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Biomedical subjects

M G Deo

Publications and source records attributed to M G Deo.

At least 55 records · Page 3Linked to original sources
PubMed1989

ICRC mouse with congenital mega-esophagus as a model to study esophageal tumorigenesis.

ICRC mouse, an inbred strain, developed at the Cancer Research Institute, Bombay, exhibits mega-esophagus with markedly hyperplastic mucosa. Diethylnitrosamine (DEN) when given in drinking water at the dose of 4 mg/kg body weight/day, induced esophageal papillomas consistently in 100% of the animals, in a short period of 12 weeks. Further, tumors were produced, even at a very low cumulative dose of 28 mg/kg body weight. Development of the esophageal papillomas was dose dependent. DEN even induces esophageal tumors transplacentally in the ICRC F1 progeny. Tobacco acts predominantly as a promoter in this system. ICRC mouse thus provides a much needed animal model to study esophageal tumorigenesis, including the two-stage carcinogenesis. An interesting feature of the study is that initiation could be induced by exposure to low doses of DEN in the intra-uterine life. Tumors develop in such F1 animals only if they are fed tobacco, a predominant promoter, post-natally.

Aging↗
PubMed1989

Oncogene amplification in squamous cell carcinoma of the oral cavity.

We have determined the prevalence of amplification of c-myc, N-myc, L-myc, H-ras, Ki-ras, and N-ras oncogenes in 23 cases of squamous cell carcinoma of the oral cavity, using Southern hybridization analysis of DNA extracted from the primary tumor tissues. Nick-translated oncogene probes and oncogene inserts labeled to high specific activities were used. We observed a 5- to 10-fold amplification of one or more of c-myc, N-myc, Ki-ras and N-ras oncogenes in 56% of the tumor tissue samples, with these oncogenes not being amplified in the peripheral blood cells of the same patients. L-myc and H-ras were not amplified in any of our samples. The oncogene amplifications seemed to be associated with advanced stages of squamous cell carcinomas, with the ras and myc family oncogenes being amplified in stages 3 and 4. Hybridization with N-myc detected an additional 2.3 kb EcoRI fragment, along with the normal 2.1 kb fragment. Our data also demonstrated amplification of multiple oncogenes in the same tumor tissue sample. About 60% of the samples with amplified oncogenes showed simultaneous amplification of 2 or more oncogenes. The results showing different oncogene amplifications in similar tumors, as well as multiple oncogene amplifications in the same tumor, suggest that these oncogenes may be alternatively or simultaneously activated in oral carcinogenesis.

Adult↗
PubMed1988

Antigenic profile of ICRC bacilli with special reference to isolation of immunogenic subunit.

A vaccine containing ICRC bacilli induces persistent immune conversion in lepromatous leprosy (LL) patients and lepromin-negative healthy subjects, in association with upgrading of the tissue responses in the former. With an idea to isolate the immunogenic 'subunit(s)', antigenicity of ICRC sonicate and its fractions were tested, with reference to both B- and T-cell responses. A very high molecular weight glycolipoprotein, named PP-I with an apparent molecular weight of 1,000,000, has been isolated using gel permeation high performance liquid chromatography (HPLC). PP-I, which focussed as a single band at pH 5 in an LKB isoelectric focussing column, quantitatively interacted with 80% of the circulating antibodies in pooled LL sera, and also induced a late (3 weeks) Mitsuda-type skin response which shows excellent correlation with host immunity against Mycobacterium leprae. These observations suggest that PP-I is a complex bifunctional antigen containing epitopes for both B and T cells. The PP-I fraction of ICRC and a similar high molecular weight HPLC fraction of M. leprae produced a line of identity against rabbit anti-ICRC serum in Ouchterlony gel diffusion and gave comparable skin responses in healthy volunteers in leprosy endemic areas. The data indicate that the PP-I fractions from the two organisms are antigenically closely related. Preliminary studies in human volunteers showed that administration of PP-I of ICRC resulted in immune conversion in lepromin-negative healthy subjects. PP-I thus appears to be the appropriate immunogen that could be used in preparation of a 'subunit' antileprosy vaccine.

Antigens, Bacterial↗
PubMed1988

Immunogenic "subunit" of the ICRC antileprosy vaccine.

The administration of a vaccine containing ICRC bacilli, which is currently undergoing clinical trials in India, induces persistent lepromin conversion in lepromatous leprosy (LL) patients and lepromin-negative healthy subjects, with "upgrading" of tissue response in the former. A sonicate of ICRC bacilli, when subjected to gel-filtration chromatography using high-pressure liquid chromatography (HPLC), yields a high molecular weight glycolipoprotein (PP-I) with an apparent molecular weight of 10(6) daltons. PP-I, which brings about lepromin conversion in lepromin-negative healthy subjects, is a major immunogen of the organism, and carries epitopes for both B and T cells. A similar high molecular weight glycolipoprotein (PP-I Mycobacterium leprae) has been isolated from the sonicate of M. leprae. The two PP-I fractions exhibit a close antigenic relatedness at both B- and T-cell levels. However, they differ in their chemical composition and carry different charges. PP-I of ICRC is not only a good immunogen. Its high lipid content provides the necessary built-in adjuvant that would make it a good candidate for a "subunit" antileprosy vaccine. Also, since it carries epitopes for both B and T cells, PP-I ICRC could be used for "molecular engineering" to obtain molecules which selectively stimulate T-cell immunity which is the dominant host defense against M. leprae.

Adult↗
PubMed1987

Growth hormone responses in isolated protein deficiency state in rhesus monkey.

We have longitudinally studied the effects of protein-deficient diet on serum growth hormone (GH) concentration in rhesus monkey. A biphasic basal GH response and a phenomenon of failure to suppress GH levels after glucose administration were observed in animals fed diet lacking proteins. GH levels remained consistently elevated in protein-deprived monkeys. Whether these elevations in GH will have any deleterious influence on the host remains to be seen.

Animals↗
PubMed1987

Effects of ICRC antileprosy vaccine in healthy subjects.

Long-term effects of the administration of the ICRC antileprosy vaccine in healthy subjects have been investigated both in household contacts of leprosy patients and noncontacts in a general population. Each volunteer received a dose of vaccine containing either 0.5 x 10(9) or 1.7 x 10(7) bacilli intradermally. The vaccine induces a dose-dependent lepromin conversion in negative subjects at 8 weeks after vaccination. One year later, the conversion rates are more than 90% in both high- and low-dose groups. Lepromin conversion is stable for at least 3 years. When administered to the lepromin-positive contacts, the vaccine induces a statistically significant increase in intensity of the reaction at 6 months. During the 3-year observation period, the subjects have remained healthy and no untoward effects, including any neurological lesions, have been observed. There has also been no change in the circulating level of antibodies against the phenolic glycolipid-I antigen of Mycobacterium leprae as a result of vaccination. The vaccine thus induces not only stable immunity but is safe and, being given as a single injection, has a high acceptability. Its field trials will begin soon.

Adolescent↗
PubMed1986

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.

Amino Acids↗
PubMed1986

Further studies on the enhancing factor and its possible mechanism of action.

In this study the nature of binding of enhancing factor (EF) and its mode of action are examined. EF binds to A431 cells through its own receptor, which is distinct from the receptor for epidermal growth factor (EGF). EF binds to the cell membrane and in turn provides a binding site for EGF. Data analyzed from Scatchard plots show that prior treatment of formalin-fixed A431 cells with EF for 30 minutes results in an increase in the number of binding sites for 125I-EGF. 3H-Thymidine incorporation studies, using the EGF-receptorless cell line NR-6, indicate that neither EF nor EGF alone stimulates the cells to synthesise DNA, but when both are added together the cells show 3H-thymidine incorporation. The role of EF may be to trap EGF and make it available to the cells through its own receptors even in the absence of EGF receptors. EF also induces anchorage-independent growth of normal fibroblasts in soft agar only in the presence of EGF.

Animals↗
PubMed1986

ICRC vaccine-induced changes in M. leprae-specific cell-mediated immunity in langur (Presbytis entellus) monkeys.

The effects of the administration of ICRC antileprosy vaccine on skin reactions and lymphocyte transformation tests (LTT) to antigens of Mycobacterium leprae have been investigated in Hanuman langur monkeys (Presbytis entellus) which live native to north India. In a majority of these monkeys, the vaccine brings about lepromin conversion associated with a change in tissue response consistent with "ugrading" of immunity. However, no concomitant changes were observed in the LTT. The significance of these observations is discussed. It is proposed that the langur monkey could be used as a laboratory model to screen "candidate" antileprosy vaccines.

Animals↗
PubMed1986

Adoptive transfer of tolerance induced by ICRC bacilli against Mycobacterium leprae in mice.

ICRC bacilli, the cultivable leprosy-derived mycobacteria, isolated from lepromatous nodules of leprosy patients were found to be immunogenic in BALB/c mice at a dose of 2 X 10(7) acid-fast bacilli when injected by the intradermal (i.d.) route. The sensitization to lepromin and ICRC antigens was measured by the foot pad enlargement (FPE) method. The same dose of bacilli when injected by intravenous (i.v.), intraperitoneal, and subcutaneous routes induced immune tolerance in mice as indicated by reduction in the FPE to the test antigens. The spleen cells obtained after i.v. injection of ICRC bacilli/Mycobacterium leprae after adoptive transfer brought about suppression of delayed-type hypersensitivity in sensitized as well as nonsensitized recipients, indicating production of suppressor cells after i.v. injection. Similarly, the tolerance induced by i.v. injection of M. leprae in mice could be partially converted to immunity by i.d. sensitization with live BCG and two strains of ICRC bacilli (C-44 and C-75).

Animals↗
PubMed1986

Oral cancer and cultural practices in relation to betel quid and tobacco chewing and smoking.

Oral cancer is the most common cancer in India, Pakistan, and Sri Lanka and ranks high in several southeast Asian countries. The association of these cancers with cultural practices like chewing was recognized almost a century ago. Continued work since then has identified tobacco use as the most important avoidable cause of oral cancer. Critical appraisal of specific cultural practices that lead to high risk of oral cancer will be presented with a focus on possible strategies for prevention programs. The need to monitor cultural changes such that these changes lead to prevention of cancer and not a shift from one type of cancer to another will be emphasized.

Areca↗
PubMed1983

Reversal reaction in lepromatous patients induced by a vaccine containing killed ICRC bacilli--a report of five cases.

Clinico-pathological features of five cases of lepromatous leprosy exhibiting "reversal" reaction with upgrading of lesions following vaccination with ICRC vaccine have been described. Two patients also developed ENL. Associated with the "reversal" reaction, the patients exhibited lepromin conversion. No evidence of fresh nerve lesions was observed in any patient. Besides lepromin conversion, occurrence of "reversal" reaction is yet another evidence of immunogenicity of the ICRC vaccine.

Adolescent↗