Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population.

Abundant biochemical evidence links deficient activity of mitochondrial alpha-ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced alpha-ketoglutarate dehydrogenase activity has also been associated with anti-mortem measures of clinical disability. One of the genes encoding this complex, namely, DLD, lies within a chromosome 7 region that is in linkage disequilibrium with AD. We therefore examined the hypothesis that variation in DLD is associated with AD risk. Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found. However, four common SNPs were identified and genotyped in a case-control series of 297 Caucasians from New York City, including 229 residents of a Jewish nursing home. Logistic regression analysis was performed for the four-locus DLD genotype, sex, and ApoE4 status to determine the association of these independent variables with AD. Significant associations with AD were observed for ApoE4 (P < 10(-6)) and sex combined with DLD genotype (P = 0.013). The association with the DLD genotypes appears only in the male population in both the Caucasian series (P = 0.0009, n = 83) and the Ashkenazi Jewish subseries (P = 0.017, n = 49). The DLD genotype appears to operate independently of APOE in conferring AD risk.     

Aluminum welding fume-induced pneumoconiosis

Chronic exposure to high concentrations of fumes during aluminum arc welding causes a severe pneumoconiosis characterized by diffuse pulmonary accumulation of aluminum metal and a corresponding reduction in lung function. Aluminum fume-induced pneumoconiosis is a rarely reported entity, of which the true incidence is unknown. We report the clinical, radiographic, microscopic, and microanalytic results of 2 coworkers, employed by the same aluminum shipbuilding facility, who died of complications from this disease. Scanning electron microscopy and energy dispersive x-ray analysis of the exogenous particle content in the lung tissue of these cases revealed the highest concentrations of aluminum particles (average of 9.26 billion aluminum particles per cm(3) of lung tissue) among the 812 similar analyses in our pneumoconiosis database. One patient had an original clinical diagnosis of sarcoidosis but no evidence of granulomatous inflammation.     

Case report: glomus tumor of the colon

Glomus tumors are tumors of pericytic origin and are usually found in the distal extremities. Glomus tumors have rarely been reported in viscera. The authors report a glomus tumor of the colon that caused rectal bleeding in a 40-yr-old man and was biopsied and excised endoscopically. The histology and immunohistochemical profile of the tumor are described and the literature on visceral glomus tumors is reviewed.     

Expression of interleukin-18 in the lung after endotoxemia or hemorrhage-induced acute lung injury

Hemorrhage and endotoxemia are important risk factors for the development of acute lung injury. Interleukin (IL)-18 is a recently described cytokine released in its mature, active form after pro-IL-18 is cleaved by the IL-1 converting enzyme (ICE). IL-18 has multiple immunomodulating properties, including induction of interferon-gamma (IFN-gamma), IL-1beta, tumor necrosis factor-alpha, and intercellular adhesion molecule-1. To examine the possible involvement of IL-18 in acute lung injury, we examined its expression, as well as that of IFN-gamma, IL-12, and ICE, using murine hemorrhage or endotoxemia models. The amounts of IL-18 messenger RNA (mRNA) increased in the lung after hemorrhage or endotoxemia. However, only endotoxemia was associated with elevations in lung and plasma concentrations of IL-18 protein. ICE expression was increased in the lungs after endotoxemia but not after hemorrhage. Although IFN-gamma expression increased in the lungs after hemorrhage or endotoxemia, elevations in lung IL-12 mRNA levels were found only after endotoxemia. These results indicate that hemorrhage and endotoxemia induce different patterns of immunomodulatory cytokine expression in the lungs. In particular, differences in the expression of ICE after hemorrhage or endotoxemia may affect generation of the active forms of downstream cytokines, including IL-18. IFN-gamma expression in the lungs after hemorrhage appears to occur through a pathway independent of IL-12 and IL-18. IL-18 may play a role in modulating the development of acute lung injury after endotoxemia but not after hemorrhage.     

Platelet-activating factor (PAF)-dependent biochemical, morphologic, and physiologic responses of human platelets: demonstration of translocation of protein kinase C associated with protein phosphorylation

Platelet-activating factor (PAF) is a potent stimulus for platelet aggregation and secretion. PAF has been shown to stimulate the phosphatidylinositol (PI) pathway in platelets, which implies that PAF should activate protein kinase C. In this study, measurements of PI metabolites, the elevation of intracellular free calcium concentration, (Ca2+)i, the activation of protein kinase C, and the phosphorylation of platelet proteins (using a two-dimensional gel electrophoretic technique) were performed before and after the addition of 10(-8) M PAF to human platelets. These findings were correlated with morphologic changes in the platelets as determined by immunoelectron microscopic studies on the cytoskeleton and by X-ray analysis of dense bodies. The results show that PAF stimulates the production of PI metabolites and causes an increase in the membrane-associated activity of protein kinase C. These changes are accompanied by a rise in the (Ca2+)i and protein phosphorylation. The increase in protein kinase C activity reaches a maximum at approximately 60 s, a time frame that is consistent with the protein phosphorylation and the subsequent morphologic and secretory events. X-ray analysis revealed two types of dense bodies containing various amounts of calcium which appeared to be released sequentially after PAF activation. These results suggest that the protein phosphorylation that controls the physiologic events resulting from PAF activation of human platelets is catalyzed by protein kinase C.     

Deduced sequence of the bovine coronavirus spike protein and identification of the internal proteolytic cleavage site

The sequence of the spike (also called peplomer or E2) protein gene of the Mebus strain of bovine coronavirus (BCV) was obtained from cDNA clones of genomic RNA. The gene sequence predicts a 150,825 mol wt apoprotein of 1363 amino acids having an N-terminal hydrophobic signal sequence of 17 amino acids, 19 potential N-linked glycosylation sites, a hydrophobic anchor sequence of approximately 17 amino acids near the C terminus, and a hydrophilic cysteine-rich C terminus of 35 amino acids. An internal Lys-Arg-Arg-Ser-Arg-Arg sequence predicts a protease cleavage site between amino acids 768 and 769 that would separate the S apoprotein into S1 and S2 segments of 85690 and 65153 mol wt, respectively. Amino terminal amino acid sequencing of the virion-derived gp 100 spike subunit confirmed the location of the predicted cleavage site, and established that gp 120 and gp 100 are the glycosylated virion forms of the S1 and S2 subunits, respectively. Sequence comparisons between BCV and the antigenically related mouse hepatitis coronavirus revealed more sequence divergence in the putative knob region of the spike protein (S1) than in the stem region (S2).     

A history of Combined-Integrated doctoral training in psychology

The history of doctoral training in psychology is reviewed, with special emphasis on the development of training models for applied psychology. Among applied psychology doctoral programs, most label themselves as being one of the three currently recognized practice areas: clinical, counseling, and school psychology; however, since the 1970s, APA also has accredited "combined" programs. The history of the development of the combined model is traced, including information from the programs themselves about the manner in which each evolved. Recently, new interest in the combined category -or Combined-Integrated (C-I) as these programs wish to become known-has emerged, and an organization representing these programs has formed. The C-I model is described, and the potential that the model may serve as a template for the future of professional training in psychology is discussed.