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Biomedical subjects

J E Castro

Publications and source records attributed to J E Castro.

At least 55 records · Page 3Linked to original sources

Malakoplakia in a cadaver renal allograft: a case study.

Malakoplakia is an uncommon chronic inflammatory disease characterized by histocytes with intracellular Michaelis-Gutmann bodies. The etiology is uncertain, but it is thought that depressed macrophage phagocytosis of bacteria is important. This presentation describes a case of malakoplakia arising in a cadaver renal transplant. The association of long term immunosuppression and repeated E. coli urinary tract infections is discussed.

Cadaver↗

Effect of Corynebacterium parvum on peripheral blood platelets.

The level of peripheral blood platelets was determined after i.v. injection of Corynebacterium parvum in normal C57BL mice and in those bearing the Lewis lung carcinoma. Twenty minutes after injection of a formalin-killed active strain (CN6134, (CN6134, which inhibited tumour metastases) or a killed inactive strain (CN 5888, which did not inhibit metastases) the number of circulating blood platelets was reduced by 50%. The level of platelets returned to control values by 8 h after the active, and by approximately 3 days after the inactive strain. The active strain alone caused a second and prolonged fall in platelet numbers, from approximately 16 h to 21 days after injection. Heparin given 3 X weekly to these mice restored the platelet count to normal values by 10 days after injection of active-strain C. parvum. The level of platelets in tumour-bearing mice was essentially similar to that in normal mice. Possible causes of the thrombocytopenia and the significance of platelets in metastasis are discussed.

Animals↗

Radiolabelling of Corynebacterium parvum and its distribution in mice.

Corynebacterium parvum was labelled by growing live bacteria in the presence of [3H]thymidine. The bacteria were killed by formalin, washed thoroughly and resuspended at a concentration of 7 mg dry weight/ml. An activity of 1-6 X 10(5) ct/min/0-1 ml was obtained. The biological properties (inhibition of tumour growth and hepatosplenomegaly) of the labelled C. parvum were compared with those of commercially available vaccine, and were found to be similar. Labelled C. parvum was injected i.v., i.p., or s.c. into normal C57BL mice and the localization of activity determined at 4 h and 1,3,7 and 14 days after injection. After i.v. or i.p. injection, highest counts were recorded in the liver. Moderate activity was found in the spleen, lungs and small gut. After s.c. injection, the majority of radioactive label was detected at the site of injection and little found in other tissues. The distribution of injected C. parvum was also studied in mice bearing Lewis tumour, and was found to be similar to that in normal mice. Moderate amounts of labelled C. parvum were recovered from tumour. There appeared to be no relationship between the antitumour effect of C. parvum given by a particular route of injection and the concentration of C. parvum recovered from the tumour.

Animals↗

Effects of C. parvum on growth and induction of intracerebral tumours in mice.

An investigation was made into the effect of Corynebacterium parvum therapy on cerebral tumours in mice. I.v. C. parvum caused a slight but significant increase in the survival of BALB/c mice injected intracerebrally (i.c.) with not more than 50 Meth A cells. C. parvum was most effective if given on the same day or 5 days after tumour. If this interval was increased there was no effect. Multiple i.v. injections were no more effective than a single dose. I.v. C. parvum had no influence on the survival of C57BL mice injected i.c. with Lewis tumour cells, and had little effect on the induction of i.c. or s.c. tumours by methylcholanthrene. It was concluded that C. parvum therapy was of little use in the treatment of cerebral tumour in mice. The clinical implications of these findings are discussed.

Animals↗

Immunological mechanisms in metastatic spread and the antimetastatic effects of C. parvum.

The effects of the host's immune response on metastatic spread was investigated by observing the numbers of pulmonary metastases that developed from an s.c. implant of the Lewis lung carcinoma in C57BL mice in which different cell populations had been suppressed. Macrophage function was impaired by treatment with silica (Si), cortisone acetate (CA), or trypan blue (TB). T-cell function was depressed by adult thymectomy and sublethal irradiation, or by treatment with antilymphocyte serum (ALS). Metastasis was significantly increased and phagocytic activity decreased by Si and CA, but were unaffected by TB. Thymectomy and irradiation had no effect on metastases, whereas ALS when given before, but not after tumour growth, reduced their number. The antimetastatic action of the immunopotentiating agent C. parvum was investigated in these immunologically impaired mice. It was unaffected by Si, CA or TB. However, the inhibiting effect of these agents on phagocytic activity was overcome by treatment with C. parvum. Its antimetastatic action was unaffected in mice which had been thymectomized and irradiated, but could be abrogated by ALS. However, ALS was only able to prevent this activity if given before tumour growth; it was ineffective if given after tumour growth. This study showed that metastatic spread was inversely related to phagocytic activity. The antimetastatic effect of C. parvum appears to be mediated through macrophages in concert with a subpopulation of T lymphocytes, which were considered to be necessary in the sensitization arm of the response as opposed to the effector arm of this response.

Animals↗

The effects of Corynebacterium parvum and surgery on the Lewis lung carcinoma and its metastases.

The effects of Corynebacterium parvum on the mouse primary Lewis lung carcinoma and its metastases were studied. C. parvum was given at the same time as subcutaneous inoculation of tumour or in combination with surgical excision of the primary after 10 days' growth. When intravenous C. parvum was given at the same time as tumour there was a reduction in the primary tumour growth rate. There was a similar reduction in growth if the drug was given intravenously 7 days after tumour inoculation. Intraperitoneal and subcutaneous administration of C. parvum had no effect on the primary tumour. The number of pulmonary metastases were significantly reduced after intravenous or intraperitoneal C. parvum given at the same time as tumour. When C. parvum and surgery were combined and C. parvum was given not more than 2 days before operation there was only a slight reduction in metastases, but when the injection was given intravenously or intraperitoneally 3-4 days before operation the number of metastases was significantly reduced. Subcutaneous administration of C. parvum had little effect on metastases. There was no difference in the number of metastases in C. parvum-treated mice were killed after 21 or 28 days. C. parvum given on the same day as surgery was more effective if tumour excision was performed before day 10 when the metastases were less well established. It was concluded that in well-defined conditions C. parvum is effective against metastases of the Lewis lung carcinoma.

Animals↗

The humoral responses of haemodialysis patients to antigen challenge.

Twenty-four patients on regular haemodialysis had repeated serum samples tested for lymphocyte cytotoxicity and for factors which inhibit the mixed lymphocyte culture (MLC). It was found that serum with a high urea content did not increase the incidence of inhibition of MLC. In 16 patients on haemodialysis there was inhibition of MLC by autologous serum and the same combinations of lymphocytes were inhibited in repeated tests. The serum from 10 of these patients was also cytotoxic for lymphocytes. Serum from 12 patients was not cytotoxic but 6 of these caused inhibition MLC. It is suggested that inhibition of MLC may be produced by factors which are not specific for HLA. Serum from patients who previously rejected kidney transplants or who had pregnancies or multiple blood transfusions showed increased cytotoxicity, but these factors did not increase the frequency of serum inhibition of MLC. The significance of serum inhibitory factors and cytotoxic antibodies in the early clinical course of 12 cadaver transplants is discussed.

Antibody Formation↗

Allograft nephrectomy.

The indications, complications and results of 54 allograft nephrectomies undertaken in 44 patients have been reviewed. There were 7 deaths following 39 nephrectomies done within 6 months of transplantation and complications occurred in a further 14 instances. Many of these resulted from pre-existing infection. When nephrectomy was carried out 6 months after transplantation there were no deaths and morbidity was less. If graft failure is diagnosed within 6 months of transplantation immediate nephrectomy is recommended to prevent future complications. When graft failure occurs later it is suggested that nephrectomy be undertaken only when definite indications for this are present.

Adolescent↗