SHINGO IWATA - Academia.edu (original) (raw)

Papers by SHINGO IWATA

Surgical Case Reports, 2020

Background We experienced a case of early stage lung cancer involving a morbidly obese patient. O... more Background We experienced a case of early stage lung cancer involving a morbidly obese patient. Obesity is associated with a higher incidence of surgical complications. We examined the effectiveness of laparoscopic sleeve gastrectomy as a primary weight loss procedure in a morbidly obese patient who required oncological surgery. Case presentation A 64-year-old morbidly obese female with a body mass index of 43.5 kg/m2 was referred to our hospital to undergo weight loss. A right-sided lung mass was found incidentally on computed tomography conducted in preparation for laparoscopic sleeve gastrectomy, which was performed prior to tumor surgery. As a result, weight loss was achieved within 2.5 months after the laparoscopic sleeve gastrectomy, and the patient’s type-2 diabetes, hypertension, and dyslipidemia, which are linked to obesity, were markedly ameliorated. After a quick intraoperative pathological inspection revealed that the tumor was malignant, thoracoscopic right lung superio...

Gastroenterology, 1991

To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone bod... more To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone body ratio (acetoacetate/%hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were investigated in normal subjects, patients with chronic liver disease (Child's class A or B), and patients with hepatic failure (Child's class C). Ketone body ratio in normal subjects increased after breakfast from 0.96 to 2.00, alter lunch from 2.17 to 2.38, and after dinner from 1.23 to 2.55 with blood glucose level ranging from 103 to 141 mg/dL (5.7 to 7.8 mmol/L). By contrast, the ketone body ratio in the Child A or B group changed little and remained within a range of 0.70-1.35 despite a large change in blood glucose level from 102 to 176 mg/dL (5.7 to 9.8 mmol/L). Ketone body ratio in Child's class C remained near or below 0.4 with no response to glucose administration, despite a marked elevation in blood glucose level. These results indicate that hepatic mitochondrial redox potential undergoes diurnal changes in sharp response to meals in normal liver function but that these fluctuations are absent in patients with liver damage (Child's class A, B, and C). Furthermore, it remains at low levels in severe liver failure (Child's class C). It is also suggested that hepatic mitochondrial redox potential plays an important role in the regulation of blood glucose levels.

Journal of Laboratory and Clinical Medicine, 1997

The arterial ketone body ratio (AKBR), an established clinical tool that reflects hepatic mitocho... more The arterial ketone body ratio (AKBR), an established clinical tool that reflects hepatic mitochondrial oxidation-reduction potential, predicts the outcome of patients with shock and multiple organ failure and the postoperative outcome in patients who have undergone major liver or heart surgery. The purpose of this study was to determine the prognostic significance of AKBR in patients with acute heart failure. The subjects of this study were 52 patients with acute heart failure. The following parameters were analyzed after Cox univariate hazard analysis was performed: AKBR, plasma norepinephrine, left ventricular ejection fraction, cardiac index, pulmonary arterial wedge pressure, sex, age, human atrial natriuretic peptide, endothelin-1, and cholesterol. The follow-up period was 30 weeks with cardiac death as the end point. Stepwise multivariate proportional hazard analysis revealed that AKBR was the most significant predictor of death, followed by norepinephrine and human atrial natriuretic peptide. Curve-fitting analysis revealed that the relationship between log (norepinephrine) and AKBR could best be described by two distinct lines, with their intersection at AKBR = 0.7 and norepinephrine = 418. With these results we conducted Kaplan-Meier analysis for AKBR > or = 0.7 and AKBR <0.7. The survival rate in patients with AKBR > or = 0.7 was 100%, whereas that in patients with AKBR <0.7 was 15% (p < 0.0001, log-rank analysis). These results indicate that AKBR is a novel independent predictor of death in heart failure.

Liver International, 2004

Inhibition of tumor necrosis factorinduced apoptosis in transgenic mouse liver expressing creatin... more Inhibition of tumor necrosis factorinduced apoptosis in transgenic mouse liver expressing creatine kinase.

Journal of Surgical Research, 1996

metabolism. Under such conditions, gluconeogenesis is Glucose and energy metabolism in rat liver ... more metabolism. Under such conditions, gluconeogenesis is Glucose and energy metabolism in rat liver after suppressed, and liver mitochondria utilize mainly fatty ischemic damage was investigated by in vivo 31 P NMR acids as substrates [1]. Therefore, glucose metabolism spectroscopy, 1 H-detected 13 C NMR spectroscopy, and would be dynamically changed during the recovery in vitro 13 C NMR spectroscopy using [1-13 C]glucose as from ischemic damage depending on the condition of a tracer. Arterial ketone body ratio (AKBR; acetoacethe liver. tate/b-hydroxybutylate) and oxygen consumption of Carbon-13 NMR spectroscopy has been widely apisolated mitochondria were also examined to evaluate plied to investigate glucose metabolism using 13 C-enhepatic function. The rats were divided into three riched substrates. However, the low sensitivity of 13 C groups: (A) without ischemia, (B) 10-min ischemia, and NMR necessitated a strong magnetic field for accurate (C) 30-min ischemia. ATP was almost depleted at 10 analysis of 13 C-incorporated metabolites. Many of these min of ischemia and recovered after reperfusion, but studies were performed with liver extracts [2-5], perthe recovery was not complete. The recovery after 30fused liver [6-10], or in vivo liver [11] using a high min ischemia was smaller than that after 10-min ischresolution NMR spectrometer. Recently, 13 C NMR has emia. [ 13 C]Glucose was infused immediately after the been applied to the human liver under clinically applireperfusion, and in vivo 1 H-detected 13 C NMR demoncable magnetic field strength with or without 13 C-enstrated sequential glucose incorporation into the liver. riched glucose. Most of these studies focused on glyco-However, the incorporation depended on the blood gen synthesis and repletion. The effect of fasting or sugar levels and did not reflect hepatic function. In hormonal control on glucose metabolism in normal subvitro 13 C NMR disclosed the glycogen C-1 signal in the nonischemic group and alanine C-3 and lactate C-3 sig-jects and diabetic patients has been intensively investinals in the ischemic groups. The intensity of glycogen gated [12-16]. However, 13 C NMR has not yet been was correlated positively (r Å 0.648, P Å 0.002) and utilized as a tool for evaluation of hepatic function. We those of alanine and lactate were correlated negatively have previously reported 1 H-detected in vivo 13 C NMR (r Å 00.831, P õ 0.005 and r Å 00.710, P Å 0.005, respecspectroscopy using gradient-enhanced heteronuclear tively) to the ATP levels as measured by in vivo 31 P multiple quantum coherence (GE-HMQC) [17]. This NMR. These results suggested that ATP level particitechnique enabled us to detect [ 13 C]glucose and its mepates in glycogenesis and gluconeogenesis in the liver. tabolites in rat brain with high sensitivity using a 2-T The AKBR and oxygen consumption of isolated mitomagnetic field. In the present study, this technique was chondria were the highest in the 10-min ischemia applied to rat liver with ischemic damage. The phosgroup, which might reflect mitochondrial compensaphoenergetic changes and glucose utilization in the tory response to the decreased ATP level. ᭧ 1996 Academic liver were concomitantly examined with in vivo 31 P and Press, Inc. 13 C NMR and in vitro 13 C NMR spectroscopy. In order to evaluate mitochondrial function of the damaged liver, we also measured the arterial ketone body ratio 393

Journal of Surgical Research, 1992

Journal of Surgical Research, 1999

The mechanism underlying the fatal complications in jaundiced states after shock has not been ful... more The mechanism underlying the fatal complications in jaundiced states after shock has not been fully clarified. The present study was designed to examine the effect of hemorrhagic shock on myocardial high-energy phosphate stores and the arterial ketone body ratio (AKBR:acetoacetate/beta-hydroxybutyrate), which reflects the redox state of the liver mitochondria, in normal and jaundiced rats. At 1 week after ligation of the common bile duct, hemorrhagic shock was induced by exsanguination (mean arterial blood pressure = 40 mmHg) and maintained for 2 h. Serial changes in AKBR were measured. The myocardial adenine nucleotides phosphocreatine (PCr) and inorganic phosphate (Pi) were determined before and after hemorrhagic shock. Before shock, myocardial ATP in the jaundiced group was lower than that in the sham group. However, the myocardial PCr levels in the two groups did not differ. After reinfusion of the shed blood, ATP and PCr recovered to the preshock levels in the sham group. However, ATP and PCr were further increased in the jaundiced group. At 60 min after reinfusion, AKBR recovered to the normal level in the sham group, but decreased below 0.7 in the jaundiced group. Metabolic acidosis was more severe in the jaundiced group than in the sham group. The decrease in AKBR indicated irreversible metabolic acidosis. As a result, fatal circulatory failure occurred, although the phosphoenergetic level in the myocardium was sufficiently maintained.

Free Radical Biology and Medicine, 1994

The production of free radicals in tissues can be continually monitored by measurement of low-lev... more The production of free radicals in tissues can be continually monitored by measurement of low-level chemiluminescence. In these experiments the effects of ethanol on luminol (1 microM)-enhanced chemiluminescence were recorded in isolated perfused livers from control rats, and from rats that had undergone a 30-min period of ischemia, followed by 3 h of reinstitution of blood flow. Our previous experiments showed considerable neutrophil accumulation at this time. A routine concentration of 100 mM ethanol added after 20 min of perfusion with Krebs-Henseleit solution caused an increase in chemiluminescence of about 2000 cpm above the resting level (1600 cpm) in both control livers and livers from rats after 3 h of ischemia reperfusion in vivo. However, if ethanol was added to the perfusing medium of the isolated liver after at least 1 h of in vitro perfusion, then the magnitude of the response was very much greater (peak approximately 27000 cpm) in livers that had undergone ischemia reperfusion than in control livers (peak approximately 7000 cpm). Experiments combining addition of ethanol and the potent neutrophil stimulator, phorbol myristate acetate (PMA), plus the use of rat antineutrophil serum have shown conclusively that the very large chemiluminescent response to ethanol after prolonged in vitro perfusion is due to stimulation of neutrophil radical production.

British Journal of Surgery, 1990

Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studi... more Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polvmorphonuclear leucocvte (PMN), focusing on energy charge and function, especially superoxide anion (O2−) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitahle reduction of ferricytochrome c, the energy charge and O2− production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A. KBR > 0.7, n = 10; and group B, KBR < 0.7, n = 8. The energy charge and O2− release in group B decreased significantly from preoperative values (P < 0.001 and P < 0.01 respectively) and when compared...

Immunology Letters, 2002

The mechanism underlying immunosuppression after partial hepatectomy remains unclear. Hepatectomy... more The mechanism underlying immunosuppression after partial hepatectomy remains unclear. Hepatectomy induces lymphopenia, which is related to immunomodulation. The aim of this study was to determine whether peripheral blood lymphocytes (PBL) are susceptible to mitochondria-mediated apoptosis after hepatic resection. We compared the changes in mitochondrial membrane potential in lymphocytes from hepatectomized patients with metastatic liver tumor with the corresponding changes in lymphocytes from cholechystectomized patients, because changes in mitochondrial membrane potential have been reported to frequently occur during the early stages of apoptosis. Mitochondrial membrane potential, subpopulation, and apoptosis of lymphocytes were estimated with flow cytometry. Hepatectomy significantly (P&amp;lt;0.001) reduced postoperative mitochondrial membrane potential, while cholecystectomy slightly decreased it. Apoptosis of lymphocytes was increased on post-hepatectomy day, and this increase was correlated with the extent of mitochondrial membrane potential reduction. The major subset of lymphocytes with low mitochondrial membrane potential consisted of CD56(+) natural killer (NK) cells, and NK cell activity and cell counts significantly decreased after hepatectomy. Mitochondrial membrane potential of PBL was reduced after hepatectomy, and some lymphocytes underwent apoptosis through the mitochondrial pathway, which was one of the causes for lymphopenia. NK cells were more responsible for the decrease of mitochondrial membrane potential after hepatectomy than other lymphocytes, and the reduction in mitochondrial membrane potential in NK cells appeared to reflect modulation of the innate immune system.

Antioxidants & Redox Signaling, 2000

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity ... more Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

Research in Experimental Medicine, 1994

Changes in lipoprotein metabolism after liver transplantation from living related donors were inv... more Changes in lipoprotein metabolism after liver transplantation from living related donors were investigated in nine pediatric patients by means of biochemical and proton nuclear magnetic resonance (NMR) analyses of lipoprotein. NMR offers rapid and nondestructive measurement of lipoprotein. The ratio of esterified cholesterol to total cholesterol, expected to be a prognostic indicator after liver transplantation, was low before the operation (0.44) and recovered to over 0.6 at 3 weeks. The half line width of the methylene peak of lipoprotein, as measured by proton NMR, was correlated with the ratio of esterified cholesterol to total cholesterol. It is suggested that proton NMR analysis can provide information about the biophysical changes in lipoprotein associated with liver transplantation.

Journal of Surgical Research, 2005

Background. Prolonged T-cell depletion after liver transplantation leads to life-threatening infe... more Background. Prolonged T-cell depletion after liver transplantation leads to life-threatening infections. Members of the anti-apoptotic Bcl-2 gene family can maintain T-cell viability. T-cell numbers and their Bcl-2 expression following living donor liver transplantation (LDLT) were analyzed in 108 surviving and 13 deceased recipients. Materials and methods. Bcl-2 mRNA levels and phenotypic changes of T-cells were examined by quantitative PCR and by measuring expression of CD45RO and CCR7. Results. Based on the restoration of peripheral T-cell numbers, the 108 surviving recipients were classified into three groups. All recipients showed T-cell depletion, down to approximately 30% of pretransplant levels within 3 h of graft reperfusion. In Group I, the T-cell numbers were rapidly restored to pretransplant levels, within 5 days, with a rapid decrease in Bcl-2 mRNA levels immediately after LDLT. In Group II, the T-cell numbers were restored to normal levels by 19 days, with down-regulation of Bcl-2 mRNA. In Group III, the T-cell numbers were maintained at low levels for much longer, with high levels of Bcl-2 mRNA. In all three groups of recipients, there was statistically significant (r ‫؍‬ ؊0.78) inverse correlation between T-cell numbers and Bcl-2 mRNA. Conclusions. For successful transplantation, homeostatic restoration of T-cells must occur as soon as possible. Evaluation of peripheral T-cell numbers and of Bcl-2 expression may have therapeutic potential in identifying those transplant patients who face increased risk of infection.

European Journal of Radiology, 2005

The Japanese Journal of Gastroenterological Surgery, 1997

Redox Report, 2002

Surgical stress is difficult to evaluate quantitatively. It has been reported that mitochondrial ... more Surgical stress is difficult to evaluate quantitatively. It has been reported that mitochondrial membrane potential (Dy m) in the peripheral blood lymphocytes (PBLs) is decreased by surgical stress. Thioredoxin (TRX), a small protein with redox-active dithiol/disulfide in the active site, is induced by a variety of oxidative stresses and secreted from the cells. Accumulating evidence shows that plasma levels of TRX are elevated in oxidative stress-associated disorders. In the present study, we examined plasma levels of TRX in cases undergoing operations for gastrointestinal cancer. Plasma levels of TRX were significantly elevated on the first postoperative day compared with the pre-operative levels. The changes in the plasma TRX levels tended to show an inverse relationship with the changes in Dy m in PBLs, which shows a significant decrease caused by surgical stress. Plasma TRX levels as well as Dy m in PBLs are valuable markers to evaluate surgical stress.

Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association), 2008