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Biomedical subjects

Y Kamiyama

Publications and source records attributed to Y Kamiyama.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of consecutive lower-dose cisplatin in enhancement of 5-fluorouracil cytotoxicity in experimental tumor cells in vivo.

It is known that cisplatin (CDDP) potentiates the cytotoxicity of 5-fluorouracil (5-FU), and that the biochemical mechanism is an increase in the intracellular reduced folate levels in the tumor cells. We investigated the effect of consecutive administration with lower-dose CDDP on intracellular accumulation of reduced folate and the activity of methionine synthase, a key enzyme in intracellular methionine synthesis. When CDDP (1 mg/kg) was administered i.p. to ascitic Yoshida sarcoma-bearing rats for 4 consecutive days, both the reduced folate levels and methionine synthase activity in the cells significantly increased, as the same as a single 5 mg/kg dose of CDDP. Furthermore, when Yoshida sarcoma-bearing rats were pre-treated with 1 mg/kg CDDP for 5 consecutive days, [14C]L-methionine incorporation into the isolated ascitic cells was significantly inhibited as compared to that in non-treated cells, suggesting that consecutive administration of lower-dose CDDP is capable of inducing the intracellular modulation of reduced folate levels and methionine synthase activity via inhibition of cellular uptake of methionine. In addition, 5-day administration of lower-dose (1 mg/kg) CDDP potentiated the antitumor effect of 5 mg/kg S-1, a new oral preparation of tegafur, given for 7 consecutive days, and this combined effect was almost similar to the antitumor effect of a combination of S-1 and a single conventional dose (5 mg/kg) of CDDP. Consecutive lower-dose CDDP also may be concluded to act as an important modulator of the enhancement of 5-FU cytotoxicity in experimental tumors.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines.

We evaluated the plasma concentrations of cytokines and platelet-derived microparticles in patients with arteriosclerosis obliterans and studied the effect of cytokines on platelet-derived microparticle generation under high shear stress. Interleukin-6 levels peaked at 48 hours after vascular surgery, while thrombopoietin started to increase at 24 to 48 hours postoperatively and peaked on the seventh day. Platelet activation markers were increased in the arteriosclerosis obliterans patients preoperatively. Levels of P-selectin and CD63 both increased further, peaking at 6 to 24 hours postoperatively. Platelet-derived microparticle levels were also increased preoperatively. At 6 hours postoperatively, the plasma level of platelet-derived microparticles was significantly increased. Plasma platelet-derived microparticle level was lower at 12 hours but only returned to the preoperative value at 7 days after grafting. There was a difference in the platelet-derived microparticle level at 7 days between patients with or without antiplatelet therapy (cilostazol). The effect of cytokines on platelet activation under high shear stress was also studied. Interleukin-6 and thrombopoietin enhanced both P-selectin expression and platelet-derived microparticle generation under high shear stress. These results suggest that platelet-derived microparticles are released by platelet activation after vascular grafting when certain cytokines increase under high shear stress and that antiplatelet therapy may reduce platelet-derived microparticle levels postoperatively.

Aged↗
PubMed2000

Vicinal dithiol-binding agent, phenylarsine oxide, inhibits inducible nitric-oxide synthase gene expression at a step of nuclear factor-kappaB DNA binding in hepatocytes.

Inflammatory cytokine interleukin 1beta induces inducible nitric-oxide synthase (iNOS) mRNA and its protein, which are followed by increasing the production of nitric oxide, in primary cultures of rat hepatocytes. Nuclear factor-kappaB (NF-kappaB), an important transcription factor for iNOS gene expression, is also activated and translocated to the nucleus. In the present study, we found that vicinal dithiol-binding agent, phenylarsine oxide (PAO), inhibited the induction of iNOS protein and mRNA as well as the release of nitrite (nitric oxide metabolite) into the culture medium. Simultaneous addition of a vicinal dithiol compound, 2, 3-dimercaptopropanol, with PAO completely abolished these inhibitions. PAO could not prevent either degradation of an inhibitory protein, IkappaB, of NF-kappaB or translocation of NF-kappaB to the nucleus. However, electrophoretic mobility shift assay demonstrated that PAO decreased the interaction between NF-kappaB and its binding consensus oligonucleotide. Transfection experiments with iNOS promoter-luciferase construct revealed that PAO inhibited NF-kappaB binding to DNA. These results indicate that PAO inhibits iNOS gene expression at a step of NF-kappaB binding to DNA by modifying its vicinal dithiol moiety, which may play a crucial role for the iNOS regulation in hepatocytes.

Animals↗
PubMed2000

Prediction of recurrence and extratumor spread of hepatocellular carcinoma following resection.

BACKGROUND AND OBJECTIVES: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy depends mostly on tumor recurrence. Portal vein invasion (Vp) and intrahepatic metastasis (IM) might strongly reflect the invasiveness of HCC, but the number of patients in the present series in whom either of these factors were detected was small. In this study, we defined Vp and IM as the extratumor spread, and we focused on the relationship between recurrence in patients after hepatectomy and the extratumor spread and the mitotic activities of cancer cells, in the hope that careful monitoring of recurrence might be possible by simply analyzing histology of the resected specimens. METHODS: Univariate and multivariate analyses were used to determine the factors potentially related to recurrence in 50 patients who underwent hepatectomy for HCC. RESULTS: The cumulative recurrence rate at 5 years was 81.0%. In univariate analysis, absence of the extratumor spread, mitotic index of four or less, and curative resection were significantly correlated with low incidence of recurrence. In multivariate analysis, the extratumor spread was the only significant variable influencing recurrence. The mitotic index in HCCs with the extratumor spread was significantly higher than the mitotic index in HCCs without the extratumor spread. CONCLUSIONS: As a predictive factor for recurrence after resection of HCC, the extratumor spread that reflects the malignant potential of cancer cells was found to be more accurate than is any single invasiveness parameter such as Vp or IM.

Analysis of Variance↗
PubMed2000

Recombinant human hepatocyte growth factor protects the liver against hepatic ischemia and reperfusion injury in rats.

BACKGROUND: Recent evidence indicates that hepatocyte growth factor (HGF) has a cytoprotective effect against hepatic injury caused by hepatotoxins and inflammatory cytokines. Studies were performed to determine whether HGF influences the survival rate of rats subjected to hepatic warm ischemia/reperfusion (WI/Rp) injury. METHODS: Male Sprague-Dawley rats were subjected to total or segmental hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct with a microvascular clip. Rats were treated with four intravenous injections of recombinant human HGF (rhHGF 1 mg/kg) or the vehicle 72, 48, 24, and 12 h before surgery. RESULTS: None of the eight animals in the control group were alive 12 h after total hepatic WI/Rp. Seven of eight animals in the rhHGF-treated group were alive more than 2 days after the reperfusion. In the model of segmental hepatic ischemia, rhHGF inhibited the increase in cytokine-induced neutrophil chemoattractant in serum. The number of neutrophils infiltrating the liver was significantly lower in the rhHGF-treated group than in the control group. rhHGF prevented increases in the activity of serum alanine transaminase and in hepatic necrosis. Experiments with proliferating cell nuclear antigen staining demonstrated that hepatocyte proliferation markedly increased in rhHGF-treated rats as compared with controls. CONCLUSIONS: These results indicate that HGF facilitates recovery of the liver from hepatic WI/Rp injury, at least in part through the prevention of neutrophil infiltration and the activation of hepatocyte proliferation.

Animals↗
PubMed2000

The role of lipid peroxidation on gastric mucosal lesions induced by water-immersion-restraint stress in rats.

This study was designed to determine the effect of water-immersion-restraint stress (WIRS) and pretreatment by reduced glutathione on both the production of gastric mucosal lesions and the content of gastric mucosal phosphatidylcholine hydroperoxide (PCOOH). Sprague-Dawley rats were divided into control and treatment groups (treated with reduced glutathione before stress). After graded durations of WIRS, the macroscopic ulcer index (UI) was measured and the PCOOH content was examined by a chemiluminescence-high performance liquid chromatography assay. The UI in the control group increased significantly in a time-dependent fashion. Elevation of the PCOOH level was observed in combination with the UI for up to 2h of WIRS, but then showed a declining tendency. Pretreatment with reduced glutathione significantly lowered both the UI and the PCOOH level. Lipid peroxidation is probably involved in the pathogenesis of gastric injury induced by WIRS at least in the early phases. However, in the late phases, other mechanisms causing gastric mucosal lesions may also be involved. We therefore believe this study to be the first to accurately and quantitatively assess the degree of lipid peroxidation in the gastric mucosa as a result of stress.

Animals↗
PubMed2000

Ionic current model of rabbit retinal horizontal cell.

We propose a mathematical model of rabbit retinal horizontal cell based on the ionic current mechanisms. Five types of ionic currents in rabbit retinal horizontal cell, I(Na), I(Ca), I(Kv), I(A) and I(Ka), are described by Hodgkin-Huxley type equations based on voltage clamp measurements. In simulation the model reproduced similar responses to voltage and current clamp experiments. Under the current clamp experiment a repetitive action potential was found on A-type rabbit horizontal cells. Our result suggests that the repetitive action potential is generated by an interaction Of I(Ca) and I(Kv).

Action Potentials↗
PubMed2000

Nitric oxide production and hepatic dysfunction in patients with postoperative sepsis.

1. Although hepatic function is well known to deteriorate following bacterial infection, the underlying mechanisms remain poorly understood. We have previously reported that nitric oxide (NO) radical leads to a decrease in the ketone body ratio (KBR) and in ATP content due to the inhibition of mitochondrial electron transport in primary cultured rat hepatocytes. 2. To evaluate the effects of NO radical on the liver in patients with postoperative sepsis, we analysed both the stable end-product of nitric oxide radical (NOx) as well as the arterial KBR (AKBR), which reflects liver tissue NAD+/NADH. 3. Twenty patients who had undergone general abdominal surgery and who developed postoperative sepsis were divided into two groups: (i) surviving; and (ii) non-surviving. Blood samples were collected before the development of postoperative sepsis and every 3 days until the patient either died or was discharged from hospital. 4. Plasma NOx levels in seven patients who subsequently died became progressively higher than those in the 13 surviving patients over the clinical course of postoperative sepsis. 5. In the non-surviving group, the AKBR was significantly lower than in surviving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non-surviving patients were significantly higher than in surviving patients. 6. Decreases in AKBR to levels below 0.7 in non-surviving patients followed high NOx levels. Moreover, plasma NOx levels were closely correlated with the AKBR, indicating that NO radical is associated with mitochondrial dysfunction in the liver. 7. It is likely that the overproduction of NO radical plays an important role in causing fatal metabolic disorders in patients with postoperative sepsis.

Aged↗
PubMed2000

Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes.

Ischemia/reperfusion contributes to the hepatic injury in resection and transplantation of the liver. However, the precise mechanisms involved in hypoxia stress remain to be clarified. Pro-inflammatory cytokines including interleukin 1beta (IL-1beta) induce a gene expression of inducible nitric oxide synthase (iNOS) and produce nitric oxide, which exerts either a cytoprotective or toxic effect. In this report, we found that hypoxia and heat markedly inhibited the induction of nitric oxide production stimulated by IL-1beta in rat cultured hepatocytes. Both treatments also abolished the induction of iNOS protein and mRNA. However, hypoxia could not prevent either degradation of an inhibitory protein (IkappaBalpha) of nuclear factor-kappaB (NF-kappaB) or translocation of NF-kappaB to the nucleus, whereas heat inhibited both of the IkappaBalpha degradation and NF-kappaB translocation. Transfection experiments with iNOS promoter construct revealed that hypoxia as well as heat significantly inhibited the transactivation of iNOS gene. Further, a hypoxia-response element located in the promoter was not involved in the inhibition of iNOS induction by hypoxia. These results indicate that hypoxia and heat suppress iNOS gene induction at the transcriptional level through different mechanisms. Reduction of nitric oxide production under hypoxic conditions may be implicated in the cellular damage or protection during hepatic ischemia/reperfusion.

Animals↗
PubMed2000

Selective thermocoagulation of unresectable pancreatic cancers by using radiofrequency capacitive heating.

Recent investigations indicated that hyperthermia has antitumor effects. Several interstitial hyperthermic techniques were developed, and their clinical usefulness and safety were evaluated. However, few authors have attempted to study the use of interstitial hyperthermia for the treatment of pancreatic carcinomas. Therefore the efficacy of local selective thermocoagulation by radiofrequency was evaluated in 20 patients with unresectable carcinomas of the pancreas. A laparotomy and radiofrequency heating were performed in 20 patients with unresectable pancreatic carcinomas after informed consent. Local heat coagulation was induced by a 13.56-MHz radiofrequency pulse, produced by the heating apparatus. Four 2-cm needle electrodes were placed in the tumor, in a square array, at intervals of 2 cm. The heat was then administered for 15 min at a controlled temperature of 50 degrees C in the radiofrequency field (2x2x2 cc). All the patients were evaluated by computed tomographic scanning. Tumor markers in the blood also were assayed before and after the heating. Follow-up computed tomographic scans demonstrated that the tumor mass was enhanced heterogeneously, and after selective thermocoagulation, images revealed a change to a homogeneous low-density area. The blood levels of tumor markers decreased to below pretreatment values in 15 patients. Of the 20 cases treated with thermocoagulation, two had critical complications. One patient had septic shock, and another had gastrointestinal bleeding. The other 18 patients had no significant complications. These observations suggest that the selective thermocoagulation of tumor tissues using this equipment was relatively safe. These results justify further clinical trials for the treatment of patients with unresectable tumors without metastasis, or patients with benign pancreatic tumors such as insulinomas.

Adenocarcinoma↗
PubMed2000

Increased extra domain-A containing fibronectin and hepatic dysfunction during septic response: an in vivo and in vitro study.

A massive inflammatory reaction resulting from systemic cytokine release is the common pathway underlying sepsis or multiple organ dysfunction. The role of extra domain sequence A-containing fibronectin (EDA+FN) formation during the septic response is not known. The present study investigates the role of EDA+FN during the septic response under in vitro and in vivo conditions. The direct effects of interleukin-1, interleukin-6, and tumor necrosis factor-alpha on EDA+FN production were evaluated in primary cultured human hepatocytes and fibroblasts. Serial plasma EDA+FN levels were measured using an enzyme-linked immunosorbent assay in 24 patients who developed postoperative sepsis following general abdominal surgery of which there were 17 survivors and 7 non-survivors. EDA+FN secretion was significantly increased in cultured hepatocytes but not fibroblasts at 24 and 48 h following exposure to IL-1 compared to controls. In the clinical setting plasma EDA+FN levels in non-survivors were significantly higher than in survivors. Moreover, the EDA+FN levels were correlated closely with liver function tests. EDA+FN levels may represent a specific marker of vascular injury or systemic inflammatory response syndrome that is associated with an adverse clinical outcome.

APACHE↗
PubMed2000

Mitotic index is the best predictive factor for survival of patients with resected hepatocellular carcinoma.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), tumor recurrence is not infrequent after resection. It is presumed that characteristics of the tumor such as cellular malignancy might influence the prognosis of the patients in association with tumor stage and radicality of the procedure. METHODS: Univariate and multivariate analyses were used to retrospectively determine the clinicopathologic factors potentially related to survival in 40 patients who underwent hepatectomy for HCC. RESULTS: In univariate analysis, tumor stage I or II, mitotic index of 4 or less/10 random high-power fields, solitary tumor, and curative resection were significantly correlated with better survival. In multivariate analysis, the mitotic index and surgical curability were independently significant variables influencing survival of patients, and the mitotic index was the best predictive factor. A highly significant correlation was found between the mitotic index and Ki-67 labeling index. Compared to tumors with a mitotic index of 4 or less, those with a mitotic index of 5 or more had a higher association with multiple tumors and advanced tumor stage, which preclude curative resection. CONCLUSION: Analysis of the mitotic index is quite simple, and the mitotic index could be a useful factor for predicting the long-term survival of patients with HCC following hepatic resection.

Carcinoma, Hepatocellular↗
PubMed2000

Hepatectomy using an ultrasonically activated scalpel for hepatocellular carcinoma.

BACKGROUND: The first retrospective studies were performed to compare the efficacy of the ultrasonic cavitational aspirator (aspirator group) and the ultrasonically activated scalpel (scalpel group) for hepatic resection in patients with hepatocellular carcinoma. PATIENTS AND METHODS: The aspirator group consisted of 8 patients (6 with liver cirrhosis and 2 with chronic hepatitis in the nontumorous liver), and the scalpel group of 7 patients (6 with liver cirrhosis and 1 with chronic hepatitis). All patients underwent limited hepatic resection, and the intermittent Pringle maneuver was applied during hepatic transection. RESULTS: There were no significant differences in preoperative hepatic function, type of hepatectomy, tumor size and maximum cross-sectional area of the resected specimen between the 2 groups. The amount of intraoperative blood loss was significantly less in the scalpel group than in the aspirator group (684 versus 1,859 ml, p < 0.05). The operation time was significanly shorter in the scalpel group than in the aspirator group (176 versus 262 min, p < 0.05). There were no significant differences in postoperative liver function and morbidity between the 2 groups. CONCLUSIONS: The ultrasonically activated scalpel is effective in reducing blood loss and in shortening the time of operation, and can be employed during limited resection of the liver with cirrhosis or chronic hepatitis.

Aged↗
PubMed2000

[Perioperative management of a patient with general lymph-congestion following total spondylectomy with posterior and anterior fusion for first thoracic vertebral hemangioma].

A 50-year-old healthy woman was scheduled for surgery of the first thoracic vertebral (T 1) hemangioma accompanying rapidly aggravated neurological deficit in three months. Anesthesia was induced with intravenous fentanyl and propofol and maintained with isoflurane-oxygen-air inhalation, followed by propofol infusion combined with sevoflurane inhalation. Following posterior decompression of T 1 with fusion of C 6-T 3, consecutive total spondylectomy of T 1 with anterior fusion of C 7-T 2 was carried out. At the end of surgery, marked edema was noticed on her face, neck and bilateral upper extremities, possibly due to long manipulation around the left jugular angle. Next morning the edema spread to her whole body and the elevation of both diaphragms and the mediastinal expansion were recognized. Mechanical ventilation in the mode of IMV was performed until subsiding of edema on the fifth postoperative day. During this period, hypoxemia was frequently observed in spite of appropriate respiratory support. On the third postoperative day, bronchoscopic bronchial toilet was performed which brought the improvement of blood oxygenation. The occasional administration of furosemide was not effective to reduce general edema, but served for the acceleration of lymphatic drainage after the release of the thoracic duct obstruction and the patient was extubated uneventfully on the sixth postoperative day.

Anesthesia, Intravenous↗
PubMed1999

A novel conception for liver preservation at a temperature just above freezing point.

BACKGROUND: It is generally accepted that 0 to 4 degreesC is a suitable temperature for organ preservation. The reason for this is based on the premise that at temperatures below 0 degreesC, intracellular ice is likely to form, with subsequent damage to cellular structures. However, it cannot be assumed that subzero temperatures will freeze the cell. In this study, we attempted to confirm the specific freezing point of rat liver and to preserve it at a temperature just above that point. METHODS: Rat livers were stored for 24, 48, 72, and 96 h either at 4 degreesC (Group N) or at -0.8 degreesC (just above the temperature ascertained to be the specific freezing point of rat liver; Group H). After cold storage, the livers were perfused for 60 min using an isolated perfused liver model for assessment of liver function. RESULTS: ATP and TAN (total adenine nucleotides) in reperfused liver tissues were significantly higher in Group H than in Group N for all preservation periods. ADP was significantly higher in Group H than in Group N for 24-, 72-, and 96-h preservation periods. Energy charge was significantly higher in Group H than in Group N for 24-, 48-, and 96-h preservation periods. CONCLUSIONS: Regarding the content of ATP, ADP, and TAN and the adenylate energy charge, our results indicate that preservation at -0.8 degreesC is advantageous. This novel preservation technique seems to prolong the period that organs can be stored.

Adenine Nucleotides↗
PubMed1999

An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy.

BACKGROUND/AIMS: Infection after a liver resection often results in hepatic failure. Nitric oxide is one of the candidates which has been suspected to cause cellular dysfunction during infection in the liver. We have previously reported that the inflammatory cytokine interleukin-1beta (IL-1beta) induced the expression of the inducible nitric oxide synthase gene in primary cultured rat hepatocytes. We hypothesized that an enhancement of nitric oxide production after the resection was implicated in a change in liver energy metabolism, thus resulting in liver dysfunction. METHODS: In this study, we performed a 70% hepatectomy or a sham operation in rats, and then isolated hepatocytes from the remnant liver by collagenase perfusion. The cultured hepatocytes were treated with cytokines including IL-1beta. The effects on nitric oxide induction, the ATP content and ketone body ratio (acetoacetate/beta-hydroxybutyrate) were then compared between the partial hepatectomized (PH) and sham-operated (control) rats. RESULTS: IL-1beta augmented the induction of nitric oxide production two-fold in hepatocytes from the PH rats as compared to the control rats. IL-1beta markedly decreased the ATP content in the PH rats, although IL-1beta also decreased the ATP content in the control rats, but to a lesser extent. IL-1beta also decreased the ketone body ratio in both groups. The addition of L-arginine further stimulated the inhibition of the ATP levels and the ketone body ratio concomitantly with increased nitric oxide production in the PH rats. N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, abolished the effects of IL-1beta on the ATP levels and ketone body ratio, as well as on the nitric oxide production. CONCLUSIONS: These results demonstrate that the decreased ATP content observed in PH rats resulted from an increase in nitric oxide production. The decrease in ketone body ratio indicates that nitric oxide-induced mitochondrial dysfunction contributes significantly to ATP attenuation in hepatocytes. Therefore, the regulation of nitric oxide induction may be crucial for preventing liver failure after a hepatic resection.

Adenosine Diphosphate↗