It has been demonstrated that progranulin (PGRN) is a neurotrophic factor that enhances neuronal survival and axonal growth. Several lines of evidence have indicated that PGRN plays a role in the pathomechanism of amyotrophic lateral sclerosis (ALS). However, there has no study of PGRN in ALS skin. We made a quantitative immunohistochemical study of the expression of PGRN in the skin from 18 patients with sporadic ALS and 13 control subjects. Immunohistochemistry for PGRN demonstrated cytoplasmic activity in the epidermis and in some blood vessels and glands. Numerous PGRN-positive (PGRN+) cells were observed in the epidermis in ALS patients, which became more marked as ALS progressed. PGRN immunoreactivity of PGRN+cells was markedly positive in the epidermis in ALS patients. The proportion of PGRN+cells in the epidermis in ALS patients was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r = 0.83, p<0.001) between the proportion and duration of illness in ALS patients. These data suggest that changes of PGRN in ALS skin are related to the disease process and that metabolic alteration of PGRN may take place in the skin of patients with ALS.

要旨:内包後脚の梗塞では多くの症例で片麻痺を合併するためにpure dysarthria を呈する症例はきわめて少ない.今回内包後脚に限局した脳梗塞により構音障害のみを呈した3 症例を経験した.症例1は67 歳男性,症例2 は68 歳男性,症例3 は80 歳女性である.いずれも主訴は呂律障害で,神経学的には構音障害のみが認められた.頭部MRI 上症例1 は右内包後脚に,症例2 および3 は左内包後脚にそれぞれ限局した急性期梗塞がみられた.現在,皮質延髄路の内包における走行については膝部を通るものとするものと,後脚内で皮質脊髄路の前方を通るものとする説が議論されている.本3 症例の検討より皮質延髄路が膝部のみならず後脚内も走行しその障害によりpure dysarthria を呈したと考えられ,後者の見解に合致すると思われた.

A catalytic probe made of a nickel thin wire is introduced into the gas flow downstream of an atmospheric pressure dielectric barrier discharge ozonizer to examine the ozone dissociation process on a catalytic surface. The probe is placed downstream far from the discharge to avoid the influence of reactive species other than ozone. The measured voltage variation across the probe wire under a constant probe heating current is used as a measure of the temperature variation of the probe surface and the nearby gas temperature. The stainless steel and copper wire made probes are also used to examine the effect of catalytic activity. Experimental results show that, for a low probe heating current of 0.2 A, the temperature of the probe decreases with increasing ozone concentration almost independent of the probe materials due to catalytic dissociation of ozone, which removes heat of reaction from the probe. When the heating current is increased to 1.5 A, the temperature of the nickel probe increases with increasing ozone concentration due to thermal dissociation of ozone followed by surface catalytic recombination of oxygen radicals, which gives heat of reaction to the probe. On the other hand, the temperature of the stainless steel and copper made probes decreases with increasing ozone concentration despite the high heating current due mainly to the low catalytic activities. (C) 2013 Elsevier Ltd. All rights reserved.

PURPOSE:The Kii Peninsula of Japan, together with Guam and West New Guines, has one of the highest incidences of amyotrophic lateral sclerosis (Kii ALS) in the world. There is a controversy whether the etiology is the same or not between sporadic ALS and Kii ALS. Skin studies from patients with sporadic ALS have shown unique pathological and biochemical abnormalities. However, there has been no report of collagen content of the skin Kii ALS patients.METHODS:The skin tissues from Kii ALS patients were studied by electron microscopy and their collagen contents were examined.RESULTS:On electron microscopy the most conspicuous finding in Ki ALS was the smaller diameter of collagen fibrils. The collagen content per dry weight (mg) of the samples in Kii LAS was significantly decreased (P<0.001) than in controls. In Kii ALS patients the more severely affected pathological samples showed the greater decrease. In addition, there was a significant negative correlation (r = -0.88, P<0.01) between the collagen and duration of illness in the Kii ALS patients, but there was no such correlation in controls. CONCLUSION; These results indicate that the metabolism of skin collagen might be affected in the disease process of Kii ALS.

Angiogenin (ANG) is a member of the ribonuclease superfamily which is implicated in angiogenesis. ANG maintains normal vasculature and thereby protects motor neurons from various stress conditions. It is suggested that ANG may play a role in pathomechanism of amyotrophic lateral sclerosis (ALS). However, there have been no studies of ANG in ALS skin. We made a quantitative immunohistochemical study of the expression of ANG in the skin from 20 patients with sporadic ALS, 20 patients with other neurologic or muscular disorders (control group A), and 20 patients without neurologic or muscular disorders (control group B). The nuclei of the epidermal cells showed a weak ANG immunoreactivity in ALS patients. These findings became more marked as ALS progressed. The optical density for ANG immunoreactivity of the nucleus in the epidermal cells in ALS patients was significantly lower (p<0.001) than in control groups A and B. There was a significant negative relationship (r=-0.82, p<0.001) between the optical density for ANG immunoreactivity of the nucleus and duration of illness in ALS patients. These data suggest that changes of ANG in ALS skin are related to the disease process and that metabolic alterations of ANG may take place in the skin of ALS patients.

Tumor necrosis factor-α (TNF-α) is a major inflammatory cytokine that elicits a wide range of biological responses and is implicated in the pathogenesis of neurodegenerative diseases. Skin studies from patients with amyotrophic lateral sclerosis (ALS) have shown unique pathological and biochemical abnormalities. The lack of bedsore formation is considered characteristic of ALS. We undertook a quantitative immunohistochemical study of TNF-α in the skin from patients with ALS and controls with other neurologic or muscular diseases. Immunohistochemistry for TNF-α demonstrated cytoplasmic activity in the epidermis and in some blood vessels and glands. The proportion of TNF-α-positive (TNF-α+) cells in the epidermis in patients with ALS was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.87, p<0.001) between this proportion and duration of illness in patients with ALS, but there was no such relationship in control subjects. The optical density of TNF-α+ cells in the epidermis in patients with ALS was markedly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.70, p<0.001) between the immunoreactivity and duration of illness in patients with ALS. However, there was no such relationship in controls. In addition, there was an appreciable positive correlation (r=0.59, p<0.01) in patients with ALS between the proportion of TNF-α+ cells and the optical density of these cells, but with no correlation in controls. These data suggest that changes in TNF-α identified in the skin of patients with ALS are likely to be related to the disease process and that metabolic alterations of TNF-α may take place in the skin of patients with ALS.

60歳，男性が頭痛，嘔吐，意識障害で入院となった．血液検査でTSH 99.099μIU/mlの上昇と，FT3 1.60pg/ml，FT4 0.58ng/dlの低下を認めた．また抗サイログロブリン抗体，抗TPO抗体の上昇を認めた．粘液水腫性昏睡と考え，甲状腺ホルモンの補充療法を実施したが症状の改善はみられなかった．その後血清中抗N末端αエノラーゼ抗体の上昇が認められたことより橋本脳症の合併を考え，ステロイドパルス療法を行ったところ，症状の速やかな改善を認めた．

要旨：視床傍正中部の限局した脳梗塞により偽性外転神経麻痺(pseudoabducens palsy)を呈した1例を報告した．症例は心房細動の既往のある78歳男性．複視と左上下肢の筋力低下で発症した．頭部MRIでは右視床傍正中部の急性期梗塞を認め，外転神経核に明らかな異常は認められなかった．以上より外転神経核ではなく，右視床傍正中部梗塞により偽性外転神経麻痺を生じたと診断した．本邦での偽性の報告は過去4例と少なく，一過性で見逃されていた可能性がある．

OBJECTIVES:The fused in sarcoma (FUS) protein is a 526 amino acid and its expression is ubiquitous. Recently, mutations in a gene coding FUS have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic forms of ALS, suggesting that FUS has an important role in the neurodegeneration occurring in sporadic disease. However, there has been no study of FUS in ALS skin.MATERIAL AND METHODS:We made a quantitative immunohistochemical study of the expression of FUS in the skin from patients with sporadic ALS and controls.RESULTS:The proportion of FUS-immunoreactive (ir) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.78, P < 0.001) between the proportion and duration of illness in ALS patients. The optical density of FUS-ir cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.49, P < 0.05) between the immunoreactivity and duration of illness in ALS patients.CONCLUSIONS:These data suggest that changes of FUS in ALS skin are related to the disease process, and that metabolic alterations of FUS may take place in the skin of patients with ALS.

Valosin-containing protein (VCP) may have a pivotal role in ubiquitin-dependent protein degradation and is implicated in the pathogenesis of neurodegenerative diseases. Skin studies from patients with amyotrophic lateral sclerosis (ALS) have shown unique abnormalities. We undertook a quantitative immunohistochemical study of VCP in the skin from patients with ALS and control participants. The proportion of VCP-positive (VCP+) cells in the epidermis in patients with ALS was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.59, p<0.01) between this proportion and duration of illness in patients with ALS. The optical density of VCP+ cells in the epidermis in patients with ALS was higher (p<0.001) than in controls. There was a significant positive relationship (r=0.61, p<0.01) between the immunoreactivity and duration of illness in patients with ALS. These data suggest that changes in VCP identified in skin from patients with ALS are likely to be related to the disease process.

The effect of pulse voltage, polarity, duty cycle, and oxygen flow rate on ozone production is studied in a coaxial cylindrical-type dielectric barrier discharge ozonizer at atmospheric pressure. For a constant oxygen flow rate, the ozone concentration increases with increasing input voltage and is nearly proportional to the ozone production efficiency. The bipolar waveform of the applied voltage results in higher ozone concentration and production efficiency than the unipolar one (positive or negative) regardless of duty cycle. A higher duty cycle increases the ozone concentration slightly for the unipolar voltage, while it affects little the ozone production efficiency for either voltage polarity. For constant pulse polarity and duty cycle, the ozone concentration decreases with increasing oxygen flow rate, however, the maximum ozone production efficiency for each flow rate shows only a minor difference for the change in flow rate. The results confirm that the ozone production efficiency depends more on the pulse power characteristics and less on the oxygen flow rate.

We described a 43-year-old Japanese man with familial amyotrophic lateral sclerosis (FALS) in whom we identified a missense mutation (Cys111→Tyr) in exon 4 of the Cu/Zn superoxidase dismutase-1 (SOD1) gene in which no pathological data have been reported. The disease duration was 5 years, and he died of respiratory failure. The initial sign was weakness of the right leg. He had no clear upper motor involvement. Neuropathological examinations showed neuronal intracytoplasmic Lewy body-like hyaline inclusions (LBHIs) not only in the anterior horn cells of the spinal cord, but also in many other affected neurons. LBHIs were seen in the anterior horn cells, Onufrowicz nucleus, Clarke's nucleus, intermediolateral nucleus, and posterior gray horn of the spinal cord. In addition, LBHIs were observed in the periaqueductal gray matter, nucleus raphe dorsalis, locus ceruleus, trigeminal motor nucleus, vestibular nucleus, dorsal vagal nucleus, hypoglossal nucleus, and reticular formation of the brain stem. These are very specific findings that neuronal LBHIs in our case are for more widespread reported cases, and similar cases to ours have never reported in FALS.

Peripheral nerve involvement in dermatomyositis (DM) has been known as neuromyositis. However, the pathogenic mechanism is not clear, and the association between DM and peripheral neuropathy is still controversial. Our patient exhibited symptomatic polyneuropathy that was documented electrophysiologically in addition to typical features of DM. The sural nerve biopsy showed evidence of a continuing neuropathic process of axonal type. There was no finding of inflammatory cells infiltrating the vessels. Neither methylprednisolone nor intravenous immunoglobulin (IVIg) improved neurological symptoms including muscle weakness and sensory disturbance. Clinical, electrophysiological, and neuropathological features in our case demonstrate the association of DM and polyneuropathy. The possibility that the same pathological process affecting skin and skeletal muscles also affected peripheral nerves in our patient should be considered.

Ubiquitin (UB)-immunoreactive filamentous inclusions, absent in normal cases and in any other disorder, have been found in patients with amyotrophic lateral sclerosis (ALS) and it has been suggested that they may be characteristic of this disorder. However, there has been no study of UB in ALS skin. We made a quantitative immunohistochemical study of the expression of UB in the skin from 19 patients with sporadic ALS and 19 control subjects. The proportion of UB-positive (UB+) cells in the epidermis in ALS patients was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.92, p<0.001) between the proportion and duration of illness in ALS patients. The optical density of UB+ cells in the epidermis in ALS patients is markedly stronger (p<0.001) than in controls. There was a significant positive relation (r=0.58, p<0.01) between the immunoreactivity and duration of illness in ALS patients. These data suggest that changes of UB in ALS skin are related to the disease process and that metabolic alterations of UB may take place in the skin of patients with ALS.

Vascular endothelial growth factor (VEGF) is a disulfide-linked dimeric glycoprotein that enhances vascular permeability, induces chemotaxis and activation of monocytes/macrophages, and promotes growth of vascular endothelial cells. Furthermore, VEGF is a multifunctional cytokine, which influences neural cells directly, enhancing neuronal survival, axonal outgrowth, and Schwann cell proliferation. So far studies of the skin of amyotrophic lateral sclerosis (ALS) have shown unique pathological and biochemical abnormalities in collagen, elastic fibers, and the ground substance. However, the expression of VEGF in ALS skin has not previously been studied. We made a quantitative immunohistochemical study of the expression of VEGF in the skin from 15 patients with ALS and 15 control subjects. VEGF immunoreactivity was markedly positive in the epidermis and moderately positive in some dermal blood vessels and glands in ALS patients. These findings became more conspicuous as ALS progressed. The optical densities for VEGF immunoreactivity of the epidermis in ALS patients were significantly higher (p<0.001) than in control subjects. In addition, there was an appreciable positive correlation (r=0.85, p<0.001) in ALS patients between the densities for VEGF immunoreactivity and duration of illness, but there was no such correlation in control subjects. These data suggest that changes of VEGF in ALS skin are likely to be related to the disease process and that metabolic alterations of VEGF may take place in the skin of patients with ALS.

A 53-year-old female patient noticed weakness and wasting of limb muscles at age 30 years.Over the following years, the sternocleidomastoid muscles became atrophic and wasted, with frontal baldness. At age 43, her eyesight began to fail because of bilateral cataracts. She had experienced increasing sleepiness since adolescence. She was always very apt to drop off to sleep and always had difficulty in getting up in the morning. Examination at age 45 years revealed a hatchet face with frontal baldness,bilateral ptosis, grasp and percussion myotonia, and muscular atrophy of the four limbs, greater distally, and at the sternocleidomastoid. Pulmonary function tests revealed ventilatory insufficiency of a restrictive type with reduction of vital capacity (1800 mL, 55% of predicted), total lung capacity (2500 mL) and maximum breathing capacity (24 I/min, 25% of predicted).The ratio of the forced expiratory volume in 1 second to the forced vital capacity was 80%, showing no sign of airway obstruction. Arterial gas analysis values at rest while awake showed marked hypercapnea and hypoxia with respiratory acidosis (PaO2 40 mmHg; PaCO2 68 mmHg; pH 7.29). The maximum inspiratory and expiratory pressure (71.3 cmH2O and 83.2 cmH2O) and the diffusion capacity for CO (15.3 mL/min/ mmHg) revealed no abnormality.The ventilatory response to CO2 inhalation was markedly impaired. However, voluntary hyperventilation lowered the CO2 by 23 mmHg. Mental changes such as inattention, apathy and memory defect, which were not noticed in her childhood, were observed. Her IQ was 48. Brain CT scan disclosed enlargement of the lateral ventricles. At age 46, the patient experienced sudden respiratory insufficiency caused by local anesthesia for a cataract operation.She died of acute pneumonia at 53 years of age.