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Biomedical subjects

A R Mehta

Publications and source records attributed to A R Mehta.

At least 19 recordsLinked to original sources

Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer.

The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers.

Adult

Primary tracheo oesophageal puncture our initial experience.

Our initial experience of 9 primary tracheo oesophageal punctures with Blom Singer prosthesis is reported. Patient selection was based on motivation, intelligence and socioeconomic status. Excellent speech resulted in 7 out of 9 patients (77%), with 2 failures (23%). There were no major complications. The results are encouraging, but a larger study is required to determine the role of this procedure in our conditions.

Esophagus

Gastric transposition & deltopectoral flap for peristomal recurrence following total laryngectomy--a case report.

Stomal recurrence following laryngectomy presents a difficult problem with an incidence of 8.3-15%. Wide excision of the recurrence with mediastinal dissection, although the operation of choice,m is technically demanding and has a high morbidity and mortality. We recommend a technically easier procedure for reconstruction after palliative excision and present a case to illustrate it.

Anastomosis, Surgical

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

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

Glutamic acid-induced shoot differentiation in tobacco callus tissues and changes in nicotine content and in activities of aminotransferases, ornithine transcarbamylase, and arginase.

Floral bud calluses of Nicotiana tabacum L. var. Anand-2 produced multiple shoots on Murashige and Skoog's (MS) medium supplemented with 2 mg/l indole-3-acetic acid (IAA), 0.4 mg/l kinetin (Kn), and L-glutamic acid (2.5 mM). However cultures of calluses on MS medium containing only the IAA and Kn did not differentiate shoots. Specific activities of phenylalanine aminotransferase, tyrosine aminotransferase, and ornithine aminotransferase were over 7-, 5- and 5-fold higher, respectively, in the glutamic acid-treated calluses than in the nonshoot-forming ones on the day of shoot emergence. Activities of ornithine transcarbamylase and arginase decreased after the onset of the differentiation process. Implications of the enzyme activities in the differentiation process and in nicotine biogenesis are discussed.

Arginase

Mortality and morbidity of primary pharyngogastric anastomosis following circumferential excision for hypopharyngeal malignancies.

Seventy-five patients underwent gastric transposition for replacement of the pharyngoesophagus. These patients had primary or recurrent malignant tumors of the hypopharynx, postcricoid region, and cervical esophagus. The operative procedure consisted of a transhiatal esophagectomy and gastric pull-up to establish gastrointestinal continuity, with a unilateral or bilateral neck dissection where indicated. Seven patients died, a mortality rate of 9.33%. The average hospital stay of uncomplicated cases was 18 days and for complicated cases was 40 days. Immediate restoration of oral intake was achieved in 70.6% of patients. We conclude that gastric transposition after circumferential laryngopharyngeal excision is a procedure with low mortality and acceptable morbidity leading to early relief of dysphagia.

Adult

Complications following surgery for cancer of the larynx and pyriform fossa.

The hospital records of patients undergoing major surgery for cancer of the larynx and hypopharynx at the Tata Memorial Hospital, Bombay, from 1981 to 1985 were reviewed. Different variables were correlated with the incidence of major complications and were analysed to find out significant factors contributing to increased complication rates. Complications included wound infection, pharyngocutaneous fistulae, flap necrosis, carotid blowout, and neo-esophageal stenosis. Postoperative deaths and delayed fatalities were also recorded. The overall fistulae rate was 34.7%, and wound infection occurred in 28% of patients. Prior radiotherapy and the need for pharyngeal reconstruction were found to be significant in determining postsurgical complications. Age, sex, site, stage, cartilage and soft tissue infiltration, preoperative tracheostomy, involvement of resection margins by tumor, and the dose of radiotherapy were not found to influence the complication rates.

Adult

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

Composite resections for oral cancers--experience with 97 consecutive cases.

A retrospective study was carried out from the evaluable records of all (N = 97) patients who underwent composite resections in unit 'Head & Neck 'C' - Tata Memorial Hospital, over the years 1980, 81, 82, for a variety of oral cancers. The purpose of this study was to assess the true value of radical ablation. Tobacco addiction was observed in all patients with adequate documentation of habits. The vast majority of operations were performed for lesions of the buccal mucosa (N = 48) and lower alveolus (20); and squamous carcinoma was the predominant histologic type. Most patients presented with advanced T3 and T4 lesions. Nodal findings revealed a conspicuous disparity between clinical and pathological findings; and the final 'N' status was the most significant prognostic determinant. The results of reconstructive methods have also been reviewed. The majority of recurrences occurred within 12 months of surgery, local recurrence being commonest.

Adult

Purification and characterization of early pregnancy factor from human pregnancy sera.

Early pregnancy factor (EPF) is a pregnancy-associated protein detected in the maternal serum by using the rosette inhibition assay and by evaluating the suppression of adoptive transfer of contact sensitivity. Because of its inhibitory effect on the functional reactivity of immunocompetent cells, EPF is thought to be involved in immunoregulation of the maternal immune system during early pregnancy. EPF was purified six million-fold from the serum of pregnant women between 5 and 12 weeks of gestation. The specific activity of purified EPF was approximately 8 x 10(8) units/mg. The purification scheme involved sequential DEAE-cellulose chromatography, S-Sepharose chromatography, concanavalin A-Sepharose chromatography, heparin-Sepharose chromatography, Mono S fast protein liquid chromatography, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified protein has an apparent molecular weight of 21,500 as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 28,000 by gel permeation high pressure liquid chromatography. The isoelectric point of purified EPF moiety is 6.5. The biological activity was susceptible to the proteolytic enzyme trypsin, acidic pH conditions, organic solvents, and sodium dodecyl sulfate, but stable to heat treatment at 56 degrees C for 30 min and the reducing agent dithiothreitol. The biological and physicochemical properties of EPF appear to be distinct from other pregnancy-associated and immunoregulatory proteins.

Chaperonin 10

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

Solasodine levels in Solanum sisymbriifolium Lam.

Solasodine content in berries, leaves and stem of S. sisymbriifolium, using three different procedures, was 0.93, 0.73 and 0.23% respectively. Further in chromatogram not only solasodine but three more alkaloids (Rf 0.22, 0.48 and 0.88) were found which could not be identified due to lack of authentic samples.

Chromatography, Thin Layer

Hypofractionated external radiation with high and low dose rates in the treatment of advanced cancer of the cervix.

Thirteen patients with cancer of the cervix Stage IIIb (heavy) were treated with high (9) and low (4) dose rates, once a week. A total dose of 4200 cGy was delivered over 7 weeks with a fraction size of 600 cGy. Six of nine patients showed complete response following high dose rate hypofractionated radiation. It is felt that synchronization of cells into a sensitive phase during low dose rate radiation is not the determinant of outcome even when duration of treatment is only 5 to 6 hours.

Female

Detection of early pregnancy factor-like activity in women with gestational trophoblastic tumors.

The presence of immunosuppressive early pregnancy factor (EPF) in the maternal serum has so far been associated with gestation. Its presence in the serum of women with gestational trophoblastic tumors was investigated. The results indicate that while EPF activity was detected in the serum of women with choriocarcinoma, no such activity was detected in the serum of women with hydatidiform mole, leading to the novel use of EPF as a marker to distinguish these two clinical situations. Results of the experiments also suggest that EPF moiety present in the maternal serum during pregnancy may be of different molecular entity than that present in the serum of women with choriocarcinoma.

Chaperonin 10

Isolation and partial characterization of early pregnancy factor (EPF) from human pregnancy serum.

The isolation and partial characterization of an immunosuppressive early pregnancy factor (EPF) present in the serum of pregnant women, between 3 and 8 weeks of gestation, is described. EPF was purified using ion-exchange chromatography, affinity chromatography and HPLC gel permeation techniques. A homogeneous, active fraction containing a single polypeptide of Mr 21,000 was obtained. This 21 kDa polypeptide appears to represent the major form of rosette-inhibiting active material present in maternal serum during early human gestation.

Chaperonin 10