Kosuke Mori

Impairment of blood-cerebrospinal fluid barrier in multiple sclerosis.

Abstract: The blood‐CSF barrier (BCB) function in active multiple sclerosis (MS) was studied by means of CSF proteins analysis using disc electrophoresis and immu‐nofixation. Forty‐five CSF samples were obtained by repeat lumbar punctures at various intervals, from four autopsy‐proven cases and three male and nine female patients with clinically definite MS. When total protein content was increased, the percentages of prealbumin and t fraction were decreased significantly in association with the presence of haptoglobin (Hp) polymers in nearly all the samples, as a result of increased permeability of the BCB. Even when the total protein content was normal, Hp polymers were detected in 56% of the samples, and the t fraction tended to be decreased. Monoclonal immunoglobulin and Hp polymers were both recognized in some cases. The results suggested a more frequent occurrence of BCB impairment in MS than had formerly been revealed by CSF albumin analysis, and accorded with the recent reports of contrast‐enhancing lesions of MS brain in computerized tomography.

Myotonic dystrophy and hyperthyroidism

The association of myotonic dystrophy and hyperthyroidism is rare. In the first such case in Japan, hyperthyroidism induced severe exacerbation of muscle weakness, which improved when the thyroid disorder was treated.

Polyacrylamide-gel disc electrophoresis of native cerebrospinal fluid proteins with special reference to immunoglobulins and some clinical applications

Polyacrylamide-gel disc electrophoresis has been applied to the fractionation of CSF samples obtained from 2m control subjects (range of age 16 to 77 yr, mean 41.0 yr) and from 157 patients with various neurological diseases, with the purpose of evaluating the diagnostic significance of separated protein bands. It was found that the immunoglobulins, with some exceptions, were fractionated in the G-zone which was defined as an area between the origin and 0.57 in terms of relative migration based on transferrin (RT). Fourty-four percent of the whole Bence Jones protein bands which were examined were detected in the area of RT 0.70-0.90. The normal values of CSF protein fractions were (means+/-SD):Pre-alb-zone, 10.97+/-2.31%; Alb-zone, 40.74+/-5.72%; A1-zone, 5.25+/-0.72%; A2-zone, 8.23+/-1.24%; B1-zone, 10.82+/-2.18%. B2-zone, 7.94+/-1.93%; G-zone, 16.05+/-2.49%. The following significant results were obtained: (1) When the total protein concentration (TP) of CSF is increased: the percentage of the Pre-alb-zone is lowered and that of the A1- and G-zones is increased in diseases such as neurosyphilis, infectious meningitis, brain tumour, multiple sclerosis, intervertebral disc protrusion and cerebral infarction. The A2-zone was diminished in cerebral infarction, and a similar change was seen in brain tumour with in addition a decrease of the B2-zone; (2) When the TP was normal: the percentage of the G-zone was increased in multiple sclerosis, brain tumour and intervertebral disc protrusion. In the latter 2 disorders the A1-zone also increased. This fraction also increased in the cases of cerebral infarction, whose mean age was, however, much higher than that of the control subjects.

Characteristic protein fractions of cerebrospinal fluid disc electrophoretic analysis

The present work was undertaken to determine characteristic proteins of normal cerebrospinal fluid (CSF) by disc electrophoresis in polyacrylamide gel, and to evaluate their usefulness as indicators of blood-brain-CSF barrier disturbance. The technique has been applied to 1280 samples of unconcentrated CSF obtained from 27 reference subjects and 847 neurological patients, with a simultaneous analysis of 361 sera. The pre-albumin content (mean +/- S.D. as a percentage of total protein, 11.0 +/- 2.3%) was higher than formerly reported. One reason for this is that preliminary concentration was not necessary, and the second is related to the principle of protein resolution. The no. 5 protein band of the post-albumin group (3.9 +/- 1.1%) was characteristic, though it has not yet been identified. The no. 3 protein band of the post-transferrin group (5.2 +/- 1.7%) was highly specific to CSF; it was found to be closely related to transferrin, and may correspond to tau fraction obtained by other methods. Barrier dysfunction was easily recognizable by the appearance of polymers of haptoglobin 2-1 or 2-2, because only haptoglobin 1-1 was detected in normal CSF. The percentage of the main region of the G-zone (13.7 +/- 2.6%) was postulated as normal content of CSF immunoglobulins.

Fast handover mechanism for high data rate ground-to-train free-space optical communication system

We developed a fast handover mechanism using a high-speed image sensor for a high data rate ground-to-train free-space optical communication system in order to achieve a continuous communication between passengers and the Internet. Using the new handover mechanism, we were able to achieve handover time of 21 milliseconds in the best case, which is short enough to offer live streaming Internet services such as Skype, YouTube, and Internet Radio.

Solid-phase immunofluorometric assay for quantification of CSF immunoglobulins: Determination of normal reference values

Because a highly sensitive method is required to quantify low concentrations of immunoglobulin (Ig) classes in cerebrospinal fluid (CSF), there have been a few papers reporting normal values of CSF IgG, IgA and IgM determined in the same samples. Enzyme immunoassay (EIA) is most frequently used, but has such drawbacks as susceptibility of enzyme to inhibition and denaturation and the requirement for additional incubation with a substrate. Therefore, solid-phase immunofluorometric assay was evaluated for quantification of CSF IgG, IgA and IgM in the nanogram range. We found this to be rapid and reproducible. The mean (SD) values of normal CSF samples obtained from 22 subjects with tension headache were 23.9 (7.6) micrograms/ml for IgG, 2.00 (0.90) microgram/ml for IgA and 197 (87) ng/ml for IgM. The normal mean (SD) values of indexes were 0.51 (0.10) for IgG, 0.25 (0.05) for IgA and 0.044 (0.017) for IgM. These values agreed quite well with those determined by EIA. The values of CSF albumin correlated significantly with those of CSF IgG or IgA, but did not with those of CSF IgM. Levels of each of the three Ig classes in CSF and serum were significantly correlated. When CSF/serum ratio was introduced, a significant correlation between the albumin ratio and each Ig ratio was found. These results suggest that the Ig content of normal CSF may depend upon that of serum and upon the characteristics of the Ig molecule.

A CASE OF MYOTONIC DYSTROPHY ASSOCIATED WITH HYPERTHYROIDISM

甲状腺機能亢進症とmyotonic dystrophyの合併は極めて希である,最近我々はその1例を経験し,甲状腺機能亢進症と神経・筋疾患との関係を考察する上で,興味ある症例と考え,報告する.症例は53才,女で,昭和50年12月頃初めて立ち上がり困難に気づいたが放置.昭和51年3月頃やせ,発汗,動悸と共に筋力低下は悪化し,立ち上がり不能となり歩行障害や嚥下障害も認めたため,同年7月入院した.入院時び漫性甲状腺腫を触知し,胸鎖乳突筋,僧帽筋をはじめ,下肢では中殿筋や大腿四頭筋にも著明な筋萎縮,筋力低下を認めた.また白内障とmyotonia現象を認め,筋電図でも典型的なmyotonic dischargeを認めた.甲状腺機能は血清サイロキシン20μg/dl以上, BMR+77.8%, 131I甲状腺摂取率81%と明らかな亢進を示した.その他の内分泌異常として,尿中17KSの軽度低下, GTT時のIRIの過剰反応, ITT時のHGHの低反応,血清LH, FSHの高値およびLH-RH試験におけるLHの高反応などがみられた.入院後, methimazole15mg/日投与により甲状腺機能が正常化すると共に嚥下障害は消失し,徐々に歩行障害は改善し,独力で立ち上がりも可能となつた.以上の経験に加え,文献的にも両者の合併は筋力低下の急速な悪化をもたらすとされており,甲状腺機能亢進症の早期発見,早期治療が肝要である.

Cerebral vascular disease and its microcirculation.

From Keio University, Tokyo, Japan. * Professor, Department of Internal Medicine. † Department of Internal Medicine. Cerebral vascular diseases, the most frequent cause of death in Japan for the last 15 years, causes more than 20% of the total deaths. Thus, the pursuance of their pathogenesis and establishment of more definite therapy have become one of the most important subjects of the medical research in this country. Regarding their pathogenesis, a number of theories have been hitherto proposed. Among them, the theory of cerebral vascular rupture for cerebral hemorrhage (Charcot and Bouchard,’Staululler,2 Spatz,3 Matsuoka4), and that of thrombus formation in intra or extra cerebral arteries for cerebral thrombosis

An Evaluation for the Serum Lipid Peroxid Detecting Methods and those Levels on the Healthy Controls

Tiobarbituric acid (TBA) 使用による血中過酸化脂質の測定には八木法, 内藤法, 武内法などが多くの施設で利用されているが, 著者らは武内法を取り上げ主として臨床応用に必要な基礎的面ならびに特定の疾患をもたない20歳代より100歳代までの健常者対照値について検討した.はじめに武内氏の原法 (分光法) に従い分光光度計 (分光法) とけい光分光光度計 (けい光法) とを使用し, 同一検体につき平行して測定したところ, けい光法による測定が再現性がよかったので, けい光法について食餌の影響, 検体保存法, 使用血清量, 煮沸時間, 回収率, 精度, 原法との相関などを検討した. なお, 分光光度計は日立181型, けい光分光光度計は日立MPF-2A形を使用した.その結果, 測定値に食餌の影響は殆んどなく, 保存は冷蔵7日までは可能であり, 使用血清量は0.1mlでよいこと, 煮沸時間は厳密に設定することが重要であることなどが分った. また, 回収率は90%以上, 精度は同一検体の10回測定で変動係数±3.32%であり, 原法との相関係数は0.71と正の相関が得られた. これらの検討より本法は試みるに値する方法と考えた.年代別健常者対照値は, 20歳代2.437±0.836nmol/ml (以下, 単位は同じ), 30歳代2.843±0.969, 40歳代3.053±0.824, 50歳代3.046±0.511, 60歳代2.969±0.607, 70歳代2.393±0.661, 80歳代2.109±0.565, 90歳代1.922±0.428, 100歳代1.651±0.461であり, 60歳代までは加齢とともに増加し, それ以後は加齢とともに減少した. このように少なくとも青年期 (20歳代), 壮年期 (30～50歳代), 老年期 (60歳代以後) の間では推計学的に有意の差が認められるため, 各種疾患についての意義を論ずる場合は, その点を考慮して比較検討すべきであろう.

Polyacrylamide Disc Electrophoresis of Cerebrospinal Fluid Proteins

近年新しく開発された蛋白分画法の中で, ディスク電気泳動法は, 検体が微量ですみ, 分離能および再現性もすぐれ, 稀薄蛋白液の泳動にも前処置に濃縮を必要としない等の利点を有している. 本法による髄液蛋白分画の研究は, 従来, 使用髄液量を一定とした泳動実験の報告を見るのみであり, 使用髄液蛋白量を一定とした論文は, 本邦にはみあたらない. 我々は泳動する蛋白量を一定にして, 総計386検体の髄液を泳動し, そのうち122検体を疾患別に検討し, 以下に述べる成績を得た.1) 髄液のディスク電気泳動法において, 使用蛋白量を一定 (約200μg) とすることによって, 泳動像およびその蛋白分画相対濃度百分率を, 各検体間でより正確に比較することができた.2) 蛋白分画を大きく5区域にわけた. 正常髄液23検体の各分画相対濃度百分率の平均値および標準偏差は, Pre.-zone: 10.9±2.7%, Alb.-zone: 40.3±5.8%, A-zone: 13.5±1.6%, B-zone: 19.2±3.9%, G-zone: 16.1±2.6%であった. G-zoneの意義については免疫グロブリンとの関係を考察した.3) 疾患により有意の増減 (危険率5%) を認めた分画は, 髄膜炎, 神経梅毒, 脳硬塞, 脳腫瘍, 多発性硬化症および椎間板ヘルニアのいずれの疾患でも, 髄液蛋白量が40mg/dl以上のときは, Pre.-zone の減少とG-zone の増加を認めた. 椎間板ヘルニアでは常にA-zone の増加があり, 髄液蛋白量が40mg/dl以下のとき Alb-zone の減少を認めた. 脳硬塞では, 常に Pre.-zone が減少し, 髄液蛋白量40mg/dl以下のときA-zone は増加した. 髄液蛋白量が40mg/dl以下でも G-zone の増加を認めた疾患は, 多発性硬化症, 脳腫瘍, 椎間板ヘルニアであった.