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K Gavin

Publications and source records attributed to K Gavin.

14 recordsLinked to original sources
PubMed1998

The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p.

The location of origins of DNA replication within the Saccharomyces cerevisiae genome is primarily determined by the origin recognition complex (ORC) interacting with specific DNA sequences. The analogous situation in vertebrate cells is far less clear, although ORC subunits have been identified in several vertebrate organisms including Xenopus laevis. Monoclonal antibodies were raised against Xenopus Orc1p and used for single-step immunoaffinity purification of the entire ORC from an egg extract. Six polypeptides ( approximately 110, 68, 64, 48, 43, and 27 kDa) copurified with Xenopus Orc1p. Protein sequencing also showed the 64-kDa protein to be the previously identified Xenopus Orc2p. Microsequencing of the 43- and 48-kDa proteins that copurified with Orc1p and Orc2p led to their identification as the Orc4p and Orc5p subunits, respectively. Peptide sequences from the 43-kDa protein also allowed the isolation of cDNAs encoding the Xenopus, mouse, and human ORC4 subunits. Human ORC5 was also cloned; its sequence displayed extensive homology to both Drosophila and yeast ORC5. Surprisingly, comparison of the amino acid sequences of Orc1p, Orc4p, and Orc5p suggests that they are structurally related to each other and to the replication initiation protein, Cdc6p. Finally, we present the sequence of the putative Xenopus and human Orc3p.

Amino Acid Sequence↗
PubMed1997

Further investigation of the alpha-adrenoceptor-mediated actions of chloroethylclonidine in rat aorta.

We have investigated the interaction between chloroethylclonidine and alpha-adrenoceptors in rat aorta. Chloroethylclonidine has two actions on rat aorta: reduction of the contraction to low concentrations of noradrenaline by alpha1-adrenoceptor antagonism and irreversible partial agonism in combination with high concentrations of noradrenaline. The former antagonist action was found to be more marked in vessels from immature rats (1 month). We have examined further the latter agonist actions in adult rats (3 month). In the absence of chloroethylclonidine, exposure to phenoxybenzamine (10 microM for 15 min) virtually abolished contractions to subsequent noradrenaline. However, when tissues were exposed to chloroethylclonidine (100 microM) for 30 min prior to exposure to phenoxybenzamine, a large contraction was produced by subsequent noradrenaline. Receptor protection with noradrenaline or the alpha2-adrenoceptor antagonists yohimbine or methoxy-idazoxan (all 10 microM), but not the alpha1-adrenoceptor antagonist prazosin (10 microM), significantly reduced the ability of chloroethylclonidine to prevent the actions of phenoxybenzamine against noradrenaline. In ligand binding studies, pre-exposure to chloroethylclonidine (100 microM) for 30 min significantly reduced the maximum binding of [3H]prazosin (Bmax) to alpha1B-adrenoceptors in rat spleen membranes to 21.4 +/- 10.2% (n = 5) and the maximum binding of [3H]yohimbine (Bmax) to alpha2D-adrenoceptors in rat submandibular gland membranes to 34.8 +/- 6.3% (n = 4), as compared to pre-exposure to vehicle. These results suggest that chloroethylclonidine interacts irreversibly with alpha2-adrenoceptors in rat aorta to make contractions to subsequent noradrenaline resistant to alpha-adrenoceptor blockade. Chloroethylclonidine appears to act as a silent irreversible agonist (i.e., an agonist which persists following multiple washout but only produces effects in combination with a classical agonist).

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Investigation of the subtype of alpha 2-adrenoceptor mediating pressor responses in the pithed rat.

We have investigated the subtype of alpha 2-adrenoceptor mediating postjunctional pressor responses in the pithed rat in comparison with alpha 2-adrenoceptor ligand binding sites. In pithed rats, postjunctional alpha 2-adrenoceptors were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the pressor potency of the alpha 2-adrenoceptor agonist xylazine. Antagonist potency at postjunctional alpha 2-adrenoceptors in the pithed rat was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of rat kidney (alpha 2B), Sf9 cells expressing human recombinant receptors (alpha 2C) and rat submandibular gland (alpha 2D) labelled with [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor mediating pressor responses in the pithed rat was better for the alpha 2D-adrenoceptor ligand binding site of rat submandibular gland (r = 0.95, n = 9, P < 0.0001) and the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.90, n = 9, P < 0.001) than with the human recombinant alpha 2C-adrenoceptor ligand binding site (r = 0.81, n = 9, P < 0.01). When the pressor potencies of three additional antagonists were included in the correlations for alpha 2B- and alpha 2D-sites only, the correlation with alpha 2D-adrenoceptor ligand binding site of rat submandibular gland (r = 0.91, n = 12, P < 0.0001) was much better than with the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.77, n = 12, P < 0.01). It is concluded that the functional postjunctional alpha 2-adrenoceptors mediating pressor responses in the pithed rat most closely resemble the alpha 2D-adrenoceptors subtype.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Investigation of the subtype of alpha 2-adrenoceptor mediating prejunctional inhibition of cardioacceleration in the pithed rat heart.

1. We have investigated the subtype of alpha 2-adrenoceptor mediating prejunctional inhibition of cardioacceleration in the pithed rat heart in comparison with alpha 2-adrenoceptor ligand binding sites. 2. In pithed rats, prejunctional alpha 2-adrenoceptors were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the inhibitory potency of the alpha 2-adrenoceptor agonist, xylazine, against the tachycardia to a single electrical stimulus given via the pithing rod. 3. Antagonist potency at prejunctional alpha 2-adrenoceptors in pithed rat heart was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of rat kidney and submandibular gland labelled with [3H]-yohimbine. 4. The correlation with the prejunctional alpha 2-adrenoceptor in pithed rat heart was best for the alpha 2D-adrenoceptor ligand binding site of rat submandibular gland (r = 0.98, n = 10, P < 0.0001), as compared to correlations with the alpha 2A-adrenoceptor ligand binding site of human platelet (r = 0.90, n = 9, P < 0.001), the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.82, n = 10, P < 0.01) and with published results for the alpha 2C-adrenoceptor ligand binding site (r = 0.48, n = 6, NS). 5. It is concluded that the functional prejunctional alpha 2-adrenoceptor of pithed rat heart closely resembles the alpha 2D-adrenoceptor ligand binding site of rat submandibular gland.

Adrenergic alpha-Agonists↗
PubMed1994

Prejunctional actions of N-ethyl-maleimide and phenoxybenzamine in rat vas deferens.

In studies of electrically evoked isometric contractions of rat vas deferens, N-ethyl-maleimide (30 microM) pretreatment significantly reduced the prejunctional inhibitory potencies of xylazine and 5-hydroxytryptamine but failed to affect the potency of the alpha 1-adrenoceptor agonist amidephrine. Phenoxybenzamine (1 microM) or N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (10 microM) produced significant shifts in the potency of xylazine and significantly reduced the maximum inhibition, but the combination of phenoxybenzamine or EEDQ and N-ethyl-maleimide (30 microM) produced no further alteration in the effects of xylazine. In displacement studies, N-ethyl-maleimide displaced the binding of [3H]MK 912 ((2S,12bS)1',3'-dimethylspiro- (1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo[2,3-a]quinazoline)- 2,4'- pyrimidin-2'one) to rat renal cortex membranes with a Ki of 466 +/- 133 microM (n = 5), and so does not bind to alpha 2-adrenoceptors in the concentration range in which it affects prejunctional receptor mediated responses. This may suggest that N-ethyl-maleimide has actions other than inactivation of G-proteins or that the irreversible alpha 2-adrenoceptor antagonists phenoxybenzamine and EEDQ inactivate G-proteins sensitive to N-ethyl-maleimide in concentrations at which they bind to alpha 2-adrenoceptors.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1994

Iron status and restless legs syndrome in the elderly.

The relationship between iron status and the restless legs syndrome (RLS) was examined in 18 elderly patients with RLS and in 18 matched control subjects. A rating scale with a maximum score of 10 was used to assess the severity of RLS symptoms. Serum ferritin levels were reduced in the RLS patients compared with control subjects (median 33 micrograms/l vs. 59 micrograms/l, p < 0.01, Wilcoxon signed rank test); serum iron, vitamin B12 and folate levels and haemoglobin levels did not differ between the two groups. Serum ferritin levels were inversely correlated with the severity of RLS symptoms (Spearman's rho -0.53, p < 0.05). Fifteen patients with RLS were treated with ferrous sulphate for 2 months. RLS severity score improved by a median value of 4 points in six patients with an initial ferritin < or = 18 micrograms/l, by 3 points in four patients with ferritin > 18 micrograms/l, < or = 45 micrograms/l and by 1 point in five patients with ferritin > 45 micrograms/l, < 100 micrograms/l. Iron deficiency, with or without anaemia, is an important contributor to the development of RLS in elderly patients, and iron supplements can produce a significant reduction in symptoms.

Aged↗
PubMed1989

Maternity care as an essential public service: a proposed role for state government.

This paper describes some of the current problems in assuring basic maternity care as an essential community service in the rural state of Vermont. Solving the cost of care problem will still leave large gaps in the ability of our maternity care system to provide continuous and high-quality maternity care for all pregnant women. The problem of access is not only a temporary aberration of the current medical care system, but a central and identifying characteristic of it. Maternity care services are as essential as other community services such as utilities and education. The authors propose that the state should assure the availability and quality of maternity care services as it would other essential services. The development of a statewide care system using a nurse midwife model of services is suggested.

Female↗
PubMed1988

Haemodynamic effects of intravenous human calcitonin-gene-related peptide in man.

1. The effects of intravenous bolus doses of human calcitonin-gene-related peptide (hCGRP) were studied in ten healthy male volunteers. 2.5, 10 and 25 micrograms of hCGRP and placebo were administered to each subject in a randomized double-blind study. 2. hCGRP had no effect on systolic or diastolic blood pressure in the supine or standing position. 3. hCGRP increased supine and standing heart rate. Both the extent and duration of the tachycardia were dose related. 4. Plasma noradrenaline levels were transiently increased after 10 and 25 micrograms of hCGRP. 5. All subjects displayed marked facial flushing after the two higher doses of hCGRP. 6. We conclude that systemic administration of hCGRP produces tachycardia and stimulation of the sympathetic nervous system in the absence of any change in blood pressure.

Adult↗
PubMed1986

Prospective survey of use of therapeutic drugs, alcohol, and cigarettes during pregnancy.

Use of drugs during pregnancy was recorded prospectively in 2765 women attending the antenatal clinics of a general hospital from October 1982 to March 1984. Of these women, 2588 (93.6%) avoided exposure to drugs during the first trimester, 1802 (65.2%) took no drugs at any stage, 963 (34.8%) took a total of 154 different drugs from 35 groups of drugs, and 243 (8.8%) took a self administered drug. The most commonly used drugs were non-narcotic analgesics, usually self administered, and antibacterials. The last survey of use of drugs in pregnancy in the United Kingdom 20 years ago showed fewer women avoiding drugs throughout pregnancy (195 of 911 (21.4%), p less than 0.001) and in taking a self administered drug (586 (64.4%), p less than 0.001) than at present. Most women nowadays abstain totally from alcohol (1786 (64.6%) v 109 (12.0%) previously, p less than 0.001), but while more women are non-smokers compared with previously (1811 (65.5%) v 392 (43%), p less than 0.001) the trend has been far less dramatic than that for use of alcohol.

Alcohol Drinking↗