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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 19 recordsLinked to original sources
PubMed2000

Measurements of the mass, total width, and two-photon partial width of the eta(c) meson.

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.

Journal Article↗
PubMed2000

The use of the substrate-heme complex approach in the design, synthesis, biochemical evaluation, and rationalization of the inhibitory activity of a range of azole compounds against cholesterol side chain cleavage enzyme.

Here, we report the synthesis and biochemical evaluation of a number of compounds as potent inhibitors of cytochrome P450 enzymes, such as aromatase (AR), but not cholesterol side chain cleavage (CSCC). This is a crucial enzyme in the steroidal cascade and its inhibition results in major side-effects, as a result, the ability of compounds to specifically inhibit enzymes such as AR but not CSCC would be an important factor in the drug design process.

Animals↗
PubMed2000

The use of the novel substrate-heme complex approach in the derivation of a representation of the active site of the enzyme cholesterol side chain cleavage.

The previously reported substrate-heme complex approach is used to study the binding of type II inhibitors of the enzyme cholesterol side chain cleavage (CSCC), a cytochrome P-450 dependent enzyme involved in the oxidative cleaveage of the C(20)-C(22) bond of cholesterol. Using the derived model, we have rationalised the inhibitory activity of a number of compounds including aminoglutethimide and pyridoglutethimide and the enantiomers of ketoconazole.

Animals↗
PubMed2000

Guillain-Barré syndrome: An unusual presentation of West Nile virus infection.

West Nile fever is a mosquito-borne febrile illness seen in Africa, Asia, and Europe, but reported in North America only once. The recent outbreak in New York City represents the first time this virus has been detected in North America. West Nile virus usually causes mild symptoms, though rarely it can cause neurologic diseases, with a fatal outcome or permanent neurologic sequelae. We describe an elderly patient with West Nile virus infection who presented with Guillain-Barré syndrome.

Aged↗
PubMed2000

First report of the investigation into the importance of pK(a) in the inhibition of estrone sulfatase by sulfamate containing compounds.

In an effort to rationalise the inhibitory activity of a range of aminosulfamate compounds and to further investigate the recently reported definitive pharmacophore estrone sulfatase (ES), we undertook extensive synthesis, biochemical evaluation and physicochemical property determination of a range of similar compounds. Here, we report the initial results of our study into a series of simple (aminosulfonate based) substituted phenol derivatives. Using these compounds, we investigated the role of pK(a) in the inhibition of ES. The results of the study suggest that there is a strong correlation between the inhibitory activity and the stability of the resulting O(-) anion (i.e., the pK(a) of the starting phenol).

Anions↗
PubMed2000

Identification of an interaction between the angiotensin II receptor sub-type AT2 and the ErbB3 receptor, a member of the epidermal growth factor receptor family.

To identify the proteins that interact and mediate angiotensin II receptor AT2-specific signaling, a random peptide library was screened by yeast-based Two-Hybrid protein-protein interaction assay technique. A peptide that shared significant homology with the amino acids located between the residues Gly-Xaa-Gly-Xaa-Xaa-Gly721 and Lys742, the residues predicted to be important for ATP binding of the ErbB3 and ErbB2 receptors, was identified to be interacting with the AT2 receptor. The interaction between the human ErbB3 receptor and the AT2 receptor was further confirmed using the cytoplasmic domain (amino acids 671-782) of the human ErbB3 receptor. Moreover, an AT2 receptor peptide that spans the amino acids 226-363, (spans the third ICL and carboxy terminal domain) could also interact with the AT2 receptor in a yeast Two-Hybrid protein-protein interaction assay. Studies using mutated and chimeric AT2 receptors showed that replacing the third intracellular loop (ICL) of the AT2 receptor with that of the AT1 abolishes the interaction between the ErbB3 and the AT2 in yeast Two-Hybrid protein-protein interaction assay. Thus the interaction between the AT2 receptor and the ErbB3 receptor seems to require the region spanning the third ICL and carboxy terminus of the AT2 receptor. Since the third ICL of the AT2 receptor is essential for exerting its inhibitory effects on cell growth, possible involvement of this region in the interaction with the cytoplasmic domain of the ErbB3 receptor suggests a novel signaling mechanism for the AT2 receptor mediated inhibition of cell growth. Furthermore, since both the AT2 and the ErbB3 receptors are expressed during fetal development, we propose that the existence of direct interaction between these two receptors may play a role in the regulation of growth during the initial stages of development.

Amino Acid Sequence↗
PubMed2000

MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans.

The germ line is an immortal cell lineage that is passed indefinitely from one generation to the next. To identify the genes that are required for germline immortality, we isolated Caenorhabditis elegans mutants with mortal germ lines--worms that can reproduce for several healthy generations but eventually become sterile. One of these mortal germline (mrt) mutants, mrt-2, exhibits progressive telomere shortening and accumulates end-to-end chromosome fusions in later generations, indicating that the MRT-2 protein is required for telomere replication. In addition, the germ line of mrt-2 is hypersensitive to X-rays and to transposon activity. Therefore, mrt-2 has defects in responding both to damaged DNA and to normal double-strand breaks present at telomeres. mrt-2 encodes a homologue of a checkpoint gene that is required to sense DNA damage in yeast. These results indicate that telomeres may be identified as a type of DNA damage and then repaired by the telomere-replication enzyme telomerase.

Amino Acid Sequence↗
PubMed2000

Synthesis and biochemical evaluation of novel inhibitors of aromatase (AR) using an enhanced representation of the active site of AR derived from the consideration of the reaction mechanism.

A novel molecular modeling study, involving inhibitors bound to the iron of cytochrome P450 heme, is described for nonsteroidal inhibitors of aromatase (AR). Study of compounds such as aminoglutethimide (AG) suggests that it utilizes hydrogen bonding group(s) at the active site which would usually H-bond to the steroid C(17) carbonyl group. Interaction between AG's carbonyl groups and the area of the active site corresponding to the substrate C(3)==O group is not possible due to steric interaction. Possible reasons for the difference in activity of enantiomers of alternative inhibitors is also suggested, as well as the mode of action of the new AR inhibitor, Arimidex-whose inhibitory activity previously has not been rationalized. The present study proposes that it is able to use hydrogen bonding groups at the active site corresponding to the steroid C(17)==O and C(3)==O area, contradicting a previous study where it is postulated that azole-type compounds only use polar groups at the active site corresponding to the steroid D ring. Using the hypotheses of the modeling study, we designed and synthesized a number of novel (enantiomerically pure) inhibitors, which upon biochemical evaluation were found to be good inhibitors; the N-nonyl derivative of the S-enantiomer was found to possess 39% inhibition at 100 microM inhibitor concentration (using androstenedione as the substrate), under similar conditions, and AG possessed 20% inhibition.

Aminoglutethimide↗
PubMed2000

Fanconi's anemia with solitary crossed renal ectopia, vesicoureteric reflux, and genital abnormalities.

Fanconi's anemia is an autosomal recessive disease, the main feature being pancytopenia secondary to bone-marrow hypoplasia. However, multiple congenital abnormalities may be encountered, urogenital malformations being common. We describe a patient with solitary crossed renal ectopia, vesicoureteric reflux, hypospadias, and unilateral undescended testis with absent vas deferens.

Child, Preschool↗
PubMed2000

Bladder-wall abscess in a girl with neurogenic bladder.

We report a case of a bladder-wall abscess in a patient with myelodysplasia and a neurogenic bladder. The aetiology of the abscess was obscure, but the patient had recurrent urinary tract infections and was being managed by clean intermittent catheterisation.

Abscess↗
PubMed2000

Lumpectomy margins, reexcision, and local recurrence of breast cancer.

BACKGROUND: The diagnosis of breast cancer is often made by excisional biopsy without margin assessment for mammographic findings or palpable masses. Many patients treated with breast conservation undergo reexcision to obtain clear margins although the relationship between clear margins and local recurrence remains controversial. METHODS: Patients undergoing breast conservation and adjuvant radiation therapy with complete follow-up over 5 years were studied. Factors associated with obtaining clear histopathologic margins and undergoing reexcision to obtain clear margins were studied in relation to the risk of local recurrence. RESULTS: Clear biopsy margins were associated with diagnosis by fine-needle aspiration cytology (fine-needle aspiration 42%, spot localization 11%, excisional biopsy 10%; P <0.001). Reexcision was significantly related to diagnostic method (spot localization 63%, excisional biopsy 36%, fine-needle aspiration 10%; P <0.001), first margin status (clear 0%, close 11%, positive 46%, unknown 48%; P <0.001), patient age (54 years for reexcised patients and 58 for non-reexcised patients; P <0.001), and tumor size (mean tumor size 1. 4 cm for reexcised patients and 1.7 cm for non-reexcised patients; P = 0.003). Patients undergoing reexcision were significantly more likely to be diagnosed by spot localization, have nonnegative excisional biopsy margins, be younger, and have smaller tumors than patients not undergoing reexcision. Local recurrence was not significantly related to margin status (8% with clear margins, 7% with positive margins, 19% with close margins, and 11% with unknown margins) or reexcision (10% local recurrence rate for patients with negative final margins after reexcision and 12% with positive, close or unknown first margin without reexcision). Estrogen receptor status was the only variable related to local recurrence in Cox proportional hazards model (P = 0.009). Estrogen receptor negative patients with nonnegative margins experienced a 20% rate of local recurrence compared with 10% for estrogen receptor negative patients with negative margins and 7% for estrogen receptor positive patients regardless of margin status (P = 0.021). CONCLUSIONS: Clear excision margins are facilitated by preoperative diagnosis by fine-needle cytology. For patients with nonnegative margins, reexcision was more commonly performed in young patients with small tumors diagnosed by spot localization biopsy. The relationship of local recurrence to margins and reexcision was not statistically significant. Estrogen receptor negative tumors with nonnegative margins had a significantly higher rate of local recurrence than estrogen receptor negative tumors with clear margins and estrogen receptor positive tumors regardless of margin status.

Adult↗
PubMed2000

Effects of lisinopril and amlodipine on antioxidant status in experimental hypertension.

The objective of this investigation was to compare changes in antioxidant status (together with other metabolites relevant to hypertension) in plasma and cardiac tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY), following 8 weeks of treatment with lisinopril (angiotensin converting enzyme inhibitor) or amlodipine (Ca(2+) channel antagonist) respectively. There was no significant difference in the levels of total antioxidant capacity, retinol, urea, albumin or triglyceride in plasma from SHR or WKY rats, with or without lisinopril or amlodipine treatment. However in SHR rats, levels of alpha-tocopherol were substantially reduced in both plasma (-54% WKY, P<0.01) and cardiac tissue (-43% WKY, P<0.05). Treatment with lisinopril ameliorated reduced levels of plasma alpha-tocopherol in SHR rats, but not in cardiac tissue. Amlodipine treatment had no effect on alpha-tocopherol levels in plasma or cardiac tissue in SHR rats. In SHR rats total cholesterol levels were significantly lower thanWKY controls (-36%, P<0.001). This effect was reversed in lisinopril treated SHR rats (+27%, P<0.01). Plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were reduced in untreated SHR rats (P<0.025) when compared to WKY controls; neither lisinopril nor amlodipine treatment significantly altered these parameters. These findings suggest possible alternative mechanisms of action for lisinopril, and reinforce its use in hypertensive patients or patients with left ventricular hypertrophy.

Amlodipine↗
PubMed2000

Spectrofluorimetric analysis of certain 4-quinolone in pharmaceuticals and biological fluids.

A highly sensitive spectrofluorimetric procedure is developed for the analysis of certain 4-quinolone antibiotics: sparfloxacin (I), oxolonic acid (II), flumequine (III) and enrofloxacin (IV) in their pharmaceutical dosage forms or in biological fluids. This procedure is based upon the intrinsic fluorescence in acetonitrile for sparfloxacin or upon the highly enhanced fluorescence obtained by the interaction of the drugs with AlCl3. The optimum pH for the maximum fluorescence intensity is 8-8.5 for I, 5-6 for II, III and pH 3.5 for IV. The different experimental parameters that affect the fluorescence intensity were carefully studied and incorporated into the procedure.

Calibration↗
PubMed2000

Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress.

The hepatoprotective activity of the 50% ethanol extract of the bark of Lawsonia alba syn. L. inermis was investigated against the carbon tetrachloride-induced oxidative stress. Pretreatment of rats with doses of 250 and 500 mg/kg of the plant extract significantly (P < 0.001) lowered serum transaminases (GOT and GPT) and LDH levels, respectively, in a dose dependent manner against the significant (P < 0.001) rise of these damage marker enzymes when challenged with CCl4 (1 ml/kg, orally). Parallel to these changes, the plant extract prevented CCl4-induced oxidative stress by significantly maintaining the levels of reduced glutathione (GSH), its metabolizing enzymes and simultaneously inhibiting the production of free radicals. Pretreatment of rats with the extract also inhibited the peroxidation of microsomal lipids in a dose-dependent manner.

Animals↗
PubMed2000

A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans.

To maintain genomic stability following DNA damage, multicellular organisms activate checkpoints that induce cell cycle arrest or apoptosis. Here we show that genotoxic stress blocks cell proliferation and induces apoptosis of germ cells in the nematode C. elegans. Accumulation of recombination intermediates similarly leads to the demise of affected cells. Checkpoint-induced apoptosis is mediated by the core apoptotic machinery (CED-9/CED-4/CED-3) but is genetically distinct from somatic cell death and physiological germ cell death. Mutations in three genes--mrt-2, which encodes the C. elegans homolog of the S. pombe rad1 checkpoint gene, rad-5, and him-7-block both DNA damage-induced apoptosis and cell proliferation arrest. Our results implicate rad1 homologs in DNA damage-induced apoptosis in animals.

Animals↗
PubMed2000

The effect of birth interval on malnutrition in Bangladeshi infants and young children.

This study was undertaken to investigate the independent effect of the length of birth interval on malnutrition in infants, and children aged 6-39 months. Data for this study were drawn from a post-flood survey conducted during October-December 1988 at Sirajganj of the Sirajgani district and at Gopalpur of the Tangail district in Bangladesh. The survey recorded the individual weights of 1887 children. Cross-tabulations and logistic regression procedures were applied to analyse the data. The proportion of children whose weight-for-age was below 70% (moderate-to-severely malnourished) and 60% (severely malnourished) of the NCHS median was tabulated against various durations of previous and subsequent birth intervals. The odds of being moderately or severely malnourished were computed for various birth intervals, controlling for: the number of older surviving siblings; maternal education and age; housing area (a proxy for wealth); age and sex of the index child; and the prevalence of diarrhoea in the previous 2 weeks for the index child. About one-third of infants and young children were moderately malnourished and 15% were severely malnourished. The proportion of children who were under 60% weight-for-age decreased with the increase in the length of the subsequent birth interval, maternal education and housing area. The proportion of malnourished children increased with the number of older surviving children. Children were at higher risk of malnutrition if they were female, their mothers were less educated, they had several siblings, and either previous or subsequent siblings were born within 24 months. This study indicates the potential importance of longer birth intervals in reducing malnutrition in children.

Adult↗