Biomedical subjects
Publications and source records attributed to M Otto.
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.
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.
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.
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).
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).
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.
Decisions or statements about the health effects of "pollutants" are often based on not exactly known exposure conditions and/or doubtful cause-effect relationships. Even searches in international databases will not always give adequate answers or produce new problems for the specialist in environmental medicine because the information may be contradictory or leave a wide scope for interpretation, perhaps requiring detailed specialized knowledge (e.g. mutagenicity testing, immunotoxicological parameters etc.). In situations like these, inter-disciplinary working is the mandatory condition. Therefore electronic communication systems might be used to resolve problems, because they provide access to well-presented knowledge of competent colleagues. However, the fundamental concept of such mailbox system for environmental medicine requires active participation by all its users who should contribute to its files and not remain passive, i.e. only call for information.
Serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone, androstenedione, estradiol, sex hormone-binding globulin, cortisol, and prolactin were measured in 12 male chronic alcoholics once during withdrawal and once after 21 days of abstinence. The results were compared with those of 14 healthy volunteers. During withdrawal, luteinizing hormone, estradiol, and cortisol levels were significantly enhanced. Estradiol and cortisol concentrations fell significantly during abstinence, whereas luteinizing hormone concentrations remained elevated. The results may be interpreted as follows: the well-known inhibitory effect of alcohol on the biosynthesis of testosterone may have led to a compensatory increase in luteinizing hormone secretion, so that normal serum concentrations of testosterone were maintained. On the other hand, peripheral conversion from androstenedione to estradiol via aromatase pathways seemed to be enhanced in chronic alcoholics, at least during withdrawal. Whether this marked increase in estradiol concentrations is implicated in different clinical and psychological symptoms seen in chronic alcoholics remains to be investigated.
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Recent studies have presented evidence that the processes of hypoxaemia and reperfusion are involved in several pathogenetic mechanisms of atherosclerotic lesions. The ability of hypoxaemia to activate circulating white blood cells (WBCs) and enhance WBC-endothelial cell (EC) interactions is suspected to be a major factor in deleterious processes in the blood vessel wall. Various groups have suggested that cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1 and E-selectin and their leukocyte ligands are involved in intercellular activities of the relevant cell types. We studied the effects of different oxygen tensions, simulating normoxic conditions, hypoxia and hyperoxia in vitro with the help of an umbilical vein EC model in order to determine the effects of oxygenation on CAM presentation on vascular ECs with and without further cytokine and endotoxin (lipopolysaccharides; LPS) stimulation. Semiquantitative analysis of ICAM-1, E-selectin and VCAM-1 was performed using cell enzyme immunoassay techniques. The presentation of ICAM-1, E-selectin and VCAM-1 remained on the whole unaffected by both hypoxia and hyperoxic conditioning after both 7 and 24 h. Stimulation of ICAM-1 by cytokines and LPS was only marginally influenced by the oxygen tension. Cytokine induction of E-selectin was not affected after 7 h and was even reduced under hypoxia, compared to the control culture after 24 h, while stimulation was increased by hyperoxia. VCAM-1 was reduced in both the hypoxic and hyperoxic culture, while being maximally stimulated by cytokines and LPS after 7 h. In general, an effect of hypoxia was not found without any further stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelial cells (EC) are very responsive to proinflammatory cytokines, e.g. interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), as well as to bacterial lipopolysaccharide. EC are stimulated by these substances to secrete chemotactic factors and to increase expression of cell adhesion molecules (CAM), leading to dramatically altered interactions with leukocytes, e.g. granulocytes and monocytes. In these interactions E-selectin, ICAM-1 and VCAM-1 are known to play an important role, as they are presented by the EC and interact with corresponding ligands on the white blood cell membranes. These adhesion molecules have been studied worldwide in a variety of in vitro experiments using cultured EC. Different passages and mixtures of passages have been used in these experiments, often without any regard to the comparability of the results. In this study the expression of E-selectin, ICAM-1 and VCAM-1 on cultured human umbilical vein EC (HUVEC) obtained from different passages (passages 1-6) was studied after 4, 8 and 24 h of exposure to IL-1 beta and TNF alpha. In previous studies, we have shown that IL-1 beta and TNF alpha increase the expression of E-selectin and ICAM-1 on the cytoplasmatic membranes of HUVEC and human adult EC from the saphenous vein and femoral artery in a similar fashion. Using a comparative quantitative cell enzyme immunoassay, we found that the expression of the adhesion molecules was significantly reduced with increasing passages. There was also a decreased persistence of CAM comparing different periods of stimulation between 6 and 24 h in the different passages. These data indicate that the number of passages plays an important role in the expression of adhesion molecules on EC. The results are relevant for the meaningful planning of comparative in vitro studies on EC presentation of CAM.
The binding of three influenza A and one influenza B virus strains to proteins of three continuously cultured cell lines was studied using protein overlay and immunostaining methods. The results obtained indicated the presence of both sialic acid-dependent and -independent binding of the virus strains; virus binding to proteins in the molecular mass range from about 40 to 103 kDa was dependent on sialic acid, whereas binding to the 33 kDa protein was independent of sialic acid. The 33 kDa binding protein was identified as annexin, a widely distributed non-glycosylated calcium-dependent phospholipid-binding protein.
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Eighteen German families with a history of paramyotonia congenita (PC) were characterised by genetic and mutational analysis at the SCN4A locus, which encodes the alpha-subunit of the adult skeletal muscle sodium channel. We concentrated our analysis primarily on these families to test the hypothesis that a predominance of one common mutation occurs in all German PC families and that this mutation arose in a common ancestor originating in the North-West of the country. The present eighteen PC families exhibit two different mutations (R1448C and R1448H) on various SCN4A dinucleotide repeat haplotypes and therefore the majority of the mutations probably occurred independently. However, the R1448H mutation is extremely frequent in the North-West of Germany (Ravensberger Land) on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. Our results suggest that the R1448C/R1448H mutations are by far the most common to be associated with the PC phenotype in the German population.
We have designed an amperometric xanthine minibiosensor based on a supported biotinylated phospholipid membrane. To this membrane streptavidin-modified xanthine oxidase was coupled. The fabricated biosensor corresponds in shape and size to a needle of 0.3 mm in diameter. The assay is based on the electrochemical detection of enzymatically generated hydrogen peroxide. The response to xanthine was linear up to 1 mmol.l-1 with a detection limit of 0.02 mmol.l-1. The response time was less than one minute and the biosensor was stable for at least five days.
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