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Biomedical subjects

G Sweeney

Publications and source records attributed to G Sweeney.

At least 55 records · Page 3Linked to original sources
PubMed1995

Induction of Ca2+/calmodulin-stimulated cyclic AMP phosphodiesterase (PDE1) activity in Chinese hamster ovary cells (CHO) by phorbol 12-myristate 13-acetate and by the selective overexpression of protein kinase C isoforms.

The cAMP phosphodiesterase (PDE) activity of CHO cells was unaffected by the addition of Ca2+ +calmodulin (CaM), indicating the absence of any PDE1 (Ca2+/CaM-stimulated PDE) activity. Treatment with the tumour promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) led to the rapid transient induction of PDE1 activity which attained a maximum value after about 13 h before slowly decreasing. Such induction was attenuated by actinomycin D. PCR primers were designed to hybridize with two regions identified as being characteristic of PDE1 forms found in various species and predicted to amplify a 601 bp fragment. RT-PCR using degenerate primers allowed an approx. 600 bp fragment to be amplified from RNA preparations of rat brain but not from CHO cells unless they had been treated with PMA. CHO cells transfected to overexpress protein kinase C (PKC)-alpha and PKC-epsilon, but not those transfected to overexpress PKC-beta I or PKC-gamma, exhibited a twofold higher PDE activity. They also expressed a PDE1 activity, with Ca2+/CaM effecting a 1.8-2.8-fold increase in total PDE activity. RT-PCR, with PDE1-specific primers, identified an approx. 600 bp product in CHO cells transfected to overexpress PKC-alpha and PKC-epsilon, but not in those overexpressing PKC-beta I or PKC-gamma. Treatment of PKC-alpha transfected cells with PMA caused a rapid, albeit transient, increase in PDE1 activity, which reached a maximum some 1 h after PMA challenge, before returning to resting levels some 2 h later. The residual isobutylmethylxanthine (IBMX)-insensitive PDE activity was dramatically reduced (approx. 4-fold) in the PKC-gamma transfectants, suggesting that the activity of the cyclic AMP-specific IBMX-insensitive PDE7 activity was selectively reduced by overexpression of this particular PKC isoform. These data identify a novel point of 'cross-talk' between the lipid and cyclic AMP signalling systems where the action of specific PKC isoforms is shown to cause the induction of Ca2+/CaM-stimulated PDE (PDE1) activity. It is suggested that this protein kinase C-mediated process might involve regulation of PDE1 gene expression by the AP-1 (fos/jun) system.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels.

We examined responses to the 5-hydroxytryptamine 1D (5-HT1D)-receptor agonist sumatriptan in bovine pulmonary artery rings (2-3 mm ID). The effects of agonist-induced tone and agents that alter intracellular cyclic AMP [cyclic AMP]i or [cyclic GMP]i on responses to sumatriptan were investigated. At resting tension, responses to sumatriptan were slight or not evident. In the presence of tone induced by U46619, responses to sumatriptan (1 nM-30 mM) were greatly potentiated, as were responses to the alpha2-adrenoceptor agonist UK14304. Responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) were potentiated only slightly. In the presence of U46619, addition of the adenylyl cyclase activator, forskolin (1 nM-0.1 microM or isoprenaline (ISO 1 microM) induced relaxations and increases in [cyclic AMP]i and resulted in further potentiation of the contractile response to sumatriptan. Addition of 0.1 microM sodium nitroprusside (SNP) inhibited sumatriptan-induced contractions. Whereas sumatriptan alone did not significantly affect [cyclic AMP]i, in the presence of U46619 it decreased [cyclic AMP]i. This effect of sumatriptan was further enhanced in the presence of forskolin. Sumatriptan increased [cyclic GMP]i. Using a nitric oxide (NO) synthase inhibitor and vessels denuded of endothelium, we showed that the increased [cyclic GMP]i in response to sumatriptan was endothelium-dependent and mediated by NO. This increase in [cyclic GMP]i was not observed in the presence of U46619. By measuring cyclic AMP and cyclic GMP phosphodiesterase (PDE) levels, we demonstrated that the point of "cross-talk" between cyclic nucleotides may not be at the level of total PDE activity. These results highlight the important role of [cyclic AMP], [cyclic GMP]i, and endothelium function in the control of 5-HT1D receptor-mediated vasoconstriction, which is dependent on a decrease in [cyclic AMP]i in the absence of an increase in [cyclic GMP]i.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Timing of antibiotic administration in knee replacement under tourniquet.

Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation. Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release. A 'tourniquet-release' dose of antibiotic increased drain fluid concentration threefold.

Cefamandole↗
PubMed1992

The amino acid sequence of glutamate decarboxylase from Escherichia coli. Evolutionary relationship between mammalian and bacterial enzymes.

The amino acid sequence of glutamate decarboxylase from Escherichia coli was solved by a combination of automated Edman degradation of peptide fragments derived by proteolytic and chemical cleavage and sequencing of DNA. Correct alignment of three peptides, for which no peptide overlaps were available, was achieved by sequencing a 1.1-kbp fragment of DNA produced by a polymerase-chain reaction using primers corresponding to sequences known to be in amino-terminal and carboxy-terminal regions of the protein. Sequence similarity (24% identity) with mammalian glutamate decarboxylase was found to be limited to a 55-residue sequence around the lysine residue that binds the coenzyme. Stronger similarity (38% identity), again confined to the same region, is seen with bacterial pyridoxal-phosphate-dependent histidine decarboxylase.

Amino Acid Sequence↗
PubMed1991

Reproducibility of the measurement of ciprofloxacin concentration in bronchial mucosa.

The reproducibility of ciprofloxacin estimations was investigated in duplicate samples of bronchial mucosa from patients undergoing fibreoptic bronchoscopy. At the time of biopsy, venous blood was collected from each patient. Between 3.5 and 5.0 h after dosing, penetration (%) into the mucosa was 162.13 (S.D. 19.77). The correlation coefficient (Pearson's) between duplicate samples was 0.93. The confidence limits (95%) for a single measurement were +/- 1.47 mg/kg.

Bronchi↗
PubMed1990

Penetration of ciprofloxacin into the aqueous humour of the uninflamed human eye after oral administration.

One hundred and one patients received oral ciprofloxacin prior to elective cataract removal. The quinolone content of the aqueous humour ranged from 2.7% to 15.4% of the corresponding serum level. The mean aqueous peak exceeded 0.4 mg/l between 2 and 3.5 h after administration. The highest aqueous concentration was achieved with a 1 g dose. In uninflamed eyes oral ciprofloxacin achieved intraocular concentrations that are bactericidal for Gram-negative bacteria including Pseudomonas aeruginosa. It may prove useful in the treatment of established intraocular infection and in prophylaxis prior to silastic implants.

Administration, Oral↗
PubMed1989

Structure and functional expression of a cloned Xenopus thyroid hormone receptor.

A clone corresponding to a thyroid hormone receptor was isolated from a Xenopus laevis cDNA library prepared from folliculated oocytes. The cDNA encodes a protein of 418 amino acid residues with a domain structure, including a putative DNA binding region with two zinc fingers, similar to other members of the v-erbA-related superfamily of receptors. The encoded protein resembles the TR alpha 1-type receptor of the rat. When expressed in COS cells the protein product binds triiodothyronine with a Kd of 0.12 nM. The receptor mediates thyroid-hormone-inducible expression of a reporter gene which includes a thyroid hormone response element in its upstream region.

Amino Acid Sequence↗
PubMed1986

Prophylaxis with tinidazole of infection in major head and neck surgery for malignant disease.

In a double-blind study, 20 patients undergoing surgery for the removal of an oropharyngeal squamous carcinoma received tinidazole either as a single perioperative prophylactic dose of 2 g or as a treatment course of 8 g given over a 7 day period. The wounds were assessed daily and specimens of fluid from the upper neck drain were submitted for culture. Four patients, two in each group, developed complications that might have been associated with infection (flap necrosis, fistula formation or both). There was no significant difference in the efficacy of these two regimens and single dose prophylaxis with tinidazole is advocated.

Adult↗
PubMed1986

Penetration of ciprofloxacin into aqueous humor.

Ciprofloxacin is a potentially useful antibiotic in eye infection. A pilot study was performed on 25 patients undergoing routine cataract surgery to assess the penetration of the drug into aqueous humor after oral administration. The mean peak level of 0.56 mg/l achieved in aqueous is above the MIC for most gram negative organisms, including Pseudomonas aeruginosa.

Administration, Oral↗
PubMed1984

Successful prophylaxis with tinidazole of infection after major head and neck surgery for malignant disease.

A prospective double-blind trial of tinidazole was carried out in a group of 8 patients, each undergoing radical surgery for the removal of a large squamous cell carcinoma (SCC) of the oropharynx. In the 4 patients given tinidazole there was no wound infection, wound healing was more rapid and the foul odour associated with infection in such patients was eliminated. Post-operatively, 3 of the 4 patients given the placebo developed wound infections. Mixed cultures of gram-negative anaerobic bacilli, predominantly bacteroides, were grown from the upper drain fluids of the infected patients. Anaerobes were not isolated from the drain fluids of patients receiving tinidazole. The efficacy of tinidazole was demonstrated in these patients who are at high risk of acquiring infection because of the extensive surgery required for tumour removal and the inevitable contamination of the tissues with the diverse, resident oral flora.

Aged↗
PubMed1984

The association of particular types of Proteus with chronic suppurative otitis media.

During a period of 12 months, 57 strains of Proteus were isolated from the ears of 38 unrelated patients with chronic suppurative otitis media. Each strain was identified, typed for bacteriocin production and sensitivity, and tested for Dienes compatibility. The majority of the strains (79%) were P. mirabilis; all but one of the remainder were P.vulgaris. Although 19 different bacteriocin production/sensitivity types were found, two rare types, P. mirabilis P7/S5,12 and P. vulgaris P0/S9, were associated with 47% of these infections. This was confirmed by Dienes typing. Patients with bilateral ear disease carried a different strain in each ear. There was no evidence that persistence of infection had arisen because of the development of antibiotic resistance. Although there was some evidence that persistence may have been the result of reinfection, the isolation of these rare types of Proteus from so many patients with chronic suppurative otitis media may indicate that they play an important role in the pathogenesis of the disease. Most of the Proteus isolates were of "non-faecal" types and it is believed that infection had arisen by a route other than the faecal-aural one.

Adolescent↗
PubMed1983

Cellular and genetic basis for suppression of cytotoxic T cell generation by haloaromatic hydrocarbons.

Generation of allospecific cytotoxic T cells in C57Bl/6 mice is significantly impaired following exposure to TCDD at doses as low as 4 ng/kg. T helper activity, as assessed by the ability to produce Interleukin 2, and frequency of CTL precursors appear unaffected in treated animals and thus the TCDD-induced suppressor cells we have described are primarily responsible for the reduction in the CTL response. Suppression of CTL generation in DBA/2 mice requires a 10--100-fold greater dose than in C57Bl/6, consistent with the observation that the Ah locus gene(s) of DBA/2 mice code for TCDD receptors with low binding affinity for TCDD. Other haloaromatic hydrocarbons (3,3'4,4'-tetrachlorobiphenyl and Aroclor 1254), capable of binding to the TCDD receptor, also suppress CTL generation, whereas the 2,2',4,4',6,6'-hexachlorobiphenyl molecule that lacks affinity for the TCDD receptor does not suppress CTL. The immunotoxic effects of TCDD in C57B/6 and DBA/2 mice occur at dose levels below those required to induce mixed-function oxidase enzymes in the liver. Suppression of CTL by TCDD is associated with increased susceptibility to lethal herpes virus type II infection. These data suggest that low levels of TCDD may interact with cytoplasmic receptors for TCDD in the thymus and induce biologically significant immunosuppression through activation of suppressor cells.

Animals↗
PubMed1983

Role of anaerobes in chronic otitis media.

A mixed bacterial flora of aerobic and anaerobic organisms can be isolated from the mucopurulent discharge in nearly 50% of individuals with active chronic otitis media. The role of the anaerobic flora has never been defined. A total of 33 patients with a mixed bacterial flora were treated with metronidazole alone or in combination with systemic antibiotics. The anaerobic flora was eliminated in 15 of 23 compliant individuals but the ears remained clinically active or mucoid in all. Anaerobic organisms would appear unlikely to be the primary pathogen in active chronic otitis media. Metronidazole alone or in combination with systemic antibiotics would also appear to be an ineffective medical treatment of active chronic otitis media as none of the 23 ears became inactive.

Adult↗