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Clin Cardiol. 2000 Nov;23(11):820-4.
Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope.

Takase B, Akima T, Uehata A, Katushika S, Isojima K, Satomura K, Ohsuzu F, Kurita A.

National Defense Medical College, Internal Medicine-1, Tokorozawa, Saitama, Japan.

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11097128&dopt=Abstract

Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1183-91.
Major histocompatibility complex class II polymorphisms and risk of cervical cancer and human papillomavirus infection in Brazilian women.

Maciag PC, Schlecht NF, Souza PS, Franco EL, Villa LL, Petzl-Erler ML.

Department of Genetics, Federal University of Parana, Curitiba, Brazil.

Infection with high-risk human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Environmental, behavioral, and ill-defined genetic factors also have been implicated in the pathogenesis of this disease. Associations between human leukocyte antigens (HLAs) and cervical cancer, precursor lesions, and HPV infections have been reported in several populations. To verify whether HLA-DRB1, -DQA1, and -DQB1 diversity is related to cervical cancer in the Brazilian population, 161 cases and 257 controls were HLA typed. Variants of DQA1 and DQB1 promoter regions were also typed in 92 cases and 228 controls. Polymorphism in HLA genes and promoters was distinguished by PCR-based methods, and the magnitude of associations was determined by logistic regression analysis. DRB1*15 [confounder-adjusted odds ratio (OR), 2.24; 95% confidence interval (CI), 1.29-3.90], DRB1*1503 (OR, 2.52; 95% CI, 1.16-5.48), and haplotype DRB1*15-DQB1*0602 (OR, 2.04; 95% CI, 1.15-3.61) were positively associated with cervical cancer. When we considered only DR15 haplotypes that did not carry the DQB1*0602 allele, the risk attributed to DRB1*15 more than doubled. A negative association was found between DQB1*05 and cervical cancer (OR, 0.57; 95% CI, 0.35-0.92), and similar trends were observed for DQA1*0101/04, DRB1*0101, and DRB1*1302. HPV positivity among controls was associated with DRB1*1503 (OR, 4.60; 95% CI, 1.33-15.9), DRB1*0405 (OR, 6.21; 95% CI, 1.66-23.2), and DQB1*0602 (OR, 2.48; 95% CI, 1.06-5.80). We suggest that HLA class II polymorphisms are involved in genetic susceptibility to cervical cancer and HPV infection in a Brazilian population from an area with a high incidence of this neoplasia.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11097225&dopt=Abstract

Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1263-6.
Association of Chlamydia pneumoniae immunoglobulin A seropositivity and risk of lung cancer.

Jackson LA, Wang SP, Nazar-Stewart V, Grayston JT, Vaughan TL.

Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, USA. lajac.washington.edu

Chlamydia pneumoniae is a common respiratory pathogen that has also been associated with risk for chronic diseases, including atherosclerotic cardiovascular disease. Two recent studies have reported an association between serological evidence of past infection with the organism and lung cancer. To further evaluate this association, we conducted a case-control study among a subgroup of white male smokers identified for a population-based case-control study of lung cancer in western Washington between 1993 and 1995. Serum specimens obtained at study enrollment from 143 cases and 147 controls were tested for C. pneumoniae IgG, IgM, and IgA antibodies. In multivariate analysis controlling for smoking variables and educational status, IgA antibody titer 216 was independently associated with risk of lung cancer among subjects <60 years of age [odds ratio (OR), 2.67; 95% confidence interval (CI), 1.21-5.89] but not among older subjects (OR, 0.69; 95% CI, 0.34-1.43). Among subjects <60 years of age, there was suggestive evidence of a stronger association among current smokers (OR 4.31; 95% CI, 1.36-13.68) than former smokers (OR 1.50; 95% CI, 0.48-4.75; P for interaction term, 0.26). Additional studies, including prospective serological evaluations, are needed to further assess the possible significance of this association.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11097237&dopt=Abstract

Parasitol Res. 2000 Nov;86(11):908-15.
Identification and localization of glutathione S-transferase as a potential target enzyme in Brugia species.

Rao UR, Salinas G, Mehta K, Klei TR.

Department of Microbiology and Parasitology, School of Veterinary Medicine, Louisiana State University, Baton Rouge, USA.

Brugia filarial nematodes are pathogenic lymphatic-dwelling parasites that, like other helminths, may modify the host's defense mechanisms by a major detoxification process involving glutathione-binding proteins such as glutathione S-transferases (GSTs). In the present study, soluble extracts of third-stage larvae, adult male and female worms, microfilariae of either B. pahangi or B. malayi or the adult worm excretory-secretory products of B. malayi were used to determine GST activity. These extracts and affinity-purified fractions of B. pahangi adult worms had a specific enzymatic activity when 1-chloro-2,4-dinitrobenzene was used as a substrate. The observance of this enzyme in all life cycle stages of Brugia spp. demonstrates its ubiquitous nature. Lavage of intraperitoneally infected jirds, but not that of uninfected jirds, also showed increased enzymatic activity, suggesting that GST is secreted in vivo. Soluble proteins of both Brugia spp. were strongly recognized by antibodies in sera from rabbits immunized with affinity-purified native GST of Onchocerca volvulus. Immunohistochemical studies localized these proteins in adult worms, demonstrating cross-reactivity between the GST of these two filarial nematodes. The effect of this enzyme on the motility and viability of adult worms, microfilariae, and larvae was tested in vitro using a battery of known GST inhibitors. Of all those tested, ethacrynic acid, N-ethylmalemide, 4-nitropyridine-oxide, or 1-chloro-2,4-dinitrobenzene at micromolar concentrations reduced the viability and motility of microfilariae, third-stage larvae, and adult worms. These results suggest that Brugia GSTs are major metabolic enzymes and may play an important role in the parasite's survival.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11097299&dopt=Abstract

Virchows Arch. 2000 Oct;437(4):380-7.
Impairment of genomic DNA binding to a putative dysfunctional receptor on erythrocytes independent of complement and antibodies in systemic lupus erythematosus.

Huss R, Haas C, Herrmann M, Kalden JR, Lohrs U.

Institute of Pathology, University of Munich, Germany. Ralf.Husrz.uni-muenchen.de

Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and other immune abnormalities indicative of an immunological hyperactivity. Antibodies against native DNA, however, are a disease-specific marker and play a major role in the pathogenesis of systemic or organ-specific disease manifestations. Nevertheless, the mechanisms causing the appearance of autoantibodies and immune complexes in SLE are not yet understood. Here, we report that chromosomal DNA and other forms of nucleic acids are usually cleared from circulation by binding to a yet unidentified receptor-like protein on the surface membrane of erythrocytes, independently from complement or antibodies. The binding kinetics of DNA and other nucleic acids to erythrocytes are significantly altered in SLE patients, showing an overall reduced binding capability and presaturated binding kinetics. Significant amounts of chromosomal DNA can be isolated from erythrocytes of SLE patients but not from normal controls. Electron microscopy shows electron-dense particles on the surface of SLE erythrocytes (approximate size 20-40 nm). Comparative genomic hybridization reveals that the nucleic acid isolated from erythrocytes of SLE patients is of genomic and random origin, leading to an accumulation of "free" nucleic acids in the periphery, which eventually induces a B-cell immune response.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11097363&dopt=Abstract

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