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Biomedical subjects

M Sakon

Publications and source records attributed to M Sakon.

At least 127 records · Page 7Linked to original sources
PubMed1996

[A patient with hepatocellular carcinoma originating from the caudate lobe, who underwent hepatectomy following microwave coagulation therapy].

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare (about 2%), and prognosis is poor due to difficulties in early diagnosis, transarterial chemoembolization (TAE), and surgical resection. Distant metastasis is also likely to develop. To prevent metastasis during surgical manipulations, we performed microwave coagulation therapy before caudate lobectomy in one patient. Although the efficacy of this procedure remains to be elucidated, the multidisciplinary treatment described in this study is essential for the improvement of prognosis in patients with HCC developing from caudate lobe.

Carcinoma, Hepatocellular↗
PubMed1996

[A patient with pancreatic acinar cell carcinoma, effectively treated by the infusion chemotherapy through hepatic artery using 5-FU, CDDP and MMC].

Chemotherapy for pancreatic acinar cell carcinoma has not been well studied. We report herein one patient, in whom arterial chemotherapy with 5-FU, CDDP and MMC was extremely effective. He underwent distal pancreatectomy associated with partial resection of transverse colon. Hepatic recurrence was detected by MRI 8 months after the surgery. 5-FU (250 mg/day), CDDP (20 mg/day), and MMC (10 mg) was injected through a catheter introduced into the proper hepatic artery. His tumor became hardly detectable by MRI, and he was discharged about 1 month after admission. 5-FU (250 mg) and CDDP (20 mg) were injected every two weeks, and recurrence was not observed for 5 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[A patient with unresectable cancer of pancreas head, effectively treated by a local injection of the mixture of OK-432, fibrinogen and thrombin].

The effective treatment of unresectable pancreatic cancer remains to be elucidated. We report herein a patient who underwent a local injection of a mixture of OK-432, fibrinogen and thrombin. Tumor size and tumor markers significantly decreased following this procedure. Local injection therapy with OK-432, fibrinogen and thrombin may be a promising treatment for unresectable pancreatic cancer.

Adenocarcinoma↗
PubMed1995

Hyperlipidemia: a novel etiologic factor in deep vein thrombosis.

The possible association of hyperlipidemia and deep vein thrombosis (DVT) was investigated in 59 consecutive patients. The incidence of hyperlipidemia, judged by the value of serum total cholesterol and triglyceride, was unexpectedly high (overall 59%, high total cholesterol alone 25%, high triglyceride alone 9%, combined 25%), as compared with 29% of the control (p < 0.001). The idiopathic DVT patients (without known etiologic factors) had a higher incidence of hypercholesterolemia (63%) than the normal subjects (20%, p = 0.0002). The idiopathic DVT patients showed higher total cholesterol level of 255 +/- 72 mg/dl than that of 194 +/- 36 in the control subjects (p < 0.0001). And 67% of the idiopathic DVT patients were hyperlipidemic. Thereby, hyperlipidemia may be an important etiologic factor in DVT, which has not been recognized previously. The low incidence of DVT in Asians may, thus, be attributable to their lower cholesterol level.

Adolescent↗
PubMed1995

Cytoskeletal reorganization of human platelets induced by the protein phosphatase 1/2 A inhibitors okadaic acid and calyculin A.

Okadaic acid (OA) and calyculin A (CLA), which are potent and specific inhibitors of serine/threonine protein phosphatases type 1 and 2A, have been shown to induce drastic changes in platelet morphology. The aim of this study was to analyse the molecular mechanisms of OA- or CLA-induced cytoskeletal reorganization, with a specific focus on microtubules and actin filaments. Confocal fluorescence microscopy revealed that OA or CLA altered the distribution of microtubules from marginal band arrangements to homogeneous patterns, consistent with the transmission-electron-microscopic finding that microtubules were fragmented and redistributed into pseudopod-like processes. In thrombin-activated platelets, OA or CLA induced extremely long pseudopods containing an array of microtubules and actin filaments, and a condensed mass of actin filaments in the centre of platelets. OA or CLA induced the constriction of actin filaments without an increase in filamentous (F)-actin, and also rather significantly inhibited actin polymerization in thrombin-activated platelets. Furthermore, neither OA or CLA enhanced phosphorylation of myosin light chain (MLC). By immunoprecipitation of platelet lysate with anti-alpha-tubulin antibody, a 90 kDa protein was co-precipitated with tubulin and was predominantly phosphorylated in the presence of OA. As the time-dependent phosphorylation of 90 kDa protein correlated well with the reorganization of microtubules, these data suggest that phosphorylation and dephosphorylation of this protein might play a role in the regulation of microtubule organization. These findings indicate that OA or CLA induces reorganization of microtubules and actin filaments via the phosphorylation of a microtubule-associated 90 kDa protein and an MLC-phosphorylation-independent mechanism. mechanism.

Actins↗
PubMed1995

Platelet talin is phosphorylated by calyculin A.

Calyculin A and okadaic acid, potent and cell permeable inhibitors of type 1 and type 2A protein phosphatases, inhibit platelet aggregation and secretion. However, the relationship between phosphatase inhibition and inhibition of platelet function is not well understood. We found that in unstimulated platelets, talin (P235) was phosphorylated at threonine residues by calyculin A. Furthermore, the extent of talin phosphorylation by calyculin A was closely correlated with its inhibition of thrombin-induced platelet aggregation. Since the binding of talin to platelet glycoprotein IIb/IIIa complex has been shown to be affected by its phosphorylation, these results suggest that type 1 and/or type 2A protein phosphatases may play a role in the regulation of membrane-cytoskeleton interaction through dephosphorylation of talin.

Alkalies↗
PubMed1995

Involvement of protein phosphatase-1 in cytoskeletal organization of cultured endothelial cells.

The phosphorylation and dephosphorylation of cytoskeletal proteins regulate the shape of eukaryotic cells. To elucidate the role of serine/threonine protein phosphatases (PP) in this process, we studied the effects of calyculin A (CLA), a potent and specific inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A) on the cytoskeletal structure of cultured human umbilical vein endothelial cells (HUVECs). The addition of CLA (5 min) caused marked alterations in cell morphology, such as cell constriction and bleb formation. Microtubules and F-actin were reorganized, becoming markedly condensed around the nucleus. Although the fluorescence intensity of phosphoamino acids was not significantly different according to immunocytochemistry between cells with and without CLA, polypeptides of 135, 140, 158, and 175 kDa were specifically phosphorylated on serine and/or threonine residues. There was no significant effect on tyrosine residues. The effects of CLA on cytoskeletal changes and protein phosphorylation were almost completely inhibited by the non-selective kinase inhibitor, K-252a. The effect of CLA on cell morphology was at least 100 times more potent than that of okadaic acid, consistent with the inhibitory potency against PP-1. The catalytic subunit of PP-1 was also identified in HUVECs by Western blotting with its monoclonal antibody antibody. These results suggest that PP-1 is closely involved in sustaining the normal structure of the cytoskeleton.

Actins↗
PubMed1995

Suppression of pseudointimal hyperplasia by a novel prostacyclin analogue: beraprost.

The aim of this study was to evaluate the effect of a novel prostaglandin I2 analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P < 0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs.

Animals↗
PubMed1995

PGI2 analogue, sodium beraprost, suppresses superoxide generation in human neutrophils by inhibiting p47phox phosphorylation.

Sodium beraprost, a newly synthesized PGI2 analogue inhibited in a dose-dependent manner formyl-methionyl-leucyl-phenylalanine (fMLP) induced superoxide generation of human neutrophils, but it had no effect on the superoxide synthesis by phorbol myristate acetate (PMA) or A23187. Sodium beraprost inhibited Ca2+ influx in fMLP stimulated neutrophils employing fluorometry and confocal microscopy. These findings suggested that the inhibitory effect of sodium beraprost on fMLP induced superoxide generation was due to suppression of Ca2+ influx. To examine the relationship between the effect of sodium beraprost and phosphorylation of p47phox (the 47kDa cytosolic phagocyte oxidase factor), immuno-precipitation of p47phox and western blotting for phospho-amino acids were performed. Phosphorylation of serine residues of p47phox induced by fMLP was reduced in the presence of sodium beraprost in a dose-dependent manner. The reduction in phosphorylation was accompanied by a reduction in p47phox and p67phox translocation to the plasma membrane and superoxide generation. These findings suggested that p47phox phosphorylation was necessary for translocation and superoxide generation in fMLP activated neutrophils, and that p47phox phosphorylation was regulated by a Ca2+ dependent mechanism. These observations suggested that sodium beraprost inhibited fMLP induced superoxide generation of human neutrophils by the inhibition of p47phox phosphorylation and translocation by a Ca2+ dependent mechanism.

Calcimycin↗
PubMed1995

Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.

Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.

Adult↗
PubMed1995

An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread.

OBJECTIVE: To develop an infection-resistant polytetrafluoroethylene (PTFE) vascular graft for potential clinical use in grafting in sites of bacterial contamination and in replacement of the infected grafts. SETTING: Experimental study in rabbits. MATERIALS AND METHODS: An antibiotic ofloxacin (OFLX) was bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine threads. The in-vitro antibacterial activity of OFLX-PTFE thread was determined by measuring the zone of growth inhibition against Escherichia coli. The thread was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft. OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC) of rabbits and the entire graft was covered with fibrin containing a fixed number of E. coli. Three or 7 days after the grafting, the grafts with perigraft tissue were harvested and subjected to bacteriological studies. RESULTS: In spite of early phase rapid elution of OFLX, a significant antibacterial activity was retained for more than 2 weeks. The antibacterial activity of OFLX-PTFE threads implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to approximately 1% after a week. The swab culture of all the control grafts was positive, while only one of 13 PTFE-OFLX grafts was positive. The number of viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in comparison with that of control grafts. Thus, the OFLX-PTFE grafts exhibited a marked in-vivo antibacterial activity. CONCLUSION: By a unique method, it was possible to furnish PTFE graft with an excellent infection-resistant property, without affecting the original biological behaviour.

Animals↗
PubMed1995

Healing of polytetrafluoroethylene vascular grafts analyzed by anti-smooth muscle myosin heavy chain isoforms.

The purpose of this study was to characterize the cellular contributions to the formation of the pseudointima (PI) using immuno-histochemistry with antibodies to specific smooth muscle myosin isoforms, SM1, SM2, SMemb, and to alpha-smooth muscle actin. The outer wall of polytetrafluoroethylene tube grafts were coated with a 10-microns silicon film except for 5 mm of the midportion and the grafts were implanted into the inferior vena cava of rabbits. The PI in the anastomotic area was mainly formed by dedifferentiation and redifferentiation of medial smooth muscle cells of the host vessel, while PI in the midgraft was formed by differentiation of myofibroblasts into smooth muscle cells in the internodal space.

Animals↗
PubMed1995

[The efficacy of transarterial immuno-embolization therapy in patients with unresectable hepatocellular carcinoma].

We devised a new therapeutic modality for multiple hepatocellular carcinoma (HCC) consisting of transarterial immuno-embolization (TIE) using OK-432 and fibrinogen, and applied the treatment to 22 patients with advanced HCC who had been insensitive to TAE, and 21 patients who had no treatment. Nineteen patients had a high AFP level of more than 200 ng/ml. The serum AFP level decreased in 15 patients after TIE, and in 7 patients the AFP level decreased to less than 30%. Furthermore, a marked reduction in tumor size was observed in 69% after TIE. We report 61% 1-year, and 3-year survival rate for cases who had been insensitive to TAE, and 86% 2-year survival rate for those who selected TIE as the first choice. A high fever of more than 38 degrees C occurred in all cases, and hypotension less than 80 mmHg was observed in 42% patients. No deterioration of liver function and no disturbance of the coagulation-fibrinolysis system due to TIE except in one patient with liver failure after TIE.

Carcinoma, Hepatocellular↗
PubMed1995

Involvement of dysplasminogenemia in occurrence of deep vein thrombosis.

Although various hematological disorders have been considered to be etiologic factors in deep vein thrombosis (DVT), the involvement of dysplasminogenemia (DPG) in DVT has not been studied in detail. In 72 consecutive DVT patients, the presence of DVT was suspected based on a history of lower limb swelling and tenderness with acute onset, and was confirmed by duplex scanning, radioisotope venography, or contrast venography. DPG was identified by the observation of dissociation between the activity and antigenicity of plasminogen. Of the 72 patients, 9 (12.5%) were diagnosed as having DPG, and several antithrombin-III deficiency and protein C and S deficiency were identified. The mean age of the genetically normal and DPG patients was 52 +/- 15 and 40 +/- 15 years, respectively (p < 0.05). Thus, these findings suggest that DPG is deeply related to the development of DVT, and that abnormality of the fibrinolytic system is one of the major etiologic factors in DVT.

Adult↗
PubMed1995

Effect of recombinant human erythropoietin on anaemia after gastrectomy: a pilot study.

OBJECTIVE: To evaluate the role of recombinant human erythropoietin in reducing the need for homologous blood transfusion during operations by studying its effect on the recovery of postoperative anaemia. DESIGN: Randomised controlled trial. SETTING: University hospital, Japan. SUBJECTS: 10 patients with gastric cancer undergoing distal gastrectomy. INTERVENTIONS: 5 Patients were given erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day intravenously for seven days before operation and 14 days afterwards, and 5 were given ferric pyrophosphate 40 mg/day alone (control group). MAIN OUTCOME MEASURES: Packed cell volume, haemoglobin concentration, and white and red cell counts. RESULTS: There was no significant change in packed cell volume after the operation in the erythropoietin group, but in the control group it dropped from a mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05). Haemoglobin concentrations were significantly higher in the erythropoietin group than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p < 0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation. CONCLUSION: Erythropoietin prevented postoperative anaemia after gastrectomy as judged by packed cell volume, haemoglobin concentration, and red cell count. Erythropoietin given before and after operation therefore has the potential to reduce the need for homologous blood transfusion during and after major operations.

Adult↗