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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1994

Estimating alcohol involvement in trauma patients: search for a surrogate.

This study explores the potential for the development of a surrogate for alcohol-involved traumatic injury. It presents a bivariate probit analysis that simultaneously models likelihoods of patients being tested for blood alcohol content (BAC) and having positive BACs given testing using 17,356 adult trauma cases selected from the California Regional Trauma Registry. It concludes that patient and injury characteristics predict both testing and BAC, and that a weighting scheme may be profitably used to determine changes in levels of alcohol-involved trauma in populations over time in the absence of empirical measurement of BAC.

Accidents, Traffic↗
PubMed1994

Pharmacological profile of UK-74,505, a novel and selective PAF antagonist with potent and prolonged oral activity.

UK-74505, a novel 1,4-dihydropyridine PAF antagonist, exhibited highly selective, time-dependent inhibition of PAF-induced aggregation of rabbit washed platelets (IC50 = 26.3 +/- 0.88 and 1.12 +/- 0.04 nM after 0.25 and 60 min preincubation, respectively), which became irreversible within 15 min, whereas inhibition by WEB-2086 was both independent of preincubation time (IC50 = 145.7 +/- 24.7 nM) and competitive (KI = 27.5 +/- 7.7 nM; Schild slope = 0.98 +/- 0.04). The selective inhibition of specific [3H]PAF binding by UK-74,505 exhibited a slower onset, the IC50 obtained without preincubation (14.7 +/- 2.6 nM) decreasing 2-fold at 45 min. UK-74,505 was 450-fold weaker as an antagonist of [3H]nitrendipine binding to bovine brain membranes and KCl-induced contraction of rat aorta. UK-74,505 was 10-30-fold more potent than WEB-2086 in vivo as an inhibitor of PAF-induced hypotension in rats (ED50 = 35 +/- 5.8 micrograms/kg, i.v.), cutaneous vascular permeability in guinea pigs (ED50 = 0.37 +/- 0.08 mg/kg, p.o.) and lethality in mice, with oral ED50 values of 0.26 +/- 0.03 and 1.33 +/- 0.19 mg/kg at 2 and 8 h, respectively. These data demonstrate that UK-74,505 is a potent, selective, long-acting irreversible PAF antagonist.

Administration, Oral↗
PubMed1994

Pulse oral calcitriol to treat hyperparathyroidism in 43 CAPD patients.

To further study the effect of pulse oral calcitriol on the level of intact parathyroid hormone (iPTH), we have studied the response of 43 patients treated with 5.0 mcg calcitriol bi-weekly for one year. Mean iPTH decreased from 603 pg/mL +/- 262 (+/- SD) to 222 pg/mL +/- 185 (p < 0.001). Thirty-six patients responded showing a decrease in iPTH from baseline; 7 patients showed no decrease in iPTH. Transient hypercalcemia (calcium > 10.5 mg/dL) was noted in 6 patients of the responder group which corrected with temporary discontinuation of pulse therapy. Pulse oral calcitriol is an effective therapy to decrease elevated iPTH levels in continuous ambulatory peritoneal dialysis (CAPD) patients with hyperparathyroidism.

Administration, Oral↗
PubMed1993

p53 antigen in cervical condylomata, intraepithelial neoplasia, and carcinoma: relationship to HPV infection and integration.

It has been proposed that wild-type p53 cell-regulating functions are annulled in human cervical carcinomas, either by mutations in the human papillomavirus (HPV)-negative cases or as a consequence of their complexing with HPV E6. The aim of this study was to test this hypothesis on 39 fresh cervical biopsies by p53 immunocytochemistry (ICC) with antibody PAb 240 and with NISH (non-isotopic in situ hybridization) and PCR (polymerase chain reaction) for HPV detection. p53 protein was present in the basal layer of pure wart virus infection; the basal to middle third of CIN (cervical intraepithelial neoplasia); in 19/22 (86 per cent) HPV-positive cervical carcinomas, ten of which contained integrated HPV; and in 4/8 (50 per cent) HPV-negative cervical carcinomas. Dual detection of p53 antigen and HPV 16 DNA in the same sections demonstrated either p53 protein or integrated HPV 16 alone in the majority of cells. Co-localization of both signals was only evident in isolated cells. These data suggest that PAb 240 immunoreactivity is not mutant-specific. They are, however, consistent with the conformation hypothesis which proposes that wild-type p53 changes from a suppressor (PAb 240-negative) to a promoter (PAb 240-positive) form during cell growth response. Hence, according to this hypothesis, p53 protein expression may represent either the wild-type promoter form or mutant p53 protein, both of which share the same conformation. This may explain co-localization of p53 and HPV in some tumours. However, the absence of p53 protein in 50 per cent HPV-negative squamous cell carcinomas suggests that not all HPV-negative tumours accumulate p53 protein.

Condylomata Acuminata↗
PubMed1993

Papillomavirus screening in cervical cell samples using dual-label dot-blot analysis.

The presence of human papillomavirus (HPV) in cervical cells is closely related to the development of cervical carcinoma. Detection of virus may be by Southern blot, dot blot or the highly sensitive polymerase chain reaction. Whatever method is employed, there are problems of false negatives due to poor clinical samples in which the DNA may be degraded or is absent altogether. Here we describe a new method of dual labelling for dot blots using a 32P-labelled probe for HPV and a 35S-labelled probe for human actin genes. The samples were counted on a Beta-plate flat-bed scintillation counter and the data analysed to separate the activities of the two isotopes. The counts from the actin probe show whether human DNA is present or not and false negatives from this cause may thereby be eliminated. The counts due to HPV when compared with those for actin give a quantitative measure of HPV abundance for the particular sample and this may have clinical relevance.

Actins↗
PubMed1993

Extraaortic intimomedial mucoid degeneration: a clinicopathological study.

Six black patients with extraaortic intimomedial mucoid degeneration of the major arterial branches of the aorta are reported. Five patients presented with aneurysmal dilatation of the arterial wall as a result of the intimomedial mucoid degeneration, and the sixth patient had superimposed occlusive thrombosis. The ages ranged from twenty to fifty years. Five patients were female. Two were hypertensive. All patients in this study underwent reconstructive vascular surgery. The clinical and histopathologic findings are discussed.

Adult↗
PubMed1993

Hyperparathyroidism in CAPD patients: therapy with pulse oral calcitriol.

Hyperparathyroidism remains a cause of significant morbidity in dialysis patients. We studied pulse oral calcitriol, 5.0 micrograms biweekly to control hyperparathyroidism in 12 continuous ambulatory peritoneal dialysis (CAPD) patients. Parathyroid hormone (PTH) levels fell, while calcium and phosphorus levels remained in good control. Pulse oral calcitriol is an effective therapy for hyperparathyroidism in CAPD patients.

Administration, Oral↗
PubMed1992

1,4-Dihydropyridines as antagonists of platelet activating factor. 1. Synthesis and structure-activity relationships of 2-(4-heterocyclyl)phenyl derivatives.

A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or 3-aminocrotonate esters. Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit the PAF-induced aggregation of rabbit washed platelets, and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF. The nature of the substituent at the dihydropyridine 2-position was found to be important for both in vitro and in vivo activity, whereas there was greater flexibility for structural variation at the 4- and 5-positions. The most potent compound was 4-(2-chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl-2-[4-(2- methylimidazo[4,5-c]pyrid-1-yl)phenyl]-5-[N-(2- pyridyl)carbamoyl]pyridine (17, UK-74,505), IC50 = 4.3 nM, ED50 = 0.26 mg/kg po, which was found to be approximately 33 times more potent in vitro (rabbit platelet aggregation) and about 8 times more potent in vivo (murine lethality) than WEB2086. Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for greater than 24 h following a single oral dose of 75 micrograms/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the [3H]nitrendipine binding site. As a result of its high oral potency, selectivity, and duration of action, UK-74,505 has been selected for clinical evaluation.

Animals↗
PubMed1992

Transient outwardly rectifying potassium channel in the rabbit corneal endothelium.

Ionic currents from freshly dissociated rabbit corneal endothelial cells were examined using patch-clamp technology and a perforated patch technique. Whole-cell current recordings revealed a transient outward K(+)-selective current that was blockable in a dose-dependent manner by 4-aminopyridine (4-AP) and quinidine. This current is similar to the 'A'-type current present in many excitable cells and is the first reported instance of such a current in any epithelial cell type. In addition to the transient current, an outwardly rectifying nonselective cation current was also observed. This current is also blocked by quinidine. To examine the possible role of these currents in the stromal volume regulatory function of the endothelium, corneas were perfused under a specular microscope with a glutathione-bicarbonate Ringer's solution (GBR) or GBR plus either 1 mM quinidine or 10 mM 4-AP. For quinidine perfusions, control corneas swelled at a rate of 6 microns/hr, while quinidine-perfused corneas swelled at a rate of 48 microns/hr. For 4-AP perfusions, control corneas swelled at a rate of -2 microns/hr, while 4-AP perfused corneas swelled at a rate of 24 microns/hr. One possible mechanism of the stromal swelling induced by these K+ channel blockers may be the result of loss of the K+ recycling pathway necessary for proper Na+/K+ ATPase function.

Animals↗
PubMed1992

Potassium currents from isolated frog lens epithelial cells.

Using the perforated patch version of whole-cell recording, we have measured currents from isolated frog lens epithelial cells. Three types of currents were seen. A time-independent outwardly rectifying potassium current was identified that sets the resting voltage. This potassium current differs significantly from any of the potassium currents recorded with the whole-cell technique in mammalian lens epithelial cells. In addition to the potassium current, the two other currents present were both outwardly rectifying: one was time-independent while the other showed distinct activation.

Animals↗