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Biomedical subjects

A Joshi

Publications and source records attributed to A Joshi.

At least 217 records · Page 12Linked to original sources
PubMed1983

Plasma membrane lipid structural order in doxorubicin-sensitive and -resistant P388 cells.

We have studied the structural order of the lipid phase of plasma membranes from P388 murine leukemia cells and from a Doxorubicin-resistant subline, P388/ADR, using electron spin resonance spectroscopy and fluorescence depolarization measurements. Measurements of the order parameter, S, following incubation of cells from both lines with the N-oxyl-4'-4'-dimethyloxazolidine derivative of 5-ketostearic acid show higher values for the resistant cells at all temperatures where S was measured (4-37 degrees). Fluorescence depolarization measurements following incubation of the cells, or cell fractions, with 1,6-diphenylhexatriene indicate more restricted motion of the probe in resistant cells. These measurements also show increased amounts of cytoplasmic lipid in the resistant cells. The higher degree of structural order in the lipid phase of the plasma membranes of P388/ADR cells and their larger intracellular lipid content may account for the decreased rate of intracellular accumulation of anthracycline drugs (and other compounds) seen in these cells and, in part, for their relative resistance to the cytotoxic effects of these drugs.

Animals↗
PubMed1982

Participation of the host protein(s) in the morphogenesis of bacteriophage P22.

Spontaneous mutants of S. typhimurium resistant to thiolutin are conditionally non-permissive for phage P22 development (Joshi and Chakravorty 1979). At 40 degree C non-infective phage particles are produced. Phage development in two nonpermissive hosts (18/MC4 and 153/MC4) has been studied in detail. The steps at which the phage morphogenesis is interfered with differ in the two mutants. The electron micrograph of the particles produced in the mutant 18/MC4 reveals the presence of normal-looking particles; these particles contain phage DNA, adsorb to the permissive host but fail to inject their DNA. The particles produced in the mutant 153/MC4 which fail to adsorb to the host are found to be tail fibre-less. These observations indicate the involvement of host protein(s) in phage P22 morphogenesis.

Bacterial Proteins↗
PubMed1982

Thiolutin-resistant mutants of Salmonella typhimurium.

Spontaneous mutants of Salmonella typhimurium isolated in our laboratory from thiolutin-containing tryptone agar plates are partially resistant to thiolutin in enriched media. In minimal media, they are not resistant. The mutants are not temperature sensitive but fail to support the development of phage P22 at higher temperatures (40 degrees C). Thiolutin did not interfere with RNA polymerase or nucleotide kinase in in vitro experiments. However, thiolutin did inhibit the rate of incorporation of exogenous uridine into the cellular pool and consequently the acid-precipitable material. It appears that one site of action of thiolutin is at the membrane level.

Anti-Bacterial Agents↗
PubMed1982

MB78, a virulent bacteriophage of Salmonella typhimurium.

The isolation and some properties of a virulent bacteriophage of Salmonella typhimurium, MB78, which is morphologically, serologically, and physiologically unrelated to P22, are reported. The phage has a noncontractile long tail with partite ends. It cannot multiply in minimal medium in the presence of citrate. MB78-infected cells are, however, killed in such medium. This phage cannot grow in rifampin-resistant mutants of the host. The latent period of growth of this phage is much shorter than that of P22. Both sieA and sieB genes of the resident P22 prophage are required to exclude the superinfecting MB78 phage, whereas all temperate phages related to P22 are excluded by either one or both of the genes individually. Restriction endonuclease cleavage patterns of P22 and MB78 are distinctly different. The absence of homology between the two phages P22 and MB78 suggests that MB78 is not related to phage P22.

Bacteriophages↗
PubMed1979

Is the injection of DNA enough to cause bacteriophage P22-induced changes in the cellular transport process of Salmonella typhimurium?

It was demonstrated earlier in this laboratory that phage P22 induces a transient depression in the cellular transport processes of the host Salmonella typhimurium immediately after infection and that an effective injection process is enough to cause the depression. By using defective phage particles that contain host DNA instead of phage DNA for infection, it has been demonstrated that the injection of phage-specific DNA is essential for this. The defective particles adsorbed to the host and injected their DNA, but the cellular transport processes of the host were not altered. Thus, the injection of host DNA by the phage fails to affect the transport process. Insensitivity of the phage DNA-induced depression in transport to chloramphenicol rules out the involvement of newly synthesized protein in this change and indirectly suggests the possible role of phage DNA-associated internal proteins of P22.

DNA, Viral↗
PubMed1978

E.s.r. of spin-trapped radicals in aqueous solutions of peptides. Reactions of the hydroxyl radical.

The reactions of hydroxyl radicals with 30 dipeptides and several larger peptides were studied in aqueous solutions. The OH radicals were generated by U.V. photolysis of H2O2. The short-lived peptide radicals were spin-trapped using t-nitrosobutane and identified by e.s.r. For dipeptides containing the amino terminal residues glycine, alanine and phenylalanine, abstraction of the hydrogen from the carbon adjacent to the peptide nitrogen was the major process leading to the spin-adducts. Such radicals will be referred to as backbone radicals. Dipeptides with a carbonyl terminal serine residue and also glycylglutamic acid form both backbone and side-chain radicals, with the latter being formed in larger quantities. For dipeptides, side-chain radicals were detected on either the carboxyl or amino terminal residues of both. The effect of pD on the e.s.r. sectrum of the spin-adducts of glycylglycine was studied and the pK of the carboxyl group of this radical was determined to be 2.5. For (Ala)3 and (Ala)n, with an average value of n = 1800, backbone and minor side-chain radicals were observed. For ribonucleases-S-peptide, containing 20 amino acid residues, both backbone and side-chain radicals were detected.

Dipeptides↗
PubMed1978

E.s.r. study of the post-radiolysis growth of spin-trapped radicals in gamma-irradiated aqueous solutions of thymine.

The post-irradiation growth of the spin-adduct nitroxide radical produced by the addition of the thymine--OD radical to t-nitrosobutane (tNB) in gamma-irradiated, de-aerated D2O solutions was investigated by e.s.r. The thymine--OD radical was formed by the addition of an OD radical to the C(5) position of thymine. Growth reached a greater maximum value and was more rapid with increasing dose. At a fixed dose, growth was also greater and more rapid if oxygen was present after gamma-radiolysis. The addition of a second radical to the spin-adduct nitroxide during radiolysis to give a diamagnetic intermediate, which can regenerate the spin-adduct radical during storage in air-free and in air-saturated solutions at room temperature, was inferred to be responsible for post-irradiation growth. U.V. photolysis at 260-280 nm of a solution containing the diamagnetic intermediate rapidly regenerates the spin-adduct nitroxide. The longer lifetime of the diamagnetic intermediate in oxygen-free solutions may be relevant to an understanding of the anoxic sensitization by nitroxides in cellular systems.

Cyclic N-Oxides↗
PubMed1977

Cyanamide mediated syntheses under plausible primitive earth conditions. II. The polymerization of deoxythymidine 5'-triphosphate.

When an aqueous solution (pH 7.0) of 3H deoxythymidine 5'-triphosphate, deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide, cyanamide and ammonium chloride was dried and heated at 60 degrees C for 18 h, oligomers were obtained in a yield of approximately 80%. After the chemical degradation of any pyrophosphate bonds present in these oligomers, linear polynucleotides of up to 7-8 units in length were isolated by DEAE cellulose column chromatography and identified by enzymatic digestion procedures. The di- and trinucleotide fractions were degraded 87% and 100% by snake venom phosphodiesterase and 39% and 9% by spleen phosphodiesterase. This synthesis of deoxythymidine oligonucleotides was conducted under potentially prebiotic conditions and may offer a possible method for the synthesis of deoxyoligonucleotides on the primitive Earth.

Aminoimidazole Carboxamide↗
PubMed1977

E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydroxyl radical.

The radicals produced by reactions of hydroxyl radicals with amino acids in aqueous solutions have been investigated. Hydroxyl radicals were formed by U.V.-photolysis of hydrogen peroxide and the short-lived amino acid radicals were spin-trapped by tert-nitrosobutane and identified by electron spin resonance spectroscopy. Nineteen amino acids were studied, and several radicals were identified which have not been observed previously by other methods. Only side-chain radicals were identified for alanine, threonine, aspartic acid, asparagine, lysine, phenylalanine, tyrosine, proline and hydroxyproline; whereas for glycine the C(2) carbon radical was spin-trapped. Both C(2) carbon radicals and side-chain radicals were assigned to valine, leucine, isoleucine, serine, glutamic acid, glutamine, arginine and methionine.

Amino Acids↗
PubMed1977

E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydrated electron.

The reactions of hydrated electrons (eaq-) with amino acids were investigated by the spin-trapping method and by electron spin resonance. Tertiary nitrosobutane was used as a spin-trap to stabilize the short-lived radicals. Hydrated electrons were produced by gamma-radiolysis of de-aerated aqueous solutions of amino acids in the presence of sodium formate or tertiary butanol to scavenge OH. Radicals produced by reductive deamination of 19 amino acids were identified. Radicals formed by scission of the CH3-S- and -S-CH2- bonds of methionine as well as by deamination were observed. In the case of phenylalanine the radical formed by electron addition followed by proton transfer was identified. The reaction of proline and of hydroxyproline with eaq- resulted in the opening of the cyclic structure.

Amino Acids↗
PubMed1976

Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole.

Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension.

Acid Phosphatase↗
PubMedDate not supplied

Effect of oral and parenteral administration of metanil yellow on some hepatic and intestinal biochemical parameters.

Metanil yellow, a non-permitted colour for food commodities, is used in the leather, paper and textile industries. In this paper the effect of oral and parenteral administration of Metanil yellow on hepatic and intestinal biochemical parameters was investigated. Oral administration of Metanil yellow (430 mg kg-1 body wt.) for 7 days caused significant depletion of hepatic and intestinal glutathione levels (33-52%) with a concomitant increase in lipid peroxidation (49-121%). Metanil yellow treatment for 7 days also led to a significant increase in cytochrome P-450 (P-450)-dependent aryl hydrocarbon hydroxylase (AHH) activity (99-223%) in the liver and intestine. Cytosolic glutathione-S-transferase (GST) (32-136%) and quinone reductase (QR) (20-92%) activities were also found to be substantially induced in hepatic and intestinal tissues following oral treatment of Metanil yellow. It is interesting to note that oral treatment of Metanil yellow showed a greater response in cytosolic enzymes of hepatic tissue as compared to intestine. Single parenteral administration of Metanil yellow (80 mg kg-1 body wt.) caused significant induction of P-450 and its dependent monooxygenases. Even after 5 days of single parenteral administration of Metanil yellow, hepatic AHH activity showed an elevation of 48% while other monooxygenases were marginally increased. Cytosolic GST and QR showed respective peak inductions of 92% and 60% after 2 and 3 days of parenteral administration of Metanil yellow, which levels off after the 5th day. It can be concluded that Metanil yellow acts as an inducer of a specific form of microsomal P-450 and cytosolic GST and QR, which may involve a cytosolic Ah receptor.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of caffeine in breast milk and plasma after single oral administration of caffeine to lactating mothers.

Six healthy lactating women ranging in age from 28 to 35 years were selected to participate in the study. The women had been nursing their infants from 3 1/2 weeks up to 17 weeks. On the morning of the study each participant received 100 mg dose of caffeine. The oral dose of caffeine was taken with a glass of water on an empty stomach. Blood samples were collected from zero time to 24 h after caffeine administration. Each subject aseptically collected breast milk from the right and left breasts by manual expression or using a mechanical breast pump, from zero time to 24 h after caffeine administration. Caffeine in plasma and breast milk was determined by gas liquid chromatography using nitrogen phosphorous detection. Caffeine was rapidly absorbed producing plasma time to peaks ranging from 0.50 to 1.00 h, with values for peak concentrations between 3.60 and 6.15 micrograms ml-1 in plasma. In breast milk, time to peak ranged from 0.75 to 2.00 h and concentration values between 1.98 and 4.30 micrograms ml-1. No significant differences were found between attainment of the time of the peak in plasma and breast milk, p greater than 0.05. In addition, peak concentration for the right and left breast were not statistically different, p greater than 0.05. However, significant differences, p less than 0.05, between plasma and both breasts in regards to the peak concentrations were found. The overall breast milk/plasma ratio obtained from the respective area under the curves were 0.815 +/- 0.0521 and 0.809 +/- 0.202 for the right and left breast, respectively, and no statistical differences were observed between the right and left breasts, p greater than 0.05. In summary, caffeine is rapidly transferred to breast milk. Multiple dose studies are needed to provide more information about caffeine concentration in breast milk of women who receive multiple doses of caffeine or who chronically consume caffeine.

Administration, Oral↗
PubMedDate not supplied

Phenotypic enhancement of longevity by environmental urea in Drosophila melanogaster.

The phenotypic enhancement of longevity through a variety of environmental treatments, including dietary manipulations, has been observed in various species of animals, both vertebrate and invertebrate. Elucidating the mechanisms underlying such effects has provided insights into the physiological processes contributing to the determination of lifespan. Here, we report the enhancement of longevity in adult Drosophila melanogaster maintained on food supplemented with urea, a metabolic waste product occurring naturally in Drosophila cultures, especially at high larval densities. The impact of urea on longevity is shown to be through a decrease in the age-independent parameter (A) of the Gompertz equation, rather than the age-dependent parameter (alpha), which reflects the "rate of aging." We also present evidence suggesting that the urea-induced increase in longevity is mediated exclusively through a reduction in some aspect(s) of reproduction in adult flies maintained on urea-supplemented food.

Animals↗