Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase.

Cyclic hematopoiesis is a stem cell disease in which the number of neutrophils and other blood cells oscillates in weekly phases. Autosomal dominant mutations of ELA2, encoding the protease neutrophil elastase, found in lysosome-like granules, cause cyclic hematopoiesis and most cases of the pre-leukemic disorder severe congenital neutropenia (SCN; ref. 3) in humans.

Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2.

Mice lacking the transcriptional repressor oncoprotein Gfi1 are unexpectedly neutropenic. We therefore screened GFI1 as a candidate for association with neutropenia in affected individuals without mutations in ELA2 (encoding neutrophil elastase), the most common cause of severe congenital neutropenia (SCN; ref. 3).

Acute and delayed hemolytic transfusion reactions secondary to HLA alloimmunization.

Background: HLA antibodies may be directed against HLA antigens on RBCs, but these antibodies are generally not considered to be clinically significant in transfusion practice. A case of a multiparous woman who had hemolytic transfusion reactions due to HLA-related Bg antibodies is reported.

Case Report: A 37-year-old woman was admitted with anemia.

Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis.

Two forms of inherited deficiency of neutrophil numbers are cyclic hematopoiesis and severe congenital neutropenia. In cyclic hematopoiesis, neutrophil counts oscillate opposite monocytes in a 3-week cycle. Severe congenital neutropenia consists of static neutropenia and a predisposition to myelodysplasia and acute myelogenous leukemia.

Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis.

Severe congenital neutropenia (SCN) is a syndrome characterized by an isolated block in granulocytic differentiation and an increased risk of developing acute myeloid leukemia (AML). Recent studies have demonstrated that the majority of patients with SCN and cyclic neutropenia, a related disorder characterized by periodic oscillations in the number of circulating neutrophils, have heterozygous germline mutations in the ELA2 gene encoding neutrophil elastase (NE). To test the hypothesis that these mutations are causative for SCN, we generated transgenic mice carrying a targeted mutation of their Ela2 gene ("V72M") reproducing a mutation found in 2 unrelated patients with SCN, one of whom developed AML.

Pulsed-field fingerprinting of vaginal group B streptococcus in pregnancy.

Objective: There is more to be learned about the epidemiology of group B beta-hemolytic streptococci infections in pregnancy. In this study, we investigated the discriminating capabilities of pulsed-field gel electrophoresis of group B streptococci strains from pregnant patients and mother/infant pairs of patients compared with serotyping.

Methods: Forty-two vaginal strains of group B streptococci cultured from pregnant patients in the third trimester and strains from 20 mother/infant pairs with documented newborn group B streptococci infection were studied.

The study of vertical zonation on rocky intertidal shores--a historical perspective.

Intertidal zonation, observed from earliest studies of the marine littoral zone, was first studied in the U.S. by ecologists with a botanical orientation.

CSF hypocretin-1 levels in schizophrenics and controls: relationship to sleep architecture.

Hypocretins/orexins are newly identified peptides of hypothalamic origin. Hypocretin deficiency is involved in the sleep disorder narcolepsy, suggesting the importance of hypocretin neurotransmission for the regulation of sleep. Hypocretin is known to excite midbrain dopaminergic neurons and to induce hyperactivity and stereotypy in animals.

Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia.

Purpose: Chronic myelogenous leukemia (CML) results from the breakpoint cluster region-Abl fusion gene product, a tyrosine kinase involved in cell division and apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster region-Abl tyrosine kinase, is capable of blocking proliferation and inducing apoptosis in CML cell lines. In this report, we describe the preclinical profile of imatinib and the data submitted in the New Drug Application that led to its marketing approval.

Health effects of embedded depleted uranium.

The health effects of embedded fragments of depleted uranium (DU) are being investigated to determine whether current surgical fragment-removal policies are appropriate for this metal. The authors studied rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate that uranium from implanted DU fragments distributes to tissues distant from implantation sites, including bone, kidney, muscle, and liver.

Preschoolers' use of reflective properties: identification of reflections on partially transparent surfaces.

This exploratory study extended past studies of children's ability to reference the mirror as a tool in locating the source of reflected images to preschoolers' ability to use the affordances of a transparency. Thirty-six children (3.5 to 5 years old) were shown nonreflected lights and lights reflected on a partially transparent, glassy surface.

In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.

Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) is an autosomal dominant familial platelet disorder characterized by thrombocytopenia and a propensity to develop AML. Mutation analyses of RUNX1 in 3 families with FPD/AML showing linkage to chromosome 21q22.1 revealed 3 novel heterozygous point mutations (K83E, R135fsX177 (IVS4 + 3delA), and Y260X).

Molecular characterization of the mouse In(10)17Rk inversion and identification of a novel muscle-specific gene at the proximal breakpoint.

Chromosomal rearrangements provide an important resource for molecular characterization of mutations in the mouse. In(10)17Rk mice contain a paracentric inversion of approximately 50 Mb on chromosome 10. Homozygous In(10)17Rk mice exhibit a pygmy phenotype, suggesting that the distal inversion breakpoint is within the pygmy locus.

In rabbits, landiolol, a new ultra-short-acting beta-blocker, exerts a more potent negative chronotropic effect and less effect on blood pressure than esmolol.

Purpose: To compare the cardiovascular and sympathetic effects of a new ultra-short-acting, highly cardioselective beta- blocker, landiolol, with esmolol, using an in vivo rabbit model.

Methods: Different bolus doses of landiolol (0.3, 1.

Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside.

Background: Fenoldopam is a novel dopamine-1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro-denervated animal models.

Methods: A total of 60 New Zealand white rabbits were divided into two groups of 30 each: the neuraxis-intact group and the totally baro-denervated group.

Biological effects of embedded depleted uranium (DU): summary of armed forces radiobiology research institute research.

The Persian Gulf War resulted in injuries of US Coalition personnel by fragments of depleted uranium (DU). Fragments not immediately threatening the health of the individuals were allowed to remain in place, based on long-standing treatment protocols designed for other kinds of metal shrapnel injuries. However, questions were soon raised as to whether this approach is appropriate for a metal with the unique radiological and toxicological properties of DU.

Upper lip asymmetry in adults during smiling.

Purpose: This study examined the incidence of upper lip asymmetry in adults while smiling.

Patients And Methods: Two-hundred ten students between the ages of 21 and 44 years were examined. Subjects determined to have an occlusal plane cant were eliminated from the study.

Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy.

The effectiveness of antineoplastic agents has been augmented by applying pulsed electric fields directly to tumours after the administration of the drug. This treatment, known as electrochemotherapy (ECT), has been successful for cutaneous malignancies in animal models and in recent clinical trials. This study was aimed at investigating the applicability of ECT in a surgical setting for hepatocellular carcinomas induced in the livers of rats.

Effects of electrochemotherapy with bleomycin on normal liver tissue in a rat model.

Preliminary studies that used electric pulses in vivo to facilitate entry of chemotherapeutic agents into tumour cells resulted in a 69% complete response rate for hepatocellular carcinoma in rats. This success motivated a focused investigation to define the adverse effects of this treatment on normal liver tissue. Bleomycin doses ranging from 0.

Clinical pathology of the domestic rabbit. Acquisition and interpretation of samples.

Diagnostic laboratories are receiving increasing numbers of samples from practitioners as they strive to diagnose complex disease processes and manage rabbit cases. Proper acquisition of diagnostic samples and interpretation of results are key skills necessary for successful management of medical cases. This article reviews the collection and interpretation of clinicopathologic samples commonly used in rabbits.