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101.
Steiner M Ocran K Genschel J Meier P Gerl H Ventz M Schneider ML Büttner C Wadowska K Kerner W Schuff-Werner P Lochs H Schmidt H 《Gastroenterology》2002,122(3):789-795
The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients. 相似文献
102.
Assessment of Microvascular Abnormalities by Nailfold Capillaroscopy in Juvenile Dermatomyositis After Medium‐ to Long‐Term Followup
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Zoltan Barth Birgit N. Witczak Berit Flatø Akos Koller Ivar Sjaastad Helga Sanner 《Arthritis care & research》2018,70(5):768-776
Objective
In juvenile dermatomyositis (DM), microvascular abnormalities, measured by nailfold capillaroscopy (NFC), are common early in the disease course. We aimed to compare the presence of NFC abnormalities in patients with medium‐ to long‐term juvenile DM with that of controls, and to explore associations between NFC abnormalities and disease activity and other disease characteristics.Methods
Fifty‐eight juvenile DM patients with a median disease duration of 16.8 (range 2–38) years were clinically examined and compared with matched controls. By NFC, we assessed nailfold capillary density (NCD), giant capillaries, scleroderma, and neovascular pattern (defined as scleroderma active or late pattern). NFC was analyzed with researchers blinded to patient/control identity and disease characteristics. We measured disease activity and damage by validated tools, and patients were categorized as having active or inactive disease according to the Paediatric Rheumatology International Trials Organisation criteria.Results
Compared to controls, patients had decreased NCD (mean ± SD 6.4 ± 2.1/mm versus 7.6 ± 0.8/mm; P = 0.001) and showed more abnormality in all other NFC parameters; 36% of patients versus 4% of controls had NCD <6/mm (P < 0.001). Giant capillaries, scleroderma, and neovascular pattern were found in 9%, 84%, and 41% of patients, respectively. Patients with active disease (n = 30) presented more frequently with neovascular pattern than patients with inactive disease (n = 28) (P = 0.041). Decreased NCD and neovascular pattern were associated with higher levels of disease activity and impaired muscle function.Conclusion
After medium‐ to long‐term followup, juvenile DM patients had decreased NCD and, often, neovascular pattern; both were associated with higher levels of disease activity and impaired muscle function. This suggests that NFC can be a biomarker for disease activity in longstanding juvenile DM too.103.
Trans-chromosomal recombination within the Ig heavy chain switch region in B lymphocytes 总被引:2,自引:0,他引:2
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Mae Kingzette Helga Spieker-Polet Pi-Chen Yam Shi-Kang Zhai Katherine L. Knight 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(20):11840-11845
Somatic DNA rearrangements in B lymphocytes, including V(D)J gene rearrangements and isotype switching, generally occur in cis, i. e., intrachromosomally. We showed previously, however, that 3 to 7% of IgA heavy chains have the VH and Cα regions encoded in trans. To determine whether the trans-association of VH and Cα occurred by trans-chromosomal recombination, by trans-splicing, or by trans-chromosomal gene conversion, we generated and analyzed eight IgA-secreting rabbit hybridomas with trans-associated VH and Cα heavy chains. By ELISA and by nucleotide sequence analysis we found that the VH and Cα regions were encoded by genes that were in trans in the germline. We cloned the rearranged VDJ-Cα gene from a fosmid library of one hybridoma and found that the expressed VH and Cα genes were juxtaposed. Moreover, the juxtaposed VH and Cα genes originated from different IgH alleles. From the same hybridoma, we also identified a fosmid clone with the other expected product of a trans-chromosomal recombination. The recombination breakpoint occurred within the Sμ/Sα region, indicating that the trans-association of VH and Cα genes occurred by trans-chromosomal recombination during isotype switching. We conclude that trans-chromosomal recombination occurs at an unexpectedly high frequency (7%) within the IgH locus of B lymphocytes in normal animals, which may explain the high incidence of B-cell tumors that arise from oncogene translocation into the IgH locus. 相似文献
104.
105.
J M Funovics A Fritsch F Herbst F Piza F Mühlbacher F L?ngle M Schemper 《Hepato-gastroenterology》1988,35(6):316-320
Between 1977 and 1986, 172 patients with primary hepatic cancer were treated at the Department of Surgery I, University of Vienna Medical School. In 76 cases (80%) males, 20% females), cirrhosis of the liver was also present. Ninety patients underwent curative surgery (hepatic resection in 64, and liver transplantation in 26 cases). There were no early tumor stages. Forty-five large tumors were confined to one lobe, 42 involved both lobes, 3 even invaded adjacent structures, the majority (74%) being hepatocellular carcinomas. Forty-four of the 64 liver resections were performed in patients with otherwise normal livers (mortality 18%), while 20 patients had associated liver cirrhosis. In view of the extremely high mortality rates after extended liver resection, only limited local resections have been performed in cirrhotic malignancies since 1982 (mortality 25%). Perioperative mortality (25% overall) was due mainly to hepatic failure and sepsis; non-fatal complications occurred in 12 patients (26%). Seventeen of the 26 liver transplants were cirrhotic hepatomas. Nine deaths (34%) were caused by technical problems (graft failure, clotting disorder after massive transfusion) and systemic infections. The outcome for the patient after the immediate postoperative period was determined by tumor regrowth (residual liver tissue, graft, distant metastases) in both groups (median life expectancy 18.4 months after radical liver resection and 18.6 months after liver transplantation). Surgery is the only alternative for these patients (50% survival of untreated hepatoma: 2.6 months), improving both their quality of life and survival. We believe that in carefully selected candidates with non-resectable tumors liver replacement may be a useful alternative. 相似文献
106.
Cappuccio FP Bell R Perry IJ Gilg J Ueland PM Refsum H Sagnella GA Jeffery S Cook DG 《Atherosclerosis》2002,164(1):95-102
This population-based cross-sectional study in South London looks at the total homocysteine (tHcy) levels in groups of different ethnic background and the possible role of environmental factors and the 677C-->T genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR). Fasting plasma tHcy was measured in 1392 men and women, age 40-59 years; 475 were white, 465 of African origin (of whom 180 were West Africans and 280 Caribbeans) and 452 South Asian (of whom 222 were Hindus and 167 Muslims). The homozygous MTHFR TT variant had observed frequencies of 0.10 in whites, 0.01 in people of African origin and 0.02 in South Asians (P<0.001). tHcy levels were 16% (95% CI 8-26) higher amongst TT than CC. tHcy levels were 25% (21-29) higher in men than women. Levels were significantly higher in South Asians than whites (8% [3-13]). Vegetarians had higher levels than non-vegetarians (25% [18-33]). These differences were present after adjustments for age, sex, smoking, body mass index (BMI), MTHFR 677C-->T polymorphism and socio-economic status. Compared with whites (10.0 [9.7-10.3] micromol/l), and allowing for confounders, Hindus had significantly higher levels of tHcy (12.1 [11.6-12.6] micromol/l). This difference was attenuated by the inclusion of vegetarianism in the model (11.3 [10.8-11.9] micromol/l). In contrast Muslims had similar tHcy levels to whites while both West Africans and Caribbeans had slightly lower levels, though differences were not significant. The reported higher levels of tHcy in South Asians are due to high levels amongst Hindus only. They are in part accounted for by their vegetarianism. These differences in tHcy are large enough to be important contributors to the risk of vascular disease and may be preventable by simple targeted population strategies. 相似文献
107.
Prof Wim Van Lerberghe Prof Zoe Matthews Endang Achadi Chiara Ancona James Campbell Amos Channon Luc de Bernis Prof Vincent De Brouwere Vincent Fauveau Helga Fogstad Marge Koblinsky Jerker Liljestrand Abdelhay Mechbal Susan F Murray Tung Rathavay Helen Rehr Fabienne Richard Petra ten Hoope-Bender Sabera Turkmani 《Lancet》2014
108.
109.
Arvin Bhana Claude A. Mellins Inge Petersen Stacey Alicea Nonhlahla Myeza Helga Holst 《AIDS care》2014,26(1):1-11
An increasing number of adolescents born with HIV in South Africa are on antiretroviral treatment and have to confront complex issues related to coping with a chronic, stigmatizing and transmittable illness. Very few evidence-based mental health and health promotion programs for this population exist in South Africa. This study builds on a previous collaboratively designed and developmentally timed family-based intervention for early adolescents (CHAMP). The study uses community-based participatory approach as part of formative research to evaluate a pilot randomized control trial at two hospitals. The paper reports on the development, feasibility, and acceptability of the VUKA family-based program and its short-term impact on a range of psychosocial variables for HIV + preadolescents and their caregivers. A 10-session intervention of approximately 3-month duration was delivered to 65 preadolescents aged 10–13 years and their families. VUKA participants were noted to improve on all dimensions, including mental health, youth behavior, HIV treatment knowledge, stigma, communication, and adherence to medication. VUKA shows promise as a family-based mental and HIV prevention program for HIV + preadolescents and which could be delivered by trained lay staff. 相似文献
110.
Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions
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