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31.
Tezak Z Prandini P Boscaro M Marin A Devaney J Marino M Fanin M Trevisan CP Park J Tyson W Finkel R Garcia C Angelini C Hoffman EP Pegoraro E 《Human mutation》2003,21(2):103-111
Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients. 相似文献
32.
Role of surface-exposed loops of Haemophilus influenzae protein P2 in the mitogen-activated protein kinase cascade 下载免费PDF全文
Galdiero S Capasso D Vitiello M D'Isanto M Pedone C Galdiero M 《Infection and immunity》2003,71(5):2798-2809
The outer membrane of gram-negative bacteria contains several proteins, and some of these proteins, the porins, have numerous biological functions in the interaction with the host; porins are involved in the activation of signal transduction pathways and, in particular, in the activation of the Raf/MEK1-MEK2/mitogen-activated protein kinase (MAPK) cascade. The P2 porin is the most abundant outer membrane protein of Haemophilus influenzae type b. A three-dimensional structural model for P2 was constructed based on the crystal structures of Klebsiella pneumoniae OmpK36 and Escherichia coli PhoE and OmpF. The protein was readily assembled into the beta-barrel fold characteristic of porins, despite the low sequence identity with the template proteins. The model provides information on the structural features of P2 and insights relevant for prediction of domains corresponding to surface-exposed loops, which could be involved in the activation of signal transduction pathways. To identify the role of surface-exposed loops, a set of synthetic peptides were synthesized according to the proposed model and were assayed for MEK1-MEK2/MAPK pathway activation. Our results show that synthetic peptides corresponding to surface loops of protein P2 are able to activate the MEK1-MEK2/MAPK pathways like the entire protein, while peptides modeled on internal beta strands are unable to induce significant phosphorylation of the MEK1-MEK2/MAPK pathways. In particular, the peptides corresponding to loops L5 (Lys206 to Gly219), L6B (Ser239 to Lys253), and L7 (Thr280 to Lys287) activate, as the whole protein, essentially JNK and p38. 相似文献
33.
Licastro F Grimaldi LM Bonafè M Martina C Olivieri F Cavallone L Giovanietti S Masliah E Franceschi C 《Neurobiology of aging》2003,24(7):921-926
Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The -174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the -174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the -174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine. 相似文献
34.
James L. Kennedy Elizabeth A. Billett Fabio M. Macciardi Massimiliano Verga Thomas J. Parsons Herbert Y. Meltzer Jeffery Lieberman Janet A. Buchanan 《American journal of medical genetics. Part A》1995,60(6):558-562
Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. © 1995 Wiley-Liss, Inc. 相似文献
35.
Summary Basing our study on serial cuts and dissections, we have analysed the various techniques for puncture and injection in the region of the shoulder, the scapulohumeral and acromioclavicular joints, the subdeltoid bursa, the peri-articular muscles and tendons and the suprascapular nerve.
Bases anatomiques des ponctions et injections de l'épaule
Résumé A partir de coupes sériées et de dissections les auteurs étudient les différentes techniques de ponctions et injections pratiquées au niveau de la région de l'épaule, articulations scapulo-humérale et acromio-claviculaire, bourse sous-deltoïdienne, tendons des muscles péri-articulaires et nerf sus-scapulaire.相似文献
36.
Long-term protective immune response elicited by vaccination with an expression genomic library of Toxoplasma gondii 总被引:2,自引:0,他引:2 下载免费PDF全文
Fachado A Rodriguez A Molina J Silvério JC Marino AP Pinto LM Angel SO Infante JF Traub-Cseko Y Amendoeira RR Lannes-Vieira J 《Infection and immunity》2003,71(9):5407-5411
Immunization of BALB/c mice with an expression genomic library of Toxoplasma gondii induces a Th1-type immune response, with recognition of several T. gondii proteins (21 to 117 kDa) and long-term protective immunity against a lethal challenge. These results support further investigations to achieve a multicomponent anti-T. gondii DNA vaccine. 相似文献
37.
38.
V Di Marino M Argème Ch Brunet R Coppens J Bonnoit 《Surgical and radiologic anatomy : SRA》1987,9(1):51-62
Summary The dissection of. 48 cadaveric specimens has been compared with operative findings for a review of the shape, size and site of this gland in the adult. The structure of the thymic compartment and the relations of the thymus, particularly with the vessels of the superior mediastinum and the base of the neck, were studied. The relative positions of the inferior parathyroid glands and the thymus were identified, with respect to the influence of this topography on the surgery of these glands. The arterial suply to the thymus, which is still very abundant in the adult, presupposes a functional organ whose physiologic involution is slow.
Etude macroscopique du thymus de l'adulte
Résumé La dissection de 48 pièces cadavériques, confrontée à des données opératoires, permet de rappeler la forme, la taille et la situation de cette glande chez l'adulte. La constitution de la loge thymique puis les rapports du thymus avec, en particulier, les vaisseaux du médiastin supérieur et la base du cou sont étudiés. Les positions respectives des glandes parathyroïdes inférieures et du thymus avec l'incidence de cette topographie dans la chirurgie de ces glandes, sont précisées. La vascularisation artérielle de la glande, encore très riche chez l'adulte est en faveur d'un organe fonctionnel dont l'involution physiologique est lente.相似文献
39.
Serodiagnosis of leprosy: relationships between antibodies to Mycobacterium leprae phenolic glycolipid I and protein antigens. 总被引:9,自引:0,他引:9 下载免费PDF全文
W R Levis H C Meeker G B Schuller-Levis T P Gillis L J Marino Jr J Zabriskie 《Journal of clinical microbiology》1986,24(6):917-921
Sera from leprosy patients and controls were assayed for immunoglobulin M (IgM) and IgG antibodies to the Mycobacterium leprae-specific phenolic glycolipid I antigen (PG) by enzyme-linked immunosorbent assay, for IgG antibodies to M. leprae protein antigens by Western immunoblot, and for antibodies to a 65-kilodalton (kDa) protein antigen of M. leprae by a competition antibody binding assay. Elevated levels of anti-PG IgM were seen in lepromatous and borderline lepromatous patients, and elevated levels of anti-PG IgG were seen in borderline lepromatous patients. There was a significant correlation between the bacillary index (BI) and anti-PG IgM whether all leprosy patients or only multibacillary patients were analyzed. A significant correlation was seen between anti-PG IgG and BI when all leprosy patients were used for analysis, but not when only multibacillary patients were used. IgG antibodies to protein antigens of M. leprae, as detected by Western immunoblot, were more prevalent in lepromatous and borderline lepromatous patients than in borderline tuberculoid patients, while one of eight controls showed one weak band. There were significant correlations between the number of M. leprae protein antigens detected by the sera of patients and both BI and the level of anti-PG IgM. The 65-kDa competition antibody binding assay detected active multibacillary leprosy. Patients positive for antibody to the 65-kDa antigen had a significantly higher BI and levels of anti-PG IgM and anti-PG IgG than did patients that were negative. In addition, the level of antibody to the 65-kDa antigen correlated with both the BI and anti-PG IgM. We conclude that testing for antibodies to protein antigens of M. leprae may provide a useful adjunct to testing for antibodies to PG. 相似文献
40.
Murray HW Jungbluth A Ritter E Montelibano C Marino MW 《Infection and immunity》2000,68(11):6289-6293
Tumor necrosis factor (TNF)-deficient mice were challenged with Leishmania donovani to characterize TNF in the response of visceral intracellular infection to antileishmanial chemotherapy. In wild-type controls (i) liver infection peaked at week 2 and resolved, (ii) discrete liver granulomas developed at weeks 2 to 4 and involuted, and (iii) leishmanicidal responses to antimony (Sb), amphotericin B (AmB), and miltefosine were intact. In TNF knockout (KO) mice (i) initial liver infection was unrestrained, plateaued, and then declined somewhat by week 6, (ii) an absent early granulomatous reaction abruptly accelerated with striking tissue inflammation, widespread hepatic necrosis, and 100% mortality by week 10, and (iii) while the initial response to AmB and miltefosine was intact, killing induced by Sb therapy was reduced by >50%. Although initial AmB treatment during weeks 2 to 3 killed 98% of liver parasites, 75% of AmB-treated KO mice subsequently relapsed and died by week 12; however, additional maintenance AmB preserved long-term survival. These results for a model of visceral infection indicate that endogenous TNF is required early on to control intracellular L. donovani, support granuloma development, and mediate optimal initial effects of Sb and prevent relapse after ordinarily curative AmB treatment. A compensatory, TNF-independent antileishmanial mechanism developed in TNF KO mice; however, its effect was uncontrolled fatal inflammation. Chemotherapeutic elimination of the parasite stimulus reversed the hyperinflammatory response and preserved survival. 相似文献