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991.
Denise D. Belsham Fred Pereira Cheryl R. Greenberg Shutsung Liao Klaus Wrogemann 《Human mutation》1995,5(1):28-33
A large Manitoba Hutterite kindred with X-linked receptor negative complete androgen insensitivity syndrome (CAIS) was studied. In attempts to identify all carriers of the syndrome in this kindred, using the androgen receptor (AR) cDNA, we have found a novel diagnostic Mspl polymorphic pattern, which cosegregates with the disease. This polymorphism was not detected in 79 unrelated X-chromosomes of which 22 were from Hutterite controls. We were able to localize the polymorphism to exon 4, which is known to encode part of the androgen receptor hormone binding domain. A single base substitution (T→C) was detected, which creates a new Mspl site. This novel transition mutation replaces Leu-676 with Pro at a site which is conserved in numerous members of the steroid receptor gene family. Sequencing all 8 exons of the AR revealed the Leu-676→Pro mutation as the only change in the primary structure of the receptor. Transfection of COS-l cells with an expression vector of the mutant AR demonstrates that this point mutation of nucleotide 2558 abolishes receptor binding activity. The mutation can easily be detected by MspI digestion of the polymerase chain reaction (PCR) amplified exon 4 product.© 1995 wiley-Liss, Inc. 相似文献
992.
Activation and proliferation signals in mouse B cells. V.A. comparison of the effects of intact (IgG) and F (ab')2 anti-mu or anti-delta antibodies. 总被引:1,自引:0,他引:1
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This study compares the effects of soluble intact (IgG) and F(ab')2 rabbit anti-mu and anti-delta antibodies on mouse B cells. The results show that while the F(ab')2 antibodies to both isotypes induce polyclonal B cell proliferation, the IgG antibodies are not mitogenic, but rather inhibit DNA synthesis induced by the homologous F(ab')2 fragments. Furthermore, intact anti-mu antibodies inhibit mitogenesis induced by F(ab')2 anti-delta, and vice versa. However, the intact antibodies to both isotypes promote early changes characteristic of B-cell activation, namely, increased Ia antigen expression, and priming for a facilitated proliferative response to F(ab')2 anti-Ig. In addition, F(ab')2 anti-mu and anti-delta both induce the breakdown of phosphatidylinositol phospholipids in B cells, an early consequence of Ig receptor cross-linking which may be involved in the induction of cell growth. These results therefore indicate that stimulating mature B cells via IgM or IgD receptors produces indistinguishable early effects, and that cross-linking Fc and surface Ig receptors by intact anti-Ig generates a dominant inhibitory signal, regardless of which isotype is involved. 相似文献
993.
994.
The effect of low external Na+ concentrations on the light-induced K+ release from crayfish photoreceptor cells was tested by labelling intracellular K+ with the isotope86Rb. The amount of isotope released per light stimulus is roughly proportional to the external Na+ concentration if the osmolarity is kept constant by replacing Na+ with Tris, choline or sucrose. When sucrose is used to replace the depleted Na+ the light-induced K+ release is a linear function of the external Na+ concentration and is reduced by approx. 95% at an external Na+ concentration of 5 mmol/l. For choline and Tris substitutions the relationships are less clear but at Na+ concentrations 56 mmol/l it seems that in comparison with sucrose the light-induced K+ release is smaller in a Tris solution and larger in a choline solution. It is suggested that the light-induced K+ release is due mainly to an activation of voltage sensitive K+ channels. 相似文献
995.
Thomas M Morgan Lan Xiao Patrick Lyons Bethany Kassebaum Harlan M Krumholz John A Spertus 《BMC medical genetics》2008,9(1):66
Background
Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown. 相似文献996.
Lee J Lee EN Kim EY Park HJ Chang CY Jung DY Choi SY Lee SK Lee KW Kwon GY Joh JW Kim SJ 《Immunology letters》2005,101(2):210-216
4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2mg of TNBS in 35% ethanol using a vinyl catheter positioned 4cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-gamma) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4(+)CD25(+) T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-gamma and proportion of CD8(+) T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4(+)CD25(+) regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD. 相似文献
997.
Muscle-type phosphofructokinase deficiency (PFKD) causes a hemolytic disorder and exertional myopathy in humans and dogs.
In humans, PFKD is accompanied by a disturbed calcium homeostasis and associated adenine nucleotide dysregulation, which may
potentiate the erythroenzymopathy associated with this inherited disorder. This study shows that canine PFKD also manifests
these erythrocyte abnormalities. Compared to normal, healthy red cells, PFK-deficient erythrocytes contain lower concentrations
of ATP and higher concentrations of IMP and calcium, the latter as per a calcium indicator dye. Adenosine monophosphate deaminase
(AMPD) enriched 5000-fold from canine erythrocytes adsorbs to immobilized calcium–calmodulin and the interaction between these
two proteins activates AMPD through a K
mapp effect. This behavior is similar to that of the human erythrocyte enzyme and provides a potential contributing mechanism
for accelerated adenine nucleotide turnover in canine PFKD. We propose that adenine nucleotide replacement strategies could
benefit the erythroenzymopathy in human and canine PFKD and that the dog model of this disorder is an appropriate vehicle
for further elucidating this hypothesis. 相似文献
998.
To examine the role that lipopolysaccharide (LPS)-like molecules from the filarial intracellular endobacteria Wolbachia might play in the development of filarial infections, a natural infection in the LPS-nonresponsive C3H/HeJ mouse strain was compared to that of the LPS-responsive C3H/HeN mouse strain. C3H/HeN mice have been shown to be susceptible to the rodent filarial nematode Litomosoides sigmodontis, with the development of adult worms including females containing mature microfilariae (first stage larvae) in the uterine tubes. However, free microfilariae are not detected. In this study the worm burden and worm length were not significantly different between the C3H/HeN and C3H/HeJ mice. However, the fertility of worms from CeH/HeJ mice was found to be higher than those from C3H/HeN mice. Significantly, mature microfilariae were found at the site of infection only in C3H/HeJ mice. These results indicate a role for TLR4 signaling in the immune response that inhibits worm embryogenesis and prevents the release of microfilariae or directly kills released microfilariae. 相似文献
999.
Kee HJ Shin JH Chang J Chung KY Shin DH Kim YS Kim SK Kim SK 《Yonsei medical journal》2003,44(1):65-74
Small cell lung cancer (SCLC) frequently shows a loss of heterozygosity (LOH) on chromosome 15q. In order to define the commonly affected region on chromosome 15q, we tested 23 primary SCLCs by microsatellite analysis. By analyzing 43 polymorphic microsatellite markers located on chromosome 15q, we found that 14 (60.8%) of 23 tumors exhibited a LOH in at least one of the tested microsatellite markers. Two (14.3%) of the 14 tumors were found to have more than a 50% LOH on chromosome 15q. LOH was observed in five commonly deleted regions on 15q. Of those regions, LOH from D15S1012 to D15S1016 was the most frequent (47.8%). LOH was also observed in more than 20-30% of tumors at four other regions, from D15S1031 to D15S1007, from D15S643 to D15S980, from D15S979 to D15S202, and from D15S652 to D15S642. Four of the 23 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.2% (29 of 914) of the loci tested. Our data suggests the presence of at least five tumor suppressor loci on chromosome 15q in SCLC, and further that these may play an important role in SCLC tumorigenesis. 相似文献
1000.
Elisabeth Ralfkiaer Klaus Hou-Jensen Kevin C. Gatter Krzysztof T. Drzewiecki David Y. Mason 《Virchows Archiv : an international journal of pathology》1987,410(4):355-361
Summary The immunological phenotypes of the lymphoid cells in 39 cutaneous malignant melanomas have been investigated by staining cryostat sections with a panel of 20 monoclonal antibodies against lymphoid cells and their subsets. Staining was performed by the alkaline phosphatase: anti-alkaline phosphatase (APAAP) method in which the substrate label (red) is easily distinguishable from melanin. The lymphoid infiltrates had an essentially identical composition in all cases, consisting of T-lymphocytes associated with both Langerhans cells and HLA-DR-positive tissue macrophages. B-lymphocytes and natural killer cells were either absent or only present in low numbers. The ratio between T8 (suppressor/cytotoxic) and T4 (helper/inducer) lymphocytes varied and showed no correlation with melanoma subtype, level of invasion or magnitude of lymphocytic response. Examination for markers associated with T-cell activation and/or with cell proliferation revealed that all lesions contained HLA-DR-positive T-lymphocytes, whereas expression of the transferrin receptor and the interleukin-2 receptor (Tac-antigen) occurred mainly in melanomas with a significant inflammatory infiltrate. These data support the concept that malignant melanomas are capable of evoking autologous T-cell immune reactions. 相似文献