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  • 1
    Electronic Resource
    Electronic Resource
    Competitive action of divalent cations and D600 in frog slow muscle fibers (1989)
    Springer
    The journal of membrane biology 112 (1989), S. 185-192 
    Details
    ISSN: 1432-1424
    Keywords: slow fiber ; K contracture ; D600 ; divalent cations ; competitive binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Single, slow muscle fibers fromRana temporaria were equilibrated in normal Ringer's. 95 mmol/liter K1-solution containing various concentrations of Ca2+, Ni2+, Mn2 or Mg2+ was applied, and the ensuing contractures were recorded isometrically. While peak tension (F max) was little affected, maintained tension (measured 1 min after onset of contracture) strongly depended on the concentration and species of divalent cations. Tension was maintained at its peak value in the presence of all species of divalent cations provided their concentrations were adequately increased. Dose-response curves were hyperbolic: Lineweaver-Burk plots revealed straight lines with different slopes intersecting near 1/F max, and indicating the following order of efficiency: Ni2+〉Ca2+〉Mn2+〉〉Mg2+. Hill plots for these cations resulted in straight lines with slopes near 1. Qualitatively similar relationships were obtained with contracture solutions containing D6000 (3–12 μmol/liter). However, under these conditions higher concentrations of Ca2+ or Ni2+ were required in order to fully maintain tension. After a step concentration change in the medium during contracture, the effects of Ca2+ or D600 were detectable only after a delay of 9 and 18 sec, respectively. It is concluded that divalent cations and D600 compete for the same binding site according to a 1:1 reaction. This site is presumably located inside the transverse tubular system and controls inactivation of the contractile force.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01871279
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  • 2
    Electronic Resource
    Electronic Resource
    Phenylalanine hydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria (1996)
    Springer
    European journal of pediatrics 155 (1996), S. S11 
    Details
    ISSN: 1432-1076
    Keywords: Key words Phenylketonuria ; Genotype ; Treatment ; IQ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interdependence of the predicted in vitro residual enzyme activity (PRA), as deduced from the complete genotypes of 64 hyperphenylalaninaemic patients, and parameters for diagnosis of hyperphenylalaninaemic disorders, the fluctuation of the phyenlylalanine (Phe) values during treatment, long-term dietary control during treatment, and a parameter for the outcome of therapy (IQ) was investigated by correlation analysis. A highly significant correlation was found between the PRA and diagnostic parameters, as well as the fluctuation of the Phe values during treatment. Significant correlations were also observed between the parameter describing the fluctuation of the Phe values and the IQ, as well as between the quality of dietary control and IQ. The PRA is a valuable tool for the differential diagnosis of hyperphenylalaninaemic disorders and for the prediction of one aspect of the course of the disease which is related to the intellectual outcome of therapy. The quality of dietary control was independent of the genotype, indicating that the outcome of therapy can be successfully manipulated in spite of the genetic make-up.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014222
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  • 3
    Electronic Resource
    Electronic Resource
    Magnetic resonance imaging of the brain in adolescents with phenyketonuria and in one case of 6-pyruvoyl tetrahydropteridine synthase deficiency (1996)
    Springer
    European journal of pediatrics 155 (1996), S. S69 
    Details
    ISSN: 1432-1076
    Keywords: Key words Phenylketonuria ; Phenylalanine ; Magnetic resonance ; imaging ; Evoked potentials ; Myelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract White matter abnormalities on MRI have been observed in phenylketonuria (PKU) patients with late onset neurological symptoms as well as in neurologically inconspicious patients. We investigated 14 early treated adolescents at an age between 12 and 17 years (mean age 14.3 years) with classical PKU as well as one retarded patient with atypical PKU by cranial MRI with spinecho T1-, T2- and proton density sequences. Clinical examination was normal. Visual evoked potential (VEP) examination showed a prolonged latency of peak P100 (mean 122.6 ms; control mean 115.9) and IQ testing showed a mean IQ of 101.1. To investigate the influence of plasma phenylalanine (Phe) levels three approaches were used: Phe was determined for the day of MRI, for a period of 6 months prior to MRI and for lifetime up to 12 years. MRI scans revealed areas of abnormally increased signal intensity on T2-weighted and proton density images in 12 (86%) patients, preferably involving the parieto-occipital lobes. MRI of the patient with atypical PKU was normal. MRI findings correlated most strongly to long-term dietary control up to 12 years. We found no correlation with the other parameters of biochemical control, IQ or VEP latency. The nature and prognosis of MRI abnormalities in neurologically normal PKU patients remain unclear although abnormalities in VEPs which were not associated with the degree of MRI abnormalities in our sample indicate a disturbance in myelination along the visual pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014255
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  • 4
    Electronic Resource
    Electronic Resource
    Intelligence and professional career in young adults treated early for phenylketonuria (1996)
    Springer
    European journal of pediatrics 155 (1996), S. S97 
    Details
    ISSN: 1432-1076
    Keywords: Key words Phenylketonuria ; Intelligence ; Education ; Professional career ; Phenylalanine ; control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The intellectual status and professional careers of 51 young adults with phenylketonuria whose treatment started before 3 months of age are described. Their mean IQ was 97 (SD = 16). Of the IQs, 4% were more than 2 SD below the norm. The distribution of types of schooling of the patients was comparable to that in the German population. The professional careers of nearly all the patients were according to their educational level. Within the sample the outcome was significantly correlated with phenylalanine (Phe) control, even when the patients’ social background was statistically taken into account. The main influence of Phe on intelligence seems to occur during the first decade of life since IQ data remain stable even after Phe levels increased during adolescence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00014262
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  • 5
    Electronic Resource
    Electronic Resource
    D600 prolongs inactivation of the contractile system in frog twitch fibres (1987)
    Springer
    Pflügers Archiv 410 (1987), S. 75-82 
    Details
    ISSN: 1432-2013
    Keywords: Twitch fibre ; K-contracture ; Inactivation ; D600
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (1) Single twitch fibres were dissected from tibialis muscles ofRana temporaria and used to study the effect of D600 (gallopamil) on potassium-induced contractures. (2) 95 mM K-Ringer's was applied for 8–15 s at intervals of generally 2.5–5 min; at temperatures of 6–8°C and in the absence of D600 the amplitude of the contractures remained fairly constant. After pretreatment with D600 (30 μM) a single (conditioning) K-contracture was sufficient to ‘paralyze’ the fibres (cf. Eisenberg et al. 1983). (3) Complete paralysis could also be achieved at 18–20°C. In three fibres a single conditioning K-application was sufficient; in two more fibres two or three conditioning K-applications were required. (4) D600-paralysis could not only be achieved with high K-concentrations but also by conditioning with subor suprathreshold K-concentrations (20–40 mM); the duration of the conditioning periods required to induce complete paralysis was approximately the same before and after D600-treatment. (5) Contractures were partially abolished by application of 20–40 mM K-Ringer's for short conditioning periods; after D600-treatment the degree of contracture loss was similar. (6) At low temperature the state of partial or complete paralysis induced by subthreshold K-concentrations and D600 was maintained for long periods of time. (7) The presence of 10 mM Ca2+ did not protect the fibres from being paralyzed by treatment with D600 and high K-Ringer's at low temperature; however, more than one conditioning K-application was required. (8) Resting and action potentials of paralyzed fibres were not significantly different from control values. However, endplate potentials were reduced in size, and failure of neuromuscular transmission was observed in some of these fibres. (9) It is concluded that D600 prolongs the state of inactivation of the contractile mechanism, while the development of inactivation does not seem to be markedly affected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00581899
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  • 6
    Electronic Resource
    Electronic Resource
    The effect of D600 on potassium contractures of slow muscle fibres ofRana temporaria (1988)
    Springer
    Pflügers Archiv 412 (1988), S. 390-396 
    Details
    ISSN: 1432-2013
    Keywords: Slow fibre ; K-Contracture ; D600 ; Inactivation ; Repriming
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (1) The effect of 30 μM D600 on the amplitude and time course of isometric contractures was studied in single slow fibres ofRana temporaria. (2) D600 only slightly reduced the amplitude of contractures evoked with 30 or 95 mM K-Ringer's. Maintenance of tension was strongly impaired by D600 only during exposure to 95 mM K. The caffeine contracture was not affected. (3) Addition of 10 mM Ca2+ or other divalent cations to the medium strongly counteracted the effect of D600 on maintained tension. The order of efficiency was Ca2+=Ni2+〉Co2+〉Mn2+〉Mg2+. (4) During 2 min exposure to 95 mM K-Ringer's the slow fibres inactivated to a variable degree; recovery from inactivation in normal Ringer's proceeded with a half time of the order of 1 min, while in the presence of D600 recovery was prolonged 3.3 to 27 times. (5) It is concluded that the effect of D600 on the contractile behaviour of slow fibres fromRana temporaria is predominantly due to a prolongation of the inactivated state. It is suggested that D600 binds to a site at the outer membrane surface which also binds divalent cations and determines the degree of contractile inactivation during exposure to potassium. Blocking of Ca2+ channels is unlikely to be the mechanism of this D600-effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907557
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