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Biomedical subjects

K Griffin

Publications and source records attributed to K Griffin.

29 records · Page 2Linked to original sources

The benzodiazepine receptor ligands RO 5-4864 and RO 15-1788 do not block the inhibition of PAF-induced platelet aggregation seen with the hetrazepine WEB2086.

The hypothesis was tested that the hetrazepine WEB 2086 acts as an inhibitor of PAF-induced platelet aggregation via interaction with the platelet benzodiazepine receptor(BDZR). WEB 2086 is a potent inhibitor of rabbit platelet aggregation and ATP secretion induced by 370 nM PAF. The two BDZR ligands RO 5-4864 and RO 15-1788 (7-96 microM) are inactive as PAF antagonists. When platelets were pretreated with either BDZR ligand, and then exposed to various concentrations of WEB 2086, there was no alteration of the dose-response relationship of the hetrazepine on PAF-induced aggregation, as reflected by threshold concentration, ED50, or maximum inhibition seen with WEB 2086. Pretreatment of platelets with the BDZR ligands also failed to block the inhibitory action of WEB 2086 on PAF-induced ATP release. The data are consistent with the notion that WEB 2086 acts as a PAF antagonist through its action at a specific PAF receptor, and is dissociated from, and independent of, interaction with the benzodiazepine receptor.

Adenosine Triphosphate↗

Activity of clavulanate-potentiated penicillins against methicillin-resistant Staphylococcus aureus.

It has been suggested that combinations of penicillins with clavulanate may be useful in treatment of infections by methicillin-resistant strains of Staphylococcus aureus (MRSA). To determine the potentiating effect of clavulanate on the antibacterial activity of penicillins, we studied MRSA in vitro by an agar-dilution method. A total of 124 clinical isolates of MRSA were tested for sensitivity to benzylpenicillin, amoxycillin, and ticarcillin alone and in combination with 1.25, 2.5, 5.0 and 10.0 mg/l of clavulanate. Most of the strains were not typable by the international reference set of bacteriophages of human staphylococci but showed typical properties of nosocomial strains. A reduction in the MIC90 of benzylpenicillin and amoxycillin to 25 mg/l was seen in the presence of 2.5 mg/l of clavulanate. The effect was less pronounced with ticarcillin. In spite of some increase in the susceptibility of MRSA to benzylpenicillin and amoxycillin produced by clavulanate, these combinations seem to be inappropriate in infections due to MRSA.

Clavulanic Acids↗

Characterization of the rec-1 gene of Haemophilus influenzae and behavior of the gene in Escherichia coli.

The rec-1 gene of Haemophilus influenzae was cloned into a shuttle vector that replicates in Escherichia coli as well as in H. influenzae. The plasmid, called pRec1, complemented the defects of a rec-1 mutant in repair of UV damage, transformation, and ability of prophage to be induced by UV radiation. Although UV resistance and recombination were caused by pRec1 in E. coli recA mutants, UV induction of lambda and UV mutagenesis were not. We suggest that the ability of the H. influenzae Rec-1 protein to cause cleavage of repressors but not the recombinase function differs from that of the E. coli RecA protein.

Bacterial Proteins↗

Anterior pituitary response to thyrotrophin releasing hormone in senile dementia (Alzheimer type) and elderly normals.

Sixteen patients with senile dementia of the Alzheimer type (SDAT) were compared with 11 age-matched normal subjects with respect to their responses of thyrotrophin (TSH) and prolactin (PRL) to thyrotrophin releasing hormone (TRH) challenge. Both groups showed a continuing rise in TSH response at 60 min, and no difference was found between the groups. A significantly exaggerated PRL response at 20 min was found in the SDAT group. There was no difference between sexes with respect to either the TSH or PRL response. These findings, albeit preliminary, may have implications for dopaminergic impairment in SDAT.

Aged↗

Plasmid containing a DNA ligase gene from Haemophilus influenzae.

A ligase gene from Haemophilus influenzae was cloned into the shuttle vector pDM2 . Although the plasmid did not affect X-ray sensitivity, it caused an increase in UV sensitivity of the wild-type but not excision-defective H. influenzae and a decrease in UV sensitivity of the rec-1 mutant.

Cloning, Molecular↗

Mechanism of acquisition of chromosomal markers by plasmids in Haemophilus influenzae.

The hybrid plasmid pNov1 readily acquired genetic information from the chromosome of wild-type, but not rec-2, cells. Most of the recombination had taken place 1 h after entrance of the plasmid into the cell, as judged by transformation of rec-2 by lysates made from wild-type cells exposed to pNov1. Measurement of physical transfer from radioactively labeled cellular DNA to plasmids recombining in wild-type cells failed, since there was little more radioactivity in plasmids from such cells than from labeled rec-2 recipients, in which no recombination took place. EcoRI digestion of pNov1 divided the DNA into a 1.7-kilobase-pair fragment containing the novobiocin resistance marker and a 13-kilobase-pair fragment containing all of the original vector and considerable portions homologous to the chromosome. Transformation by the large fragment alone resulted in a plasmid the size of the original pNov1. Our hypothesis to explain the data is that genetic transfer from chromosome to plasmid took place by a copy choice mechanism.

Base Sequence↗

A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis.

OBJECTIVE: To evaluate the effects of a combination of micronutrient antioxidants (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol in patients with limited cutaneous systemic sclerosis (SSc). METHODS: The study was designed as a placebo-controlled double-blind crossover study. A carryover effect was detected retrospectively for some of the prescribed antioxidants, and so the data were analysed as: (a) a between group comparison of the first 10 week treatment period; and (b) a within group comparison of the first and second 10-week periods in those who received placebo treatment first. Study end-points were plasma von Willebrand factor (vWF), thermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical parameters (fatty acid profiles, antioxidants and markers of free radical injury). RESULTS: Thirty-three patients were recruited. The median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the active-first group and 10 years (range 4 to 53 years) in the placebo-first group. In the 10-week study, there were no differences between the active and placebo groups in the change from baseline for vWF, for the parameters of the rewarming curve, or for patients' symptoms. Despite a rise in circulating antioxidant levels, there was no fall in markers of free radical mediated injury. In the 20-week cross-over study, patients did not experience any clinical benefit from active treatment compared to placebo. CONCLUSION: No clinical benefit could be demonstrated from active treatment. There are several possible explanations for this negative result, including the short duration of therapy. It is possible that antioxidant therapy, to be effective, needs to be given early in the SSc disease process, before the onset of irreversible tissue damage.

Adult↗

Leading the way.

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Education, Nursing, Baccalaureate↗