bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal distribution of EHSH1/intersectin: Molecular linker between clathrin‐mediated endocytosis and signaling pathways
Authors: Ma Yong Jie , Okamoto Masaya , Gu Feng , Obata Kyoko , Matsuyama Tomohiro , Desaki Junzo , Tanaka Junya , Sakanaka Masahiro
Published: January 2003

Recent research indicates that the novel multimodular adaptor protein EHSH1 plays an important role in a partnership between clathrin‐mediated endocytosis and intracellular signaling pathways, including the MAPK pathway, receptor‐tyrosine kinase/ras‐mediated pathway, and the rho family of the GTPase‐dependent pathway. We report the detailed expression pattern of EHSH1 in the rat CNS, using separate cultures of neurons, astrocytes, and microglia, and biochemical and immunohistochemical analyses. Cultured neurons from the cortex express primarily the long isoform EHSH1‐l, as well as a small amount of the short isoform EHSH1‐s. Cultured astrocytes express EHSH1‐s, at a level similar to neurons, and a trace of EHSH1‐l. Cultured microglia express only EHSH1‐s. Double immunofluorescent staining of cortical sections showed that EHSH1 is expressed predominantly in neurons. These results suggest that EHSH1‐l is a primary isoform and that EHSH1‐l is highly enriched in neurons in the rat adult CNS. Immunohistochemistry of a series of brain sections revealed widespread distribution of EHSH1 throughout the brain. Particularly intense immunoreactivity was observed in the somatodendritic region of neurons in Layer III of the neocortex, hippocampus, globus pallidus, subthalamic nucleus, and substantia nigra. Interestingly, all pyramidal neurons in Layer III of the neocortex and hippocampus did not necessarily exhibit equal levels of immunostaining. In contrast, little EHSH1 immunoreactivity was detected in septofimbrial nucleus and subfornical organ of the septal region, and solitary tract and external cuneate nuclei of the medulla. Variety in the expression of EHSH1 in neurons of different regions may reflect different conditions in clathrin‐mediated endocytosis and the following signal transduction. © 2002 Wiley‐Liss, Inc.
Gastrodin decreases immunoreactivities of γ‐aminobutyric acid shunt enzymes in the hippocampus of seizure‐sensitive gerbils
Authors: An Sung‐Jin , Park Seung‐Kook , Hwang In Koo , Choi Soo Young , Kim Sang Kook , Kwon Oh‐Shin , Jung Sung Je , Baek Nam‐In , Lee Hyeon Yong , Won Moo Ho , Kang Tae‐Cheon
Published: January 2003

Gastrodin is one of the natural compound isolated from Gastrodia elata and has known anticonvulsant effects, although the exact pharmacological principles of this natural compound and its effects on other aspects of γ‐aminobutyric acid (GABA) metabolism in vivo have not been explored. Therefore, in the present study, the effects of gastrodin on GABA metabolism in the gerbil hippocampus were examined, in an effort to identify the antiepileptic characteristics of this substance. Gastrodin reduced the seizure score in the treated group, although the immunoreactivities of GABA synthetic enzymes and GABA transporters were unaltered in gastrodin‐treated animals. Interestingly, in the gastrodin‐treated group, GABA transaminase (GABA‐T) immunoreactivity in the hippocampus, particularly in neurons, was significantly decreased. In the gastrodin‐treated group, both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities in the hippocampus was also decreased significantly, which stood in contrast to the nontreated group, in which strong SSADH and SSAR immunoreactivities were detected. From the neuroanatomical viewpoint, these findings suggest that gastrodin may cause the elevation of GABA concentration by inhibiting the GABA shunt. © 2002 Wiley‐Liss, Inc.
Human neuronal cells (NT2‐N) express functional substance P and neurokinin‐1 receptor coupled to MIP‐1β expression
Authors: Li Yuan , Douglas Steven D. , Pleasure David E. , Lai Jianping , Guo Changjiang , Bannerman Peter , Williams Marge , Ho Wenzhe
Published: January 2003

Substance P (SP), the most extensively studied and potent member of the tachykinin family, is a major modulator of inflammation and immunomodulatory activities within the central and peripheral nervous systems. We have examined the gene expression of SP and its receptor in a human neuronal cell line (NT2‐N). Using reverse transcribed polymerase chain reaction (RT‐PCR), the four isoforms of preprotachykinin‐A gene transcripts (α, β, γ, and δ) were detected in the NT2‐N. We also identified the presence of mRNA for neurokinin‐1 receptor (NK‐1R), a primary receptor for SP, in the NT2‐N cells. Concomitant with NT2 cell differentiation into neurons, SP and NK‐1R mRNA expression increased consistently. Intracellular SP and cell membrane NK‐1R immunoreactivity were all observed in NT2‐N cells. Most importantly, we demonstrated that SP and NK‐1R presented in NT2‐N cells are functionally involved in the regulation of macrophage inflammatory protein 1 beta (MIP‐1β), an important β‐chemokine participating in the activation and directional migration of immune cells to sites of central nervous systems (CNS) inflammation. Thus, SP and its receptor may play an important role in modulation of neuronal functions related to regulation of immune activities within the CNS. The NT2‐N cell line is well suited for in vitro investigations of the SP‐NK‐1R pathway in immune responses and inflammation in the CNS. © 2002 Wiley‐Liss, Inc.
Inactivation of aconitase during the apoptosis of mouse cerebellar granule neurons induced by a deprivation of membrane depolarization
Authors: Tabuchi Akiko , Funaji Kouhei , Nakatsubo Jun , Fukuchi Mamoru , Tsuchiya Tomofusa , Tsuda Masaaki
Published: January 2003

During the excitotoxic neuronal cell death which accompanies an overflow of extracellular Ca2+ into neurons, aconitase, an oxidative stress‐sensitive enzyme of the tricarboxylic acid (TCA)‐cycle in mitochondria, is inactivated due to the generation of oxidative stress (Patel et al. [1996] Neuron 16:345–355). In this study, we investigated whether aconitase could be inactivated during the apoptosis of mouse cerebellar granule cells (CGCs), which was caused by a deprivation of membrane depolarization followed by a stoppage of Ca2+ influx into CGCs. Upon lowering the potassium (K+) concentration in medium from 25 to 5 mM (low K+), aconitase was inactivated in accordance with the decrease in methylthiazoletetrazolium (MTT)‐reducing activity although its mRNA expression did not change. The blockade of Ca2+ influx into CGCs mediated by nicardipine at 25 mM KCl also caused the inactivation of aconitase, accompanying induction of the apoptosis of CGCs. Suppression of the apoptosis of CGCs mediated by the Ca2+ influx or neurotrophic factors such as brain‐derived neurotrophic factor (BDNF) and adenylate cyclase activating polypeptide‐38 (PACAP‐38) attenuated the aconitase inactivation as well as the lactate dehydrogenase (LDH)‐release and the decrease in MTT reduction. On the other hand, the levels of intracellular glutathione and manganese superoxide dismutase‐2 mRNA decreased under the low K+ condition, supporting a cause for oxidative stress at low K+ due to a loss of anti‐oxidant activity. Thus, the inactivation of aconitase is also caused by a deprivation of Ca2+ influx into neurons, suggesting that aconitase is a key mitochondrial enzyme influencing the viability of neurons in response to oxidative stress. © 2002 Wiley‐Liss, Inc.
Enhanced tissue plasminogen activator synthesis by the sympathetic neurons that innervate aging vessels
Authors: Jiang Xi , Hand Arthur R. , Shen Shujing , Cone Robert E. , O'Rourke James
Published: January 2003

We investigated the source of the increased release of tissue plasminogen activator (t‐PA) into the circulation that occurs during natural aging. Both the basal release and the acute stress‐associated release induced by sympathetic stimulations are greater in older subjects. It is widely assumed that the source of these increases is vascular endothelium. However, the sympathetic neurons that densely innervate resistance vessel walls were recently shown to synthesize and transport active t‐PA to axon terminals in vascular smooth muscle, suggesting an alternative source. These fine t‐PA‐bearing axons lie in the seldom‐studied deep adventitia of vessel walls, where they are less visible than endothelium in tissue sections. Using Northern blot analysis, we observed that t‐PAmRNA synthesis is increased 54% in the ganglion parent neuron cell bodies that innervate aged vessels. The t‐PA release from isolated, aged ganglia in cultures was twofold greater than that from younger controls. In addition, aged whole‐artery explants showed a 20% greater basal and a 50% greater acute release of stored t‐PA in vitro. In vivo levels of active t‐PA were 33% greater in the blood and 40% greater in the aqueous humor. These results are consistent with an increased infusion of the active t‐PA protease from sympathetic axon terminals into the vessel wall extracellular matrix and the blood during natural aging, in addition to the basal endothelial release. We suggest that the cumulative impact of an accelerated plasmin production and matrix degradation within vessel walls, especially during repetitive stress, may play an unrecognized role in the pathogenesis of vascular aging. The possibility that increased sympathetic nervous system plasminogenesis influences the aging process in nonvascular tissues also deserves further investigation. © 2002 Wiley‐Liss, Inc.
Involvement of microglia–neuron interactions in the tumor necrosis factor‐α release, microglial activation, and neurodegeneration induced by trimethyltin
Authors: Eskes C. , Juillerat‐Jeanneret L. , Leuba G. , Honegger P. , Monnet‐Tschudi F.
Published: January 2003

Trimethyltin (TMT) is a neurotoxicant known to induce early microglial activation. The present study was undertaken to investigate the role played by these microglial cells in the TMT‐induced neurotoxicity. The effects of TMT were investigated in monolayer cultures of isolated microglia or in neuron‐enriched cultures and in neuron–microglia and astrocyte–microglia cocultures. The end points used were morphological criteria; evaluation of cell death and cell proliferation; and measurements of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and nitric oxide (NO) release in culture supernatant. The results showed that, in cultures of microglia, TMT (10−6M) caused, after a 5‐day treatment, an increased release of TNF‐α, without affecting microglial shape or cell viability. When microglia were cocultured with astrocytes, TNF‐α release was decreased to undetectable levels. In contrast, in neuron–microglia cocultures, TNF‐α levels were found to increase at lower concentrations of TMT (i.e., 10−8M). Moreover, at 10−6M of TMT, microglia displayed further morphological activation, as suggested by process retraction and by decrease in cell size. No morphological activation was observed in cultures of isolated microglial cells and in astrocyte–microglia cocultures. With regard to neurons, 10−6M of TMT induced about 30% of cell death, when applied to neuron‐enriched cultures, whereas close to 100% of neuronal death was observed in neuron–microglia cocultures. In conclusion, whereas astrocytes may rather dampen the microglial activation by decreasing microglial TNF‐α production, neuronal–microglial interactions lead to enhanced microglial activation. This microglial activation, in turn, exacerbates the neurotoxic effects of TMT. TNF‐α may play a major role in such cell–cell communications. © 2002 Wiley‐Liss, Inc.
Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats
Authors: Paulson Linda , Martin Peter , Persson Anders , Nilsson Carol L. , Ljung Elisabeth , Westman‐Brinkmalm Ann , Eriksson Peter S. , Blennow Kaj , Davidsson Pia
Published: January 2003

cDNA microarrays and two‐dimensional gel‐electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK‐801‐treated rats. The rats were divided in two groups; group 1 (short‐term treated) and group 2 (long‐term treated). In group 1, four genes were up‐regulated and five down‐regulated. In group 2, seven genes were up‐regulated and six down‐regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and γ‐enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c‐jun proto‐oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)‐ribosylation factors, platelet‐derived growth factor, fructose‐bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+‐transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, β‐actin and α‐enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N‐methyl‐D‐aspartate (NMDA)‐receptor antagonist treatment as an animal model of schizophrenia. © 2002 Wiley‐Liss, Inc.
GDNF elicits distinct immediate‐early gene responses in cultured cotical and mesencephalic neurons
Authors: Pezeshki Gita , Franke Barbara , Engele Jürgen
Published: January 2003

Glial cell line‐derived neurotrophic factor (GDNF) has been recognized as a survival‐promoting molecule for several neuronal populations in the central nervous system (CNS), including midbrain dopaminergic neurons and cortical neurons. Whereas it is well established that GDNF affects dopaminergic cell survival through a receptor complex composed of the tyrosine kinase, Ret, and the glycosylphosphatidylinositol (GPI)‐anchored protein, GFRα‐1, c‐Ret is basically undetectable in cortical neurons. In the present study, we have compared GDNF signaling in cortical and mesencephalic neurons by using GDNF‐induced expression of the immediate‐early genes, c‐fos and mgif, as a readout. We found that stimulation of embryonic day (E)17 cortical cultures for 3 hr with GDNF at concentrations ranging from 10 to 80 ng/ml did not result in detectable c‐fos expression. In contrast, c‐fos expression occurred in E14 mesencephalic cultures exposed to both low and high GDNF concentrations. Vice versa, cortical neurons responded to high GDNF concentrations (80 ng/ml) with an increase in mRNA encoding mGIF, while a similar mGIF response was absent in mesencephalic cultures. Cleavage of GFRα receptor subunits from their GPI anchors by phosphatidylinositol‐specific phospholipase C (PIPLC) abolished GDNF‐induced c‐fos expression in mesencephalic cultures, but did not interfere with the effects of GDNF on cortical mgif expression. Together, these findings point to distinct differences in the GDNF recognition and/or signal transduction machinery of cortical and mesencephalic neurons. © 2002 Wiley‐Liss, Inc.
Hyperbilirubinemia protects against focal ischemia in rats
Authors: Kitamura Yoshihisa , Ishida Yuji , Takata Kazuyuki , Mizutani Hiroto , Kakimura Jun‐ichi , Inden Masatoshi , Nakata Junko , Taniguchi Takashi , Tsukahara Tetsuya , Akaike Akinori , Shimohama Shun
Published: January 2003

Heme oxygenase‐1 (HO1) catalyzes oxidation of the heme molecule in concert with NADPH‐cytochrome P450 reductase following the specific cleavage of heme into carbon monoxide, iron, and biliverdin, which is rapidly metabolized to bilirubin. HO1 is a stress‐inducible protein that protects cells against oxidative injury, but its protective mechanism is not fully understood. The Eizai hyperbilirubinemic rat (EHBR), a mutant strain derived from the Sprague‐Dawley rat (SDR), has a mutation in the gene for the canalicular multispecific organic anion transporter, which results in a phenotype of hyperbilirubinemia, and thus is a model of Dubin‐Johnson syndrome in humans. In this study, we compared EHBR and SDR with regard to neuronal death induced by 2 hr of occlusion of the middle cerebral artery and reperfusion. In EHBR, the area that was immunoreactive for microtubule‐associated protein‐2 was significantly reduced, and the HO1‐immunoreactive area was smaller than that in SDR. These results suggest that bilirubin has essentially a neuroprotective effect against focal ischemia and may participate in HO1‐induced neuroprotection. © 2002 Wiley‐Liss, Inc.
Expression of delta opioid receptor mRNA and protein in the rat cerebral cortex and cerebellum is decreased by growth hormone
Authors: Persson Anders I. , Åberg N. David , Oscarsson Jan , Isaksson Olle G.P. , Rönnbäck Lars , Frick Fredrik , Sonesson Christian , Eriksson Peter S.
Published: January 2003

Hormones released from the pituitary have been shown to regulate the expression of different proteins in the central nervous system. We wanted to examine whether peripheral administration of bovine growth hormone (bGH) regulates the expression of delta‐opioid receptor (DOR) in the cerebral cortex and cerebellum. Expression of the DOR protein was quantified using Western blot densitometry. DOR mRNA was quantified with a solution hybridization RNase protection assay. Hypophysectomized (Hx) and untreated normal female rats were included in the study. All Hx rats were hormonally treated with cortisol (400 μg/kg/day) and L‐thyroxine (10 μg/kg/day) for 19 days. Hypophysectomy resulted in a threefold increase in cerebral cortex and a twofold increase in cerebellum of the DOR protein compared with normal rats. One subgroup of Hx rats received bGH (1 mg/kg body weight) as a daily subcutaneous injection for 19 days. This treatment normalized the levels of DOR protein in the cerebral cortex and cerebellum. Immunohistochemical experiments showed that GH decreased DOR expression especially in layers II–VI in cerebral cortex and in stratum moleculare in cerebellum. Quantification of DOR mRNA by solution hybridization RNase protection assay corresponded to the DOR protein measurements. We conclude that the expression of DORs in cerebral cortex and cerebellum is regulated by GH. © 2002 Wiley‐Liss, Inc.
Issues concerning the construction of a metabolic model for neuronal activation
Authors: Mangia S. , Giove F. , Bianciardi M. , Di Salle F. , Garreffa G. , Maraviglia B.
Published: January 2003

The metabolic events underlying neuronal activity still remain the object of intense debate, in spite of the considerable amount of information provided from different experimental techniques. Indeed, several attempts at linking the cellular metabolic phenomena with the macroscopic physiological changes have not yet attained foolproof conclusions. The difficulties in drawing definitive conclusions are due primarily to the heterogeneity of the experimental procedures used in different laboratories, and also given the impossibility of extrapolating the findings obtained under stationary conditions (prolonged stimulation) to dynamic and transient phenomena. Recently, lactate has received much attention, following its proposal by Pellerin and Magistretti (1994; Proc. Natl. Acad. Sci. USA 91:10625–10629), instead of glucose, as the main substrate for neurons during activity. Several challenging aspects suggest the return to a more conventional view of neuronal metabolism, in which neurons are able to metabolize ambient glucose directly as their major substrate, also during activation. © 2002 Wiley‐Liss, Inc.
Stem cell route to neuromuscular therapies
Authors: Partridge Terence A.
Published: January 2003

As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body‐wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology. Muscle Nerve 27: 133–141, 2003
Iatrogenic and toxic myopathies
Authors: Sieb Joern P. , Gillessen Thomas
Published: January 2003

There has been increasing awareness of the adverse effects of therapeutic agents and exogenous toxins on the structure and function of muscle. The resulting clinical syndrome varies from one characterized by muscle pain to profound myalgia, paralysis, and myoglobinuria. Because toxic myopathies are potentially reversible, their prompt recognition may reduce their damaging effects or prevent a fatal outcome. Interest in the toxic myopathies, however, derives not only from their clinical importance but also from the fact that they serve as useful experimental models in muscle research. Morphological and biochemical studies have increased our understanding of the basic cellular mechanisms of myotoxicity. Toxins may produce, for instance, necrotizing, lysosomal‐related, inflammatory, anti‐microtubular, mitochondrial, hypokalemia‐related, or protein synthesis–related muscle damage. Muscle Nerve 27: 142–156 2003
Spastic muscle cells are shorter and stiffer than normal cells
Authors: Fridén Jan , Lieber Richard L.
Published: January 2003

The mechanical properties of isolated single muscle fiber segments were measured in muscle cells obtained from patients undergoing surgery for correction of flexion contractures secondary to static perinatal encephalopathy (cerebral palsy). “Normal” muscle cells from patients with intact neuromuscular function were also mechanically tested. Fiber segments taken from subjects with spasticity developed passive tension at significantly shorter sarcomere lengths (1.84 ± 0.05 μm, n = 15) than fibers taken from normal subjects (2.20 ± 0.04 μm, n = 35). Elastic modulus of the stress–strain relationship in fibers from patients with spasticity (55.00 ± 6.61 kPa) was almost double that measured in normal fibers (28.25 ± 3.31 kPa). The fact that these muscle cells from patients with spasticity have a shorter resting sarcomere length and increased modulus compared with normal muscle cells suggests dramatic remodeling of intracellular or extracellular muscle structural components such as titin and collagen. Such changes in muscles of patients with spasticity may have implications for therapy. Muscle Nerve, 27: 157–164 ,2003
Full‐length dystrophin cDNA transfer into skeletal muscle of adult mdx mice by electroporation
Authors: Murakami Tatsufumi , Nishi Toru , Kimura En , Goto Tomoaki , Maeda Yasushi , Ushio Yukitaka , Uchino Makoto , Sunada Yoshihide
Published: January 2003

We showed that a LacZ expression plasmid (pCAG‐lacZ) injection followed by electroporation increased the expression of the LacZ gene in the skeletal muscles of adult mdx mice up to ninefold higher as compared with simple intramuscular DNA injection. When full‐length mouse dystrophin plasmid (pCAG‐dys) and pCAG‐lacZ were co‐transfected by electroporation, 56% of dystrophin‐positive fibers were stained for β‐galactosidase activity suggesting most of these myofibers are not revertants but transfected ones. Our data indicate that electroporation in vivo could introduce large full‐length dystrophin cDNA into skeletal muscle of adult mdx mice. Muscle Nerve 27: 237–241, 2003
Electrophysiologic changes during exercise testing in patients with chronic obstructive pulmonary disease
Authors: Gosselin Nadège , Matecki Stéphane , Poulain Magali , Ramonatxo Michèle , Ceugniet François , Préfaut Christian , Varray Alain
Published: January 2003

To determine whether skeletal muscle is involved in the exercise limitation of chronic obstructive pulmonary disease (COPD), we investigated electrical adaptations in muscle during incremental cycling exercise testing. Changes in quadriceps activity were compared using surface electromyography (SEMG) and motor point stimulation in ten COPD patients and ten healthy subjects. Patients showed significantly lower exercise capacity, and M‐wave duration was increased from exercise onset (P< 0.05) with a parallel decrease in amplitude (P< 0.05). The SEMG power spectrum median frequency was always higher (P< 0.04) in patients and its decline was earlier (P< 0.01). The ratio of the root mean square of the SEMG to oxygen uptake was decreased (P< 0.001) during exercise in patients, although it remained constant in controls. Electromyographic parameters were significantly more involved in the exercise limitation than ventilatory factors. Thus, modified electrical activity in muscle appeared in COPD patients from exercise onset, indicating that skeletal muscle function is clearly implicated in the exercise intolerance of these patients. Muscle Nerve 27: 170–179, 2003
Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels
Authors: Simmons Zachary , Peterlin B. Lee , Boyer Philip J. , Towfighi Javad
Published: January 2003

The utility of muscle biopsy in patients with modest elevations of serum creatine kinase (CK) level but normal neurological examinations and nondiagnostic electrodiagnostic studies is uncertain. We performed systematic, extensive studies on muscle biopsies of 20 such patients. A definitive diagnosis was arrived at in only 1 by histochemical studies, although 4 others demonstrated minor myopathic changes. Biochemical evaluation led to a diagnosis in an additional 5. Muscle biopsy is useful for evaluating such patients, but extensive studies of the muscle are necessary. Muscle Nerve 27: 242–244, 2003
Fatigue and abnormal neuromuscular transmission in Kennedy's disease
Authors: Meriggioli Matthew N. , Rowin Julie
Published: January 2003

We describe a patient with Kennedy's disease (X‐linked bulbospinal neuronopathy) who experienced leg muscle fatigue with long‐distance running. The patient also reported muscle twitching involving the face and extremities and long‐standing muscle cramps. Aside from mild facial and tongue weakness (and fasciculations), his examination was normal, including completely preserved muscle strength in the extremities. Electrodiagnostic evaluation revealed evidence for a chronic motor axonopathy/neuronopathy and abnormal sensory nerve action potentials. In addition, repetitive nerve stimulation studies were normal, but neuromuscular jitter tested in the same muscle was markedly abnormal. The normal clinical strength and repetitive nerve stimulation studies in a muscle showing markedly increased neuromuscular jitter suggested a mechanism for this patient's symptoms of muscle fatigue, related to failure of neuromuscular transmission at a critical number of endplates during extremes of physical activity. Muscle Nerve 27: 249–251, 2003
Severe prognosis in a large family with hypokalemic periodic paralysis
Authors: Caciotti Anna , Morrone Amelia , Domenici Raffaele , Donati Maria Alice , Zammarchi Enrico
Published: January 2003

Hypokalemic periodic paralysis (HypoPP) is a channel disorder caused primarily by mutations in the human skeletal muscle α1 subunit (CACNA1S) of the dihydropyridine‐sensitive calcium channel. Molecular, clinical, and biochemical studies were aimed at establishing genotype/phenotype correlations in a large Italian family affected by a severe form of HypoPP. Whereas patients with HypoPP usually show a normal life span, in this family three male patients died young, one of them from anesthetic complications resembling malignant hyperthermia. Our patients carried the c1583G>A genetic lesion (R528H), which has been associated with a mild phenotype and with incomplete penetrance in women. Surprisingly, the R528H amino acid substitution in the family presented here correlated with an unfavorable prognosis in both male and female patients. We conclude that genetic characterization is an important requirement to alert physicians about the management of similar patients, especially when anesthesia is considered. Muscle Nerve 27: 165–169, 2003
Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis
Authors: Maselli Ricardo A. , Chen Darlene , Mo Delores , Bowe Constance , Fenton Grace , Wollmann Robert L.
Published: January 2003

The myasthenic syndrome due to abnormal acetylcholine resynthesis is characterized by early onset, recessive inheritance, and recurrent episodes of potentially fatal apnea. Mutations in the gene encoding choline acetyltransferase (CHAT) have been found to account for this condition. We have identified five patients from three independent families with features of this disease including, in four patients, a paradoxical worsening of symptoms with cold temperatures. Electrodiagnostic studies demonstrated impaired neuromuscular transmission in all patients. In vitro microelectrode studies performed in the anconeus muscle biopsies of two patients showed moderate reduction of quantal release. Electron microscopy of the neuromuscular junction was normal in both patients. Each patient had two heterozygous CHAT mutations including L210P and P211A (family 1), V194L and V506L (family 2), and R548stop and S694C (family 3). Three of these mutations have previously been reported and suggest that, in this syndrome, some molecular defects may be more prevalent than others. Muscle Nerve 27: 180–187, 2003
Sensory neuropathy with monoclonal IgM binding to a trisulfated heparin disaccharide
Authors: Pestronk Alan , Choksi Rati , Logigian Eric , Al‐Lozi Muhammad T.
Published: January 2003

We studied clinical and serological features of five patients with polyneuropathy and serum immunoglobulin M (IgM) binding to the trisulfated disaccharide IdoA2S‐GlcNS‐6S (TS‐HDS), the most abundant disaccharide component of heparin oligosaccharides. The patients all had painful, predominantly sensory polyneuropathies. Sensory loss was distal and panmodal. Electrophysiological and pathological studies were consistent with axonal loss, especially of unmyelinated axons. Immunohistochemistry showed IgM and κ light chains deposited around the rim of intermediate‐sized veins in the perimysium and epineurium. Serum IgM binding to TS‐HDS was selective, present in high titer (>12,000), and limited to κ light chains. We conclude that TS‐HDS is a newly identified target carbohydrate antigen of some IgM M‐proteins. Monoclonal IgM binding to TS‐HDS is associated with a painful, predominantly sensory, polyneuropathy syndrome with axonal loss and deposition of IgM in veins. The role of IgM binding to TS‐HDS in the pathogenesis of the neuropathy remains to be determined. Muscle Nerve 27: 188–195, 2003
Evidence for strength imbalances as a significant contributor to abnormal synergies in hemiparetic subjects
Authors: Lum Peter S. , Burgar Charles G. , Shor Peggy C.
Published: January 2003

Abnormal synergies in the paretic shoulder and elbow of hemiparetic subjects were quantified during maximal voluntary contractions (MVCs) in 27 subjects with a history of stroke and 8 age‐matched control subjects. A six‐axis load cell allowed simultaneous measurement of the primary torque the subject was attempting to maximize and the secondary torques at other joint actions. For example, during MVC of shoulder flexion, shoulder flexion is the primary torque and the secondary torques are internal/external rotation, abduction/adduction, and elbow flexion/extension. In general, the stroke subjects had increased secondary torques compared to controls, resulting in abnormal joint torque coupling within the set consisting of elbow flexion, internal rotation, adduction, shoulder flexion. Unlike previous studies, abnormal secondary torques in several cases were due to strength imbalances, which occur when the strength deficit for a particular joint action is greater than the strength deficit in the opposite joint action. This hypothesis was supported by electromyographic recordings and by the finding that subjects with larger strength imbalances tended to produce larger secondary torques. Possible mechanisms and consequences for rehabilitative treatments are discussed. Muscle Nerve 27: 211–221, 2003
Endurance training alters the biophysical properties of hindlimb motoneurons in rats
Authors: Beaumont Eric , Gardiner Phillip F.
Published: January 2003

The purpose of the study was to determine the effect of daily endurance treadmill training (2 h/day, 30 m/min) on motoneuron biophysical properties. Electrophysiological properties of tibial motoneurons were measured in situ in anesthetized (ketamine/xylazine) control and trained rats using sharp glass microelectrodes. Motoneurons from trained rats had significantly hyperpolarized resting membrane potentials and spike trigger levels, and faster antidromic spike rise‐times. “Fast” motoneurons (after‐hyperpolarization half‐decay time <20 ms) in trained rats also had a significantly larger mean cell capacitance than those in control rats, suggesting that they were larger, although this had no effect on indices of excitability (rheobase, cell input resistance). Motoneurons are thus targets for activity‐induced adaptations, which may have clinical significance for the role of physical activity as a therapeutic modality in cases of neurological deficit. The specific adaptations noted, which reflect alterations in ionic conductances, may serve to offset decreases in membrane excitability that occur during sustained excitation. © 2003 Wiley Periodicals, Inc. Muscle Nerve 27: 228–236, 2003
Size of motor unit potential sample
Authors: Podnar Simon , Mrkaić Mićo
Published: January 2003

In quantitative electromyography (EMG), a sample size of 20 motor unit potentials (MUPs) is standard. The effect of increase in the number of MUPs above 20 is not known, although advanced MUP analysis techniques make such samples practical. In the present study, using multi‐MUP analysis, pools of 3,720 neuropathic and 2,526 control MUPs were obtained from external anal sphincter muscles. From each pool, 10,000 random samples of 5, 10, 15, 20, 30, 40, 50, and 100 MUPs were obtained by a computer. For each sample size, 95% normative limits for mean values, SDs, and “outliers,” and sensitivities were calculated for eight MUP parameters. As the magnitude of MUP samples increased, normative limits narrowed and sensitivities increased (at 5: 20–30%; at 20: 30–55%; at 100: 80–100%) for all statistics of all MUP parameters. Our results demonstrated a substantial increase in sensitivity by increasing the MUP sample to more than 20. This option deserves consideration in an attempt to improve the usefulness of quantitative EMG. Muscle Nerve 27: 196–201, 2003
Early prednisone treatment in Duchenne muscular dystrophy
Authors: Merlini Luciano , Cicognani Alessandro , Malaspina Elisabetta , Gennari Monia , Gnudi Saverio , Talim Beril , Franzoni Emilio
Published: January 2003

The purpose of this long‐term, open parallel‐group, double‐consent study of alternate‐day, low‐dose prednisone in 2–4‐year‐old patients with Duchenne muscular dystrophy (DMD) was to determine whether prednisone produces a beneficial effect when given earlier than usual. Muscle function was evaluated by timed tests, and muscle strength with a hand‐held myometer. After 55 months of treatment, the five patients (mean age 8.3 years) in the prednisone group were still able to get up from the floor, whereas two of the three in the control group had lost this ability. Side effects included a decline in growth rate in the prednisone‐treated patients and excessive weight gain in one control and three treated patients. Because steroids are effective in prolonging function, but not in recovering lost function, we propose that treatment be started with low‐dose prednisone in DMD patients as soon as the diagnosis is definite. Muscle Nerve 27: 222–227, 2003
Individual attributes versus composite scores of nerve conduction abnormality: Sensitivity, reproducibility, and concordance with impairment
Authors: Dyck Peter J. , Litchy William J. , Daube Jasper R. , Harper C. Michel , Dyck P. James B. , Davies Jenny , O'Brien Peter C.
Published: January 2003

Composite scores may be more sensitive and reproducible than single attributes of nerve conduction for detection of peripheral neuropathy, but this requires validation in large patient cohorts. Also, the concordance of individual attributes versus composite scores with clinical measures of severity has not been tested. Here, we study these issues in prospectively studied cohorts: diabetic patients from Rochester, Minnesota (RDNS; n = 396); chronic inflammatory demyelinating polyneuropathy (CIDP) patients (n = 55); and multifocal motor neuropathy (MMN) patients (n = 18). With specificity fixed at the 97.5 percentile, we found that, in generalized polyneuropathies (diabetic and CIDP), composite scores (especially ones including conduction velocity, distal latencies, and F‐waves) of individual or multiple nerves tended to be more sensitive than individual attributes. By contrast, for multiple mononeuropathies, some individual attributes or composite scores of individual nerves were more sensitive than composite scores. In diabetic polyneuropathy, composite scores tended to be more reproducible than individual attributes of nerve conduction. Highly significant correlations were found between individual attributes or composite scores and neurologic impairment in diabetic polyneuropathy and in CIDP; in general, correlation coefficients were higher for composite scores. These correlations were higher for amplitudes than for conduction velocities or distal latencies. We conclude that, with the availability of microprocessors and normative databases, electromyographers may increasingly seek to express nerve conduction abnormality also as composite scores of individual or several nerves. Muscle Nerve 27: 202–210, 2003
Factors affecting the adsorption of ethoxylated nonyl phenol onto synthetic rubber
Authors: El‐Feky A. A. , Shalaby M. N.
Published: January 2003

Adsorption of non‐ionic surfactant (ethoxylated nonyl phenol; ENP) from aqueous solution is studied at 30 °C using butyl rubber (II R) mixed with two types of carbon black: high abrasion furnace (HAF) and general purpose furnace (GPF) as fillers with different concentrations. The results indicate that butyl loaded with HAF is more efficient as adsorbent surface than that loaded with GPF irrespective of the carbon black concentration and the adsorption increases as the immersion time increases. The experimental data of adsorption isotherms could be fitted to the Langmuir equation below the critical micelle concentration (CMC) of ENP. Copyright © 2003 John Wiley & Sons, Ltd.
Morphology and properties of ternary polyamide 6/polyamide 66/elastomer blends
Authors: Tomova D. , Radusch H.‐J.
Published: January 2003

The aim of the work presented is to evaluate the mechanisms and phase interactions in ternary blends based on different polyamides and functionalised elastomers, and to establish a correlation between the morphology controlled by the specific binary interactions, and physical and technological properties, respectively.

The properties of the ternary system polyamide 6/polyamide 66/ elastomer depend on the specific blend morphology which is determined mainly by the differences of the surface tension of the components. A phase‐in‐phase structure was observed by microscopic study (AFM) in the ternary polyamide 6/polyamide 66/elastomer blends with maleic anhydride grafted ethene‐octene copolymer, and a “quasi” phase‐in‐phase structure in blends with maleic anhydride grafted ethene‐propene‐diene copolymer as the elastomer phase. An incorporation of polyamide inside of the elastomer particles was observed in the first case due to the difunctionality of polyamide 66. This type of morphology causes an increased elongation at break and toughness of these blends.

In comparison to the binary polyamide based blends the ternary blends show an increased elastic modulus, elongation at break and yield stress as well as a high impact strength at low temperatures up to −20 °C. Copyright © 2003 John Wiley & Sons, Ltd.
Catalysis of intumescent flame retardancy of polypropylene by metallic compounds
Authors: Lewin Menachem , Endo Makoto
Published: January 2003

Divalent and multivalent metallic compounds catalyze the flame retardancy performance of intumescent systems based on ammonium polyphosphate (APP) and pentaerythritol (petol) in poly(propylene) (PP). The catalytic effect is shown by increases in the oxygen index (OI) and UL‐94 ratings. The effect is exerted by small concentrations of the metallic compounds in the range of 0.1–2.5 wt% of the compositions. The effect increases with the concentration of the catalyst until a maximum is reached. At higher concentrations of the catalyst a decrease in the flame retardancy parameters is observed, accompanied in several cases by a degradation and discoloration of the composition. The catalyst replaces melamine in intumescent systems. Catalytic effectiveness is defined and calculated for a number of compounds. Thermogravimetric parameters, such as initial decomposition temperature, temperature of the transition point and residue‐after‐transitions (RAT) change in parallel with the catalytic effect of the metal compound concentration. Metal compounds investigated include oxides, acetates, acetyl acetonates, borates and sulfates of Mn, Zn, Mg, Al, Ca, Ba, V, Co, Ni, Cu, Mo, Zr, and Cr. Mechanistic considerations on the activity of the catalysts are presented. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis of new chitosan derivatives and combination with biodegradable polymer
Authors: Omura Yoshihiko , Renbutsu Eiko , Morimoto Minoru , Saimoto Hiroyuki , Shigemasa Yoshihiro
Published: January 2003

New chitosan derivatives are synthesized by the reductive N‐alkylation reaction of chitosan with various aldehydes, such as 2,4‐dihydroxybenzaldehyde, cholesteryl 4‐formylbenzoate, and N‐dehydroabietyl‐4‐formylbenzamide. The palladium‐adsorption ability of the newly synthesized derivatives is found to be as good as that of chitosan. A blend of chitosan and other biodegradable polymers is also found to exhibit palladium‐adsorption ability. In comparison to the starting chitosan, the chitosan derivative having dehydroabietyl‐type side chains exhibited an improved solubility in methanol. The chitosan derivatives are successfully applied as plastic coating materials for electroless plating. Copyright © 2003 John Wiley & Sons, Ltd.
Regioselective synthesis and biological activity of oxidized chitosan derivatives
Authors: Terada Naofumi , Morimoto Minoru , Saimoto Hiroyuki , Okamoto Yoshiharu , Minami Saburo , Shigemasa Yoshihiro
Published: January 2003

Oxidized chitosan derivatives with various degrees of oxidation (DS, 0.1–1.0) were prepared by the treatment of chitosan with CrO3/aq HClO4 or by the oxidation of ­3‐O‐ and N‐protected chitosan with 30% aq H2O2/Na2WO4 followed by 3‐O‐ and N‐deprotection. The oxidized products were then N‐acetylated with Ac2O in order to improve their water‐solubility. Although the oxidized chitosan derivative of DS 0.28 and the degree of N‐acetylation of chitosan (DA) 38% was insoluble in the pH 3–8 region, that of DS 0.26 and DA 76% was soluble in the neutral pH range. The newly‐prepared acetylated and oxidized chitosan derivatives were found to suppress the chemiluminescence response of inflammatory cells such as canine polymorphonuclear cells (PMNs). Analysis by the surface plasmon resonance method revealed that the bind and release behavior of PMNs to acetylated oxidized chitosan derivatives was similar to that against carboxymethylated chitosan derivatives. The amount of water‐soluble chitosan derivative bound to cytokine IL‐8 was found to be affected by the structural and electronic features of the chitosan substituents in the chitosan chain. Copyright © 2003 John Wiley & Sons, Ltd.
A novel oligothiophene derivative as a hole‐transport with emitting material for OLED
Authors: Cho Jun‐Sang , Kojima Yojiro , Yamamoto Kimihisa
Published: January 2003

A novel oligothiophene derivative containing the triphenylamine moiety with high glass transition temperature (Tg; 135 °C), 5,5′‐{bis[4‐di(4‐thiophenyl)amino]phenyl}‐2,2′‐bithiophene (TTPA‐dimer) was synthesized by the dimerization of tris[4‐(2‐thienyl)phenyl]amine (TTPA) with a palladium catalysis. Some types of electroluminescent (EL) devices that use the amorphous material for a hole‐ and an electron‐transporting with an emitting layer were fabricated. These devices emitted a bright green‐yellowish light (λemi; around 510 nm) with a small full width at half maximum (FWHM) rather than that of Alq3. The single layer EL device showed a maximum luminance of 221 cd/m2 at 8 V (0.06 lm/W at 100 cd/m2). On the other hand, the double layer (TTPA‐dimer/Alq3) EL device that used Alq3 as the electron transport material was increased up to 10830 cd/m2 at 12 V (0.89 lm/W at 300 cd/m2) and with a lower turn‐on voltage (3.2 V at 0.1 cd/m2) than other types of EL devices. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and characterization of polyethylene‐g‐polystyrene as the compatibilizer for polypropylene/ Polystyrene blends
Authors: Kim J. , Kwak J. , Kim D.
Published: January 2003

Polyethylene‐g‐polystyrene (PE‐g‐PS) was synthesized as a compatibilizer for polypropylene/polystyrene­(PP/PS) blends by the living radical polymerization of styrene with polyethylene‐co‐glycidylmethacrylate (PE‐co‐GMA). The compatibilizer effect of PE‐g‐PS on the morphology and thermal properties of PP/PS blends was investigated. The crystalline temperature of PP in PP/PS blends decreased with increasing PE‐g‐PS contents. Morphologies of PP/PE‐g‐PS/PS blends showed much better dispersion of each domain for higher PE‐g‐PS contents. The molecular weight of PS segment in PP/PE‐g‐PS/PS blend was increased by addition of styrene monomer during the post melt blending process where post living radical polymerization reaction proceeded. Copyright © 2003 John Wiley & Sons, Ltd.
Organic/Inorganic NLO materials based on reactive polyimides and a bulky alkoxysilane dye via sol/Gel process
Authors: Jeng Ru‐Jong , Hung Wei‐Yu , Chen Chih‐Ping , Hsiue Ging‐Ho
Published: January 2003

A series of the organic–inorganic materials based on reactive polyimides and a bulky alkoxysilane dye (ASD) for second‐order nonlinear optics have been developed. Sol‐gel reaction of ASDs is utilized to grow a network in polymer matrices (composite) or to create inter‐polymer network among polyimide chains (hybrid). Moreover, a full interpenetrating polymer network (IPN) was formed through simultaneous free radical polymerization of a methacryloyl group containing polyimide, and sol‐gel process of ASDs. Scanning electron microscopy (SEM) results indicate that the inorganic networks are distributed uniformly throughout the polymer matrices on the molecular scale. The silica particle sizes are well under 1 µm based on AFM study. Second harmonic coefficients, d33 of 4.5 to 48.5 pm/V have been obtained for the optically clear poled/cured polyimide/ASD samples. Excellent temporal stability was obtained for these NLO materials at 100 °C. The dynamic thermal and temporal stabilities of the IPN system were much better than those of composite and hybrid systems. Copyright ­© 2003 John Wiley & Sons, Ltd.