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S T Hsieh

Publications and source records attributed to S T Hsieh.

17 recordsLinked to original sources
PubMed1995

Prolonged axonal survival in transected nerves of C57BL/Ola mice is independent of age.

Interrupted nerve fibres from the C57BL/Ola strain of mouse degenerate after an extraordinary delay compared to nerves of standard laboratory mice. Other investigators, using electrophysiologic methods, concluded that the mutant phenotype diminishes with age, implying that the mutation in C57BL/Ola mice affects a developmentally regulated gene. In an effort to confirm this observation, we studied the course of Wallerian degeneration in C57BL/Ola mice aged 1 through 16 months by using quantitative morphometry, immunohistochemistry, and immunoblotting, but found the period of axonal survival after nerve transection to be no different in old versus young C57BL/Ola mice. We conclude that the C57BL/Ola phenotype of prolonged survival of transected nerves is not affected by age, although certain physiologic measures may degrade in older animals. The persistence of axoplasm after nerve injury in C57BL/Ola mice may be the feature most closely related to the function of the mutant gene.

Action Potentials↗
PubMed1995

Effects of alcohol moderation on blood pressure and intracellular cations in mild essential hypertension.

It is known that moderation of alcohol intake reduces blood pressure, although the exact mechanism has not yet been established. To clarify the hypotensive mechanism of alcohol reduction, we evaluated the change in cellular magnesium and sodium metabolism during alcohol reduction in mild hypertensive patients. We measured intraerythrocyte sodium and magnesium, intraplatelet free magnesium concentrations, and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) in 17 mild essential hypertensive patients regularly consuming more than 40 g/day of alcohol, before and after 4 weeks of alcohol reduction, and 12 age-matched nondrinking hypertensives. Intraerythrocyte magnesium (P < .01) and intraplatelet free magnesium (P < .05) concentrations were significantly lower in drinkers than in nondrinkers. In drinkers, advice to reduce alcohol intake for 4 weeks resulted in a reduction in self-reported alcohol consumption from 461.7 to 71.6 g/week, a significant fall in both supine systolic blood pressure (136.3 +/- 10.8 to 130.8 +/- 11.3 mm Hg, P < .001) and supine diastolic blood pressure (85.1 +/- 8.6 to 82.6 +/- 8.7 mm Hg, P < .05). The fall in mean blood pressure correlated positively with the reduction in weekly alcohol consumption. Intraerythrocyte magnesium and Kos were increased (P < .05, P < .01, respectively), while intraerythrocyte sodium was decreased (P < .01). The increase in intraerythrocyte magnesium correlated negatively with the fall in mean blood pressure and positively with the increase in Kos, which correlated negatively with the decrease in intraerythrocyte sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor neurons.

The carboxy-terminal tail domains of neurofilament subunits neurofilament NF-M and NF-H have been postulated to be responsible for the modulation of axonal caliber. To test how subunit composition affects caliber, transgenic mice were generated to increase axonal NF-M. Total neurofilament subunit content in motor and sensory axons remained essentially unchanged, but increases in NF-M were offset by proportionate decreases in both NF-H and axonal cross-sectional area. Increase in NF-M did not affect the level of phosphorylation of NF-H. This indicates that (a) in vivo NF-H and NF-M compete either for coassembly with a limiting amount of NF-L or as substrates for axonal transport, and (b) NF-H abundance is a primary determinant of axonal caliber. Despite inhibition of radial growth, increase in NF-M and reduction in axonal NF-H did not affect nearest neighbor spacing between neurofilaments, indicating that cross-bridging between nearest neighbors does not play a crucial role in radial growth. Increase in NF-M did not result in an overt phenotype or neuronal loss, although filamentous swellings in perikarya and proximal axons of motor neurons were frequently found.

Amino Acid Sequence↗
PubMed1995

Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy.

OBJECTIVE: To use punch skin biopsies to evaluate the loss of intra-epidermal nerve fibers in sensory neuropathies. BACKGROUND: Previous assessments of epidermal nerve fibers have been constrained by relatively insensitive staining techniques and variability in quantification. METHODS: Punch skin biopsies were performed on the heel and leg of HIV-seronegative controls, HIV-seropositive individuals without neuropathy, and patients with sensory neuropathies, including HIV-seronegative and HIV-positive individuals. After formalin fixation, 50-microns free-floating sections were stained with a monoclonal antibody to neuron-specific ubiquitin hydrolase, PGP9.5. The number of intraepidermal fibers/mm in at least three sections from each patient was counted by one observer blinded to site and clinical status. RESULTS: Dermal and epidermal nerve fibers were readily identified and quantified. The immunostaining technique reliably demonstrated a dermal plexus of myelinated and unmyelinated fibers parallel to the surface of the skin. In the epidermis, unmyelinated fibers ascended vertically between the keratinocytes to reach the stratum corneum. The number of intra-epidermal fibers/mm in the distal leg (mean +/- SEM) was 17.84 +/- 3.03 in seven HIV-seronegative controls. Epidermal fiber number was significantly reduced (p = 0.01) in five HIV-infected patients with sensory neuropathies associated with didanosine or zalcitabine therapy (1.07 +/- 0.40) and in eight HIV-seronegative patients with sensory neuropathies (3.1 +/- 3.1). Four of five neurologically normal HIV-seropositive subjects had reduced numbers of epidermal fibers, suggesting a subclinical neuropathy. Serial biopsies in one individual demonstrated the evolution of degenerating epidermal fibers after development of zalcitabine-induced sensory neuropathy. CONCLUSION: Skin biopsies stained with the sensitive panaxonal marker anti-PGP9.5 demonstrated significant reduction in intraepidermal fibers in sensory neuropathies. This simple and repeatable technique is a reliable method for quantitation of small cutaneous sensory fibers. In addition, skin biopsies may be useful in assessing the course and spatial distribution of involvement in peripheral nerve disease.

Adult↗
PubMed1994

Neurofilament distribution and organization in the myelinated axons of the peripheral nervous system.

The nature of neurofilament organization within the axonal cytoskeleton has been the subject of controversy for many years. Previous reports have suggested that neurofilaments are randomly distributed in the radial dimension of the myelinated axon. Randomness of distribution implies that there is no interaction between neurofilaments, while order in distribution suggest the presence of forces between neurofilaments. To address the issue of randomness vs. order, we evaluated neurofilament distribution by two different statistical approaches--nearest-neighbor distance and the Poisson tile-counting method. Neurofilament nearest-neighbor distances in a myelinated axon differ from nearest-neighbor distances of a set of random points with similar density (40.6 +/- 7.0 nm vs. 30.7 +/- 12.9 nm, P < 0.0001). The Poisson tile-counting method also indicated that neurofilament distribution is different from a random distribution, under conditions of appropriate tile size and masking of other organelles. To further characterize the distribution of neurofilaments, we compared the relationship between nearest-neighbor distance and density for three sets of data: evenly spaced points, randomly distributed points and measured neurofilament coordinates. Neurofilaments do not conform to either evenly spaced or random distribution models. Instead, neurofilament distribution falls into an intermediate position between evenly spaced and random distributions. This study also demonstrates that the nearest-neighbor distance method of assessing neurofilament distribution offers several technical and theoretical advantages to the Poisson tile-counting method.

Animals↗
PubMed1994

Regional modulation of neurofilament organization by myelination in normal axons.

Previous studies in the hypomyelinating mouse mutant Trembler have suggested that demyelinating axons are smaller in caliber compared to normal axons, and that there are differences in the organization of axonal neurofilaments. In the normal PNS, however, the relationship between neurofilament organization and myelination has not been investigated extensively. In normal axons, only the initial segments, the nodes of Ranvier (approximately 1 micron), and the terminals are not covered by myelin. We took advantage of an unusual feature of the primary sensory neurons in the dorsal root ganglion, the relatively long nonmyelinated stem process (up to several hundred micrometers), to determine if the presence of myelination correlates with differences in cytoskeletal organization and neurofilament phosphorylation. Axonal caliber and neurofilament numbers were substantially greater in the myelinated internodes than in the stem process or nodes of Ranvier. Neurofilament spacing, assessed by measuring the nearest-neighbor neurofilament distance, was 25-50% less in the stem processes and nodes of Ranvier than in the myelinated internodes. In the myelinated internodes, neurofilaments had greater immunoreactivity for phosphorylated epitopes than those in the stem process. These findings indicate that interactions with Schwann cells modulate neurofilament phosphorylation within the ensheathed axonal segments, and that increased phosphorylation within myelinated internodes leads to greater interfilament spacing. Lastly, the myelinated internodes had three fold more neurofilaments, but the same number of microtubules. Both the increased neurofilament spacing and the increase in neurofilament numbers in myelinated internodes contribute to a greater axonal caliber in the myelinated internodes.

Animals↗
PubMed1992

Expression of Fos-like immunoreactivity by yohimbine and clonidine in the rat brain.

To elucidate the role of alpha 2-adrenoceptors in transcriptional control in the rat brain, we localized the Fos-like immunoreactivity (Fos-LI) induced by alpha 2-adrenoceptor agonists and by an antagonist. Injections of yohimbine (5 mg/kg, i.p.) into rats led to the induction of Fos-LI in areas with a dense alpha 2-adrenoceptor binding such as the locus coeruleus, the bed nucleus of stria terminalis, the central nucleus of amygdaloid complex, the paraventricular nucleus, the nucleus tractus solitarius, and ventrolateral medulla oblongata. Clonidine (500 micrograms/kg, i.p.) suppressed the Fos expression by yohimbine in these nuclei, and clonidine (100 micrograms/kg, i.p.) or guanabenz (4 mg/kg, i.p.) induced Fos-LI in oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus. Thus, the alpha 2-adrenoceptor is involved in transcriptional control via Fos expression in neurons related to autonomic and other functions.

Animals↗
PubMed1992

Magnesium supplementation prevents the development of alcohol-induced hypertension.

The effect of chronic alcohol administration on blood pressure was investigated in 7-week-old Wistar rats. Tail-cuff blood pressure was significantly higher in rats who received 15% ethanol in drinking water than in control rats. Intracellular free calcium concentration of lymphocytes was increased, while magnesium concentration of erythrocyte, aorta, and skeletal muscle and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) were decreased in alcohol-induced hypertensive rats but not in control rats. Extracellular fluid volume was also increased in alcohol-administered rats. Oral magnesium supplementation (1% MgO in rat chow) attenuated the development of alcohol-induced hypertension accompanied by increased magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos and decreased intraerythrocyte sodium concentration. Norepinephrine half-life time of the heart and spleen was also increased in magnesium-supplemented rats. Blood pressure significantly correlated positively with intracellular calcium concentration and extracellular fluid volume, negatively with magnesium concentration of erythrocyte, aorta, skeletal muscle, and Kos. These results suggest that increased intracellular calcium, which was partly due to magnesium depletion and suppressed sodium pump activity, and expanded body fluid volume had a possible role in the development of alcohol-induced hypertension. It is also suggested that oral magnesium supplementation had a hypotensive effect on alcohol-induced hypertension possibly through decreased intracellular sodium concentration caused by an activation of sodium pump and decreased sympathetic nervous activity.

Animals↗
PubMed1987

Direct power-frequency electric field effects on mammalian endocrine tissue.

A number of studies have investigated the in vivo biological effects of power-frequency electric fields (EF). Direct effects of EF on mammalian tissues, however, have rarely been reported. We now report that a 60-Hz EF can directly enhance the steroidogenic response of superfused rat adrenocortical tissue. The EF did not influence basal steroidogenic activity, however, the corticosterone response to 10 mU of ACTH was almost doubled by an unperturbed 1000 kV/m EF during the initial 2 hr of exposure and was enhanced fourfold by 5.5 to 7 hr of exposure with a 10 kV/m EF. Other EF intensities (e.g., 5 and 100 kV/m) were without effect at these times. Turning the 1000 kV/m EF on and off at 30-min intervals did not influence the initial enhanced steroidogenic response but did cause an additional two- to threefold elevation in the response following 5.5-7 hr of exposure. It is not clear what EF exposure parameters or mechanisms were primarily responsible for these bioeffects, but it appears that direct exposure of mammalian endocrine tissue to a 60-Hz EF is capable of significantly influencing important cellular processes.

Adrenal Cortex↗
PubMed1986

Chronic 60-Hz electric field exposure-induced subtle bioeffects on hematology.

The effects of 120 days of high-intensity (80-kV/m) 60-Hz electric field exposure on hematologic constituents were investigated using a three-generation design including 135 field-exposed and 135 sham-exposed male Sprague-Dawley rats. Statistical tests performed included the multivariate analysis of variance, the univariate analysis of variance, and tests of simple effects. Total white cell count, lymphocyte count, and eosinophil count were significantly lower in field-exposed subjects; however, none of the red cell parameters differed significantly. The observed hematologic variations related to the exposure of a high-intensity electric field are consistent with those observed in animals responding to a mild stressor.

Analysis of Variance↗
PubMed1976

Electromagnetic induced kinetic effects on charged substrates in localized enzyme systems.

An analytical expression for the rate efficiency factor of planar localized enzyme systems is derived. The derivation takes into account the isothermal kinetic effect under the externally imposed perturbation of combined electrostatic and high frequency time-varying fields. The contribution of each individual field to the enzyme reaction is examined through the basic mechanism in which charged substrates interact with the specific perturbing field. The interaction mechanisms for the electrostatic and for the time-varying fields are found to be different. This difference regulates the different manners in which enzymatic reaction rates are altered. Enzymatic reactions under electrostatic perturbation can be retarded or enhanced depending on the field polarization. At sufficiently high field intensities the reaction rate may approach zero or approach a maximum value equal to the turnover number of the enzyme. Time-varying field perturbations, on the other hand, always enhance the enzymatic reactions if bunching effects are negligible. At sufficiently high field intensities, the reaction may approach a value equal to that of the free enzyme system. Several typical numerical examples on pure eletrostatic field perturbations, pure time-varying field perturbations, and combined field perturbations are also presented.

Electromagnetic Phenomena↗
PubMed1976

Reaction of nitrosamines in the Udenfriend system: principal products and biological activity.

Reaction of diethylnitrosamine in the non-enzymatic, ascorbic acid-dependent, hydroxylating system of Udenfriend yielded N-nitroso-2-(ethylamino)-ethanol as the major product extracted into methylene chloride. The major product derived from nitrosopiperidine in the same system was N-nitroso-4-piperidone. These products, however, were mutagenic to Salmonella typhimurium TA 1535 only when activated by a rat liver microsomal preparation.

Animals↗
PubMed1975

Chromatographic separation of conformers of substituted asymmetric nitrosamines.

The syn and anti conformers of N-nitrosoproline, N-nitrososarcosine and N-nitroso-2-(ethylamino)-ethanol, have been separated by liquid chromatography. These conformers result from hindered rotation about the N-N bond. Separation was achieved using adsorption, reversed-phase, and ion-exchange modes. For the nitroso-amino acids, a shift in the equilibrium conformer concentration was observed with changes in pH.

Chromatography↗