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Biomedical subjects

B Jasani

Publications and source records attributed to B Jasani.

169 records · Page 10Linked to original sources

Multiple hormone storage by 'polycrine' cells in the pancreas (from a case of nesidioblastosis).

Pancreatic tissue from a case of neonatal hypoglycaemia with nesidioblastosis has been studied by routine light and electron microscope techniques and by highly sensitive light and electron microscope immunolocalization methods. A hyperplastic nodule within the pancreas from this case contained enlarged distorted haemorrhagic islets, with a variable rim of exocrine tissue. Islet cells in these areas were shown to contain more than one hormone in separate granules. An immunoperoxidase system using hapten-labelled primary antibodies and photochemical amplification applied to serial semithin sections suggested a consistent overlap between insulin and glucagon immunoreactive cells. Serial ultrathin sections of tissue embedded in LR White showed that some heteromorphous cells with predominantly beta-granules also contained a minority population of granules which had either glucagon or glicentin immunoreactivity. In adjacent studies, the same techniques confirmed that the majority population of granules did indeed contain insulin, and immunocolloidal gold methods were used to show that glucagon and glicentin containing granules were present in the same cells. The significance of these findings is discussed, including the possibility that cells containing more than one granule type might represent a subpopulation of facultative cells in transit from producing one hormone to producing a second. The importance of sensitive immuno-electron microscopy in the investigation of endocrine lesions is stressed.

Cytoplasmic Granules↗

Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.

Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial.

Ascites↗

Metallothionein expression in canine and feline mammary and melanotic tumours.

Moderate to strong immunohistochemical metallothionein (MT) positivity (MT expression) is associated with a poor prognosis in some human tumours. The aim of this study was to determine MT expression in mammary tumours and cutaneous melanomas in dogs and cats. Canine (67) and feline (47) mammary tumours, and cutaneous melanomas (canine 40, feline 26) were immunolabelled with MT monoclonal antibody E9. The overall incidence of MT expression of these tumours was similar to that observed in various human neoplasms. However, a striking interspecies difference was detected. In dogs, MT expression occurred in 100% of benign and 57% of malignant mammary tumours. In cats, however, 30% of malignant mammary tumours expressed MT but benign mammary tumours and cases of fibroadenomatous hyperplasia did not. Moderate to strong MT immunoreactivity was detected in 30% of benign and 25% of malignant cutaneous melanomas in dogs, and in 6% of malignant melanomas in cats. The findings in feline mammary tumours resembled findings reported in human breast cancer, but the cause of tumour-associated MT expression is unknown. Studies are in progress to determine whether the MT state (apo [metal-free] or holo [metal-bound]) accounts for the paradoxical association of MT expression with individual types of tumours and the animal species in which they arise.

Adenocarcinoma↗

Immunocytochemical localization of the terminal complement complex in multiple sclerosis.

Granular deposits of C9 and the terminal complement complex, measuring 0.3-1.2 microns, have been demonstrated immunocytochemically in association with capillary endothelial cells, predominantly within plaques and adjacent white matter, in tissue obtained at autopsy from 5/7 patients with multiple sclerosis (MS) and one individual with subacute sclerosing panencephalitis but not from 7/7 controls. This finding suggests that the evolution of focal tissue damage in MS may involve complement activation associated with passage of humoral and cellular mediators of the immune system through the blood-brain barrier.

Adolescent↗

Tamm-Horsfall protein in human renal tumours.

Tamm-Horsfall Protein (THP) is found to be localised in the ascending loop of Henle and the distal tubules of normal and foetal kidneys. We have used an anti-THP monoclonal antibody (D2) to stain foetal, normal and kidney tumours. The dinitrophenyl hapten staining technique was the most specific and sensitive staining procedure. The staining of Tamm-Horsfall Protein in foetal and normal kidney was in agreement with most other investigators. The majority of renal cell carcinoma (22/24) and rhabdoid renal tumours (3/4) stained positively for THP. None of the Wilms' tumours, mesoblastic nephromas or bone metastasising renal tumours of childhood gave positive staining. The findings would suggest that renal cell carcinomas and rhabdoid kidney tumours arise from ascending loop of Henle or distal tubules. The lack of positive staining in the majority of childhood renal tumours raises the possibility of a different histogenesis for these neoplasms.

Carcinoma, Renal Cell↗