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.     

Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: A study on multibacillary leprosy patients from North India

118 multibacillary leprosy patients with differential manifestations were studied for the antigens they expressed at MHC loci to investigate the role of human leukocyte antigens in the differential response to the same causative agent. While the lepromatous leprosy (LL) patients showed a significant increase of Bw60, DR2, DRw8 and DQw1, borderline lepromatous (BL) patients had Bw52, DR9 and DQw7 significantly more often as compared to the normal controls. A comparison of LL, BL and mid-borderline (BB) patients showed a significantly higher frequency of Bw60 in LL patients as compared to the BL. However, Bw52, Bw53, DR9 and DQw7 were found significantly more often in the BL patients as compared to the LL patients but the difference failed to reach significance after pc. A comparison of HLA antigens in BB patients with those of either the LL or BL patients did not show any significant differences.     

Molecular epidemiology of norovirus variants detected in children under five years of age in Hyderabad,India

PurposeNoroviruses are common viral agents in acute diarrhea in all age groups worldwide. Norovirus has been classified into 10 genogroups, GI to GX with over 48 genotypes among them the GII.4 genotype has evolved over time with a clear pattern of periodic variant replacement. Immunity is strain or genotype specific with little or no protection conferred across genogroups. The present study was aimed to determine the epidemiology, prevalent genotypes of norovirus in children below five years of age in the Hyderabad region, India.MethodsThe stool samples and clinical data were collected from 458 children below 5 years of age comprising of cases with acute gastroenteritis (n ?= ?366) and a control group (n ?= ?92) admitted to the pediatric ward. All the samples were tested for Norovirus by ELISA and RT-PCR. Sequencing was done for predominant strains.Results10.3% (n ?= ?38) of cases and 3.2% (n ?= ?3) of the control group were found to be Norovirus positive. Predominant genotypes were GII-82.5% followed by GI-12.5%.ConclusionSequencing and Phylogenetic analyses of 20 GII.4 strains was done. All of the isolates are clustered away from published the GII.4 variants thus suggesting the appearance of a new variant.     

Association of HLA antigens with differential responsiveness toMycobacterium w vaccine in multibacillary leprosy patients

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness toMycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium,Mycobacterium w, which has cross-reactive antigens withM. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8+9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to theM. w vaccine. However, these associations were not significant afterP correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness toM. w vaccine.     

Alteration in plasma glucose levels in Japanese encephalitis patients

A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia.     

Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups

We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.     

Correlation between chemical composition of biliary calculi and sera of stone formers

A quantitative chemical analysis of total cholesterol, bilirubin, calcium, inorganic phosphate and iron of three types of biliary calculi (cholesterol, pigment and mixed) of 40 gall stone former was carried out and correlated to with those of there sera. A moderately positive correlation for inorganic phosphate, Ca2+ and Fe2+ content of sera and calculi of cholesterol stone patient was found. A Good positive correlation for total cholesterol, a moderately positive correlation for bilirubin and iron but no correlation for inorganic phosphate and calcium content of sera and calculi of pigment stone patient was observed. A good moderately positive correlation for iron but no correlation for total cholesterol, bilirubin, inorganic phosphate and Ca2+ content of sera and calculi of stone patient was found.