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641.
Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7) 总被引:11,自引:4,他引:11
David G; Durr A; Stevanin G; Cancel G; Abbas N; Benomar A; Belal S; Lebre AS; Abada-Bendib M; Grid D; Holmberg M; Yahyaoui M; Hentati F; Chkili T; Agid Y; Brice A 《Human molecular genetics》1998,7(2):165-170
Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable
CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7
mutation in 19 families and one isolated case of various geographical
origins, presenting with autosomal dominant cerebellar ataxia with
progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77
patients and in 11 at-risk individuals, with alleles containing from 37 to
130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on
normal alleles contained from 7 to 35 CAGs. There was a strong negative
correlation (r = -0.84) between the age at onset and the size of the CAG
repeat expansion in SCA7 patients. Larger expansions were associated with
earlier onset, a more severe and rapid clinical course, and a higher
frequency of decreased vision, ophthalmoplegia, extensor plantar response
and scoliosis. The frequency of other clinical signs such as dysphagia and
sphincter disturbances increased with disease duration. The mutation was
highly unstable during transmission, with a mean increase of 10 +/- 16 CAG
repeats, which was significantly greater in paternal (15 +/- 20) than in
maternal (5 +/- 5) transmissions. This correlated well with the marked
anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism,
observed in the sperm of a patient, was particularly important, with
expanded alleles ranging from 42 to >155 CAG repeats. The degree of
instability during transmission, resulting mostly in expansions, is greater
than in the seven other neurodegenerative disorders caused by polyglutamine
expansions.
相似文献
642.
Repeat Expansion Detection (RED) is an efficient and simple method for
detecting repeat expansions in the human genome, including expansion
mutations resulting in disease. Here we report the first population survey
of CTG/CAG repeat lengths in humans using the RED method; we have
determined maximum CTG/CAG repeat length in 244 individuals from six human
populations: Danes, Chinese, Japanese, Rondonian Surui, Maya and
Mbuti/Biaka Pygmies. We have also sampled a number of non-human primates
including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla
gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees
(Pan troglodytes) and three Hylobatidae (one Hylobates lar, one H.klossii,
and one H.syndactylus). Our results demonstrate the existence of
significant variation in the sizes and frequencies of the longest CTG/CAG
repeat length seen per individual both within and between human
populations. The population differences argue that overall mutation rates
at CTG/CAG repeat loci are sufficiently low that mutation does not
obliterate the effect of random genetic drift and clearly indicate that
population stratification could occur in disease association studies using
the RED method. No significant differences were detected among the
non-human primates sampled. Our results also show that both common
chimpanzees and pygmy chimpanzees (bonobos) are polymorphic for maximum
length of any CTG/CAG repeats while no variation was found for gorillas and
orang-utans.
相似文献
643.
克罗恩病的第一个易感基因,NOD2(CARD15) 总被引:3,自引:1,他引:3
炎症性肠病 (IBD)具有遗传易感性 ,主要表现在家族聚集现象和双胎同胞的共患率[1] 。近年来 ,随着人类基因组和多基因疾病研究以及统计学方法的进展 ,相继发现IBD的基因易感位点 ,证实IBD的遗传易感性涉及多个基因位点[2 ] 。 1996年Hugot等[3 ] 采用非参数连锁分析 (nonparametriclinkageanalysis,NPL)法 ,对IBD患病同胞 (affectedsiblingpairs,ASP)进行基因组位点微卫星标记研究 ,发现克罗恩病 (CD)的易感位点位于第 16条染色体的着丝点附近 ,称为IBD1位点 … 相似文献
644.
645.
Polymorphic glycoprotein-1 on mouse platelets: possible role of Pgp-1 and LFA-1 in antibody-dependent platelet cytotoxicity involving complement 总被引:2,自引:0,他引:2
The presence of the Pgp-1 glycoprotein on mouse platelets is demonstrated by antibody-binding techniques, by immunoprecipitation, and by transblotting using the monoclonal antibody (MoAb) C71/26 against Pgp-1. C71/26 immunoprecipitates as a broad band of mol wt 87,000 to 100,000 as determined by radioiodination of the platelet cell surface and by the 3H-sodium borohydride labeling technique. Immunoblotting showed Pgp-1 expression on platelets to be quantitatively similar to its presence on macrophages and resolved platelet Pgp-1 into two bands of mol wt 87,000 and 97,000 whereas Pgp-1 on parasite-elicited peritoneal macrophages showed 82,000 and 87,000 mol wt species. Platelets and monocyte/macrophage cells from either peripheral blood or from the peritoneal cavity showed homogeneous binding of Pgp-1 antibody to greater than 97% of cells by flow cytometry. In contrast, lymphocytes from peripheral blood or from the spleen showed a heterogeneous binding pattern with 20% to 30% of cells being negative, and the majority weakly positive. In functional studies, MoAbs against CR1 and CR3 substantially inhibited platelet immune adherence, whereas C71/26 showed only marginal inhibitor. In contrast, C71/26 and other MoAbs against Pgp-1 inhibited platelet- dependent cytotoxicity of antibody-coated sheep erythrocytes in the presence of C5-deficient mouse plasma whereas M1/70 against CR3 showed no effect. In this assay, MoAbs against the alpha- and beta-subunits of leukocyte functional molecule LFA-1 also inhibited platelet cytotoxicity. These results show that the platelet cell surface moieties Pgp-1 and LFA-1 are involved in or closely associated with antibody-dependent cellular cytotoxicity by platelets. 相似文献
646.
Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas 总被引:3,自引:0,他引:3
Molot RJ; Meeker TC; Wittwer CT; Perkins SL; Segal GH; Masih AS; Braylan RC; Kjeldsberg CR 《Blood》1994,83(6):1626-1631
Flow immunophenotyping, DNA content analysis, and polymerase chain reaction (PCR) amplification for t(11;14) and t(14;18) were performed on 11 cases of typical mantle cell lymphoma (MCL), 5 cases of apparent MCL with proliferation centers (MCL-PC), and 5 cases of small lymphocytic lymphoma (SLL). Immunophenotyping showed IgM (P < .001), Ig light (P < .001), and CD20 (P < .001) expression to be more intense in MCL than in SLL. In MCL-PC, the mean intensity of IgM, Ig light chain, and CD20 expression was intermediate to the intensities observed in MCL and SLL. Furthermore, in contrast to SLL, all MCL and 4 of 5 MCL-PC cases exhibited stronger CD20 than CD19 expression. CD10 expression was not observed in any case and CD5 expression was present in all SLL and MCL-PC cases and in 9 of 11 MCL cases. DNA content analysis showed an S- phase fraction of less than 3% in all cases studied and, except for 1 MCL case, all lymphomas were DNA diploid. The t(11;14) breakpoint junctions involving the bcl-1 major translocation cluster were amplified by PCR in 4 of 11 (36%) MCL cases and in none of the MCL-PC or SLL cases. The t(14;18) involving the bcl-2 major breakpoint region was not identified by PCR in any case. We conclude that the level of expression of surface antigens and the rapid detection of t(11;14) by PCR are potentially useful for distinguishing MCL and SLL in the clinical setting. Further investigations as to the biologic relationship between MCL, MCL-PC, and SLL, and the utility of t(11;14) PCR in these lymphomas are warranted. 相似文献
647.
Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies 总被引:2,自引:0,他引:2
Rabinowe SN; Soiffer RJ; Tarbell NJ; Neuberg D; Freedman AS; Seifter J; Blake KW; Gribben JG; Anderson KC; Takvorian T 《Blood》1991,77(8):1837-1844
One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function. 相似文献
648.
Characterization of novel akermanite:poly‐ϵ‐caprolactone scaffolds for human adipose‐derived stem cells bone tissue engineering
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AS Zanetti GT McCandless JY Chan JM Gimble DJ Hayes 《Journal of tissue engineering and regenerative medicine》2015,9(4):389-404
In this study, three different akermanite:poly‐?‐caprolactone (PCL) composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of structure, compression strength, degradation rate and in vitro biocompatibility to human adipose‐derived stem cells (hASC). Pure ceramic scaffolds [CellCeramTM, custom‐made, 40:60 wt%; β‐tricalcium phosphate (β‐TCP):hydroxyapatite (HA); and akermanite] and PCL scaffolds served as experimental controls. Compared to ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL composites would have improved compression strength and comparable biocompatibility to hASC. Electron microscopy analysis revealed that PCL‐containing scaffolds had the highest porosity but CellCeramTM had the greatest pore size. In general, compression strength in PCL‐containing scaffolds was greater than in ceramic scaffolds. PCL‐containing scaffolds were also more stable in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were observed in all scaffold types. Reduced hASC metabolic activity and increased cell detachment were observed after acute exposure to akermanite:PCL extracts (wt%: 75:25, 50:50). Among the PCL‐containing scaffolds, hASC cultured for 21 days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability, increased expression of osteogenic markers (alkaline phosphatase and osteocalcin) and lowest IL‐6 expression. Together, the results indicate that akermanite:PCL composites may have appropriate mechanical and biocompatibility properties for use as bone tissue scaffolds. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
649.
JB Haddow H Adwan SE Clark S Tayeh SS Antonowicz P Jayia DW Chicken T Wiggins R Davenport S Kaptanis M Fakhry CH Knowles AS Elmetwally E Geddoa MS Nair I Naeem S Adegbola LJ Muirhead 《Annals of the Royal College of Surgeons of England》2014,96(5):352-358
Introduction
The surgical Apgar score (SAS) can predict 30-day major complications or death after surgery. Studies have validated the score in different patient populations and suggest it should be used to objectively guide postoperative care. We aimed to see whether using the SAS in a decisive approach in a future randomised controlled trial (RCT) would be likely to demonstrate an effect on postoperative care and clinical outcome.Methods
A total of 143 adults undergoing general/vascular surgery in 9 National Health Service hospitals were recruited to a pilot single blinded RCT and the data for 139 of these were analysed. Participants were randomised to a control group with standard postoperative care or to an intervention group with care influenced (but not mandated) by the SAS (decisive approach). The notional primary outcome was 30-day major complications or death.Results
Incidence of major complications was similar in both groups (control: 20/69 [29%], intervention: 23/70 [33%], p=0.622). Immediate admissions to the critical care unit was higher in the intervention group, especially in the SAS 0–4 subgroup (4/6 vs 2/7) although this was not statistically significant (p=0.310). Validity was also confirmed in area under the curve (AUC) analysis (AUC: 0.77).Conclusions
This pilot study found that a future RCT to investigate the effect of using the SAS in a decisive approach may demonstrate a difference in postoperative care. However, significant changes to the design are needed if differences in clinical outcome are to be achieved reliably. These would include a wider array of postoperative interventions implemented using a quality improvement approach in a stepped wedge cluster design with blinded collection of outcome data. 相似文献650.
SK Joshi T Murari AS Narula KV Baliga VD Charan 《Medical Journal Armed Forces India》2008,64(2):111-114