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Biomedical subjects

H Moser

Publications and source records attributed to H Moser.

At least 37 records · Page 2Linked to original sources
PubMed1998

Concomitance of childhood absence and Rolandic epilepsy.

Five children (3 girls and 2 boys) who showed generalized synchronous 3/sec spike and wave complexes as well as centrotemporal spikes in the same EEG or in different EEGs are described. Among these five patients only 1 boy and 1 girl showed clinically both absence seizures and partial motor seizures with or without secondary generalization. One girl and 1 boy have only absences and the other girl only partial motor seizures. A concomitance of generalized synchronous 3/sec spike and wave discharges and centrotemporal spikes in the same patient is rarely found. The clinical manifestation of absences and partial motor seizures in the same patient is extremely rare.

Child↗
PubMed1997

Uptake of various trace elements during germination of wheat, buckwheat and quinoa.

The practice of sprouting is widely used to improve the nutritional value of grain seeds. Several nutritive factors such as vitamin concentrations and bioavailability of trace elements and minerals increase during germination. The objective of this work was to study the enrichment of various essential trace elements during germination of wheat (Triticum aestivum), buckwheat (Fagopyrum esculentum), and quinoa (Chenopodium quinoa) seeds in order to improve their nutritional role as a source of bioavailable trace elements. Seeds were sprouted either in distilled- or tap-water and in five different electrolyte solutions to investigate the concentration-dependent uptake. The time-dependence was investigated by analyzing aliquots of the sprouts after certain germination periods. Samples were analyzed after freeze drying for their Li, V, Cr, Fe, Mn, Co, Cu, Zn, Sr, Mo, As and Se concentrations with inductively-coupled plasma mass-spectrometry (ICP-MS). As a control for possible changes in the biochemical metabolism of the sprouts, the biosynthesis of vitamin C was also determined by using reversed-phase ion-pair HPLC. It was shown that quinoa was the most resistant to the applied electrolyte solutions and had the highest uptake rates for almost all elements, followed by buckwheat and wheat. Greatest increases were observed for Co, Sr, and Li. No significant changes in vitamin C biosynthesis were observed between sprouts grown in different electrolyte solutions. The time-dependent uptake for most elements was characterized by a significant absorption during soaking of the seeds, followed by a lag phase during the first day of germination and an increased uptake during the second and third day. Se and As showed distinctly different uptake behaviors.

Ascorbic Acid↗
PubMed1997

A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype.

We have analysed 1173 cystic fibrosis (CF) chromosomes from Switzerland for eight mutations in the CF transmembrane conductance regulator (CFTR) gene. This permitted the identification of 88.5% of all mutations present. A novel insertion mutation in exon 20 of the CFTR gene, 3905insT, was discovered. This mutation accounted for 4.8% of CFTR gene mutations in Switzerland and has since been identified in other populations of probable Swiss descent. It is associated with a highly variable clinical phenotype but always with pancreatic insufficiency. Haplotype analysis with three intragenic microsatellites in the CFTR gene showed that the mutation is associated with a haplotype rarely identified on other CFTR alleles and, therefore, that the frequency of the mutation in Switzerland is explained by a founder effect of a relatively recent mutation event.

Cystic Fibrosis↗
PubMed1997

Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata.

Rhizomelic chondrodysplasia punctata (RCDP) is a rare autosomal recessive phenotype that comprises complementation group 11 of the peroxisome biogenesis disorders (PBD). PEX7, a candidate gene for RCDP identified in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2). By homology probing we identified human and murine PEX7 genes and found that expression of either corrects the PTS2-import defect characteristic of RCDP cells. In a collection of 36 RCDP probands, we found two inactivating PEX7 mutations: one, L292ter, was present in 26 of the probands, all with a severe phenotype; the second, A218V, was present in three probands, including two with a milder phenotype. A third mutation, G217R, whose functional significance is yet to be determined, was present in five probands, all compound heterozygotes with L292ter. We conclude that PEX7 is responsible for RCDP (PBD CG11) and suggest a founder effect may explain the high frequency of L292ter.

Amino Acid Sequence↗
PubMed1997

Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases lethal in early infancy. Although the clinical features of PBD patients may vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologues of yeast PEX genes have been shown to be defective in some groups of PBD patients. We identified a putative human orthologue of ScPEX12 by screening the database of expressed sequence tags for cDNAs capable of encoding a protein similar to yeast Pex12p. Although its sequence similarity to yeast Pex12 proteins was limited, PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane. PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complement group 3 (CG3) and frameshift mutations in PEX12 were detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import.

Amino Acid Sequence↗
PubMed1996

Sequence-specific antitumor activity of a phosphorothioate oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense mechanism of action in vivo.

To determine the mechanism of action responsible for the in vivo antitumor activity of a phosphorothioate antisense inhibitor targeted against human C-raf kinase (ISIS 5132, also known as CGP69846A), a series of mismatched phosphorothioate analogs of ISIS 5132 or CGP69846A were synthesized and characterized with respect to hybridization affinity, inhibitory effects on C-raf gene expression in vitro, and antitumor activity in vivo. Incorporation of a single mismatch into the sequence of ISIS 5132 or CGP69846A resulted in reduced hybridization affinity toward C-raf RNA sequences and reduced inhibitory activity against C-raf expression in vitro and tumor growth in vivo. Moreover, incorporation of additional mismatches resulted in further loss of in vitro and in vivo activity in a manner that correlated well with a hybridization-based (i.e., antisense) mechanism of action. These results provide important experimental evidence supporting an antisense mechanism of action underlying the in vivo antitumor activity displayed by ISIS 5132 or CGP69846A.

Animals↗
PubMed1996

Biosynthesis of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine of cyclosporin A: enzymatic analysis of the reaction sequence including identification of the methylation precursor in a polyketide pathway.

3(R)-Hydroxy-4(R)-methyl-6(E)-octenoic acid, the C9-backbone of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (Bmt), is biosynthesized as a coenzyme A thioester from acetyl-CoA, malonyl-CoA, NADPH, and S-adenosylmethionine via a polyketide pathway. Here we present detailed enzymatic studies about the basic assembly process. After attachment of the activated building units to Bmt polyketide synthase the intermediates remained enzyme-bound throughout the cycle. Premature cutoff of biosynthesis led to the release of the intermediates from the enzyme, either as coenzyme A thioesters or, in the case of reactive C8-intermediates, as lactones. Enzyme-bound 3-oxo-4-hexenoic acid, the condensation product of the second elongation cycle, could be identified as the exclusive substrate for the introduction of the methyl group. Part of the biosynthesis including the first elongation cycle, the second condensation reaction, and the methylation step was shown to follow a processive mechanism. All activated intermediates of this processive part could be introduced into the correct pathway at the respective steps, whereas 2-methyl-3-oxo-4-hexenoyl-CoA and all following methylated intermediates were not able to enter the cycle any more. Obviously, the region of Bmt polyketide synthase responsible for this latter part of the biosynthetic pathway is inaccessible for externally supplied coenzyme A thioesters. Butyryl-CoA was recognized by Bmt polyketide synthase with an efficiency comparable to that of crotonyl-CoA and processed to 3-hydroxy-4-methyloctanoyl-CoA, the saturated analog of the natural basic assembly product, indicating a relaxed specificity of Bmt polyketide synthase with respect to the starter unit.

Chromatography, Thin Layer↗
PubMed1996

[Molecular genetic diagnosis and deletion analysis in Type I-III spinal muscular atrophy].

Autosomal recessive spinal muscular atrophy (SMA) is, after cystic fibrosis, the second most common fatal monogenic disorder. The disease is characterized by degeneration of anterior horn cells leading to progressive paralysis with muscular atrophy. Depending on the clinical type (Werdnig-Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III), SMA causes early death or increasing disability in childhood. The SMA-critical region on the long arm of chromosome 5q13.1 contains many duplicated genes and polymorphisms. Recently, two presumptive SMA genes (survival motoneuron gene = SMN, and neuronal apoptosis inhibitory protein = NAIP) have been identified. Deletions involving critical regions of these genes are very often associated with SMA, and the extent of the deletions seems to correlate in part with disease severity. We have evaluated the diagnostic and prognostic value of molecular analysis in a large number of SMA patients. 57 patients and 78 healthy relatives were molecularly screened for deletions in the SMA critical region. We demonstrated homozygous deletions removing the SMN genes in over 90% of patients, whereas nearly 45% of patients exhibited NAIP gene deletions. Large deletions involving both genes on each chromosome are generally found in patients with severe SMA (Werdnig-Hoffman cases), while mildly affected Kugelberg-Welander cases frequently show only deleted SMN genes. Molecular classification based on combined deletion sizes, however, seems not to be exact, especially for the group with chronic SMA (type II and III). Direct DNA testing of patients in whom SMA is suspected is a highly reliable, fast, and noninvasive method. The ability to detect homozygous gene deletions in a high percentage of typical SMA patients will much improve genetic counselling and prenatal diagnosis in affected families.

Adult↗
PubMed1996

Effect of the CO2 milliwatt laser on neuroma formation in rats.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether the milliwatt laser can suppress neuroma formation at the end of a divided nerve. STUDY DESIGN/MATERIALS AND METHODS: The peripheral nerves of eight rats were transected with microscissors and the cross-sectional area of their proximal ends was irradiated using the CO2 milliwatt laser. The power ranges used were similar to those applied to weld neural tissue. RESULTS: None of the eight irradiated nerve ends formed a neuromatous bulb and only one of them regenerated into the surrounding tissues. Histologically, these nerve ends did not show the disorganized picture of classic neuromas. On morphometric measurements, they contained less connective tissue than the control nerve ends (P < 0.001) and their nerve fibers were larger in diameter (P < 0.001) and better myelinated (P < 0.001). CONCLUSION: These findings in rats show that the CO2 milliwatt laser has the ability to suppress neuroma formation at the end of a divided nerve.

Animals↗
PubMed1996

Effect of erucic acid on platelets in patients with adrenoleukodystrophy.

In a clinical trial for the management of adrenoleukodystrophy, we analyzed the effect of erucic acid (a component of Lorenzo's oil) on platelet number, fatty acid composition, and function. Analysis of variance was performed to compare platelet counts before starting treatment with Lorenzo's oil and at 6 and 12 months. We measured platelet fatty acid composition in subjects and control patients and correlated these values with their platelet counts using discriminant analysis. After 6 months, the mean platelet count decreased from 247,000/mm3 to 169,000/mm3 (+/- 1 standard deviation 58,000,n =39), P < 0.0001 compared to 18 subjects on a control diet having a mean baseline platelet count of 259,000/mm3 (+/- 1 standard deviation 67,000, n = 19) and at 6 months 267,000/mm3 (+/- 1 standard deviation 71,000). We found at P < 0.05 that the platelet counts showed a strong inverse relationship with erucic acid levels and other omega 9 fatty acids that form from the administration of the erucic acid component of Lorenzo's oil. Morphologic and platelet sizing measurements suggest that the physical properties of platelets may also be affected by erucic acid. Our studies show that the ingestion of erucic acid affects platelet biology. This indicates that platelet counts and properties are influenced by monounsaturated fatty acids, in addition to the well-known effects of polyunsaturated fatty acids. In areas of the world where erucic acid is widely ingested, the biology of platelets in these populations may be affected.

Adrenoleukodystrophy↗
PubMed1996

Predominantly posterior instrumentation and fusion in neuromuscular and neurogenic scoliosis in children and adolescents.

We studied the results in 46 patients with neuromuscular and neurogenic scoliosis (average age 13.5 years, range 6-19 years) who had had posterior fusion with a modified Luque technique between May 1985 and June 1992. The main criteria to recommend surgery were curve progression, loss of balance when sitting, control of the head and difficulties in wearing an external orthotic support. The mean preoperative curve was 63 degrees, the postoperative value was 24 degrees, representing a correction of about 62%. The average number of stabilized segments was 13. In 39 out of 46 patients, lumbosacral fixation was included in the construct. Failure of implants, pseudarthroses and major losses of correction in purely neuromuscular scolioses could be avoided by using rigid segmental fixation and a dorsolateral fusion with a mixture of autologous and allogenous bone. The scoliosis most difficult to influence was found to be Friedreich's ataxia. In Duchenne muscular dystrophy the best method of treatment was surgery performed as early as possible, i.e. at the time of loss of walking capacity in the case of a scoliosis exceeding 20 degrees and with two consecutive X-rays proving curve progression. Analysis of our series does not confirm the morbidity and complication rates of previous studies.

Adolescent↗
PubMed1996

Extracellular Ca2+ and its effect on acid extrusion in the crayfish stretch receptor neurone

1. In the stretch receptor neurones of the crayfish Astacus astacus, the intracellular pH (pHi), the intracellular Na+ concentration ([Na+]i) and the membrane potential (Em) were measured simultaneously using ion-selective and conventional microelectrodes. Normal Astacus saline (NAS), and salines containing varying amounts of Ca2+ (Ca2+-NAS) but of constant ionic strength, with Na+, Mg2+ or Ba2+ as substituting ions, were used to investigate the effects of extracellular Ca2+ concentration ([Ca2+]o) on pHi and pHi regulation, on [Na+]i and on Em. The maximum rate of pHi recovery was used as a measure of pHi regulation. Acid loads were imposed using the NH4+/NH3 rebound technique. 2. [Ca2+]o affected pHi, pHi regulation, [Na+]i and Em. The magnitudes of the effects were inversely related to [Ca2+]o and were specific to the ion used for [Ca2+]o substitution. 3. Compared with controls, increasing [Ca2+]o threefold (in exchange for Na+) elicited some alkalization, a 7 % faster maximum rate of pHi recovery and generally lower values of [Na+]i. 4. In low-Ca2+ or Ca2+-free NAS (substitutions by Na+ or Mg2+), pHi became more acid, the maximum rate of pHi recovery was reduced by up to 50 % and [Na+]i was generally higher. The effects were faster and larger at lower [Ca2+]o, and stronger with Na+ than with Mg2+ as the substituting ion. 5. In Ca2+-free NAS (Ca2+ substituted for by Ba2+), the effects on pHi, on the maximum rate of pHi recovery and on [Na+]i were generally small. In this respect, Ba2+ had similar physiological properties to Ca2+ and was almost equally effective. 6. Changes in Em, including rapid depolarizations and occasional burst activity in Ca2+-free NAS, indicate that alterations in the properties of the membrane, such as a change in its permeability or selectivity, are occurring. Measurements of [Na+]i support this view. In addition, Ba2+ per se induced a (small) depolarization, as shown when Ba2+ was present in NAS or in low-Ca2+ NAS. 7. Changes in [Ca2+]o affected [Na+]i. *[Na+]i is defined as [Na+]i determined at the onset of the maximum rate of pHi recovery, and the ratio *[Na+]i/[Na+]o at that instant was calculated. A linear relationship between the maximum rate of pHi recovery and the *[Na+]i/[Na+]o ratio was found, irrespective of the amount and of the ion species used for [Ca2+]o substitution. This is strong evidence that pHi and pHi regulation were indirectly affected by [Ca2+]o, which altered membrane properties and thus caused a change in [Na+]i. We could find no evidence for a direct contribution of [Ca2+]o to acid extrusion or to a direct modulatory action on the transport protein of the Na+/H+ antiporter.

Journal Article↗
PubMed1995

The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies.

Clinical differences exist between the three forms of myotubular myopathy. They differ regarding age at onset, severity of the disease, and prognosis, and also regarding some of the clinical characteristics. The autosomal dominant form mostly has a later onset and milder course than the X linked form, and the autosomal recessive form is intermediate in both respects. These differences are, however, quantitative rather than qualitative. Muscle biopsy studies of family members are useful in some cases, and immunohistochemical staining of desmin and vimentin may help distinguish between the X linked and autosomal forms. Determining the mode of inheritance and prognosis in individual families, especially those with a single male patient, still poses a problem. Current molecular genetic results indicate that the gene for the X linked form is located in the proximal Xq28 region. Further molecular genetic studies are needed to examine the existence of genetic heterogeneity in myotubular myopathy and to facilitate diagnosis.

DNA↗
PubMed1995

Interactions of a very long chain fatty acid with model membranes and serum albumin. Implications for the pathogenesis of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an inherited disorder of fatty acid metabolism marked by accumulation of very long chain saturated fatty acids (VLCFA), especially the 26-carbon acid, hexacosanoic acid (HA), in membranes and tissues. We have studied interactions of 13C-enriched HA with model membranes (phospholipid bilayer vesicles) and bovine serum albumin (BSA) by 13C NMR spectroscopy to compare properties of HA with those of typical dietary fatty acids. In phospholipid bilayers the carboxyl group of HA is localized in the aqueous interface, with an apparent pKa (7.4) similar to other fatty acids; the acyl chain must then penetrate very deeply into the membrane. Desorption of HA from vesicles (t1+2 = 3 h) is orders of magnitude slower than shorter chain fatty acids. In mixtures of vesicles and BSA, HA partitions much more favorably to phospholipid bilayers than typical fatty acids. BSA binds a maximum of only 1 mole of HA at one binding site. Calorimetric experiments show strong perturbations of acyl chains of phospholipids by HA. We predict that disruptive effects of VLCFA on cell membrane structure and function may explain the neurological manifestations of ALD patients. These effects will be further amplified by slow desorption of VLCFA from membranes and by the ineffective binding to serum albumin.

Adrenoleukodystrophy↗
PubMed1995

X-linked adrenoleukodystrophy presenting as neurologically pure familial spastic paraparesis.

The familial spastic paraplegias (FSPs) are heterogeneous neurologic disorders that are known to occur clinically as "pure" or "complicated" forms. Although some of the complicated FSPs have been linked to specific metabolic defects, the pure forms of this disorder remain idiopathic and are considered to be primary system degenerations. We report the case of a 28-year-old man who has evidenced a neurologically pure spastic paraparesis since age twenty-five. Consistent with this diagnosis were the findings of magnetic resonance imaging, which revealed atrophy of the thoracic spinal cord without evidence for white matter disease in the cerebrum, cerebellum, or brainstem. His 32-year-old brother has also evidenced progressive spastic paraparesis since age 30, but his case is confounded by a severe head injury at age 24 that caused a skull fracture and a focal demyelinating lesion of the right frontal lobe. Both patients have had hypogonadism, requiring treatment with testosterone, since age 20. Measurement of plasma levels of very long-chain fatty acids (VLCFA) revealed that both brothers had concentrations diagnostic of adrenoleukodystrophy; their mother had plasma VLCFA levels in the heterozygous range. We conclude that neurologically pure FSP can be an early manifestation of adrenoleukodystrophy and that levels of plasma VLCFA should be determined for all cases of FSP in which X-linked inheritance appears tenable. These considerations may have bearing on the ongoing linkage studies for these disorders.

Adrenoleukodystrophy↗
PubMed1995

[Diagnostic studies in patients and relatives with hereditary neuromuscular diseases].

Preclinical and prenatal diagnosis as well as detection of healthy carriers is now theoretically possible for more than 200 monogenic inherited neurological and neuromuscular diseases and practically performed in many of them. However, it has to be made a condition, that the diagnosis in the index patient is secured by all clinical and laboratory methods available today, and that the specific mutation has been localized or even sequenced, and of course the families must give their full consent to the examinations. It is important to submit material for the different laboratory investigations from patients and their relatives as early as possible [biopsies, blood samples for DNA, etc.], at least for rapidly progressive diseases with a poor prognosis. In order to obtain very high probabilities in diagnostic predictions a family has to be examined either with mutation-specific DNA-probes and/or with probes for closely linked polymorphic DNA-markers. This requires a close cooperation between genetic services and DNA-laboratories on the one hand and the family doctors, specialists and clinics on the other. Specific strategies are discussed for hereditary sensory and motor neuropathy [HMSN la or Charcot-Marie-Tooth disease], Duchenne und Becker muscular dystrophy and childhood spinal muscular atrophies.

Charcot-Marie-Tooth Disease↗