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Biomedical subjects

I Diamond

Publications and source records attributed to I Diamond.

At least 55 records · Page 3Linked to original sources
PubMed1996

Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to the nucleus.

Short- and long-term ethanol exposures have been shown to alter cellular levels of cAMP, but little is known about the effects of ethanol on cAMP-dependent protein kinase (PKA). When cAMP levels increase, the catalytic subunit of PKA (C alpha) is released from the regulatory subunit, phosphorylates nearby proteins, and then translocates to the nucleus, where it regulates gene expression. Altered localization of C alpha would have profound effects on multiple cellular functions. Therefore, we investigated whether ethanol alters intracellular localization of C alpha. NG108-15 cells were incubated in the presence or absence of ethanol for as long as 48 h, and localization of PKA subunits was determined by immunocytochemistry. We found that ethanol exposure produced a significant translocation of C alpha from the Golgi area to the nucleus. C alpha remained in the nucleus as long as ethanol was present. There was no effect of ethanol on localization of the type I regulatory subunit of PKA. Ethanol also caused a 43% decrease in the amount of type I regulatory subunit but had no effect on the amount of C alpha as determined by Western blot. These data suggest that ethanol-induced translocation of C alpha to the nucleus may account, in part, for diverse changes in cellular function and gene expression produced by alcohol.

Animals↗
PubMed1996

Updating small area population estimates in England and Wales.

"Population estimates have important implications for resource allocation within government and commerce, and are often assumed to be without error. Currently, central government provides annual population estimates for all the local and health authority districts in Britain, but estimates are needed for smaller areas, typically for electoral wards and postal sectors. Small area estimates are provided by some local authorities and commercial organizations, using different methods; the accuracy of these estimates is modelled here within a multilevel framework. Certain characteristics of the small area and of the method of estimation are included as explanatory variables. Results show that the method of estimation used is of great importance."

Developed Countries↗
PubMed1996

Activation of cyclic AMP-dependent protein kinase reverses tolerance of a nucleoside transporter to ethanol.

Adenosine mediates some of the acute and chronic effects of ethanol in neural cells. In cultured NG108-15 cells, ethanol inhibits adenosine uptake via a specific facilitative nucleoside transporter leading to an increase in extracellular adenosine, activation of adenosine A2 receptors and increases in intracellular cyclic AMP (cAMP). After chronic ethanol exposure, an adaptive decrease in receptor-stimulated cAMP levels occurs. Additionally, the transporter becomes insensitive to rechallenge with ethanol and adenosine uptake is not inhibited. cAMP levels are decreased in cells chronically exposed to ethanol and we show here that cAMP-dependent kinase (PKA) activity in cellular homogenates also is decreased. Therefore, decreased cAMP-dependent phosphorylation may be responsible for loss of ethanol sensitivity. To test this hypothesis, NG108-15 cells were treated with agents that alter PKA activity and the ethanol sensitivity of adenosine transport was measured. In naive cells, decreasing PKA activity with the cAMP antagonist, Rp-adenosine-3',5'-cyclic phosphorothioate, resulted in ethanol-insensitive adenosine uptake. This effect was blocked by the phosphatase inhibitor, okadaic acid. These results suggest that loss of ethanol sensitivity is correlated with decreased PKA activity. Therefore, stimulating PKA activity in chronically treated cells should restore sensitivity of adenosine uptake to inhibition by ethanol. Indeed, the cAMP agonist, Sp-adenosine-3',5'-cyclic phosphorothioate, restored ethanol sensitivity of transport in cells treated chronically with ethanol. Our results suggest that ethanol sensitivity of adenosine transport is regulated by PKA and protein phosphatase activities in NG108-15 cells. Moreover, the effects of chronic ethanol exposure on adenosine transport can be reversed by activating PKA.

Adenosine↗
PubMed1996

The determinants of the duration of contraceptive use in China: a multilevel multinomial discrete-hazards modeling approach.

Often in demography, individuals may change state over time for a variety of reasons. Competing-risks hazards models have been developed to model such situations. This paper describes the extension of the discrete-time competing-risks hazards model to a multilevel framework that allows for data at different levels of aggregation. The model is illustrated with data from the 1988 Chinese National Survey of Fertility and Contraceptive Prevalence, which collected complete contraceptive histories. Women may stop using a method of contraception for a number of reasons; this paper describes how one can control for correlations between the outcomes of repeated spells of contraceptive use.

Adolescent↗
PubMed1995

Determinants of infant mortality in Malawi: an analysis to control for death clustering within families.

The 1988 Malawi Traditional and Modern Methods of Child Spacing Survey data are used to identify determinants of infant mortality in Malawi. The logistic binomial analysis shows that socioeconomic factors are significant even during the neonatal period while the length of the preceding birth interval is significant in the post-neonatal period only. There is a strong familial correlation of mortality risks during both the neonatal and post-neonatal periods but the effect of geographical area of residence is stronger in the post-neonatal period.

Adult↗
PubMed1995

The impact on fertility of contraceptive failure in China in the 1980s.

Contraceptive failure was an important determinant of fertility in China in the 1980s. Based on the data from the China Two-per-Thousand Fertility Survey, this study shows that about 7% of the general fertility rate of currently married women aged 15-49 for a 12-month period is attributed to contraceptive failure, mainly due to the high failure rate associated with IUD use. A number of demographic characteristics are associated with contraceptive use, and with contraceptive failure and its outcome. Relevant socioeconomic differentials are also identified.

Adolescent↗
PubMed1994

The role of adenosine in mediating cellular and molecular responses to ethanol.

We have found that ethanol-induced increases in extracellular adenosine activate adenosine receptors which, in turn, mediate many of the acute and chronic effects of ethanol in the nervous system. Several laboratories have demonstrated the importance of adenosine in mediating the acute and chronic effects of ethanol at multiple levels of investigation in the nervous system. These include genetic selection for ethanol sensitivity in mice, behavioral responses to ethanol in naive and tolerant animals, neurophysiologic responses in hippocampal slices, and at the level of cAMP signal transduction and gene expression in cultured neural cells. In this review we present results from our laboratory which document the role of adenosine in mediating ethanol-induced changes in neural function at a cellular and molecular level. A schematic summary of our findings is: Etoh-->decreases Ado uptake-->increases Extracellular Ado-->Activation of Adenosine A2 receptor-->increases cAMP-->increases PKA-->-->-->Heterologous Desensitization (decreases cAMP)-->-->-->insensitivity of adenosine uptake to ETOH

Adenosine↗
PubMed1994

Adenosine receptors mediate cellular adaptation to ethanol in NG108-15 cells.

Acute ethanol treatment of NG108-15 neuroblastoma x glioma hybrid cells results in inhibition of adenosine uptake with consequent increases in extracellular adenosine and intracellular cAMP concentrations. Chronic exposure to ethanol, however, causes heterologous desensitization of receptors coupled to adenylyl cyclase via stimulatory guanine nucleotide regulatory protein. This heterologous desensitization is correlated with a decrease in the amount of protein and mRNA for the GTP-binding subunit of stimulatory guanine nucleotide regulatory protein. In addition, after chronic exposure to ethanol, the adenosine transporter becomes tolerant to acute ethanol inhibition of adenosine uptake, and there is no longer an increase in extracellular adenosine. We have previously shown that extracellular adenosine is required for the development of ethanol-induced heterologous desensitization. To examine the role of adenosine receptors in mediating these responses to ethanol, we used BW A1434U, an adenosine receptor antagonist that does not inhibit nucleoside transport. BW A1434U caused a concentration-dependent inhibition of (-)-N6-(R-phenyl-isopropyl)-adenosine-stimulated cAMP production in NG108-15 cells. BW A1434U also completely blocked acute ethanol-induced increases in intracellular cAMP levels and prevented the development of ethanol-induced heterologous desensitization and the reduction in the GTP-binding subunit of stimulatory guanine nucleotide regulatory protein. In addition, BW A1434U prevented the development of tolerance to ethanol-induced inhibition of adenosine transport. Our results indicate that in NG108-15 cells, adenosine receptors mediate ethanol-induced changed in cAMP signal transduction and adenosine transport and that an adenosine receptor antagonist can block both these acute and chronic affects of ethanol.

Adaptation, Physiological↗
PubMed1994

Neurologic effects of alcoholism.

Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy).

Alcoholic Intoxication↗
PubMed1994

Selective inhibition by ethanol of the type 1 facilitative glucose transporter (GLUT1).

Ethanol appears to modulate the function of selective mammalian receptors and transporters by interacting with highly specific membrane protein sites. Of the multiple types of nucleoside transporters known to be present in mammalian cells, we observed that ethanol inhibits only one class of facilitative nucleoside transporters, that inhibited by nitrobenzylmercaptopurine riboside. Because there are biochemical similarities between facilitative glucose transporters and nitrobenzylmercaptopurine riboside-sensitive nucleoside transporters, we tested whether ethanol might selectively inhibit a unique class of facilitative glucose transporters. We report here that ethanol inhibits hexose uptake in human lymphocytes and several cell lines expressing the ubiquitous facilitative type 1 glucose transporter (GLUT1). Ethanol inhibition of hexose uptake by GLUT1 is independent of ethanol inhibition of facilitative nucleoside transport. We also determined the ethanol sensitivity of various cloned human facilitative glucose transporters expressed in Chinese hamster ovary cells and we found that ethanol inhibits hexose uptake by GLUT1 but not uptake by GLUT3 or GLUT4 transporters. Our results suggest that a protein motif or motifs present in the GLUT1 amino acid sequence but absent in GLUT3 or GLUT4 proteins may confer ethanol sensitivity.

Animals↗
PubMed1993

The relationship between marital breakdown and childbearing in England and Wales.

"The paper uses data on women from the General Household Surveys for 1986-89 [for England and Wales] to form combined multiple decrement tables on the transitions from first marriage through childbearing, divorce and remarriage. It shows that ultimately women who experience one marital breakdown tend to have around the same number of children...as those who remain married. However, their time to complete childbearing is rather longer with this extra time being concentrated largely in the birth interval in which the marital breakdown takes place. The group of women who experience more than one marital breakdown tend to have more children and consequently shorter birth intervals."

Birth Intervals↗
PubMed1993

Inhibition of adenosine uptake by ethanol is specific for one class of nucleoside transporters.

Adenosine uptake via nucleoside transporters is inhibited when S49 and NG108-15 cell lines cells are exposed to ethanol. This inhibition leads to an accumulation of extracellular adenosine that binds to adenosine A2 receptors and increases cAMP production. Subsequently, there is a heterologous desensitization of receptors coupled to adenylyl cyclase for which adenosine also is required. There are multiple classes of facilitative and concentrative nucleoside transporters that could be inhibited by ethanol to initiate this cascade of events. In this paper, we establish that adenosine uptake by only one type of nucleoside transporter, an NBMPR-sensitive facilitative transporter, is inhibited by ethanol. There is no effect on other classes of nucleoside transporters even when present in the same cell. Thus, ethanol-induced extracellular accumulation of adenosine results specifically from inhibition of NBMPR-sensitive facilitative nucleoside transporters. We also find that human lymphocytes express only facilitative nucleoside transporters and that the NBMPR-sensitive type is predominant. Thus, inhibition of this type of transporter by ethanol may be related to the desensitization of cAMP signal transduction that we have reported in lymphocytes from alcoholics.

Adenosine↗
PubMed1993

Birth interval and family effects on postneonatal mortality in Brazil.

In this paper random-effects logistic models are used to analyze the effects of the preceding birth interval on postneonatal mortality in Brazil, controlling for the correlation of survival outcomes between siblings. The results are compared to those obtained by using ordinary logistic regression. Family effects are found to be highly significant in the random-effects model, but the substantive conclusions of the ordinary logistic model are preserved. In particular, birth interval effects remain highly significant.

Birth Intervals↗
PubMed1993

Fertility in Botswana: the recent decline and future prospects.

Recent estimates of fertility in Botswana suggest a rapid decline of more than two births per woman between 1981 and 1988. This paper proposes that the baseline fertility was overestimated but that nonetheless fertility declined by about one birth per woman during the 1980s. The decline in fertility was linked to a deterioration in social and economic conditions caused by a major drought in the early 1980s and to the increased availability of family planning services in the same period. Fertility apparently began to rebound in the late 1980s in response to improved conditions, which came about as a result of a successful drought relief program. Future declines in fertility depend on the continued success of the family planning program, particularly in rural areas.

Adolescent↗
PubMed1992

Into the twenty-first century with British households.

"This paper takes [U.K.] General Household Survey (GHS) data at the micro level and ages these households by simulation to the year 2001. Differing scenarios are considered in order to accommodate high and low variants of each household type in the British household distribution."

Age Factors↗
PubMed1992

Simulating the effect of demographic events on the household composition.

"The aim of this paper is to measure the effects on household composition of changes in demographic events, e.g. mortality, fertility, marriage, divorce. British household data are taken from the General Household Survey and aged by simulation to 2001 using a 'Most Likely' model. Subsequently different assumptions of each demographic event are taken from 1991 so that the effects of perturbations within each event can be studied. Special features of the simulation model are the differentiations between cohabitation and marriage and separation and divorce, and the detailed breakdowns of household types such as lone parents into single and previously married women and men with children aged 0-4, 5-15 and 16 and over."

Demography↗