PubMed Health⌕ Search

Biomedical subjects

G Huber

Publications and source records attributed to G Huber.

At least 37 records · Page 2Linked to original sources
PubMed2001

[How far is psychopathology still meaningful for the treatment of schizophrenia?].

The paper gives reasons for the view that psychopathology has to be not only the fundamental method for clinical psychiatry, but also an essential prerequisite for a rational therapy of schizophrenia and related disorders. Because schizophrenic patients present very different types of psychopathological cross-sectional syndromes, the choice of a distinct neuroleptic or antidepressant compound and their dosage has to be guided along the psychopathological target syndrome. The clinical-therapeutical effects of neuroleptics and antidepressants are above all symptom- (Freyhan) or syndrome-directed. The differentiation of positive and negative symptoms, acute and chronic or residual schizophrenia, or of the prodromal symptoms according to contemporary approaches seems to be not sufficient for the early detection of psychopathological predictors of an impending psychosis and the special indication and choice of a distinct drug and dosing strategy. This is valid for maintenance treatment of patients in remission, for early intervention in the prodromal stages before the first and later psychotic episodes and in preventing relapses. Relapse rates can be reduced by a low dose maintenance therapy with basic symptom oriented early adaptation of the dosage in the prodromes before psychotic remanifestations. Some presuppositions of an effective psychopharmacological and psychological therapy in view of clinical psychopathology (K. Schneider) and the "phenomenological attitude" (K. Jaspers) are outlined. A necessary condition for the secondary as well as for the primary prevention of psychotic episodes is the detailed knowledge of the interindividual different dynamic and cognitive basic symptoms, defined in the Bonn Scale BSABS, that are experiential in kind and not identical with the negative and behavioral "Prodromal and Residual Symptoms" of DSM and ICD-10. The early detection and preventive intervention of schizophrenic psychoses is most likely possible by means of a subtle, descriptive-analytical phenomenology and psychopathology. Also "chronic" patients beyond acute psychoses, e. g. those with persisting pure residues, characterized not by true negative, but by basic symptoms, often respond to distinct atypical neuroleptics and/or antidepressants. The knowledge of the prodromal symptoms and the coping strategies, frequently developed by the patients themselves, is an essential component of a basic symptom oriented psychoeducational concept.

Humans↗
PubMed2001

Blood volume and hemoglobin mass in elite athletes of different disciplines.

Although it is well known that athletes have considerably larger blood volumes than untrained individuals, there is no data available describing the blood volume variability among differently trained athletes. The first aim of the study was to determine whether athletes from different disciplines are characterized by different blood volumes and secondly to what extent the blood volume can possibly limit endurance performance within a particular discipline. We investigated 94 male elite athletes subdivided into the following 6 groups: downhill skiing (DHS), swimming (S), running (R), triathlon (TA), cycling junior (CJ) and cycling professional (CP). Two groups of untrained subjects (UT) and leisure sportsmen (LS) served as controls. Total hemoglobin (tHb) and blood volume (BV) were measured by the CO-rebreathing method. In comparison to UT (mean +/- SD: tHb 11.0 +/- 1.1 g/kg, BV 78.3 +/- 7.9 ml/kg) tHb and BV were about 35 - 40 % higher in the endurance groups R, TA, CJ, and CP (e. g. in CP: tHb 15.3 +/- 1.3 g/kg, BV 107.1 +/- 7.0 ml/kg). Within the endurance groups we found no significant differences. The anaerobic discipline DHS was characterized by very low BV (87.6 +/- 3.1 ml/kg). S had an intermediate position (BV 97.4 +/- 6.1 ml/kg), probably because of the immersion effects during training in the water. VO(2)max was significantly related to tHb and BV not only in the whole group but also in all endurance disciplines. The reasons for the different BVs are an increased adaptation to training stimuli and probably also individual predisposing genetic factors.

Adult↗
PubMed2001

Development of verteporfin therapy: a collaboration between pharmaceutical companies, device manufacturers and clinical investigators.

The potential for photodynamic therapy to provide new treatment options for patients with choroidal neovascularization has been of interest to ophthalmologists for many years. Verteporfin (Visudyne, Novartis AG) is the first photodynamic drug to receive regulatory approval for use in ophthalmology. The development of verteporfin therapy was more complex than that of many other drugs because of the need to develop both the light-activated drug and the laser system used to activate it. This article provides an overview of the development of verteporfin therapy, focussing on the contributions of the pharmaceutical companies, device manufacturers, and investigators who were involved in the program.

Choroidal Neovascularization↗
PubMed2001

Left ventricular wall motion during diastolic filling in endurance-trained athletes.

PURPOSE: The purpose of this study was to assess left ventricular (LV) wall motion in highly endurance-trained athletes to evaluate LV diastolic function in physiologically hypertrophied hearts. BACKGROUND: Diastolic filling dynamics have previously been examined in endurance-trained athletes by measuring pulsed-wave mitral inflow velocities during the early and atrial filling phase, indicating an unimpaired LV function. Assessment of LV wall motion may give additional information about the LV diastolic function in endurance-trained athletes. METHODS: Left ventricular mass (LVM) and volume (LVV) were determined by M-mode echocardiography. Peak LV wall motion in the region of the basal septum close to the mitral anulus were measured during the early rapid and atrial filling phase by tissue Doppler in 30 endurance-trained athletes (T) and 16 sedentary control subjects (C) presumed to be healthy. RESULTS: Myocardial LVM and LVV in T (LVM 159.4 +/- 18.0 g.m(-2), LVV 100.4 +/- 13.0 mL.m(-2)) were significantly higher than in C (LVM 105.7 +/- 12.0.m(-2), LVV 70.1 +/- 11.9 mL.m(-2)), and heart rate (HR) was significantly lower (HR C: 69.6 +/- 11.0 bpm, T 50.9 +/- 8.7 bpm),which is consistent with endurance training (P < 0.01 for both). Peak LV wall motion during the early rapid filling phase did not differ significantly between the groups (T: 10.69 +/- 1.46 cm.(s-)1; C: 10.61 +/- 1.52 cm.(s-)1). Peak atrial wall motion was significantly lower in T (4.53 +/- 0.84 cm.s-1) versus C (5.74 +/- 0.75 cm.s(-1)), and the ratio of peak early diastolic to atrial wall motion was consequently higher in athletes (P < 0.01 for both). CONCLUSION: Regional wall motion at the basal septum near the mitral anulus during the early rapid filling phase is not altered by an increase in LVM or LVV when associated with endurance training.

Adult↗
PubMed2001

Different binding modes of amphibian and human corticotropin-releasing factor type 1 and type 2 receptors: evidence for evolutionary differences.

The binding characteristics of corticotropin-releasing factor (CRF) type 1 (CRF(1)) and type 2 (CRF(2)) receptors from human (hCRF(1) and hCRF(2alpha)) and Xenopus (xCRF(1) and xCRF(2)) were compared using four different (125)I-labeled CRF analogs, the agonists (125)I-CRF and (125)I-sauvagine, and the antagonists (125)I-astressin ((125)I-AST) and (125)I-antisauvagine-30 ((125)I-aSVG). The hCRF(2alpha) and xCRF(2) receptors bound all four radioligands with different affinities, whereas hCRF(1) did not bind (125)I-aSVG, and xCRF(1) bound neither (125)I-sauvagine nor (125)I-aSVG. Competitive binding studies using unlabeled agonists and antagonists with hCRF(1) and hCRF(2alpha) receptors revealed that most agonists exhibited higher affinity in displacing agonist radioligands compared with displacement of antagonist radioligands. Exceptions were the agonists human and rat urocortin, which displayed high-affinity binding in the presence of either (125)I-labeled agonist or antagonist ligands. In contrast, the affinities of antagonists were independent of the nature of the radioligand. We also found that, in contrast to the mammalian CRF receptors, the affinity of ligand binding to xCRF(1) and xCRF(2) receptors strongly depended on the nature of the radioligand used for competition. For xCRF(1), competitors showed different rank order binding profiles with (125)I-CRF compared with (125)I-AST as the displaceable ligand. Similarly, binding of competitors to the xCRF(2) receptor showed markedly different profiles with (125)I-CRF as the competed ligand compared with the other radioligands. These data demonstrate that amphibian CRF receptors have distinctly different binding modes compared with their mammalian counterparts.

Animals↗
PubMed2000

Evidence for the abundant expression of arginine 185 containing human CRF(2alpha) receptors and the role of position 185 for receptor-ligand selectivity.

The abundance of a histidine residue at position 185 (His(185)) of the human corticotropin-releasing factor (CRF) type 2 alpha receptor (hCRF(2alpha)) was investigated. His(185) has only been reported in hCRF(2); CRF(2) proteins from other species and all CRF(1) receptors encode an arginine (Arg(185)) at the corresponding position. Cloning of partial and full-length hCRF(2) cDNAs from a variety of neuronal and peripheral tissues revealed the existence of receptor molecules encoding Arg(185) only. Sequence analysis of the hCRF(2) gene verified the existence of Arg(185) also on genomic level. Full-length cDNAs encoding either the His(185) (R2H(185)) or the Arg(185) (R2R(185)) variants of hCRF(2alpha) were stably expressed in HEK293 cells and tested for ligand binding properties. In displacement studies R2H(185) and R2R(185) displayed a similar substrate specificity, human and rat urocortin, and the peptide antagonists astressin and alpha-helical CRF((9-41)) were bound with high affinity whereas human and ovine CRF were low-affinity ligands. Significant differences were observed for sauvagine and urotensin I, which bound with 3-fold (sauvagine) and 9-fold (urotensin I) higher affinity to R2R(185). These data indicate that hCRF(2), like all vertebrate CRF(1) and CRF(2) proteins encodes an arginine residue at the junction between extracellular domain 2 and transmembrane domain 3 and that this amino acid plays a role for the discrimination of some CRF peptide ligands.

Amino Acid Sequence↗
PubMed2000

Molecular characterization reveals identity of microtubule-associated proteins MAP3 and MAP4.

The identity of two microtubule-associated proteins, MAP3 and MAP4, was verified both immunologically and biochemically. MAP3 was enriched from the heat-stable fraction of rat brain extracts by reverse-phase HPLC and preparative two-dimensional gel electrophoresis. Both MAP3 and MAP4 antibodies reacted with the corresponding spots on two-dimensional Western blots. Amino acid sequences of internal peptides derived from rat MAP3 matched with corresponding sequence stretches of mouse MAP4. In the kidney cortex, the MAP3 antibody stained not only glomerular podocytes but also interstitial cells. This distribution pattern of MAP3 is identical to that of MAP4 reported previously. These results indicate that MAP3 and MAP4 are identical.

Amino Acid Sequence↗
PubMed2000

Bistable helices.

We extend elasticity theory of filaments to encompass systems, such as bacterial flagella, that display competition between two helical structures of opposite chirality. A general, fully intrinsic formulation of the dynamics of bend and twist degrees of freedom is developed using the natural frame of space curves, spanning from the inviscid limit to the viscously overdamped regime applicable to cellular biology. Aspects of front propagation found in flagella are discussed.

Bacillus subtilis↗
PubMed2000

Controlling polymerization of beta-amyloid and prion-derived peptides with synthetic small molecule ligands.

The Alzheimer beta-amyloid peptide (Abeta) and a fragment of the prion protein have the capacity of forming amyloid-like fibrils when incubated under physiological conditions in vitro. Here we show that a small amyloid ligand, RO-47-1816/001, enhances this process severalfold by binding to amyloid molecules and apparently promote formation of the peptide-to-peptide bonds that join the monomers of the amyloid fibrils. This effect could be antagonized by other ligands, including analogues of RO-47-1816/001, as well as the structurally unrelated ligand Congo red. Analogues of RO-47-1816/001 with low affinity for amyloid did not display any antagonistic effect. In conclusion, these data suggest that synthetic molecules, and possibly also small natural substances present in the brain, may act in a chaperone-like fashion, promoting Abeta polymerization and growth of amyloid fibrils in vitro and possibly also in vivo. Furthermore, we demonstrate that small organic molecules can be used to inhibit the action of amyloid-enhancing compounds.

Amyloid beta-Peptides↗
PubMed2000

Hemisynaptic distribution patterns of presenilins and beta-APP isoforms in the rodent cerebellum and hippocampus.

Healthy brain neurons co-express Alzheimer's disease (AD) related proteins presenilins (PS) and beta-amyloid precursor protein (beta-APP). Deposition of beta-amyloid and PS in the senile plaques of AD brain and their ability to interact in vitro suggest that AD pathology could arise from a defect in the physiological interactions between beta-APP and PS within and/or between neurons. The present study compares the immunocytochemical distribution of PS (1 and 2) and beta-APP major isoforms (695 and 751/770) in the synapses of the cerebellum and hippocampus of the adult rat and mouse. In the cerebellar cortex of both species, the four molecules are immunodetected in the presynaptic or the postsynaptic compartments of synapses, suggesting that they are involved in interneuronal relationships. In contrast, PS and beta-APP are postsynaptic in almost all the immunoreactive synapses of the hippocampus. The different distribution patterns of these proteins in cerebellar and hippocampal synapses may reflect specific physiological differences, responsible for differential vulnerability of neurons to AD synaptic pathology. Defective interactions between beta-APP and PS at the synapses could impede the synaptic functions of beta-APP, inducing the selective loss of synapses that accounts for cognitive impairment in AD.

Amyloid beta-Protein Precursor↗
PubMed2000

Characterization of transgenic mice expressing apolipoprotein E4(C112R) and apolipoprotein E4(L28P; C112R).

Apolipoprotein E (ApoE), which is genetically polymorphic, is a constituent of different lipoproteins. Two variants, ApoE4(C112R) and ApoE4(L28P; C112R) have been linked to the risk of developing Alzheimer's disease. Transgenic mice carrying ApoE4(C112R) (AD71) and ApoE4(L28P; C112R) (AD61) were generated and compared to wild-type mice. The use of glial fibrillary acidic protein as promoter led to transgene expression mainly in glial cells but also in neurons. Transgene protein levels were approximately three-and-a-half-fold that of endogenous ApoE in the glial fibrillary acidic protein-ApoE4(C112R) (AD71) and nearly twofold in the glial fibrillary acidic protein-ApoE4(L28P; C112R) (AD61) mouse lines. Neither transgenic mouse differed from wild-type in cognitive tests at the age of approximately one-and-a-half years. The locomotor activity of AD61 mice was similar to controls, whereas AD71 mice exhibited a clearly reduced level of motor activity. Immunohistological and biochemical brain protein analyses revealed no difference between strains.Thus, in the absence of morphological changes over-expression of ApoE4(C112R) on a background of endogenous mouse ApoE, may result in behavioral deficits while for the ApoE4(L28P; C112R) transgene higher expression might be required or some compensatory mechanisms might protect these animals from the behavioral abnormalities.

Alzheimer Disease↗
PubMed2000

Haemoglobin, haematocrit and red blood cell indices in elite cyclists. Are the control values for blood testing valid?

BACKGROUND: In international cycling and cross-country skiing competitions, blood tests are used to unmask the performance enhancing misuse of erythropoietin. Haematocrit (cycling) and haemoglobin (cross-country skiing) limits have been set by international sporting federations (haematocrit 50%, haemoglobin 18.5 g/dl). Athletes tested above these cut-off values are declared unfit for competition. To investigate the validity of these regulations, we studied haemoglobin, haematocrit and red blood cell indices of elite cyclists before erythropoietin became commercially available. MATERIAL AND METHODS: We investigated 523 blood samples of 92 male elite cyclists (age 16-31 years) from 1978 to 1987. Haematocrit, haemoglobin and red blood cell count were analysed automatically, erythrocyte indices were calculated. RESULTS: Haemoglobin (-0.3 +/- 1 g/dl), haematocrit (-1.2 +/- 2.8%) and red blood cell count (-0.2 +/- 0.4 x 10(6)/mm3) decreased significantly (p < 0.05) with increasing training workload. The erythrocyte indices showed no significant change. Fifty-four blood samples (10.3%) showed a haematocrit above 50%, one sample presented a haemoglobin mass higher than 18.5 g/dl. During periods of increased workload, less athletes tested above the haematocrit limit. CONCLUSION: The current haematocrit limit used in blood tests might lead to a high number of false positive tests.

Adolescent↗
PubMed2000

Contact line deposits in an evaporating drop

Solids dispersed in a drying drop will migrate to the edge of the drop and form a solid ring. This phenomenon produces ringlike stains and occurs for a wide range of surfaces, solvents, and solutes. Here we show that the migration is caused by an outward flow within the drop that is driven by the loss of solvent by evaporation and geometrical constraint that the drop maintain an equilibrium droplet shape with a fixed boundary. We describe a theory that predicts the flow velocity, the rate of growth of the ring, and the distribution of solute within the drop. These predictions are compared with our experimental results.

Journal Article↗
PubMed1999

[Functional dynamics of impending overt hypothyroidism: spontaneous evolution in patients in the years before the beginning of treatment].

The syndrome of subclinical hypothyroidism, with its clinical and metabolic consequences, is frequent. Only a minority of these patients will eventually become overtly hypothyroid. It was the aim of the present study to analyse the spontaneous evolution over 10 years of 27 patients with subclinical hypothyroidism who became overtly hypothyroid (group A). For comparison, 27 patients remaining subclinically hypothyroid and matched for their TSH concentrations were characterised (group B). In group A, continuous increase of TSH concentrations was observed over the whole observation period (p = 0.002; ANOVA). The concentrations of fT4 remained initially stable, and only fell at a late stage in the three years before overt hypothyroidism (p = 0.0001; ANOVA). The concentrations of total T3 remained normal throughout the observation period. Thyroid reserve was already impaired at the beginning and during the whole study period. In contrast, these thyroid parameters of patients of group B remained unchanged over 10 years, and thyroid reserve remained normal. The pathogenesis of overt hypothyroidism is a graded process. Increasing concentrations of TSH, a decrease of fT4 and impaired thyroid reserve are predictors of overt thyroid failure.

Analysis of Variance↗
PubMed1999

cDNA cloning of a novel secreted isoform of the human receptor for advanced glycation end products and characterization of cells co-expressing cell-surface scavenger receptors and Swedish mutant amyloid precursor protein.

The receptor for advanced glycation end products (RAGE) has been proposed as a cell surface receptor that binds amyloid-beta protein (Abeta), thereby triggering its cytotoxic effects [S.D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, T. Slattery, L. Zhao, M. Nagashima, J. Morser, A. Migheli, P. Nawroth, D. Stern, A.M. Schmidt, RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease, Nature 382 (1996) 685-691.]. A cDNA library of human lung was screened for RAGE with an appropriate hybridization probe. In addition to cell surface RAGE, one clone was found which encodes a new version of RAGE, termed hRAGEsec, which lacks the 19 amino acids of the membrane-spanning region and is therefore secreted. Comparison with the genomic sequence revealed that the synthesis of the secreted isoform requires alternative splicing. The deduced protein sequence of the mature hRAGEsec consists of 321 amino acids with a predicted molecular mass of 35.66 kDa. The pattern of expression of hRAGEsec in human brain was analyzed by in situ hybridization histochemistry. The most intense expression of the gene in contrast to cell surface RAGE was detected in hippocampal CA3 pyramidal cells, dentate gyrus granule cells, cortical neurons as well as glial cells in white matter. To investigate the interaction between Abeta and RAGE and another scavenger receptor, SRA, under physiological conditions, they were co-expressed with human betaAPP(695)-SFAD in a human cell and the level of Abeta in the condition medium was assessed by immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) analysis. A nearly 100% reduction of Abeta from the conditioned medium of hRAGE cells and approximately 40% reduction from the SRA-cells implied that hRAGE could be a prominent cell surface receptor interacting with Abeta.

Amino Acid Sequence↗