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  • 1
    Electronic Resource
    Electronic Resource
    Calcium regulation in the human myocardium affected by dilated cardiomyopathy: A structural basis for impaired Ca2+-sensitivity (1999)
    Springer
    Molecular and cellular biochemistry 194 (1999), S. 301-313 
    Details
    ISSN: 1573-4919
    Keywords: ATPase activity ; cardiomyopathy ; heart failure ; myosin light chains ; troponin-tropomyosin ; mekratin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Calcium regulation in the human heart is impaired during idiopathic dilated cardiomyopathy (IDC). Here, we analyze the structural basis for impairment in the regulatory mechanism. Regulation of contractility was monitored by MgATPase and Ca2+-binding assays as a function of calcium. Myofibrillar proteolysis and expression of troponin T isoforms were established by gel electrophoresis and by Western blots. Myofibrillar ATPase assays in low salt however, revealed a drastic lowering of calcium sensitivity in IDC myofibrils as indicated by reductions in both activation by high calcium and in EGTA-mediated inhibition of MgATPase. Structural changes in myofilament proteins were found in most IDC hearts, specifically proteolysis of myosin light chain 2 (LC2), troponin T and I (TnT and TnI), and sometimes large isoform shift in TnT. IDC did not induce mutations in LC2 and troponin C (TnC), as established by cDNA sequence data from IDC cases, thus, calcium binding to IDC myofibrils was unaffected. Reassociation of IDC myofibrils with native LC2 raised MgATPase activation at high Ca2+ to control levels, while repletion with intact, canine TnI/TnT restored inhibition at low Ca2+. A model, identifying possible steps in the steric blocking mechanism of regulation, is proposed to explain IDC-induced changes in Ca2+-regulation. Moreover, shifts in TnT isoforms may imply either a genetic or a compensatory factor in the development and pathogenesis of some forms of IDC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006980405359
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  • 2
    Electronic Resource
    Electronic Resource
    Cloning of the cDNA and nucleotide sequence of a skeletal muscle protease from myopathic hamsters (1998)
    Springer
    Molecular and cellular biochemistry 181 (1998), S. 125-135 
    Details
    ISSN: 1573-4919
    Keywords: cardiomyopathy ; serine proteases ; myosin light chain 2 ; cDNA cloning ; mast cells ; mekratin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A neutral protease with an estimated Mr of about 26 kD and responsible for cleavage of myosin LC2 was isolated from hamster skeletal muscle. Complementary DNAs were generated by RT-PCR using total hamster muscle RNA and degenerate oligonucleotide primers based on the sequences of two internal peptides. The nucleotide sequences of the resultant cDNAs were subsequently determined and the complete amino acid sequence of the protease deduced. Although the hamster protein shared 63-85% identity in nucleotide and amino acid sequences with rat and mouse mast cell proteases, it had a higher degree of specificity for myosin LC2 than mast cell proteases which also digested myosin LC1 and myosin heavy chains. As a result, the hamster protease was designated mekratin because of its unique enzymatic specificities to distinguish it from other mast cell proteases. A polyclonal antibody was raised specific to the hamster muscle and human cardiac muscle mekratins without apparent cross-reaction with rat mast cell proteases. We have earlier demonstrated the presence in excess of a neutral protease that specifically cleaves LC2 in human hearts obtained at end stage idiopathic dilated cardiomyopathy (IDC). Western analyses revealed that heart tissue from patients with IDC contained 5-10 fold more mekratin than control samples. Furthermore, the level of the protease in human IDC tissues was similar to that seen in myopathic hamster skeletal muscle. No bands were recognized by the antibody when IDC myofibrils were probed due to the removal of soluble proteins during sample preparation. Thus, these results strongly suggest that the anti-mekratin antibody will provide positive identification of IDC in many cases and diagnosis by exclusion may be replaced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006842332340
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Evaluation of two population-based input functions for quantitative neurological FDG PET studies (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 299-304 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Fluorodeoxyglucose ; Positron emission tomography ; Autoradiography ; Cerebral metabolic rate of glucose ; Population-based input function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The conventional measurement of the regional cerebral metabolic rate of glucose (rCMRGlc) with fluorodeoxyglucose (FDG) and positron emission tomography (PET) requires arterial or arterialised-venous (a–v) blood sampling at frequent intervals to obtain the plasma input function (IF). We evaluated the accuracy of rCMRGlc measurements using population-based IFs that were calibrated with two a–v blood samples. Population-based IFs were derived from: (1) the average of a–v IFs from 26 patients (Standard IF) and (2) a published model of FDG plasma concentration (Feng IF). Values for rCMRGlc calculated from the population-based IFs were compared with values obtained with IFs derived from frequent a–v blood sampling in 20 non-diabetic and six diabetic patients. Values for rCMRGlc calculated with the different IFs were highly correlated for both patient groups (r≥0.992) and root mean square residuals about the regression line were less than 0.24 mg/min/100 g. The Feng IF tended to underestimate high rCMRGlc. Both population-based IFs simplify the measurement of rCMRGlc with minimal loss in accuracy and require only two a–v blood samples for calibration. The reduced blood sampling requirements markedly reduce radiation exposure to the blood sampler.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728767
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Evaluation of two population-based input functions for quantitative neurological FDG PET studies (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 299-304 
    Details
    ISSN: 1619-7089
    Keywords: Fluorodeoxyglucose ; Positron emission tomography ; Autoradiography ; Cerebral metabolic rate of glucose ; Population-based input function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The conventional measurement of the regional cerebral metabolic rate of glucose (rCMRGlc) with fluorodeoxyglucose (FDG) and positron emission tomography (PET) requires arterial or arterialised-venous (a–v) blood sampling at frequent intervals to obtain the plasma input function (IF). We evaluated the accuracy of rCMRGlc measurements using population-based IFs that were calibrated with two a–v blood samples. Population-based IFs were derived from: (1) the average of a–v IFs from 26 patients (Standard IF) and (2) a published model of FDG plasma concentration (Feng IF). Values for rCMRGlc calculated from the population-based IFs were compared with values obtained with IFs derived from frequent a–v blood sampling in 20 non-diabetic and six diabetic patients. Values for rCMRGlc calculated with the different IFs were highly correlated for both patient groups (r≥0.992) and root mean square residuals about the regression line were less than 0.24 mg/min/100 g. The Feng IF tended to underestimate high rCMRGlc. Both population-based IFs simplify the measurement of rCMRGlc with minimal loss in accuracy and require only two a–v blood samples for calibration. The reduced blood sampling requirements markedly reduce radiation exposure to the blood sampler.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728767
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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