The physiology of the vitamin D endocrine system

It is clear that the vitamin D endocrine system plays a central role in the maintenance of calcium and phosphate homeostasis. It may be involved in the cellular differentiation and growth of various cells. Investigation of these properties in the future is likely to yield interesting information concerning the biology of this sterol hormone.     

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate

Epidemiological studies have indirectly linked compounds ofchromium, nickel and arsenic to human carcinogenesis. However,there is no evidence that metal compounds can transform humancells to the tumorigenic phenotype in culture. We show herethat exposure to 36 µM NiS0₄ for 48–96 h resultsin transformation of an immortal, non-tumorigenic, osteoblast-likecell line, HOS TE85, to the tumorigenic phenotype. Continuouspassaging following treatment leads to the formation of a fewdense foci. The cells isolated and expanded from the foci aremorphologically transformed, and form anchorage-independentcolonies of the size and abundance comparable to that formedby Kirsten murine sarcoma virus transformed HOS TE85 cells.The transformed cells from tumors in nude mice, have enhancedlevels of plasminogen activators and have lost the ability toform model bone matrix on extended culture in the presence ofascorbic acid and ß-glycerophosphate. A number ofcell lines have been established from nude mouse tumors. Cytogeneticanalysis reveals 16 marker chromosomes and an aberrant chromosome16. This is the first report of the transformation of a humancell line to tumorigenic phenotype by a metal carcinogen.     

Estimation of high density lipoprotein cholesterol in the diagnosis of lepromatous leprosy

A high incidence of increased plasma level of high density lipoprotein cholesterol (HDL-C) has been reported in cases of lepromatous leprosy. HDL-C levels were estimated in 96 (50 under treatment and 46 untreated) lepromatous leprosy patients and 84 randomly selected matched control patients suffering from other skin diseases attending skin out-patients department. HDL-C estimations were performed for the diagnosis of lepromatous leprosy in patients aged below 60 years, taking plasma HDL-C levels as 28-71 mg./dl. in men and 34-91 mg./dl. in women, as range of normal values. The study revealed that HDL-C levels in lepromatous leprosy group were raised and significantly different when compared with control group (t = 35.1668 and P less than 0.001). The sensitivity of the test was very high, 97.9 per cent (94/96), but specificity was low 80.95 per cent (68/84). False positive and false negative results were 19.04 per cent (16/84) and 2.08 per cent (2/96) respectively. It is opined that a negative test will be mainly useful in excluding diagnosis of lepromatous leprosy.     

Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum.

Endothelin receptors (ETRs) display subtype heterogeneity and are widely distributed throughout the tissues of the periphery and central nervous system. In order to gain further insight into the potential molecular differences of ETRs, we initiated molecular cloning of ETR genes by screening for the appearance of 125I-ET-1 binding activity in COS cells transfected with pools of a porcine cerebellum cDNA expression library. Two independent clones (pPCETR 1.1 and pPCETR 5.6) were identified and isolated by repeated rounds of pool enrichment and COS cell expression. DNA sequence analysis of pPCET 1.1 and pPCET 5.6 indicated that both clones have the same nucleotide sequence; the deduced amino acid sequence indicated that the porcine cerebellum ETR is 443 residues in length and consists of seven potential transmembrane domains, with homology to members of the GTP-binding protein-coupled receptor superfamily. Northern analysis indicated a single mRNA species of about 5 kilobases, which is expressed significantly in cerebellum, lung, kidney, and pituitary. Expression of functional receptor was demonstrated by endothelin-1 (ET-1)-mediated Ca2+ mobilization in COS cells transfected with pPCETR 1.1 (COS/ETR 1.1) and ET-1-mediated electrophysiological responses in Xenopus oocytes injected with RNA derived from pPCETR 1.1. Quantitative comparison of saturation binding of 125I-ET-1 to either porcine cerebellum or COS/ETR 1.1 membranes indicated an identical apparent dissociation constant. The relative efficacy of ET-related peptides to compete for binding of 125I-ET-1 to receptor from porcine cerebellum and COS/ETR 1.1 indicated that both preparations encode a nonselective or ETBR subtype. Chemical cross-linking of 125I-ET-1 to receptor derived from cerebellum or COS/ETR 1 revealed two bands, with apparent molecular masses of 47 and 35 kDa. These data demonstrate that the pPCETR 1.1 encodes the major ETR subtype in the porcine cerebellum.     

Conformational changes in the IgG molecule of lepromatous sera using laser Raman spectroscopy

In the present work we report our studies on IgG separated from the serum of lepromatous patients and non-lepromatous leprosy cases using Laser Raman Spectroscopy. Striking spectral changes in LL cases have been observed in the following special regions: (a) the amide I and III, (b) the S-S and C-S stretching (c) the skeletal bending and (d) skeletal stretching regions. These changes indicate a decrease in the amount of beta-structure and a transition towards alpha-helical conformation.     

Protection of mouse oesophageal mucosa against gamma rays injury.

The alterations in the oesophageal epithelium were studied in mice after a single whole-body exposure to 7.5 Gy of Co-60 gamma rays in presence or absence of 2-mercaptopropionyl glycine. The epithelium showed an increase in the thickness which reached a maximum on the third day and then decreased gradually up to seventh day after irradiation in the non-drug treated group. In the 2-mercaptopropionyl glycine treated animals the epithelial thickness remained in the normal range except on the day 7 when it was significantly lower than normal. The total cell population registered a steady decline from one to seven days post-irradiation in both groups, but the number of cells was more in the 2-mercaptopropionyl glycine treated group. The number of pycnotic nuclei showed an inverse relationship to the total cell population, it increased continuously up to seven days in both the protected and non-protected groups. However, pycnotic nuclei were significantly lower in the protected group on days 3, 5 and 7 in non-protected group.     

Primary exophytic laryngeal amyloidosis presenting as sudden airway obstruction

Primary amyloidosis of larynx is an uncommon phenomenon, the precise etiopathogenesis of which is not yet clear. It can present with slowly increasing hoarseness or difficulty in breathing. It presents more commonly as infiltrative lesion, exophytic presentation is a rare occurrence.