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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 217 records · Page 12Linked to original sources

[Value of psychotherapy in expert assessment of skin diseases. Recommendations and indications for additional psychotherapy evaluation in expert assessment from the viewpoint of dermatology].

Skin diseases, the psyche and psychological changes are often intertwined, especially in patients presenting for expert dermatologic opinion. In many cases an additional evaluation provided by psychotherapeutic medicine may be necessary. This resource may help with the diagnosis, explanation of the problem and estimation of the degree of disability. The different legal guidelines of the various evaluation boards must be considered. The role of psychotherapeutic evaluation is demonstrated through case examples. The evaluation of new possibly occupationally-related disorders such as multiple chemical sensitivity and mobbing is considered.

Adult↗

Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence.

Aspergillus fumigatus is an important pathogen of the immunocompromised host causing pneumonia and invasive disseminated disease with high mortality. Previously, we identified a mutant strain (white, W) lacking conidial pigmentation and, in addition, the conidia showed a smooth surface morphology, whereas wild-type (WT) conidia are grey-green and have a typical ornamentation. W conidia appeared to be less protected against killing by the host defence, e.g., were more susceptible to oxidants in vitro and more efficiently damaged by human monocytes in vitro than WT conidia. When compared to the WT, the W mutant strain showed reduced virulence in a murine animal model. Genetic analysis suggested that the W mutant carried a single mutation which caused all of the observed phenotypes. Here. we report the construction of a genomic cosmid library of A. fumigatus and its use for complementation of the W mutant. Transformation of the W mutant was facilitated by co-transformation with plasmid pHELP1 carrying the autonomously replicating ama1 sequence of A. nidulans which also increased the transformation efficiency of A. fumigatus by a factor of 10. Using this cosmid library a putative polyketide synthase gene, designated pksP (polyketide synthase involved in pigment biosynthesis) was isolated. The pksP gene has a size of 6660 bp. pksP consists of five exons separated by short (47-73 bp) introns. Its deduced open reading frame is composed of 2146 amino acids. The pksP gene complemented both the white phenotype and the surface morphology of the W mutant conidia to wild type. Whereas W mutant conidia caused a strong reactive oxygen species (ROS) release by polymorphonuclear leukocytes, the ability of pksP-complemented W mutant conidia to stimulate ROS release was significantly reduced and comparable to that of WT conidia. In addition, the complemented strains showed restored virulence in a mouse model.

Amino Acid Sequence↗

Hypochondriasis: the role of fear-confirming reasoning.

We investigated whether hypochondriacal patients are prone to selectively search for danger-confirming information when asked to judge the validity of conditional rules in the context of general and health threats. Therefore, hypochodtriacal patients (n = 27) and a healthy control group (n = 27) were presented with modified Wason Selection Tasks (WSTs) pertaining to general and health threats. The WSTs contained safety rules (If P then safe) and danger rules (If P then danger). Subjects adopted a verificationistic strategy in case of danger rules and tended to look for falsifications in case of safety rules. This danger-confirming reasoning pattern was similar for both types of contexts and not particularly pronounced in hypochondriacal persons. These findings argue against the idea that such a reasoning pattern directly causes hypochondriasis. Yet, in the presence of anxiogenic (hypochondriasis related) convictions such danger-confirming reasoning pattern logically serves to maintain or even enhance hypochondriacal complaints.

Adult↗

Forced eruption technique: rationale and clinical report.

This article describes a refined, simplified forced eruption technique, and compared it with previous methods. This simplified method is easy to perform and encourages the use of adjunctive orthodontics in general practice. This relatively uncomplicated, quick, and cost-effective treatment can benefit patients.

Adult↗

New evidence for presence of tyrosinase in substantia nigra, forebrain and midbrain.

Tyrosinase and tyrosinase-related proteins (TRP-1 and TRP-2) are essential for melanin synthesis and are expressed in neural crest-derived melanocytes and in the pigment epithelium of the retina. Recent results suggest expression of all three proteins within the central nervous system. We performed a transgenic assay using beta-galactosidase as reporter gene to monitor tyrosinase promoter activity in vivo. During embryogenesis, we found expression in several locations of developing forebrain and midbrain. Tyrosinase, TRP-1 and TRP-2 had been equally found in extracts of adult mouse brain. In adult brain, we detected tyrosinase promoter activity in cortex, olfactory system, hippocampus, epithalamus and substantia nigra, areas corresponding to positive staining during embryogenesis. Thus, tyrosinase promoter is active throughout murine brain development, and tyrosinase could be implicated in neuromelanin formation in the substantia nigra, and in neurodegenerative disorders like Parkinson's disease.

Animals↗

lacZ transgenic mice to monitor gene expression in embryo and adult.

In transgenic experiments, lacZ can be used as a reporter gene for activity of a given promoter. Its main advantage is the ease of visualization in situ, on sections or in whole mount preparations, and the availability of simple protocols. In the following, we describe our procedure for detecting promoter activity in transgenic mice, including choice of lacZ vectors, generation of the transgenic mice, and analysis of expression. We had recently used this protocol to detect tyrosinase gene promoter activity in embryonic and adult brain.

Animals↗

Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome by analysis of Wilms' tumour gene expression.

In patients presenting with immature eosinophilic precursors it is notoriously difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in situ hybridization (FISH) can help in discriminating between these rare haematological disorders, but often treatment decisions cannot wait for the results of these time-consuming techniques. Recently, we and others found Wilms' tumour (WT1) gene expression to be increased in virtually all patients with acute leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much lower levels or not at all. To determine whether detection of WT1 gene expression is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR protocol, we found WT1 gene expression to be restricted to EoL patients. By detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were also able to diagnose isolated CNS-relapsed leukaemia, initially confused with bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR is a powerful complementary diagnostic tool to distinguish acute eosinophilic leukaemia from the hypereosinophilic syndromes. This observation needs confirmation in a larger series of EoL and HES patients.

Adult↗

Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque.

BACKGROUND: The chemokine receptor, CCR5, has been identified as an essential co-receptor with CD4, which permits entry of human immunodeficiency virus (HIV) into mammalian cells. This receptor may also mediate leukocyte and parenchymal responses to injury by virtue of its binding to locally released chemokines such as RANTES, MIP-1 alpha and MIP-1 beta during inflammation. The localization of CCR5 in human or primate kidney is unknown. In this study we sought to identify sites of CCR5 synthesis through localization of mRNA coding for this peptide. METHODS: CCR5 cDNA cloned into an expression vector was transcribed into a 1.1 Kb antisense riboprobe that was utilized for in situ hybridization (ISH) and Northern blotting studies. RESULTS: Northern analysis demonstrated positive hybridization for CCR5 mRNA in total RNA isolated from allograft nephrectomy tissue with features of severe transplant rejection as well as in kidney tissue with focal interstitial nephritis. No comparable hybridization signal was achieved with human kidney tissue uninvolved by disease. CCR5 mRNA was not identified in intrinsic renal cell types by ISH in normal human (N = 6), normal macaque kidney (N = 5), in kidneys from macaques with established infection by HIV-2 (N = 9), kidneys from macaques infected with HIV-1 (N = 4), nor in kidneys from SIV-infected macaques (N = 5). CCR5 was identified by ISH in human kidneys with features of interstitial nephritis (N = 3) and in rejected human allograft kidneys (N = 14). The expression of CCR5 was restricted to infiltrating mononuclear leukocytes at sites of chronic tubulointerstitial injury and at sites of vascular and interestitial rejection, respectively. CONCLUSIONS: Understanding the localization of CCR5 as well as other chemokine receptors may help us understand how specificity in leukocyte trafficking is achieved in renal inflammatory processes such as allograft rejection and interstitial nephritis. They provide additional evidence that chemokines may be critical mediators of leukocyte trafficking in renal allograft rejection. These findings may account in part for the difficulty in demonstrating HIV infection of renal cells in human HIV infection, since these cells appear to lack constitutive expression of an essential co-receptor needed for viral entry.

Animals↗

[Is Candida septicemia in premature infants a nosocomial infection?].

Yeast colonization of the vagina is found in about 30% of all pregnant women. Premature infants are severely endangered by generalized fungal infections due to their immature immune system. The objective of this study was to elucidate the relationship between vaginal yeast colonization of the mothers and Candida septicemia in their premature babies. In a prospective study, running from 12/1994 to 8/1996, 176 mothers, facing probable premature birth, were investigated, when hospitalized, for vaginal yeast colonization. 150 premature infants (birth weights ranging from 550 to 2390 g) of these mothers were culturally examined for yeasts in specimens from the mouth, ear, stool and urine immediately after birth as well as once weekly in the following weeks. The patients were divided into two groups. In group A, oral prophylaxis with nystatin was practiced only in infants with at least one positive yeast culture. In group B, all patients received nystatin prophylaxis. Candida septicemia developed one or two weeks after birth mainly in infants with birth weights below 1000 g. Primary oral prophylaxis with nystatin lowers considerably the risk of developing Candida infection.

Candidiasis↗

Genetic variation in a human immunodeficiency virus type 2 live-virus Macaca nemestrina vaccine model.

Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2KR) and subsequently challenged with a highly pathogenic strain, HIV-2287, together with two naive control animals. After challenge, two animals inoculated with a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity in protection, fragments of the env gene were amplified from peripheral blood mononuclear cell DNA and plasma RNA of challenged animals by PCR, examined by using a heteroduplex tracking assay (HTA), and sequenced. By HTA, variation was detected principally within the V1 and V2 regions of envelope. Extent of variation in viral DNA clones as assessed by HTA correlated with inoculum size, as did the degree of variation in sequences of clones derived from viral DNA. Conversely, a rapid reduction in the number of plasma viral RNA variants was noted by HTA at 8 weeks postinfection in protected animals; this reduction was not present in naive or unprotected macaques. Sequences derived from plasma viral RNA were found to be more closely related than corresponding viral DNA sequences, and protection correlated with a significant reduction in variation in plasma RNA sequences in animals given the identical inocula of HIV-2287. Nonsynonymous mutations were significantly less prevalent in the protected animals. An additional potential glycosylation site was predicted to be present in the V2 region in all but one clone, and amino acid signatures related to protection were identified in viral DNA and RNA clones within both the V1 and V2 regions. Examination of the role of viral variation in this HIV-2 live-virus vaccine model may provide valuable insights into immunopathogenesis.

Amino Acid Sequence↗

Signaling to the actin cytoskeleton.

The actin cytoskeleton is a highly dynamic network composed of actin polymers and a large variety of associated proteins. The main functions of the actin cytoskeleton are to mediate cell motility and cell shape changes during the cell cycle and in response to extracellular stimuli, to organize the cytoplasm, and to generate mechanical forces within the cell. The reshaping and functions of the actin cytoskeleton are regulated by signaling pathways. Here we broadly review the actin cytoskeleton and the signaling pathways that regulate it. We place heavy emphasis on the yeast actin cytoskeleton.

Actins↗

Angiotensin-converting enzyme gene polymorphism determines the antiproteinuric and systemic hemodynamic effect of enalapril in patients with proteinuric renal disease. Austrian Study Group of the Effects of Enalapril Treatment in Proteinuric Renal Disease.

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce blood pressure and proteinuria in a variety of different glomerular diseases. Nonetheless, a marked interindividual difference in the efficacy of these agents exists. The activity of the ACE and therefore of the renin-angiotensin-aldosterone system (RAAS) has been shown to be under genetic influence. Patients with a deletion genotype at the intron 16 of the ACE gene have been shown to exhibit higher activity of plasmatic ACE when compared to patients with the insertion genotype. We therefore studied prospectively the hemodynamic and antiproteinuric effect of a 6-month therapy with enalapril in patients with biopsy-proven proteinuric glomerular diseases and the DD (n = 10) and ID/II (n = 26) genotype. Although patients with the DD genotype received a slightly higher dose of enalapril, blood pressure and proteinuria did not change significantly. However, both were significantly reduced in the II/ID group after 10 weeks and 6 months of therapy. Creatinine clearance decreased steadily in DD patients. In II/ID patients, creatinine clearance was reduced significantly after 10 weeks of therapy but increased again thereafter and the value at 6 months was again comparable to the one obtained in the DD patients. We conclude from our study that the ACE genotype influences the blood pressure-lowering and antiproteinuric effect of enalapril in patients with proteinuric glomerular disease.

Adult↗

Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes.

Pro-opiomelanocortin (POMC) is the precursor of melanocortins (adrenocorticotropin: ACTH, beta-endorphin, beta-lipotropin: beta-LPH, corticotropin like intermediate peptide, alpha-, beta- and gamma-melanocyte-stimulating hormone: alpha-, beta- and gamma-MSH) some of which act in the brain to reduce food intake and are potential mediators of leptin action. Recently, three different mutations in the POMC gene (POMC) were identified in two unrelated children that lead to early-onset extreme obesity, adrenal insufficiency, and red hair pigmentation. In the present study we systematically screened the coding region of POMC in 96 extremely obese children and adolescents, 60 healthy underweight individuals and 46 patients with anorexia nervosa (AN) and identified several variants. a) A 9 and an 18 base pair insertion (9bp and 18bp: AGC AGC GGC and AGC AGC GGC AGC AGC GGC, respectively, between codon 73 and 74; 1,2). These in-frame variants lead to the insertion of three or six amino acids (Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal to gamma-MSH. Frequencies of the 9bp insertion allele varied between 3 and 5% among the different study groups (Pearson's chi2 P>0.5). b) Both an out-of-frame 6 bp insertion (within codon 176: GGG CCC) leading to the insertion of two amino acids (Arg-Ala) and a premature stop-codon (G-7316-T: Glu-180-Stop) within the gamma-LPH sequence were maternally inherited in an obese female proband. This proband inherited another missense mutation from her father (Glu-188-Gly). c) A missense mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with AN who also harboured the 9bp insertion on a paternally derived haplotype. d) The allelic co-occurence of two silent mutations (C-6982-T and C-7285-T) was detected in two obese subjects. e) Two further silent mutations (C-3832-T; C-7111-G) were detected in an underweight and an obese subject, respectively. We conclude that the POMC gene harbors several different polymorphisms and mutations, none of which can readily be associated with the phenotypes under study.

Adolescent↗

High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells.

Osteoblasts and adipocytes originate from common mesenchymal precursors. With aging, there is a decrease in osteoprogenitor cells that parallels an increase of adipocytes in bone marrow. We observed that rabbit serum (RS) induces adipocyte-like differentiation in human osteosarcoma SaOS-2/B10 and MG-63 cell lines, in rat ROS17/2.8 cells, and in mouse calvaria-derived osteoblastic MB1.8 cells, as evidenced by the accumulation of Oil Red O positive lipid vesicles and the decrease in alkaline phosphatase expression. Both SaOS-2/B10 and MG-63 cells, but not ROS17/2.8 nor MB1.8 cells, express significant levels of PPARgamma mRNA, a member of the peroxisome proliferator activated receptor (PPAR) family that has been implicated in the control of adipocyte differentiation. However, both ROS17/2.8 and MG-63 cells express significant levels of the adipocyte selective marker, aP2 fatty acid binding mRNA, which can be further increased by RS. These cell types express PPARdelta/NUC-1 but not PPARalpha, indicating that cells that do not express either PPARgamma or PPARalpha are capable of differentiating into adipocyte-like cells. Transfection experiments in COS cells showed that compared with fetal bovine serum (FBS), RS is rich in agents that stimulate PPAR-dependent transcription. The stimulatory activity was ethyl acetate extractable and was 35-fold more abundant in RS than in FBS. Purification and analysis revealed that the major components of this extract are free fatty acids. Furthermore, the same fatty acids, a mixture of palmitic, oleic, and linoleic acids, activate the PPARs and induce adipocyte-like differentiation of both ROS17/2.8 and SaOS-2/B10 cells. These findings suggest that fatty acids or their metabolites can initiate the switch from osteoblasts to adipocyte-like cells.

Adipocytes↗

[Hypertrophic cardiomyopathy treated by interventional technique of septal reduction].

A 75-year old woman with obstructive hypertrophic cardiomyopathy and class IV dyspnea refractory to medical management had relative contraindications for both pacemaker implantation and surgical approach. Percutaneous intervention was devised to perform the selective injection of absolute alcohol in the first septal branch of the left anterior descending coronary artery. This led to a limited septal infarction documented by ST elevation, enzymatic elevation and the appearance of complete right bundle branch block on the electrocardiogram. A baseline left ventricular outflow tract pressure gradient of 66mmHg was immediately abolished and no unexpected complications supervened. Currently, two months after the procedure, marked symptomatic relief is present and associated with the absence of obstructive outflow gradient, as documented by echocardiography.

Aged↗

[Gerog Fresenius and the species Aspergillus fumigatus].

The species Aspergillus fumigatus was first extensively described by G. Fresenius. J. B. Georg W. Fresenius was born in Frankfurt/Main, Germany, in 1808 and also died there in 1866. He studied medicine and finished his doctorate thesis (MD) in 1829. Afterwards he started his career as a physician and surgeon in Frankfurt/Main in the same year. In 1831 Fresenius became a university lecturer for botany at the "Senckenbergisches medicinisches Institut"; this institute specialized in botany. In this year Fresenius also became the director of the botanical gardens of Frankfurt/Main. Apart from his collaboration in the institute for agriculture he actively participated in the microscopical association of Frankfurt as well as the "Senckenbergische medicinische Gesellschaft". Almost over the whole period, Fresenius also worked as a physician taking care of miserable people. The outstanding publications of Fresenius are "Die Flora von Frankfurt" (Flora of Frankfurt) and "Beiträge zur Mykologie" (Contributions to Mycology). The monograph "Beiträge zur Mykologie" was published by Fresenius as a dedication for the centennial celebrations of the Senckenberg foundation ("Senckenbergische Stiftung"). It contains 132 pages and 13 excellent lithographic figures (Camera lucida). The third part of this monograph also contains the description of the species A. fumigatus. Fresenius was an engaged physician as well as an outstanding researcher and expert in natural sciences who described numerous new fungal species some of which are still accepted nowadays in accordance with the "International Code of Botanical Nomenclature".

Aspergillus fumigatus↗