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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mediators of inflammation and acute phase response in the liver.

The acute phase response is a generalized response of the organism to multiple disturbances of its physiological homeostasis. It consists of local and systemic reactions. Inflammatory processes are the main causes for the initiation of these defence mechanisms. Responsible mediators for the acute phase response are predominantly cytokines, whereby the liver is the predominant target organ. Changes in hepatocyte gene expression profiles result in dramatic changes in serum concentrations of specific plasma proteins, called acute phase proteins. IL-6 was identified as the principal mediator of this reaction. Via its cellular signal transducer gp130 IL-6 induces DNA-binding of STAT transcription factors on regulatory elements of target genes. While IL-6 dependent processes are mainly conferred to be protective other inflammatory cytokines are attributed to be cytotoxic for the liver. TNF-alpha was shown to be involved in several models of liver failure as a mediator for both cytotoxicity and cell proliferation. TNF-alpha leads via caspases to the onset of apoptosis, the so-called programmed cell death. On the other hand it activates NF-kappaB thereby triggering inflammatory processes. In this review we display the relevance for intracellular actions of both cytokines in several models of liver injury. Especially we refer to the T-cell mediated Concanavalin A induced liver failure and to liver regeneration induced by CCL4 and partial hepatectomy. Both cytokines contribute in concert to a cellular balance during these pathophysiological conditions.

Acute-Phase Reaction↗
PubMed2000

Improvement of myocardial perfusion reserve early after coronary intervention: assessment with cardiac magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to determine the potential value of magnetic resonance myocardial perfusion in the follow-up of patients after coronary intervention. BACKGROUND: In some patients a residual impairment of myocardial perfusion reserve (MPR) early after successful coronary intervention has been observed. In this study we evaluated an MPR index before and after intervention with magnetic resonance. METHODS: Thirty-five patients with single- and multivessel coronary artery disease were studied before and 24 h after intervention. The signal intensity time curves of the first pass of a gadolinium-diethylene triamine pentacetic acid bolus injected via a central vein catheter were evaluated before and after dipyridamole infusion. The upslope was determined using a linear fit. Myocardial perfusion reserve index was estimated from the alterations of the upslope. RESULTS: The MPR index in segments perfused by the stenotic artery was significantly lower than in the control segments (1.07 +/- 0.24 vs. 2.18 +/- 0.35, p < 0.001) and improved significantly after intervention (1.89 +/- 0.39, p < 0.001) but did not normalize completely (p < 0.01). After intervention the MPR index remained significantly lower in the balloon percutaneous transluminal coronary angioplasty group (1.72 +/- 0.38; n = 13) in comparison with the stent group (1.99 +/- 0.36, n = 18, p < 0.05). In the stent group a complete normalization of the MPR index was found 24 h after stenting. CONCLUSIONS: Magnetic resonance perfusion measurements allow a reliable assessment of MPR index. An improvement of MPR index can be observed after coronary intervention, which is more pronounced after stenting. Magnetic resonance perfusion measurements allow the assessment and may be useful for the follow-up of patients with coronary artery disease after coronary intervention.

Angioplasty, Balloon, Coronary↗
PubMed2000

Transoral decompression, anterior plate fixation, and posterior wire fusion for irreducible atlantoaxial kyphosis in rheumatoid arthritis.

STUDY DESIGN: Fifteen consecutive patients with irreducible atlantoaxial kyphosis caused by rheumatoid arthritis were treated by combined transoral odontoid resection, anterior plate fixation, and posterior wire fusion. OBJECTIVES: To investigate the clinical results of this new surgical procedure. SUMMARY AND BACKGROUND DATA: Irreducible atlantoaxial kyphosis in rheumatoid arthritis results from a destruction of the craniocervical joint ligaments and the anterior aspects of the lateral atlantoaxial joints. The development of a paradental synovial pannus and atlantoaxial joint impaction prevents reduction by conservative treatment, such as skull traction. Posterior surgical procedures for the treatment of the irreducible atlantoaxial kyphosis with spinal cord compression have been associated with high morbidity and mortality. METHODS: Fifteen consecutive patients were treated by transoral odontoid resection. The fixation was performed with anterior plating, according to the method of Harms in combination with posterior wire fusion according to Brooks. Before and after surgery, evaluation was performed using the parameters of pain (visual analog scale), range of motion, and subjective assessment of improvement and the Health Assessment Questionnaire. The neurologic deficit was defined according to the classifications proposed by Ranawat, Frankel, and Nurwick. Plain radiographs, including lateral flexion and extension views, and magnetic resonance scans were obtained. RESULTS: No perioperative fatality occurred. The average clinical and radiographic follow-up was 50.7 +/- 15.6 months (range, 26-77). Postoperative pain was relieved (mean pain score before surgery, 7.9 +/- 1.87; after surgery, 3.8 +/- 1.27), and the range of motion of all patients increased (mean 21.5 +/- 14.0 degrees for rotation; mean 17.2 +/- 5. 54 degrees for bending). The score on the Health Assessment Questionnaire increased in three patients, remained unchanged in three and decreased in six patients (three had died). All patients improved at least one Ranawat level after surgery, except a patient in Ranawat Class II, whose condition remained unchanged. All patients were satisfied with the procedure and reported subjective improvement. CONCLUSION: Transoral plate fixation combined with posterior wire fixation after transoral odontoid resectionis an effective, reliable, and safe procedure for the treatment of irreducible atlantoaxial kyphosis in rheumatoid arthritis.

Adult↗
PubMed2000

A major locus for myoclonus-dystonia maps to chromosome 7q in eight families.

Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.

Chromosome Mapping↗
PubMed2000

H reflex behavior in Parkinson's disease patients. Effect of stimulus duration.

Electrical stimulus, with duration starting at 0.1ms and gradually increasing to 1.0ms, was used for eliciting the H reflex in 21 normal subjects and 48 patients with Parkinson's disease (PD). In 19 normal subjects (90.5%), the threshold for sensory fibers was lower than for motor fibers, and the H reflex was obtained before the M response for all duration stimuli. In 19 PD patients (39.6%), with mild or moderate rigidity (according to the motor part of UPDRS), the threshold for the H reflex and M response was the same or the M response threshold was lower in at least one of the legs for short stimulus duration (0.1-0.2ms). In 15 PD (31.2%) patients (most of them with severe rigidity), the threshold for M response was lower for all stimulus duration, and it was obtained before the H reflex. In 14 PD (29.2%) patients, the H reflex behavior was the same as in most normal subjects in one or both legs.These very significant differences in the behavior of the H reflex in PD patients (Fisher exact test, P<0.0001) could possibly be explained by changes in agonist-antagonist inhibition, and could be used as another parameter in the clinical assessment of extrapyramidal rigidity in PD patients.

Journal Article↗
PubMed2000

Genetic variation in the B7-1 gene in patients with multiple sclerosis.

Co-stimulation of T cells by B7-1, a protein that is expressed on antigen presenting cells, favors a T helper type1 (Th1) cellular response. Th1/Th2 bias may influence disease susceptibility or course of MS. We screened the entire coding sequence as well as the 5'- and 3'-untranslated regions of the B7-1 gene using a mutation scanning technique, dideoxyfingerprinting, in DNA from 111 patients with MS from Olmsted County, Minnesota. We identified five genetic variants. None alter protein structure nor have apparent functional significance. Selected variants of sufficient frequency were tested for an association with course and severity of MS and one was tested for an association with susceptibility; none of the association tests were positive.

3' Untranslated Regions↗
PubMed2000

Expression of bcl-X(L) restores cell survival, but not proliferation off effector differentiation, in CD28-deficient T lymphocytes.

Lymphocytes deficient in the T cell costimulatory molecule CD28 exhibit defects in cell survival, clonal expansion, and differentiation into effector cells. It is known that CD28-mediated signaling results in the upregulation of the Bcl family member Bcl-X(L). To investigate the role that Bcl-X(L) plays in the various functions of CD28, we expressed Bcl-X(L) in CD28-deficient primary T lymphocytes using retrovirus-mediated gene transfer. T cells were activated in vitro and infected with Bcl-X(L) or control retroviruses; this method allows gene expression in activated, cycling cells. Expression of Bcl-X(L) in naive T cells was achieved by reconstitution of the immune system of lethally irradiated recipient mice with retrovirus-infected purified bone marrow stem cells from CD28(-/)- or wild-type donor mice. Our studies demonstrate that Bcl-X(L) prolongs the survival of CD28(-/)- T cells but does not restore normal proliferation or effector cell development. These results indicate that the various functions of CD28 can be dissociated, and provide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28.

Animals↗
PubMed2000

Impaired modulation of the saccadic contingent negative variation preceding antisaccades in schizophrenia.

BACKGROUND: The contingent negative variation (CNV) is considered to reflect prefrontal functioning and can be observed before manual and ocular motor responses. Schizophrenic patients exhibit reduced CNV amplitudes in tasks requiring manual motor responses. A number of studies has also found normal prosaccades, but delayed antisaccades and an augmented rate of erroneous prosaccades during the antisaccade task in schizophrenia. In this study we examined the CNV during pro- and antisaccade tasks in schizophrenic patients and healthy control subjects. METHODS: Data of 17 medicated schizophrenics (ICD-10, F20) and 18 control subjects, matched with patients for age, gender, and education were analyzed. Horizontal pro- and antisaccades were elicited in four blocks, each consisting of 80 trials. Electroencephalogram was recorded from 32 channels with a DC amplifier. RESULTS: Patients exhibited delayed correct responses and more erroneous prosaccades during the antisaccade task than control subjects, but normal prosaccadic reaction times. In control subjects, the vertex-predominant saccadic CNV was generally larger than in patients, and larger during the anti- than during the prosaccade task. This task-related amplitude augmentation was absent in patients. Analyses of additional components suggested specificity of impaired event-related potential modulation to the saccadic CNV. CONCLUSIONS: In accordance with the presumed prefrontal dysfunction, our results suggest deficient preparation and execution of antisaccades in schizophrenia.

Adult↗
PubMed2000

Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines.

We have directly compared the efficacy of two immunotherapeutic strategies for the treatment of cancer: "vaccination" of tumor-bearing mice with genetically modified dendritic cells (DCs), and vaccination with genetically modified tumor cells. Using several different preexisting tumor models that make use of B16F10 melanoma cells expressing a target tumor antigen (human melanoma-associated gene [MAGE]-1), we found that vaccination with bone marrow-derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model. In contrast, vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)-transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model. Further engineering of DCs to express either GM-CSF, tumor necrosis factor alpha, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model. The immunological mechanism, as shown for GM-CSF-transduced DCs, involves MAGE-1-specific CD4(+) and CD8(+) T cells. Expression of GM-CSF by DCs led to enhanced cytotoxic T lymphocyte activity, potentially mediated by increased numbers of DCs in draining lymph nodes. Our results suggest that clinical studies involving the vaccination with genetically modified DCs may be warranted.

Animals↗
PubMed2000

The DYT1 phenotype and guidelines for diagnostic testing.

OBJECTIVE: To develop diagnostic testing guidelines for the DYT1 GAG deletion in the Ashkenazi Jewish (AJ) and non-Jewish (NJ) primary torsion dystonia (PTD) populations and to determine the range of dystonic features in affected DYT1 deletion carriers. METHODS: The authors screened 267 individuals with PTD; 170 were clinically ascertained for diagnosis and treatment, 87 were affected family members ascertained for genetic studies, and 10 were clinically and genetically ascertained and included in both groups. We used published primers and PCR amplification across the critical DYT1 region to determine GAG deletion status. Features of dystonia in clinically ascertained (affected) DYT1 GAG deletion carriers and noncarriers were compared to determine a classification scheme that optimized prediction of carriers. The authors assessed the range of clinical features in the genetically ascertained (affected) DYT1 deletion carriers and tested for differences between AJ and NJ patients. RESULTS: The optimal algorithm for classification of clinically ascertained carriers was disease onset before age 24 years in a limb (misclassification, 16.5%; sensitivity, 95%; specificity, 80%). Although application of this classification scheme provided good separation in the AJ group (sensitivity, 96%; specificity, 88%), as well as in the group overall, it was less specific in discriminating NJ carriers from noncarriers (sensitivity, 94%; specificity, 69%). Using age 26 years as the cut-off and any site at onset gave a sensitivity of 100%, but specificity decreased to 54% (63% in AJ and 43% in NJ). Among genetically ascertained carriers, onset up to age 44 years occurred, although the great majority displayed early limb onset. There were no significant differences between AJ and NJ genetically ascertained carriers, except that a higher proportion of NJ carriers had onset in a leg, rather than an arm, and widespread disease. CONCLUSIONS: Diagnostic DYT1 testing in conjunction with genetic counseling is recommended for patients with PTD with onset before age 26 years, as this single criterion detected 100% of clinically ascertained carriers, with specificities of 43% to 63%. Testing patients with onset after age 26 years also may be warranted in those having an affected relative with early onset, as the only carriers we observed with onset at age 26 or later were genetically ascertained relatives of individuals whose symptoms started before age 26 years.

Adolescent↗
PubMed2000

A G protein-coupled receptor for UDP-glucose.

Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism.

GTP-Binding Proteins↗
PubMed2000

Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance.

BACKGROUND: Myocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated. METHODS AND RESULTS: In 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity-time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08+/-0.23 and 2.33+/-0.41; P<0.001) was found that resulted in a cutoff value of 1.5 (mean minus 2 SD of normal segments). In the prospective analysis, sensitivity, specificity, and diagnostic accuracy for the detection of coronary artery stenosis (> or =75%) were 90%, 83%, and 87%, respectively. Interobserver and intraobserver variabilities for the linear fit were low (r=0.96 and 0.99). CONCLUSIONS: MR first-pass perfusion measurements yielded a high diagnostic accuracy for the detection of coronary artery disease. Myocardial perfusion reserve can be easily and reproducibly determined by a linear fit of the upslope of the signal intensity-time curves.

Coronary Angiography↗
PubMed2000

Isolation and characterization of glycosylphosphatidylinositol-anchored, mucin-like surface glycoproteins from bloodstream forms of the freshwater-fish parasite Trypanosoma carassii.

Wild and farmed freshwater fishes are widely and heavily parasitized by the haemoflagellate Trypanosoma carassii. In contrast, common carp, a natural host, can effectively control experimental infections by the production of specific anti-parasite antibodies. In this study we have identified and partially characterized mucin-like glycoproteins which are expressed in high abundance [(6. 0+/-1.7)x10(6) molecules.cell(-1)] at the surface of the bloodstream trypomastigote stage of the parasite. The polypeptide backbone of these glycoproteins is dominated by threonine, glycine, serine, alanine, valine and proline residues, and is modified at its C-terminus by a glycosylphosphatidylinositol membrane anchor. On average, each polypeptide carries carbohydrate chains composed of about 200 monosaccharide units (galactose, N-acetylglucosamine, xylose, sialic acid, fucose, mannose and arabinose), which are most probably O-linked to hydroxy amino acids. The mucin-like molecules are the target of the fish's humoral immune response, but do not undergo antigenic variation akin to that observed for the variant surface glycoprotein in salivarian trypanosomes. The results are discussed with reference to the differences between natural and experimental infections, and in relation to the recently delineated molecular phylogeny of trypanosomes.

Amino Acids↗
PubMed2000

[CT-assisted volumetry and densitometry of distraction osteogenesis lengthened mandibular areas].

Gradual callus distraction in the correction of hypoplastic areas in the viscerocranial skeleton is an established method due to its efficacy. Whereas functional and esthetical improvements can be seen easily, it is impossible to get the increase of the bony mass right using the distractor scale or by clinical investigation. Only in animal studies can volumetric and densitometric measurements be done directly. By permission of the local ethics commission, in a clinical study, CT data of 24 children (12 unilateral and bilateral hypoplasias each) taken before and after mandibular distraction osteogenesis were used to get information on the amount of created bone and the grade of ossification of the callus at the time of the distractor removal. The CT data were prepared for computer evaluation using software which had been especially developed for this investigation. The quality of the investigation was influenced by disturbed data acquisition (insufficient sedation, Gantry deviation, different axial cuts). Therefore, the estimation of the real increase of bone was not possible, but all in all an increase of the volume could be seen. Using a grey scale analysis, the grade of new bone ossification was over 90% at the time of distractor removal. In our opinion, these results argue against the use of CT scans for the validation of a mandibular distraction. The estimation of the volume is very imprecise, the grade of ossification of the new bone very constant.

Absorptiometry, Photon↗
PubMed2000

[Genetics of dystonia].

To date, at least 12 types of primary dystonia can be distinguished on a genetic basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor in one large family (DYT11) has recently been implicated in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia (DYT8-10), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia-parkinsonism (DYT12). No positive linkage results have yet been obtained for autosomal recessive TD (DYT2) and several other families of different types of dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may occur as part of familial diseases of the basal ganglia, metabolic and storage disorders, and various X-linked and other familial neurodegenerative syndromes affecting the basal ganglia. It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.

Dystonia↗