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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 235 records · Page 13Linked to original sources
PubMed1992

Liposomes as antigen delivery systems in viral immunity.

Since their first description, liposomes have been put to a wide variety of uses. Encapsulation or incorporation of antigens into liposomes markedly enhances the immunogenicity of the antigen. The type of immune response elicited by the liposome is found to depend on their chemical and structural properties. Immunization with viral glycoproteins encapsulated in liposomes has resulted in enhancement of the humoral response seen as a rise in the serum antibody levels which is several fold higher than that elicited by free antigen alone. Furthermore, liposome encapsulation of peptide antigens which are poor immunogens by themselves not only increases the immunogenicity of the peptide but also play an important role in delivery. The adjuvant effect afforded by liposomes can be further enhanced by the concomitant encapsulation of adjuvants like lipid A or muramyl tripeptide-phosphatidylethanolamine. Formation of liposomes with special characteristics such as pH sensitivity has resulted in the use of liposomes to deliver soluble antigen to the cytosol where it can undergo class I pathway of processing and presentation. Therefore liposomes could provide valuable tools to further understand the pathways of antigen processing and the requirements for induction of cell mediated immunity.

Animals↗
PubMed1991

Flow cytometric monitoring of glutathione content and anthracycline retention in tumor cells.

We have used an enzymatic (spectro-photometric) and a flow cytometric (GSH-MBCL) method to compare the glutathione (GSH) content of doxorubicin sensitive (P388) and resistant (P388/R-84) murine leukemic and human lung cancer cells. The flow cytometric analysis revealed that GSH-MBCL conjugate formation was dependent on glutathione-S-transferase (GST) activity. The human solid tumor cell lines exhibited extensive heterogeneity, high GSH content, and GST activity. In contrast to the enzymatic method, the flow cytometric method did not accurately reflect the 95% reduction in GSH content of cells treated for 24 h with 100 microM BSO. Possible reaction of MBCL with other sulfhydryl groups (other than GSH) in BSO-treated cells may be responsible for this discordance. We have also shown the feasibility of using dual parameter flow cytometry to monitor cellular anthracycline (daunorubicin) retention and GSH-MBCL conjugate fluorescence in human tumor cells. These two parameters, which measure drug retention and cellular detoxification, are believed to be the important determinants of chemoresistance in tumor cells.

Adenocarcinoma↗
PubMed1991

Radical proposal for the treatment of malignant astrocytoma.

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles.

Astrocytoma↗
PubMed1991

Cloning and expression in Escherichia coli of a recA homologue from Mycobacterium tuberculosis.

A 3.8 kb PstI fragment of Mycobacterium tuberculosis was cloned in a recA-deleted Escherichia coli by selecting transformants with increased EMS resistance. The cloned fragment restored homologous recombination in Hfr crosses and conferred resistance to long wave (302 nm) but not short wave (254 nm) UV light. E. coli containing the 3.8 kb PstI fragment produced a 38-40 kDa protein which cross-reacted with antibodies raised against the E. coli RecA protein. The cloned DNA thus probably encodes a RecA homologue.

Antibodies, Bacterial↗
PubMed1991

Respi-Care. An innovative home care program for the patient with chronic obstructive pulmonary disease.

The purpose of the present study was to evaluate the effectiveness of a hospital-based home care program for a group of patients with severe COPD. Respi-Care was a multidisciplinary home care program administered by Norwalk Hospital in cooperation with the public health nursing departments of the city of Norwalk and the town of Wilton, Conn. The overall goal of Respi-Care was to provide more comprehensive home care services to patients previously requiring frequent hospitalizations by combining the advantages of hospital resources and community agencies through a unique cooperative effort. Preprogram and on-program data were collected on the following variables for the 48 months of Respi-Care operation: hospitalizations; hospital days; emergency room visits; home care services; and the costs of these services. Costs of operating the Respi-Care program were included in on-program data. Seventeen subjects completed 320.5 months on Respi-Care. Each subject was matched to an equal length of time prior to entering the program, for a total of 641 months analyzed. There were 88 preprogram hospitalizations for the group; hospitalizations while participating in Respi-Care dropped to 53 (p = 0.022; paired t statistics). On-program hospital days showed a significant decrease, from 1,181 preprogram days to 667 on-program days (p = 0.024). Emergency room visits decreased from 105 before the program to 64 during the program (p = 0.017). Costs of care also decreased. Costs for hospitalizations, emergency room visits, and home care fell from $908,031 to $802,999, resulting in a $105,032 savings or $328 per patient per month.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Intracranial cystic meningioma.

Two cases of intracranial cystic meningiomas are reported. Neuroradiological and intraoperative diagnoses in both cases were cystic astrocytoma. However routine biopsy during the intra-operative period and an accurate interpretation during frozen-section will establish the diagnosis of cystic meningioma. Complete excision of cyst wall of the meningioma during the surgery will minimise the incidence of recurrence of these benign tumours.

Adult↗
PubMed1991

Effect of chromium on growth of Pseudomonas aeruginosa.

Tolerance level to trivalent chromium-Cr(salen)(H2O)2+ and hexavalent chromium-K2Cr2O7 was assessed in P. aeruginosa isolated from tannery effluent soil. It could tolerate 80 and 100 ppm in liquid cultures and up to 100 and 200 ppm in plate count agar in the presence of trivalent and hexavalent chromium respectively. Unadapted cells took a longer time to grow than adapted cells in the presence of K2Cr2O7. Chromium influenced the cellular contents, morphology and respiration of P. aeruginosa. The chosen trivalent salt of chromium was more toxic than the hexavalent one.

Chromium↗
PubMed1990

Anthracycline resistance in murine leukemic P388 cells. Role of drug efflux and glutathione related enzymes.

Energy-dependent drug efflux is a major factor in cellular resistance of P388/R84 mouse leukemic cells to anthracyclines such as doxorubicin (DOX), and blocking of efflux increases sensitivity. However, efflux does not play a significant role in resistance to N-trifluoroacetyladriamycin-14-valerate (AD 32), a DOX analog. Since drug efflux alone cannot account for resistance to anthracyclines, we have, in the present study, measured cellular glutathione (GSH) content and activity of GSH cycle related enzymes to determine their role in resistance. Cellular GSH content was similar in DOX-sensitive and -resistant mouse leukemic cells (P388 and P388/R84). GSH peroxidase, glucose-6-phosphate dehydrogenase and glutathione reductase activities were 1.36-, 1.58- and 1.14-fold higher in P388/R84 cells. Incubation of P388/R84 cells with 100 microM buthionine-S,R-sulfoximine (BSO) for 24 hr reduced cellular GSH content to 6% of control and reduced their resistance to DOX [dose modification factor (DMF) 3.9]. GSH depletion had no significant effect on the cytotoxicity of AD 32 (DMF 1.5). Exposure of P388/R84 cells to BSO (for GSH depletion) and trifluoperazine (for efflux blocking) further reduced their resistance to DOX (DMF 14). These results indicate that DOX resistance in P388/R84 cells is multifactorial and that changes in GSH cycle related enzymes such as GSH peroxidase may also contribute to their resistance.

Animals↗
PubMed1990

Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats.

Rat plasma distribution data obtained following IV administration of 99mTc(DTPA) alone or after co-administration of 99mTc(DTPA) and 153Gd-labeled Gd(DTPA)2- at 0.001, 0.1, and 1.0 mmol Gd/kg were evaluated using compartmental modeling techniques. A three-compartment open model was found to fit the data significantly better (P less than 0.01) than a two- or four-compartment open model. This model incorporates and links the plasma and urine data and includes a delay to account for the transit time through the kidneys/ureters. The two nonplasma compartments of the model were assumed to be related to rapidly and slowly equilibrating tissues. Tc(DTPA) and Gd(DTPA)2- had nearly identical pharmacokinetic profiles in plasma and the rate constants were essentially the same. No significant dose dependent pharmacokinetic differences were found for the range of Gd(DTPA)2- doses tested. Simulations of the proposed three-compartment model were used to generate concentration-time curves for each of the three compartments.

Animals↗
PubMed1990

A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.

Adolescent↗
PubMed1990

Non-Hodgkin's lymphoma in a south Indian Hospital--our experience with the International Working Formulation.

There were 836 biopsy cases of Malignant Lymphomas over a seven year period, among which Non-Hodgkin's Lymphomas (70 percent) predominated over Hodgkin's Disease (30 percent). Non-Hodgkin's lymphomas could be easily classified using the IWF. The Diffuse variety was much commoner than the Follicular variety. The Diffuse Large cell type was the commonest histologic type. The Gastrointestinal tract was the commonest site for extranodal lymphomas. Though sophisticated immunological methods are available for lymphoma analysis, histologic classification will continue to remain the principal method of lymphoma typing in our country.

Adolescent↗
PubMed1989

Glutathione S-transferases and glutathione peroxidases in doxorubicin-resistant murine leukemic P388 cells.

Energy-dependent rapid drug efflux is believed to be a major factor in cellular resistance to doxorubicin (DOX). However, several recent studies have demonstrated that cellular DOX retention alone does not always correlate with its cytotoxicity and suggest that mechanisms other than rapid drug efflux may also be important. In the present study, we have compared glutathione (GSH) S-transferase (GST), selenium-dependent GSH peroxidase and selenium-independent GSH peroxidase II activities in DOX-sensitive (P388/S) and resistant (P388/R) mouse leukemic cells. The GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid (EA) was markedly higher in P388/R cells compared to P388/S cells. Purification of GST by GSH-affinity chromatography from an equal number of P388/S and P388/R cells revealed an increased amount of GST protein in P388/R cells. Immunological studies indicated that alpha and pi type GST isoenzymes were 1.27- and 2.2-fold higher, respectively, in P388/R cells compared to P388/S cells. Selenium-dependent GSH peroxidase activity was similar in both the cell lines, whereas selenium-independent GSH peroxidase II activity was approximately 1.36-fold higher in P388/R cells compared to P388/S cells. These results suggest that increased GSH peroxidase II activity in P388/R cells may contribute to cellular DOX resistance by enhancing free radical detoxification in this cell line.

Animals↗
PubMed1989

Angiosarcoma of the nasal cavity and maxillary antrum.

Angiosarcoma (malignant haemangioendothelioma) of the nasal cavity and paranasal sinuses is extremely rare. Only a few cases have been reported in literature. A case of angiosarcoma of the nasal cavity and maxillary antrum in a 38-year-old male patient is reported. He was treated with pre-operative external radiotherapy followed by wide excision of the tumour. He currently remains free of the disease 10 months after diagnosis (and seven months after completing therapy).

Adult↗
PubMed1989

Noninvasive face mask ventilation in patients with acute respiratory failure.

Noninvasive face mask ventilation has been used successfully in patients with paralytic respiratory failure. This study evaluated whether noninvasive face mask ventilation can be used for patients with acute respiratory failure due to intrinsic lung disease. Six patients with hypercapnia and four with hypoxemic acute respiratory failure met clinical and objective criteria for mechanical ventilation, which was delivered with pressure control and pressure support via a tightly strapped, clear face mask. No patient terminated the study because of inability to deliver adequate ventilation or to improve oxygen exchange; three eventually required endotracheal intubation. The mask was generally well tolerated. All patients had a nasogastric tube placed on suction, and none vomited or aspirated. The mean duration of treatment was 33 h (range, 3 to 88). The physiologic response was considered similar to that which would have been achieved with conventionally delivered ventilation. Noninvasive face mask ventilation may have a role in managing respiratory failure.

Adult↗
PubMed1988

Electrophoretic mobility studies on doxorubicin-resistant and -sensitive murine P388 leukemic cells.

The electrokinetic properties of doxorubicin (DOX)-resistant (P388/R) and -sensitive (P388/S) murine leukemic cells were studied in a free-flow electrophoresis (FFE) system. The electrophoretic mobilities (EM) of P388/S and P388/R cells were 1.07 and 1.35 x 10(-4) cm2 V-1 s-1, respectively, suggesting a higher net negative charge on the P388/R cells. Neuraminidase treatment decreased the EM of both the P388/S and P388/R cells by 15-20% but had no effect on cellular doxorubicin retention. Total and cell surface sialic acid contents were similar in both the cell lines. Our studies show that no direct correlations may exist among surface charge, cell surface sialic acid content, and doxorubicin retention in DOX-resistant and -sensitive P388 cells; however, differences in cell surface charge between these cell types were used to separate them by preparative FFE.

Animals↗
PubMed1987

Distribution and significance of heterotrophic marine bacteria with antibacterial activity.

Bacteria with antibacterial activity were isolated from seawater, sediments, phytoplankton, and zooplankton of Suruga, Sagami, and Tokyo Bays and from soft corals and sponges collected from the Taiwan coast. Of the 726 strains isolated, 37 showed antibacterial activity against either Vibrio parahaemolyticus (ATCC 17802) or Staphylococcus aureus (P209). Sediment harbored the lowest number of these forms of bacteria, and those from Tokyo Bay did not show any activity. Attached isolates showed greater activity compared with free-living forms. Relatively high numbers of strains with antibacterial activity were associated with phytoplankton. Among the zooplankton isolates, cladocerans harbored the maximum number of antibacterial strains. Isolates were more inhibitory to gram-positive test cultures. Autoinhibition was observed only among 8% of the isolates. Marine nonproducers were more susceptible. Pseudomonas/Alteromonas species made up 81.0% of isolates, of which 30% were pigmented strains. The absence or reduction in number of bacteria with antibacterial activity in Tokyo Bay is attributed to its eutrophic nature, which may tend to moderate the production of antibacterial compounds.

Anti-Bacterial Agents↗