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Panton–Valentine leukocidine (PVL) is a distinctive virulence factor of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA), and arginine catabolic mobile element (ACME) is a staphylococcal genomic island that enhances fitness and the ability of bacterial cells to colonize on skin and mucous membranes. ACME is characteristically found in USA300, which is a predominant CA-MRSA clone [sequence type (ST) 8] in the USA and is spreading globally, and has also been detected in non-ST8 MRSA at low frequency. In Japan, spread of MRSA with PVL and/or ACME and their genetic traits have not yet been well characterized. In the present study, the prevalence and genetic diversity of PVL+/ACME+ MRSA were investigated for 422 MRSA clinical isolates collected from outpatients in northern Japan over a period of 1 year. All the isolates were genotyped for the staphylococcal cassette chromosome mec (SCCmec) and coagulase genes (coa), and screened for PVL and ACME genes. The PVL+/ACME+ isolates were studied further by genetic analysis, including single-nucleotide polymorphism (SNP) analysis based on PVL genes (lukS-PV-lukF-PV), ACME (arc and opp3 clusters) and the sarU promoter region. Among all the isolates examined, PVL genes and ACME were detected in eight (SCCmec-II, n = 1; SCCmec-IV, n = 6; SCCmec-V, n = 1) and 20 (SCCmec-II, n = 14; SCCmec-IV, n = 5; SCCmec-V, n = 1) isolates, respectively. Five isolates were found to have both PVL genes and ACME (type I), and were classified into ST8/spa-t008/agr-I/coa-IIIa, which is the same genetic traits as USA300. Fifteen PVL−/ACME+ isolates had type ΔII-ACME, belonging to either ST5 or ST764 [clonal complex (CC) 5], and spa-t001, -t002 or -t3557. All the ST8 PVL+/ACME-I+ MRSA had identical sequences of PVL genes (haplotype R) and ACME arc/opp3 clusters as those of USA300. In contrast, in the CC5 PVL−/ACME-ΔII+ MRSA, SNPs in the arc cluster were detected in 11 sites (four haplotypes), with some different profiles of virulence/resistance factors. These results indicated single clonality of ST8 PVL+/ACME-I+ MRSA and heterogeneity of CC5 PVL−/ACME-ΔII+ MRSA, and suggest their potential spread in northern Japan.

Background: Multidrug-resistant Escherichia coli, especially a lineage of O25b:H4-ST131, has increased and spread worldwide. The surveillance of cross-resistance of E. coli is necessary. Methods: Cross-resistance to fluoroquinolones (FQs) and aminoglycosides (AGs) was examined in E. coli isolated in Hokkaido Prefecture, Japan, between 2008 and 2009. Results: Gentamicin (GEN) resistance was more common in FQ-resistant isolates (30/112 strains; 26.8%) than in FQ-susceptible isolates (2/100 strains; 2%). The frequency of GEN resistance was similar in two groups of FQ-resistant strains, O25b:H4-ST131 genotype (22/87 strains; 25.3%) and a group of other FQ-resistant genotypes (8/25 strains; 32.0%). The main AG resistance gene was aac(3)-II (87.5% of GEN-resistant strains). The only amikacin-resistant strain which was FQ resistant carried the aac(6')-Ib-cr gene. CTX-M type extended-spectrum β-lactamase (ESBL) genes were also found in FQ-resistant strains at a high frequency. However, the number of strains with both ESBL and AG-modifying enzyme genes was relatively low (8 strains). Conclusion: All FQ-resistant strains, not only O25b:H4-ST131, appeared to preferentially acquire ESBL genes and/or genes encoding AG-modifying enzymes; however, the acquisitions of these genes seemed to occur independently.

Background: Fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-carrying multidrug-resistant Escherichia coli have become severely problematic. In particular, a lineage of multilocus sequence-type ST131 which belongs to O25:H4 and carries ESBL CTX-M-15 has spread worldwide. Methods: Fluoroquinolone-resistant E. coli strains were isolated from various clinical specimens in a commercial clinical laboratory in 2008 and 2009 in Hokkaido Prefecture, Japan. Results: Among 478 clinical isolates, 112 strains (23.4%) showed levofloxacin (LVX) resistance. About 80% of the fluoroquinolone-resistant strains (88 strains) showed common features, namely O25:H4-ST131, phylogenetic group B and the same mutation pattern in quinolone resistance-determining regions. Pulsed field gel electrophoresis patterns suggested numerous lineages of O25:H4-ST131. The fluoroquinolone-resistant strains, including strains of O25:H4-ST131 and other types, more frequently shared CTX-type ESBL genes than did fluoroquinolone-susceptible strains. The ESBL genes fell into the CTX-M-9 and CTX-M-2 groups. CTX-M-15 (CTX-M-1 group) was not found among any of the strains isolated in this study. Sitafloxacin showed markedly potent activity against E. coli isolates compared with LVX, ciprofloxacin and ulifloxacin. Conclusion: The most prevalent fluoroquinolone-resistant strains of E. coli isolated in Hokkaido Prefecture, Japan, are O25:H4-ST131. However, similar to other areas of Japan, the ST131 clones represent distinct lineages from the general worldwide dispersal of multidrug-resistant clones which carry CTX-M-15.

Prevalence and molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) were studied in Hokkaido, the main northern island of Japan. Among the 1,015 S. aureus isolates derived from clinical specimens of outpatients collected in 2009, methicillin resistance gene mecA was detected in 189 isolates (18.6%). The most frequent staphylococcal cassette chromosome mec (SCCmec) type in MRSA was II (83.1%), followed by IV (6.9%) and V (3.2%). MRSA with type II-SCCmec showed multiple drug resistance and harbored various toxin and virulence factor genes except for Panton-Valentine leucocidin (PVL) gene. These isolates were mostly classified into sequence type 5 (ST5) (or other STs in CC5) and coagulase genotype II and were thus genetically similar to hospital-acquired MRSA, which have been predominating in Japan (New York/Japan clone). PVL gene was detected in three MRSA strains belonging to ST6 (two strains) and ST59 (one strain), having type IVa- and Vt-SCCmec, respectively, and also in two methicillin-susceptible S. aureus ST121 and ST188. The arcA gene within the arginine catabolic mobile element (ACME) was detected in the two PVL-negative ST5 MRSA strains, which had type IIa- or V-SCCmec. The PVL gene-positive ST6 and ST59 CA-MRSA strains were susceptible to more antimicrobials and had less virulence factor genes than the PVL-negative ST5 MRSA, including the ACME-arcA-positive strains. In the present study, ST6 was identified as a lineage of PVL-positive CA-MRSA, the ACME-arcA was first detected in ST5 MRSA with type V-SCCmec, and ST59 Taiwanese CA-MRSA strain was isolated in Hokkaido for the first time. These findings suggest a potential spread of these emerging CA-MRSA clones in Japan.

Any increase in beta-lactam-resistant Haemophilus influenzae is a serious problem in respiratory and otolaryngology medicine. In this study, we examined the antibiotic susceptibility and genotype of 457 clinical Haemophilus influenzae strains isolated in Hokkaido Prefecture, Japan. Strains with beta-lactam-resistant mutations in gene encoding penicillin-binding protein 3 were more frequently found in lower respiratory tract specimens (sputa) than in upper respiratory tract specimens, such as rhinorrhea. The existence of the TEM-1 beta-lactamase gene occurred more frequently in adult patients than in pediatric patients. The results suggest that beta-lactam-resistant or nonsusceptible strains are more prevalent in adult patients with respiratory diseases. We observed only a very few strains which were nonsuscpetible to third-generation cephalosporins (CEPs) and carbapenems. However, 12%-13% of the strains were shown to be resistant to penicillins and second-generation CEPs, and approximately 4% of the strains were shown to be nonsusceptible to fourth-generation CEPs. In addition, we identified tetracycline-resistant (2.8%), chloramphenicol-resistant (0.6%), clarithromycin-resistant (2.6%), and fluoroquinolone-nonsusceptible (approximately 2%) H. influenzae strains.

Comparative fishing trials were undertaken with two commercial collapsible pots for the crab Charybdis japonica. One pot was box-shaped with two slit entrances at the ends, while the other was dome-shaped with two open funnel entrances. Pots were placed at the bottom of a pond that is connected to Kagoshima Bay. Fishing trials were carried out using a 1-day soaking time; the bait used was mackerel. The box-shaped pot had higher catches of crabs and non-target organisms, ***DIRECT SUPPORT *** A02OT006 00004 but the number of large crabs (carapace width \s>8 cm) was almost half as many as that caught with the dome-shaped pot. The catch of non-target species was also greatly reduced in the dome-shaped pot, and fish caught were mostly enmeshed in the netting. The reduction in catches of small crabs and non-target organisms was due to the nature of the dome-shaped pot’s larger mesh size and open entrances, which allowed for escape. The dome-shaped pot seemed more efficient for harvesting commercial size crabs, while the box-shaped pot seemed better for removing all crab sizes.

We examined the macrolide susceptibility and the presence of macrolide-resistance genes in 780 Streptococcus pneumoniae strains that were isolated and collected at trunk hospitals and commercial clinical laboratories in Hokkaido prefecture, Japan, between 1999 and 2003. Of the 780 strains, 57.0% and 49.6% were found to bear the macrolide-resistance genes erm(B) and mef(A), respectively, while 87.9% had either or both of these genes. The mef(A)-positive strains were more frequently found in patients who were younger than 10 years (43.4%) compared to patients who were 10 years or older (30.3%), whereas the erm(B)-positive strains were similarly frequent in both groups (57.2% vs 54.9%). Strains that were extremely resistant to erythromycin (≥256μg/ml) were frequently found in strains isolated at trunk hospitals but were rarely found in strains that had been collected at commercial clinical laboratories. In conclusion, the high frequency of emergence of macrolide resistance in S. pneumoniae strains was similar to reports from other areas of Japan and other east Asian countries. However, the distribution of resistant genes to macrolides and the distribution of the minimum inhibitory concertrations (MICs) differed depending on patients’ ages and depending on whether the strains were isolated at trunk hospitals or commercial clinical laboratories.

We identified and genetically characterized seven fluoroquinolone-resistant Streptococcus pneumoniae strains among 293 clinical strains isolated from 1999 to 2001 in Japan. The resistant strains were isolated only from adults, and 7 of 31 isolates (22.6%) were from patients more than 20 years old. Resistant strains were not found in 262 isolates from children under age 10.

Background. Neonatal tolerance is a very interesting phenomenon, because even allogeneic skin grafts are not rejected in these mice at the adult stage. However, the underlying mechanism remains unclear. Methods. In this study we prepared such tolerant C57BL/6 (B6) mice (H-2 b ) by the injection of allogeneic lymphocytes of BALB/c origin (H-2 d ) at the neonatal stage. Results. The total number of liver lymphocytes in these tolerant mice was found to increase when it was examined at the adult stage. Nevertheless, the retention of allogeneic lymphocytes that were injected at the neonatal stage was highest in the spleen. It is speculated that these allogeneic lymphocytes stimulate the hepatic immune system via the portal vein and that such stimulation maintains the tolerance phenomenon. Indeed, these tolerant mice showed elevated levels of IL-2Rβ + CD3 int cells (i.e., extrathymic T cells) and NK1.1 + CD3 int cells (i.e., NKT cells) in the liver. Even more interestingly, the number and proportion of CD8 + NKT cells, which are usually a minor population in normal mice, increased among NKT cells in the liver of tolerant mice. This became much more prominent when tolerant mice were grafted with allogeneic (H-2 d ) skin. Conclusion. In conjunction with additional data from a cell-transfer experiment and a splenectomy experiment, our results suggest that CD8 + NKT cells in the liver of tolerant mice might be intimately associated with the neonatal tolerance phenomenon.

Distribution of serotypes, prevalence of resistance to penicillin and/or erythromycin (EM), and its genetic traits were analyzed for a total of 1,061 noninvasive or colonization isolates of Streptococcus pneumoniae (998 and 61 isolates from children and adults, respectively) in Hokkaido, northern main island of Japan, in the year 2011, the pre-PCV7 routine immunization period. Serotype deduction was performed by sequential multiplex polymerase chain reaction (PCR), employing mutagenic PCR-restriction fragment length polymorphism for discrimination of 6A/C and 6B/D. Unaltered three PBP genes and macrolide resistance genes erm(B) and mef(A/E) were detected by multiplex PCR. Among isolates from children, 25 serotypes, including the prevalent types 6B (17.5%), 19F (15.6%), 23F (12.2%), and 6C (11.6%), were identified, revealing the PCV7 and PCV13 coverage rates as 48.2% and 60.3%, respectively, while serotype 3 was the most frequent (19.0%) among isolates from adults. Most of the pediatric isolates (96.8%) exhibited resistance to EM (minimum inhibitory concentration [MIC], ≥1 μg/ml), with a higher prevalence of erm(B) (67.2%) than mef(A/E) (39.7%). erm(B) was associated with high-level EM resistance (MIC, ≥128 μg/ml) and distributed at high detection rates to major serotypes 23F (85.2%) and 6B (85.1%), as well as minor serotypes 3, 10A, 14, 15B, 15C, 19A, and 23A (90%). While penicillin-resistant S. pneumoniae (PRSP) (penicillin G-MIC, 2-3 μg/ml) was detected in 7.8% of isolates from children, the most common PBP gene genotype was gPRSP (three altered genes pbp1a, 2x, and 2b; 38.3%), which was detected at higher rates (60%) in the dominant serotypes 23F, 6B, and 19F, and minor serotypes 6D and 15A. Dominant serotypes in the S. pneumoniae isolates were generally similar to those reported for invasive strains, despite lower coverage rates by PCV7/13. The importance of further surveillance on incidence and drug resistance in the post-PCV7 period was suggested for non-PCV7/13 serotypes 6C, 6D, 10A, 15A, 15B, 15C, 23A, and 35B.

Multidrug-resistant Escherichia coli, especially a lineage of O25b:H4-ST131, has increased and spread worldwide. The surveillance of cross-resistance of E. coli is necessary.Cross-resistance to fluoroquinolones (FQs) and aminoglycosides (AGs) was examined in E. coli isolated in Hokkaido Prefecture, Japan, between 2008 and 2009.Gentamicin (GEN) resistance was more common in FQ-resistant isolates (30/112 strains; 26.8%) than in FQ-susceptible isolates (2/100 strains; 2%). The frequency of GEN resistance was similar in two groups of FQ-resistant strains, O25b:H4-ST131 genotype (22/87 strains; 25.3%) and a group of other FQ-resistant genotypes (8/25 strains; 32.0%). The main AG resistance gene was aac(3)-II (87.5% of GEN-resistant strains). The only amikacin-resistant strain which was FQ resistant carried the aac(6')-Ib-cr gene. CTX-M type extended-spectrum β-lactamase (ESBL) genes were also found in FQ-resistant strains at a high frequency. However, the number of strains with both ESBL and AG-modifying enzyme genes was relatively low (8 strains).All FQ-resistant strains, not only O25b:H4-ST131, appeared to preferentially acquire ESBL genes and/or genes encoding AG-modifying enzymes; however, the acquisitions of these genes seemed to occur independently.

Objective: the purpose of this study was to clarify the prognosis of resected non-small cell lung cancer (NSCLC) patients with carcinomatous pleuritis of minimal disease which might be considered as the next advanced stage of positive pleural lavage cytology. Method: the data were collected from a questionnaire survey on the survival of the patients with carcinomatous pleuritis found at thoracotomy from 1985 to December 1994 which was conducted by the Japan Clinical Oncology Group (JCOG). Results: out of 227 patients with carcinomatous pleuritis found at thoracotomy who had available information on a survival, 100 patients who underwent a resection of the primary tumor had carcinomatous pleuritis of minimal disease defined based on the criteria of the Japan Lung Cancer Society. The mean malignant fluid volume (±S.E.) was 37.1 (6.3) ml and the mean number of pleural disseminated nodules was 5.6 (0.9). A lobectomy was performed in 79 patients, a pneumonectomy in 11 and a limited resection in ten. The 3- and 5-year survival rates were 31.8 and 22.8%, respectively. Conclusions: the prognosis of resected NSCLC patients with carcinomatous pleuritis of minimal disease was unexpectedly good. This indicates that no fine line may exist between positive pleural lavage cytology findings and the aforementioned lesion.

Non-small cell lung cancer with carcinomatous pleuritis is considered to be a contraindication of surgical resection. The objective of this study was to clarify the prognosis of patients with non-small cell lung cancer in whom carcinomatous pleuritis was found at thoracotomy. A questionnaire survey on the survival of patients with carcinomatous pleuritis found at thoracotomy between January 1985 and December 1994 was conducted by the Japan Clinical Oncology Group. According to the data collected from 21 hospitals, 8813 patients with non-small cell lung cancer underwent thoracotomy, 284 (3.2%) of whom were found to have carcinomatous pleuritis. Information on survival was available for 227 of these patients, 34 (15%) of whom underwent thoracotomy alone without resection, whereas 193 (85%) underwent surgical resection. Of the 193 resected patients, 155 had no macroscopical residual tumor apart from the carcinomatous pleuritis. The 5-year survival rate was 14%. According to a univariate analysis, female sex, the presence of adenocarcinoma, a tumor size of less than 3.0 cm, no clinical lymph node metastasis, and no macroscopical residual tumor had a significantly favorable impact on survival. A multivariate analysis revealed that the extent of clinical lymph node metastasis (P = 0.006), histology (P = 0.028), and the absence or presence of a macroscopic residual tumor after the operation (P = 0.045) were predominant prognostic factors. The 5-year survival rate of 83 patients with three positive variables was 24%. The prognosis of patients with adenocarcinoma found to have carcinomatous pleuritis at thoracotomy was not necessarily unfavorable if there was no clinically detected lymph node metastasis and no residual tumor apart from the carcinomatous pleuritis.

小細胞肺癌91切除症例をretrospectiveに解析し, その治療成績から外科治療の適応と早期症例に対する化学療法の必要性について検討した.3年生存率・5年生存率はそれぞれ, overallで40.8%・34.0%, 臨床病期別に c-stage I53.5%・45.6%, c-stage II19.2%・19.2%, c-stage IIIA 12.5%・0%, 病理病期別に p-stage I 55.8%・47.0%, p-stage II 50.0%・50.0%, p-stage IIIA 4.5%・0%であった.また, p-stageI-IIの絶対的または相対的治癒切除例では, 化学療法を施行した症例の3年・5年生存率は61.4%・57.0%で, 施行しなかった症例の14.8%・14.8%に比し予後良好で, 4コース以上の化学療法を施行した症例の3年・5年生存率は87.5%であった.これらの結果から, 小細胞肺癌に対する手術適応はc-stage Iまたはp-stage I-IIまでの症例にあると考えられ, これらの症例に対しても周術期に4コース以上の化学療法が必要と思われる.

気管分岐部形成術は吻合部の合併症が高率に発生すると報告されている.今回, 吻合部にかかる過剰な張力と変形を避けることで, これらの合併症の予防を試みた.Grillo の方法による気管分岐部形成術では吻合部狭窄や縫合不全はしばしば気管気管支端側吻合部に発生する.そこで吻合部の狭い範囲に張力がかからないように, 結節縫合の代わりに連続縫合を行った.気管分岐部楔状切除術では口径を一致させるために膜様部を縫縮すると合併症が生じやすい.このため気管軟骨部を襖状に切除し口径を縮めた.更に両症例とも気管と気管支の吻合にテレスコープ縫合を行った.手術後の気管支鏡所見では吻合部の肉芽増生, 狭窄, 縫合不全等の問題はみられなかった.

1986年から1995年の間に国立療養所肺癌研究会所属施設で経験した胸腺癌は38例であった.このうち症例数の多い扁平上皮癌22例と未分化癌7例を対象として, その治療内容と予後との関連についてretrospectiveに検討した.胸腺腫に対する正岡の臨床病期分類にあてはめると, 扁平上皮癌では1期1例, II期6例, III期7例, IVa期3例, IVb期5例で, 未分化癌では, III期3例, IVa期1例, IVb期3例であった.中間解析での組織型別の5年生存率は, 扁平上皮癌が52%, 未分化癌が35%であった.1, II期の症例は手術を先行し, 術後に放射線治療を追加することで良好な予後が期待できると考えられた.III期以上の症例に対しては, 術前に放射線と化学療法の同時併用によるinduction therapyを行い, その後に手術を行う方が治療成績の向上に貢献する可能性が示唆された.

気管支形成術では一般にテレスコープ吻合を避けて気管支断端の軟骨輪を一致させる縫合が行われている.しかし気管支断端は口径差があるために軟骨輪間に縫合糸をかけると自然に1軟骨輪が重なるテレスコープ吻合となる.我々は1991年以降の形成術症例29例中14例の気管支形成症例に積極的にこのテレスコープ吻合を行ってきた.組織型は扁平上皮癌6, 腺癌4, カルチノイド2, 腺様嚢胞癌1, 神経線維腫1でこの内5例に術前放射線化学療法が施行された.気管支形成術の6術型が行われ, 気管支吻合部に肉芽増生, 狭窄, 縫合不全を認めなかった.主要な術後合併症として膿胸2, 乳び胸1がみられたが保存的あるいは手術的治療で軽快した.テレスコープ吻合はこれまでの吻合法に劣らず安全であり, 気管支形成術の術式の1つになりうると考えられた.

43歳男性.右上葉原発の腺癌が主気管支から気管へ3軟骨輪, 左主気管支へ2軟骨輪連続性に浸潤していた.右肺動脈と食道浸潤も疑われた.c-T4N2MO-IIIBと診断し, 局所制御を目的として化学療法 (CDDP+VDS) を3クール, 原発巣から縦隔に対しLinac26Gyを同時併用とする術前治療を行なった.腫瘍は著しく縮小し, 治癒切除可能と判断され手術を施行した.気管から左主気管支まで3軟骨輪切除し右管状肺摘除術とR2b郭清を行なった.左房, 上大静脈, 食道筋層の部分切除を要した.再建は気管と左主気管支の端々吻合を行なった.術後吻合部に軽度の肉芽形成をみたが, 重篤な合併症はなかった.摘出標本の検索では治癒切除であり, 術後病期はyp-T2NIMO-IIであった.術後1年6ヵ月に食道に再発し, 放射線化学療法により軽快したが, 治療開始後3年4ヵ月, 術後2年10ヵ月に原病死した.

A 79-year-old man with prostatic hypertrophy was performed trans-ureteral resection of prostate, and the transfusion of red cell concentrates stored in mannitol-adeninne-phosphate solution (RC-MAP) was required because of massive postoperative bleeding, despite of preparation for the autologous blood transfusion. On postoperative day 7 high fever developed, followed by widespread erythema, liver dysfunction, watery diarrhea and pancytopenia. Skin biopsy findings showed typical changes of transfusion associated graft-versus-host disease (TA-GVHD). Despite intensive treatment with methylpredonisolone, cyclosporine A, colony-stimulating factor and other supportive therapy, he died day 31 after surgery. The containing of foreign DNA fragments in his blood was detected by the analysis of microsatellite DNA polymorphism of his finger nail and peripheral blood.We emphasize that the transfusion of RC-MAP can cause TA-GVHD though the contaminated lymphocyte of RC-MAP is markedly reduced compared with the ordinary packed red cells.

In order to clarify the relation between cigarette smoking and lung cancer, a case-control study was conducted. The case series consisted of 1,376 lung cancer patients (1,082 males and 294 females) who were newly diagnosed and admitted to eight hospitals in Osaka during 1986-88. Smoking histories were compared with those of 2,230 controls (1,141 males and 1,089 females) admitted to the same hospitals during the same period without established smoking-related diseases. Odds ratios of current smoker versus nonsmoker were 18.1, 1.9, 21.4, and 3.8 for squamous, adeno, small, and large cell carcinoma, respectively, for males, and 9.7, 1.3, 12.1, 3.7, respectively, for females. Compared to the results from previous studies in Japan, the magnitude of the odds ratios for squamous and small cell carcinoma is approaching the level of Western Europe in the late 1970s. Population attributable risk of exsmokers has also been increasing to the level of Western Europe. Among male current smokers, smoking intensity, such as number of cigarettes per day or fraction smoked per cigarette, seemed to have a slightly greater influence on squamous cell carcinoma than adenocarcinoma, while factors associated with the spread of cigarette smoke, such as inhalation, seemed to have greater influence on adenocarcinoma. The difference in the distribution of these smoking characteristics between Japan and Western Europe could not fully explain the difference in lung cancer incidence and distribution of histologic types between the two areas.

針生検痕への播種をきたした脂肪肉腫胸壁転移の一例を経験した. 症例は70歳女性で, 8年前に後腹膜原発脂肪肉腫の摘出術を受けている. 右胸壁から胸腔内に突出する胸壁腫瘍に対し, 18G注射針および19G相当の千葉大生検針を用いて針生検を施行したが, 軟部腫瘍という以上の限定はできなかった. 摘出術後の病理診断は粘液型脂肪肉腫であり, 後腹膜からの転移と判明した. 手術の8ヵ月後, 針生検痕に沿って皮下・肋間筋内・肺内に局所再発を認め, 右上葉部分切除術・胸壁切除術を施行した. 再手術後1年4ヵ月の現在再々発を認めていない. 針生検痕への播種は肺癌からのものが多いが, 諸家の報告ではその発生率は概ね1%以下である. 脂肪肉腫においては, 今回我々が検索した限りでは, 針生検痕播種の報告例は認められなかった. この合併症の予防のためには, 術前に確定診断された場合は針生検痕も含めて摘出することが必要と思われた.

Fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-carrying multidrug-resistant Escherichia coli have become severely problematic. In particular, a lineage of multilocus sequence-type ST131 which belongs to O25:H4 and carries ESBL CTX-M-15 has spread worldwide.Fluoroquinolone-resistant E. coli strains were isolated from various clinical specimens in a commercial clinical laboratory in 2008 and 2009 in Hokkaido Prefecture, Japan.Among 478 clinical isolates, 112 strains (23.4%) showed levofloxacin (LVX) resistance. About 80% of the fluoroquinolone-resistant strains (88 strains) showed common features, namely O25:H4-ST131, phylogenetic group B and the same mutation pattern in quinolone resistance-determining regions. Pulsed field gel electrophoresis patterns suggested numerous lineages of O25:H4-ST131. The fluoroquinolone-resistant strains, including strains of O25:H4-ST131 and other types, more frequently shared CTX-type ESBL genes than did fluoroquinolone-susceptible strains. The ESBL genes fell into the CTX-M-9 and CTX-M-2 groups. CTX-M-15 (CTX-M-1 group) was not found among any of the strains isolated in this study. Sitafloxacin showed markedly potent activity against E. coli isolates compared with LVX, ciprofloxacin and ulifloxacin.The most prevalent fluoroquinolone-resistant strains of E. coli isolated in Hokkaido Prefecture, Japan, are O25:H4-ST131. However, similar to other areas of Japan, the ST131 clones represent distinct lineages from the general worldwide dispersal of multidrug-resistant clones which carry CTX-M-15.

症例は57歳男性で, 右下肺野の腫瘤陰影は4年8カ月前より存在し, その間2回の気管支鏡下擦過細胞診で悪性所見なく, 当科で行った気管支鏡検査でも診断を得ないまま, 右下葉切除を施行した. 術中穿刺細胞診では異型性に乏しく刷子縁様構造, 線毛様構造を認めたが, 細胞は大型で核の不同, 切れ込みを有するため, 高分化乳頭型腺癌と判断した. 病理病期は, pT2N0M0であった.この症例は, 刷子縁様構造や線毛様構造という腺癌としては稀な細胞像を有しており, 良性・悪性を判断する場合注意を要すると思われた. また, 肺腺癌の亜型分類によれば気管支上皮細胞型と考えられるが, 緩徐な経過と切除リンパ節に転移のなかったことは, この組織亜型の腺癌の悪性度を考える上で興味深いと思われた.

The cellular uptake of D-aspartic acid (D-Asp) as a model compound for glutamic acid transport was studied in rat hippocampal slices. D-Asp is accumulated by both Na(+)-dependent and Na(+)-independent processes in hippocampal slices, and both processes are dependent on temperature. The Na(+)-dependent uptake is assumed to be high in affinity (apparent Km = 0.17 mM), but low in capacity, whereas the Na(+)-independent uptake is much lower in affinity (Km = 2.86 mM), but higher in capacity. L-Aspartic acid, L-glutamic acid, dihydrokainic acid, and threo-3-hydroxy-DL-aspartic acid markedly inhibited the uptake of D-Asp with Na+ in the medium, whereas D-glutamic acid, glycine, and L-lysine had no significant effect. The Na(+)-dependent uptake of D-Asp was significantly reduced under "hypoglycemic," "anoxic," and "ischemic" conditions, whereas the Na(+)-independent uptake was unaffected. Metabolic inhibitors such as NaCN and ICH2COOH significantly inhibited the Na(+)-dependent uptake, but not the Na(+)-independent uptake. These results suggest that the Na(+)-dependent component of D-Asp transport in rat hippocampal cells is inactivated under ischemic conditions, whereas the Na(+)-independent component is unaffected.

Seven cases of intestinal tuberculosis diagnosed after laparotomy were analyzed. All cases were accompanied by perforation or obstruction of the small intestine. Four of them had active pulmonary tuberculosis. All cases were recieving antituberculosis therapy from preoperative period. Histological examination of the intestine revealed a tuberculose nodule in only two cases. Detection of the causative bacteria could be achieved also in only one case. On the other hand, his tological examination of the mesenteric lymph node offered available information in 5 cases. In the diagnosis of small intestinal tuberculosis, we should be careful not to enmeshed in histological findings of the lesion which might lead to misdiagnosis. Global consideration based on histological findings of the mesenteric lymph node, intraoperative findings and reactivity to the antibiotics would make a correct diangosis. For the intestinal tubercdulosis medical therapy is the first choice and surgical therapy should be done to the patients associating with some complications such as perforation and obstruction.

A 64-year-old male developed intussusception due to jejunal metastasis from lung cancer which was operated on 4 months earlier, and a jejunal resection was performed. After the laparotomy, the patient was able to perform oral intake. But he died of brain metastasis on the 31st day. Forty-two cases which underwent laparotomy for small bowel metastases from the lung cancer have been reported in Japan. The survival period following laparotomy was at the longest of 12 months and about 80% of the patients died within 6 months. Although lung cancer metastases to the small bowel indicate a poor prognosis, surgical therapy is necessary for gaining better quality of life.

歳の女性.1989年9月より咳漱, 喀痰が出現し, 11月13日近医を受診した.胸部X線検査で右下葉に7.0×4.0cmの鏡面像を伴った空洞陰影と, その周囲に多発性の小空洞陰影を認め1990年1月5日, 当院へ入院した.気管支鏡検査等を施行したが悪性腫瘍との診断は得られず, なんらかの感染により鏡面像と散布巣を形成した気管支性嚢胞と診断し, 1990年1月25日, 右下葉切除術を施行した。病理組織診断は細気管支肺胞上皮癌であった.また胃癌を合併していたため, 1カ月後に胃切除術を行った.病理組織所見は低分化腺癌, 深達度は固有筋層内で, リンパ節転移はなかった.原発性肺癌の中で多発性空洞陰影を呈する症例は, 本邦では文献上8例のみで, そのうちの6例が細気管支肺胞上皮癌であった.それら6例は診断時には既に病巣が両側肺に存在し, 外科的治療は施行されなかった.本例は病巣が一葉に限局し多発性空洞を形成したため, きわめて特異な画像を呈した.

非小細胞肺癌に対する術後化学療法の有効性を多施設共同無作為法で実施, 検討した. 1982年6月から1988年4月まで術後に無作為法で組織別 (腺癌: 206例, 扁平上皮癌: 205例), 病期別 (JJC 1978) に術後化学療法群 (T群) と対照群 (C群) とに割付け実施した.腺癌のT群にはI期はTegafur, II, III期はdoxorubicin (ADR) + mitomycin C (MMC) +Tegafur, 扁平上皮癌のT群にはI期はTegafur, II期はcisplatin (CDDP) + Tegafur, III期はCDDP+Tegafur+放射線治療を行った.C群には化学療法は行わず, ただし扁平上皮癌のIII期には放射線治療を行った.腺癌および扁平上皮癌についてみると, T群とC群との間には生存率, 健存率に統計学的有意差はなかった.

Lung cancer risk among exsmokers according to years since cessation of smoking was assessed by means of a case-control study. The case series consisted of 1,052 lung cancer patients who were newly diagnosed and admitted to eight hospitals in Osaka in 1986-88. Smoking histories were compared with those of 1,111 controls admitted to the same hospitals during the same period without any diagnosis of smoking-related disease. The odds ratio of lung cancer for exsmokers compared to current smokers was estimated to be 0.90, 0.50, 0.51, 0.59, 0.48 and 0.29, for 1-4, 5-9, 10-14, 15-19, 20-24 and greater than or equal to 25 years after cessation of smoking, respectively. Risk reduction appeared to be greater for those who smoked less than the 1200 cigarette index, compared to those who smoked more. In classification according to histologic type, small cell and large cell carcinoma showed a rapid decrease compared to adenocarcinoma, while squamous cell carcinoma showed an intermediate pattern. Quantitative estimates for reduction of lung cancer risk among exsmokers can be used for projecting lung cancer incidence in the future, by assuming future trends of smoking prevalence, as well as for health education among individual smokers.

症例は, 初診時59歳の男性で, 1984年より5年8ヵ月の経過中に3度の原発性肺癌を発症した.第1癌は, 右S2の扁平上皮癌, T2N1aM0, Stage IIで, 1984年10月右上葉切除術を施行した.第2癌は, 左S1+2の扁平上皮癌, TIN1aM0, Stage IIで, 1985年6月, 左上葉切除術を施行した.第3癌は, 右S6の早期扁平上皮癌, TIN0M0, Stage Iで, 1989年4月, 術前の術後残存肺機能の予測値より右S6区域切除術を施行し, 術後放射線療法を併用した.1990年12月現在, 健存中である.原発性肺癌に対して, 多発癌を考慮にいれた注意深い診断と術後の経過観察の必要性がある.多発癌の治療としては, 残存肺機能の問題もあるが, Limited operationを含めた積極的な外科治療が第一と考える.

Neonatal tolerance is a very interesting phenomenon, because even allogeneic skin grafts are not rejected in these mice at the adult stage. However, the underlying mechanism remains unclear.In this study we prepared such tolerant C57BL/6 (B6) mice (H-2b) by the injection of allogeneic lymphocytes of BALB/c origin (H-2d) at the neonatal stage.The total number of liver lymphocytes in these tolerant mice was found to increase when it was examined at the adult stage. Nevertheless, the retention of allogeneic lymphocytes that were injected at the neonatal stage was highest in the spleen. It is speculated that these allogeneic lymphocytes stimulate the hepatic immune system via the portal vein and that such stimulation maintains the tolerance phenomenon. Indeed, these tolerant mice showed elevated levels of IL-2R beta+ CD3int cells (i.e., extrathymic T cells) and NK1.1+ CD3int cells (i.e., NKT cells) in the liver. Even more interestingly, the number and proportion of CD8+ NKT cells, which are usually a minor population in normal mice, increased among NKT cells in the liver of tolerant mice. This became much more prominent when tolerant mice were grafted with allogeneic (H-2d) skin.In conjunction with additional data from a cell-transfer experiment and a splenectomy experiment, our results suggest that CD8+ NKT cells in the liver of tolerant mice might be intimately associated with the neonatal tolerance phenomenon.

✓ Paraplegia secondary to pulmonary surgery occurred in two patients because of epidural migration of hemostatic agents. Computerized tomography following myelography revealed the lesion clearly. Both patients achieved satisfactory neurological recovery through prompt diagnosis and treatment.

The acoustic impedance distribution of functionally gradient materials (FGM) in which the impedance change gradually along a certain direction is to be reconstructed. Based on the formulation by Howard, the impedance of Al–SiC structured FGM is successfully reconstructed by measuring the acoustic reflection impulse response, and compared with the SAW velocity, show a good correspondence between the two quantities. Ni–ZrO2 structured FGM is also examined as a direct scattering problem.

Lung cancer incidence rate after the cessation of smoking was assessed for male ex-smokers according to the age at cessation, using the results from a case-control study for ex-smoker versus continuing smoker, and the lung cancer incidence rate function for continuing smoker estimated from Japan Vital Statistics and the "Six-prefectural Cohort Study" in Japan. This hospital-based case-control study consisted of 776 lung cancer cases (553 current smokers and 223 ex-smokers) and 772 controls (490 current smokers and 282 ex-smokers) who started smoking at ages 18-22. The odds ratio of developing lung cancer for ex-smokers compared to continuing smokers according to years since the cessation of smoking was estimated for four age groups (55-64, 60-69, 65-74 and 70-79). Given that the number of years since cessation of smoking is the same, reduction of the odds ratio appeared to be greater for the younger age group than for the older age group, reflecting the shorter period of exposure for the younger age group. Lung cancer incidence rate (per 100,000) was assumed to be expressed by the following function; 1.7 x 10(-5) x (age -24.3) for continuing smokers and 0.15 x 10(-5) x (age) for nonsmokers. Lung cancer incidence rate among ex-smokers according to years since cessation was then estimated to be the above function multiplied by the odds ratio from the case-control study for each age group. In contrast to the greater reduction of the odds ratio among younger ex-smokers, reduction of the incidence rate, in terms of rate difference, was considerably greater for older ex-smokers due to a high incidence rate of lung cancer for older continuing smokers. This indicates that the absolute magnitude of reduction of the lung cancer incidence rate after cessation of smoking is greater for older ex-smokers, although the relative magnitude of reduction is greater for younger ex-smokers.

We evaluated the sensitivity of CT for detecting mediastinal lymph node metastases in patients with nonsmall cell bronchogenic carcinoma. Computed tomography of 208 cases of surgically proven bronchogenic carcinoma from three institutes was evaluated retrospectively using specific diagnostic criteria. These consisted of two size thresholds for specific mediastinal node regions: 13 mm short transverse diameter for nodes in the subcarinal, precarinal, and tracheobronchial regions and 10 mm for other regions. Based on these criteria, the overall sensitivity of CT was 69%, specificity 94%, and accuracy 86% for detection of metastasis. In cases of adenocarcinoma, sensitivity was 61%, specificity 93%, and accuracy 81%, and in those of squamous cell carcinoma the respective values were 86, 94, and 92%. Comparison between the results using the present criteria with the former criterion of 10 mm short transverse diameter for all mediastinal nodes revealed that the number of false-positive cases decreased markedly. We conclude that more accurate CT evaluation of mediastinal lymph node metastasis in nonsmall cell bronchogenic carcinoma can be achieved with specific size criteria for specific mediastinal regions.

Three groups of a total of 26 puppies were subjected to surface-induced hypothermia with or without limited left-heart bypass to seek recovery after 2.5-hr total circulatory arrest. In spite of various protective measures, surface-induced hypothermia which was carried out until the effective circulation ceased, failed to protect the animal from 2.5-hr circulatory arrest. With a combination of limited leftheart bypass, the central nervous tissue tolerated the procedure better than expected. Metabolic derangements, although severe immediately after the procedure, were reversible. Respiratory distress was a serious problem, which was considerably alleviated in the 3rd group of 10 puppies by perfusion of the lung with a solution approximating the intracellular electrolyte composition. Six puppies of this group survived the procedure, 5 without any persistent disorders. These results indicate the possibility of 2.5-hr hypothermie circulatory arrest.

66歳女性.1984年某病院で左下葉S6に異常陰影を指摘され, 結核腫として治療されたが増大傾向あり.当院に1986年8月入院気管支鏡で左B6に腫瘍を認め, 粘液癌と診断.既往歴に1963年乳癌根治術あり.両者が同一の粘液癌であることから乳癌肺転移が考えられた.一側肺単発で他に遠隔転移がないため, 9月11日左下葉・気管支管状切除を施行した.乳癌根治術24年後に肺転移を診断し切除した症例は極めて稀である.

The single-stage omental pedicle flap closure method was successful in three out of eight patients with chronic empyema between September 1987 and August 1988. In this procedure, an omental pedicle flap, supplied by the right gastroepiploic artery, is made and transposed into the cureted and irrigated empyema space by fixing it to the bronchopleural fistula. Thoracoplasty is added if a residual dead space is present.The omental pedicle flap nourished by the right gastroepiploic artery is large enough and long enough to reach all areas in the thoracic cavity in most persons.The omentum has angiogenesis, immunological competence and absorptive capacity and is effective in the treatment of chronic empyema with bronchopleural fistula.

Morphological features of modified and unmodified bilateral lung allografts were studied in 87 dogs. Immunosuppressive treatment consisted of various combinations of azathioprine, methotrexate, prednisolone, methylprednisolone and antilymphocyte serum. The classic acute rejection was observed in the unmodified dogs, which died between 4 and 9 days. Progression of the lesion was confined to a certain stage in these lung allografts charged with providing total pulmonary function, so that hemorrhagic necrosis was never encountered. Immunosuppressive drugs decrease the speed and intensity of classic rejection, and increase the complications of respiratory infection in the protracted course. Of 14 dogs surviving more than 14 days, 4 died of chronic rejection at 72, 84, 177, and 396 days after transplantation. Death of the remaining animals was attributed to acute rejection (3 dogs); severe anemia (3 dogs); pulmonary infection and sepsis (3 dogs); and arterial thromboembolism (1 dog). In these long-functioning lung allografts, the alveolar lining cells were frequently replaced by very atypical cells presumed to be type 2 pneumocytes. The bronchus was occluded by mucus plugs, and the alveolar surface was covered with hyaline membrane, or obliterated by organized fibrocellular precipitate. The alveolar walls and perivascular area were thickened by fibrosis. Obliterative intimal thickening of pulmonary arteries was not observed. Although the immunologic and non-immunologic mechanisms responsible for the development of these lesions are difficult to separate, these cumulative changes apparently accompany the deterioration of the vital function of the graft until ultimate death.

To clarify the organ specific nature of hyperacute rejection, 14 puppies were presensitized by multiple skin grafts and spleen cell injections prior to receiving either a heart or kidney allograft from the respective donors. Of this group, 7 received orthotopic heart allografts and 7 received kidney allografts. All heart allografts were rejected between 3 and 28 hours, and all kidneys between 0 and 24 hours as judged by cessation of urine flow from the ureterostomies. In contrast, all 11 animals in a recent series of heart allografts in non-sensitized puppies survived the operation, and rejected between 7 and 17 days. There was a significant correlation in both groups between preoperative cytotoxic antibody titer in the recipient serum and graft survival time. The preoperative titers were all above 1:1,024 but were greatly reduced within 2 hours after transplantation. At the time of rejection, antibody could be eluted from the rejected organs. In contrast to the kidneys, in which 2 of 7 grafts ceased to function immediately after revascularization, all hearts resumed beating and functioned well for at least several hours. At autopsy, the myocardium was pale and edematous and histologically polymorphonuclear leukocytes were prevalent in and around the small vessels and among myofibers. Both IgG and IgM antibody was detected in sarcolemma of the myocardium and to a lesser extent in the intima and adventitia of the small vessels by the fluorescent antibody technique. Biopsies of the rejected kidneys showed polymorphonuclear leukocyte infiltration, typical of hyperacute rejection. Marked fluorescence of IgG and IgM in the glomeruli and peritubular capillaries was observed. This study indicates that both organs rejected hyperacutely in our experimental model and participation of the preformed antibody in effecting this change was strongly suggested.

J Thorac Cardiovasc Surg 1999;117:618-9