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本研究では、北海道・函館の事例を中心に「村落小学」の実態の一端の解明を試みた。具体的には、函館における小学校の制度化の過程がどのように展開し、村落小学がどのような普及の経過をたどっていったのかについて検討した。函館における教育の整備は、開拓使に求められる社会的要請のもとで進められたため、官吏の子弟を対象とした中等教育から着手された。この状況にあって、庶民に対する教育については普通小学、変則小学、村落小学の各形態の事例が確認された。函館では、村落小学に関して「学制」頒布後の早い時期から学校改革案において小学校に夜学校を付設し、「一二歳以上一六歳以下で働いている者に」小学校教科を教えるため「夕学筵」（夜学校）を設置することを明示した。また、普通小学が設置される以前から複数の「教育所」が開設され、これらが村落小学の原初形態となった。函館の村落小学は明治11年～12年に集中して開設されたが、その背景には教則（村落小学教則）の存在があった。

本稿では、明治元年から「学制」頒布（明治五年）以前までを中心に、明治新政府が掲げた近代学校教育制度の政策をふまえ、我が国における義務教育制度の基盤の形成について検討、考察した。特に、明治維新直後から新政府によって構想された小学校制度構築に向けた諸政策が、どのようなかたちで示されたのかを明らかにし、その政策が義務教育制度の基盤の形成にどう影響したのかついて、実態の一端の解明を試みた。まず、明治維新後の新政府による教育施策について、京都および東京の動向をふまえ政府指導者の主張と京都の大学校構想を確認した。また、教育政策における洋学派の台頭にも言及した。次に、国民全般を対象とした普通教育機関の構想について、維新期において東京府に設立された小学校の事例を中心に跡づけるとともに、小学校設立にかかる事例の一部を掘り下げ実態の一端を明らかにした。さらに、摂津国、近衛家領川邊郡伊丹の事例に基づいて、郷学に託された庶民対象の教育がどのように行われていたのかについて、伊丹の郷学の動向を複数の観点から考察し、地域における郷学の実態の一端を明らかにした。

昭和20年代における新制中学校の生活指導からみた徳育とその教育方法について、「学習指導要領における教育目標からみた生活指導と徳育の視点」「赤塚第一中学校の発足」「学校便覧：教育目標、訓育年間計画、風紀要項」の各項目により考察した。その結果、修身科はGHQの勧告によって授業停止と教科書回収に追い込まれたが、修身の教育的機能を代替するものとして、新制中学校における生活指導に徳育の役割が期待されたことが明らかとなった。また赤塚第一中学校においては、生活指導の目標を達成するため、訓育の全体の計画（年間計画）を作成し、さらに同校独自の「風紀要項」を提示することによって学校生活における望ましい態度や振る舞いの詳細を生徒に示すことで、重視されるべき生徒の道徳性や道徳的心情をはぐくむ指針にしたと考えられる。同校では、生活指導部等の組織を中心に生徒会（生徒自治会）やホーム・ルームを中心として教科外および教科活動も含めた学校生活全般から学校の教育目標の達成が目指され、指導方法の観点からは、生徒に対する全体指導と個別指導の両面から取り組むことで、民主的思考と公民的教養を備えた人間形成に生徒を導くための道徳性涵養を追求した。

戦後日本の新制中学校に導入された生徒指導と教科外教育活動について、制度化に向けた教育行政側の構想や教育活動としての位置づけを、占領期の教育改革構想もふまえながら東京都板橋区の新制中学校の教育状況に焦点をあて実態の解明を試みた。まず、昭和22年５月に11校の中学校を開校した板橋区の状況を事例や当時の社会背景などをふまえて検討した結果、新制中学校発足当時においては中学校としての教育環境をいかに確保するかが最重要課題であった点が浮かび上がった。また、義務就学として学ぶ者とそうでない生徒が混在するという特殊な状況により、生徒を受け入れた学校や教師が適切な指導を求めて試行錯誤する状況が露呈した。次に、昭和20年代前半における生徒指導と教科外の教育活動に関する教育行政側の構想を中心に整理・分析を行った結果、各校の教育目標と生徒指導の関係性は確認できたものの、昭和20年代前半にあっては生徒指導に関する指針が確立されていなかったことから、生徒指導の概念を明確にはできなかった。教科外の教育活動については名称の固定化はみられず、また教科と教科外の混在や諸活動や行事等が未分化であった点が考察できた。さらに、板橋区の中学校の事例に着目し、昭和20年代前半の史料による実態の把握を通して検証・分析を行った。これにより、生徒指導については現職教員と補充教員の経験や力量の差異により、教育行政側が示した生徒指導の内容や指導水準に至らないという懸念が考察の結果として表出した。また、教科外の教育活動については開校初年度から各校で積極的な取り組みがなされたが、年度によっては行事や活動の実施に差がみられた点も跡付けられた。

本稿では、保育内容に関する史的研究の一環として、愛国婦人会茨城支部の農村託児所事業に着目し、大正期の農村託児所で展開した保育の実状の考察を通して、農村託児所設立の社会的背景や保育の内容の実際を考察した。本稿の考察内容としては、まず、大正期の保育からみた農村託児所とその設置に係る社会的背景について、保育制度のなかの農村託児所、および愛国婦人会による農村託児所設置の社会的背景の跡付けを行った。次に、保育の内容をかたちづくる側面や設置諸規定からみた保育の内容、農村託児所における保育の内容の展開とその意義について検討した。以上により、愛国婦人会による農村託児所設置の社会的背景の一端が明らかとなった。また、茨城支部が身体的側面に関する保育の内容に関する考え方として、農村の子育て事情に着眼しその衛生上の生活課題を改善に導く意図を示していた点も確認することができた。一方、教育的側面については、託児所の保育に必要な保育上の配慮や託児所の諸規定において身体面、精神面、休養面といった視点から保育の内容の組み立てを構想しているという点も明らかとなった。さらに、大正14年実施の眞壁郡關本町託兒所の事例の検討から当時の農村託児所の実態の一端が浮かび上がった。

日本の教育の史的側面からみた道徳教育の実態の一端を明らかにするために、明治期の小学校における修身教育の形成について、師範学校附属小学校の事例をふまえて小学校修身科の教育的位置づけやその教育目的、教育方法などにかかる諸法令や史料等の分析を通して考察した。以上の検討により、日本の学校教育の近代化とともに進められた小学校の修身教育が、特に「教育勅語」渙発以降「小学校教則大綱」の趣旨に則って綿密に進められたという点が明らかとなった。また、修身科の教育目的や教育方法については、文部省による「小学校修身科教授方法」（訓令）発令以降の諸状況について、師範学校附属小学校の実態の一端が明らかとなった。

大学の教職課程における特別活動の指導法等に関する科目について教育行政側の視点をふまえて「特別活動の指導法」のシラバスのモデルを提示し、その記載内容とそれによって行われる各回の授業における指導法や教育的アプローチについての考察を通して、履修学生がより効果的に特別活動の指導法の授業を受講するための諸側面について検討するとともに、アクティブ・ラーニングの手法を手がかりとした教育方法の可能性を考察した。

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with

Two types of in-grown stacking faults in 4H-SiC epitaxial layers (SFs) were investigated using a new photoluminescence (PL) topographic imaging system, macro/micro PL mapping system, TEM and molten KOH etch pit observation. Shockley type SFs (SSFs) of 3C and 8H inclusion were identified as two different types of triangular PL emission patterns with corner angle of 60° and 30° spreading to the down step direction. The peak wavelengths are 423nm and 465nm, respectively. The 60° triangular SSFs are 3C inclusion related with threading edge dislocations. The 30° triangular SSFs are 8H inclusions related with basal plane dislocations. Such SFs are caused by dislocation- related disturbance of the step flow growth resulting in insertion of new cubic sites in between the 4H hexagonal turns. The substrate surface roughness at the early stage of the epitaxial growth and the growth rate may correlate with the might be deeply related in the SFs formation of SFmight be deeply related in the SFs.

Radiofrequency ablation (RFA) is an effective modality for treatment of hepatocellular carcinoma (HCC), because it can induce large coagulation necrosis in a few sessions. The aim of this study is to evaluate whether we can assess the therapeutic effect of RFA immediately after RFA.Twenty-one patients (25 nodules) with HCC undergoing RFA treatment were enrolled in this study. Fourteen patients were treated with combination therapy of lipiodol chemoembolization and RFA, while 7 patients were treated with RFA alone. Dynamic computed tomography (CT) using multidetector row helical CT (MD-CT) was performed before, immediately after and 1 week after RFA. Simultaneously, multiplanar reconstruction (MPR) images were also obtained for comparison.With or without chemoembolization, the size of coagulated necrosis was almost the same between the time immediately after and 1 week after RFA. The therapeutic effect was able to be evaluated by dynamic CT scans immediately after RFA in all patients. Moreover, MPR images facilitate the detailed evaluation of the therapeutic effect.Examination of dynamic CT using MD-CT immediately after RFA is useful to evaluate the therapeutic effect and may enable a shorter hospital stay.

Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment. A retrospective study was performed using the liver biopsy specimens obtained before IFN treatment from 69 patients with chronic serotype 1 hepatitis C virus (HCV) infection. TRX and TBP-2 mRNA levels in the liver biopsy specimens were amplified by real-time RT-PCR. The serum TRX protein level was estimated with a sandwich enzyme-linked immunosorbent assay kit, and the expression of TRX protein in the liver was examined immunohistochemically in 19 patients. There was no association between the serum TRX level and the TRX level in the liver. There was a significant correlation between the expression level of TRX protein in the liver and the TRX mRNA level in the liver. TRX and TBP-2 levels in the liver tended to decrease slightly with increased fibrosis stage, although not significantly. The TRX level in the liver tended to increase with hepatitis activity index, although not significantly. TBP-2 mRNA levels in the liver were significantly higher in responders than non-responders to the IFN therapy (p0.05). Among patients who had a high viral load of850 KIU/ml, the TRX level in the livers of non-responders was significantly lower than that in the livers of responders (p0.05). TRX and TBP-2 mRNA levels in the liver before IFN therapy may predict the outcome of IFN therapy in patients with chronic serotype 1 HCV infection.

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P < 0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.

The long-term usefulness of interferon-alpha (IFN-alpha) in chronic hepatitis B remains controversial. To investigate the long-term efficacy of IFN-alpha therapy in chronic hepatitis B, 62 Japanese patients, including 27 patients treated with IFN-alpha (IFN group) and 35 patients without antiviral therapy matched by age and sex as controls (control group), were followed up for 2-14 years. At entry, the serum alanine aminotransferase (ALT) level in the IFN group was significantly higher than that in the control group (238.6+/-250.1 vs. 142.3+/-152.1 IU/l, P0.05). The prevalence of genotype C was 89%, with no difference between the two groups (93 vs. 86%). There was no significant difference in the presence of the precore mutation or the dual core promoter mutations between the IFN and control groups (37 vs. 46%, 74 vs. 66%). After long-term follow-up, the rate of sustained HBeAg seroconversion was comparable in the two groups (33 vs. 31%). Normalization of serum ALT level was seen in 44% of the IFN group and 51% of the control group, with no difference. There was also no difference in the percentage of cases with loss of serum HBV-DNA by PCR assay between the two groups (33 vs. 29%). During follow-up, two patients of the control group and three patients of the IFN group developed cirrhosis, and one of the IFN- treated patients progressed to hepatocellular carcinoma. The results of this long-term follow-up study showed that no benefit of IFN-alpha treatment was detectable during long-term follow-up in Japanese patients with chronic hepatitis B.

OBJECTIVE We compared serum hepatitis B virus (HBV)-DNA levels in different states of hepatitis B infection, and investigated whether there is an HBV-DNA value that can be used for differentiating inactive carriers from patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis. METHODS A retrospective study using sera at a followed endpoint from 64 Japanese patients with chronic HBV infection seen in Kobe University Hospital between 1989 and 2002. Sera of patients were assayed using a polymerase chain reaction-based assay. RESULTS Genotype C was dominant (95.4%). Patients with chronic hepatitis with an elevation of the serum alanine aminotransferase (ALT) level had significantly higher HBV-DNA levels than patients with persistently normal ALT. For one time observation at a followed endpoint, the mean HBV-DNA level of HBeAg-negative inactive carriers was significantly lower than that of HBeAg-negative chronic hepatitis patients (3.6+/-1.0 versus 4.8+/-1.5 log copies/ml, P

Goals We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-alpha in patients with chronic hepatitis B. Background Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. Study Thirty-one Japanese patients with hepatitis B e antigen-positive chronic hepatitis were treated with natural interferon-alpha. HBV DNA with the precore mutation was assayed in serum using a mutation site-specific assay before and after treatment. Results Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). Conclusions Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-alpha.

Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome and less favorable response to interferon (IFN) α therapy compared to genotype B. We evaluated the response to IFN a therapy and long-term clinical outcome in Japanese patients with chronic active HBV genotype C infection. Thirty Japanese patients with chronic active hepatitis who received natural IFN α therapy were followed for 2-12 years (mean 5.9 years). Twenty-four patients were treated short-term (daily for 4 weeks at a mean total dosage of 174 million units) and 6 patients were treated long-term (total of 26 weeks at a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an antiviral response at 6 months after therapy. Clinical data before treatment in both responders and non-responders were comparable. Although not significant, responders tended to have younger age, a higher serum transaminase level, a lower frequency of precore mutation (G 1 8 9 6 A) (67% vs. 92%) and a higher frequency of core promoter mutation (A 1 7 6 2 T/G 1 7 6 4 A) (89% vs. 58%) than non-responders. The patients treated long-term responded significantly better than those treated short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher percentage of responders than non-responders had sustained clearance of HBeAg with seroconversion and normalization of transaminase concentration at the followed end point (83% vs. 17%, P

Genotype C of hepatitis B virus (HBV) has been shown to be associated with a poor clinical outcome and less favorable response to interferon (IFN) alpha therapy compared to genotype B. We evaluated the response to IFN alpha therapy and long-term clinical outcome in Japanese patients with chronic active HBV genotype C infection. Thirty Japanese patients with chronic active hepatitis who received natural IFN alpha therapy were followed for 2-12 years (mean 5.9 years). Twenty-four patients were treated short-term (daily for 4 weeks at a mean total dosage of 174 million units) and 6 patients were treated long-term (total of 26 weeks at a mean total dosage of 687 million units). Twelve of 30 (40%) patients had an antiviral response at 6 months after therapy. Clinical data before treatment in both responders and non-responders were comparable. Although not significant, responders tended to have younger age, a higher serum transaminase level, a lower frequency of precore mutation (G1896A) (67% vs. 92%) and a higher frequency of core promoter mutation (A1762T/G1764A) (89% vs. 58%) than non-responders. The patients treated long-term responded significantly better than those treated short-term (83% vs. 29%, P=0.026). Up to 12 years after therapy, a higher percentage of responders than non-responders had sustained clearance of HBeAg with seroconversion and normalization of transaminase concentration at the followed end point (83% vs. 17%, P0.001). Two non-responder patients had cirrhosis after long-term follow-up. One non-responder patient died of hepatocellular carcinoma 8 years after IFN therapy; except in this patient there was no development of decompensated cirrhosis. Early responsiveness to IFN alpha therapy in Japanese patients with chronic active HBV genotype C infection improves the long-term clinical outcome.

Interferon (IFN)-alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the clonal expansion of pre-neoplastic hepatocytes. To clarify the mechanism by which IFN-alpha prevents hepatocarcinogenesis, we examined the effect of IFN-alpha in a chemically induced hepatocarcinogenesis model initiated by diethylnitrosamine (DEN) and promoted by 2-acetylaminofluorene (2-AAF) and partial hepatectomy, in which hepatocellular carcinoma (HCC) arises through pre-neoplastic foci without inflammation or fibrosis. The protocols of IFN-alpha administration were started simultaneously with chemical initiation and lasted for either 4 or 40 weeks. The pre-neoplastic foci and neoplastic HCC were evaluated at 4 or 40 weeks after chemical initiation, respectively. The effects of IFN-alpha were assessed by the expression of tumor-related genes and cell cycle-related genes in the pre-neoplastic foci, using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). As a result of IFN-alpha treatment, the numbers and average volume of pre-neoplastic foci were reduced. The proliferating cell nuclear antigen index and the expression of G(1) cyclins were also reduced in the pre-neoplastic foci in the IFN-treated group. The expression of p21, which is an inhibitor of cyclin-kinase complexes was higher in the foci of the IFN-treated group, while p53 expression was not altered in this group, compared with the control group. IFN-alpha also suppressed the tumor development at 40 weeks after initiation. And in the long-term IFN-alpha-treated group, both the tumor numbers and average tumor size were markedly more reduced than those in the short-term-treated group. Therefore, it was demonstrated that longer treatment with IFN-alpha was more effective, compared with shorter treatment. In conclusion, it was shown that IFN-alpha directly prevented and delayed hepatocarcinogenesis through the suppression of pre-neoplastic cell proliferation and that it may partially depend on p21 induction through a p53-independent pathway.

Alkalization of the intestinal tract by oral administration of sodium bicarbonate has been reported to be a promising method for preventing delayed diarrhea, a dose-limiting toxicity in patients receiving chemotherapy with irinotecan hydrochloride. However, it is feared that this method may adversely affect the pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that of its active metabolites. We compared the pharmacokinetics and toxicity of irinotecan with and without oral alkalization in a cross-over study that enrolled 10 colorectal cancer patients. We found that alkalization did not decrease the blood levels of irinotecan and its active metabolite. In fact, the area under concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with and without oral alkalization. Also, the AUC of SN-38 with alkalization was statistically equivalent or larger than that without alkalization. Oral alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and these adverse effects were not worsened by long-term administration. These results suggest that oral alkalization can control diarrhea and gastrointestinal toxicity without decreasing the blood levels of irinotecan and its active metabolites, thus improving the tolerability of long-term chemotherapy without reducing efficacy.

A 65-year-old man was referred to our hospital because of weight loss. Endoscopic examination and computed tomography (CT) revealed an advanced gastric cancer with multiple abdominal lymph node swellings. Distal partial gastrectomy was performed but lymph node resection was not done, since it was not thought to be curative. Adjuvant chemotherapy was performed for 4 courses with a regimen of ADM 20 mg/m2 day 1, CDDP 50 mg/m2 day 1, ETP 100 mg/day days 3-7, 5-FU 600 mg/m2 every other day on days 3-29. After 3 courses of ACVF therapy, the patient's serum CEA and SCC level normalized and the lymph node metastases became undetectable by CT scan. No severe side effects were observed at any time during the administration of these medications. In this case, serum SCC level was elevated even though histologic examination did not reveal squamous cell carcinoma but poorly differentiated adenocarcinoma. On immunohistochemical analysis, these tissues were stained diffusely with CEA, locally with AE1 + 3, and partially with PAS or Alcian blue. We speculate that this tumor could have developed the potency of SCC secretions without structural change into squamous metaplasia.