Biomedical subjects
Publications and source records attributed to G Huber.
Hot springs and hydrothermal systems occurring within volcanic areas are inhabited by hyperthermophilic microorganisms, some of which grow at temperatures up to 110 degrees C. Hyperthermophiles grow anaerobically or aerobically by diverse metabolic types. Within the high temperature ecosystems, primary production is independent from solar energy.
Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug-free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamine's precursors and to the neuroendocrine regulation of prolactin.
Blood extent and localization visible in CCT predicts complications and prognosis in patients suffering from subarachnoid haemorrhage (SAH). Plasma renin activity (PRA) elevation is one of the hormonal parameters of autonomic disorders after SAH and its prognostic relevance could be confirmed by this study, too. But the correlation of PRA with blood amount and distribution was the main target of this study. Large amounts of blood are connected with higher PRA-levels and more PRA-rises. Even a linear correlation between the amount of blood defined by a CCT-score and PRA in ng ml h-2 could be established. A significant correlation was found between intraventricular, suprasellar blood, ventricular enlargement of the third/lateral ventricles and PRA-elevations. Disorders of hypothalamic and/or medullary centres of sympathetic control are thought to be the underlying cause and to depend on blood extent and distribution.
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We have investigated the synthesis, axonal transport, and processing of the beta-amyloid precursor protein (APP) in in vivo rabbit retinal ganglion cells. These CNS neurons connect the retina to the brain via axons that comprise the optic nerve. APP is synthesized in retinal ganglion cells and is rapidly transported into the optic nerve in small transport vesicles. It is then transferred to the axonal plasma membrane, as well as to the nerve terminals and metabolized with a t1/2 of less than 5 h. A significant accumulation of C-terminal amyloidogenic or nonamyloidogenic fragments is seen in the optic nerve 5 h after [35S]-methionine, [35S]cysteine injection, which disappears by 24 h. The major molecular mass species of APP in the optic nerve is approximately 110 kDa, and is an APP isoform that does not contain a Kunitz protease inhibitor domain. Higher molecular mass species containing this sequence are seen mostly in the retina. A protease(s) that can potentially cleave APP to generate an amyloidogenic fragment is present in the same optic nerve membrane compartment as APP.
Abundant senile plaques are a histological hallmark in the brain of Alzheimer's disease patients. Such plaques consist of, among many other constituents, aggregated beta A4 amyloid peptide. This peptide is derived from an amyloid precursor protein (APP) by irregular proteolytic processing and is considered to be involved in the development of Alzheimer's disease. To study possible interactions of brain proteins with beta A4 amyloid or other fragments of APP, beta A4 amyloid and beta A4 amyloid extended to the C-terminus of APP were recombinantly produced as fusion proteins termed "Amy" and "AmyC," respectively. Using Amy and AmyC affinity chromatography, a 35-kDa protein from rat brain was isolated that bound tightly to AmyC but not to Amy, thus indicating an interaction of the protein with the C-terminus of APP. This 35-kDa protein was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Binding of GAPDH to AmyC but not to Amy was confirmed by gel filtration. Although AmyC slightly reduced the Vmax of GAPDH, the same reduction was observed in the presence of Amy. These findings suggest that the interaction of the cytoplasmic domain of APP with GAPDH is unlikely to influence directly the rate of glycolysis but may serve another function.
Cerebral blood flow was investigated during alcohol withdrawal in 15 male alcoholics by single photon emission computerized tomography with 99mTc-HMPAO and compared with the results of a second study 3 weeks later when all symptoms of withdrawal had disappeared and when the patients had been free of medication for at least 1 week. Slice images were reconstructed parallel to the orbitomeatal plane, and tracer activity was analyzed in 8 regions of interest per hemisphere. During alcohol withdrawal a special pattern of cerebral blood flow distribution could be observed. Relative perfusion was elevated in both inferior temporal regions, whereas it was reduced in the superior temporal region of both hemispheres. The changes of cerebral blood flow distribution did not correlate with neuropsychological findings nor with the severity of withdrawal syndrome.
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To address the question of the possible functions of different Alzheimer's disease beta-amyloid precursor protein (beta-APP) isoforms in the brain, we studied their expression at different times during postnatal rat brain development and in various regions of the adult rat brain. Polyclonal antibodies directed to two peptide antigens were used. The majority of all beta-APP forms was found to be soluble as revealed by western blot analysis. The highest level of most beta-APP forms was reached in the second postnatal week, which is the time of brain maturation and completion of synaptic connections. Strikingly high concentrations of the Kunitz protease inhibitor-containing beta-APP were present in the adult olfactory bulb, where continuous synaptogenesis occurs in the adult animal. These findings support the idea of an involvement of beta-APPs in the processes of cell differentiation and, probably, in the establishment of synaptic contacts.
A novel protein was identified in rat brain microtubules using a monoclonal antibody. The immunoreactive protein is a microtubule-associated protein (MAP) by the criteria of co-purification with tubulin through repeated cycles of microtubule polymerisation in vitro. It belongs to the class of thermostable MAPs and runs as a closely spaced polypeptide doublet of 120 kDa on SDS-PAGE gels. MAP-120 kDa is brain- and neuron-specific and is localized predominantly in Purkinje cell bodies and dendrites in the cerebellum and in dendritic compartments of pyramidal and granule neurons in the hippocampus and dentate gyrus. During postnatal brain development, MAP-120 kD levels increase about 3 to 4-fold.
The question of determining prognostically relevant features for schizophrenia was approached with multivariate statistical methods applied to the data from the Bonn longitudinal study of 502 schizophrenic patients. In this study, personal interviews according to a clinical classification scheme allowed every patient to be ranked within each of three different outcome classes: psychopathological remission, occupational remission, and course type. Our multivariate analysis encompassed a total of 50 items pertinent to the time up to and including the first 6 months after the first psychotic manifestation. Despite the introduction of mathematical methods considerably more sophisticated than those employed in earlier studies, no satisfactory solution could be found to the problem of predicting end states of schizophrenia. Reliable predictions could be made only for 'extreme' end states (i.e. full remission versus (1) characteristic residues in the narrower sense; (2) total unemployment, or (3) surging or simple courses to mixed residues or to typical schizophrenic defect psychoses). Accordingly, sufficiently reliable assertions applied only to a minority of about 1/3 of patients, whereas for the majority of 2/3, no generalizable prognostication was possible (67-71% true-positive predictions on 36-63% of total population in extreme states). By contrast, our analyses have clearly uncovered a fundamental problem of investigations into the long-term prognosis of schizophrenia: the extreme dependence of results on the clinical definition of end states. The further the phenomenon 'end state' is qualitatively subdivided, the poorer and less reproducible is the mutual discrimination between intermediate states and the less reliable are allocations of patients to these intermediate states by means of multivariate classifiers. Furthermore, our analyses have also demonstrated the usefulness of multivariate, adaptive procedures for investigations into the structural properties of long-term courses, so that predictions might be considerably improved if more reliable definitions of schizophrenic end states are available.
In contrast to angiography, MRI not only allows the diagnosis of DVA (developmental venous anomaly, so-called venous angioma), but also shows up cavernomas and other angiographically occult vascular malformations. It also differentiates between DVAs and occult true malformations. This has completely changed the pathological assessment of DVAs. In a retrospective study on 31 patients with angiographically proven DVAs neighbouring cavernoma was a frequent finding (15 patients, 48% group I). Symptoms caused by cavernoma were present in 6 (40%) of these 15 patients. The following associations were also found: cerebral arterial aneurysm (2), spinal arterio-venous dural fistula (1), dermal haemangioma (1), Klippel-Trénauny syndrome (1). Only 16 (52%) of the 31 cases with DVA were free of associated cavernoma (group II). Only 3 (19%) of these patients with a solitary DVA were symptomatic. In our series we have seen no case of bleeding from a DVA. A DVA is a vascular anomaly characterized, like other anomalies, by reduced resistance and limited capacity for regulation and adaptation. In rare cases this can result in haemodynamic disturbances, thrombosis and ischaemia. Wall rupture with bleeding does not occur in DVA. It must be assumed that bleeding reported in patients with DVAs before the availability of MRI resulted from an associated true vascular malformation in most cases.
Clinical presentation of a child with port-wine stain and seizures leads to the suspicion of Sturge-Weber disease (SWD). This diagnosis can be confirmed by the detection of a meningeal angiomatosis. In rare cases, early detection of meningeal pathology by ultrasound has been reported. Key findings are brain atrophy, gyriform cortical calcifications demonstrated by skull radiographs after the first year of life or earlier by cranial CT, and dys- or aplasia of the deep cerebral veins on angiography. Radionuclide imaging shows focal or diffuse tracer accumulation over the affected brain regions. MR demonstrates an abnormal appearance of the affected meninges, especially thickening and pathologically increased signal intensity after Gd-DTPA application. This, in association with the demonstration of abnormal enhancement in deep medullary veins, is the most characteristic finding. Contrast-enhanced MR allows early and non-invasive diagnosis of SWD, mainly by revealing leptomeningeal angiomatosis and abnormal venous vessels.
Radionuclide cisternography is indicated in the clinical work-up for hydrocephalus, when searching for CSF leaks, and when testing whether or not intracranial cystic lesions are communicating with the adjacent subarachnoid space. This paper demonstrates the feasibility and diagnostic value of SPECT and subsequent 3D surface rendering in addition to conventional rectilinear CSF imaging in eight patients. Planar images allowed the evaluation of CSF circulation and the detection of CSF fistula. They were advantageous in examinations 48 h after application of 111In-DTPA. SPECT scans, generated 4-24 h after tracer application, were superior in the delineation of basal cisterns, especially in early scans; this was helpful in patients with pooling due to CSF fistula and in cystic lesions near the skull base. A major drawback was the limited image quality of delayed scans, when the SPECT data were degraded by a low count rate. 3D surface rendering was easily feasible from SPECT data and yielded high quality images. The presentation of the spatial distribution of nuclide-contaminated CSF proved especially helpful in the area of the basal cisterns.
In this review the traditional concepts of endogenous depression and modern trials of classification in operationalized diagnostic systems, especially in DSM and ICD, are critically discussed. The psychopathological and other phenomenological symptomatologies of endogenous (cyclothymic) depression within monopolar and bipolar affective psychoses and the diagnosis and differential diagnosis above all against schizophrenia, organic brain diseases and psychoreactive disorders, are described. The possibilities and limitations of operationalized classifications with regard to diagnostic reliability and validity are presented. At present state of research homogeneous groups of patients with regard to affective and other idiopathic psychoses and here depressive syndromes and episodes cannot be defined, neither with the traditional concepts nor with the up to now available operationalized diagnostic classifications. In contemporary operationalized diagnostic systems among others the psychopathological and other phenomenological criteria are not sufficiently or too vaguely defined, the different significance of the requested inclusion-criteria and the intraindividual variability with regard to single episodes and subsequent phases of the depression are too little considered. Up to now all trials failed to validate different diagnostic concepts of depression by biological markers. Clinical psychopathological diagnosis of endogenous depression according to the traditional psychiatry criteria may reach a better validity under certain conditions than diagnoses according to DSM-III-R or ICD 10. To use exclusively operationalized diagnostic systems instead of clinical diagnosis in the diagnostic practice but also in research would be too early at present. Modern diagnostic systems can complete the clinical diagnosis but not replace it.
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The efficacy of gentamicin given intravenously once daily in a single, individually-adapted dose in form of a short infusion was confirmed in 30 patients with febrile urogenitary infections, taking nephrotoxicity into consideration. Antibiotic therapy was given for 7 days in each case, the individual dose of gentamicin being chosen from the dosage schedule according to Mawer. Depending on weight, age and renal function we used daily doses ranging from 160 to 480 mg (i.e. 2 to 5 mg/kg) of gentamicin. All patients were cured and all gram-negative bacteria were eliminated; no nephrotoxicity was recorded, as verified by constantly low serum levels of gentamicin (below the recommended peak level of 2 micrograms/ml) and non-significant changes in serum creatinine level. According to our results and to the findings of other investigations cited in the literature we conclude that in gentamicin therapy the once-daily individually--adapted intravenous dosage regimen is superior to to continuous administration by means of repeated daily doses with regard to efficacy and absence of nephrotoxicity.