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Biomedical subjects

S Ramakrishnan

Publications and source records attributed to S Ramakrishnan.

At least 145 records · Page 8Linked to original sources
PubMed1994

A mixed micellar formulation suitable for the parenteral administration of taxol.

Taxol is a promising antitumor agent with poor water solubility. Intravenous administration of a current taxol formulation in a non-aqueous vehicle containing Cremophor EL may cause allergic reactions and precipitation upon aqueous dilution. In this study a novel approach to formulate taxol in aqueous medium for i.v. delivery is described. The drug is solubilized in bile salt (BS)/phospholipid (PC) mixed micelles. The solubilization potential of the mixed micelles increased as the total lipid concentration and the molar ratio of PC/BS increased. Precipitation of the drug upon dilution was avoided by the spontaneous formation of drug-loaded liposomes from mixed micelles. The formulation can be stored in a freeze-dried form as mixed micelles to achieve optimum stability, and liposomes can be prepared by simple dilution just before administration. As judged by a panel of cultured cell lines, the cytotoxic activity of taxol was retained when formulated as a mixed-micellar solution. Further, for the same solubilization potential, the mixed-micellar vehicle appeared to be less toxic than the standard nonaqueous vehicle of taxol containing Cremophor EL.

Animals↗
PubMed1994

Degradation of ricin A chain by endosomal and lysosomal enzymes--the protective role of ricin B chain.

We investigated the role of intracellular processing of ricin A chain (RTA) by proteolytic enzymes on the expression of its ribosome inhibitory activity. Endosomal and lysosomal proteases extracted from Jurkat cells and purified cathepsins B, D and G were incubated with RTA, resulting in generation of a 28-kDa fragment by proteolytic cleavage. This process was reminiscent of the nicking of Pseudomonas exotoxin and Diphtheria toxin by intracellular proteases to produce functionally active toxin fragments. However, the ribosome inhibitory activity of the purified 28-kDa fragment of RTA was 11,000-fold less than that of native RTA, suggesting that such cleavage is not an essential step in the cytotoxic activity of the toxin. Addition of ricin B chain (RTB) in degradation assays resulted in the protection of RTA from proteolytic activities of lysosomes and cathepsins. However, RTB did not protect another RNA acting protein, RNAase; nor did excess amounts of unlabeled RTA or IgG protect labelled RTA from degradation, suggesting that the protective effect of RTB was specific to its interaction with RTA. Such a protective role for RTB may partially account for the higher toxicity of immunotoxins (ITs) containing whole ricin compared to ITs containing only RTA.

Cathepsins↗
PubMed1993

Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in patients with ovarian epithelial cancer.

BACKGROUND: Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor-alpha (TGF-alpha). Concomitantly, the serum levels of one of the growth factors (M-CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second-look patients. The authors evaluated the serum levels of IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. RESULTS: In serum, TNF-alpha and IL-6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF-alpha and IL-6 were also significantly higher than the levels found in second-look patients (P < 0.007 for TNF-alpha, and P = 0.0002 for IL-6). The levels of IL-1 alpha and beta were not elevated in ovarian cancer. TNF-alpha in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut-off point between 71-110 pg was selected (P < 0.005). The levels of IL-6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. CONCLUSIONS: Levels of IL-1, IL-6, and TNF-alpha were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL-6 and TNF-alpha in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

Ascitic Fluid↗
PubMed1993

Ascites levels of haptoglobin in patients with ovarian cancer.

BACKGROUND: Haptoglobin is an acute-phase reactant protein involved in immune regulation. It has been isolated from malignant ovarian ascites and has been shown to be capable of mediating nonspecific immune suppression in vitro in humans and in vivo in experimental animals. The range of concentrations under which such a nonspecific suppression is observed lies well within concentrations of haptoglobin observed in vivo. This immune suppression could adversely affect patient outcome. METHODS: Based on this information, ascites haptoglobin levels of 21 consecutive patients with ovarian cancer who underwent initial surgical debulking were determined. After the patients received chemotherapy, they were divided into those having a positive and those have a negative second-look operation. RESULTS: Seventeen patients with positive pathology at second look had an initial mean ascites haptoglobin level of 99 +/- 49 mg/dl. The mean haptoglobin level in the four patients with negative findings was 67 +/- 42 mg/dl. The difference in these mean haptoglobin levels is not statistically significant (P > 0.05). CONCLUSION: Although the number of patients in this study is small, the wide range of values documented in both groups make it doubtful that an initial absolute ascites haptoglobin level will prove clinically prognostic of eventual disease status at the time of second look laparotomy.

Adenocarcinoma↗
PubMed1993

Constitutive production of macrophage colony-stimulating factor and interleukin-6 by human ovarian surface epithelial cells.

Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal epithelial cells from which epithelial ovarian neoplasms are thought to arise. Epithelial cells from the surface of premenopausal human ovaries were established in short-term cultures. The cells bound anti-cytokeratin antibodies and exhibited characteristic epithelial morphology by light and transmission electron microscopy. M-CSF and IL-6 were detected in supernatants from cultures of these cells, using assays specific for each factor. Cytokine levels were comparable to those in supernatants from ovarian and breast cancer cell lines. M-CSF expression could also be demonstrated by immunohistochemical analysis with specific rabbit heteroantiserum. Thus, M-CSF and IL-6 are produced constitutively by normal as well as by neoplastic ovarian epithelium.

Cells, Cultured↗
PubMed1993

Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis.

The amino acid lysine has been reported to delay cataractogenesis by 'some unknown mechanism'. Lysine and glycine were found to react with glucose at physiological pH and temperature and undergo non-enzymic glycation. The formation of glycated lysine was shown by paper and thin-layer chromatography, HPLC and using an authentic sample of epsilon-fructosyl lysine. Confirmation was made by studies on incorporation of U-[14C]glucose into lysine and glycine. The extent of glycation of lysine was 15.5% in 96 hr and rose to 20% in 20 days. Lysine and glycine alone of varying concentrations lowered the extent of glycation of lens proteins significantly in glucose-treated homogenates of normal lens from humans and goats. Scavenging of intracellular glucose and thereby protecting the lens proteins from excessive glycation appears to be the mechanism of action by which lysine and glycine could exercise beneficial effect on cataract.

Animals↗
PubMed1993

Undergraduate medical teaching in departments of oncology in the United Kingdom: a questionnaire survey.

A questionnaire survey has been conducted to assess the nature and extent of teaching given to undergraduate medical students in departments of Oncology within the United Kingdom. Postal questionnaires were sent to 58 departments of Radiotherapy/Oncology and 30 departments of Medical Oncology. This included both teaching and nonteaching departments. Response rates were 84.5% (49 replies) and 90% (27 replies), respectively. Of the responders, 26 Radiotherapy/Oncology departments (53%) and 21 Medical Oncology departments (78%) have a regular commitment to undergraduate medical teaching, the majority being units affiliated to teaching hospitals. The time spent in teaching, methods of teaching, the teaching curriculum, and other details have been documented and are summarised. The information obtained leads us to conclude that there is a considerable variation between departments with regard to teaching commitments and the curriculum. Such variations appear to be primarily centre oriented rather than specialty biased. The survey also raises a number of issues regarding undergraduate medical teaching with reference to oncology, which are discussed.

Academic Medical Centers↗
PubMed1993

Fermentation of lactose by yeast cells secreting recombinant fungal lactase.

Strains of Saccharomyces cerevisiae transformed with a yeast multicopy expression vector carrying the cDNA for Aspergillus niger secretory beta-galactosidase under the control of ADH1 promoter and terminator were studied for their fermentation properties on lactose (V. Kumar, S. Ramakrishnan, T. T. Teeri, J. K. C. Knowles, and B. S. Hartley, Biotechnology 10:82-85, 1992). Lactose was hydrolyzed extracellularly into glucose and galactose, and both sugars were utilized simultaneously. Diauxic growth patterns were not observed. However, a typical biphasic growth was observed on a mixture of glucose and galactose under aerobic and anaerobic conditions with transformants of a haploid S. cerevisiae strain, GRF167. Polyploid distiller's yeast (Mauri) transformants were selected simply on the basis of the cloned gene expression on X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside) plates. Rapid and complete lactose hydrolysis and higher ethanol (0.31 g/g of sugar) and biomass (0.24 g/g of sugar) production were observed with distiller's yeast grown under aerobic conditions. A constant proportion (10%) of the population retained the plasmid throughout the fermentation period (48 h). Nearly theoretical yields of ethanol were obtained under anaerobic conditions on lactose, glucose, galactose, and whey permeate media. However, the rate and the amount of lactose hydrolysis were lower under anaerobic than aerobic conditions. All lactose-grown cells expressed partial galactokinase activity.

Aerobiosis↗
PubMed1993

Hypokalemic paralysis.

A case of Hypokalemic paralysis is reported which had an atypical onset and clinical features. The paralysis totally recovered on replacement of potassium.

Adult↗
PubMed1993

Dietary protein and cholesterol metabolism in small intestines.

Effect of quality and quantity of dietary protein on blood cholesterol and cholesterol metabolism in small intestines of rat was examined. Compared to casein, bengalgram in the diet decreased blood and intestinal cholesterol. It is suggested that this effect may be due to low levels of leucine in bengalgram protein and less release of insulin, an activator of HMG CoA Reductase. Low casein in the diet (12%) caused a decrease of blood and intestinal cholesterol while high casein in the diet (24%) caused a decrease of intestinal cholesterol only. It is suggested that both qualitywise and quantitywise, dietary protein influences body cholesterol. It is known that the nature and the quality of dietary fat and carbohydrates directly influence the metabolism of cholesterol. The dietary proteins might also have a significant role. Proteins are needed for the synthesis of enzymes required for the anabolism and catabolism of cholesterol and a few protein-aminoacids like leucine have a direct influence on cholesterol metabolism. Bengalgram was chosen for studying the effect of the quality of protein on cholesterol metabolism as there are reports in the literature that bengalgram feeding reduces blood cholesterol. Different amounts of casein-containing diet were used in a separate set of experiments to investigate the effects of low and high protein diets on cholesterol metabolism i.e. quantitative effects of dietary protein. For many years, liver was enjoying the privilege of maintaining the homeostasis of blood cholesterol. Recently it has been shown that small intestines also synthesises considerable amounts of cholesterol. Hence, cholesterol metabolism was investigated separately in duodenum, jejunum and ileum.

Animals↗