Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of the BRCA1 and BRCA2 germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. Comprehensive BRCA mutation screening was performed using a range of techniques, including denaturing high-pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ-line mutations were identified in the 176 families (17.0%), including 23 in BRCA1 and 7 in BRCA2. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identified BRCA1 mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence of BRCA1 or BRCA2 mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early-onset breast cancer (30 years) and was 9.0% for single cases of early-onset ovarian cancer (45 years). Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer and early-onset breast and ovarian cancer cases in Pakistan. ' 2006 Wiley-Liss, Inc.Key words: BRCA1; BRCA2; germ line mutations; hereditary breast/ ovarian cancer; Pakistan Breast cancer is the most common malignancy among Pakistani women, accounting for 34.6% of all female cancers. Ovarian cancer is the third most common malignancy.1 Among Asian countries, Pakistan not only has the highest rate of breast cancer (excluding Jewish women in Israel) 2 but also of ovarian cancer. 3The Karachi Cancer Registry reported an age-standardized (world) annual rate of breast cancer of 69.1 per 100,000. These rates resemble those reported in parts of Europe and North America. 1,4Affected women typically present below 40 years of age. 5,6Approximately 5% of breast cancers and 10% of ovarian cancers are due to germ-line mutations in the BRCA1 (MIM 113705) and BRCA2 (MIM 600185) genes. 7,8 Mutations in these genes are responsible for familial clustering for the majority of breast and ovarian cancer families and for about one-half of site-specific breast cancer families.9-11 It has been estimated that women carrying deleterious mutations in either of these genes face a lifetime risk of breast cancer ranging from 36 to 92%11-14 and of ovarian cancer between 16 and 63%.11,14 Women and men who carry BRCA2 mutations also have increased risks of pancreatic cancer, prostate cancer and melanoma. 15 The frequency and spectrum of mutations within these genes show considerable variation by ethnic group and by geographic region. To date, the majority of studies on the prevalence of the BRCA1 and BRCA2 mutations have been performed in white populations, but recently studies have also been conducted on Asian populations. 16 Little is known about the contribution...

The progressive differentiation of both normal rat osteoblasts and HL-60 promyelocytic leukemia cells involves the sequential expression of specific genes encoding proteins that are characteristic of their respective developing cellular phenotypes. In addition to the selective expression of various phenotype marker genes, several members of the heat shock gene family exhibit differential expression throughout the developmental sequence of these two cell types. As determined by steady state mRNA levels, in both osteoblasts and HL-60 cells expression of hsp27, hsp60, hsp70, hsp89 alpha, and hsp89 beta may be associated with the modifications in gene expression and cellular architecture that occur during differentiation. In both differentiation systems, the expression of hsp27 mRNA shows a 2.5-fold increase with the down-regulation of proliferation while hsp60 mRNA levels are maximal during active proliferation and subsequently decline post-proliferatively. mRNA expression of two members of the hsp90 family decreases with the shutdown of proliferation, with a parallel relationship between hsp89 alpha mRNA levels and proliferation in osteoblasts and a delay in down-regulation of hsp89 alpha mRNA levels in HL-60 cells and of hsp89 beta mRNA in both systems. Hsp70 mRNA rapidly increases, almost twofold, as proliferation decreases in HL-60 cells but during osteoblast growth and differentiation was only minimally detectable and showed no significant changes. Although the presence of the various hsp mRNA species is maintained at some level throughout the developmental sequence of both osteoblasts and HL-60 cells, changes in the extent to which the heat shock genes are expressed occur primarily in association with the decline of proliferative activity. The observed differences in patterns of expression for the various heat shock genes are consistent with involvement in mediating a series of regulatory events functionally related to the control of both cell growth and differentiation.

A gram-positive, chromium (Cr)-resistant bacterial strain (ATCC 700729) was isolated from effluent of tanneries. It was grown in media containing potassium dichromate concentration up to 80 mg ml(-1) of the medium. The dichromate reducing capability of the bacterium was checked by estimating the amount of Cr VI in the medium before and after introduction of bacterial culture. The influence of factors like pH of the medium, concentration of Cr, and the amount of the inoculum was studied to determine the ability of the bacterium to reduce Cr VI in the medium under various conditions. In a medium containing dichromate 20 mg ml(-1) more than 87% reduction of dichromate ions was achieved within 72 h. The feasibility of the use of this bacterial strain for detoxification of dichromate in the industrial wastewater has been assessed. The isolated strain can be exploited for specific environmental clean-up operations.

No abstract

A cypermethrin-mixed diet was fed uninterrupted to male albino rats for six months to evaluate toxicity in nontarget organisms. The rats consumed cypermethrin at a dose of 420 mg active ingredient (AI) per kilogram body weight per day. At the end of the stipulated period, the blood and liver were analyzed for insecticidal toxicity. The hemoglobin content and white blood cell (WBC) count remained unaltered, while the red blood cell (RBC) count and packed-cell volume (PCV) decreased significantly. The blood serum lactate dehydrogenase (LDH), isocitrate dehydrogenase (ICDH), and amylase activities were elevated 61%, 30%, and 46%, respectively, after six months of insecticide feeding, suggesting liver and possibly pancreas malfunction. The glutamate oxaloacetate transaminase (GOT) and creatine phosphokinase (CPK) activities, on the other hand, decreased 37% and 40%, respectively. The blood serum protein and free amino acids (FAA) content increased 12% and 31%, respectively, while cholesterol content decreased 49%. Consequent to cypermethrin administration the hepatic GOT, LDH, and ICDH activities increased 250%, 20%, and 30%, respectively. The soluble proteins, FAA, and glucose contents exhibited significant increases of 28%, 61%, and 71%, respectively. Histological changes were marked by hypertrophied hepatic cells and nuclei.