Search PubMed⌕ Search

Biomedical subjects

M Huber

Publications and source records attributed to M Huber.

At least 19 recordsLinked to original sources
PubMed2002

[Early childhood psychosis versus early childhood autism? Differential diagnosis based on one week observation in an inpatient setting].

We report on the case of a 4-year old child suffering for the past six months from a lingering psychotic development. Several months of outpatient observation did not permit a clear differential diagnosis of either childhood autism or an early psychosis. During a one-week inpatient stay at our hospital recurring productive-psychotic episodes were observed that finally led to the exclusion of the diagnosis of "childhood autism" (ICD-10 F 84.0 (Dilling et al., 1993)) and to the diagnosis of "other disintegrative childhood disorder" (ICD-10: F 84.3 (Dilling et al., 1993)).

Autistic Disorder↗
PubMed2002

Off-flavour release from packaging materials and its prevention: a foods company's approach.

Off-flavours in packed food are causes for consumer complaints. Often, they are related to packaging materials. For food companies, this represents not only costs related to production, but also a possible loss of brand confidence and market share. The origin of packaging-related off-odours are many sided. Odours derive from the degradation of base packaging materials and their converting processes, including printing, coating and lamination as well as the interaction between food and packaging. Many substances and groups of substances have been identified so far. In spite of the fact that the quality of packaging materials is clearly defined in the specifications (e.g. limit for residual solvents, standardized odour and taste transfer tests), off-flavour cases still do occur. This paper sets out ways of avoiding such problems, even in factories and laboratories which are not so well equipped. Prevention at Nestlé is based on several pillars. For a number of years, a sensory panel at the central laboratory has been specialized in and trained on packaging off-favours. The panel can describe and identify odours and their origin. To confirm the results by instrumental analysis, various extraction and separation techniques are available, including distillation/extraction techniques and direct thermal desorption followed by gas chromatography coupled with mass spectroscopy and an olfactory sniffing port. However, this knowledge must also be present in the operational plants where the problem usually originates. To manage this knowledge transfer, two tools were introduced to build up sensory panels that can evaluate packaging material. First, an aroma library kit was developed that contained odours that are often involved in off-odour cases. For each odour, a typical descriptor and the chemical composition are given. Beside that, information is added about the occurrence. Second, a glossary, which contains descriptors for packaging-related off-odours, was published. This small booklet helps to unify the odour descriptions, especially thanks to its translation into three important languages. This paper describes the tools mentioned above, as well as examples and limitations for their application.

Food Contamination↗
PubMed2001

Phase memory relaxation times of spin labels in human carbonic anhydrase II: pulsed EPR to determine spin label location.

Phase memory relaxation times (T(M) or T(2)) of spin labels in human carbonic anhydrase II (HCA II) are reported. Spin labels (N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl)iodoacetamide, IPSL) were introduced at cysteines, by site-directed mutagenesis at seven different positions in the protein. By two pulse electron paramagnetic resonance (EPR), electron spin echo decays at 45 K are measured and fitted by stretched exponentials, resulting in relaxation parameters T(M) and x. T(M) values of seven positions are between 1.6 micros for the most buried residue (L79C) and 4.7 micros for a residue at the protein surface (W245C). In deuteriated buffer, longer T(M) are found for all but the most buried residues (L79C and W97C), and electron spin echo envelop modulation (ESEEM) of deuterium nuclei is observed. Different deuterium ESEEM patterns for W95C and W16C (surface residue) indicate differences in the local water concentration, or accessibility, of the spin label by deuterium. We propose T(M) as a parameter to determine the spin label location in proteins. Furthermore, these systems are interesting for studying the pertaining relaxation mechanism.

Carbonic Anhydrase II↗
PubMed2001

Detection of single base alterations in genomic DNA by solid phase polymerase chain reaction on oligonucleotide microarrays.

DNA microarray technology holds significant promise for human DNA diagnostics. A number of technical approaches directed at the parallel identification of mutations or single nucleotide polymorphisms make use of polymerase-based specificity, like minisequencing or allele-specific primer elongation. These techniques, however, require separate laborious sample amplification, preparation, and purification steps, making large-scale analyses time and cost consuming. Here, we address this challenge by applying an experimental setup using simultaneous solid and liquid phase PCR on polyethyleneimine-coated glass slides, a novel microarray support allowing on-chip amplification reactions with exquisite specificity. A gene-specific oligonucleotide tiling array contains covalently attached allele-specific primers which interrogate single nucleotide positions within a genomic region of interest. During a thermal cycling reaction amplification products remain covalently bound to the solid support and can be visualized and analyzed by the incorporation of fluorescent dyes. Using the described procedure we unequivocally defined the presence of point mutations in the human tumor suppressor gene p53 directly from a natural DNA source. This semi-multiplex solid phase amplification format allowed the rapid and correct identification of 20 nucleotide positions from minute amounts of human genomic DNA. Our results suggest that this approach might constitute a vital component of future integrated DNA chip devices used in gene analysis.

Base Composition↗
PubMed2001

Quality of care and outcomes of adults with asthma treated by specialists and generalists in managed care.

BACKGROUND: The growth of managed health care in the United States has been accompanied by controls on access to specialty physician services. We examined the relationship of physician specialty to treatment and outcomes of patients with asthma in managed care plans. METHODS: We conducted a mail survey of adult asthma patients who were enrolled in 12 managed care organizations and had at least 2 contacts for asthma (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x) during the previous 24 months; we also surveyed their treating physicians. This report concerns 1954 patients and their 1078 corresponding physicians. Treatment indicators included use of corticosteroid inhalers, use of peak flow meters, allergy evaluation, discussion of triggers, and patient self-management knowledge. Outcome measures included canceled activities, hospitalization or emergency department visits, asthma attacks, workdays lost, asthma symptoms, physical and mental health, overall satisfaction with asthma care, and satisfaction with communication with physicians and nurses. RESULTS: Significant differences were noted for patients of specialists and experienced generalists compared with those of generalist physicians. Peak flow meter possession was reported by 41.9% of patients of generalists, 51.7% of patients of experienced generalists, and 53.8% of patients of pulmonologists or allergists. Compared with patients of generalists, outcomes were significantly better for patients of allergists with regard to canceled activities, hospitalizations and emergency department visits for asthma, quality of care ratings, and physical functioning. Patients of pulmonologists were more likely to rate improvement in symptoms as very good or excellent. CONCLUSIONS: In a managed health care setting, physicians' specialty training and self-reported expertise in treating asthma were related to better patient-reported care and outcomes.

Adolescent↗
PubMed2001

Analysis of the proliferative responses to peptides in individuals with vigorous Gag protein-specific proliferation.

Proliferative responses to recombinant HIV proteins in infected individuals may represent a correlate of protection from disease progression. In this study, the proliferative responses to HIV p24, p55 and gp120 were evaluated in infected subjects. Whereas, vigorous proliferative responses directed at the Gag proteins were detected in several individuals, Env-specific proliferation was observed in only one subject. Epitope mapping using overlapping peptides demonstrated proliferative responses of PBMC to Gag peptides. Responses were broadly directed at multiple peptides in some subjects. Although several of the peptides that induced proliferative responses also contain CTL epitopes potentially relevant in the particular individuals, many additional Gag T cell epitopes were present in each subject. This finding may be relevant for the design and testing of HIV candidate vaccines.

AIDS Vaccines↗
PubMed2001

Paramagnetic resonance of biological metal centers.

The review deals with recent advances in magnetic resonance spectroscopy (hf EPR and NMR) of paramagnetic metal centers in biological macromolecules. In the first half of our chapter, we present an overview of recent technical developments in the NMR of paramagnetic bio-macromolecules. These are illustrated by a variety of examples deriving mainly from the spectroscopy of metalloproteins and their complexes. The second half focuses on recent developments in high-frequency EPR spectroscopy and the application of the technique to copper, iron, and manganese proteins. Special attention is given to the work on single crystals of copper proteins.

Binding Sites↗
PubMed2001

Characterization of HIV-specific proliferative T cell responses in HIV-infected persons.

Virus-specific helper T cell responses are thought to be an important host defense in HIV infection. The proliferative responses to HIV p24, p55, and gp120 were tested in a cohort of 27 HIV-infected subjects. Vigorous proliferative responses directed at the Gag protein with stimulation indices in excess of 6 were detected in 10 of the individuals tested but an Env-specific response was present in only 1 subject. Viral load and proliferative activity to Gag were inversely correlated in untreated individuals. Proliferation was also observed in some individuals treated in the chronic phase of infection, and responses were maintained over time in the absence of detectable viremia. Positive proliferative responses could also occasionally be detected in treated persons with CD4(+) cell counts below 200/microl. Thus, vigorous Gag-specific proliferative responses are present in a minority of HIV-infected individuals and can be detected in individuals receiving highly active antiretroviral therapy at advanced disease stages. Proliferative responses are maintained for an extended time period in the presence of antiviral therapy.

Adult↗
PubMed2001

Mutations in the gene encoding SLURP-1 in Mal de Meleda.

Mal de Meleda (MDM) is a rare autosomal recessive skin disorder, characterized by transgressive palmoplantar keratoderma (PPK), keratotic skin lesions, perioral erythema, brachydactyly and nail abnormalities. We report the refinement of our previously described interval of MDM on chromosome 8qter, and the identification of mutations in affected individuals in the ARS (component B) gene, encoding a protein named SLURP-1, for secreted Ly-6/uPAR related protein 1. This protein is a member of the Ly-6/uPAR superfamily, in which most members have been localized in a cluster on chromosome 8q24.3. The amino acid composition of SLURP-1 is homologous to that of toxins such as frog cytotoxin and snake venom neurotoxins and cardiotoxins. Three different homozygous mutations (a deletion, a nonsense and a splice site mutation) were detected in 19 families of Algerian and Croatian origin, suggesting founder effects. Moreover, one of the common haplotypes presenting the same mutation was shared by families from both populations. Secreted and receptor proteins of the Ly-6/uPAR superfamily have been implicated in transmembrane signal transduction, cell activation and cell adhesion. This is the first instance of a secreted protein being involved in a PPK.

Amino Acid Sequence↗
PubMed2001

Extracellular matrix proteins in cardiac fibroblasts derived from rat hearts with chronic pressure overload: effects of beta-receptor blockade.

Left ventricular hypertrophy (LVH) is accompanied by progressive accumulations of extracellular matrix proteins. They are produced predominantly by cardiac fibroblasts that surround the cardiac myocytes. The aim of this study was to emphasize the role of a combined approach using both in vivo and in vitro studies to elucidate the effects of carvedilol on cardiac remodeling. We therefore used an established model of supravalvular aortic banding and cardiac fibroblasts. LVH was induced by banding of the ascending aorta. Male Wistar rats were allocated to four groups: sham-operated, sham+carvedilol, aortic stenosis (AS), and AS+carvedilol. Treatment time was four weeks. Fibroblasts were isolated from the entire left ventricle of sham and AS rats. Carvedilol/metoprolol/prazosin were added (0.1, 1.0 and 10 microM; 24 h). In addition, interferon- gamma was applied for 24 h (10, 100 and 1000 IU). AS rats revealed increased LV weights (+27%) and cardiomyocyte widths as compared to sham-operated rats (1.6-fold, P<0.01). Carvedilol reduced LVH by 20%. This finding was accompanied by a decrease of laminin, fibronectin, collagen I and III in vivo. Collagen I/III and fibronectin were increased in fibroblasts of AS v sham rats (P<0.0001, each). Carvedilol reduced collagen I, III and fibronectin by 40/60/35% (0.1 microM; P<0.001) irrespective of LVH. Carvedilol had no effects on collagen IV and laminin. Carvedilol dose-dependently reduced the proliferation rate by 20% at 0.1 microM(P<0.0001). Metoprolol and prazosin had no effect on the expression of extracellular matrix proteins and on the proliferation of the cells of either origin. Interferon- gamma blunted the proliferation rate of cultured fibroblasts and lead to a significant decrease in extracellular matrix deposits. These results indicate that the effects of carvedilol may be due to the antiproliferative or antioxidative properties of this unselective beta-adrenergic receptor antagonist. These changes of the extracellular matrix represent a new mechanism of carvedilol that may contribute to the observed beneficial effects in congestive heart failure.

Adrenergic beta-1 Receptor Antagonists↗
PubMed2001

[Clinical aspects of liver cirrhoses and its complications and diagnostic problems].

Liver cirrhosis is the end-stage of chronic liver disease with a prevalence of 0.5-0.8 percent in the German population. The main causes are chronic viral hepatitis B and C and alcohol abuse. Liver cirrhosis is often oligosymptomatic and frequently only diagnosed when complications occur (laboratory tests, ultrasound, computertomography or nuclear resonance imaging and histology). Complications include portal hypertension, gastrointestinal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, hepatic encephalopathy and hepatocellular carcinoma. Therapeutic management should mainly focus on the treatment of the underlying chronic liver disease in a precirrhotic stage. In the case of cirrhosis, prevention and treatment of complications are clinically most important.

Diagnosis, Differential↗
PubMed2001

Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival.

Although IgE binding to mast cells is thought to be a passive presensitization step, we demonstrate herein that monomeric IgE (mIgE) in the absence of antigen (Ag) stimulates multiple phosphorylation events in normal murine bone marrow-derived mast cells (BMMCs). While mIgE does not induce degranulation or leukotriene synthesis, it leads to a more potent production of cytokines than IgE + Ag. Moreover, mIgE prevents the apoptosis of cytokine-deprived BMMCs, likely by maintaining Bcl-X(L) levels and producing autocrine-acting cytokines. The addition of Ag does not increase this IgE-induced survival. Since IgE concentrations as low as 0.1 microg/ml enhance BMMC survival, elevated plasma IgE levels in humans with atopic disorders may contribute to the elevated mast cell numbers seen in these individuals.

Animals↗
PubMed2001

Elevated endosomal pH in HeLa cells overexpressing mutant dynamin can affect infection by pH-sensitive viruses.

Many viruses gain access to the cell via the endosomal route and require low endosomal pH for infectivity. The GTPase dynamin is essential for clathrin-dependent endocytosis, and in HeLa cells overexpressing the nonfunctional dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a human minor group rhinovirus, is internalized by members of the low-density lipoprotein receptor family in a clathrin-independent manner. The low endosomal pH then leads to conversion of the capsid to C-antigen, which is required for release (uncoating) and transfer of the viral RNA into the cytosol and de novo synthesis of infectious virus. We here demonstrate that overexpression of dynaminK44A reduces this antigenic conversion and results in diminished viral synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence, HRV2 uncoating is diminished early after internalization but attains control levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in addition to trafficking defects, results in an elevated endosomal pH and thereby affects virus infection and most likely endosomal sorting and processing.

Binding Sites↗
PubMed2001

Rottlerin-independent attenuation of pervanadate-induced tyrosine phosphorylation events by protein kinase C-delta in hemopoietic cells.

The understanding and control of many pathophysiological conditions is based on knowledge of subtly regulated intracellular signaling networks. We have found that in pervanadate (PV)-treated J558L myeloma cells, amongst other signaling proteins, protein kinase C (PKC)-delta and src homology 2-containing inositol phosphatase (SHIP) are tyrosine phosphorylated on expression of the B cell receptor, suggesting a role for these proteins in the preformed B cell receptor transducer complex. Rottlerin, a widely used PKC-delta-specific inhibitor, efficiently blocks these PV-induced tyrosine phosphorylation events. Furthermore, PV treatment of bone marrow-derived mast cells (BMMC) also results in tyrosine phosphorylation of PKC-delta, SHIP, and additional proteins. Rottlerin also inhibits these responses, indicating that PKC-delta might play an important enhancing role in the propagation of phosphotyrosine signals in B cells and mast cells and hence in the regulation of function of both cell types. Therefore, BMMC from PKC-delta -/- mice were generated by in vitro differentiation and assayed for tyrosine phosphorylation events in response to PV. Intriguingly, and opposite to the Rottlerin data, PKC-delta -/- BMMC show a stronger response to PV than wild-type cells, suggesting an attenuating role for PKC-delta. This response can be inhibited equally well by Rottlerin, indicating clearly that Rottlerin is not specific for PKC-delta in vivo. A comparison between Rottlerin and the panspecific PKC inhibitor bisindolylmaleimide suggests that Rottlerin also targets kinases beyond the PKC family. Moreover, Ser473 phosphorylation of protein kinase B (PKB) after PV treatment is blocked by Rottlerin as efficiently as by the phosphatidylinositol 3-kinase inhibitor LY294002. In this report, we provide evidence that PKC-delta constitutes a crucial attenuating factor in B cell and mast cell signal transduction and suggest that PKC-delta is important for the regulation of physiological B and mast cell functions as well as for their pathophysiology. Furthermore, dominant PKC-delta-independent effects of Rottlerin are presented, indicating restrictions of this inhibitor for use in signal transduction research.

Acetophenones↗
PubMed2001

Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita.

Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

DNA Mutational Analysis↗
PubMed2001

Pharmacokinetics and pharmacodynamics of antiulcer agents in llama.

Plasma concentration time curves following intravenous (i.v.) administration of 1.5 mg/kg of ranitidine, 0.2 mg/kg, 0.4 mg/kg and 0.8 mg/kg of omeprazole, respectively, were analysed in six llamas. Plasma profiles after i.v. administration of both drugs showed plasma concentrations declining in a biexponential manner with a rapid distribution phase. Pharmacokinetics parameters after ranitidine administration to six llamas showed a mean elimination half-life of 1.53 +/- 0.26 h. The mean volume of distribution (Vdss) in llamas was 1.77 +/- 0.31 L/kg, and mean body clearance in llamas was 0.778 +/- 0.109 L/kg/h. Ranitidine produced only a small transitory (<1 h) decline in acid production when administered i.v. at a dose of 1.5 mg/kg. Omeprazole showed dose-dependent nonlinear pharmacokinetics. The mean half-life of 0.2 mg/kg i.v. omeprazole was shorter than that of 0.4 and 0.8 mg/kg i.v. omeprazole, i.e. 0.61, 0.72 and 1.07 h, respectively. The area under the curve (AUC) and mean residence time (MRT) increased with increasing dose, while clearance decreased as dose increased. The decline in acid production following 0.2 mg/kg i.v. omeprazole was highly variable and did not produce a clinically useful suppression of third compartment acid production. In contrast, both 0.4 mg/kg and 0.8 mg/kg omeprazole i.v. administration significantly reduced third compartment acid production. The reduction in acid production following 0.8 mg/kg omeprazole was not significantly greater than the reduction observed following 0.4 mg/kg dosage. Misoprostol (10 microg/kg) was administered i.v. in an absolute alcohol solution. Two animals collapsed following drug administration. While the side-effects could have been produced by either misoprostol or the alcohol vehicle, the clinical changes were more consistent with an adverse drug reaction. Unfortunately, the limitation of UV detection did not provide the sensitivity needed to quantify the amount of misoprostol in llama plasma, and the pharmacokinetics could not be evaluated.

Animals↗
PubMed2001

HCf-6, a novel class II hydrophobin from Cladosporium fulvum.

C. fulvum, a fungal tomato pathogen, has previously been shown to express a complex family of hydrophobin genes including four class I hydrophobins and one class II hydrophobin. Here we describe a gene for HCf-6, a sixth member of the hydrophobin family and the second class II gene. The protein is predicted to consist of a signal sequence, an N-terminus rich in glycine and asparagine and a C-terminal hydrophobic domain which bears the hall-marks of hydrophobins. In contrast to the previously described class II hydrophobin HCf-5, HCf-6 is expressed in mycelium growing in pure culture and mRNA levels do not increase during sporulation. It is down-regulated by carbon starvation but not by depletion of nitrogen in the growth medium.

Amino Acid Sequence↗