首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 23 毫秒
1.
Beta-amyloid (Aβ) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of Aβ in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low Aβ levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of Aβ. In subjects with mild cognitive impairment, increased brain Aβ levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between Aβ and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Aβ levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Aβ. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Aβ years before the onset of dementia but also that HC with substantial Aβ levels show higher Aβ pathology resistance, lack other pathologies that condition neurotoxic effects of Aβ, or accumulated Aβ for a shorter time period.  相似文献   

2.
ObjectivesTo determine the expression patterns and prognostic value of S100A4 and Annexin A2 for urothelial carcinoma of the urinary bladder.Methods and materialsImmunohistochemical staining for S100A4 and Annexin A2 was performed in 315 archived radical cystectomies and 63 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors.ResultsProtein levels of S100A4 and Annexin A2 were up-regulated in urothelial carcinoma compared with adjacent nontumor tissues. The increased expressions of S100A4 and Annexin A2 were associated with invasion depth, lymph node metastasis, and distant metastasis (P<0.05). High expression of S100A4 correlated with expression of Annexin A2. These alterations in expression were also associated with greater risk of disease progression and decreased chance of carcinoma-specific survival. Further multivariate analysis suggested that expressions of S100A4 and Annexin A2 were independent prognostic indicators for overall survival in urothelial carcinoma. The patients with S100A4-positive/Annexin A2-positive carcinomas presented the lowest 5-year survival rate compared with the other 3 groups.ConclusionsS100A4 and Annexin A2 proteins could be useful prognostic markers to predict tumor progression and prognosis in urothelial carcinoma. The expression patterns of S100A4/Annexin A2 interaction correlated well with the pathologic stage, disease progression, and carcinoma-specific survival. This finding could aid in identifying more biologically aggressive carcinomas and thus patients who might benefit from more intensive adjuvant therapy.  相似文献   

3.
Adenosine 2A receptor (A(2A)R) activation was recently shown to be renoprotective in diabetic nephropathy. A(2A)R are found in glomeruli and have been shown to associate with the podocyte cytoskeletal protein alpha-actinin-4, but the effect of their activation on podocyte structure and function is unknown. Podocyte injury was induced in C57BL/6 mice with puromycin aminonucleoside, and the selective A(2A)R agonist ATL313 was found to attenuate the resulting albuminuria and foot process fusion. The selective A(2A)R antagonist ZM241385 reversed the effects of ATL313. In vitro, A(2A)R mRNA and protein were expressed in a conditionally immortalized podocyte cell line, and A(2A)R-like immunoreactivity co-localized with the actin cytoskeleton. Treatment with ATL313 also blocked the increased podocyte permeability to albumin and disruption of the actin cytoskeleton that accompanied puromycin aminonucleoside-induced injury in vitro. ATL313 was ineffective, however, in the presence of the A(2A)R antagonist and in A(2A)R-deficient podocytes. It was concluded that A(2A)R activation reduces glomerular proteinuria, at least in part, by preserving the normal structure of podocyte foot processes, slit diaphragms, and actin cytoskeleton.  相似文献   

4.
T E Kanakis  J Cordey 《Injury》1991,22(3):185-189
Comminuted fractures of the long bones present problems of mechanical instability. We therefore used a plate and six screws as the main osteosynthesis combined with supplementary lag screws or cerclage wire. These two supplementary methods were compared. As a model, we used 60 plastic tibias with standard midshaft butterfly fractures. These models, depending on the osteosynthesis applied for the fixation of the butterfly onto the main fracture, were split into three groups of 20 bones. Group A1 with two lag screws, group A2 with two lag screws and two double cerclages, and group A3 with two double cerclages with no lag screws. The models were tested in torque and axial load. The results were: 1. In torque, group A1 was the most unstable with significant statistical difference from group A2 (P less than 0.01) and from A3 (P less than 0.05). There was no significant statistical difference between groups A2 and A3. 2. In axial load, group A3 was stable with significant statistical difference from A2 (P less than 0.05). There was no difference between A1 and A3. The experiment showed that if the cerclage is used double, anchored at the end of the screws and tensioned, it acts like a spring and is mechanically more stable than lag screws in torque. In axial load, no mechanical difference exists between lag screws and double cerclage.  相似文献   

5.
BACKGROUND: The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane is affected in the inherited renal disorder Alport's syndrome (AS). Approximately 85% of the AS patients are expected to carry a mutation in the X-chromosomal COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is also present in the epidermal basement membrane (EBM). It is predicted that approximately 70% of the COL4A5 mutations prevent incorporation of this chain in basement membranes. METHODS: We investigated whether or not COL4A5 defects could be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were obtained from 22 patients out of 17 families and two biopsy specimens from healthy males were used as controls. RESULTS: In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female). In three other patients with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively, the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was found in three patients of six families with a diagnosis of AS and in one family of a group of four families with possible AS. CONCLUSIONS: The (focal) absence of COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and prenatal DNA diagnosis are possible in the family of the patient.  相似文献   

6.
BACKGROUND: Carriers of autosomal-recessive and X-linked Alport syndrome often have a thinned glomerular basement membrane (GBM) and have mutations in the COL4A3/COL4A4 and COL4A5 genes respectively. Recently, we have shown that many individuals with thin basement membrane disease (TBMD) are also from families where hematuria segregates with the COL4A3/COL4A4 locus. This study describes the first COL4A4 mutation in an individual with biopsy-proven TBMD who did not have a family member with autosomal-recessive or X-linked Alport syndrome, inherited renal failure, or deafness. METHODS: The index case and all available family members were examined for dysmorphic hematuria> 50,000/mL using phase contrast microscopy and for segregation of hematuria with the COL4A3/COL4A4 and COL4A5 loci using DNA satellite markers. COL4A4 exons from the index case were then studied using the enzyme mismatch cleavage method, and exons that demonstrated abnormal cleavage products were sequenced. RESULTS: Hematuria in this family segregated with a haplotype at the COL4A3/COL4A4 locus (P = 0.031) but not with haplotypes at the COL4A5 locus. A mutation in COL4A4 that changed C to T resulting in an arginine residue being replaced by a stop codon (R1377X) was demonstrated in exon 44, which encodes part of the alpha 4(IV) collagen sequence close to the junction with the noncollagenous domain. This mutation was present in all five family members with hematuria, but not in the four unaffected family members, 33 unrelated individuals with TBMD, or 22 nonhematuric normals. CONCLUSIONS: R1377X has been described previously in a compound heterozygous form of autosomal-recessive Alport syndrome. Our observation is evidence that TBMD can represent a carrier state for autosomal-recessive Alport syndrome in at least some individuals.  相似文献   

7.
目的:探讨域含蛋白7A(THSD7A)基因在肝细胞癌(HCC)中的表达情况及临床意义。方法:分别用RT-PCR与免疫组化法检测30例新鲜HCC及癌旁组织标本中THSD7A m RNA表达及75例HCC及癌旁组织石蜡标本中THSD7A蛋白的表达,分析其与HCC患者临床病理因素及预后的关系。结果:与癌旁组织比较,在HCC组织中THSD7A m RNA表达下调(P0.05);THSD7A在HCC组织中的阳性表达率明显低于癌旁组织(24.0%vs.87.0%,P0.05)。THSD7A蛋白的表达与患者结节数目(P=0.011)、Edmondson-Steiner分级(P=0.013)、BCLC分期(P=0.048)有关。THSD7A蛋白低表达患者总体生存率(P=0.016)与无瘤生存率(P=0.013)均明显低于THSD7A高表达患者。结论:THSD7A在HCC中可能发挥抑癌基因的作用,THSD7A表达降低患者预后不良。  相似文献   

8.
We investigated residual digital flexor pulley strengths after 75% excision of the A2 and A4 pulleys. For direct pull-off tests, A2 and A4 pulleys from cadaveric fingers were tested by pulling on a loop of flexor digitorum profundus tendon through the pulley. For functional loading tests, fingers were positioned with the metacarpophalangeal joint flexed to 90 degrees for A2 testing, and with the proximal interphalangeal joint in 90 degrees flexion for A4 testing (with all other joints in full extension). Excision of 75% of A2 and A4 pulleys reduced pulley strengths determined by both testing methods. For the functional loading tests, which are more clinically relevant, mean tendon forces at failure after partial excision of A2 and A4 pulleys were 224 and 131 N respectively, which is sufficient to withstand flexor tendon forces expected during activities of daily living.  相似文献   

9.
目的:应用TaqMan荧光定量技术,了解前列腺癌患者CYP1A2 IVS4+43A/G位点基因表型。方法:应用ABI Prism7300型荧光定量PCR仪,通过序列检测系统测定85例前列腺癌患者CYP1A2 IVS4+43A/G的各种基因型,并分析不同基因型患者与前列腺癌分化之间的相关性。结果:85例前列腺癌患者中CYP1A2 IVS4+43A/G位点基因表型为AA5例(5.9%),AG33例(38.8%),GG47例(55.3%)。且各基因表型与前列腺癌Gleason评分无明显相关性。结论:CYP1A2 IVS4+43A/G各基因表型与前列腺癌分化之间无明显相关性。  相似文献   

10.
Purpose  The dopamine D2 receptor (DRD2) is considered to be involved in the development of postoperative nausea and vomiting (PONV). Our aim was to examine the relationship between DRD2 Taq IA polymorphism and the occurrence of PONV. Methods  We enrolled 1070 patients who were scheduled to undergo elective surgery under general anesthesia. Patients who vomited or required rescue antiemetics for severe nausea at two time points (within 6 and within 24 h after surgery) were defined as having early and total PONV, respectively. A polymerase chain reaction with confronting two-pair primers (PCR-CTPP) technique was adopted for DRD2 genotyping allele (A1A1, A1A2, or A2A2). The relationship between DRD2 Taq IA polymorphism and the occurrence of PONV was examined by multivariate logistic regression analysis. Results  The incidences of early PONV were 9.0%, 9.3%, and 14.4% in patients with the A1A1, A1A2, and A2A2 alleles, respectively. Sex, nature of the disease, smoking status, type of surgical department, duration of anesthesia, and the DRD2 Taq IA polymorphism were related to the emergence of early PONV. On multivariate analysis, the relative risk associated with the A2A2 allele in comparison with the A1A1 or A1A2 allele was 1.58 (95% confidence interval [CI], 1.05–2.37) for early PONV. The incidences of total PONV were 12.5%, 13.6%, and 17.2% in patients with the A1A1, A1A2, and A2A2 alleles, respectively. Sex, smoking status, type of surgical department, and duration of anesthesia were related to the emergence of total PONV. On multivariate analysis, the relative risk associated with the A2A2 allele in comparison with the A1A1 or A1A2 allele was 1.27 (95% CI, 0.88–1.84) for total PONV. Conclusion  The DRD2 Taq IA polymorphism affected the occurrence of early PONV. Analysis of patients’ genetic backgrounds may improve risk-stratification for PONV. This work was presented at the 51st Annual Meeting of the Japanese Society of Anesthesiologists, Nagoya, Japan, May 27–29, 2004.  相似文献   

11.
Source of plasma chromogranin A elevation in gastrinoma patients   总被引:1,自引:0,他引:1  
Chromogranin A (Cg A) is a protein that is coreleased with peptide hormones from gut endocrine cells and tumors. Plasma levels of Cg A, pepsinogen group I, and gastrin were measured in 31 patients with gastrinoma. Mean Cg A level in 10 patients with gastrinoma who were not operated on was 169 +/- 32 ng/mL, while in 9 control patients it was 28 +/- 5 ng/mL. In 18 patients with gastrinoma with residual tumor after total gastrectomy, the mean Cg A level was 45 +/- 6 ng/mL, and in 10 patients with normal gastrin levels after total gastrectomy and tumor excision, the mean Cg A level was 40 +/- 4 ng/mL. In 7 patients in whom pregastrectomy and postgastrectomy Cg A levels were measured, the mean reduction was 94 +/- 27 ng/mL, or 66%. There was no correlation between Cg A levels and amount of tumor, presence of metastases, or multiple endocrine neoplasia type I syndrome. There was a significant correlation between Cg A and pepsinogen I levels but no correlation between Cg A and gastrin levels. The results suggest that the elevated plasma Cg A levels in patients with gastrinoma are determined primarily by the trophic effects of gastrin on gastric enterochromaffinlike cells rather than by corelease from the gastrin-producing tumor itself.  相似文献   

12.
A rare abnormality of the A1 segment of the anterior cerebral artery (ACA) is reported. The right ACA bifurcated into two parts at the middle point of the A1 segment, and these segments did not rejoin. The superior right A1 segment connected with the left A1 and formed a single pericallosal artery. The inferior right A1, from which the right ophthalmic artery originated, had no connection with the left A1.  相似文献   

13.
Previously, dialysate contained small amounts of acetate as an alkaline buffer. Recently, acetate‐free dialysate (A[?]D) has been available. We evaluated the clinical effect of A(?)D over acetate‐containing dialysate (A(+)D) on acid–base balance, anemia, and nutritional status in maintenance hemodialysis (MHD) patients. Twenty‐nine patients on MHD were treated with A(+)D for 4 months (first A(+)D), switched to A(?)D for 4 months, and returned to A(+)D for the next 4‐month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3) levels did not change in patients with normal HCO3 levels (≥20 mEq/L) throughout the study. Meanwhile, in patients with initially low HCO3 levels, it was significantly increased during the A(?)D period only. Anemia: In patients with target hemoglobin (Hb) ≥10 g/dL, Hb levels were maintained during the study period, even if the dose of erythropoiesis‐stimulating agents (ESAs) decreased. In patients with low Hb levels, it was significantly increased in the A(?)D period without increasing ESA or iron doses. Nutritional Condition: In patients with normal albumin levels (≥3.8 g/dL), albumin did not change throughout the study period. However, in patients with lower albumin levels, it was significantly increased during the A(?)D period. These improvements in metabolic acidosis, anemia, and nutrition in the A(?)D period completely dissipated during the second A(+)D period. Hemodialysis (HD) with A(?)D may improve a patient's clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA, and malnutrition that were not normalized in HD with A(+)D.  相似文献   

14.
中国维吾尔族男性CYP17基因多态性与前列腺癌发生的关系   总被引:1,自引:1,他引:0  
目的:探讨维吾尔族男性CYP17基因多态性与前列腺癌发生危险性的关系。方法:收集31例前列腺癌患者和104例对照组的血液标本并提取DNA,设计引物,通过PCR扩增包括基因多态位点的片段,用限制性内切酶M spA1 I进行酶切,产物在2%琼脂糖凝胶上电泳,确定CYP17基因的3种基因型,即A1/A1、A1/A2、A2/A2,并经测序证实,同时测定血清标本中前列腺特异性抗原(PSA)含量。结果:基因型A1/A2、A2/A2频数与A1/A1比较,A1/A2和A2/A2在前列腺癌中的频数与对照组相比,其OR值分别为1.49和2.87,P值分别为0.321和0.052,肿瘤组3种基因型间的PSA值差异无显著性。而对照组中A1/A2组的PSA值高于A1/A1组,但差异无显著性(P=0.062),而A2/A2组显著高于A1/A1组(P=0.018)。结论:A2/A2基因型在前列腺癌中的频数有显著高于对照组的趋势,提示A2/A2基因型可能与维吾尔族男性前列腺癌发生危险性之间有密切关系,而对照组中A2/A2基因型组的PSA值的显著增高也支持了这一观点。  相似文献   

15.
目的:探讨SLC34A1(rs6420094)和RGS14(rs4074995)单核苷酸多态性与长期服用阿德福韦酯治疗的慢性HBV感染者血磷浓度的相关性。方法选取2012年10月至2013年8月河北医科大学第三医院连续服用阿德福韦酯(10 mg/d)单药或联合治疗至少2年的慢性HBV感染者91例,其中低磷血症患者31例,血磷正常患者60例。应用聚合酶链反应-限制性片段长度多态性分析法测定两位点的基因型,应用χ^2检验分析两位点等位基因分布频率与血磷浓度的关系。结果低磷血症组中,rs6420094基因A/A、A/G和G/G型的例数分别为13,13和5例,而血磷正常组上述基因型的例数分别为35,24和1例。此位点的等位基因A在血磷正常组出现的频率高于低磷血症组(78.3%∶62.9%),两组比较差异有统计学意义(χ^2=4.947,P<0.05)。低磷血症组中,rs4074995基因A/A、A/G和G/G型的例数分别为2,11和18例,而血磷正常组上述基因型的例数分别为1,21和38例,等位基因分布频率在两组间差异无统计学意义(χ^2=0.625,P>0.05)。结论 rs6420094多态性可能会影响长期服用阿德福韦酯治疗的慢性HBV感染者的血磷浓度。  相似文献   

16.
Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from a single center. South Asian and white patients with at least one CYP3A5*1 allele achieved twofold lower dose-normalized tacrolimus blood concentrations compared with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1 SNP. There was a significant delay in achieving target blood concentrations in those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3 genotype could be used to predict the tacrolimus dose requirement and, given incomplete linkage, would be better than determination of the CYP3AP1 genotype.  相似文献   

17.
Cytochrome P4501A1 (CYP1A1) is a key enzyme in phase I bioactivation of polycyclic aromatic hydrocarbons (PAHs), which have potential reproductive toxicity. The aim of this study was to investigate the association of the CYP1A1 polymorphisms with male infertility in a Han-Chinese population. We genotyped two polymorphisms, CYP1A1*2A and CYP1A1*2C, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study including 192 infertile patients with non-obstructive azoospermia or severe oligozoospermia and 226 fertile controls. We found that the genotype distribution of CYP1A1*2C was significantly different between the patients and the controls (p = 0.019). Analysis showed that CYP1A1*2C AG genotype was associated with a significantly decreased risk of male infertility [odds ratio (OR) = 0.56, 95% confidence interval (95% CI) = 0.36-0.86, p = 0.005] compared with the AA genotype. A statistically significantly decreased risk of male infertility was found to be associated with the CYP1A1*2C AG genotype plus GG genotype compared with CYP1A1*2C AA genotype (OR = 0.60, 95% CI = 0.40-0.91, p = 0.011). No significant association was detected between CYP1A1*2A polymorphism and male infertility. Haplotypic analysis showed a significantly increased risk of male infertility associated with the C-A haplotype compared with the T-A haplotype (OR = 1.98, 95% CI = 1.27-3.09), indicating a synergic effect of the two polymorphisms. Our results suggest that the CYP1A1 polymorphisms may contribute to the pathogenesis of male infertility in the Han-Chinese population.  相似文献   

18.
Treatment of intravertebral pseudarthroses by balloon kyphoplasty   总被引:2,自引:0,他引:2  
OBJECTIVE: This paper presents an open prospective investigation of the efficacy of balloon kyphoplasty in the treatment of intravertebral pseudarthrosis. Several described intravertebral radiolucent lines-the so-called vacuum phenomenon-originated from degenerative diseases. Pain arose from intravertebral dynamic mobility and local kyphosis. METHODS: We reduced and stabilized 24 intravertebral pseudarthroses with the balloon kyphoplasty. Pain and disability showed a rapid and distinct decrease. Radiologic features and life quality were compared with respect to the different shapes of fractures type A1, A3.1, and A3.3. The follow up was 2 years. RESULTS: The patients with fractures type A3.3 were older than those of type A1 and A3.1. In pseudarthrosis of type A3.1 fractures, the kyphotic wedge could be reduced to 13 degrees and the height could be increased to 85% with balloon kyphoplasty. In the A3.3 group, the wedge could be reduced to 8 degrees but the height could be increased only to 75%. No restoration of deformity was achieved in fractures type A1. A long-lasting effect on pain and disability was seen only after balloon kyphoplasty of fractures type A3.1. CONCLUSIONS: The treatment of intravertebral dynamic mobility with balloon kyphoplasty is useful in fractures type A3.1. In pseudarthroses type A1, the negligible reduction and only short-lasting reduction of pain stands against the costs. In pseudarthroses type A3.3, the lack of a long-lasting benefit could be the consequence of the disadvantageous shape of the vertebral body, the higher age of patients or the primary diseases.  相似文献   

19.
BACKGROUND: Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. METHODS: CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio. RESULTS: The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. CONCLUSIONS: Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.  相似文献   

20.
电化学疗法联合平阳霉素注射治疗大面积静脉畸形   总被引:1,自引:0,他引:1  
目的:分析电化学疗法联合平阳霉素治疗大面积静脉畸形的临床疗效。方法:回顾性分析自1998年1月~2009年6月治疗大面积静脉畸形的方法变迁及临床疗效。期间单纯采用平阳霉素瘤体内注射治疗91例,单纯采用电化学疗法治疗78例,电化学联合平阳霉素瘤体内注射治疗41例,随访时间为6~12月。结果:所有治疗病例全部有效,但电化学联合平阳霉素治疗组治愈率明显高于单用电化学治疗或单用平阳霉素治疗组(均P〈0.01),而且治愈的时间较单用电化学治疗或单用平阳霉素治疗明显缩短(均P〈0.01),并发症的发生率也显著低于其他两组(均P〈0.05)。结论:电化学疗法联合平阳霉素注射治疗大面积静脉畸形具有治愈率高、疗程短及并发症低等优点,是一种行之有效的方法。  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号