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H Moser

Publications and source records attributed to H Moser.

At least 91 records · Page 5Linked to original sources
PubMed1988

Analysis of sub-microgram quantities of nucleotides by fast atom bombardment mass spectrometry.

Nucleotides of the structure P1,Pn-di(adenosine-5')-n-phosphate (n = di- through penta-) in the form of salts, and P1,P4-di(guanosine-5')tetraphosphate sodium salt have been analyzed by fast atom bombardment (FAB) mass spectrometry. A 0.2 molar solution of p-toluenesulfonic acid in glycerol has been evaluated as a matrix. In this matrix, the metal ions of the nucleotide salts are readily exchanged for protons, resulting in a simple spectrum with only one peak in the molecular ion region corresponding to the free phosphoric acid of the nucleotide plus or minus a proton (positive or negative mode), instead of the multiplicity of peaks arising from a series of metal and matrix adduct ions found with glycerol as matrix. The detection limit for analytes using this matrix is improved by a factor of ten compared to glycerol alone. It appears that the high acidity and the surfactant properties of p-toluenesulfonic acid both contribute to this result. Useful spectra are obtained from 250 ng of each of the above mentioned nucleotides, with the detection limit being somewhat lower in the positive mode. However, both positive and negative FAB spectra are useful and the results are complementary.

Chemical Phenomena↗
PubMed1988

Olivopontocerebellar atrophy with retinal degeneration. A clinical and ocular histopathologic study.

The ocular histopathologic and electron microscopic findings were determined in eyes obtained at autopsy from twins with dominant olivopontocerebellar atrophy (OPCA) and retinal degeneration (OPCA type III). On light microscopy, a retinal degeneration that involved primarily the photoreceptor layer was present and appeared to start in the macular area and spread to involve the peripheral fundus. The retinal pigment epithelium was variably hypopigmented and hyperpigmented. On electron microscopy, osmiophilic, multimembranous, and complex lipofuscin inclusions were present in conjunctival cells, keratocytes, lens epithelium, iris and ciliary body fibrocytes, occasional outer retinal cells, and retinal pigment epithelial cells. The twins' father and an older sister were also affected and had classic neurologic and ophthalmologic abnormalities. The similarities were noted between the clinical and ultrastructural findings between OPCA type III and the neuronal ceroid lipofuscinoses.

Adult↗
PubMed1988

Selenium treatment in neuronal ceroid-lipofuscinosis.

Neuronal ceroid-lipofuscinosis (NCL) refers to a group of disorders with devastating effects on the central nervous system. The accumulation of autofluorescent lipopigments containing lipid peroxides is considered a pathogenetic mechanism of the cell damage seen in NCL. Therapy aimed at preventing further lipid peroxidation, such as the Zeman regimen, did not slow progression of the disease. Therefore, Santavuori and Westermarck [Santavuori and Westermarck 1984] introduced treatment with a combination of selenium and vitamin E and reported favorable results with few side effects. We present information on the rationale for the use of selenium, recommendations on the daily intake, and reported side effects. However, our limited experience with selenium in this disorder does not permit conclusions. Additionally, careful studies are indicated before this treatment is dispensed routinely.

Child↗
PubMed1988

Effects of procaine on intracellular pH and its regulation: measurements with pH-selective micro-electrodes in Retzius neurones of the leech.

The experiments were performed with double-barelled micro-electrodes in Retzius neurones of the leech in order to see if the tertiary amine local anesthetic procaine affects intracellular pH (pHi) and its regulation. Lasting about 20 min, exposures to procaine (3 mM) saline caused an intracellular alkalosis of about 0.2 pH units which gradually degradated; its removal initiated a fast decrease of pHi resulting in an acidosis, fron which the cells recovered. Detailed studies, involving CO2 or NH4+ acid loaded cells as well as inhibition of the pHi regulating exchange mechanism by various drugs or exposures to Na-free salines suggest, that neither the Na+ -H+, nor a probably Na+ -dependent HCO3-(-)Cl- exchange are affected by procaine. We propose a model for procaine action on pHi assuming that neutral procaine passes the membrane easily through lipophilic pathways. The degradation of alkalinity during procaine exposure hints on an entry of loaded procaine, some possible transport paths of which are discussed.

Animals↗
PubMed1988

Intracellular calcium changes in Balanus photoreceptor. A study with calcium ion-selective electrodes and Arsenazo III.

Intracellular Ca2+ concentration (Cai) in the dark and during light stimulation, was measured in Balanus photoreceptors with Ca2+ ion-selective electrodes (Ca-ISE) and Arsenazo III absorbance changes (AIII). The average basal Cai of 17 photoreceptors in darkness was 300 +/- 160 nM determined with liquid ion-exchanger (t-HDOPP) Ca-ISE. Ca-ISE measurements indicated that light increased Cai by 700 nM (average), whereas AIII indicated an average change of 450 nM. The time course of AIII absorbance changes matched the time course of changes in the receptor potential more closely than did the Ca-ISE. Changes in Cai were graded with light intensity but the change in Cai was much greater for a decade change in intensity at high light intensity than at low intensity. The peak light induced conductance change of voltage clamped cells had a relationship to light intensity similar to that of the change in Cai. The peak Cai level measured with Ca-ISE was in good agreement with the free Ca2+ concentration of injected buffer solutions. Control Cai levels were usually restored within 5 min following injection of Ca2+ buffers. Injection of Ca2+ buffers with free Ca2+ of 0.6 microM produced a membrane depolarization. Larger increases in Cai (greater than microM) produced by injection of CaCl2 or release of Ca2+ from injected buffers by acidifying the cell, produced a pronounced membrane hyperpolarization. Increasing Cai with all of these techniques reduced the amplitude of the receptor potential. The time course of the receptor potential recovery was usually similar to that of Cai recovery.

Animals↗
PubMed1988

An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus.

Deletions giving rise to Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) occur in the same large gene on the short arm of the human X chromosome. We present a molecular mechanism to explain the clinical difference in severity between DMD and BMD patients who bear partial deletions of the same gene locus. The model is based on the breakpoints of intragenic deletions and their effect on the translation of triplet codons into amino acids of the protein product. Deletions identified in three DMD patients are shown to shift the translational open reading frame (ORF) of triplet codons for amino acids, and each deletion is predicted to result in a truncated, abnormal protein product. Deletions identified in three BMD patients are shown to maintain the translational ORF for amino acids and predict a shorter, lower molecular weight protein. The smaller protein product is presumed to be semifunctional and to result in a milder clinical phenotype. The same ORF mechanism is also applicable to potential 5' and 3' intron splice mutations and their effect on protein production and clinical phenotype.

Adolescent↗
PubMed1988

Recommendations regarding handling of the necropsy in Rett syndrome.

In order to maximize biochemical, neurochemical, molecular, and pathologic information from patients with Rett syndrome, a uniform procedure has been developed for the conduct of the postmortem examination. Tissue should be prepared for freezing, for electron microscopy studies, and for standard histologic examination. For the purposes of uniformity, three central repositories for necropsy materials have been established and are available at all times. In the event of the death of a patient with Rett syndrome, parents who consent to necropsy should request that materials be handled according to the protocol and transported under appropriate conditions to the central repository. The National Neurological Research Bank (Los Angeles), the Brain Tissue Bank (Belmont, Mass), and the Department of Neuropathology at Johns Hopkins Hospital (Baltimore) have agreed to serve as repositories for tissues. A committee of the International Rett Syndrome Association medical advisory panel will monitor this process in cooperation with the directors of the respective tissue banks.

Ammonia↗
PubMed1988

Zellweger syndrome amniocytes: morphological appearance and a simple sedimentation method for prenatal diagnosis.

Zellweger syndrome is the prototype of a growing group of genetic diseases caused by an absence or deficiency of peroxisomes. The defect causes the enzyme catalase to remain in the cytosol instead of being packaged into peroxisomes. This mislocalization can be easily detected by sedimentation analysis. Amniocytes were homogenized and then centrifuged to pellet organelles. Catalase was found to sediment with the peroxisomes in the homogenates of normal cells, but to remain in the supernatant with Zellweger syndrome amniocyte homogenates. This striking difference is unambiguous and reproducible, and provides a simple method for prenatal diagnosis. Moreover, it allows one to differentiate diseases in which peroxisomes are deficient from other peroxisomal diseases in which the organelle is intact, but one enzyme is defective. Electron microscopic observations support the biochemical determinations. Normal amniocytes contain small peroxisomes in which a weak cytochemical reaction for catalase may be demonstrated. Zellweger amniocytes appear to lack these organelles, although some cells have rare structures that might be residual or abnormal peroxisomes.

3,3'-Diaminobenzidine↗
PubMed1987

[Carrier diagnosis and prenatal prognosis using DNA analysis in X-chromosome-linked Duchenne and Becker muscular dystrophy].

Haplotypes for 7 flanking and 16 "intragenic" X-linked DNA polymorphisms were determined in 204 members of 31 families with Duchenne (DMD) and 27 members of 4 families with Becker type muscular dystrophy (BMD) and combined with CK and pedigree data to estimate carrier and fetal risks. All of the 27 younger female relatives of the familial cases (8 DMD, 2 BMD) could either be identified (11) or ruled out (16) as carriers with 95% or higher probability. Out of 49 possible carriers in the 23 DMD and 2 BMD families with isolated cases, 19 were classified as carriers and 18 as homozygote-normal females. In 3 families the mutation could be traced indirectly to a defined ancestor (mother, grand-parent), and in 5 families a molecular deletion was found. In all identified carriers and in medium risk females an informative DNA-constellation for prenatal predictions was present for at least one "intragenic" or two flanking markers. Prenatal DNA-investigations were carried out during pregnancy in 9 possible DMD carriers. There was one termination due to an XYY karyotype. Of the remaining 8 cases, the carrier state could be ruled out in 4 mothers, the fetal sex was female in another 3, and one male fetus was predicted normal. All babies (3 boys, 5 girls) are healthy. The practical significance of these findings with regard to the prevention of DMD/BMD and the present diagnostic strategies are discussed.

Child↗
PubMed1987

Familial deletion in Becker type muscular dystrophy within the pXJ region.

A family of an isolated patient with Becker muscular dystrophy has been investigated by DNA analysis. Southern blotting and hybridization were performed with six probes (C7, pERT87.15, pERT87.1, pXJ1.1, pXJ2.3, 754) mapping in the Xp21 region. A deletion within the pXJ region was demonstrated in the proband, his mother and all three sisters. The segregation pattern for the restriction fragment length polymorphisms (RFLPs) observed with the pXJ probes as well as with pERT87.15, pERT87.1 and 754 probes indicates that the deletion is of grandpaternal origin.

Child↗
PubMed1987

Rett syndrome: new observations.

Two elderly females with Rett syndrome are reported with evidence of a slowly progressive central and distal peripheral nervous system involvement. Thermography in 4 girls confirmed distal hypothermia of the extremities in a glove and stocking distribution. Unilateral sympathectomy during surgery for scoliosis in one of them resulted in increased warmth and physical growth of the foot and nails, compared to the uninjured side. This suggests increased sympathetic tone as the probable cause of distal hypothermia, vasomotor instability and dystrophy of the feet in this disorder. In an attempt to identify a marker, girls with clinically classical Rett syndrome had plasma and urinary cell evaluation for an unusual glycolipid. A blind study using a small number of patients failed to prove absolute specificity and additional studies are required to evaluate its validity as a marker for Rett syndrome.

Adult↗
PubMed1987

Electrophysiological evidence for ammonium as a substitute for potassium in activating the sodium pump in a crayfish sensory neuron.

Electrophysiological studies were performed on slowly adapting cells of the crayfish (Astacus astacus) stretch receptor to examine some aspects of the operation of the sodium pump. Intracellular sodium activity (aiNa) and pH (pHi) were measured with liquid ion exchanger microelectrodes and the effects of NH3/NH+4 were observed. In cells in which the sodium pump was inhibited by K+-free solution, NH+4 induced a decrease of aiNa that can be explained only in Na+ extrusion is assumed. pHi measurements provide indirect evidence that NH+4 was taken up at the same time as Na+ was extruded. Ouabain blocks the operation of the sodium pump in the presence of K+ and NH+4. This result suggests that the ammonium-mediated decrease in aiNa in K+-free solution was caused by activation of the sodium pump. The results obtained by electrophysiological methods in a living cell are qualitatively in good agreement when compared with biochemical investigations on assays of crustacean Na+-K+ ATPase.

Ammonia↗
PubMed1986

Creatine kinase isoenzymes in spermatozoa.

Two isoforms of creatine kinase (CK, E.C. 2.7.3.2), the brain type BB-CK and the mitochondrial-bound MiMi-CK, as well as adenylate kinase (myokinase, E.C. 2.7.4.3) were identified in washed spermatozoa from chicken and man by cellulose polyacetate electrophoresis and immunoblots. BB-CK was localized by indirect immunofluorescence staining within the sperm tail but not in the head portion. MiMi-CK is confined to the midpiece region rich in mitochondria and has been localized directly by immunogold staining within the mitochondria. In contrast to chicken, seminal plasma from man was also found to contain considerable amounts of BB-CK. Total creatine content of spermatozoa (8-15 mM) and seminal plasma (3.8 +/- 0.4 mM) as well as preliminary experiments with metabolic blockers indicate a dependence of sperm motility on CK and phosphoryl creatine (CP). The presence of two CK isoforms located in different 'compartments' of spermatozoa suggests a CP-shuttle in sperm similar to that described for cross-striated muscle.

Animals↗
PubMed1986

High content of creatine kinase in chicken retina: compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells.

Two isoforms of creatine kinase (CK; ATP:creatine N-phosphotransferase, E.C. 2.7.3.2), brain type (BB-CK) and mitochondrial type (MiMi-CK), but not the muscle types (MM- or hybrid MB-CK), were identified by cellulose polyacetate electrophoresis and immunoblots in retina from adult chickens. Indirect immunofluorescence labeling of cryosections of retinas revealed high concentrations of BB-CK in both rod and cone photoreceptor cells. Most of the fluorescence staining with anti-B-CK antibodies was found within the myoid and the ellipsoid portions of inner segments and the peripheral region of the outer segments. Significant staining with anti-B-CK antibodies was also found in horizontal cells and in the optical nerve fibers, with additional stratified staining in the inner plexiform layer. MiMi-CK was solely demonstrated in the ellipsoid portion of the photoreceptor cells. The presence of high concentrations of compartmentalized CK isoenzymes within photoreceptor cells (approximately equal to 30 enzyme units/mg) as well as the relatively high concentration of total creatine in these cells (approximately equal to 10-15 mM) indicates an important physiological function for CK and phosphocreatine in the energy transduction of vision.

Animals↗
PubMed1986

Presence of the peroxisomal 22-kDa integral membrane protein in the liver of a person lacking recognizable peroxisomes (Zellweger syndrome).

Peroxisomes have not been detected in liver and kidney of patients with Zellweger syndrome. Some peroxisome proteins are missing; others are present in normal amounts but are located in the cytosol. We have prepared an antiserum against the 22-kDa integral membrane protein characteristic of rat liver peroxisomes. The antiserum crossreacts with the human liver counterpart, which likewise has a mass of 22 kDa. By immunoblot analysis, we demonstrate that the 22-kDa protein is present in normal amount in Zellweger liver and is integral to a membrane. The result suggests that peroxisome membranes are assembled in Zellweger syndrome but may be defective for the import of matrix proteins. As a result, newly synthesized proteins are left in the cytosol, where some persist and others are degraded. Lacking their usual content, such aberrant peroxisomal membranes would be unrecognizable morphologically. Immunoblot analyses also showed that the peroxisomal hydratase-dehydrogenase is deficient in Zellweger kidney as well as liver, but catalase is present in both organs.

Catalase↗
PubMed1986

The ionic mechanism of intracellular pH regulation in crayfish muscle fibres.

The ionic mechanism of intracellular pH (pHi) regulation was investigated in isolated muscle fibres of the carpopodite adductor in the crayfish Astacus fluviatilis by electrophysiological means with pH, Na+ and Cl- -sensitive liquid ion exchanger micro-electrodes. In eighty-six cells a mean pHi of 7.14 +/- 0.12 (S.D.) at a membrane potential of--79.7 +/- 3.4 mV was found under control conditions which is about one pH unit more alkaline than predicted from passive distribution and indicates the presence of an acid-extrusion mechanism. In order to study pHi recovery the cells were acid loaded by exposure either to NH4 Cl or CO2. The effects of HCO3- and DIDS (an inhibitor of the anion exchange) on pHi recovery as well as the HCO3- -dependent decrease of intracellular Cl- during pHi recovery indicate that in pHi regulation a mechanism of acid extrusion is involved which exchanges extracellular HCO3- for intracellular Cl-. In CO2/HCO3- -free solution or in salines with DIDS, pHi recovery was retarded to the same degree, but the effects were not additive. Because of this the remaining pHi recovery must originate from an HCO3- -independent acid-extrusion mechanism. In Na+ -free solution any pHi recovery was blocked; if pHi recovery occurred it was accompanied by an increase of intracellular Na+ activity (aiNa). From these results it was concluded that all acid extrusion mechanisms which contributed to pHi recovery are coupled to an influx of Na+. A Na+/H+/HCO3-/Cl-, and a separate Na+/H+, exchange are proposed as a model of pHi regulation in the crayfish muscle fibre. Similar kinds of acid extrusion mechanisms are found in the neurone of the crayfish (Moody, 1981), with the difference that in the muscle fibre pHi regulation is achieved mainly by the former process. The rate of pHi recovery is considerably lower in the muscle fibre than in the neurone or in the sensory cell (Moser, 1985) of crayfish.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗