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Biomedical subjects

P Cook

Publications and source records attributed to P Cook.

At least 109 records · Page 6Linked to original sources
PubMed1986

Rat cerebral cortical estrogen receptors: male-female, right-left.

We determined the concentration of cytosol estrogen receptors in the postnatal, developing right and left cerebral cortices of Long-Evans male or female rats 2 to 3, 7 to 8, 14 to 15, and 25 to 26 days of age. Under anesthesia, the rats were gonadectomized and 24 h later they were killed by decapitation, and the dorsal right and left cerebral cortices were separated from the underlying white matter and placed on ice. Sephadex LH-20 gel filtration chromatography was used to dissociate the majority of alpha-fetoprotein-bound [3H]estradiol while leaving the receptor [3H]estradiol complex intact. The correction for the residual nonreceptor binding, including alpha-fetoprotein, was made using parallel incubation containing unlabeled diethylstilbesterol. The amount of residual nonreceptor binding was subtracted from [3H]estradiol-bound protein to calculate high-affinity estradiol binding receptors. The results showed that in both sexes, estrogen receptor concentration was highest at postnatal days 2 to 3 in both the right and the left cerebral cortex and then decreased until 25 days of age. In the female, the right cerebral cortex, at postnatal day 2 to 3, had a higher estrogen receptor concentration than the left cortex (P less than 0.02). In the male, the left cortex had a higher cytoplasmic estrogen receptor concentration (P less than 0.02) than the right. Considering the reported growth-inhibiting effects of estrogen on the cerebral cortex, the results indicated that one determinant of cerebral dominance in both sexes may be the differential exposure to estrogen, in the case of the male testosterone converted to estrogen, during a critical period of development.

Animals↗
PubMed1986

Measles virus nucleic acid sequences in human brain.

We constructed a measles virus genomic recombinant DNA library, and used clones coding for portions of the viral P, M and H proteins to probe for measles virus nucleic acid sequences in post-mortem multiple sclerosis, SSPE and control brains. By dot blot hybridization, the probes detected measles virus nucleic acid sequences in as little as 3 nanograms of total RNA extracted from measles virus-infected cells and also in highly diluted RNA extracted from SSPE brain, but did not detect measles virus sequences in RNA extracted from 11 multiple sclerosis or 8 control brains, even at a 1 000-fold higher concentration of RNA. By in situ hybridization, these probes detected measles virus nucleic acid sequences in virtually every cell and the surrounding neuropile of SSPE brain, but again did not detect such sequences in multiple sclerosis or control brains. Our findings using these highly specific probes confirm that measles virus is found in SSPE brains and indicate that measles virus genome is unlikely to be present in multiple sclerosis or normal brains.

Base Sequence↗
PubMed1986

Transcriptional map of the measles virus genome.

We have constructed a recombinant DNA library of the measles virus genome and identified gene-specific clones containing sequences coding for portions of each of the six viral structural proteins, as well as clones coding for intercistronic sequences. By Northern blotting, we could order the clones according to the pattern of individual gene-specific and readthrough mRNAs. Clones corresponding to the N, P/C and M genes were identified by correlation of the mRNAs with their in vitro translation products; clones corresponding to the H, F and L genes were identified by indirect evidence. The results indicated that the gene order in measles virus is that of a typical paramyxovirus (3'-N,P/C,M,F,H,L-5'), but that the M and F transcripts each contain 1.5 times the coding capacity needed for synthesis of these proteins in vivo.

Cloning, Molecular↗
PubMed1986

Na+-K+ pump stoichiometry and basolateral membrane permeability of frog corneal epithelium.

The Na+-K+ pump flux ratio and the Na+ and K+ permeability of the basolateral membrane of the isolated frog corneal epithelium were studied with the aid of microelectrodes by analyzing the effects of ouabain, Ba2+, and amphotericin B. The experiments were done in Cl(-)-free solutions, a situation that approximates that of static head. Ouabain produced a quick depolarization of the potential difference across the basolateral membrane (PDb) from -72 to -62 mV without a change in resistance. Ba2+ (3 mM) rapidly lowered PDb from -74 to -57 mV and decreased the apical-to-basolateral resistance ratio. The effects of ouabain and Ba2+ were additive. The Na+-K+ flux ratio at the pump was calculated to be 1.78, substantially less than when the tissue is in a level flow condition, suggesting a variable stoichiometry. The K+ and Na+ resistances of the basolateral membrane were 15.7 and 5.5 k omega X cm2, respectively, allowing K+ and Na+ currents that approximately matched those produced by the Na+-K+ pump. The resistance of the basolateral membrane (4.0 k omega X cm2) was double that reported in Cl(-)-rich solutions, suggesting that Cl- contributes to the conductance of this membrane.

Amphotericin B↗
PubMed1985

Danazol for lupus thrombocytopenia.

Danazol therapy was used in the treatment of three consecutive patients with lupus-associated thrombocytopenia refractory to high-dose prednisone therapy (two patients) or in whom high-dose prednisone therapy was considered contraindicated (one patient). Treatment was associated in each case with an increase in platelet count but was complicated in two of three patients by the development of a diffuse maculopapular rash that promptly resolved following discontinuation of danazol therapy. Retreatment of one patient with danazol was associated with immediate recurrence of the rash. We suggest that danazol therapy deserves further evaluation in the treatment of lupus-associated thrombocytopenia, but advise that patients be carefully monitored for rash.

Adult↗
PubMed1984

Comparison of central gastric antisecretory effects of desmethylimipramine, doxepin and pirenzepine in rats.

Certain tricyclic drugs, some of which are primarily used clinically as antidepressants, have been shown to act as gastric antisecretory agents. The anatomical site(s) and mechanism(s) of action of these agents is, however, in most cases unclear. In this study, we found that desmethylimipramine (DMI) was approximately 28 times more potent in inhibiting gastric acid secretion when administered intracerebroventricularly (i.c.) than when administered intravenously (i.v.) in pylorus-ligated rats, which is indicative of a site of action in the central nervous system. Qualitatively similar results were obtained with pirenzepine where the i.c./i.v. potency ratio was 8. Doxepin also preferentially inhibited acid secretion when given i.c. at low but not at high doses. Atropine and chlorpromazine were equipotent antisecretory agents by both routes of administration. Doxepin and DMI but not pirenzepine were effective inhibitors of brain stem norepinephrine uptake in vitro thus making this an unlikely common mechanism to explain the central actions of these compounds.

Animals↗
PubMed1983

A reinterpretation of schedule-induced behaviors based on a systematic analysis of behavior.

Confusion exists regarding the criteria to be used in determining whether or not particular behaviors are schedule-induced. Four critical characteristics of schedule-induced behaviors are suggested and a comparison made of the complete range of behaviors exhibited by body weight-reduced rats drinking in response to one of three stimuli. These were (1) a fixed-time food reinforcement schedule, (2) a meal of dry food, and (3) 24 hour water deprivation. Drinking, locomotion, rearing and oral and perioral behaviors occurred in accordance with the defining characteristics of schedule-induced behaviors. Rats in the fixed-time reinforcement condition also deposited significantly greater numbers of fecal boli. Sniffing and food bowl related behaviors occurred as terminal responses for this group. It is concluded that animals which receive reinforcers intermittently maintain high levels of arousal for extended periods, and that the presence of the schedule may mimic conditions experienced by wild rats in non-laboratory settings. In such conditions ambulatory behaviors may be particularly adaptive. In contrast, reinforcing sensory feedback and a stress reducing role may be particularly important in the mediation of oral behaviors (such as drinking) which occur during intermittent reinforcement.

Animals↗
PubMed1983

Studies on MK-208 (YM-11170) a new, slowly dissociable H2-receptor antagonist.

MK-208 [3-(((2-(aminoiminomethyl)amino)-4-thiazolyl)-methyl)thio)-N'-(a minosulfonyl) propanimidamide], also known as YM-11170, is a highly potent histamine H2-receptor antagonist in guinea-pig atria, acting via a unique binding mechanism. Unlike ranitidine, the onset of action of this compound was slow and its inhibitory action was difficult to remove from the tissues by repeated washing. Preincubation of atria with ranitidine, however, protected the H2-receptor from these prolonged inhibitory effects of MK-208. The H2-receptor antagonism produced by MK-208 was not surmountable by increasing concentrations of dimaprit. The compound did not alter the response of this tissue to isoproterenol or affect basal atrial rate under conditions where maximal H2-receptor blockade was achieved. In dogs, MK-208 was effective in inhibiting gastric acid secretion evoked by histamine, gastrin and 2-deoxy-D-glucose. Orally, it was approximately 7 times as potent as ranitidine against histamine-induced secretion, and its duration of action was substantially longer. The compound was also highly effective in inhibiting basal acid secretion in chronic gastric fistula rats.

Animals↗
PubMed1982

Near-drowning complicated by brain abscess due to Petriellidium boydii.

Extracutaneous infection from Petriellidium boydii is an unusual occurrence despite the ubiquity of the organism in nature. Central nervous system infection by this organism is extremely rare, only seven previous reports having been found. The rarity of this manifestation prompted the report of a brain abscess occurring in a previously healthy youth after a near-drowning. The source of the infection was likely to have been the river water at the accident site, from which P boydii was isolated. Although previous in vitro susceptibility data and failure of amphotericin B therapy in a similar infection suggested miconazole treatment might be beneficial, the organism causing the brain abscess was resistant to miconazole and amphotericin B. This report emphasizes the urgent need for safer and more predictably effective alternatives to currently available antifungal agents.

Adult↗