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Biomedical subjects

M Kume

Publications and source records attributed to M Kume.

At least 37 records · Page 2Linked to original sources

Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in rat liver after ischemia-reperfusion: distinct localization of the two oxidatively modified products.

Ischemia-reperfusion (IR) injury is an intractable process associated not only with therapeutic recanalization of vessels, but also with partial resection or transplantation of solid organs including liver. To develop methods for predicting the degree of hepatic IR injury and further to identify injured cells, we studied the formation of 8-hydroxy-2'-deoxy-guanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE)-modified proteins in the normothermic hepatic IR model of rats using immunohistochemistry, high-performance liquid chromatography (HPLC) determination and Western blot. The Pringle maneuver for either 15 or 30 min duration produced reversible or lethal damage, respectively. The levels of both products were significantly increased in proportion to ischemia duration 40 min after reperfusion, suggesting the involvement of hydroxyl radicals. Increased immunoreactivity of 8-OHdG was observed not only in the nuclei of hepatocytes but also in those of bile canalicular and endothelial cells. However, immunoreactivity of HNE-modified proteins was detected in the cytoplasm of hepatocytes, which was confirmed by Western blot, and in addition, in the nuclei of hepatocytes after severe injury. Thus, localization of the two oxidatively modified products was not identical. Our data suggest that these two products could be used for the assessment of hepatic IR injury in tissue, but that the biological significance of the two products might be different.

8-Hydroxy-2'-Deoxyguanosine↗

The 7alpha-methoxy substituent in cephem or oxacephem antibiotics enhances in vivo anti-Helicobacter felis activity in mice after oral administration.

The in vivo antibacterial activities of 7alpha-methoxy-cephems or 7alpha-methoxy-1-oxacephems and their demethoxy congeners after oral administration were compared in a mouse model of gastric infection with Helicobacter felis. The MICs of all four pairs of compounds with and without the 7alpha-methoxy substituent were within one two-fold dilution for H. felis and Helicobacter pylori, but the 7alpha-methoxy compounds were at least four-fold more active at bacterial eradication than their demethoxy congeners. Since these compounds are not absorbed after oral administration, they are likely to have gained direct access to the bacteria from the gastric cavity. Thus the 7alpha-methoxy substituent may enhance in vivo activity by promoting the gastric mucus permeability of the compounds or by allowing the compounds to remain longer in the gastric cavity.

Animals↗

Treatment of deep vein thrombosis using temporary vena caval filters after allogeneic bone marrow transplantation.

Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.

Anticoagulants↗

[Usefulness of preadmission autologous blood donation and intraoperative autotransfusion using the "cell saver" for the patients with abdominal aortic aneurysm repair].

To evaluate the effectiveness of preadmission autologous blood donation (PABD) and intraoperative autotransfusion (IAT) in reducing the homologous transfusion requirement of abdominal aortic aneurysm (AAA) resection, we retrospectively reviewed 232 AAA cases from January 1991 to December 1999. The patients were separated into three groups. The group I (n = 101) received no PAPD and IAT. The group II (n = 58) received only IAT. The group III (n = 73) received both PAPD and IAT. Surgical data indicating operative time and intraoperative blood loss did not differ among the three groups. However, the incidence of requirement for homologous transfusion in group III (19.2%) is significantly less than those of group I (63.4%) or group II (51.7%), although there was no significant difference between group I and group II. We concluded that the combination of PAPD and IAT are useful for reducing the incidence of requirement for homologous transfusion in the patients with aneurysmal resection.

Aged↗

Successful resection of superior mesenteric artery aneurysm. A case report and review of the literature.

Superior mesenteric artery aneurysms are rare, comprising only 8% of all visceral artery aneurysms. Aneurysms at the site are very susceptible to rupture, irrespective of size and may be difficult to manage even in the case of elective surgery. In the absence of serious complicating factors, the treatment of choice is excision of the aneurysm and reconstruction of the artery, if necessary, to maintain patency. We report the successful resection of an aneurysm and the subsequent reconstruction of the superior mesenteric artery which was directly anastomosed to the aorta after resection of an aneurysm.

Anastomosis, Surgical↗

Multivariate analysis of long-term results after an axillobifemoral and aortobifemoral bypass in patients with aortoiliac occlusive disease.

BACKGROUND: Controversy still remains regarding the long-term results and indications for axillofemoral bypass (AxFB). A comparison of axillobifemoral bypass (AxBFB) and aortobifemoral bypass (ABFB) was thus conducted to determine whether AxFB is an acceptable alternative vascular procedure to anatomic bypass for high-risk patients. METHODS: Sixty-three patients who underwent a total of 25 AxBFBs and 38 ABFBs for aortoiliac occlusive disease were reviewed retrospectively, and both univariate and multivarate analyses were perfomed. RESULTS: The overall survival was 82.8% at five years. A univariate analysis revealed significantly lower survival rates for patients with limb-threatening ischemia, coronary disease, and cerebrovascular disease. A multivariate analysis disclosed no significant factors influencing survival rates. The overall primary patency was 79.8% at five years. The primary patency rates for AxBFB (67.7% at five years) were significantly lower than for ABFB (88.5% at five years) based on a univariate analysis (p=0.0045). In addition, the secondary patency rates for AxBFB (80.3% at five years) were significantly lower than for ABFB (96.5% at five years, p=0.0025). A multivariate analysis disclosed significantly lower primary patency rates for grafts with a higher angiographic outflow score and simultaneous infrainguinal reconstructive procedures, but the differences between AxBFB and ABFB were not significant. CONCLUSIONS: The survival and primary patency for the AxBFB group were both inferior to the ABFB group, however a multivarate analysis disclosed no significant differences between the two groups. Poor femoral run-off and the presence of synchronous infrainguinal reconstructive procedures significantly affected graft patency, and these factors modulated the patency of AxBFB. AxFB for aortoiliac occlusive disease is therefore considered to be an acceptable procedure in appropriately selected patients.

Adult↗

Total Synthesis of Quinoxapeptin A-C: Establishment of Absolute Stereochemistry.

The relative and absolute stereochemistry of the naturally occurring potent HIV reverse transcriptase (RT) inhibitors 1 and 2, quinoxapeptin A and B, were established by total synthesis. Their synthetic precursor 3 (dubbed quinoxapeptin C) was found to be a more potent HIV-1 RT inhibitor and to lack the potent cytotoxic activity characteristic of 1 and 2.

Journal Article↗

Heat shock preconditioning on mitochondria during warm ischemia in rat livers.

BACKGROUND: The aim of this study was to investigate the effects of stress tolerance from heat shock preconditioning on changes in mitochondrial functions during ischemia-reperfusion injury of the liver. MATERIALS AND METHODS: Rats were divided into a heat shock group (group HS) and a control group (group C). In group HS, rats received heat shock pretreatment 48 h prior to ischemia-reperfusion. Heat shock pretreatment was performed in a water bath at 42 degrees C for 15 min under general anesthesia. In group C, the same treatment was done with the water bath at 37 degrees C instead of at 42 degrees C. A 30-min warm ischemia by cramping the hepatoduodinal ligament (Pringle's maneuver) followed by a 60-min reperfusion was administered to all rats. Changes in membrane potential of hepatic mitochondria (MPM); mitochondrial respiratory function before ischemia (n = 5), after ischemia (n = 10), and after reperfusion (n = 10); and ATP recovery after reperfusion were compared between the groups. RESULTS: After a 30-min ischemia, MPM in group C decreased significantly and did not recover even after reperfusion. On the other hand, MPM in group HS was maintained even after a 30-min ischemia and 60 min into reperfusion as well. The respiratory control ratio (RCR) of the mitochondria in group C decreased to as low as 5.06 +/- 0.72 after a 30-min ischemia, but in group HS, RCR was maintained near a normal level. The ATP level recovered significantly earlier in group HS than in group C after reperfusion. CONCLUSIONS: Heat shock preconditioning of the liver protected mitochondria from loss of membrane integrity during ischemia and contributed to their ability to produce energy-rich phosphates during reperfusion.

Adenosine Triphosphate↗

New simple technique for hepatic parenchymal resection using a Cavitron Ultrasonic Surgical Aspirator and bipolar cautery equipped with a channel for water dripping.

We have developed a new technique to resect hepatic parenchyma without inflow occlusion by using the Cavitron Ultrasonic Surgical Aspirator (CUSA) and bipolar cautery with a saline irrigation system. The significance of this method in hepatectomy was analyzed in comparison with historical control of hepatectomy using Pringle's maneuver. An ordinary bipolar cautery was remodeled with an infusion line to bring saline droplets down the inner surface of one arm of the tweezers through an opening about 1.5 cm proximal to its tip. The optimal flow rate of saline was approximately one drop per second. The power of bipolar cautery was adjusted to 50 watts. When the tweezer blades were approximated to 1 or 2 mm, saline droplets were directed to the tip of tweezers and could be immediately evaporated. After sonicating parenchymal cells, the tissue of small branches of Glisson's tree or small tributaries of the hepatic vein were coagulated by bipolar cautery. The coagulated cords were then easily cut by scissors. The impact of this technique on ordinary liver resections was evaluated by analyzing the postoperative clinical course in relation to the hepatic functional reserve necessary for major hepatectomy, duration of hepatectomy, and intraoperative blood loss. Hepatic resection without vascular occlusion using this technique could decrease the morbidity in patients who have less hepatic functional reserve. It could also decrease intraoperative blood loss. This new technique effectively decreased the surgical load of the remnant liver during parenchymal resection by avoiding ischemic stress. Consequently it extends the safety limits of major hepatectomy.

Electrocoagulation↗

Effects of melatonin and superoxide dismutase on free radical formation in the postischemic reperfused heart.

PURPOSE: Melatonin has been reported to protect against oxygen free radicals. We investigated whether melatonin or superoxide dismutase (SOD) would decrease hydroxyl radical concentration in the postischemic reperfused heart. METHODS: An isolated rat heart-lung preparation was used. Eighty-one male Wistar rats were allocated into control (no drug), S1 (SOD 400 U.ml(-1)), S2 (SOD 2000 U.ml(-1)), M1 (melatonin 0.1 microg.ml(-1)), M2 (melatonin 1.0 microg.ml(-1)), M3 (melatonin 10 microg.ml(-1)), SM (SOD 400 U.ml(-1) and melatonin 1.0 microg.ml(-1)) groups. The heart was perfused initially at the cardiac output of 30 ml.min(-1) and the mean arterial pressure of 70 mmHg. Drugs were administered into the reservoir 7 min after the start of perfusion. Ten minutes after the start of perfusion, the heart was rendered globally ischemic for 10 min by reducing the preload and afterload to zero and then reperfused for 10 min. At the end of reperfusion, the heart was freeze-dried for 6 days. The perfusate blood was collected just before and after ischemia and at the end of reperfusion. The formation of hydroxyl radicals in perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding 2,3-, 2,4-, 2,5-, and 3,4-dihydroxybenzoic acid (DHBA). RESULTS: Before and after ischemia, there were no significant differences among the groups in cardiac output, systolic pressure, heart rate, and right atrial pressure. The concentrations of DHBAs in the perfusate blood and heart after ischemia and reperfusion in all groups were significantly higher than those before ischemia. DHBAs in the heart of all drug-administered groups were significantly lower than those in the control group. In the perfusate blood, DHBAs in the S2 group were significantly lower than those in the control group. CONCLUSIONS: SOD and melatonin decrease hydroxyl radical concentration in the postischemic reperfused heart.

Journal Article↗

Pharmacologic stimulation of adenosine A2 receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers.

BACKGROUND: Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process. METHODS: Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia. Changes in the adenosine concentrations in liver tissue were evaluated, and the effects of adenosine A1 or A2 receptor agonists or antagonists were examined either in place of or against IPC. RESULTS: The 7-day animal survival was significantly better in the IPC group than in the control group (87% vs 53%; n = 15, P < .05). The release of liver-related enzymes during reperfusion was suppressed better in the IPC group (P < .01). Recovery of adenosine triphosphate levels was faster in the IPC group (P < .01). After IPC, adenosine concentrations in liver tissue immediately increased to 1555 +/- 299 pmol/g wet tissue and were maintained at that level during a subsequent 45-minute ischemia. The ischemic tolerance generated by IPC was mimicked by the administration of adenosine A2 receptor agonist and opposed by adenosine A2 receptor antagonist. CONCLUSIONS: The ischemic tolerance of the liver immediately after IPC can be supplanted by selective pharmacologic stimulation of adenosine A2 receptors.

Adaptation, Physiological↗

Properties of endothelium and smooth muscle cells in canine femoral arteries after lumbar sympathectomy.

OBJECTIVE: To find out whether the lumbar sympathectomy modulated the endothelial function (as measured by nitric oxide (NO) and prostacyclin (PGI2), and blood flow in the canine femoral artery. DESIGN: Laboratory experiments. SETTING: Teaching hospital, Japan. ANIMALS: 16 mongrel dogs. INTERVENTION: Unilateral sympathectomy from L3 to L6. MAIN OUTCOME MEASURES: Five weeks later, the changes in blood flow, the endothelium-dependent responses and the PGI2 production in the canine femoral arteries were measured. RESULTS: The median (range) blood flow of left (denervated) and right (innervated) femoral arteries was 162 ml/min (122-330) and 65 ml/min (40-92), respectively. There was a significant difference between the two groups (p < 0.01). The endothelium-dependent relaxations to acetylcholine, adenosine diphosphate (ADP) and A23187 were comparable. The amounts of PGI2 produced in the two groups were similar. Direct relaxation in response to sodium nitroprusside was also similar in the two groups. CONCLUSIONS: Lumbar sympathectomy did not alter the endothelial function, although the median blood flow in the denervated femoral arteries was significantly higher than in the innervated ones. The continuous vasodilatation after sympathectomy may be a more potent factor in the regulation of vascular tonus than the physiological regulation of NO and PGI2.

Animals↗

[Usefulness of endovascular grafting for abdominal aortic aneurysm].

The purpose of this study was to determine the usefulness of endovascular grafting for abdominal aortic aneurysm (AAA) compared to conventional open repair. During the period from May 1998 through to April 1999, 16 patients (control group) with AAA underwent conventional open surgery and 6 patients (stent group) underwent endovascular grafting. Surgical data including operative time and intraoperative blood loss did not differ between the two groups. However, the postoperative parameters including the initiation of oral intake, the onset of flatus and the permission to walk were significantly sooner in the stent group than the control group. The postoperative changes of coagulopathy-fibrinolytic factor were comparable between the two groups. We conclude that the endovascular grafting is minimally invasive compared to conventional open surgery. In addition, there was no consumption coagulopathy in the endovascular grafting. However, it was necessary to develop new approach with new devices in order to perform endovascular grafting more safely.

Aged↗

Cytokine patterns and the effects of a preoperative steroid treatment in the patients with abdominal aortic aneurysms.

BACKGROUND: The aim of this study was to investigate the cytokine patterns of patients with abdominal aortic aneurysms and the effects of preoperative steroid administration on surgical stress. METHODS: From January 1996 to August 1996, 20 consecutive patients underwent an elective reconstruction of infrarenal abdominal aortic aneurysms. The patients were randomly divided into two groups consisting of a control group (n=10) and a steroid group (n=10), in whom 1 g of methylprednisolone was intravenously administered two hours before the operation. MEASURES: Interleukin-6 was serially measured and the perioperative parameters including C-reactive protein were compared between both the control and the steroid groups. RESULTS: The interleukin-6 values in the steroid group immediately after declamping, as well as at one and three postoperative days were significantly lower than those in the control group. C-reactive protein values at one postoperative day in the steroid group were also significantly lower than those in the control group. In one patient with a ruptured abdominal aortic aneurysm, the interleukin-6 values were higher than those in the patients undergoing elective surgery throughout the study. CONCLUSIONS: These results thus suggest that preoperative steroid administration using methylprednisolone in patients with abdominal aortic aneurysms appears to reduce surgical stress by decreasing cytokine release.

Aged↗

Double lung cancer combined with idiopathic thrombocytopenic purpura. A case report.

A 68-year-old woman was admitted because of two abnormal lung shadows, which later proved to be differentiated double cancer. Preoperative hematology tests showed a low platelet count and the result of bone marrow aspiration was compatible with idiopathic thrombocytopenic purpura (ITP). A normal platelet count was once obtained by preoperative percutaneous partial splenic arterial embolization (PSE). However, as there was a tendency for the platelet count to decrease just before surgery, one shot high-dose immunoglobulin (Ig) was administered, which is thought to have a short term effect. The operation was performed successfully. After resection of lung cancer, her platelet count was maintained at around 15x10(4) mm3 without taking drugs for ITP. These findings suggest a relationship between lung cancer and ITP.

Adenocarcinoma↗

A new variant translocation of t(15;17) in a patient with acute promyelocytic leukemia (M3): t(15;19;17)(q22;p13;q12).

The reciprocal translocation (15;17) is specifically associated with acute promyelocytic leukemia [APL; M3 subtype according to French-American-British (FAB) classification]. A few patients with this disease have complex variant translocations. We describe a patient with M3 carrying t(15;19;17)(q22;p13;q12), which is a new type of variant translocation. The karyotypic interpretation was confirmed by Southern blot analysis with the use of RAR alpha and by fluorescence in situ hybridization (FISH) with the use of painting probes of chromosomes 15, 17, and 19 and a (15;17) translocation DNA probe. The results support the idea that the key event in APL is the formation of fusion gene PML/RAR alpha on the der(15).

Adolescent↗

Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers.

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2-nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.

Adenosine Triphosphate↗