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Antoon H van Lierop Neveen AT Hamdy Herman Hamersma Rutger L van Bezooijen Jon Power Nigel Loveridge Socrates E Papapoulos 《Journal of bone and mineral research》2011,26(12):2804-2811
Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss‐of‐function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino‐terminal propeptide (P1NP), and cross‐linked C‐telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls. Chips of compact bone discarded during routine surgery were also examined from 6 patients and 4 controls. Sclerostin was undetectable in serum of patients but was measurable in all carriers (mean 15.5 pg/mL; 95% confidence interval [CI] 13.7 to 17.2 pg/mL), in whom it was significantly lower than in healthy controls (mean 40.0 pg/mL; 95% CI 36.9 to 42.7 pg/mL; p < 0.001). P1NP levels were highest in patients (mean 153.7 ng/mL; 95% CI 100.5 to 206.9 ng/mL; p = 0.01 versus carriers, p = 0.002 versus controls), but carriers also had significantly higher P1NP levels (mean 58.3 ng/mL; 95% CI 47.0 to 69.6 ng/mL) than controls (mean 37.8 ng/mL; 95% CI 34.9 to 42.0 ng/mL; p = 0.006). In patients and carriers, P1NP levels declined with age, reaching a plateau after the age of 20 years. Serum sclerostin and P1NP were negatively correlated in carriers and age‐ and gender‐matched controls (r = 0.40, p = 0.008). Mean CTX levels were well within the normal range and did not differ between patients and disease carriers after adjusting for age (p = 0.22). Our results provide in vivo evidence of increased bone formation caused by the absence or decreased synthesis of sclerostin in humans. They also suggest that inhibition of sclerostin can be titrated because the decreased sclerostin levels in disease carriers did not lead to any of the symptoms or complications of the disease but had a positive effect on bone mass. Further studies are needed to clarify the role of sclerostin on bone resorption. © 2011 American Society for Bone and Mineral Research 相似文献
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急性淋巴细胞白血病(上) 总被引:2,自引:0,他引:2
急性淋巴细胞白血病是淋巴前体细胞异常引起的恶性疾病,儿童与成人均可能发生。儿童发病高峰2~5岁。有效治疗的稳步进展使本病在儿童中的治愈率80%以上,同时为新的治疗方案提供了良机,新方案将保留我们在白血病无病生存病例中获得的治疗经验,同时减轻当前强化治疗方案中的毒副作用。 相似文献
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5 风险评估对病人的复发风险进行评估以确保只有高危病例才被施予极强治疗.研究表明采用成人方案治疗的青少年病人,其效果要显著差于使用儿童方案治疗的同年龄组. 相似文献
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OBJECTIVES: Oral hairy leukoplakia (HL) is an acan-thotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa.
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection. 相似文献
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection. 相似文献
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S Satyanarayana AT Kalghatgi A Muralidhar RS Prasad KZ Jawed A Trehan 《Medical Journal Armed Forces India》2002,58(1):33-37
Lymphadenopathy is the commonest presentation in HIV positive individuals. Fine needle aspiration cytology of 196 HIV positive patients was studied during six monthly review. 75% paients in this study who were asymptomatic were detected to have lymphadenopathy during the surveillance. 82% had lymph nodes smaller than 1cm size. Lymphadenopathy at more than one site was observed in 46.8% cases. Commonest opportunistic infection noticed was tuberculosis (TB) in 34.2%. Cyto-morphologically reactive pattern with Add fast bacilli (AFB) positivity was observed in 16.4% of TB cases. In 2.9% cases AFB were detected even in the tissue fluid. Negative images of AFB were observed in the macrophages in 3 cases. TB was detected with equal frequency in both asymptomatic and symptomatic groups. Axillary nodes pose problem due to deeper location. False positives were a case of dermatopathic lymphadenopathy and a case of Kimura''s disease. False negatives include two cases of TB lymphadenitis. Pathogens should be looked for irrespective of cyto-morphology. Biopsy should be done to confirm cases of lymphomas. Fine needle aspiration cytology should be included in the protocol of six monthly review of HIV infected cases.KEY WORDS: AIDS, FNAC, HIV, Lymph node, Tuberculosis 相似文献
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