Biomedical subjects
Publications and source records attributed to K Ryan.
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Experimental work suggests that dermatan sulphate has potential as an antithrombotic agent: it can inhibit venous thrombi yet has less effect upon bleeding than heparin. While heparin functions as an anticoagulant primarily by its ability to accelerate the action of the plasma protein inhibitor antithrombin III, dermatan sulphate acts selectively through a structurally related inhibitor, heparin co-factor II, to inhibit thrombin. We have done a series of dose-finding studies of the use of dermatan sulphate as an anticoagulant/antithrombotic agent in patients on maintenance haemodialysis. Dermatan sulphate proved to be an effective anticoagulant in this setting.
In this double-blind study, we have allocated randomly 40 ASA I-III patients to one of four groups. After a standard anaesthetic induction, patients received vecuronium 0.08 mg kg-1 or 0.10 mg kg-1, or atracurium 0.4 mg kg-1 or 0.5 mg kg-1. Using an electromyogram (Datex Relaxograph) the train-of-four (TOF) response was measured during onset of and recovery from neuromuscular block. A greater degree of fade of TOF was observed with atracurium during onset of neuromuscular block than with equivalent doses of vecuronium. During recovery of neuromuscular transmission, vecuronium was associated with more fade than atracurium. The differences in the TOF profiles of these two drugs may be important when judging the adequacy of antagonism of neuromuscular block using the TOF response.
A multivariate approach was used to determine the pattern of predictors associated with engaging in dating violence. Predictors were selected whose relationship to dating violence has been established by earlier research: attitudes toward violence, sex-role attitudes, romantic jealousy, general levels of interpersonal aggression, verbal aggression, and verbal and physical aggression received from one's partner. Participants included 305 introductory psychology student volunteers (227 females and 78 males) who completed a set of scales related to dating relationships. Expecting different patterns of predictors to emerge for men and women, we performed separate multiple regression analyses for each. Of the set of predictors employed, receipt of physical violence from one's partner emerged as the largest predictor of expressed violence for both men and women. In addition, higher scores on attitudes toward violence and verbal aggression, and less traditional sex-role attitudes emerged as significant predictors of expressed violence for men. For women, less accepting attitudes toward violence, more traditional sex-role attitudes, feelings of romantic jealousy, higher general levels of interpersonal aggression, and verbal aggression were predictive of expressed violence. The implications of our findings for future research are discussed.
The circadian clock in the unicellular alga Gonyaulax polyedra is accelerated by a substance in extracts from the cells themselves. The extracts have been fractionated using the circadian rhythm of bioluminescence as bioassay. The active substance, termed gonyauline, has been isolated and characterized as a novel low molecular weight cyclopropanecarboxylic acid (S-methyl-cis-2-(methylthio) cyclopropanecarboxylic acid). Synthetic gonyauline has a similar shortening effect on the period of the circadian clock.
The synthesis and in vitro and in vivo characteristics of 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1, CP-93,129) are described. This rotationally restricted phenolic analogue of RU-24,969 is a potent (15 nM) and selective (200x vs the 5-HT1A receptor, 150x vs the 5HT1D receptor) functional agonist for the 5-HT1B receptor. Direct infusion of 1 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regulating feeding behavior in rodents. 3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (1) has also been shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor. The source of the selectivity of 1 appears to lie in the ability of a pyrrolo[3,2-b]pyrid-5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole.
One hundred two patients undergoing abdominal aortic reconstructive surgery were prospectively, randomly allocated to two groups, one of which was monitored with a central venous catheter and the other with a pulmonary artery catheter. Patients with uncompensated cardiopulmonary or renal disease were excluded from the study. General anesthesia was administered for the surgical procedure, and the patients were followed through hospital discharge. No statistically significant differences occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequelae), mortality rate, duration of intensive care, postoperative hospital stay, or cost of hospitalization. The one statistically significant difference between groups was the professional fee charged for anesthetic care, which was higher for patients with pulmonary artery catheters than for those with central venous catheters. In conclusion, we prospectively gathered data from most patients presented for abdominal aortic reconstructive surgery. Our data seem to indicate that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic reconstructive surgery, and that for many patients pulmonary artery catheters are not necessary to give appropriate, adequate care. Because of the size of the sample, however, declarations of epidemiologic significance would be unfounded. Therefore large-scale, multicenter studies addressing such outcomes remain necessary.
The intergenic spacer of the mouse ribosomal genes contains repetitive 140-base-pair (bp) elements which we show are enhancers for RNA polymerase I transcription analogous to the 60/81-bp repetitive enhancers (enhancers containing a 60-bp and an 81-bp element) previously characterized from Xenopus laevis. In rodent cell transfection assays, the 140-bp repeats stimulated an adjacent mouse polymerase I promoter when located in cis and competed with it when located in trans. Remarkably, in frog oocyte injection assays, the 140-bp repeats enhanced a frog ribosomal gene promoter as strongly as did the homologous 60/81-bp repeats. Mouse 140-bp repeats also competed against frog promoters in trans. The 140-bp repeats bound UBF, a DNA-binding protein we have purified from mouse extracts that is the mouse homolog of polymerase I transcription factors previously isolated from frogs and humans. The DNA-binding properties of UBF are conserved from the mouse to the frog. The same regulatory elements (terminators, gene and spacer promoters, and enhancers) have now been identified in both a mammalian and an amphibian spacer, and they are found in the same relative order. Therefore, this arrangement of elements probably is widespread in nature and has important functional consequences.
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We have examined the mechanism by which transcriptional initiation at the mouse rDNA promoter is augmented by the RNA polymerase I terminator element that resides just upstream of it. Using templates in which terminator elements are instead positioned at the opposite side of the plasmid rather than proximal to the promoter, or conditions where transcription is terminated elsewhere in the plasmid by UV-induced lesions, we show that the terminator's stimulatory effect is not position dependent. Mouse terminator elements therefore do not stimulate via the previously postulated 'read-through enhancement' model in which terminated polymerases are handed off to an adjacent promoter in a concerted reaction. The position independence and orientation dependence of the terminator also makes it unlikely that the terminator functions as a promoter element or as an enhancer. Instead, terminators serve to augment initiation by preventing polymerases from reading completely around the plasmid and through the promoter from upstream, an event which we show interferes with subsequent rounds of initiation. Notably, this transcriptional interference arises because polymerase passage across a promoter disrupts the otherwise stable transcription complex, specifically releasing the bound transcription factor D. These liberated D molecules can then bind to other templates and activate their expression. The rDNA transcriptional interference is not due to a steric impediment to the binding of new polymerase molecules, and it does not similarly liberate the initiation-competent polymerase (factor C). These studies have also convincingly demonstrated that multiple rounds of transcription are obtained from rDNA template molecules in vitro.
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To further define the sarcolemmal effects of ethanol and acetaldehyde, their effects on Na pump function were studied in synchronously contracting monolayers of neonatal rat myocardial cells. The effects of ethanol (10 mg/dl to 1000 mg/dl: 2 X 10(-3) M-0.2 M) and acetaldehyde (10(-6) M to 10(-4) M) on total 42K influx, ouabain-sensitive 42K influx, Na pump density (from specific 3H-ouabain binding) and pump turnover rates were measured. Applied acutely ethanol had no effect on 42K influx but after 30 min of treatment 42K influx was decreased by 13%, 23% and 48% in 100 mg/dl, 300 mg/dl and 1000 mg/dl ethanol respectively. This primarily reflected a decrease in mean ouabain-sensitive K+ influx from a control of 12.54 to 9.90, 8.95 and 6.68 (p-mol/cm2/s) in 100, 300 and 1000 mg/dl (2 X 10(-2) M, 6 X 10(-2) M) ethanol. Acetaldehyde in the concentrations tested had no effect on K+ influx. Ethanol treatment produced a decrease in Na pump density, maximum within 30 min and dose-dependent, at concentrations of 100 mg/dl (22%), 300 mg/dl (37%) and 1000 mg/dl (55%). Acetaldehyde had no effect on Na pump density. In the presence of ethanol (300 mg/dl and 1000 mg/dl) intracellular Na+ increased significantly and the Na+ efflux declined in parallel with the K+ influx. From the ouabain-sensitive K+ and Na+ fluxes and the Na pump density individual pump turnover rates were calculated at 62.5/s in control cells and 66/s and 84/s in cells treated with 300 mg/dl (6 X 10(-2) M) and 1000 mg/dl (0.2 M) respectively. We conclude that ethanol, but not acetaldehyde has a depressant effect on sarcolemmal Na pump function. The results suggest this is due primarily to a decrease in the number of sarcolemmal Na pump sites.
The effects of acute low-dose maternal alcohol exposures were investigated in C57B1/10J mice offspring. Pregnant mice were randomly placed into three alcohol groups and were injected twice intraperitoneally on gestation day 7, 0 hours and gestation day 7, 4 hours, with one of the following dosages of 25% alcohol: Group 2 received 1.25 Gm/Kg body weight; Group 3 2.50 Gm/Kg body wt.; Group 4 3.75 Gm/Kg body wt. A control group (Group 1) received .015 ml/gm body wt. of physiological saline. At birth all offspring were weighed and observed for any gross physical abnormalities. On day 25, all female offspring and mothers were sacrificed. The male pups were maintained until day 61. On day 61, the male pups were placed in individual metabolic cages where food and water consumption, and urine excretion were monitored for 24 hrs. On day 62, these animals were sacrificed. Blood was drawn for serum calcium (Ca) and phosphorous (P) determination. Brains, kidneys, testes, hearts and thymus glands were removed and weighed. Ca and P levels were also measured in the urine. No significant difference in litter size and fetal weight was obtained among the four groups. There was no evidence of physical abnormalities in the alcohol groups compared to the control one. The 62 day old pups from all three alcohol groups had significantly lower serum and urine levels of Ca and P than the control group, with the lowest values recorded for Group 4. There was no significant difference in final body weight but small organ size differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
There is increasing interest in the role of social support in determining risk for child abuse and neglect. The present study assessed the relationship between maternal social support and two areas: stress in the mother-child relationship: and level of stimulation provided in the home. Maternal social support was assessed prenatally and at a two-year follow-up, while the latter variables were compiled at the two-year follow-up. The data were obtained from 38 urban, low SES (80% on public assistance) mothers and their 2-year-old children. Maternal social support correlated positively with level of stimulation and negatively with level of mother-child stress, and was the best predictor of both, relative to any SES, mother or child variables. In addition, high stress, low support mothers provided significantly less stimulation to their children. The theoretical implications for social support as a mediator variable as well as its implications for early identification and prevention efforts in abuse and neglect are discussed.
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In vitro time course studies of progesterone and protein synthesis by hamster preovulatory follicles (harvested prior to the proestrous gonadotropin surge) were done. LH appears to stimulate progesterone synthesis in 2 phases. The first phase lasts 0 to 4 or 5 hr and is not inhibited by either puromycin or cycloheximide. The second phase (apparent by 4-5 hr) is distinguished from the first phase by its inhibition by puromycin and cycloheximide, and by the differential dose response of dibutyryl cyclic AMP on the respective 2 phases. Incorporation of a H-labelled mixture of amino acids into protein is not seen in LH-stimulated follicles in 2 hr incubations but is apparent by 4 hr. The LH-stimulated protein synthesis is inhibited by puromycin. The results indicate that although LH stimulates both phases of progesterone synthesis, the mechanisms may be different for each phase.
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