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排序方式: 共有732条查询结果,搜索用时 0 毫秒
21.
Hiroyuki Isayama Yousuke Nakai MD PhD Yoshihide Toyokawa MT Osamu Togawa MD Chimyon Gon MT Yukiko Ito MD Yoko Yashima MD Hiroshi Yagioka MD Hirofumi Kogure MD Takashi Sasaki MD Toshihiko Arizumi MD Saburo Matsubara MD Natsuyo Yamamoto MD PhD Naoki Sasahira MD PhD Kenji Hirano MD PhD Takeshi Tsujino MD PhD Nobuo Toda MD PhD Minoru Tada MD PhD Takao Kawabe MD PhD Masao Omata MD PhD 《Gastrointestinal endoscopy》2009,70(1):37-44
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23.
Baron PL Bianchi R Livraghi S Bussini S Bava L Scarpini E Conti G Scarlato G Tacconi MT Oggioni N Petruccioli Mg Cavaletti G Tredici G. 《Journal of the peripheral nervous system : JPNS》2001,6(1):40-41
Experimental lead intoxication is an important model for the study of cellular and molecular mechanisms of segmental demyelination in peripheral nerve. In this report we have compared pathological changes with the molecular and immunohistochemical expression of the proteins of compact and non-compact myelin in the demyelinating neuropathy induced in Sprague-Dawley rats after chronic administration (3 and 6 months) of lead acetate in drinking water. All the rats underwent the neurophysiological determination of the conduction velocity in the tail nerve at baseline and 3, 4.5 and 6 months after the beginning of the lead acetate administration. At the end of the treatment period the rats were sacrificed and sciatic nerve specimens were obtained. The neurophysiological study demonstrated a significant decrease in the nerve conduction velocity, which was already evident at the first determination (3 months) and persisted along the entire experiment. The neurophysiological results were in agreement with the pathological observations performed in the sciatic nerve, where several large demyelinated fibers were observed in the lead-intoxicated rats. Northern and Western blot analysis demonstrated that steady state mRNA and protein levels for P0, MBP, PMP22 and PLP were not changed comparing treated and control rats. Immunohistochemistry on teased fibers revealed that those proteins were distributed in areas of compact myelin along the internodes. In control fibers, as expected, MAG was found in the periaxonal cytoplasm, at nodes of Ranvier, and in the Schmidt-Lanterman incisures. In lead neuropathy, MAG was still limited to discrete regions, but the intensity of staining was reduced, in accordance with changes of paranodal structures. Immunohistochemical localization of other proteins of non-compacted myelin, including connexin-32, E-cadherin and β-catenin was also examined. Our data further suggest that chronic lead intoxication in the rat produces segmental demyelination due primarily to Schwann cell dysfunction. 相似文献
24.
Lucie MT Byrne-Davis Peter Salmon Katja Gravenhorst Tim OB Eden Bridget Young 《BMC medical research methodology》2010,10(1):101
Background
High accrual to clinical trials enables new treatment strategies to be tested rapidly, accurately and with generalisability. Ethical standards also must be high so that participation is voluntary and informed. However, this can be difficult to achieve in trials with complex designs and in those which are closely embedded in clinical practice. Optimal recruitment requires a balance of both ethical and accrual considerations. In the context of a trial of stratified treatments for children with acute lymphoblastic leukaemia (UKALL2003) we examined how recruitment looked to an observer and how it felt to the parents, to identify how doctors' communication could promote or inhibit optimal recruitment. 相似文献25.
Paul JM Savelkoul Fabrizio De Mattia Yuedan Li Erik‐Jan Kamsteeg Irene BM Konings Peter van der Sluijs Peter MT Deen 《Human mutation》2009,30(10):E891-E903
Vasopressin regulates human water homeostasis by re‐distributing homotetrameric aquaporin‐2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells, a process in which phosphorylation of AQP2 at S256 by cAMP‐dependent protein kinase A (PKA) is thought to be essential. Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by AQP2 gene mutations. Here, we investigated a reported patient case of dominant NDI caused by a novel p.R254Q mutation. Expressed in oocytes, AQP2‐p.R254Q appeared to be a functional water channel, but was impaired in its transport to the cell surface to the same degree as AQP2‐p.S256A, which mimics non‐phosphorylated AQP2. In polarized MDCK cells, AQP2‐p.R254Q was retained and was distributed similarly to that of unstimulated wt‐AQP2 or AQP2‐p.S256A. Upon co‐expression, AQP2‐p.R254Q interacted with, and retained wt‐AQP2 in intracellular vesicles. In contrast to wild‐type AQP2, forskolin did not increase AQP2‐p.R254Q phosphorylation at S256 or its translocation to the apical membrane. Mimicking constitutive phosphorylation in AQP2‐p.R254Q with the p.S256D mutation, however, rescued its apical membrane expression. These date indicate that a lack of S256 phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a loss of function instead of a gain of function mutation in dominant NDI. © 2009 Wiley‐Liss, Inc. 相似文献
26.
27.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
28.
Dongari-Bagtzoglou AI; Warren WD; Berton MT; Ebersole JL 《International immunology》1997,9(9):1233-1241
CD40, a member of the tumor necrosis factor-alpha receptor family, is
constitutively expressed by cells of hematopoietic and non- hematopoietic
origin, including fibroblasts. Signaling through this receptor molecule
regulates inflammatory cytokine secretion by many cell types. Based on the
recently described cytokine secretory heterogeneity of fibroblast cell
subsets, we hypothesized that secretion of inflammatory cytokines by
gingival fibroblast cultures may be dictated by the existence of
differential proportions of cytokine- secreting subpopulations which
express high levels of CD40. After examining a large number of gingival
fibroblast (GF) cultures we find that the frequency of IL-6- and
IL-8-secreting cells mirrors the frequency of cells expressing high levels
of CD40 in these cultures. In addition, we demonstrate a direct functional
relationship between CD40 expression and IL-6 or IL-8 secretion by showing
that ligation of this molecule on GF, and CD40+ fibroblast subsets in
particular, up- regulates secretion of these cytokines in vitro.
相似文献
29.
Kim YH; de Kretser DM; Temple-Smith PD; Hearn MT; McFarlane JR 《Molecular human reproduction》1997,3(4):307-313
Using mechanical and chemical dissection methods, fibrous sheath was
isolated both from normal ejaculated human spermatozoa and from rabbit
cauda epididymal spermatozoa. The same techniques did not produce a pure
preparation of fibrous sheath from ejaculated rabbit spermatozoa,
suggesting that further cross-linking and stabilization of sperm structures
occurs in response to components of the seminal plasma. The isolation
procedures were monitored by phase contrast microscopy and the purity of
the fibrous sheath was verified by electron microscopy. Sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human
fibrous sheath revealed at least 14 protein bands of which the most
intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5
kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which
the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid
composition of the purified fibrous sheath from human and rabbit
spermatozoa was similar, being high in aspartic acid and/or asparagine and
glutamic acid and/or glutamine, serine, alanine, leucine, lysine and
glycine, but low in histidine, tyrosine and isoleucine. This composition is
similar to that reported for the rat and suggests that mammalian sperm tail
fibrous sheaths are composed of similar types of proteins, although there
are apparent differences in protein components between species.
相似文献
30.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献