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11.
High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions 总被引:5,自引:3,他引:5
Baumer A; Dutly F; Balmer D; Riegel M; Tukel T; Krajewska-Walasek M; Schinzel AA 《Human molecular genetics》1998,7(5):887-894
Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in
the vast majority of patients affected by CATCH 22 syndromes and the
Williams-Beuren syndrome, respectively. In a group of 15 Williams- Beuren
patients, we have shown previously that a large number of 7q11.23 deletions
occur in association with an interchromosomal rearrangement, indicative of
an unequal crossing-over event between the two homologous chromosomes 7. In
this study, we show that a similar mechanism also underlies the formation
of the 22q11.2 deletions associated with CATCH 22. In eight out of 10
families with a proband affected by CATCH 22, we were able to show that a
meiotic recombination had occurred at the critical deleted region based on
segregation analysis of grandparental haplotypes. The incidences of
crossovers observed between the closest informative markers, proximal and
distal to the deletion, were compared with the expected recombination
frequencies between the markers. A significant number of recombination
events occur at the breakpoint of deletions in CATCH 22 patients (P =
2.99x10(-7)). The segregation analysis of haplotypes in three- generation
families was also performed on an extended number of Williams-Beuren cases
(22 cases in all). The statistically significant occurrence of meiotic
crossovers (P = 4.45x10(-9)) further supports the previous findings. Thus,
unequal meiotic crossover events appear to play a relevant role in the
formation of the two interstitial deletions. The recurrence risk for
healthy parents in cases where such meiotic recombinations can be
demonstrated is probably negligible. Such a finding is in agreement with
the predominantly sporadic occurrence of the 22q11.2 and 7q11. 23
deletions. No parent-of-origin bias was observed in the two groups of
patients with regard to the origin of the deletion and to the occurrence of
inter- versus intrachromosomal rearrangements.
相似文献
12.
Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies. 总被引:5,自引:0,他引:5
J Droese A W Langerak P J T A Groenen M Brüggemann P Neumann I L M Wolvers-Tettero M C van Altena M Kneba J J M van Dongen 《Leukemia》2004,18(9):1531-1538
The BIOMED-2 Concerted Action BMH4-CT98-3936 on 'Polymerase chain reaction (PCR)-based clonality studies for early diagnosis of lymphoproliferative disorders' developed standardized PCR protocols for detection of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, including TCR beta (TCRB). As no comparable TCRB PCR method pre-existed and only a limited number of samples was tested within the BIOMED-2 study, we initiated this study for further validation of the newly developed TCRB PCR approach by comparing PCR data with previously generated Southern blot (SB) data in a series of 66 immature (ALL) and 36 mature T-cell malignancies. In 91% of cases, concordant PCR and SB results were found. Discrepancies consisted of either failure to detect SB-detected TCRB rearrangements by PCR (6.5%) or detection of an additional non-SB defined rearrangement (2.5%). In 99% of cases (99/100), at least one clonal TCRB rearrangement was detected by PCR in the SB-positive cases. A predominance of complete Vbeta-Jbeta rearrangements was seen in TCRalphabeta(+) T-cell malignancies and CD3-negative T-ALL (100 and 90%, respectively), whereas in TCRgammadelta(+) T-ALL, more incomplete Dbeta-Jbeta TCRB rearrangements were detected (73%). Our results underline the reliability of this new TCRB PCR method and its strategic applicability in clonality diagnostics of lymphoproliferative disorders and MRD studies. 相似文献
13.
ANA JP MORAES POLLYANA MF SOARES AURA L ZAPATA ANA PN LOTITO ADRIANA ME SALLUM CLOVIS AA SILVA 《Pediatrics international》2006,48(1):48-53
Background: The purpose of the present paper was to describe the clinical manifestations and treatment of patients with panniculitis. Methods: From January 1983 to December 2002, 4294 patients were treated for pediatric rheumatological diseases at Pediatric Rheumatology Unit, University of São Paulo, Brazil. Of these, 35 children and adolescents (0.8%) presented with panniculitis: erythema nodosum (EN) or Weber–Christian disease (WCD). Clinical characteristics, laboratory exams, biopsy of the lesion, treatment and clinical course were studied. Results: Of the 35 patients, 29 presented with EN and six with WCD, one of these with cytophagic histiocytic panniculitis. Mean age at symptom onset was 85 months (6–204 months) and the mean duration of follow up was 55 months (1–144 months). All the patients presented with inflammatory subcutaneous nodules. The patients with WCD presented with systemic manifestations and cutaneous atrophy. The principal etiologies of EN were streptococcal infection (42%), undetermined (13.5%), pulmonary tuberculosis (10%), and acute rheumatic fever (10%). Biopsy of the nodules indicated septal panniculitis in 14 patients with EN and lobular panniculitis without vasculitis in the patients with WCD, one of which had cytophagic histiocytic panniculitis. There was recurrence in 11 patients (38%) with EN and in all those with WCD. Non‐steroidal anti‐inflammatory drugs were used in 15 patients with EN and corticosteroids and/or immunosuppressive drugs in the six patients with WCD. Three patients died. Conclusions: EN is the most frequent panniculitis, with a benign course and is mainly associated with infections. WCD is a severe disease, with systemic involvement, that proceeds with cutaneous atrophy and requires the use of corticosteroids and or immunosuppressive drugs. 相似文献
14.
WBG Macdonald AP Patrikeos RI Thompson BD Adler AA Van Der Schaaf 《Journal of Medical Imaging and Radiation Oncology》2005,49(1):32-38
The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses. 相似文献
15.
H Khalili A Soudbakhsh M Hajiabdolbaghi S Dashti-Khavidaki A Poorzare AA Saeedi R Sharififar 《BMC infectious diseases》2008,8(1):165
Background
Human immunodeficiency virus infected individuals are prone to malnutrition due to increased energy requirements, enteropathy and increased catabolism. Trace elements such as zinc and selenium have major role in maintaining a healthy immune system. This study was designed to evaluate the nutritional status of Iranian subjects who were newly diagnosed with human immunodeficiency virus infection and to compare serum level of zinc and selenium in these patients with those of the sex and aged match healthy subjects. 相似文献16.
背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。 相似文献
17.
Kim van der Weerd Willem A. Dik Benjamin Schrijver Ad J.J.C. Bogers Alexander P.W.M. Maat Francien H. van Nederveen P. Martin van Hagen Jacques J.M. van Dongen Anton W. Langerak Frank J.T. Staal 《Molecular immunology》2013,53(3):302-312
T-cell receptor (TCR) repertoire diversity, thymic output, clonal size and peripheral T-lymphocyte numbers largely depend on intra-thymic and post-thymic T-lymphocyte proliferation. However, quantitative insight into thymocyte and T-lymphocyte proliferation is still lacking. We developed a new TCRG-based TCR excision circle (TREC) assay, the Vγ-Jγ TREC assay, which we used together with an adjusted δREC-ψJα TREC assay to quantify the proliferative history of human thymocyte and T-lymphocyte subpopulations from children and adults. This revealed that thymocytes undergo ~6–8 intra-thymic cell divisions from the double negative (DN) 3 developmental stage onwards, which appeared independent of age. Thus thymocyte proliferation after the DN3 developmental stages is stable and therefore not contributing to the reduced thymic output upon ageing. Cord blood naive T lymphocytes had already undergone ~2–3 post-thymic cell divisions, which increased to ~6–7 cell divisions in naive T lymphocytes of middle-aged adults, indicating the importance of homeostatic naive T-lymphocyte proliferation from a young age onwards in the maintenance of peripheral T-lymphocyte numbers. In conclusion, our data provide quantitative insight into the proliferative history of thymocyte and T-lymphocyte subpopulations and alterations herein upon ageing. This novel TREC assay approach could prove valuable in immune status monitoring in a variety of conditions. 相似文献
18.
R. W. J. Meijers N. H. R. Litjens E. A. de Wit A. W. Langerak A. van der Spek C. C. Baan W. Weimar M. G. H. Betjes 《Clinical and experimental immunology》2013,174(3):424-432
Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End‐stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD‐related premature T cell ageing. 相似文献
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