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21.
Reevaluation of a genetic model for the development of exostosis in hereditary multiple exostosis 总被引:3,自引:0,他引:3
EXT1 and EXT2 are genes that have been shown to cause hereditary multiple exostosis (HME), a syndrome marked by the formation of bony growths juxtaposed to the growth plate. These genes are members of a growing family of proteins with glycosyltransferase activity required for the synthesis of heparan sulfate chains. This protein activity is predicted to play a role in the expression of proteoglycans on the cell surface and in the extracellular matrix. We and others have previously suggested that a two-hit mutational model applies to the development of an exostosis where a germline mutation coupled with a somatic mutation results in the loss of EXT1 or EXT2 function and subsequent tumor formation. We report the direct sequencing and loss of heterozygosity (LOH) analysis of 12 exostoses from 10 HME families, 4 solitary exostoses, and their corresponding constitutional DNA. Of the 16 exostoses screened, we find only one solitary case in which two somatic mutations, a deletion and an LOH, are present. This provides limited support for the two-hit hypothesis involving the EXT1 and EXT2 genes for the development of an exostosis. Alternative models are developed based on the functional significance of EXT proteins in heparan sulfate biosynthesis. 相似文献
22.
A T-cell growth factor (TCGF) is produced by antigen- or mitogen-stimulated T
lymphocytes from the South African clawed frog Xenopus laevis. This study further
defines the physical and biological properties of this cytokine and demonstrates that
TCGF is biochemically similar to mammalian interleukin-2 (IL-2). Biologically active
TCGF eluted from SDS-PAGE displays a Mr of 16 kD and lectin-affinity chromatography
indicates that the three-dimensionmal configuration of carbohydrates on TCGF and
human IL-2 is similar. Secretion of TCGF is detectable 1 day after stimulation of
splenocytes with the T-cell mitogen phytohemagglutinin (PHA) and peaks following 2
to 3 days of stimulation. Finally, despite the biological and physical similarities between
Xenopus TCGF and mammalian IL-2, anti-human IL-2 monoclonal antibodies do not
recognize Xenopus TCGF. 相似文献
23.
Role of nitric oxide in the biology, physiology and pathophysiology of reproduction 总被引:13,自引:0,他引:13
Following its benchmark discovery, nitric oxide (NO) is nowknown to play important functional roles in a variety of physiologicalsystems. Within the vasculature, NO induces vasodilation, inhibitsplatelet aggregation, prevents neutrophil/platelet adhesionto endothelial cells, inhibits smooth muscle cell proliferationand migration, regulates programmed cell death (apoptosis) andmaintains endothelial cell barrier function. NO generated byneurons acts as a neurotransmitter, whereas NO generated bymacrophages in response to invading microbes acts as an antimicrobialagent. Because neurons, blood vessels and cells of the immunesystem are integral parts of the reproductive organs, and inview of the important functional role that NO plays in thosesystems, it is likely that NO is an important regulator of thebiology and physiology of the reproductive system. Indeed, inthe past 10 years, NO has established itself as a polyvalentmolecule which plays a decisive role in regulating multiplefunctions within the female as well as the male reproductivesystem. This review provides an overview of the role of NO invarious reproductive organs under physiological and pathologicalconditions. 相似文献
24.
Linda R. Gannon Stephen N. Haynes Jackie Cuevas Ralph Chavez 《Journal of behavioral medicine》1987,10(4):411-423
The psychophysiological correlates of induced headaches were examined. Subjects with frequent muscle-contraction headaches, frequent migraine headaches, or infrequent headaches were exposed to a 1-h cognitive stressor while multiple electromyographic and cardiovascular measures were monitored. The stressor was associated with significant changes in all psychophysiological measures. Eleven of 16 headache subjects and 2 of 8 control subjects developed headaches. Significant associations between several psychophysiological variables and headache occurrence were found and individual differences in the association between psychophysiological variables and headaches intensity were examined. The results were consistent with the hypothesized role of cardiovascular factors in the pathophysiology of muscle-contraction headache. This was the first controlled demonstration of headaches occurring as a function of environmental stressors.This research was supported by Grant 5-R01-NS-1875 from the National Institute of Health. 相似文献
25.
Sandford R; Sgotto B; Aparicio S; Brenner S; Vaudin M; Wilson RK; Chissoe S; Pepin K; Bateman A; Chothia C; Hughes J; Harris P 《Human molecular genetics》1997,6(9):1483-1489
PKD1 is the major locus of the common genetic disorder autosomal dominant
polycystic kidney disease (ADPKD). Analysis of the predicted protein
sequence of the human PKD1 gene, polycystin, shows a large molecule with a
unique arrangement of extracellular domains and multiple putative
transmembrane regions. The precise function of polycystin remains unclear
with a paucity of mutations to define key structural and functional
domains. To refine the structure of this protein we have cloned the genomic
region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA
and has greater complexity with 54 exons compared with 46 in man.
Comparative analysis of the predicted protein sequences shows a lower level
of homology than in similar studies with identity of 40 and 59% similarity.
However key structural motifs including leucine rich repeats (LRR), a
C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A
region of homology with the sea urchin REJ protein was also confirmed in
Fugu but found to extend over 1000 amino acids. Several highly conserved
intra- and extra- cellular regions, with no known sequence homologies, that
are likely to be of functional importance were detected. The likely
structure of the membrane associated region has been refined with
similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels
highlighted over part of this area. The overall protein structure has
therefore been clarified and this comparative analysis derived structure
will form the basis for the functional study of polycystin and its
individual domains.
相似文献
26.
Lam GK Liao HX Xue Y Alam SM Scearce RM Kaufman RE Sempowski GD Haynes BF 《Journal of clinical immunology》2005,25(1):41-49
CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell activation and cytokine production. Recently, an epithelial cell secreted protein, K12, was identified as a CD7 ligand. Although CD7 is expressed intrathymically, it is not known if K12 is produced in human thymus. To determine roles that K12 might play in the human thymus, we analyzed expression of K12 in human thymocytes, thymic epithelial cells (TE), and thymic fibroblasts. We found that recombinant human K12 bound strongly to soluble hCD7, with a Keq of 37.6×10–9M, and this interaction was inhibited by a novel antihuman K12 monoclonal antibody (K12-A1). K12 mRNA was detected by RT–PCR and northern analysis in human TE and thymic fibroblasts, but not in human thymocytes. Expression of K12 in TE cells was upregulated by IFN- . Taken together, these data demonstrated that K12 is produced by human TE cells and thymic fibroblasts, and is regulated in thymus by IFN- . These data suggest a role for thymic microenvironment-produced K12 in regulation of thymocyte signaling and cytokine release, particularly in the setting of thymus pathology where IFN- is upregulated such as myasthenia gravis. 相似文献
27.
Human T Lymphocyte Antigens as Defined by Monoclonal Antibodies 总被引:21,自引:0,他引:21
28.
L Binder D Smith T Kupka B Nelson B Glass M Wainscott J Haynes 《Archives of pathology & laboratory medicine》1989,113(1):73-76
A prospective observational study of 229 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. Both urine tests exhibited remarkably similar characteristics overall once they were adjusted to maximize accuracy and predictive values (occurring at a normal or abnormal "threshold," respectively, of 3.4 or 5.07 mumol/d for urobilinogen and 0 or 1+ for urine bilirubin). The percentage of cases correctly identified were 81% to 83% for serum bilirubin assays, 68% to 72% for other LFTs, but only 62% to 63% for screens for cases with at least one abnormal LFT finding. Poor sensitivities (47% to 49%) limited the detection of abnormal findings by the screen; both screens were reasonably specific (79% to 89%), but negative predictive values were suitable (89%) for serum bilirubin results only and were prohibitively lower (49% to 50%) in predicting all patients without LFT abnormalities. We conclude that spot urine urobilinogen and urine bilirubin determinations, although good screens for isolated serum bilirubin elevations, have unacceptable statistical properties as predictors of other LFT results due to a high proportion of false-negative results. 相似文献
29.
Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection
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R G Owen A P Haynes P A Evans R J Johnson A C Rawstron G McQuaker G M Smith M C Galvin D L Barnard N H Russell J A Child G J Morgan 《Journal of clinical pathology》1996,49(2):M112-M117
Aims—To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection. 相似文献
30.