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91.
Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ‘mutome’). With the advent of next‐generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole‐genome sequencing (WGS) has the potential to identify all disease‐causing or disease‐associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene‐coding sequences for those disease‐causing or disease‐associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation‐screening strategies but also for enhancing the interpretation of findings derived from genome‐wide association studies, whole‐exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology. 相似文献
92.
Lauener RP; Huttner S; Buisson M; Hossle JP; Albisetti M; Seigneurin JM; Seger RA; Nadal D 《Blood》1995,86(4):1400-1407
One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome. 相似文献
93.
94.
Ventilator-associated pneumonia (VAP) is a common cause of morbidity, antibiotic use, increased length of stay and, possibly,
increased mortality in ICU patients. Colonization of the oropharyngeal cavity with potentially pathogenic micro-organisms
is instrumental in the pathogenesis of VAP, and selective oropharyngeal decontamination (SOD) with antibiotics (AB-SOD) or
antiseptics, such as chlorhexidine gluconate (CHX-SOD), has been associated with reduced incidences of VAP. In a recent issue
of Critical Care Scannapieco and colleagues investigated differences in oropharyngeal colonization between mechanically ventilated patients
receiving oropharyngeal decontamination with 0.12% CHX-SOD either once or twice daily compared to placebo. CHX-SOD was associated
with a reduction in Staphylococcus aureus colonization, but the study was underpowered to demonstrate a reduction in VAP incidence. We urgently need well-designed
and adequately powered studies to evaluate the potential benefits of CHX-SOD on patient outcome in ICUs. 相似文献
95.
JM Toohey K Ismail D Lonergan CR Lewis 《Journal of Medical Imaging and Radiation Oncology》2007,51(6):594-596
Amyloid involvement of the breast is infrequently reported and may have clinical and radiological features suspicious for a primary breast malignancy. We describe a case of amyloid of the breast in which asymptomatic mammographic findings were suspicious for locally recurrent disease in a patient with previously treated breast cancer. 相似文献
96.
GB Fogarty R Cassumbhoy JM Martin M Fay J Ainslie 《Journal of Medical Imaging and Radiation Oncology》2007,51(3):267-275
High‐risk skin cancer arising on the upper limb or trunk can cause axillary nodal metastases. Previous studies have shown that axillary radiotherapy improves regional control. There is little published work on technique. Technique standardization is important in quality assurance and comparison of results especially for trials. Our technique, planned with CT assistance, is presented. To assess efficacy, an audit of patients treated in our institution over a 15‐month period was conducted. Of 24 patients treated, 13 were treated with radical intent, 11 with this technique. With a follow up of over 2 years, the technique had more than a 90% (10/11) regional control in this radical group. Both of the radical patients who were not treated according to the technique had regional failure. One case of late toxicity was found, of asymptomatic lymphoedema in a radically treated patient. This technique for axillary radiotherapy for regional control of skin cancer is acceptable in terms of disease control and toxicity as validated by audit at 2 years. 相似文献
97.
98.
Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong 总被引:1,自引:0,他引:1
RYT Sung JM Ling SM Fung SJ Oppenheimer DW Crook JTF Lau AFB Cheng 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(11):1262-1267
Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children. 相似文献
99.
After the introduction of the colposcope for the examination of children suspected of being sexually abused in Leeds, a study was undertaken to describe the findings in detail. A total of 109 consecutive prepubertal girls, mean age 70.4 months were assessed including colposcopic genital and anal examination, and peer group review of reports and photographs. Fifty nine children had signs consistent with blunt force penetrating trauma (hymenal transection/major notch, scar, or hymenal attenuation). Transections were encountered most commonly at 6 o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh abduction only and in 47 the hymenal orifice transverse diameter was greater than 4 mm on labial separation. Overall, physical findings were commonly present and in only two cases were no signs recorded. Non-specific and frequent findings included patterns of labial and introital reddening. Supportive hymenal signs including swelling, rounding of edge, thickening, distortion, and loss of symmetry were common. Labial fusion was present in 20. Urethral dilatation with labial separation was noted in 14. Physical findings including normality are consistent with abuse and even minor anogenital signs as well as negative findings should be documented. Colposcopy and photography are valuable tools in peer review, teaching, and case management. 相似文献
100.
We analysed the effect of exposure to tobacco smoke during pregnancy on fetal growth parameters in 129 term newborns. Children were classified into four depending on exposure on the basis of a questionnaire completed by the mother. The results confirmed that tobacco smoking reduced weight, length, cranial and thoracic perimeters at birth when exposure was due to either active or passive smoking. Weight deficits of infants whose mothers smoked heavily (458 g) were higher than those whose mothers were exposed to passive smoking (192 g). We conclude that passive smoking is a very important variable and should be taken into account in any study of neonatal growth parameters. 相似文献