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Biomedical subjects

G Huber

Publications and source records attributed to G Huber.

At least 91 records · Page 5Linked to original sources

[Angiographic quantification of stenoses of the internal carotid artery].

BACKGROUND AND PURPOSE: The method of measuring cartid stenosis is under discussion since different methods of quantifying carotid stenosis were used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Stenosis Trial (ECST). METHODS: Angiograms from 80 patients (105 cases of stenosis of the internal carotid artery), performed in a simultaneous biplanar manner, were retrospectively analyzed using the NASCET, the ECST method and a method based on measurement of the common carotid (CC) artery lumen diameter. Each linear measurement was converted into the ¿squared¿ method (NASCET2, ECST2, CC2). The linear NASCET and ECST measurements of both views (stenosis 1, stenosis 2) were used to calculate the biplanar stenosis according to the formula: stenosis = stenosis 1 + stenosis 2 - stenosis 1 * stenosis 2, and termed ¿local stenosis ECST-bi¿ and ¿distal related stenosis NASCET-bi¿ Furthermore each stenosis was approximated by two neuroradiologists. RESULTS: Direct visualization proved agreement with measured local stenosis ECST-bi. Squared methods correlated exactly with linear measurements (Spearmancorrelation), thus providing no further data. Biplanar calculation caused considerable change in the order of the stenosis. The different results of the local stenosis ECST-bi and the distal related stenosis NASCET-bi are not contradictory, but complementary. CONCLUSIONS: Direct visualization should be replaced by measurement of the local stenosis ECST-bi. Biplanar calculation seems to give a better estimate of the degree of the stenosis, causing questions since the results of ECST and NASCET cannot be applied.

Adult↗

[Dopamine (D2) receptor SPECT with 123I-iodobenzamide (IBZM) in diagnosis of Parkinson syndrome].

For effective drug therapy of Parkinson's syndrome (PS), it is necessary to distinguish between idiopathic and secondary genesis and PS in neuronal systemic degeneration. [123I]Iodobenzamide ([123I] IBZM) is a radiolabelled benzamide and binds specifically to the cerebral dopamine receptor (D2) in the basal ganglia. The purpose of this study was to determine the value of the [123I]IBZM D2-receptor SPECT in the differential diagnosis of PS. A total of 38 patients (20 females, 18 males; age 61 +/- 13.3 years), with typical extrapyramidal symptoms were investigated. Twenty suffered from idiopathic and 11 from secondary PS. Seven patients in whom a neurological disease could be excluded, served as controls. SPECT data were acquired 90 min after i.v. injection of 185-200 MBq [123I]IBZM. After reconstruction with a Butterworth filter (cutoff frequency 0.5) and attenuation correction (coefficient 0.12 cm(-1)) we quantify the IBZM basal ganglia uptake as ratio to teh frontal D2-receptor-free cortex (BG/FC). The patients with idiopathic PS (IPS) and the controls revealed high and specific IBZM uptake in the basal ganglia compared to the adjacent frontal brain tissue (IPS: BG/FC = 1.44 +/- 0.10; controls: BG/FC = 1.48 +/- 0.10). A significant decreased striatal IBZM uptake is found in cases with secondary PS (BG/FC = 1.25 +/- 0.10; p<0.0001, t-test compared to controls and IPS). The patient group with IPS can be subdivided into patients without L-dopatherapy (BG/FC = 1.49 +/- 0.07), patients with longstanding L-dopa-therapy demonstrating significantly decreased striatal IBZM uptake (BG/FC = 1.31 +/- 0.04; p<0.0001, t-test compared to controls and other IPS), which correlates pathophysiological with a reduction of free D2 receptors, and patients with de novo PS showing a slight increased striatal IBZM uptake (BG/FC = 1.56 +/- 0.05), which represents D2-receptor stimulation. [123I]IBZM-SPECT is a sensitive and non-invasive test for striatal D2-receptor density and activity which permits relatively clear discrimination between idiopathic and secondary PS and yields important information for differential therapy.

Adult↗

Purification and characterization of a novel metalloprotease from human brain with the ability to cleave substrates derived from the N-terminus of beta-amyloid protein.

The main component of amyloid plaques in Alzheimer's disease (AD) is the beta-amyloid peptide (beta/A4), derived from beta-amyloid precursor proteins (beta-APPs). In order to identify proteases possibly involved in the cleavage at the N-terminal site of beta/A4 a chromogenic peptide corresponding to this region of beta-APP was used. Here the purification and characterization of a new human brain protease with the ability to cleave the beta-APP peptide as well as beta-APP in vitro are described. The enzyme has a molecular mass of 100 kDa and belongs likely to the class of metalloproteases. It should further be named "MP100". The enzyme has a very broad substrate specificity in vitro.

Amino Acid Sequence↗

Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia.

Circadian rhythm abnormalities have been described mostly with respect to manic-depressive illness; little information is available concerning circadian rhythms and schizophrenia or their influence on neuroleptic drugs. We showed previously that the MESOR of dopamine is higher in schizophrenic patients than in healthy subjects and that women who are drug-free schizophrenic have lower prolactin MESORs and lower amplitudes than healthy women. We now report the data of a cosinor analysis of tryptophan, serotonin, melatonin, and pituitary hormones in the blood of 34 healthy subjects, 90 drug-free schizophrenics, and 25 neuroleptic-treated schizophrenic patients. This data indicated a significant phase advance of serum tryptophan, prolactin, and melatonin concentrations, a trend toward a phase advance in serotonin. Thyroid stimulating hormone (TSH), and growth hormone concentrations, and decreases in the TSH MESORs among patients compared to healthy subjects. These results suggest that circadian changes, such as phase advances and alterations in MESOR, are not only present in depression but also in schizophrenia. Although neuroleptic treatment raised the prolactin MESOR and amplitude, it did not elicit any change in circadian rhythmicity among the other parameters.

Adolescent↗

Using protein synthesis inhibitors to establish the phylogenetic relationships of the Sulfolobales order.

The sensitivity of the cell-free protein synthesis systems from Acidanus brierleyi, Acidianus infernus, and Metallosphaera sedula, members of the archaeal order Sulfolobales, to 40 antibiotics with different specificities has been studied. The sensitivity patterns were compared to those of Sulfolobus solfataricus and other archaeal, bacterial, and eukaryotic systems. The comparative analysis shows that ribosomes from the sulfolobales are the most refractory to inhibitors of protein synthesis described so far. The sensitivity results have been used to ascertain in phylogenetic relationships among the members of the order Sulfolobales. The evolutionary significance of these results are analyzed in the context of the phylogenetic position of this group of extreme thermophilic microorganisms.

Anti-Bacterial Agents↗

[Thermal side effects after use of the pulsed IR laser on meniscus and bone tissue].

Thermal effects on meniscus and bone tissue after application of 314 boreholes using five different infrared (IR) lasers: Nd:YAG, Tm:YAG, Ho:YAG, Er:YAG, Cr,Er:YSGG (application energy 200 mJ, 400 mJ, 600 mJ, 800 mJ, 1000 mJ; repetition rate 2 Hz, 5 Hz; medium air, water rinse) were analyzed. The experimental set-up comprised for the beam guiding a focussing lens (f = 100 mm) or a flexible fiber (Ho:YAG). Damaged tissue was investigated macroscopically, histologically, and by scanning electron microscopy. Application in air caused carbonisation in all cases. Application in water showed thermal brown discoloring using Tm:YAG, Ho:YAG laser on meniscus tissue. The Nd:YAG did not ablate. The Er:YAG laser showed macroscopically precise boreholes without any discoloring of the adjacent tissue as well in meniscus as in bone. Cr:ErYSGG laser results were comparable with the results using an Er:YAG laser although ablation on bone tissue created higher thermal effects. For the aim of developing minimal invasive operating techniques the Er:YAG laser showed best results.

Animals↗

Accumulation of a 50 kDa N-terminal fragment of beta-APP695 in Alzheimer's disease hippocampus and neocortex.

Proteolytic processing of beta-amyloid precursor protein (beta-APP) is a key event in the formation of beta-amyloid deposits in Alzheimer's disease (AD) brains and is likely to be accompanied by the accumulation of cleavage products other than the beta/A4 protein. Using a beta-APP695-specific monoclonal antibody in quantitative immunoblotting, a 50 kDa N-terminal fragment of beta-APP695 was detected in neocortex, hippocampus and cerebellum of AD patients and control individuals. The mean level of this fragment was higher in AD hippocampus and neocortex as compared to controls, suggesting that beta-APP695 fragments are generated in various brain regions but that the proteolytic processing is increased in pathologically affected brain areas.

Adult↗

Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography.

The aetiology and pathogenesis of Alzheimer's disease are currently poorly understood, but symptomatic disease is associated with amyloid plaques, neurofibrillary tangles, neuronal loss and numerous alterations of neurotransmitter systems in the CNS. Monoamine oxidase type B is known to be increased in Alzheimer diseased brains. The distribution and abundance of catalytic sites for monoamine oxidases A and B in post mortem human brains of 11 Alzheimer disease cases and five age-matched controls were investigated by quantitative enzyme radioautography. Using tritiated monoamine oxidase inhibitors (Ro41-1049 and lazabemide)--as high affinity substrates selective for monoamine oxidases A and B, respectively--it was found that monoamine oxidase B activity increased up to three-fold exclusively in temporal, parietal and frontal cortices of Alzheimer disease cases compared with controls. This increase was restricted to discrete patches (approximately 185 microns in diameter) which occupied approximately 12% of the cortical areas examined. In other brain regions (hippocampal formation >> caudate-putamen > cerebellum), patches of [3H]lazabemide-enriched binding were less abundant. [3H]Ro41-1049 binding (i.e. monoamine oxidase A) was unchanged in all tissues of diseased versus control brains. The monoamine oxidase B-enriched patches in all cortical regions correlated, in their distribution and frequency, with glial fibrillary acidic protein-immunoreactive clusters of astrocytes. Diffuse and mature beta-amyloid-immunoreactive senile plaques as well as patches of high density binding of [3H]PK-11195--a high-affinity ligand for peripheral-type (mitochondrial) benzodiazepine binding sites in microglia/macrophages--were found throughout Alzheimer diseased cortices. The up-regulation of monoamine oxidase B in plaque-associated astrocytes in Alzheimer's disease--in analogy to its proposed role in neurodegenerative disorders such as Parkinson's disease--might, indirectly, be a potential source of cytotoxic free radicals. Lazabemide, a selective reversible monoamine oxidase B inhibitor, is currently under clinical evaluation for the treatment of Parkinson's and Alzheimer's diseases. We conclude that enzyme radioautography with [3H]lazabemide is a reliable high resolution assay for plaque-associated astroglioses in Alzheimer's disease. Its clinical diagnostic utility for positron emission tomography or single photon emission computer tomography studies is being investigated.

Aged↗

Competence and responsibility in schizophrenia.

In a survey of the historical background it is shown that the classical doctrine on responsibility in schizophrenia has left its mark on the wordings of the psychiatric textbooks of the different countries. Closely combined with the imputation of enduring irresponsibility in schizophrenia was the opinion that civil rights are largely suspended if a person is given the diagnosis of schizophrenia. By the more recent research results of the studies of course and long-term outcome of schizophrenia and related psychoses and the development of the basic symptom concept has shown that it is not justified on principle to summarily deprive a person, diagnosed as schizophrenia, of civil rights as well as of criminal responsibility. New directions and some guidelines for an adequate assessment of competence and responsibility in schizophrenia are described. The knowledge of the newer findings and the application and utilization of the concept of basic symptoms and non-psychotic basic stages enable to overcome the doctrines of incurability, principle heterogeneity and numinous singularity and may lead to a rather appropriate and adequate social appreciation of the disease. Insight, freedom, responsibility, and competence of a person diagnosed as schizophrenia are in the postpsychotic pure residues and basic stages much more frequently preserved and available than hitherto assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Civil Rights↗

alpha-Tocopherol supplementation in racing cyclists during extreme endurance training.

This study was undertaken to evaluate the effects of 5 months of alpha-tocopherol supplementation on physical performance during aerobic exercise training in 30 top-class cyclists. Antioxidative effects of supplementation were also studied. Plasma alpha-tocopherol concentration increased significantly in the vitamin E-supplemented group, whereas the placebo group showed a trend toward decrease. Physical performance did not improve in the alpha-tocopherol-supplemented group compared to the placebo group. Heart rates were also not significantly different. Lactate concentrations at the aerobic threshold and the anaerobic threshold were identical. Thus, there was no performance improvement in the alpha-tocopherol-supplemented group. However there was a significant reduction in CK in serum of the E-supplemented group. A trend toward decrease in GOT, GPT, and LDH was observed with alpha-tocopherol supplementation. Moreover, significantly reduced malondialdehyde serum levels were measured in the E-supplemented group. The findings indicate a protective effect of alpha-tocopherol supplementation against oxidative stress induced by strenuous exercise.

Adult↗

Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

Animals↗

Differing effects of airway obstruction on physical work capacity and ventilation in men and women with COPD.

BACKGROUND: Although the natural history of COPD is thought to be well known, studies assessing differences in the onset and course of the disease by gender are surprisingly lacking. This study is a cross-sectional analysis using progressive cycle ergometry exercise testing to assess male and female patients at specific levels of airway obstruction to see if they differ in their exercise capacity and decline in functional capacity. METHODS: The study group included 417 patients with COPD, 55 to 85 years of age, who were compared with 29 controls of similar age; all patients had COPD (FEV1/FVC < 75% predicted) without restrictive disease. Exercise testing in groups based on the level of pulmonary dysfunction defined by FEV1/FVC ratios (mild, 60.5 to 69.5%; moderate, 50.5 to 60.5%; severe < 50.5%) was analyzed. Data were evaluated using the Statistical Analysis System, analyzing gender and degree of airway obstruction and adjusting for any difference in age and peak exercise heart rate (covariate analysis of variance). RESULTS: Men demonstrated progressive reductions of body weight, exercise ability (assessed by the VO2), oxygen pulse (O2P, an indicator of stroke volume), and maximum exercise ventilation (VEmax) even with mild pulmonary dysfunction. Women did not lose weight, and maintained usual exercise ability (VO2, VEmax) and O2P until moderate or severe disease was present. Additional confirmation of a decrease in cardiac function for men with mild airway obstruction (p < 0.0001, controls), but not for women with mild airway disease, was obtained by estimation of cardiac output. Further, women presented with COPD at lower levels of tobacco smoke exposure than men for the entire group (43.8 vs 63.0 pack-years, p < 0.0001) and for each subgroup of disease severity. There were proportionally more life-time female nonsmokers than male nonsmokers with COPD (16 vs 5, p < 0.001). CONCLUSIONS: Male and female patients with COPD differed in their decline of functional aerobic capacity even at equivalent levels of pulmonary dysfunction. One reason for this appeared to be a decrease in the O2P occurring early in the natural history of the disease in the men and not in the women. Although general body de-conditioning may be the cause, heart disease may also be a contributing aspect. The relative delay in the loss of exercise capacity and body mass by the women may relate to predisease differences in physical activity. Women manifested significant lung disease with less cigarette smoking than men. This may be attributable to a different susceptibility to cigarette smoke between the sexes. These results suggest that there appear to be differences in the natural history of COPD in men and women.

Aged↗

[Leisure and social contact clubs for psychiatric patients--an assessment of club members].

55 visitors from five recreation and social clubs for mentally ill clients have been described, related to some sociographic data including the number of times the club is frequented, the duration of membership in the club as well as the source of information. They were asked to give their opinions on the frequency and the duration of the meetings and the quality of the clubrooms, the care and the programmes. They give the reasons for attending the clubs and the resulting main effects. They make wishes and complaints about the clubs. The results of the questioning are compared to the description of tasks and aims of clubs as seen from the professional point of view in order to find conformities and/or differences. On the whole a consensus is to be seen. Differences can be ascertained, where the professional aim is mainly of therapeutic nature. Such a target does not meet the needs of the visitors. For them the social aspect is of main importance in a surrounding offering protection, acceptance, understanding and support.

Adult↗

Characterization of proteases with the specificity to cleave at the secretase-site of beta-APP.

The beta-amyloid precursor protein (APP) can be proteolytically processed in at least two different ways either in a secretory pathway or in a lysosomal pathway. The proposed sites for the 'secretase' cleavage are the Gln15-Lys16 and Lys16-Leu17 peptide bonds within the beta A4 domain. Using chromogenic peptide substrates derived from these APP sites, proteolytic enzymes were investigated in the brain of AD patients and control individuals. Mean differences in enzyme activity were observed between the two groups, although no statistical significance was reached. Further analysis in rat brain allowed identification of the lysosomal cathepsin B and the cytosolic proteasome as secretase-like enzymes. They are probably not involved in APP secretion but possibly in removal of amyloidogenic fragments.

Alzheimer Disease↗

Modulation of beta-amyloid precursor protein secretion in differentiated and nondifferentiated cells.

The regulation of beta-amyloid precursor protein (beta-APP) secretion was compared in differentiated and nondifferentiated PC12 and B104 cells. Phorbol esters stimulated the release of beta-APP in all cells examined. However, differentiated PC12 cells were much more sensitive to phorbol ester treatment than nondifferentiated PC12 cells and their beta-APP release was also induced by the protein phosphatase inhibitor okadaic acid and the Ca(++)-ionophore A23187. In contrast, beta-APP release from B104 cells was strongly stimulated by A23187 and to lesser degree by phorbol esters. This effect was most pronounced in nondifferentiated B104 cells, which might be due to a higher basic release of beta-APP from differentiated B104 cells. Thus, the regulation of beta-APP cleavage and release varies depending on the cell type and differentiation state of the cell.

Amyloid beta-Protein Precursor↗

Involvement of amyloid precursor protein in memory formation in the rat: an indirect antibody approach.

The potential role of different isoforms of amyloid precursor proteins (APPs) in memory and learning processes was investigated in rats using antibodies differentiating between APP isoforms containing or lacking the Kunitz protease inhibitor (KPI) domain. Rats received intracerebroventricular injection of control immunoglobulins (IgGs), anti-KPI-APP (= anti-P3) or anti-N-terminus-APP (= anti-P4). No immediate effects on learning of a passive avoidance task were observed; however, performance evaluated 1 day later was somewhat impaired by the anti-P3 antibody (reacting with APPKPI) and even more markedly impaired by the anti-P4 antibody (reacting with both APP695 and APPKPI) relative to control antibody. The antibodies did not affect performance of an active avoidance task acquired prior to the experimental treatment or active avoidance learning 8 days post-treatment. These results suggest that blockade of APP by an antibody injected intracerebroventricularly impairs the consolidation and/or retrieval of memory in rats.

Amyloid beta-Protein Precursor↗