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OBJECTIVES This study aimed to investigate whether pretreatment skeletal muscle mass index (SMI) is a predictor for the risk of aspiration pneumonia and to explore the relationship between low SMI and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) receiving chemoradiotherapy (CRT). METHODS We retrospectively reviewed the data of patients with HNSCC who received CRT during 2010-2019. Patients received a combination of radiotherapy and cisplatin-based chemotherapy (3 cycles of 80 mg/m2 cisplatin on days 1, 22, and 43). Aspiration pneumonia were defined as the presence of both subjective and objective symptoms. Kaplan-Meier curves were generated to analyze survival. RESULTS Among the 159 patients, 36 (22.6%) developed aspiration pneumonia during treatment. Median SMI in patients with and without pneumonia was 12.4 cm2 /m2 (9.0-20.7) and 13.6 cm2 /m2 (8.1-19.7), respectively (P

Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein‐Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre‐invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1‐expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but it still has a pivotal role during all stages of NPC development.

Conclusion: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. Objectives: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). Methods: Between 1999–2012, 50 patients with stage II–IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2–5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66–70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. Results: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively. © 2016 Informa UK Limited, trading as Taylor & Francis Group, Embargo Period 12 months

Conclusion: SPARC-expression is an indicator of the prognosis in terms of OS, independent of HPV-infection. HPV-negative patients with SPARC-Low show survival as favorable as HPV-positive patients, probably because of their higher salvage rate after relapse than SPARC-High patients. Objective: The objectives of the study were to clarify the correlation between the expression of secreted protein acidic and rich in cysteine (SPARC) and HPV-status, and to determine the prognostic value of SPARC-expression in oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: Fifty-three formalin-fixed and paraffin-embedded tissues were obtained from patients with OPSCC who underwent curative treatment. The SPARC protein was detected by immunohistochemistry. SPARC-expression level was divided into two categories, SPARC-High and SPARC-Low, according to the staining index. Results: Twenty-two out of the 53 OPSCC patients were HPV-positive. There was no significant correlation between the HPV-status and SPARC-expression level. Multivariate Cox proportional hazards regression analysis revealed that the HPV-status and SPARC-expression are independent prognostic indicators of favorable and unfavorable overall survival (OS) (p = 0.021 and p = 0.012), respectively. For disease-free survival, the HPV-status was the only predictive factor (p = 0.022). After stratification by the HPV-status, high SPARC-expression was a significant predictor of poor OS in HPV-negative OPSCC patients using Kaplan-Meier analysis and the log-rank test (p = 0.014). Ten out of 28 SPARC-Low patients relapsed, among which six patients (60%) were salvaged. However, 14 out of 25 SPARC-High patients relapsed, and only three patients (21.4%) were salvaged. © 2015 Taylor & Francis., Embargo Period 12 months

Paradoxical vocal cord motion (PVCM) during vocal cord dysfunction (VCD) generally occurs spasmodically and transiently. After we had experienced 36 cases of VCD and successfully treated with conservative treatment including "pursed lips inspiration" method, we experienced a boy who had persistent PVCM. It was observed his PVCM vanished when he breathed in through pursed lips, while it appeared again when he stopped pursed lips inspiration. An airway reflex has been reported where the negative pressure in the subglottic space resulting from the inspiratory effort against a narrowed glottis activates the vocal cord adductor. VCD is considered to have both acceleration of laryngeal closure reflex against airway stimuli and active adductive movement of vocal cords against negative pressure in the subglottic space as underlying factors. The pursed lips inspiration method enables VCD patients not only to accomplish slow and light breathing but also to decrease the difference in the pressure between the supra--and subglottic space by occluding the nasal cavity and voluntary puckering up of the mouth which generate negative pressure in the supraglottic space. This is the first report of the pursed lips inspiration method as a treatment for VCD. Pursed lips inspiration is a simple method which is easy to perform anytime, anywhere without any special equipment, and is considered to be worth trying for VCD.

78歳女．約40年前に左乳癌に対し胸筋合併乳房切除術および術後放射線照射の既往あり．2006年秋に左胸部の術後瘢痕部付近に小皮疹が出現し，徐々に拡大したため2007年8月28日紹介受診．初診時，左胸部術後瘢痕中央部付近に7.5×3.5cmの紫紅褐色の板状硬結を認めた．生検により皮膚血管肉腫と診断した．本人の強い意向により積極的加療は行わず外来にて経過観察のみ行っているが，腫瘍は拡大しほぼ左胸部全体を占めているものの，症状発現より2年半以上の間入院加療等を要さずQOLを保ったまま生存中である．皮膚血管肉腫は稀ではあるものの非常に予後不良な腫瘍であり，放射線照射は皮膚血管肉腫発生のリスクとなるため，今後乳癌患者の急激な増加に伴い放射線照射後の皮膚血管肉腫が発生する症例も増加する可能性が高い．そのため，外科医は放射線照射後の皮膚血管肉腫発症の可能性を必ず周知しfollow upを行うべきと考える．

The natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) in patients with various chronic liver diseases, and its in vitro response to human interferon-alpha(Le) were investigated using a 16-h 51-Cr releasing cytotoxicity assay against YAC-1 or RSa target cells. The NK cell activity was found to be higher in chronic active hepatitis (CAH) and liver cirrhosis (LC) patients without HCC, whereas it was slightly lower in LC patients with hepatocellular carcinoma (HCC), than in normal controls. By the addition of IFN-alpha(Le) in vitro, the NK cell activity was clearly and dose-dependently augmented, even in chronic liver diseases, as well as in normal controls. The magnitude of this augmentation by 10,000 IU/ml of IFN-alpha(Le) in the various chronic liver diseases was not significantly different from that in normal controls. The results suggested that the response of NK cells to IFN-alpha(Le) is not impaired even in chronic liver disease conditions, while the level of NK cell activity may vary according to the type of chronic liver disease and may decrease in patients with HCC.

上腕骨骨幹部偽関節および遷延癒合症例4例を前方進入による plate 固定と腸骨移植で治療した．手術時年齢は27歳から60歳で，男1例・女3例であった．初回治療は functional brace による保存療法2例，エンダー釘による骨接合術2例で，受傷から偽関節手術までの期間は3から63ヵ月であった．全例6ヵ月以内に骨癒合した．Plate 固定の最大の利点は強固な圧迫固定性と，肩肘を損傷しないので術直後から関節可動域訓練が行えることである．

稀な遠位橈尺関節掌側脱臼を2例経験したので報告する．症例1 44歳男性．倒れて来た人を左手で支えようとした時に，左手関節を受傷した．左手関節部痛が出現し，前腕回内が出来なくなった．受診時 X 線，CT で遠位橈尺関節の掌側脱臼を認めた．全身麻酔下に徒手整復を行い，前腕からのギブス固定を6週間行った．症例2 29歳男性．ラクビーのレフリーをしていて，右手関節を捻って受傷した．右手関節部痛が出現し，前腕回内が出来なくなった．受診時 X 線，CT で遠位橈尺関節の掌側脱臼を認めた．全身麻酔下に徒手整復を行い，前腕からのギブス固定を4週間行った．最終調査時には2例とも疼痛はなく，手関節，前腕の可動域制限は認めなかった．遠位橈尺関節掌側脱臼は早期に徒手整復，ギブス固定を行うために，早期診断することが重要である．

横止め髄内釘法で手術を行った上腕骨骨幹部骨折7骨折を調査した．性別は男性3骨折，女性4骨折，受傷時年齢は平均67歳（40～91歳）であった．骨折型はAO分類でA2：2骨折，A3：1骨折，B1：1骨折，B2：2骨折，B3：1骨折で，骨折部位は全て中1/3であった．経過観察期間は平均12ヵ月（4～18ヵ月）であった．その結果，骨癒合は6骨折で得られたが，1骨折は偽関節となった．術後肩痛などの症状を訴えたものはなく，橈骨神経麻痺などの合併症もなかった．これらの事より，高齢者に対する順行性横止め髄内釘法は有効な手術方法であると考えられた．

Synovial cyst is a relative disease. We report a synovial cyst with literature. The cyst reduced remarkably after arthrography. A 45-year-old woman had been suffering back pain and left leg pain for seven months, and was unable to stand or walk. MRI indicated a tumor in the left side between L5 and S1, and arthrography was performed to remove the synovial cysts. After arthrography, pain of the left leg reduced remarkably and the cystic component was found to have disappeared in MRI. No lumbar pain nor left leg pain recurred. Way of curing synovial cysts include resting, use of instruments, steroid injection, and operation to remove a part of the vertebral arch, and removal of the synovial cysts. In this case, the wall of the cysts broke when the needle of the arthrography was injected, and the components of the cyst leaked out. In the removal of synovial cysts, arthrography is sometimes useful for diagnosis and curing.

Six cases with displaced fracture of the distal end of the clavicle (Neer Type II) were treated using the Scorpion plate. All cases had bone union. In addition, all cases except one for the most part achieved full range of motion at the shoulder joint in early post operation. The Scorpion plate provides stable fixation which allows an early range of motion of the shoulder joint without impairing the acromioclavicular joint.

BACKGROUND Intensifying the dose of paclitaxel given in a weekly schedule is useful towards improving the therapeutic index of paclitaxel in treating a variety of advanced and recurrent malignancies and is suitable for outpatient administration. This pilot study was carried out to evaluate the safety of weekly paclitaxel administration by 1 h infusion in the outpatient setting. METHODS Eleven patients with recurrent gynecological tumors who had previously been treated with at least one platinum-based chemotherapy regimen participated in the study between May 1999 and March 2000. Paclitaxel was given at a dose of 70 mg/m(2 ) as a 1 h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS The 11 patients received a total of 166 cycles of therapy. All patients received 70 mg/m(2 ) doses of paclitaxel without treatment delay. No hypersensitivity reactions were elicited. Grade 3 or 4 leukopenia and neutropenia occurred in 9 and 36% of the patients, respectively. Granulocyte colony-stimulating factor was required for only one patient and no patients experienced febrile neutropenia. Neurotoxicity was the most serious adverse effect and all patients experienced grade 1 or 2 peripheral neuropathy. Grade 1 or 2 myalgias were observed in 45% of the patients. Alopecia was universal. No Grade 3 or higher non-hematological toxicities were observed. CONCLUSION Weekly 1 h paclitaxel administration is considered safe as a salvage therapy for recurrent gynecological tumors, making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

Information-guided stereotaxis, assisted by visualization of medical information, will become the next generation of neurosurgical systems. We performed 76 open MRI surgeries at Tokyo Women’s Medical University between March 3, 2000 and April 12, 2001. Of them, comparisons of pre- and post-operative MR images for malignant gliomas in 21 cases revealed an average resection rate of 90.3% (the maximum 100%, the minimum 55%). In this article we describe real time updated navigation, augmented reality navigation, three-dimensional navigation, chemical navigation, information-guided navigation system (High definition visual Computer Aided Surgery System: HivisCAS), and open MRI-guided surgery that we are developing.

Objective: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. Methods: Paclitaxel (70 mg/m2 by 1-h infusion weekly) was administered to two patients with recurrent endometrial cancer of the lung. Results: After 5 cycles, both patients with platinum-resistant disease achieved clinical partial responses confirmed by computed tomography (CT) scan. The serum CA125 levels of case 1 decreased to cut-off level. The response duration of both patients was 4 months. The toxicity was acceptable and probably less pronounced than that characterize of the standard tri-weekly schedules. Conclusion: Although conclusions regarding survival are premature, weekly paclitaxel might offer better quality of life during treatment.

Metastases to the nasal tip from gynecological malignancies are extremely rare. We present a case of a tumor metastatic to the nasal tip from a carcinoma of the uterine cervix. We administered high-dose focal irradiation to the site of the tumor. The literature on metastases to the nose, maxillary sinuses, and paranasal sinuses from gynecologic malignancies is reviewed.

Objectives: Epstein-Barr virus (EBV)-related micoRNAs (miRNAs), BamHI-A rightward transcripts (BART)-miRNAs, are released in a stable form from viable cells, which are abundant in patients with EBV-positive nasopharyngeal carcinoma (NPC). We estimated copy numbers of circulating miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p as well as BamHI-W DNA as biomarkers. Materials and Methods: Serums from 31 EBV-positive (confirmed by in situ hybridization for EBV-encoded small RNAs) NPC patients and 40 non-NPC controls were analyzed. Among the 31 NPC patients, serums at the initial diagnosis and three months after treatment were obtained from 20 patients, and serums only at three months after treatment were obtained from 11 patients. Results: The sensitivity/specificity of circulating BamHI-W DNA, miR-BART2-5p, miR-BART17-5p, and miR-BART18-5p for the diagnosis of NPC before treatment were 100/100, 85/85, 60/95, and 25/100%, respectively. For BamHI-W DNA, NPC patients with stage IV disease had significantly higher copy numbers than those with I-III. Copy numbers decreased significantly post-treatment. In contrast, copy numbers of the three BART-miRNAs showed no significant correlation with the clinical stage at diagnosis or any significant post-treatment change. After treatment, BamHI-W DNA and miR-BART17-5p were detected in 5 and 6 cases out of 11 patients with recurrent or residual tumors, respectively. However, BamHI-W DNA and miR-BART17-5p were absent in all 20 patients without relapse or residual tumors. Conclusion: The copy number of circulating BamHI-W DNA is a more useful biomarker for the initial diagnosis of NPC than the three BART-miRNAs examined. Post-treatment detection of miR-BART17-5p is a potential biomarker of a poor prognosis. © 2016 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We reviewed a case of myasthenia gravis leading to degenerative scoliosis. The patient was a 62-year-old woman, who has been receiving treatment for myasthenia gravis since 33 years old. Her spinal deformity progressed rapidly during the last 7 years. Magnetic Resonance Image revealed atrophy of the paravertebral muscle and severe compression of the spinal cord. Instrumentation from Th11 to the ilium and posterior decompression were performed. After the operation, low back pain and intermittent claudication disappeared.

Aerodynamic forces, drag and lift were estimated by the body attached inertia sensors and high speed videography in ski jumping. Last ISEA conference, the authors presented our new method for the aerodynamic study on ski jumping. In this paper, we propose more robust and reliable measurement system by using wireless technology. Wireless 6DOF inertia sensor platform, which has a built-in tri-axial accelerometer and three single axial gyroscopes, was attached on the jumper’s low back. The authors adopted IEEE802.15.4 for the start trigger and real time monitoring during long training session. Sensor also has a flush memory inside for one hour data storage at 250Hz. The primary target of the present study is to extract the aerodynamic force data during real jumping flight. Angular velocity on the sagittal plane was directly measured from the gyroscope. Then we could obtain the jumper’s body pitch angle by its time integration. The accelerations with respect to the body local coordinate system which was determined by the body pitch angle, indicated the drag and lift forces. The assessment of the aerodynamic forces of ski jumping was examined by both of the sensor data and the kinematical data in this study.

We investigated HER2 expression immunohistochemically in 12 patients with a gastrointestinal (GI) carcinoid tumor. The tumors were located in the stomach in three patients, the duodenum in four, the vermiform appendix in one, and the rectum in four. HER2 was highly expressed in the nine intestinal, but not in the three gastric carcinoid tumors. These findings suggest that HER2 might be highly expressed in intestinal, but not in gastric, carcinoid tumors.

Obesity has increased at an alarming rate throughout the world and has been regarded as a global epidemic disease in light of its close association with a cluster of cardiovascular risk factors, including hypertension, dyslipidemia, and hyperglycemia. This clustering of metabolic disorders is known as the metabolic syndrome, which is associated with insulin resistance (1). BMI is an estimate of total body fat mass and is probably the most useful scale to define obesity. Obesity has been defined as a BMI >30.0 kg/m2 in World Health Organization (WHO) classification (2), but this does not take into account the morbidity and mortality associated with more modest degrees of overweight. A significant increase in risk of death from cardiovascular disease was found for all BMIs of >25.0 kg/m2 in women and >26.5 kg/m2 in men in a prospective study conducted in the U.S. (3). The relation between BMI up …

We report the use of paclitaxel in the successful treatment of a patient with recurrent adenocarcinoma of the cervix. Paclitaxel, 70 mg/m2 by 1-h infusion weekly, was administered to a 59-year-old patient with cervical adenocarcinoma showing lung metastasis. She showed partial clinical response after seven cycles, and at the completion of 20 cycles she showed complete response, which was confirmed by chest X-ray and computed tomography scan. Toxicities including neurotoxicity were mild. She showed an objective response to treatment for over 8 months, and she enjoyed a favorable quality of life during and after treatment. Weekly paclitaxel was very well tolerated, yet was effective for recurrent cervical adenocarcinoma.

画像診断にて嚢胞性肝腫瘍が疑われ,開腹生検にて確診し,肝動脈塞栓療法(TAE)および化学療法が奏効した多発性嚢胞性病変を呈した肝硬変非合併肝細胞癌の1例を経験したので報告する.症例は52歳の女性.主訴は腹部膨満感.身体所見では著明な肝腫大を認め,各種画像診断から多発性嚢胞性病変を伴う肝細胞癌が疑われ,開腹生検を施行.肝右葉全体を占める巨大な塊状型の腫瘍で一部に嚢胞性病変が認められ,肝左葉に数個の娘結節を認めた.肝生検組織所見から非硬変肝に合併した肝細胞癌と診断した.TAE, 5-FU持続動注,CDDP動注の併用による治療を行ったところ,肝腫の縮小率は63.8%で奏効度PRを呈した.また,画像診断上も腫瘍および嚢胞性病変の明らかな縮小を認めた.本例は多発性嚢胞性病変を伴う肝細胞癌で,肝硬変を合併していない点で特徴的であり,嚢胞性病変の発生機序および治療効果を検討する上で,興味深い症例と考えられた.

B型慢性肝炎の経過中に,e抗原からe抗体にseroconversionした症例のうち,e抗原,e抗体陽性時におのおの肝生検を施行しえた7症例について,病理組織学的推移について検討を加えた.e抗原陽性時では,門脈域の拡大,限界板の破壊,ロゼット形成,肝細胞の風船化,parenchymal inflammation は中等度から高度にみられる症例が多くみられたが,e抗体陽性時には,これらの所見は全例改善傾向を示した.しかし中等度のlobular dysorganizationを認めた5例中2例は高度に進展した.e抗原,e抗体陽性時における肝組織像の診断への推移について検討すると,慢性活動性肝炎のmoderate typeを呈した4例のうち1例は慢性持続性肝炎,2例はthin septa formationを伴う持続性肝炎,1例は不変,severe typeの慢性活動性肝炎を呈した3例では,1例はthin septa formationを伴う持続性肝炎を呈したが,2例はinactive肝硬変への移行が認められた.

HIRAI, N., HATTORI, N., HILL, N.O. and OSTHER, K. Antiproliferative Assay of Human Leucocyte Interferon. Tohoku J. exp. Med., 1987, 151(3), 309-316-An in vitro microtitration system of the antiproliferative effect of human leucocyte interferon (IFN-α(Le)) was investigated. The preliminary experiments suggested that the antiproliferative effect of IFN-α(Le) was increased by prolonging the incubation period, by reducing the target cell concentration, and might be prescribed by the total IFN amounts in the challenge medium. By employing a system consisted of 1.5×104 Daudi cells in 0.2ml of medium containing IFN dilutions and an incubation period of 3 days at 37°C, the antiproliferative effects of twenty-one lots of partially purified IFN-α(Le) (PIF-α(Le)) preparations were titrated. The interassay variations in the antiproliferative titers of three PIF-α(Le) established in the present system were found to be in the same range as those in the antiviral titers estimated by a standard macroplaque reduction assay. The each titration curve was parallel, and the antiproliferative titers, assessed by the reciprocals of the IFN dilutions which suppress the cell growth in 50%, were significantly (p

原発性硬化性胆管炎(PSC)の肝内型の1例を報告し,既報告例16例とともに検討を加えた.症例は54歳,女性.昭和54年,健診にて肝機能異常を指摘され,精査目的に入院した.肝機能検査では,著明な胆汁うっ滞型異常を呈し,IgMは軽度上昇し,抗ミトコンドリア抗体(AMA)は低力価陽性であった.肝組織像では,グ鞘のリンパ・形質球浸潤,胆管消失および非定型胆管増生を認め,probable PBC (primary biliary cirrhosis)と診断し,D-penicillamineの投与を開始した.約4年間の外来治療中,ALP, γ-GTP, IgM値は徐々に改善した.昭和58年,患者はfollow-up検査の目的に入院し,ERCP検査にて肝内胆管に広汎な不整硬化・狭窄を認め,典型的な“beaded appearance”を呈し,肝内型のPSCと診断された.肝外胆管には異常はなく,膵管像では,尾部分枝ののう胞状拡張がみられた.肝組織像ではグ鞘の軽度の線維化と細胆管増生が認められ,検査成績では,胆汁うっ滞型異常は軽減し,AMAは陰性であった.

Influences of different incubation temperatures within the physiological range on three different biological activities of human leukocyte-derived alpha interferon (IFN) (the antiviral effect, the antiproliferative activity, and the augmentation of natural killer cell (NK) activity) were investigated in vitro. Using the plaque-reduction assay (U cells challenged with VSV), the antiviral activity by IFN was found to be lower at 35 degrees C and higher at 38 degrees C and 39 degrees C than at 37 degrees C. Using the CPE (cytopathogenic effect) inhibition technique (Vero cells challenged with VSV), the antiviral activity was slightly enhanced at 38 degrees C, 39 degrees C, and 40 degrees C, respectively, when compared with 37 degrees C. The antiproliferative activity on Daudi cells and G-361 melanoma cells was enhanced at elevated temperatures. On the other hand, the antiproliferative activity on PLC/PRF/5 hepatoma cells was lower at 38 degrees C and 39 degrees C than at 37 degrees C, but higher at 40 degrees C. NK activity of PBL after 2 h incubation at 41 degrees C was remarkably lower than that at 37 degrees C, while it was not affected by 2 h incubation at 35 degrees C and 39 degrees C, respectively. When PBL was treated with IFN for 2 h at the temperatures described above, NK activity was equally augmented at all temperatures tested. Our results suggest that elevated incubation temperature potentiates the antiviral and the antiproliferative activities, but does not affect the NK augmenting activity of HuIFN-alpha (Le).

A recently recognized unique cytotoxic substance, CTS-51, was tested for the hear or acid stability, trypsin digestion and dialysis. Moreover, influences of elevated incubation temperatures or serum concentrations of medium on the cytotoxic activity of CTS-51, and the combination effects of CTS-51 and human leucocyte interferon (HuIFN-alpha (Le)) were investigated. The cytotoxic activity of CTS-51, which is promoted by a small molecule easily passable the dialysis membrane, was found to be very stable to heat (even at 100 degrees C for 30 min) or acid (pH 2.0 for 24 hr at 4 degrees C) treatments. The treatment with 0.75% trypsin for 1 hr did not diminish the CTS-51 activity. The susceptibility of Daudi lymphoma cells to the antiproliferative action of HuIFN-alpha (Le) was further potentiated by treating the cells with CTS-51 for 16 hr. On the other hand, the CTS-51 activity which was revealed to be prescribed by its concentration in the medium, was not potentiated at 39 degrees C when compared to that at 37 degrees C in contrast to HuIFN-alpha (Le) action, and was reduced according to the increase of the fetal calf serum concentration in the medium.

The influence of cimetidine on antiviral activity of leukocyte interferon (IFN-alpha (Le] was studied in plaque-reduction assays using Utrecht (U) amnion cells challenged with vesicular stomatitis virus (VSV) and in CPE inhibition assays using A549 cells challenged with encephalomyocarditis (EMC) virus and WISH cells challenged with VSV. The IFN-alpha (Le)-induced antiviral activity was slightly enhanced in cells treated with cimetidine, whereas cimetidine treatment alone did not show any antiviral effect. The observed titer (OT) was significantly higher (p less than 0.05) in cells treated with cimetidine together with IFN-alpha (Le) compared with the control without cimetidine. The effect of cimetidine on IFN-alpha (Le)-induced cell growth inhibition was studied on Daudi (a Burkitt's lymphoma cell line) and on G361 (a melanoma cell line) cells. The growth of these cells was slightly suppressed by cimetidine alone. When cells were treated with IFN-alpha (Le)/cimetidine, the cell growth inhibition rates were significantly higher (p less than 0.02) than the rates obtained with IFN-alpha (Le) or cimetidine alone. These results indicate that cimetidine can enhance the antiviral as well as the antiproliferative activities of IFN-alpha (Le) in "in vitro" studies.

Changes in the host interferon system during short-term steroid hormone (prednisolone) withdrawal therapy in seven patients with HBeAg-positive chronic hepatitis B were investigated by estimating the in vitro interferon-alpha production in peripheral blood lymphocytes and 2-5 oligoadenylate synthetase activity in the serum. The interferon-alpha production induced by the Sendai virus and estimated in lymphocyte cultures was rapidly and significantly (p less than 0.01) reduced by prednisolone administration and subsequently followed by a recovery corresponding to its withdrawal. The serum 2-5 oligoadenylate synthetase activity showed a similar tendency to diminish under prednisolone administration and to revive during its withdrawal. In all four patients who developed an acute and transient post-prednisolone withdrawal exacerbation a significant initial increase in serum HBV-DNA levels was noted in accordance with the reduction in the host interferon system activity. The results suggest that the changes in the host interferon system activity, i.e. an initial fall and subsequent recovery as caused by a short-term steroid administration with gradual withdrawal, appear to promote viral replication in the early phase and the development of acute and transient exacerbation of hepatitis in the post-steroid withdrawal phase, which may lead to HBeAg/anti-HBe seroconversion in HBeAg-positive chronic hepatitis B patients.

Effects of cimetidine on the augmentation of natural killer (NK) cell activity by human leukocyte interferon (Hu IFN-alpha (Le] and on the IFN production from donor leukocytes were investigated in vitro. NK cell activity of PBL was suppressed after 16 hours pretreatment with 0.3, 3.0, and 30.0 micrograms/ml of cimetidine. On the other hand, there was dose dependent suppression of Hu IFN-alpha (Le) production in PBL by cimetidine. The NK cell activity of PBL augmented by Hu IFN-alpha (Le) was further enhanced when the effector cells were pretreated with cimetidine or when cimetidine was added together with IFN. K562, G361, and PLC/PRF/5 cells were used as target cells. Our results suggest that a 16 hour treatment with cimetidine alone may suppress NK cell activity of PBL, probably due to reduced IFN production by leukocytes. On the other hand, cimetidine may enhance the IFN induced NK augmentation in PBL in vitro.

HIRAI, N., HATTORI, N., HILL, N.O. and OSTHER, K. Effects of Cimetidine on Various Biological Activities of Human Leucocyte Interferon and on Interferon Production in Lymphocytes. Tohoku J. exp. Med., 1985, 147 (2), 199-212-In vitro effects of cimetidine on the antiviral, the antiproliferative and the natural killer (NK) cell stimulating activities of human leucocyte interferon (IFN-α (Le)), and on the Sendai virus induced interferon production in lymphocytes were investigated. The antiviral activity of IFN-α (Le) was dosedependently enhanced by cimetidine, which alone did not demonstrate any antiviral action. The observed titer of the same IFN preparation titrated with 60μg/ml of cimetidine was significantly higher (p

— Intrahepatic bile ducts were examined histologically and ultrastructurally in wedge-biopsied liver specimens from three patients with primary sclerosing cholangitis. Bile ducts with periductal concentric fibrosis, which is a characteristic finding in primary sclerosing cholangitis, revealed ultrastructurally finger-like projections or fine undulations of the basal free surfaces with markedly duplicated basal lamina. The lamina was collared by a layer of elongated fibroblasts and thickened bundles of collagen fibers outwards. These changes were consistently found in all sizes of ducts examined, and might be related to progressive periductal fibrosis. Serial section observations showed that some severely affected ducts actually disappeared when accompanying severe periductal fibrosis. It would therefore appear that progressive periductal fibrosis may interrupt fluid and nutrient exchange between the bile duct epithelia and peribiliary capillary plexus, followed by obliteration of the biliary lumina. Although the bile ducts showed segmentally periductal lymphocytic infiltration and, ultrastructurally, point contacts between infiltrating lymphocytes and biliary epithelial cells were observed occasionally, the exact role of infiltrating lymphocytes in the pathogenesis of primary sclerosing cholangitis remains unclear.