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Biomedical subjects

A H Ahmed

Publications and source records attributed to A H Ahmed.

At least 19 recordsLinked to original sources
PubMed1998

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma.

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.

Adult↗
PubMed1998

Rheumatic manifestations and immunological abnormalities in patients with chronic hepatitis C. A study in the Middle East.

Hepatitis C virus infection and rheumatic disorders are both common in the Middle East and share many clinical and immunological manifestations, raising diagnostic problems. We compared the prevalence of extrahepatic clinical manifestations and immunological disorders in 40 patients with chronic hepatitis C and in 42 carefully matched healthy controls. Polyarthralgia or polyarthritis was the most common rheumatic manifestation (35%) in the cases, followed by cutaneous vasculitis (15%). Glomerulonephritis and xerophthalmia were uncommon, and none of the cases had systemic vasculitis. Immunological abnormalities included serum rheumatoid factor (47.5%), cryoglobulins (30%), and one or more antitissue antibodies (37.5%). The prevalences of polyarthralgia, cutaneous vasculitis, rheumatoid factor, cryoglobulinemia, and anti-tissue antibodies were significantly higher in the hepatitis C group than in the control group. Our data suggest that patients in the Middle East who present with features of rheumatic or autoimmune diseases should be screened for hepatitis C.

Adult↗
PubMed1998

Seasonal variation in molluscicidal activity of Solanum nigrum L.

Solanum nigrum L. leaves and fruits were shown to have molluscicidal activities against snails transmitting schistosomiasis and fascioliasis. In the present study, their molluscicidal activity against adult Biomphalaria alexandrina snails was assessed to determine whether plants collected at various seasons would have different degrees of toxicity. Leaves and fruits of three S. nigrum varieties were collected from Faiyoum and/or Giza during the four seasons. Leaves collected in autumn had the highest effect (LC50-35.4) followed by spring (LC50 = 44.36), summer (LC50 = 46.7) and winter (LC50 = 100.4). Toxicity of plant extracts was also affected by other seasonal dependent factors. These are the duration of plant exposure to direct sunlight and the size of the fruits. S. nigrum (black fruits) was more toxic (LC50 = 18.1) than the other two types, S. nigrum v. vellosum (yellow fruits) (LC50 = 38.9) and S. nigrum v. juidaicum (red fruits) (LC50 = 34.7).

Animals↗
PubMed1997

Evidence for a role of G protein beta gamma subunits in the enhancement of cAMP accumulation and DNA synthesis by adenosine in human cells.

The expression of both A1- and A2a-adenosine receptors occurs in human foreskin and lung fibroblasts (Ahmed et al., 1995, Biochem. Biophys. Res. Commun. 208:871-878). Studies with highly specific A1- and A2a-adenosine receptor agonists provide indirect evidence that binding of adenosine activates Gs and Gi, after which Gs alpha interacts with beta gamma subunits released from Gi. The interaction of Gs alpha with beta gamma augments cyclic adenosine monophosphate (cAMP) accumulation, more than does Gs alpha alone. In the present study, we have provided direct evidence for a role of the beta gamma complex in the augmentation of cAMP accumulation by using a recombinant His6 fusion protein containing the carboxyl third of beta ARK1. This portion of beta ARK1 contains G beta gamma binding sequences and acts as a specific beta gamma scavenger (Koch et al., 1994, Proc. Natl. Acad. Sci. USA 91:12706-12710). In permeabilized fibroblasts, the His6 fusion protein inhibited the augmentation of cAMP accumulation resulting from adenosine binding to both A1 and A2a receptors. In addition, the specific G beta gamma scavenger inhibited the further rise in cellular cAMP levels caused by pretreating cells with pertussis toxin before incubation with adenosine. Finally, we observed that specific A1-adenosine receptor agonists augmented the cAMP accumulation stimulated by A2a-receptor agonists, and this cAMP augmentation was also suppressed by the G beta gamma scavenger. Similar results were obtained when the cells were treated with extracellular ATP and lysophosphatidic acid (LPA) to stimulate Gs and release G beta gamma subunits, respectively.

Adenosine↗
PubMed1997

Influenza vaccination in patients with asthma: effect on peak expiratory flow, asthma symptoms and use of medication.

This pilot study was undertaken to examine whether killed influenza vaccine causes exacerbations in asthmatic adults. Thirty-three stable asthmatics recorded peak expiratory flow (PEF), asthma symptoms, and use of asthma medication for 2 weeks, and then received killed influenza vaccine. Thereafter they recorded PEF, asthma symptoms and use of medication for a further 2 weeks. Comparison of recordings during the 2 weeks before and after vaccination revealed that influenza vaccine was not associated with reduction in PEF (P = 0.76), increase in asthma symptoms (P = 0.17) or use of asthma medication (P = 0.58). Similar results for PEF (P = 0.49), asthma symptoms (P = 0.17), and asthma medication (P = 0.16) were obtained when the analysis was restricted to the 2 days before and after vaccination.

Adult↗
PubMed1997

Effectiveness of influenza vaccine in reducing hospital admissions during the 1989-90 epidemic.

The effectiveness of influenza vaccine in reducing hospital admissions for pneumonia, influenza, bronchitis, or emphysema was assessed by a case-control study of people aged 16 years and older who were admitted to 10 Leicestershire hospitals between 1 December 1989 and 31 January 1990. Hospital and general practitioners' records for 156 admissions (the cases) and 289 controls matched for age and sex were reviewed. Information was collected on demography, the usual place of residence (institutional or non-institutional), the existence of chronic illness, and vaccination during the 5 years before admission. The odds ratio for hospital admission among vaccinees was 0.67 (95% CI 0.39-1.12) giving an estimate of vaccine effectiveness in this setting of 33% (95% CI 0-61). However, multivariate logistic regression, adjusting for the effects of institutional care and chronic illness, revealed that influenza vaccination reduced hospital admissions by 63% (95% CI 17-84%). There was a strong trend towards improved vaccine effectiveness when used in institutional settings. Influenza vaccine is effective in reducing hospital admissions for influenza, pneumonia, bronchitis and emphysema, and effectiveness is comparable to that observed for influenza and pneumonia admissions in North America.

Adolescent↗
PubMed1997

Laboratory assessment of the molluscicidal and cercaricidal activities of the Egyptian weed, Solanum nigrum L.

The molluscicidal properties of Solanum nigrum L. were tested against three Egyptian snail species (Biomphalaria alexandrina, Bulinus truncatus and Lymnaea natalensis), each an intermediate host of parasites causing human schistosomiasis or fascioliasis. The plant was collected in two regions within Egypt: Fayium and Giza. Snails were exposed for 24 and 48 h, to the dry powdered fruits and leaves or to crude water extracts of the powders, and mortality was recorded. The water extract of the leaves collected in Fayium (FLWE) had the highest molluscicidal activity, with median lethal concentrations (LC50) of 18.6 mg/litre for Bi. alexandrina, 14.5 mg/litre for Bu. truncatus and 17.7 mg/litre for L. natalensis. When Bi. alexandrina infected with Schistosoma mansoni were exposed to FLWE (20 or 25 mg/litre), they shed significantly fewer cercariae than unexposed snails (P < 0.02). The cercaricidal properties of FLWE were directly tested against S. haematobium, S. mansoni and Fasciola gigantica cercariae and a time-concentration relationship was observed; the concentrations needed to kill all cercariae (LC100) within 30 min of exposure were 30 mg/litre for both S. haematobium and S. mansoni and 40 mg/litre for F. gigantica.

Animals↗
PubMed1996

Delays and diversity in the practice of local research ethics committees.

OBJECTIVES: To compare the practices of local research ethics committees and the time they take to obtain ethical approval for a multi-centre study. DESIGN: A retrospective analysis of outcome of applications for a multi-centre study to local research ethics committees. SETTING: Thirty-six local research ethics committees covering 38 district health authorities in England. MAIN MEASURES: Response of chairmen and women, the time required to obtain approval, and questions asked in application forms. RESULTS: We received replies from all 36 chairmen contacted: four (11%) granted their approval, and 32 (89%) required our proposal to be considered by their local research ethics committee. Three committees asked us to attend their meetings. The application was approved by all 36 local research ethics committees but the time to obtain ethical approval varied between six to 208 days. One third of the committees did not approve the project within three months, and three took longer than six months. There was considerable variation in the issues raised by local research ethics committees and none conformed exactly to the Royal College of Physicians' guidelines. CONCLUSION: Obtaining ethical approval for a multi-centre study is time-consuming. There is much diversity in the practice of local research ethics committees. Our data support the recommendation for a central or regional review body of multi-centre studies which will be acceptable to all local research ethics committees.

England↗
PubMed1995

Presence of both A1 and A2a adenosine receptors in human cells and their interaction.

We have obtained pharmacological evidence for the expression of both A1- (inhibitory) and A2a- (stimulatory) adenosine receptors in cultured human foreskin fibroblasts and lung fibroblasts. The A1 receptors were sufficiently abundant in foreskin fibroblasts so that binding studies with a radioactively labeled specific ligand confirmed their existence. Both receptors were activated during the stimulation of cAMP accumulation and DNA synthesis by adenosine.

Adenosine↗
PubMed1993

Photoreactivation in a phrB mutant of Escherichia coli K-12: evidence for the role of a second protein in photorepair.

In Escherichia coli, the light-dependent repair of pyrimidine dimers in UV-irradiated DNA is now accepted as being due to enzymatic photoreactivation (PR) by a 50 kDa enzyme, photolyase (EC 4.1.99.3). The gene for this enzyme has been mapped at 16.2 min and designated phr. This gene was earlier described as phrB, another locus phrA having been proposed in association with PR. The relevance of the putative phrA gene has now been placed in doubt. The recent report of the discovery of a photoreactivating enzyme in Drosophila melanogaster, which specifically repairs pyrimidine (6-4) pyrimidone photoproducts ([6-4] photoproducts), and that E. coli does possess a protein with specific affinity for the (6-4) photoproduct, has cast new light on the prospective role of phrA in PR. We have determined the nucleotide sequence of the putative phrA gene, which suggests it codes for a protein of 38 kDa. When the putative phrA gene was cloned into an expression vector and transformed into a phrA phrB mutant of E. coli, a level of photorepair was observed, which could correspond to repair of (6-4) photoproducts.

ATP-Binding Cassette Transporters↗
PubMed1992

Extracellular ATP stimulates increases in Na+/K+ pump activity, intracellular pH and uridine uptake in cultures of mammalian cells.

Using 3T3 and 3T6 mouse fibroblasts and A431 epidermoid carcinoma cells, we previously observed that extracellular ATP and ADP were mitogens and they synergized with other growth factors (Huang, N., Wang, D. and Heppel, L. A. (1989) Proc. Natl. Acad. Sci. USA 86, 7904-7908). We now report that ATP and ADP stimulated Na+ entry, intracellular alkalinization and Na+/K+ pump activity, which are early events that had been proposed to play a central role in DNA synthesis. In addition, ATP, ADP and AMPPNP stimulated uridine uptake by a pathway involving arachidonic acid metabolism. In A431 cells, activation of protein kinase C also contributed to ATP-dependent stimulation of uridine uptake. Concentrations of indomethacin and pertussis toxin which inhibited uridine uptake also blocked arachidonic acid metabolism and DNA synthesis. ATP acted as a competence factor. Interestingly, ATP did not have to be continuously present to stimulate uridine uptake. It was equally effective even when it was washed away after brief treatment of cells.

3T3 Cells↗
PubMed1990

Covalent incorporation of 3'-O-(4-benzoyl)benzoyl-ATP into a P2 purinoceptor in transformed mouse fibroblasts.

ATP, 3'-O-(4-benzoyl)benzoyl-ATP (BzATP), a photoaffinity analog of ATP, and several other ATP analogs induced an increase in plasma membrane permeability to monovalent ions and normally impermeant metabolites, including nucleotides, in transformed 3T6 mouse fibroblasts. The rank order of agonist potency for induction of nucleotide channels was BzATP (EC50 = 15 microM) greater than ATP (EC50 = 50 microM) approximately adenosine 5'-O-(1-thiotriphosphate) (ATP alpha S) greater than 2-methylthio-ATP (EC50 = 75 microM) approximately 3'-amino-3'-deoxy-ATP greater than adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) (EC50 = 175 microM). Long wavelength UV illumination of 3T6 cells in the presence of greater than or equal to 20 microM BzATP at 4 degrees C, a nonpermeabilizing temperature, followed by removal of unbound BzATP, resulted in the efflux of 86Rb+ and the release of a prelabeled pool of cytoplasmic nucleotides when the temperature was shifted to 37 degrees C. Photoincorporation of BzATP was inhibited by ATP, ATP alpha S, ATP gamma S, and other ATP analogs that induced an increase in plasma membrane permeability to nucleotides in 3T6 cells under nonphotoactivating conditions. GTP, ITP, UTP, adenosine, and ATP analogs that did not alter plasma membrane permeability to nucleotides under nonphotoactivating conditions also had no effect on BzATP photoincorporation. Photoincorporation of BzATP occurred optimally between pH 6.6 and pH 8.2 but was inhibited at pH 6.0. Photoincorporation of BzATP was also modulated by the osmolarity and the divalent cation concentration of the assay medium. The increase in plasma membrane permeability to nucleotides induced by photoincorporated BzATP occurred at the same rate and had the same temperature, pH, ionic strength, and divalent cation requirements as the increase in plasma membrane permeability to nucleotides induced by ATP and BzATP under nonphotoactivating conditions. These findings support the hypothesis that BzATP can be covalently incorporated into a P2 purinoceptor in 3T6 cells that is coupled to plasma membrane channels for ions and other metabolites.

Adenine Nucleotides↗
PubMed1989

Permeabilization of transformed mouse fibroblasts by 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate and the desensitization of the process.

A photoreactive analogue of ATP, 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP) altered the plasma membrane permeability of transformed 3T6 mouse fibroblasts to normally impermeant molecules as previously reported for ATP, but at lower concentrations. BzATP-induced permeabilization was modulated by pH, temperature, and the ionic composition of the medium similar to the permeabilizing effects of ATP. Conditions known to enhance ATP-induced permeabilization, such as treatment with the mitochondrial uncoupler carbonyl cyanide-m-chlorophenylhydrazone (CCCP) or the Ca2+-calmodulin antagonist trifluoperazine also enhanced BzATP-induced permeabilization. Conditions inhibitory to ATP-induced permeabilization, including chloride replacement or treatment with furosemide or dithiothreitol (DTT), inhibited permeabilization induced by BzATP. The ionic strength of the medium modulated the responsiveness of the cells to ATP and BzATP; a decrease in the ionic strength below isotonicity increased the sensitivity of the cells to the nucleotides, whereas an increase in ionic strength above isotonicity inhibited permeabilization. Prolonged exposure to ATP under non-permeabilizing conditions caused the cells to become insensitive to ATP and BzATP. The densensitization phenomenon provides support for the theory that the permeabilization process is mediated by a receptor for ATP.

Adenosine Triphosphate↗
PubMed1979

Consanguinity and schizophrenia in Sudan.

The rate of first-cousin marriages among the patients of schizophrenics was compared with a control group in an isolated highly inbred sudanese community, no significant difference being found.

Adolescent↗