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41.
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Marsh JC; Will AJ; Hows JM; Sartori P; Darbyshire PJ; Williamson PJ; Oscier DG; Dexter TM; Testa NG 《Blood》1992,79(12):3138-3144
We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. 相似文献
43.
A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes. 下载免费PDF全文
R W Tindle G J Fernando J C Sterling I H Frazer 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(13):5887-5891
We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a role in cell transformation and is the most abundant viral protein in HPV-associated neoplastic cervical epithelial cells, the data have implications for vaccine strategies. 相似文献
44.
Zhu Y Jong MC Frazer KA Gong E Krauss RM Cheng JF Boffelli D Rubin EM 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(3):1137-1142
To accelerate the biological annotation of novel genes discovered in sequenced regions of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450-kb region on mouse chromosome 11, which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities, including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation, and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450-kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine, and hepatic triglyceride production is of particular importance because of the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion. 相似文献
45.
Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors. 相似文献
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G P Jeffrey A M Brind D G Ormonde C K Frazer J Ferguson R Bell A Kierath W D Reed A K House 《The Australian and New Zealand journal of surgery》1999,69(10):717-722
BACKGROUND: A review of biliary tract complications was performed in 32 patients who underwent liver transplantation by the Western Australian Liver Transplantation Service during a 2-year period. METHODS: A review was made of patient data collected prospectively, and confirmed by retrospective casenote review. RESULTS: A total of 30 patients (31 grafts) survived more than 2 days after transplantation, and of these 28 had an end-to-end biliary anastomosis. Analysis of these 28 patients found that eight of 17 patients with T-tubes had complications: three leaks at T-tube removal; two strictures and leaks; and three strictures. Six of 11 patients without a T-tube had complications: one leak; three strictures and leaks; and two strictures. Predisposing factors were present in eight of the 14 patients with biliary tract complications: hepatic artery stenosis in three; and one each with hepatic artery thrombosis; biliary calculi; donor-recipient bile duct mismatch; severe cellular rejection: and prolonged postoperative hypotension. Acute rejection, steroid-resistant rejection and cytomegalovirus infection were all significantly more common in those patients with biliary tract complications compared with those without. There was no difference in cold ischaemic time or donor age. Twelve of the 14 patients with biliary complications required endoscopic stenting with or without balloon dilation, and eight patients required radiological percutaneous drainage of bile collections. Only one patient required biliary reconstruction and two patients required re-transplantation. One patient died of uncontrolled infection. Of three patients who underwent choledochojejunostomy, biliary leak developed in two patients, both of whom required operative biliary and hepatic repair. One of the three patients died from disseminated Aspergillus infection. The median total hospital stay of patients with biliary complications was 61 days (range: 30-180 days) compared with 33.5 days (range: 22-70 days) for patients without. Of patients with end-to-end biliary anastomosis, 50% had biliary tract complications and more than half of these had predisposing factors. The majority of biliary complications were managed without the need for surgery. CONCLUSION: A total of 50% of patients with end-to-end biliary anastomosis had biliary tract complications. Biliary strictures presented later than leaks, and the majority of these complications were managed without the need for surgery. 相似文献
48.
Does Physical Activity in Adolescence Have Site‐Specific and Sex‐Specific Benefits on Young Adult Bone Size,Content, and Estimated Strength? 下载免费PDF全文
Rachel L Duckham Adam DG Baxter‐Jones James D Johnston Hassanali Vatanparast David Cooper Saija Kontulainen 《Journal of bone and mineral research》2014,29(2):479-486
The long‐term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSIp) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSIc) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z‐scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSIp, p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSIp in males, and greater CoA, CoC, and TrC in females. © 2014 American Society for Bone and Mineral Research. 相似文献
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