PubMed Health⌕ Search

Biomedical subjects

G Huber

Publications and source records attributed to G Huber.

At least 55 records · Page 3Linked to original sources
PubMed1999

Metalloprotease MP100: a synaptic protease in rat brain.

Proteases are expressed widely throughout the nervous system and perform essential functions. We have earlier characterized and cloned the metalloprotease MP100, an enzyme originally described as a beta-amyloid precursor protein (beta-APP) processing candidate. In the present study we describe the cellular and subcellular localization of MP100 in rat brain. A punctuate intracellular immunostaining in cortical, hippocampal and cerebellar neurons suggests its high abundance in vesicular intracellular structures. The MP100 staining pattern resembled that of the presynaptic protein synaptophysin. In gel filtration chromatography of isolated rat brain synaptosomal membranes, MP100 co-fractionated with synaptophysin and beta-APP. Furthermore, pre-embedding immunoelectron microscopy of the cerebellum revealed MP100 to be localized at synaptic sites. All together, these data might indicate a role for MP100 in functions such as proteolytic modification of synaptic proteins.

Animals↗
PubMed1999

Central adenosine A(2A) receptors: an overview.

Recent advances in molecular biology, biochemistry, cell biology and behavioral pharmacology together with the development of more selective ligands to the various adenosine receptors have increased our understanding of the functioning of central adenosine A(2A) receptors. The A(2A) receptor is one of four adenosine receptors found in the brain. Its expression is highest in striatum, nucleus accumbens and olfactory tubercles, although it also occurs in neurons and microglia in most other brain regions. The receptor has seven transmembrane domains and couples via Gs to adenyl cyclase stimulation. Antagonistic interactions between A(2A) receptors and dopamine D(2) receptors have been described, as stimulation of the A(2A) receptor leads to a reduction in the affinity of D(2) receptors for D(2) receptor agonists. The A(2A) receptor is thought to play a role in a number of physiological responses and pathological conditions. Indeed, A(2A) receptor antagonists may be useful for the treatment of acute and chronic neurodegenerative disorders such as cerebral ischemia or Parkinson's disease. A(2A) receptor agonists may treat certain types of seizures or sleep disorders. This review discusses the characteristics, distribution, pharmacochemical properties and regulation of central A(2A) receptors, as well as A(2A) receptor-mediated behavioural responses and their potential role in various neuropsychiatric disorders.

Animals↗
PubMed1999

cDNA cloning and molecular characterization of human brain metalloprotease MP100: a beta-secretase candidate?

Metalloprotease MP100 was originally isolated as a beta-secretase candidate from human brain using a beta-amyloid precursor protein (beta-APP)-derived p-nitroanilide (pNA) peptide substrate. Peptide sequences from purified MP100 were now found to resemble sequences reported for a puromycin-sensitive aminopeptidase (PSA) highly enriched in brain, and cDNA cloning revealed nearly complete homology of MP100 to PSA, with only a single bp difference resulting in an amino acid change at position 184. Another MP100 cDNA encoded a protein with a 36-amino acid deletion (positions 180-217) and a two-amino acid insertion after Val533. Purified recombinant human MP100 cleaved the original pNA substrate as well as a free beta-site-spanning amyloid beta (A beta) peptide (A beta(-10/+10)), generating A beta(1-10). The latter substrate, however, remained uncleaved, if N- and C-terminally blocked, and also purified beta-APP was not cleaved. Double immunoimaging revealed partial, patchy, colocalization of beta-APP and MP100 in doubly transfected human embryonic kidney cells (HEK cells) and in normal neuroblastoma cells, and both proteins could be coimmunoprecipitated from rat brain extracts, suggesting their close vicinity in vivo. Coexpression of MP100 and beta-APP695, however, did not boost A beta levels in HEK cells, although active enzyme was produced. Thus, MP100 does not exert true beta-secretase-like function in cells, although it may well act as a secondary exoprotease in a complex beta-APP/A beta metabolism.

Amino Acid Sequence↗
PubMed1999

Behaviors that cause clinical instructors to question the clinical competence of physical therapist students.

BACKGROUND AND PURPOSE: Clinical instructors (CIs) observe behavior to determine whether students have the skills assumed necessary for safe and effective delivery of physical therapy services. Studies have examined assumptions about necessary skills, but few studies have identified the types of student behaviors that are "red flags" for CIs. This study examined the student behaviors that negatively affect students' clinical performance, which can alert CIs to inadequate performance. SUBJECTS: Twenty-eight female and 5 male CIs discussed the performance of 23 female and 17 male students who were anonymous. METHODS: Using questionnaires and semistructured interviews that were taped and transcribed, CIs described demographics and incidents of unsafe and ineffective physical therapy. After reading the transcripts, investigators identified and classified the behaviors into categories and checked their classification for reliability (kappa=.60-.75). RESULTS: Behaviors in 3 categories emerged as red flags for CIs: 1 cognitive category--inadequate knowledge and psychomotor skill (43% of 134 behaviors)--and 2 noncognitive categories--unprofessional behavior (29.1%) and poor communication (27.6%). The CIs noticed and valued noncognitive behaviors but addressed cognitive behaviors more often with students. Students who did not receive feedback about their performance were unlikely to change their behavior. The CIs used cognitive behaviors often as reasons to recommend negative outcomes. CONCLUSION AND DISCUSSION: Clinical instructors need to identify unacceptable cognitive and noncognitive behaviors as early as possible in clinical experiences. Evidence suggests that they should discuss their concerns with students and expect students to change.

Adult↗
PubMed1998

[Prospective study of predicting hospital length of stay for internal medicine patients].

We conducted a prospective study to see how accurately hospital doctors can predict length of patient stays on an acute medical ward. The study covered an 18-month period and included all internal medicine patients admitted to Clinic B of Basel University Hospital. 1989 patients (57% male and 43% female) were included. Average age was 62.5 years. Average stay was 15.3 days against an average predicted 14.6 days (S.D. 0.7, not significantly different at 5% C.I. Correlation coefficient 0.44-slight correlation). The discharge destination was accurately predicted in 90% of patients going home and in 80% of patients who later died. However, prediction of those patients who would require further rehabilitation or a nursing home place was poor (60% and 50% respectively). The results show that although the average predicted hospital stay was fairly accurate, for individuals it varied widely. Short hospital stays were generally overpredicted and longer stays underpredicted. The causes of prolonged stays were medical in 60% of cases, social in 20%, inefficient organization in 10% and other in 10%. Patients requiring only nursing care accounted for only 6% of all bed occupancies.

Aged↗
PubMed1998

[Long-term study of subclinical hypothyroidism: spontaneous course and predictors of manifest hypothyroidism].

The syndrome of subclinical hypothyroidism is frequent and predominantly affects females over 40. Only limited data on its natural course is available. It was the aim of our prospective trial to analyze the spontaneous evolution of this syndrome, to identify risk factors of the development of overt hypothyroidism and to develop guidelines for the management of such patients. 154 female patients were followed over a mean observation period of 10 years. After 10 years, 34% had developed overt hypothyroidism, 57% remained in the subclinical stage, and in 9% thyroid function had normalized. The initial grading of TSH-concentration (< 6 mU/l, 6-12 mU/l, > 12 mU/l) was highly predictive for thyroid failure: 7.3%, 25% and 78%, respectively, overt hypothyroidism occurred. Further risk factors for thyroid failure included an impaired thyroid reserve (T3-stimulation after TRH) and elevated titers of microsomal antibodies. We therefore recommend to controlling patients with a TSH-concentration < 6 mU/l, start thyroxine hormone replacement therapy in patients with a TSH-concentration > 12 mU/l and, depending on the additional risk factors, either controlling or treating patients with a TSH-concentration of 6-12 mU/l.

Adolescent↗
PubMed1998

[Injury risk of competitive, handicapped cross-country skiers in training nd competition].

Injuries caused by cross country skiing have been poorly investigated in handicapped athletes. The dynamic sliding shape of motion makes this sport to a suitable discipline for people with a deficit of locomotion. Visual handicapped people with a guide are able to improve their motoric skills, co-ordination, orientation and body self-consciousness in the track. Since handicapped athletes are performing in international competitions the training intensity to fulfill the requirements, but also the risk of overstrain induced injuries got increased, like in other high-performance sports. Our study examined injuries and overuse syndromes of the German National Team Ski Nordic during the Paralympics in Tignes/ Albertville (1992). Lillehammer (1994) and the training period in preparation for the Paralympics in Nagano (March 1998). The incidence and kind of injuries in the competitive handicapped cross country skier was comparable with non-handicapped athletes, but the injury pattern was different.

Adult↗
PubMed1998

Introduction of hereditary disease-associated mutations into the beta-amyloid precursor protein gene of mouse embryonic stem cells: a comparison of homologous recombination methods.

Two different approaches for introducing pathogenic mutations into the beta-amyloid precursor protein gene in mouse embryonic stem cells were compared. Both approaches require two sequential modifications of the targeting locus by homologous recombinations. One approach was a "targeting-in-out" procedure that is based on a double-replacement strategy, and the other was a "hit-and-run" procedure that makes use of an unstable genomic duplication after vector integration. Both approaches showed similar targeting frequencies for the first step. In the targeting-in-out procedure, targeted-in embryonic stem cell clones with the desired mutation and an intron-located selection cassette were obtained at a high frequency after the first step. Targeting out, however, resulted not only in the expected loss of the intron-located selection cassette but also in unavoidable reversion to wild type. In contrast, pure mutants, i.e., those without additional genomic changes, were generated by the hit-and-run procedure. Although targeted-in embryonic stem cells might be used to generate animals with modified beta-amyloid precursor protein, the hit-and-run procedure appears to be the superior way to target gene modifications in vivo, leading to pure, correct mutants. For further improvements, optimization of the homologous recombination efficiency could be envisaged.

Alzheimer Disease↗
PubMed1998

Alteration of cerebral blood flow in patients with bacterial and viral meningoencephalitis.

PURPOSE: Our purpose was to investigate cerebral blood flow disturbances in patients with bacterial and viral meningoencephalitis. METHODS: Forty-two patients with acute bacterial and viral meningoencephalitis and 14 control subjects were studied using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). SPECT images were evaluated semiquantitatively. The results were compared with clinical severity of the meningoencephalitis assessed at the time of the SPECT study with the Hunt and Hess scale, with separately recorded focal clinical signs, and with the Glasgow outcome scale (GOS) after 3 weeks. RESULTS: Count density values were significantly reduced in patients with bacterial meningoencephalitis as compared with the control subjects. Inhomogeneous tracer accumulation assessed by asymmetry indexes was significantly greater in patients than in the control group. With increasing Hunt and Hess scores, the count density values decreased and the asymmetry indexes increased. Patients with a poor outcome (GOS 1 to 3) had significantly higher asymmetry indexes and lower CDV values than did patients with a good outcome. CONCLUSION: Global and focal alterations of cerebral perfusion are frequent in bacterial and viral meningoencephalitis and correlate with acute clinical state.

Adult↗
PubMed1997

The heterogeneous course of schizophrenia.

Findings on the course and outcome of schizophrenia, the limitations of Kraepelin's opinion, and data supporting a continuum hypothesis of endogenous psychoses are presented. The European long-term investigations, the Zürich, Lausanne and Bonn studies are consistent with the view that diagnoses must be made independently of outcome; nearly a quarter show full psychopathological and 56% a social remission. Several factors are relevant to the long-term course and outcome. In the Bonn Study, 43% of subjects showed long-term remission, with only a mild deficit state ('pure defect') consisting of dynamic and cognitive basic symptoms, and 35% revealed characteristic schizophrenic residues. Eighty-seven per cent were living at home permanently at the most recent follow-up; 56% were socially recovered, i.e., fully employed, yet only 38.6% were at their previous occupational level. Twelve course types could be differentiated and were ranked according to social remission rate. The results led to a revision of classical descriptions of an incessant progression of schizophrenia. The outcome is largely independent of the duration of illness; there is no increasing deterioration in the later decades of the disease, often showing a trend toward improvement (the 'second, positive bend'), even 20-40 years after onset. According to Zubin, the results of the European long-term studies and the Vermont Study have revolutionized our knowledge about schizophrenia and emancipated it from the yoke of inevitable chronicity. The findings of the Bonn Study, the first systematic study of prodromes, and of the prospective basic symptom-oriented study on the early diagnosis of schizophrenia led, in parallel with the gradual development of the basic symptom concept, to a new view of the evolution of schizophrenia.

Disease Progression↗
PubMed1997

Identification and characterization of wheat grain albumin/globulin allergens.

Bakers' asthma, an immediate-type allergic response to the inhalation of cereal flours, is an important occupational disease among workers of the baking and milling industries, and the salt-soluble proteins of wheat and rye flour dust are considered the most relevant allergens. In order to identify and characterize the major IgE-binding proteins, the polypeptide composition of the albumin/globulin protein fraction obtained from different cultivars was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and high-resolution two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimension (IPG-Dalt), followed by immunoblotting with sera from asthmatic bakers. Relevant allergens were isolated by micropreparative IPG-Dalt and blotting onto polyvinylidenedifluoride membranes and identified by amino acid composition analysis or N-terminal amino acid sequence analysis. SDS-PAGE, IPG-Dalt, and immunoblotting demonstrated that the sera of the bakers allergic to flour contained IgE antibodies which bound to numerous albumin/globulin polypeptides in the 70, 55, 35, 26-28, and 14-18 kDa areas. More detailed investigations using IPG-Dalt revealed cultivar-specific differences in IgE-binding. It was also demonstrated that the majority of the allergens were not single polypeptide spots, but consisted of up to ten isoforms of similar molecular mass but different isoelectric points. Amino acid composition analysis and N-terminal amino acid sequence analysis, which were performed for nine allergens located in the 14-18, 26-28, and 35 kDa areas, revealed homologies to amylase/protease inhibitors, acyl-CoA oxidase and fructose-bisphosphate-aldolase from wheat, barley, maize, and rice, respectively.

Albumins↗
PubMed1997

[Are self-perceivable neuropsychological deficits in patients with neuroses or personality disorder diagnoses indicative of later schizophrenia?].

For the first time, the present study assessed the achievable predictive value of early self-experienced neuropsychological deficits for the fater development of schizophrenia. Ninety-six patients with DSM-III-R diagnoses mainly of the formerly neurotic or personality disordered field, of whom 81% had shown such basic disorders at the time of the index examination and therefore were classified as persons at high risk of developing schizophrenia, were re-examined for schizophrenia. After an average follow-up period of about 8 years, more than half of the re-examined sample had developed a schizophrenic disorder according to DSM-III-R. The outcome of schizophrenia versus no schizophrenia was predicted correctly in 77% of cases by the presence or absence of self-experienced disturbances of perception, thought, speech or action.

Adolescent↗
PubMed1997

Expression and characterization of human beta-secretase candidates metalloendopeptidase MP78 and cathepsin D in beta APP-overexpressing cells.

Human beta-secretase candidates, MP78 (h-MP78, EC 3.4.24.15) and cathepsin D (Cat D, EC 3.4.23.5), were evaluated for their ability to enhance amyloid-beta-protein (A beta) secretion when overexpressed in beta APP-containing cells. HEK-293 cells stably co-expressing h-MP78 or Cat D and h-beta APP695 were metabolically labeled with [35S]methionine and A beta secretion was quantified in the conditioned media by immunoprecipitation and ELISA without showing any significant increase in A beta production. Because Cat D is known to have a higher affinity for APP-substrate containing the Swedish familial Alzheimer's disease double mutation (SFAD, K595N and M596L substitutions in beta APP695) than for the wild type substrate [Dreyer et al., Eur. J. Biochem., 224 (1994) 265-271], the effect of Cat D overexpression was tested in a HEK293/beta APPSFAD stable cell line. ELISA analysis of the conditioned media from these cells did also not reveal any increase in A beta generation. In addition, recombinant h-MP78 purified from E. coli cleaved an APP-derived substrate spanning the beta-secretase site (ISEVKMD1AEFRHDS) at multiple sites, but the beta-site cleavage was only a minor one; cleavage occurred predominantly at K-M and E-F bonds. Human liver Cat D also cleaved the same substrate at multiple sites, yet the major cleavage at pH 4.0 occurred at the amyloidogenic D1 site. These findings indicate that h-MP78 does not have the cleavage specificity required for a beta-secretase protease and although Cat D fulfilled the amyloidogenic cleavage specificity, the results of the co-expression experiments make both enzymes less likely candidates as relevant beta-secretases.

Amino Acid Sequence↗
PubMed1997

Synaptic beta-amyloid precursor proteins increase with learning capacity in rats.

The precursor proteins of Alzheimer's disease beta-amyloid peptide, the beta-amyloid precursor protein isoforms, comprise a family of neuronal proteins with synaptic localization whose physiological roles in brain are poorly understood. One possible role for synaptic proteins is involvement in neuronal plasticity. After exposure to an enriched environment compared to impoverished conditions, rats exhibited superior cognitive capacity. Up to approximately four-fold increased overall levels of beta-amyloid precursor proteins were found in cortical/subcortical tissue of the enriched animals displaying significantly more synapses immunoreactive for the different beta-amyloid precursor protein isoforms (beta-amyloid precursor protein695- and beta-amyloid precursor protein751/770) in hippocampus and adjacent occipital cortex. This correlation thus provides in vivo evidence for an association of beta-amyloid precursor proteins with plastic changes induced by complex environment with consequences for cognitive functions and suggests that impaired beta-amyloid precursor protein metabolism at synapses might contribute to brain dysfunction in Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1997

Medialization of the patella in total knee arthroplasty.

Patellar complications of total knee arthroplasty remain the most common cause of pain and reoperation. Laboratory studies have suggested that medialization of the patella will improve tracking of the patella on the trochlea of the femoral component. The purpose of this study was to determine if clinical medialization of the patellar component on the patellar bone would improve tracking of the patella as demonstrated radiographically. Sixty-two knees were randomized so that 31 knees had a centrally placed patellar component and 31 had the patellar component placed on the medial two thirds of the patellar bone. There was no difference between the two groups with respect to either clinical or radiographic results in the first year after surgery. There was no improvement compared with previous reports in the incidence of tilt and displacement. The one improvement was a reduction in the incidence of lateral release. Thus, consequences of lateral release such as postoperative morbidity, avascular necrosis of the patella, and stress fracture of the patella can be avoided. It is recommended that the patellar component be placed on the medial two thirds of the patella to reduce the occurrence of lateral release. Tracking of the patella during surgery can be assessed using a single suture placed at the superior pole of the patella, and this technique in combination with the no-thumbs test provides an additional means of evaluation for patellar tracking.

Adult↗
PubMed1997

[Computed tomographic and magnetic resonance tomographic findings in pilocytic astrocytoma].

PURPOSE: In a retrospective study we examined the predilection sites, the CT and MR morphology and the contrast behaviour of intracranial pilocytic astrocytoma (PA) in a large number of patients. MATERIAL AND METHODS: The study consists of 47 patients (18 male, 29 female, mean age 10.1 years) with histologically proven PA. RESULTS: The chief predilection site turned out to be the hypothalamic region (15/47 = 32%). The other regions involved were (in descending order): brain hemispheres 8/47 = 17%; cerebellar vermis 7/47 = 15%, cerebellar hemispheres; thalamic nuclei and pontomedullar region 4/47 = 8.5% each; pineal gland 2/47 = 4%; pons, lamina tecti and optic fascicle 1/47 = 2% each. The PA presented 24/47 = 51% cysts; 7/47 = 15% calcifications; 2/47 = 4% necrosis and 1/47 = 2% perifocal oedema. In three cases (3/47 = 6%) CT and MRI showed no contrast enhancement. CONCLUSION: PA appear in almost all brain regions but there is a clear preference of the hypothalamic region. PA of the hypothalamic region are a special subgroup. They are often associated with neurofibromatosis 1, tend to infiltrate surrounding structures, and to disseminate into the intracranial and spinal subarachnoid space.

Adolescent↗