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Biomedical subjects

M König

Publications and source records attributed to M König.

At least 19 recordsLinked to original sources
PubMed1999

[Residues of antibiotics and chemotherapeutics in meat].

Antibiotics and chemotherapeutics in food may only be present in concentrations below a toxicologically approved level. To check the established limits laboratories depend on reliable methods: on the one hand rapid and inexpensive screening tests (biological and immunological methods), on the other hand rather costly but very specific chemical-analytical reference methods. The results of residue testing in a big slaughter plant are presented. Residues of antibiotics were mainly found in calves. The most frequently detected drugs were tetracyclines, sulfonamides and aminoglycosides.

Abattoirs↗
PubMed1998

Membrane-anchored incorporation of a foreign protein in recombinant influenza virions.

The RNA polymerase I system for in vivo synthesis of recombinant influenza vRNA molecules was used for the expression of a chimeric protein, consisting of the 341-amino-acid ectodomain of the glycoprotein E2 of classical swine fever virus and the 37-amino-acid C-terminal membrane anchor of the influenza virus hemagglutinin (HA). During infection with an influenza A helper virus the amplified pseudo-viral RNA was packaged into progeny virions together with influenza vRNA segments. The foreign fusion protein E2-HA was shown to be physically incorporated into the viral envelope. Incorporation of a third major glycoprotein into the envelope did not affect biological functions of HA and neuraminidase that are required for the generation of infectious virus particles. Based on mutational analyses of the cytoplasmic tail of E2-HA fusion proteins three modes of interaction during virus budding have been observed: nonspecific low-level incorporation (truncated tails), specific full-level incorporation (wild-type amino acid sequence or minor variations of it), and exclusion from incorporation (elongated tails).

Amino Acid Sequence↗
PubMed1998

Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene.

The tachykinin neuropeptides, substance P and substance K, are produced in nociceptive primary sensory neurons and in many brain regions involved in pain signaling. However, the precise role and importance of these neuropeptides in pain responses has been debated. We now show that mice that cannot produce these peptides display no significant pain responses following formalin injection and have an increased pain threshold in the hotplate test. On the other hand, the mutant mice react normally in the tail flick assay and acetic acid-induced writhing tests. These results demonstrate that substance P and/or substance K have essential functions in specific responses to pain.

Acetic Acid↗
PubMed1998

Synthesis and biodistribution of a short nonionic oligonucleotide analogue in mouse with a potential to mimic peptides.

A nonionic RNA analogue of the sequence r(USO2GSO2ASO2C) has been synthesized where each bridging phosphate diester is replaced by a dimethylene sulfone unit (rSNA). The rSNA was synthesized in solution from 3',5'-bishomo-beta-ribonucleoside derivatives as building blocks. Full experimental procedures are provided, and the product and all synthetic intermediates are fully characterized. The tetramer is nonionic but highly dipolar due to multiple hydrogen bonding opportunities. It is freely soluble in water only at higher pH's, permitting it to be radiolabeled by exchange of the acidic protons alpha to the sulfones with tritiated water. The tritiated molecule was administered intravenously into the tail vein (2.6 mg/kg) of mice, and its distribution was monitored over 48 h. The rSNA was widely distributed in the biological tissues, including the brain, and excreted in both the feces and the urine. The accumulation of radioactivity was significantly higher in liver and kidney than in other tissues. Radiolabel was recovered from the urine, analyzed by HPLC, and shown to be intact oligonucleotide sulfone. This is the first bioavailability study on a short nonionic oligonucleotide analogue, a class of molecules with potential biomedical applications.

Animals↗
PubMed1998

An experimental evaluation of effects and side effects of asymmetric face-bows in the light of in vivo measurements of initial tooth movements.

By using a magnetic sensing system, the translational and rotational molar movements under the application of various asymmetric face-bows were measured two-dimensionally in human subjects to evaluate their primary effects and side effects. The asymmetric face-bow designs tested were three types of power arm face-bows, swivel offset face-bow, and internal hinge face-bow. Although all face-bow designs were considered to be effective in achieving asymmetric distalizations of the molars, they generated lateral displacements that may lead to an undesirable crossbite. The swivel offset face-bow may produce unexpected results and its fabrication is complicated. The internal hinge face-bow is remarkably effective for asymmetric molar distalizations. Unfortunately, it causes a strong crossbite tendency on the molar to be more distalized. Therefore the use of the power arm face-bow is thought to be relatively recommendable because it showed an acceptable asymmetric effect and is easily fabricated from a commercially available face-bow. It is concluded that all asymmetric face-bows generate lateral forces as side effects as long as the force delivery system with a combination of an asymmetric face-bow and a neck strap or head cap is applied. The current study suggests a method whereby the side effect of asymmetric face-bows can be eliminated.

Adult↗
PubMed1998

Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer.

Single-agent therapy with paclitaxel is effective against both squamous cell carcinoma and adenocarcinoma of the oesophagus. However, only limited data are available on the combination of paclitaxel with other cytotoxic drugs in this entity. Patients with unresectable stage III, recurrent or metastatic tumours were treated in a multicentre setting with paclitaxel 90 mg m(-2) given over 3 h intravenously, followed by cisplatin 50 mg m(-2). The courses were repeated every 14 days. Twenty patients with squamous cell carcinoma or adenocarcinoma of the oesophagus were evaluable for response. The overall remission rate was 40% (8/20), including 15% (3/20) clinically complete responses. Clinical benefit response, defined as relief of dysphagia and/or significant gain in weight, was achieved in 70% of the patients. Neutropenia of CTC grade 3 occurred only in 10% of the patients; no grade 4 neutropenia and no severe thrombocytopenia was encountered. CTC grade 4 neurotoxicity was seen in 5% of patients. Cisplatin/paclitaxel administered every 14 days, was effective in patients with poor prognosis oesophageal cancer and toxicity was acceptable.

Adenocarcinoma↗
PubMed1998

Infection with classical swine fever virus: effects on phenotype and immune responsiveness of porcine T lymphocytes.

T lymphocytes obtained from pigs infected with a lethal dose of classical swine fever virus were analysed for phenotypic changes in the composition of T-cell subpopulations and for alterations in their immune responsiveness in vitro during the course of disease. Viral antigen detected in all subpopulations and the selective depletion of CD4- CD8- gamma/delta T cells showed that peripheral blood T lymphocytes were affected in the terminal stage (14-19 days post-infection) of classical swine fever whereas no implications for T lymphocytes were obvious during the first 10 days after infection. Furthermore, a depletion of CD1+ CD4+ CD8+ 'common thymocytes' was characteristic for the infected animals. Studies on immune functions of peripheral T lymphocytes revealed an abrogation of cellular immune responses as early as 3-5 days after infection and thus before detection of viral antigens in these cells. The data suggest that early immunosuppression represents a crucial event for the manifestation of classical swine fever.

Animals↗
PubMed1998

Detection of viral proteins after infection of cultured hepatocytes with rabbit hemorrhagic disease virus.

The calicivirus rabbit hemorrhagic disease virus (RHDV), which replicates predominantly in the livers of infected rabbits, cannot be propagated in tissue culture. To enable the performance of in vitro studies, rabbit hepatocytes were isolated by liver perfusion and gradient centrifugation. After inoculation with purified RHDV, more than 50% of the cells proved to be infected. Protein analyses led to the detection of 13 RHDV-specific polypeptides within the infected cells. These proteins were assigned to defined regions of the viral genome, resulting in a refined model of RHDV genome organization.

Animals↗
PubMed1997

Impaired episodic memory retrieval in a case of probable psychogenic amnesia.

A patient with severe, selective retrograde amnesia for personal material diagnosed as probable psychogenic amnesia, was investigated intensively neuropsychologically with cranial computed tomography (CCT), magnetic resonance imaging (MRI), and single photon emission tomography (SPECT). The patient was of average intelligence and memory with no anterograde amnesia. No evidence for structural brain damage was detected in CCT and MRI. SPECT, performed about 3 weeks after the onset of symptoms, demonstrated reduced perfusion in right temporal and frontal areas, that is, in areas which have been suggested as critical for episodic memory retrieval. To study episodic memory retrieval, positron-emission-tomography (PET) blood flow (rCBF) measurements were performed 6 months after the onset of symptoms. During episodic memory retrieval bilateral neuronal activations were observed in the precuneus, the lateral parietal and the right dorsolateral and polar prefrontal cortex. Compared to the results of previous functional imaging studies on episodic memory retrieval, our findings suggest an underlying functional disturbance of brain areas previously demonstrated to be involved in episodic memory retrieval.

Adult↗
PubMed1997

Phylogenetic analysis of pestiviruses from domestic and wild ruminants.

Infections with pestiviruses occur in cattle, sheep, pigs and also in numerous other ungulate species. In the present study, pestiviruses from goat, buffalo, deer and giraffe were analysed at the molecular level; unusual strains from cattle and pigs were also included. A phylogenetic analysis of the respective pestiviruses was undertaken on the basis of a fragment from the 5' noncoding region as well as the gene encoding autoprotease Npro. Statistical analyses of the respective phylogenetic trees-based on the 5' NCR revealed low confidence levels for most of the branches, while the structure of the tree based on the Npro gene was supported by high bootstrap values. Accordingly, the isolates from goat, buffalo and deer can be grouped together with bovine viral diarrhoea virus (pestivirus type 1); within this genotype three subgroups and one disparate virus have been identified. One isolate from pig and one from cattle belong to the group of 'true' border disease virus (pestivirus type 3), which can be further subdivided into two major subgroups. Interestingly, the giraffe isolate does not belong to one of the four established pestivirus genotypes. The phylogenetic analysis strongly suggests that genotype 1 pestiviruses occur world-wide in many ruminant species. Furthermore, phylogenetic trees based on the Npro gene nucleotide sequences show that the respective sequences do not segregate into discrete lineages based on host-species origin.

Amino Acid Sequence↗
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↗