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Biomedical subjects

A Rahman

Publications and source records attributed to A Rahman.

At least 217 records · Page 12Linked to original sources
PubMed1993

Gamma-hemolysin genes in the same family with lukF and lukS genes in methicillin resistant Staphylococcus aureus.

Cloning and DNA sequencing of gamma-hemolysin genes from two strains of Staphylococcus aureus showed three open reading frames, transcribed serially within the sequenced 4353 nucleotide bases. In this report, from the nucleotide sequence, we demonstrate that leukocidin and gamma-hemolysin share the F or H gamma I component and the specificity of both toxins depends on this component.

Amino Acid Sequence↗
PubMed1993

Effect of rifampicin on the enterohepatic recycling of estrogen in female tuberculous patients.

Enterohepatic recycling of estrogen after oral administration of 1 mg non-radioactive estriol was studied in ten women taking rifampicin as one of the antitubercular drugs and in fourteen healthy women selected as control subjects. The extent of enterohepatic recycling of estriol (E(3)) during early follicular phase of menstrual cycle was assessed by monitoring for 48 hours the urinary excretion of its two major metabolites i.e., estriol-16alpha-glucuronide (E(3)-16alpha-G) and estriol-3-glucuronide (E(3)-3-G). Of these metabolites the former is synthesized in liver as well as in the gut where as later is synthesized exclusively in the gut, hence the change in urinary level of H(3)-3-G with respect to E(3)-16alpha-G was considered to reflect the extent of enterohepatic recycling of E(3). The levels of both metabolites in urine were determined by radioimmunoassay. Lower values of variables including E(3)-3-G output, E(3)-3-G output as % of the total (E(3)-16alpha-G + E(3)-3-G) excretion and total E(3) (E(3)-16alpha-G + E(3)-3-G) output as % dose and the diurnal variation in urinary excretion of these metabolites show that the final elimination of E(3) from the body was quicker in these patients as compared with the control subjects, probably due to the reduced extent of enterohepatic recycling of E(3) as a result of long term chemotherapy with rifampicin.

Journal Article↗
PubMed1993

Reversal of resistance to adriamycin by 8-chloro-cyclic AMP in adriamycin-resistant HL-60 leukemia cells is associated with reduction of type I cyclic AMP-dependent protein kinase and cyclic AMP response element-binding protein DNA-binding activities.

8-Chloro-cyclic AMP (8-Cl-cAMP) produces growth-inhibitory and differentiating activity in the promyelocytic leukemia cell line HL-60. Adriamycin (ADR)-resistant HL-60 (HL-60/AR) cells exhibit the multidrug-resistant phenotype but do not express the mdr1 gene product P-glycoprotein. To explore potential signaling processes that may be involved in this atypical form of drug resistance, 8-Cl-cAMP was used as a modulator of the cAMP second messenger signal transduction pathway. Treatment for 48 hr with a 10% inhibitory concentration of 8-Cl-cAMP potentiated ADR cytotoxicity 14-fold in HL-60/AR cells but not in the parental cell line. 8-Cl-cAMP was stable to hydrolysis in the medium after 48 hr and was present intracellularly predominantly as phosphorylated metabolites (70%) and the parent compound (30%). No difference occurred in ADR accumulation in HL-60/AR cells after treatment with 8-Cl-cAMP. Accompanying the 8-Cl-cAMP-mediated increase in ADR cytotoxicity in HL-60/AR cells was a reduction in the cytosolic type I cAMP-dependent protein kinase (PKA) and disappearance of the nuclear PKA holoenzyme. Coincident with these changes in drug-resistant cells was a marked reduction in the DNA-binding activity of the cAMP response element-binding protein to levels equivalent to those in sensitive cells. This effect appears to result from reduced phosphorylation of the cAMP response element-binding protein. These results suggest that the potentiation by 8-Cl-cAMP of ADR cytotoxicity in HL-60/AR cells occurs through down-regulation of nuclear type I PKA and cAMP response element-binding factors whose activities are regulated by PKA.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Liposome-mediated modulation of multidrug resistance in human HL-60 leukemia cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment. Resistance of cultured tumor cells to major classes of cytotoxic drugs is frequently due to expression of a plasma membrane P-glycoprotein encoded by MDR genes. We have demonstrated that liposome-encapsulated doxorubicin is more toxic than the free drug and that it modulates MDR in Chinese hamster LZ cells and human colon cancer cells. PURPOSE: To investigate further the association between expression of P-glycoprotein and modulation of MDR by liposome-encapsulated doxorubicin, we studied vincristine-resistant HL-60/VCR leukemia cells, which express P-glycoprotein, and doxorubicin-resistant HL-60/ADR leukemia cells, which do not. METHODS: Cells were exposed to various concentrations of free doxorubicin and liposome-encapsulated doxorubicin. The cellular content of doxorubicin was determined by fluorescence analysis, and cytotoxicity was determined by cell growth inhibition. Photoaffinity-labeling studies of P-glycoprotein binding were performed on HL-60/VCR and HL-60/ADR cells and KB-GSV2 cells transfected with the MDR1 gene (also known as PGY1). RESULTS: The concentrations that caused 50% inhibition of growth (IC50) for free doxorubicin in HL-60, HL-60/ADR, and HL-60/VCR cells were 30 nM, 9 microM, and 0.9 microM, respectively. The values for liposome-encapsulated doxorubicin in parental HL-60 cells and HL-60/ADR cells were 20 nM and 9 microM, respectively, indicating little or no sensitization. In contrast, HL-60/VCR cells were fivefold more sensitive to liposome-encapsulated doxorubicin than to free doxorubicin, and IC50 was reduced to 0.17 microM. In HL-60 cells exposed to liposome-encapsulated doxorubicin, intracellular doxorubicin accumulation was less than that seen with free drug. In contrast, in HL-60/VCR cells, accumulation was twofold to threefold higher than that with free doxorubicin. Liposome-encapsulated doxorubicin completely inhibited the photoaffinity labeling of P-glycoprotein by azidopine in membrane vesicles of HL-60/VCR cells, with a potency comparable to that of azidopine, suggesting that circumvention of MDR by liposomes is related to their specific interaction with P-glycoprotein. The studies with KB-GSV2 cells indicated that blank liposomes can directly inhibit photoaffinity labeling of P-glycoprotein. CONCLUSIONS: These results demonstrate the effectiveness of liposome-encapsulated doxorubicin in overcoming resistance in the multidrug-resistant phenotype of HL-60/VCR cells by direct interaction with P-glycoprotein. Furthermore, they indicate that liposome-encapsulated doxorubicin may be an effective treatment for human cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effect of liposomes on P-glycoprotein function in multidrug resistant cells.

Presentation of doxorubicin in liposomes has shown to enhance the sensitivity of multidrug resistant CH LZ cells to the drug (Thierry et al. Cancer Commun. 1:311-316, 1989). We confirmed that liposomally encapsulated doxorubicin may partially overcome multidrug resistance in the human ovarian carcinoma SKVLB cell line and that this effect is, at least in part, due to an increase of cellular drug accumulation. When used at high concentration, empty liposomes appear to be specifically cytotoxic in the MDR SKVLB and CH LZ cells. As observed with certain multidrug resistance modulators, empty liposomes inhibited the specific [3H]-vincristine binding to P-glycoprotein-enriched membranes isolated from CH LZ cells (60% at 0.2 mg lipid/ml). Our data suggest that liposomes may alter the P-glycoprotein function by direct interaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Molecular cloning and nucleotide sequence of leukocidin F-component gene (lukF) from methicillin resistant Staphylococcus aureus.

A lukF gene encoding F-component of Staphylococcal leukocidin from methicillin resistant Staphylococcus aureus (MRSA) was cloned. The nucleotide sequence of lukF gene was determined. The sequence data have revealed an open reading frame, which encodes a polypeptide with 323 amino acid residues. Inspection of the amino acid sequence deduced from nucleotide sequence of lukF and that from F-component of leukocidin from S. aureus V8 clarified that pre-matured F-component contains a typical signal peptide at the NH2 terminus and ATG starting codon for pre-matured F-component was present one base downstream to the TGA which is translation termination codon for S-component of leukocidin [A. Rahman et al. (1991) Biochem. Biophys. Res. Commun. 181, 138-144]. The nucleotide sequence of 5'-flanking region of lukF showed the presence of the consensus sequence of ribosome binding site in the internal region of the structural gene of S-component. The lukF was transcribed in the same direction as that of lukS. No Pribnow box can be discerned in the intercistronic region between the lukS and lukF genes. The amino acid sequence homology between S- and F-components was 31%. F-component was expressed in Escherichia coli DH5 alpha harboring plasmid pFRK92 which contained lukF gene.

Amino Acid Sequence↗
PubMed1992

Mutation(s) of the thymidylate synthase gene of human adenocarcinoma cells causes a thymidylate synthase-negative phenotype that can be attenuated by exogenous folates.

Biological characterization of a human colon adenocarcinoma cell line deficient in thymidylate synthase (TS-) is described. The clone, designated TS-C1/C1, was derived from the parental line GC3/C1 by selection in medium containing aminopterin, thymidine (dThd), and low concentrations of 5-formyltetrahydrofolate (5-CHO-H4PteGlu), and was subsequently reselected by single-step cloning in 500 microM methotrexate in the presence of dThd. This clone retained its TS- phenotype, was highly resistant to methotrexate (greater than 100,000-fold), and remained tumorigenic in mice (P.J. Houghton, et al., Proc. Natl. Acad. Sci. USA, 86: 1377-1381, 1989). In studies reported, it is shown that high levels of exogenous folate can support the growth of the TS- C1/C1 clone in the absence of dThd. Activation of dTMP biosynthesis de novo was demonstrated within 6 h of exposing cells to 20 microM [6R,S]5-CHO-H4PteGlu, and greater than or equal to 80% of activity was lost within 24 h of removing this folate from the medium. The labeling index was determined by autoradiographic techniques using [6-3H]2'-deoxyuridine. None of the greater than 6,000 cells radiolabeled in the absence of [6R,S]5-CHO-H4PteGlu, whereas 33.5% labeled in the presence of 20 microM exogenous folate. Relative to the parental (TS+) clone, there was a greater than 87,500-, an 8,182-, and a 425-fold higher requirement for 5-methyltetrahydrofolate ([6R,S]5-CH3-H4PteGlu), PteGlu, and [6R,S]5-CH3-H4PteGlu to support 50% maximal colony formation in the absence of dThd. Quantitative analysis of the combined pools of 5,10-methylenetetrahydrofolate (CH2-H4PteGlun) and H4PteGlun showed that parental GC3/C1 cells had higher endogenous folate pools compared to TS-C1/C1 cells [168 +/- 40 (SD) and 10.9 +/- 0.3 fmol/10(6) cells, respectively]. Qualitatively the distribution of polyglutamate species and their redistribution in cells exposed to 20 microM [6R,S]5-CHO-H4PteGlu were similar in the two lines. Analysis of pools in a second, independently derived, TS- clone (TS-C3/C3, a transcription-negative mutant) demonstrated undetectable levels of CH2-H4PteGlun and H4PteGlun. This line cannot be rescued by exogenous folate. The data thus suggest that deletion of dTMP synthase activity may cause redistribution of reduced folate pools. In cytosolic extracts from parental GC3/C1 (TS+) cells, [6R]CH2-H4PteGlu1 acted as a cofactor in the release of 3H2O from [5-3H]dUMP, whereas no activity was detected in cytosols from TS-C1/C1. In contrast dTMP synthase activity was detected in cytosols from TS- C1/C1 cells in the presence of [6R]CH2-H4PteGlu5.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission.

The naturally occurring flavonoid, quercetin, in the presence of Cu(II) and molecular oxygen caused breakage of calf thymus DNA, supercoiled pBR322 plasmid DNA and single stranded M13 phage DNA. In the case of the plasmid, the product(s) were relaxed circles or a mixture of these and linear molecules depending upon the conditions. For the breakage reaction, Cu(II) could be replaced by Fe(III) but not by other ions tested [Fe(II), Co(II), Ni(II), Mn(II) and Ca(II)]. Structurally related flavonoids, rutin, galangin, apigenin and fisetin were effective or less effective than quercetin in causing DNA breakage. In the case of the quercetin-Cu(II) reaction, Cu(I) was shown to be essential intermediate by using the Cu(I)-sequestering reagent, bathocuproine. By using Job plots we established that, in the absence of DNA, five Cu(II) ions were reduced by one quercetin molecule; in contrast two ions were reduced per quercetin molecule in the DNA breakage reaction. Equally neocuproine inhibited the DNA breakage reaction. The involvement of active oxygen in the reaction was established by the inhibition of DNA breakage by superoxide dismutase, iodide, mannitol, formate and catalase (the inhibition was complete in the last case). The strand scission reaction was shown to account for the biological activity of quercetin as assayed by bacteriophage inactivation. From these data we propose a mechanism for the DNA strand scission reaction of quercetin and related flavonoids.

Animals↗
PubMed1992

Crossed immunoelectrophoretic analysis of antigenic composition of B-subunit/whole-cell and whole-cell only killed oral cholera vaccines.

Crossed immunoelectrophoresis was used to identify antigens preserved in the whole-cell component of oral cholera vaccines tested in the field trial in Bangladesh. The composition and immunogenicity of the vaccine antigens were compared with those of antigens obtained from live cells of Vibrio cholerae 01 of both biovars and serovars. The whole-cell component of the vaccine contained ten antigens in comparison with the live Vibrio cells which revealed the presence of 30 antigens. The whole-cell component contained lipopolysaccharide, flagellar antigen, one cell-bound haemagglutinin and at least six outer membrane protein antigens.

Administration, Oral↗
PubMed1992

Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species.

The activities of several flavonoids and the related nonflavonoid compound epicatechin were compared with respect to Cu(II)-induced strand scission of DNA by using two different assays. The same series of compounds was used to study the stoichiometry of Cu(II) reduction in the absence of DNA. The compounds were compared for their ability to generate superoxide, hydrogen peroxide and the Cu(II)-dependent production of hydroxyl radicals. Flavonoids were examined to assess the production of a charge-transfer complex with Cu and the rate of decay of the complexes were compared. All the compounds tested had some ability to cause DNA strand scission in the presence of Cu(II), with myricetin being the most active and galangin the least active. The ability to cause such scission correlated with the rate of decay of the charge-transfer complex, the ability to generate active oxygen species and with the stoichiometry of Cu(II) binding. Analysis of the data in the light of the structural differences between the flavonoids led to a discussion of alternative Cu(II)-sequestering mechanisms.

Copper↗
PubMed1992

Perceived workload and performance of shift workers.

The present paper is based on the results of a study conducted to investigate whether the relationship between perceived workload and quality of performance, if any, holds true if controlled for shift system, type of task, age, and skill level of the workers. The sample of the study comprised 279 blue-collar workers of a jute industry operating under fixed three-shift system. The subjects were all males selected by random sampling method. The method of data collection was a field study through questionnaire. The collected data were analyzed by employing zero-order and partial correlation coefficients. The results indicate that workload and performance were negatively correlated but the strength of the relationship reduced substantially when the effects of the control variables were partialled out simultaneously. It was concluded that the control variables had joint effect on the relationship between workload and performance but skill level of the employees appeared to be the variable having the greatest contaminating effect.

Adolescent↗
PubMed1991

Nucleotide sequence of leukocidin S-component gene (lukS) from methicillin resistant Staphylococcus aureus.

The nucleotide sequence of lukS gene encoding S-component of Staphylococcal leukocidin from methicillin resistant Staphylococcus aureus (MRSA) was determined. The structural gene of lukS consisted of 857 base pairs. An open reading frame that could encode a 35,556 dalton polypeptide consisting of 315 amino acids was assigned. The molecular size of the polypeptide predicted from the amino acid composition was close to the value of pre-matured S-component determined in DNA-directed transcription/translation system. Inspection of the amino acid sequence deduced from nucleotide sequence of lukS and that from S-component of leukocidin clarified that pre-matured S-component contains a typical signal sequence at the NH2 terminus. The amino acid sequence of predicted matured S-component correlated exactly with the known N-terminal 50 amino acid sequence of S-component from MRSA and S. aureus V8. The molecular size of the predicted matured protein was also close to the value of S-component determined in both MRSA and S. aureus V8. The nucleotide sequence of the 5'-flanking region showed the presence of the consensus sequence of ribosome binding site, Pribnow box and the RNA polymerase recognition site in Escherichia coli.

Amino Acid Sequence↗
PubMed1991

Patterns of transgene inheritance in rainbow trout (Oncorhynchus mykiss).

There have been very few studies of the inheritance of introduced genes (transgenes) in fish. We have followed the inheritance of the mammalian fusion gene MTrGH from founder generation transgenics (originating from eggs microinjected with the MTrGH DNA) to offspring in crosses with control fish. Initial screening of the founder generation transgenics was by analysing DNA from blood samples. Only three out of six fish which carried the novel gene in blood DNA transmitted it to their offspring, despite the presence of the gene in DNA extracted from the sperm of all four male fish in this group. The frequency of transgenics in the progeny groups from the three fish which transmitted the gene varied widely: in one of these groups more than one type of MTrGH restriction pattern was found. These results suggest widespread mosaicism in founder generation transgenics.

Animals↗
PubMed1991

Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes.

The effectiveness of liposome-encapsulated doxorubicin in overcoming multidrug resistance was studied in various human colon cancer cells. Colon-cancer cell lines SW403, HT29, SW620, and SW620/R overexpressed P-glycoprotein as determined by immunoflow cytometry, thereby confirming the presence of the multidrug-resistant phenotype. Important differences were observed in the cytotoxicity of free doxorubicin as represented by IC50 values of 0.168, 0.058, 0.023, and 9.83 microM for SW403, HT29, SW620, and SW620/R, respectively. Liposomally encapsulated doxorubicin provided an IC50 that was 1.4 times lower than that of the free drug in the doxorubicin-resistant SW 620/R cell line, whereas no difference was evident in the sensitive parental SW620 cells. In addition, liposome-encapsulated doxorubicin exhibited 1.31- and 2.33-fold cytotoxicity to HT-29 and SW403 cells, respectively. The intracellular drug accumulation in SW620/R cells was enhanced by liposomally encapsulated doxorubicin, whereas it was reduced in all other cell lines as compared with that of free drug. The colon-cancer cell lines demonstrated different degrees of doxorubicin-induced DNA strand breakage that correlated with their sensitivities to drug-induced cytotoxicity. However, no difference was observed between DNA breakage caused by the free drug and that induced by liposome-encapsulated doxorubicin in any of the cell lines. The results suggest that the enhanced cytotoxicity of liposomal doxorubicin to colon cancer cells was due to some secondary non-DNA target. However, liposomally encapsulated doxorubicin appears to be effective in diminishing the multidrug-resistant phenotype and may have clinical applications.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Reaction of furfural and methylfurfural with DNA: use of single-strand-specific nucleases.

The furans, furfural and methylfurfural, are dietary mutagens that are present in various food products and beverages. AT base-pair-depleted calf thymus DNA was prepared by the action of pea seed single-strand-specific nuclease on native DNA. Compared with furan-treated native DNA, furan-treated AT-depleted DNA showed a reduced rate of S1 nuclease hydrolysis and a reduced formation of single-strand breaks, as determined using an alkaline unwinding assay. These results indicate that furfural and methylfurfural primarily react with AT base pairs in duplex DNA, and demonstrate the usefulness of single-strand-specific nucleases in such studies.

Animals↗
PubMed1991

Toxicities in rats with free versus liposomal encapsulated cisplatin.

Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections. Rats in the free drug group showed significantly less weight gain; two rats died during the study. At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups. The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis. No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin. These results are encouraging and warrant further investigation.

Animals↗
PubMed1991

Evidence for direct estrogen regulation of the human gonadotropin-releasing hormone gene.

This study is an attempt to determine whether estrogen could directly regulate human gonadotropin-releasing hormone (GnRH) gene expression. Human GnRH expression vectors were constructed by fusing various 5' flanking regions of the human GnRH gene upstream of the luciferase reporter gene (LUC) or the thymidine kinase promoter linked to the chloramphenicol acetyltransferase reporter gene (CAT). These constructs were transiently transfected into a human choriocarcinoma cell line (JEG-3) and LUC or CAT activity was measured after either no treatment or treatment with various concentrations of estradiol. A stimulatory estrogen response element (ERE) was localized to a 32-bp region between -547 and -516 bp. To determine whether estrogen receptor bound to this region of the gene, we performed DNase I footprinting using purified calf uterine estrogen receptor. DNase I footprinting demonstrates a strong footprint between -567 and -514 bp of the human GnRH gene. In addition, an avidin-biotin complex DNA-binding assay demonstrated that a biotinylated DNA fragment containing -541 to -517 bp of the human GnRH gene bound 35S-labeled estrogen receptor as well as a biotinylated DNA fragment containing the xenopus vitellogenin ERE. On the other hand, the negative control biotinylated DNA fragment derived from adenovirus 5 bound insignificant amounts of 35S-labeled estrogen receptor. Both the GnRH ERE and vitellogenin ERE bound 35S-labeled estrogen receptor with high affinity (approximately 1 nM). These data indicate that the human GnRH gene contains an ERE sufficient to mediate a stimulatory response to estrogen in heterologous cells. Based upon these data we hypothesize that the human GnRH gene might also be directly regulated by estrogen in the hypothalamus, and that this regulation may explain the GnRH hypersecretion observed at the time of the preovulatory luteinizing hormone (LH) surge.

Base Sequence↗