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991.
Ozren Pola?ek Grgo Gunja?a Ivana Kol?i? Lina Zgaga Snje?ana D?ijan Robert Smoli? Martina Smoli? Jasminka Milas-Ahi? Vatroslav ?eri? Josip Gali? Sandra Tucak-Zori? Antun Tucak Igor Rudan Gordan Lauc 《Croatian medical journal》2010,51(1):48-53
Aim
To investigate the association of nephrolithiasis and solute carrier family 2, facilitated glucose transporter, member 9 (SLC2A9), also known as glucose transporter type 9, Glut9.Methods
A total of 145 participants were recruited in the period April-October 2008 from the Department of Mineral Research of the Medical School Osijek, Osijek, Croatia; 58 (40%) had confirmed nephrolithiasis and 87 (60%) were asymptomatic. Four single nucleotide polymorphisms (SNP) from the SLC2A9 gene were genotyped in both groups (rs733175, rs6449213, rs1014290, and rs737267).Results
There was a weak but significant association of all 4 SNPs and nephrolithiasis (P = 0.029 for rs733175; P = 0.006 for rs6449213; P = 0.020 for rs1014290, and P = 0.011 for rs737267). Logistic regression in an age- and sex-adjusted model suggested that genotype C/T for rs6449213 had odds ratio for nephrolithiasis of 2.89 (95% confidence interval 1.13-7.40). This SNP explained a total of 4.4% of nephrolithiasis variance.Conclusion
Development of nephrolithiasis may be associated with SLC2A9 gene. Further studies are needed to clarify the role of SLC2A9 gene as a link between uric acid and nephrolithiasis.Renal stone formation (nephrolithiasis) is a disease characterized by the existence of solid deposits in the upper parts of the urinary tract (1). It is estimated to affect between 3%-9% of the population, with large differences between various populations (2,3). There is a number of causes that may lead to the renal stones formation, including diet and obesity status, some drugs, other diseases, climate changes, metabolic disorders, and genetic factors (2,4,5). The complexity of this disease caused researchers to consider nephrolithiasis as one feature of a broader systemic disease, rather than a local disease restricted to a single organic system (6). This is especially interesting in relation to gout and metabolic syndrome, which are both systemic disorders in close relation to nephrolithiasis (6-8). Even the cohort studies have confirmed the association of gout and kidney stones, suggesting that the history of gout increases the risk for kidney stones (9). Another study showed that, in the age-adjusted model, gout had an odds ratio of 1.97 for previous kidney stones (95% confidence interval [CI], 1.37-2.83) and that even after adjustment for sex, race, body mass index, and presence of hypertension the odds ratio remained significant (10).Genetic contribution to renal stones formation has been identified long time ago (2). In line with these suggestions, heritability of some of the traits associated with nephrolithiasis has been shown to be as high as 95% (11). Heritability of the urinary stones was reported to be lower (56%) (12), but still sufficiently high to be considered a substantial genetic proportion of variance and suggesting that it may be under genetic control. So far, a number of studies have established a link between predominantly oxalate kidney stones and several genes, including vitamin-D receptor gene (VDR) and calcitonin receptor (CTR) gene (13), heparan sulfate (HSPG2) gene (14), or fibronectin gene (FN1) (14).The quantitative trait associated with nephrolithiasis is the serum uric acid concentration, which is under strong genetic control by the gene for glucose transporter type 9 (SLC2A9 or Glut 9) (15). The gene was initially described in an isolated island community (16,17), where genetic properties of the population are expected to act in favor of facilitated gene mapping efforts (18). Subsequent meta-analysis of 14 populations confirmed the association of this gene with serum uric acid concentrations (19). This led to a number of clinical studies that have confirmed its involvement in the uric acid metabolism, including urate handling in the kidney and uptake in the liver (20,21). Based on the previous suggestions that gout and nephrolithiasis may share a common pathway (15), it might be interesting to see if SLC2A9 could explain the commonalities in patients with any of the following conditions. Therefore, the aim of this study was to investigate the association of nephrolithiasis and genetic variants of the SLC2A9. 相似文献992.
Andreas Gast Dominique Scherer Bowang Chen Sandra Bloethner Stephanie Melchert Antje Sucker Kari Hemminki Dirk Schadendorf Rajiv Kumar 《Genes, chromosomes & cancer》2010,49(8):733-745
We performed DNA microarray‐based comparative genomic hybridization to identify somatic alterations specific to melanoma genome in 60 human cell lines from metastasized melanoma and from 44 corresponding peripheral blood mononuclear cells. Our data showed gross but nonrandom somatic changes specific to the tumor genome. Although the CDKN2A (78%) and PTEN (70%) loci were the major targets of mono‐allelic and bi‐allelic deletions, amplifications affected loci with BRAF (53%) and NRAS (12%) as well as EGFR (52%), MITF (40%), NOTCH2 (35%), CCND1 (18%), MDM2 (18%), CCNE1 (10%), and CDK4 (8%). The amplified loci carried additional genes, many of which could potentially play a role in melanoma. Distinct patterns of copy number changes showed that alterations in CDKN2A tended to be more clustered in cell lines with mutations in the BRAF and NRAS genes; the PTEN locus was targeted mainly in conjunction with BRAF mutations. Amplification of CCND1, CDK4, and other loci was significantly increased in cell lines without BRAF‐NRAS mutations and so was the loss of chromosome arms 13q and 16q. Our data suggest involvement of distinct genetic pathways that are driven either through oncogenic BRAF and NRAS mutations complemented by aberrations in the CDKN2A and PTEN genes or involve amplification of oncogenic genomic loci and loss of 13q and 16q. It also emerges that each tumor besides being affected by major and most common somatic genetic alterations also acquires additional genetic alterations that could be crucial in determining response to small molecular inhibitors that are being currently pursued. © 2010 Wiley‐Liss, Inc. 相似文献
993.
Sarah J Zardawi Ibrahim Zardawi Catriona M McNeil Ewan K A Millar Duncan McLeod Adrienne L Morey Paul Crea Niamh C Murphy Mark Pinese Elena Lopez‐Knowles Samantha R Oakes Christopher J Ormandy Min Ru Qiu Anne Hamilton Andrew Spillane Cheok Soon Lee Robert L Sutherland Elizabeth A Musgrove Sandra A O’Toole 《Histopathology》2010,56(3):286-296
Zardawi S J, Zardawi I, McNeil C M, Millar E K A, McLeod D, Morey A L, Crea P, Murphy N C, Pinese M, Lopez‐Knowles E, Oakes S R, Ormandy C J, Qiu M R, Hamilton A, Spillane A, Soon Lee C, Sutherland R L, Musgrove E A & O’Toole S A(2010) Histopathology 56, 286–296 High Notch1 protein expression is an early event in breast cancer development and is associated with the HER‐2 molecular subtype Aims: Activation of Notch signalling results in hyperplasia and tumorigenesis in murine mammary epithelium. However, there is little information regarding the expression of Notch1 in premalignant lesions and early breast cancer. We investigated expression of Notch1 in breast cancer development and its association with molecular subtypes. Methods and results: Immunohistochemical expression of Notch1 was determined in a murine model of mammary carcinogenesis and in breast tissue from two cohorts of breast cancer patients, the first (n = 222) comprising a histological progression series and the second an outcome series of 228 patients with operable invasive ductal carcinoma. Enhanced expression of Notch1 protein was an early event in both murine and human breast cancer development with progressive increases in expression with the development of hyperplasia and malignancy. High Notch1 was not prognostic in the outcome cohort. There was, however, a highly significant association of high Notch1 protein with the HER‐2 molecular subtype of breast cancer (P = 0.008). Conclusions: These data demonstrate that aberrant Notch regulation is an early event in mammary carcinogenesis and is associated with the HER‐2 molecular subtype of breast cancer, and suggest the Notch signalling pathway may be a potential therapeutic target worthy of further investigation. 相似文献
994.
Nadia Zepeda Sandra Solano Natalia Copitin Ana María Fernández Lilián Hernández Patricia Tato José L. Molinari 《Parasitology research》2010,107(5):1129-1135
After an intraperitoneal infection of mice with Taenia crassiceps metacestodes, peritoneal inflammatory cells labeled with fluoresceinated MoAb anti-mouse were analyzed by flow cytometry. Apoptosis was studied by annexin A/PI, TUNEL assays, DNA laddering, caspase-3 activity, and electron microscopy. An important continuous decrease of CD4+, CD8+ and CD19+ lymphocytes, and an increase of eosinophils and macrophages throughout the observation time were found. Apoptosis of eosinophils was quantified during the observation period with a peak at 6 days post-infection (67.27%). In an additional experiment at 12 days post-infection using TUNEL staining, a high level of apoptosis of eosinophil (92.3%) and a significant decrease of CD4+, CD8+, and CD19+ lymphocytes were confirmed. Caspase-3 activity in peritoneal fluid, peritoneal cells' DNA fragmentation, and apoptosis of eosinophils and monocytes were found. The dramatic decrease of peritoneal inflammatory T and B cells and the high level of apoptosis of inflammatory eosinophils induced in mice by infection with T. crassiceps cysticerci may be important factors of the immunosuppression observed in cysticercosis. 相似文献
995.
Kinnunen T Buhot C Närvänen A Rytkönen-Nissinen M Saarelainen S Pouvelle-Moratille S Rautiainen J Taivainen A Maillère B Mäntyjärvi R Virtanen T 《European journal of immunology》2003,33(6):1717-1726
We have proposed earlier that the poor capacity of the lipocalin allergen Bos d 2 to stimulate highly allergic subjects' peripheral blood mononuclear cells could be ascribed to endogenous lipocalins and could be related to the allergenic potential of the molecule. Here, we have characterized the proliferative and cytokine responses of human T cell clones against the immunodominant epitope of Bos d 2. We observed, for clone F1-9, that a substitution of aspartic acid for asparagine in the core region of the epitope increased the stimulatory capacity of the peptide about 100-fold in comparison with the natural peptide. For clone K3-2, from a different patient, the substitution of lysine for glutamine or isoleucine for leucine in the core region resulted in about 30-fold and 10-fold increases in the stimulatory capacity of the peptides, respectively. The clones also recognized self-protein-derived peptides but not the peptides derived from other lipocalins. We suggest that the poor recognition of the immunodominant epitope of Bos d 2 can be a factor accounting for Bos d 2-allergic subjects' weak cellular responses. Suboptimal recognition of self and allergen epitopes by T cells may be of significance for the allergenicity of proteins. 相似文献
996.
Wang H Chu W Das SK Zheng Z Hasstedt SJ Elbein SC 《Molecular genetics and metabolism》2003,79(3):176-182
The retinoid-related orphan receptor gamma (RORC) is a member of the nuclear hormone superfamily which maps to the 1q21-q23 region. Linkage of type 2 diabetes (T2DM) to this region is well replicated. Several factors argue that RORC is a strong candidate for T2DM susceptibility within this region. RORC may form heterodimers with peroxisome-proliferator activated receptor gamma, it is expressed at high levels in skeletal muscle, and expression is induced in adipocytes during differentiation. To test the hypothesis that sequence variation in RORC is a risk factor for T2DM, we screened approximately 21kb of DNA for sequence variation, including 11 exons of the RORC gene, a region 1-kb upstream (5' flanking region), intronic regions flanking the exons, and the entire 3' untranslated region (UTR). Screening was performed using single strand conformation polymorphism (SSCP) analysis in Caucasian individuals of northern European ancestry and in African American individuals. We detected 11 single nucleotide polymorphisms (SNPs), ranging from the promoter region to intron 10. We also confirmed 2 SNPs from public databases that were in regions not included in our screening. Only 1 SNP was nonsynonymous, resulting in Ala to Gly at residue 464 (exon 10). All other SNPs were noncoding. One SNP (intron 3) was unique to Caucasians, and three SNPs (Ala464Gly, intron 2, intron 6) were specific to African American subjects. We typed 7 SNPs spanning the gene from the promoter to 3' UTR in unrelated cases with T2DM and controls of Northern European ancestry. We also tested linkage of a microsatellite within the RORC gene. Modest evidence for linkage (LOD=1.47) was seen on two-point analysis, but no linkage to the RORC region was found on multipoint analysis. However, transmission of the microsatellite alleles from parents to affected offspring showed a trend to deviate from the expected 50% (p=0.078). No association of any other SNP with T2DM was found, but the Ala454Gly variant was 3-fold more common among African American patients with diabetes than in controls. SNPs 1, 2 and 4 were in strong linkage disequilibrium (D>0.85) and may constitute a haplotype block. Our data suggest that RORC cannot explain the linkage of T2DM in this region. The role of the unusual Ala454Gly variant will require a much larger study size to evaluate. 相似文献
997.
We report the case of a 43 year-old man, smoker, who used to live in Africa, consulting for a chronic ulcer of the mobile tongue. An initial biopsy did not show any carcinoma. A second biopsy highlighted an inflammation with numerous tuberculoid granulomas. However, the Ziehl-Neelsen stain was negative. Histoplasmosis of the tongue was then suspected as some round structures looking like yeasts and stained by the Gomori Grocott method were seen within the cytoplasm of giant cells. However, immunohistochemistry using anti-Histoplasma antibodies was negative. Polymerase chain reaction (PCR) assay performed on deparaffinized sections allowed the diagnosis of infection by Mycobacterium tuberculosis. A third biopsy confirmed the diagnosis of tuberculosis by showing some exceptional acid-fast bacilli. Culture was negative. Tuberculosis of the tongue is a very rare condition with different differential diagnosis including carcinoma in smoker population or histoplasmosis in endemic area. 相似文献
998.
Calarota SA Otero M Hermanstyne K Hermanstayne K Lewis M Rosati M Felber BK Pavlakis GN Boyer JD Weiner DB 《Journal of immunological methods》2003,279(1-2):55-67
The enzyme-linked immune spot (ELISPOT) assay is receiving increased attention as a means for quantifying antigen-specific CD8 T-cell responses in rhesus macaques. Further improving the sensitivity of this assay could aid in the evaluation of vaccine candidates and/or immune therapeutic candidates. Interleukin (IL)-15 has been demonstrated to stimulate expansion of human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) and to regulate homeostatic proliferation of CD8+ memory cells. We evaluated the in vitro effect of IL-15 to increase the detection of interferon-gamma (IFN-gamma) production by antigen-specific stimulated lymphocytes from a group of rhesus macaques exposed to simian-human immunodeficiency virus (SHIV) and a second group infected with SIVmac251, before and after antiretroviral treatment (ART). Results from these studies demonstrate that the presence of IL-15 during stimulation in a peptide-based ELISPOT assay greatly enhanced IFN-gamma production in both SHIV and simian immunodeficiency virus (SIV)-infected macaques. IFN-gamma production was mainly mediated by CD8 lymphocytes. The optimal concentrations of IL-15 that give enhancement of IFN-gamma production to specific antigen, without a significant increase in the spontaneous IFN-gamma release, ranged from 0.5 to 2.5 ng/ml. The mean number of IFN-gamma spots was increased 3.1- to 3.6-fold in response to SIV gag or HIV env peptide pools, respectively, in peripheral blood mononuclear cells (PBMC) from SHIV-infected macaques. Similarly, in SIV-infected macaques, IL-15 increased the mean number of IFN-gamma spots 2.7-fold in response to both SIV gag and env peptide pools. In samples obtained after ART in the same macaques, the increase factor was 2.5 for SIV gag and 1.8 for the env peptide pools. Thus, the sensitivity of the ELISPOT assay can be enhanced by addition of IL-15. This modified assay will be useful for detection of low frequencies of IFN-gamma producing cells in rhesus macaques. 相似文献
999.
Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas. 总被引:3,自引:0,他引:3
Helenice Gobbi Jean F Simpson Roy A Jensen Sandra J Olson David L Page 《Modern pathology》2003,16(9):893-901
Micropapillomas/papillomas and complex sclerosing lesions of the breast have been associated with a slightly increased risk for subsequent carcinoma, although benign squamous metaplasia and reactive hypercellular stroma are seen within these lesions. There are few reports of these fibrosclerotic lesions associated with metaplastic tumors. Here we describe a series of metaplastic tumors arising within fibrosclerotic breast lesions. Thirty-three metaplastic tumors associated with fibrosclerotic lesions were selected from a breast pathology consultative practice. Relevant clinical and pathological features were reviewed. Representative sections were evaluated immunohistochemically for expression of cytokeratins, vimentin, and smooth muscle and muscle-specific actins. Both the metaplastic component (spindled and squamous cells) and the glandular elements were graded. The metaplastic tumors arose within papillomas (20 cases), complex sclerosing lesions (7 cases), both papilloma and complex sclerosing lesions (3 cases), and nipple adenoma (3 cases). A majority of the metaplastic tumors showed a dominant spindle cell component with various degrees of atypia, ranging from fibromatosis-like (16 cases) to low-grade (13 cases), intermediate-grade (2 cases), and high-grade (2 cases) fibrosarcoma phenotype. Squamous metaplasia was present in 25 cases, and low-grade glandular elements, in 21 cases. Eleven tumors had a low-grade adenosquamous growth pattern. Ductal carcinoma in situ was present in 7 cases, and invasive mammary carcinoma, in 5 cases. The very low-grade tumors were histologically similar to limited areas of stromal reaction and myofibroblastic proliferation, seen in partially sclerotic micropapillomas/papillomas and complex sclerosing lesions, but usually more cellular. Cytokeratin positivity (13+/13 tested) supports the metaplastic nature of the more plump spindled cells. The spindle cells were also positive for vimentin (8+/8 tested) and smooth muscle (2+/5 tested) and muscle-specific actins (6+/6 tested). Spindle cell metaplastic tumors, from fibromatosis-like to fibrosarcoma, may arise within a variety of fibrosclerotic breast lesions. 相似文献
1000.
Multilaboratory Evaluation of a Viability Assay for Measurement of Opsonophagocytic Antibodies Specific to the Capsular Polysaccharides of Streptococcus pneumoniae 下载免费PDF全文
Sandra Romero-Steiner Carl Frasch Nelydia Concepcion David Goldblatt Helena Kyhty Merja Vkevinen Craig Laferriere Dominique Wauters Moon H. Nahm Mark F. Schinsky Brian D. Plikaytis George M. Carlone 《Clinical and Vaccine Immunology : CVI》2003,10(6):1019-1024
Opsonophagocytosis is a correlate of protection that measures the functional activity of vaccine-induced antibodies. A standardized opsonophagocytosis assay (OPA) should be used as part of the evaluation of current and future pneumococcal (Pnc) polysaccharide (Ps)-based vaccines. We enrolled five laboratories to evaluate a previously standardized viability OPA. Each laboratory was provided with a detailed OPA protocol, seven target Pnc strains (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), two quality control sera and 12 paired sera (blinded) from adult donors who received one dose of the 23-valent Pnc Ps vaccine. Laboratories sent their results to the Centers for Disease Control and Prevention for analysis. Sera were tested in duplicate (single run), and the results were averaged to yield a single OPA titer (≥50% killing) for each serum sample. The percentage of sera within one or two dilutions of the calculated median OPA titer was determined for each laboratory and for each serotype. In general, laboratories were capable of detecting OPA titers within one or two dilutions of the median for at least 75 and 88%, respectively, of the sera tested. The level of agreement with the median OPA titers varied depending on the participating laboratory (overall agreement = 0.8 [99% confidence interval = 0.75 to 0.85]). All OPA median titers reported for quality control sera were within one dilution of the expected titer. We conclude that this OPA can be done in multiple laboratories with a high degree of interlaboratory reproducibility. 相似文献