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Biomedical subjects

T Kamiyama

Publications and source records attributed to T Kamiyama.

At least 73 records · Page 4Linked to original sources

Intraluminal tumor of the common bile duct as a metastasis of renal cell carcinoma.

A 57-year-old woman was admitted for evaluation of liver dysfunction. A physical examination revealed jaundice and a left abdominal mass, which was diagnosed as being a large renal tumor. Cholangiography showed a smooth filling defect 1 cm in diameter at the common bile duct. Left nephrectomy, and resection of the common bile duct were performed. The pathological diagnosis was metastasis of the common bile duct wall resulting from renal cell carcinoma. Metastatic common bile duct tumors are extremely rare. However, it is important to consider that this is one of the causes of obstructive jaundice.

Carcinoma, Renal Cell↗

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↗

Ice-based altitude distribution of natural radiation annual exposure rate in the Antarctica zone over the latitude range 69 degrees S-77 degrees S using a pair-filter thermoluminescence method.

Both ice-based altitude distributions of natural ionizing radiation exposure and the quasi-effective energy of natural radiation over Antartica over the latitude range 69 degrees S - 77 degrees S during approx. 500 days were measured using thermoluminescent dosimeters. The results shows that dependence on altitude above sea level of the exposure rate increases by almost three-fold with each increase of 2000 m of altitude, thus deviating from the general rule stating that the exposure rate should double with each 2000 m. Although the exposure rate shows a dependence on altitude, altitude dependence of the quasi-effective energy of natural radiation over Antartica is not observed. In the present study it is observed that natural radiation occurring over the ice base of Antartica consists mainly of cosmic rays.

Altitude↗

Design of an antifungal methionine inhibitor not antagonized by methionine.

Only a few biosynthetic pathways in fungal cells have been used as antifungal targets. Therefore, the number of antifungals has been limited, and a cross-drug resistance among them has emerged in the therapy of mycoses. Under such circumstances, the identification of an antifungal with a new mode of action is highly desirable. By infecting mice with a mutant of C. albicans deficient in the sulfate assimilation pathway, we have discovered a new target for the discovery of antifungal agents. We have proven that azoxybacilin inhibits the sulfate assimilation pathway by showing its inhibitory activity for [35S]SO4 incorporation into proteins. We have also demonstrated that azoxybacilin was taken up into fungal cells via an active transport system specific for methionine. This sharing of the uptake system with methionine may explain the mechanism by which the antifungal activity of azoxybacilin is antagonized by methionine, and led us to design azoxybacilin derivatives that lack the structural feature of amino acids and, at the same time, have increased hydrophobicity to give higher non-specific permeability through the cell membrane. As a result, we have found that ester derivatives of azoxybacilin were not antagonized by methionine in their uptake, and that they showed antifungal activity independent of methionine. The benzyl ester of azoxybacilin was the same as azoxybacilin in its mode of action, but was not markedly antagonized by methionine at concentrations up to 1 mg/ml. These results suggest that azoxybacilin may not merely interfere with the sulfate assimilation pathway.

Aminobutyrates↗

Monamidocin, a novel fibrinogen receptor antagonist. I. Production isolation, characterization and structural elucidation.

Monamidocin, a novel fibrinogen receptor antagonist, has been isolated from the culture broth of Streptomyces sp. NR 0637 BY carbon adsorption, n-BuOH extraction, SP-Toyopearl, silica gel 60 silanised and Sephadex LH-20 column chromatographies and preparative HPLC. The molecular formula of monamidocin has been determined to be C15H22N4O4 from HRFAB-MS and 13C NMR spectral data. The structure of monamidocin has been determined to be N-[(S)-5-guanidino-2-hydroxypentanoyl]-L-phenylalanine by 2D NMR experiments.

Chemical Phenomena↗

Monamidocin, a novel fibrinogen receptor antagonist. II. Biological activity and structure-activity relationships.

Monamidocin, a fibrinogen receptor binding inhibitor produced by Streptomyces sp. NR 0637, inhibits the binding of fibrinogen to its receptor with an IC50 of 0.21 microM. It also inhibits ADP-collagen- and thrombin-induced aggregation of human platelet with IC50S of 46, 30, and 77 microM, respectively. To obtain more potent inhibitors, twenty analogs have been synthesized, among which N-[(R)-5-guanidino-2-hydroxypentanoyl]-L-tyrosine is the most potent. It inhibits the binding of fibrinogen to its receptors with an IC50 of 0.022 microM and is about ten times more potent than monamidocin.

Adenosine Diphosphate↗

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↗