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Biomedical subjects

T O'Hare

Publications and source records attributed to T O'Hare.

15 recordsLinked to original sources

The current status of academic-mental health linkages in Rhode Island.

The purpose of this study is to describe the current status of academic-public mental health linkages in the State of Rhode Island by querying key informants concerning their opinions in the following areas: clinical orientation and preferred clinical interventions, specific approaches to academic-mental health linkages, training and educational opportunities, obstacles to a career working with persons who have persistent and severe mental illness, and recommendations to improve academic-mental health linkages. Forty-eight of sixty key informants, among them academics, mental health administrators, clinical practitioners and consumer advocates, responded to the mailed survey. More than half the respondents rated affective disorders, schizophrenia and substance abuse to be their highest concern as professionals; most subscribed to biological models of mental illness as well as a variety of prevailing treatment strategies employed in the care of persons with severe mental illness; generally they rated the current status of academic-mental health linkages to be low, but recommended a range of remedies to improve and increase collaborative efforts.

Community Mental Health Services

Mental health problems and alcohol abuse: co-occurrence and gender differences.

A growing body of research has demonstrated that alcohol abuse co-occurs with a broad range of mental health problems. To date, however, there is a scarcity of data concerning the co-occurrence of alcohol abuse and other problems in people who seek mental health outpatient services and, consequently, about gender differences among them. The present study surveyed 376 clients receiving outpatient services at a mental health center. Results demonstrate that women self-reported significantly more psychophysiological distress and family pathology and men reported more community problems and health concerns. Men drank significantly more than women, were more likely to have had a problem with alcohol over the past year, and were more likely to have been treated for substance abuse. For both men and women, the level of alcohol consumption varied directly with the severity of psychophysiological symptoms and community and health problems.

Adolescent

Interfacial catalysis by phospholipase A2: evaluation of the interfacial rate constants by steady-state isotope effect studies.

The kinetics of hydrolysis of phospholipid vesicles by phospholipase A2 (PLA2) in the scooting mode can be described by the Michaelis-Menten formalism for the action of the enzyme in the interface (E*). E* + S in equilibrium E*S in equilibrium E*P in equilibrium E* + Products The values of the interfacial rate constants cannot be obtained by classical methods because the concentration of the substrate within the lipid bilayer is not easily manipulated. In the present study, carbonyl-carbon heavy atom isotope effects for the hydrolysis of phospholipids have been measured in both vesicles and in mixed micelles in which the phospholipid was present in the nonionic detergent Triton X-100. A large [14C]carbonyl carbon isotope effect of 1.12 +/- 0.02 was measured for the cobra venom PLA2-catalyzed hydrolysis of dipalmitoylphosphatidylcholine in Triton X-100. In contrast, no isotope effect (1.01 +/- 0.01) was measured for the action of the porcine pancreatic and cobra venom enzymes on vesicles of dimyristoylphosphatidylmethanol in the scooting mode. In a second experiment, the hydrolysis of vesicles was carried out in oxygen-18 enriched water. Analysis of the released fatty acid product by mass spectrometry showed that it contained only a single oxygen-18. All of these results were used to estimate both the forward and reverse commitments to catalysis. The lack of doubly labeled fatty acid demonstrated that the product is released from the E*P complex faster than the reverse of the esterolysis step. The small isotope effect in vesicles demonstrated that the E*S complex goes on to products faster than substrate is released from the enzyme. The relevance of these results to an understanding of substrate specificity and inhibition of PLA2 is discussed. In addition, the conditions placed on the values of the rate constants obtained in the present study together with results obtained in the other studies described in this series of papers have led to the evaluation of most of the interfacial rate constants for the hydrolysis of phospholipid vesicles by PLA2.

Animals

Reliability of self-reports of alcohol use by community clients.

Eighty-five of 116 randomly selected clients receiving case management services at a comprehensive community mental health center responded anonymously to a survey questionnaire that included two measures of self-reported alcohol use: questions about frequency and quantity and a retrospective diary for reporting the number of drinks consumed daily in the preceding week. Forty-two patients reported using alcohol; consumption was higher among younger patients. A significant correlation was found between responses to the frequency-quantity questions and the information provided in the retrospective diary, indicating that self-reports of alcohol consumption are reasonably reliable for the clients studied. Future research is needed to establish the reliability and validity of self-reported alcohol and drug use in typical treatment settings.

Affective Disorders, Psychotic

Measuring alcohol consumption: a comparison of the retrospective diary and the quantity-frequency methods in a college drinking survey.

As part of a larger study of college drinking, the quantity-frequency (Q-F) measure of alcohol consumption was compared to the retrospective diary (RD) method with 494 drinkers out of 606 respondents (75.8%) of 800 randomly selected undergraduates. Respondents were representative by sex and year in school of virtually all full-time undergraduates at Rutgers, the State University of New Jersey. The study tested the hypothesis that the RD would yield higher estimates of average alcohol consumption and of "heavy drinking" as defined by NIAAA typology (average two or more drinks per day) and of "peak drinking," a Q-F standard consisting of five or more drinks at least once per week. The study also compared the two methods as correlates of self-reported problems related to drinking. Results supported the major hypotheses that the RD would detect more overall consumption, heavy drinking and peak drinking than the Q-F. Results also demonstrated good consistency between the Q-F and RD as well as comparable correlations with the alcohol problem score.

Adult

The endogenous functional turkey erythrocyte and rat liver insulin receptor is an alpha 2 beta 2 heterotetrameric complex.

Previous studies have indicated that turkey erythrocyte and rat liver membranes contain endogenous alpha beta heterodimeric insulin receptors in addition to the disulphide-linked alpha 2 beta 2 heterotetrameric complexes characteristic of most cell types. We utilized 125I-insulin affinity cross-linking to examine the structural properties of insulin receptors from rat liver and turkey erythrocyte membranes prepared in the absence and presence of sulphydryl alkylating agents. Rat liver membranes prepared in the absence of sulphydryl alkylating agents displayed specific labelling of Mr 400,000 and 200,000 bands, corresponding to the alpha 2 beta 2 heterotetrameric and alpha beta heterodimeric insulin receptor complexes respectively. In contrast, affinity cross-linking of membranes prepared with iodoacetamide (IAN) or N-ethylmaleimide identified predominantly the alpha 2 beta 2 heterotetrameric insulin receptor complex. Similarly, affinity cross-linking and solubilization of intact turkey erythrocytes in the presence of IAN resulted in exclusive labelling of the alpha 2 beta 2 heterotetrameric insulin receptor complex, whereas in the absence of IAN both alpha 2 beta 2 and alpha beta species were observed. Turkey erythrocyte alpha 2 beta 2 heterotetrameric insulin receptors from IAN-protected membranes displayed a 3-4-fold stimulation of beta subunit autophosphorylation and substrate phosphorylation by insulin, equivalent to that observed in intact human placenta insulin receptors. Turkey erythrocyte alpha beta heterodimeric insulin receptors, prepared by defined pH/dithiothreitol treatment of IAN-protected membranes, were also fully competent in insulin-stimulated protein kinase activity compared with alpha beta heterodimeric human placenta receptors. In contrast, endogenous turkey erythrocyte alpha beta heterodimeric insulin receptors displayed basal protein kinase activity which was insulin-insensitive. These data indicate that native turkey erythrocyte and rat liver insulin receptors are structurally and functionally similar to alpha 2 beta 2 heterotetrameric human placenta insulin receptors. The alpha beta heterodimeric insulin receptors previously identified in these tissues most likely resulted from disulphide bond reduction and denaturation of the alpha 2 beta 2 holoreceptor complexes during membrane preparation.

Animals

Intrinsic kinase activity of the insulin receptor.

Since the identification of the insulin receptor by insulin-binding activity almost two decades ago, our understanding of the structure and function of the insulin receptor has progressed tremendously. The importance of the intrinsic tyrosine protein kinase activity of the insulin receptor is implied by the fact that the insulin receptor belongs to a family of receptor tyrosine kinases which play a role in growth control, by experiments demonstrating the intimate association of normal kinase activity and insulin action, and by evidence that the intrinsic kinase activity can be regulated under certain conditions. There are still some major gaps in our knowledge concerning the structure/function of the insulin receptor such as how activation of the intrinsic kinase activity of the receptor leads to altered cellular physiology. The kinase may phosphorylate endogenous substrates or autophosphorylation may simply alter beta subunit conformation so it can then interact with an effector system (i.e. a serine kinase) directly, or indirectly through a G-protein. The truth may lie somewhere between these two pathways.

Animals

Intrinsic kinase activity of the insulin receptor. The intact (alpha 2 beta 2) insulin receptor from rat liver contains a kinase domain with greater intrinsic activity than the intact insulin receptor from human placenta.

We are interested in developing methods to rigorously characterize the intrinsic enzymatic activity of the insulin receptor. We have previously shown that the intact, kinase active form of the receptor can be separated from inactive forms isolated from human placenta. Therefore, the determination of kinase activity, when normalized to the number of receptors based on binding, is not complicated by the presence of insulin receptor forms which bind insulin normally, but are kinase inactive. We now have extended this separation technique to insulin receptor preparations from rat liver. Thus, the determination and comparison of the intrinsic kinase activity of insulin receptor from human placenta and rat liver was performed. When normalized to the same number of insulin receptors which are autophosphorylated to the same degree, the rat liver insulin receptor catalyzes the transfer of phosphate from ATP to three different substrates, on average, 2.8-fold quicker than receptor from human placenta. This probably represents an inherent difference in the intrinsic kinase activity (Vmax), since the values for KM of the substrates are essentially identical, for insulin receptors from both sources. Intrinsic kinase differences may reflect different biological roles and/or differential regulation by exogenous factors. We are now examining this hypothesis in light of reports that demonstrate regulation of intrinsic kinase activity of the insulin receptor in certain physiological and pathological states.

Female

Protein phosphotyrosine phosphatase purified from the particulate fraction of human placenta dephosphorylates insulin and growth-factor receptors.

Protein phosphatase activity specific for Tyr(P) (phosphotyrosine) residues (PTP-phosphatase) was found in the cytosol and particulate fractions of human placenta. In the particulate fraction, half of the PTP-phosphatase activity could be extracted with 1% Triton X-100. The PTP-phosphatase remaining in the Triton-insoluble residue was solubilized with 0.6 M-KCl plus 1% CHAPS (3-[(3-cholamidopropyl)-dimethylammonio]propane-1-sulphonate) and was purified 1850-fold by adsorption to DEAE-Sepharose, affinity chromatography on Zn2+-iminodiacetate-agarose, phosphocellulose adsorption, Fractogel filtration and Mono Q chromatography. The cytoskeleton-associated PTP-phosphatase was distinguished from acid, alkaline and other protein Ser(P) (phosphoserine)/Thr(P) (phosphothreonine) phosphatases by its neutral pH optimum, activity in the presence of EDTA, inhibition by Zn2+, vanadate, or molybdate, and low activity with either [Ser(P)]phosphorylase a or p-nitrophenyl phosphate. The PTP-phosphate displayed a Km of 0.15 microM with [Tyr(P)]serum albumin as substrate, 10-100-fold lower than the Km for previously described protein phosphatases. The cytoskeleton-associated PTP-phosphatase catalysed the dephosphorylation of receptors for insulin, insulin-like growth factor-1 and epidermal growth factor labelled by autophosphorylation. The properties of this PTP-phosphatase suggest that it plays a role in the regulation of hormone receptors and cytoskeleton proteins by reversible phosphorylation on tyrosine residues.

Cell Fractionation

Separation and characterization of three insulin receptor species that differ in subunit composition.

Partially purified human placental insulin receptor preparations give rise to three distinct insulin-binding peaks when eluted from a Mono Q high-performance liquid chromatography anion-exchange column. We analyzed the basis for this phenomenon by affinity cross-linking of insulin to each peak, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We find that the three insulin-binding peaks represent different molecular weight complexes with the following subunit composition: (alpha beta)2, (alpha beta)(alpha beta'), and (alpha beta')2, where beta' represents a proteolytically derived fragment of the beta subunit. This analysis of subunit composition was confirmed by silver staining of affinity-purified insulin receptor following resolution of the forms on a Mono Q column as described previously. We have characterized the three isolated insulin receptor forms with regard to ligand binding by LIGAND and Scatchard analysis. We also measured insulin-stimulatable autophosphorylation and exogenous kinase activity directed toward poly(Glu/Tyr) (4:1). The three forms of the insulin receptor exhibit similar KD's for insulin binding to the high- and low-affinity sites. The (alpha beta)2 and (alpha beta)(alpha beta') forms of the insulin receptor display superimposable curvilinear Scatchard plots. In contrast, only the intact holoreceptor (alpha beta)2 form demonstrates insulin-stimulatable autophosphorylation and exogenous kinase activity. The (alpha beta)(alpha beta') form has reduced basal kinase activity which was not increased by prior incubation with insulin. The (alpha beta')2 form lacks a kinase domain and consequently demonstrated no kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels

The ligand binding subunit of the insulin-like growth factor 1 receptor has properties of a peripheral membrane protein.

125I-insulin-like growth factor 1 was cross-linked to its receptor in human placenta microsomal membranes. The microsomes were treated with urea, with dithiothreitol or with both reagents prior to centrifugation at 100,000 X g. We found that greater than 80% of the label was membrane-associated following separate treatment with urea or dithiothreitol, but greater than 80% of the radioactivity remained in the supernatant after simultaneous exposure to both reagents. In identical experiments employing 125I-epidermal growth factor, no condition led to the release of greater than 10% of label from the membrane. We conclude that the ligand binding subunit of the insulin-like growth factor 1 receptor, like peripheral membrane proteins, lacks a membrane anchoring domain.

Dithiothreitol

Analyzing the hospice market.

Hospitals should base decisions about hospice services on need rather than on subjective feelings. Marketing methods can be used to identify the potential population for hospice care.

Adolescent

Differences in Asian and white drinking: consumption level, drinking contexts, and expectancies.

Despite the heterogeneous nature of interethnic drinking differences within racial groups, research has demonstrated that cautious generalizations can be made when comparing Asian and White drinking patterns. Persons in the United States who identify their race as "Asian" drink much less than their White counterparts, and they report fewer problems. Some have speculated that drinking patterns between racial groups are mediated by culturally influenced social learning. To date there has been very little research examining the expectancy of reinforcement from drinking between different racial, cultural or ethnic groups. The current study of 637 white and 179 Asian university students examined differences in alcohol consumption and problem levels, the social context of drinking, and alcohol expectancies. Results show considerable differences between Asian and White drinking and level of associated problems, as well as similarities and differences in social drinking contexts. It also appears that Asians expected greater tension reduction from drinking despite drinking less overall. Implications for further research are suggested that would link racial, and more specifically, ethnic drinking differences with culturally defined alcohol expectancies.

Adult