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451.
Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases 下载免费PDF全文
Celia L Gregson Lawrie Wheeler Sarah A Hardcastle Louise H Appleton Kathryn A Addison Marieke Brugmans Graeme R Clark Kate A Ward Margaret Paggiosi Mike Stone Joegi Thomas Rohan Agarwal Kenneth ES Poole Eugene McCloskey William D Fraser Eleanor Williams Alex N Bullock George Davey Smith Matthew A Brown Jon H Tobias Emma L Duncan 《Journal of bone and mineral research》2016,31(3):640-649
High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52‐kb intronic deletion 3′). Family members were assessed for HBM segregation with identified variants. Three‐dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (~prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non‐LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5‐HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST‐LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z‐scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z‐scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (~3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance. © 2015 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
452.
C.C.G. Silva M.S. dos Santos J.L.G.C. Monteiro S.C. de Aguiar Soares Carneiro B.C. do Egito Vasconcelos 《International journal of oral and maxillofacial surgery》2021,50(1):96-103
The aim of this systematic review was to evaluate published evidence on the association between the use of antidepressants and complications involving dental implants. Two reviewers independently performed electronic searches of the MEDLINE/PubMed, Cochrane Library, and Scopus databases for relevant articles published up to May 30, 2019. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle–Ottawa Scale was used for the appraisal of the methodological quality of the studies included. A meta-analysis was performed to determine the risk of dental implant failure in individuals taking antidepressants. Five comparative observational studies were selected for this review; these included a total of 2056 participants with 5302 implants. The results suggest a risk ratio of 3.73 (95% confidence interval 1.85–7.52, P = 0.0002) for implant failure in antidepressant users submitted to oral rehabilitation when compared to non-users. However, these studies did not present methodological rigour or standardize the drugs used. Thus, there is insufficient evidence for an association between antidepressant use and dental implant complications. 相似文献
453.
Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia. 相似文献
454.
Aim: To describe the epidemiology of infants admitted to Paediatric Intensive Care (PIC) with acute respiratory failure including bronchiolitis. Methods: Data from all consecutive admissions from 2004 to 2007 in all 29 designated Paediatric Intensive Care Units (PICUs) in England and Wales were collected. Admission rates, risk‐adjusted mortality, length of stay, ventilation status, preterm birth, deprivation and ethnicity were studied. Results: A total of 4641 infants under 1 year of age had an unplanned admission to PIC with acute respiratory failure (ARF), an admission rate of 1.80 per 1000 infants per year. There was a reduced rate of admission with bronchiolitis in South Asian children admitted to PICU, which is not explained by case‐mix. Children born preterm had a higher rate of admission and longer stay, but a similar low mortality. Risk‐adjusted mortality was higher in South Asian infants and the highest in those with ARF (OR 1.76, 95% CI 1.20–2.57) compared with the rest of the PICU population. Conclusion: Acute respiratory failure in infants causes most of the seasonal variation in unplanned admission to intensive care. Socioeconomic deprivation and prematurity are additional risk factors for admission. Fewer South Asian infants are admitted to PICU with a diagnosis of bronchiolitis, but risk‐adjusted mortality is higher in South Asian infants overall. 相似文献
455.
Amália Cínthia Meneses Rêgo Rachel Alcântara Oliveira Ramalho Eryvaldo Sócrates Tabosa Egito Irami Araújo-Filho Ítalo Medeiros Azevedo Christopher J. Palestro Aldo Cunha Medeiros 《Applied radiation and isotopes》2010,68(12):2169-2173
This study evaluated the effects of total colectomy on the biodistribution of technetium-99m pertechnetate (99mTcO4?) on the 28th postoperative day in rats. Samples of several organs were harvested for counting the percent of injected radioactivity/g of tissue (%ATI/g). The %ATI/g in colectomy rats was higher in the stomach and ileum than in sham and controls (p<0.05). Increase in mucosa and muscularis size of ileum was observed. Colectomy was associated with lower biodistribution in bladder and thyroid, T3, and T4, than in controls. 相似文献
456.
457.
C I BRODSKYN A BARRAL M A BULH
ES T SOUTO W C MACHADO M BARRAL-NETTO 《Clinical and experimental immunology》1996,105(3):450-455
There are few studies on cell-mediated cytotoxicity in human Chagas' disease. In the present study, we evaluated peripheral blood mononuclear cell (PBMC) cytotoxicity activity from chagasic patients with different clinical forms of disease. To verify the cytotoxic response, we performed cell lysis assays using 51Cr-labelled K562 cells as targets. Results are reported as lytic units (LU=number of cells required for 30% lysis) per million PBMC. Exposure of patients’ PBMC to Trypanosoma cruzi antigen led to an increase in cytotoxic activity compared with unstimulated patient cells against K562. Asymptomatic cardiomyopathy patients had higher responses (37.8±5.0 LU/106 PBMC; mean±s.d.) than indeterminate (11.5±3.6 LU/106) and symptomatic cardiomyopathy (7.8±2.5 LU/106). Normal control PBMC stimulated with T. cruzi antigen had 4.36±1.31 LU/106 PBMC against K562. Addition of recombinant interferon-gamma (IFN-γ) did not lead to significant increase in cytotoxicity in any group of patients. On the other hand, recombinant human IL-12 significantly increased cytotoxic responses from symptomatic cardiomyopathy patients and normal controls who presented low levels of cytotoxicity induced by T. cruzi antigen. The combined use of IL-12 and a neutralizing anti-IFN-γ antibody did not change IL-12-induced cytotoxic responses, showing the direct role of this cytokine on natural killer (NK) cells. NK cells were the main cells responsible for the lysis of K562 target cells as evidenced by testing cell subsets following magnetic cell sorting. These data demonstrate that chagasic patients with different clinical forms of disease have PBMC which respond to T. cruzi antigen with a cytotoxic response, and this response is up-regulated by IL-12. 相似文献
458.
Aim:
To evaluate the cytokeratin pattern of expression of hyalinizing trabecular adenomas and to verify whether or not these tumours, that share morphological features with papillary carcinomas, present the stratified epithelial-type cytokeratins commonly found in ordinary papillary carcinomas.
Methods and results:
This study consisted of the immunohistochemical detection of simple and stratified epithelial type cytokeratin filaments in a series of six hyalinizing trabecular adenomas, three papillary carcinomas with a trabecular growth pattern and two carcinomas combining hyalinizing trabecular and papillary patterns. Simple epithelial-type cytokeratins 7, 8, 18 and 19 were found in every case. Expression of the stratified epithelial-type cytokeratins 1, 5/6 and/or 13 was detected in four hyalinizing trabecular adenomas.
Conclusion:
Based on this, as well as on the cytological features and on the frequent co-occurrence of hyalinizing trabecular adenoma and papillary carcinoma, we suggest that the former lesion may be considered a peculiar encapsulated variant of papillary carcinoma. 相似文献
459.
ES Kolo 《African health sciences》2012,12(4):459-463