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Biomedical subjects

J E Castro

Publications and source records attributed to J E Castro.

At least 19 recordsLinked to original sources
PubMed1998

Detection of rare apoptotic T cells in vivo.

The flow cytometric analysis of apoptosis in lymphocytes from in vivo samples has been difficult because of the low frequency of apoptotic events. To overcome this obstacle, many investigators have relied on in vitro incubations to increase the number of apoptotic cells before analysis. In this report, we show that an adaptation of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay for use in flow cytometry can be used to detect rare apoptotic lymphocytes from freshly harvested LN suspensions. This approach is both specific and extremely sensitive. This method also is amenable to multiparameter analyses and allows a phenotypic analysis of these rare apoptotic cells. However, we observed that some monoclonal antibodies can stain apoptotic-but not viable-cells nonspecifically. Therefore, the specificity of all antibodies to stain apoptotic cells was confirmed in competition assays.

Animals↗
PubMed1996

Fas modulation of apoptosis during negative selection of thymocytes.

A major mechanism maintaining immune tolerance is the deletion of potentially autoreactive thymocytes by apoptosis during development in the thymus. Previous reports suggest that apoptosis is induced by high avidity signals transduced via the T cell receptor; however, the role of signals transduced by other cell surface receptors during thymic selection remains poorly understood. Fas, a member of the TNF receptor family, has been shown to induce apoptosis in mature peripheral T cells; however, the effects of Fas on negative selection of thymocytes have not been previously detected. Using a sensitive terminal deoxynucleotidyl transferase method to detect apoptotic cells, we found that mutant Fas molecules in lpr mice decrease the sensitivity of thymocytes to T cell receptor-mediated apoptosis and that blockade of Fas-Fas ligand interactions in vivo can inhibit antigen-induced apoptosis of thymocytes in non-lpr mice. Thus, we have shown that Fas, in conjunction with antigen-specific signals, can modulate apoptosis during negative selection of thymocytes.

Amino Acid Sequence↗
PubMed1983

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Adolescent↗
PubMed1983

Histocompatibility antigens in coal miners with pneumoconiosis.

Twenty-five histocompatibility antigens have been measured in 100 coal miners with pneumoconiosis attending a pneumoconiosis medical panel and the results compared with a panel of 200 normal volunteers not exposed to dust. Chest radiographs were read independently by three readers according to the ILO U/C classification. On a combined score, 40 men were thought to have simple pneumoconiosis and 60 men complicated pneumoconiosis. The number of antigens tested and associations between antigens caused difficulties in assessing the statistical significance of differences in prevalence of antigens between groups of men. Using stringent criteria for statistical significance, no significant differences were found in antigen prevalences between miners and controls, or miners with simple or complicated pneumoconiosis. When a less stringent statistical approach was applied, three antigens appeared to have abnormal prevalences in these 100 miners by comparison with the normal volunteers. More detailed examination of these antigen prevalences in relation to radiographic category of pneumoconiosis did not provide any supportive evidence that these slight associations were of statistical or clinical significance. Reports on histocompatibility antigens in miners with pneumoconiosis are reviewed briefly and the results compared. There is no good evidence that any of the histocompatibility antigens so far tested are associated with a clinically important altered risk of simple or complicated pneumoconiosis when dust is inhaled.

Aged↗
PubMed1981

Proliferative glomerulonephritis in mice given intravenous Corynebacterium parvum.

Mice given a killed suspension of Corynebacterium parvum (C.p.) developed nephritis as part of an immune complex disease. The nephritis was dose-related. After a single dose of 70 microgram (a human-equivalent dose) or of 466 microgram there was a mesangiopathic glomerulonephritis and after repeated human-equivalent doses there was a mesangiocapillary glomerulonephritis. Antibodies to C.p. increased and circulating immune complexes were detected. Mice receiving repeated doses also developed an arteritis. Study of this model may help in the understanding of human immune complex disease and the pathogenesis of glomerulonephritis.

Animals↗
PubMed1981

Vesicoureteric reflux following renal transplantation: a simple method of ureteric implantation.

We have used a simple method of ureteroneocystostomy in renal transplant patients. This entails a no-tunnel "drop-in" with a long free segment protruding into the bladder lumen. The incidence of vesicoureteric reflux was investigated in 81 transplant patients who had a follow-up period ranging from 4 months to 15 years (mean 3.7 years); 29 of these patients had recurrent urinary tract infections. Micturating cystography demonstrated reflux in 6 patients (7.4%). In these 6 patients the presence of reflux had no deleterious effect on renal function and the infections were easily controlled with long-term antibiotics. In the 52 patients without injury infection no reflux was demonstrated. The conclusions based on this study indicate that (1) in the absence of recurrent infection there are no indications for micturating cystography and (2) this method of ureteroneocystostomy is expedient and has a low incidence of reflux.

Follow-Up Studies↗
PubMed1980

Cystine stones.

We report on 9 patients, 5 men and 4 women, with cystine stones. Eight were seen previously at other hospitals, and a total of 18 operations were performed for stones before the diagnosis of cystinuria was made and medical treatment instituted. The pathogenesis and rational for medical treatment is reviewed, and the need for early diagnosis is emphasized.

Adolescent↗
PubMed1980

Mechanisms of C. Parvum-induced coagulopathy in mice.

I.v. injection of Corynebacterium parvum (CP) into C57BL and BALB/c mice caused profound coagulation changes, featuring thrombocytopenia, decreased fibrinogen, increased fibrin/fibrinogen degradation products, and a concomitant microangiopathic haemolytic anaemia. These changes were greatest on the 9th day after CP, with recovery by Day 21. I.p. injection caused similar effects but s.c. injection was ineffective. Radiolabelled-platelet kinetics and distribution after i.v. CP indicated disseminated intravascular coagulation with rapid fibrinolysis; EACA treatment exacerbated the thrombosis. The coagulopathy correlated with hepatosplenomegaly, and both were dose dependent. Splenectomy did not effect the coagulopathy, but indomethacin totally abrogated the changes, suggesting that prostaglandin biosynthesis is involved in the pathogenesis.

Aminocaproates↗
PubMed1980

Immune-complex disease in mice and humans given C. parvum.

The present studies in mice and cancer-bearing patients, treated with C. parvum (CP) immunotherapy, were to determine the effects of CP on the production of immune complexes (IC) and associated disease. Using the Clq-binding assay, circulating immune complexes were detected in mice given a single high dose of CP (466 microgram) and repeated human-equivalent doses (70 microgram). All mice treated with CP developed proliferative glomerulonephritis, the severity of which was dose-related. The histological and immunofluorescent patterns of the nephritis were those attributed to immune-complex disease. The mice had haematuria but were not in renal failure. Fifty patients with inoperable lung cancer were studied. All received radiotherapy. Twenty-two had no other treatment (controls) and 28 were treated with infusions of CP. Using 2 immune-complex assays (Clq binding and monoclonal rheumatoid-factor binding) IC were found in 10/22 control patients but these did not develop haematuria or proteinuria. Twenty-four of the 28 patients treated with CP developed transient haematuria and/or proteinuria with red-cell and hyaline casts, the changes resolving over 5 days. Immune complexes were detected in 5 of these 28 patients before CP treatment. Although 16/28 had IC at the time of haematuria and proteinuria, these findings were difficult to interpret because IC may occur in response to the tumour, the radiotherapy, or the CP. Although no patient developed renal failure, we believe that those treated with CP should have regular assessment of their renal function.

Adult↗
PubMed1980

Single versus multiple human-equivalent doses of C. parvum in mice: neutralization of the anti-metastatic effect.

The murine dose of i.v. C. parvum (466 microgram) was compared with a single, low, human-equivalent dose of 70 microgram and with repeated weekly low doses. All treatments increased the antibody titre against C. parvum (CP). However, repeated doses stimulated a much higher titre than single doses. In all treated animals spleen weight peaked at 2 weeks and then fell. A single low dose caused a 3-fold increase, a single high dose or multiple low doses a 6-fold increase. Liver weight changes followed a similar pattern. Hepatosplenomegaly was prolonged by multiple doses. The effects of these treatments on Lewis tumour metastases were studied. A single high dose and a single low dose on the day of tumour implantation (Day 0) were equally effective at inhibiting pulmonary metastases. Repeated low doses starting on Day 0 were no more effective than a single dose. The effect of CP on survival after primary-tumour excision on Day 10 was observed. Low dose CP on Day 7 doubled the harmonic mean of survival time. Repeated doses were no more effective than a single dose. Low-dose prophylaxis up to 2 weeks before tumour significantly inhibited metastases. However, when repeated low-dose prophylaxis was combined with a single low dose on Day 0, the anti-metastatic effect was abrogated. This neutralization of the anti-metastatic effect of CP given on Day 0 was found to persist after a 13-week treatment-free interval. Possible mechanisms for this phenomenon are discussed.

Animals↗
PubMed1980

Serial urinary and cervical cytological studies in women undergoing renal transplantation.

Cervical dysplasia has been reported to occur more frequently in female renal transplant patients. The incidence of pre-existing dysplasia is unknown. A prospective study of several urinary and cervical cytological screenings of 50 transplant patients was undertaken. Two of 38 patients studied before transplantation had pre-existing dysplasia. No new cases of dysplasia were found during the study (mean surveillance 3 years). A high incidence of urinary viral infection was found, but a relation to cervical dysplasia was not noted. The frequency of cervical abnormalities previously reported might have been due to different immunosuppressive regimes or to failure to exclude pre-existing disease. Despite the low incidence of abnormalities the use of cytological screening provided valuable reassurance to our patients, and its use is recommended.

Adult↗
PubMed1979

Cimetidine in the treatment of peptic ulceration following renal transplantation.

Seven patients who developed peptic ulceration following renal transplantation have been treated by cimetidine. One died before its value could be assessed. The remaining 6 were symptom-free within 48 h. In 3 patients the ulcer appeared healed on gastroscopy, in one there was no change, another required operation for gastrointestinal bleeding 1 month after beginning cimetidine and the other patient has been lost to follow-up after 5 months' treatment. Two patients had a significant rise of serum creatinine whilst on the drug, but there is no evidence of increased immunological reactivity towards the graft and no agranulocytosis.

Adult↗
PubMed1979

Acid phosphatase after examination of the prostate.

We report the effect of rectal examination of the prostate and transurethral resection of the prostate (TURP) on the serum level of tartrate labile acid phosphatase (TLAP) in 18 normal cases, 31 with benign enlargement of the prostate and 20 with carcinoma. Rectal examination had no effect on TLAP in normal patients, those with benign enlargement and those with carcinoma, either after 5 min or the following morning. TURP for both benign and malignant disease raised the TLAP transiently with a rapid return to normal. We believe that there is no justification for postponing estimation of TLAP following rectal examination.

Acid Phosphatase↗
PubMed1979

Effects of intravenous injection of two different strains of Corynebacterium parvum in the mouse.

A strain of C. parvum, CN6134, known to have antitumour activity, caused thrombosis in the sites where the organism is phagocytosed. It bound to macrophages in vitro and activated the alternate pathway of complement. A strain of C. parvum, CN5888, which fails to show antitumour activity, did not show thrombosis. It did not bind to macrophages or activate guinea-pig complement. It did, however, cause marrow infarction which seems to result from a diminished clearance of the organism from the circulation.

Animals↗