Prognostic limitations of the Daumas-Duport grading scheme in infratentorial neuroglial tumors in children.

The Daumas-Duport grading scheme (DDGS) utilizes four histologic features in an additive method (grade 1 if none present, grade 2 if only one is present, etc.). Its efficacy in achieving prognostically homogeneous groups of childhood infratentorial neuroglial tumors and its concordance with World Health Organization (WHO) diagnoses has not been evaluated.

Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors.

Background: In the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database.

Methods: The Cox proportional models were used to identify class survival covariates.

Association of arrhythmia and sudden death in macrocephaly-cutis marmorata telangiectatica congenita syndrome.

Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) constitutes a distinct entity characterized by prenatal overgrowth, macrosomia, hemihypertrophy, macrocephaly, nonobstructive hydrocephaly, frontal bossing, hypotonia, developmental delay, generalized or facial capillary malformation with upper philtral nevus flammeus and cutis marmorata, joint hypermobility, loose skin, toe syndactyly, and postaxial polydactyly. All but one of the cases reported previously had benign clinical courses without showing an increased risk of early infant death. We describe three additional cases with poor clinical outcomes including severe postnatal growth failure, intractable cardiac arrhythmia in two cases, and sudden infant death in two cases.

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

Background: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme.

Methods: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors.

Results: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas.

Definitive classes of childhood supratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database.

TGF-beta3-null mutation does not abrogate fetal lung maturation in vivo by glucocorticoids.

Newborn transforming growth factor (TGF)-beta3-null mutant mice exhibit defects of palatogenesis and pulmonary development. Glucocorticoids, which play a central role in fetal lung maturation, have been postulated to mediate their stimulatory effects on tropoelastin mRNA expression through TGF-beta3 in cultured lung fibroblasts. In the present study, we analyzed the abnormally developed lungs in TGF-beta3-null mutant mice and compared the effects of glucocorticoids on gene expression and lung morphology between TGF-beta3 knockout and wild-type mice.

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group.

Purpose: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of > or =5 days.

Methods: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs).

Systemic mast cell disease associated with primary ovarian mixed malignant germ cell tumor.

A 12-year-old girl with a mixed malignant germ cell tumor of the ovary, treated by surgery and chemotherapy, developed systemic mast cell disease (SMCD) approximately 3 months after chemotherapy. Hematologic malignancies have previously been noted in patients with mediastinal germ cell tumors but this is the first report of a primary ovarian germ cell neoplasm associated with SMCD.

Use of the bnx/hu xenograft model of human hematopoiesis to optimize methods for retroviral-mediated stem cell transduction (Review).

The potentiality of primitive human hematopoietic cells can be profoundly affected by in vitro culture. Due to the growing number of protocols proposed for stem cell gene therapy and ex vivo expansion, it is crucial to define methods to preserve the generative capacity of human stem cells in culture while promoting self-renewal divisions. Stem cell division, homing, and subsequent lineage development can only be studied definitively by marking of pluripotent cells, followed by tracking and clonal analysis of the progeny in a long-term transplantation system.

Groups of histopathologic abnormalities in brains of very low birthweight infants.

The neuropathologic changes in brains of very premature infants are well recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury. The goal of this study is to identify which, if any, combinations of histologic features occur together.

Clusters of histologic characteristics in children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses and identified 11 clusters of children's tumors. Each had statistically significant differences in histology and relative histologic homogeneity.

Structural requirements for the ectodomain cleavage of human cell surface macrophage colony-stimulating factor.

One form of human macrophage colony-stimulating factor (CSF-1(256), M-CSFalpha) is a member of a restricted set of cell surface transmembrane proteins, which is selected to undergo proteolytic ectodomain cleavage. To determine the substrate requirements for this cleavage, we have constructed a series of mutations in the cytoplasmic tail, transmembrane domain, and juxtamembrane region of CSF-1(256) and stably expressed the mutated genes in NIH 3T3 cells. Our results demonstrate that membrane association of the CSF-1 precursor is required for cleavage of its growth factor ectodomain and furthermore that the juxtamembrane region Pro161-Gln162-Leu163-Gln164-Glu165 (PQLQE) (residues 161-165 of the ectodomain) is an essential determinant of cell surface CSF-1(256) cleavage and that the cleavage site is partially sequence-specific.

A role for Shc, Grb2, and Raf-1 in FcgammaRI signal relay.

The activation of the serine/threonine kinase, Raf-1, serves to connect upstream protein tyrosine kinases to downstream signaling events. We previously reported that FcgammaRI stimulation of interferon gamma-differentiated U937 cells (termed U937IF cells) induces a mobility shift in Erk2. Herein, we report that cross-linking of FcgammaRI receptor in U937IF cells induces a marked tyrosine phosphorylation of Raf-1 (10-fold increase).