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991.
Mendelian diseases and conditions in Croatian island populations: historic records and new insights 总被引:1,自引:0,他引:1
Among Croatian islands, there are several which are known for unusual autochthonous diseases and specific medical conditions that result from the reproductive isolation and specific population genetic structure. These populations are characterized by high degree of genetic isolation, consanguinity, and inbreeding. The reported diseases include Mal de Meleda on Mljet island, hereditary dwarfism on Krk island, familial learning disability on Susak island, familial ovarian cancer on Lastovo island, and several other rare diseases and conditions inherited in Mendelian fashion. We present a historical perspective on how these conditions were first described, interpreted, and assessed. We reviewed the information obtained through genetic research in the past several years, when the genetic etiology of some of these conditions was explained. The disease gene causing Mal de Meleda was first localized at 8q chromosome, and mutations in the ARS (component B) gene encoding SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1) protein were identified subsequently. The genetic etiology of dwarfism on the island of Krk is explained by a mutation in the PROP1 gene, responsible for the short stature. The search for mutations underlying other monogenic diseases in Croatian islands is under way. 相似文献
992.
Dauwalder O Thomas D Ferry T Debard AL Badiou C Vandenesch F Etienne J Lina G Monneret G 《Journal of leukocyte biology》2006,80(4):753-758
The severity of Staphylococcus aureus sepsis is positively associated with staphylococcal enterotoxin A (SEA) and negatively associated with the enterotoxin gene cluster (egc), which encodes five staphylococcal enterotoxins. We postulated that the variable, clinical severity of S. aureus sepsis might be a result of differences in the inflammatory properties of staphylococcal superantigens. We therefore compared the inflammatory properties of SEA with those of staphylococcal entérotoxin G (SEG), a member of the five egc superantigens. We found that SEA and SEG had similar superantigenic properties, as they induced CD69 expression on T lymphocytes and selective expansion of Vbeta subpopulations. Contrary to SEG, however, SEA induced a strong proinflammatory/Th1 response, including TNF-alpha and MIP-1alpha production. These results suggest that the association of SEA with the severity of S. aureus septic shock, characterized by a deleterious, inflammatory cascade, may be explained partly by the specific proinflammatory properties of this superantigen. 相似文献
993.
Senkal CE Ponnusamy S Rossi MJ Sundararaj K Szulc Z Bielawski J Bielawska A Meyer M Cobanoglu B Koybasi S Sinha D Day TA Obeid LM Hannun YA Ogretmen B 《The Journal of pharmacology and experimental therapeutics》2006,317(3):1188-1199
In this study, a cationic water-soluble ceramide analog L-threo-C6-pyridinium-ceramide-bromide (L-t-C6-Pyr-Cer), which exhibits high solubility and bioavailability, inhibited the growth of various human head and neck squamous cell carcinoma (HNSCC) cell lines at low IC50 concentrations, independent of their p53 status. Consistent with its design to target negatively charged intracellular compartments, L-t-C6-Pyr-Cer accumulated mainly in mitochondria-, and nuclei-enriched fractions upon treatment of human UM-SCC-22A cells [human squamous cell carcinoma (SCC) of the hypopharynx] at 1 to 6 h. In addition to its growth-inhibitory function as a single agent, the supra-additive interaction of L-t-C6-Pyr-Cer with gemcitabine (GMZ), a chemotherapeutic agent used in HNSCC, was determined using isobologram studies. Then, the effects of this ceramide, alone or in combination with GMZ, on the growth of UM-SCC-22A xenografts in SCID mice was assessed following the determination of preclinical parameters, such as maximum tolerated dose, clearance from the blood, and bioaccumulation. Results demonstrated that treatment with L-t-C6-Pyr-Cer in combination with GMZ significantly prevented the growth of HNSCC tumors in vivo. The therapeutic efficacy of L-t-C6-Pyr-Cer/GMZ combination against HNSCC tumors was approximately 2.5-fold better than that of the combination of 5-fluorouracil/cis-platin. In addition, liquid chromatography/mass spectroscopy analysis showed that the levels of L-t-C6-Pyr-Cer in HNSCC tumors were significantly higher than its levels in the liver and intestines; interestingly, the combination with GMZ increased the sustained accumulation of this ceramide by approximately 40%. Moreover, treatment with L-t-C6-Pyr-Cer/GMZ combination resulted in a significant inhibition of telomerase activity and decrease in telomere length in vivo, which are among downstream targets of ceramide. 相似文献
994.
BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves infiltration by monocyte-derived macrophages, we investigated whether sCD163 may act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical features were identified and plasma was collected from 147 consecutive patients presenting for coronary angiography. Patients were classified as having CAD+, or being free of CAD- haemodynamically significant (>50% luminal diameter) coronary stenoses in one or more major coronary arteries (1, 2 or 3 vessel disease), and sCD163 concentration was measured by ELISA. Plasma sCD163 was non-parametrically distributed, being significantly higher in CAD+ patients (median 2.47 mg/L, 25th-75th percentile, 1.79-3.5mg/L) than in CAD- patients (2.09, 1.31-2.72 mg/L) (p=0.021, Mann-Whitney U-test). LogsCD163 increased significantly with increasing CAD extent (p=0.0036) and was significantly greater in patients with 3 vessel disease than in CAD- patients (p<0.001). Whereas logsCD163 correlated with CAD extent (Spearman r=0.22, p=0.008), logCRP did not, and sCD163 was only weakly correlated with CRP (r=0.19, p=0.039). Importantly, multivariate linear regression identified that sCD163 (p=0.0021) was a significant predictor of CAD extent and was independent of conventional risk factors age (p<0.0001), hypercholesterolemia (p=0.0023), hypertension (p=0.068), and current smoking (p=0.066). CONCLUSIONS: The monocyte-specific marker sCD163 is a novel potential plasma marker of coronary atherosclerotic burden. 相似文献
995.
Classic identity negative priming involves accessing semantic representations in the left anterior temporal cortex 总被引:1,自引:0,他引:1
Classic identity negative priming (NP) refers to the finding that when an object is ignored, subsequent naming responses to it are slower than when it has not been previously ignored (Tipper, S.P., 1985. The negative priming effect: inhibitory priming by ignored objects. Q. J. Exp. Psychol. 37A, 571-590). It is unclear whether this phenomenon arises due to the involvement of abstract semantic representations that the ignored object accesses automatically. Contemporary connectionist models propose a key role for the anterior temporal cortex in the representation of abstract semantic knowledge (e.g., McClelland, J.L., Rogers, T.T., 2003. The parallel distributed processing approach to semantic cognition. Nat. Rev. Neurosci. 4, 310-322), suggesting that this region should be involved during performance of the classic identity NP task if it involves semantic access. Using high-field (4 T) event-related functional magnetic resonance imaging, we observed increased BOLD responses in the left anterolateral temporal cortex including the temporal pole that was directly related to the magnitude of each individual's NP effect, supporting a semantic locus. Additional signal increases were observed in the supplementary eye fields (SEF) and left inferior parietal lobule (IPL). 相似文献
996.
Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France 总被引:1,自引:0,他引:1 下载免费PDF全文
Durand G Bes M Meugnier H Enright MC Forey F Liassine N Wenger A Kikuchi K Lina G Vandenesch F Etienne J 《Journal of clinical microbiology》2006,44(3):847-853
Methicillin-resistant Staphylococcus aureus (MRSA) clones harboring the toxic shock syndrome toxin 1 (tst) gene have been detected in France and in Switzerland since 2002. During a passive survey conducted between 2002 and 2003, we collected 103 tst-positive S. aureus isolates from 42 towns in France, of which 27 were resistant to methicillin. The tst-positive MRSA belonged to two clones: a major clone comprising 25 isolates of sequence type (ST) 5 and agr group 2 and a minor clone comprising two isolates of ST30 and agr3. The tst-positive MRSA clones were associated with both hospital-acquired (12 cases) and community-acquired (8 cases) infections. The MRSA clones were mainly isolated from children (overall median age, 3 years). They caused a variety of clinical syndromes, including toxic shock syndrome and suppurative infections. Both clones were found to harbor a type IV staphylococcal chromosomal cassette mec (SCCmec) and to have similar antibiotic resistance profiles (usually resistant to oxacillin, kanamycin, and tobramycin and with intermediate resistance to fusidic acid). The origin of these clones is unclear. The tst-positive agr2 MRSA clone has the same sequence type (ST5) of two pandemic nosocomial MRSA clones, namely, the Pediatric clone and the New York/Japan clone. These findings suggest that all these clones are phylogenetically related. The pulsotype of the tst-positive MRSA clones differed from that of methicillin-sensitive S. aureus (MSSA) clones by a single band involving the SCCmec element. These findings suggest that the tst-positive MRSA clones may have emerged from their respective MSSA counterparts. 相似文献
997.
998.
999.
Guanghui Xu Shanhong Tang Jianjun Yang Kang Chen Jianqin Kang Guohong Zhao Fan Feng Xuewen Yang Lina Zhao Qun Lu Li Sun Liu Hong Taiqian Gong Hongwei Zhang 《Digestive diseases and sciences》2013,58(7):1871-1879
Background
Our previous study showed that BMP7 revealed significantly higher levels in esophageal squamous cell carcinoma (ESCC) tissues with lymph node metastasis compared with non-lymph node metastasis, using gene expression profiling assays. The roles of BMP7 in ESCC is not fully understood.Aim
The aim of this study was to investigate the effect of BMP7 on lymph node metastasis of ESCC and to explore its potential mechanism.Methods
Expression of BMP7 in ESCC tissues was evaluated by immunohistochemistry. BMP7 were down-regulated by RNA interference. The protein and mRNA levels of BMP7 were detected by western blot and RT-PCR, respectively. High content screening and transwell assay were used to identify the metastatic ability of tumor cells.Results
Positivity of BMP7 staining was 57.5 % in the tissues of primary carcinoma with lymph node metastasis compared to tissues without lymph node metastasis, and expression of BMP7 was significantly higher in the cell lines with highly metastatic capacity than that in the cell lines without metastatic ability. Suppression of endogenous BMP7 expression by siRNA in the highly metastatic cell lines resulted in significant reduction in ability of cell migration and invasion in both in vitro and in vivo studies. In addition, inhibition of BMP7 by siRNA also leads to up-regulation of E-cadherin and down-regulation of MMP-9 in the highly metastatic cell lines.Conclusions
These findings indicate that BMP7 modulates the expression of E-cadherin and MMP-9, and by which mechanism it may regulate cell migration and metastasis of ESCCs. 相似文献1000.
TXNDC5(硫氧还蛋白5)在一些人类肿瘤中存在高表达.但人们对TXNDC5在胃腺癌的地位和作用却了解甚少.目的:在本研究中,我们旨在研究TXNDC5在胃腺癌的组织中的表达与患者临床特点的相关性.方法 通过免疫组化法检测54份胃癌患者及对照正常组织的TXNDC5的表达情况,并通过统计学方法分析该分子组织表达情况与患者临床表现的相关性.结果 在所有54个胃腺癌标本中,有23个(42.6%)高表达TXNDC5.腺癌组织中的具有较强的TXNDC5表达,在低分化腺癌的比例中表达更显著(P<0.05).高表达TXNDC5的病例在淋巴结转移和肿瘤浸润深度方面更显著.预后分析结果显示,患者标本中高表达TXNDC5比低表达TXNDC5的预后较差,差异有统计学意义(P<0.05).结论 TXNDC5的表达与胃腺癌的分化,侵袭和转移存在相关性.目前,可以被认为是与胃癌相关性较高的潜在性癌基因. 相似文献