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Biomedical subjects

D M Vasudevan

Publications and source records attributed to D M Vasudevan.

At least 19 recordsLinked to original sources

Defective interleukin-2 R gene expression in gastric carcinoma patients.

Peripheral blood T lymphocytes from 15 patients with gastric carcinoma and 6 normal healthy controls were evaluated for Interleukin-2 R gene expression. Total RNA was extracted from T cell-enriched fractions of patients as well as from control peripheral blood lymphocytes, with or without mitogenic stimulation. The presence of mRNA for IL-2 R alpha evaluated by Northern blot analysis revealed that unstimulated T cells expressed lower levels of IL-2 R mRNA than PHA stimulated T cells. Expression of both IL-2 R alpha transcripts (3.5 and 1.5 Kb) were either not detectable or only weakly detectable on T lymphocytes from patients even after mitogenic stimulation. In contrast, a significant rise in the expression of both IL-2 R alpha transcripts was observed on T cells from normal controls followed by mitogenic challenge. This paper reports on the defective IL-2 R alpha gene expression in gastric carcinoma patients, which may explain one of the causes of immunodeficiency associated with neoplastic transformation and progression.

Carcinoma

WR-1065 as a chemoprotector in Adriamycin chemotherapy.

The protective effect of WR-1065 against the side effects of Adriamycin was studied in tumor bearing mice. It has been noticed that WR-1065 pretreatment improved the Adriamycin toxicities such as increased enzyme levels, pathological lesions in lung, liver and heart and increased rate of lipid peroxidation, without reducing its anticancer property.

Animals

Augmentation of murine natural killer cell and antibody dependent cellular cytotoxicity activities by Phyllanthus emblica, a new immunomodulator.

When administered orally, Phyllanthus emblica, an excellent source of vitamin C (ascorbate), has been found to enhance natural killer (NK) cell activity and antibody dependent cellular cytotoxicity (ADCC) in syngeneic BALB/c mice, bearing Dalton's lymphoma ascites (DLA) tumor. P. emblica elicited a 2-fold increase in splenic NK cell activity on day 3 post tumor inoculation. Enhanced activity was highly significant on days 3, 5, 7 and 9 after tumor inoculation with respect to the untreated tumor bearing control. A significant enhancement in ADCC was documented on days 3, 7, 9, 11 and 13 in drug treated mice as compared to the control. An increase in life span (ILS) of 35% was recorded in tumor bearing mice treated with P. emblica. This increased survival was completely abrogated when NK cell and killer (K) cell activities were depleted either by cyclophosphamide or anti-asialo-GM1 antibody treatment. These results indicate: (a) an absolute requirement for a functional NK cell or K cell population in order that P. emblica can exert its effect on tumor bearing animals, and (b) the antitumor activity of P. emblica is mediated primarily through the ability of the drug to augment natural cell mediated cytotoxicity.

Adjuvants, Immunologic

Papilloma virus in cervical carcinoma: detection of viral antigen in cancer cells.

Paraffin sections of biopsies from histopathologically confirmed cases of uterine cervical carcinoma, cervical scrapings from dysplasia, chronic cervicitis, tumour cells from carcinoma of the oral cavity and normal tissues from healthy normal cervix and oral cavity scrapings were examined for the presence of Human papilloma virus antigens. The techniques adopted were the Indirect Immunofluorescence Stainig and the Peroxide-Anti-Peroxidase techniques. The HPV-antigen was present in 38 percent and 41 percent of invasive carcinoma cervix, by PAP and IIF methods respectively. In cervical dysplasia 8-13% revealed HPV antigen while oral carcinoma cells and normal tissue samples were totally negative.

Antigens, Viral

Detection of herpes simplex virus type-2 DNA and human papilloma virus DNA sequences in cervical carcinoma tissue by molecular hybridization.

Biopsy samples from one hundred and two patients with squamous cell carcinoma of the uterine cervix and tissues from twelve healthy normal cervical tissues (post hysterectomy) were examined for HSV-type 2 and HPV-11 DNA sequences by molecular hybridization technique. In the carcinoma tissue extracts 53% contained HSV-2 DNA, 27% -HSV-1-DNA and 36% showed HPV-11 gene sequences while 5.7% were found to contain both HPV and HSV-2 DNA. Biopsies from healthy cervix were completely negative for HSV-2 and HPV-11 DNA sequences.

Base Sequence

Anti-HHV-6 antibodies in normal population and in cancer patients in India.

The prevalence and titre of IgG antibodies to human herpesvirus type 6 (HHV-6) were assayed in the serum samples from normal subjects and patients with Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), acute lymphoblastic leukaemia (ALL) and oral cancer (OC) using immunofluorescence and immunoperoxidase techniques. This forms the first study on the sero-prevalence and titre of antibodies to HHV-6 in India. There was no considerable difference in the prevalence (76%) and titre (10-160) of the antibodies in normal population from those reported for normal adults in other parts of the world. All the HL and ALL patients studied showed no significant elevation in the antibody titre, though a slight increase in the prevalence (95%) was noted. Antibody titre and prevalence were found highly elevated in OC. OC remained totally unstudied for the presence of anti-HHV-6 antibodies, and this is the first report of elevated levels of the antibody in this cancer. The role of HHV-6, if any, in the pathogenesis of OC is worth investigating.

Antibodies, Viral

Effect of a preparation from Viscum album on tumor development in vitro and in mice.

The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Dalton's lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.

Animals

Jack fruit lectin binding pattern in carcinoma of the uterine cervix.

A lectin was isolated and purified from the seeds of Jack Fruit (Artocarpus integrifolia) using a column of immobilized N-acetyl D-Galactosamine. The Jack Fruit lectin (JFL) was conjugated to horse radish peroxidase (HRP). The purified conjugate was used to study the binding properties of tissues from carcinomas of the uterine cervix. The binding to cancer tissues was compared with that of normal controls. The carcinomatous cells showed varying degrees of binding towards JFL in contrast to normal controls which generally had uniform binding. The nature and intensity of binding of the lectin with the cancer tissues suggest that this lectin may be used as a diagnostic marker in carcinoma of uterine cervix.

Carcinoma, Papillary

Chromosome abnormalities in squamous cell carcinoma of the human oral cavity.

Cytogenetic studies carried out in tissues of 75 patients with squamous cell carcinoma of the oral cavity gave satisfactory results in 12 cases. Remarkable variation characterized the modal chromosome numbers of these tumors, ranging from marked hypodiploidy to tetraploidy. Chromosomes which were lost belonged to group A whereas chromosomes which were gained belonged to groups C, D, E, F and G. Marker chromosomes were present in three cases. There was no correlation between the chromosome abnormalities observed and the clinical stages of the disease. The pattern of chromosome abnormalities ranging from marked hypodiploidy to tetraploidy observed in oral cancer tissues suggests an association of DNA oncogenic virus possibly Herpes simplex virus Type I (HSV-1) with oral cancer.

Adult

Serum levels of iron and proteins in oral submucous fibrosis (OSMF).

Serum proteins, serum iron and total iron binding capacity were estimated in 50 patients with oral submucous fibrosis and 50 patients with oral leukoplakia. The values were compared with that of 50 age- and sex-matched controls. A significant depression in hemoglobin and serum iron was observed in both groups of patients, whereas total iron binding capacity showed significant change only in the oral submucous fibrosis patients. Serum protein values were significantly lower in all the patients. The role of iron deficiency anemia in the causation of this premalignant lesion is discussed.

Adult

Total hemolytic complement (CH50) and its fractions (C3 and C4) in the sera of patients with premalignant and malignant lesions of the oral cavity.

Total hemolytic complement (CH50) and its fractions (C3 and C4) were estimated in the sera of 50 patients with oral leukoplakia, 50 patients with oral submucous fibrosis and 50 oral cancer patients. The values were compared with that of 50 normal controls. No significant alterations in the values of CH50, C3 or C4 were observed in the sera of patients with either leukoplakia or oral submucous fibrosis whereas the values were found to be altered significantly in oral cancer (P less than 0.001). In the case of oral submucous fibrosis the mean complement levels were slightly lower than those of normal controls and leukoplakia. Age and sex had no influence either on the total complement activity or its fractions (C3 and C4). The serum complement levels may be useful as a biological marker for the early detection of tissue dysplasia.

Adult

Presence of a receptor for the active component of Iscador in ascites fluid of tumour bearing mice.

Tumour bearing mice exhibit a specific "receptor" in the ascites fluid which binds with the active component isolated from Iscador. This "receptor" was found to be a protein which inhibited the cytotoxicity of Iscador and its isolated active component at low concentration. The receptor protein was also found in the sonicates of tumour cells which are susceptible to the action of Iscador but not in lymphocytes which were not susceptible to Iscador or its isolated active component. The receptor was separated on a Sephadex G-50 column. Activity was lost upon heat denaturation and dialysis.

Animals

An alternative pathogenetic pathway for oral submucous fibrosis (OSMF).

Oral submucous fibrosis is a potent pre-cancerous condition which occurs almost exclusively in Indians but cases have been reported from several countries. The definite aetiology of OSMF is still unknown and there is no known treatment for it. Chilles, tobacco use, vitamin deficiencies and betel quid chewing have been implicated. Ramanathan is of the view that OSMF seems to be the Asian version of sideropenic dysphagia. He suggests that OSMF appears to be an altered oral mucosa following prolonged period of chronic deficiency of iron and/or vitamin "B" complex especially folic acid. This changed state of the oral mucosa subsequently appears to develop more easily a hypersensitivity to oral irritants such as spices especially chillies and to the betel quid. We hold that the hypersensitivity caused by local irritants and the resultant persistent juxta epithelial inflammatory response noted in OSMF (in a host system already primed by an intrinsic genetic defect) act as the initiating factor leading to a defective inflammatory--reparative response, culminating in fibrotic healing. The role of iron and "B"complex together with others may be contributory (promotor) to this pre-existing pathologic response of the lamina propria.

Anemia

Ackerman's tumour (Verrucous carcinoma) of the oral cavity: a histopathologic study of 426 cases.

Salient histopathological features of four hundred and twenty six (426) cases of verrucous carcinoma of the oral cavity reported jointly by the Department of Oral Pathology, Dental College and Department of Pathology, Medical College, Trivandrum, during the period from January 1975 to December 1984 were evaluated. They constituted 5.27% of 7,988 primary malignant neoplasms of the oral cavity detected during the period. Locally aggressive behaviour with bone, muscle and salivary gland invasion occurred in 53% of cases. Examination of the neighbouring areas of the lesion, which showed some light on the natural evolution of the disease, is described. The gradual transformation of a hyperplastic verrucous lesion into carcinoma is appraised. Evidence suggestive of a distant metastatic spread of the tumour could not be detected.

Carcinoma, Papillary

Assessment of immunological parameters during tumour development in a murine model.

Natural Killer activity assessed by 51Cr release assay from K-562 cells showed detectable activity from 5th day after tumour transplantation, reaching a peak on 12th day and thereafter showing a gradual decline in the activity. Antibody dependent cell mediated cytotoxicity estimated by 51Cr labelled sheep red blood cells anti SRBC system demonstrated a peak activity on 5th day. Cytotoxic T lymphocyte activity detected by 51Cr release of Dalton's lymphoma ascites target cells showed a peak on 10th day. Antibody complement mediated cytotoxicity revealed a similar pattern as natural killer cell activity.

Animals

Isolation and identification of a tumour reducing component from mistletoe extract (Iscador).

Using a combination of gel filtration and paper chromatography, a tumour reducing component from mistletoe extract (Iscador) was isolated and identified to be a peptide of approximate molecular weight 5000. The isolated peptide reduced the solid tumour induced by Dalton's lymphoma ascites tumour cells (DLA cells) in mice. The isolated component was very cytotoxic to the DLA cells but was not cytotoxic to normal lymphocytes, indicating a cell dependent specificity.

Animals