Psychological,situational, and gender predictors of cardiovascular reactivity to stress: A multivariate approach

This study examined whether relationships between anger expression, hostility, social evaluative anxiety, and a presumed mechanism for coronary heart disease development, cardiovascular reactivity (CVR) to stress, are moderated by stress situation and gender and whether such relationships are attenuated by inadequate assessments. Subjects (47 men, 47 women) were assigned randomly to either a Harassment or a Social Evaluation condition, under which they performed a reaction time task. SBP, DBP, and HR measures were recorded during baseline and task. Multiple regression analyses indicated that expressed anger was related to CVR only among men in the Harassment condition; that hostile men who express anger showed the most CVR across situations, and that the traits assessed here did not predict CVR among women. Results suggest that assessments of coronary-risk and interventions to reduce risk may need to take into account attitudes, styles of emotional expression, environmental factors, and gender.This research was supported in part by an NIMH predoctoral fellowship (F31MH09836) awarded to John W. Burns and by a grant from the American Heart Association (89-01-3G) awarded to Edward S. Katkin.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Silent supraglottic carcinoma

In a review of 51 consecutive patients with previously untreated squamous cell carcinoma of the supraglottic larynx, five (9.8%) patients were found to have no mucosal abnormality on initial evaluation by both computed tomography (CT) and direct laryngoscopy. All five patients who manifested submucosal disease had at least one endoscopic procedure done with a biopsy negative for cancer before definitive diagnosis, resulting in an average delay from initial endoscopy to diagnosis of 19.8 weeks. These inapparent or "silent" neoplasms present unique problems in regard to establishing a diagnosis by routine biopsy techniques, even though CT reliably demonstrates their presence. Early diagnosis requires aggressive biopsy techniques based on CT findings.     

Chronic stressors and maternal depression: implications for prevention.

We report on the use of an instrument to measure exposure to stressors among 149 women presenting with their children for pediatric care at an urban primary care center. Overall, 38.3 percent of the women had significant levels of depressive symptoms; 71.4 percent of those in the "high stress" group had an adjusted prevalence odds ratio of 5.00 [95% CI = 2.12, 11.82]. We conclude that screening in the pediatric office is feasible for identifying women at high risk of becoming depressed.     

Development of immunofiltration assay by light addressable potentiometric sensor with genetically biotinylated recombinant antibody for rapid identification of Venezuelan equine encephalitis virus

A genetically biotinylated single chain fragment variable antibody (scFv) against Venezuelan equine encephalitis virus (VEE) was applied in a system consisting of an immunofiltration enzyme assay (IFA) with a light addressable potentiometric sensor (LAPS) for the rapid identification of VEE. The IFA involved formation of an immunocomplex sandwich consisting of VEE, biotinylated antibody, fluoresceinated antibody and streptavidin, capture of the sandwich by filtration on biotinylated membrane, and labeling of the sandwich by anti-fluorescein urease conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies was investigated and optimized. By the IFA/LAPS assay, the limit of detection (LOD) of VEE was approximately 30 ng/ml, similar to that achieved when chemically biotinylated monoclonal antibody (mAb) was applied. Total assay variance of the IFA/LAPS assay for both intra- and inter-assay precision was less than 20%. Assay accuracy was measured by comparing VEE concentrations estimated by IFA/LAPS standard curve to those obtained by conventional protein assay. VEE concentrations were found to differ by no more than 10%. The IFA/LAPS assay sensitivity was approximately equal to that of a conventional enzyme-linked immunosorbent assay (ELISA) utilizing polystyrene plates and a chromogenic substrate; however, less time and effort were required for performance of the IFA/LAPS assay. More importantly, use of genetically biotinylated scFv in the IFA/LAPS assay obviates the need for chemical biotinylation of antibody with resultant possible impairment of the antigen-binding site. Furthermore, the potential for batch-to-batch variability resulting from inequality in the number of biotin molecules labeled per antibody molecule is eliminated.     

The Complement-Fixation Test in Hepatic Coccidiosis of Rabbits

Antibodies to Eimeria stiedae were measured in rabbit serum by complement fixation. The titre rose to a maximum at about the 22nd day after infection, remained at this level for about 20 days and then declined. Antibodies were still detectable up to 160 days after infection.

Evidence of past or present slight E. stiedae infection was found in clinically normal rabbits whose sera fixed complement with E. stiedae antigens.

Challenge of rabbits which had recovered from a near-fatal infection had no effect upon the complement fixation titres of their sera.

The serum of a rabbit which had been injected with alum-precipitated antigen fixed complement with E. stiedae antigens. However, the animal was still susceptible to a superimposed oral infection which had the effect of further increasing the serum titre.

     

Holt-Oram syndrome associated with the hypoplastic left heart syndrome

We present the first case of Holt-Oram syndrome associated with the lethal congenital heart defect of hypoplastic left heart syndrome. The possible pathophysiological link is explored and the need for careful genetic and cardiologic evaluation in these patients is reiterated.     

The activation of red blood cell transketolase in groups of patients especially at risk from thiamin deficiency

Erythrocyte transketolase activation by thiamin diphosphate has been studied in elderly patients with moderate or severe chronic dementia, acute alcoholic admissions and chronic alcoholics with evidence of brain damage, mostly of the Wernicke-Korsakoff type. Significantly more patients in each group than controls showed abnormal activation of transketolase, not only by 0.3 mM thiamin diphosphate (TDP) but also in further activation by increase to 3 mM. This indicated the presence in a proportion of the alcoholic and the demented patients of an abnormal enzyme variant, similar to that previously found in vitro. The modified transketolase activation test may warn not only of marginal thiamin deficiency but also independently, of susceptibility to brain damage in patients at risk.     

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Anti-HLA class I antibody-mediated activation of the PI3K/Akt signaling pathway and induction of Bcl-2 and Bcl-xL expression in endothelial cells

Anti-human leukocyte antigen (HLA) antibodies (Ab) have long been implicated in the process of acute and chronic allograft rejection, yet their mechanism(s) of action is not well understood. The aim of this study was to determine whether ligation of HLA class I molecules by anti-HLA Ab on the surface of human endothelial cells (EC) activates the PI3 Kinase (PI3K)/Akt signaling pathway and downstream target proteins of the cell death apparatus. We report that Ab ligation of major histocompatibility complex (MHC) class I molecules on the surface of EC triggers phosphorylation of Akt, PI3K, and recruitment of PI3K and Akt into a signaling unit with focal adhesion kinase. Signaling through class I also stimulated phosphorylation of Bad and upregulated expression of Bcl-2 and Bcl-xL. Pretreatment of EC with the PI3K inhibitor wortmannin blocked class I-mediated expression of Bcl-2, but not Bcl-xL, suggesting a role for the PI3K/Akt signaling pathway in regulation of class I-induced Bcl-2 expression. The intracellular events initiated by class I ligation were influenced by the concentration of the anti-HLA Ab with the lowest tested concentrations of Ab stimulating the highest level of Akt phosphorylation, Bcl-xL and Bcl-2 expression. Consistent with the in vitro experiments, analysis of biopsy samples from heart transplant recipients with evidence of Ab-mediated rejection exhibited increased Bcl-2 expression on the vascular endothelium. These results suggest that exposure of the graft endothelium to low concentrations of anti-HLA Ab may promote cell survival by transducing signals resulting in upregulation of cell survival genes.