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Biomedical subjects

R Mehta

Publications and source records attributed to R Mehta.

At least 109 records · Page 6Linked to original sources

In vitro interaction of M. leprae-infected Schwann cells and splenic cells.

The interaction between M. leprae-infected cultured Schwann cells and sensitized splenic cells was noted both under light and electron microscopy. No evidence of cytomorphological changes in infected Schwann cells was obtained. However, sensitized splenic cells were noted to undergo degenerative changes suggestive of the phenomenon of apoptosis. Subsequently a large number of these degenerated cells were observed within the Schwann cell. Such a process has not been hitherto reported in the histopathology of leprous nerves. Nevertheless, these findings indicate an aberrant metabolic function in M. leprae-infected Schwann cells.

Animals↗

The L protein of vesicular stomatitis virus modulates the response of the polyadenylic acid polymerase to S-adenosylhomocysteine.

TsG16(I) is a temperature-sensitive (ts) mutant of vesicular stomatitis virus, Indiana serotype, which overproduces polyadenylic acid [poly(A)] in an in vitro transcription system due to a mutation in the L protein. Others have reported that L-S-adenosylhomocysteine (S-Ado-Hcy) causes wild-type (wt) virus to overproduce poly(A) in vitro. The possibility that tsG16(I) constitutively expresses a property induced by S-Ado-Hcy in the case of wt virus was found not to be so since polyadenylation by the mutant was still sensitive to S-Ado-Hcy. Indeed, S-Ado-Hcy caused tsG16(I) to overproduce poly(A) in vitro to a greater extent than its parental wt virus. The increase in polyadenylation observed in response to saturating levels of S-Ado-Hcy differed for tsG16(I), for its parental wt virus and for another wt strain. To characterize which viral protein modulated the polyadenylation response to S-Ado-Hcy, purified virions were fractionated and their phenotypes in homologous and heterologous reconstitution assays were examined. The results indicated that the viral L protein modulated the response in all three stocks of virus. These data provide further evidence to suggest that the L protein of vesicular stomatitis virus plays a role in polyadenylation of the viral mRNA.

Adenosine Monophosphate↗

Isolation and structure determination of Pachybasium cerebrosides which potentiate the antifungal activity of aculeacin.

A set of four cerebrosides was isolated from a Pachybasium species and purified by preparative reversed-phase HPLC. All four products displayed activity in a natural product screen aimed at detecting novel cell wall-active antifungal agents based on synergy with the known glucan synthetase inhibitor, aculeacin. Based on degradation studies, fast atom bombardment mass spectrometry and 13C and high field 1H NMR techniques, the structure of the major cerebroside was determined to be (4E,8E)-N-D-2'-hydroxy-(E)-3'- hexadecenoyl-1-O-beta-D-glucopyranosyl-9-methyl-4,8-sphingadiene. The other components were found to be the corresponding 2'-hydroxypalmitic acid analog with one less double bond and an analogous pair containing 2'-hydroxystearic acid with and without the 3' double bond.

Antifungal Agents↗

Amsacrine treatment of patients with supraventricular arrhythmias and acute leukemia.

Three patients with a history of supraventricular arrhythmia presented with relapse of acute leukemia. Two of the three patients were in sinus rhythm, receiving digoxin and/or verapamil daily. The third patient was in atrial fibrillation, but her heart rate was controlled with daily digoxin. All three patients received amsacrine without the occurrence of cardiac events. Although amsacrine may cause ventricular arrhythmias in the setting of hypokalemia, correction of the electrolyte abnormality permits its use in patients with a history of supraventricular arrhythmias.

Acute Disease↗

Micronucleus formation induced in rat liver and esophagus by nitrosamines.

The rat hepatocarcinogen nitrosodimethylamine and the esophageal carcinogens nitrosomethylbenzylamine and nitrosomethylamylamine were shown to produce chromosomal damage, as manifested by micronucleus formation, in their target tissues. There was cross-reactivity in the two tissues, however, at high dose levels. Nitrosodiethylamine, which produces tumors in both the liver and esophagus in the rat, also produced micronuclei in both tissues.

Animals↗

Synergistic antifungal activity and reduced toxicity of liposomal amphotericin B combined with gramicidin S or NF.

Amphotericin B (AmpB) disrupts membrane integrity by binding to sterols in fungal and mammalian cell membranes. The gramicidins, which form pores in all membranes but exhibit poor antifungal activity, are too toxic to mammalian cells to be used systemically. This study demonstrated synergistic antifungal activity of free and liposomal forms of AmpB when combined with the free and liposomal forms of gramicidin S and gramicidin NF against five Candida strains. In vitro erythrocyte lysis was prevented by using the liposomal forms of all drugs tested alone or in combination. Presumably, AmpB increases accessibility of the fungal cell membrane to the gramicidins, while liposome encapsulation decreases the rate of transfer of the drugs to the mammalian cell membrane. Liposome encapsulation of inactive or toxic drugs, used in combination with liposomal AmpB, may give new life to drugs previously believed to be inactive or too toxic for therapeutic consideration.

Amphotericin B↗

A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia.

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.

Acute Disease↗

Polymerized phospholipid vesicles containing amphotericin B: evaluation of toxic and antifungal activities in vitro.

We have prepared lipid vesicles (liposomes) composed of polymerized bis[12-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidylcholine (DPL) which contain the antifungal polyene antibiotic amphotericin B (AMB). It was necessary to devise a novel method for incorporating AMB into the liposomes subsequent to polymerization. The polymer liposome AMB was as effective as AMB in "conventional" liposomes in terms of inhibiting fungal growth in vitro. However, in contrast to "conventional" liposomes, the polymerized DPL vesicles did not protect mammalian cells against AMB induced toxicity.

Amphotericin B↗

Acute and long term effect of nifedipine on pulmonary hypertension secondary to chronic obstructive airways disease.

To determine whether Nifedipine reduces pulmonary artery pressure and pulmonary vascular resistance in patients with hypoxic pulmonary hypertension, we have studied ten clinically stable patients with chronic obstructive airways disease following acute administration of sublingual Nifedipine 20 mg and also after three months long term treatment with Nifedipine tablets 20mg bd. In the acute study, Nifedipine significantly raised mean pulmonary artery pressure from 30.32 +/- 13.07 mm Hg to 34.15 +/- 14.33 mm Hg (p less than 0.001) and pulmonary wedge pressure from 6.15 +/- 5.09 mm Hg to 7.6 +/- 3.39 mm Hg (p less than 0.1). There was a significant fall in mean systematic artery pressure from 99.06 +/- 12.05 mm Hg to 89.47 +/- 10.04 mm Hg (p less than 0.005) and a rise in heart rate from 79 +/- 9.7 beats/minute to 85.45 +/- 13.46 beats/minute (p less than 0.5). There was a significant change in cardiac index from 2.96 +/- 0.76 l/min/m2 to 3.2 +/- 0.51 l/min/m2 p(less than 0.1). There was no statistically significant change in pulmonary vascular resistance from 5.06 +/- 3.45 mm Hg/l/min to 4.92 +/- 3.10 mm Hg/l/min. In the long term study, no statistically significant differences over the base line values were found in measurements of mean pulmonary artery and pulmonary wedge pressures, mean systemic artery pressure, cardiac index and PO2. There was a greater fall in pulmonary vascular resistance in comparison with the acute study. The pulmonary vascular resistance fell from 5.06 +/- 3.45 mm Hg/l/min to 4.24 +/- 2.31 mm Hg/l/min but did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study.

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Adolescent↗