Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease

Epidemiological and pathogenetic evidences suggest a strong association between vascular risk factors and sporadic Alzheimer's disease (sAD). In agreement with the vascular hypothesis of AD, the role of various candidate genes for atherosclerosis has been investigated, leading to conflicting results. In order to clarify the significance of angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism in a group of patients with sAD, we conducted a case-control study including 149 cases and 149 age and sex matched controls. All subjects were genotyped for ACE and Apolipoprotein E (APOE). There were no significant differences in ACE genotype or allele frequencies between cases and controls, even after stratification for APOE4 carrier status. Our data suggest that the ACE I/D polymorphism is not associated to genetic susceptibility in sAD patients.     

Discrete and discontinuous action of brown widow spider venom on the presynaptic nerve terminals of frog muscle.

1. A study was made of the effects of the venom of the brown widow spider (Latrodectus geometricus) on end-plates of the frog sartorius muscle. 2. The increase in the frequency of the minature end-plate potentials (m.e.p.p.s), elicited by the venom in normal-"Ca2+" Ringer solution, occurs in discrete volleys having a sharp onset and end. The frequency of the m.e.p.p.s is high (up to 300 sec-1) and relatively constant during the volley. 3. The volleys recur at intervals during a period from 5 to 10 min after addition of the venom until the onset of electrical silence, up to 4 hr later. The activity occurs in groups containing volleys of loing and short duration. 4. Simultaneous intracellular and extracellular recording from single end-plates indicates that the volleys originate at highly localized areas of the nerve terminals. The high-frequency release of m.e.p.p.s in hypertonic sol solutions, which was studied for comparison purposes, occurs randomly over the entire end-plate. Volleys originating simultaneously at different sites are often superimposed in the intracellular recordings. 5. In high-"Ca2+" Ringer solution, the initial frequency of the m.e.p.p.s in a volley is comparatively higher. However, the frequency drops to one half its value in a few seconds. The volley then terminates or else the frequency of m.e.p.p.s remains high for some time and the volley has no sharp end. Activity occurs in groups containing both long and short volleys. Many more short (less than 5 sec) and long (greater than 30 sec) volleys occur in high-"Ca2+" solution than in normal-"Ca2+" solutions. 6. In low-"Ca2+", high-"Mg2+" Ringer solution, the volleys of m.e.p.p.s are fewer in number and much longer in duration. Intra- and extra-cellular recording of uninterruped activity during long periods suggests that in this solution the m.e.p.p.s originate diffusely rather than at discrete areas of the nerve terminals. 7. Implications of the above data on possible modes of action of the venom are discussed.     

Immune regulatory mechanisms influence early pathology in spinal cord injury and in spontaneous autoimmune encephalomyelitis

Injuries to the central nervous system (CNS) trigger an inflammatory reaction with potentially devastating consequences. In this report we compared the characteristics of the inflammatory response on spinal cord injury (SCI) caused by a stab wound between the T7 and T9 vertebrae and spontaneous experimental autoimmune encephalomyelitis (EAE). SCI and EAE were compared in two types of myelin basic protein Ac1-11-specific T-cell receptor transgenic mice: T/R+ mice harbor regulatory T cells, and T/R- mice lack regulatory T cells. Our results show that 8 days after SCI, T/R- mice developed a strong T-cell infiltrate in the spinal cord, with remarkable down-modulation of CD4 expression that was accompanied by a local increase in Mac-3+ and F4/80+ reactivity and diffuse local and distal astrogliosis. In contrast, T/R+ mice exhibited a modest increase in CD4+ cells localized to the site of injury, without CD4 down-modulation; focal astrogliosis was restricted to the site of the lesion, although Mac-3+ and F4/80+ cells were also present. Similarly to T/R- mice that underwent SCI, T cells displaying down-modulated CD4 expression were found in the CNS of older T/R- mice afflicted by spontaneous EAE. Overall, our results suggest that common mechanisms regulate T-cell accumulation in CNS lesions of different causes, such as mechanic lesion or autoimmune-mediated damage.     

Occupational asthma in a grain worker due to Lepidoglyphus destructor, assessed by bronchial provocation test and induced sputum

BACKGROUND: Occupational asthma (OA) can be a debilitating disease even when removal from the workplace is achieved. Today, the "gold standard" in the assessment of OA is the bronchial provocation test (BPT). Induced sputum is a non-invasive method of exploring airway inflammation which can provide additional information about such challenges and thus could be applied in OA diagnosis and monitoring. METHODS: We report the study carried out in a grain worker sensitized to Lepidoglyphus destructor (Ld), who suffered from mild asthma at the workplace. Skin prick test and specific serum IgE were measured. Ld-BPT was performed, and the changes in eosinophil rates, and ECP and tryptase levels in induced sputum were studied 30 min and 18 h after Ld-BPT. We also determined the changes in nonspecific bronchial hyperresponsiveness (NSBH), given as PD20 values. To assess the specificity of the changes, we also carried out sputum induction and methacholine challenge after barley-BPT. RESULTS: An isolated immediate response was obtained with Ld-BPT, while barley-BPT was negative. Induced sputum showed higher tryptase levels 30 min after Ld-BPT, and higher eosinophil and epithelial cell percentages and ECP levels 18 h after Ld-BPT. There was also a decrease in methacholine PD20 values after Ld-BPT. Those changes were not observed after barley-BPT. CONCLUSIONS: The study of eosinophilic and mast-cell markers in induced sputum provides additional knowledge about the inflammatory process occurring in the airways, suggesting that the study of induced sputum should be considered in the assessment of OA.     

Evaluation of a western blot method for the detection of Yersinia antibodies: evidence of serological cross-reactivity between Yersinia outer membrane proteins and Borrelia burgdorferi

Yersinia enterocolitica and Yersinia pseudotuberculosis have been identified as causative organisms of reactive arthritis in humans. We evaluated a Western blot assay which uses Yersinia outer membrane proteins as antigens for the detection of Yersinia antibodies as a replacement for the complement fixation (CF) assay. Clinical agreement, sensitivity, and specificity were determined by testing 19 positive and 21 negative serum samples by the CF assay, Western blot assay, and enzyme-linked immunosorbent assay (ELISA). The CF assay and ELISA were compared to the Western blot assay, which was the reference method used in this study. Sera with antibodies that could potentially cross-react with Yersinia were also tested by the Western blot assay. The agreement, sensitivity, and specificity of the CF method were 61%, 26%, and 95%, respectively; and those for the ELISA were 89%, 95%, and 82%, respectively. The prevalences of Yersinia antibodies in 50 healthy donors were 6% for immunoglobulin G (IgG), 2% for IgA, and 2% for IgM. Sera positive for Bartonella henselae, Brucella, Chlamydia pneumoniae, and Rickettsia rickettsii antibodies showed cross-reactivity by the Western blot assay. The highest cross-reactivity was observed with Borrelia burgdorferi; 5 of 11 (45%) specimens were cross-reactive by the IgM-specific assay. Overall, the Western blot assay performs acceptably and is more sensitive than the CF assay, warranting replacement of the CF assay in the laboratory. Due to the evidence of cross-reactivity, particularly with B. burgdorferi, which can cause an oligoarthritis similar to reactive arthritis, the diagnosis of reactive arthritis should be based on clinical findings and complete serologic analysis of the potential causative infectious pathogens.     

Comparative evaluation of the Eiken and API 20E systems and conventional methods for identification of members of the family Enterobacteriaceae

To evaluate the accuracy and utility of the Eiken Systek No. 1 (Eiken system; Eiken Chemical Co., Ltd., Tokyo, Japan), we conducted a clinical comparison, with 345 Enterobacteriaceae isolates, of the Eiken System with API 20E (Analytab Products, Inc., Plainview, N.Y.) and conventional methods. The Eiken system is a 21-biochemical-test battery tray stored at 25 degrees C and inoculated in one step. It is similar to the API 20E except that the Eiken system contains malonate, adonitol, and maltose; lacks gelatin, sucrose, melibiose, amygdalin, and arabinose; and uses reagent strips instead of liquid reagents. The API 20E and Eiken systems correctly identified 339 (97.7%) and 276 (79.5%), respectively, and misidentified 3 (0.9%) and 13 (3.7%), respectively, of the isolates. There were no identification codes for 5 (1.4%) organisms with the API 20E and 58 (16.7%) organisms with the Eiken system; of these latter unidentified organisms, 42 were identified as Proteus spp., Morganella sp., and Providencia rettgeri by conventional methods. There was no significant difference between the two rapid systems in total time required for inoculation and reading. Modifications for interpretation of decarboxylase and oxidase tests were needed for the Eiken system, and manipulation of reagent strips required considerable dexterity. However, the Eiken system was easier to inoculate than the API 20E, and, with minor increases in the data base to include more of the Proteus and Morganella spp. and P. rettgeri, the system should be reliable for identification of members of the family Enterobacteriaceae.