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Biomedical subjects

M Korn

Publications and source records attributed to M Korn.

At least 19 recordsLinked to original sources

GTP-binding proteins in adrenocortical mitochondria.

We have identified two GTP-binding proteins in mitochondria from bovine adrenal cortex (fasciculata). Sub-mitochondrial particles were fractionated into inner membrane, contact point and outer membrane vesicles on sucrose density gradients. These sub-mitochondrial fractions were identified by the presence of enzyme markers and electron microscopy. Photoaffinity labelling with [gamma-32P]GTP identified a 45 kDa GTP-binding protein in outer mitochondrial membranes and a 19 kDa protein in the contact points. The molecular weight of 45 kDa and requirement for Mg2+ ions raise the possibility that this protein is an alpha subunit of a heterotrimeric GTP-binding protein or a novel GTP-binding protein. The specificity of nucleotide binding, the requirement for low concentrations of Mg2+ (0.1 mM) and molecular weight of 19 kDa suggest that this protein is a typical member of the so-called small GTP-binding protein family. The location of 45 kDa in the outer membrane and that of 19 kDa in the contact points suggest roles for these proteins in the interaction with the extramitochondrial environment and in the regulation of mitochondrial membranes, respectively.

Adrenal Cortex

[Differential diagnosis of round opacities after lung transplantation].

Incidence, aetiology, diagnosis and treatment of round lesions in the lungs were analysed in 64 patients after lung transplantation (33 men, 31 women; mean age 45 [21-68] years; postoperative survival > 2 weeks). These lesions were found in 8 patients 1-10 months (median of 5.8 months) after the transplantation, singly in two, multiple in six. In six patients it was an incidental finding, further elucidated by computed tomography or fine-needle biopsy. The aetiology varied from B-cell "lymphoma" (posttransplant lymphoproliferative disorder-PTLD) in three patients, aspergilloma in two, and bacterial abscess in one. Two patients died of septicaemia (Aspergillus; Pseudomonas aeruginosa/Staphylococcus aureus), while four had a full remission. The solitary lesions disappeared without specific treatment in 2-3 weeks. If round lesions are noted after lung transplantation, rapid histological and microbiological diagnosis and aggressive treatment are necessary to combat an otherwise high death-rate. PTLD and infection (bacterial or mycotic) are the most frequent causes.

Adult

Styrene-7,8-oxide in blood of workers exposed to styrene.

A field study was carried out on 13 workers exposed to styrene vapors at time-weighted average concentrations between 10 and 73 ppm. The reactive intermediate styrene-7,8-oxide was determined in blood samples using a direct gas chromatographic method. Styrene-7,8-oxide concentrations were in the range between 0.9 and 4.1 micrograms/l blood. Linear correlations were found between styrene-7,8-oxide in blood and styrene in ambient air and blood. For an exposure concentration of 20 ppm styrene (German MAK value) a steady-state level of about 1 microgram styrene-7,8-oxide/l blood was calculated.

Adult

The composition of the intracellular domains of the B cell antigen receptor complex studied from the cytoplasmic side of the membrane.

Immunoglobulins of the classes M and D function as antigen receptors on B lymphocytes. They are linked to other proteins to form B cell antigen receptor (BCR) complexes which transduce the signal triggered by the binding of antigen. In order to study the components that interact with BCR complexes in the cell it is essential that they are accessible to biochemical studies. Therefore, we have developed a simple and rapid method that allows the purification and labelling of B lymphocyte plasma membranes. For this, B cells are attached to polyacrylamide beads. Upon disruption of the cells, bead-bound membranes are obtained which expose the cytoplasmic side into the medium. The membrane proteins can then be radioiodinated and eluted with detergents. The combination of the improved methods for the preparation of bead-attached membrane patches and radiolabelling of the proteins has allowed for the first time an investigation into the cytoplasmic side of the BCR complex. All the subunits that had been previously described could be detected in 2D autoradiographs. Furthermore, it could be shown that the protein Ig-beta, which is part of an Ig-associated heterodimer, is predominantly labelled at the extracellular domain. The second component, Ig-alpha, is labelled to a higher degree at its intracellular domain. In addition, further proteins could be detected exclusively at the cytoplasmic side of the membrane. Results from 2D autoradiographs show that they may form heterodimers. These proteins are candidates for the interaction of BCR complexes with further members of the signalling cascade, such as protein tyrosine kinases and/or G proteins.

Animals

Calcium/calmodulin induces phosphorylation of vimentin and myosin light chain and cell rounding in cultured adrenal cells.

In previous reports on adrenal cells we have shown that calcium/calmodulin regulates cholesterol transport to mitochondria and induces phosphorylation of cytoskeleton homogenates. In this study, we have used bovine fasciculata cells permeabilized in situ to identify the phosphorylated proteins and to investigate the manner in which the cytoskeleton components may act together in any subsequent reorganization of the cell. The main cytoskeletal proteins namely vimentin, tubulin, actin, and the associated protein myosin light chain were identified on polyacrylamide gel electrophoresis by their molecular weights and by Western blotting using affinity-purified monoclonal antibodies. In permeabilized cells, calcium/calmodulin promoted phosphorylation of vimentin and myosin light chain within the first 10 min. When incubation time was extended in the presence of 1 mM non-radiolabeled ATP, cell contraction was seen after 15 min. Immunofluorescent microscopy showed that actin microfilaments and myosin light chain displayed a similar pattern of distribution which indicates the actomyosin. Electron microscopy revealed the actomyosin as a dense ring around the cell beneath the plasma membrane. Intermediate filaments (10 nm) were seen within this ring which gave rise to a mixed network in which microfilaments appeared to interconnect intermediate filaments. Immunogold electron microscopy revealed that the 10-nm filaments, found within the actomyosin ring, are vimentin intermediate filaments. It is proposed that calcium/calmodulin causes phosphorylation of the myosin light chain which triggers contraction, and this process involves the intermediate filament protein vimentin. The redistribution of the cytoskeleton and hence the cell rounding is due, in part to the interconnection between vimentin intermediate filaments and actin microfilaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

CD45-deficient RBL-2H3 cells. Cellular response to Fc epsilon R- and ionophore-induced stimulation.

The CD45 protein is a transmembrane tyrosine phosphatase that is required for normal T and B cell receptor-mediated signaling. In order to study the function of this phosphatase in mast cells, we have isolated a CD45-deficient variant from the rat basophilic leukemia cell line (RBL-2H3), a tumor analog of mucosal mast cells. The secretory response as well as the inositol 1,4,5-triphosphate (InsP3) formation to Fc epsilon RI and ionophore stimuli were similar in the RBL-2H3 cell line and its derived CD45-deficient subpopulation. However, pretreatment with the phorbol ester TPA, which directly activates protein kinase C (PKC), caused a marked increase in mediator release and InsP3 production in the CD45-deficient variant compared to the parental RBL-2H3 cells. These findings suggest that CD45 might directly or indirectly modify the activity of PKC or the InsP3-dephosphorylating phosphatase.

Animals

[Imaging procedures in varicosities].

A prospective study was performed to compare the diagnostic potential of color-coded duplex sonography (CCDS) and that of ascending pressure phlebography (APP) in 61 patients before venous stripping. Varicosis of the long saphenous vein was correctly diagnosed and graded by CCDS in 87% of cases, and varicosis of the short saphenous vein in 97%. CCDS was inaccurate in 3 of 4 cases of recurrent varicosis of the long saphenous vein. Anterior femoral cutaneous varicosis (n = 3), mild postthrombotic syndrome (n = 1) and variant venous anatomy (n = 1) were not diagnosed on CCDS. One Baker cyst was diagnosed by CCDS. In the assessment of venous reflux CCDS seems to be superior to APP. Our results suggest that CCDS is a valuable diagnostic tool for routine imaging before venous stripping. However, patients with ambiguous or inconclusive CCDS results (eg. recurrent varicosis, venous variants) should be examined by APP.

Adult

Stereometabolism of ethylbenzene in man: gas chromatographic determination of urinary excreted mandelic acid enantiomers and phenylglyoxylic acid and their relation to the height of occupational exposure.

Ethylbenzene is an important industrial solvent and a key substance in styrene production. Ethylbenzene metabolism leads to the formation of mandelic acid, which occurs in two enantiomeric forms, and phenylglyoxylic acid. To decide which enantiomer is preferably formed, 70 urine samples of exposed workers were taken at the end of shifts and--after 3-pentyl ester derivatisation--gas chromatographically analysed. The R/S ratio of mandelic acid enantiomers in urine amounts to 19:1, which means that R-mandelic acid is a major metabolite and S-mandelic acid is one of the minor urinary metabolites of ethylbenzene in man. The R/S ratio is independent of ambient air concentration of ethylbenzene within the investigated range. Compared to an ethylbenzene monoexposure the height of total mandelic acid excretion is decreased in the case of coexposure to other aromatic solvents.

Benzene Derivatives

Serotonin receptor sensitivity and aggression.

This study investigated the relationship between increased serotonin (5-hydroxytryptamine, 5HT) receptor sensitivity and human aggression. A low oral dose of meta-chlorophenylpiperazine (MCPP), a postsynaptic 5HT receptor agonist, was administered in a placebo-controlled design to depressed (n = 22) and panic disorder (n = 20) patients classified with or without signs of outwardly directed aggression, patients with a history of suicide attempts (inwardly directed aggression) (n = 11), and normal controls (n = 19). Hormones under 5HT control were measured at 30-min intervals. Results were as follows: (1) MCPP did not induce or reduce anger, (2) patients with outwardly directed aggression did not have significantly greater MCPP-induced cortisol or prolactin release than did patients without signs of outwardly directed aggression, (3) patients with a history of suicide attempts did not have significantly greater MCPP-induced cortisol or prolactin release than did normal controls, and (4) MCPP-induced hormone release was unrelated to measures of aggression.

Adult

[Sonographic detection of gas in the vascular system of the liver: an image essay].

Gas within the vascular system of the liver was demonstrated sonographically in 5 patients. In contrast, plain films of the abdomen in these patients failed to demonstrate this serious finding. 3 patients presented with gas within the hepatic portal venous system, 1 patient with gas in the liver veins. In these patients, gas formation was probably caused by sepsis with gas-producing bacteria. In the last patient, air within the hepatic arterial system was caused by insufflation of air thru a port-a-cath catheter located in the main hepatic artery. The characteristic sonographic appearance of intravascular gas are highly echogenic particles flowing within the vessels. Different pathophysiologic mechanisms of gas formation in the hepatic portal venous system include sepsis with gas forming organisms, gastrointestinal necrosis of various origin in combination with elevation of intramural pressure and alteration of gas solubility of blood. The significance of sonography as a very sensitive and specific modality is outlined.

Adult

[The percutaneous ultrasonic-guided fluoroscopy-controlled drainage of pericardial fluids].

The results of 25 ultrasonographically guided percutaneous pericardial drainage procedures and of one pericardiocentesis performed in 25 patients with pericardial fluid collections are reported. After initial puncture of the pericardial cavity under sonographic guidance, dilatation and placement of 5F to 8.3F catheters in Seldinger technique was controlled fluoroscopically in 22 procedures. Clinical indications were emergency treatment of tamponade (n = 6) or urgent treatment of large (n = 14) pericardial effusions. The remaining 6 procedures were performed to establish specific diagnoses of small effusions. Puncture sites were subxiphoid in 23 and left parasternal in 3 cases. The volume of aspirated fluid ranged from 20 to 1710 ml (median: 615 ml). Median duration of pericardial drainage was 3 days (range less than 1 day to 21 days). A specific diagnosis was obtained in 48% of patients. 4 patients had subsequent elective surgical intervention for recurrent effusion or for pericardial biopsy. Three minor complications included one vasovagal reaction and two asymptomatic pneumothoraces. Percutaneous ultrasonically guided and fluoroscopically controlled placement of a pericardial catheter is safe and effective for treatment and diagnosis of pericardial effusions.

Adolescent

Interrelationships among anxiety, aggression, impulsivity, and mood: a serotonergically linked cluster?

Serotonin abnormalities appear to be related to a variety of psychopathological dimensions such as anxiety, depressed mood, impulsivity, and aggression dysregulation. We hypothesized that the psychopathological dimensions related to serotonin would be significantly intercorrelated since they seem to have a common biological basis. Sixty psychiatric inpatients were examined on a series of psychometric tests measuring suicidality, violence potential, impulsivity, depressive mood, and anxiety. The scores on all of these measures tended to be significantly correlated with one another. These findings support the additional hypothesis that biological markers may be more closely related to basic psychological dimensions than to nosological categories.

Adult

Nosological tunnel vision in biological psychiatry. A plea for a functional psychopathology.

Classical nosology has been the major cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, one we have designated as "functional," seems possible, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. We have pursued this route for many years, and based on the resulting findings we formulated the following hypothesis. Signs of diminished dopamine, serotonine, and noradrenaline metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions; i.e., hypoactivity/inertia; increased aggression/anxiety and anhedonia, independent of the nosological framework in which these dysfunctions occur (van Praag et al. 1990). In this paper only the 5-HT data have been discussed. Implications of the functional approach for psychiatry are discussed, including a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-oriented and therefore inevitably geared towards utilizing drug combinations. This prospect is hailed as progress, both practically and scientifically.

5-Hydroxytryptophan

Monoamines and abnormal behaviour. A multi-aminergic perspective.

Classical nosology has been the cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, designated as 'functional', is advanced here, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. Signs of diminished DA, 5-HT and NA metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions (hypoactivity/inertia, increased aggression/anxiety, and anhedonia) independent of the nosological framework in which these dysfunctions occur. Implications of the functional approach for psychiatry include a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-orientated and therefore geared towards utilising drug combinations. This prospect is hailed as progress, both practically and scientifically.

Arousal

[A posttraumatic pseudoaneurysm of the hepatic artery. Duplex sonographic diagnosis and follow-up in spontaneous thrombosis].

Guided percutaneous biopsy represents a standard procedure in establishing specific diagnosis of focal liver lesions. We report a case of left hepatic artery pseudoaneurysm diagnosed by means of Duplex Doppler sonography (DS) immediately before percutaneous biopsy should be performed. Selective hepatic artery embolization was planned, but spontaneous thrombosis of the pseudoaneurysm was documented by DS and angiography, respectively. DS is able to identify the vascular nature of a lesion and is helpful to avoid puncture of an aneurysm.

Abdominal Injuries

[Surgical masks--effective protection against cytostatic aerosols?].

A surgical mask, a coarse-dust mask and five types of fine-dust masks were tested by enhanced light microscopy and cross-sectional thickness measurements for their effectiveness against inhalation of cytostatic aerosols. The construction of surgical masks most nearly resembles that of coarse-dust masks with respect to quality and number of layers. They are thus not suitable as protection against inhalation of cytostatic aerosols. Such masks must be at least particle-filtering half-masks of type DIN 58645 FHM - P2 (fine-dust masks of protective stage P2).

Aerosols