A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31).

The molecular nature of cell adhesion mediated by platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) was examined using stably transfected L cells in a PECAM-dependent aggregation assay. This adhesion was temperature sensitive and divalent cation dependent, with Mg2+ supporting aggregation to a greater degree than Ca2+. PECAM-dependent aggregation was heterophilic: PECAM-1 transfectants bound as readily to control-transfected L cells as to other PECAM-1 transfectants, demonstrating that a molecule endogenously expressed on the L cells serves as the ligand for PECAM in this system and presumably substitutes for the natural human ligand.

Relationship of prolactin response to d-fenfluramine to behavioral and questionnaire assessments of aggression in personality-disordered men.

Prolactin (PRL) responses to acute challenge with the serotonin (5-HT) releaser/uptake inhibitor, d-fenfluramine (PRL[d-FEN]), were correlated with three different measures of aggression in 14 male personality-disordered subjects. Consistent with previous work, PRL[d-FEN] responses were inversely correlated with scores on the Buss-Durkee Hostility Inventory-Assault scale (BDHI-Assault) and with the Brown-Goodwin Aggression-Revised (BGA-R) Aggression scale. In addition, PRL[d-FEN] responses were inversely correlated with a direct laboratory measure of aggressive behavior (Point-Subtraction Aggression Paradigm: PSAP). Although all measures of aggression correlated with PRL[d-FEN] response, differences among the intercorrelations of these measures were found. Specifically, BGA-R Aggression scores correlated with both BDHI-Assault and PSAP scores, but no relation was found between BDHI-Assault and PSAP scores. The results suggest that central 5-HT function may be associated with both self-report and behavioral measures of aggressive behavior, which may represent somewhat separate aspects of aggressive behavior.

Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding.

The purpose of this study was to examine the relationship between platelet 5-HT2A receptor binding and aggressive behavior. 125I-LSD Bmax and Kd values were measured for 22 subjects meeting DMS-III-R criteria for one or more personality disorders and 12 healthy volunteer subjects. Aggression and impulsivity were assessed using the Buss-Durkee Hostility Inventory (BDHI) Assault scale, Life History of Aggression (LHA) scale, and the Barratt-11 Impulsiveness scale (BIS-11). Bmax and Kd values did not differ between personality disordered subjects and healthy volunteers. However, both Bmax and Kd values correlated positively with BDHI Assault scores in personality-disordered subjects but not in healthy volunteer subjects. These results suggest that assaultiveness in personality-disordered subjects may covary with increasing numbers, but decreasing affinity, of platelet 5-HT2A receptor sites labeled by 125I-LSD.

Biopsychosocial approaches to understanding human aggression: the first 30 years.

Theorists and researchers have long been aware of the potential utility of multidimensional explanations of human behavior, including human aggressive behavior. Biopsychosocial models are multidimensional explanations that attempt to provide a framework for understanding how biologic, contextual, and individual difference variables combine to influence human behavior. In this paper, the rationale for giving contemporary investigators a forum to discuss research findings on aggressive behavior from a biopsychosocial perspective is developed. The advantages and potential shortcomings of viewing aggressive behavior from a biopsychosocial perspective are briefly discussed.

The serotonin hypothesis of aggression revisited.

Many contemporary theorists believe serotonin (5-HT) neurotransmitter functioning plays a role in the regulation of human aggressive behavior. We argue that the evidence supporting this 5-HT hypothesis of human aggression is less compelling than commonly assumed, due to (a) conflicting study results, and (b) significant methodological limitations of existing studies. Recent models that integrate the role of psychological and contextual variables in 5-HT--associated aggression are reviewed. The need to incorporate psychometrically sound measures of aggression in 5-HT studies, to use experimental and longitudinal designs, and to test hypotheses drawn from multifactorial models in future research is advocated.

The relationship between personality psychopathology and aggressive behavior in research volunteers.

Theorists and clinicians have long believed that personality psychopathology is a risk factor for aggressive behavior. Previous investigations in this area, however, have provided mixed results. In this study, the relationship between personality psychopathology and aggressive behavior was examined in 137 research volunteers. The influences of gender and coexisting major mental disorders were statistically controlled. Aggressive behavior was associated with criteria for 7 of the 11 personality disorders listed in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.). Except for schizoid criteria, all relationships with aggressive behavior were in the positive direction. When all personality disorders were considered simultaneously, paranoid and passive-aggressive criteria were significant predictors of aggressive behavior.

Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting.

The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service. Thirty-seven highly agitated patients exhibiting psychotic symptoms were randomly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate. Symptom ratings were conducted each hour using double-blind procedures. Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale. Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study. However, Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings. The groups did not differ on the Brief Psychiatric Rating Scale at any rating time. No differences were found either in the number of doses administered or in the administration route selected. Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol, lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting.

Effects of clorazepate, diazepam, and oxazepam on a laboratory measurement of aggression in men.

The effects of three benzodiazepines on human aggressive behavior were examined in 44 medically healthy men. Volunteers were administered either placebo, 10 mg diazepam, 15 mg chlorazepate, or 50 mg oxazepam orally using double-blind procedures. Approximately 90 min after drug ingestion, participants were given the opportunity to administer electric shocks to an increasingly provocative fictitious opponent during a competitive reaction-time task. Aggression was defined as the level of shock the participant was willing to administer to the opponent. Results support the notion that diazepam (but not all benzodiazepines) can elicit aggressive behavior under controlled, laboratory conditions. Implications regarding the clinical use of various benzodiazepines for the tranquilization of potentially assaultive patients are discussed.

Assessment of life history of aggression: development and psychometric characteristics.

The Life History of Aggression (LHA) assessment was administered to up to 252 subjects. In addition to a total LHA score, subscale scores for Aggression, Social Consequences and Antisocial Behavior, and Self-directed Aggression were calculated. Test-retest stability, interrater agreement, and internal consistency reliability were excellent both for the LHA Total score and the LHA Aggression subscore. There were moderately strong correlations between these scores and both self-reports of aggressive tendency (Buss-Durkee Hostility Inventory: n = 214) and recent overt aggression (Overt Aggression Scale-Modified for Out-patients: n = 61). LHA Total scores were highest among subjects with Antisocial or Borderline Personality Disorder. These results support the use of the LHA assessment, and especially the LHA Aggression subscore, as a measure of life history of aggressive behavior.

Accruing knowledge on the biological bases of aggression: comment on Giancola (2000).

The author contends that research on the biological correlates of aggression and violence follows a predictable course. The executive functioning model proposed by P. R. Giancola (2000) is a logical outcome of this progression and underscores the relative maturity of knowledge accrual for the alcohol-aggression link compared with other bio-behavioral models of human aggression.

Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18).

Platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) is a member of the Ig gene superfamily expressed on the surfaces of monocytes (Mo), neutrophils (PMN), and some T cell subsets, as well as on platelets and the intercellular junctions of endothelial cells. We used mAbs (mAb) against PECAM on Mo and PMN to mimic interaction with natural ligand. Such treatment resulted in the rapid increase of leukocyte beta 2 integrin-mediated adhesive function, as measured in two in vitro assays. Anti-PECAM-treated Mo bound more rapidly and in a CD18-dependent manner to cultured endothelial cells. Monovalent Fab fragments augmented binding significantly and intact IgG, bivalent F(ab')2 fragments, and secondarily cross-linked Fab fragments were even more effective. In a direct assay of CD11b/CD18 (CR3) function, PMN settling on surfaces coated with anti-PECAM mAb (including Fab fragments) were stimulated to bind C3bi-coated erythrocytes. These studies demonstrate that, in addition to the previously described functions of PECAM-1, this molecule is capable of participating in an adhesion cascade resulting in the activation of Mo and PMN beta 2 integrins. This activation may be important for the CR3-dependent adhesion events that are critical in the emigration of Mo and PMN at sites of inflammation.

Water stress and crop load effects on fruit fresh and dry weights in peach (Prunus persica).

Effects of water stress on fruit fresh and dry weights were investigated in peach trees, Prunus persica (L.) Batsch., with varying crop loads: light, moderate and heavy. In well-watered controls, tree water status was independent of crop load. In trees receiving reduced irrigation, the degree of water stress increased with increasing crop load. Water stress induced fruit fresh weight reductions at all crop loads. Fruit dry weight was not reduced by water stress in trees having light to moderate crop loads, indicating that the degree of water stress imposed did not affect the dry weight sink strength of fruit. Water-stressed trees with heavy crop loads had significantly reduced fruit dry weights, which were likely due to carbohydrate source limitations resulting from large crop carbon demands and water stress limitations on photosynthesis.

Neurobiologic correlates of violence: relevance to criminal responsibility.

Studies addressing the relationship between neurotransmitter functioning and violent crime are reviewed. A rich literature exists to support the notion that monoamine (i.e., serotonin, dopamine, and norepinephrine) neurotransmitter functioning is related to human aggressive behaviour. Results from these studies provide, at best, indirect evidence that neurotransmitter abnormalities are involved in violent criminal behavior. Few studies have specifically addressed the role of neurotransmitter functioning in violent crime. To illustrate how current knowledge in this area has been applied in forensic settings, a case study in which neurotransmitter functioning was introduced as evidence to support an insanity defense is presented. Potential problems associated with such defenses are discussed.

Crop load and water stress effects on daily stem growth in peach (Prunus persica).

We investigated crop load and water stress effects on diurnal stem extension growth of field-grown peach (Prunus persica (L.) Batsch) trees. Neither the presence of fruit nor reduced irrigation significantly altered the timing of diurnal fluctuations in stem growth rate. Stems with subtending fruit had significantly reduced growth compared to stems with no subtending fruit. Crop load had no significant effect on relative stem extension rates and the majority of the reduction in absolute growth was the result of a smaller zone of elongation in fruit-bearing stems than in stems with no subtending fruit. Fruit removal did not increase growth rates within 24 h. When irrigation was reduced, the length of the stem elongation zone and total daily stem growth were significantly decreased relative to well-irrigated controls and the decreases were highly correlated with stem water potential. Compared with well-irrigated controls, relative stem extension rates of water-stressed trees were reduced at several times during the 24-h period, but the degree of reduction was not proportional to the difference in stem water potentials between the treatments.

Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural killer cell transendothelial migration and beta 2 integrin activation.

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a glycoprotein expressed on the surfaces of monocytes, neutrophils, platelets, a subpopulation of T cells, and, as described in this work, on NK cells. It is also concentrated at the junctions between endothelial cells (EC) in culture, and is expressed on continuous endothelia in all tissues. PECAM has been shown to be involved in monocyte and neutrophil transendothelial migration in vitro and in vivo. The function of PECAM in NK cell interaction with EC has never been studied. In this work, we demonstrate that ligation of PECAM on the surface of NK cells activates their beta 2 integrins. Anti-PECAM Abs added to NK cells caused a 2.5- to 4-fold increase in the binding of these cells to monolayers of EC or 3T3 cells transfected with ICAM-1, and this was inhibited by a mAb against CD18. PECAM also plays a role in NK cell transendothelial migration. Anti-PECAM Abs inhibited 50% of NK cell transmigration through resting EC in an in vitro system. The transmigration of CD56dim and CD56bright cells was inhibited equally. IFN-gamma increased NK cell transmigration; the transmigration of CD56bright cells was increased to a much greater extent than CD56dim transmigration (4-fold vs 1.5-fold). Anti-PECAM inhibited the transmigration of CD56dim cells by 30%, while that of CD56bright cells was not blocked. These studies demonstrate that PECAM-1 could play an important role in the extravasation of NK cells into tissues for constitutive surveillance and into sites of inflammation.

Intermittent explosive disorder-revised: development, reliability, and validity of research criteria.

The study of human aggression has been hindered by the lack of reliable and valid diagnostic categories that specifically identify individuals with clinically significant displays of impulsive aggressive behavior. DSM intermittent explosive disorder (IED) ostensibly identifies one such group of individuals. In its current form, IED suffers from significant theoretical and psychometric shortcomings that limit its use in clinical or research settings. This study was designed to develop a revised criteria set for IED and present initial evidence supporting its reliability and validity in a well characterized group of personality disordered subjects. Accordingly, research criteria for IED-Revised (IED-R) were developed. Clinical, phenomenologic, and diagnostic data from 188 personality disordered individuals were reviewed. IED-R diagnoses were assigned using a best-estimate process. The reliability and construct validity of IED-R were examined. IED-R diagnoses had high interrater reliability (kappa = .92). Subjects meeting IED-R criteria had higher scores on dimensional measures of aggression and impulsivity, and had lower global functioning scores than non-IED-R subjects, even when related variables were controlled. IED-R criteria were more sensitive than DSM-IV IED criteria in identifying subjects with significant impulsive-aggressive behavior by a factor of four. We conclude that in personality disordered subjects, IED-R criteria can be reliably applied and appear to have sufficient validity to warrant further evaluation in field trials and in phenomenologic, epidemiologic, biologic, and treatment-outcome research.