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31.
32.
Wenge Lu Steven H. Seeholzer Mingda Han Anne‐Sophie Arnold Maria Serrano Barbara Garita Nancy J. Philp Cassandra Farthing Peter Steele Jizhen Chen Kersti K. Linask 《Developmental dynamics》2008,237(12):3577-3590
Flectin, a protein previously described to be expressed in a left‐dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC‐II) protein class. During looping, both NMHC‐IIA and NMHC‐IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC‐IIB, rather than NMHC‐IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full‐length human NMHC‐IIA and ‐IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC‐IIB antibody does not. Abnormally looping hearts of the NodalΔ 600 homozygous mouse embryos show decreased NMHC‐IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC‐II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577–3590, 2008. © 2008 Wiley‐Liss, Inc. 相似文献
33.
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
34.
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
35.
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
36.
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
37.
Induction of a differentiated ciliated cell phenotype in primary cultures of Fallopian tube epithelium 总被引:5,自引:1,他引:5
Human Fallopian tubal epithelial cells in culture lose morphological
features associated with the epithelium in situ and the extent to which
they retain their in-vivo phenotype or function is unknown. In order to
address this question, immunocytochemical markers were identified which
distinguish secretory (HMFG2+, LhS28-) from ciliated (HMFG2-, LhS28+)
epithelial cells in tissue sections of Fallopian tube. These markers were
used to analyse the phenotype of tubal cells in vitro. Primary cultures of
human tubal epithelial cells were seeded onto glass and grown to confluence
before addition of oestradiol-17beta. In the absence of hormone, tubal
epithelial cells expressed cytokeratins and nuclear receptors for oestrogen
and progesterone and adopted a homogeneous (HMFG2+, LhS28-) secretory cell
phenotype. Following the addition of oestradiol-17beta, a proportion of
cells became positive for LhS28. The induction of a ciliated epithelial
cell phenotype was confirmed by scanning electron microscopy, where on
permeable collagen membranes, approximately one-third of tubal epithelial
cells became ciliated in the presence of oestradiol-17beta. We suggest that
in vitro, tubal epithelial cells adopt an immature secretory-like phenotype
and that oestrogen can induce differentiation to a ciliated epithelial cell
phenotype.
相似文献
38.
Montero R Serrano L Dávila V Segura Y Arrieta A Fuentes R Abad I Valencia L Sierra P Camacho R 《Environmental and molecular mutagenesis》2003,42(3):216-222
Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed. 相似文献
39.
Sierra B Serrano N Larrañaga P Plasencia EJ Inza I Jiménez JJ Revuelta P Mora ML 《Artificial intelligence in medicine》2001,22(3):233-248
Combining the predictions of a set of classifiers has shown to be an effective way to create composite classifiers that are more accurate than any of the component classifiers. There are many methods for combining the predictions given by component classifiers. We introduce a new method that combine a number of component classifiers using a Bayesian network as a classifier system given the component classifiers predictions. Component classifiers are standard machine learning classification algorithms, and the Bayesian network structure is learned using a genetic algorithm that searches for the structure that maximises the classification accuracy given the predictions of the component classifiers. Experimental results have been obtained on a datafile of cases containing information about ICU patients at Canary Islands University Hospital. The accuracy obtained using the presented new approach statistically improve those obtained using standard machine learning methods. 相似文献
40.
Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis 总被引:2,自引:0,他引:2
Redondo M García J Villar E Rodrigo I Perea-Milla E Serrano A Morell M 《Human pathology》2003,34(12):1283-1289
Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens. 相似文献