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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 127 records · Page 7Linked to original sources

Novel inhibitors of the enzyme estrone sulfatase (ES).

We report the initial results of our study into a series of simple 4-sulfamated phenyl alkyl ketones as potential inhibitors of the enzyme estrone sulfatase. The results of the study show that these compounds are potent inhibitors, possessing greater inhibitory activity than COUMATE, but weaker activity than EMATE. Furthermore, the compounds are observed to be irreversible inhibitors.

Alkanes↗

First observation of the decays B(0) --> D(*-)p_p pi+ and B(0) --> D(*-)p_n.

We report the first observation of exclusive decays of the type B-->D(*)N_NX, where N is a nucleon. Using a sample of 9.7x10(6)B_B pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B0-->D(*-)p_p pi(+)) = (6.5(+1.3)(-1.2)+/-1.0)x10(-4) and B(B0-->D(*-)p_n) = (14.5(+3.4)(-3.0)+/-2.7)x10(-4). Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.

Journal Article↗

Measurement of the relative branching fraction of upsilon(4S) to charged and neutral B-meson pairs.

We analyze 9.7x10(6) B_B pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Upsilon(4S) resonance. We measure the rates for B0-->J/psiK((*)0) and B+-->J/psiK((*)+) decays and use the world-average B-meson lifetime ratio to extract the relative widths f(+-) / f(00) = gamma(Upsilon(4S)-->B+B-) / gamma(Upsilon(4S)-->B0 B-0)) = 1.04+/-0.07(stat)+/-0.04(syst). With the assumption that f(+-)+f(00) = 1, we obtain f(00) = 0.49+/-0.02(stat)+/-0.01(syst) and f(+-) = 0.51+/-0.02(stat)+/-0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Upsilon(4S) resonance.

Journal Article↗

First observation of the sigma(*+)(c) baryon and a new measurement of the sigma(*+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

Journal Article↗

Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin.

Cdc42Hs is involved in cytoskeletal reorganization and is required for neurite outgrowth in N1E-115 cells. To investigate the molecular mechanism by which Cdc42Hs regulates these processes, a search for novel Cdc42Hs protein partners was undertaken by yeast two-hybrid assay. Here, we identify the 58-kD substrate of the insulin receptor tyrosine kinase (IRS-58) as a Cdc42Hs target. IRS-58 is a brain-enriched protein comprising at least four protein-protein interaction sites: a Cdc42Hs binding site, an Src homology (SH)3-binding site, an SH3 domain, and a tryptophan, tyrptophan (WW)-binding domain. Expression of IRS-58 in Swiss 3T3 cells leads to reorganization of the filamentous (F)-actin cytoskeleton, involving loss of stress fibers and formation of filopodia and clusters. In N1E-115 cells IRS-58 induces neurite outgrowth with high complexity. Expression of a deletion mutant of IRS-58, which lacks the SH3- and WW-binding domains, induced neurite extension without complexity in N1E-115 cells. In Swiss 3T3 cells and N1E-115 cells, IRS-58 colocalizes with F-actin in clusters and filopodia. An IRS-58(1267N) mutant unable to bind Cdc42Hs failed to localize with F-actin to induce neurite outgrowth or significant cytoskeletal reorganization. These results suggest that Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing protein complexes via adaptor proteins such as IRS-58 to F-actin.

Actins↗

Study of B Decays to Charmonium States: B-->eta(c)K and B --> chi(c0)K.

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

Journal Article↗

In early development of the rat mRNA for the major myelin protein P(0) is expressed in nonsensory areas of the embryonic inner ear, notochord, enteric nervous system, and olfactory ensheathing cells.

The myelin protein P(0) has a major structural role in Schwann cell myelin, and the expression of P(0) protein and mRNA in the Schwann cell lineage has been extensively documented. We show here, using in situ hybridization, that the P(0) gene is also activated in a number of other tissues during embryonic development. P(0) mRNA is first detectable in 10-day-old embryos (E10) and is at this time seen only in cells in the cephalic neural crest and in the otic placode/pit. P(0) expression continues in the otic vesicle and at E12 P(0) expression in this structure largely overlaps with expression of another myelin gene, proteolipid protein. In the developing ear at E14, P(0) expression is complementary to expression of serrate and c-ret mRNAs, which later are expressed in sensory areas of the inner ear, while expression of bone morphogenetic protein (BMP)-4 and P(0), though largely complementary, shows small areas of overlap. P(0) mRNA and protein are detectable in the notochord from E10 to at least E13. In addition to P(0) expression in a subpopulation of trunk crest cells at E11/E12 and in Schwann cell precursors thereafter, P(0) mRNA is also present transiently in a subpopulation of cells migrating in the enteric neural crest pathway, but is down-regulated in these cells at E14 and thereafter. P(0) is also detected in the placode-derived olfactory ensheathing cells from E13 and is maintained in the adult. No signal is seen in cells in the melanocyte migration pathway or in TUJ1 positive neuronal cells in tissue sections. The activation of the P(0) gene in specific tissues outside the nervous system was unexpected. It remains to be determined whether this is functionally significant, or whether it is an evolutionary relic, perhaps reflecting ancestral use of P(0) as an adhesion molecule.

Animals↗

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population.

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.

Abatacept↗

Broken kidney: traumatic fracture of a renal allograft.

Although many renal transplant recipients are protective of their grafts and often express concern about the possibility of traumatic injury, such injury has been reported only rarely. We describe a case report of a boy who sustained an injury to his renal allograft after a bicycle accident. Despite a dramatic anatomic abnormality seen on magnetic resonance imaging, he suffered only minor and self-limited symptomatic and clinical consequences. We reviewed the literature addressing traumatic injuries affecting renal allografts. The long-term consequences of such injuries on allograft function and survival are unknown.

Accidents, Traffic↗

Anti-tumor promoting activity of Asteracantha longifolia against experimental hepatocarcinogenesis in rats.

Vegetables, natural products of plant origin and numerous non-nutritive dietary constituents have been shown to play a salutary role in cancer chemoprevention. The present study aims to evaluate the chemopreventive efficacy of the methanol fraction of Asteracantha longifolia seed extract against development of 2-acetylaminofluorene (2-AAF)-selected gamma-glutamyl transpeptidase (gamma-GT)-positive foci following diethylnitrosamine (DEN) initiation. Treatment of rats with doses 200 and 400 mg/kg body weight of methanol extract of A. longifolia seeds on alternate days, subsequent to carcinogen treatment, for 6 weeks significantly reduced the incidence and size distribution of gamma-GT-positive foci and tumor formation. Administration of A. longifolia seeds significantly (P<0.001) ameliorated the activities of antioxidant enzymes, glutathione peroxidase (GPx) and catalase (CAT), in a dose-dependent manner. Prophylactic administration of seed extract simultaneous to 2-AAF in the diet, at same doses, significantly suppressed 2-AAF and partial hepatectomy (PH)-induced ornithine decarboxylase (ODC) activity and [(3)H]thymidine incorporation into hepatic DNA, in a dose-dependent manner. Assimilation of the quantitative foci data together with the findings of the modulation of tumor promoting markers give ample evidence to the anti-tumor promoting potential of A. longifolia seeds against chemically-induced hepatocarcinogenesis in Wistar rats.

2-Acetylaminofluorene↗

Comparison of drug substance impurity profiles generated with extended length columns during packed-column SFC.

The current study assesses the effect of extending column length during gradient packed column sub/supercritical fluid chromatography (PCSFC) experiments on the detection of known and unknown impurities in a drug substance sample. Quantitative drug substance impurity profiles were generated and compared using multiple column PCSFC and HPLC conditions. Also, chromatographic figures of merit were estimated and compared for components of a standard mixture during PCSFC experiments, which used one column, four columns, and six columns in series.

Chromatography, High Pressure Liquid↗

Hydrophobicity and functionality maps of farnesyltransferase.

Farnesyltransferase (FTase) catalyzes the attachment of a 15-carbon isoprenoid moiety, farnesyl, through a thioether linkage to a cysteine near the C-terminus of oncogenic Ras proteins. These transform animal cells to a malignant phenotype when farnesylated. Hence, FTase is an interesting target for the development of antitumor agents. In this work we first investigate the active site of FTase by mapping its hydrophobic patches. Then the program SEED is used to dock functional groups into the active site by an exhaustive search and efficient evaluation of the binding energy with solvation. The electrostatic energy is SEED is based on the continuum dielectric approximation and consists of screened intermolecular energy and protein and fragment desolvation terms. The results are found to be consistent with the sequence variability of the tetrapeptide substrate. The distribution of functional groups (functionality maps) on the substrate binding site allows for identification of modifications of the tetrapeptide sequence that are consistent with potent peptidic inhibitors. Furthermore, the best minima of benzene match corresponding moieties of an inhibitor in clinical trials. The functionality maps are also used to design a library of disubstituted indoles that might prevent the binding of the protein substrates.

Alkyl and Aryl Transferases↗

Epidemiological investigation of the central Scotland outbreak of Escherichia coli O157 infection, November to December 1996.

On Friday, 22 November 1996, the microbiologist at a hospital in Lanarkshire, Scotland, identified presumptive Escherichia coli O157 in faecal specimens submitted by three patients with bloody diarrhoea, and confirmed its presence in one. Over the next 6 h, 12 more potential cases were identified. Investigations first indicated then confirmed a single food premises as the source of infection. Effective control measures were applied promptly. The outbreak was declared over on 20 January 1997, by which time 512 cases had been identified, and infection with the outbreak strain confirmed in 279. Twenty deaths occurred in cases during the outbreak and there were two more in cases during 1997. Seventeen of these deaths resulted from the outbreak. This paper describes the outbreak's epidemiological investigation, referring to other investigations, and control measures, where appropriate.

Adolescent↗

Isolation and characterization of a pseudomonas strain that degrades 4-acetamidophenol and 4-aminophenol.

Though many microorganisms that are capable of using phenol as sole source of carbon have been isolated and characterized, only a few organisms degrading substituted phenols have been described to date. In this study, one strain of microorganism that is capable of using phenol (3,000 ppm), 4-aminophenol (4,000 ppm) and 4-acetamidophenol (4,000 ppm) as sole source of carbon and energy was isolated and characterized. This strain was obtained by enrichment culture from a site contaminated with compounds like 4-acetamidophenol, 4-aminophenol and phenol in Pakistan at Bhai Pheru. The contaminated site is able to support large bacterial community as indicated by the viable cell counts (2 x 10(4) - 5 x 10(8)) per gram of soil. Detailed taxonomic studies identified the organisms as Pseudomonas species designated as strain STI. The isolate also showed growth on other organic compounds like aniline, benzene, benzyl alcohol, benzyl bromide, toluene, p-cresol, trichloroethylene and o-xylene. Optimum growth temperature and pH were found to be 30 degrees C and 7, respectively, while growth at 4, 25 and 35 degrees C and at pH 8 and 9 was also observed. Non growing suspended cells of strain ST1 degraded 68, 96 and 76.8% of 4-aminophenol (1,000 ppm), phenol (500 ppm) and 4-acetamidophenol (1,000 ppm), respectively, in 72 hrs. The isolation and characterization of Pseudomonas species strain STI, may contribute to efforts on phenolic bioremediation, particularly in an environment with very high levels of 4-acetamidophenol and 4-aminophenol.

Acetaminophen↗

Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis.

Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, alpha-tocopherol status is poor in myopathic alcoholics. Reduced alpha-tocopherol may pre-dispose the muscle to metabolic injury. However, experimental alpha-tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired alpha-tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover.

Alcoholic Neuropathy↗