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Objective – To investigate whether phrenic nerve conduction in the early phase of Guillain– Barre syndrome (GBS) predicts the need for respiratory assistance during the subsequent clinical course. Material and methods – We performed electrophysiological examinations of conventional peripheral nerve conduction and phrenic nerve conduction for GBS patients within 14 days from the onset. We excluded patients who had already been treated with immuno-related therapy and respiratory assistance. Results – Fifteen patients were enrolled. Three patients with the sum of phrenic nerve latency longer than 30 ms and the sum of bilateral diaphragmatic compound muscle action potential amplitude smaller than 0.3 mV required respiratory assistance after the conduction test. Conclusion – Our findings showed that not only delayed distal latency but also decreased amplitude may predict the need for respiratory assistance during the subsequent disease course.

Objective – To investigate the efficacy of low dose of botulinum toxin type A (BTX-A) for facial synkinesis and hyperlacrimation. Material and methods – Eleven patients suffering from facial synkinesis after Bell's palsy or facial nerve injury were treated with a low dose of BTX-A, 0.5–1.25 U per point into several points. One patient showing hyperlacrimation was also treated with BTX-A. The whole observational period was 43 months. Results – On average, 5.76 U of BTX-A, which was lower than that of previous reports, was injected per treatment. In seven cases, synkinesis disappeared completely after three or fewer sessions of BTX-A injection. The mean interval between treatments was 14.5 weeks. Hyperlacrimation was completely suppressed after a single subcutaneous injection of BTX-A. Only mild subcutaneous hemorrhage was observed as adverse reactions. Conclusion – Facial synkinesis can be treated with a lower dose of BTX-A without relevant adverse reactions.

The authors examined skeletal muscle specimens from four patients with myositis and hepatitis C virus (HCV) infection. PCR analysis identified HCV RNA in muscle homogenates from two patients. In situ hybridization signals for HCV RNA were detected within muscle fibers as well as in infiltrating lymphocytes from the same patients. The results may relate to the pathomechanism of myositis in patients with HCV infection.

We present a series of tailward-to-Earthward particle anisotropy reversals observed by the GEOTAIL spacecraft in the distant magnetotail plasma sheet at a distance of | x |≈ -90RE during the 2.5-day period of 11/01/94 1200 UT to 13/01/94 2400 UT. The reversals were detected in the first order anisotropy of energetic protons and the first moment of the low energy plasma distribution function. The X-component of the cross-field flow exhibits the clearest indicator of a particle anisotropy reversal. A comprehensive examination of ground magnetometer and geosynchronous, satellite data reveals that each distant tall anisotropy reversal occurred during the late expansion or recovery phase of a magnetospheric substorm. Out of 14 substorms during which adequate monitoring of the geomagnetic activity and the plasma sheet was possible all but possibly one exhibited a tailward-to-Earthward reversal in the cross field flow ∼1-2 hours after substorm onset. The median time delay between substorm onset and the beginning of the subsequent Earthward convective flow was 94 min. Some uncertainty is associated with this time delay due to the commonly observed exits of the spacecraft to the lobe/mantle. The lower limit on the time delay based on the time of exit of the spacecraft to the lobe/mantle is 61 min. The implications of the particle anisotropy reversals for substorm dynamics are considered.

Smad ubiquitination regulatory factor-2 (Smurf2), an E3 ubiquitin ligase, can interact with Smad proteins and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signalling mediators. We previously reported that phosphorylated Smad2/3 (pSmad2/3) was sequestered in transactive response DNA-binding protein-43 (TDP-43) inclusions in the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Recent biochemical and immunohistochemical studies on spinal cord and brain of ALS patients demonstrated that the composition of the TDP-43 inclusions is regionally distinct, suggesting different underlying pathogenic processes. We aimed to elucidate regional differences in pathomechanisms and composition of TDP-43 inclusions in relation to pSmad2/3 and Smurf2.The spinal cord and brain tissues of 13 sporadic ALS (SALS) patients were investigated using immunohistochemical analysis.TDP-43-positive inclusions in lower motor neurones of SALS patients were immunopositive for Smurf2 and pSmad2/3. Multiple immunofluorescence staining for Smurf2, pSmad2/3, TDP-43 and ubiquitin revealed co-localization of these four proteins within the inclusions in lower motor neurones of SALS patients. Furthermore, the loss of nuclear pSmad2/3 immunoreactivity was observed in cells bearing TDP-43 inclusions. In contrast, TDP-43-positive inclusions in the extramotor neurones in the brain of SALS patients were noticeably negative for Smurf2 and pSmad2/3. In addition, pSmad2/3 immunoreactivity was preserved in the nuclei of inclusion-bearing cells.This regional difference in the expression of Smurf2 and pSmad2/3 within TDP-43-positive inclusions might be one of the pathomechanisms underlying the loss of lower motor neurones and comparatively spared cortical neurones seen in ALS.

AIMS--To investigate the morphological and histopathological associations between an individual pit seen on stereomicroscopy or magnifying colonoscopy and an individual crypt seen in histological sections; and to examine these associations in colorectal tumours. METHODS--Fourteen thousand and twenty three cases were examined by colonoscope at Akita Red Cross Hospital. The surface mucosal pits of the lesions were observed using a magnifying endoscope in vivo and the pits of the extracted specimens were observed in vitro using a stereo microscope. Histological diagnoses were determined by light microscopy: the pit patterns in 100 glands were analysed. RESULTS--Pit pattern was classified into seven principal types: (1) normal round pit; (2) small round pit; (3) small asteroid pit; (4) large asteroid pit; (5) oval pit; (6) gyrus-like pit; and (7) non-pit. There was a correlation between pit pattern and the structure of the underlying crypt or gland. Furthermore, there was an association between pit pattern and the histology of the cells in the gland. Macroscopically, types 3, 4, 5, and 6 were common in protruding lesions. Type 2 was common in depressed lesions. The non-pit pattern was recognised in both. The depressed lesions had invaded the deeper layers more rapidly than protruding lesions. CONCLUSIONS--There were associations between individual pits and crypts. The branching carcinoma gland is thought to be the result of malignant transformation of the adenoma gland. The straight carcinoma gland is thought to result from the normal gland becoming malignant. The gland of the small round pit is thought to change from normal to the straight carcinoma gland via malignant transformation.

We investigated the possible renal protective effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, against gentamicin (GM)-induced acute renal failure (ARF) in rats. ARF was induced by subcutaneous injection of GM at 80 mg/kg/day for 12 days. KW-3902 (0.001-0.1 mg/kg, p.o., twice daily) attenuated the increases of serum creatinine and urea nitrogen and the decrease of creatinine clearance in rats treated with GM. In contrast, furosemide and trichlormethiazide aggravated the GM-induced nephrotoxicity. These results suggest that KW-3902 can ameliorate the GM-induced ARF and that endogenous adenosine may be involved in GM-induced ARF via the adenosine A1-receptor.

早期大腸癌の治療方法は時代とともに大きく変遷している.診断がポリープだけであった時代と表面型の時代さらに表面陥凹型の診断ができるようになった現在とでは内視鏡治療も大きく変わってきた1).病変の診断の質的レベルにより内視鏡治療方法も変わってきた.早期大腸癌の肉眼形態は大別し隆起型(.1型)と表面型とに分類され,表面型はさらに表面隆起(IIa,IIa+dep,IIa+IIc),表面平坦(IIb),表面陥凹型(IIc,IIc+IIa)に亜分類される,(図1).中でも表面陥凹型が最も悪性度が高いと見なされている。すなわち早期大腸癌の診断のターゲットが隆起型から表面型へと変わり,その中でも表面陥凹型が重要な早期大腸癌として考えられるようになってきた.したがって従来の隆起型に対するpolypectomyだけでは不十分となり,表面型早期癌の治療にはEMR4-6)が自ずと行われるようになってきた.本稿では早期大腸癌の内視鏡治療の中で最近行われるようになってきたEMRを中心に解説する.

HtrA2/Omi is a mitochondrial serine protease that promotes the apoptotic processes, but the relationship between HtrA2/Omi and amyotrophic lateral sclerosis (ALS) is still unknown. The purpose of the present study was to determine whether abnormal expression of HtrA2/Omi occurs in patients with ALS.We prepared autopsied spinal cord tissues from 7 control subjects, 11 patients with sporadic ALS (SALS) and 4 patients with Cu/Zn superoxide dismutase (SOD1)-related familial ALS (FALS). We then performed immunohistochemical studies on HtrA2/Omi using formalin-fixed, paraffin-embedded sections from all of the cases.In the control subjects, the anterior horn cells were mildly to moderately immunostained with HtrA2/Omi. In the patients with SALS, strong HtrA2/Omi immunoreactivity was found in some skein-like inclusions and round hyaline inclusions as well as many spheroids, but Bunina bodies were immunonegative for HtrA2/Omi. In the patients with SOD1-related FALS, Lewy body-like hyaline inclusions were observed in three cases and conglomerate inclusions were observed in the remaining case, and both types of inclusions were intensely immunopositive for HtrA2/Omi.These results suggest that abnormal accumulations of HtrA2/Omi may occur in several types of motor neuronal inclusions in the anterior horn from SALS and SOD1-linked FALS cases, and that HtrA2/Omi may be associated with the pathogenesis of both types of ALS.

A case of toxic multinodular goiter associated with repetitive monomorphic ventricular tachycardia (VT) is reported. A 4-year-old boy was found to have asymptomatic VT. When treatment with antiarrhythmic agents turned out to be ineffective, thyrotoxicosis was suspected due to the rapid enlargement of the left thyroid gland and associated thyroid function studies. A diagnosis of toxic multinodular goiter was made on the basis of subsequent scintigraphy and ultrasonography. Treatment with antithyroid drugs and inorganic iodine restored the thyroid function to normal, and was accompanied by the disappearance of VT. A left thyroid lobectomy was performed, and the pathological findings were compatible with toxic multinodular goiter. After the operation, the patient was transiently hypothyroid and had no VT without medication. A review of the literature revealed no previously documented cases of VT with toxic multinodular goiter.

We investigated a family manifesting progressive ataxia, with expanded SCA8 CTA/CTG repeats. Neuropathologically, degeneration of Purkinje, inferior olivary, and nigral neurons and periaqueductal gliosis were evident. The sites of Purkinje cell loss were occupied by fibrillary accumulations. The remaining Purkinje cells showed somatic sprouts, and intracytoplasmic 1C2-positive granular structures were recognizable. This characteristic distribution of neurodegeneration and Purkinje cell cytopathology were distinct from those of other hereditary spinocerebellar ataxias previously reported.

Objective: To integrate an immune-mediated mechanism and the disturbed protein expression in sporadic inclusion body myositis (IBM). Background: In IBM, abnormal fibers harbor inclusions of some proteins found in the brains of patients with Alzheimer disease (AD). Poly(A)-binding protein 1 (PABP1) is the RNA binding protein that attaches to the poly(A) tail of mRNA and is involved in translation and mRNA degradation. Under stresses, mRNA combined with PABP1 forms cytoplasmic granules called stress granules. Methods: Using 12 muscle biopsies with sporadic IBM and 46 controls, the authors localized PABP1 by immunohistochemistry, and poly(A)-containing RNA (poly(A) + RNA) using the in situ hybridization method. They also immuno-localized HuR, one of the components of stress granules. Results: In IBM, a proportion of fibers, including those vacuolated, showed an abnormal accumulation of PABP1 immuno-positive deposits. An immunofluorescence study indicated that large PABP1 positive deposits formed conglomerates with poly(A) + RNA and PABP1 colocalized with HuR. Although PABP1-positive cytoplasmic inclusions were found in disease controls, their aggregates combined with poly(A) + RNA were only detected in IBM. Conclusions: The localization of PABP1 positive deposits in inclusion body myositis (IBM) and other diseases may correspond to the stress granules that are formed under exposure to cellular stresses and the sites of mRNA turnover. The concomitant aggregation of poly(A) + RNA that is specifically found in IBM may be due to the inhibition of mRNA degradation, which may affect translation. The authors speculate that an autoantibody against mRNA degradation machinery could play a role in this inhibition.

We present a method for phase recovery in QAM communication systems based on higher order statistics. Under the assumption that the QAM signals have independent, identically distributed (i.i.d.) in-phase and quadrature components, we derive the relation between the phase error and the fourth-order cumulant of the output. Numerical performance of the approach is demonstrated by computer simulation.

In this paper, the performances of DS-CDMA communication systems with the band limitation and narrow-band rejection filters are investigated. We assume that the ideal filter and the filter constructed of a cascade connection of the 7 numbers of the first-order Butterworth filter are used as the band limitation in the system transmission line. And, using the ideal and the prediction error filters, we show the limitation of the bandwidth of the interference wave.

Objective: To investigate alterations in protein kinases and phosphatases that regulate the activity of mitogen activated protein kinase (MAPK) in sporadic inclusion body myositis (IBM). Background: In vacuolated fibers in IBM, several studies reported upregulation of the extracellular regulated kinase (ERK) subclass of MAPK family. Whereas MAPK kinases (MKK) activate MAPK, MAPK phosphatases (MKP) inactivate MAPK. MKP-1 is involved in muscle fiber differentiation and it is downregulated during myotube formation. Methods: Immunolocalization of MKK1 through MKK4 and MKP-1 to MKP-3 was tested in muscle specimens from 10 patients with IBM and controls. Results: In IBM, strong and focal deposits of MKP-1 were observed in vacuolated fibers. The MKP-1-positive deposits were colocalized with ERK. MKP-2, MKP-3, and MKK were not associated with vacuolated fibers. Conclusions: In IBM, MKP-1 is abnormally induced in vacuolated fibers probably to inactivate ERK. Although direct activators other than those tested in the current study might induce ERK, the absence of activation of MKK suggests that the aggregation of ERK protein itself causes the seeming upregulation of the protein kinase in IBM. Like ERK and its nuclear substrate, MKP-1 is an enzyme that forms aggregates in vacuolated fibers and is involved in myogenesis.

We have prepared (1-x)CoSb/sub 3/-x(oxide) composite (x=0.1-0.3) where the oxide particles are dispersed in the CoSb/sub 3/ matrix by the MG (mechanical grinding) technique. The electrical resistivity of CoSb/sub 3/ is reduced by addition of MoO/sub 2/ or WO/sub 2/, but it is enhanced by addition of Al/sub 2/O/sub 3/. This is because the electrical resistivity of MoO/sub 2/ or WO/sub 2/ is smaller than that of CoSb/sub 3/, while Al/sub 2/O/sub 3/ is an insulator. The electrical resistivity increases with an increase of the MG time. The thermal conductivity is reduced by the addition of oxide and it decreases with increasing MG time. As a result, 0.7CoSb/sub 3/-0.3MoO/sub 2/ composite exposed to 3h MG treatment or 0.9CoSb/sub 3/-0.1WO/sub 2/ composite exposed to 7h MG treatment has a maximum figure of merit of 3.6/spl times/10/sup -4/ K/sup -1/ at about 580K, which is slightly larger than that of CoSb/sub 3/ at 482K, 3.2/spl times/10/sup -4/.

This paper proposes an improvement method of the deteriorated characteristics on account of the nonlinearity in direct sequence spread spectrum multiple access (DS-SSMA) communication systems. Where, a traveling wave tube (TWT) is adopted as nonlinear circuit in which the amplitude nonlinearity and AM/PM conversion are assumed to be relatively small. The transmission signal is expressed in two quadrature components and an equalizer of feed-forward transversal type is used to improve the nonlinear characteristics. The calculation results show that the significant improvement can be obtained from a simple equalizer using the least mean square algorithm.

We analyze the effects of the amplitude nonlinearity and AM/PM conversion in a traveling wave tube (TWT) used in an asynchronous direct sequence spread spectrum multiple access (DS-SSMA) communication system, assuming that the nonlinearity is represented by the power series of the input signal and the conversion is relatively small. We propose an analytical method of the signal-to-noise ratio at the output of the correlation detector in the receiver. We also justify our method by comparing the theoretic results with the computer simulations in when the amplitude nonlinear circuit is modeled by an error function as a typical example and show that the third order intermodulation product can be almost neglected in the sense of the signal-to-noise ratio. >

This paper proposes an improvement method of the performance characteristics of a quadriphase phase-shift-keyed code-division multiple-access (CDMA/QPSK) system with a nonlinear channel such as a satellite repeater which consists of a traveling-wave tube (TWT). Two adaptive decision feedback equalizers are used to improve the system performance degraded by the nonlinear channel. From calculation results, it is shown that the degradations are improved considerably.

Bunina body is known to occur in cases of sporadic amyotrophic lateral sclerosis (ALS), ALS with dementia (a so-called Mitsuyama type), and Guamanian ALS, and seems to lend a diagnostic priority to the presence of Bunina bodies. Absence of Bunina body in a subset of familial ALS with posterior column and spinocerebellar tract involvement or motor neuron disease with basophilic inclusion also adds credence to the specificity of Bunina body in ALS. However, despite its bright eosinophilia, distinct expression of cystatin C, and conspicuous ultrastructure, the origin of Bunina body is still unknown and remain several unsolved problems. Bunina bodies are usually seen within the cytoplasm or dendrites of degenerated and/or sometimes normal-looking large neurons. However, so far, no Bunina body has been found within the axoplasm. Bunina bodies are mainly distributed in the lower motor neurons. Only a single report described it in the Betz cell. Furthermore, several recent studies have revealed the occurrence in neurons which are so far considered to be exempt from the pathology of ALS, i.e. the oculomotor nucleus, Onufurowicz's nucleus, Clarke's nucleus, reticular formation of the brain stem, and subthalamic nucleus. In addition to the occurrence in neurons other than motor neurons, ultrastructurally similar or identical inclusions are reported in neurons of aged rats, the olfactory bulb of aged human, the spinal cord of a patient without ALS, and gangliocytoma. Bunina body probably represents a facet of the degenerating process of a neuron. A high incidence in ALS, particularly in lower motor neurons, awaits a further study of the pathogenesis of Bunina body.

This report concerns the characterization of the alpha-tocopherol transfer protein (alpha-TTP) gene in a Japanese family affected by ataxia with isolated vitamin E deficiency (AVED). The sequence analysis revealed a G-to-A transition at the 3' end of exon 3 in both alleles, which predicts outsplicing of this exon from premessenger RNA and the concomitant frame shift in the ataxic patient. We used reverse transcriptase-polymerase chain reaction to analyze alpha-TTP gene transcripts. All transcripts in peripheral blood lymphocytes of the AVED patient, who was treated with large doses of vitamin E, lacked exon 3. The deduced truncated protein shares only 43% of the normal alpha-TTP. Normal control tissues and cells contained normal transcripts and, unexpectedly, also the same mutant transcripts as those of the patient, although with different transcription levels. Treatment of normal fibroblasts with clinically relevant concentrations of vitamin E increased production of transcripts in a dose-dependent manner. We propose that exon skipping of all transcripts through the complete inactivation of the splice site accounts for the clinical onset of AVED and for the clinical resistance to vitamin E in our patient.

This report concerns an autopsy case of corticobasal degeneration (CBD). The patient was a 64-year-old woman with slowly progressing clumsiness and gait disturbance who died approximately 7 years after the onset of symptoms. The salient neuropathological findings were focal loss of neurons of the cerebral cortex, ballooned neurons and gliosis of the subcortical white matter, thalamus, and basal ganglia. In addition, there were marked neuronal loss and gliosis in the substantia nigra. The ballooned neurons were positively immunostained for phosphorylated neurofilament, alpha B-crystallin and synaptophysin; staining for the latter was intraneuronal. The examination of silver impregnated and Tau immunostained preparations revealed numerous basal neurofibrillary tangles, neuropil threads, and glial inclusions; their presence was most pronounced in the brainstem tegmentum, basal ganglia, and thalamus. Neurofibrillary tangles consisting of straight tubules with a diameter of approximately 13-15 nm and constricted tubules were identified in the substantia nigra. The results of the present study indicate that the cytopathology of the subcortical gray matter and brainstem in CBD patients resembles that of progressive supranuclear palsy.

Protruded polyps can usually be treated with conventional polypectomy technique. Slightly elevated lesions without malignant findings are treated with hot biopsy method if they are small enough (less than 5 mm). In order to treat flat or slightly depressed lesions or slightly elevated lesions larger than 5 mm, endoscopic mucosal resection (EMR) technique has been invented. Cancers confined to the mucosa or those only minimally invading the submucosa can be completely removed with this method. However, if histological analysis of the resected specimen shows that the cancer invades the submucosa massively or permeating the vessels, surgical treatment should be added, because otherwise there would be risk of cancer residue or metastasis. When a lesion is suspected to be a submucosal cancer by endoscopic findings and pit pattern analysis from the beginning, then surgical resection is the treatment of choice. Laterally spreading tumors, especially the homogeneous granular type, are good indication for EMR or endoscopic piecemeal mucosal resection (EPMR). It is important to remove the lesion completely confirming that the resection margin is covered with normal pits.

This report concerns a case of sporadic amyotrophic lateral sclerosis (ALS) with dementia and Lewy body-like hyaline inclusions (LBHIs). The patient was a 70-year-old woman who initially showed memory disturbance and later developed bulbar palsy, muscle atrophy and weakness. The total clinical course was 51 months. The postmortem examination revealed superficial sponginess and subcortical gliosis in the frontotemporal cortices. Ubiquitin-positive intraneuronal inclusions were found in small cortical neurons of the frontotemporal lobe. Neuronal loss was marked in the spinal anterior horn with degeneration of the pyramidal tracts. The anterior horn cells had ubiquitin-immunoreactive skein-like inclusions and Bunina bodies. LBHIs were present in the lumbar horn; ultrastructurally they were composed of randomly arranged thick filamentous structures studded with granules. The LBHIs were intensely stained with anti-ubiquitin antibody. As in familial ALS and in certain cases of sporadic ALS, some of these inclusions reacted with an antibody against Cu/Zn superoxide dismutase, the enzyme whose gene was recently found to be mutated in some forms of familial ALS.

From April 1985 to March 1995, colonoscopy was carried out at our institution in 24,059 patients, 31,800 times in symptomatic and/or asymptomatic average risk persons. 184 submucosal invasive carcinomas were detected. Unlike protruding-type lesion, the depressed-type invades the submucosal layer, even though the size is within 10 mm. The depressed type of invasive carcinoma accounted for 20 lesions, and represented 10.9% (20 of 184) of all the invasive carcinomas. The pit pattern of depressed-type lesions shows a small round pit (type IIIs pit pattern) and that of carcinoma lesions shows the irregular pit and non-structure (type V pit pattern).

Two cases of acute leukoencephalopathy are reported. Both patients were Filipino women who had lived together in Japan for one month at the time of the onset. The first patient, 26 years old, suddenly developed right hemiplegia without fever. Small, high signal intensity lesions of the cerebral white matter were disseminated on T2-weighted magnetic resonance images. One week later, the patient became delirious, developed seizures, and lapsed into a comatose state with spastic quadriplegia. Corticosteroid was administered, resulting in improvement of consciousness levels. The patient was transferred to our hospital. Neurological examination disclosed severe pseudobulbar palsy and spastic quadriplegia without meningeal signs. Results of a cerebrospinal fluid examination were unremarkable. With magnetic resonance imaging, large irregularly-shaped lesions were seen in both centrum semiovale as high signal intensity areas on T2-weighted images and low signal intensity areas on T1-weighted images. Concentric structures in the lesions were particularly observed on T1-weighted images. One year later, the patient improved from a bedridden state to a wheel-chair bound state. The second patient, 23 years old, also developed right hemiplegia one week after the onset of the first case. MR imaging revealed small disseminated lesions in the cerebral white matter similar to those disclosed in the first case. From the onset, the patient was given corticosteroid, and experienced good recovery within one month. The clinical features, results of the laboratory examination, and MRI findings particularly in the first case suggest the diagnosis of so-called Baló's concentric sclerosis, despite the absence of pathological confirmation.(ABSTRACT TRUNCATED AT 250 WORDS)

A 26-year-old male patient gradually developed muscular atrophy of the right lower leg over a two-year period. Neurological examination revealed absent Achilles tendon reflex and muscular atrophy of the right lower leg and right hamstring muscles. Conduction velocity of the F waves was delayed in the right posterior tibial nerve. A computerized tomography scan and magnetic resonance imaging revealed a mass lesion along the proximal segment of the right sciatic nerve. Exploration revealed a fusiformly swollen sciatic nerve. Histological examination showed that a swollen segment of the sciatic nerve was filled with onion-bulb formations of perineurial cells, consistent with the diagnosis of localized hypertrophic neuropathy. This condition should be added to several etiologies of monomelic amyotrophy. Electrophysiological studies and neuroimaging techniques were useful in obtaining differential diagnosis.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disease that causes episodes of recurrent mononeuropathies following minor trauma or pressure. It was recently reported that deletion of the peripheral myelin protein-22 (PMP-22) gene was associated with HNPP in three unrelated American pedigrees and one Dutch pedigree, but not in another Dutch pedigree. We tested a Japanese family with HNPP for PMP-22 gene deletion. HNPP diagnosis was established by a history of recurrent mononeuropathies following moderate compression, delayed distal latencies and F-wave latencies, and the characteristic focal thickening of the myelin sheath ("tomacula") in sural nerves. Genomic DNA of the HNPP patients was extracted from peripheral blood lymphocytes. The DNA was cut by the restriction endonuclease BamHI, separated by electrophoresis and the fragments hybridized with probes for PMP-22 cDNA and human muscle specific phosphoglycerate mutase (PGAM) cDNA (used as internal control). The intensity of the autoradiographs of patients was measured densitometrically and compared to that of normal controls. Our analysis revealed that the PMP-22 and PGAM autoradiograph intensity ratio in the specimens of the HNPP patients was 60% of that of control individuals, thus suggesting that the patients only had a single copy of the PMP-22 gene. From these data we conclude that the PMP-22 gene also was deleted in the Japanese family with HNPP.

This study investigated the expression of ubiquitin in anterior horn cells of various subgroups of adult-onset motor neuron diseases (MNDs). Ubiquitin-positive skein-like inclusions (SLIs) were found in all 11 cases of sporadic amyotrophic lateral sclerosis (ALS) patients, two patients with lower MND, 3 sporadic cases of ALS with dementia, 3 sporadic ALS cases with long-term use of respirators, and two cases of sporadic ALS with Lewy body-like hyaline inclusions. This result suggests that a similar pathomechanism is involved in the degeneration of the lower motor neurons in these subgroups. SLIs were not detected in two cases of adult-onset MND with basophilic inclusions. This may indicate that adult-onset MND with basophilic inclusions is a distinct nosological entity of classical ALS and some relationship to juvenile ALS with basophilic inclusions is suggested.

We report a 64-year-old male with angiotropic lymphoma. He developed subacute dementia with right hemiparesis. Laboratory abnormalities included elevated serum lactic dehydrogenase (LDH) (715 U/l) erythrocyte sedimentation rate (38 mm/hr) and CSF protein (90 mg/dl). Precontrast MR imaging of the brain demonstrated lesions involving the left internal capsule, subcortical white matter in the right frontal lobe and splenium within the atrophic corpus callosum. A brain biopsy revealed intravascular lymphoid cells, strongly suggestive of angiotropic lymphoma. By combination chemotherapy (CHOP), serum LDH and CSF protein normalized through the patient remained demented. He died of bronchopneumonia about 2 years and 5 months after the onset. Coronal sections of the brain showed infarct in the left internal capsule as well as markedly thin corpus callosum with necrotic lesions involving both the genu and splenium. Microscopic examination showed many small vessels occluded by lymphoma cells (B-lymphocyte) predominantly in the corpus callosum, cerebral white matter, thalamus, midbrain, medulla oblongata, thoracic and lumbar segments of the spinal cord. By combination chemotherapy, our patient survived longer than most of previous patients with angiotropic lymphoma. An early diagnosis and subsequent combination chemotherapy may improve neurological manifestations, and make possible longer survival in angiotropic lymphoma.

We experienced two siblings of type 3 GM1 gangliosidosis. A 33-year-old woman developed dysarthria, dysbasia and bradykinesia at around the age of 30. Her 28-year-old brother showed locomotor retardation and skeletal deformity in infancy. He lost the ability to stand walk at childhood, and developed progressive dystonia. The major neurologic manifestations were parkinsonian symptoms in the elder sister, and progressive dystonia in her brother. Both had markedly reduced beta-galactosidase activity in peripheral blood lymphocyte and were diagnosed as having type 3 GM1 gangliosidosis. Gene analysis revealed that these patients were homozygotes of the adult type mutant gene. The two siblings are unique in that the clinical manifestations and the age of onset of symptoms differed markedly between them despite the same mutant gene in both cases.

A 72-year-old man suddenly developed right blepharoptosis and diplopia and subsequently experienced motor and sensory disturbances in his upper and lower limbs. Soon he developed violet eruptions on his trunk and extremities. Approximately 2 months after the onset of his neurological symptoms, laboratory tests confirmed a diagnosis of B-cell type acute lymphocytic leukemia. The patient died 5 days later. Autopsy findings comprised prominent intrafascicular infiltration of leukemic cells in multiple peripheral nerves, including cranial and dorsal roots. However, there was no parenchymal involvement except in the dorsal root ganglia. In acute leukemia, infiltration of malignant cells in the peripheral nervous system has been reported to be uncommon compared with that in malignant lymphoma. This case of acute lymphocytic leukemia was considered to be unique with regard to the onset of neurological symptoms and autopsy findings.

One type of motor neuron disease (MND) associated with dementia is well known for the fact that it displays atrophy of the frontal and temporal lobes, neuronal loss and sponginess of the superficial layers of the cortex, and subcortical gliosis (so-called Mitsuyama type). In an attempt to determine characteristics of the pathology of motor neurons, three cases of MND with dementia were examined and compared with 16 cases of sporadic classical amyotrophic lateral sclerosis (ALS) with light and electron microscopes. All these cases with dementia showed loss of motor neurons, chromatolysis, spheroids, and Bunina bodies. Quantitative analyses of the 5th lumbar anterior horns showed no significant differences in incidences of chromatolysis and Bunina bodies between cases with and without dementia. Ultrastructures of the anterior horns were essentially identical in both groups. Therefore, the pathology of motor neurons at least in one type of MND with dementia seems to share common features with that in sporadic classical ALS without dementia.

This report concerns immunocytochemical and ultrastructural studies on the basophilic inclusions in two cases of sporadic juvenile amyotrophic lateral sclerosis (ALS). The inclusion had a globular, irregular-shaped, or sometimes fragmented appearance. Ultra-structurally, the inclusions consisted mainly of thick filamentous structures associated with granules. Focal neurofilamentous accumulations were occasionally observed among the granulofilamentous structures. The basophilic inclusions occasionally showed granular reaction product deposits with an antibody to ubiquitin. The inclusions did not react with antibodies to phosphorylated neurofilament and to tau protein.

In a 62-year-old man with an 8-month course of sporadic classical amyotrophic lateral sclerosis, many Lewy body-like hyaline inclusions (LI) were observed in spinal anterior horn cells, hypoglossal nuclei, nucleus ambiguus, and motor nuclei of the trigeminal nerve. These motor neurons showed a mild degree of neuronal loss, several Bunina bodies, spheroids and chromatolytic neurons. Tract degeneration was limited to pyramidal tracts. In addition to intensely stained LI, immunoreactive skeins or granules were recognized by a polyclonal anti-ubiquitin antibody. Thick filaments of 15 to 20 nm in diameters with granules formed conglomerated masses with varying amounts of neurofilaments in the anterior horns, corresponding to light microscopically observed LI. More commonly, these thick granulofilamentous profiles were dispersed in small bundles or individually in the cytoplasm. Electron microscopically, there was no close association of filaments with Bunina bodies.

The effects of intravenously administered almitrine (0.3 or 1.0 micrograms/kg/min, for 30 min) on hemodynamics and pulmonary gas exchange were assessed in eight dogs with acute lung injury induced by paraquat under controlled ventilation. Arterial blood gases, pulmonary and systemic hemodynamics, and ventilation-perfusion distribution (VA/Q) using the multiple inert gas elimination technique were examined before (control) and during infusion of almitrine. Almitrine produced significant increases in mean pulmonary arterial pressure from 17.4 +/- 3.3 (control, mean +/- SD) to 20.4 +/- 1.5 mmHg (1.0 micrograms/kg/min), and in total pulmonary vascular resistance. There was no change in other hemodynamic parameters, arterial gas tensions, or VA/Q distribution. These results indicate that almitrine causes pulmonary vasoconstriction without changing ventilation-perfusion distribution in dogs with paraquat-induced lung injury.

Tracheal dimensions at total lung capacity (TLC) and residual volume (RV) were analyzed roentgenographically in 17 pairs of male adolescent twins (mean age 16.3 yr; 12 monozygotic pairs and 5 dizygotic pairs). Genetic factors dominated environmental traits in intra- as well as extrathoracic tracheal width at RV. Extrathoracic tracheal width at TLC was also governed by genetic components. Intrathoracic tracheal depth (anteroposterior diameter), length, and cross-sectional area did not seem to be genetically controlled at TLC and RV. Intrathoracic tracheal cross-sectional area increased by 14.4% and became more elliptical from RV to TLC, owing mainly to an increase in tracheal depth (16.7%). Increments from RV to TLC in tracheal depth but not width correlated with increases in lung width, depth, and height. Intrathoracic trachea was elongated 14% in association with increase in lung height from RV to TLC. At TLC, extrathoracic tracheal width was larger than intrathoracic tracheal width, but this dimension did not differ at RV. These results indicate that genetic factors influence, at least at RV, the tracheal rings more strongly than membranous parts. Intrathoracic tracheal depth but not width increases during inspiration in accordance with increase in lung volume. Extrathoracic tracheal width widens more than intrathoracic trachea from RV to TLC.

A 73-year-old woman with ureteral cancer and multiple systemic metastasis was admitted complaining of dyspnea on exertion after administration of recombinant human tumor necrosis factor (rH-TNF). On chest examination, coarse crackles were heard during inspiration throughout the lungs. Chest roentgenogram revealed a ground glass infiltration, an air bronchogram in the right lung field and an ill-defined right pulmonary artery. Her symptom and chest roentgenological finding improved and coarse crackles were not heard after discontinuation of rH-TNF. Neutrophils and lymphocytes of bronchoalveolar lavage fluid increased and transbronchial lung biopsy specimens showed slight thickening of alveolar septa with infiltration of inflammatory cells. The pulmonary edema was thought to be caused by rH-TNF which induces adherence of neutrophils to endothelium and stimulates them to increase lysosomal enzyme release and oxygen radical production. As a results, it is thought pulmonary permeability might be increased.