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11.
12.
Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy 总被引:3,自引:0,他引:3
Kelsell RE; Gregory-Evans K; Payne AM; Perrault I; Kaplan J; Yang RB; Garbers DL; Bird AC; Moore AT; Hunt DM 《Human molecular genetics》1998,7(7):1179-1184
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to
within an 8 cM interval on chromosome 17p12-p13. The retinal- specific
guanylate cyclase gene (RETGC-1), which maps to within this genetic
interval and previously was implicated in Leber's congenital amaurosis, was
screened for mutations within this family and in a panel of small families
and individuals with various cone and cone- rod dystrophy phenotypes. A
missense mutation (E837D) was identified in affected members of the CORD6
family, as well as a second missense mutation (R838C) in three other
families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene
to be implicated in cone-rod dystrophy and this is the first report of
dominant mutations in this gene.
相似文献
13.
14.
Transforming growth factor-beta1 increases CXCR4 expression, stromal-derived factor-1alpha-stimulated signalling and human immunodeficiency virus-1 entry in human monocyte-derived macrophages 总被引:3,自引:0,他引:3
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Chen S Tuttle DL Oshier JT Knot HJ Streit WJ Goodenow MM Harrison JK 《Immunology》2005,114(4):565-574
Stromal-derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 play crucial roles in leukocyte migration and activation, as well as embryogenesis, angiogenesis, cancer and viral pathogenesis. CXCR4 is one of the major human immunodeficiency virus-1 (HIV-1) coreceptors on macrophages. In many tissues macrophages are one of the predominant cell types infected by HIV-1 and act as a reservoir for persistent infection and viral dissemination. In patients infected by HIV-1, blood and tissue levels of transforming growth factor-beta1 (TGF-beta1) are increased. The purpose of this study was to evaluate the effects of TGF-beta1 on CXCR4 expression and function in primary human monocyte-derived macrophages (MDMs) and rat microglia. TGF-beta1 up-regulated CXCR4 and enhanced SDF-1alpha-stimulated ERK1,2 phosphorylation in these cells. The increased CXCR4 expression in human MDMs resulted in increased susceptibility of the cells to entry by dual-tropic CXCR4-using HIV-1 (D-X4). In contrast, TGF-beta1 failed to increase CCR5 expression or infection by a CCR5-using virus in MDMs. Our data demonstrate that TGF-beta1 enhances macrophage responsiveness to SDF-1alpha stimulation and susceptibility to HIV-1 by selectively increasing expression of CXCR4. The results suggest that increased expression of CXCR4 on macrophages may contribute to the emergence of dual-tropic X4 viral variants at later stages of HIV-1 infection. 相似文献
15.
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
16.
Zelinski-Wooten MB; Slayden OD; Chwalisz K; Hess DL; Brenner RM; Stouffer RL 《Human reproduction (Oxford, England)》1998,13(2):259-267
Large doses of antiprogestin typically disrupt menstrual cyclicity. A
chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which
permits continued menstrual cyclicity but alters gonadal- reproductive
tract activity, was established. Rhesus monkeys received vehicle (n = 6) or
0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight
daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and
gonadotrophin profiles were normal during cycles involving vehicle and 0.01
and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle
oestradiol and gonadotrophin surges, and subsequent progesterone
production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied
by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half
the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group
were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of
C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and
cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily
treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in
macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed
ovarian cyclicity, menstruation was disrupted in some animals. Increasing
the dose to 0.1 mg/kg antagonized pituitary function and resulted in
anovulation and amenorrhoea. A chronic low-dose regimen of the
antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity,
has potential as a contraceptive in women.
相似文献
17.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
18.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献19.
0 引言 我科 1996 / 1998分别应用消痔灵与强的松龙混合液、消痔灵液、强的松龙液行鼻息肉内 ,鼻息肉蒂部注射治疗鼻息肉各 5 0例 ,并设对照组为鼻腔滴入及口服类固醇激素 5 0例 ,合计 2 0 0例 ,观察并对比其疗效 .1 对象和方法1.1 对象 男 12 8例 ,女 72例 ,年龄 8~ 78(平均 38)岁 ,病程 32 a~ 45 (平均 4.5 ) a.其中在本次治疗前做过一次鼻息肉摘除术后复发的 2 7例 ,做过 2次或 2次以上手术的 12例 .主要症状为鼻塞、流脓涕、头痛及嗅觉减退 .全部病例治疗前均行鼻窦 X线拍片 ,其中上颌窦炎 12 5例、筛窦炎 5 8例、蝶窦炎 2例、… 相似文献
20.
To respond to a cost reduction crisis, Strong Memorial Hospital implemented an aggressively managed program of accelerated improvement teams. "Fast-track" teams combined the application of many management tools (total quality management, breakthrough thinking, reengineering, etc.) into one problem-solving process. Teams and managers were charged to work on specific cost reduction strategies. Teams were given additional instruction on interpersonal skills such as communication, teamwork, and leadership. Paradoxically, quality improvement in our hospital was advanced more through this effort at cost reduction than had previously been done in the name of quality itself. 相似文献