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991.
Méndez-Sánchez N King-Martínez AC Ramos MH Pichardo-Bahena R Uribe M 《The American journal of gastroenterology》2004,99(11):2166-2170
BACKGROUND: It has been suggested that genes related to Amerindian ancestry account for the high prevalence of gallstone disease (GD) observed in Mexican-Americans. The HLA-B39 is an allele found in higher frequency in Amerindians whereas HLA-B15 is rarely found. The aim of this study was to test the hypothesis that gallstone susceptibility genes are more prevalent in Mexicans with recent Amerindian ancestry. METHODS: We carried out a prospective case-controlled study. Subjects were divided into those who had stones visible on gallbladder ultrasound (cases), and those whose ultrasounds were negative for gallstones (controls). Body mass index (BMI) was calculated, and serum lipids and lipoprotein, and glucose levels were measured. Class I HLA (HLA-B) typing was performed by PCR amplification of genomic DNA. RESULTS: Of the 1,101 subjects, 146 were classified as subjects with GD (cases) and 955 as subjects without GD (controls). Mean age of the cases was 53.5 +/- 12.5 yr versus 44.78 +/- 12.0 yr for the controls, p= 0.001. A family history of GD was observed in 48% of the cases versus 28.4% of the controls, p= 0.001. HLA-B39 was more frequently increased in GD subjects (0.162), compared with controls (0.063), p= 0.008. The odds ratio of having HLA-B39 was 2.8 and 95% (CI 95%= 1.3-6.3) for GD; HLA-B15 was more frequently increased in controls than in cases. CONCLUSIONS: The most prevalent HLA alleles detected in these GD cases are characteristic of Amerindian populations, supporting the role of genetics in the high prevalence of the development of GD in Mexican mestizos. 相似文献
992.
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994.
Olfactory receptor surface expression is driven by association with the beta2-adrenergic receptor 下载免费PDF全文
Hague C Uberti MA Chen Z Bush CF Jones SV Ressler KJ Hall RA Minneman KP 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(37):13672-13676
Olfactory receptors (ORs) comprise more than half of the large class I G protein-coupled receptor (GPCR) superfamily. Although cloned over a decade ago, little is known about their properties because wild-type ORs do not efficiently reach the cell surface following heterologous expression. Receptor-receptor interactions strongly influence surface trafficking of other GPCRs, and we examined whether a similar mechanism might be involved in OR surface expression. Olfactory neurons are known to express beta-adrenergic receptors (ARs), and we found that coexpression with beta(2)-ARs, but not any other AR subtypes, dramatically increased mouse 71 (M71) OR surface expression in human embryonic kidney 293 cells. A persistent physical interaction between M71 ORs and beta(2)-ARs was shown by coimmunoprecipitation and by cointernalization of the two receptors in response to their specific ligands. Also, coexpression of wild-type M71 ORs with beta(2)-ARs resulted in cAMP responses to the M71 ligand acetophenone. Finally, in situ hybridization studies showed extensive colocalization of M71 OR and beta(2)-AR expression in mouse olfactory epithelium. These data demonstrate the successful heterologous surface expression of a functional wild-type OR and reveal that persistent physical association with other GPCRs can control OR surface expression. 相似文献
995.
Cristina d’Agostino Pietro Romeo Vito Lavanga Salvatore Pisani Valerio Sansone 《Rheumatology international》2014,34(11):1513-1518
There is no gold standard for treatment of bone marrow edema syndrome of the hip (BMESH). Usually, treatment is conservative, owing to the favorable and self-limiting prognosis. In musculoskeletal disorders, the effectiveness of extracorporeal shock wave therapy (ESWT) has been widely recognized and recent research supports its use in the treatment of the first stages of avascular osteonecrosis of the proximal femur and in other conditions where bone marrow edema is present. On this basis, we performed a prospective study to evaluate the effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH. Twenty consecutive symptomatic patients underwent two treatments of high-energy ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up at mean 15.52 ± 1.91 months. Patients underwent magnetic resonance imaging of the hip and were evaluated according to the Harris hip score. The mean improvement in HHS over the course of the study was of 58.5 ± 14.9 points (p < 0.0001), and the mean edema area reduced from 981.9 ± 453.2 mm2 pre-treatment to 107.8 ± 248.1 mm2 at 6 months. ESWT seems to be a powerful, non-pharmacological tool that produces rapid pain relief and functional improvement and aids the normalization of the vascular and metabolic impairments which characterize BMESH. 相似文献
996.
Alfonso Rubio‐Navarro Maria Dolores Sanchez‐Niño Melania Guerrero‐Hue Cristina García‐Caballero Eduardo Gutiérrez Claudia Yuste Ángel Sevillano Manuel Praga Javier Egea Elena Román Pablo Cannata Rosa Ortega Isabel Cortegano Belén de Andrés María Luisa Gaspar Susana Cadenas Alberto Ortiz Jesús Egido Juan Antonio Moreno 《The Journal of pathology》2018,244(3):296-310
Recurrent and massive intravascular haemolysis induces proteinuria, glomerulosclerosis, and progressive impairment of renal function, suggesting podocyte injury. However, the effects of haemoglobin (Hb) on podocytes remain unexplored. Our results show that cultured human podocytes or podocytes isolated from murine glomeruli bound and endocytosed Hb through the megalin–cubilin receptor system, thus resulting in increased intracellular Hb catabolism, oxidative stress, activation of the intrinsic apoptosis pathway, and altered podocyte morphology, with decreased expression of the slit diaphragm proteins nephrin and synaptopodin. Hb uptake activated nuclear factor erythroid‐2‐related factor 2 (Nrf2) and induced expression of the Nrf2‐related antioxidant proteins haem oxygenase‐1 (HO‐1) and ferritin. Nrf2 activation and Hb staining was observed in podocytes of mice with intravascular haemolysis. These mice developed proteinuria and showed podocyte injury, characterized by foot process effacement, decreased synaptopodin and nephrin expression, and podocyte apoptosis. These pathological effects were enhanced in Nrf2‐deficient mice, whereas Nrf2 activation with sulphoraphane protected podocytes against Hb toxicity both in vivo and in vitro. Supporting the translational significance of our findings, we observed podocyte damage and podocytes stained for Hb, HO‐1, ferritin and phosphorylated Nrf2 in renal sections and urinary sediments of patients with massive intravascular haemolysis, such as atypical haemolytic uraemic syndrome and paroxysmal nocturnal haemoglobinuria. In conclusion, podocytes take up Hb both in vitro and during intravascular haemolysis, promoting oxidative stress, podocyte dysfunction, and apoptosis. Nrf2 may be a potential therapeutic target to prevent loss of renal function in patients with intravascular haemolysis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
997.
998.
Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing 下载免费PDF全文
Sandra G. Guerra Winnie Chong Colin J. Brown Cristina V. Navarrete 《International journal of immunogenetics》2018,45(4):230-235
The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high‐resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high‐resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9‐loci (HLA‐A, ‐B, ‐C, ‐DRB1,‐DRB345 ‐DQB1 and ‐DPB1). Concordance rates of 91%–98% were obtained (for HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1) when compared to historical PCR‐SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA‐DRB1*04:07:01/04:92, HLA‐DRB1*09:01:02/*09:21 and HLA‐DRB1*12:01:01/*12:10). This study has demonstrated high‐resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed. 相似文献
999.
La Starza R Testoni N Lafage-Pochitaloff M Ruggeri D Ottaviani E Perla G Martelli MF Marynen P Mecucci C 《Haematologica》2002,87(2):143-147
BACKGROUND AND OBJECTIVES: Around 5% of chronic myeloid leukemias (CML) are characterized by complex variant Philadelphia (Ph) translocations involving one or more chromosomal regions in addition to 9 and 22. The BCR/ABL1 fusion gene is usually found on der(22). The additional gene(s) involved in complex variant Ph rearrangements have not been characterized. DESIGN AND METHODS: We performed fluorescent in situ hybridization (FISH) in three complex variant Ph translocations involving the short arm of chromosome 6 in addition to 9 and 22. The BCR/ABL1 D-FISH probe was applied to localize the BCR/ABL1 fusion gene as well as the 5'ABL1 and the 3'BCR. Locus-specific probes were used to narrow the 6p breakpoint. RESULTS: In all cases the BCR/ABL1 fusion gene was located on the Ph chromosome whereas the reciprocal ABL1/BCR gene was detected only in patient #2. On 6p, breakpoints were narrowed to three different regions: centromeric to the human major histocompatibility complex (MHC), between PAC 524E15 and PAC162J16, in the first patient, and telomeric to the MHC, between PAC 329A5 and PAC 145H9, and between PAC 136B1 and PAC 206F19, in the second and third patients, respectively. In patients #2 and 3 a chromosomal rearrangement different from a true complex variant was discovered. In both cases, a classical t(9;22) was associated with an additional translocation involving the der(9)t(9;22). INTERPRETATION AND CONCLUSIONS: Rearrangements at 6p in complex Ph aberrations involve more than one gene/locus. Classical t(9;22), masked by additional chromosomal rearrangements, can resemble complex variant Ph translocations, and can be detected only using appropriate FISH probes. 相似文献
1000.