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Objective The continuous increase in the number of patients presenting with late-onset myasthenia gravis (LOMG) underscores the need for a better understanding of the clinical course and the establishment of an optimal therapeutic strategy. We aimed to clarify factors associated with clinical outcomes in LOMG. Methods We retrospectively reviewed the clinical profiles of 40 patients with early-onset MG (EOMG) (onset age: 49 years or younger), 30 patients with non-elderly LOMG (onset age: 50–64 years), and 28 patients with elderly LOMG (onset age: 65 years or older) and compared the subgroups according to onset age and thymus status. The evaluated parameters were MGFA classification before treatment, MG-ADL score, complicating diseases, antibody titer, treatment, and MGFA post-intervention status. Results Elderly LOMG patients showed transition to generalized symptoms at a higher frequency and underwent thymectomy less frequently than EOMG and non-elderly LOMG patients (p, Highlights • Elderly LOMG patients showed transition to generalized symptoms at a higher frequency. • Thymectomized LOMG patients without thymoma showed crisis less frequently. • Our study showed that elderly LOMG patients are more prone to severity.

Although dysphagia is an important symptom associated with prognosis in patients with Parkinson's disease (PD), dysphagia tends to be overlooked until swallowing difficulties reach an advanced phase. We assessed dysphagia with videofluoroscopic examination of swallowing in 31 patients with mainly mild or moderate PD. Swallowing problems were observed in the pharyngeal phase in 28 patients, oral phase in 19 patients, esophageal phase in 15 patients, and oral preparatory phase in 1 patient. Therefore, dysphagia in the pharyngeal phase was observed in almost all patients with mild or moderate PD. In contrast, no dysfunction was detected in most patients when screening was conducted via questionnaire or other methods. Assessment of clinical parameters in the present study suggests that latent swallowing dysfunction may be present even in the early disease stage in PD. A future prospective study to follow swallowing functions in a pre-symptomatic phase in PD would be fruitful to find whether swallowing dysfunction is one of the prodromal symptoms.

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy characterised by length-dependent degeneration of the motor and sensory nerve fibres with consequent distal muscle weakness, atrophy and mild sensory loss, primarily in lower limbs. The historic prevalence of CMT in the general population is 1 in 2500 individuals,1 while the present prevalence is 1 in 1214 individuals.2 Missense mutations in the mitofusion 2 gene ( MFN2 ; OMIM*608506) have been found in most axonal forms (CMT type 2; CMT2) with autosomal dominant inheritance, and truncation mutations can be found in a few cases with seemingly autosomal recessive inheritance or sporadic cases. A dominant negative or toxic gain-of-function mechanism has been postulated in the autosomal dominant mode; however, the biological effect(s) by mutant MFN2 may vary depending on the nature of the mutations.3 This report describes a unique pathomechanism identified in a large Japanese MFN2 -CMT2A2 family. The currently living family members were examined by movement disorder specialists (TK, RM, HN, YN and YI). Neurological assessments, including the Charcot-Marie-Tooth disease neuropathy score V.2, electrophysiology of peripheral nerves and neuroimaging analyses, were carried out. Genetic analyses were conducted as described in online supplementary data, including targeted resequencing, Sanger sequencing, restriction fragment length polymorphism (RFLP) analysis and semiquantitative reverse-transcription (RT)-PCR. Peripheral T-cells were cultured with a nonsense-mediated decay (NMD) inhibitor, emetine, in order to evaluate the effect by NMD system. A bioinformatic analysis and literature review were also carried out. The details are described in online supplementary data. ### Supplementary data [jnnp-2015-312646supp.pdf] The family is composed of a three-generation kindred, with autosomal dominant inheritance (figure 1A). Nine individuals were diagnosed as ‘certainly affected’ and classified as having Charcot-Marie-Tooth disease. Clinical and laboratory features of all affected individuals are summarised in online supplementary tables S1 and S2, and figure S1. Age-at-onset was 5 or …

Aims Among the pathological findings in Alzheimer's disease (AD), the temporal and spatial profiles of granulovacuolar degeneration (GVD) bodies are characteristic in that they seem to be related to those of neurofibrillary tangles (NFTs), suggesting a common mechanism underlying the pathogenesis of these structures. Flotillin-1, a marker of lipid rafts, accumulates in lysosomes of tangle-bearing neurones in AD patients. In addition, recent reports have shown that GVD bodies accumulate at the nexus of the autophagic and endocytic pathways. The aim of this study was to elucidate the distribution of the lipid component of lipid rafts, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2], in AD and other neurodegenerative disorders. Methods We compared PtdIns(4,5)P2 immunoreactivity in the hippocampus, entorhinal cortex and neocortex of five AD cases, 17 cases of other neurodegenerative disorders and four controls. In addition, we performed double staining using markers of GVD, NFTs and lipid rafts for further characterization. Results Immunohistochemical analysis revealed that PtdIns(4,5)P2 was selectively enriched in GVD bodies and NFTs. Although immunoreactivity for PtdIns(4,5)P2 was also evident in NFTs composed of hyperphosphorylated tau, PtdIns(4,5)P2 was segregated from phosphorylated tau within NFTs by double immunofluorescence staining. In contrast, PtdIns(4,5)P2 colocalized with the lipid raft markers flotillin-1 and annexin 2, within GVD bodies and NFTs. Conclusions These results suggest that lipid raft components including PtdIns(4,5)P2 play a role in the formation of both GVD bodies and NFTs.

We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.

Stiff person syndrome (SPS) is a rare neurological disease with features of an autoimmune disease. SPS is characterised by severe progressive muscle stiffness of the spine and lower extremities with superimposed muscle spasms triggered by external stimuli such as noise, touch and emotional distress.1 Patients with SPS respond to high doses of muscle relaxants, such as diazepam and baclofen, several anticonvulsants, and gabapentin. Previous studies have reported that several causal treatments with corticosteroids, plasmapheresis, intravenous immunoglobulin (Ig) and new immunomodulating agents can reduce stiffness and lower sensitivity to stimuli and stress in patients with SPS.2 ,3 Because SPS is a chronic disease, patients generally require long-term treatments, which may be effective but difficult to take for long periods. Tacrolimus (Prograf, FK506) is a macrolide molecule belonging to the same immunosuppressant class as cyclosporine. Tacrolimus has a lower molecular weight and is 100-fold more potent in inhibiting T cell proliferation than cyclosporine. It acts through inhibition of the calcium-calcineurin (CaN) pathway and exerts its immunosuppressive effect by reducing the proliferation of activated T cells.4 We now report the successful treatment of patients with SPS using tacrolimus as the immunosuppressive agent. ### Patients We assigned two patients with SPS who had incomplete responses to conventional therapies and fulfilled the defined clinical criteria (online supplementary table 1).3 ### Clinical evaluations At baseline and each month thereafter, a neurologist used the distribution of stiffness index, the most consistent indicator of stiffness among patients and within patients, to evaluate the patients with SPS.3 Scores on this index range from 0 to 6 and reflect the extent of stiffness. The same neurologist also assessed the patients for changes in frequency of spasms with use of the heightened-sensitivity scale, which has been a reproducible and consistent means of assessing the number of factors triggering spasms.3 …

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory.

We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866 + 1G > A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis.

We present a patient who initially developed diffuse painful muscle cramps who had elevated antibodies against voltage-gated potassium channel (VGKC) complex. Despite the initial improvement after immunomodulatory therapy, she later developed progressive atrophy and weakness of the limb muscles whose electrophysiological finding mimicked that in lower motor neuron disease. A potential causal relationship between anti-VGKC complex antibody-associated hyperexcitability and lower motor axon loss is discussed.

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

alpha-Mannosidosis is an autosomal recessive lysosomal-storage disorder caused by a deficiency of lysosomal alpha-mannosidase activity. This disease shows a wide range of clinical phenotypes, from a severe, infantile form (type I), which is fatal at

We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.

Seven patients, aged 10–17 years, with Duchenne muscular dystrophy were treated orally with prednisolone (PSL) at a dose of 0.8–1.0 mg/kg per day for 8 weeks. During the treatment their muscle strength, serum creatine kinase (CK) activity, serum levels of myoglobin (Mb), and urinary excretion of 3-methyl-histidine (3-MeH) and glycine (Gly) were measured serially. In all the patients, the motor function or muscle strength improved, and the serum CK activity and Mb level decreased during PSL treatment. Urinary excretion of 3-MeH, a unique constituent of muscle contractile proteins, decreased to 51–63% of the baseline value in weeks 6–9 after the start of PSL administration, and returned to the baseline level in week 12. The ratios of 3-MeH to creatinine and to Gly also decreased during the treatment. Urinary excretion of Gly, which is ubiquitous in all tissues including muscle, did not decrease during the treatment. These findings suggest that PSL inhibits proteolysis of muscle contractile protein.

Background: Chronic progressive external ophthalmoplegia (CPEO), which includes Kearns-Sayre syndrome, is a mitochondrial disorder with large deletions of mitochondrial DNA. Recently, mtDNA deletions in cardiac muscle cells were thought to be a cause of dilated cardiomyopathy. However, the cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system. Hypothesis: The purpose of this study was to evaluate left ventricular function in patients with CPEO. Methods: We evaluated the cardiac function of five patients with CPEO by means of carotid pulse recording and Doppler echocardiography. Results: The ratio of the pre-ejection period to ejection time was increased to 0.67 in one patient and to 0.50 in another. Echocardiography showed left ventricular dilatation and diffuse hypokinetic wall motion in both cases. Left ventricular fractional shortening was decreased to 5 and 19%, respectively, and the mean rate of circumferential shortening was decreased to 0.12 and 0.63 circ/s, respectively. One of the two patients died of congestive heart failure 2 months after the study. The Doppler pattern of left ventricular filling in the three remaining patients showed a decrease in the ratio of peak flow velocity in early diastole to that in late diastole, with an increase in deceleration time. Conclusion: Although cardiac involvement in patients with CPEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of patients with CPEO.

Inhalation of organic solvents has long been known to damage various nervous systems, including cerebellum, brainstem, and pyramidal tract. However, little is known about the damage of the dopaminergic system. We report two patients with occupational long-term solvent exposure who developed postural instability without other features of parkinsonism. The concentration of HVA in CSF was decreased and the retropulsion was dramatically improved after the administration of levodopa. These findings indicate that the nigrostriatal dopaminergic neurons were disturbed by chronic solvent exposure, resulting in the loss of postural reflexes.

OBJECTIVES Mutational analysis of the sterol 27-hydroxylase ( CYP27 ) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism. METHODS Clinical evaluations, brain MRI studies, and laboratory analyses were completed on the three patients. The CYP27 gene was analysed for mutations by PCR amplification of gene segments followed by direct sequencing. RESULTS Two different, homozygous mutations were identified in these families. One is a novel transition, substituting T for G at Glu162 (GAG) resulting in a stop codon (TAG). The other is also a transition, substituting T for C at Arg441 (CGG) resulting in Trp (TGG). The second is located in two amino acids ahead of the heme ligand binding site (Cys443) of the protein likely rendering it non-functional. It is the most common CTX mutation in Japanese patients. CONCLUSIONS CTX with parkinsonism is caused by mutations with a severe impact on enzyme function. The two mutations described here are likely to cause loss of function because they are chain terminating or affect an essential site in the protein.

We examined the effect of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on the neurotoxicity of L-glutamate in organotypic cultures of rat spinal cord. Eighteen-day-old cultures were incubated with 500 microM L-glutamate, 1 mM PDC, or both. After 72 hours, the tissues were stained for acetylcholinesterase (AChE), and the ventral horn AChE-positive neurons (VHANs) analyzed using morphometry. Neither L-glutamate nor PDC affected AChE staining, but in combination they produced markedly reduced AChE staining in the dorsal horn and a significant decrease in the number of VHANs (especially the smaller VHANs) as compared with the control. Moreover, treatment with 200 microM PDC for 2 weeks preferentially affected the smaller VHANs. The neurotoxicity of L-glutamate plus PDC was blocked by the N-methyl-D-aspartate (NMDA) antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Results suggest that glutamate uptake system has an important protective function in the aggravation of acute neuronal damage.

Activities of nine lysosomal enzymes and pH-dependent isozyme patterns of α-mannosidase were examined in the skeletal muscle of patients with neuromuscular diseases, and the ratios of these enzyme activities in leukocytes to those in myocytes (UM ratio) were determined. The activities of enzymes with a high UM ratio were markedly increased in the muscles of patients with Duchenne muscular dystrophy (DMD), myotonic dystrophy (MyD), or polymyositis (PM). In contrast, those which showed a low UM ratio were increased in the muscles of amyotrophic lateral sclerosis (ALS) and disuse muscle atrophy (DUA). The isozyme pattern of α-mannosidase in DMD muscle resembled that in leukocytes, while those in ALS and DUA muscle resembled that in normal muscle. These results may suggest that the increased activity of lysosomal enzymes in the muscles of patients with DMD, MyD, or PM is due primarily to infiltrating leukocytes, while that in patients with ALS or DUA is due to intramyofiber lysosomes. 1995 John Wiley & Sons, Inc. . neuromuscular disease MUSCLE & NERVE 18 :1009-10151995

We report a Japanese family with chronic progressive external ophthal-moplegia (CPEO) with autosomal dominant inheritance, and review 54 reported CPEO patients in seven families (including the present family) with autosomal dominant inheritance and mtDNA deletions in the skeletal muscle. Mean age at onset in the CPEO was 26 years, which is older than that in published solitary cases. In addition to blepharoptosis and external ophthalmoplegia, proximal muscle atrophy and weakness were found in 62%, hearing loss in 25%, and ataxia in 17% of the patients. Retinal degeneration was not found, and cardiac involvement was very rare. mtDNA deletions in the muscle were multiple and large scale, and all such deletions were located in the non–D-loop region. Autosomal dominant CPEO has unique clinical features which differ from those of solitary CPEO, and is associated with multiple large-scale mtDNA deletions. Thus, autosomal dominant CPEO can be considered a clinical and genetic entity of mitochondrial diseases. © 1995 John Wiley & Sons, Inc.

Expression of the myoglobin (Mb) gene in skeletal muscle was studied in patients with Duchenne muscular dystrophy (DMD), polymyositis (PM), or amyotrophic lateral sclerosis (ALS) by measuring Mb concentration by radioimmunoassay and Mb messenger ribonucleic acid (RNA) (MbmRNA) levels by Northern blot analysis. Mb concentrations in the muscle cells (Mb/noncollagenous protein) were decreased in patients with DMD, PM, or ALS. However, while Mb concentrations per MbmRNA content (Mb/MbmRNA) were decreased in DMD and PM patients, these values were normal in ALS patients. These results suggest that Mb synthesis is increased in muscles of DMD and PM patients, but is not sufficient to compensate for the excessive loss of Mb from the affected muscles, and that the synthesis is decreased in the muscles of ALS patients. © 1994 John Wiley & Sons, Inc.

The localizations of myoglobin in skeletal muscle cells of patients with Duchenne muscular dystrophy (DMD), myotonic dystrophy (MyD), and amyotrophic lateral sclerosis (ALS) were studied by immunohistochemistry and immunoelectron microscopy. In normal skeletal muscle cells, myoglobin was localized mainly in the I-band region. In degenerating muscle cells of patients with DMD and MyD, myoglobin was also demonstrated in the distended lumen of the internal membrane system and in the intermyofibrillar space, through which it seemed to pass into the extracellular space. No myoglobin was detected in opaque fibers or in some of small-sized fibers in DMD muscle. In patients with ALS the staining intensities of myoglobin varied in different muscle cells, but myoglobin was restricted to the I-band region in many muscle cells. These findings suggest that changes in the localization of myoglobin in skeletal muscle cell sensitively reflect the pathologic status of muscle cells.

The isozyme patterns of leukocyte α-d-mannosidase in two sisters with mannosidosis, their parents and a patient with trisomy 19 were studied. The isozyme pattern of liver mannosidase of a normal subject was also studied. In the patients with mannosidosis the neutral isozyme (isozyme C or fraction C) was present, but the acidic isozymes (isozyme A and B or fraction A and B) were not detectable. In their parents the activity of the acidic isozymes was one-third of the normal activity. These findings suggest that the patients are homozygous and their parents are heterozygous in terms of deficiency of acidic isozymes. In the patients with trisomy 19, the activity of α-d-mannosidase was 4.9 times the upper limit of the normal value, while the levels of other lysozomal enzymes were normal. This increase was mainly due to increases of the A and B isozymes of mannosidase. This finding suggests that the gene encoding acidic isozymes, but not that encoding the neutral isozyme, is located on chromosome 19. The isozyme pattern of α-d-mannosidase differed in different tissues of normal subjects, and the difference in severity of lesions in different organs of the patients with mannosidosis could be explained by differences in the isozyme patterns of the enzyme in these organs.

A method is presented to test the validity of the impulse approximation without or with nuclear distortion in the calculation of inelastic scattering of high energy nucleons by nuclei. The inelastic scattering of 182 MeV protons by C12 with the excitation of the 4.43, 7.66 and 9.63 MeV levels is investigated as example. In the impulse approximation without nuclear distortion the relevant matrix element can be obtained empirically by means of the experimental data regarding the inelastic electron scattering on C12. The effect of the nuclear distortion by a square well optical potential is investigated in detail for the excitation of the 4.43 MeV level. That part in the relevant matrix element which contains the wave functions of the ground and excited states can empirically be determined by means of the inelastic electron scattering data and the observed life time of the level against E2 transition to the ground state. The calculation indicates that the nuclear distortion mainly makes the position of the maximum in the differential cross section shift towards smaller scattering angles. The result of the present analysis shows that whether the impulse approximation without or with nuclear distortion is valid or not depends sensitively on the level structure. It is concluded that the single inelastic collision mechanism involved in the present impulse approximation calculations is valid for the excitation of an independent particle level, while the stronger the many-particle features in a level become, the less valid it becomes and the more significant the effect of the multiple inelastic scattering becomes.

The off-shell amplitudes for nucleon-nucleon scattering are calculated for nucleon scattering from complex nuclei, under the assumption that the two-nucleon interaction is given by a spin-dependent Gaussian potential with Serber exchange character. It is shown that the approximation method previously proposed by the writer and collaborators in connection with other problems is applicable also to this case, in spite of the fact that the conditions are rather different here. While the present approach assumes an artificial potential between two nucleons, this has the advantage that the off-shell amplitudes can be written in closed form and the accuracy of the method can be insensitive to the energy difference between the initial and final states. It is confirmed by numerical investigations that the present approach enables one to obtain the off-shell amplitudes with remarkable accuracy for a very wide range of initial and final energies, as well as for all scattering angles. Finally, the accuracy of the conventional procedure which consists in replacing the off-shell amplitudes by the on-shell ones with the same momentum transfer is examined. It is shown that in such a replacement the use of the initial on-shell amplitudes is much more accurate than that of the final on-shell ones, and the former approximation has a fair success in predicting the off-shell amplitudes for a wide range of angles in the forward scattering hemisphere and for a large region of incident energies.

A simple approximation method is proposed to investigate the scattering of high-energy Schrodinger particles by some spherically symmetrical potentials which have no sharp boundaries but whose shapes do not deviate much from a square well form. The method is applicable when the strength of the potential is substantially smaller than the incident energy and k0R is greater than unity, where k0 is the wave number of the incident particle and R is a rough measure of the range of the potential. The procedure consists in making use of the Hart-Montroll internal wave function for the square well potential which is equivalent to the original potential in the least-square sense as a trial function on solving an integral equation for the scattering wave function. Then, it is shown that the scattered amplitude can be written in a similar form to that of the second Born approximation. As examples, the method is applied to the scattering by Gaussian and harmonic well potentials which may be complex. In these cases, the scattered amplitudes can be written in tractable forms and furthermore it is expected that they can be used with good accuracy for a fairly wide range of scattering angles including those around (k0R)−12 in contrast with the Schiff or Glauber approximation. Finally, numerical illustrations are given and the results are compared with those of the exact method and other approximations, and thereby the validity and usefulness of the present method are confirmed.

Two siblings with congenital myopathy showing myasthenic manifestations together with congenital cataract are reported. Their muscle weakness fluctuated and was alleviated by edrophonium chloride. Their serum creatine kinase activity was elevated, and the waning phenomenon was observed on repetitive nerve stimulation. Biopsied muscle showed degenerative changes with type 1 fibre predominance and abnormal morphology of neuromuscular junctions.

Inelastic scattering of high energy nucleons by nuclei is an important tool to investigate properties of nuclear levels. It is shown that a test regarding the impulse approximation can be performed. The inelastic scattering of 182 Mev protons by C/sup 12/ with energy losses of 4.43, 7.66, and 9.63 Mev is investigated. (W.D.M.)

A sensitive sandwich enzyme immunoassay (EIA) for human myoglobin (Mb) was developed. Serum Mb was assayed by incubation with an anti-Mb rabbit IgG-coated polystyrene ball and then with affinity-purified anti-Mb Fab'-horseradish peroxidase (HRP) conjugate. The HRP activity bound to the polystyrene ball was assayed fluorimetrically. The sensitivity was 3.1 pg/tube and serum Mb levels of 0.4-1000 micrograms/l could be determined. The recoveries of Mb added to human sera at 3 concentrations were 92.8-99.8%. The within- and between-assay coefficients of variations (CV values) were both below 10%. The regression equation of values determined by EIA and radioimmunoassay (RIA) was y(EIA) = 0.964x (RIA)--2.30 and the correlation coefficient was 0.984. The mean normal serum concentration of Mb was 21.5 +/- 6.0 micrograms/l (mean +/- SD) in males and 16.9 +/- 5.8 micrograms/l in females. The significance of serum Mb determination by the EIA in various diseases was confirmed. The present EIA for Mb is more sensitive and economical than RIA and should be useful for determining Mb in biological materials.

The localization of myoglobin in human skeletal muscle cell was studied by immunoelectron microscopy. The Fab'-horseradish peroxidase (HRP) conjugate was prepared by the maleimide method recently developed by Ishikawa et al. This method gave better recovery and less polymerization of HRP than the periodate method. By the direct immunoperoxidase method using this conjugate, myoglobin was shown to be localized in the I-band region of skeletal muscle cells. The outer membrane of mitochondria and triads stained intensely, but A-bands were not stained. Myonuclei and intermyofibrillar spaces were also not stained. The localization of myoglobin in the I-band implies its function in energy generation.

To estimate the replication of the human T-cell leukemia virus type I (HTLV-I) in patients with HTLV-I-associated myelopathy (HAM), or tropical spastic paraparesis (TSP), HTLV-I DNA integrated into lymphocyte genomes was analyzed by Southern blot hybridization. HTLV-I DNA was detected in 125 (82%) of 153 patients and most showed random integration. This incidence was much higher than the 29% found in asymptomatic carriers. Therefore, HAM/TSP development is associated with a high level of HTLV-I replication. In addition, lymphocytes from 3 patients with HAM/TSP showed monoclonal integration of HTLV-I DNA, indicating adult T-cell leukemia.

常染色体優性の遺伝性を示す家族性特発性大脳基底核石灰化症(FIBGC)の1家系3症例を報告した.発端者16才,女性で, 12才時に拍動性の頭痛を訴えるようになり, 16才で軽度の小脳性運動失調を認めた.そして,頭部X線像および頭部CT像で両側の大脳基底核部と視床に石灰化像を認めた.不随意運動や筋緊張の異常はなく,副甲状腺機能も正常であった.母と母方祖父にも大脳基底核の石灰化像がみられたが,神経症状はみられなかった.本家系では石灰化像の軽い若年の発端者にのみ神経症状が出現しているのが特徴であり,従来のFIBGCの報告例と異なっている.また,錐体外路症状はなく,基底核部石灰化による神経障害は少ないと考えられた.

A 37-year-old Japanese man in previously good health was hospitalized because of swelling of the auricles had discoid erythema of the face. Clinical and laboratory findings satisfied the diagnostic criteria for systemic lupus erythematosus proposed by the American Rheumatism Association. However, serologic studies showed weakly positive antinuclear factor and absence of anti-DNA antibody and lupus erythematosus cells. A striking abnormality was the total absence of serum hemolytic complement activity (CH50). Further studies showed selective complete deficiency of C1q, a subunit of the first component of complement (C1). This is the first reported case of lupus erythematosus-like syndrome with selective complete deficiency of C1q.

Fig. a, Angular distribution of 85 Mev neutrons' elastically scattered by A!. Absorption coefficient K =1.97 x 10l2cm-l , increase in the magnitude of the propagation vector of a nucleon upon entering the nucleus kl =2.76 x 1012cm-1, nuclear radii R=4.49 xlO-13cm. al.,2) which is appropriate for treating the scattering of waves by soft obstacles. The energy range considered is from 85 Mev to 400 Mev. The shape of the potential chosen is that of square well. The calculated total cross sections are in agreement with experimental values, although slight systematic deviations are observed. The differential cross sections are calculated in the same way and compared with the 85 Mev neutron experiment of Cook et a!. 3) and the 340 Mev proton experiment of Richardson et a1.4) Agreement between theoretical and experimental values is good, except for too deep minima on the theoretical diffraction patterns, as has already been reported by other authors.4, 5) Some typical examples are given below.