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81.
82.
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
83.
Bode G Marchildon P Peacock J Brenner H Rothenbacher D 《Clinical and diagnostic laboratory immunology》2002,9(2):493-495
The prevalence of Helicobacter pylori infection in a population-based sample of 477 children (mean age plus minus standard deviation, 5.8 plus minus 0.5 years) determined by the [(13)C]urea breath test ([(13)C]UBT) was 10.7% (95% confidence interval [CI], 8.1 to 13.8%), and that determined by salivary enzyme-linked immunosorbent assay (ELISA) was 11.9% (95% CI, 9.2 to 15.2%). Compared to the [(13)C]UBT, the sensitivity and specificity of the salivary ELISA were 80.9% (95% CI, 66.3 to 90.4%) and 95.3% (95% CI, 92.7 to 97.1%), respectively. 相似文献
84.
Chaturvedi V Chu MD S Carrol BS M Brenner BS JW Nickoloff BJ 《Archives of pathology & laboratory medicine》2002,126(4):420-424
OBJECTIVE: It has been suggested that keratinocyte (KC) stem cells reside at the epicenter of a clonal population of cells. To estimate the territory or surface area covered by a single stem-cell-derived KC population in human skin, clonal skin maps were created from 3 healthy adult women and from normal skin of a psoriatic patient. DESIGN: Two hundred fifty-eight punch biopsy samples of various sizes (ranging from 2 to 8 mm in diameter) were analyzed for clonality employing X chromosome inactivation patterns at the human androgen receptor gene (HUMARA) locus. DNA was isolated and clonality established by significant decrease of either maternal or paternal X chromosome band patterns following restriction enzyme digestion, polymerase chain reaction amplification, and gel electrophoresis. RESULTS: Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35 five-mm biopsies revealed a clonal population of KCs. By contrast, in 5 different biopsies from a psoriatic patient, including 4- or 5-mm sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal population of KCs. Mantel-Haenszel chi(2) analysis revealed a P value of.001, reflecting a strong trend in probability for presence of a single clone of KCs as related to size of the biopsy sample. By sequentially analyzing 30 contiguous 2-mm biopsy samples within a given strip of skin, 10 clonal domain changes, as reflected in maternal versus paternal switches, were observed. CONCLUSIONS: These results provide direct evidence of a clonal population of KCs in normal and psoriatic lesion-free skin, and indicate that a clonal epidermal unit of KCs frequently can be detected in small biopsies (2 mm), but that in normal skin sampling, overlapping clones are apparently present in larger (ie, 4-5-mm) biopsies, producing nonclonal patterns. The clonal domain of progeny in normal skin has a rather limited territorial boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic patient, there may be clonal expansion of KCs due to perturbation in epidermopoiesis and/or stem cell distribution. 相似文献
85.
Christina T Teng Wesley Gladwell Clara Beard David Walmer Ching S Teng Robert Brenner 《Molecular human reproduction》2002,8(1):58-67
We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium. 相似文献
86.
Expression of T cell receptor delta chains in benign and malignant T lineage lymphoproliferations 总被引:4,自引:3,他引:4 下载免费PDF全文
Recent studies in both human and murine systems have demonstrated the existence of a second CD3-associated T cell receptor (the gamma delta-TCR) distinct from the alpha beta heterodimer associated with antigen recognition by classical T cells. Using a monoclonal antibody specific for the delta component of the human gamma delta-TCR, the expression of this antigen in both benign, reactive lymphoid tissues and T lineage lymphomas was studied with immunohistologic techniques. In the normal thymus, TCR-delta+ cells constituted less than 5% of the CD3+ thymocytes and were located primarily in the medulla or juxtamedullary cortex. Within the T zones of 16 histologically varied reactive peripheral lymphoid tissues, including four patients with marked predominantly paracortical hyperplasia, the authors identified from less than 1% to a maximum of 5% TCR-delta+ cells. While these results are consistent with the hypothesis that TCR-gamma delta+ cells comprise a small distinct subpopulation of peripheral T cells in humans, selective localization or recruitment of these cells could not be demonstrated in any of a number of tissues or reactive situations. Among 62 T lineage lymphomas, including 14 CD3+/TCR-beta- cases, only two TCR-delta+ neoplasms were identified, both lymphoblastic lymphomas displaying the CD3+/CD4-/CD8- phenotype known to be associated with normal TCR-gamma delta+ T cells. Because the majority of CD3+/TCR-beta- lymphomas did not display TCR-delta, these results argue against the hypothesis that the high incidence of CD3/TCR-beta discordance noted in T lineage lymphomas represents preferential transformation of the TCR-delta-expressing subset. 相似文献
87.
Brouwer AM Brenner E Smeets JB 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,143(2):198-211
We investigated what information subjects use when trying to hit moving targets. In particular, whether only visual information about the target's position is used to guide the hand to the place of interception or also information about its speed. Subjects hit targets that moved at different constant speeds and disappeared from view after varying amounts of time. This prevented the subjects from updating position information during the time that the target was invisible. Subjects hit further ahead of the disappearing point when the target moved faster, but not as much as they should have on the basis of the target's speed. This could be because more time is needed to perceive and use the correct speed than was available before the target disappeared. It could also be due to a speed-related misperception of the target's final position. The results of a second experiment were more consistent with the latter hypothesis. In a third experiment we moved the background to manipulate the perceived speed. This did not affect the hitting positions. We conclude that subjects respond only to the changing target position. Target speed influences the direction in which the hand moves indirectly, possibly via a speed-related misperception of position. 相似文献
88.
S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration 总被引:14,自引:0,他引:14
Nagy N Brenner C Markadieu N Chaboteaux C Camby I Schäfer BW Pochet R Heizmann CW Salmon I Kiss R Decaestecker C 《Laboratory investigation; a journal of technical methods and pathology》2001,81(4):599-612
It has been previously shown that S100A2 is down-regulated in tumor cells and can be considered a tumor suppressor. We have recently shown that this down-regulation can be observed particularly in epithelial tissue, where S100A2 expression decreases remarkably in tumors as compared with normal specimens. In the present paper we investigate whether S100A2 could play a tumor-suppressor role in certain epithelial tissues by acting at the cell migration level. To this end, we made use of five in vitro human head and neck squamous cell carcinoma lines in which we characterized S100A2 expression at both RNA and protein level. To characterize the influence of S100A2 on cell kinetic and cell motility features, we used two complementary approaches involving specific antisense oligonucleotides and the addition of S100A2 to the culture media. The different expression analyses gave a coherent demonstration of the fact that the FADU and the RPMI-2650 cell lines exhibit high and low levels of S100A2 expression, respectively. Antisense oligonucleotides (in FADU) and extracellular treatments (in RPMI) showed that, for these two models, S100A2 had a clear inhibitory influence on cell motility while modifying the cell kinetic parameters only slightly. These effects seem to be related, at least in part, to a modification in the polymerization/depolymerization dynamics of the actin microfilamentary cytoskeleton. Furthermore, we found evidence of the presence of the receptor for advanced glycation end-products (RAGE) in RPMI cells, which may act as a receptor for extracellular S100A2. The present study therefore presents experimentally based evidence showing that S100A2 could play a tumor-suppressor role in certain epithelial tissues by restraining cell migration features, at least in the case of head and neck squamous cell carcinomas. 相似文献
89.
Transport of molecules across renal glomerular capillaries 总被引:7,自引:0,他引:7
90.
Quantitative assessment of proximal tubule function in single nephrons of the rat kidney 总被引:7,自引:0,他引:7
B M Brenner T M Daugharty I F Ueki J L Troy 《The American journal of physiology》1971,220(6):2058-2067