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Biomedical subjects

M König

Publications and source records attributed to M König.

At least 19 recordsLinked to original sources
PubMed1996

Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin.

Enkephalins are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein. They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance. Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the pre-proenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk-/- animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk-/- genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk-/- mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain.

Aggression↗
PubMed1996

Positron emission tomography helps to diagnose tumor emboli and residual disease in choriocarcinoma.

BACKGROUND: Positron emission tomography (PET) has been shown capable of identifying malignant tissues. PATIENTS AND METHODS: WB-PET imaging in two women with metastatic choriocarcinoma is described. RESULTS: In a woman with tumor emboli secondary to a choriocarcinoma, WB-PET was the only noninvasive investigation to differentiate between tumor and blood clots. Moreover, PET helped to localize residual tumor tissue in another woman with persisting high beta-HCG serum levels after chemotherapy. CONCLUSIONS: WB-PET helps to localize tumor tissue in patients suffering from choriocarcinoma.

Adult↗
PubMed1996

A novel technique for identification of doppler microembolic signals based on the coincidence method: in vitro and in vivo evaluation.

BACKGROUND AND PURPOSE: The applicability of a novel differentiation technique in embolus detection based on the coincidence principle and using a multigate probe was evaluated in this study. METHODS: According to the coincidence method, high-intensity transients should only be classified as microembolic signals if they appear sequentially in the two sample volumes monitored and within a defined time window calculated from the blood velocity and the spatial distance between the insonation depths. Part A: microbubbles were introduced in a continuous flow bench model of the middle cerebral artery to evaluate the accuracy of the multigate probe in embolus detection. Part B: in the subjects and patients, the minimal and maximum time delays in the appearance of microembolic signals in the two middle cerebral artery sample volumes were calculated as 0.01 second and set at 0.1 second, respectively. The multigate probe was used to monitor (1) 5 normal volunteers in whom 1008 artifact signals were produced,(2) 2 patients undergoing aortic valve replacement surgery, and (3) 12 patients with potential cardiac or carotid embolic sources. RESULTS: In the bench model, 95.5% of microembolic signals produced by microbubbles appeared in the two sample volumes with a time delay between 0.02 and 0.05 second, while in the remaining 4.5% a shorter passage time of 0.01 second was measured. A total of 1968 high-intensity signals were recorded in subjects and patients. All but 20 of these (99%) appeared in both monitoring channels within the above time frame. To summarize, 996 (98.8%) of the 1004 artifact signals and 943 (98.1%) of the 961 microembolic signals were correctly classified. CONCLUSIONS: Application of the coincidence theory to distinguish microembolic signals from artifacts provides a promising new technique with high sensitivity and specificity that could decisively improve the validity of embolus detection.

Adult↗
PubMed1995

Further characterization of border disease virus isolates: evidence for the presence of more than three species within the genus pestivirus.

The molecular analysis of three ovine pestivirus strains revealed the existence of two distinct groups of sheep-derived pestiviruses, namely "true" border disease virus strains (BDV) and bovine viral diarrhea virus (BVDV)-like strains. As an extension of these studies RT-PCR and nucleotide sequencing of the autoprotease (Npro) and nucleocapsid protein (C) encoding regions of additional serologically defined ovine pestivirus strains were performed. A comparison of Npro and C revealed that three ovine isolates belong to the group of true BDV while two were clearly different from these as well as from BVDV and CSFV. The amino acid identity between the latter two ovine strains is 85% for Npro and 92% for C and thus similar to values found within the three pestivirus species defined so far. In order to allow comparison with additional pestiviruses the nucleotide sequences of a part of the 5' noncoding region were determined for the ovine pestivirus strains. The comparative analysis showed that recently described BVDV strains associated with acute lethal infection were very similar to two ovine isolates. The latter represent a fourth group within the genus pestivirus different from the so far defined pestivirus species BVDV, true BDV, and CSFV. The data lead to the question whether the current nomenclature of pestivirus species according to the host origin and the induced diseases is still appropriate.

Amino Acid Sequence↗
PubMed1995

Cold acclimation and endurance training in guinea pigs: changes in lung, muscle and brown fat tissue.

The effects of an intermittent high intensity stimulus (running) or a chronic low intensity stimulus (cold acclimation) of oxidative metabolism on maximal oxygen uptake (VO2,max), lung O2 diffusing capacity (DLO2) and skeletal muscle as well as fat tissue mitochondrial content in growing guinea pigs are described. Young male guinea pigs were assigned to three experimental groups (n = 5): control (C), endurance trained (T; at 70% VO2max) or cold acclimated (CA; 5-7 degrees C) for six weeks. Animals were sacrificed at the end of the experimental period and tissue for morphometric analysis of the lung, muscle and interscapular fat was sampled. T and CA animals significantly increased weight specific VO2max by 23% and 29%, respectively. Despite a significant increase in absolute lung volume in T (+10%) and in weight specific lung volume in CA (+20%) neither absolute nor weight specific DLO2 was significantly affected by the experimental treatments. In trained animals the total volume of mitochondria remained unchanged in samples representative for the entire musculature but was significantly increased in M. vastus intermedius (+72%). Intramyocellular lipids increased significantly both in M. vastus intermedius (+244%) as well as in the whole body musculature (+164%). Cold acclimation increased the mitochondrial content of the interscapular fat pad by approximately 20-fold but had no effect on total mitochondrial volume in muscle. We conclude that the increase in oxygen demand resulting from exercise training or from cold acclimation could be accomodated by the existing lung diffusing capacity and did not induce a global change of oxidative capacity in skeletal muscle tissue in growing guinea pigs. Exercise training caused oxidative capacity to increase only in a locomotor muscle activated during running whereas cold acclimation greatly increased interscapular fat tissue oxidative capacity.

Acclimatization↗
PubMed1995

2D and 3D CT reconstructions of the facial skeleton: an unnecessary option or a diagnostic pearl?

The introduction of spiral computed tomography (CT) has been a major advance in CT scanning, particularly considering the reduction in acquisition time and improvements in 2-dimensional (2D) and 3D reconstructions. 314 out of 1262 CT examinations of the midface and jaws executed from September 1993 to September 1994 were performed in the spiral mode. Our experience is critically reviewed and a guideline for the use of spiral CT scanning of the midface and jaws for various diagnostic purposes is established: Complex midface fractures require axial spiral CT scanning with secondary coronal reconstructions Because of the long processing time 3D reconstructions are reserved for planning surgical repair of craniofacial malformations. Dental CT scans with calculation of panoramic images provide important information prior to dental implant surgery and repair of alveolar clefts.

Computer Simulation↗
PubMed1995

Classical swine fever virus-specific cytotoxic T lymphocytes and identification of a T cell epitope.

Classical swine fever virus (CSFV)-specific cytotoxic T lymphocytes (CTL) were derived from peripheral blood mononuclear leukocytes of immunized NIH-minipigs (MHC d/d haplotype) after in vitro restimulation with infectious CSFV. Their cytotoxic activity was determined against CSFV-infected target cells obtained from simian virus 40 (SV40) large T antigen-transfected immortalized kidney cells of a syngeneic miniature swine. Experiments with separated effector cell populations revealed that the CSFV-specific cytotoxic activity was mediated by CD4(-)CD6+CD8+ MHC class I-restricted T lymphocytes. Infection of target cells with various vaccinia virus/CSFV recombinants led to the identification of a major antigenic site for CSFV-specific CTL near the cleavage site between the non-structural proteins p80 (NS3) and p10 (NS4a). Using synthetic overlapping nonapeptides which covered this protein region the sequence ENALLVALF is the first sequence to be identified as an MHC class I-restricted T cell epitope recognized by CSFV-specific CTL.

Amino Acid Sequence↗
PubMed1995

Classical swine fever virus: independent induction of protective immunity by two structural glycoproteins.

To study which proteins of classical swine fever virus (CSFV) are able to confer protective immunity in swine, N-terminal autoprotease, viral core protein, and the three structural glycoproteins were expressed via vaccinia virus recombinants (VVR). CSFV proteins synthesized in cells infected with VVR showed migration characteristics on sodium dodecyl sulfate gels identical to those of their respective CSFV counterparts. Apparently authentic dimerization of the recombinant glycoproteins was observed. The glycoproteins E0 and E2 were detected on the surfaces of VVR-infected cells. In protection experiments, swine were immunized with the different VVR, and the generation of humoral immune response was monitored. Only animals vaccinated with VVR expressing E0 and/or E2 resisted a lethal challenge infection with CSFV. Glycoprotein E0 represents a second determinant for the induction of protective immunity against classical swine fever.

Animals↗
PubMed1995

Aura alphavirus subgenomic RNA is packaged into virions of two sizes.

The alphavirus genome is 11.8 kb in size. During infection, a 4.2-kb subgenomic RNA is also produced. Most alphaviruses package only the genomic RNA into virions, which are enveloped particles with icosahedral symmetry, having a triangulation number (T) = 4. Aura virus, however, packages both the genomic RNA and the subgenomic RNA into virions. The genomic RNA is primarily packaged into a virion that has a diameter of 72 nm and which appears to be identical to the virions produced by other alphaviruses. The subgenomic RNA is packaged into two major, regular particles with diameters of 72 and 62 nm. The 72-nm-diameter particle appears to be identical in construction to virions containing genomic RNA. The 62-nm-diameter particle probably has T = 3. The large and small Aura virions can be partially separated in sucrose gradients. In addition to these two major classes of particles, there are other particles produced that appear to arise from abortive assembly. From these results and from previous studies of alphavirus assembly, we suggest that during assembly of alphavirus nucleocapsids in the infected cell there is a specific initiation event followed by recruitment of additional capsid subunits into the complex, that the triangulation number of the complex is not predetermined but depends upon the size of the RNA and interactions that occur during assembly, and that budding of assembled nucleocapsids results in the acquisition of an envelope containing glycoproteins arranged in a manner determined by the nucleocapsid.

Alphavirus↗
PubMed1995

Variability of Doppler microembolic signal counts in patients with prosthetic cardiac valves.

BACKGROUND AND PURPOSE: The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. METHODS: From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. RESULTS: No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). CONCLUSIONS: The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart.

Cerebral Arteries↗
PubMed1994

Ellagitannins and complex tannins from Quercus petraea bark.

The ellagitannins 2,3-(S)-hexahydroxydiphenoyl-glucose, pedunculagin, vescalagin, and castalagin; the flavanoellagitannins acutissimin A, acutissimin B, eugenigrandin A, guajavin B, and stenophyllanin C; and the procyanidinoellagitannin mongolicanin have been isolated from the bark of Quercus petraea. The ellagitannin fraction had a weak antisecretory effect.

Anthelmintics↗
PubMed1994

[High resolution computerized tomography of the temporal bone in mandibulofacial dysostosis].

High resolution CT (HR-CT) scanning of the temporal bone was performed in three patients with a fully expressed mandibulofacial dysostosis for preoperative assessment of temporal bone abnormalities. The external auditory canal was absent in five of six ears. Scans revealed a dysplastic middle ear cleft with dysplastic and partly dislocated ossicles. The ossicles were absent in two temporal bones. In no patient was the mastoid bone pneumatised. The inner ear was affected in only one patient in whom a shortening of the lateral semicircular canal could be found bilaterally. The role of HR-CT of the temporal bone as a preoperative diagnostic tool for the assessment of abnormalities of surgical import is discussed.

Adult↗
PubMed1994

Detection of trisomy 12 in chronic lymphocytic leukaemia: comparison of a polymerase chain reaction based technique with fluorescence in situ hybridization.

Trisomy 12 is the most frequent chromosomal aberration in chronic lymphocytic leukaemia (CLL) and seems to indicate a poor prognosis. To detect this abnormality we tested the applicability of the polymerase chain reaction (PCR) and compared it to the current standard fluorescence in situ hybridization (FISH). Two DNA regions containing variable numbers of tandem repeats (VNTR) located on (a) the long and (b) the short arm of chromosome 12 were chosen for PCR analysis. 8/72 patients (11%) were trisomy 12 positive compared to 16% by FISH. Chromosomal imbalances were only detected by PCR if at least 20% of the cells carried the numerical aberration.

Chromosomes, Human, Pair 12↗
PubMed1994

A paediatric Crohn's disease activity index (PCDAI). Is it useful? Study Group on Crohn's Disease in Children and Adolescents.

Since 1976, various activity indices for Crohn's disease have been developed but none has been suitable for use in the paediatric age group. Therefore, the German-Swiss Study Group on Crohn's Disease in Children and Adolescents decided to develop their own paediatric Crohn's disease activity index (PCDAI) by multiple regression analysis of prospectively collected data. The result was a simple index consisting of two clinical (appetite, number of stools/week) and four laboratory variables (erythrocyte sedimentation rate, serum iron and alpha 2-globulin concentrations and bands as percentage of white blood cells). Applying the index to patients who were followed-up, it could be demonstrated that the changes in PCDAI inversely reflected the changes in weight and that the surgical removal of the inflamed parts of the gut reduced the disease activity index to levels comparable to those obtained in patients after successful, exclusively conservative, treatment. Low disease activity was maintained for at least three years.

Adolescent↗
PubMed1993

Hypoxia of diabetic feet with abnormal arterial blood flow.

Necrotic ulcers of the feet are a dangerous complication of the diabetic foot syndrome. Besides peripheral vascular disease (PVD) peripheral neuropathy is an important factor in the pathogenesis of necroses. We examined whether the reserve of circulation during reactive hyperemia at the feet of patients with type I diabetes mellitus with abnormal blood flow (n = 17) is decreased compared with diabetic (n = 14) and nondiabetic (n = 20) controls. Further we analyzed whether there is a correlation with the oxygen supply of the foot. PVD was excluded by clinical check-up, oscillography, and Doppler ultrasound. The reserve of circulation of the foot was measured during reactive hyperemia and oxygen supply of the foot by oximetry. Abnormal blood flow of the foot was diagnosed by the pulsation index. On examination it was found that the reserve of circulation of diabetic feet with abnormal blood flow is about 52% less than in diabetic and about 50% less than in nondiabetic controls (P < or = 0.005). The decreased reserve of circulation correlates with the oxygen supply of the feet; this is about 21% less compared to diabetic feet with normal blood flow and about 16% less in comparison to nondiabetic feet. The present study shows that diabetic feet suffer from disturbed circulation although there is no evidence of PVD. This disturbed circulation is correlated with a decreased oxygen supply of the feet. Hypoxia during strain could be of great importance in the pathogenesis and treatment of necrotic ulcers of diabetic feet.

Adult↗
PubMed1993

Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity.

The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating DLO2 from morphometric data breaks the diffusion path for O2 into four steps, three of which represent the membrane part of DLO2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for DMO2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance--or mean proximity--between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of DMO2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of DLO2 by 10-20%.

Animals↗
PubMed1993

Production and characterization of monoclonal antibodies differentiating subpopulations of porcine B lymphocytes in blood and lymphoid tissues.

Monoclonal antibodies (mAbs) against various subclasses of immunoglobulin molecules are important reagents for the characterization and differentiation of serum immunoglobulins (Ig) generated during immune responses. Furthermore, Ig-specific mAbs can be powerful tools for the detection of B lymphocytes in blood and lymphoid organs. Here we describe two mAbs generated in our laboratories, named 1G6 and 2E8, which react with distinct epitopes on porcine immunoglobulin molecules. MAb 1G6 recognizes an epitope of an immunoglobulin chain with apparent molecular mass of 25 Kd. This chain represents an immunoglobulin light chain and might be the porcine equivalent of the murine and human kappa chain. MAb 2E8 is directed against porcine IgM molecules, recognizing an epitope of the porcine mu chain. The use of these mAbs was shown to avoid some common disadvantages of anti-Ig polyclonal antisera, like the high background staining of cells and tissue culture sections in immunohistochemistry. Furthermore, the use of these mAbs in two-color flow cytometry (FCM) versus a polyclonal anti-porcine Ig antiserum enables distinct B-lymphocyte subpopulations in blood and lymphoid organs to be detected. Our mAbs seem therefore to represent important and powerful reagents to identify and characterize porcine Ig isotypes and surface-Ig positive porcine B lymphocytes; their discriminating power between distinct B lymphocyte subpopulations could prove useful in different fields of both applied and fundamental immunological research.

Animals↗