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Biomedical subjects

S Madan

Publications and source records attributed to S Madan.

34 records · Page 2Linked to original sources
PubMed1993

Potentiation of ricin cytotoxicity by liposomal monensin under in vitro and in vivo conditions.

Effect of monensin, intercalated in liposomes on the cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in phagocytic and non-phagocytic cells as well as in mice has been studied. Intercalation does not disturb the integrity of the liposomal bilayer and substantially enhances the cytotoxicities of ricin and Pseudomonas exotoxin A in both phagocytic and non-phagocytic cells while it has no effect on diphtheria toxin. The observed effect is highly dependent on the liposomal lipid composition as well as cell types. The potentiating ability of monensin in neutral vesicle is 2.2-fold higher than in negatively charged vesicles in non-phagocytic cells while no difference was observed in phagocytic cells. Incorporation of stearylamine in liposomes reduces the potentiating effect of monensin. Liposomal monensin has also been found to enhance the cytotoxicity of ricin in mouse in vivo in a dose-dependent manner and is maximal when ricin is injected within 60 min of monensin injection. Liposomal monensin remains in circulation for 2 hr while free monensin remains only for 15 min. Tissue distribution studies reveal that liposomal monensin is present mainly in the liver and spleen which are also the major sites for ricin accumulation. Thus liposome is found to be an effective delivery vehicle for monensin to potentiate the cytotoxicity of immunotoxins or hormonotoxins and could prove useful for selective elimination of cancer cells.

ADP Ribose Transferases↗
PubMed1992

Monensin intercalation in liposomes: effect on cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in CHO cells.

Monensin, a carboxylic ionophore was intercalated in liposomes (liposomal monensin) and its effect on cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in CHO cells was studied. Intercalation of monensin in liposomal bilayer is found to have no effect on its stability and interaction with cells. Liposomal monensin (1 nM) substantially enhance the cytotoxicities of ricin (62-fold) and Pseudomonas exotoxin A (11.5-fold) while it has no effect on diphtheria toxin. This observed effect is highly dependent on the liposomal lipid composition. The potentiating ability of monensin (1 nM) in neutral vesicles is significantly higher (2.2-fold) as compared to negatively charges vesicles. This ability is drastically reduced by incorporation of stearylamine in liposomes and is found to be dependent on the density of stearylamine as well as on the concentration of serum in the medium. Monensin in liposomes containing 24 mol% stearylamine has a very marginal effect on the cytotoxicity of ricin (7.5-fold) which is further reduced (1.5-fold) in the presence of 20% serum. The uptake of 125I-gelonin from neutral vesicles is significantly higher (approximately 2.0-fold) than that from the negative vesicles. The uptake from positive vesicles is highly dependent on the concentration of stearylamine. The reduction in the lag period (30 min) of ricin action by monensin in neutral and negative vesicle is comparable with free monensin. However, monensin in positive vesicle has no effect on it. These studies have suggested that liposomes could be used as a delivery vehicle for monensin for selective elimination of tumor cells in combination with hybrid toxins.

ADP Ribose Transferases↗
PubMed1992

First prenatal diagnosis of X-linked lymphoproliferative disease.

A family study was performed in order to diagnose X-linked lymphoproliferative (XLP) disease in a fetus. The molecular genetic analysis indicated that the fetus, as well as its healthy 7-year-old brother, inherited XLP. Analysis of immunoglobulin subclasses from the 7-year-old brother supported the DNA-based diagnosis. This is the first XLP family of African descent.

Autoradiography↗
PubMed1992

In vivo potentiation of ricin toxicity by monensin delivered through liposomes.

Monensin, a carboxylic ionophore, which is known to raise intravesicular pH, was intercalated in liposomes and its effect on the toxicity of ricin in mice was studied. The toxicity of ricin in vivo was found to be significantly enhanced by the administration of monensin intercalated in liposomes (liposomal monensin). The observed enhancement of the toxicity of ricin by monensin was highly dose-dependent and was maximal when ricin was injected within 60 min of monensin injection. The survival time was found to be reduced in the range of 8-20 h, depending on the dose of ricin used, by liposomal monensin. Stability of liposomes containing monensin as inferred from the release of entrapped calcein or FITC-dextran under both in vivo and in vitro conditions was comparable to that observed for liposomes without monensin. Liposomal monensin remains in circulation for 2 h and was cleared from the blood stream after 4 h. In contrast, 15 min was required for the clearance of monensin when administered in free form. Studies on the distribution of liposomal monensin and 125I-ricin in various tissues have revealed that monensin is mainly localized in the liver and spleen which are also the major sites for ricin accumulation. Our observation on the substantial enhancement of ricin toxicity in vivo by liposomal monensin strongly supports the potential usefulness of the latter as a potentiating agent in the enhancement of the toxicity of immunotoxin or hormonotoxin for selective elimination of cancer cells.

Animals↗
PubMed1992

Liposome immune lysis assay (LILA) for gelonin.

A complement-mediated liposome immune lysis assay using entrapped calcein was developed for a plant toxin gelonin. Gelonin was covalently coupled to DPPE, and then adsorbed on to the surface of liposomes. Such antigen-bearing liposomes when incubated with anti-gelonin antibody in the presence of guinea pig complement undergo lysis. The detection range is from 3 ng to 60 ng. The method was used to monitor isolation of gelonin by affinity chromatography. It was observed that a minor peak in addition to the major one comes with gelonin, shared common epitopes/epitope with gelonin in immunological reaction. This was further confirmed by SDS-gel electrophoresis indicating the former being an isoform of gelonin. A comparative study of the immunocross-reactivity of ricin and ricin A chain with anti-gelonin antibody was carried out. It was found that while ricin A chain cross-reacted extensively with gelonin antibody and intact ricin elicited little or no cross-reactivity. It is suggested that the present LILA may be employed for the detection and quantitation of ricin A chain by this LILA method.

Binding, Competitive↗
PubMed1992

Interaction of gelonin with macrophages: effect of lysosomotropic amines.

The cytotoxic effects of gelonin on various phagocytic and nonphagocytic cells were studied. Peritoneal exudate cells (PEC) are found to be more sensitive to gelonin compared to P388D1 and J774A.1 cells, nonphagocytic cells being the least sensitive. While chloroquine markedly enhances the cytotoxicity of gelonin in macrophages (greater than 100-fold) ammonium chloride confers protection. A higher rate of uptake of 125I-gelonin in PEC (7 times the rate observed in other cells) is probably mediated by an interaction of terminal mannose residues of gelonin with mannose receptors on PEC plasma membrane as inferred from a pronounced inhibitory effect of mannan. In contrast to a pronounced inhibitory effect of mannan on the uptake of gelonin in PEC (7-fold), the cytotoxicity is reduced only by 2-fold. On the other hand, mannan has little or no effect on enhancement of the toxicity of gelonin by chloroquine. The studies have suggested that the internalization of gelonin in PEC may involve two pathways: (a) mannose receptor-mediated endocytosis, which plays a minor role in the intoxication process, and (b) nonspecific fluid phase pinocytosis, which is susceptible to enhancement by chloroquine and has a major role to play in the manifestation of the toxic effect of gelonin. In macrophage-like cells only the latter pathway operates.

Ammonium Chloride↗
PubMed1992

Enhancing potency of liposomal monensin on ricin cytotoxicity in mouse macrophage tumor cells.

Monensin, a carboxylic ionophore, which is known to disrupt intracellular trafficking of proteins was intercalated in liposomes and its effect on the stability of liposomes and cytotoxicities of ricin and Pseudomonas exotoxin A in mouse macrophage tumor cells J774A.1 was studied. Stability of liposomes containing monensin was comparable to liposomes without monensin. The cytotoxicity of ricin and Pseudomonas exotoxin A was significantly enhanced by 1nM liposomal monensin (15.7 and 3.6 fold respectively). The enhancing potency of monensin in neutral and negative vesicles was found to be similar, while it was drastically reduced in positive vesicles. The specific uptake of 125I-gelonin from neutral and negative vesicles was not significantly different, whereas from positive vesicles no uptake was observed. Serum strongly influenced the binding at 4 degrees C of positive vesicles as well as the enhancing potency of monensin in these vesicles. Monensin in neutral and negative vesicles significantly reduced the lag period of ricin action, while in positive vesicles, it had no effect. These studies clearly indicate that liposomes could be used as a delivery vehicle for monensin.

ADP Ribose Transferases↗
PubMed1991

Inter-relationship between dental, skeletal and chronological ages in well-nourished and mal-nourished children.

Dental casts, wrist roentgenograms and full mouth radiographs of teeth of 80 mal-nourished and 40 well-nourished children were evaluated and compared for correlation of dental, skeletal and chronological ages. The findings revealed (1) very high correlation between dental and skeletal ages (r = 0.9584); (2) high correlation of chronological age with dental and skeletal ages (r = 0.8635 and r = 0.8716); (3) out of all the three correlations considered, dental and skeletal ages had the maximum correlation; (4) malnutrition had a significant adverse effect on the skeletal and dental ages. Greater the severity of malnutrition, more pronounced was its effect on the dental and skeletal ages; and (5) no evidence of severity of malocclusion with retarded skeletal and dental ages.

Adolescent↗
PubMed1988

Monosomy, trisomy, fragile sites, and rearrangements of chromosome no. 1 in a mentally retarded male with multiple congenital anomalies.

A 17-year-old male was referred for evaluation because of short stature and severe mental retardation. Major clinical findings included microphthalmia, micrognathia, low-set ears, a prominent beaked nose, clubbing of digits, and premature graying of hair. Cytogenetic analysis revealed a 45,XY,-1/46,XY/47,XY,+1 mosaicism in lymphocytic culture, a 45,XY,-1/46,XY mosaicism in skin fibroblasts, and fra(1p) sites in 2% of the metaphases from lymphocyte, fibroblast and bone marrow cultures. Post-zygotic non-disjunction causing this mosaicism is believed to be responsible for the patient's phenotype.

Abnormalities, Multiple↗
PubMed1985

Once-daily use of glyburide.

Ideally, metabolic control with sulfonylureas should be maintained for 24 hours. To determine an optimal glyburide dosage schedule, the effects of glyburide once (every morning) or twice daily and chlorpropamide once daily (every morning) were compared in 18 men with non-insulin-dependent diabetes mellitus in a randomized, double-blind fashion. After discontinuation of previous hypoglycemic agents for 10 days, patients were admitted to a metabolic ward for two weeks (Study A). Glycemic measurements were performed on Day 14. Subjects were readmitted after 12 weeks of outpatient therapy for another two weeks (Study B), and glycemic determinations were repeated. Weight was kept constant during and between Studies A and B. Effective hypoglycemic action of each drug regimen was demonstrated. When six glycemic parameters were compared, there was no significant difference between groups. Thus, over a 14-week period, both glyburide regimens were similar and as effective as chlorpropamide once daily.

Blood Glucose↗
PubMedDate not supplied

Patients' recollection of day case knee arthroscopy procedure.

A prospective study of 103 consecutive patients who underwent day case knee arthroscopy was performed. The purpose was to evaluate the information delivery system, patient comprehension, and issues of informed consent pertaining to day case arthroscopy procedures. There were 34 females and 69 males in the study group and their mean age was 38.6 years (range: 14.4 to 74.9 years). The diagnosis, procedure, and aftercare were explained to the patients in the outpatients clinic by a trained nurse and by the operating surgeon just prior to the operation. The nurse before the operation gave the patients an information booklet. Postoperatively the patients were informed about the findings and diagnosis prior to their discharge from the day care facility. Patients were requested to complete a questionnaire. Three weeks later they were given the same questionnaire, prior to consultation, in the outpatient clinic. These two forms were compared with the operative findings and diagnosis documented in the copy, of the questionnaire completed by the surgeon as well as the case notes. Most patients (38.8%; 40 patients) had no recollection; 3.9% (4 patients) had partial recollection at their consultation three weeks later; 19.4% (20 patients) found that the arthroscopic photograph was not helpful in making them understand the procedure; and 9.7% (10 patients) found the information booklet to be unhelpful. Further, 23.3% (24 patients) said that it would not help if the booklet were sent to them prior to the operation. The recollection rate was also correlated to their position on the operating list, to ascertain the effect of the anesthetic. There was a 65.9% (58 patients) recollection rate in those patients who were on the first half of the list and there was only a 33.33% recollection rate in those patients who were last or second to the last [p = 0.0225]. We recommend regular evaluation and improvement in the communication and information delivery system provided to patients.

Adolescent↗