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Cellular senescence is a state of irreversible cell proliferation arrest provoked by a persistent DNA damage induced by a variety of potentially oncogenic signals, and it functions as a primary tumor-suppression mechanism. Recent studies, however, revealed that senescent cells have the potential to secrete numerous inflammatory cytokines, chemokines, growth factors and matrix-remodeling factors, since unlike apoptotic cells, senescent cells are viable for a long period of time. This newly identified phenotype of cellular senescence, called senescence-associated secretory phenotype(SASP or senescence-associated secretome), could potentially provide beneficial effects, such as tissue repair, but sometimes could induce deleterious side effects, such as cancer progression, depending on the biological context.

It has recently become apparent that obesity is associated with chronic inflammation and several common types of cancer development. Although several events were proposed to be involved in these pathologies, the precise mechanisms underlying obesity-associated inflammation and cancer largely remain unclear. Here, we show that senescence-associated secretory phenotype (SASP) plays crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of a bacterial metabolite that cause DNA damage. The enterohepatic circulation of the bacterial metabolites provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn, secretes various inflammatory and tumour promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Importantly, reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the induction of SASP by the gut bacterial metabolite in HSCs plays key roles in obesity-associated HCC development. Interestingly, moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with nonalcoholic steatohepatitis (NASH), implying that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer.

A 78-year-old female presented with a chief complaint of palpitations. She was diagnosed with a large unruptured aneurysm of the sinus of Valsalva accompanying aortic regurgitation and right coronary artery ostial stenosis. When the aneurysm was resected following cardiac arrest, it was found to be an aneurysm with the right Valsalva sinus at the orifice. Root replacement was not required because there was no aortic annular dilatation. Patch closure as well as aortic valve replacement were conducted. The right coronary artery was diverged from the aneurysm and the aperture thereof was severely stenosed. Therefore, bypass surgery was additionally conducted. Postoperative course was uneventful. An unruptured aneurysm of the sinus of Valsalva, which is a relatively rare disease, is asymptomatic in many cases and tends to have grown large when found. Because the postoperative results were relatively good, we believe that surgery should be performed at an early stage in order to avoid rupture.

In this prospective multicenter study, we investigated the changes in serum prostate-specific antigen (PSA) and testosterone levels after treatment with antiandrogen chlormadinone acetate (CMA) in patients with benign prostatic hyperplasia (BPH). The inclusion criteria for the patients were as follows : PSA value of C10 ng/ml, maximum urine flow rate of ＜15 ml/s, estimated prostate volume of B20 ml, International Prostate System Score (IPSS) of B8, and IPSS-quality of life (QOL) index of B2. Of the 115 patients who registered, 114 qualified for this study. The patients were treated with CMA (50 mg/day) for 16 weeks ; this was followed by a no-CMA phase of 32 weeks. When compared with the baseline PSA level, the levels at 8 and 16 weeks of treatment had decreased by 56.4% (95% confidence interval [CI], 51.1-1.2) and 57.6% (95% CI, 52.3-62.4), respectively. Similarly, when compared with the baseline testosterone level, the levels at 8 and 16 weeks of treatment had decreased by 90.1% (95% CI, 87.8-91.9) and 84.4% (95% CI, 80.7-87.4), respectively. After treatment discontinuation, the PSA levels gradually increased and returned to baseline in 32 weeks. However, the testosterone levels returned to baseline in only 8 weeks. Although patients over 80 years of age showed a gradual decrease in these levels when compared with younger patients, the changes in the levels of PSA and testosterone were not affected by age. Thus, in order to use antiandrogen agents including CMA for treating BPH, we need to determine the PSA value that converted it into double.

Problems associated with arterial access can sometimes occur in elder patients with arteriosclerosis. This study examined the management of patients with restricted arterial access using thoracic endovascular aortic repair (TEVAR). Thirty-four consecutive patients underwent TEVAR at our institution. TEVAR was performed using a Gore TAG device (n = 20), Talent thoracic stent graft (n = 10), and a homemade endoprosthesis device (n = 3). The sizes of the applied sheath introducer or delivery catheter were 20 Fr (n = 1), 22 Fr (n = 12), 24 Fr (n = 17), and 25 Fr (n = 4). Although the procedure was completed in all cases, additional procedures for catheter preparation were required in 8 patients (23.5%). Percutaneous transluminal angioplasty (PTA) with stents placed in the iliac artery (n = 3) or the installation of a bypass conduit (n = 4) was also carried out. For the remaining cases, in which advancement of the TAG sheath introducer to the appropriate position was not possible, the endoprosthesis was deployed without the sheath introducer. Two cases required PTA after the procedure due to an injury of the iliac artery. Although some additional procedures may be required, TEVAR can be performed in patients with problems of arterial access.

We report a case of tricuspid valve endocarditis with a ventricular septal defect (VSD). A 54-year-old female who had a history of dental therapy admitted to our hospital with a fever of unknown origin. Echocardiography showed vegetation attached to the tricuspid valve and small VSD. The direct closure of VSD and tricuspid valve replacement was performed. The patient's postoperative course was uneventful.

The ruptured thoracic aortic aneurysm is still a dramatic even with very poor outcome, whereby its survival depends largely on early diagnosis and operation. We report a successful case of aortic arch replacement for ruptured aortic arch aneurysm with cardiac tamponade. Lethal hemopericardium causing cardiac tamponade is most commonly seen as a complication of acute myocardial infarction or acute aortic dissection, and subsequent rupture of the heart or ascending aorta leads to the rapid accumulation of blood within the poorly distensible pericardial sac. Our case was operated upon emergency basis due to hemopericardium. On operative findings, the aortic aneurysm located the minor curvature of aortic arch and was a huge saccular shape. In surgical procedure, the total arch replacement was completed using selective cerebral antegrade perfusion with deep hypothermia. Postoperative course was uneventful and no cerebral complication was observed after surgery.

We report here a unique case of acute-onset dementia caused by a posterior fossa dural arteriovenous fistula (AVF), which was successfully treated by surgical resection of the isolated transverse-sigmoid sinus combined with endovascular procedures. A 70-year-old female was admitted to our hospital with acute-onset dementia and pulsatile tinnitus on the left side. CT scan revealed a low-density area in the parieto-temporal region. Cerebral angiography revealed a dural AVF of the transverse-sigmoid sinus with retrograde drainage into cerebral cortical veins. After transarterial endovascular embolization of the dural AVF, a xenon-CT scan revealed increased cerebral blood flow. Four months postoperatively, however, she was admitted to our hospital again with seizure and aphasia due to recanalizaion of the dural AVF. After trans-arterial embolization, transvenous embolization was attempted, but was unsuccessful due to inaccessibility of the isolated sinus segment. Since this patient could not be cured by endovascular embolization, an open surgical resection of the isolated sinus segment was performed. Following this, CT scans revealed that the low density area present on the first admission had disappeared. The patient's dementia resolved postoperatively. We discuss the pathophysiological mechanism by which venous ischemia due to dural AVF can cause reversible dementia.

In this paper, we report the purification and partial characterization of human platelet aggregation factor form the extracellular products (ECP) of Streptococcus mitis (S. mitis) isolated from a patient with Kawasaki disease (KD). Platelet aggregation reaction was carried out using platelet-rich plasma (PRP) and washed platelets suspended in ACD-PBS. The aggregation factor was designated as S. mitis-derived human platelet aggregation factor (Sm-hPAF). The results obtained were as follows. 1) Sm-hPAF was isolated by chromatography on DEAE-Sepharose CL-6 B, hydroxyapatite and Superdex 75 columns. The purified Sm-hPAF showed a single band upon SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and molecular weight of approximately 66 kDa on SDS-PAGE. The isoelectric point (pI) of Sm-hPAF was 8.5, and Sm-hPAF showed an absorption peak at 278 nm on absorption spectra. When the platelet aggregation activity of the Sm-hPAF was compared with that of ECP, the specific aggregation activity of the of Sm-hPAF was significantly increased (up to 28-fold). Sugars were not found in Sm-hPAF. The sequence of the first 15 amino-terminal amino acid residues were H.Asp-Glu-Gln-Gly-Asn-Arg-Pro-Val-Glu-Thr-Glu-Asn-Ile-Ala-Arg. The platelet aggregation activity of Sm-hPAF was inactivated by heating at 45 degrees C for 10 min. 2) PGE2 was released from platelets after incubation for 10 min with Sm-hPAF in a dose-dependent fashion. Platelet aggregation by the Sm-hPAF was totally inhibited by either PGE1, or GRGDS, but these reagents did not inhibit the platelet aggregation by collagen. 3) Histological examination of the rabbit skin sites showing an early reaction revealed increased dilatation of the veins and capillaries with cellular infiltration in the perivascular space of the dermis. Hyperplasia of the endothelial cells was noted. Degeneration of the vascular walls was observed in the later stages of the reaction. Aggregation of red cells in the vascular endothelium was also observed. Sm-hPAF was capable of producing vasculitis. 4) Twenty (76.9%) platelet-rich plasma samples (PRP) derived from 26 healthy human volunteers reacted with Sm-hPAF, but the remaining 6 PRPs were not reactive. Preliminary study suggests the existence of an inhibitory factor in plasma from nonreactive donors.

In order to develop a non-invasive monitor of cerebral blood flow during aortic arch surgery, reliability of the laser Doppler flowmetry of the bulbar conjunctiva was evaluated. The blood flow of the bulbar conjunctiva may represent the cerebral blood flow because the ophthalmic artery originating from the internal carotid artery supplies the blood to the bulbar conjunctiva. A laser Doppler flowmeter (Advance Co., ALF201) and a specially designed probe was prepared to measure the blood flow of the bulbar conjunctiva. The probe was designed to stay in a fixed position on the bulbar conjunctiva when the eye lid is closed, so that it can maintain a stable measurement. The shape of probe is a small box, 7.5 x 4.0 x 2.0 mm connected to a glass fiber cable 2 mm in diameter, as the signal to convey to the flowmeter. Eight mongrel dogs were used for the experimental study. The brachiocephalic vessels were exposed to measure the pressure and the blood flow of the carotid arteries. The blood flow of the cerebral cortex and the bulbar conjunctiva was measured by the laser Doppler flowmetry. When the carotid artery was clamped, the blood flow of the bulbar conjunctiva fell instantaneously in 1.35 +/- 0.85 seconds and reached the plateau in 9.60 +/- 4.15 seconds. The flow returned to the previous value in 7.70 +/- 3.75 seconds after the clamp was removed. A significant positive correlation between the blood flow of the bulbar conjunctiva and that of the cerebral cortex was observed (r = 0.78, p < 0.001, n = 2). When the extracorporeal circulation was used, the waveform of the bulbar conjunctival blood flow was synchronized to the small pulse wave generated by the pump. Although the measurement of the bulbar conjunctival blood flow by laser Doppler flowmetry is an indirect method of monitoring the cerebral blood flow, it can provide non-invasive, continuous, and reliable measurement. We conclude that this is a useful method to monitor the cerebral blood flow during aortic arch surgery.

Correlation between gastric emptying time measured by a radioisotope method and plasma acetoaminophen level was studied in 11 preoperative early gastric cancer in semisolid meal. A significant correlation was found between both gastric emptying half-time and plasma acetoaminophen level at 30, 45 minutes after ingestion of meal, and plasma acetoaminophen level at maximum. We conclude that acetoaminophen analysis is useful to measure gastric emptying at semisolid meal.

Recent advances in the field of peripheral arterial reconstruction have been remarkable. These advances are mainly derived from the development of diagnostic technology such as Doppler ultrasound analysis, further refinement of surgical technique including surgical instruments and materials, and naturally improvement of patient care in the pre-, peri- and postoperative period. During the past 14 years we have performed peripheral arterial reconstruction in 1,200 cases (1,660 limbs) mainly with occlusive lesion due to arteriosclerosis obliterans. In our hand, aorto-iliac occlusive lesion has been routinely bypassed with Dacron prostheses and the secondary patency rate at eleven years reached 96.5%. The main problems encountered in this region were anastomotic aneurysm in the femoral artery (3.9%) and graft infection (1.2%). In the infrainguinal region there are still problems to be solved, although the primary (secondary) 5 year patency rates of reversed vein graft as well as in situ vein graft including femoro-popliteal below knee and femoro-crural bypasses have exceeded 70% (85%). First, there is no graft material comparable to the autogenous vein (AVG). Secondly, many of the AVG should suffer occlusive pathological changes from the environment in the long term following surgery. At the present time, we have no effective method to solve these problems, therefore we should follow up the patients heedfully to maintain the graft patency as well as to improve their quality of life and prognosis.

Two cases of broncholithiasis, removed bronchoscopically, are reported. Case 1 was a 38-year-old female who was admitted with hemoptysis. The chest tomogram showed calcification near the right middle lobe bronchus. Bronchoscopy revealed a broncholith in B4. Component analysis showed that more than 98% of this stone consisted of calcium carbonate. Case 2 was a 75-year-old male who was hospitalized because of continuous cough. The chest radiograph showed calcification and atelectasis in the right upper lobe. Bronchoscopically, right B3 was obstructed by a broncholith. After removal of the stone, the distal part of B3 was noted to be filled with pus. Analysis of the stone's composition revealed calcium phosphate (77%) and calcium carbonate (23%).

In clinical and experimental studies we assessed images of digital subtraction coronary angiography (DSA) for evaluating regional myocardial perfusion. Myocardial perfusion was assessed by injecting contrast medium into the coronary artery, and by imaging the regional myocardium using DSA. On the time-density curve obtained from the myocardial region of interest, we calculated the time to peak concentration (TPC) and the exponential washout rate (T). TPC and T were measured in five patients with stable effort angina pectoris (AP) and left anterior descending (LAD) lesions before and after percutaneous transluminal coronary angioplasty (PTCA). The values of 1/T increased significantly from 0.09 +/- 0.02 l/sec to 0.21 +/- 0.04 l/sec (p less than 0.01) after PTCA, but l/TPC did not change. No significant difference in ejection fractions was observed between the patients with AP and the normal subjects (n = 7), while the regional percent area shrinkage in the anterolateral and apical regions supplied by the LAD was significantly decreased in the patients with AP compared with those of normal subjects (anterolateral: 39.8 +/- 8.8% vs 51.3 +/- 6.8%, apical: 36.6 +/- 8.4% vs 52.4 +/- 13.4%, both p less than 0.01). In 10 anesthetized dogs with varying degrees of reduction in the left circumflex coronary artery (LCX) blood flow (CBF: categories of stenosis (S1-S5), we compared 1/TPC and 1/T with regional myocardial function (systolic wall thickening: %WTh). With varying LCX stenosis, there were no significant changes in heart rate and mean aortic pressure and significant linear correlations were observed between %WTh and 1/TPC (r = 0.51), between %WTh and 1/T (r = 0.55). At S1 (CBF: 100-90% of the control), neither %WTh nor 1/TPC differed from that of the controls, but 1/T was significantly decreased (80% of the controls, p less than 0.01). From S3 (CBF: 79-60%) to S5 (CBF: 39-0%), %WTh, 1/TPC and 1/T were significantly decreased from those of the control levels (all p less than 0.01). However, at S5 (CBF: 39-0%) the values of 1/TPC (71% of controls) and 1/T (33%) did not differ from those at S4; whereas, %WTh was markedly reduced and the systolic thinning of the ventricular wall occurred at S5. Therefore, in critical coronary stenosis, 1/T was more sensitive than 1/TPC or wall dynamics for assessing myocardial ischemia. Both 1/TPC and 1/T, as well as %WTh, were useful for assessing moderate myocardial ischemia; however, these DSA indices had considerable limitations for evaluating the severity of myocardial ischemia when CBF was markedly reduced.

Mitochondrial enzymes in rat livers or intestines were investigated in experimental models with ethanol- or other hepatotoxic agent-induced liver injuries and extrahepatic cholestasis. In clinical experiment, activities of mitochondrial GOT (mGOT) and ornithine carbasmyl transferase (OCT) were examined in alcoholisms and patients with other various liver diseases. Results obtained are as follows; 1) The activities of OCT and mGOT were increased particularly at onset of acute hepatitis, in chronic active hepatitis and intrahepatic cholestasis, showing that mitochondria were injured strikingly in these diseases. The activities in alcoholics were not so great, however mGOT/total-GOT ratio was increased in level than in other diseases. 2) Changes in mitochondrial enzymes of rat liver treated with ethanol were too varied to catch the actual tendency in this pathologic state. 3) Administration of galactosamine, carbon tetrachloride, or alpha-naphthyl isothiocyanate (ANIT) caused a significant fall in activities of succinate cytochrome C reductase and OCT, along with increase in serum activity of OCT, indicating severe mitochondrial injury with these drugs. Extrahepatic cholestasis following bile duct ligation showed the same changes of mitochondrial enzymes in liver tissue and serum. 4) These data indicate that observation of activities of serum OCT, mGOT, along with mGOT/total-GOT ratio are useful for estimation of mitochondrial damage in extra- and intra-hepatic cholestasis, and acute or chronic active hepatitis. The changes in alcoholic fatty liver was not so subtle as compared with other liver diseases. 5) It is surmized that smooth endoplasmic reticulum was increased in content and pentose phosphate shunt was inhibited by chronic ethanol treatment, estimating from increased activities of NADH-ferricyanide reductase and gamma-glutamyl transpeptidase, and decreased activity of glucose-6-phosphate dehydrogenase. 6) The changes in hepatic enzymes with ethanol treatment were paralleled with those of intestinal ones, indicating that metabolic changes in intestine contribute someway in the formation of alcoholic fatty liver. 7) Chronic ethanol treatment induced lowered active transport in intestinal mucosa, which indicates inhibition in absorption of various nutrients by ethanol.

Forty-two cases of hematological malignancy (18 cases of CML, three cases of polycythemia vera, 10 cases of malignant lymphoma and 11 cases of multiple myeloma) were treated with MCNU. The results obtained were as follows. MCNU was markedly effective on CML cases, being especially useful during the chronic phase, and a partial remission was observed in one of three patients with CML blastic crisis. A good response was observed in all cases with polycythemia vera. In some cases of malignant lymphoma, a fair response was observed. No response was observed in any of the cases of multiple myeloma. Myelosuppression was a major side effect of MCNU, but other side effects other than melena were not severe.