Cytochrome P4501B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones, including 17beta-oestradiol (E2) and testosterone. We report a significant difference in the allele frequencies of two point mutations in the coding region of the CYP1B1 gene among Caucasian (n = 189), African-American (n = 52) and Chinese (Linxian) (n = 109) populations. A (C to G) transversion at position 1666 in exon 3, which results in an amino acid substitution of Leu432 to Val, was present in African-Americans with an allele frequency for Va1432 of 0.75, in Caucasians of 0.43, and in Chinese of 0.17. A (C to T) transition at position 1719 in exon 3, with no amino acid change (Asp449), appeared to be closely linked with the Val432 variant. Results using human lung microsomal preparations from individuals with the CYP1B1Val/Val and CYP1B1Leu/Leu genotypes indicate that Val432 variant may be a high activity allele and thus may contribute to the interindividual differences in CYP1B1 activity. Because CYP1B1 is involved in hormone and carcinogen metabolism, and given the disparate rates of prostate cancer among ethnic groups, we also evaluated the association of the CYP1B1 Leu432Val polymorphism with prostate cancer risk in a pilot case-control study. Among Caucasians, 34% of men with cancer (n = 50) were homozygous for the Val432 polymorphism, while only 12% of matched control subjects (n = 50) had this genotype. These preliminary data indicate that genetic polymorphisms in CYP1B1 might play an important role in human prostate carcinogenesis.

Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and lowpenetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (P enrich ‫؍‬ .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n ‫؍‬ 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer.

Arthrogryposis Multiplex Congenita is a descriptive term with various etiologies and complex clinical features including multiple joint contractures of various limb joints. It is associated with malformations, malfunctions and neurologic deficiencies. We report the case of a new born term female child admitted at Rural Medical College, Ahmednagar (Maharashtra) with positive family history and evident clinical features of arthrogryposis multiplex congenita. Multidisciplinary management was instituted. This case is presented for its rarity.

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Asphyxia is an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs.1 National Neonatology Forum of India has defined asphyxia as gasping or ineffective breathing or lack of breathing at 1 min of life.2Birth asphyxia is one of the most important causes of neonatal brain injury whose incidence ranges from 3.7 to 9/1000 deliveries in the west.3 With the advent of therapeutic hypothermia (TH), improved outcomes are being reported in moderate HIE. TH, however, has not demonstrated improvement in outcomes related to severe HIE. . This has led clinicians and researchers to continue evaluating complementary and/or alternative therapies for infants with HIE. In this review, we will discuss current and emerging therapies in the management of HIE, other than hypothermia. With issues of access to health care and the burden of birth asphyxia shifting to developing and least developed nations, there is a need for alternative and supplementary neuroprotective agents. Low cost and easy availability along with ease of use would assist in ensuring that these therapies have global applicability. So global efforts must be taken to increase such studies as birth asphyxia is causing more morbidity & mortality globally.