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Biomedical subjects

M G Deo

Publications and source records attributed to M G Deo.

At least 37 records · Page 2Linked to original sources
PubMed1992

T-cell responses of leprosy patients and healthy contacts toward separated protein antigens of Mycobacterium leprae.

Sonicated extracts of Mycobacterium leprae were separated by two-dimensional gel electrophoresis and electroeluted into 400 distinct soluble fractions. These fractions were probed with T lymphocytes from leprosy patients of different disease types, healthy contacts, and unexposed healthy individuals. Proliferative responses were visualized using three-dimensional stimulation profiles. T cells from many patients and contacts responded to a multitude of antigen fractions of different molecular masses and isoelectric points. T cells from unexposed individuals gave significant responses to lysates or whole organisms of M. leprae, but no or only marginal responses to separated antigen fractions. T cells of polar tuberculoid (TT) and the majority of polar lepromatous (LL) leprosy patients responded only to separated antigen fractions but not to lysates or whole organisms of M. leprae. The remaining LL patients were totally unresponsive and even failed to respond to separated M. leprae fractions. Thus, in some leprosy patients unresponsiveness to M. leprae seems to be caused by distinct components and can be broken by using separated antigen fractions; whereas in others, anergy remains. T cells of borderline tuberculoid (BT) patients, who were under chemotherapy, responded to separated antigen fractions as well as to lysates of M. leprae organisms. In contrast, BT patients who were untreated failed to react with any of the M. leprae preparations. Similarly, T cells of the majority of LL patients responding to separated fractions were under chemotherapy; whereas T cells from untreated LL patients gave no or only marginal responses to any of the M. leprae antigen preparations. These findings suggest some linkage between the degree of T-cell responsiveness and antileprosy drug treatment.

Antigens, Bacterial↗
PubMed1991

Expression of enhancing factor gene and its localization in mouse tissues.

Enhancing factor (EF), a 14 kDa protein, isolated from mouse small intestines, has been reported from this laboratory. Based on our earlier studies EF has been implicated in cell proliferation. Preliminary immunohistochemical studies have shown EF to be localized in the Paneth cells of small intestines. In this paper we report the tissue distribution of EF using conditions optimized for immunohistochemical staining. In addition, the data are supported by northern blot analysis using a nick translated cDNA probe specific for EF. The results indicate that EF gene is actively transcribed mainly in the intestines. The chief source of synthesis of EF appears to be the Paneth cells located at the base of the crypts of Lieberkühn.

Animals↗
PubMed1991

Ontogeny of enhancing factor in mouse intestines and skin.

Enhancing Factor (EF) is a 14 kDa protein isolated from mouse small intestines, which enhances the binding of 125I-EGF to A431 cells. This observation as well as our earlier in vitro studies have indicated that EF is a modulator of EGF. In adult mice, localization of EF by immunohistochemistry shows it is present predominantly in the Paneth cells of the small intestines and to a lesser extent in the stomach and colon. This study of the ontogeny of EF shows that the appearance of the protein coincides with the appearance of mature Paneth cells. In new born mouse skin EF is localized in the hair follicles in the first hair cycle from day 2 to day 8. It is however absent in the adult skin. Thus EF is associated with tissues which have a high growth rate.

Animals↗
PubMed1991

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.

Adult↗
PubMed1991

High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.

57 primary tumour samples from Indian oral cancer patients with a 5-15 year tobacco chewing habit, were examined for mutational activation in codons 12, 13 and 61 of the H-ras, K-ras and N-ras oncogenes. The highly sensitive assay based on specific oligonucleotide hybridisation following in vitro amplification of unique sequences by polymerase chain reaction was employed. Mutations were detected in twenty (35%) of the samples and were restricted to H-ras, codons 12, 13 and 61. Two cases had concurrent mutations in codons 12 and 61. The majority of the mutations were at H-ras 61.2 (Glutamine to Arginine) and H-ras 12.2 (Glycine to Valine). Three of the less frequent mutations are apparently novel. Interestingly, eight of the samples with H-ras mutations also showed loss of wild-type H-ras, as judged by absence of signals for wild-type codons 12 or 61 on dot blots. The specific H-ras mutations in these oral malignancies associated with tobacco chewing, may represent an important example of an environmental carcinogen-induced step, in a pathway leading to malignant transformation.

Adult↗
PubMed1991

Mitogen induced proliferation and cytokine production by lymphocytes from leprosy patients.

In this paper we have assessed the mitogen responses of leprosy patients and healthy donors in terms of proliferation and cytokine production (Interleukin 2 and Interferon gamma). The patients investigated included untreated and multidrug therapy non-responsive LL patients and MDT responsive LL and TT patients. The mitogen responses of untreated and multidrug therapy non responsive LL patients were not significantly different from those of the healthy donors. It was interesting to note that TT and multidrug therapy responsive LL patients showed higher responses to mitogens than healthy donors as assessed by all three parameters. The results suggest a correlation of increased mitogenic responses with improvement in clinical status in leprosy.

Cell Division↗
PubMed1991

Anti-leprosy vaccines: current status and future prospects.

Different types of leprosy vaccines are currently used in field trials in India. The rationale behind their use, the parameters for determining their efficacy, their merits and demerits are discussed and the future prospects are highlighted.

Animals↗
PubMed1990

Restriction fragment length polymorphism of the L-myc gene in oral cancer patients.

Restriction fragment length polymorphism (RFLP) of the L-myc gene was examined in DNAs from primary tumour tissues and peripheral blood cells (PBC) of 76 Indian patients with squamous cell carcinoma of the oral cavity, and PBC from 101 normal healthy volunteers. The patients and the normal healthy volunteers were classified into three genetic types according to the polymorphic patterns defined by the two alleles (6.6 kb, S fragment; and 10.0 kb, L fragment). DNA isolated from the PBC of each patient always exhibited the same pattern of L-myc alleles as that observed for the corresponding tumour DNA. However, a striking correlation was found between the RFLP pattern and the stage of differentiation of the tumours, as well as the size of the tumour. Thus, a preponderance of the S fragment was observed in the poor to moderately differentiated tumours and the larger (greater than 4 cm) sized tumours. Further, analysis of L-myc RFLP with the clinical pattern of the malignancy showed no significant correlation with nodal metastasis, TNM staging or recurrence of the tumour. The relative ratios of the three genotypes (L-L, L-S, S-S) in the oral cancer patients were not significantly different from those seen in the healthy Indians, implying no predisposition to oral cancer by either allele. However, our results showed that oral cancer patients with a genotype including an S fragment are more likely to develop a poor to moderately differentiated tumour or a larger tumour than a patient without an S fragment. The L and S alleles were equally distributed in the population, with the frequency of each allele being 0.50, consistent with Hardy-Weinberg's law.

Adult↗
PubMed1990

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.

Adolescent↗
PubMed1990

Natural killer-cell-mediated and antibody-dependent cellular cytotoxicity in leprosy.

We have assessed the natural killer (NK) cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) in the peripheral blood lymphocytes (PBL) from untreated lepromatous leprosy (LL) patients, LL patients on multidrug therapy (MDT) with favorable responses (MDT-R), LL patients clinically classified as nonresponders to MDT (MDT-NR), treated tuberculoid leprosy (TT) patients, and healthy donors. NK cytotoxicity was modulated by treating the PBL with recombinant interferon-alpha (IFN-alpha) and recombinant interleukin-2 (IL-2). The mean percent NK cytotoxicity of untreated LL patients (15 +/- 3), treated MDT-R patients (20 +/- 4), and treated MDT-NR patients (12 +/- 4) was significantly lower than that of TT patients (39 +/- 6) and healthy donors (37 +/- 5). Treatment of effectors with IL-2 or IFN-alpha enhanced NK cytotoxicity in 5 of 6 untreated LL patients, 6 of 6 treated MDT-R LL patients, 4 of 5 and 3 of 5 treated MDT-NR LL patients, respectively, and 5 of 8 and 3 of 8 treated TT patients, respectively. Although PBL from TT patients showed initial NK activity comparable to that of healthy donors, fewer TT patients showed modulation of NK activity by IL-2, and IFN-alpha to a lesser extent. The ADCC activity was lower in untreated LL patients compared to treated patients, while TT patients had normal ADCC activity. The results indicate that although LL patients show lowered spontaneous cytotoxicity, it can be modulated favorably by lymphokines.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

ICRC 'anti-leprosy vaccine'.

A vaccine containing ICRC bacilli, which are leprosy-derived cultivable mycobacteria, induces lepromin conversion in LL patients and lepromin-negative persons. 'Up-grading' of lesions and reversal reaction are observed in some vaccinated patients. The bacillus shows antigenic cross-reactivity with Mycobacterium leprae. These observations provided the basis for launching a large-scale field trial of the vaccine in India in February 1987. The objective of the two-arm trial is to assess efficacy of the ICRC vaccine against BCG, which forms the control arm, in lowering the incidence of leprosy in healthy household contacts of leprosy patients. Recently, a very high molecular weight fraction, named PP-I, has been isolated from the sonicate of ICRC bacilli. PP-I, which is a glycolipoprotein, is a strong T-cell immunogen and shows antigenic cross-reactivity with a similar fraction isolated from M. leprae. A 'subunit' vaccine containing the PP-I of ICRC bacilli is currently undergoing phase I and II clinical trials in India.

Adolescent↗