bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractWe 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

AbstractTrimethyltin (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

AbstractcDNA 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

AbstractGlial 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

AbstractHeme 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

AbstractHormones 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

AbstractThe 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

AbstractAs 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

AbstractThere 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

AbstractThe 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

AbstractWe 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

AbstractTo 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

AbstractThe 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

AbstractWe 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

AbstractHypokalemic 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

AbstractThe 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

AbstractWe 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