PubMed HealthSearch

Biomedical subjects

T Kamiyama

Publications and source records attributed to T Kamiyama.

At least 19 recordsLinked to original sources

Mexiletine and lidocaine reduce post-ischemic functional and biochemical dysfunction of perfused hearts.

The present study was undertaken to determine whether class Ib antiarrhythmic agents, mexiletine and lidocaine, exert beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-min reperfusion and the functional and metabolic alterations were examined with and without mexiletine or lidocaine treatment. Ischemia/reperfusion resulted in a lack of recovery of contractile function, a sustained rise in left ventricular end-diastolic pressure and increased coronary perfusion pressure of the perfused heart during reperfusion. Contractile dysfunction was associated with increases in tissue Na+ and Ca2+ levels, decreases in K+ and Mg2+ levels, and release of creatine kinase and purine nucleosides and bases (ATP metabolites) from the heart. Treatment of the perfused heart with either 10-100 microM of either mexiletine or lidocaine during pre-ischemia resulted in an enhancement of post-ischemic contractile recovery, a suppression of changes in tissue Na+, K+, Ca2+ and Mg2+ contents and an attenuation of the release of creatine kinase and ATP metabolites in an almost concentration-dependent manner. Tissue sodium accumulation was observed at the end of ischemia, which was also attenuated by pretreatment with these agents. The prevention of Na+ overload and accompanying Ca2+ overload in cardiac cells may be the mechanism underlying the improvement of post-ischemic contractile function of perfused hearts by these agents.

Adenosine Triphosphate

Sulfobacins A and B, novel von Willebrand factor receptor antagonists. I. Production, isolation, characterization and biological activities.

Sulfobacins A and B, novel von Willebrand factor (vWF) receptor antagonists, have been isolated from the culture broth of Chryseobacterium sp. (Flavobacterium sp.) NR 2993 by ethyl acetate extraction, and by Sephadex LH-20 and silica gel column chromatographies. The physico-chemical properties of the sulfobacins indicate that their structures are completely different from that of aurintricarboxylic acid, the one known vWF receptor antagonist. Sulfobacins A and B inhibit the binding of vWF to its receptor with IC50S of 0.47 and 2.2 microM, respectively. Sulfobacin A also inhibits ristocetin-induced agglutination in human platelets fixed with paraformaldehyde with an IC50 of 0.58 microM.

Alkanesulfonic Acids

Sulfobacins A and B, novel von Willebrand factor receptor antagonists. II. Structural elucidation.

Sulfobacins A and B are novel von Willebrand factor (vWF) receptor antagonists produced by Chryseobacterium sp. NR 2993. The structures of sulfobacins A and B have been determined to be (2R,3R)-3-hydroxy-2-[(R)-3-hydroxy-15-methylhexadecanamido]-15- methylhexadecanesulfonic acid and (2R,3R)-3-hydroxy-15-methyl-2-[13-methyltetradecanamido]- hexadecanesulfonic acid, respectively, by various 2D NMR experiments and by methanolysis. The absolute configurations of the sulfobacins were determined by a modified MOSHER's method. The structures are related to sulfonolipids, major components of the cell envelope of gliding bacteria of the genus Cytophaga.

Alkanesulfonic Acids

[Advantages and disadvantages of the intraarterial chemotherapy using a reservoir as postoperative adjuvant therapy for hepatocellular carcinoma].

We conducted a retrospective study on the efficacy and disadvantages of intraarterial chemotherapy using a reservoir (ICUR), as postoperative adjuvant therapy for hepatocellular carcinoma (HCC). One hundred and seventy HCC patients who underwent hepatectomy since 1987 to 1992 in our institute were enrolled in this study. Ninety-two patients were postoperatively treated with ICUR (group R), and seventy-eight patients without it (group N). There were no significant differences between the two groups in the preoperative evaluations of the characteristics of patients, tumors, and operative procedures. Although statistical significances were not found, disease-free rates within 1 year and cumulative survival rates appeared to be higher in group R than in group N. Patency of the catheter of reservoirs at one and two years were maintained in 80.3 and 44.1% of the patients, respectively. HCC recurred after an occlusion of the reservoir in 18 patients. In four out of these 18 patients, transcatheter arterial embolization (TAE) for recurrent tumors was not feasible, because of occlusion of the hepatic artery. TAEs for recurrent lesions would have been impossible in about 10% of all patients treated with ICUR. Thus, both the advantages and disadvantages should be taken into consideration on the indication of ICUR, and the maintainance of the catheter is important for successful ICUR.

Antineoplastic Combined Chemotherapy Protocols

[Two hepatocellular carcinoma patients with biloma after transarterial embolization with lipiodol (Lip-TAE) leading to occlusion of portal vein].

We presented two patients with post-Lip-TAE biloma resulting in portal occlusion, and reviewed 20 previous studies including our cases to investigate their clinical characteristics. Case 1. A 31-year-old woman suffered from an HCC located at the S8 segment, and had a superselective embolization of feeding arteries using 3 ml of Lip, 300 mg of CBDCA, and 40 mg of Epi-Adriamycin (Epi-ADM). Eleven weeks later, CT showed multiple cystic lesions, and the percutaneous transhepatic drainages of the lesions were established. At 21 weeks after Lip-TAE, we found occlusion of the right branch of portal vein on CT, but she recovered from this condition, and was discharged 1 year later. Case 2. A 62-year-old man was diagnosed as HCC located at S7-6 segments, and was infused with 3 ml of Lip, 150 mg of CBDCA, and 30 mg of Epi-ADM through a right hepatic artery. Ten weeks later, CT showed a cystic lesion in the S7-8 segments, occlusion of the right anterior segmental branch of the portal vein, and the same drainage was also established. Unfortunately, he died of liver failure 18 weeks later. In the literature, biloma after Lip-TAE occurred at 71.2 mean days, ranging from 7 to 180 days, a with remarkable increase in biliary tree-associated enzymes. Seven (35%) of 20 patients died of liver failure or sepsis during 3 weeks and 1 year, and 3 (60%) of 5 patients accompanied by occlusion of a certain portal branch frequently died. We consider that these patients need intensive care and should be under long follow-up.

Adult

[Effects of intraarterial chemotherapy after hepatectomy in hepatic cancer patients].

We conducted a retrospective study on the effects of intra-hepatic arterial chemotherapy in patients with liver cancer, and 118 patients with stage II hepatocellular carcinoma (HCC) who had undergone hepatectomy were enrolled. Patients were divided into three groups: group R (n = 41) was treated by intraarterial infusion of Epi-adriamycin 30-40 mg/body and CDDP 100 mg/body via reservoir every two weeks post-operatively; group O (n = 57) was given one-shot infusion of Epi-adriamycin or adriamycin, and group N (n = 20) served as the control. No significant differences were observed among the three groups in postoperative disease-free survival rates. The better prognosis of survival rates found in group R suggested the influence of treatment on the recurrent lesions. Six of 14 long-term survivors were in group N. The selection of the patients group should be studied more in order to obtain the full potential of postoperative intraarterial chemotherapy in stage II HCC.

Antineoplastic Combined Chemotherapy Protocols

Effects of one-year cadmium exposure on livers and kidneys and their relation to glutathione levels.

To study the effects of a long-term cadmium exposure on livers and kidneys, rats were administered cadmium chloride (0.228 mg Cd/kg, 3 days/week ip), for one year. Significant accumulation of cadmium was observed in livers (183 +/- 40 micrograms/g liver) and kidneys (92 +/- 17 micrograms/g kidney). Serum urea nitrogen and creatinine levels were significantly elevated in the cadmium-treated rats, while liver function tests were minimally affected. Histological observations showed interstitial fibrosis with minimal cell necrosis and inflammatory cell infiltration in livers, and apparent degeneration of proximal tubules and infiltration of inflammatory cells in parenchyma of kidneys. Lipid peroxidation in livers and kidneys, as assessed by thiobarbituric acid reactive substances, revealed no differences between the cadmium-treated rats and the controls. Glutathione contents were significantly increased in the cadmium treated rats both in livers (p < 0.001), and in kidneys (p < 0.001) compared with the controls. Increased glutathione levels in livers may contribute, in part, to the prevention of serious hepatotoxicity during chronic cadmium exposure, while nephrotoxicity due to cadmium may not be prevented by glutathione.

Animals

A possible involvement of sodium channel blockade of class-I-type antiarrhythmic agents in postischemic contractile recovery of isolated, perfused hearts.

The present study was undertaken to test the hypothesis that the degree of sodium channel blockade by class-I-type antiarrhythmic agents accounts for enhancement of postischemic contractile recovery of ischemic/reperfused hearts. Electrophysiological studies showed that the class-I-type antiarrhythmic agents quinidine, disopyramide, procainamide, lidocaine, mexiletine, flecainide and pilsicainide suppressed the Vmax value of the rat left ventricular muscle cell, a marker of sodium channel blockade, in a concentration-dependent manner. Isolated rat hearts were subjected to 35 min of ischemia and 60 min of reperfusion. Postischemic contractile recovery, which was never detected in untreated hearts, was enhanced in hearts pretreated with these antiarrhythmic agents during the last 3 min before ischemia at concentrations ranging from 3 to 300 microM. Tissue Na, but not Ca, accumulation was also detected in the ischemic heart, and tissue Na and Ca accumulation was observed in the reperfused heart, which suggests that sodium overload occurs during ischemia, followed by sodium and calcium overload during reperfusion. The degree of postischemic contractile recovery seen in the presence of these antiarrhythmic agents was inversely related to tissue Na or Ca accumulation after reperfusion, which suggests that class-I-type antiarrhythmic agents inhibit sodium overload occurring in ischemic/reperfused myocardial cells. A close relationship between postischemic contractile recovery of the perfused heart and depression in the Vmax value of the ventricular muscle was also observed. These results suggest that the ability class-I-type antiarrhythmic agents to inhibit myocardial sodium channels plays a significant role in the enhancement of postischemic contractile recovery of the ischemic/reperfused heart.

Animals

cDNA cloning and expression of a novel human desmocollin.

We have cloned a human cDNA encoding for a novel transmembrane protein from a bladder carcinoma cell line (HT-1376) cDNA library. Sequence analysis of this clone revealed an open reading frame of 2,691 bases encoding a protein of 896 amino acids. Sequence comparison showed that this clone has significantly homology to desmocollins, intracellular adhesion molecules belonging to the cadherin superfamily. This protein consists of a signal peptide of 30 amino acids, a precursor segment of 105 amino acids, and a mature protein of 761 amino acids. We expressed this cDNA clone in COS1 cells and found that the predicted cell adhesion molecule remained in the membrane fraction. Antibodies recognizing the predicted mature adhesion molecule of the protein stained antigens along the cell boundaries of both HT-1376 cells and normal human keratinocytes resembling the pattern of desmosome localization. These findings suggest that our clone might be a new member of the desmocollin family, and we have tentatively called this clone human desmocollin type 4.

Alternative Splicing

Tetrafibricin has a high selectivity for GPIIb/IIIa: comparison of the effects of tetrafibricin and RGDS on GPIIb/IIIa and the vitronectin receptor.

The specificity of tetrafibricin was examined by comparing its activities on GPIIb/IIIa and on the vitronectin receptor (alpha v beta 3) with those of Arg-Gly-Asp-Ser (RGDS) on the same receptors. Tetrafibricin, which inhibited fibrinogen-GPIIb/IIIa binding 10 times more potently than RGDS, was three orders of magnitude less potent compared to RGDS on the inhibition of fibrinogen binding to alpha v beta 3. Furthermore, tetrafibricin potently inhibited platelet adhesion to both fibrinogen and von Willebrand factor. Whereas, there was no significant inhibition observed in the GPIIb/IIIa-independent cellular adhesions. These results suggest that tetrafibricin is highly selective for GPIIb/IIIa.

Amino Acid Sequence

Tetrafibricin, a novel non-peptide fibrinogen receptor antagonist, induces conformational changes in glycoprotein IIb/IIIa.

Arg-Gly-Asp (RGD) is an amino acid sequence in fibrinogen recognized by platelet glycoprotein (GP) IIb/IIIa. Recently, it was found that RGD peptide binding to GPIIb/IIIa leads to conformational changes in the complex that are associated with the acquisition of high-affinity fibrinogen-binding function. In this study, we found that tetrafibricin, a novel non-peptidic GPIIb/IIIa antagonist, induced similar conformational changes in GPIIb/IIIa as did RGD peptides. Tetrafibricin increased the binding of purified inactive GPIIb/IIIa to immobilized pl-80, a monoclonal antibody that preferentially recognizes ligand-occupied GPIIb/IIIa. Exposure of the pl-80 epitope by tetrafibricin was also observed on resting human platelets by flow cytometry. On intact platelets, the conformational changes transformed GPIIb/IIIa into a high-affinity receptor for fibrinogen and triggered subsequent platelet aggregation. Tetrafibricin is the first non-peptidic GPIIb/IIIa antagonist reported that has the capacity to induce conformational changes in GPIIb/IIIa.

Amino Acid Sequence

Cyclothialidine, a novel DNA gyrase inhibitor. II. Isolation, characterization and structure elucidation.

Cyclothialidine is a novel DNA gyrase inhibitor produced by Streptomyces filipinensis NR 0484. It was isolated from the culture broth by charcoal adsorption, Diaion HP-21, Amberlite CG-50, DEAE Toyopearl, and Toyopearl HW-40 SF column chromatography. The structure of cyclothialidine was determined to be a unique twelve membered lactone by amino acid analysis and various 2D-NMR experiments. Cyclothialidine inhibited Escherichia coli DNA gyrase with an IC50 of 30 ng/ml.

Amino Acid Sequence

Bacithrocins A, B and C, novel thrombin inhibitors.

Novel thrombin inhibitors, bacithrocins A, B and C, have been isolated from the culture broth of Bacillus laterosporus Laubach NR 2988. The structures of these inhibitors have been determined to be N-acyl-L-phenylalanyl-DL-arginal by the 2D-NMR experiments on their oxidation products and by amino acid analysis. Bacithrocin A inhibits thrombin, factor Xa and trypsin with IC50s of 48, 13 and 0.65 microM, respectively, which are similar to those of bacithrocins B and C. Bacithrocins prolong the clotting time induced by thrombin and factor Xa.

Amino Acid Sequence

[Efficacy of transarterial embolization combined with percutaneous ethanol injection therapy for recurrent hepatocellular carcinoma].

One hundred and eighty-nine patients with hepatocellular carcinoma (HCC) underwent hepatectomy since 1987 to 1992 in our institute. Recurrences were detected on residual liver in 84 patients up to December 1993. Sixty-seven of 84 patients were treated with re-resection (group-O, n = 11), transarterial embolization (TAE) combined with percutaneous ethanol injection therapy (PEIT) (group-TP, n = 13), TAE alone (group-T, n = 34) and intraarterial chemotherapy (group-IA, n = 9). Among these 67 cases, the efficacy of treatment for recurrences was investigated. There was no significant difference in age, positive ratio of hepatitis B virus, ICG R15 and percentage of underlying liver cirrhosis among the 4 groups. However, the frequency of patients with 2 nodules or less, was significantly higher in group-O than in other groups. Cumulative 1-, 2- and 3-year survival rates (%) were 88.9, 64.8 and 51.9 in group-O, 92.1, 55.4 and 55.4 in group-TP, 70.9, 49.6 and 31.0 in group-T, and 16.9, 0 and 0 in group-IA, respectively. The survival rate after recurrences in group-TP was higher than in group-IA and group-T, and almost equivalent to that of group-O. Either re-resection or TAE combined with PEIT might assure- a favorable prognosis in patients with recurrent HCC.

Carcinoma, Hepatocellular