Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis

Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.     

N-取代多亚甲基二甲酰胺类癌细胞分化诱导剂的合成

N-Alkyl polymethylene dicarboxamides are known potent inducers of erythroid differentiation in murine erythroleukemia cells. The most active inducer N, N, N', N'-tetramethyl-1, 6-hexane-dicarboxamide has the same effectiveness as HMBA which has entered clinical trials as a differentiating agent. These compounds also have inducing activity in HL-60 human promyelocytic leukemia cells. In this paper, the synthesis of a series of N,N'-bis[2-(2-thiazolinyl)], N,N'-bis [5-(1-methyl-2-pyridonyl)], N, N'-bis [3-(1- phenyl- 5- pyrazolonyl )] polymethylene dicarboxamides and 3,3'-(polymethylene dicarbonyl)bis(1-methyl-2-imidazolidine-thiones) is reported. The inducing activities of the compounds were evaluated in vitro with HL-60 human promyelocytic leukemia cell line. Among them, N, N'-bis[-2- (2-thiazolinyl)]-1,8-octamethylene-dicarboxamide (Ⅰ₄) and N, N'-bis[5- (1-methyl- 2-pyridonyl)]-1,6-hexamethylenedicarboxamide (Ⅱ₃) were shown to be relatively effective inducers of differentiation.     

Modulated expression of notch1 during thymocyte development

The Notch gene family encodes transmembrane proteins that have been implicated in control of diverse cellular differentiation events in the fly, frog, and mouse. Mammalian Notch1 is expressed at high levels in thymus and is mutated in a subset of human T-cell acute lymphoblastic neoplasms, suggesting a role in T-cell differentiation. To investigate the patterns of expression of NOTCH1 protein in thymocytes of the developing and mature thymus, antibodies raised against NOTCH1 were used to perform immunohistochemical and flow cytometric analyses. Strong staining for NOTCH1 within the fetal murine thymus was observed as early as 13.5 days postcoitum. By 17.5 days postcoitum, preferential staining of superficial cortical thymocytes was observed, with weak staining of developing medulla. Flow cytometric analysis and immunohistochemical staining of flow-sorted cells confirmed that the highest levels of NOTCH1 expression in adult murine thymus were present in immature cortical thymocytes (CD24high, CD4-CD8-). In contrast, NOTCH1 expression was low or absent in more mature cortical thymocytes (CD24low, CD4+CD8+), whereas intermediate levels of expression were observed in CD4+CD8- and CD4-CD8+ cells. These data indicate a dynamic pattern of NOTCH1 expression during T-cell differentiation and suggest that downregulation of NOTCH1 may be required for maturation of cortical thymocytes.     

Neonatal ovarian cysts: sonographic-pathologic correlation

The authors reviewed the prenatal (11 infants) and postnatal (17 infants) sonograms and the clinical, surgical, and pathologic findings in 17 infants with an ovarian cyst to determine the sonographic features and natural history of neonatal ovarian cysts. An uncomplicated cyst (nontwisted, nonhemorrhagic) was completely anechoic and the cyst wall was imperceptible with sonography (five cases). A twisted or hemorrhagic cyst was cystic with a fluid-debris level, cystic with a retracting clot, septated with or without internal echoes, or solid (12 cases). These complicated cysts contained liquid and/or organized hematoma. Eleven of the 12 complicated cysts had a thin, highly echogenic wall. Cyst torsion commonly occurred in utero and could be diagnosed on prenatal sonograms by a typical sonographic appearance (eight cases). All of these infants were asymptomatic after birth. Four infants with hemorrhagic or twisted cysts were symptomatic. All cysts except one that resolved spontaneously were treated surgically, including three twisted cysts that showed no change in size over a 1-8-month interval. All of the cysts were of follicular origin.     

Pediatric choroid plexus neoplasms: MR, CT, and pathologic correlation

Choroid plexus papillomas are rare, constituting approximately 0.5% of all intracranial neoplasms. Four benign choroid plexus papillomas and one choroid plexus carcinoma were retrospectively reviewed in patients aged 4-20 months who had been examined with magnetic resonance (MR) imaging with a field strength of 0.5 T or 1.0 T and with computed tomography (CT) before and after the administration of contrast material. In general, the tumors were of intermediate signal intensity on T1-weighted images and of either intermediate or increased signal intensity (T2 lengthening) with T2 weighting. All demonstrated variable areas of internal signal void interpreted as signifying regional blood flow, calcification, or old hemorrhage. CT findings included relatively uniform contrast enhancement. Microscopic pathologic changes of the benign lesions mimicked the appearance of normal choroid plexus and confirmed the highly vascular nature of these tumors. MR imaging, with its high-resolution multiplanar techniques, offers direct visualization of these lesions in relation to normal anatomy and better discrimination and confirmation of their intraventricular location, facilitating surgery and postoperative follow-up.     

A monovalent C{micro}4-specific ligand enhances the activation of human B cells by membrane IgM cross-linking ligands

The ligand-receptor binding requirements for achieving fullB cell activation through the membrane immunoglobulin mIg signalingpathway are relatively demanding, and mIg-antigen engagementswhich fall below these critical thresholds cause, at most, onlythe partial activation of B cells. In an effort to resolve newmeans of enhancing the efficacy of mIgM-medlated signal transduction,as well as to further understand the process by which mIgM-mediatedsignals are initiated, we have explored the mechanism for apreviously reported synergy between certain mixtures of murineanti-IgM mAbs in eliciting human B cell DNA synthesis. We herereport that striking synergy occurs when any of several relativelyhigh affinity mAbs specific for diverse domains of mlgM arecombined in culture with the relatively low affinity Cµ4-specificligand, mAb IG6. Although B cell activation was dependent uponthe bivalency, and hence mIgM cross-linking potential, of thehigh affinity ligand, low affinity mAb IG6 could enhance theactivation process when present as a monovalent Fab' fragment.This did not appear due to F(28ab')² contamination or Fab' aggregation,since IG6 Fab' preparations were notably compromised in severalother functions requiring ligand bivalency. Pulsing studiesrevealed that the Cµ4-specific ligand exhibits its functionaleffects only when stimulatory mIgM receptor cross-links arebeing formed by bivalent ligands, and that IG6 Fab' enhancementis most notable during the later interval of the prolonged mIgMsignaling process that leads to S phase entry. A unique regionof the membrane-proximal IgM domain may be important for Fab'-mediatedenhancement, since Fab' fragments that bind with higher affinitiesto distinct sites on Cµ4 were not as effective at mediatingthis phenomenon. Several possibilities for the adjuvant effectsof this Cµ4-speclfic Fab' on B cell responses triggeredby mIgM crosslinking ligands are discussed, including the possibilitythat IG6 Fab' influences the potential for mIgM dimer formationor interactions of mIgM with other signal-transducing molecules. Received 13 October 1994, accepted 9 November 1994.