Biomedical subjects

G Wakabayashi

Publications and source records attributed to G Wakabayashi.

At least 19 recordsLinked to original sources

PubMed2001

The role of tumor necrosis factor-alpha and interleukin-1beta in ischemia-reperfusion injury of the rat small intestine.

BACKGROUND: To determine the role of tumor necrosis factor (TNF) and interleukin (IL)-1 in small-intestinal ischemia-reperfusion (I-R) injury, we investigated the effect of FR 167653, a specific IL-1 and TNF inhibitor, on warm I-R injury of the rat small intestine. MATERIALS AND METHODS: Male rats treated with either saline (NS group) or FR 167653 (FR group) underwent 150 min of warm small-intestinal ischemia by applying a vascular clip at the origin of the superior mesenteric artery. In addition to the survival analyses, we investigated plasma TNF-alpha and endotoxin levels, intestinal tissue TNF-alpha and IL-1beta levels, hematocrit values and the amount of exudates in the intestinal lumen, glutamic aspartate aminotransferase (AST), and histological findings up to 120 min after reperfusion. RESULTS: TNF-alpha and IL-1beta levels in the intestinal tissue, and plasma TNF-alpha and endotoxin levels, were significantly (P < 0.05) reduced in the FR group. Severe mucosal damage on histological findings (120 min after reperfusion) and a large amount of intraluminal exudates (60 min after reperfusion) were shown in the NS group, but these findings were significantly (P < 0.05) ameliorated in the FR group. Serum AST levels in the NS group increased 120 min after reperfusion, but this change was significantly (P<0.05) reduced in the FR group. The 30-day survival rate was 80% in the FR group and 30% in the NS group (P<0.05). CONCLUSIONS: Dual inhibition of TNF and IL-1 effectively alleviated intestinal I-R injury, suggesting the key role of TNF and IL-1 in this pathophysiology.

Animals↗

PubMed2001

Detection of IL-2 receptor gene expression in peripheral blood from renal transplant patients.

Cytokine monitoring is a potentially useful tool in the management of transplant patients. This study was conducted to analyze interleukin (IL)-1, tumor necrosis factor (TNF), IL-2, and IL-2 receptor gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral whole blood from healthy volunteers and patients who underwent laparotomy or renal transplantation. In the patients who underwent laparotomy, IL-1 and TNF expression was detected postoperatively, but IL-2 and IL-2 receptor expression was not. IL-1, TNF, and IL-2 receptor gene expression was detected in all the renal transplant patients, including those with signs of rejection. No cytokine gene expression was detected preoperatively, pretransplant, or in the healthy volunteers. We were able to discriminate transplantation from laparotomy by the cytokine profile. These results indicate that our method may be a useful tool for the immunological monitoring of transplant patients.

Adult↗

PubMed2001

Domino split-liver transplantation from a living donor: case reports of in situ and ex situ splitting.

The liver from a patient with familial amyloid polyneuropathy (FAP) scheduled for living donor liver transplantation can be split and transplanted into 2 adult patients with end-stage liver disease. We have performed this procedure, called domino split transplantation, twice. The native liver was split in situ in 1 patient with FAP and ex situ in the other patient with FAP. The recipients of the livers from the patients with FAP and their living donors are doing well without serious complications. Of the 4 secondary recipients, 3 patients survived. Domino split-liver transplantation from a living donor thus appears to be a promising procedure for expansion of the donor pool.

Adolescent↗

PubMed2001

Development of endoscopic surgery for the minimally invasive treatment of digestive and other diseases.

Minimally invasive surgery has rapidly changed the performance of surgical practice in a wide range of surgical specialities in the last decade of the 20th century. The marked progress in endoscopic surgery has been conducted especially in general and digestive surgery. The Department of Surgery, School of Medicine, Keio University has contributed to the development and establishment of endoscopic surgery in every subspeciality of general and digestive surgery. Our achievements include the development of original methods for laparoscopic wedge gastrectomy and endoscopic thyroidectomy, establishment of surgical techniques in endoscopic surgery for esophageal, gastric, colorectal and hepatobiliary diseases, and the introduction of robotics and tele-communicative technologies to endoscopic surgery.

Digestive System Surgical Procedures↗

PubMed2001

[En bloc resection of the hepatoduodenal ligament for advanced carcinoma of the biliary tract].

Theoretically, en bloc resection of the hepatoduodenal ligament is considered to be the most radical procedure for advanced carcinoma of the biliary tract. However, this procedure involves perioperative difficulties such as hepatic ischemia, portal congestion, patency of reconstructed vessels, and high incidence of operative mortality, moreover, when it is combined with resection of the liver and/or pancreas. We developed several tactics in vascular reconstruction, hepatic resection, and pancreatoduodenectomy in order to decrease the operative morbidity and mortality. We preferred to anastomose the portal vein and hepatic artery separately to avoid total hepatic ischemia, and used the porto-systemic bypass during prolonged portal reconstruction. We resected the liver without vascular clamping to minimize hepatic ischemia, and employed the simplified method of pancreatojejunostomy. To date, we performed 4 hepatoligamentectomies and 4 hepatoligament-pancreatoduodenectomies with no operative mortality, although long-term survivors were not encountered. This procedure should be evaluated with more clinical experiences after its safety and indication was established.

Aged↗

PubMed2001

Interleukin 18 levels reflect the severity of acute pancreatitis.

The serum interleukin 18 (IL-18) levels were significantly increased in cases of acute pancreatitis, corresponding to the severity of the disease. The IL-18 levels were also significantly correlated with the serum tumor necrosis factor alpha (TNF-alpha) and bilirubin levels. The possible involvement of IL-18 in the development of liver dysfunction in acute pancreatitis is suggested.

Acute Disease↗

PubMed2000

Increased fibrinolytic activity and body cavity coagula.

When a large volume of coagulum remains in the body cavity after trauma or surgery, secondary fibrinolysis occurs, which disturbs the hemostatic balance and results in rebleeding. To better understand this condition, we conducted a clinical study on patients with and without coagula and an experimental study on fibrinolytic activity in a rat model. The results of the clinical study showed that when coagula existed in the body cavity, the blood levels of the fibrin degradation products D-dimer and fibrinopeptide Bbeta15-42 remained high compared with when subjects were under similar stress but without the presence of coagula. In the experimental studies, fibrinolytic activity of the omentum, measured by the fibrin plate method, was higher in rats with hemoperitoneum. This suggests that increased fibrinolytic activity may lead to rebleeding from the area of transient hemostasis when coagulum is present in the body cavity.

Adolescent↗

PubMed2000

Nitrite/nitrate (NOx) levels and hemodynamics during septic shock.

Nitric oxide (NO) acts as a vasorelaxant. We investigated the relationship between nitrite/nitrate (NOx), which are the final metabolites of NO, and hemodynamics during septic shock. We also examined tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and endotoxin. A significant negative correlation was observed between NOx levels and pulmonary capillary wedge pressure (PCWP; r = -0.6075, P = 0.0028). A significant positive correlation was noted between NOx levels and the cardiac index (CI; r = 0.5934, P = 0.0038). A significant negative correlation was found between NOx levels and the systemic vascular resistance index (SVRI; r = -0.4354, P = 0.0485). A significant positive correlation was observed between NOx levels and the stroke volume index (SVI; r = 0.5040, P = 0.0186). A significantly close positive correlation was also observed between TNF-alpha levels and NOx levels (r = 0.7848, P < 0.0001). These findings suggest that NOx levels are closely associated with hemodynamics during septic shock, resulting in a vascular relaxing effect.

Adult↗

PubMed2000

Are nitrite/nitrate (NOx) levels elevated by inhalation injury?

The relationship between airway burn and nitric oxide (NO) levels in the early burn stage was investigated by quantifying nitrite/nitrate (NOx), which are the final metabolites of NO, in 22 burn patients. Although total body surface area (TBSA) and burn index (BI) were significantly higher in patients with airway-burn than in patients without airway burn (P=0.0347 and 0.0422, respectively), no significant difference in NOx levels was observed between the two groups (P=0.6196). The NOx levels were found to correlate significantly with TBSA (r=0.4775, P=0.0246). A significant correlation was also noted between the NOx levels and BI (r=0.4391, P=0.0409). These results suggest that NO reflects the intensity of inflammation in the early burn stage, but that excessive NO formation is unlikely to be induced by stress, such as that caused by airway burn.

Adult↗

PubMed2000

Tumor necrosis factor-alpha and tumor necrosis factor receptor I, II levels in patients with severe burns.

Tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor receptor I and II (TNFRI and TNFRII) were studied in 24 burn patients who had a total burn surface area (TBSA) of 50.2 +/- 20.4%. Immediately after the injury, both the TNFRI and TNFRII levels correlated significantly with TBSA (r = 0.7344, P < 0.0001; r = 0.6074, P = 0.0012). The TNFRI and TNFRII levels immediately after the injury were significantly higher in the 11 patients who later died of their burns than in the 13 patients who survived (0.8 +/- 0.4 ng/ml vs. 1.8 +/- 0.7 ng/ml, P = 0.0002; 2.3 +/- 1.1 ng/ml vs. 4.5 +/- 1.6 ng/ml, P = 0.0009). The TNF-alpha levels immediately after the injury did not differ significantly between the group that survived and the group that died. The TNFRI and TNFRII values for the entire follow-up period also correlated significantly with TBSA. Peak TNFRI and TNFRII levels were significantly higher in the group that died than in the group that survived (6.0 +/- 4.7 ng/ml vs. 14.1 +/- 7.8 ng/ml, P = 0.0009; 7.0 +/- 5.1 ng/ml vs. 16.7 +/- 5.2 ng/ml, P = 0.0003). The TNF-alpha levels correlated significantly with both the TNFRI and the TNFRII levels. The TNFRI and TNFRII levels thus closely reflected the severity of the burns in both the acute postburn period and the subsequent follow-up period. In other words, these parameters well reflected the severity and outcome of the burns, irrespective of the presence or absence of accompanying infection.

Adult↗

PubMed2000

Overexpression of truncated IkappaBalpha induces TNF-alpha-dependent apoptosis in human vascular smooth muscle cells.

Dysregulation of apoptosis is one of the likely underlying mechanisms of neointimal thickening, a disorder in which proinflammatory cytokines may influence the function of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis. One of these cytokines, tumor necrosis factor-alpha (TNF-alpha), induces 2 possibly conflicting pathways, 1 leading to the activation of nuclear factor-kappaB (NF-kappaB) and the other leading to caspase-mediated apoptosis. We investigated whether specific inhibition of NF-kappaB affects TNF-alpha-dependent apoptosis in human VSMCs. To inhibit NF-kappaB activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein IkappaBalpha (AdexIkappaBDeltaN) that lacks the phosphorylation sites essential for activation of NF-kappaB. The IkappaBDeltaN was overexpressed by adenoviral infection and was resistant to stimulus-dependent degradation. Electromobility gel shift and luciferase assays demonstrated that overexpression of IkappaBDeltaN inhibited NF-kappaB activation induced by TNF-alpha or interleukin-1beta (IL-1beta). In cells overexpressing IkappaBDeltaN, TNF-alpha dramatically induced apoptosis, whereas IL-1beta had no effect. The induction was suppressed by treatment with a selective inhibitor of the caspase-3 family, Z-DEVD-fmk, and the overexpression of IkappaBDeltaN induced TNF-alpha-mediated caspase-3 and caspase-2 activity. These results indicate that overexpression of IkappaBDeltaN induces TNF-alpha-dependent apoptosis by efficient and specific suppression of NF-kappaB and upregulation of caspase-3 and caspase-2 activity in human VSMCs. Our findings suggest that adenovirus-mediated IkappaBDeltaN gene transfer may be useful in the treatment of disorders associated with inflammatory conditions, such as the response to vascular injury and atherosclerosis.

Adenoviridae↗

PubMed2000

[Surgery using master-slave manipulators and telementoring].

Master-slave manipulators enhance surgeons' dexterity and improve the precision of surgical techniques by filtering out surgeons' tremors and scaling the movements of surgical instruments. Among clinically available master-slave manipulators, the epoch-making system called "da Vinci" developed by Intuitive Surgical Inc. (Mountain View, CA, USA), equipped with 2 articulated joints at the tip of the surgical instruments allowing 7 degrees of freedom, mimics the movements of surgeons' wrists and fingers in the abdominal or thoracic cavity. Today advanced telecommunications technology provides us excellent motion images using only 3-ISDN telephone lines. Experienced surgeons at primary surgical sites have been able to perform complex procedures successfully by consulting specialists at remote sites. Because telecommunications costs have become lower each year, telementoring will be come a routine surgical practice in the near future. The usefulness of surgical telementoring has been greatly enhanced by the development of a technique to illustrate on video images from two directions. Moreover, remote advisory surgeons will be able to provide the optimal operative field to operating surgeons using robotic camera holders with voice-recognition systems. In the near future, when master-slave manipulators will also be coupled with telementoring systems, remote experts could actually perform complex surgical procedures.

Humans↗

PubMed2000

[Three-dimensional cholangiography and angiography for hilar cholangiocarcinoma].

Cholangiography is the most fundamental and reliable examination for diagnosis of the extent of bile duct carcinoma. Hepatic angiography is also informative for diagnosis of vascular invasion. However, an accurate understanding of three-dimensional biliary and vascular anatomy at the hepatic hilum is not easily gained by conventional cholangiography and angiography. We have performed three-dimensional cholangiography and angiography (3D-CG & AG) using rotational DSA (Advantx ACT) and a 3D spinning digital imaging system in 29 patients with hilar cholangiocarcinoma, etc. 3D-CG & AD provides clear three-dimensional visualization of the biliary tract and blood vessels affected by bile duct cancer, and useful information on optimal resection. Of 13 patients with hilar cholangiocarcinoma undergoing resection, curative resection was carried out in 11 (85%). 3D-CG & AG is considered to be an indispensable imaging modality for evaluation of the extent and staging of hilar cholangiocarcinoma.

Angiography↗

PubMed2000

Interleukin 18 (IL-18) levels in patients with sepsis.

IL-18 levels in the blood of 13 sepsis patients were assessed. The IL-18 values were significantly correlated with their Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and they were a good reflection of the severity of the disease. There was also a strong correlation between the IL-18 values and the patients' inflammatory cytokine levels. The results suggested strong involvement of IL-18 in the pathogenesis of sepsis.

APACHE↗

PubMed2000

Nuclear matrix protein (NMP) levels in patients with acute pancreatitis.

Nuclear matrix protein (NMP) is an index of apoptosis. We measured NMP in 22 patients with acute pancreatitis and investigated the relationship between severity and NMP. We also measured tumor necrosis factor-alpha (TNF-alpha) and investigated the relationship between NMP and TNF-alpha. The NMP value increased significantly as the pancreatitis became more increasingly severe, and the NMP values were significantly higher in the group with multiple organ dysfunction syndrome (MODS) than in the group without MODS. A comparison of the NMP values in the group that survived and the group that died revealed higher NMP values in the former. A significant correlation was found between the NMP values and the TNF-alpha values, suggesting that apoptosis may contribute to the pathophysiology of acute pancreatitis.

Acute Disease↗

PubMed2000

Soluble Fas and soluble Fas L levels in patients with acute pancreatitis.

The FasL-Fas system is an apoptosis induction system and plays an important role in homeostasis and biophylaxis. The present study was conducted to investigate soluble Fas (sFas), soluble Fas ligand (sFasL), and tumor necrosis factor alpha (TNF-alpha) in patients with acute pancreatitis. As acute pancreatitis became severe, the levels of sFas in the serum increased significantly, while those of sFasL decreased significantly. A significant inverse correlation was observed between the serum levels of sFas and those of sFasL. Also, a significant positive correlation was observed between the levels of TNF-alpha and sFas. A greater increase in serum sFas and decrease in serum sFasL levels was observed in patients with complicating multiple organ dysfunction syndrome (MODS) than in those without it. The results of the study suggest that the pathological aggravation of acute pancreatitis could be related to changes in the Fas-FasL system.

Acute Disease↗

PubMed1999

Kupffer cell-independent acute hepatocellular oxidative stress and decreased bile formation in post-cold-ischemic rat liver.

The purpose of this study was to examine distribution and time history of oxidative stress during the hyperacute period of reperfusion in the liver grafts undergoing cold ischemia and to investigate roles of Kupffer cells as a potential oxidant source. Rat livers were harvested at 4 degrees C in University of Wisconsin solution and followed by reperfusion with Krebs-Henseleit buffer under monitoring bile excretion. To investigate oxidative changes, laser-confocal microfluorography was performed in reperfused livers preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescence precursor sensing intracellular hydroperoxide generation. Livers undergoing the 16-hour cold storage displayed an impaired recovery of bile acid-dependent bile output concurrent with a marked increase in hydroperoxide generation in hepatocytes, which occurred as early as 5 minutes after the onset of reperfusion, whereas the status of lobular perfusion was well maintained. Pretreatment with liposome-encapsulated dichloromethylene diphosphonate, a Kupffer cell-depleting reagent, did neither alter the reperfusion-induced periportal oxidative changes nor improve the recovery of bile output in the graft. On the other hand, EPCK, a hepatotropic antioxidant composed of vitamin E phosphate ester bound to vitamin C, not only diminished the oxidative changes but also improved the reduction of bile acid-dependent bile output. Furthermore, the reagent was capable of inhibiting H(2)O(2)-induced oxidative stress in cultured hepatocytes. These results suggest that hepatocytes constitute a major site of the oxidative insult triggered through Kupffer cell-independent mechanisms and serve as an important cellular component to be protected by antioxidant therapeutics.

Animals↗

PubMed1999

Intraportal perfusion of prostaglandin E1 attenuates hepatic postischaemic microcirculatory impairments in rats.

BACKGROUND: The efficacy of intraportal perfusion with prostaglandin E1(PGE1) in decreasing postischaemic hepatic microcirculatory damage was studied in rats. METHODS: An extrahepatic portosystemic shunt was created by attaching the spleen to a subcutaneous site on the left lateral wall of the abdomen in male Wistar rats weighing between 200 and 350 g. Four weeks later, when the shunt was mature, the portal vein and hepatic artery were occluded for 60 min. The animals were divided into the following three groups according to the type of intraportal perfusion during the ischaemic phase: group 1 consisted of untreated animals; group 2, animals perfused with lactated Ringer's solution; and group 3, animals perfused with PGE1 (0.1 microg/kg per min). The hepatic microcirculation was observed under an inverted intravital microscope after the injection of fluorescent dyes to label leucocytes and damaged cells 30 and 60 min after reperfusion. The liver was removed 60 min after reperfusion and stained immunohistochemically using 1A29, an anti-rat intercellular adhesion molecule-1 (ICAM-1) antibody. RESULTS: The leucocyte velocity during reperfusion was lowest in group 1 and highest in group 3. Of the three groups, group 3 showed the least leucocyte adhesion to the sinusoidal walls and terminal venules, the lowest damaged cell count and the lowest ICAM-1 expression on the sinusoidal walls. CONCLUSION: The results of this study suggest that hepatic perfusion with PGE1 markedly alleviates microcirculatory damage associated with ischaemia and reperfusion through the inhibition of leucocyte-endothelium interactions.

Alprostadil↗