bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain‐specific expression of human microtubule‐associated protein 1A (MAP1A) gene and its assignment to human chromosome 15
Authors: Fukuyama Ryuichi , Rapoport S. I.
Published: January 2005

We isolated several cDNA fragments by immunoscreening a human cDNA library with our monoclonal antibody, BG5, that showed neuronal staining on human and rat brain sections. A 1,570 bp sequence of one cDNA fragment showed 75% homology to the rat microtubule‐associated protein 1A (MAP1A) cDNA sequence. This rat MAP1A‐like human cDNA was highly specific to the adult brain among human tissues tested, and was expressed in various brain regions including white matter. The size of the mRNA detected with Northern blot analysis in adult human brain equaled 10 kb. The gene of this cDNA was assigned to human chromosome 15 that has a syntenic region of mouse chromosome 2, where the mouse MAP1A gene has been assigned. These results indicate that this rat MAP1A‐like cDNA is a portion of human MAP1A and is a conserved molecular species among humans and rodents. © 1995 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.
On a molecular comparison of strong and weak antagonists at the glycinergic receptor
Authors: Aprison M. H. , Galvez‐Ruano E. , Lipkowitz K. B.
Published: January 2005

Using molecular modeling techniques, we studied nine glycine antagonists in order to try to identify the molecular descriptors that characterize strychnine as a strong antagonist and N, N‐dimethyl‐muscimol, iso‐THIA, THIA, N‐methyl‐THIP, iso‐THAZ, THAZ, iso‐THPO, and iso‐THAO (see Experimental for chemical names) as weak glycine antagonists. We confirm that all nine compounds have the three‐atom regions (two negative and one positive) that we have postulated are necessary to permit such compounds to attach to the recognition site in the glycinergic synapse. Furthermore, in the case of antagonists we have postulated the presence of a fourth atom that can attach to the top of the chloride ion channel. Each of the nine antagonists has such a fourth negative atom and the latter property gives each of these compounds their antagonistic characteristic. Further, only in the case of strychnine is there evidence that at its positively charged end does the positive charge extend to cover a region that could bind through electrostatic domains to a tertiary carboxyl group in an amino acid like aspartate. Published molecular biological data show that such an amino acid is present in the portion of the polypeptides identified in the glycine receptor. The bidentate binding is superior to the single site attachment that is present in the other eight weak glycine antagonists. In addition, the two negative atom sites in each antagonist are also in a position to participate in electrostatic binding through bidentate involvement with the positively charged guanidinium group of arginine. The latter amino acid also has been identified in the portion of the polypeptide chain at the glycine receptor. Finally, our molecular data predict that after strychnine, the eight weak glycine antagonists listed above are in order of decreasing potency, i.e., N,N‐dimethyl‐muscimol is the best of the weak antagonists and iso‐THAO should be the weakest. © 1995 Wiley‐Liss, Inc.
Generation of cell lines from embryonic quail retina capable of mature neuronal differentiation
Authors: Pollerberg G. E. , Kuschel C. , Zenke M.
Published: January 2005

The avian embryonic retina is widely used as a model system for cellular and molecular studies on central nervous system neurons. We aimed at the generation of cell lines from the early embryonic quail retina by retroviral oncogene transduction. For this, we made use of the retina organ culture system which exhibits both proliferation, necessary for stable oncogene transduction, and initial neuronal differentiation, a prerequisite for the generation of cell lines with mature neuronal properties. The oncogene myc was chosen ac it is both proliferation‐inducing and differentiation‐compatible. A chimeric gene, mycER, containing v‐myc and the hormone‐binding domain of the estrogen receptor, was used for transduction in order to allow for hormone regulation of myc activity. Transduced organ‐cultured cells from temporal and nasal retina were passaged into sparse single cell cultures. From these, colonies of rapidly dividing cells were isolated and the progeny expanded as cell lines. The lines contained cells with features of neuroepithelial cells, showing vimentin and A2B5. They also contained spontaneously differentiated neuronal cells showing neurofilament L and N‐CAM18O. A subpopulation of the neuronal cells exhibited the morphological characteristics of retinal ganglion cells, i.e., large pear‐shaped somata each emitting one long process with a distinct growth cone. In addition, they showed the marker profile of retinal ganglion cells, i.e., expression of Thy‐1, G4, DMGRASP, Nr‐CAM, neurofilament H, and tau. Neuronal differentiation could be induced by the addition of db cAMP and retinoic acid. The mature neuronal features of the lines open new possibilities to study properties of retinal neurons, including ganglion cells, in a defined and manipulable experimental system. © Wiley‐Liss, Inc.
Alteration of corticotropin‐releasing factor immunoreactivity in MPTP‐treated rats
Authors: Huang C. C. , Lee E. H. Y.
Published: January 2005

A decrease of corticotropin‐releasing factor (CRF) concentration has been reported in patients with Parkinson's disease (PD). The present study further examined the role of CRF in an animal model of parkinsonism induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Results indicated that both subchronic (2 days) and chronic (7 days) MPTP treatments decreased the number of CRF immunoreactive neurons in both the paraventricular nucleus (PVN) of the hypothalamus and the central nuelcus of the amygdala (ACN). This effect lasted for almost a month after withdrawal of chronic MPTP injections. In addition, nomifensine pretreatment protected against MPTP's toxicity on DA neurons, as assessed by tyrosine hydroxylase immunoreactivity in the substantia nigra. However, the same treatment did not prevent the toxicity of MPTP on CRF neurons. Further, no significant difference was notable in the number of CRF immunoreactive neurons between normal young adult and normal middle‐aged rats in both the PVN and the ACN. These results suggest that MPTP also produces a neurotoxicity on CRF neurons, and this effect is not secondary to MPTP's effect on DA neurons. Besides, altered CRF neuronal activity is involved in the process of pathological ageing, but not physiological ageing. Further, reduced CRF immunoreactivity in the PVN and ACN may imply alterations of neuroendocrine, autonomic as well as central functions caused by MPTP. © 1995 Wiley‐Liss, Inc.
Gangliosides have a bimodal effect on DNA synthesis in U‐1242 MG human glioma cells
Authors: Saqr H. E. , Lee M.‐C. , Burkman A. M. , Yates A. J.
Published: January 2005

GM1, GD1a, and GT1b inhibit both PDGF‐stimulated and serum‐stimulated DNA synthesis in Swiss 3T3 cells and the human glioma cell line U‐1242 MG in a dose‐dependent manner. The ganglioside inhibitory effect is counteracted in a dose‐responsive fashion by serum such that ganglioside‐induced inhibition is essentially abolished in 10% serum. Because of the potentially important role that gangliosides play in growth regulation of human gliomas, this phenomenon was studied in detail using U‐1242 MG cells. Stimulation of DNA synthesis by low doses of serum in U‐1242 MG cells is inhibited in a dose‐responsive fashion by ganglioside GM1. However, serum itself counteracts the inhibitory effect of ganglioside in a dose responsive way. Kinetic analyses demonstrate that GM‐1 competes with some components of serum for sites on U‐1242 MG cells (Kb of GM1 =12.5 μM). On the other hand, GM1, GD1a, and GT1b stimulate DNA synthesis in quiescent U‐1242 MG cells in both sparse and confluent conditions, indicating that ganglioside‐stimulated DNA synthesis is dependent on the phase of cellular growth rather than cellular density. This growth stimulatory effect of gangliosides is more potent on quiescent, confluent cells than quiescent, sparse cells. These results demonstrate that exogenously added gangliosides can have opposite (bimodal) effects on progression of human glioma cells through the cell cycle depending upon the growth phase of the cells. © 1995 Wiley‐Liss, Inc.
β‐Amyloid peptide fragment 25–35 potentiates the calcium‐dependent release of excitatory amino acids from depolarized hippocampal slices
Authors: Arias C. , Arrieta I. , Tapia R.
Published: January 2005

β‐Amyloid protein (βAP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that βAP, particularly its fragment 25ndash;35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25–35 on the release of endogenous amino acids from hippocampal slices of young adult (3–3.5‐month‐old) and aged (23–25‐month‐old) rats, under basal, K+ ‐depolarization, and post‐depolarization conditions, in the presence and absence of Cat2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1‐hr preincubation of slices from young animals with 10 μM 25–35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control‐stimulated release. These effects were strictly dependent on external Ca2+ Neither the K+ ‐stimulated release of γ‐amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25–35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25–35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K+ ‐induced release of both aspartate and glutamate was also higher. Fragment 25–35 also potentiated the K+ ‐induced release of these two amino acids, although to a lesser extent than in young tissue. These results indicate that glutamate is retained less by the aged hippocampus and that fragment 25–35 is able to augment the release of glutamate and aspartate under excitatory conditions, an effect that could be involved in the mechanisms of neurotoxicity of β‐amyloid peptides. © 1995 Wiley‐Liss, Inc.
Protein kinase C‐α and ‐ε are enriched in growth cones of differentiating SH‐SY5Y human neuroblastoma cells
Authors: Parrow V. , Fagerström S. , Meyerson G. , Nånberg E. , Påhlman S.
Published: January 2005

SH‐SY5Y cells differentiate into neuronal‐like cells and express marker proteins like growth‐associated protein (GAP‐43) and neuropeptide tyrosine when treated with a low concentration (16 nM) of the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in the presence of growth factors or serum. Both control and differentiated cells expressed protein kinase C‐α (PKC‐α), PKC‐ε, and PKC‐ζ as revealed by Western blot analyses, but the subcellular distribution of the three isoforms was not uniform, indicating specific localized functions of the enzymes. In growth cones prepared from differentiating cells PKC‐α and PKC‐ε were enriched. In contrast, PKC‐ζ was more evenly distributed within the differentiating cell. Cells treated with a high concentration of TPA (1.6 μM) differentiate poorly and continue to proliferate. In those cells, PKC‐α and PKC‐ε were found to be down‐regulated while PKC‐ζ remained present. Thus, down‐regulation of PKC‐α and PKC‐ζ appears to be incompatible with neuronal differentiation of SH‐SY5Y cells. These cells also differentiate when treated with a combination of basic fibroblast growth factor and insulin‐like growth factor I. Growth cones isolated from such cells are also enriched in PKC‐α and PKC‐ε, but not in PKC‐ζ. Based on the subcellular distribution of PKC‐α and ε, and that PKC substrates like GAP‐43 and pp60c‐src are enriched in SH‐SY5Y growth cones, a role during neurite growth is suggested. © 1995 Wiley‐Liss, Inc.
Altered lipid metabolism in the presence and absence of extracellular Ca2+ during combined oxygen‐glucose deprivation in primary astrocyte cultures
Authors: Murphy E. J. , Haun S. E. , Rosenberger T. A. , Horrocks L. A.
Published: January 2005

The effect of combined oxygen‐glucose deprivation (COGD) on lipid metabolism in primary rat cortical astrocyte cultures was studied in both the presence and absence of extracellular Ca2+. In this study, increases in intracellular Ca2+ from internal Ca2+ stores were not inhibited nor were internal Ca2+ levels buffered. Combined oxygen‐glucose deprivation resulted in a quantitative reduction in phospholipid levels and an increase in free fatty acid and lysophospholipid levels. Four hours after the onset of COGD, ethanolamine‐ and choline glycerophospholipid levels were decreased by 40 and 46% from control levels in the presence of Ca2+, respectively. A similar decrease was found 6 hr after onset of COGD in the absence of Ca2+. These changes were accompanied by elevated levels of the corresponding lysophospholipids. However, the increases in lysophospholipid content did not account for the entire loss of ethanolamine‐ or choline glycerophospholipid. Phosphatidylserine was reduced in both the presence and absence of extracellular Ca2+ but phosphatidylinositol was only decreased in the absence of Ca2+. Statistically significant increases in total fatty acid (FA) and polyunsaturated fatty acid (PUFA) levels occurred at 30 min and 3 hr after the onset of COGD in the absence and presence of Ca2+, respectively. Arachidonic acid levels were increased in both groups by 1 hr. These increases in FA, PUFA, and specifically arachidonic acid were time‐dependent and increased over the 12 hr of COGD. Collectively, these results indicate the activation of an acylhydrolase mechanism in the possible presence of an inhibited reacylation pathway. The lack of measurable increases in diacylglycerol content suggests either the lack of phospholipase C activation or the rapid removal of diacylglycerol. These early alterations in lipid metabolism begin prior to any appreciable loss of cell viability. © 1995 Wiley‐Liss, Inc.
Norepinephrine but not epinephrine stimulates the release of corticotropin‐releasing factor from in vitro superfused rat hypothalamus
Authors: Orliaguet G. , Parsadaniantz S. Mélik , Lenoir V. , Duval P. , Kerdelhué B.
Published: January 2005

To clarify the controversy concerning the role of catecholaminergic systems in regulating hypothalamic corticotropin‐releasing factor (CRF) secretion, we assessed the direct effects of norepinephrine and epinephrine, alone and in association with mixed α and β antagonists on hypothalamic CRF secretion. An in vitro rat mediobasal hypothalamus perifusion system was used, in which CRF secretion from a single explant was evaluated by a specific radioimmunoassay. We found that norepinephrine stimulated CRF secretion, with peak effects at 10‐8 M concentration, whereas epinephrine had no effect on CRF secretion. The effect of norepinephrine was antagonised by the mixed a antagonist phentolamine and by the mixed β antagonist propranolol.

We conclude that norepinephrine, but not epinephrine, stimulate hypothamic CRF secretion via a and β receptors. The data support the idea that the central noradrenergic systems are excitatory upon CRF‐41 secretion when acting directly at the hypothalamic level. © 1995 Wiley‐Liss, Inc.
Gliali repair at the lesion site in regenerating goldfish spinal cord: An immunohistochemical study using species‐specific antibodies
Authors: Nona S. N. , Stafford C. A.
Published: January 2005

We have used fish‐specific antibodies to show that repair in regenerating goldfish spinal cord is accompanied by the recovery of the astrocytic environment and restoration of the central canal. Astrocyte processes trailed the regenerated axons bridging the new cord, suggesting that they are not needed for axonal regrowth. © 1995 Wiley‐Liss, Inc.
Preservation of the substanitia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four‐year period
Authors: Quinn Niall , Parkes David , Janota Ivan , Marsden C. D.
Published: January 2005

A 72‐year‐old hypertensive man developed parkinsonism and was treated with Sinemet for 4 years but then died of a bronchial carcinoma. Necropsy revealed cerebrovascular disease and amyloid angiopathy. The substantia nigra and locus coeruleus were normal on light microscopy.
Effectiveness of trihexyphenidyl against pendular nystagmus and palatal myoclonus: Evidence of cholinergic dysfunction
Authors: Jabbari Bahman , Rosenberg Michael , Scherokman Barbara , Gunderson Carl H. , McBurney John W. , McClintock William
Published: January 2005

Palatal myoclonus and acquired pendular nystagmus result from lesions in dentatorubroolivary pathways. We have investigated the effect of high doses of the anticholinergic drug trihexyphenidyl in four patients with palatal myoclonus and in four patients with acquired pendular nystagmus. The movements of each patients were videotaped three times: before administration of trihexyphenidyl, at the time of maximum or effective dosage, and after withdrawal from trihexyphenidyl. In five patients the movements were also electrographically recorded. A neurologist not familiar with the patients reviewed the tapes and rated the changes. In seven of eight patients, administration of the trihexyphenidyl resulted in marked improvement of both movements and complaints by patients. This observation indicates that disturbance of cholinergic mechanisms plays an important role in the pathophysiology of these two movement disorders.
Familial paroxysmal dystonic choreoathetosis: A family study
Authors: Kurlan Roger , Behr Jill , Medved Louis , Shoulson Ira
Published: January 2005

We interviewed and examined 12 members of a single family affected by paroxysmal dystonic choreoathetosis. Three subjects experienced characteristic painful dystonic spasms, often precipitated by cold and prolonged physical activity. Three other family members suffered painful cramping of their limbs, without involuntary movement, following physical exertion. Based on the clinical features of affected subjects, we suggest that exertional cramping may represent a “forme fruste” of paroxysmal dystonia.
Computed tomographic findings in progressive supranuclear palsy: Correlation with clinical grade
Authors: Schonfeld Steven M. , Golbe Lawrence I. , Sage Jacob I. , Safer Jan N. , Duvoisin Roger C.
Published: January 2005

We report clinical and computed tomography (CT) findings in 17 patients with progressive supranuclear palsy (PSP). Patients were divided into four clinical groups according to the severity of the disease and functional disability. In Grade 1, patients demonstrated minor disability and decreased anteroposterior (AP) diameter of the midbrain tegmentum was present. As the disease progressed clinically to Grade 2, more severe atrophy of the pons and midbrain and dilation of the quadrigeminal plate cistern were noted. The most severe stages of clinical disability (Grades 3 and 4) were characterized radiologically by dilatation of the aqueduct, progressive dilatation of the third and fourth ventricles and atrophy of the temporal lobes. Cortical atrophy was variable and not a prominent radiological feature. Midbrain and pontine AP diameters were significantly smaller in PSP patients than normal patients. Serial studies showed progressive involution of the pons and midbrain and enlargement of the third ventricle. While the most obvious CT changes in PSP occur late in the disease, CT may in fact suggest the correct diagnosis long before the classic clinical picture is evident.
Glycine involvement in DDT‐induced myoclonus
Authors: Truong Daniel Dung , De Yebenes Justo Garcia , Pezzoli Gianni , Jackson‐Lewis Vernice , Fahn Stanley
Published: January 2005

The DDT syndrome in rats consists of tremor, myoclonus, running seizures, hyperthermia, episodic boxing, and excessive grooming. DDT did not change whole‐brain glycine levels when the rats had stimulus‐sensitive myoclonus, spontaneous myoclonus, or seizures. However, regional analysis showed a decrease in glycine levels in the pons and medulla initially, but they rose again despite worsening of the myoclonus. Glycine given intraventricularly and the glycine prodrug, milacemide, given intraperitoneally suppressed DDT‐induced myoclonus. A dose of milacemide that prevented DDT‐induced myoclonus caused a significant increase in glycine levels in cortex, septum accumbens, cerebellum, striatum, hypocampus, diencephalon, midbrain, pons, and medulla. The increase was most marked in the forebrain structures. There was no change in serine levels in these areas. These data suggest that the glycinergic system may be playing an important role in the manifestation of DDT‐induced myoclonus.
Validity of a mailed epidemiological questionnaire and physical self‐assessment in Parkinson's disease
Authors: Golbe Lawrence I. , Pae Jeen
Published: January 2005

The large‐scale mail questionnaire is a useful tool in epidemiological investigation and will probably come into wider use in the search for an environmental cause of Parkinson's disease (PD). To determine the validity of mail questionnaires in patients with PD, we administered a 17‐item questionnaire by in‐person interview, as a standard, to 68 patients (and/or a relative when necessary) and compared the results with the same questionnaire mailed at least 1 month before or after the interview. Questions in three formats requested recall of the clinical course and past environmental factors. Each patient also completed a multiple‐choice physical self‐assessment (a modification of four items on the Columbia Scale) immediately before seeing the neurologist, who completed the same form after the examination. Percent of patients with zero discordance between mail and interview responses averaged 52% for the nine fill‐in‐a‐year items, 53% for the three list‐generation items. Kappa statistics for the five multiple‐choice items, which each offered four choices, averaged 0.67 (range 0.40–0.89). Kappa for the physical examination items, each rated on a 0–3 scale, was finger‐tap 0.12, gait 0.34, tremor 0.35, and chorea 0.20. Patients' ratings tended to be more severe than neurologists' ratings. We conclude that mail surveys in PD should either be avoided or rigorously pretested for validity.
Somatosensory phenomena in Huntington's disease
Authors: Albin Roger L. , Young Anne B.
Published: January 2005

Sensory symptons are generally not associated with Huntington's disease (HD). We describe two patients with HD who had painful sompatosensory symptons. One patient also had auditory hallucinations. No other cause was found for these symptoms. Both patients also had significant depression and one patient committed suicide. Somatosensory symptons may be a marker for depression in HD.
Pure akinesia due to lewy body Parkinson's disease: A case with pathology
Authors: Quinn N. P. , Luthert P. , Honavar M. , Marsden C. D.
Published: January 2005

The case of a patient with levodopa‐responsive pure akinesia and freezing of gait for 17 years, whose brain showed the classical changes of Lewy body Parkinson's disease at postmortem is presented. A short trial of DL‐threo–DOPS was ineffective. Intellectual function was preserved despite the presence of Lewy bodies and mild cell loss in subcortical cholinergic nuclei. Pure akinesia is likely to be a heterogeneous condition, with most cases having little or no response to levodopa therapy. However, this case demonstrates that this clinical picture may be caused by Lewy body Parkinson's disease.
The antiparkinsonian actions and pharmacokinetics of transdermal (+)‐4‐Propyl‐9‐hydroxynaphthoxazine (+ PHNO): Preliminary results
Authors: Coleman R. J. , Lange K. W. , Quinn N. P. , Loper A. E. , Bondi J. V. , Hichens M. , Stahl S. M. , Marsden C. D.
Published: January 2005

(+)‐4‐Propyl‐9‐hydroxynaphthoxazine (+ PHNO) is a potent dopamine agonist that has been administered transdermally to four patients with Parkinson's disease and “on‐off” fluctuations. Skin patches of increasing size were used to treat these patients, who also received infrequent doses of oral levodopa if required. The effect of +PHNO was measured as an increased duration of action of individual levodopa doses. The clinical effect measured in this way was directly proportional to the plasma concentrations of +PHNO achieved. The plasma concentrations of + PHNO began to rise 4–6 h after patch application and reached a steady state by 24 h. The final plasma concentration of + PHNO was proportional to the area of skin covered.
Spasmodic torticollis due to a midbrain lesion in a case of multiple sclerosis
Authors: Plant G. T. , Kermode A. G. , du Boulay E. P. G. H. , McDonald W. I.
Published: January 2005

A case of multiple sclerosis is described in which spasmodic torticollis occurred abruplty and abated after 1 year. Magnetic resonance imaging (MRI) demonstrated a lesion in the mesencephalon. Other symptoms and physical signs that developed at the same time as the spasmodic torticollis were compatible with the lesion that had not been present on MRI 18 months previously. There are very few reports of spasmodic torticollis due to an identified focal lesion; there is evidence form experimental work on animals that midbrain lesions may cause spasmodic torticollis but there has been no previous human example.
Absorption of apomorphine by various routes in parkinsonism
Authors: Gancher Stephen T. , Nutt John G. , Woodward William R.
Published: January 2005

We wanted to determine the absorption and clinical effect of sublingual (SL) and transdermal apomorphine in parkinsonism. Patients received single SL apomorphine doses (N = 7) and the absorption was compared with parenteral (N = 5) and oral (N = 4) doses. One patient received a transdermal dose of apomorphine. The relative bioavalability of SL apomorphine ranged from 10 to 22% of a parenteral apomorphine dose. Oral apomorphine was less than 4% bioavailable, and the transdermal dose did not produce detectable plasma levels. Three patients with motor fluctuations responded to SL apomorphine, with a latency to effect of 20‐40 min and a duration of effect of 15‐100 min. One patient used SL apomorphine as an adjunct with levodopa, and during 1 month reported a large decrease in “off” periods. We conclude that apomorphine is effectively absorbed by the sublingual route.
Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome
Authors: Trenkwalder Claudia , Seidel Victor Collado , Gasser Thomas , Oertel Wolfgang H.
Published: January 2005

Idiopathic restless legs syndrome (RLS) frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. We describe the largest German kindred of familial RLS with 20 affected and investigated members in four generations with a variety of clinical symptoms. Patients were examined clinically, and polysomnography was performed in selected cases. The diagnosis was set according to the diagnostic criteria of the International RLS study Group. All patients showed sensory symptoms of their legs and a worsening of symptoms with increasing age. Older patients, who needed treatment, responded well to opioids. Segregation ratios were close to 0.5, confirming a virtually complete penetrance. The mean age of onset fell from 51.5 years in the second generation to 19.8 years in the fourth generation (ANOVA, p=0.025). The identification of presymptomatic carriers in the fourth generation in the following years, however, may prejudice this result. This large family showed the variety of clinical RLS symptoms with decreasing age of onset in generations II‐IV, suggesting at least the possibility of anitcipation.
Motor innervation and fiber type pattern in amyotrophic lateral sclerosis and in Charcot‐Marie‐Tooth disease
Authors: Telerman‐Toppet N. , Coërs C.
Published: January 2005

A quantitive study of the terminal innervation ratio (TIR) was conducted using 18 amyotrophic lateral sclerosis (ALS) and 12 Charcot‐Marie‐Tooth disease (CMT) muscle biopsies. Morphometric and histochemical analyses of muscle fibers were performed in 9 ALS and 6 CMT biopsies. The results revealed that TIR and type grouping were significantly greater in CMT than in ALS. The proportion of type 3 fibers was higher in ALS, though the proportion of intermediate and type 0 fibers was significantly higher in CMT. The atrophy factor was significantly greater in type 3 than in types 1 and 2 fibers, but it was not significantly different in type 0 and intermediate fibers as compared to types 1 and 2. It appears, therefore, that CMT has a better capacity for collateral reinnervation than ALS. Type 0 and intermediate fibers may represent altered endproducts of successful collateral reinnervation.
Screening for peripheral neuropathy in patients treated by chronic hemodialysis
Authors: Thomas P. K.
Published: January 2005

Observations were made on the occurrence of peripheral neuropathy in a series of 139 patients admitted to a chronic dialysis program over a 10‐year period. Evidence of neuropathy was obtained in approximately 50% of these patients over the total period. Once dialysis was instituted, distal paresthesiae evident before the inception of dialysis tended to clear rapidly. Occurrence of the symptom of “restless legs” correlated positively with the presence of neuropathy. Persistent neuropathy was more commonly sensory than motor, and its features were consistent with a predominant loss of large myelinated fibers. This analysis suggests that multiple factors may be involved in the origin of uremic neuropathy.
Prednisone‐neostigmine interactions at cholinergic junctions
Authors: Noble Mark David , Peacock John Hollis , Lacher Jeffrey Allen , Hofmann William Ward
Published: January 2005

The effect of corticosteroid (prednisone) and/or chronic anticholinesterase (neostigmine) treatment on α‐bungarotoxin binding was examined in the diaphragms of male rats. In endplate regions of the diaphragm, prednisone treatment had no effect on the density of toxin binding sites, either when given alone or when administered in conjunction with neostigmine, while neostigmine was observed to reduce specific binding to less than half after one week.
Freeze‐fracture study of muscle plasmalemma in normal and dystrophic chickens
Authors: Costello Brian R. , Shafiq S. A.
Published: January 2005

We compared the freeze‐fracture morphology of the plasmalemma of the pectoralis major muscle taken from normal and dystrophic chickens at adult, embryonic, and early posthatching stages. Developmental changes were more conspicuous in surface caveolae than in intramembranous particles. The most striking differences between normal and dystrophic muscles were seen in the densities of the caveolae (17/μm2 in the normal adult; 30/μm2 in the dystrophic adult) and in their distribution (rectangular pattern in normals; random arrangement in dystrophics). These differences had already become significant at seven days posthatching and before the appearance of clinical symptoms. This is the earliest developmental stage at which morphologic abnormalities of plasmalemma have been reported for dystrophic muscle. Variations of surface topography and caveolar morphology, presumably representing secondary changes, were common in adult dystrophic muscle.
Myopathy due to epsilon amino‐caproic acid
Authors: Kennard C. , Swash M. , Henson R. A.
Published: January 2005

A subacute necrotizing myopathy developed in a patient treated with epsilon amino‐caproic acid (EACA) for subarachnoid hemorrhage. The muscle biopsy showed features suggesting that the muscle fiber necrosis might have been due to capillary damage. An attempt to induce EACA myopathy in the rat was made, but no abnormality developed.
Is Kugelberg‐Welander spinal muscular atrophy a fetal defect?
Authors: Hausmanowa‐Petrusewicz I. , Fidziańska A. , Niebróaj‐Doposz I. , Strugalska M. H.
Published: January 2005

Twelve children who had developed Kugelberg‐Welander (K‐W) spinal muscular atrophy (SMA) before the age of six years were investigated. Electrophysiological, histochemical, ultrastructural, and biochemical studies demonstrated features of immature muscle fibers suggesting a fetal defect as in the Werdnig‐Hoffmann (W‐H) form of SMA. Comparison with known patterns of human myogenesis and of experimental denervation of immature muscle suggested that the defect in K‐W SMA probably takes place in fetal life at a stage later than in W‐H SMA. In contrast to W‐H SMA, a considerable percentage of mature fibers of normal structure and diameter were present. The immature fibers impair the normal development of muscle cells by preventing the increase in number of mature fibers and causing an overloading of the normal fibers with consequent hypertrophy and eventually destructive changes. This is the pattern in K‐W disease that distinguishes the juvenile form of SMA from W‐H disease.
Acute effects of phenytoin on peripheral nerve function in the rat
Authors: Marcus Donald J. , Swift Thomas R. , McDonald Thomas F.
Published: January 2005

The acute effect of intraperitoneal injection of phenytoin on rat peripheral nerve was studied. Conduction velocities in the ventral caudal nerve were measured hourly and phenytoin blood levels were obtained 4 to 5 hours after injection. Conduction velocity decreased by 23% in the 25 phenytoin‐treated animals from a control value of 30.0 ± 1.3 m/sec (mean ± SEM) to a 4‐hour value of 23.0 ± 1.3 m/sec (P < 0.001). The phenytoin blood level 4 hours after injection was 45.0 ± 1.3 μg/ml. Amplitudes of evoked muscle action potentials in the treated group decreased by 37% from control values. High levels of phenytoin induce prompt slowing of nerve conduction velocity within hours, which may be mediated by mechanisms similar to those responsible for toxic central effects.
Localization of choline acetyltransferase at neuromuscular junctions
Authors: Kan K. ‐S. Karen , Chao Li‐Pen
Published: January 2005

Choline acetyltransferase (ChAc) was localized at the neuromuscular junctions of rabbit diaphragm with immunohistochemical staining, which produced a brown color, in combination with histochemical staining for cholinesterase, which produced a blue color, in the same section. The innervations of nerve terminals at the neuromuscular junctions were comparable when a silver impregnation was substituted for the immunohistochemical staining of ChAc.
Adenylosuccinase in human muscular dystrophy
Authors: Kar Nirmal C. , Pearson Carl M.
Published: January 2005

The level of adenylosuccinase was measured in muscle from patients with Duchenne and other major forms of progressive muscular dystrophies and certain related neuromuscular diseases. The activity was found to be unaltered in all diseases that were examined.
Acquired canine myasthenia gravis: Immunocytochemical localization of immune complexes at neuromuscular junctions
Authors: Pflugfelder Christina M. , Cardinet George H. , Lutz Hans , Holliday Terrell A. , Hansen Robert J.
Published: January 2005

In the acquired form of myasthenia gravis in dogs, there are circulating antibodies to acetylcholine receptors (AChRs) and a reduction in the number of AChRs in the postsynaptic membrane. In this study, immune complexes were localized at the neuromuscular junctions in biopsy samples from 10 myasthenic dogs by immunocytochemical means employing conjugates of staphylococcal protein A and horseradish peroxidase. Immune complexes were observed in approximately 70% of the neuromuscular junctions studied in both type 1 and type 2 myofibers. Thus, acquired canine myasthenia gravis appears to involve immune‐mediated mechanisms that destroy AChRs in a manner similar to myasthenia gravis in humans. Protein A was also observed to bind principally to elastic fibers in small arteries and arterioles of some myasthenic and control dogs; however, the significance of that localization is unknown.
Increased [32P]‐phosphorylation of tryptic peptides of erythrocyte spectrin in duchenne muscular dystrophy
Authors: Mabry Michael E. , Roses Allen D.
Published: January 2005

Increased [32P]‐incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was [32P]‐phosphorylated by cyclic AMP‐independent endogenous membrane protein kinase in the presence of [γ‐32P]ATP. [32P]‐labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high‐resolution 5%/15% stacking SDS‐polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad [32P]‐labeled band containing a number of [32P]‐polypeptides was found to be more highly [32P]‐phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8–5.2 kilodaltons and contained approximately 55% of total [32P] radioactivity covalently bound to spectrin peptides. These data demonstrated an increased [32P]‐phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 [32P]‐phosphrylation in DMD.
Nerve conduction velocity varies inversely with height
Authors: Campbell William W. , Ward L. Charles , Swift Thomas R.
Published: January 2005

Even when all known factors affecting the determination of nerve conduction velocity are controlled, large individual variations persist. In 40 normal controls, we found that peroneal and sural conduction velocities varied inversely with body height (P < 0.001). This height effect is not due to temperature differences, and it explains almost 50% of the intersubject variability in conduction velocity. We hypothesize that the height influence reflects abrupt, rather than gradual, tapering of axons distally. This mode of tapering may help explain the decrements in conduction velocity from proximal to distal nerve segments and from upper to lower extremities, which have long been observed in clinical electromyography. Clinical recognition of this height effect is important lest one label as abnormal an individual with mildly slowed peripheral nerve conduction velocity solely related to large stature.
Increase of muscle mitochondrial content with age in murine muscular dystrophy
Authors: Silverman Harold , Atwood Harold L.
Published: January 2005

Comparison of morphological features of gastrocnemius muscle fibers in normal and dystrophic (dy2J) mice during development was undertaken to determine the time course of increased oxidative capacity in dystrophic fibers. Measurements of mitochondrial volume percent and of Z‐line width were made in superficial fast‐twitch fibers using electron microscopy and stereological techniques. Dystrophic fibers develop a progressively higher mitochondrial volume percent than normal fibers after 1 month of age. Z‐line width is positively correlated with mitochondrial volume percent. The results support the hypothesis that progressive changes in muscle fiber properties result from abnormal neural activity (pseudomyotonia) in dystrophic animals.
Stereometric estimation of the area of the freeze‐fractured membrane
Authors: Engel Andrew G. , Fukunaga Hidetoshi , Osame Mitsuhiro
Published: January 2005

Stereo‐pair micrographs of freeze‐fracture replicas taken at +6 and −6 degrees and enlarged 55,000 diameters were precisely aligned on a digitizing pad linked to a plotter and programmable calculator. A point grid spaced at 0.23 μm was placed over the left photo‐pair. Under stereoscopic observation, matching points were placed by hand on the right photo‐pair for every point in the applied grid that fell over the membrane surface of interest in the left photo‐pair. The x, y coordinates of every point in the two photos were read with the digitizer. These data allowed the calculation of the X, Y, Z coordinates of all points in the untilted object space, 3‐D reconstruction of the analyzed surface, and estimation of the membrane surface area.
Evidence for a motor nerve growth factor
Authors: Slack J. R. , Hopkins W. G. , Pockett S.
Published: January 2005

We review the evidence that a motor nerve growth factor released from muscle has wide ranging effects on the development and maintenance of muscle innervation. The actions of this putative factor on motor neurons are analogous to the actions of the well known nerve growth factor (NGF) on sympathetic and sensory neurons.
Effects of insulin on protein synthesis in muscles from normal and dystrophic mice
Authors: Ballard F. John , Nield Michelle K. , Tomas Frank M.
Published: January 2005

Protein synthesis in soleus and extensor digitorum logus (EDL) muscles was measured in vitro to test the hypothesis that the lack of muscle protein accumulation in dystrophic conditions could be caused by a reduced sensitivity to insulin. We demonstrate that physiological insulin concentrations stimulate protein synthesis in soleus muscles from normal mice but not from muscles obtained from dystrophic (dy) animals. The difference is lost at very high insulin concentrations (1 μM) and could not be shown at any concentration with EDL muscles. These results, together with the reported reduced inhibitory effect of insulin on protein synthesis in dystrophic hamsters and on protein breakdown in dystrophic mice, suggest, that protein metabolism in certain muscles from dystrophic animals may be less responsive to the anabolic effects of insulin.
The CO‐dispersion index for the measurement of fiber type distribution patterns
Authors: Lester James M. , Silber Dennis I. , Cohen Michael H. , Hirsch Robert P. , Bradley Walter G. , Brenner John F.
Published: January 2005

There is a need for a practical and statistically manageable quantitative index of fiber type co‐dispersion in skeletal muscle to allow investigation of the distribution of motor units in normal muscle and their rearrangement in pathological states. A new measure for this purpose, the Co‐Dispersion Index (CDI), is introduced. This measure is based on contingency table analysis of nearest‐neighbor relationships between muscle fibers. The CDI has a continuous range of values from −1 to +1, in which larger negative values indicate a greater tendency toward regular intermixing of fibers of different types, and larger positive values a greater segregation of fiber types. CDI evaluation overcomes the limitations of previously published quantitative methods for codispersion measurement and is well correlated with subjective human estimates of fiber type grouping.
Axonal regeneration in wobbler motor neuron disease: Quantitative histologic and axonal transport studies
Authors: Mitsumoto Hiroshi
Published: January 2005

The regenerative capacity of the cervical anterior horn cells was studied at 4 and 7 days following forelimb nerve crush in 19 Wobbler mice and 18 normal littermates. Quantitative histologic and radiolabeled axonal transport techniques showed that the axotomized neurons of the wobbler mouse supported active axonal elongation. However, the average axon outgrowth rate determined by histologic technique was diminished by 25% and the fastest axon outgrowth rate determined by axonal transport technique was also decreased by 30% in wobbler mice as compared to controls. The distal labeled peak was absent in the wobbler mouse at 7 days, indicating that the regeneration rate of individual axons was widely dispersed. Histologic studies also showed that the wobbler axons grew slowly. This study suggests that axonal regeneration does occur in motor neurons undergoing a primary neuronopathy. However, the regenerative capacity was reduced and this appears to reflect an impairment of functional integrity in the anterior horn cells of the wobbler mouse.
Ligature‐induced injury in peripheral nerve: Electrophysiological observations on changes in action potential characteristics following blockade of potassium conductance
Authors: Waxman Stephen G. , Kocsis Jeffery D. , Eng Douglas L.
Published: January 2005

The effects of the potassium channel blocking agent 4‐aminopyridine (4‐AP) on action potential properties were studied in chronically injured rat sciatic nerves. In normal, mature myelinated fibers, application of 4‐AP does not lead to any significant change in action potential waveform or firing pattern in response to single stimuli. In contrast, application of 4‐AP to nerves injured by the placement of loose ligatures results in the appearance of late rippled components in the compound action potential. This alteration in waveform is present at the injury site, but not at nerve segments proximal or distal to this region. Paired stimulation experiments demonstrate that this oscillation of the whole nerve resporse reflects repetitive firing in response to single stimuli following application of 4‐AP. Intra‐axonal recording following 4‐AP application demonstrates bursts of action potentials, with several spikes of reduced amplitude arising from a depolarizing potential following the initial spike. Refractory period for the late spike is grater than that of the primary action potential. These results demonstrate that potassium channels are present and functional in chronically injured nerves, where blockage of these channels results in repetitive firing in response to single stimuli.
Measurement of junctional acetylcholine receptors in myasthenia gravis: Clinical correlates
Authors: Pestronk Alan , Drachman Daniel B. , Self Steven G.
Published: January 2005

We measured the number of acetylcholine receptors (AChRs) at neuromuscular junctions (NMJs) in motor point biopsies from 76 patients with myasthenia gravis (MG) and 49 control subjects, using an α‐bungarotoxin binding technique. The mean number of AChRs/NMJ was significantly lower (P < 0.001) in muscles of MG patients (deltoid 0.7 ± 0.1 × 107) than in controls (2.1 × 0.2 × 107). None of the control muscles had fewer than 0.9 × 107 AChRs/NMJ, and 75% of MG muscles were below that level. Conversely, 88% of controls had 1.5% × 107 or more AChRs/NMJ, whereas only one of the MG muscles (2.5%) was at or above that level. The reduction of AChRs correlated approximately with the clinical severity of weakness (P < 0.02). Patients with focal weakness had reduced numbers of AChRs/NMJ in clinically strong muscles. The only other condition in which junctional AChRs were reduced was polyositis. These findings in a large sample of patients confirm the reduction of junctional AChRs in MG, the relationship of available junctional AChRs to clinical manifestations, and the systemic nature of the disorder even in cases with focal weakness. Measurement of AChRs can be useful diagnostically in situations where other tests are inconclusive.