The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function.

Introduction: Polymicrobial sepsis causes acute anorexia (loss of appetite), leading to lipolysis in white adipose tissue and proteolysis in muscle, and thus release of free fatty acids (FFAs), glycerol and gluconeogenic amino acids. Since hepatic peroxisome proliferator-activated receptor alpha (PPARα) and glucocorticoid receptor (GR) quickly lose function in sepsis, these metabolites accumulate (causing toxicity) and fail to yield energy-rich molecules such as ketone bodies (KBs) and glucose. The mechanism of PPARα and GR dysfunction is not known.

Causes of hypereosinophilia in 100 consecutive patients.

Background: Hypereosinophilia (HE, persistent peripheral blood eosinophilia > 1.5 × 10 /L) and hypereosinophilic syndrome (HES, HE with end-organ damage) are classified as primary (due to a myeloid clone), secondary (due to a wide variety of reactive causes), or idiopathic. Diagnostic evaluation of eosinophilia is challenging, in part because secondary causes of HE/HES such as lymphocyte-variant HES (L-HES) and vasculitis are difficult to diagnose, and emerging causes such as immunoglobulin G4-related disease (IgG4-RD) have rarely been examined.

Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer.

Introduction: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals.

Adaptive noise suppression for a dual-microphone hearing aid.

An adaptive beamformer for behind-the-ear dual-microphone hearing aids has been optimized for speech intelligibility enhancement in the presence of disturbing sounds or noise. The noise reduction approach is based on the scheme presented by Vanden Berghe and Wouters (1998). A real-time implementation of the signal processing is realized in Audallion, a wearable, small digital signal processing (DSP) platform.

Increased incidence of spontaneous apoptosis in the bone marrow of hyperdiploid childhood acute lymphoblastic leukemia.

Objective: Hyperdiploidy of 51-65 chromosomes is associated with a good prognosis in childhood B-lineage acute lymphoblastic leukemia (ALL). Blasts from childhood ALL patients with a hyperdiploid karyotype have a tendency to apoptosis when cultured on stromal layers in vitro. In this study, we apply a novel method to investigate the relationship between apoptosis and hyperdiploidy in lymphoblasts of childhood ALL.

Static cytometry identifies hyperdiploid childhood ALL.

Hyperdiploid acute lymphoblastic leukemia of childhood has long been identified with a good prognosis. Identification of this subgroup before treatment commences would enable the most appropriate regimen to be selected. Static cytometry permits an assessment of the DNA content of morphologically selected interphase cells.

Rapid sexing of human embryos by non-radioactive in situ hybridization: potential for preimplantation diagnosis of X-linked disorders.

Sixty spare human embryos at various stages of preimplantation development were prepared for cytogenetic analysis. Fluorescent staining of those with metaphases allowed scoring for the presence of a Y chromosome. In situ hybridization was then performed using a biotinylated Y-specific sequence, and the probe was detected by a standard streptavidin-linked alkaline phosphatase system.

The association of Angelman's syndrome with deletions within 15q11-13.

The inheritance of Angelman's syndrome, a disorder characterised by mental retardation, epilepsy, ataxia, and a happy disposition, is debated because affected sibs occur less frequently than expected with autosomal recessive inheritance. After discovering two unrelated patients with a small deletion of the proximal long arm of chromosome 15, 10 further patients with Angelman's syndrome were reassessed. Five had apparently normal karyotypes, four had a deletion within 15q11-13, and one had a pericentric inversion, inv(15)(p11q13) involving the same chromosomal region.

Three infants having null acute lymphoblastic leukemia with chromosome rearrangements at 11q23: no involvement of a heritable fragile site in this band.

Three families are presented in which an infant with null acute lymphoblastic leukemia had a karyotype rearrangement involving a break at 11q23. Peripheral blood was obtained, where possible, from both parents and from the child during periods of remission. The blood was stimulated with phytohemagglutinin and cultured under conditions that enhance expression of heritable folate-sensitive fragile sites.

Regional chromosomal localisation of APOA2 to 1q21-1q23.

Using in situ hybridisation, we have mapped APOA2 to the 1q21-1q23 region of chromosome 1. DNA hybridisation to somatic cell hybrids made from cells carrying a balanced translocation between X and 1 confirms the localisation as proximal to 1q23. This was further confirmed by the presence of two polymorphic alleles in a cell line carrying a deletion of 1q25-1q32.

Novel non-isotopic in situ hybridization technique detects small (1 Kb) unique sequences in routinely G-banded human chromosomes: fine mapping of N-myc and beta-NGF genes.

A novel in situ hybridization technique is described. This non-radioactive technique combines, for the first time, the high spacial resolution and rapid signal development of the non-isotopic approach with the previously unrivalled sensitivity of autoradiography. The procedure, which employs biotin labelled DNA probes and a streptavidin-alkaline phosphatase based detection system, is compatible with pre G-banding and can be performed on archival material.

High-resolution in situ hybridization technique using biotinylated NMYC oncogene probe reveals periodic structure of HSRs in human neuroblastoma.

Gene amplification in mammalian cells commonly manifests itself as homogeneously staining chromosomal regions (HSRs). These are frequently seen in neuroblastoma and have been shown to be the site of amplification of the NMYC oncogene. We have used a nonisotopic, high-resolution in situ hybridization technique to reveal a hitherto unrecognized periodic microstructure within HSRs of a human neuroblastoma cell line.

Comparative studies between a new human rhabdomyosarcoma cell line, JR-1 and its tumour of origin.

A new human embryonal rhabdomyosarcoma cell line, designated JR-1, is described that closely resembles the tumour from which it was derived. Comparative studies, by light and electron microscopy reveal morphological features such as myofibre formation, that are concordant with embryonal rhabdomyosarcoma. Immunohistological investigations using a panel of monoclonal antibodies indicate that the cell surface antigen profile of the JR-1 cell line is similar to other embryonal rhabdomyosarcomas.

Effect of a high dosage of ketoconazole all or not combined with ovariectomy on N-nitroso-N-methylurea-induced mammary cancer in the rat.

Rats bearing mammary carcinomas induced by N-nitroso-N-methylurea (NMU) were subjected to either no treatment (C), to ovariectomy (O), to continuous ketoconazole dosing at 400 ppm into the diet (K) or to both ovariectomy and ketoconazole dosing (O + K). In both C and K groups survival over the experimental period of 15 weeks was low (12.5% and 15.