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Biomedical subjects

K Bhargava

Publications and source records attributed to K Bhargava.

At least 19 recordsLinked to original sources

Expression of human tumor mucin-associated carbohydrate epitopes, including sialylated Tn, and localization of murine monoclonal antibodies CC49 and B72.3 in a syngeneic rat colon carcinoma model.

Using immunohistochemical techniques and whole-cell enzyme-linked immunosorbent assay, we have determined that monoclonal antibodies (mAbs) B72.3 and CC49, which are widely used in the diagnosis and treatment of several human epithelial cancers, are expressed in a transplantable rat colon carcinoma cell line, K12-TRb. MAbs B72.3 and CC49 react with tumor-associated glycoprotein-72 (TAG-72) which is a carcinoma mucin molecule expressed in colon, breast, pancreatic, ovarian, lung, and gastric cancers. The carbohydrate epitope for mAb B72.3 is sialylated Tn (sTn), whereas CC49 reacts with an unknown carbohydrate epitope. K12-TRb is a transplantable rat colon carcinoma cell line derived from a dimethylhydrazine tumor which grows as progressive tumors in syngeneic BD IX rats. We found that the carbohydrate epitopes for mAbs B72.3 and CC49, including sTn, were more tumor-restricted in the rat than in humans. The only binding these had mAbs to normal rat tissue was to small-intestinal mucosa. MAbs B72.3 and CC49 were radiolabeled with iodine-125 (125I) and injected intravenously into BD IX rats containing subcutaneously grown syngeneic K12-TRb tumors. Biodistribution experiments were conducted by dissecting groups of three rats on days 2, 4, 7, and 14 after injection of radiolabeled mAbs. These experiments confirmed that maBs B72.3 and CC49 localize to K12-TRb tumors in vivo, and that the higher affinity mAb CC49 localized better than mAb B72.3. Gamma-camera imaging of subcutaneous K12-TRb tumors was successfully performed using 125I-labeled mAb CC49. The importance of this model is that mAbs B72.3 and CC49, immunoconjugates of these mAbs, and vaccines containing their corresponding carbohydrate epitopes, including sTn, can be studied in a relevant immunocompetent syngeneic rat colon carcinoma model.

Animals

Immobilization of active urokinase on albumin microspheres: use of a chemical dehydrant and process monitoring.

A method of immobilizing urokinase on albumin microspheres has been developed. Laser scattering, which was used to follow particle size from the initial emulsification stage to the final aqueous resuspension of the microsphere stage, showed that particle coalescence and crosslinking were critical parameters in manufacturing the microspheres. Chemical dehydration with 2,2-dimethoxypropane was used to convert an albumin emulsion into an albumin suspension and to reduce coalescence. An optimal amount of dehydrant produced 0.3-micron particles which resisted a 50 degrees C temperature challenge. Since oil/glutaraldehyde emulsion resulted in large particles with no urokinase activity, the cross-linking concentration of glutaraldehyde was reduced by solubilizing 25% (w/v) glutaraldehyde in the oil phase with n-propanol. A concentration of 0.015% (v/v) glutaraldehyde effectively immobilized urokinase and stabilized albumin microspheres. Amidolytic activity using the specific chromogenic substrate for urokinase, S-2444, showed that enzyme activity could be retained during this glutaraldehyde cross-linking.

Albumins

Experience with oral morphine for cancer pain relief.

The authors report a prospective survey of 88 patients with cancer pain who were treated with oral morphine solution during a period of 140 days at the Pain Relief Unit, Kidwai Memorial Institute of Oncology, Bangalore. A high percentage of pain relief was achieved at the end of the first week of titrated therapy; relief was maintained at satisfactory levels throughout the study period in a majority of patients (86%). Interruption of oral morphine administration was necessitated by intractable vomiting in two patients. The majority of patients (65%) did not manifest any side effects, and appropriate medication successfully managed those who did. Oral morphine therapy for cancer pain offers effective pain relief with minimal side effects in the majority of patients.

Administration, Oral

An evaluation of cross-bite ridge relationships. A study of articulated jaw records of 150 edentulous patients.

Data were collected from 150 men and women complete-denture patients. Their jaw records were evaluated with a specially designed instruments. The extent of deviation of the maxillary and the mandibular ridges in the horizontal plane was calculated at various interridge distances, at a constant interalveolar crest-line angle of 80 degrees. It was found that: 1. Most patients of both sexes revealed a normal horizontal ridge relationship. 2. Next to the normal ridge relationship, there was a tendency for a unilateral cross-bite ridge relationship on the left sides of those patients who had recent extractions (up to 6 months previously). 3. True bilateral cross-bite ridge relationships were found only in those patients who gave a history of prolonged edentulousness. 4. The decision to arrange the posterior teeth in normal or cross-bite ridge relationship should take into consideration the deviations in the ridge relationship as well as the interridge distance. A method of evaluating interridge deviations in the horizontal plane in the posterior region of articulated jaw records of edentulous patients was developed.

Adult

Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India.

In Gujarat, India, 6718 industrial workers, over 35 years of age, with oral leukoplakia (confirmed clinically and microscopically), were studied. After 2 years, 4762 (71%) of the individuals were re-examined. The buccal mucosa was the most common site of occurrence; 98.3% of these individuals had oral habits, with smoking alone or smoking in combination with "pan" or "supari" chewing accounting for 74.9% of the habit forms. Six individuals (0.13%) with oral leukoplakia developed oral carcinomas within 2 years. This incidence of malignant transformation was equivalent to 63/100,000 per year, which far exceeds that of new oral cancers expected even in high-risk populations. While 57.3% the leukoplakic lesions remained unchanged during a 2-year interval, 31.6% disappeared and 11% had an altered appearance. This study confirmed the precancerous nature of oral leukoplakia.

Adult

A histologic comparison of palatal mucosa before and after wearing complete dentures.

A histologic investigation to study the tissue changes occurring under complete dentures was done. Biopsies were obtained from 40 patients from the area of left side of the hard palate at the first molar region, midway between the median raphe and the residual ridge. The same patients were examined 3 months after placement of well-fitted dentures. Thirty of the 40 patients responded. A second biopsy was taken from the same area on the right side of these patients. On the basis of the microscopic examination, the following conclusions were drawn. 1. The average thickness of the palatal epithelium of edentulous non-denture wearers was 0.222 mm. in the rete peg region. 2. There was a general increase in the thickness of the palatal epithelium following 3 months of wearing complete dentures. 3. The increase in the palatal epithelium was more marked in the rete peg region than in the inter-rete peg region. 4. There was an increase in the thickness of the keratin layer in most patients. 5. No significant changes were found in the granular-cell layer or the prickle-cell layer. 6. The oral mucous membrane responded favorably to well-fitted dentures.

Adult

Occurrence of oral sebaceous glands in 43,654 industrial workers of Gujarat, India.

In 10 cancer patients platelet concentration, platelet consumption, platelet half-life time and plasma concentration of platelet factor 4 were determined. A high frequency of thrombocytosis and increased platelet consumption were observed, and the plasma concentration of platelet factor 4 was increased. However, no significant correlation was found between platelet consumption and the result of a single determination of platelet factor 4 concentrations in plasma.

Adult

Antigenic differences in human sperm samples related to various morphological abnormalities.

Sperm samples were collected from male partners of fertile and infertile couples having unexplained and male factor infertility and analyzed for morphological abnormalities. After a staining procedure, sperm samples of these infertile men showed a variety of abnormalities. The sperm samples were also studied for their binding with the Abs directed against protamine (the nuclear protein), fertilization antigen (FA-1, sperm surface antigen), and the lithium diiodosalicylate- (LIS-) solubilized sperm preparation, and the binding was correlated with the percentage of morphologically abnormal sperm in the sample. Abs used in the present study were raised in female rabbits and had high titers (ELISA titers, 1:4096 to 1:8196), and recognized no band (anti-protamine), one 49,000- +/- 2000-dalton band (anti-FA-1), and at least 8 bands of various molecular identities in the 14,000- to 92,000-dalton range (anti-LIS sperm) on the Western blot of LIS-solubilized human sperm. The affinity-purified Fab' antibodies were iodinated and used in a radioimmunobindingassay for testing their binding with the sperm cells. Anti-protamine Fab's showed minimal binding and the binding activity (cpm bound/10 x 10(6) sperm cells) did not correlate (head defect, r = .12; midpiece defect, r = .07; tail defect, r = .11) significantly with percentage of abnormal cells in the sample. The binding of the anti-FA-1 Fab's also did not show a significant correlation (head defect, r = .29; midpiece defect, r = .48; tail defect, r = .23), though a positive trend (p = .05) was observed with the midpiece defect. In contrast, the binding of anti-LIS sperm Fab's demonstrated a significant correlation with the percentage of abnormal sperm cells in the sample (head defect, r = .51, p = .04; midpiece defect, r = .80, p less than .0001; tail defect, r = .23, p = .039). With an increased percentage of abnormal sperm cells, especially those with midpiece defect, there was an increased binding of anti-LIS sperm Fab's. These results suggest that with an increase in percentage of abnormal sperm, there is a change in antigenicity of the sperm cells. An increase in structural abnormality may enhance antibody binding to an abnormal sperm cell, thus causing a further decrease in its fertilizing capacity.

Antigens