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Biomedical subjects

M Lynch

Publications and source records attributed to M Lynch.

At least 253 records · Page 14Linked to original sources
PubMed1986

Exclusion of an interactive effect of combined x-irradiation and activated cyclophosphamide in tissue culture.

The effect of Cyclophosphamide (CY) on the X ray survival of clonogenic tumor cells has been studied in vitro. Two activated derivatives of the drug, Peroxycyclophosphamide and Hydroperoxycyclophosphamide, were employed. Two cell lines, repair-competent human HeLa cells and the repair-deficient rat REQ line, were investigated. Neither form of CY had any effect on the X ray survival curve of either cell line, indicating that any interaction anticipated in vivo could be expected to be additive.

Animals↗
PubMed1986

Cloning and characterization of a rat-specific repetitive DNA sequence.

A 2.1-kb EcoRI fragment of rat DNA has been cloned and sequenced. This fragment contained a repetitive element which was highly specific for rat DNA and widely dispersed throughout the rat genome. The repetitive element is homologous to a sequence found in the 3' end of the rat LINE family. Because of its high degree of species specificity and its heterodisperse distribution, this sequence provided a useful marker for rat DNA in DNA transfection experiments into mouse host cells.

Animals↗
PubMed1986

Behavior management of aggressive sequela after Reye's syndrome.

This study describes the use of behavior management procedures to reduce the occurrence of severe behavioral sequela in a 14-year-old, post-Reye's syndrome male. Prior to intervention the client exhibited severe self-injurious, hyperaggressive, and food refusal behaviors that precluded any opportunities for rehabilitation, placed him at severe medical risk, and made him a candidate for institutional placement. With contingent restraint, in vivo desensitization, and reinforcement contingencies it was possible to control these behaviors and begin intensive rehabilitation. Subsequently, the client returned to his family and community day school for the severely handicapped where he remains five years later.

Adolescent↗
PubMed1986

Embedding of skeletal tissue in plastic for vascular and histological study to demonstrate delayed endochondral ossification in Leghorn type fowl.

A method is described which enables visualisation of the blood supply in developing avian long bones, followed by the preparation of undecalcified histological sections from the same material. The circulatory system was perfused with a solution of fixative, dye and barium sulphate. The skeletal tissue was cleared in plastic resin before embedding and tissue blocks were cut into 1 mm slabs. The vascular canals were then examined with a dissecting microscope. Slabs were re-embedded in resin and 5 microns sections cut for routine undecalcified histological staining. Focal areas of delayed endochondral ossification were demonstrated in slabs prepared from the proximal ends of femora of White Leghorns. These lesions are considered a less severe form of the dyschondroplastic condition occurring in broilers.

Animals↗
PubMed1985

Urinary kallikrein: assay validation and physiological variability.

Decreased urinary kallikrein (UK) output has been suggested as a preclinical indicator of essential hypertension. In preparation for UK studies in hypertension prone Utah kindreds, we assessed selected UK assay parameters and physiological variability. Precision for the colorimetric kallikrein assay was quite acceptable, coefficient of variation (CV) less than 5% within run and 14% day-to-day at a concentration of 9.5 TU/l. The mean recovery was 105% and assay results were correlated with results from the 3H-TAME esterase method, r = 0.990. Urine specimens were stable at room temperature for up to 4 days, frozen at -20 degrees C for 6 weeks, or frozen at -80 degrees C after Sephadex treatment for a year. UK output varied significantly throughout the day with excretion highest in the morning. Urine collections at 10.00, 12.00 and 14.00 had significantly (p less than 0.05) more UK than the overnight collection. Intra- and inter-individual variations were of the same magnitude, mean 20%. In children UK output increased with age until the adult levels were reached at age 15. Male and female values were similar. Smoking; consumption of alcohol, coffee, tea, cola of chocolate; and female hormone medications did not significantly influence the 12-hour UK output in the 1110 caucasian subjects.

Adolescent↗
PubMed1984

The selective value of alleles underlying polygenic traits.

To define the genetic and ecological circumstances that are conducive to evolution via genetic drift at the allelic level, the selection coefficient for a constituent allele of arbitrary effect is derived for a polygenic character exposed to stabilizing selection. Under virtually all possible conditions, alleles within the class for which the absolute value of the average effect is less than 10(-2) phenotypic standard deviations are neutral with respect to each other. In addition, when the mean phenotype is at the optimum and the genetic variance is in selection-drift-mutation equilibrium, a considerable amount of neutral evolution is expected in the class of alleles with intermediate effects on the phenotype. These results help clarify how molecular evolution via genetic drift may occur at a locus despite intense selection and provide a potential mechanistic explanation for the neutral theory of molecular evolution.

Alleles↗
PubMed1983

Alpha-adrenoceptor number and function in rat cortex after ethanol and immobilization stress.

Alpha-Adrenoceptor number and function were assessed in rat cortex after ethanol and immobilization stress. Rats subjected to immobilization stress for 2 h/day/7 days showed a significant reduction in alpha 2-adrenoceptors in cortex ( [3H]clonidine binding) but no change in alpha 1-adrenoceptors ( [3H]prazosin binding). The inhibitory effect of clonidine (500 nM) on 3H efflux from cortical slices preincubated with [3H]norepinephrine was reversed in the stressed animals. These effects on alpha 2-adrenoceptor number and function were reduced when stress was accompanied by chronic administration of ethanol (35% of calories in a liquid diet) although when given alone ethanol produced small changes in the same direction as those produced by stress. It is suggested that, in its effects on cortical alpha-adrenoceptors, chronic ethanol administration attenuates the effects of severe stress though itself perhaps acting as a mild stressor when given as part of a liquid diet regimen.

Animals↗
PubMed1983

Regulation by glucocorticoids of rat-liver phenylalanine hydroxylase in vivo.

Phenylalanine hydroxylase, a liver-associated enzyme, is induced markedly by glucocorticoids in two permanent rat-hepatoma cell lines. In order to gain evidence that this phenomenon also occurs in vivo, we examined the effect of adrenalectomy and/or hormone supplementation on the levels of phenylalanine hydroxylase in the livers of adult rats: glucocorticoid administration increases, and adrenal ablation reduces, the activity of the hepatic enzyme, and the diminution occurring in the latter instance is entirely prevented by concurrent hormone replacement. These results thus corroborate earlier findings from a single experiment and are consistent with the hypothesis that adrenal corticosteroid hormones participate in modulating phenylalanine-hydroxylase levels within the diploid hepatocyte.

Adrenalectomy↗
PubMed1983

Regulation of expression of genes for enzymes of the mammalian urea cycle in permanent cell-culture lines of hepatic and non-hepatic origin.

We present here the results of investigations conducted by ourselves and others on the regulation of the expression of genes encoding the enzymes of the mammalian urea cycle as manifest in cultured cells of both hepatic and extrahepatic origin. Upon consideration of the recently discovered discrete non-hepatic arginase genetic locus in man and our consequent hypothesis that the form of arginase thus transcribed in such extrahepatic cells functions principally in providing ornithine for protein anabolism and polyamine biosynthesis, rather than in detoxifying ammonia through urea formation, we have chosen instead to study permanent cell lines that are derived from liver and continue to perform a variety of hepatic functions in culture as experimental models for probing the molecular mechanisms underlying the control of ureagenesis within the mature liver cell. Of two such arginase-positive rat-hepatoma lines, we have characterized extensively in one (H4-II-E-C3) the mode of action of glucocorticoids in augmenting the cellular levels of this enzyme as well as of argininosuccinate synthetase. To this end, we have recently demonstrated that these stimulations are both mediated by binding of the hormones to classical cytoplasmic steroid receptors in a specific and saturable fashion and have thus concluded that the H4-II-E-C3 line will provide a suitable cell culture system for subsequent more detailed experiments from which the information garnered will continue to be relevant to the ureagenic pathway as modulated in the differentiated hepatocyte in vivo.

Animals↗
PubMed1983

Resource availability, maternal effects, and longevity.

Experiments with a clone of the cladoceran Daphnia pulex indicate that the nutritional conditions of the maternal environment play a major role in determining the progeny's phenotype. Apparently, by influencing the physiology and/or morphology of individuals during early development, maternal investment not only enhances juvenile survival but has long-lasting, favorable effects on the progeny's ability to convert resources into growth and reproduction as well as negative repercussions for adult survival of the progeny. Life-span may also be radically altered by modifying food schedules within an individual's life. Neither reproductive effort nor rate of living hypotheses can explain longevity variation within Daphnia clones; rather the onset of senescence appears to be associated with a general breakdown in the ability to incorporate energy into biomass. Analysis of our results as well as earlier data with a "rate of aging-threshold vitality" model suggests that increasing the availability of food to an individual increases the rate of aging while decreasing the threshold vitality necessary for survival and that increasing maternal investment increases both the vitality at birth and the rate of aging of the progeny.

Animals↗
PubMed1982

Regulation of glucocorticoids of arginase and argininosuccinate synthetase in cultured rat hepatoma cells.

We have examined and characterized the regulation by glucocorticoids of the levels of arginase and argininosuccinate synthetase in two rat hepatoma cell lines (H4-II-E-C3 and MH1C1). Hydrocortisone elevates the activity of both enzymes in a time- and dose-dependent fashion. This effect was blunted markedly by small amounts of ethanol (0.1 to 0.9% [v/v]) and blocked substantially by a high molar excess of the "anti-inducer" steroid fluoxymesterone. The other "optimal" inducers dexamethasone and corticosterone were as effective as hydrocortisone in elevating the levels of these enzymes at saturating concentrations. Inhibition of these stimulations by cycloheximide indicated that ongoing cellular protein synthesis was required for both effects, and the admixture of extracts from fully stimulated and basal cells gave no evidence for the existence of direct inhibitors or activators of either enzyme. The results corroborate findings from earlier whole-animal studies and provide evidence for the following conclusions. (i) This stimulation by hydrocortisone of urea-cycle enzymes in the cultured hepatoma cells is mediated by a classical glucocorticoid mechanism involving initial binding to specific cytoplasmic steroid receptors and the eventual accumulation of new enzyme molecules. (ii) These cell lines thus constitute valid experimental models for use in further detailed studies on the molecular mechanism(s) through which glucocorticoids and intermediary metabolites effect a selective modulation of arginase and argininosuccinate-synthetase gene expression in the differentiated mammalian liver.

Animals↗