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排序方式: 共有915条查询结果,搜索用时 15 毫秒
41.
As a candidate for active vitamin D analogs that have selective effects on bone, 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) has been synthesized and is currently under clinical trials. In ovariectomized rat model for osteoporosis, ED-71 caused an increase bone mass at the lumbar vertebra to a greater extent than 1alpha-hydroxyvitamin D3 (alfacalcidol), while enhancing calcium absorption and decreasing serum parathyroid hormone levels to the same degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters of bone resorption more potently than alfacalcidol, while maintaining bone formation markers.An early phase II clinical trial was conducted with 109 primary osteoporotic patients. The results indicate that oral daily administration of ED-71 (0.25, 0.5, 0.75, and 1.0 microgram) for 6 months increased lumbar bone mineral density in a dose-dependent manner without causing hypercalcemia and hypercalciuria. ED-71 also exhibited a dose-dependent suppression of urinary deoxypyridinoline with no significant reduction in serum osteocalcin. These results demonstrate that ED-71 has preferential effects on bone with diminished effects on intestinal calcium absorption. ED-71 offers potentially a new modality of therapy for osteoporosis with selective effects on bone. 相似文献
42.
(20S)-[7,7,21,21-2H(4)]-3beta-(tert-Butyldimethylsilanyloxy)-20-methyl-pregn-5-en-21-ol, an intermediate for the preparation of deuterated isotopomers of sterols to be used as standards for biomedical studies, was prepared by reduction with dichloroaluminum deuteride of ethyl (20S)-3beta-(tert-butyldimethylsilanyloxy)-7-oxo-pregn-5-en-20-carboxylate. Using controlled experimental conditions, it has also been shown that the dichloroaluminum hydride reduction of a 7-keto steroid affords the corresponding 7beta-hydroxy derivative in a highly stereoselective manner. 相似文献
43.
44.
Brady MS Lee F Petrie H Eckels DD Lee JS 《Cancer immunology, immunotherapy : CII》2000,48(11):621-626
Purpose: Most melanoma cell lines express HLA class II antigens constitutively or can be induced to do so with interferon γ (IFNγ).
We have previously demonstrated that peptide-specific CD4+ T cells proliferate in response to HLA-class-II-antigen-mediated peptide presentation by melanoma cells in vitro and produce
interleukin-10 (IL-10) and (IFNγ). We asked whether the responding T cells kill the tumor cells and, if so, whether direct
cell contact was required. Methods: Two HLA class II+ melanoma cell lines derived from metastases were co-cultured with a human CD4+ T cell clone specific for influenza hemagglutinin peptide (HA). T cells, melanoma, and HA were co-cultured for 48 h. Melanoma
cells with and without HA and/or T cells served as controls. After 36 h, the medium was removed for cytokine analysis by enzyme-linked
immunosorbent assay (ELISA). Twelve hours later non-adherent cells were washed away and the adherent melanoma cells were trypsinized
and counted. Dual-chamber culture plates were used to determine whether cell contact and/or exposure to cytokine were required
for tumor cell death. Results: Melanoma cell counts were over 80% lower in wells containing T cells than in wells with melanoma and peptide alone (P < 0.05). ELISA of supernatants revealed production of IFNγ and IL-10 by the responding T cells. Direct T cell contact with
tumor cells was not required for tumor cell death, as melanoma cells were killed when they shared medium but had no contact
with T cells responding to peptide presentation by HLA-class-II-antigen-positive melanoma cells in a separate chamber. Blocking
antibody to IFNγ but not IL-10 prevented melanoma cell death at levels of cytokine similar to that present in co-culture assays.
Conclusions: Peptide-specific CD4+ T cells kill melanoma cells in vitro when they recognize peptide presented by the tumor cell in the context of HLA class
II antigen. Direct cell contact is not required, suggesting that it is a cytokine-mediated event. Immunotherapy, using primed
CD4+ T cells and peptide, may be beneficial in patients whose tumors express HLA class II antigens or can be induced to do so
with IFNγ.
Received: 1 July 1999 / Accepted: 17 September 1999 相似文献
45.
Genetic mapping of ossification of the posterior longitudinal ligament of the spine. 总被引:11,自引:0,他引:11 下载免费PDF全文
H Koga T Sakou E Taketomi K Hayashi T Numasawa S Harata K Yone S Matsunaga B Otterud I Inoue M Leppert 《American journal of human genetics》1998,62(6):1460-1467
Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1. 9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provided by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P = .000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P = .0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p. 相似文献
46.
A new method will be presented which allows the perception of body odors in humans to be studied objectively. The analysis
of body odor‐evoked potentials was used to investigate if and how the human brain is able to differentiate self from non‐self
body odor for the first time. Six subjects (three females) participated in two experimental sessions. In each session, two
body odors (axillary hair) were presented within an olfactory oddball paradigm. One of the odors was collected from the subject
and the other from an odor donor of the same sex. In the first session the subjects' attention was distracted to a secondary
task (passive paradigm), in the second session the subjects were asked to actively differentiate the odors (active paradigm).
For the EEG recordings the odors were presented within a constantly flowing airstream. The results show that the subjects
could hardly differentiate the body odors subjectively. However, it could be demonstrated that the central nervous processing
of one's own odor was faster than the processing of the chemosensory non‐self signal. Moreover, in the active paradigm, the
potentials appeared to be larger when the subjects perceived their own body odor. The conclusion is reached that the measurement
of chemosensory event‐related potentials (CSERP) is the method of choice for the investigation of HLA‐associated body odors.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
47.
A yeast artificial chromosome (YAC) contig from the C57BL/6 (H2
b
) mouse was created from the major histocompatibility complex (Mhc, H2 in mouse) class Ib subregion, H2-M. It spans approximately 1.2 megabase (Mb) pairs and unites the previous >1.5-Mb YAC contigs (Jones et al. 1995) into a single
contig, which includes 21 Mhc class I genes distal to H2-T1. A bacterial artificial chromosome (BAC) contig from the 129 (H2
bc
) mouse, spanning approximately 600 kilobases, was also built from Znf173 (Afp, a gene for acid finger protein), through Tctex5 (t-complex testis expressed-5) and Mog (myelin oligodendrocyte glycoprotein), to H2-M2. Twenty-four sequence-tagged site (STS) markers were newly developed, and 35 markers were mapped in the YAC/BAC contigs,
which define the marker order as Cen –Znf173–Tctex5 – Mog–D17Tu42–D17Mit232–H2-M3–D17Leh525–H2-M2– Tel. The gene order of Znf173 – Tctex5 – Mog – D17Tu42 is conserved between mouse and human, showing that the middle H2-M region corresponds to the subregion of the human Mhc surrounding HLA-A.
Received: 25 July 1997 / Revised: 10 September 1997 相似文献
48.
Sequence variation at the major histocompatibility complex DRB loci in beluga (Delphinapterus leucas) and narwhal (Monodon monoceros) 总被引:2,自引:2,他引:0
The variation at loci with similarity to DRB class II major histocompatibility complex loci was assessed in 313 beluga collected from 13 sampling locations across North
America, and 11 narwhal collected in the Canadian high Arctic. Variation was assessed by amplification of exon 2, which codes
for the peptide binding region, via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded
conformation polymorphism analysis. Two DRB loci were identified in beluga: DRB1, a polymorphic locus, and, DRB2, a monomorphic locus. Eight alleles representing five distinct lineages (based on sequence similarity) were found at the
beluga DRB1 locus. Although the relative number of alleles is low when compared with terrestrial mammals, the amino acid variation found
among the lineages is moderate. At the DRB1 locus, the average number of nonsynonymous substitutions per site is greater than the average number of synonymous substitutions
per site (0.0806 : 0.0207, respectively;P<0.01). Most of the 31 amino acid substitutions do not conserve the physiochemical properties of the residue, and 21 of these
are located at positions implicated as forming pockets responsible for the selective binding of foreign peptide side chains.
Only DRB1 variation was examined in 11 narwhal, revealing a low amount of variation. These data are consistent with an important role
for the DRB1 locus in the cellular immune response of beluga. In addition, the ratio of nonsynonymous to synonymous substitutions is similar
to that among primate alleles, arguing against a reduction in the balancing selection pressure in the marine environment.
Two hypotheses may explain the modest amount of Mhc variation when compared with terrestrial mammals: small population sizes at speciation or a reduced neutral substitution
rate in cetaceans.
Received: 15 July 1997 / Revised: 24 March 1998 相似文献
49.
PCR-SSP技术对广东汉族人HLA-DR基因分型 总被引:13,自引:0,他引:13
探索具有高分辨率、高特异性和简捷快速的方法对HLA-DR基因分型,为临床器官移植配型和疾病相关性分析提供实用的方法和基础资料.利用DR1~DRw18序列特异性的19组引物及1对内参照引物进行PCR扩增即PCR-SSP对HLA-DR进行基因分型,扩增产物经琼脂糖凝胶电泳,溴乙锭染色,在紫外光下观察分型结果.每个被检个体的DR型别可由特异引物扩增出现的电泳谱带直接判断.双盲检测22例的结果100%正确.在102例中国广东地区汉族人中,DR9和DR2的基因频率最高,分别为0.2205和0.1912,DR10为最低(0.0098).与用PCR-SSO方法分型获得的结果比较,基因型别分布基本一致,但一些等位基因的频率有差异,表明HLA-DR基因频率的分布在不同地区、不同种族的人群间存在着差异.PCR-SSP法分辨率和特异性虽不及PCR-SSO法但比血清学方法精细,分型的全过程只需2~4h能满足临床器官移植配型的要求.基因频率调查结果为器官移植配型和疾病相关性分析提供了基础资料. 相似文献
50.
Significance of tumour cell HLA‐G5/‐G6 isoform expression in discrimination for adenocarcinoma from squamous cell carcinoma in lung cancer patients 下载免费PDF全文
Wei‐Hua Yan Di Liu Hai‐Yan Lu Ying‐Ying Li Xia Zhang Aifen Lin 《Journal of cellular and molecular medicine》2015,19(4):778-785
Human leucocyte antigen (HLA)‐G has seven isoforms, of which HLA‐G1‐G4 are membrane‐bound and HLA‐G5‐G7 are soluble. Previous studies reinforced HLA‐G expression was strongly related to poor prognosis in different types of cancers. Among these studies, the monoclonal antibody (mAb) 4H84 was used which detects all HLA‐G isoform heavy chain; unfortunately, leaves the specific types of isoforms expressed in lesions undistinguished and its clinical significance needs to be clarified. To explore clinical significance of lesion soluble HLA‐G (sHLA‐G) in non‐small‐cell lung cancer (NSCLC), mAb 5A6G7 recognizing HLA‐G5/‐G6 molecules was used. Tumour cell sHLA‐G expression in 131 primary NSCLC lesions (66 squamous cell carcinoma, 55 adenocarcinoma and 10 adenosquamous carcinoma) were analysed with immunohistochemistry. Data showed that sHLA‐G expression was observed in 34.0% (45/131) of the NSCLC lesions, which was unrelated to patient age, sex, lymph nodal status, tumour–node–metastasis stage and patient survival. However, tumour cell sHLA‐G expression in lesions was predominately observed in adenocarcinoma lesions (73.0%, 40/55) which was significantly higher than that in squamous cell carcinoma (6.0%, 4/66) and adenosquamous carcinoma lesions (10.0%, 1/10, P < 0.001). The area under the receiver operating characteristic curve for lesion sHLA‐G was 0.833 (95% CI: 0.754–0.912, P < 0.001) for adenocarcinoma versus squamous cell carcinoma. Our findings for the first time showed that tumour cell sHLA‐G was predominately expressed in lung adenocarcinoma, which could be a useful biomarker to discriminate adenocarcinoma from squamous cell carcinoma in NSCLC patients. 相似文献