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Biomedical subjects

D Singh

Publications and source records attributed to D Singh.

At least 271 records · Page 15Linked to original sources

A new protein (J1-31 antigen, 30 kD) is expressed by astrocytes, Müller glia and ependyma.

Monoclonal antibody (MAb) J1-31 raised using human brain homogenate as immunogen in mice can be used as a cell type marker for certain types of CNS macroglia, namely astrocytes, Müller cells and tanycytes as well as ciliated ependymal cells. Except for the ciliated ependymal cells, these types of macroglia express glial fibrillary acidic protein (GFAP). J1-31 antigen is an intracellular protein which has a MW of 30 kD under reducing conditions for gel electrophoresis (Singh et al., 1986). This protein is distinct from GFAP (MW 50 kD) and vimentin (MW 55 kD), the two core proteins of 10 nm IFs known to be expressed in the above types of macroglia. This conclusion is based on several criteria including temporal differences in the onset of expression of GFAP and J1-31 antigen during development of the rat cerebellum. Also, there is no detectable (by immunofluorescence microscopy) expression of J1-31 antigen in the prenatal CNS or outside the CNS where vimentin has been reported to be abundant. The most direct evidence that J1-31 antigen and GFAP are distinct proteins comes from studies on the mature ciliated ependymal cells which do not express GFAP and yet show intense immunostaining for J1-31 antigen.

Animals↗

Chronic histological effects of ultrasonic hyperthermia on normal feline brain tissue.

The histopathological changes associated with ultrasonic heating of normal cat brain have been correlated with thermal distributions. Ultrasound energy was applied for 50 min at different intensities to generate tissue temperatures from 42 to 48 degrees C. Animals were sacrificed at various intervals from 1 to 56 days. The organization and resolution of thermal damage was characterized by three stages of histopathological changes within the nervous tissue. The acute stage (Days 1-3) was defined by (1) extensive coagulation necrosis, (2) pyknosis of neuronal elements in the gray matter, (3) edema and vacuolation in the white matter, and (4) polymorphonuclear leukocytes. The subacute stage (Days 3-21) was characterized by (1) the appearance of lipid-laden macrophages, (2) liquefaction of the necrotic regions, (3) fibroblastic proliferation, and (4) vascular proliferation with some perivascular inflammatory infiltration (lymphocytes). Lastly, the chronic stage (Days 21-56) was defined by (1) fibrosis (reticulin and collagen formation) and (2) gliosis (reactive astrocytic proliferation) occurring around the fluid-filled necrotic center. Analysis of these data has also included a study of the lesion size versus the dose (temperature for 50 min) of heating. The results demonstrate a significant linear dose-response correlation. The results of this study indicate that the histological appearance and time course of repair of thermal injury in the normal brain tissue are analogous to acute brain necrosis resulting from cerebral infarction, except the thermal damage does not result in significant hemorrhage.

Animals↗

Response of nitrosomethylurea-induced rat mammary tumor to endocrine therapy and comparison with clinical response.

We have compared the response of the N-methyl-N-nitrosourea-induced rat mammary tumor to various endocrine agents with response in patients with breast cancer. To do this, we have induced tumors in 228 animals (65% of intact rats developed tumors but only 14% of ovariectomized rats developed tumors). In intact rats, 4-hydroxyandrostenedione, tamoxifen, and a combination of tamoxifen, aminoglutethimide (AG), and danazol induced significant tumor regression (P less than 0.001, P = 0.01, P = 0.04, respectively), whereas danazol, AG, and trilostane were ineffective when used singly. Further investigation showed that the inactivity of AG in the rat was due to extensive acetylation of this compound. In order to mimic postmenopausal breast cancer, we ovariectomized rats after N-methyl-N-nitrosourea administration. In ovariectomized animals, AG was again ineffective in inducing tumor regression but 4-hydroxyandrostenedione was highly active when compared to controls (P = 0.002). Comparison with response of this model to endocrine therapy with response in patients indicates that this has good predictive capacity since it shows that agents which have minor activity in human breast cancer such as danazol and trilostane are inactive in the model. The intact rat model does not, however, predict whether a drug will be useful for pre- or postmenopausal patients. We recommend that before committing large numbers of patients to clinical trials on the basis of this model, the metabolism of new compounds should be compared in humans and rats.

Aminoglutethimide↗