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61.
Surveillance data on incidence of twins among reported cases of pediatric AIDS in New York City are presented. Most pairs are concordant for HIV infection. Three discordant pairs have been described elsewhere. Possible reasons for the association are discussed, including the most likely explanation that twins show symptoms early and are overrepresented in the early years of surveillance of pediatric AIDS. 相似文献
62.
Neville CE Robson PJ Murray LJ Strain JJ Twisk J Gallagher AM McGuinness M Cran GW Ralston SH Boreham CA 《Calcified tissue international》2002,70(2):89-98
Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood. 相似文献
63.
64.
Havranek EP Masoudi FA Ralston DL Susman NJ Krumholz HM Taylor JP 《Congestive heart failure (Greenwich, Conn.)》2002,8(6):342-345
This is the final installment in a series reporting on the Centers for Medicare & Medicaid Services (CMS) initiatives to improve care for Medicare beneficiaries with heart failure through its Quality Improvement Organization (QIO) contractors during the 1999-2002 contract cycle. Previous columns have reported on a nation-wide hospital-based effort, the National Heart Failure project, and a more limited outpatient-based effort, the Heart Failure Practice Improvement Effort. After 3 years of experience with the National Heart Failure project, it is appropriate to highlight the issues pertinent to future quality improvement initiatives in heart failure care. 相似文献
65.
Abraham P Ralston SH Hewison M Fraser WD Bevan JS 《Postgraduate medical journal》2002,78(926):752-753
Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy. 相似文献
66.
缺血性中风(中经络)证候分类与血脂、血压、血液流变学关系的研究 总被引:13,自引:3,他引:13
目的探讨缺血性中风证侯分类的客观量度。方法本研究对118例缺血性中风患者按中医证类进行分组,观察各证类组病例的血脂、血压及血液流变学改变。结果研究表明,风痰阻络证、痰热腑实证及气虚血瘀证组脂质变化较正常组明显升高(P<0.05~0.01),其中风痰阻络证、痰热腑实证与气虚血瘀证组存在显著差异(P<0.05);气虚血瘀证、风痰阻络证及痰热腑实证组血液流变学指标较正常组有显著差异(P<0.05~0.01);肝阳暴亢证、痰热腑实证组血压明显高于气虚血瘀证、风痰阻络证及阴虚风动证组(P<0.05~0.01)。结论血脂、血压及血液流变学指标可为缺血性中风证候分类提供客观量度。 相似文献
67.
Wang WS; Fan FS; Hsieh RK; Chiou TJ; Lin JK; Lin TC; Yen CC; Liu JH; Hsu H; Chen PM 《Japanese journal of clinical oncology》1997,27(3):174-179
5-Fluorouracil in combination with leucovorin has been shown to be active
in therapeutic trials of metastatic colorectal carcinoma. In this study, we
administered these drugs to 72 patients with metastatic colorectal
carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil
were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and
leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36
patients with or without prior 5-fluorouracil treatment received
5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous
infusion every two weeks. Clinical efficacy and toxicity were assessed by
WHO criteria. Variables were tested for relations to response and survival
by univariate and multivariate analysis. The response rate was 19.4% in
weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527).
Median survivals in the two arms were 18.4 months (weekly) and 21 months
(biweekly) respectively (P = 0.708). Gastrointestinal side effects
including nausea, vomiting, diarrhea and mucositia were the major
toxicities of these regimens. By multivariate analysis, the only factor to
influence response rate was the site of metastases (P = 0.009). The only
factor to affect survival was performance status of the patient (P =
0.0001). We concluded that the two 5-fluorouracil based regimens are
well-tolerated and shown to have a response rate comparable with previous
reports of similar regimens in patients with metastatic colorectal cancer.
Only liver metastases seemed to have a better response to therapy.
Performance status is the most important prognostic factor in patients with
metastatic colorectal cancer.
相似文献
68.
A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation 总被引:10,自引:0,他引:10
Chappell SA LeQuesne JP Paulin FE deSchoolmeester ML Stoneley M Soutar RL Ralston SH Helfrich MH Willis AE 《Oncogene》2000,19(38):4437-4440
The 5' untranslated region of the proto-oncogene c-myc contains an internal ribosome entry segment (IRES) (Nanbru et al., 1997; Stoneley et al., 1998) and thus c-myc protein synthesis can be initiated by a cap-independent as well as a cap-dependent mechanism (Stoneley et al., 2000). In cell lines derived from patients with multiple myeloma (MM) there is aberrant translational regulation of c-myc and this correlates with a C-T mutation in the c-myc-IRES (Paulin et al., 1996). RNA derived from the mutant IRES displays enhanced binding of protein factors (Paulin et al., 1998). Here we show that the same mutation is present in 42% of bone marrow samples obtained from patients with MM, but was not present in any of 21 controls demonstrating a strong correlation between this mutation and the disease. In a tissue culture based assay, the mutant version of the c-myc-IRES was more active in all cell types tested, but showed the greatest activity in a cell line derived from a patient with MM. Our data demonstrate that a single mutation in the c-myc-IRES is sufficient to cause enhanced initiation of translation via internal ribosome entry and represents a novel mechanism of oncogenesis. 相似文献
69.
Lynne J Hocking Gavin J A Lucas Anna Daroszewska Tim Cundy Geoff C Nicholson Judit Donath John P Walsh Catriona Finlayson James R Cavey Barbara Ciani Paul W Sheppard Mark S Searle Robert Layfield Stuart H Ralston 《Journal of bone and mineral research》2004,19(7):1122-1127
Three novel missense mutations of SQSTM1 were identified in familial PDB, all affecting the UBA domain. Functional and structural analysis showed that disease severity was related to the type of mutation but was unrelated to the polyubiquitin-binding properties of the mutant UBA domain peptides. INTRODUCTION: Mutations affecting the ubiquitin-associated (UBA) domain of Sequestosome 1 (SQSTM1) gene have recently been identified as a common cause of familial Paget's disease of bone (PDB), but the mechanisms responsible are unclear. We identified three novel SQSTM1 mutations in PDB, conducted functional and structural analyses of all PDB-causing mutations, and studied the relationship between genotype and phenotype. MATERIALS AND METHODS: Mutation screening of the SQSTM1 gene was conducted in 70 kindreds with familial PDB. We characterized the effect of the mutations on structure of the UBA domain by protein NMR, studied the effects of the mutant UBA domains on ubiquitin binding, and looked at genotype-phenotype correlations. RESULTS AND CONCLUSIONS: Three novel missense mutations affecting the SQSTM1 UBA domain were identified, including a missense mutation at codon 411 (G411S), a missense mutation at codon 404 (M404V), and a missense mutation at codon 425 (G425R). We also identified a deletion leading to a premature stop codon at 394 (L394X). None of the mutations were found in controls. Structural analysis showed that M404V and G425R involved residues on the hydrophobic surface patch implicated in ubiquitin binding, and consistent with this, the G425R and M404V mutants abolished the ability of mutant UBA domains to bind polyubiquitin chains. In contrast, the G411S and P392L mutants bound polyubiquitin chains normally. Genotype-phenotype analysis showed that patients with truncating mutations had more extensive PDB than those with missense mutations (bones involved = 6.05 +/- 2.71 versus 3.45 +/- 2.46; p < 0.0001). This work confirms the importance of UBA domain mutations of SQSTM1 as a cause of PDB but shows that there is no correlation between the ubiquitin-binding properties of the different mutant UBA domains and disease occurrence or extent. This indicates that the mechanism of action most probably involves an interaction between SQSTM1 and a hitherto unidentified protein that modulates bone turnover. 相似文献
70.