Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602)

Of 1,036 children with newly diagnosed non-T, non-B acute lymphoblastic leukemia (ALL) and a demonstrated cytogenetic abnormality treated on the frontline Pediatric Oncology Group (POG) therapeutic trial 8602, there were 33 patients with trisomy 21 as the sole abnormality. Of these 33, 14 had Down syndrome (DS). Although the non-DS (NDS) trisomy 21 cases tended to be older than the DS cases, there were no other significant differences in clinicobiologic features nor in treatment outcomes between the DS and NDS groups, nor between the entire trisomy 21 group and the other chromosome abnormality group. Among NDS patients with +21 and one additional abnormality, +X, +16, -20, and structural abnormalities involving 6q or 12p were common findings. Kaplan-Meier event-free survival (EFS) curves showed a 4-year EFS of 80% (SE, 12%) in NDS trisomy 21 cases, 71% (SE, 22%) in DS cases with trisomy 21 as the sole abnormality, and 69% (SE, 2%) in cases with other chromosome abnormalities. Trisomy 21 as a sole acquired abnormality in NDS patients suggests a good prognosis.     

Recurrence of unexpected infant death

Families which had experienced two or more unexpected infant deaths were the subject of detailed confidential enquiries, including necropsy examination. Cases were derived from two main sources: first, deaths occurring during a nationwide programme of support for families with a subsequent baby (8 families) plus 2 families from a scries of confidential enquiries in Sheffield, and second, direct referrals from paediatricians (17 families). Fifty-seven deaths were studied. Twenty-four families had experienced 2 and three had experienced 3 deaths: 11 deaths (19%) were found to be adequately explained by history or post-mortem findings; 7 (12%) were probably accidental; 31 (55%) were most probably due to an action by one of the parents (filicide); only 5 (9%) were considered to be true or idiopathic sudden infant death syndrome; in 3 (5%) cases there was insufficient information to draw a conclusion. Five (18%) of the families lived in circumstances of serious social deprivation. A history of psychiatric illness was present in one or both parents in 18 (67%) of the families.     

Superficial granulomatous pyoderma: an idiopathic granulomatous cutaneous ulceration

A 70-year-old male with a superficial granulomatous ulcer is reported. Histopathological findings were the same as those described for superficial granulomatous pyoderma, a recognized variant of classic pyoderma gangrenosum. The differences between pyoderma gangrenosum and its variant superficial granulomatous pyoderma are highlighted.     

Increased Pyridinoline Cross‐Link Levels in Fibrosis is Accomplished by TGFβ Induced Lysyl Hydroxylases 2B Expression

Differentiation of fibroblasts into contractile, α‐smooth muscle actin (α‐SMA) expressing myofibroblasts depends on the action of the cytokine TGFβ in conjunction with mechanical tension. The goal of this study was to assess whether mechanical stress may play a role in activating TGFβ. Previous studies have shown that myofibroblasts secrete TGFβ1 as a large latent complex, consisting of the latency associated protein (LAP), the latent TGFβ1 binding protein (LTBP‐1) and TGFβ1. LTBP‐1 targets the small latent complex of LAP and TGFβ1 to the extracellular matrix (ECM), providing a stock of latent TGFβ1. To reveal the mechanisms triggering the release of active TGFβ1 from LAP and LTBP‐1, myofibroblasts were cultured on flexible silicone membranes for 3d before being subjected to unique 5% uniaxial stretch. After stress application we observed the course of TGFβ1 activation over 24 h by quantifying luciferase synthesis under the control of the TGFβ‐inducible PAI‐1 promoter. TGFβ activation showed two distinct peaks 1 h and 6 h after stretch. TGFβ1 mRNA levels were increased after 6 h as assessed by semi‐quantitative RT‐PCR. To further determine if rapidly activated TGFβ1 was released from ECM stores, we stretched myofibroblast‐derived ECM after cells have been removed by desoxycholate or EDTA treatment. Finally, we assessed the importance of the actin cytoskeleton in TGFβ1 activation by stretching Triton‐X‐100‐ and cytochalasin‐D‐treated myofibroblasts. Our results suggest that mechanical activation of TGFβ in myofibroblast culture requires cell activity and a functional cytoskeleton.     

巨颅伴皮层下海绵样囊肿性脑白质病的病变基因定位于染色体22q13.3上250kb区域内

目的 :巨颅伴皮层下海绵样囊肿性脑白质病 (MLC)是近来被证实的一种新的常染色体隐性遗传病 ,该病的可能病变基因被确定在染色体 2 2qtel上的 3 cM区域内 ,通过研究将病变基因的可能范围进一步缩小。方法 :收集 3 3个家庭中的 3 9例MLC病人 ,对其中能提供丰富遗传信息的 1 2例家庭成员 ,运用 7个微卫星标识和 4个单核苷酸多态性标识进行连锁分析和单倍体型分析。结果 :在重组值为 0 0 2下微卫星标识 3 55c1 8的最大两点LOD值是6 65;采用单倍体型分析进一步将位于 2 2qtel上的MLC病变基因的关键位置缩小在 2 50kb内。结论 :MLC病变基因位于 2 2qtel上 2 50kb内 ,有 4个候选基因被考虑。另外 ,由于其中一个家庭成员存在遗传异质性 ,故考虑MLC可能存在第二个病变基因位点。