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The effect of mercuric chloride at two different doses, 0.5 mg/kg body weight (low dose), 1 mg/kg body weight (high dose), for 30 days, was seen on the circulating hormones in the mature male albino rats. Testosterone level was markedly decreased in the low dose (P < 0.01) and high dose (P < 0.001) treated animals. The level of luteinizing hormone (LH) was also reduced in the low dose (P < 0.01) as well as in the high dose (P < 0.001) treated animals. However, follicle stimulating hormone (FSH) and prolactin (PRL) levels were found to be decreased only in the high dose (P < 0. 05) treated animals and no change was observed in the low dose treated animals. The changes in the hormone levels caused by the mercuric chloride treatment suggest the dysfunction of pituitary-testicular axis.

Infantile and juvenile neuronal ceroid lipofuscinosis (NCLs) are progressive neurodegenerative disorders of childhood with distinct ages of clinical onset, but with a similar pathological outcome. Infantile and juvenile NCL are inherited in an autosomal recessive manner due to mutations in the CLN1 and CLN3 genes, respectively. Recently developed Cln1- and Cln3-knockout mouse models share similarities in pathology with the respective human disease. Using oligonucleotide arrays we identified reproducible changes in gene expression in the brains of both 10-week-old Cln1- and Cln3-knockout mice as compared to wild-type controls, and confirmed changes in levels of several of the cognate proteins by immunoblotting. Despite the similarities in pathology, the two mutations affect the expression of different, non-overlapping sets of genes. The possible significance of these changes and the pathological mechanisms underlying NCL diseases are discussed.

Aim: To study the effect of mercuric chloride on the membrane-bound enzymes., Methods: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane-bound enzymes in the testis of adult albino rats., Results: Mercuric chloride significantly decreased the body weight and testis weight in the high dose group (P< 0.05), but not in the low dose group. The activities of 5'nucleotidase and adenosine triphosphatases were markedly decreased (P< 0.01) in the testis of both groups. Alkaline phosphatase and ggr-glutamyl transferase activities were significantly increased (P< 0.01) in both groups. However, the effect was more pronounced in the high than in the low dose groups., Conclusion: The dose dependent effect of mercuric chloride on these enzymes may affect the membrane characteristics and thereby the fertility of the animal.

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase that regulates a wide variety of cellular processes. The enzymatic activity and intracellular localization of PP2A are determined by three distinct families of cellular regulatory subunits (B, B'', and B''). The B' subunit, also known as B56, is the most diverse, consisting of five isoforms (alpha, beta, gamma, delta, and epsilon). The gene encoding B56gamma has been designated as PPP2R5C and encodes three differentially spliced variants: B56gamma1, -gamma2, and -gamma3. However, conflicting chromosomal loci have been reported in human genomic databases. The original cytogenetic mapping placed the gene on chromosome 3p21.3, whereas subsequent studies using radiation hybrid analysis localized PPP2R5C to chromosome 14q. In this study, by radiation hybrid mapping, FISH analysis, BAC clone sequencing, and RT-PCR analysis, we show that the functional gene PPP2R5C exists at 14q32.2 and gives rise to three splicing variants, B56gamma1, -gamma2, and -gamma3, whereas a nonfunctional B56gamma1 pseudogene, PPP2R5CP, is present at 3p21.3. We also report the genomic organization of both the functional gene and the pseudogene.

The enzymes involved in carbohydrate metabolism and their relationship with circulating estradiol (ET2) and prolactin (Prl) were studied in premenopausal and postmenopausal women with fibroadenoma and carcinoma of breast. The activities of all the glycolytic enzymes studied were increased in breast carcinoma tissues except for glyceraldehyde-3-phosphate dehydrogenase which showed decreased activity. Among the glycolytic enzymes studied, hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase were found to be stimulated by elevated levels of serum ET2 and further stimulated by a simultaneous increase in Prl. However, the activity of lactate dehydrogenase was more specifically stimulated by Prl rather than ET2. None of the glycolytic enzymes studied was altered in fibroadenoma breast tissues.

Alkaline phosphatase, 5'nucleotidase and gammaglutamyl transferase were studied in premenopausal and post-menopausal women with fibroadenoma and breast carcinoma tissues. The relationship of circulating estradiol (E2) and prolactin (Prl) with these enzymes was also investigated. All the three enzyme activities were found to be elevated in the breast carcinoma tissues of both pre- and postmenopausal groups. None of the membrane bound enzymes studied was altered in fibroadenoma breast tissues. The activities of all the three enzymes in breast carcinoma tissues were stimulated by the elevated level of serum Prl and further stimulated by a simultaneous increase in E2.

Different serum hormones were studied in patients with benign breast diseases and breast carcinoma in respect of different phases of the menstrual cycle, as well as in postmenopausal women. In premenopausal breast carcinoma subjects 10% showed elevated serum estradiol alone, 7% showed elevated serum prolactin alone, and 12% subjects exhibited elevated levels of both serum estradiol and prolactin. Similarly, in postmenopausal breast carcinoma subjects 12% showed elevated serum estradiol alone, 10% showed elevated serum prolactin alone, and 22% exhibited elevated level of both serum estradiol and prolactin. On the other hand, in patients with benign breast disease only 5 showed an elevated level of prolactin alone. More than 50% of premenopausal women with carcinoma of the breast had low level of serum progesterone during the luteal phase as compared to normal subjects. No variations in serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were evident between normal subjects and women with breast carcinoma or benign breast disease. The increased level of serum estradiol and prolactin may be useful in the diagnosis of human breast cancer.

The structure of isocitrate dehydrogenase [threo-DS-isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42] from Escherichia coli has been solved and refined at 2.5 A resolution and is topologically different from that of any other dehydrogenase. This enzyme, a dimer of identical 416-residue subunits, is inactivated by phosphorylation at Ser-113, which lies at the edge of an interdomain pocket that also contains many residues conserved between isocitrate dehydrogenase and isopropylmalate dehydrogenase. Isocitrate dehydrogenase contains an unusual clasp-like domain in which both polypeptide chains in the dimer interlock. Based on the structure of isocitrate dehydrogenase and conservation with isopropylmalate dehydrogenase, we suggest that the active site lies in an interdomain pocket close to the phosphorylation site.