Multicentric study on prevalence and risk factors for hypertension and diabetes in tribal communities in Western and Northern Maharashtra.

BACKGROUND AND OBJECTIVES: Although a number of studies have been conducted on the prevalence of hypertension (HTN) and diabetes on tribal populations in different parts of India, comparative tribe-specific information is very meager. The main objective of this study is to generate tribe-specific information on the noncommunicable disorders (NCDs) and associated risk factors in scheduled tribes (STs) in Coastal and Western Maharashtra. METHODS: The study was conducted on 1864 (females 960) adults (≥18 years) of both sexes in four dominant tribes in the region, namely, Bhils (748), Katkaris (560), Kokana (352), and Thakars (204), using the protocols approved by the Institutional Review Board. The study areas were geographically separated by large distances (250-500 km apart). Prevalence of overweight, diabetes, HTN, and hypercholesterolemia was measured using standard field-based techniques described in our earlier publication. RESULTS: All STs in this study are grossly underweight; the Katkaris are worst affected. The prevalence of obesity (body mass index ≥30 kg/m2), HTN (blood pressure ≥140 mmHg), diabetes (capillary blood glucose >126 mg/dl), and hypercholesterolemia (cholesterol ≥200 mg/dl) was 0.9%, 11.7%, 6.7%, and 0.6% respectively. There are no statistically significant inter-tribal differences in the prevalence of these parameters. Age and obesity appeared to be the most dominant risk factors for HTN. However, there is no clear-cut picture about the influence of risk factors on diabetes or hypercholesterolemia. INTERPRETATION AND CONCLUSION: The prevalence of NCDs is still very low in STs, probably due to near absence of the risk factors such as obesity, sedentary lifestyle, and hyperlipidemia. STs are highly endogamous, and the study areas are separated by large distances ruling out intermingling of tribes. Yet, there is no consistent inter-tribal prevalence pattern for NCDs. Although the sample size is small, the results support the view that environmental factors are likely to be more important than host genetics in the causation of NCDs.

Prevalence and risk factors of hypertension and diabetes in the Katkari tribe of coastal Maharashtra.

BACKGROUND AND OBJECTIVES: Urban and rural India are both going through health epidemiological transition and will soon face huge burden of noncommunicable diseases (NCDs). Information on the status of NCDs in tribals is limited. Although the prevalence of hypertension in scheduled tribes (STs) has been studied in several states by the National Nutrition Monitoring Bureau, tribe-specific data are very scanty. The objective of this study was to generate data on the status of hypertension and diabetes, the two objectively measurable NCDs in Katkaris, the dominant ST in the Raigad district of coastal Maharashtra. METHODS: The study was conducted in 410 adult Katkaris (women 219) of both sexes of ≥18 years of age in three adjoining tehsils of the district. Using the Institution Review Board approved protocol; information was obtained on sociodemographic parameters, educational level, dietary pattern, and substance abuse. Prevalence of overweight, hypertension, and diabetes was measured using standard field-based procedures and techniques. RESULTS: Katkaris, who are mostly landless manual laborers, subsist on a protein-poor, imbalanced diet. About half of women and one-third of men have body mass index (BMI) <18.5 kg/m2, an indication of undernutrition. On the other hand, about 2% of participants were obese (BMI ≥30 kg/m2). The overall prevalence of hypertension and diabetes was 16.8% and 7.3%, respectively. Hypercholesterolemia was recorded in about 3% of the participants. INTERPRETATION AND CONCLUSIONS: Prevalence of diabetes and hypertension in Katkaris is still lower than that of urban and rural populations, closer to the latter. This may be due to the absence of known risk factors such as obesity, sedentary lifestyle, and hyperlipidemia in this community. Fast acculturation of the STs suggests that NCDs will soon become a major health issue in them too. It is time to launch a multicentric national study to gather baseline information on the status of NCDs in STs.

Undernutrition and the developing cerebellar cortex in the rat.

Undernutrition of the newborn rats, produced during the first 3 weeks by increasing the litter size and restricting the mother's diet, resulted in reduction of the body and brain weights of the experimental animals. One group of undernourished animals showed especially severe reduction of body and cerebellar weights. These animals, on the 10th postnatal day, had an immature cerebellar cortex corresponding to that of the 7th day postnatal control animals. The external granular layer persisted in the cerebellar cortex of the underweight animals until the 23rd day, while it disappeared by 20th day in the control animals. Mitotic activity was evident until the 21st postnatal day in these animals while it stopped in the normal animal by 16th postnatal day. There was no marked difference in the fine structure of the various cell types in the control and undernourished animals. Midsagittal tracings of the cerebellar cortex showed a reduced surface area in the undernourished animals, while the thickness of the external granular layer and molecular layer did not show any significant difference when compared to that of the control animals, thus showing a reduction in total cell number, but not per unit area. The normal morphological appearance of the cerebellar cortex in the underfed animals of higher weight probably indicates that these animals are adequately nourished in spite of the reduction in weight when compared to the control animals, which probably are overfed.

Purification of the enhancing factor from mouse intestines.

A unique polypeptide, called enhancing factor (EF), which enhances the binding of labeled epidermal growth factor (EGF) to cells, has been isolated. It has been purified to homogeneity from the acid-soluble proteins of mouse intestines. Earlier, EF was partially purified by two cycles of gel-permeation chromatography on Bio-Gel columns. We now report the final purification of EF on high-performance liquid chromatography (HPLC), using a reverse-phase column (mu Bondapak C18). The purity of the protein was confirmed when a single peak was obtained in HPLC. Also, a single protein band was obtained in SDS-PAGE. Purified EF has the same properties in vitro as those reported earlier for partially purified EF.

Enhancing factor protein from mouse small intestines belongs to the phospholipase A2 family.

Enhancing factor (EF), a growth regulatory molecule, isolated from mouse small intestines, has been well characterized in this laboratory. It increases the binding of epidermal growth factor in a unique manner via its own receptor. In the first 20 N-terminal amino acids sequenced, EF showed 50% homology to human Group II phospholipase A2 (PLA2). Here we propose that EF is yet another, unidentified isoform of PLA2 which regulates cell proliferation via modulation of EGF binding. To our knowledge, this is the first report implicating PLA2-II-like molecules in growth regulation.

Restriction fragment length polymorphism of the L-myc oncogene in non-Hodgkin's lymphoma patients from India.

We examined 89 non-Hodgkin's lymphoma (NHL) patients of Indian origin for EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene with a view to testing the hypothesis that the presence of the L-myc S-allele predisposes towards NHL. We found no significant difference either in the distribution of the LL, LS and SS genotypes or in the allelic frequencies between the patient group and the control group with the frequencies of L-myc alleles, L (10.0 kb) and S (6.6 kb), being 0.56 and 0.44, respectively, in the patient group and 0.54 and 0.46, respectively, in the control group. However, a higher proportion (70%) of the S-allele was observed in our control group of normal healthy volunteers. Thus, the presence of L-myc S-allele did not indicate increased susceptibility or predisposition to the malignancy.

Establishment of a human squamous cell carcinoma cell line of the upper aero-digestive tract.

A human squamous cell carcinoma (SCC) cell line has been established from the surgical specimen of an untreated, upper aero-digestive tract tumour, diagnosed as a squamous carcinoma, grade III, of the pyriform fossa. The tumour tissue was grown as a xenograft in an athymic nude mouse and was designated as NT-8. Histological examination of the surgical specimen and the nude mouse tumour showed that the two were identical. NT-8 was subsequently passed by subcutaneous injections into nude mice. After the 6th passage in nude mouse, the tumour was cultured in vitro where it grew as an epithelial cell line, with a typical cobblestone appearance. This cell line was designated as NT-8e. Both the primary tumour as well as xenograft and the cells in culture have retained several common morphological and biochemical characteristics. Immunological markers for epithelial cells including epithelial membrane antigen and cytokeratins were seen in all three, confirming the epithelial lineage. Characterization of the NT-8e cell line including growth parameters, anchorage-independent growth and tumorigenicity in nude mice, chromosome counts and DNA content by flow cytometry have been carried out.

Implications of malnutrition in chemical carcinogenesis.

Epidemiological data indicate that life style, including dietary "imbalances", play a major role in etiology of human cancers. Although two thirds of the world population suffer from varying grades of protein-caloric malnutrition (PCM) today, no consistent pattern is found to be associated wih PCM both in man and laboratory animals. At the tissue level, depression of cellular proliferation by prolongation of DNA-synthetic phase is a characteristic lesion of PCM. Due to changes in liver mixed function oxidases, metabolism of drugs is affected. The cell-mediated immunity is depressed and there is a defective mobilisation of macrophages. These alterations would modulate carcinogenesis; some tend to enhance, while others inhibit tumorigenesis. The balance of evidence suggest that PCM is unlikely to have dominant modulating influence on carcinogenesis.

Loss of allelic heterozygosity at the harvey ras locus in human oral carcinomas.

The Harvey ras locus was examined for restriction fragment polymorphism and loss of allelic heterozygosity in 62 oral cancer patients. Southern blot analysis on BamHI digests of the tumour tissue DNA, revealed 23 patients with H-ras-1 heterozygosity. The probes used to study the polymorphism were the BamHI 6.6-kb fragment encoding the complete H-ras-1 sequence plus the variable tandem repeat (VTR) region, and the 1-kb MspI fragment encoding the VTR region. The allelic heterozygosity was better resolved by PvuII and further confirmed by TaqI. In addition, TaqI digestion demonstrated a unique VTR rearrangement indicated by 2.1-kb, 0.9-kb and 0.6-kb fragments, implying additional TaqI sites, in three of the patients. Further analysis of matched tumor tissue and peripheral blood cell DNA from the same patient demonstrated tumor-associated loss of one of the allelic fragments in 7/23 (30%) of the patients with H-ras-1 heterozygosity. However, the loss was not significantly correlated to clinicopathological parameters staging the disease. Thus, our data showing loss of H-ras-1 alleles and VTR rearrangement, with relatively high incidence (9/23; 39%) in the oral cancer patients at various stages of the disease, implies H-ras-1 involvement as an early event in the process of oral carcinogenesis.

Adrenocortical function in experimental protein malnutrition.

Adrenocorticoid activity was investigated in experimentally induced protein malnutrition in Rhesus monkeys. Control studies were carried out in the same animals before inducing protein malnutrition. Plasma cortisol levels were elevated in the protein malnourished state. There was a total abolition of the diurnal rhythm of cortisol secretion. Fasting hypoglycemia was also observed in the protein malnourished state. It is concluded that increased adrenocorticoid activity and sustained steroidogenesis result from protein deficiency. Hypoglycemia may be an important stimulus, in addition to the metabolic stress imposed by the protein deprivation. The recognition of increased adrenocorticoid activity is important in a protein-deficient host, since the defense against infections might be impaired in such a situation.

The sociocultural dimension in leprosy vaccine trials.

This paper briefly describes organizational, operational, and sociocultural aspects of the phase-III clinical trials of the ICRC anti-leprosy vaccine in Maharashtra, India. Our experience is that vaccine trials can be launched quickly and more cost effectively by using the services of health personnel from the existing public health infrastructure. That is why the trials could be launched in just 4 months after receiving the financial grant from the Indian Council of Medical Research, New Delhi (India). At the community level, a person-to-person approach in Health Education scores over audio-visual aids and the mass media. The compliance in target groups is increased when preventive programmes are backed-up by curative services and when their privacy and daily routine are not disturbed.

Aflatoxin B1-induced injury in monkeys.

Short-term effects of small doses of aflatoxin (0.05 mg/kg of body weight twice a week) were studied in rhesus monkeys fed low-protein and high-protein diets. Animals on high- and low-protein diets without aflatoxin administration served as controls. There was no difference in weight gain, hemogram, serum protein levels, and liver function test results between aflatoxin-treated and control animals. However, morphological alterations in hepatocytes in the form of mild degenerative changes, focal areas of necrosis, and increased regenerative activity were seen in the aflatoxin-treated monkeys. Data on cell cycle analysis done by DNA content estimation through microfluorimetry on DNA-fluorescent, acriflavin-stained liver imprints revealed larger number of cells in the S and Gi2 phases in animals given aflatoxin. However, the changes in cell cycle, as well as in morphology, were more marked in the aflatoxin-treated, low-protein-diet group.

Anti-leprosy vaccines--field trials and future prospects.

Development of a vaccine for prevention of leprosy is today one of the major challenges for bio-medical sciences. Two vaccines containing (i) M. leprae + BCG and (ii) ICRC, a cultivable mycobacterium, have reached advanced stage with reference to human trials. This article describes comparative features of two vaccines and mechanism of their action. Future possibilities with reference to anti-leprosy vaccine are also discussed.

Loss of p53 gene as a biomarker of high risk oral leukoplakias.

We have investigated loss of heterozygosity of p53 tumor suppressor gene in Indian oral cancer patients, individuals with premalignant leukoplakia lesions, and corresponding normal mucosa, to study the status of p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral mucosa from 18 individuals, were analysed. Peripheral blood cells (PBCs) from all the individuals and 47 normal healthy volunteers were also included in the study. Polymerase chain reaction(PCR) of p53 Exon4, followed by restriction enzyme digestion with AccII due to the enzyme polymorphic site at Exon4 codon72, was used to detect homozygosity/heterozygosity of p53 alleles, and compared with the allelic pattern in the corresponding PBC. The PCR product subjected to AccII digestion detected 259 bp, 160/99 bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribution in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 allele in early and advanced stages of oral cancers, as well as leukoplakias, perhaps indicating p53 LOH as one of the early events in oral carcinogenesis. Thus, p53 LOH may be useful as a biomarker in defining a certain population of high risk leukoplakias that may progress to oral cancer.

Restriction fragment length polymorphisms of the human N-myc gene in normal healthy individuals and oral cancer patients in India.

Southern blot hybridization with N-myc oncogene probes coding for different regions of the N-myc gene demonstrated three polymorphic restriction sites in the Indian population. The SphI and PvuII polymorphic pattern due to the SphI polymorphic site in the second intron and the PvuII polymorphic site in the 3'-region of the human N-myc oncogene respectively, was similar to that reported in the Japanese population. The allelic frequency distribution for SphI polymorphism did not differ significantly for the S1 and S2 alleles representing presence (allele S1) or absence (allele S2) of a SphI site. However, the allelic frequency distribution was distorted in the case of PvuII polymorphism, as the frequency of P1 allele (0.7) indicating presence of PvuII site, was higher than the P2 allele (0.3) indicating absence of PvuII site, in the Indian population. An additional polymorphic HindIII site localised in the second intron of the N-myc gene was also observed in both the Indian oral cancer patients and the normal healthy individuals, indicating that this RFLP was not tumor associated and may perhaps represent N-myc alteration in the Indian population.