Oncogenesis in utero: fetal death due to acute myelogenous leukaemia with an MLL translocation

The incidence of translocations involving the 11q23 gene MLL is markedly increased in leukaemias that occur in infants < 1 year of age. Epidemiological and molecular data have demonstrated that at least some of these translocations occur in utero . In this report we describe a case of fetal death at 36 weeks of gestation. At autopsy the fetus was found to have widely disseminated acute myelogenous leukaemia (AML), FAB subtype M5. Molecular cytogenetic studies of nuclei recovered from paraffin-embedded tissue sections demonstrated that the leukaemic cells contained an MLL translocation. This is the first detailed report, to our knowledge, of fetal death due to acute leukaemia, and directly demonstrates oncogenesis in utero .     

Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.

Besides a prominent mononuclear cell infiltration of the islets of Langerhans, nonobese diabetic (NOD) mice also show massive cellular infiltrates of the submandibular and lacrimal glands concomitant with histological signs of tissue damage. To obtain insights into the mechanisms operative during the initiation and progression of tissue damage, we followed by in situ hybridization the appearance of cells containing mRNA of the gene encoding the proinflammatory cytokine TNF-alpha in the cellular infiltrates. Cells expressing TNF-alpha are mainly located in infiltrates, are absent in nonaffected glands, and are preferentially found among CD4 T cells. Secretion of TNF-alpha by gland-infiltrating cells was confirmed by an ELISPOT procedure. Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided by the observed significant reduction in the extent of infiltration in nonobese diabetic mice transgenic for a soluble TNF receptor p55 fused to the Fc part of human IgG3. This protection from infiltration is paralleled by decreased expression of the adhesion molecules ICAM-1 and VCAM-1 in submandibular and lacrimal glands. These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.     

Kindliche suprakondyläre Oberarmfrakturen

Stage-adapted treatment for supracondylar humeral fractures in children is demonstrated with our own collective of patients. From 1997 to 2001, 88 children were treated for the diagnosis of supracondylar humeral fractures. The follow-up of 81 patients was possible (within 34 months). Based on the classification of von Laer, 36 stable injuries (types I and II) were treated conservatively on an outpatient basis and 52 unstable injuries (types III and IV) were treated operatively with a short stay in the hospital. The conservative treatment included immobilization in a cast or a Blount bandage. The operative treatment included closed or open reposition of the fracture and stabilization by crossed pinning (K-wires). Two of the conservatively treated type II fractures dislocated so that an additional operative treatment was necessary. Accompanying injuries besides the fracture were one primary vessel lesion and three traumatic nerve lesions. The follow-up according to Flynn's criteria showed 80% excellent, 19% good, and 1% fair results. The classification of von Laer can be recommended for stage-adapted treatment of supracondylar humeral fractures in children.     

合欢皮中新皂甙的结构鉴定

从合欢皮(Albizziae cortex)的95%乙醇提取物的正丁醇萃取部分中分离得到3个新的三萜皂甙,用化学方法及¹H-和¹³C-NMR,DEPT,COSY,TOCSY,HMQC-COSY,HMQC-TOCSY,HMBC,NOESY等波谱方法鉴定其结构为:I(1个三萜,9个糖,2个单萜),命名为合欢皂甙(julibroside)J₁;II(1个三萜,8个糖,2个单萜),命名为合欢皂甙J_{2;II(1个三萜,9个糖,2个单萜),命名为合欢皂甙J3。}     

Childhood acute lymphoblastic leukemia: Integrating genomics into therapy

Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer‐related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for the development of new therapeutic approaches in the era of precision medicine. In this review, the authors delineate the current genetic landscape of childhood ALL, emphasizing patient outcomes with contemporary treatment regimens as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. Cancer 2015;121:3577–3590 . © 2015 American Cancer Society.     

Characterization of the IgG-Fc receptor on human platelets

To determine quantitatively the number and avidity of receptors for the Fc portion of IgG on human platelets, we have measured the binding to platelets of human monomeric monoclonal IgG, and of small covalently crosslinked polymers of IgG1 labeled with 125I. The binding of labeled IgG1 monomers to platelets is too weak to permit quantitation. The binding of dimers or larger polymers of IgG1 is much more avid (greater at 4 degrees C than 37 degrees C), is readily reversible, and is saturable. The number of receptor sites ranges from 400 to 2000 per platelet and the mean equilibrium association constant (Ka) for the binding of dimers at 4 degrees C is 2.2 x 10(7) M-1 +/- 0.9 x 10(7) M- 1. The binding is specific for the Fc portion of IgG, and IgG1 and IgG3 bind to the receptors much more avidly than IgG2 or IgG4. Unlabeled IgG1 dimers are about 7--8-fold more potent in inhibiting binding than are IgG1 monomers, and larger polymers are even more potent than dimers. Thus, the Fc receptors on platelets bind human IgG1 with the same specificity and similar avidity as Fc receptors on polymorphonuclear leukocytes (PMNs), but PMNs have about 300-fold more receptors per unit of surface area than platelets.