Search PubMed⌕ Search

Biomedical subjects

H Moser

Publications and source records attributed to H Moser.

At least 109 records · Page 6Linked to original sources
PubMed1985

Isolation and characterization of acetylcholine receptor membrane-associated (nonreceptor v2-protein) and soluble electrocyte creatine kinases.

Creatine kinase has been identified as a most prominent component of Torpedo electric organ and a minority constituent of the acetylcholine receptor (AChR) membranes obtained therefrom. Purification by low temperature ethanol extraction, precipitation of the Mg2+-enzyme complex, and mercurial-agarose chromatography yield preparations of soluble kinase with specific activities greater than 550 units/mg protein. Retention times in ion-exchange high performance liquid chromatography, electrophoretic behavior, immunochemical properties, tryptic mapping, and amino acid composition enable the comparison of creatine kinase isoenzymes. The denatured subunits of the predominant species have pI values of 6.3-6.8 and Mr = 40,000-42,000 characteristic of the so-called v2 proteins and show cross-reactivity with antibodies against the BB ("brain" type) creatine kinase. The MM ("muscle" type) antigens could be detected in the total electrocyte, but not in the AChR membranes; they have a slightly lower molecular weight and higher pI. The in situ membrane association of the BB isoenzyme is confirmed by immunocytochemistry. The apparent Km values for the substrate creatine phosphate are 2.2 mM for the AChR membrane-associated enzyme and 2.5 mM for the muscle form. The apparent Km values for Mg2+-ADP are 0.54 and 0.22 mM, respectively. Thus, a 2-fold higher affinity in the binding of ADP to the binary enzyme-creatine-P complex results from membrane association.

Amino Acids↗
PubMed1985

First trimester prenatal diagnosis of adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis to a DNA probe.

A first trimester prenatal diagnosis of adrenoleukodystrophy has been done on chorionic villi biopsy in the pregnancy of a carrier woman. Two different approaches allowed one to determine that the male fetus was affected: the linkage analysis of DNA from chorionic villi using the highly polymorphic probe St 14 and the determination of very long chain fatty acid levels in cultured chorionic villi.

Adrenoleukodystrophy↗
PubMed1985

[Genetic aspects of heart and circulatory diseases].

Cardiovascular diseases (CVD) are common, heterogenous and of multifactorial origin with a variety of more or less known environmental risk factors interacting with a certain genetic predisposition. Beside some rare monogenic conditions the hereditary risk factors are polygenic and acting either on a given CVD or again on particular predisposing conditions. This is well known for type II hyperlipoproteinemia, which can be observed as a rare monogenic metabolic disorder or as the more common polygenic variant. The relative proportions of genetic and environmental risk factors for CVD can be estimated only approximately due to the various interactions. The current methods are investigations for a given phenotype (e.g. LDL-cholesterol) in first-degree relatives of index patients and studies of concordance rates in mono- and dizygotic twins. The results of a large number of epidemiological studies are indicating that there is a considerable genetic component in the liability for ischemic heart disorders (especially for cardiac infarction in younger age groups), as well as for essential hypertension.

Adult↗
PubMed1985

Heart C-protein is transiently expressed during skeletal muscle development in the embryo, but persists in cultured myogenic cells.

The expression of cardiac and white skeletal C-protein isoforms was analyzed in developing chicken embryos and in primary skeletal muscle cell cultures by immunoblot and immunofluorescence staining using polyclonal antibodies specific for both of the two different proteins. In the embryo, cardiac C-protein was detected in the developing heart from very early stages through adulthood. In skeletal muscle, cardiac C-protein is shown to be transiently expressed between Days 3 and 15 during development. In contrast, the expression of white skeletal C-protein is gradual and progressive starting approximately from Day 15 on in development. In primary cell cultures of skeletal muscle, however, cardiac C-protein remained expressed throughout prolonged culture time, this in conjunction with white skeletal C-protein. Thus the down regulation of cardiac C-protein and the transition from cardiac C-protein to adult skeletal (white) C-protein which was observed during skeletal muscle development in vivo, does not seem to go to completion in the in vitro system.

Animals↗
PubMed1985

Quantification of haemagglutinin of influenza Tween-ether split vaccines by immunodiffusion.

The haemagglutinin content of monovalent influenza whole virus and Tween-ether split vaccines derived therefrom, were assayed comparatively using single radial immunodiffusion (SRID, the only test recommended for influenza vaccines by the European Pharmacopoeia Commission), quantitative SDS-polyacrylamide gel electrophoresis and immunization of guinea pigs. If SRID was performed with split vaccines, reduced haemagglutinin values were consistently recorded which were 50-25% of values obtained before disruption of virions. If, however, disruption was conducted in the presence of excess detergent thus preventing aggregate formation of solubilized haemagglutinin, test values comparable to those of whole virus vaccines were obtained. In agreement with these results, immunization experiments revealed that whole virus and the corresponding split vaccines exhibited comparable immunogenicity in guinea pigs. From SDS-polyacrylamide gel electrophoresis and densitometer tracings obtained by scanning the gels after staining with either Coomassie Blue or fluorescein isothiocyanate-labelled concanavalin A it was calculated that about 90% of whole virus HA2 was recovered in Tween-ether split vaccines. From our experiments we conclude that precise quantification of solubilized haemagglutinin is not achievable by the single radial immunodiffusion test alone. Aggregate formation of solubilized haemagglutinin frequently occurs when the applied detergent is removed and, therefore, a physico-chemical method including an effective disaggregation procedure like SDS treatment in combination with PAGE is recommended.

Animals↗
PubMed1985

Subcellular localization of creatine kinase in Torpedo electrocytes: association with acetylcholine receptor-rich membranes.

Creatine kinase (CK, EC 2.7.3.2) has recently been identified as the intermediate isoelectric point species (pl 6.5-6.8) of the Mr 40,000-43,000 nonreceptor, peripheral v-proteins in Torpedo marmorata acetylcholine receptor-rich membranes (Barrantes, F. J., G. Mieskes, and T. Wallimann, 1983, Proc. Natl. Acad. Sci. USA, 80: 5440-5444). In the present study, this finding is substantiated at the cellular and subcellular level of the T. marmorata electric organ by immunofluorescence and by protein A-gold labeling of either ultrathin cryosections of electrocytes or purified receptor-membrane vesicles that use subunit-specific anti-chicken creatine kinase antibodies. The muscle form of the kinase, on the one hand, is present throughout the entire T. marmorata electrocyte except in the nuclei. The brain form of the kinase, on the other hand, is predominantly located on the ventral, innervated face of the electrocyte, where it is closely associated with both surfaces of the postsynaptic membrane, and secondarily in the synaptic vesicles at the presynaptic terminal. Labeling of the noninnervated dorsal membrane is observed at the invaginated sac system. In the case of purified acetylcholine receptor-rich membranes, antibodies specific for chicken B-CK label only one face of the isolated vesicles. No immunoreaction is observed with anti-chicken M-CK antibodies. A discussion follows on the possible implications of these localizations of creatine kinase in connection with the function of the acetylcholine receptor at the postsynaptic membrane, the Na/K ATPase at the dorsal electrocyte membrane, and the ATP-dependent transmitter release at the nerve ending.

Animals↗
PubMed1985

Intracellular pH regulation in the sensory neurone of the stretch receptor of the crayfish (Astacus fluviatilis).

The ionic mechanisms of intracellular pH (pHi) regulation were studied in the slowly adapting sensory cell of the crayfish stretch receptor by using pH-, Na+- and Cl(-)-sensitive liquid ion exchanger electrodes. Under control conditions a mean pHi of 7.23 +/- 0.12 (S.D.) at a mean membrane potential of 68.3 +/- 4.1 mV S.D. was found in sixteen cells. Thus pHi is about 1 pH unit more alkaline than predicted from passive distribution, implying the presence of an acid extrusion mechanism. In order to acidify the cytoplasm, the cell was either acid-loaded by NH4Cl or exposed to CO2 and CO2/HCO3- solutions. During CO2 exposures pHi was regulated only if calculated amounts of HCO3- were added to keep external pH (pHo) constant. The pHo per se was found to be an important determinant of pHi and its regulation. Substitution of external Na+ by choline inhibited pHi recovery almost completely. As soon as Na+ was readmitted H+ extrusion occurred immediately at a rate similar to that of the control. The internal Na+ activity (aiNa) ranged between 6 and 13 mM with a mean of approximately 9.1 +/- 2.5 mM (S.D.; n = 8). The effects of various solutions on aiNa and the temporal relationship between aiNa and pHi in NH4Cl acid-loaded cells were investigated. The amount of aiNa increased during cell internal acidification and recovered in parallel with pHi recovery in NH4Cl acid-loaded cells. Experiments with 10(-4) M-ouabain and K+-free conditions suggest that neither the Na+-K+ pump nor external K+ are directly involved in pHi regulation. The internal chloride activity (aiCl), which was lower than predicted from a passive distribution, fell during exposure to HCO3-/CO2. Regulation of pHi was inhibited if the cell was completely depleted of Cl- by prolonged exposures to Cl(-)-free solution (isethionate and/or gluconate substituted). The pHi-regulating system of the sensory cell requires Na+ and Cl- which probably operate in a combined mechanism such as Na+ -H+-Cl(-)-HCO3- or an equivalent.

Acid-Base Equilibrium↗
PubMed1985

[Genetic heterogeneity and pathology of congenital nephrotic syndrome and its significance in prenatal diagnosis].

Familial occurrence of congenital nephrotic syndrome (CN) has been most extensively studied in Finland where it is known to be inherited as an autosomal recessive disease. In this Finnish type of congenital nephrotic syndrome (CNF) prenatal diagnosis by alphafetoprotein (AFP) determination in the amniotic fluid has been reported to be conclusive. Within the last six years we observed 10 cases of CN occurring in 5 families. In all patients renal histology has been studied. Although each family presented a different type of CN, the appearance within the same sibship was always identical.

Adult↗
PubMed1984

Duchenne muscular dystrophy: pathogenetic aspects and genetic prevention.

Duchenne muscular dystrophy (DMD) is the most common sex linked lethal disease in man (one case in about 4000 male live births). The patients are wheelchair bound around the age of 8-10 years and usually die before the age of 20 years. The mutation rate, estimated by different methods and from different population studies, is in the order of 7 X 10(-5), which is higher than for any other X-linked genetic disease. Moreover, unlike other X linked diseases such as hemophilia A or Lesh-Nyhan's disease, there seems to be no sex difference for the mutation rates in DMD. Several observations of DMD in girls bearing X-autosomal translocations and linkage studies on two X chromosomal DNA restriction fragment length polymorphisms indicate that the DMD locus is situated on the short arm of the X chromosome, between Xp11 and Xp22. It may be of considerable length, and perhaps consisting of actively coding and non-active intervening DNA sequences. Thus unequal crossing over during meiosis in females could theoretically account for a considerable proportion of new mutations. However, there is no structurally or functionally abnormal protein known that might represent the primary gene product, nor has any pathogenetic mechanism leading to the observed biochemical and histological alterations been elucidated. Among the numerous pathogenetic concepts the hypothesis of a structural or/and functional defect of the muscular plasma membrane is still the most attractive. It would explain both the excess of muscular constituents found in serum of patients and carriers, such as creatine kinase (CK), as well as the excessive calcium uptake by dystrophic muscle fibres, which, prior to necrosis, could lead to hypercontraction, rupture of myofilaments in adjacent sarcomeres and by excessive Ca uptake to mitochondrial damage causing crucial energy loss. The results of studies on structural and functional membrane abnormalities in cells other than muscle tissue, e.g., erythrocytes, lymphocytes and cultured fibroblasts, indicate that the DMD mutation is probably demonstrable in these tissues. However, most of the findings are still difficult to reproduce or even controversial. DMD is an incurable disease; therefore most effort, in research as well as in practical medicine, is concentrated upon its prevention.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Early manifestations of multiple sulfatase deficiency.

We describe two boys, presenting by 1 year of age, with developmental delay from birth, mildly coarse facial features, and hepatomegaly. These clinical features were most suggestive of a mucopolysaccharidosis, particularly MPS II. Biochemical studies, including sulfate incorporation in fibroblasts and lysosomal enzyme analyses in fibroblasts, leukocytes, and serum, showed abnormalities in both sulfatide and mucopolysaccharide metabolism and led to the diagnosis of multiple sulfatase deficiency. With time, both patients developed an ichthyotic rash and profound intellectual deterioration. We conclude that findings in the first year of life in some patients with MSD may closely resemble those in patients with a MPS disorder rather than the late infantile form of metachromatic leukodystrophy, as is classically described. Thus, MSD should be considered in the young patient suspected of having a MPS disorder.

Cerebroside-Sulfatase↗
PubMed1984

A new inactivated tissue culture rabies vaccine for use in man. Evaluation of PCEC-vaccine by laboratory tests.

A new inactivated rabies vaccine (purified chick embryo cell vaccine) has been developed using the Flury LEP-C 25 strain of rabies virus propagated in primary chick embryo cell cultures. The antigen was purified and concentrated by continuous density gradient centrifugation and inactivated by betapropiolactone. This vaccine was tested for innocuity, tolerability and protective capacity in a series of laboratory tests and compared with human diploid cell strain (HDC)-vaccines of similar antigenicity. The results indicated that this new vaccine was excellently tolerated and that its protective activity met the high standard of HDC-vaccine, conditions which were imposed on this vaccine before entering clinical trials in man.

Animals↗
PubMed1984

Hypergonadotropic hypogonadism in two sisters with galactosaemia.

Two sisters with transferase deficiency galactosaemia presented with hypergonadotropic hypogonadism. In the younger girl galactosaemia was documented first at 9 months of age, although she had never been exposed to exogenous galactose in utero or after birth.

Child, Preschool↗
PubMed1983

Isoenzyme-specific localization of M-line bound creatine kinase in myogenic cells.

Experiments using isolated fibre bundles or myofibrils of chicken skeletal muscle have shown that a relatively small portion of the muscle-specific MM-type of creatine kinase (CK) (EC 2.7.3.2) is specifically bound to the M-line and yet greatly contributes to the electron-dense M-line structure. Here we demonstrate the presence of M-line bound CK in cultured myogenic cells by removing the unbound sarcoplasmic CK through permeabilization with Triton X-100 and extensive washing of the cells prior to immunofluorescence staining. When stained with antibodies specific for M-CK subunits these cells exhibit bright fluorescence within the M-line region of myofibrils. Occasionally this cross-striated pattern is also observed in mononucleated presumably postmitotic myoblasts. Anti-B-CK incubation, in contrast, results in a weak, diffuse fluorescence at the Z-band. Even though these cells contain appreciable amounts of B-type CK, specific fluorescence at the M-line is never observed with anti-B-CK antibody thus ruling out the presence of BB-type or MB-type CK at this location. Therefore the presence of CK within the M-line structure of myogenic cells which contain all three CK isoenzymes seems to be restricted to the MM-type isoenzyme.

Animals↗