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Biomedical subjects

R Weil

Publications and source records attributed to R Weil.

At least 73 records · Page 4Linked to original sources

Cyclosporine-induced tolerance requires antigens capable of initiating an immune response.

We studied two example where indefinite graft survival could be obtained in rats. In the first, strain DA hearts were permanently accepted in allogeneic PVG rats if the recipients were treated for at least 7 consecutive days with cyclosporine A (CsA) after transplantation. In the second, DA pancreatic islets were permanently accepted in PVG rats if the islets were cultured in vitro for 14 days in high oxygen. When cultured islet-grafted PVG rats were injected with lymphocytes from other PVG rats previously sensitized to DA alloantigens, the islet grafts were destroyed within 14 days. By contrast, it was difficult to cause the DA heart allografts to cease beating with the same adoptive transfer protocol; approximately two-thirds of the heart-grafted animals maintained their grafts. This difference was not due to the CsA as cultured islets transplanted in the presence of CsA were still susceptible to rejection by sensitized lymphocytes. However, islets that had not been cultured in high oxygen prior to transplantation and that were maintained with CsA were not rejected after the injection of sensitized lymphocytes. These results suggest that CsA can most readily induce a state of tolerance when the graft is capable of initiating an immune response.

Animals↗

Atrial natriuretic factor (ANF) levels are elevated in rats bearing rejecting heart-lung allografts.

Intra-abdominal heart-lung grafts were transplanted into 8 rats across a major histocompatibility barrier. Four of the 8 rats were treated with Cyclosporin A (CsA) to prevent rejection. Atrial natriuretic factor (ANF) levels measured 6 days after transplantation revealed a significantly (p less than .005) higher mean ANF concentration in rats bearing a rejecting heart-lung allograft (642 +/- 148.0 pg/ml) compared to rats bearing a heart-lung allograft not undergoing rejection (200.8 +/- 13.07 pg/ml). ANF might be a useful noninvasive marker in the diagnosis of rejection in heart and heart-lung transplants.

Animals↗

31P nuclear magnetic resonance study of acute renal dysfunction in rat kidney transplants.

31P NMR spectroscopy was used to study renal allografts in rats subjected to allograft rejection, cyclosporine toxicity, ischemia, and ureteral obstruction. Parameters of relative peak areas and intracellular pH were accurately distinguished among the different causes of graft dysfunction. Ureteral obstruction was clearly identified by elevations in the phosphodiester/urine phosphate peak. Ischemia and rejection were both associated with increases in inorganic phosphates and phosphomonesters and decreases in the beta-phosphate peak of adenosine triphosphate but were distinguishable from each other by differences in intracellular pH which was normal in rejected allografts (7.33 +/- 0.07, n = 3) but low in ischemic allografts (7.00 +/- 0.05, n = 3, P less than 0.05). Grafts insulted with cyclosporine toxicity were not distinguishable from normal allografts by any of the parameters studied. These data suggest that 31P NMR spectroscopy may have potential clinical application in differentiating among the causes of graft failure of human renal allografts.

Animals↗

P-31 nuclear magnetic resonance spectroscopic evaluation of heterotopic cardiac allograft rejection in the rat.

P-31 nuclear magnetic resonance (NMR) spectroscopy was used to evaluate heterotropic cardiac allograft rejection in the rat. To enable optimal application of NMR spectroscopy for the in vivo study of myocardial metabolism in the transplanted organ, an accessory heart transplantation to groin in the rat was used. The allografts were studied in a 1.89 Tesla horizontal bore magnet. Each spectrum was obtained by Fourier transform of 512 scans using 60-degree pulses with 2-sec delays. Changes in phosphocreatine (PCr), adenosine 5-triphosphate (ATP), and inorganic phosphate (Pi) and intracellular pH as determined by P-31 NMR were compared with rejection process as judged by histological studies. Allografts treated with cyclosporine (CsA) did not show any rejection (NR) and had relatively high levels of PCr, and low levels of Pi. Allografts that did not receive any CsA revealed both vascular and cellular rejection. These rejected allografts (R) had relatively low levels of PCr and high levels of Pi. It is concluded that P-31 NMR spectroscopy may have potential application to the clinical diagnosis of cardiac allograft rejection.

Adenosine Triphosphate↗

Ultrasonographic diagnosis of infected lymphocele after kidney transplantation.

Lymphoceles after kidney transplantation are usually not infected and are drained into the peritoneal cavity, if their size requires treatment. Infected lymphoceles should be drained externally rather intraperitoneally, to avoid peritonitis. Ultrasonographic examinations of 2 febrile patients identified complex echoes that were correctly interpreted as infection within lymphoceles. The ultrasonographic diagnosis of infected lymphocele facilitates early and appropriate operative treatment.

Adult↗

Effect of an in-patient education programme upon the knowledge, behaviour and glycaemic control of insulin dependent diabetic patients.

The aim of this study was to evaluate the efficiency of a diabetes education programme (5 days in hospital) in type I diabetic patients by comparing their diabetes-related knowledge, behaviour and the level of HbA1 before with that 6 months and 1 year after the teaching session. The patients were divided into 2 groups according to whether they answered a questionnaire after 6 months (group I; 41 "responder" patients) or not (group II; 38 "non-responder" patients). Their usual regime of insulin therapy (2 daily injections of a mixture of regular and intermediate-acting insulins) was not modified during their hospitalization for teaching; the total daily doses of insulin and the percentages of regular insulin were comparable before and after the teaching session. In group I, we observed an improvement in knowledge and behaviour indices (evaluated by a written questionnaire) from 69 +/- 3 and 67 +/- 4% (mean +/- SEM) before the teaching session to 86 +/- 2 and 85 +/- 2% 6 months after, respectively (p less than 0.001). HbA1 decreased from 12.1 +/- 0.3% to 11.2 +/- 0.3% (p less than 0.05) and to 10.7 +/- 0.4% (p less than 0.025) after 6 and 12 months respectively. This improvement was observed in patients with or without residual insulin secretion. In group II patients, the index of knowledge increased similarly from 67 +/- 4 to 85 +/- 2% (p less than 0.001). No significant decrease of HbA1 was observed in this group after 6 and 12 months, however whether the patients possessed residual insulin secretion or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

On the functional roles of simian virus 40 large and small T-antigen in the induction of a mitotic host response.

The early gene of wild-type (wt) SV40 specifies two related proteins, referred to as large (Mr 88,000) and small (Mr 19,000) T-antigen. Infection with wt SV40 of Go/G1-arrested monkey kidney and CV-1 cell cultures induced in virtually 100% of the cells T-antigen synthesis, followed by a mitotic reaction and the production of SV40 DNA. Parallel cultures were infected with SV40 deletion mutants that produce either no small T-antigen (d1883) or only trace amounts of a truncated form (d1891). Kinetics of synthesis and accumulation of large T-antigen was closely similar to that observed with wtSV40 whereas apparently only 50-60% of the cells participated in the mitotic reaction and the production of viral DNA. These results and those obtained from a comparative study on the abortive (transforming) infection in Go-arrested mouse tissue culture cells indicate that synthesis of large T-antigen alone is sufficient to trigger in 50-60% of the infected cells a mitotic reaction.

Antigens, Polyomavirus Transforming↗

Cyclosporin A prevents induction of the interleukin 2 receptor gene in cultured murine thymocytes.

Blast formation and mitotic activation of G0-arrested mouse thymocytes were triggered by the addition of concanavalin A plus interleukin 2 (IL-2) to the culture medium. When added alone, Con A induces within 6 hr a complex reprogramming ("priming") that comprises the activation of the IL-2 receptor gene. The primed thymocytes are competent to interact with IL-2 and to respond to its growth-promoting effect, which corresponds to blast formation and mitotic activation. Cyclosporin A, an immunosuppressive cyclic peptide of fungal origin, prevents in T lymphocytes the activation of a set(s) of genes encoding lymphokines and the IL-2 receptor but does not affect their expression once they have been activated. The biomedical implications of these observations are discussed.

Animals↗

Pneumatosis cystoides intestinalis with pneumoperitoneum in renal transplant patients on cyclosporine and prednisone.

Pneumatosis cystoides intestinalis has been detected in 3/103 kidney transplant patients (3%) treated with CsA and prednisone, in contrast to less than 1% of kidney transplant patients treated with Aza and prednisone. In these three patients, the diagnosis of PCI was made by plain x-rays, 10 to 25 days after transplantation. PCI may be more likely to occur in patients with CsA trough blood levels above the recommended therapeutic range. There was associated pneumoperitoneum in all three patients, but none were subjected to exploratory laparotomy. PCI and associated pneumoperitoneum were not associated with adverse effects in any of our three patients. Antibiotics and exploratory laparotomy appear to be unnecessary.

Adolescent↗

Double fluorescence technique for measurement of complement-fixing antibody to lymphocyte subsets.

A double fluorescent antibody method for quantitating human complement-fixing antibody to lymphocyte subclasses has been developed. The indicators in this system are a C6-deficient serum as a non-lytic source of complement, rhodamine-labeled anti-C3 and fluorescein-labeled murine monoclonal antibodies to human lymphocyte subsets. The basic procedure is to incubate lymphocytes with the unknown serum and then to add C6-deficient serum. The binding of C3 is indicated by staining with rhodamine-labeled anti-C3 and the subset class of the lymphocyte so stained is determined by binding of fluorescein-tagged anti-OKT4 or -OKT8 antibodies. The occurrence of both red and green cell surface fluorescence denotes the presence of a complement-binding antibody to the lymphocyte subset defined by the monoclonal antibody. In addition to defining the specificity of complement-fixing anti-lymphocyte antibodies, this technique is more sensitive than the microcytotoxicity assay.

Acquired Immunodeficiency Syndrome↗

Serum-induced stimulation of snRNA synthesis in mouse 3T3 fibroblasts.

Small nuclear RNAs (snRNAs) from quiescent and serum-stimulated 3T3 cultures, labeled with [3H]uridine [( 3H]U), were electrophoresed in polyacrylamide-urea slab gels and revealed by staining with ethidium bromide and by fluorography. Judged by labeling with [3H]U, synthesis of 7S and U1-U6 RNAs was very low or absent in quiescent cultures. The serum-induced transition of 3T3 cells from a resting to a growing state was accompanied by an early, apparently sequential stimulation of snRNA synthesis; stimulated synthesis of 7S, U1, U2, U3, U4 and U6 RNAs coincided in time with serum-induced stimulation of 45S pre-ribosomal RNA (pre-rRNA) and heterogeneous nuclear RNA (hnRNA) synthesis.

Animals↗

Legionella lung abscess after renal transplantation.

Although Legionella infections have been widely reported, the clinical importance of Legionella lung abscess has not been sufficiently emphasised. A renal transplant recipient with a pulmonary abscess due to Legionella pneumophila is presented and 21 other cases from the literature are reviewed. Seven abscesses arose in renal transplant patients. Even though an abscess may develop during treatment, superimposed infection with other micro-organisms appears to be uncommon, and an abscess may be expected to resolve with prolonged appropriate antimicrobial therapy alone. Recognition of lung abscess as a complication of legionella infection will therefore prevent unnecessary operations.

Adult↗