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ABSTRACT: We performed a retrospective review of 45 consecutive patients with metachronous multiple primary lung cancer who underwent resection between 1990 and 2009. Surgical treatment of the 1st tumor consisted of 39 lobectomies and 3 segmentectomies, and 3 wedge resections. The 2nd tumor was removed by means of a lobectomy in 9 patients, a segmentectomy in 17 patients, a wedge resection in 19 patients. No postoperative mortality was observed. Histologic classification was similar in 86.4% of patients and different in 13.6%. Postoperative stage of the 2nd tumor was IA in 31 patients, IB in 7, IIA in 1, IIIA in 3, IIIB in 3. Median follow-up was 48.4 months after 2nd operation. The 5-year survival rate was 90.8% after 1st operation and 85.6% after 2nd operation. The 5-year survival rate in patients with p-stage IA was 96.4%. Patients with metachronous lung cancer could have a favorable outcome. Thus we need careful follow-up of the patients after treatment on the 1st lung cancer, and moreover an aggressive surgical treatment is recommended as long as their performance state or residual pulmonary function allows.
Kyobu geka. The Japanese journal of thoracic surgery 10/2010; 63(11):952-5.
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ABSTRACT: We analyzed relationships between histological subtypes of pulmonary adenocarcinomas and three gene alterations (p53, K-ras, and epidermal growth factor receptor gene), or thyroid transcription factor-1 (TTF-1) expression, and also studied prognoses by the subtypes, with or without combined multiple gene mutation status. Our purpose was to clearly determine pathogenesis, along with the best predictive value for biology and therapy-related traits. A total of 223 consecutively resected pulmonary adenocarcinomas were sub-classified using either the World Health Organization (WHO) or our five-cell type (FCT) classification system (hobnail, columnar/cuboidal, mixed, polygonal/oval, and goblet cell types). DNAs extracted from frozen samples of the adenocarcinomas were examined for gene alterations, and TTF-1 expressions were determined using immunohistochemistry. Next, relationships among the various data and clinicopathological factors were analyzed. The most striking result was: while almost 70% of adenocarcinomas were sub-classified as a mixed subtype by WHO, the FCT classified many of them as other cell subtypes. The FCT closely reflected differences in etiological factors, cellular lineages, and frequencies of gene mutations; and whether the data from combined gene mutations were used or not, differences among the cell types in postoperative survivals appeared. In contrast, subtypes of WHO did not show any association with the gene alteration or prognosis, and the FCT more suitably indicated sensitivity to gefitinib therapy than did WHO. The FCT combined with multiple gene mutation status appears to be useful in indicating pathogenesis and predicting the biological nature of pulmonary adenocarcinomas, and it could facilitate development of new therapies for each subtype.
Cancer Science 07/2010; 101(7):1745-53. · 3.33 Impact Factor
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ABSTRACT: A 6-day-old girl underwent pacemaker implantation for complete atrioventricular block through a subxiphoid incision. Epicardial leads were sutured on the right ventricle, and the pulse generator was buried in a subcutaneous pocket on the abdomen. After 3 days, the pacemaker site became infected. The whole pacing system was extracted immediately and replaced by temporary pacing leads. After the infection was controlled, a new pacemaker was implanted through a left thoracotomy during which an original Blalock-Taussig shunt was established. The new pulse generator was buried in a subcutaneous pocket in the left precordial area. The patient's postoperative course was uneventful, and there have been no signs of lead problems or re-infection. Using temporary pacing leads as a bridge to implant a new system and choosing a precordial subcutaneous pocket for the implantation site following suturing of the leads on the left ventricle through a left thoracotomy were useful in this case.
Kyobu geka. The Japanese journal of thoracic surgery 02/2010; 63(2):116-8.
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Ryuji Makita,
Akatsuki Kokaze,
Tadahiro Ohtsu,
Mamoru Ishikawa,
Naomi Matsunaga,
Kanae Karita,
Masao Yoshida,
Nobukazu Tanaka,
Minoru Yamamoto, Junichi Hayashi,
Yutaka Takashima,
Kiyoshi Kitamoto
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ABSTRACT: Reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism, is reportedly associated with longevity in the Japanese population. The ND2-237Met genotype may exert resistance to atherogenic diseases, such as myocardial infarction or cerebrovascular disorders. To investigate whether ND2-237 Leu/Met polymorphism is associated with yearly changes in serum lipid levels, we conducted a longitudinal study of 107 healthy Japanese male subjects. Analysis of covariance revealed that the interaction between the ND2-237 Leu/Met genotypes and habitual drinking was significantly associated with yearly changes in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels (p=0.036 and p=0.006, respectively). In multiple regression analysis, daily drinking was significantly and positively associated with yearly changes in serum LDLC levels in men with ND2-237Met (p=0.026). After adjusting for covariates, yearly changes in serum LDLC levels were significantly lower in non-daily drinkers with ND2-237Met than in those with ND2-237Leu (p=0.047). These results suggest that ND2-237Met has a beneficial impact on yearly changes in serum LDLC in non-daily drinkers but not in daily drinkers.
Acta medica Okayama 12/2009; 63(6):331-8. · 0.84 Impact Factor
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Manabu Isoda,
Haruo Hanawa,
Ritsuo Watanabe,
Tsuyoshi Yoshida,
Ken Toba,
Kaori Yoshida,
Mayuko Kojima,
Keita Otaki,
Kazuhisa Hao,
Limin Ding,
Komei Tanaka,
Tsugumi Takayama,
Kiminori Kato,
Yuji Okura,
Makoto Kodama,
Yoshimi Ota, Junichi Hayashi,
Yoshifusa Aizawa
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ABSTRACT: The micronutrient iron is an essential component that plays a role in many crucial metabolic reactions. The peptide hormone hepcidin is thought to play a central role in iron homeostasis and its expression is induced by iron overloading and inflammation. Recently, hepcidin has been reported to be expressed also in the heart; however, the kinetics of altered hepcidin expression in diseases of the heart remain unknown. In this study, we examined cardiac expression of hepcidin in rat experimental autoimmune myocarditis (EAM), human myocarditis and rat acute myocardial infarction (AMI). In rat EAM and AMI hearts, hepcidin was expressed in cardiomyocytes; ferroportin, which is a cellular iron exporter bound by hepcidin, was also expressed in various cells. Analysis of the time course of the hepcidin to cytochrome oxidase subunit 6a (Cox6a)2 expression ratio showed that it abruptly increased more than 100-fold in hearts in the very early phase of EAM and in infarcted areas 1 day after MI. The hepcidin/Cox6a2 expression ratio correlated significantly with that of interleukin-6/gamma-actin in both EAM and AMI hearts (r=0.781, P<.0001 and r=0.563, P=.0003). In human hearts with histological myocarditis, the ratio was significantly higher than in those without myocarditis (0.0400+/-0.0195 versus 0.0032+/-0.0017, P=.0045). Hepcidin is strongly induced in cardiomyocytes under myocarditis and MI, conditions in which inflammatory cytokine levels increase and may play an important role in iron homeostasis and free radical generation.
The Journal of nutritional biochemistry 08/2009; 21(8):749-56. · 4.29 Impact Factor
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ABSTRACT: Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.
Metabolism: clinical and experimental 07/2009; 58(6):739-45. · 2.59 Impact Factor
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ABSTRACT: The pathophysiological effects of the activation or inhibition of the nitric oxide (NO)-mediated pathway on the deformability of red blood cells (RBC) were evaluated in the presence of hypercholesterolemia induced in rabbits fed a cholesterol-rich diet. RBC deformability was assessed using a microchannel array flow analyzer system. The maximum passage time (MPT) by flowing a suspension of RBC through the microchannels was used as an index of RBC deformability. During cholesterol feeding for 12 weeks, MPT gradually increased with no significant elevation in the serum asymmetric dimethylarginine (ADMA) and arginine/ADMA ratio. The reduction in RBC deformability associated with hypercholesterolemia was significantly improved during incubation with each of three different NO pathway activators: a NO donor, 8-bromo-cyclic GMP, and arginine; however, no additional reduction was observed with ADMA administration. The inhibition of NO synthase due to ADMA caused a significant reduction in the deformability of normal RBC, which was reversed with NO pathway activation. These results suggest that impaired RBC deformability may be associated with a dysfunction in the NO pathway that is partially dependent upon the accumulation of ADMA in RBC, and exogenous NO pathway activators may improve the microcirculation by restoring RBC deformability in the presence of hypercholesterolemia.
Journal of atherosclerosis and thrombosis 01/2007; 13(6):286-94. · 2.69 Impact Factor
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ABSTRACT: Flexible treatments for intimal hyperplasia after angioplasty are still needed. The aim of this study was to demonstrate the long-term effects of vascular photodynamic therapy with talaporfin sodium on intimal hyperplasia following interventional injury. Intimal hyperplasia was induced by balloon distension injury to the carotid artery in 31 rabbits. Talaporfin, 5.0 mg/kg, was delivered systemically immediately after balloon injury. The injury site was irradiated with a diode laser light of wavelength 664 nm using a fluence of 50 J/cm2 after 30 min. At day 3 and weeks 3, 6, 9, 15, and 25 after photodynamic therapy, the treated artery of each rabbit was excised and examined immunohistochemically. Thirty minutes after talaporfin administration, drug fluorescence was found only in the balloon-injured carotid artery wall. At 3 days, no smooth muscle cells were seen in the media of the photodynamic therapy-treated arterial segments. Intimal hyperplasia developed progressively in the balloon-injured and untreated segments; however, in the segments treated with photodynamic therapy, intimal hyperplasia was markedly suppressed until 25 weeks and the media was repopulated by smooth muscle cells without macrophages. Vascular photodynamic therapy with talaporfin may be used to inhibit restenosis after vascular intervention.
Medical Molecular Morphology 01/2006; 38(4):225-32. · 1.39 Impact Factor
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ABSTRACT: A 45-year-old female who had cardiac surgery 40 years earlier was transferred to our hospital because of refractory fever. Echocardiography showed an intrapericardial mass. Gallium-67 (67Ga) scintigraphy revealed abnormal accumulation at the same site of the intrapericardial mass and thoracoscopy revealed that the mass was a pericardial abscess (PA). After surgical resection, drainage and antibiotic therapy, her fever subsided and the abnormal accumulation of 67Ga disappeared. This case showed a very rare clinical course of PA and the importance of 67Ga scintigraphy for its diagnosis.
International Heart Journal 12/2005; 46(6):1119-22. · 1.16 Impact Factor
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ABSTRACT: In patients with Brugada syndrome, implantable cardioverter defibrillator (ICD) is the only reliable treatment to prevent sudden death though, in some cases, internal defibrillation may be unsuccessful. The aim of this study was to examine the determinants of defibrillation failure, with a focus on electrophysiologic characteristics.
The study included 51 patients treated with ICD: 22 with Brugada syndrome and 29 with structural heart disease (SHD). The prevalence of defibrillation energy requirement precluding the programming of a 10-J safety margin, the mean right ventricular effective refractory period (ERP), and mean induced ventricular fibrillation cycle length (VFCL) from the stored ICD electrograms, were compared between the two patient groups.
High defibrillation requirements were observed in 18% of patients with Brugada syndrome versus 0% of patients with SHD. However, the patients with SHD had larger heart size than those with Brugada syndrome. Mean VFCL and mean ERP were both significantly shorter in patients with Brugada syndrome than in patients with SHD, and ERP and VFCL were significantly correlated.
Patients with Brugada syndrome have a high prevalence of high defibrillation energy requirement, and short ventricular ERP and VFCL.
Journal of Cardiovascular Electrophysiology 04/2005; 16(3):262-6. · 3.06 Impact Factor
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ABSTRACT: We investigated the relation of arterial stiffness, considered an independent predictor of cardiovascular events, to cardiovascular risk factors in a population-based study of 1023 subjects. An Arterial Stiffness Index (ASI) was developed to evaluate arterial stiffness based on an analysis of the pulse wave amplitude pattern acquired from measurements of brachial blood pressure. In control subjects (n = 266) without any major risk factors, the ASI was 46 +/- 11, and increased with age (r = 0.346). The ASI was significantly higher in women ranging from 50 to 54 years of age than in age-matched men. The ASI rose in correlation with the number of risk factors. Subjects with two risk factors showed a significantly higher ASI than those without any risk factors (54 +/- 26 vs. 46 +/- 11). The ASI was significantly increased in diabetic subjects with hypertension in comparison to those without hypertension. Furthermore, hyperlipidemic subjects with hypertension showed significantly higher values than those without hypertension. ASI could be a useful predictor of cardiovascular events in hypertensive subjects with multiple risk factors.
Journal of atherosclerosis and thrombosis 02/2005; 12(3):175-80. · 2.69 Impact Factor
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ABSTRACT: Osteogenic protein, a member of the transforming growth factor-beta superfamily, has been reported to decrease the expression of intercellular adhesive molecules and prevent neutrophil accumulation and activity in tissue injury.
To examine the effects of osteogenic protein on ischemia/reperfusion in rat hearts.
Reperfusion was established after a 90 min ligation of the proximal left coronary artery in rats. Recombinant human osteogenic protein-1 (200 mug/kg) was administered via the femoral vein just before reperfusion. Intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) expression and infarct size were evaluated using Northern blotting and triphenyl tetrazolium chloride staining, respectively. Terminal deoxynucleotidyl transferase mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick end labeling (TUNEL) staining was also performed.
In osteogenic protein-1 treated rats, the expression of ICAM-1 mRNA in ischemia/reperfusion hearts rapidly increased 4 h after reperfusion, although, the increase was lower than that observed in the vehicle-treated hearts (7.4+/-1.6-fold versus 14.6+/-3.7-fold increase compared to the increase observed in preligation control hearts, respectively). Similarly, in day 1 and day 7 hearts, the increase in ICAM-1 mRNA expression was significantly lower in ischemia/reperfusion hearts from rats treated with osteogenic protein-1 than in vehicle-treated rats (2.5+/-0.1-fold versus 5.8+/-2.3-fold and 1.5+/-0.3-fold versus 3.5+/-0.2-fold, respectively). Infarct size in rats treated with osteogenic protein-1 was significantly smaller than that observed in rats treated with vehicle (13.1+/-1.2% versus 28.5+/-5.7% of the left ventricle, P<0.01). The percentage of TUNEL-positive cardiomyocytes in ischemia/reperfusion hearts in rats treated with osteogenic protein-1 was significantly lower than in rats treated with vehicle (17.1+/-5.3% versus 31.1+/-4.5%, P<0.01).
The present study demonstrated that recombinant human osteogenic protein-1 suppressed ICAM-1 mRNA expression, reduced infarct size and decreased TUNEL-positive cardiomyocytes in ischemic/reperfused rat hearts.
Experimental and clinical cardiology 02/2003; 8(4):195-200. · 0.58 Impact Factor
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ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is mitogenic and chemotactic for many cell types. HB-EGF is induced in pathological states which require cell mitogenesis and proliferation, including angiogenesis, and has been reported to interact functionally with basic fibroblast growth factor (bFGF). To test our hypothesis that HB-EGF mRNA expression is increased in myocardial infarction, we used Northern hybridization in rats to investigate the expression of HB-EGF and EGF receptor mRNAs expression in the infarct zone compared to the expression of bFGF and FGF receptor mRNAs. We also performed in situ hybridization to identify the cells responsible for HB-EGF mRNA production. HB-EGF mRNA rapidly increased after ligation (mean +/- SE, 5.6+/-0.23-fold increase at 6 hours compared to the preligation heart levels) and reached a maximum level (9.1+/-0.42-fold increase) around 12 hours. HB-EGF mRNA then gradually decreased on day 1 (5.8+/-1.0-fold increase), day 2 (3.2+/-0.94-fold increase) and day 3 (1.9+/-0.33-fold increase) after ligation. Parallel changes in bFGF mRNA expression were observed (6, 12 hours, days 1, 2 and 3; 3.6+/-0.42-, 5.3+/-0.12-, 2.3+/-0.12-, 1.7+/-0.03- and 0.95+/-0.03-fold increase, respectively). EGF receptor (ErbB-1) mRNA was gradually increased on day 2 (2.4+/-0.53-fold increase), day 7(4.0+/-0.61-fold increase) and day 14 (7.0+/-0.61-fold increase). Similarly, FGF receptor (FGF receptor-1) mRNA was gradually increased (days 2,7 and 14; 1.3+/-0.13-, 1.5+/-0.17- and 2.3+/-0.15-fold increase, respectively). Reperfusion after a 2-hour ligation (too late to salvage myocytes) enhanced HB-EGF (12 hours, 16.8+/-1.8-fold increase) and bFGF (12 hours, 10.4+/-1.1-fold increase) mRNA expression. The cells responsible for the increased production of HB-EGF mRNA were shown by in situ hybridization to be surviving myocytes located in the infarct peripheral zone around infarct necrotizing tissue. In conclusion, our results demonstrated a rapid increase in HB-EGF mRNA expression concomitant with an increase in bFGF mRNA expression, suggesting that HB-EGF and bFGF might play some role in the course of pathological changes in the infarct in the early inflammatory phase. Reperfusion at times too late to salvage myocytes accelerated sequential changes in the expression of both HB-EGF and bFGF mRNAs.
Archiv für Kreislaufforschung 06/2002; 97(3):214-22. · 7.35 Impact Factor
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ABSTRACT: A new photosensitizer, PH-1126, was administered intravenously into the ear veins of cholesterol-fed atherosclerotic rabbits
at a dose of 1 mg/kg of body weight. At 24 hr after PH-1126 administration, the atherosclerotic abdominal aorta was irradiated
with a krypton ion laser with a wavelength of 647 nm by 100 J/cm2 by the laparoscopical approach. Twenty-four hours later, the abdominal aorta irradiated by the laser beam was excised for
histological analysis. In the atherosclerotic plaques with photodynamic treatment, damaged foam cells were observed by scanning
electron microscopy and transmission electron microscopy. Some of these cells were exposed to the aortic lumen. No significant
changes were shown in the abdominal aorta either with plaques not injected with PH-1126 or without plaques after photodynamic
treatment. These findings suggest that atherosclerotic plaques of the abdominal aorta could be selectively degraded by laparoscopical
photodynamic treatment.
Medical Electron Microscopy 11/1996; 29(3):137-144.
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ABSTRACT: Osteonectin and osteopontin, two secreted matricellular proteins, have a variety of functions that are exerted through interaction with matrix components. These proteins appear in response to tissue injury. To test our hypothesis that osteopontin and osteonectin are expressed with spatially and temporally different patterns in myocardial infarct tissue, we investigated osteonectin and osteopontin expression in experimentally induced myocardial infarction in rats, in comparison with Type I collagen expression. Northern blotting demonstrated that osteonectin mRNA did not markedly increase on Day 2 after the infarction, but it increased on Days 7 and 14 by 1.7+/-0.12- and 1.8+/-0.01-fold compared to that in preligation hearts. In contrast, osteopontin mRNA was increased on Day 1 (41.9+/-11.3-fold increase) and on Day 2 (58.3+/-7.6-fold increase), and then it declined on Days 7 and 14 (24.8+/-9.0- and 13.5+/-4.7-fold increase, respectively). In situ hybridization revealed that osteonectin mRNA signals were observed in fibroblasts, myofibroblasts and macrophages around infarct necrotic tissue on Days 7 and 14. Osteopontin mRNA signals were observed in macrophages in the infarct marginal zone on Day 2. Immunopositive staining for both osteonectin and osteopontin showed the same pattern as that obtained by in situ hybridization. The time course of osteonectin mRNA was almost parallel with that of Type I collagen mRNA, while that of osteopontin was not. These results demonstrated spatially and temporally different expression patterns of osteonectin and osteopontin in myocardial infarction and suggest that osteonectin appears to be involved in the pathological course in the late phase after infarction concomitantly with Type I collagen, while osteopontin may play a role in the early phase.
Cardiovascular Pathology 12(4):186-94. · 2.07 Impact Factor
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Takuya Ozawa,
Kiminori Kato,
Hirofumi Sanada,
Yashiro Makiyama,
Takashi Saigawa,
Satoru Souda,
Shigeo Hashimoto,
Tatsuo Furukawa,
Ken Toba,
Makoto Kodama,
Hiroshi Fujiwara,
Osamu Namura, Junichi Hayashi,
Nobuhiko Yoshimura,
Yoshifusa Aizawa
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ABSTRACT: The authors performed autologous bone marrow mononuclear cells implantation (BMI) in a 79-year-old man with critical limb ischemia. After BMI, the resting pain of the ischemic leg improved gradually. They measured the plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and serum hepatocyte growth factor (HGF) in the blood from bilateral femoral veins. Before BMI, the plasma VEGF and bFGF concentrations were much greater in the ischemic leg than in the other lower limb, but decreased to the same concentrations as those in the contralateral lower extremity after BMI. The large concentrations of the angiogenic factors VEGF and bFGF in plasma indicate the severity and extent of the leg ischemia. BMI resulted in lower levels of VEGF and bFGF, and this fall is the hallmark of the effectiveness of BMI in the treatment of peripheral artery disease.
Angiology 57(2):235-9. · 1.51 Impact Factor
