Glycosaminoglycans of normal and malignant cultured human mammary cells.

Glycosaminoglycans have been characterized from a normal human breast cell line (HBL-100) and two different cell lines from human breast carcinoma (MDA-MB-231 and MCF-7). The glycosaminoglycans were labeled by exposure of cell cultures to [3H]glucosamine and [35S]sulfate and then isolated from both spent media and cells by pronase digestion and cetylpyridinium chloride fractionation. They were further characterized by (a) hexosamine composition, (b) controlled-pore glass exclusion chromatography, (c) reactivity with specific enzymes (hyaluronidase chondroitinase, heparitinase, and heparinase), (d) nitrous acid degradation, and (e) DEAD-Sephadex chromatography. The results indicate that the HBL-100 line synthesizes mainly hyaluronic acid, most of which is secreted into the medium. Chondroitin sulfate and heparan sulfate are the predominant glycosaminoglycans synthesized by the cancer lines; both are found mainly in the spent medium, but the hyaluronic acid synthesized by the MDA-MB-231 line remains cell associated. The cell-associated heparan sulfate had a molecular weight in excess of 13,000 and may contain linkages susceptible to testicular hyaluronidase. The MCF-7 cells produce significantly lower amounts of glycosaminoglycans than do the other two lines.     

Surface proteins of simian-virus-40-transformed cells

Mammalian cells transformed in tissue culture by SV40 were shown to contain, in addition to the SV40-coded 94,000 d large T antigen and the 20, 000 d small t antigen, a ～ 56,000 d cellular protein, which specifically precipitates with sera of animals bearing SV40-induced tumor (s) (tumor or T serum). We investigated the presence of these three proteins at the surface of logarithmically growing SV40-transformed cloned mouse cells, after metabolic labelling with [³⁵S]-methionine for 3 h. The 56,000 d protein was found to be susceptible to digestion by trypsin under conditions which did not disrupt the cells, while no small t antigen was found to be digested. Both the 56,000 d cellular protein and the SV40 large T antigen were susceptible to lactoperoxi-dase-catalyzed iodination from the outside of intact cells. Trypsin treatment removed both the iodinated 56,000 d protein and the iodinated SV40 large T antigen. These experiments indicated that (a certain amount of) the 56,000 d protein and a relatively small amount of the large T antigen (which is present mainly in the nucleus) are present on the cell surface. The results confirm and extend independent experiments using subcellular frac-tionation techniques (Luborsky and Chandrasekaran, 1980; Soule and Butel, 1979). After heat treatment (at 50°C for 30 min) of the whole-cell extract the 56,000 d cellular protein was precipitated by the tumor serum in the absence of precipitation of SV40 large T antigen. This result showed that the 56,000 d protein is more (thermostable (in the whole-cell extract) than the SV40 large T antigen, and also indicated that the tumor serum employed had antibodies against the 56,000 d cellular antigen. The heat-treated whole-cell extract of SV40-transformed mouse cells was able to immunize and fully protect mice against a lethal tumorigenic dose of SV40-transformed cells. These results suggest the need for further experiments to characterize the chemical and immunologic properties of the 56,000 d protein.     

DOTS reaches socially marginalized population in the community: a study from a rural area of South India

We report here that the Directly Observed Treatment, Short course (DOTS) is reaching all tuberculosis patients in the community irrespective of social classification based on the analysis from the tuberculosis prevalence survey and programme performance during 1999-2003 from a rural area in Tamilnadu, South India. New smear- positive cases treated under a DOTS programme were classified in two groups namely; scheduled caste living in colony and other population. The prevalence of smear- positive cases among the scheduled caste population was 1.9 times higher than the other population and this was reflected in the notification also. The successful treatment outcome was also similar in these two groups (75% and 78% respectively; overall 77%). From these findings it is concluded that people living in colony have equal access to DOTS as those in the village.     

Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients

Objective  

Cytochrome P450 2C9 and 2C19 (CYP2C9 and CYP2C19, respectively) genetic polymorphisms play an important role in phenytoin (PHT) metabolism. We have evaluated whether these genetic polymorphisms have an effect on PHT-induced neurological toxicity in Tamilian (ethnic group native to southern India) patients with epilepsy.