Novel heterozygous COL4A3 mutation in a family with late-onset ESRD.

Thin basement membrane nephropathy (TBMN) and Alport syndrome (ATS) are genetically heterogeneous conditions characterized by structural abnormalities in the glomerular basement membrane (GBM). TBMN presents with hematuria, minimal proteinuria, and normal renal function. Although TBMN is an autosomal dominant disease (COL4A3 and COL4A4), ATS can be inherited X-linked (COL4A5), autosomal recessive, or autosomal dominant (both COL4A3 and COL4A4).

The effect of BDNF gene variants on asthma in German children.

Background: Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain-derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation.

Aim: We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases.

Extrinsic afferent nerve sensitivity and enteric neurotransmission in murine jejunum in vitro.

Enteric and extrinsic sensory neurons respond to similar stimuli. Thus they may be activated in series or in parallel. Because signal transmission via synapses or mediator release would depend on calcium, we investigated its role for extrinsic afferent sensitivity to chemical and mechanical stimulation.

Neuronal activation in the nucleus of the solitary tract following jejunal lipopolysaccharide in the rat.

Introduction: Inflammation during systemic lipopolysaccharide (LPS) seems to be modulated by the CNS via afferent and efferent vagal pathways. We hypothesized that similar to systemic inflammation, local LPS in the gut lumen may also activate central neurons and aimed to identify potential molecular mechanisms.

Methods: Male Wistar rats were equipped with an exteriorized canula in the proximal jejunum.

Leflunomide: a treatment option for ganciclovir-resistant cytomegalovirus infection after renal transplantation.

Cytomegalovirus (CMV) infection after renal transplantation is a problem of increasing concern resulting in significant morbidity and mortality. Widespread use of ganciclovir (GCV) and valganciclovir (VGCV) may cause an increase of CMV resistance to these first line drugs. Other treatment options are sparse and often complicated by adverse events, namely nephrotoxicity associated with foscarnet and cidofovir.

IL15 gene variants are not associated with asthma and atopy.

Background: Interleukin 15 (IL15) promotes activation and proliferation of CD8+ T cells and enhances the differentiation into Th2 cells. A previous study described five polymorphisms in the IL15 gene to be associated with asthma in a haplotype analysis.

Aim: We selected HapMap tagging single nucleotide polymorphisms (SNPs) from IL15 to systematically investigate these IL15 associations in a large population-based sample.

IRF-1 gene variations influence IgE regulation and atopy.

Rationale: The development of atopic diseases is characterized by skewed immune responses to common allergens. Only recently, interferons have been identified to play a crucial role in these mechanisms.

Objectives: Because interferon regulatory factor (IRF)-1 is critical for interferon expression, we tested the hypotheses that genetic changes in this essential transcription factor may have consequences for the development of atopy.

Postoperative complications have little influence on long-term quality of life in Crohn's patients.

Purpose: The purpose of the study was to determine the influence of postoperative complications on long-term quality of life in patients after abdominal operations for Crohn's disease.

Materials And Methods: From 1996 to 2002, 305 Crohn's patients underwent abdominal surgery, and 66 patients developed postoperative complications. Quality of life was studied using a standardized questionnaire and four quality of life instruments.

STAT1 gene variations, IgE regulation and atopy.

Background: Signal transducer and activator of transcription 1 (STAT1), an intracellular signal transducer and activator of transcription centrally involved in many inflammatory pathways, was recently suggested to play an important role in allergy related immune responses.

Aim: Thus, we investigated the effect of polymorphisms in the STAT1 gene on the development of atopic sensitization and allergic diseases.

Methods: Haplotype tagging single nucleotide polymorphisms (SNPs) previously described in the STAT1 gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology in a cross-sectional study population of 3099 German children recruited and phenotyped by the International Study of Asthma and Allergy in Childhood, phase II (ISAAC II).

The role of polymorphisms in ADAM33, a disintegrin and metalloprotease 33, in childhood asthma and lung function in two German populations.

Background: ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms (SNPs) in a genetic analysis of German case control and longitudinal populations.

Gene by environment interactions and the development of asthma and allergy.

Asthma is the most common chronic disease during childhood in modern societies. Prevalence rates differ between countries, but on an average, 10-20% of the children in Western Europe and the US are affected. While the true cause of the disease is not yet known, it is common perception that genetic alterations and environmental factors act together in the development of atopic diseases such as asthma, allergic rhinitis and atopic eczema.

Candidate gene association studies and evidence for gene-by-gene interactions.

Candidate gene studies in asthma are a powerful and valuable tool in asthma genetics. Although the quality of small-scale, freely associating studies has been questionable, increasingly serious efforts are made to establish, replicate, and verify association results. Association studies may help us to better understand the mechanisms underlying asthma.

Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype.

Nucleophosmin (NPM1) exon-12 gene mutations are the hallmark of a large acute myelogenous leukemia (AML) subgroup with normal karyotype, but their prognostic value in this AML subset has not yet been determined. We screened 401 AML patients with normal karyotype treated within the German AML Cooperative Group Protocol 99 (AMLCG99) study for NPM1 mutations. Results were related with partial tandem duplications within the MLL gene (MLL-PTD), Fms-like tyrosine kinase 3-length mutations (FLT3-LM), the tyrosine kinase domain of FLT3 (FLT3-TKD), NRAS, KIT, and CEBPA mutations and with clinical characteristics and outcome.

A promoter polymorphism in the CD14 gene is associated with elevated levels of soluble CD14 but not with IgE or atopic diseases.

Background: A polymorphism in the promoter region of the CD14 gene, C-159T, has been shown to be associated with increased levels of soluble CD14 (sCD14) and decreased serum immunoglobulin E (IgE) and the expression of a more severe atopic phenotype in previous studies.

Methods: To test if these associations are consistently found in different populations and different age groups, we genotyped 2048 children of different age groups as well as 888 adults from different regions of Germany for the CD14 C-159T polymorphism.

Results: While an association between this promoter polymorphism and levels of sCD14 could be confirmed in our study population (CC: 1017 ng/ml vs TT: 1370 ng/ml, P = 0.

Immune-modulatory actions of arginine in the critically ill.

Current trials of immune-enhancing diets suggest several beneficial clinical effects. These products are associated with a reduction in infectious risk, ventilator days, ICU and hospital stay. However, methodological weaknesses limit the inferences we can make from these studies.

Occurrence of an invertebrate iridescent-like virus (Iridoviridae) in reptiles.

Viral isolates were obtained in 1998, 1999 and 2000 from the lung, liver and intestine of two bearded dragons (Pogona vitticeps) and a chameleon (Chamaeleo quadricornis) and from the skin of a frill-necked lizard (Chamydosaurus kingii) by using viper heart cells (VH2) at 28 degrees C. Electron microscopic examination of infected VH2 cells revealed the assembly of icosahedral iridovirus-like particles measuring 139 nm (side to side) and 151 nm (apex to apex). Negatively stained virus particles had dimensions of 149 nm (side to side) and 170 nm (apex to apex).

Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction.

Background: Endoscopic extraction of bile duct stones after sphincterotomy has a success rate of up to 95%. Failures occur in patients with extremely large stones, intrahepatic stones, and bile duct strictures. This study examined the efficacy and the safety of extracorporeal shock-wave lithotripsy in a large cohort of patients in whom routine endoscopic measures including mechanical lithotripsy had failed to extract bile duct stones.

Replication of reptilian paramyxovirus in avian host systems.

The reptilian paramyxovirus GOV replicated in chicken embryo fibroblasts, in embryonated chicken eggs and in explanted chorio-allantoic membrane with titres of up to 10(8.2) TCID50/ml at 28 degrees C. The virus did not multiply above 30 degrees C.

Geriatrics in canine and feline internal medicine.

The increasing life expectancy in humans--at least in the developed countries--including all medical, social, and political consequences is a generally accepted phenomenon at the end of this century. In earlier examinations it could be noticed that also in dogs and cats a remarkable increase of the life span seems to occur in the last 15 years (Beelitz 1988; Danckert and Kraft 1997; Davis 1996; Eichelberg and Seine 1996; Goldston 1989; Kraft 1978, 1990, 1997 a-c; Kraft and Danckert 1997; Kraft et al. 1989; Pauling 1990; Trimborn 1990).

Postoperative spiral computed tomography and magnetic resonance angiography after aneurysm clipping with titanium clips.

Objective: To reduce morbidity and mortality after subarachnoid hemorrhage, it is imperative to evaluate the results of the surgical treatment of cerebral aneurysms. We investigated the usefulness of spiral computed tomography (CT) and magnetic resonance angiography as postoperative control examinations after cerebral aneurysms were clipped with titanium clips.

Methods: Eleven patients with 13 treated aneurysms were studied prospectively with postoperative digital subtraction angiography, spiral CT, and magnetic resonance angiography.

Effect of antiretroviral combination therapy (zidovudine/didanosine or zidovudine/lamivudine) on quantitative plasma human immunodeficiency virus-ribonucleic acid in children and adolescents infected with human immunodeficiency virus.

Objective: To assess human immunodeficiency virus (HIV) ribonucleic acid load in children and adolescents with HIV infection who are being treated with antiretroviral combination therapy.

Study Design: Five patients whose disease progressed with their prior antiretroviral therapy had treatment regimens changed to zidovudine (ZDV)/didanosine (DDI) (group A), and the regimens of six patients were changed to ZDV/lamivudine (3TC) (group B). Patients were followed every 4 to 8 weeks for an average period of 8.

Effects of ultra-purified polymerized bovine hemoglobin on the microcirculation of striated skin muscle in the hamster.

Since the beginning of this century, the development of hemoglobin based oxygen carriers has been propagated for replacement of the oxygen carrying properties of red blood cells. A breakthrough has been impeded by problems related to the hemoglobin molecule itself and the ingredients of the solution, resulting in nephrotoxic side effects, limited intravascular half-life, vasoconstrictor potential and potential catalysis of oxygen free radical formation. Using intravital fluorescence microscopy and the dorsal skin fold chamber model of the awake Syrian golden hamster, the microcirculatory changes occurring in the thin striated skin muscle were quantitatively analyzed before and after administration of an ultrapurified polymerized bovine hemoglobin solution (U-PBHb) under the following experimental conditions: (1) Hypervolemic infusion of U-PBHb at approximately 10% of calculated blood volume, (2) isovolemic exchange transfusion with U-PBHBb by replacing approximately 50% of calculated blood volume and (3) severe hemorrhagic shock by acute bleeding of approximately 50% of calculated blood volume to a MAP of 35 +/- 5 mm Hg for 45 min followed by resuscitation with U-PBHb.