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Biomedical subjects

M Kume

Publications and source records attributed to M Kume.

At least 55 records · Page 3Linked to original sources
PubMed1998

Implications of heat shock proteins during liver surgery and liver perfusion.

Cells primed by sublethal stress transiently overproduce heat shock proteins (HSPs) and thereby develop tolerance to the next lethal stress. This response in organisms is called the stress response and involves the induction of HSPs. To assist the liver in developing tolerance for warm ischemia-reperfusion injury, which sometimes jeopardizes the patients after extended surgery for malignancies with vascular invasion in the liver, basic experiments to activate the stress response using stress preconditioning were performed. Heat shock preconditioning in rat livers has been shown to induce tolerance against warm ischemia-reperfusion injury in normal, fibrotic, and steatotic livers. Ischemic preconditioning using short-term Pringle's maneuver and pharmacological preconditioning using doxorubicin were also effective. In rats, heat shock preconditioning protected livers from free radical injury induced by the oral administration of carbon tetrachloride. The above data were supported by animal survival, suppression of serum transaminase levels, and improved energy status of the liver after intervention. Increased production of HSP72 was observed after preconditioning. In addition, the significance of HSP production as a stress parameter was demonstrated during the reperfusion of congested portal blood to the ischemic liver. The ill effect of congested portal blood could not be detected by conventional parameters but was detected by observing the increase in HSP72 production. Stress preconditioning seems to be a promising strategy to counter the damaging effect of hepatic warm ischemia during liver surgery and liver perfusion.

Animals↗
PubMed1998

Induction of heat shock response: effect on the rat liver with carbon tetrachloride-induced fibrosis from ischemia-reperfusion injury.

The role of heat shock pretreatment in the induction of tolerance for ischemia-reperfusion injury was investigated in rat livers with fibrosis produced by carbon tetrachloride (CCI4) injected subcutaneously. The control group (group C, n = 56) received no pretreatment except anesthesia, and the heat shock group (group HS, n = 56) were exposed to heat shock (42 degrees C) for 15 minutes. After a 48-hour recovery all rats were subjected to 30 minutes of warm ischemia. Western blotting analysis was employed for heat shock protein (HSP) 72 detection. The adenine nucleotide levels in liver tissue and the liver enzyme levels in serum were measured before and after ischemic intervention (seven animals were used at each of six time point measurements in both groups). HSP72 was induced in group HS at greater intensity than in group C. The survival rate on postoperative day 7 in group C (3/14) was significantly poorer than that in group HS (14/14) (p < 0.01). The higher survival rate in group HS was accompanied by more rapid recovery of the adenosine triphosphate level and lower serum levels of liver enzymes after reperfusion (p < 0.01 vs. group C). Heat shock preconditioning induces HSP72 in the rat liver with fibrosis and provides significantly increased tolerance of warm-ischemia reperfusion injury.

Animals↗
PubMed1998

Heat shock protein 72 production in liver tissue after experimental total hepatic inflow occlusion.

BACKGROUND: The pathogenesis of hepatic ischaemia-reperfusion injury is incompletely understood. This study examined the effects of reperfusion with congested portal blood on ischaemia-reperfusion injury of the liver following Pringle's manoeuvre, as monitored by heat shock protein (HSP) 72 production in rat liver tissue. METHODS: Rats were randomized to three groups. In group 1 hepatic ischaemia with portal congestion was induced by Pringle's manoeuvre for 15 min; in group 2 Pringle's manoeuvre was applied for 15 min with an extracorporeal portasystemic shunt; and in group 3 the superior mesenteric vein was occluded for 15 min. The production of HSP72 in liver tissue was measured by Western blotting at 48 h after each intervention. Conventional parameters for hepatic function were examined at 1, 3 and 48 h after reperfusion. RESULTS: There was marked HSP72 expression in group 1, but not in group 2 or 3, showing that a combination of liver ischaemia and reperfusion of congested portal blood is required to induce strong expression of HSP72 in the tissue. On the other hand, biochemical parameters were raised equally in both groups 1 and 2, reflecting a similar degree of ischaemic hepatocyte injury. CONCLUSION: The additional stress impact of temporary portal occlusion upon ischaemia-reperfusion injury of the liver was clearly detected by in situ hepatic HSP72 production in this study.

Animals↗
PubMed1998

Effects of sevoflurane and isoflurane on free radical formation in the post-ischaemic reperfused heart.

Sevoflurane has been reported to generate oxygen free radicals. We have investigated whether sevoflurane or isoflurane enhances oxygen free radical formation in the post-ischaemic reperfused heart. An isolated rat heart-lung preparation was used. Thirty male Wistar rats were allocated to four groups: control, no drug, 2.5% sevoflurane and 1.4% isoflurane. The heart was perfused initially at a cardiac output of 30 mL min-1 and a mean arterial pressure of 70 mmHg. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero. Then, the heart was 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 just after ischaemia 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). Before and after ischaemia, there were no significant differences in cardiac output, systolic pressure, heart rate and right arterial pressure among the groups. The concentrations of 2,3-, 2,4-, 2,5- and 3,4-DHBA in the perfusate blood after ischaemia and reperfusion were significantly higher than those before ischaemia in all groups. However, there were no differences in the DHBA levels among groups. This study indicates that sevoflurane and isoflurane do not enhance hydroxyl radical formation in the post-ischaemic reperfused heart.

Anesthetics, Inhalation↗
PubMed1998

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature.

A case of pure red cell aplasia (PRCA), myasthenia gravis (MG) and thymoma is reported. A 70-year-old woman presented with severe anemia. She had been diagnosed as having MG 8 years earlier and her symptoms were adequately controlled with ambenonium chloride. When she visited our hospital, her hematocrit was 13.7% with a hemoglobin concentration of 4.7 g/dl and her reticulocyte counts were persistently abnormal at 0.1%. Although both direct and indirect Coombs' tests were positive, there was no evidence of hemolysis. Routine screening tests for other etiologies of anemia were negative. Serological tests for anti-DNA and anti-acetylcholine receptor antibodies gave positive results. A bone marrow examination revealed severe erythroid hypoplasia. PRCA was diagnosed and the patient was treated with periodic transfusions. A lateral view chest roentgenogram and a computed tomography scan of the thorax showed the presence of an anterior mediastinal mass which was suspected to be thymoma. The patient underwent thymothymectomy and the tumor was diagnosed as a thymoma. Although the patient received no treatment for MG and PRCA after surgery, her hematological test results rapidly improved and she was discharged from the hospital on the 29th postoperative day. At that time, her hematocrit was 33.2%, her hemoglobin concentration was 10.0 g/dl, her peripheral reticulocyte level was 1.8% and her left partial ptosis had improved. She is doing well, 9 months after surgery. For a patient to remain in remission without treatment for PRCA and MG after thymothymectomy is extremely rare.

Aged↗
PubMed1998

Effect of multidisciplinary treatment with high dose rate intraluminal brachytherapy on survival in patients with unresectable esophageal cancer.

BACKGROUND: Since carcinoma of the esophagus is usually diagnosed at an advanced stage, many cases of esophageal cancer are beyond possible radical resection and only palliative treatment can be performed in such cases. Therefore, a great deal of discussion has taken place concerning indications for treatment modality, and various procedures have been performed to palliate such patients. The prognosis for such patients is still poor, even though many kinds of palliation have already been developed and applied. To improve the prognosis of such patients we developed a multidisciplinary treatment which includes high dose rate intraluminal brachytherapy (HDR-ILBRT) and evaluated its effectiveness, especially the HDR-ILBRT component. PATIENTS AND TREATMENT METHODS: Sixty-six patients with unresectable esophageal cancer enrolled in this study. Twenty-seven patients underwent bypass operations. Seven of the 27 patients received external irradiation only (group BE), 11 received external irradiation and HDR-ILBRT (group BEH), while the remaining 9 did not receive radiotherapy (group B). Another 39 patients without bypass operations were all treated with radiotherapy, 22 with external irradiation only (group E) and 17 were treated with external irradiation and HDR-ILBRT (group EH). After completion of radiotherapy, all patients received chemotherapy with 5-FU (2,500 mg/body) and CDDP (100 mg/body). RESULTS: Mean survival time and the 5-year survival rate of group BEH (13.3 +/- 1.5 months and 20%) were significantly improved compared with group BE + B (p < 0.05). In the patients without bypass operations, there were significant differences in the mean survival time and the 3-year survival rate in groups EH and E (group EH 16.5 +/- 2.5 months, 21.8%, group E 9.0 +/- 1.3 months, 0%, p < 0.05). The bypass operation itself and chemotherapy did not significantly affect the prognosis of patients with unresectable esophageal cancer. CONCLUSION: These results strongly suggest the use of HDR-ILBRT, as a component of multidisciplinary treatment for unresectable esophageal cancer, was significantly effective and HDR-ILBRT contributed to improve outcomes in patients with advanced esophageal cancer. HDR-ILBRT should be established as a component of treatments for unresectable esophageal cancer.

Aged↗
PubMed1998

[Effects of lactated Ringer solution and acetated Ringer solution on hepatic ATP and L/P ratio in rats subjected to acute hemorrhage].

This study aimed to clarify the difference in the effects of lactated Ringer solution (LR) and acetated Ringer solution (AR) on hepatic ATP level and L/P ratio during acute hemorrhage in rats. There were no significant differences in the hepatic ATP levels and L/P ratios among 3 groups. Glycogen in LR group was higher than that in the control group. However pH and the base excess in LR and AR group were significantly higher than those in the C group. These results suggest that LR as well as AR may improve the metabolic acidosis, and LR may be more useful than AR with regard to glucose supply during acute hemorrhage.

Acute Disease↗
PubMed1998

[Complete disappearance of metastatic pulmonary tumors in a case of hepatocellular carcinoma treated with UFT].

The disappearance of multiple pulmonary metastatic lesions in hepatocellular carcinoma patient following the oral administration of UFT is reported. Pulmonary and pelvic metastases were detected in a 71-year-old female hepatocellular carcinoma patient treated by TAE (Trans-Arterial Embolization with epirubicin, mitomycin C, lipiodol and Gelform) three times in one year. Four months after beginning oral administration of UFT-E granule 1.5 g/day (tegafur 300 mg/day, uracil 672 mg/day), three pulmonary metastatic lesions markedly reduced in size, and disappeared completely 6 months after beginning UFT. A pelvic metastatic tumor markedly reduced in size by the combined effect of radiation, TAE (epirubicin, mitomycin C, lipiodol, Gelform) and oral UFT. We consider UFT was effective in the disappearance of multiple pulmonary metastatic lesions, because three TAE administrations of epirubicin and mitomycin C could not prevent systemic spreading of hepatocellular carcinoma.

Administration, Oral↗
PubMed1998

[Effects of hypertonic lactated Ringer's solution on hepatic ATP and L/P ratio in rats subjected to acute hemorrhage].

This study aimed to clarify the difference in the effects of hypertonic lactated Ringer's solution (HLS) on hepatic ATP level and L/P ratio during acute hemorrhage in rats. The hepatic ATP level in HLS 230 group was lower, and L/P ratio in HLS 300 group was higher than those in the control group. There was no significant difference in glycogen among 4 groups. However, pH and the base excess in HLS 230 and HLS 300 group were significantly higher than those in the C group. Heart rate in HLS 300 group was significantly lower than that in the C group. These results suggest that HLS may not be useful with regard to the hepatic energy metabolism, although it improves the metabolic acidosis during acute hemorrhage.

Acute Disease↗
PubMed1997

Translocation (8;12;21)(q22.1;q24.1;q22.1): a new masked type of t(8;21)(q22;q22) in a patient with acute myeloid leukemia.

The translocation t(8;21)(q22;q22) is found in 40% of cases of acute myeloid leukemia (AML) designated as the subtype M2 in the French-American-British (FAB) classification. The 8;21 translocation is clinically of interest because patients with this subtype have a good prognosis. We describe a masked type of the translocation, t(8;12;21)(q22.1;q24.1;q22.1). The translocation was first interpreted as t(8;12)(q22;q24) based on cytogenetics, but was reevaluated as a result of Southern blot and fluorescence in situ hybridization (FISH) analyses.

Acute Disease↗
PubMed1997

The well-balanced nucleoside-nucleotide mixture "OG-VI" for special medical purposes.

Nucleotides and nucleosides are essential components in all cells. However, nucleotides have not been supplied in parenteral nutrition regimens. We developed a well-balanced nucleoside-nucleotide mixture "OG-VI" and examined its effect in animals under some stressed conditions. OG-VI was composed of 30 mmol/l of inosine, 30 mmol/l of guanosine monophosphate, 30 mmol/l of cytidine, 22.5 mmol/l of uridine and 7.4 mmol/l of thymidine. The whole body protein turnover increased significantly in rats receiving total parenteral nutrition (TPN) with OG-VI solution after 70% hepatectomy, compared with rats receiving normal TPN without OG-VI (122.1 +/- 20.9 mgN.kg-1.h-1 vs. 97.4 +/- 10.1 mgN.kg-1.h-1, P < 0.01, n = 10). OG-VI significantly enhanced protein synthesis while it did not decrease protein breakdown. The effect of OG-VI on myocardium after hypoxic challenge was also examined in rats. The creatine phosphate (PCr)/inorganic phosphate (Pi) was decreased in normal rat myocardium after hypoxic challenge. However, in the rats administered OG-VI, PCr/Pi was maintained at baseline level and did not decrease after hypoxia. There was no significant change in the level of adenosine triphosphate (ATP) between before and after hypoxic challenge in myocardium of the rats administered OG-VI. In the rats receiving normal saline, instead of OG-VI, the ATP level decreased significantly after hypoxic challenge (4132 +/- 276 nmol/g tissue, n = 3, vs. 3439 +/- 465 nmol/g tissue, n = 5, P < 0.05). These data suggested that the well-balanced nucleoside-nucleotide mixture, OG-VI improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Animals↗
PubMed1997

Somatic hypermutations in the VH segment of immunoglobulin genes of CD5-positive diffuse large B-cell lymphomas.

De novo CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to be elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CD5+ B-cell malignancies such as mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia (B-CLL) cells represent pre-germinal center (pre-GC) stage B cells in contrast with the post-GC stage of most DLBLs, which show somatic hypermutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre-GC stage, as do other CD5+ B-cell malignancies, or the post-GC stage, as is typical of DLBL. All eight cases (four CD5+ DLBL and four CD5-negative (CD5-) DLBL) examined by us showed somatic hypermutations in the VH segment and two of the CD5- DLBL cases showed intra-clonal diversity, suggesting that CD5+ DLBLs were derived from the same maturation stage as CD5- DLBL, but were distinct from the other indolent CD5+ B-cell lymphomas of B-CLL and MCL. These data suggest that de novo CD5+ DLBLs do not merely lie within a continuous spectrum with B-CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B-cell lymphoma.

Adult↗
PubMed1997

[Effects of steroids on hepatic ATP and L/P ratio in rats subjected to acute hemorrhage].

Both steroids and hemorrhage may affect the hepatic energy metabolism. The effects of steroids (5 mg.kg-1 of methylpredonisolone, 50 mg.kg-1 of methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of hydrocortisone) on hepatic ATP level and L/P ratio were evaluated in rats under acute hemorrhage. There were no significant differences in the hepatic ATP levels and L/P ratio among 5 groups. However, the base excess in 3 steroid groups (50 mg.kg-1 of methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of hydrocortisone) was significantly higher than that in the control group. This result suggests that steroids may improve the metabolic acidosis during acute hemorrhage.

Acidosis, Lactic↗
PubMed1997

[A case of aneurysm of the descending thoracic aorta associated with Behçet's disease].

A 66-year-old male with Behçet's disease admitted again with hemoptysis. He underwent the resection and direct closure of descending aortic aneurysm 3 years ago, followed without the use of steroid. Chest CT scanning demonstrated a recurrent aneurysm of the descending aorta which was could not be detected on the previous CT only 23 days before. In the current operation, we performed resection, direct closure and wrapping of the aneurysm. The pathological examination showed a true aneurysm of Behçet's disease. The patient is free from recurrence for 17 months since the operation under steroid therapy.

Aged↗
PubMed1997

[Autologous peripheral blood stem cell transplantation for CHOP-resistant mediastinal diffuse large B-cell lymphoma].

We report two cases of CHOP-resistant mediastinal diffuse large B-cell lymphoma (MDLCL) treated by autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were 17 and 28 year old female, and they had anterior mediastinal bulky masses at presentation. The clinical stage was IV in both patients. They were initially treated with 6 courses of bi-weekly CHOP therapy following by irradiation of the mediastinal tumors. During the last few cycles of CHOP therapy, their disease had become progressive. They underwent auto-PBSCT after high-dose chemotherapy consisting of busulfan, cyclophosphamide and etoposide, but failed to achieve remission. They died within one year after the auto-PBSCT because of the disease progression. Our experience suggests that this conditioning regimen is not effective for CHOP-resistant MDLCL, and it is necessary to develop new conditioning regimens.

Adolescent↗
PubMed1996

Translocation (9;11;22)(p22;q23;q11). A new type of complex variant translocation of t(9;11)(p22;q23) with MLL rearrangement.

We describe a patient with acute monocytic leukemia (M5a, FAB classification) associated with a new type of variant translocation (9;11). Southern blot analysis showed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Fluorescence in situ hybridization (FISH) with painting probes of chromosomes 9, 11, and 22 revealed the translocation as t(9;11;22) (p22;q23;q11). This is more evidence that the production of chimeric mRNA following the translocation of the LTG9 (MLLT3/AF9) gene at 9p22 to 11q is a critical event in this leukemia subtype.

Adult↗
PubMed1996

Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury.

It has been reported that ischemic preconditioning of the heart or brain has a possible relevance to heat shock protein (HSP). It is still unknown, however, whether HSP induced by means of ischemic preconditioning of the liver is a direct factor in the acquisition of tolerance to succeeding ischemia-reperfusion injury. In the present study we used ischemic preconditioning of the liver to verify the effects of induced HSP72 in the liver on the subsequent longer warm ischemia and reperfusion. Rats preconditioned with short-term (15-minute) ischemia were compared with rats preconditioned by heat exposure or with control rats. After a 48-hour recovery from the sublethal stress for preconditioning, all rats were exposed to longer (30-minute) warm ischemia and reperfusion. Forty-eight hours after ischemic preconditioning, HSP72 was clearly induced in the liver, as well as in the liver preconditioned with heat shock, but not in the kidney or heart. This ischemic preconditioning also attenuated the liver damage in the subsequent ischemia-reperfusion injury, improving the restoration of hepatic function during reperfusion and resulting in higher postischemic rat survival. According to the proposed model of tolerance acquisition for ischemia-reperfusion injury by stress preconditioning, these observations support the speculation that the induced HSP72 plays some beneficial role in this protection mechanism.

Adaptation, Physiological↗