Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse alpha-cardiac myosin in the laser trap assay.

Point mutations in cardiac myosin, the heart's molecular motor, produce distinct clinical phenotypes: hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Do mutations alter myosin's molecular mechanics in a manner that is predictive of the clinical outcome? We have directly characterized the maximal force-generating capacity (F(max)) of two HCM (R403Q, R453C) and two DCM (S532P, F764L) mutant myosins isolated from homozygous mouse models using a novel load-clamped laser trap assay. F(max) was 50% (R403Q) and 80% (R453C) greater for the HCM mutants compared with the wild type, whereas F(max) was severely depressed for one of the DCM mutants (65% S532P). Although F(max) was normal for the F764L DCM mutant, its actin-activated ATPase activity and actin filament velocity (V(actin)) in a motility assay were significantly reduced (Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Proc Natl Acad Sci USA 103: 14525-14530, 2006.). These F(max) data combined with previous V(actin) measurements suggest that HCM and DCM result from alterations to one or more of myosin's fundamental mechanical properties, with HCM-causing mutations leading to enhanced but DCM-causing mutations leading to depressed function. These mutation-specific changes in mechanical properties must initiate distinct signaling cascades that ultimately lead to the disparate phenotypic responses observed in HCM and DCM.

Kinetics of heat shock protein 70 synthesis in the human heart after cold cardioplegic arrest.

OBJECTIVE: Protection of the myocardium against ischemia/reperfusion injury is a major challenge in cardiac surgery and cardiology. A cardioprotective role of heat shock proteins (Hsp), in particular Hsp 70, against ischemia has been demonstrated. A prerequisite for clinical exploitation of high Hsp 70 levels in the heart during ischemia is the determination of the efficacy and the kinetics of cardiac Hsp synthesis in vivo. METHODS: We examined Hsp 70 and other immediate early genes, that are induced by cardioplegia and reperfusion, in right atrial biopsies taken from 15 patients during coronary artery bypass grafting. Specimens were obtained before cardioplegia and after ending of reperfusion and subsequently studied by immunohistochemistry and Western blot analyses. RESULTS: Overall Hsp 70 increased 2.0+/-1.1-fold (P<0.01) in the nucleus as well as in the cytosol of myocytes and endothelial cells during open-heart surgery. As determined by comparison to a dilution series of recombinant protein, Hsp 70 levels amounted up to 6 per thousand of total cellular protein. The increase of Hsp 70 correlated well with the duration of cardioplegia and reperfusion (P<0.005) showing a markedly accelerated increase at periods longer than 2 h. Further, the immediate early gene c-Fos also increased 2.4+/-2.2-fold during open-heart surgery (P<0.05), whereas other members of the Hsp family, like Hsp 27 and Hsp 90, showed no significant changes in protein levels during cardioplegia and reperfusion. CONCLUSIONS: These findings demonstrate that protein levels of Hsp 70 in the myocardium increase to significant amounts within few hours after induction. The optimum time point for induction of Hsp 70 appears to be at least 2 h before open-heart surgery.

A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease.

Heterozygous Tbx5(del/+) mice were generated to study the mechanisms by which TBX5 haploinsufficiency causes cardiac and forelimb abnormalities seen in Holt-Oram syndrome. Tbx5 deficiency in homozygous mice (Tbx5(del/del)) decreased expression of multiple genes and caused severe hypoplasia of posterior domains in the developing heart. Surprisingly, Tbx5 haploinsufficiency also markedly decreased atrial natriuretic factor (ANF) and connexin 40 (cx40) transcription, implicating these as Tbx5 target genes and providing a mechanism by which 50% reduction of T-box transcription factors cause disease. Direct and cooperative transactivation of the ANF and cx40 promoters by Tbx5 and the homeodomain transcription factor Nkx2-5 was also demonstrated. These studies provide one potential explanation for Holt-Oram syndrome conduction system defects, suggest mechanisms for intrafamilial phenotypic variability, and account for related cardiac malformations caused by other transcription factor mutations.

[Glanzmann's thrombasthenia and pregnancy. Contribution of plasma exchange before scheduled cesarean section]. / Thrombasthénie de Glanzmann et grossesse. Apport des échanges plasmatiques avant césarienne programmée.

Glanzmann's thrombasthenia is a thrombopathy which affects primary hemostasis due to a qualitative or quantitative abnormality of membrane glycoproteins IIb-IIIa. The treatment of hemorrhages is usually associated with the transfusion of packed red blood cells and platelet concentrates. If massive allo-immunisation occurs, the transfusion will prove to be inefficient. A case of a cesarean section was scheduled after therapeutic plasmapheresis and platelet transfusions in a massively allo-immunised patient with Glanzmann's thrombasthenia. The plasma exchange made it possible to reduce to trace levels the concentrations of anti-PLA1 and anti-PLA2 antibodies, thus making platelet transfusions hemostatically efficient. The cesarean section was therefore safely performed when the bleeding time was normalized.

[Captopril potentiation of the hypotension induced by halothane]. / Potentialisation par le captopril de l'hypotension induite par l'halothane.

In a double-blind study, twenty-four ASA 1 and II patients scheduled for otosclerosis surgery were randomized in two groups according to the premedication given orally 1 h before anaesthesia: placebo (group P; n = 12) or 25 mg captopril (group C; n = 12). Anaesthesia was induced with thiopentone, fentanyl and vecuronium and was maintained, after oral tracheal intubation, with N2O/O2 (50/50); 5 min after intubation, the inspired halothane concentration (FIH) was set at 1.8-2% in order to obtain a mean arterial pressure (Pa) of 45-55 mmHg; thereafter, FIH was increased or decreased (+/- 0.5% every 3 min) in order to maintain this Pa value. Ventilation was controlled in order to assure normocapnia (35-40 mmHg). Inspired and expired (FEH) halothane concentrations were monitored by an halothane analyser. The plasma renin (ARP) and conversion enzyme activities (AEC) were measured before anaesthesia (ARP1, AEC1), 5 min (ARP2) and 55 min (ARP3, AEC2) after the start of anaesthesia. In group C, AEC1 and AEC2 were reduced by half, confirming the efficiency of captopril in inhibiting the conversion enzyme. ARP1 and ARP2 were increased in group C (5.42 +/- 4.2 and 9.92 +/- 7.35 micrograms.l-1.h-1. ARP3 increased in both groups (20.75 +/- 8.42 micrograms.l-1.h-1 in group C, and 24.60 +/- 15.40 in group P). Pa decreased to 55 mmHg more rapidly in group C (9 min in group C; 18 min in group P; p less than 0.05) and FEH could be reduced by a third (1.38 +/- 0.29% in group P; 0.90 +/- 0.17% in group C; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Personality correlates of positive identity and relationship involvement in gay men.

Six personality variables (social anxiety, trait anxiety, locus of control, sensitization, depression, and self concept) were correlated with variables relevant to a positive gay identity (degree of communication about sexual preference and degree of comfort being gay) and to relationship involvement (being in a gay relationship, number of months in a gay relationship, and living with a partner) in a volunteer, nonclinical sample of 51 gay males. Men who informed others of their sexual preference were low on trait anxiety, sensitization, and depression and high on self concept. Men comfortable with their gay identity were low on social anxiety, sensitization, and depression and high on self concept. Men involved in long-term relationships were low in trait anxiety, had an internal locus of control, and were low in depression. Men living with a partner had a higher self concept than men not living with a partner. Results are discussed in terms of previous studies of gay male relationships.

[Passage of propofol in the colostrum. Preliminary data]. / Passage du propofol dans le colostrum. Données préliminaires.

So as to ascertain whether propofol passed into human milk, a study was carried out in five women who had undergone general anaesthesia with propofol in the puerperium. Concentrations of propofol were measured both in plasma and colostrum. The results showed clearly the excretion of propofol in the colostrum, and the similar time-courses of propofol levels in the blood and colostrum; the ratio of concentrations blood:colostrum was close to 1.

Perceived emotional support from family and friends in members of homosexual, married, and heterosexual cohabiting couples.

The purpose of this study was to examine factors that influenced perceptions of emotional support from friends and family in members of gay, lesbian, married, and heterosexual cohabiting couples. Both the individual partner and the couple were used as units of analysis. Using the individual partner scores, perceived emotional support was related to Type of Couple (married perceived more emotional support from family than did gays and lesbians); Sex-Role Self-Concept (undifferentiated individuals perceived the least emotional support from both friends and family); and Source of Support (friends were perceived to provide more emotional support than family). Gays and lesbians, in particular, perceived more emotional support from friends than from family. Individuals reporting high degrees of emotional support from friends were less psychologically distressed than those reporting low degrees of emotional support from friends. Using the couple scores, the above Type of Couple and Source of Support effects were replicated. In addition, partner differences were obtained only in married couples in which wives perceived more emotional support than husbands. Results are discussed in terms of current research in the area of social support.

Relationship quality of partners in heterosexual married, heterosexual cohabiting, and gay and lesbian relationships.

The relationship quality of partners in 44 married, 35 heterosexual cohabiting, 50 gay, and 56 lesbian monogamous couples was studied. Each couple lived together and did not have children living with them. Relationship quality was dimensionalized as love for partner, liking of partner, and relationship satisfaction. Cohabiting partners had the lowest Love for Partner and Relationship Satisfaction scores. Differences were also found among partner types on: barriers to leaving the relationship, alternatives to the relationship, a belief that mindreading is expected in the relationship, masculinity, femininity, androgyny, dyadic attachment, shared decision making, and perceived social support from family. The four partner groups did not differ in psychological adjustment. For each type of partner, love for partner was related to many barriers to leaving the relationship and high dyadic attachment; liking of partner was related to few alternatives to the relationship, high dyadic attachment, and high shared decision making; and relationship satisfaction was related to many attractions, few alternatives, few beliefs regarding disagreement is destructive to the relationship, high dyadic attachment, and high shared decision making. Stepwise multiple regression procedures were used to identify the best set of predictors for each partner type. Results are discussed in the context of existing models of relationship quality.

Interaction of sex role self-concept with relationship quality and relationship beliefs in married, heterosexual cohabiting, gay, and lesbian couples.

The relation between sex role self-concept (masculine, feminine, undifferentiated, and androgynous) and both relationship quality and dysfunctional relationship beliefs was examined in 370 monogamous partners who represented four types of couples (married, heterosexual cohabiting, gay, and lesbian). Analyses used both the individual partner and the couple as the unit of analysis. The individual partner analyses revealed that relationship quality and relationship beliefs differed by subjects' sex role self-concept. Androgynous and feminine subjects reported higher relationship quality than masculine and undifferentiated subjects; androgynous subjects had fewer "disagreement is destructive" beliefs than feminine subjects; and androgynous subjects had fewer "partner cannot change" beliefs than undifferentiated subjects. The couple analyses revealed a relation between partners' sex role self-concept only for the heterosexual cohabiting couples. For these couples, masculine men tended to pair with feminine or undifferentiated women, and androgynous partners tended to pair together. Relative to other couples, couples in which one or both partners were androgynous or feminine reported the highest relationship quality, whereas couples in which one or both partners were undifferentiated or masculine reported the lowest relationship quality. These effects did not vary by type of couple. The study concluded that sex role self-concept is a robust factor in appraisals of relationship quality. Relative to masculine and undifferentiated individuals, androgynous and feminine individuals report greater positive relationship functioning.

Age and gender differences in and personality correlates of loneliness in different relationships.

This study examined age and gender differences in and personality correlates of loneliness in different relationships. Loneliness was measured in three groups of subjects (college men, college women, and elderly women) with the Differential Loneliness Scale which assesses dissatisfaction with four types of relationships (Family, Larger Groups, Friendships, and Romantic/Sexual). Age and gender differences were significant. Compared to elderly women, college women expressed more dissatisfaction with their Family and Large Group relationships. Compared to college women, elderly women expressed more dissatisfaction with their Friendships and Romantic/Sexual relationships. With regard to gender differences, college men expressed more dissatisfaction with Family, Large Group, and Friendship relationships than college women. For each subject group, dissatisfaction scores were correlated with health status, locus of control, social support, depression, and self-consciousness. Correlations varied with type of relationship as well as with age and gender. The group differences and the varying patterns of correlations support the use of a multidimensional approach to the study of loneliness. Results are discussed in terms of previous research and future investigations.

Relationship quality of gay men in closed or open relationships.

This study compared gay men in monogamous ("closed") relationships (n = 98) and gay men in nonmonogamous ("open") relationships (n = 34). Partners in open relationships were living together significantly longer than partners in closed relationships. Partners in the two types of relationships did not differ in Psychological Adjustment. Controlling for length of time living together, partners in closed relationships reported higher Affiliation/Dependency, more Favorable Attitudes toward the Relationship, and lower Tension than partners in open relationships. Global relationship quality for both types of couples was related to many Attractions, many Barriers, and few Alternatives to the relationship; few beliefs regarding both Disagreement is Destructive and Partners Cannot Change; high Dyadic Attachment; high Shared Decision Making; and low Psychological Maladjustment. Partners in both types of relationships were more similar to each other than different from each other, especially on the variables of Relationship Quality, a belief in Partner Changeability, and Dyadic Attachment.

Correlates of social anxiety in college students and homosexuals.

The relationship between social anxiety and measures of trait anxiety, self-concept, locus of control, repression-sensitization and depression was examined in volunteer college student (39 males and 53 females) and homosexual (51 males and 11 females) samples. Social anxiety was significantly related to all variables of interest, except depression. Within both samples, subjects high in social anxiety had an external locus of control, were low in positive self-concept, and were high in both sensitization and anxiety. The correlational patterns were remarkably similar in both samples, and sensitization emerged as the best single predictor of social anxiety for both college and homosexual groups. Results are discussed in terms of theoretical predictions, previous studies of social anxiety, and implications for personality assessment.

Contribution of patient and hospital characteristics to adverse patient incidents.

The 1974 medical malpractice "crisis" brought about extensive legislation and insurance regulation in the United States. Hospitals in many states are now required to support risk management programs that include investigation and systematic analyses of adverse patient incidents. However, no research supports the hypothesis that systematic analysis of adverse patient incidents can identify contributory factors. In this study, a simple prediction model was used to estimate relationships between adverse incidents and selected patient and environmental characteristics in a large hospital. While some of the incident-characteristic relationships were significant, none of the estimated equations yielded results that could be logically translated into policy recommendations for the hospital. These results point to the need for further research. The benefits that positive research results would have for patients, hospitals, an the bill-paying public are obvious. Additional negative results would suggest that many legislative bodies and regulatory agencies were presumptions in requiring hospitals to conduct analyses of incidents.