate control of the hypertension and reversal of its sequelae were achieved with aggressive medical management. At present, both patients, aged 9 and 12 years respectively, have discontinued all medication, have achieved normal growth, are normotensive and have normal renal function.

Antihypertensive Agents↗
PubMed1984

Aldosterone concentrations in dehydrated infants.

The mean serum aldosterone concentration of 37 infants with acute gastroenteritis and dehydration was markedly elevated on admission (mean +/- SE 94.3 +/- 12.1 ng/ml) and approximated to normal values (18.2 +/- 3.7 ng/ml) following recovery from the acute disease (t=3.56 p less than 0.005). Serum aldosterone levels were significantly positively correlated with the percent weight loss (r=0.41, p less than 0.05) and with the blood urea nitrogen levels (r=0.55, p less than 0.001). There was no correlation between either serum sodium levels or blood osmolarity and aldosterone concentrations. Serum potassium levels were positively correlated with aldosterone levels (r=0.53, p less than 0.001). These findings indicate that small infants when dehydrated respond appropriately with elevated aldosterone levels. The amount of body fluid depletion and hyperkalemia are the major factors determining the amount of aldosterone response.

Aldosterone↗
PubMed1984

Comparison of the effect of various stimuli on the leishmaniacidal capacity of human monocytes in vitro.

Leishmania organisms are obligate intracellular parasites of mammalian mononuclear phagocytes in vivo. In order to study the interactions of these parasites and mononuclear phagocytes, we have used a model of infection of Leishmania major in human monocytes in vitro. The presence of intracellular parasites did not alter the normal secretion of lysozyme or result in increased secretion of prostaglandin E2 (PGE2) or superoxide anion by the monocytes. Addition of concanavalin A (Con A), which binds to a specific membrane receptor, zymosan particles or endotoxin to infected monocyte monolayers, resulted in the expected increase in PGE2 secretion. In addition, the production of superoxide by infected monocytes treated with phorbol myristate acetate was not different from control uninfected cultures. Despite this evidence of biochemical activation, neither endotoxin, zymosan nor Con A had any parasiticidal effect on the intracellular parasites. In contrast, Con A-induced lymphokines from human mononuclear cells resulted in an increased killing of the intracellular amastigotes. These studies have shown that the induction of leishmaniacidal capacity of human monocytes is dependent on the type of stimulus used to induce activation.

Cells, Cultured↗
PubMed1983

Monocyte PGE2 secretion in Hodgkin's disease and its relation to decreased cellular immunity.

The secretion of PGE2 from monocytes of newly diagnosed patients with Hodgkin's disease (HD) was compared to that of patients in remission, who were not receiving either chemotherapy or radiotherapy, and normal controls. We found that monocyte monolayers of some patients, both newly diagnosed and those in remission, secreted markedly elevated levels of PGE2. The lymphocyte proliferative response to PHA was increased to a similar extent in both newly diagnosed patients and those in remission when cultured in the presence of indomethacin. PGE2 concentrations in the medium of mononuclear cultures correlated with the lymphocyte proliferative response to PHA (P less than 0.05). However, no correlation of monocyte PGE2 production with decreased E rosette forming lymphocytes, anergy or clinical stage could be demonstrated. We suggest that PGE2 secretion by monocytes is indicative of an 'activated' state of these cells. It is, however, unlikely that PGE2 is the only molecular species responsible for the decreased cellular immune function in HD. 'Activated' monocytes may be part of the immune response in this disease and may be responsible for the decreased cellular immunity.

Adolescent↗