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Biomedical subjects

I M Thomas

Publications and source records attributed to I M Thomas.

At least 37 records · Page 2Linked to original sources

Cytogenetic investigations in Down syndrome patients & their parents.

A total of 1343 mentally retarded patients referred for cytogenetic evaluation were studied. Of these Down syndrome was confirmed in 365 (21.17%). There were 316 patients of trisomy 21 (86.58%); 21 of mosaicism (5.75%) and 28 of translocation (7.67%). Trisomy 21 patients with chromosomal variants were observed in 17 (4.65%). A 1.37:1 male:female ratio was seen. Karyotyping was also done on 182 parents (of patients of mosaic Down, translocation Down and trisomy 21 with chromosomal variants and in parents with suspected low mosaicism). Mosaic trisomy 21 cell line was found in one mother (0.27%); 6 parents (1.65%) were seen to be translocation carriers and 7 had chromosomal variants (1.92%). Cytogenetic investigations help to give appropriate genetic counselling to patients and their families.

Adolescent↗

Cytogenetic studies in leprosy patients before and after chemotherapy.

The frequencies of chromosome aberrations and sister chromatid exchanges (SCEs), cell proliferation kinetics and mitotic indices were studied in peripheral blood lymphocyte cultures of leprosy patients both before and after chemotherapy. The differences in the frequencies of chromosome aberrations and SCEs between controls, paucibacillary and multibacillary patients were found to be statistically highly significant (P less than 0.001). The extent of cytogenetic damage seemed to depend on the severity of the disease. Lymphocytes of untreated leprosy patients showed a low mitotic index and a slow rate of cell proliferation. Following combined treatment with dapsone and rifampicin there was an increase, but to a lesser degree (P less than 0.01), in the frequency of SCEs and chromosome aberrations while the drug combination of dapsone, rifampicin and clofazamine had a nonmutagenic effect on chromosomes of the patient. Furthermore, after drug treatment, the cell proliferation rate and mitotic indices in paucibacillary patients were comparable to that of controls. These results indicate the clastogenic potency of Mycobacterium leprae and the remedial effects that follow therapeutic drug treatment.

Adult↗

Chromosomal aberrations in tuberculosis patients before and after treatment with short-term chemotherapy.

Cytogenetic effects of 4 common anti-tubercular drugs, isoniazid (H), streptomycin (S), rifampicin (R) and pyrazinamide (Z), in 3 different combinations (2 SHRZ, 2 HRZ and 2 H2R2Z2) were evaluated in the lymphocytes of tuberculosis patients undergoing chemotherapy, in order to estimate their mutagenic potential in combination. All 3 regimens showed an increased frequency of chromosomal aberrations after treatment compared to before treatment. These findings are of significance in the treatment of tuberculosis, as the drugs in question are observed to be mutagenic/clastogenic.

Chromosome Aberrations↗

Chromosome damage in untreated tuberculosis patients.

The frequency of chromosomal aberrations and sister chromatid exchanges (SCEs) were estimated in the lymphocytes of 95 untreated tuberculosis patients to evaluate the chromosomal damage with reference to bacterial invasion. The frequency of chromosomal aberrations was significantly higher in tuberculosis patients compared to controls (p less than 0.001) while the SCE frequency did not show any statistically significant differences. These findings indicate that the basic mechanism of formation of chromosomal aberrations and SCE are different and they suggest that the tubercle bacillus might be capable of inducing chromosome damage.

Adolescent↗

Sister chromatid exchanges in the lymphocytes of tuberculosis patients receiving short-term chemotherapy.

The frequency of sister chromatid exchanges was estimated in tuberculosis patients undergoing three different short term chemotherapy regimens (2SHRZ, 2HRZ and 2H2R2Z2), to evaluate the possible genetic damage caused by anti-tuberculous drugs. Of the three combinations studied, two combinations (2SHRZ and 2HRZ), which were administered daily, enhanced the frequency of sister chromatid exchanges significantly (p less than 0.05), while the third bi-weekly combination (2H2R2Z2) did not show any significant enhancement in the frequency of sister chromatid exchanges. These results are of importance in the treatment of tuberculosis, and indicate the need to select a drug combination that is equally efficient in the control of disease and at the same time less harmful to the genome of the patient.

Antitubercular Agents↗

Differential sensitivity of peripheral blood lymphocytes of untreated leprosy patients to mitomycin C.

The effects of a bifunctional alkylating agent mitomycin C (MMC), an effective inducer of chromosome aberrations and sister-chromatid exchanges (SCEs), have been studied in untreated leprosy patients. This was done to study the mutagen sensitivity of the leprosy patients. The frequency of chromosomal aberrations induced by MMC (conc. 0.01 microgram/ml) was 2.5% in controls, 3.6% in paucibacillary (PB), and 6.8% in multibacillary (MB) patients. The difference in the frequency of MMC-induced chromosome aberrations between the 3 groups studied was highly significant (p less than 0.01). Cultures grown with MMC showed the frequency of SCEs/cell to be 12.70 +/- 1.19 in controls, 19.97 +/- 3.51 in PB, and 29.66 +/- 5.92 in MB patients. The differences in the frequency of MMC-induced SCEs between the 3 groups were found to be highly significant (p less than 0.01). The enhanced frequencies of spontaneous and MMC-induced chromosome aberrations and SCEs observed in PB and MB patients indicate a clear differential mutagen sensitivity between PB and MB patients who are known to have different immunological status and thereby differ in the severity of the disease.

Cells, Cultured↗

Effects of lepromatous leprosy (LL) serum factor(s) on normal blood lymphocytes.

To investigate the clastogenic activity of sera from leprosy patients, normal peripheral blood lymphocytes were cultured in both inactivated and noninactivated lepromatous leprosy (LL) sera. An increase in the frequency of chromosome aberrations was observed in normal lymphocyte cultures supplemented with both inactivated (5.2%) and noninactivated (5.0%) LL serum compared to that of cultures supplemented with normal human AB+ serum (2.4%). An enhanced frequency of sister chromatid exchanges (SCEs) was also observed in normal lymphocyte cultures supplemented with both inactivated (8.2 +/- 3.85) (mean +/- S.D.) and noninactivated (8.3 +/- 4.61) LL serum compared to that of controls (6.8 +/- 3.45). The normal blood lymphocyte cultures with LL serum have revealed a slow cell-cycle kinetics at a 48-hr incubation period, but a slightly faster proliferation rate was observed at 72 hr compared to cultures supplemented with normal human AB+ serum, indicating a depressive effect of LL serum on normal blood lymphocyte proliferation. The results obtained from the inactivated LL serum showed that the factor(s) which induce chromosomal damage, depress the mitotic index and the cell proliferation rate were not destroyed at 56 degrees C. These results are the first documentation of cytogenetic effects of LL sera on normal human peripheral blood lymphocytes.

Adult↗

Variation in spontaneous chromosomal damage as a function of biologic rhythms in women.

An unequivocal observation of a higher rate of cellular genetic damage in terms of increased frequencies of sister chromatid exchanges (SCEs) and chromosome aberrations during "ovulatory" and "estrogenic" stages as compared with those of "progestogenic" stage of the menstrual cycle in women and the reported fluctuations in SCEs as a function of time in men indicate that chronobiologic considerations are essential in the design of studies of humans and animals experiments. It seems that female subjects are more influenced by biologic rhythms because of specific hormonal cycles and are sensitive to genetic damage during ovulatory/estrogenic stages of the menstrual cycle.

Adult↗

Significance of acquired nonrandom 7/14 translocations.

We have detected eight patients with a single metaphase having a 7/14 translocation. In all cases, the breakpoint on chromosome 14 was 14q12, while the breakpoint on chromosome 7 was 7q35 in three cases and 7p13 in five cases. The factors that may be involved in these nonrandom translocations are discussed.

Adult↗

Cytogenetic investigations in 150 cases with complaints of sterility or primary amenorrhea.

Cytogenetic investigations were carried out on 150 individuals. Out of these 107 were females and 43 males. Eighty seven of the above (43 males and 44 females) had been referred for sterility. Sixty three patients had primary amenorrhea and had been referred directly to this laboratory by clinicians, having been suspected of genetic abnormalities. Twenty-two cases (14.7%) involved in this study chromosomal abnormalities and seven cases (4.7%) showed chromosomal polymorphism. Of the 107 females (44 sterile and 63 with primary amenorrhea), 11 (10.2%) showed numerical or structural sex chromosomal abnormalities. Five patients (4.67%) showed chromosomal polymorphism (involving the paracentromeric and centromeric regions of chromosomes 1 and 9, double satellites, and giant satellites. Of the 43 males, 11 (25.59%) showed numerical and structural abnormalities. Ten cases were anomalies involving the sex chromosomes. One case of a triple autosomal translocation in an otherwise phenotypically normal azoospermic male was of particular interest. Two cases (4.65%) showed double satellites of the acrocentrics.

Adolescent↗