A proposed mechanism for the action of 9-beta-D-arabinofuranosyladenine as an inhibitor of the growth of some ascites cells.
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Biomedical subjects
Publications and source records attributed to J L York.
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Adult Fischer 344 rats were fed an alcohol diet (7-9 g/kg/day) for 12 weeks and were compared to pair-fed controls with regard to the contraction and fiber characteristics of the gastrocnemius and plantaris muscles of the leg. Muscles were isolated in situ with blood and nerve supplies intact. The muscles were stretched by 1 mm increments and were stimulated at each muscle length with a voltage (1 msec pulse) that had been observed to produce maximal twitch force at the initial muscle length. Maximal twitch tension was found to be only 10% less in alcohol than pair-fed rats and the increase in force resulting from stretching was approximately 15% less in alcohol than pair-fed rats. No significant changes in sciatic nerve conduction velocities were produced by alcohol exposure. Moreover, no significant differences in muscle weight or the number and size of Type I, Type IIa or Type IIb muscle fibers were observed. Although the 12 weeks of alcohol exposure affected muscle physiology and histology in the direction of increased impairment, the differences were not large enough to be statistically significant.
Female, Long-Evans hooded rats (N = 10, 4 months of age) were given ethanol via intragastric intubation in doses of 2.0, 3.0 or 4.0 g/kg (repeated measures design). After-effects (hypothermia, free operant activity, motor performance) were measured at six, twelve and sixteen hours, respectively, for the above doses and were compared to the effects observed after the intubation of equivolume amounts of tap water. The after-effects of ethanol on rectal temperature were varied. Both rotarod performance and free operant activity were impaired after each of the above doses of ethanol. Blood ethanol analyses revealed low blood levels of ethanol (range 6.6 +/- 1.5 to 24.6 +/- 3.4 mg/100 ml) at the time behavioral tests were performed. Thus, quantifiable behavioral impairment was observed after blood ethanol values had declined following acute intoxication episodes. These changes may be related to "hangover" symptomatology in man and may serve as a model for investigating the influence of a variety of factors related to drug dosage, rate of ethanol ingestion, type of alcoholic beverage, and prophylactic or acute intervention therapeutics.
Selected characteristics of arm and leg muscle contraction were examined in a racially mixed group of male detoxified alcoholics (N = 45, ages 20-49) and age-matched controls (N = 75). Lifetime drinking histories estimated the mean lifetime consumption of ethanol to be 8.96, 12.1 and 20.4 kg ethanol/kg body weight for alcoholic subjects aged 20-29, 30-39 and 40-49, respectively. The severity of the alcohol dependence syndrome (ADS scale) was marked in alcoholics, but was not age-dependent. Alcoholics did not differ significantly from controls on health status or physical activity scales. The performance of alcoholic subjects was impaired on all muscle function measures, with relatively more impairment found in older alcoholics. Maximal knee extension force generated at 3 muscle lengths (hip, angle, 45 degrees, 90 degrees, 180 degrees) was impaired only in alcoholics 30-49 years of age. Forearm (handgrip) muscle strength was impaired in all age groups of alcoholics. Maximal muscle (biceps) contraction speed at 3 levels of resistance was impaired only in alcoholics in their fifth decade of life. The greatest deficit in alcoholics (all age groups) was observed in the anaerobic power (bicycle ergometer) test. Thus, the magnitude of dysfunction and the extent of age-relatedness was found to be a function of the muscle test employed.
Male Fischer 344 (F-344) rats of three different ages (4, 13, and 25 months) and male Brown Norway (BN/BIRIJ) rats (4 months) were injected (IP) with a hypnotic dose of ethanol (3.0 g/kg, 10% w/v in saline). Half of the animals were decapitated and brains extracted immediately upon loss of the righting reflex (LRR), while the other half were allowed to reach recovery of the righting reflex (RRR), at which time brains were extracted. Brain alcohol analyses revealed significantly higher concentrations in young F-344 rats at both LRR and RRR, indicating less sensitivity of target tissue to ethanol hypnosis in the young of that strain. All age groups of the F-344 rats as well as the young BN/BIRIJ rats displayed lower brain concentrations of ethanol at RRR than at LRR, a finding opposite to that characteristic of acute tolerance. The relationship of LRR to RRR values did not differ among the age groups of F-344 rats. We conclude that the F-344 and BN/BIRIJ strains do not develop acute tolerance to ethanol hypnosis. The findings are consistent with the hypothesis that animals with low ethanol preferences, such as the F-344 and BN/BIRIJ strains, also have low capabilities to develop acute tolerance to ethanol hypnosis.
Ethanol "titration" is offered as a possible explanation for the poor correlation of typical quantity-frequency measures of alcohol consumption with the extent of neuropsychological and other performance deficits in detoxified alcoholics. This view asserts that there are large variations in the susceptibility of individuals to alcohol toxicities and that individual alcoholics may regulate their ethanol consumption in accordance with their individual susceptibility, such that usual doses and their effects fall within personally acceptable limits. Thus, the dose chosen for chronic administration is determined, in part, by the biological impact of the ethanol ingested during drinking episodes. Owing to individual differences in susceptibilities to toxic effects, this titration behavior may result in a situation in which two- or even threefold differences in alcohol intake are associated with the same levels of toxicity or performance deficits in a group of alcoholics. Under these conditions, a graded dose-response relationship cannot be expected.
In large-scale epidemiologic studies of drinking behavior there is a need for simple and reliable estimates of the body water compartment of subjects. This, in turn, provides an estimate of the volume of distribution of ingested ethanol and a better estimate of tissue exposure levels than the use of total body weight as the volume of distribution for alcohol. The volume of distribution for ethanol (total body water, TBW) was estimated in a racially mixed group of 276 alcoholics and 166 nonalcoholics (aged 20-59 years) by means of bioelectric impedance methodology (BIA) and by means of prediction equations based upon age, body weight, and height. Estimations of mean TBW from BIA were found to be only slightly higher (1-4%) than those provided by the prediction equations. TBW values generated from both prediction equations were also highly correlated with TBW values obtained by impedance methodology, with the highest correlations observed in females (particularly black) and in alcoholics (particularly female).
We describe an in vitro organ culture system that can be used to test the effect of various substances and compounds on the wound healing process in the fibrocartilaginous substance of the knee joint meniscus. Using culture medium containing either 10% fetal bovine serum (FBS) or our recently developed serum-free, defined culture medium (DM), we have demonstrated the ability of meniscal fibrochondrocytes from intact rabbit menisci to extricate themselves from their surrounding matrix and migrate into an exogenous, purified fibrin clot in vitro. After 4 weeks of culture in FBS-containing medium, the cells which had invaded the clot had initiated the early aspects of a typical reparative response; the same response did not occur in DM alone. Morphologically, the cells on the surface of the clot resembled the original superficial fibrochondrocytes, whereas those cells within the substance of the clot more closely resembled the original deep fibrochondrocytes. After 10 weeks, the reparative response had progressed only to a certain point and then failed to progress further under these culture conditions. However, use of this culture system should now make it possible to rapidly identify and quantitate those factors which would most likely be useful in continuing the reparative response and in affecting meniscal wound repair. Elucidation of the mechanisms and requirements for meniscal healing will eventually allow the practicing orthopaedic surgeon to effect in situ meniscal repair and obviate the need for meniscectomy and its morbid sequelae.
As children and adults with developmental disabilities and special health care needs are integrated into home, school, and community life, nurses are being required to provide leadership, advocacy, and training in community settings to a much greater extent than in the past. To assess the school and community need for formal graduate preparation for nurses who work with individuals with developmental disabilities and/or special health care needs, 25 nurses in leadership positions representing urban and rural health agencies throughout Minnesota took part in a 5-hour focus group discussion. Analysis of data summarized from this process shows five features of the recommended curriculum necessary for advanced practitioners in this specialty area: (a) discipline-specific core competencies, (b) discipline-specific specialty competencies, (c) genetic competencies not specific to nursing but necessary to function in nursing roles, (d) interdisciplinary and intradisciplinary learning experiences, and (e) clinical experiences with preceptors. The authors recommend the development of interdisciplinary graduate programs designed to prepare nurses to assume leadership roles in school health, public health, home health care, and systems management that will affect public policy and, ultimately, promote change in the systems charged with responsibility to serve this population.