Biomedical subjects

G Huber

Publications and source records attributed to G Huber.

At least 37 records · Page 2Linked to original sources

PubMed1996

[Biomechanics of the shoulder and therapeutic applications].

The influence of biomechanics in surgery of the locomotor apparatus has been constantly increasing over the last few decades. The purpose of this study was to determine wether biomechanical studies can significantly influence therapy and treatment of shoulder injuries, especially shoulder instability. The investigation was performed on 23 fresh human specimens with intact capsular ligaments of the glenohumeral joint. A Bankart lesion from 3 o'clock to 6 o'clock was repaired, and a Bankart repair and anterior inferior capsular shift, as described by Neer, were performed. The measurement was done on six clinically relevant positions of instability: superior, anterior, anterior-inferior, inferior, posterior-inferior, posterior. Measurement was done using a specially developed strain-gauge system. It was demonstrated that both instability and too much stability of the shoulder joint lead to a significant change in shoulder biomechanics. The anatomical O-position of the glenohumeral joint in 110 degrees of abduction is a position of about 60 degrees of external rotation compared to the O-position for clinical measurement. From the therapy point of view, one has to ask for anatomical reconstruction instead of tight repair in soft-tissue repair in the glenohumeral joint. Immediate post-operative rehabilitation in a 60 degrees range of motion is possible.

Adult↗

PubMed1995

Cloning and functional expression of a metalloendopeptidase from human brain with the ability to cleave a beta-APP substrate peptide.

Using a combination of PCR and hybridization screening, we have isolated a cDNA clone for a metalloendopeptidase (h-MP78) from a human temporal cortex library. This 2.5-kb cDNA encodes a 689-amino acid protein with a predicted molecular mass of approximately 78.5 kDa. The primary structure of h-MP78 exhibits high similarity to those of porcine (94%) and rat (92%) thimet oligopeptidase. Expression of the cDNA in HEK-293 resulted in the production of an active enzyme able to cleave a chromogenic beta-APP derived substrate peptide KTEEISEVKM-P-nitro-anilide. RNA blot analysis of various human tissues revealed one major species of h-MP78 mRNA of approximately 2.55 kb. The highest level of mRNA was found in the brain.

Amino Acid Sequence↗

PubMed1995

Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones, and cortisol in schizophrenia.

Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid hormones, and cortisol have been observed in psychiatric disorders, most notably in depression. With respect to schizophrenia, the literature is scanty. We report here on the circadian parameter estimates of the vital signs, epinephrine, norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are based on the cosine model to fit the experimental data. The circadian profiles of heart rate, blood pressure, and oral temperature are similar among schizophrenic patients and healthy subjects. Neuroleptic-treated patients have significantly higher MESORs (the daily mean) of serum norepinephrine and epinephrine than healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients; the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower in schizophrenic patients compared with control subjects. The circadian serum thyroxine and cortisol profiles are similar in the three groups. The data show that the circadian profiles of vital signs in drug-free chronic schizophrenic patients who are not chronically hospitalized are similar to those of healthy subjects and that the increase in serum catecholamines and the apparent lowering in some thyroid indices might induce a down-regulation in the noradrenergic receptor system that could contribute to the pathophysiology of schizophrenia.

Adolescent↗

PubMed1995

Inflammatory processes induce beta-amyloid precursor protein changes in mouse brain.

In Alzheimer disease, a combination of genetic predisposition and environmental factors may contribute to changes in beta-amyloid precursor protein (APP) expression, beta-amyloid peptide deposition, and neuronal loss. Factors such as head injury or acute infection that trigger inflammatory processes may play a crucial role in development of the disease. In the present in vivo study, we showed that, in mouse brain, peripheral stimulation with lipopolysaccharide (LPS) induced a transient increase in the inflammatory cytokine mRNAs (interleukin 1 beta and interleukin 6), followed by changes in expression of APP isoforms in the cerebellum but not in the cerebral cortex. These changes consisted of a decrease in the APP-695 and an increase in the Kunitz protease inhibitor-bearing isoforms (KPI-APP). In the cerebellum of the staggerer mouse mutant, where a severe loss of Purkinje and granule cells occurs, basal mRNA levels of these interleukins were elevated and an increase in the KPI-APP/APP-695 ratio compared to wild-type mice was observed. These abnormalities were further accentuated by LPS stimulation. This study shows that acute and chronic inflammatory processes play an important role in changes in APP expression possibly associated with neurodegeneration.

Amyloid beta-Protein Precursor↗

PubMed1995

A biotechnological method provides access to aggregation competent monomeric Alzheimer's 1-42 residue amyloid peptide.

Senile plaques, a neuropathological hallmark of Alzheimer's disease, consist primarily of insoluble aggregates of beta-amyloid peptide (A beta). A 42-residue peptide (A beta 1-42) appears to be the predominant form. In contrast to A beta 1-40, A beta 1-42 is characterized by its extreme tendency to aggregate into fibers or precipitate. A tailored biotechnological method prevents aggregation of A beta 1-42 monomers during its production. The method is based on a protein tail fused to the amino terminus of A beta. This tail leads to a high expression in E. coli, and a histidine affinity tag facilitates purification. Selective cleavage of the fusion tail is performed with cyanogen bromide by immobilizing the fusion protein on a reversed phase chromatography column. Cleavage then occurs only at the methionine positioned at the designed site but not at the methionine contained in the membrane anchor sequence of A beta. Furthermore, immobilization prevents aggregation of cleaved A beta. Elution from the HPLC column and all succeeding purification steps are optimized to preserve A beta 1-42 as a monomer. Solutions of monomeric A beta 1-42 spontaneously aggregate into fibers within hours. This permits the investigation of the transition of monomers into fibers and the correlation of physico-chemical properties with biological activities. Mutations of A beta 1-42 at position 35 influence the aggregation properties. Wild-type A beta 1-42 with methionine at position 35 has similar properties as A beta with a methionine sulfoxide residue. The fiber formation tendency, however, is reduced when position 35 is occupied by a glutamine, serine, leucine, or a glutamic acid residue.

Amino Acid Sequence↗

PubMed1995

Apoptotic cell death induced by beta-amyloid 1-42 peptide is cell type dependent.

beta-Amyloid peptide (A beta), a proteolytic fragment of the beta-amyloid precursor protein, is a major component of senile plaques in the brain of Alzheimer's disease patients. This neuropathological feature is accompanied by increased neuronal cell loss in the brain and there is evidence that A beta is directly neurotoxic. In the present study reduced cell viability in four different neuroblastoma cell types was observed after treatment with human A beta 1-42 for 1 day. Of the cell types tested rat PC12 and human IMR32 cells were most susceptible to A beta toxicity. Chromosomal condensation and fragmentation of nuclei were seen in PC12, NB2a, and B104 cells but not in IMR32 cells irrespective of their high sensitivity to A beta. Electrophoretic analysis of cellular DNA confirmed internucleosomal DNA fragmentation typical for apoptosis in all cell types except IMR32. These findings suggest that the form of A beta-induced cell death (necrosis or apoptosis) may depend on the cell type.

Amyloid beta-Protein Precursor↗

PubMed1995

[Prodromal symptoms in schizophrenia].

This review deals with the opinions and findings of the last six decades regarding occurrence, frequence, and phenomenology of precursor stages of schizophrenic and schizoaffective psychoses. Already in his classical delineation of the onset of schizophrenia Mayer-Gross (1932) differentiated between uncharacteristic and characteristic precursors of schizophrenia and anticipated essential aspects of the concept of basic stages and basic symptoms which has been gradually developed by clinical psychiatrists and psychologists since the 50s. In his monograph "The beginning schizophrenia" Conrad (1958) resumed the "promisingly undertaken, but prematurely coming to a standstill" work of the descriptive-phenomenological psychopathology of the Heidelberg School (Jaspers, K. Schneider, Mayer-Gross, Gruhle) and investigated systematically early abnormalities of behaviour with the method of morpho-analysis. However, the study of Conrad refers already to the onset of the first psychotic episode, the "trema" which is not identical with the outpost syndromes and prodromes in the sense of Mayer-Gross and the authors of the basic symptom concept. The "trema" is characterized mainly by disorders of behaviour and expression, the precursor syndromes by dynamic and cognitive basic deficiencies, experiential and not behavioural in kind, typically only recognizable by the self-reports of the patients. The ability of recognition and realization of the basic symptoms as complaints and disorders and to develop coping strategies was the presupposition for a standardized survey and assessment of basic symptoms in the Frankfurt Questionnaire (FBF) and the Bonn Schedule for the Assessment of Basic Symptoms (BSABS).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1995

Significant reversibility of alcoholic brain shrinkage within 3 weeks of abstinence.

Chronic alcoholism is often associated with brain shrinkage or atrophy. During recent years, it has been demonstrated that this shrinkage is, at least in part, reversible when abstinence is maintained. There are different hypotheses concerning the mechanisms for this reversibility, but many questions are still open. Especially the time conditions for these reversible changes are subject of discussion. Twenty-eight male patients with severe alcohol dependence were investigated in a computed tomographic study at the beginning of abstinence and 3 weeks later. Planimetric evaluation of 5 selected slices revealed a significant decrease in liquor areas and an increase of brain volume. The densitometric analysis showed an increase in brain tissue density. In a multiple regression approach it was shown that the reversibility was mostly influenced by the age of the patients. Our results support neither the hypothesis of an increase in brain water as the most important principle for reversibility in alcoholic brain shrinkage nor the hypothesis of augmented dendritic growth. Other mechanisms like reduced (during chronic intoxication) and normalized (during abstinence) cerebral hemoperfusion have to be considered as possible mechanisms for the reversibility of alcoholic brain shrinkage.

Adult↗

PubMed1995

[Manometric and clinical long-term outcome after grade III perineal rupture].

OBJECTIVE: To investigate the manometrical and clinical long-term results following a tear III. PATIENTS: 27 Primiparae with a tear III following a spontaneous vaginal delivery were retrospectively compared with 22 Primiparae without sphincter injury (follow-up: 27 months). METHODS: Water-Perfusion-Manometry and clinical assessment (modified Kelly-Score). Manometric parameter (at rest and during contraction): sphinctertone and - length, vectorvolume, radial asymmetry. Wilcoxon-Text (p < 0.05). RESULTS: Tear III patients showed a significant decrease in sphincter length and vector volume both at rest and during contraction. On clinical assessment there was no difference. CONCLUSION: A tear III weakens the anal sphincter by decreasing sphincter length and vector volume. This weakness can be demonstrated only manometrically but not clinically.

Adult↗

PubMed1995

[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↗

PubMed1995

[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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

[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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

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↗