Biobehavioral basis of coronary-prone behavior in middle-age men. Part II: Serum cholesterol, the Type A behavior pattern, and hostility as interactive modulators of physiological reactivity.

Prior research suggests that the Type A behavior pattern, Cook and Medley Hostility (Ho) scores, and Total Serum Cholesterol (TSC) are positively associated with physiological changes to behavioral stressors. The objective of the present study was to determine whether TSC interacts with the Type A behavior pattern and hostility to affect cardiovascular and neurohormonal responses to a mental arithmetic task (MATH). For Type A individuals, elevated TSC was associated with larger catecholamine and cortisol responses to MATH. In contrast, for Type B subjects, cholesterol was negatively associated with neurohormonal responses. The interaction between Ho score and TSC predicted a similar pattern of responses whereby, in high hostile men only, TSC was positively associated with MATH-induced changes in catecholamines and heart rate. While the mechanisms responsible for the differences in the lipid-reactivity association as a function of coronary-prone behavior measures remain to be elucidated, this differential association may play a role in the heightened risk of coronary disease among hostile Type A men.     

Type A behavior pattern and alcohol intake in middle-aged men

Eighty-one sedentary but healthy, middle-aged men were studied. Type A behavior pattern (TABP) was determined by "structured interview", and dietary intake was assessed by alcohol questionnaire and 3-day diet record. Type A men reported drinking approximately twice as much alcohol as their non-Type A counterparts (mean +/- SD: 21.7 +/- 18.2 vs. 9.4 +/- 9.1 g of ethanol per day; p = 0.0003), and a strong, positive association between TABP and alcohol intake was found. The TABP-alcohol relationship was not confounded by concomitant differences in income level or years of formal education, and remained highly significant in subsequent analyses of nonsmokers alone. Type As and non-Type As did not differ significantly in their consumption of any other nutrient measured. The association between TABP and alcohol intake may have confounded conclusions from previous studies that focused on one or the other as a risk factor for coronary heart disease.     

Extramarital sexual relationships of middle-aged Danish men: attitudes and behavior.

This study explored Danish men's attitudes and behavior towards extramarital sexual relations (ESR), seen from two sides: men who had engaged in such relations (involved) and men who had not (non-involved). The participants, 439 men aged 51, completed a questionnaire concerning sexuality (behavior, attitudes and experience) as a part of a Danish cohort-investigation of health risk-factors. Thereafter 100 of the 439 men were interviewed. A high degree of permissiveness toward ESR emerged in both involved and non-involved individuals but approval of ESR was higher among the participants who were involved in ESR. The frequency of ESR increased with higher social rank. Both involved and non-involved participants mostly did not consider the ESR as a serious threat to the marital happiness. Attitudes-behavior discrepancies are discussed seen in the light of the social norms and known attitudes-behavior models.     

Macrophage activation during experimental murine brucellosis: a basis for chronic infection.

Evidence is presented that the chronicity of infection in CBA mice after injection of Brucella abortus 19 is related to a number of factors: (i) the relative resistance of B. abortus to macrophage killing, which allowed some bacteria to survive the peak of macrophage activity occurring at 14 days; (ii) the decline in macrophage activity thereafter (this decline was related in part to the presence of fewer bacteria to stimulate the bactericidal activity and also to specific, active suppressor mechanisms not identified in this study); and (iii) the insensitivity of the persistent Brucella organisms to activated macrophages. This was not due to a selection of genetically resistant bacteria, but possibly to their inaccessibility, either within "incompetent" macrophages or outside macrophages altogether.     

The basis of autoimmunity: Part I mechanisms of aberrant self-recognition

In this two-part series, Argyrios N. Theofilopoulos summarizes the current state of affairs in the field of autoimmunity. Part I integrates the collective mechanistic theories of autoimmune diseases. The most straightforward explanation to emerge with regard to organ-specific diseases is the concept that these are caused by inappropriate, yet conventional, immunological responses against self-antigens for which tolerance has never been established. A similar mechanism may be operative in systematic autoimmunity, but other abnormalities such as defects in the apoptosis machinery may also be invoked. Part II will address the genetic contributions predisposing to autoimmune syndromes.     

Mechanisms of immunity to leishmaniasis. I. Evidence for a changing basis of protection in self-limiting disease.

Methods of adoptive immunization have been employed to analyse the mechanisms of acquired immunity to leishmanial infection in the guinea pig. It was found that resistance developed 2 weeks after infection and that protection could be passively transferred to normal recipients with short-lived T lymphocytes. Although cells taken from animals at progressive stages of the disease were consistently able to adoptively immunize normal recipients their effectiveness waned from 8 weeks onward. Concomitant serum transfer performed at progressive times during the infection failed to augment the level of immunity generated in normal recipients, and at certain times appeared to have an inhibitory effect on this phenomenon. Serum from convalescent animals however did augment the level of adoptive immunity expressed in recipients. Further experiments revealed that serum taken from recovered animals, 24 hr after re-challenge, was alone capable of transferring immunity to normal recipients. Using immunofluorescent techniques to assay titres of anti-leishmanial antibody, a temporal relationship was found between high antibody titres and the ability of serum to contribute positively to the adoptive immunization of normal recipients. These observations were taken as evidence that the basis of the protective immune response to leishmanial infection may change the course of the disease from a purely cell-mediated mechanism to one involving protective antibody.     

Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem drinking behavior in middle-aged Japanese men

Among ethanol-metabolizing enzymes, the ALDH2^*2 allele, ADH2^*2 allele, and c2 allele of the cytochrome P450-2E1 (CYP2E1) gene are unique to Orientals. This prompted us to analyze their contribution to drinking behavior in 322 middle-aged Japanese men. The ALDH2^*2 allele, detected in nearly half of the subjects, showed an overwhelming protective effect against a high level of alcohol consumption and problem drinking behavior, as determined by the Kurihama Alcoholism Screening Test (KAST). The ADH2^*2 allele, in 95% of the subjects, exhibited an additive suppressive effect on alcohol consumption, whereas the c2 allele of CYP2E1, in 40% of the subjects, was associated with greater alcohol consumption. Problem drinkers showing a KAST score of 2.0 or higher were frequent among the few subjects with the ADH2^*1/1 genotype, but not in the large number of subjects having the c2 allele of CYP2E1. These findings may explain, at least in part, why in Japan the number of alcoholic patients is small relative to the number of heavy drinkers.     

Emotional behavior in middle-aged rats: Implications for geriatric psychopathologies

Clinical findings reveal that middle-aged patients are more susceptible to suffer from psychiatric disorders than older ones. However, little is known about the emotional behavior of aging rodents. This study aimed to investigate behavioral alterations in male middle-aged Wistar rats in the open-field (OF) test (at illuminated and dimly light conditions), elevated plus maze (EPM), forced swimming (FST) and inhibitory avoidance task (IA). In the EPM, middle-aged rats displayed reduced percentages of the time spent in and entries into open arms. The ambulatory activity measured in the OF under dimly light conditions was identical among groups. However, under illuminated conditions, a reduction in the number of crossings was detected in older rats, reinforcing that aged animals display a genuine anxiogenic-like phenotype. Additionally, aged rats showed an increase in the immobility time in the FST, and a reduction in the latency to step down the platform in the IA. A negative correlation was found between the immobility time and latency to step down the platform, suggesting a relationship between depressive-behavior and cognitive impairment in old rats. Altogether, male middle-aged rats are more anxious, depressed, and display aversive memory impairments. These observations contribute to investigate biological mechanisms and therapeutic interventions for geriatric anxiety and depression.     

T-cell activation. I. Evidence for a functional linkage between class I MHC antigens and the Tc-Ti complex

This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4 and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells.     

Bipolar pharmacotherapy and suicidal behavior. Part I: Lithium, divalproex and carbamazepine

INTRODUCTION: The anti-suicidal benefit of lithium on suicidal behavior in bipolar disorder is well-established. Data are mixed on the effects of divalproex and carbamazepine. METHODS: Retrospective chart review study of 405 veterans with bipolar disorder followed for a mean of 3 years, with month by month review of clinical progress notes, and systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of suicide event rates (events/100 patient years) between mood stabilizers and during-vs-after discontinuation of mood stabilizers, with linear regression analysis for influence of potential confounding variables, and robust bootstrap confirmation analysis. RESULTS: No completed suicides occurred during or after discontinuation of monotherapy. Rates of non-lethal suicidal behavior were similar during lithium (2.49), divalproex (4.67) and carbamazepine (3.80) monotherapies. There was a sixteen fold greater, highly statistically significant non-lethal suicidal event rate after discontinuation compared with during mood stabilizer monotherapy (55.89 vs. 3.48 events/100 patient years; Chi2=13.95; df=1; p<0.0002). On compared with off treatment differences were similar for the three different agents. LIMITATIONS: Treatments were uncontrolled in this naturalistic setting, and data were analyzed retrospectively. CONCLUSIONS: Lithium and the anticonvulsants may show similar benefits in protecting bipolar patients from non-lethal suicidal behavior when careful analysis of clinical data is done to confirm medication adherence/non-adherence. Findings in this study were similar to those of a previous study that applied the same methodology in a private practice setting.     

Quantitative morphology of human cirrhotic livers. Part I: Parameter expression of pattern as a basis for computerized classification

Although classification is a long-used method of histopathology, a reproducible one has yet to be created. We established a most adequate classification of cirrhosis from a geometric and statistical point of view, by reducing its form to a set of quantities and submitting the data to multivariate analysis. In this article, methods for quantification are described as a preliminary step for the Statistical treatment that appears in another paper. The pattern was reduced to a set of four quantities: (i) the mean nodular radius: (ii) the coarseness; (iii) the mean septal thickness; and (iv) the degree of nodular separation. A model of dispersed spheres with various radii r was employed to assimilate cirrhosis; r was assumed to follow a logarithmic normal distribution. The parameters of this distribution were estimated stereologically from measurements on microscopic sections of chord lengths Λ generated from nodules by a test line. The coarseness was defined as the volume % of nodules larger than 1.5 mm in r . The mean septai thickness was determined stereologically on a plate model, into which the actual septa were transformed without changing their volume or surface density. The degree of nodular separation p_θ was defined as a two-dimensional parameter, based on the curvature of nodulo-septal borders. It was demonstrated in several examples how accurately a set of these quantltles describes various patterns of cirrhosis.     

Evidence of in vivo basophil activation in chronic idiopathic urticaria

BACKGROUND: Approximately 40% of chronic idiopathic urticaria (CIU) subjects have autoantibodies to either FcepsilonRIalpha or IgE. The effect of such autoantibodies on circulating basophil activation status is unknown. OBJECTIVE: The expression of cell surface activation markers on basophils from CIU, non-allergic, and allergic subjects were compared. Further, the relationship between marker expression and serum factors reported in CIU, such as histamine-releasing activity (HRA) and immunoreactivity to FcepsilonRIalpha were examined. METHODS: Peripheral blood was obtained from CIU, allergic, and non-allergic donors and fractionated by density gradients. Enriched basophils (1-12%) were analysed by flow cytometry for expression of activation markers including CD63, CD69, and CD203c. Dilutions of serum (5-50%) were analysed for HRA on basophils from a normal donor. Serum was tested for immunoreactivity by western blotting to a standard cell lysate prepared from an RBL-SX38 cell line transfected with human FcepsilonRIalpha. RESULTS: CIU subjects (n=9) and allergic subjects (n=8) exhibited enhanced expression of CD63 and CD69, as compared with non-allergic subjects (n=7); however, no difference was seen among groups for CD203c expression. Five CIU and two non-allergic subjects had evidence of significant serum HRA (>20%), whereas two CIU, two allergic, and three non-allergic subjects had evidence of serum immunoreactivity to FcepsilonRIalpha. Serum HRA and serum immunoreactivity to FcepsilonRIalpha were not associated with enhanced surface marker expression. CONCLUSION: Basophil activation marker expression is increased in CIU subjects and is not associated with serum factors. In addition, serum HRA and FcepsilonRIalpha immunoreactivity are not unique to CIU, or related to enhanced circulating basophil marker expression.     

Identification of a coronary-prone profile for business managers: comparison of three approaches to Type A assessment

This study compares three approaches to Type A assessment for identifying a coronary-prone profile for business managers. The Survey of Work Styles (SWS), a profile measure of the Type A behavior pattern, was compared with the Structured Interview (SI), a categorical measure, and with the Jenkins Activity Survey (JAS) and Framingham Type A Scale, both continuous measures. The blood pressure, heart rate, and cardiac effort of 163 middle-aged male business managers (107 of whom were classified as Type A by the SI) were assessed during the SI. Neither the classification by the SI of the subjects into Type A and non-Type A groups nor Type A1, A2, X, B3, and B4 revealed differences in physiological arousal. Similarly, no relationship was found between physiological variables and Type A behavior that was assessed on a continuum by the JAS or Framingham Type A Scale. When business managers were classified by the SWS according to their pattern of Type A components, however, the results showed that men high on Anger but low on Competitiveness and Job Dissatisfaction had significantly higher levels of systolic blood pressure during the SI. The importance of recognizing individual differences in the expression of Type A behavior when assessing coronary-prone physiological reactivity is discussed.     

Additional evidence for the relationship between Type A behavior and social support in men

This study examined social support as a mediator of susceptibility to coronary disease in Type A individuals. Sixty-four male subjects completed the Jenkins Activity Survey and the Sarason Social Support Questionnaire. The correlations between Type A scores, the speed and impatience and hard-driving competitiveness factors of the Jenkins survey, and Sarason's social support were found to be negative, which was contrary to earlier findings. The authors hypothesize that these differing results may be a function of age and environment. Finally, and pertinent to the mechanism by which social support may be associated with coronary heart disease, systolic blood pressure was negatively correlated to satisfaction with social support.     

Evidence for increased activation of persistent inward currents in individuals with chronic hemiparetic stroke

Despite the prevalence of hyperactive stretch reflexes in the paretic limbs of individuals with chronic hemiparetic stroke, the fundamental pathophysiological mechanisms responsible for their expression remain poorly understood. This study tests whether the manifestation of hyperactive stretch reflexes following stroke is related to the development of persistent inward currents (PICs) leading to hyperexcitability of motoneurons innervating the paretic limbs. Because repetitive volleys of 1a afferent feedback can elicit PICs, this investigation assessed motoneuronal excitability by evoking the tonic vibration reflex (TVR) of the biceps muscle in 10 awake individuals with chronic hemiparetic stroke and measuring the joint torque and electromyographic (EMG) responses of the upper limbs. Elbow joint torque and the EMG activity of biceps, brachioradialis, and the long and lateral heads of triceps brachii were recorded during 8 s of 112-Hz biceps vibration (evoking the TVR) and for 5 s after cessation of stimulation. Repeated-measures ANOVA tests revealed significantly (P 相似文献   

Weaning in rats: I. Maternal behavior

Maternal behavior during the weaning period (postpartum Days 14-35) was described from continuous timelapse videorecordings of Norway rat dams and their litters. Time spent nursing declined steadily after Day 20 but persisted until Day 34, about a week longer than suggested by reports of milk transfer. Most of the decline in nursing was due to progressively fewer nursing bouts per day; milk letdowns per day were consequently diminished. Although a private feeding chamber was available to the dams, they did not use this chamber to spend more time away from the pups as weaning progressed. Instead, the dams remained with the pups in the nesting chamber but devoted increasingly less time to nursing. Subtle, progressive changes in maternal behavior are closely orchestrated and coordinated with pup development.