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Biomedical subjects

G Subramaniam

Publications and source records attributed to G Subramaniam.

12 recordsLinked to original sources
PubMed2006

SHV-5 extended-spectrum beta-lactamases in clinical isolates of Escherichia coli in Malaysia.

Escherichia coli isolates resistant to ceftazidime isolated in the University Malaya Medical Center (UMMC) Kuala Lumpur, Malaysia, between the years 1998 and 2000 were studied for extended-spectrum beta-lactamase (ESBL) production. All strains were analysed phenotypically and genotypically and found to be ESBL-producing organisms harbouring SHV-5 beta-lactamase. This was confirmed by PCR-SSCP and nucleotide sequencing of the blaSHV amplified gene. As there was no evidence of ESBL activity in E. coli prior to this, coupled with the fact that there was a predominance of SHV-5 beta-lactamases in Klebsiella pneumoniae isolates in UMMC, we postulate that the E. coli obtained the SHV-5 beta-lactamase genes by plasmid transfer from the ESBL-producing K. pneumoniae.

Anti-Bacterial Agents↗
PubMed2005

Faecal prevalence of extended-spectrum Beta-lactamase (ESBL)-producing coliforms in a geriatric population and among haematology patients.

Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly reported worldwide. In the local setting, nosocomial infections with multi-resistant Gram-negative bacilli are not uncommon and are a growing concern. However, there is limited data on the carriage rates of such organisms in the local setting. In May 2001, a prospective study was carried out to determine the enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB) among residents of nursing homes and from in-patients of the geriatric and adult haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram-negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6 were from nursing home residents, 5 from geriatric in-patients and 14 from the haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10) and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta-lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in the haematology ward, the six nursing home residents with CAZ-R GNB were enteric carriers of ESBL-producing coliforms. Prior exposure to antibiotics was associated with carriage of ESBL organisms and to a lesser extent, the presence of urinary catheters.

Aged↗
PubMed2001

Solution structure of a guanine-N7-linked complex of the mitomycin C metabolite 2,7-diaminomitosene and DNA. Basis of sequence selectivity.

2,7-Diaminomitosene (2,7-DAM), the major metabolite of the antitumor antibiotic mitomycin C, forms DNA adducts in tumor cells. 2,7-DAM was reacted with the deoxyoligonucleotide d(GTGGTATACCAC) under reductive alkylation conditions. The resulting DNA adduct was characterized as d(G-T-G-[M]G-T-A-T-A-C-C-A-C) (5), where [M]G stands for a covalently modified guanine, linked at its N7-position to C10 of the mitosene. The adducted oligonucleotide complements with itself, retaining 2-fold symmetry in the 2:1 drug-duplex complex, and provides well-resolved NMR spectra, amenable for structure determination. Adduction at the N7-position of G4 ([M]G, 4) is characterized by a downfield shift of the G4(H8) proton and separate resonances for G4(NH(2)) protons. We assigned the exchangeable and nonexchangeable proton resonances of the mitosene and the deoxyoligonucleotide in adduct duplex 5 and identified intermolecular proton-proton NOEs necessary for structural characterization. Molecular dynamics computations guided by 126 intramolecular and 48 intermolecular distance restraints were performed to define the solution structure of the 2,7-DAM-DNA complex 5. A total of 12 structures were computed which exhibited pairwise rmsd values in the 0.54-1.42 A range. The 2,7-DAM molecule is anchored in the major groove of DNA by its C10 covalently linked to G4(N7) and is oriented 3' to the adducted guanine. The presence of 2,7-DAM in the major groove does not alter the overall B-DNA helical structure. Alignment in the major groove is a novel feature of the complexation of 2,7-DAM with DNA; other known major groove alkylators such as aflatoxin, possessing aromatic structural elements, form intercalated complexes. Thermal stability properties of the 2,7-DAM-DNA complex 5 were characteristic of nonintercalating guanine-N7 alkylating agents. Marked sequence selectivity of the alkylation by 2,7-DAM was observed, using a series of oligonucleotides incorporating variations of the 5'-TGGN sequence as substrates. The selectivity correlated with the sequence specificity of the negative molecular electrostatic potential of the major groove, suggesting that the alkylation selectivity of 2,7-DAM is determined by sequence-specific variation of the reactivity of the DNA. The unusual, major groove-aligned structure of the adduct 5 may account for the low cytotoxicity of 2,7-DAM.

Alkylating Agents↗
PubMed2001

Psychostimulants in preschool children with attention-deficit/hyperactivity disorder: clinical evidence from a developmental disorders institution.

OBJECTIVE: To examine psychostimulant response in preschool children with attention-deficit/hyperactivity disorder (ADHD) in an outpatient child psychiatry clinic (housed within a developmental disorders institution) over 3, 12, and 24 months of treatment. METHOD: A systematic retrospective chart review was conducted for 27 preschool children with ADHD who were started on psychostimulants between the ages of 3 and 5 years, inclusive. Two child and adolescent psychiatrists reviewed each chart independently, using the Clinical Global Impressions (CGI) scale to rate the severity of illness and global improvement and the Side Effects Rating Form to rate side effects. RESULTS: Over 24 months, psychostimulants were stopped in three children (11%) because of side effects and concomitant psychotropic medications were added in seven children (26%). The CGI severity-of-illness ratings showed a significant effect of time over 3, 12, and 24 months of psychostimulant treatment (all p values < .0001). Rate of response was 74% at 3 months and 70% at 12 and 24 months. Side effects were mostly mild and occurred in 63% of the children at 3 months, 41% at 12 months, and 29% at 24 months. CONCLUSIONS: The findings suggest that preschool children with developmental disorders respond to psychostimulants but need close monitoring because of frequent side effects. Inasmuch as the study participants were recruited from a child psychiatry clinic housed within a developmental disorders institution and had a high rate of developmental disorders, the findings may not generalize to other preschool children with ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Reversal of multidrug resistance by kopsiflorine isolated from Kopsia dasyrachis.

Kopsiflorine, an indole alkaloid of the aspidofractinine-type isolated from Kopsia dasyrachis, was examined for its effect in enhancing drug cytotoxicity in multidrug-resistant tumor cells. The cytotoxicity of vincristine was enhanced in a concentration-dependent manner by kopsiflorine in drug-resistant KB cells (VJ-300). Kopsiflorine alone had no effect on the growth of drug sensitive or resistant cells, but the intracellular accumulation of vincristine was enhanced by kopsiflorine in VJ-300 cells. Kopsiflorine (10 micrograms/ml) significantly inhibited the binding of [3H]azidopine to P-glycoprotein in VJ-300 cells. The results suggest that kopsiflorine interacts directly with P-glycoprotein and inhibits the efflux of antitumor agents in drug-resistant cells.

Drug Resistance, Multiple↗
PubMed1999

Microbial dynamics in oil-impacted prairie soil.

A remote site in the Tallgrass Prairie Preserve (Osage County, OK) was contaminated with crude oil by a pipeline break in 1992. In 1996, the contaminated soil was bioremediated by blending with uncontaminated soil, prairie hay, buffalo manure, and commercial fertilizers, and spreading in a shallow layer over uncontaminated soil to create a landfarm. The landfarm was monitored for two years for aerobic and anaerobic bacteria, soil gases indicative of microbial activity, and for changes in the concentration of total petroleum hydrocarbons (TPH). Levels of hydrocarbon degraders and soil gas indicators of aerobic degradation were stimulated in the landfarm during the first warm season relative to uncontaminated prairie soil. However, these same indicators were less conclusive during the second warm season, indicating depletion of the more easily degradable hydrocarbons, although the landfarm still contained 6,800 mg/kg TPH on the average at the beginning of the second warm season. Methane formation and methanogen counts were clearly stimulated in the first warm season relative to uncontaminated prairie soil, indicating that methanogenesis plays an important role in the mineralization of hydrocarbons even in these shallow soils.

Journal Article↗
PubMed1998

Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids.

A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.

Alkaloids↗
PubMed1998

Design of organic molecules with large two-photon absorption cross sections.

A strategy for the design of molecules with large two-photon absorption cross sections, delta, was developed, on the basis of the concept that symmetric charge transfer, from the ends of a conjugated system to the middle, or vice versa, upon excitation is correlated to enhanced values of delta. Synthesized bis(styryl)benzene derivatives with donor-pi-donor, donor-acceptor-donor, and acceptor-donor-acceptor structural motifs exhibit exceptionally large values of delta, up to about 400 times that of trans-stilbene. Quantum chemical calculations performed on these molecules indicate that substantial symmetric charge redistribution occurs upon excitation and provide delta values in good agreement with experimental values. The combination of large delta and high fluorescence quantum yield or triplet yield exhibited by molecules developed here offers potential for unprecedented brightness in two-photon fluorescent imaging or enhanced photosensitivity in two-photon sensitization, respectively.

Aniline Compounds↗
PubMed1997

A study of the effects of tamoxifen in the frail elderly: difficulties encountered in nursing home research.

OBJECTIVE: This study was conducted in order to determine whether the effects of tamoxifen in elderly, frail nursing home residents are similar to those that have been previously reported for younger postmenopausal women. DESIGN: A chart review study. SETTING: The Jewish Home and Hospital for Aged (JHHA), a subacute long-term care facility. PARTICIPANTS: One hundred fifty-eight women who had been at the JHHA at any time since 1986. One hundred ten had a history of breast cancer; 43 of these had been treated with tamoxifen while at the JHHA (Group I), and 66 had not (Group II). The remaining 49 women had no history of breast cancer (Group III). MEASUREMENTS: Data were collected from the time of admission to the JHHA through August, 1994 on: chemistry profiles, bone fractures apparently not a consequence of metastasis, gynecological parameters, and thromboemboli. RESULTS: The lack of pre-admission clinical information presented problems regarding research design and the interpretation of our findings. Nevertheless, compared to women who had not been treated with tamoxifen, treated women had a significantly elevated incidence of vaginal discharge (P = 0.01) and a lower prevalence of elevated total cholesterol (P = 0.04). Although not statistically significant, they also had decreased levels of low density lipoprotein cholesterol and an increased incidence of thromboemboli and bone fractures. CONCLUSIONS: While some of the effects of tamoxifen in elderly, frail women are similar to those observed in younger, postmenopausal women, others may be different. Our results suggest a need for further innovative studies that focus on the consequences of tamoxifen treatment in the elderly, frail population.

Age Factors↗