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There is no proven medical therapy to inhibit the progression of abdominal aortic aneurysm (AAA) in the clinical setting. To develop a novel therapeutic approach for the treatment of AAA, we focused on vaccination targeting Ang II (angiotensin II) and assessed the effect of an Ang II peptide vaccine on the progression of AAA using a rat model. Ang II peptide was conjugated with KLH (keyhole limpet hemocyanin) carrier protein to induce a sufficient immune response. Male rats were subcutaneously immunized with Ang II–KLH with an adjuvant on days 0, 14, and 28. Aortic dilatation was induced by intraluminal incubation with elastase on day 35. Treatment with Ang II vaccine successfully induced the production of a high titer of anti-Ang II antibodies. Immunization with Ang II vaccine resulted in a significant reduction in expansion of the aortic diameter compared with control rats, without a blood pressure–lowering effect. Four weeks after operation, the increase in Ang II in the aneurysm wall was significantly inhibited by treatment with Ang II vaccine. Inhibition of Ang II action led to suppression of the inflammatory response in the AAA wall through attenuation of the NFκB (nuclear factor kappa B) and c-jun N-terminal kinase signaling cascades. Treatment with Ang II vaccine inhibited accumulation of macrophages in the AAA wall. In addition, expression of TNF-α (tumor necrosis factor alpha) and activation of MMP (matrix metalloproteinase)-2 and MMP-9 were also inhibited by treatment with Ang II vaccine, resulting in protection against the destruction of elastic fibers. This vaccine therapy could become a potent therapeutic option to treat patients with AAA.

Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.

Introduction: New treatments to inhibit neointimal formation after percutaneous transluminal angioplasty (PTA) are needed for patients undergoing chronic hemodialysis (HD). We compared the efficacy and safety of AMG0102, a balloon catheter containing nuclear factor κB (NF-κB) decoy oligodeoxynucleotide (ODN) with the PTA balloon catheter (control group) for arteriovenous fistula (AVF) stenosis. Methods: In total, 175 patients (age ≥20 years, undergoing HD, with venous stenosis at the anastomotic region) were registered in this prospective open-label, randomized study. Patients were followed postoperatively for 36 weeks. The duration of primary patency on the targeted venous stenosis site (primary endpoint) was estimated by the Kaplan–Meier method. Results: A lower restenosis risk was observed for the AMG0102 group, but it was not statistically significant (stratified log-rank test P = 0.250, hazard ratio [HR] 0.774; 95% confidence interval [CI]: 0.500–1.198). The median duration of primary patency was 245 days and 172 days in the AMG0102 and control groups, respectively. After stratification based on the status of diabetes complications, the HR was 0.666 (95% CI: 0.366–1.212; P = 0.183) and the median duration of primary patency was prolonged by 108 days in the AMG0102 group with diabetes complications (245 days) compared with the control group (137 days). Adverse event (AE) incidence up to 36 postoperative weeks did not differ between groups. Four device failures occurred in 3 patients (AMG0102 group), but none resulted in AEs. Conclusion: Further modifications to enhance NF-κB decoy ODN uptake and efficacy are necessary to show its clinical utility for AVF stenosis in chronic HD. Keywords: arteriovenous fistula stenosis, balloon catheter, diabetes, hemodialysis, nuclear factor κB, percutaneous transluminal angioplasty

Angiotensin II is thought to participate in aneurysm formation, because of its ability to induce and perpetuate inflammation in the aortic wall. Because activation of renin is the first step of the renin–angiotensin system, renin inhibition could inhibit all components of this system effectively. Therefore, we examined the hypothesis that direct inhibition of renin activity could decrease the expansion of aortic aneurysm using a rabbit model. Aortic dilatation was induced by incubation with elastase around the rabbit abdominal aorta. Continuous administration of a direct renin inhibitor, aliskiren, was started at 1 week before incubation with elastase and continued for 5 weeks. Treatment with aliskiren markedly inhibited tissue renin activation and resulted in a significant reduction in angiotensin I and II production in the aneurysm wall. Consequently, the inhibition of renin activity prevented the expansion of experimental aortic aneurysm associated with preservation of the medial layer, independent of its blood pressure–lowering effect. Administration of aliskiren led to the inhibition of activation of NF-κB (nuclear factor-κB), AP-1 (activator protein-1), and CREB (cAMP response element–binding protein), which are thought to cooperatively regulate the inflammatory gene expression profile associated with aneurysm formation. As a result, treatment with aliskiren inhibited macrophage accumulation through suppression of MCP-1 (monocyte chemoattractant protein-1) and CCL4 (C-C motif chemokine ligand 4) expression, and TNF-α (tumor necrosis factor-α) production and activation of MMP-2 (matrix metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9) were also suppressed in the aneurysm wall. In addition, inhibition of (pro)renin receptor elevation was also observed after treatment with aliskiren. Direct inhibition of renin activity using aliskiren prevented the progression of aortic aneurysm, suggesting it as a therapeutic option to treat abdominal aortic aneurysm.

Tropical animals are characterized by their showy ornaments and conspicuous colors, and numerous studies on sexual selection have been conducted using tropical species as a model system. In this study, hypothesizing that sexual selection pressures are stronger at lower latitudes, we examined the latitudinal variation in the degree of (1) male aggressiveness in male–male competitions, (2) male eagerness in courtship, and (3) female choosiness to mates in the medaka fish (Oryzias latipes complex). Laboratory mating experiments revealed that males from lower-latitude populations fight each other and court females more frequently than males from higher-latitude populations, supporting the hypothesis that both intra- and intersexual selection pressures are stronger at lower latitudes. In addition, females from lower-latitude populations, where males are more conspicuous, did not accept males easily, especially when mated with higher-latitude males, suggesting that female choosiness has also coevolved across latitudes through Fisherian runaway process. We suggest that latitudinal cline in reproductive seasonality, which is the case not only in the medaka but also among a variety of taxa, leads to latitudinal cline in operational sex ratios of local populations, which ultimately results in latitudinal cline in sexual selection pressures.

Background The aim of this study was to determine the intrahepatic kinetics of different types of nitric oxide (NO) synthase, such as endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS), during repeated ischemia/reperfusion (I/R). Methods Three different protocols of hepatic I/R in rats were designed as follows: 60 min of ischemia and 30 min of reperfusion (I/R 60/30); 5 min of ischemia and 5 min of reperfusion (I/R 5/5); and repeating 15 min of ischemia and 5 min of reperfusion for four cycles (I/R 15/5 × 4). Intrahepatic NO levels were measured using a selective NO sensor. Changes in hepatic microcirculation during I/R 5/5 were investigated using intravital microscopy. Hepatic expression of eNOS, phospho-eNOS, and iNOS were evaluated during repeated I/R by Western blot, reverse transcription polymerase chain reaction, and immunohistochemistry. Results During I/R 60/30, intrahepatic NO levels gradually increased and then reached a plateau approximately 15 min after starting ischemia. During I/R 5/5, the sinusoids after 5 min reperfusion were dilated compared with the sinusoids before ischemia. The expression of phospho-eNOS during I/R 15/5 × 4 markedly increased during the first ischemia, and then the levels attenuated during the subsequent repeating I/R cycles; however, the expression of iNOS gradually increased, as observed by Western blot, reverse transcription polymerase chain reaction, and immunohistochemical analysis. An impact of NO production by phospho-eNOS activation during the superacute phase of I/R was also confirmed using pharmacologic NOS inhibitors. Conclusion Our results firstly demonstrated an altered activation of the phospho-eNOS system and iNOS over the course of repeated hepatic I/R.

The effectiveness of angioplasty and stenting in intracranial atherosclerotic diseases is controversial due to high rates of delayed restenosis and hemorrhage compared with extracranial arteries. However, the mechanisms underlying these differences are still unclear, because their pathophysiology is yet to be examined. To address this issue, we established a novel vascular injury model in the intracranial internal carotid arteries (IICAs) in mice, and analyzed the remodeling process in comparison to that of the femoral arteries (FAs). In IICAs, neointimal hyperplasia was observed from day 14 and grew until day 56. Although smooth muscle cells (SMCs) emerged in the neointima from day 28, SMCs in the injured media were continuously lost with eventual extinction of the media. Re-endothelialization was started from day 7 and completed on day 28. Accumulation of macrophages was continued in the adventitia until day 56. Compared with FAs, the following points are unique in IICAs: (1) delayed continuous formation of neointima; (2) accumulation of macrophages in the media on day 14;(3) continuous loss of SMCs in the media followed by extinction of the media itself; and (4) continuously growing adventitia. These pathophysiologic differences might be associated with unfavorable outcomes in percutaneous transluminal angioplasty and stenting in intracranial arteries.

In the present study, we investigated whether α-bisabolol, a sesquiterpene alcohol present in essential oils derived from a variety of plants, has antitumor effects against pancreatic cancer. α-Bisabolol induced a decrease in cell proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1, MIA Paca2), but not in pancreatic epithelial cells (ACBRI515). α-Bisabolol treatment induced apoptosis and suppressed Akt activation in pancreatic cancer cell lines. Furthermore, α-bisabolol treatment induced the overexpression of early growth response-1 (EGR1), whereas EGR1 siRNA decreased the α-bisabolol-induced cell death of KLM1 cells. Tumor growth in both subcutaneous and peritoneal xenograft nude mouse models was significantly inhibited by intragastric administration of 1000 mg/kg of α-bisabolol, once a week for three weeks. The results indicate that α-bisabolol could be a novel therapeutic option for the treatment of pancreatic cancer.

壊死性筋膜炎は急速に進行する致死性の高い疾患で，基礎疾患として糖尿病が多い。今回，仙骨部褥瘡に起因した壊死性筋膜炎で，広範囲の切開排膿，洗浄ドレナージとデブリードマンを行ない救命できた症例を2例経験したので報告する。症例1は74歳男性で，既往歴に糖尿病とうつ病を認めた。症例2は82歳男性で，既往歴に糖尿病，脊椎損傷による対麻痺，仙骨部褥瘡を認めた。いずれも壊死性筋膜炎発症早期に臀部と背部の広範囲の切開排膿，洗浄ドレナージとデブリードマンを行ない，広域スペクトルの抗菌薬投与で救命できた。また術前の全身状態，糖尿病などの基礎疾患や術後の創部からの蛋白漏出により，術後に栄養状態が著明に悪化したため，糖尿病のコントロールとそれに伴う栄養管理で栄養状態は改善した。活動性低下に対しては，体圧分散寝具の使用，体位交換やリハビリテーションが創の早期改善のために必要であった。

Rationale: Arterial calcification and osteoporosis are associated in postmenopausal women. RANK (the receptor activator of nuclear factor κB), RANKL (RANK ligand), and osteoprotegerin are key proteins in bone metabolism and have been found at the site of aortic calcification. The role of these proteins in vasculature, as well as the contribution of estrogen to vascular calcification, is poorly understood. Objective: To clarify the mechanism of RANKL system to vascular calcification in the context of estrogen deficiency. Methods and Results: RANKL induced the calcification inducer bone morphogenetic protein-2 by human aortic endothelial cells (HAECs) and decreased the calcification inhibitor matrix Gla protein (MGP) in human aortic smooth muscle cells (HASMCs), as quantified by real-time PCR and Western blot analysis. RANKL also induced bone-related gene mRNA expression and calcium deposition (Alizarin red staining) followed by the osteogenic differentiation of HASMCs. Estrogen inhibited RANKL signaling in HAECs and HASMCs mainly through estrogen receptor α. Apolipoprotein E–deficient mice fed with Western high-fat diet for 3 months presented atherosclerotic calcification (Oil red and Alizarin red staining) and osteoporosis (microcomputed tomographic analysis) after ovariectomy and increased expression of RANKL, RANK, and osteopontin in atherosclerotic lesion, as detected by in situ hybridization. Estrogen replacement inhibited osteoporosis and the bone morphogenetic protein osteogenic pathway in aorta by decreasing phosphorylation of smad-1/5/8 and increasing MGP mRNA expression. Conclusions: RANKL contributes to vascular calcification by regulating bone morphogenetic protein-2 and MGP expression, as well as bone-related proteins, and is counteracted by estrogen in a receptor-dependent manner.

Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in older men. Elective surgical or endovascular repair is performed to prevent rupture of large AAAs. In contrast, despite gradual expansion, small AAAs have a low risk of rupture, and there is currently no well-defined treatment strategy for them. Therefore, a pharmacological approach for AAA is expected in the clinical setting. Indeed, several therapeutic effects of pharmacological agents have been reported in experimental models, and some agents have undergone clinical trials. Treatment with statins, angiotensin-converting enzyme-inhibitors, antibiotics, and anti-inflammatory agents appears to inhibit the growth rate of AAA in humans. However, as the sample size and follow-up period were limited in these studies, a large randomized study with long-term follow-up of small AAA should be performed to clarify the effect of these agents. Recently, the regression of AAA using molecular pharmacological approaches was reported in experimental studies. The characteristics of these strategies are the regulation of multiple molecular mediators and the signalling networks associated with AAA formation. On the basis of the results of these investigations, it may be possible to repair the injured aortic wall and obtain the remission of AAA using pharmacological therapy.

Summary We have developed a new and effective method for bone marrow transplantation (BMT): bone marrow cells (BMCs) are injected directly into the bone marrow (BM) cavity of recipient mice. The intrabone marrow injection of BMCs (IBM-BMT) greatly facilitates the engraftment of donor-derived cells, and IBM-BMT can attenuate graft-versus-host reaction (GVHR), in contrast to conventional intravenous BMT (i.v.-BMT). Here, we examine the mechanisms underlying the inhibitory effects of IBM-BMT on GVHR using animal models where GVHR is elicited. Recipient mice (C57BL/6) were irradiated and splenic T cells (as donor lymphocyte infusion: DLI) from major histocompatibility complex-disparate donors (BALB/c) were injected directly into the BM cavity (IBM-DLI) or injected intravenously (i.v.-DLI) along with IBM-BMT. The BM stromal cells (BMSCs) from these recipients were collected and related cytokines were examined. The recipient mice that had been treated with IBM-BMT + i.v.-DLI showed severe graft-versus-host disease (GVHD), in contrast to those treated with IBM-BMT + IBM-DLI. The suppressive activity of BMSCs in this GVHD model was determined. The cultured BMSCs from the recipients treated with IBM-BMT + IBM-DLI suppressed the proliferation of responder T cells remarkably when compared with those from the recipients of IBM-BMT + i.v.-DLI in mixed leucocyte reaction. Furthermore, the level of transforming growth factor-β and hepatocyte growth factor in cultured BMSCs from IBM-BMT + IBM-DLI increased significantly when compared with those from the recipients of IBM-BMT + i.v.-DLI. Thus, the prevention of GVHD observed in the recipients of IBM-BMT + IBM-DLI was attributable to the increased production of immunosuppressive cytokines from BMSCs after interaction with host reactive T cells (in DLI).

はじめに: 大腸癌に対してmoving window法を用いた小開腹大腸癌根治術を施行した症例について検討を行った. 対象と方法: 2002年11月から2007年3月までに当院で大腸癌の診断で7cmの皮膚切開によるmoving window法により切除術が施行された175例を対象とした.これは同期間での当院の大腸癌手術症例数606例の29%に該当した. 吻合はfunctional end to end anastomosisもしくはdouble stapling techniqueによる器械吻合を用いた. 結果: 21名の外科医によって施行され, うち69例 (39%) が, 卒後3年目から9年目の12名の外科医であった. 39例 (22%) で創が10cmに延長された. 平均手術時間は127分, 平均出血量97mLで, 術中合併症としては, 縫合器による腸管損傷を1例 (0.6%) に認め, 翌日再手術を行った. 術後合併症を27例 (15%)(イレウス: 11例 (6%), SSI: 4例 (2%), ドレーンの逆行性感染: 3例 (2%) など) に認めたが, 縫合不全はなかった. 癌性腹膜炎の増悪, 認知症がきっかけの肺炎の悪化による在院死をそれぞれ1例に認めたが, 手術関連死亡はなかった. 82例 (47%) にクリニカルパスを使用し, 75例 (91%) がパスを完遂した. 全症例の平均術後在院日数は14日であった. 考察: 本法は通常の開腹手術と同様の直視下の3次元の手術であるため, 一般の外科医でも安全に施行できる低侵襲手術である.

SummaryMRL/lpr mice (H-2k) with Fas gene mutation develop severe autoimmune diseases, and their haematolymphoid cells such as bone marrow and spleen cells showed a low apoptotic activity by irradiation. Therefore, conventional bone marrow transplantation (BMT) cannot be used to treat autoimmune diseases in these mice (chimeric resistance). In the present study, we examine the effects of additional adult thymus transplantation (TT) from the same donor on successful BMT. When the MRL/lpr mice were lethally irradiated (9·5Gy) and reconstituted with 3 × 107 of C57BL/6 mouse (H-2b) bone marrow cells (BMCs) in conjunction with TT, the mice significantly survived long term and showed a high donor-derived chimerism in comparison with those treated with BMT alone. Interestingly, the numbers of not only donor-derived T cells but also B cells increased significantly in the mice treated with BMT plus TT, even at the early phase of BMT. The number of aberrant CD3+B220+ cells decreased significantly, and the numbers of lymphocyte subsets were also normalized 4 weeks after the treatment. Finally, the autoimmune diseases in MRL/lpr mice could be cured by BMT with TT. These results indicate that the combination of BMT plus TT can overcome the chimeric resistance and treat the autoimmune diseases in MRL/lpr mice.

Background/Aims: This study investigated the effect of perioperative synbiotics on bacterial translocation to mesenteric lymph nodes (MLNs) and occurrence of infectious complications following pancreatoduodenectomy (PD; University Hospital Medical Information Network ID 000003705). Methods: Patients who were scheduled to undergo PD were randomized to receive preoperative synbiotics or no synbiotics (control group). MLNs were harvested at laparotomy (MLN-1) and after the resection (MLN-2). Blood samples were collected before laparotomy (Blood-1) and on postoperative day 1 (Blood-2). Microorganisms in each sample were detected using a bacterium-specific ribosomal RNA-targeted reverse transcriptase-quantitative polymerase chain reaction. Results: Forty-four patients were included. In all samples, the bacterial detection rate in the MLN-1, MLN-2, Blood-1, and Blood-2 was lower in the synbiotics group than in the control group, although it did not reach a statistically significant difference. There was a significant correlation between the positivity of bacteria in the MLN-2 and Blood-2 samples (p = 0.009). The incidence rate of overall infectious complications was not significantly different between the 2 groups. Among various perioperative factors, the incidence of pancreatic fistula was the only factor that had a significant association with the incidence of infectious complications. Conclusion: The preoperative use of synbiotics did not affect the incidence of infectious complications following PD.

In this study, we focused on the effect of hypertension on the transcription factors nuclear factor kappaB (NFkappaB) and ets in the mechanisms of abdominal aortic aneurysm (AAA), and we investigated how hypertension affects the progression of AAA. AAA was produced by elastase perfusion in hypertensive rats and normotensive rats. The size of AAA rapidly increased in hypertensive rats as compared with normotensive rats. Western blot analysis demonstrated that the expression of matrix metalloproteinase (MMP)-2, -3 , -9, and -12, as well as intercellular adhesion molecule, was increased in hypertensive AAA rats, accompanied by upregulation of NFkappaB and ets. Moreover, in situ zymography showed that the activity of MMPs was increased in the aorta of a hypertensive AAA model as compared with that in a normotensive AAA model. Interestingly, transfection of chimeric decoy oligodeoxynucleotide (ODN) resulted in significant inhibition of aortic dilatation both in normotensive and hypertensive rats at 4 weeks after transfection. Destruction of elastic fibers was also significantly inhibited by transfection of chimeric decoy ODN in both hypertensive rats and normotensive rats. The expression of MMP-2, -3, -9, and -12, as well as intercellular adhesion molecule, was significantly attenuated by the chimeric decoy ODN, accompanied by inhibition of the migration of macrophages. Also, the effect of chimeric decoy ODN was confirmed in an organ culture. The present study demonstrated that hypertension accelerated the progression of experimental AAA through upregulation of NFkappaB and ets. Inhibition of NFkappaB and ets could be a novel therapeutic strategy to treat AAA in hypertensive patients.

The pathophysiology of abdominal aortic aneurysms (AAA) is considered to be complicated. As matrix degradation contributes to the progression of AAA, the destruction and degradation of elastin fibers caused by an increase in matrix metalloproteinases (MMPs) plays a pivotal role in the development of AAA. Although ets, an essential transcription factor for angiogenesis, regulates MMPs, the role of ets in the development of AAA has not yet been clarified. Thus, we evaluated the role of ets in a rat AAA model using a decoy strategy. Transfection of ODN into AAA was performed by transient aortic perfusion of elastase and by wrapping the AAA in a delivery sheet containing decoy ODN. The inhibitory effect of ets decoy ODN on ets binding activity was confirmed by gel mobility shift assay. MMPs expression was decreased in the aorta transfected with ets decoy ODN as compared to scrambled decoy ODN. Also, ultrasound study demonstrated that elastase-induced aneurismal dilation was significantly suppressed by transfection of ets decoy ODN at 4 weeks after treatment as compared to scrambled decoy ODN. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with ets decoy ODN, accompanied by a reduction of MMPs expression. An inhibitory effect of decoy ODN on MMP expression was confirmed by ex vivo experiments showing that transfection of decoy ODN into an organ culture of human aorta resulted in significant inhibition of the secretion of both MMP-1 and MMP-9. Here, we demonstrated that ets may play a pivotal role in the progression of AAA through the activation of MMPs in a rat model. Ets might be a potential target to develop pharmacotherapy/gene therapy to treat AAA through the inhibition of MMPs.

Background— Two phenomena, inflammation and matrix degradation, contribute to the progression of abdominal aortic aneurysm (AAA). Importantly, the inflammation is regulated by the transcription factor nuclear factor (NF)–κB, whereas the destruction and degradation of elastin fibers by matrix metalloproteinases (MMP) are regulated by ets. Thus, we developed a novel strategy to treat AAA by simultaneous inhibition of both NF-κB and ets by using chimeric decoy oligodeoxynucleotides (ODN). Methods and Results— AAA was induced in rats by transient aortic perfusion with elastase, whereas transfection of decoy ODN was performed by wrapping a delivery sheet containing decoy ODN around the aorta. Gel-mobility shift assay at 7 days after treatment demonstrated that both NF-κB and ets binding activity were simultaneously inhibited by chimeric decoy ODN. Transfection of chimeric decoy ODN resulted in significant inhibition of the progression of AAA such as aneurysmal dilation at 4 weeks after treatment as compared with control, accompanied by a reduction of MMP expression. Moreover, the destruction of elastin fibers was inhibited in the aorta transfected with chimeric decoy ODN. Importantly, transfection of chimeric decoy ODN demonstrated potent inhibition of aneurysmal dilatation compared with NF-κB decoy ODN alone, whereas scrambled decoy ODN had no effects. Interestingly, the migration of macrophages was significantly inhibited by chimeric decoy ODN. Conclusions— We demonstrated that inhibition of the progression of AAA was achieved by a novel strategy with chimeric decoy ODN used against NF-κB and ets in rat model. NF-κB and ets are considered to play an important role in the pathogenesis of AAA.

症例は67歳の女性で,胸腺腫に対し拡大胸腺摘出術を施行した.組織学的にはWHO分類のtype ABで,臨床病期はI期であった.退院後外来にて観察していたが,術後3カ月に全身倦怠感を訴え,血液検査で貧血を認めた.骨髄検査にて赤芽球をほとんど認めず,赤芽球癆と診断された.輸血により自覚症状は消失し,確定診断後プレドニゾロンの内服を開始したが貧血は改善せず,追加の輸血を必要とした.サイクロスポリンの内服を開始したところ貧血は改善し,現在サイクロスポリン投与量を漸減しつつある.胸腺腫に赤芽球癆や重症筋無力症を合併することはよく知られているが,胸腺腫摘出後に赤芽球癆を発症した報告は少ない. PRCAと胸腺腫との関連につき考察を加えた.胸腺腫摘出後も赤芽球癆や重症筋無力症などの発症に注意して経過観察する必要がある.

今回われわれは,鼠径ヘルニア内嵌頓壊死にて汎発性腹膜炎を呈したS状結腸腹膜垂炎の1例を経験した.症例は86歳の男性で,腹痛にて発症し当院を受診した.腹部全体に自発痛・圧痛があり,板状硬であった.左鼠径部に疼痛を伴う鶏卵大の腫脹がみられ,鼠径ヘルニア嵌頓による汎発性腹膜炎の診断で手術を行った.全身麻酔下に開腹したところ,腹腔内には混濁腹水が中等量存在し,膿苔が浮遊していた.腸管を全長にわたって検索したが穿孔はみられず, S状結腸腹膜垂のひとつが褐色に壊死しており,この腹膜垂が鼠径ヘルニア内に嵌頓壊死して腹膜炎を呈したと判断した.腹膜垂炎は稀な疾患であり,さらに合併症として鼠径ヘルニア内に嵌頓壊死して腹膜炎を呈した報告例はなく,若干の文献的考察を加え報告する.

Background— Despite the advent of drug-eluting stents, restenosis after endovascular intervention is still a major limitation in the treatment of cardiovascular disease. To regulate the multiple biological mechanisms underlying restenosis, we focused on inhibition of an important transcription factor, nuclear factor-kappaB (NFκB), using a decoy strategy. Methods and Results— For site-specific application of NFκB decoy oligodeoxynucleotides into target vessels during angioplasty, we developed a balloon catheter–based delivery system combined with biocompatible nanoparticles as oligodeoxynucleotides carriers. To clarify the therapeutic effect at the site of neointima, balloon angioplasty of the rabbit carotid arteries was performed at 4 weeks after initial endothelial denudation. This delivery system exhibited successful transfer of fluorescence-labeled nanospheres into the neointima in short-term contact with target vessels, and fluorescence could be detected ≥1 week after angioplasty. Consistently, local application of NFκB decoy oligodeoxynucleotides -loaded nanospheres resulted in significant inhibition of neointimal formation, associated with inhibition of NFκB binding activity in the injured arteries. The therapeutic effects were caused by inhibition of macrophage recruitment through the suppression of monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, and CC chemokine ligand 4 expression and inhibition of vascular smooth muscle cell growth via a decrease in the expression of cyclin A and proliferating cell nuclear antigen. Importantly, application of NFκB nanospheres accelerated restoration of the endothelial cell monolayer, associated with enhanced expression of phosphorylated Bcl-2 in endothelial cells. Conclusions— A drug-coated balloon catheter using NFκB decoy oligodeoxynucleotides significantly inhibited the development of neointimal hyperplasia in rabbits. The present study indicates the possibility of a novel therapeutic option to prevent restenosis after angioplasty.

The background factors and surgical results of 546 patients with arteriosclerosis obliterans (ASO) in an early group (between January 1976 and December 1989) were compared with those of 454 patients in a later group (between January 1990 and July 1998). The later group was older than the early group and had less critical leg ischemia. In the later group, there were more patients with diabetes mellitus and renal failure. There were no significant differences between the two groups in bypass patency rates and hospital deaths. It is necessary to develop a new therapy which prevents intimal hyperplasia and arteriosclerosis.

超音波法による骨質測定を用いた骨粗鬆症巡回検診に参加した女性9,459人, 男性260人を対象とし, 得られた3種類のパラメータ: BUA (超音波の減衰率), SOS (速度) およびStiffness (標準化したBUAとSOSの平均値) は, 女性では測定した最も若いグループ (15～17歳) で最高値を示し, 各々116±9, 1,572±23および97±11, 男性ではSOSとStiffnessは最も若い15～16歳, BUAは22～29歳で最高値を示し, 各々1,590±20,107±11,124±14であった。これらパラメータは, 年齢の増加とともに減少し, Stiffnessの減少率は, 女性では51～55歳の間が1.0%/年と最大であった。またStiffnessやSOSの加齢による減少に比べBUAの減少は軽度であった。閉経後の3つのパラメータの減少率は最初の5年間が最も大きくStiffnessで2.0%/年であった。閉経の遅かったグループ (53歳以上) の骨量は, 閉経の早かったグループ (45歳以下) に比べて, 50歳代後半から60歳代後半で有意に高く, 70歳代以後では有意差が認められなかった。また各パラメータと身長, 体重, 肥満度との間には, SOSと肥満度との間を除いて, 全て有意な正相関が認められた。

Objective— Vascular calcification is accelerated by hypertension and also contributes to hypertension; however, it is an enigma why hypertension and vascular calcification are a vicious spiral. The present study elucidates the cross-talk between renin–angiotensin II system and receptor activator of nuclear factor-κB ligand (RANKL) system in vascular calcification. Approach and Results— Angiotensin (Ang) II (10 −7 mol/L) significantly increased calcium deposition as assessed by Alizarin Red staining, associated with a significant increase in the expression of RANKL, RANK, and bone-related genes, such as cbfa1 and msx2, in human aortic vascular smooth muscle cells. Infusion of Ang II (100 ng/kg per minute) in ovariectomized ApoE −/− mice under high-fat diet significantly increased the expression of RANKL system and calcification in vivo, whereas administration of Ang II receptor blocker (olmesartan, 3 mg/kg per day) decreased the calcification and bone markers’ expression. In addition, male OPG −/− mice showed a significant increase in vascular calcification followed by Ang II infusion as compared with wild type. Conversely, RANKL significantly increased Ang II type 1 receptor and angiotensin II–converting enzyme expression in vascular smooth muscle cells via extracellular signal–regulated protein kinase phosphorylation. Conclusions— The present study demonstrated that Ang II significantly induced vascular calcification in vitro and in vivo through RANKL activation. In addition, RANKL activated renin–angiotensin II system, especially angiotensin II–converting enzyme and Ang II type 1 receptor. Cross-talk between renin–angiotensin II system and RANKL system might work as a vicious cycle to promote vascular calcification in atherosclerosis. Further studies to inhibit renin–angiotensin II system and RANKL may provide new therapeutic options to prevent and regress vascular calcification.

An unusual case of a toothpick perforating the stomach, then penetrating the liver, and thereafter forming a liver abscess is reported. A 48-year-old woman who had ingested a toothpick 1 month earlier was admitted to our hospital because of severe epigastralgia which had progressively worsened. A laparotomy was performed because a granulomatous abscess in the liver due to this ingested foreign body was suspected. We found a granulomatous abscess in the liver due to the penetration of the toothpick through the stomach. The toothpick had become completely embedded about 2 cm deep in the left lobe of the liver. When dissecting the tumor, a 5.5-cm toothpick was removed, and a partial lateral resection of the liver was performed. The histological diagnosis was a hepatic abscess with granulomatous change. This was a rare case of a migration of an ingested toothpick into the liver through the stomach.

Recent progress in molecular and cellular biology has resulted in the development of numerous effective drugs. However, there are still a number of diseases for which no known effective therapy exists, such as ischemic heart disease, vascular bypass graft failure and heart failure. Despite its limitations, oligodeoxynucleotide (ODN)-based therapy is emerging as a potential strategy for the treatment of patients with cardiovascular disease that is resistant to current therapeutic approaches. Indeed, several nucleic acid drugs and delivery methods for heart disease have been developed and their efficacy has been investigated in animal models. Among them, some agents have undergone clinical trials, such as cmyc antisense ODN, E2F and NFκB decoy ODN. However, none of the large randomized placebo-controlled trials has shown conclusive evidence of clinical benefit. Recent experimental studies suggested that siRNA- and miRNA-based strategies have potential as a potent therapeutic approach for the treatment of restenosis. In addition, simultaneous regulation of multiple intracellular signaling pathways is expected to enhance the therapeutic effects. This review focuses on the potential of recent ODN-based gene therapy for the treatment of heart disease, especially restenosis after revascularization.

Treatment with angiotensin type 1 receptor blockers (ARBs) is known to improve renal dysfunction and glucose metabolism in obese diabetic animal models and humans. This study examined the effects of irbesartan, a unique ARB with PPARγ activation, on endothelial dysfunction, renal dysfunction, abnormal lipid profile, and liver dysfunction in obese fa/fa Zucker diabetic fatty (ZDF) rats. ZDF rats were administered irbesartan (30 mg/kg/day p.o.) for 12 weeks. Blood pressure, glucose metabolism, lipid profile and renal function were measured every 4 weeks. Response of mesenteric artery rings to acetylcholine was also evaluated as an index of endothelial function after 12 weeks of treatment. Although irbesartan did not affect glucose and insulin levels in both glucose and insulin tolerance tests, decreases in systolic blood pressure, dyslipidemia, and urinary protein excretion were noted from 4 weeks after the start of treatment and continued until 12 weeks. Endothelial and liver dysfunctions were also improved after 12 weeks of treatment. Compared to previous reports showing the effects of irbesartan at later time points such as 6 or 12 months, the present study demonstrated that a low-dose of irbesartan had favorable effects from the early period of treatment, independent of glucose metabolism. Our findings suggest that a low-dose of irbesartan improves diabetic complications quickly after starting treatment, and may support the use of irbesartan for preventing progression of diabetic complications.

Recent reports have shown that nifedipine, a calcium channel blocker, increases peroxisome proliferator-activated receptor-γ (PPARγ) activity. Since PPARγ agonists, such as pioglitazone and rosiglitazone, are effective in reducing non-alcoholic steatohepatitis (NASH) and cirrhosis in animal models, we examined the protective effects of nifedipine, as compared with bezafibrate, a PPARα agonist, in a NASH model induced by an L-methionine- and choline-deficient (MCD) diet. An MCD diet for 20 weeks changed the color of the rat liver to yellow with an irregular surface, whereas the color of the liver in both the bezafibrate and nifedipine treatment groups was markedly changed to yellow-brown with a smooth surface. Furthermore, nifedipine, as well as bezafibrate, significantly prevented liver fibrosis induced by an MCD diet, as assessed by Masson's trichrome staining, accompanied by a significant decrease in serum AST. Overall, nifedipine treatment resulted in an improvement in NASH, similar to bezafibrate, in a rat model. In hypertensive patients with metabolic syndrome, nifedipine may provide additional benefits, beyond its blood pressure-lowering effects, to prevent NASH and fatty liver disease.

Chlamydia pneumoniae was isolated from the throat swab of a 5-year-old girl with acute bronchitis. The titers of IgM and IgG antibodies to C. pneumoniae in the serum were 1:20 and 1:2560, respectively. C. pneumoniae genome was detected by polymerase chain reaction in the throat swab and the infected cells after three passages, while C. pneumoniae was isolated from the throat swab after five passages by cell culture. PCR is considered to be a helpful method to isolate C. pneumoniae efficiently in routine cell-cultures.

The favorable metabolic effects of telmisartan have been attributed to its angiotensin II receptor blockade and action as a partial agonist of peroxisome proliferator-activated receptor (PPAR)-gamma. We previously reported that administration of telmisartan markedly inhibited lipid accumulation in the liver in mice fed a high-fat diet. In the present study, we further examined the protective effect of telmisartan in a non-alcoholic steatohepatitis (NASH) model induced by feeding Wistar rats an L-methionine- and choline-deficient (MCA) diet. In the first experiment, rats were fed an MCA diet for 8 weeks with or without telmisartan (3 mg/kg/day). Liver fibrosis was observed by Masson trichrome staining, and co-treatment was shown to attenuate liver fibrosis. In the second experiment, Wistar rats were fed an MCA diet for 20 weeks, and telmisartan (3 mg/kg/day) was administered during weeks 0-20 as a preventive model or weeks 8-20 as a therapeutic model. As a result, telmisartan administration in both models significantly attenuated liver fibrosis and an increase in serum AST. Of importance, the HGF concentration in the liver was significantly increased in the telmisartan-treated group. Overall, telmisartan showed a potential action to improve NASH induced by an MCA diet, possibly due to increased HGF production through partial agonist of PPAR-gamma. These favorable characteristics of telmisartan as a partial agonist of PPAR-gamma may provide a benefit in the treatment of metabolic syndrome beyond its blood pressure-lowering effect.

We sometimes have difficulities to treat fistulae which are formed due to anastomotic leakage after surgery for gastrointestinal disease. Here we describe our study of infusing fibrin glue to such fistulae which could successfully close them. From May 1988 to October 1989, 321 cases underwent operation of GI tract. Anastomotic leakage was recognized in 27 cases, and 12 were subjected to this study. The patients were comprized of each 6 males and females, and had undergone total gastrectomy in 5, pancrreatoduodenectomy in 3, rectal amputation in 3, and other in one. Each patient received conservative treatment for 2 weeks to 5 months, which could not yield cure. Then fibrin glue was infused, and in 9 cases fistulae were closed and cured. Excepting such fistulae as those producing sustained and large quantity of exudate, those in acute stage of infection, and those infiltrated by a tumor, this technique is able to heal almost intractable fistulae for a short period without any surgical treatment. Extremely effective this method would be recommended.

Cerebral aneurysm (CA) causes catastrophic subarachnoid hemorrhage which is characterized by a high mortality and morbidity rate. CA is a common disease worldwide but to date there is no medical treatment against unruptured CAs. Thus, it is important to study the mechanisms of CA formation. Our previous report demonstrated that chronic inflammatory response in cerebral arterial bifurcation by hemodynamic stress deteriorated arterial walls and formed CA. Therefore, drugs with anti-inflammatory effects might effectively treat CA formation. As renin angiotensin system (RAS) is a major inflammatory cascade and related to various vascular diseases, including aortic aneurysms, the role of angiotensin (Ang) II type 1 receptor might contribute to the progression of CAs. However, in cerebral aneurysmal walls, Ang II type 1 receptor was not up-regulated. In addition, subcutaneously administered Ang II type 1 receptor blocker did not inhibit CA formation, nor inflammation in cerebral aneurysmal walls in rat models at a sub-suppressor dose. These results indicate that RAS might play a less important role in CA formation compared to aortic anuerysms or other vascular diseases. This suggests that there are different mechanisms between the pathogenesis of cereberal and aortic aneurysms.

Aims Neointimal formation remains a major limitation after arterial reconstruction. To overcome this problem, we focused on two important transcription factors, nuclear factor-kappaB (NFkB) and E2F. The purpose of this study was to determine the effects of simultaneous inhibition of these transcription factors on the formation of neointimal hyperplasia. Methods and results We employed chimeric decoy oligodeoxynucleotides (ODN) to inhibit both NFkB and E2F simultaneously, and examined the effects of chimeric decoy ODN on the proliferation and migration of cultured vascular cells and on the formation of neointimal hyperplasia using prosthetic graft placement in a rabbit hypercholesterolemia model. Our in vitro study demonstrated that transfection of chimeric decoy ODN inhibited platelet-derived growth factor (PDGF)-induced proliferation and migration of vascular smooth muscle cells, whereas endothelial cell proliferation was not inhibited. In an in vivo study, treatment with chimeric decoy ODN significantly inhibited proximal and distal anastomotic intimal hyperplasia, and accelerated re-endothelialization. a-Smooth muscle actin (a-SMA)positive cell proliferation was inhibited at the anastomotic sites. Expression of PDGF-BB and PDGF receptor-b was also suppressed by chimeric decoy ODN, resulting in a reduction of a-SMA-positive cell accumulation. In addition, chimeric decoy ODN treatment inhibited macrophage accumulation, which was accompanied by a reduction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 gene expression. Conclusion The present study demonstrates the feasibility of chimeric decoy ODN treatment for preventing neointimal formation. This strategy might be useful to improve the clinical outcome after arterial reconstruction.

Because current therapy to treat abdominal aortic aneurysm (AAA), and particularly to manage small AAA, is limited to elective surgical repair, we explored less invasive molecular therapy by simultaneous inhibition of the transcription factors nuclear factor (NF)kappaB and ets using a decoy strategy. Both NFkappaB and ets were shown to be markedly activated in human AAA. In addition, NFkappaB- and ets-positive cells were increased in the aneurysm wall, and a part of the expression of NFkappaB and ets was detected in migrating macrophages. Thus, we used chimeric decoy oligodeoxynucleotides (ODNs) containing consensus sequences of both NFkappaB and ets binding sites to treat AAA. Inhibitory effects of chimeric decoy ODNs on matrix metalloproteinase-1 and -9 expression were confirmed by ex vivo experiments using a human aorta organ culture. To examine the regressive effect in a rabbit already-formed AAA model, transfection by wrapping a delivery sheet containing chimeric decoy ODNs around the aneurysm was performed 1 week after incubation with elastase. Importantly, treatment with chimeric decoy ODNs significantly decreased the size of AAA. Interestingly, significant preservation of elastic fibers was observed with chimeric decoy ODN treatment, accompanied by a reduction of matrix metalloproteinase-2 and -9 and induction of macrophage apoptosis. Regression of AAA was also associated with an increase in elastin and collagen type I and III synthesis in the aneurysm wall. Minimally invasive molecular therapy targeted to the inhibition of NFkappaB and ets is expected to be useful for AAA through the rebalance of matrix synthesis and degradation.

We have recently found that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive donor lymphocyte infusion (DLI) is carried out. In the present study, in conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The extent of GvHD was compared with that of recipients that had received allogeneic IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]). GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed macroscopically and histopathologically. The frequency of regulatory T cells (Tregs) detected as CD4+CD25+ and CD4+Foxp3+ cells was significantly higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of transforming growth factor-β and hepatocyte growth factor from bone marrow stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to preferentially induce Tregs and Th2, resulting in the prevention of GvHD. Disclosure of potential conflicts of interest is found at the end of this article.

Recently, atherosclerosis has been considered to be the result of inflammation. Interestingly, hydroxymethylglutaryl-coenzyme (HMG-Co) A inhibitors (statins), which are clinically used as lipid-lowering agents, have been reported to have various anti-inflammatory effects. As abdominal aortic aneurysm (AAA) is a common degenerative condition associated with atherosclerosis, this study was designed to investigate the inhibitory effect of a statin, atorvastatin, on aneurysm formation apart from its lipid-lowering effect. We employed an elastase-induced rat AAA model, as statins do not lower cholesterol in rats. Mean aneurysm diameter was significantly smaller in the atorvastatin treatment group as compared to control at 4 weeks after surgery (P0.05). Interestingly, atorvastatin inhibited the expression of ICAM and MCP-1, followed by the suppression of macrophage recruitment into the aortic wall at 1 week after operation. A significant reduction in MMP-12, but not MMP-2, -3 and -9, expression was also observed by treatment with atorvastatin at 1 week after surgery. In addition, synthesis of collagen and elastin in the vascular wall were significantly increased by atorvastatin. Here, the present study demonstrated a direct effect of atorvastatin to inhibit the progression of aortic aneurysm, independent of its lipid-lowering effect. This study suggests new therapeutic aspects of statins to inhibit the progression of aneurysms.

Aims: To study the relationship between comedonecrosis formation and morphology, apoptosis, and p53, Bcl-2, Ki-67 index and E-cadherin expression in early invasive breast cancer. Experimental design: Early invasive breast cancers were first divided into two groups according to the presence (CN+ tumours) or absence (CN− tumours) of comedonecrosis. The histological grade, apoptosis, and expression of E-cadherin, Ki-67, p53 and Bcl-2 in the cancer-affected area, and in normal ducts from the specimen, were then examined. Results: Less tubule and gland formation was seen in CN+ tumours than in CN− tumours, although the histological grade between the groups was not different. During early comedonecrosis, cells undergo apoptosis and subsequent necrosis. p53 was higher in CN+ tumours than in CN− tumours and normal ducts, whereas Bcl-2 was lower in CN+ tumours than in CN− tumours and normal ducts. Both tumours had higher Ki-67 than in normal ducts, but no difference was evident between the tumours. CN+ tumours had slightly higher E-cadherin than that in CN− tumours, but lower than that in normal ducts. The level of comedonecrosis was positively correlated with p53, but inversely correlated with Bcl-2 in all tumours, and p53 and Bcl-2 were inversely correlated with each other. Furthermore, comedonecrosis and p53 were correlated with Ki-67 in CN+ tumours, and Bcl-2 was correlated with Ki-67 in CN− tumours. Conclusion: Comedonecrosis may be actively regulated through an apoptotic procedure in massive cancers for their survival and progression, and the above proteins may be associated cooperatively in this process. CN+ and CN− tumours may have opposite proliferative systems under the p53–Bcl-2 pathway.

Autologous vein remains the commonly used conduit for bypass grafts; however, neointimal hyperplasia is known to be one of the major disease processes in vein graft failure. In this study, we focused on the important role of NFkappaB which controls the expression of numerous genes for various cytokines and adhesion molecules in the mechanism of graft failure. Thus, we investigated the inhibitory effect of NFkappaB decoy oligodeoxynucleotides (ODN) on vein graft failure in a rabbit hypercholesterolemic model. Jugular vein to carotid artery interposition grafts in rabbits were transfected intraoperatively with NFkappaB decoy ODN (40 micromol/l) by ex-vivo pressure-mediated transfection (300 mm Hg, 10 min). Treatment with NFkappaB decoy ODN significantly suppressed intimal hyperplasia 4 weeks after vein implantation as compared to scrambled decoy ODN, and increased medial thickness, leading to a significant reduction in intima-to-media ratio. Treatment with NFkappaB decoy ODN significantly inhibited the recruitment of macrophages and the proliferation of vascular smooth muscle cells (VSMC), while apoptosis in VSMC was significantly increased by NFkappaB decoy ODN. In addition, a study of vascular reactivity demonstrated that transfection of grafts with NFkappaB decoy ODN significantly improved endothelium-mediated vasorelaxation as compared to scrambled decoy ODN. Here, we demonstrated that inhibition of NFkappaB activation using decoy ODN inhibited the development of neointimal hyperplasia, followed by suppression of inflammatory changes and accumulation of VSMC in the neointima of rabbit vein grafts. The present study raises the possibility of a novel strategy for prevention of graft failure.

Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.

Pulmonary sequestration is abnormal pulmonary tissue that has separated from the normal pulmonary parenchyma, is not connected to the tracheobronchial tree, and is supplied by a systemic artery. We describe herein a case of intralobar pulmonary sequestration found in a 66-year-old man who was admitted to our hospital with hemoptysis, coughing, and fever. Angiography showed that the branches of the 11th left intercostal artery and a bronchial artery had formed a hypervascular area in the lower part of the left lung. Bronchial artery embolization and subsequent embolization of the left 11th intercostal artery were performed in an attempt to control the recurrent hemoptysis. These treatments were unsuccessful, and he was transferred to our department of surgery after coughing up about 400 ml of fresh blood. A left lower lobectomy was performed. The resected lung contained a large feeding artery, some acute and partly organizing inflammatory lesions within collapsed lung parenchyma, and massive intra-alveolar hemorrhage in the peripheral area. The patient had an uneventful recovery and was discharged 22 days after his operation.

A 76-year-old male with anterior mediastinal tumor was admitted to our hospital. He had undergone mediastinal lipoma surgery 3 years earlier. The tumor was excised surgically. Microscopic sections of the tumor showed liposarcoma composed of myxoid tissue. Further examination of prior specimens taken from this patient proved this case to be a recurrence of liposarcoma. Poorly differentiated tumors, which pathologically tend to be more cellular with less fat per cell component, are likely to have high CT numbers. But CT number is not sufficient to distinguish well-differentiated liposarcoma from benign lipoma.

Angiotensin (Ang) II exerts direct effects on the arterial wall to influence atherosclerosis and aneurysm development with the induction of vascular inflammation. Therefore, we examined the hypothesis that the inhibition of Ang II would decrease the expansion of abdominal aortic aneurysm (AAA) in a rat model. We used the Ang II receptor blocker (ARB) valsartan to inhibit the effect of Ang II. Additionally, we employed a dosage of valsartan (1 mg/ kg/day) that does not affect blood pressure, to avoid the effect of blood pressure lowering. Notably, progression of elastase-induced AAA was inhibited in rats treated with valsartan (P< or =0.05). To clarify the mechanism, we focused on matrix metalloproteases (MMPs) and inflammatory related factors. Western blot analysis demonstrated that the expression of MMPs was significantly decreased in an AAA model treated with continuous ARB infusion compared to an AAA model treated with vehicle (P< or =0.05), through suppression of nuclear factor kappaB activation (P< or =0.05). Consistently, valsartan significantly inhibited infiltration of macrophages into the aortic wall, accompanied by a reduction of protein expression of intercellular adhesion molecule-1. Importantly, the inhibitory effect of valsartan on MMP-2 and MMP-9 expression was also confirmed using isolated peritoneal macrophages from a rat AAA model. Moreover, treatment with valsartan protected against the destruction of elastic fibers. Overall, the present study demonstrated that treatment with valsartan, significantly prevented the progression of experimental AAA in a rat model. These data suggest that blockade of Ang II has an inhibitory effect on the development of AAA, independent of its antihypertensive effect.

We evaluated the prevalence of Coxiella burnetii antibodies in 626 human serum samples (275 from veterinarians, 107 from meat-processing workers, 184 from respiratory-disorder patients, and 60 from healthy humans) by the indirect immunofluorescence test. Of the serum samples examined, 54 (8.6%) and 103 (16.5%) reacted positively to phase I and II antigens, respectively, of C. burnetii. The rates differed for healthy humans and respiratory-disorder patients. Antibody prevalence was high for healthy humans living in close contact with animals (e.g., veterinarians and meat-processing workers).