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Biomedical subjects

S Muramatsu

Publications and source records attributed to S Muramatsu.

At least 55 records · Page 3Linked to original sources
PubMed1997

[A case of multiple colonic liver metastases treated successfully with percutaneous isolated liver chemoperfusion using cisplatin].

We herein report a case of multiple colonic liver metastases treated with repeated percutaneous isolated liver chemoperfusion of cisplatin under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) as an inductive treatment. The patient was a 70-year-old man who underwent curative resections for metachronous rectal and descending colonic cancer in 1979 and 1995, respectively. During outpatient follow-up, he showed increases of serum CEA level. An abdominal CT study demonstrated multiple low-density lesions in the bilateral lobes of the liver, indicating colonic liver metastases. The patient had a total of 2 treatments with percutaneous isolated liver chemoperfusion of cisplatin (total dose, 500 mg) under HVI.CHP. His post-treatment course was uneventful without side effects, including leukopenia and renal dysfunction. Serum CEA levels showed a sharp decrease to 160 ng/ml 3 months after treatment from the pretreatment value of 1,064 ng/ml. CT scan 3 months after treatment revealed remarkable tumor regression along with liquefaction of liver tumors, showing a partial response. These results suggested that repeated percutaneous isolated liver chemoperfusion of cisplatin under HVI.CHP is a potent inductive treatment for patients with multiple colonic liver metastases.

Aged↗
PubMed1997

[Efficacy of combined use of sodium thiosulfate in percutaneous isolated liver chemoperfusion of cisplatin under complete hepatic venous isolated and charcoal hemoperfusion].

We herein evaluated the efficacy of combined use of sodium thiosulfate (STS) in isolated liver chemoperfusion of cisplatin (CDDP) under complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 5), CDDP (4 mg/kg) + STS (4 g/body) and group II (n = 5), CDDP (4 mg/kg). In both groups, CDDP was intraarterially administered for 20 minutes under HVI.CHP. In addition, in group I, STS infusion was administered for 20 minutes via the outlet side of CHP filter. The adsorption rates of free and total CDDP of CHP filter were in a range of 50-80%, and the rates in group I were higher than in group II. At all sampling points, the AUC (microgram.min/ml) of free CDDP was not different between the two groups. However, the AUC of total CDDP at postfilter [group I: 35.3 +/- 2.7 (mean +/- SD); group II: 63.5 +/- 21.5] and systemic serum (group I: 24.9 +/- 8.6, group II: 43.5 +/- 13.5) was significantly lower in group I than in group II (p < 0.05). The cumulative amounts of urinary excretion of CDDP (microgram/kg) were 39.5 +/- 12.1 and 13.5 +/- 9.3 in groups I and II, respectively, showing a significant increase in group I (p < 0.01). These results indicated that the use of STS in percutaneous isolated liver chemoperfusion of CDDP under HVI.CHP could further reduce systemic toxicities of CDDP, by increasing CDDP filter extraction of CHP filter and urinary CDDP excretion.

Animals↗
PubMed1997

Effect of procaine and oxethazaine on muscarinic receptors of parietal cells.

Several reports have shown that local anesthetics have a high affinity for muscarinic receptors and competitively inhibit the effects induced by cholinergic agents in various tissues, but there have been no reports on the muscarinic receptors of parietal cells. The effects of five doses of procaine (10(-8)M approximately 10(-4)M) and seven doses of oxethazaine (10(-8)M approximately 10(-5)M) on 14C-aminopyrine accumulation in isolated parietal cells of guinea pigs induced by 10(-4)M carbachol were studied. Procaine showed a potentiating effect with peak potentiation at a dose of 10(-5)M, while oxethazaine showed an inhibitory effect in a dose-dependent manner at doses higher than 3 x 10(-8)M and suppression below the control levels at doses higher than 3.5 x 10(-7)M. Procaine alone increased 14C-aminopyrine accumulation with peak response at a dose of 10(-5)M, while oxethazaine alone showed an inhibitory effect in a dose-dependent manner at doses higher than 3 x 10(-8)M. Oxethazaine shifted the carbachol dose-response curves to the right with suppression of maximal response. In conclusion, in parietal cells, procaine appears to display roughly similar action to carbachol through muscarinic receptors, while oxethazaine displays inhibitory action mainly by mechanisms other than inhibition at the muscarinic receptor site.

Aminopyridines↗
PubMed1996

Suppression of actinomycin D-induced apoptosis by the NS3 protein of hepatitis C virus.

The NS3 protein of hepatitis C virus is a multifunctional protein that is indispensable for virus replication. Little is known, however, about the possible effects of the NS3 on host cell function(s). In the present study, we demonstrated that NIH3T3 cells constitutively expressing a carboxy-terminally truncated NS3 (NS3DeltaC) were more resistant to actinomycin D-induced apoptosis than the control cells. We also observed that induction of p53 expression by actinomycin D treatment was weaker in the NS3DeltaC-expressing cells than in the control cells. However, induction of WAF1 expression by the same treatment was not different between the two groups. Taken together, our results suggest the possibility that expression of NS3DeltaC suppressed actinomycin D-induced apoptosis of NIH3T3 cells through at least partly, if not solely, a p53-dependent, WAF1-independent pathway.

3T3 Cells↗
PubMed1996

Nucleotide sequencing and generation of an infectious clone of adeno-associated virus 3.

We have determined the complete nucleotide sequences of adeno-associated virus 3 (AAV-3) and generated an infectious clone. The single-stranded DNA genome of AAV-3 is 4726 nucleotides in length. The positive strand contains two large open reading frames; the left open reading frame encodes the nonstructural proteins and the right open reading frame encodes the structural proteins. The coding regions are flanked by identical inverted terminal repeat sequences containing palindromes. AAV-3 has little homology with the autonomous parvoviruses or erythroviruses but has 82% overall sequence homology with AAV-2. At the amino acid level there was 88% homology with AAV-2 nonstructural (Rep) proteins and 87% homology with AAV-2 capsid proteins. In addition, AAV-3 differed importantly from AAV-2 in the lack of a typical promoter sequence (TATA box) at p40 and the presence of the consensus sequence for adenovirus-related transcription factor E4F binding within the upstream region of the p5 promoter. These results suggest that AAV-3 not only consists of serologically distinct structural proteins but that viral propagation also may be controlled by different gene regulatory elements at the transcription level. The infectious clone confirmed the sequence and may be useful for developing new vectors for gene therapy.

Amino Acid Sequence↗
PubMed1996

Calcitonin gene-related peptide enhances apoptosis of thymocytes.

The effect of calcitonin gene-related peptide (CGRP), a neuropeptide, on the apoptosis of murine thymocytes was investigated. CGRP enhanced apoptosis of thymocytes beyond the spontaneous level at concentrations of 10(-11) M or higher, and the effect attained a plateau at 10(-9) M, mainly by stimulating cAMP formation. Implication of cAMP-independent mechanism was also suggested in the CGRP-induced apoptosis. Flow cytometric analysis revealed that CGRP caused apoptosis preferentially in CD4+8+ thymocytes. In addition, RNA and protein synthesis was required for apoptosis induced by CGRP.

Animals↗
PubMed1996

Enzyme-linked immunosorbent assay of pravastatin, a HMG-CoA reductase inhibitor, in human plasma.

An enzyme-linked immunosorbent assay (ELISA) was developed for sensitive and specific determination of pravastatin (PS) sodium, a HMG-CoA reductase inhibitor. Preparation of immunogens to obtain antisera was carried out using chemically modified PS; beta-alanine derivative of PS (for ELISA-1) and 5-deoxy- PS (for ELISA-2) were linked to bovine serum albumin via its terminal carboxylic acid by the N-succinimidyl ester method, to avoid intramolecular lactonization of PS. Enzyme-labeled antigens were prepared similarly by coupling with horseradish peroxidase, and were used by homogeneous combination of antisera. The enzymic activity was determined using a microtiter plate coated with second antibody and tetramethylbenzidine as a chromogenic substrate. Both of the ELISA systems enabled the determination of PS in a range of 5 to 500 pg/well, with an IC50 of 36 to 130 pg/well. Cross-reactivties with main metabolites in plasma, which differed from PS in decaline moiety, were less than a few percent. When ELISA-1 was applied to the determination of PS in human plasma directly after dilution with the ELISA buffer, the detection limit and the intra-assay coefficient (5 ng/ml of PS) were 500 pg/ml and 4.5%, respectively. Further, ELISA-1 was validated by gas chromatography-mass spectrometry with the determination of PS in human plasma after oral administration at a dose of 10 mg/body.

Administration, Oral↗
PubMed1996

Determination of interferon-alpha-producing capacity in whole blood cultures from patients with various diseases and from healthy persons.

To assess the clinical value of determination of the interferon (IFN)-producing capacity of patients, IFN production induced by Sendai virus (HVJ) in vitro was measured in cell cultures of whole blood from patients with various diseases. IFN production in patients with lung cancer, myelodysplastic syndromes, noninsulin-dependent diabetes mellitus, pulmonary tuberculosis, and asymptomatic HIV-1 infection was lower than that in healthy persons. Furthermore, periodic measurements of IFN production revealed decreasing IFN producing capacities in patients with lung cancer with progression of the tumor stage. However, increased IFN-producing capacities were observed in patients with tuberculosis after standard therapy. Further experiments showed that the main type of IFN induced in whole blood cultures was IFN-alpha, and decreased IFN production in patients did not result from a decreased number of leukocytes but rather from an impairment of cellular IFN production. The evaluation of IFN production in whole blood cell cultures may be a feasible method of assessing the impaired immune status.

Adult↗
PubMed1996

The effect of Helicobacter pylori on gastric acid secretion by isolated parietal cells from a guinea pig. Association with production of vacuolating toxin by H. pylori.

BACKGROUND: One of the features of Helicobacter pylori infection in the human stomach seems to be disordered gastric acid secretion. The effect of vacuolating toxin (VT) produced by H. pylori on gastric acid secretion was examined. METHODS: VT(+)(toxigenic) and VT(-)(nontoxigenic) strains of H. pylori were cultured in brucella broth. The culture supernatant was added to isolated parietal cells, and acid secretion and intracellular adenosine 3'5'-cyclic phosphate (cAMP) and Ca2+ levels were measured with the 14C-aminopyrine (14C-AP) method, with 125I radioimmunoassay (RIA), and with the fura-2 fluorescence method, respectively. RESULTS: In the VT(+) strain a considerable inhibitory effect on 14C-AP accumulation was observed. However, the VT(-) strain had no significant effect on intracellular c-AMP and Ca2+. CONCLUSIONS: The VT(+) strain of H. pylori has an inhibitory effect on gastric acid secretion, whereas the VT(-) strain does not. This inhibitory effect was not associated with the response of second messengers. It is speculated that VT produced by H. pylori has a direct action on H(+)-K+ adenosine triphosphatase in parietal cells.

Animals↗
PubMed1996

[Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion].

It is difficult to administer an effective dose of cyclosporin A (CsA), a potent inhibitor of P-glycoprotein, to prevent multiple drug resistance due to its side effect. We herein evaluated the efficacy of concomitant use of this agent and complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 4), intraarterial infusion of only adriamycin (ADM) and group II (n = 4), intraarterial infusion of CsA and ADM. In both groups, ADM was intraarterially administered for 10 minutes under HVI.CHP. In addition, in group II, CsA infusion (0.3 mg/min.kg) was initiated 20 min prior to the start of ADM infusion and maintained for 30 min. The AUC (micrograms.min/ml) of ADM were 21.2 +/- 8.6 (mean +/- SD) and 28.4 +/- 10.3 in groups I and II, respectively, at prefilter (hepatic venous level) and 8.1 +/- 4.6 and 4.8 +/- 3.8, respectively, at postfilter, showing an effective drug elimination in both groups. The Cmax (micrograms/ml) were 14.1 +/- 2.2 at prefilter, 2.4 +/- 0.5 at postfilter, and 3.4 +/- 1.2 in systemic level. These results indicated that HVI.CHP allowed the high-dose CsA infusion required for P-gp inhibition in the liver and could reduce extraregional CsA leakage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Evaluation of a single catheter technique for percutaneous isolated liver perfusion].

We have established a single catheter technique of percutaneous isolated liver perfusion using a 4-lumen-2-balloon (4L - 2B) catheter for treatment of unresectable malignant liver tumors. Herein reported are the technique, safety and pharmacokinetics of the system in comparison with the original double-balloon technique. This study included 19 patients with malignant liver tumors treated by adriamycin at a dose of 100 mg/m2. Seven patients had the double-balloon technique (group D), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other 12 patients had single catheter technique (group S). In group S, hepatic effluent was solely isolated and directed to CHP filters. All patients except for one in group S showed good hemodynamic stability. The hepatic venous flow rate of group S was significantly higher than in group D (p < 0.05). Although the mean area under the time concentration curve at systemic serum was significantly lower in group S compared to group D, the rate of side effects was similar in both groups. A 4L. 2B single catheter allowed safe and repeated percutaneous isolated liver perfusion for technical simplification of the treatment.

Aged↗
PubMed1995

Calcitonin gene-related peptide enhances cytokine-induced IL-6 production by fibroblasts.

The effect of calcitonin gene-related peptide (CGRP) was investigated on cytokine-induced IL-9 production by Swiss 3T3 fibroblasts. CGRP by itself had little effect on IL-6 production, and substantially enhanced that induced by IL-1 beta or TNF alpha at concentrations of 10(-8) M or higher. The action of CGRP was mediated by a CGRP-specific receptor. In contrast, calcitonin had no effect at all. A kinetic study of IL-6 activity in the culture supernatant showed that CGRP not only accelerated but also increased IL-6 production. Enhancement by CGRP of cytokine-dependent IL-6 production was ascribed to the increased accumulation of IL-6 mRNA. IL-1 beta-induced IL-6 production was maintained by CGRP after removal of IL1 beta. The addition of CGRP to the culture following stimulation with IL-1 beta or IL-1 beta plus CGRP decelerated the decay of IL-6 mRNA. These results indicate that the augmenting effect of CGRP is mediated, at least in part, by the stabilization of IL-6-specific mRNA.

3T3 Cells↗
PubMed1995

Enhancement of murine bone marrow macrophage differentiation by beta-endorphin.

The present study was performed to investigate the effect of beta-endorphin on macrophage colony-stimulating factor (M-CSF)-induced differentiation of macrophages from bone marrow cells in a semisolid culture system. beta-endorphin increased the number of macrophage colonies when bone marrow cells were cultured in the presence of M-CSF plus lipopolysaccharide (LPS). This was not the case with LPS-unresponsive C3H/HeJ mouse bone marrow cells. alpha-endorphin and gamma-endorphin were as effective as beta-endorphin in enhancing the colony formation. Exogenous interleukin-1 (IL-1), but neither IL-6 nor tumor necrosis factor (TNF), collaborated with beta-endorphin even in the absence of LPS, suggesting that IL-1 is a primary mediator of the effect of LPS. Indeed, anti-IL-1 antibody abolished the collaborative effect of beta-endorphin with LPS. Moreover, IL-1 was effective even for C3H/HeJ mouse bone marrow cells. Naloxone, an antagonist of endorphins for opioid-receptors, completely abrogated the effect of beta-endorphin. In a single-cell culture system, the collaboration between beta-endorphin and IL-1 was revealed by the increase in number and size of macrophage colonies, but collaboration between beta-endorphin and LPS did not occur. These results indicate that, in mixed cell culture, beta-endorphin acts in concert with paracrinal IL-1 induced by LPS to enhance M-CSF-dependent macrophage differentiation from immature precursor cells.

Animals↗
PubMed1995

Plasma lipoproteins as targeting carriers to tumour tissues after administration of a lipophilic agent to mice.

We synthesized 14C-warfarin hexadecyl ether (14C-WHE) by addition of a palmityl moiety to the hydroxyl group at the 4-position of 14C-warfarin, a compound known to bind to serum albumin. 14C-WHE preferentially bound to the lipoproteins, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), in mouse plasma both in vitro and in vivo. 14C-Warfarin mainly concentrated in the liver immediately after intravenous administration to mice bearing M5076 sarcoma, and was found at only low concentrations in other tissues including the tumour. 14C-WHE highly distributed to the tumour, adrenal, and spleen, as well as the liver. These tissues coincided with those in which human 125I-LDL was vigorously incorporated. The results indicate that chemical modification of an agent, giving it high lipophilicity, will enable it to bind to lipoproteins after intravenous administration. These modifications raise the possibility of lipoproteins as endogenous targeting carriers into tumour cells, which have high LDL-receptor activity.

Albumins↗
PubMed1995

Counteracting effect of interferon-alpha and -beta on interferon- gamma-induced production of nitric oxide which is suppressive for antibody response.

We investigated the nitric oxide (NO)-mediated immunosuppressive activity of macrophages and the regulatory effect of type I (alpha and beta) interferons (IFNs) on IFN-gamma-induced NO production by macrophages. In the sheep red blood cell (SRBC)-specific secondary antibody response in vitro, the addition of macrophages to the culture of primed spleen cells substantially decreased the number of plaque-forming cells. The concentration of nitrite in the culture supernatant showed a positive correlation with the number of macrophages added in a dose- dependent manner, and the addition of NMMA, a potent inhibitor of NO production, resulted in the restoration of of the response. In addition, anti-IFN-gamma antibody abolished the ability of the immune culture supernatant to stimulate macrophages to produce NO. Therefore, the macrophage-dependent immunosuppression was due primarily to NO that was produced by macrophages in response to IFN-gamma derived from responding lymphocytes. The pretreatment of macrophages with IFN-alpha or -beta gave rise to a dramatic reduction of IFN-gamma-mediated NO production. In addition, the suppressive activity of these macrophages was much lower than that of untreated macrophages. These results indicate that type I IFNs can regulate the immune response by modulating IFN-gamma-induced production of immunosuppressive NO.

Animals↗
PubMed1995

Exogenous and endogenous type I interferons inhibit interferon-gamma-induced nitric oxide production and nitric oxide synthase expression in murine peritoneal macrophages.

We investigated the effect of type I IFNs (IFN-alpha and IFN-beta) on IFN-gamma-induced nitric oxide (NO) production by murine peritoneal macrophages. It was found that exogenous and also endogenous type I IFNs suppressed IFN-gamma-induced NO production, cytosolic inducible NO synthase (iNOS) activity, and iNOS mRNA accumulation in macrophages. Furthermore, we show here that type I IFNs prevent the NO-mediated deterioration of mitochondrial respiratory activity in macrophages. These results seem to indicate a possible protective role of type I IFNs against the NO-mediated immunosuppressive and/or cytotoxic effect of macrophages.

Animals↗