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Biomedical subjects

M Otto

Publications and source records attributed to M Otto.

At least 109 records · Page 6Linked to original sources
PubMed1997

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Adult↗
PubMed1997

Diagnosis of Creutzfeldt-Jakob disease and related human spongiform encephalopathies.

Spongiform encephalopathies are transmissible diseases (TSE) of animals and humans. With the appearance of bovine spongiform encephalopathy (BSE) in 1986 and in 1996 with the identification of an apparently new variant of the human spongiform encephalopathy Creutzfeldt-Jakob disease (CJD), great concerns of a potential transmission of BSE to humans have been voiced. The agent known to transmit CJD and other human and animal spongiform encephalopathies is designated as prion, i.e., proteinaceous infectious agent, due to the absence of evidence for the involvement of a nucleic acid in disease transmission. In humans the clinical diagnosis of typical CJD cases can now be supported by paraclinical parameters. Electroencephalographic changes, so called periodic sharp wave complexes, are pathognomonic for CJD but by no means specific. The detection of neuronal enzymes in the cerebrospinal fluid (CSF) such as neuron specific enolase (NSE) or glial proteins such as S-100 aids greatly in the diagnosis of a human spongiform encephalopathy. By far the most specific marker in CSF are a group of proteins designated 14-3-3. Current evidence suggests that by including elevated levels of NSE (> or = 35 ng/mL), S-100 (> or = 8 ng/mL) and tau protein in the CSF and the presence of 14-3-3, a laboratory supported diagnosis of CJD can be achieved which in the appropriate clinical setting has a better diagnostic accuracy than the currently used clinical and paraclinical diagnostic criteria alone.

Animals↗
PubMed1997

Stability of bilayer lipid membranes on different metallic supports.

In order to arrive at an optimized s-BLM protocol, the influence of various metallic supports (silver, iridium and stainless steel) of different diameters (from 0.14 to 0.33 mm) on the process of forming and stability of supported phospholipid bilayer membranes was studied. In addition, experiments were made using different membrane-forming solutions, ionic strength and pH. The transmembrane resistance and the current ratio between bare and lipid-coated wire at +670 mV were measured. Teflon-coated stainless steel support (0.33 mm in diameter) covered with 2% crude ox brain fraction of phospholipids was most convenient for the formation of supported bilayer lipid membranes on solid support. The well-known stabilizing effect of cholesterol was confirmed for the s-BLM system. Both the pH in the range 5.0-8.0 (silver and stainless steel supports) and the ionic strength (for all types of supports) in the range from 0.025 to 0.1 mol/l at pH 7.0 were found not to be crucial.

Hydrogen-Ion Concentration↗
PubMed1997

Dynamic blood cell contact with biomaterials: validation of a flow chamber system according to international standards.

The increasing number of patients requiring prosthetic substitution of segments of the vascular system strongly supports the need to optimize a relevant, standardized testing panel for new materials designed for synthetic vascular prostheses. The ISO gives the standard requirements for testing biomaterials provided for implantation. Our primary interest was the establishment of a reliable in vitro panel as a useful and relevant screening system for vascular implant devices to evaluate blood/device interactions under flow conditions. The aim of the present study was to evaluate influences of different flow conditions on blood cell-biomaterial interactions with special emphasis on the interactions of human granulocytes (PMN) and polymeric surfaces. PMN were isolated and vital cells were quantified by flow cytometrical analysis directly before, as well as immediately after the experiments. The viscosity of the final cellular suspension was analysed by using a computerized cone-plate rheometer. As reference materials we used FEP-teflon, PVC-DEHD, PU, PP and PE. Dacron and ePTFE synthetic vascular protheses were tested in a comparative way to those references. The adhesion processes were observed over a period of 40 minutes under arterial (shear stress 0.74 Pa) and venous (shear stress 0.16 Pa) flow conditions in a parallel plate flow chamber system under highly standardized conditions and laminar flow. The cells were observed with the help of inverse light microscopy. Cell behaviour was recorded and analysed in both analogue (video) and digital (imaging system) modes. Samples of the cell suspensions were obtained at regular time intervals and analysed by enzyme linked immuno sorbent assay (ELISA) to quantify LTB4 release. Irrespective of the material, approximately 3 to 4 times more PMN adhered to the biomaterial surfaces under venous flow conditions compared to the arterial. Shear intensity did not influence the running order of biomaterials with respect to cell numbers. This response in descending order at the end of the experiments was as follows: PU, PVC-DEHD, PP, PE and ePTFE. The biochemical analyses indicate that in the system used only a weak effect on LTB4 release induced by the different materials could be determined. A significant effect caused by flow conditions was not observed. Further experiments, both static as well as dynamic, must be performed for multiple, relevant parameters of haemocompatibility, for potential biomaterials as well as those currently in use in vascular prostheses.

Journal Article↗
PubMed1997

The cell and molecular biological approach to biomaterial research: a perspective.

The past two decades have witnessed a revolution in our understanding of chemical processes in living organisms. This is mainly a result of the massive advances in the fields of cell and molecular biology. These techniques are highly relevant to the biomaterials sector, as they offer the scientist the possibility to better understand the mechanisms involved in the interactions between cells and a material surface-a prerequisite for the rational development of medical devices with optimal biocompatibility. The purpose of the present article is to explain the rationale of the cell and molecular biological approach to biomaterial research and to present typical examples from the authors' laboratory, as well as from the literature, to illustrate its application. Important aspects of interfacial biology, including the underlying biological mechanisms and methodology, are presented. Of the latter the combination of morphological techniques with methods of cell and molecular biology as well as molecular genetics (so-called "combinative techniques") are particularly useful. The applicability of this approach is illustrated from a study on the pathomechanisms of metal ion-induced inflammation. In addition, the approach is essential to the development of targeted intervention strategies, as for example in the luminal surface modification of vascular prostheses to permit endothelial cell seeding.

Journal Article↗
PubMed1997

Physiology and cell biology of the endothelium: a dynamic interface for cell communication.

This manuscript presents a brief overview of the physiology and cell biology of the endothelium, which is the basis for understanding the role of endothelial cells in pathological processes as diverse as atherosclerosis, tumour intravasation and multiple organ failure. Following consideration of general aspects of endothelial function in regulating haemostasis, vascular tone and growth, special emphasis will be placed on endothelial regulation of the inflammatory response, which centres on the microcirculation. A particular role in inflammation is played by cell adhesion molecules (CAM), expressed both on endothelial and blood cells. Cell and molecular biological methods to investigate the expression of CAM in endothelial cells in vitro will be presented, as well as novel data, indicating that cytokine-induced up-regulation of CAM in the endothelium may involve signal transduction pathways other than those culminating in the activation of NF-kappa B. Finally, the phenomenon of angiogenesis will be briefly reviewed as a characteristic of endothelial cell activity of central importance to both physiology and pathology and new experimental data presented from an in vitro model to study the ability of individual endothelial cells to form vessel-like structures. In comparative studies to investigate the roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, the dominant role of VEGF in the formation of capillary networks could be unequivocally demonstrated.

Animals↗
PubMed1997

Proximal myotonic myopathy with MRI white matter abnormalities of the brain.

Proximal myotonic myopathy (PROMM) is an autosomal dominantly inherited multisystemic disorder characterized by myotonia, proximal muscle weakness, and cataracts. This disorder is not linked to the gene locus of myotonic dystrophy (DM). We describe three new families with PROMM. In all patients, CTG repeats of the DM gene in DNA from blood leukocytes were normal. MRI of the brain revealed a consistent pattern of marked white matter hyperintensity on T2-weighted images in four patients; two additional patients had similar but mild to moderate MRI abnormalities. The morphology of these abnormalities is unknown. Clinical symptoms of brain disease were not consistent and included mental changes with hypersomnia, parkinsonian features, stroke-like episodes, and seizures. The causative relationship of these clinical features with the MRI white matter abnormalities remains to be established. Our observations suggest that PROMM may involve the brain.

Adult↗
PubMed1996

Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid.

BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on clinical and electroencephalographic criteria which do not allow a reliable diagnosis to be made during life. METHODS: Serum and cerebrospinal fluid (CSF) samples were obtained after informed consent from relatives of suspected cases of CJD referred to the German CJD surveillance unit. CSF samples from 58 definite (neuropathologically verified), 46 probable, and 34 possible CJD cases, and from 44 patients without CJD were analysed by two-dimensional gel electrophoresis (2-DE). Two investigators blinded to clinical findings recorded the presence of two proteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared with the determination of neuron-specific enolase (NSE) in CSF. NSE concentrations of more than 35 ng/mL were considered indicative of CJD. FINDINGS: p130/131 was detected in 81% of definite (47/58), 80% of probable (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases. NSE concentrations of more than 35 ng/mL were seen in 79% of definite (46/58), 80% of probable (37/46), 59% of possible (20/34) CJD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% CI 0.86-0.99). Of 13 cases initially classified as possible and later reclassified as definite, ten cases were identified correctly by the 2-DE analysis, indicating a better diagnostic accuracy of this test compared with the current clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE. INTERPRETATION: 2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG.

Adult↗
PubMed1996

Six new polymorphic microsatellite markers used for the integration of genetic and physical maps of human chromosome 7.

We report the isolation and characterization of six new polymorphic dinucleotide repeat microsatellite markers (D7S1491, D7S1492, D7S1493, D7S1494, D7S1495, and D7S1496), their integration into the genetic map of human chromosome 7 by analysis of 40 CEPH (Centre d'Etude du Polymorphisme Humain) pedigrees, and their use for integration of physical and genetic maps of this chromosome.

Alleles↗
PubMed1996

"IR-Spectroscopy" - computer-program for the interpretation of infrared spectra.

A computer-program "IR-Spectroscopy" for the interpretation of infrared spectra of organic compounds is described. It contains the following basic items for preprocessing and execution of the computer based interpretation process: handling of the rule-base CorTab, routines for automatic rule generation and interpretation modules on the basis of the programming languages PROLOG and C.

Journal Article↗
PubMed1996

Confidence intervals for calibration with neural networks.

Based on neural network calibration the confidence intervals of aromaticity determination from infrared reflectance spectra of raw brown coals were estimated by means of the bootstrap method, a simplified Monte Carlo Simulation. The standard deviations and the confidence intervals were estimated to characterise the analysis error.It is shown that confidence intervals of non-linear analysis methods like Back Propagation Neural Networks (BPNN) can be estimated by the bootstrap method. The estimated confidence intervals of the calibration confirm the analysis by BPNN.

Journal Article↗
PubMed1996

Germline mosaicism in 4q35 facioscapulohumeral muscular dystrophy (FSHD1A) occurring predominantly in oogenesis.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominantly inherited neuromuscular disorder affecting facial and shoulder girdle muscles with subsequent progression to the pelvic girdle and lower extremities. The major gene involved has been localized to chromosome 4q35 (FSHD1A). The 4q35 DNA marker p13E-11 (D4F104S1) detects a de novo EcoRI DNA rearrangement of < 30 kb in isolated and familial cases. The intrafamilial size of the fragment is constant, inversely correlated with the severity, and directly correlated with the age of onset of the condition. There has been evidence of parental mosaicism in FSHD1A for the D4F104S1 locus. Four female and three male clinically unaffected parents have been described to be carriers of EcoRI fragments of the same size as their affected offspring, but with a markedly less intensive hybridization signal (semi-quantitative evidence). In our total sample of 42 FSHD1A families, we found semi-quantitative evidence of parental D4F104S1 mosaicism in 11 families (EcoRI fragment size range: 12-27 kb). On analysis with adjacent 4q35 probes (D4S163, D4S139), additional qualitative evidence of germline mosaicism could be obtained in two families. In our mosaic families and in the families reported in the literature, a female predominance of mosaicism carriers (13 females versus 5 males) could be noted. In our sample, mosaicism was observed in multigeneration families, in families with isolated cases, and in families with two and three affected children from seemingly unaffected parents. A short EcoRI fragment once having emerged in a mosaicism carrier was found to be transmitted autosomal dominantly to subsequent generations. Of all reported sporadic patients, 19% have a mosaic parent. Finding evidence of parental mosaicism in all our families with more than one affected child of seemingly unaffected parents suggests that there is no autosomal recessively inherited form of FSHD1A.

Adult↗
PubMed1996

European Gene Mapping Project (EUROGEM): breakpoint panels for human chromosomes based on the CEPH reference families. Centre d'Etude du Polymorphisme Humain.

Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 17, 18, 20 and X were constructed from genotypes from the CEPH reference families. Each recombinant chromosome included has a breakpoint well-supported with reference to defined quantitative criteria. The panels were constructed at both a low-resolution, useful for a first-pass localization, and high-resolution, for a more precise placement. The availability of such panels will reduce the number of genotyping experiments necessary to order new polymorphisms with respect to existing genetic markers. This paper shows only a representative sample of the breakpoints detected. The complete data are available on the World Wide Web (URL http:/(/)www.icnet.uk/axp/hgr/eurogem++ +/HTML/data.html) or by anonymous ftp (ftp.gene.ucl.ac.uk in/pub/eurogem/maps/breakpoints).

Chromosome Mapping↗
PubMed1996

Clinical implications of nucleic acid amplification methods for the diagnosis of viral infections of the nervous system.

Amplification of viral nucleic acids from the cerebrospinal fluid (CSF) has considerably improved the diagnosis of several acute, subacute and chronic viral infections of the nervous system. In herpes simplex virus (HSV) encephalitis (HSE) the polymerase chain reaction (PCR) has become the method of choice for the rapid, non invasive diagnosis. Other herpes virus associated diseases which can now be reliably diagnosed are encephalitis, ventriculoencephalitis, polymyeloradiculitis, myelitis and an inflammatory polyradiculoneuropathy caused by cytomegalovirus (CMV), HSV, varicella-zoster virus (VZV) or Epstein-Barr virus (EBV), EBV associated primary B-cell-lymphoma of the brain, acute aseptic meningitis in young adults allied with VZV, and meningoencephalitis with recurrent seizures due to human herpes virus type 6 (HHV-6). In AIDS patients, PCR has helped to differentiate lesions either due to the human immunodeficiency virus (HIV) itself or to opportunistic infections such as progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) or CMV related complications. HIV can be detected early in the course of infection in the CSF and the amount of proviral DNA in CSF cells seems to be correlated with the severity and/or progression of neurological signs and symptoms. Acute epidemic aseptic meningitis caused by enterovirus infections can now be reliably diagnosed and typed by reverse transcriptase PCR (RT-PCR). Meningitis cases caused by vaccination with the Jeryl Lynn and Urabe vaccine strain of mumps virus have been identified using RT-PCR and sequencing of the amplified products (amplicon).

Central Nervous System↗
PubMed1996

[The ultrasound scalpel in laparoscopic surgery].

The ultrasonically activated scalpel works by means of the longitudinally vibrating sharp blade. The most important advantages- compared with electrosurgery-are the lack of current flow through the patient and limited local heat generation. It can be used as an instrument for coagulation, dissection and preparation. There is no generation of smoke. It is easy to use. Disadvantages are the slow speed of cutting and the high costs. In the future it could be an alternative to preparation on with dissector, scissors, and electrosurgery.

Dermatologic Surgical Procedures↗