Search PubMed⌕ Search

Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 307 records · Page 17Linked to original sources
PubMed1994

Inhibition of Ca(2+)-induced aggregation of porcine intestinal brush-border membranes by lipid peroxidation.

The effects of lipid peroxidation on Ca(2+)-induced aggregation of porcine intestinal brush-border membranes were examined using a system consisting of ascorbic acid/Fe2+/tert-butyl hydroperoxide (t-BuOOH). Incubation of the membranes with ascorbic acid/Fe2+/t-BuOOH resulted in inhibition of Ca(2+)-induced aggregation of the membranes with the formation of thiobarbituric acid-reactive substances, depending on the hydroperoxide concentration and the incubation time. The inhibition of the membrane aggregation associated with ascorbic acid/Fe2+/t-BuOOH treatment was effectively prevented by the addition of an antioxidant, 3(2)-tert-butyl-4-hydroxyanisole, to the reaction mixture. Studies with 8-anilino-1-naphthalenesulfonate (ANS) revealed that there is a linear relationship between the apparent dissociation constants (Kd) of ANS-membrane complexes and the aggregating efficiencies of the membranes with different levels of lipid peroxidation This suggests that inhibition of the membrane aggregation by lipid peroxidation involves a change in the membrane surface charge density. Modification of the membranes with malondialdehyde also resulted in a decrease in the aggregating efficiency of the membranes with a decrease in the Kd value of ANS-membrane complex. In addition, the contribution of the lipid organization to membrane aggregation was examined by measuring the fluorescence anisotropy of diphenylhexatriene-labeled membranes in the presence of a lipid fluidizer, benzyl alcohol. The results are discussed in terms of peroxidation-induced inhibition of intramembrane interactions of the membranes.

Animals↗
PubMed1994

Inhibition of T-cell proliferation induced by a cell-free Salmonella typhimurium extract does not involve a nitric oxide-mediated mechanism.

In a previous study, we observed that a cell-free Salmonella typhimurium extract induced suppression of mitogen-induced T-cell proliferation and that this suppression involved nonresponsiveness of T-cells to interleukin-2 (IL-2) and augmentation of IL-2 receptor (IL-2R) expression. In this study, we found that inhibition of phytohemagglutinin (PHA)-stimulated murine spleen cell proliferation induced by a cell-free S. typhimurium extract was reversed by treatment with an anti-interferon-gamma monoclonal antibody (anti-IFN-gamma Ab), but not by interleukin-4 or NG-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO)-secretion from spleen cells in culture. However, IL-2R expression was augmented by treatment with the extract, although this was independent of an NO-mediated mechanism. Only anti-IFN-gamma Ab treatment reduced the augmented IL-2R expression to a normal level. These results suggest that the suppression of T-cell proliferation induced by the Salmonella cell-free extract is associated with augmentation of IL-2R expression in an NO production-independent manner.

Animals↗
PubMed1994

A cell-free extract of Salmonella typhimurium inhibits mitogen-induced proliferation of murine splenic T lymphocytes.

In this study, a cell-free extract of Salmonella inhibited T cell mitogen-induced proliferation of spleen cells from non-immunized mice. The proliferation of murine spleen cells stimulated with a T cell mitogen, such as phytohaemagglutinin (PHA) or concanavalin A (ConA) was suppressed significantly when the cells were treated with a sonicate of S. typhimurium, but not of E. coli. The agent(s) responsible for the suppressive effect existed mainly in the soluble fraction of S. typhimurium, whereas the membrane fraction possessed minimal activity. The T cell proliferation suppression paralleled the level of interleukin-2 (IL-2) secretion. Addition of phorbol 12-myristate-13 acetate (PMA) to the cultures restored IL-2 secretion to normal levels, although proliferation remained suppressed and was not reversed by treatment with recombinant IL-2. These results suggest that the suppression of T cell proliferation induced by a soluble Salmonella fraction is associated with inhibition of IL-2 secretion and the response of T cells to IL-2 and the former effect is dependent upon the inhibition of the stimulatory activity of protein kinase C on IL-2 secretion. This type of suppression may explain a mechanism of immunosuppression induced by murine typhoid fever.

Animals↗
PubMed1994

A cell-free Salmonella typhimurium extract modulates interleukin-2 (IL-2) receptor expression but not IL-2-stimulated responses of murine splenic lymphocytes.

In a previous study, we observed that a cell-free Salmonella typhimurium extract induced suppression of mitogen-induced T-cell proliferation and this suppression involved non-responsiveness of T-cells to interleukin-2 (IL-2). In this study, we found that a cell-free S. typhimurium extract modulated IL-2 receptor (IL-2R) expression on phytohemagglutinin (PHA)-stimulated murine spleen cells and this was a mechanism of T-cell non-responsiveness to IL-2, but did not affect IL-2 binding to IL-2R and the consequent responses. Western blotting using anti-phosphotyrosine antibodies showed that IL-2R-mediated tyrosine phosphorylation of protein substrates in PHA-activated murine splenic T-cells, which express a high-affinity IL-2R (alpha- and beta-chains), was not affected by treatment with the S. typhimurium cell-free extract. Furthermore, PHA-activated spleen T-cells responded to recombinant IL-2 and this was not inhibited by the extract. Surprisingly, IL-2R expression was augmented by treatment with the extract, although this was independent of IL-2 production. These results suggest that the suppression of T-cell proliferation induced by the Salmonella cell-free extract was associated with augmentation of IL-2R expression, rather than down-regulation of the IL-2 response. This may be a mechanism responsible for the Salmonella extract-evoked suppression of mitogen-induced T-cell proliferation.

Animals↗
PubMed1994

[The mechanism of antigen-presentation of porin from Salmonella typhimurium to T lymphocytes].

Porins from wild type strains of Salmonella typhimurium are known to consist of three species of proteins named 34, 35 and 36K. It is understood that these three species of proteins construct porin trimers and the porin trimers from the wild type strain of S. typhimurium are constructed from homologous species of porin subunits. However, we have demonstrated previously that only porin trimers from wild type strains but not mixtures of homologous porin trimers from mutant strains of S. typhimurium could induce antigen-specific cell-mediated immunity (CMI). In this study, therefore, a mechanism of antigen-presentation of porin from a wild type strain of S. typhimurium to T cells was studied. Our data showed that porin proteins from the wild type strain received antigen-processing as well as other protein antigens in murine macrophages and were presented with Ia antigen to T cells. These results suggested that porin trimers from wild type strains of S. typhimurium were constructed from heterologous species of porin subunits and only heterologous porin trimers held epitopes for a CMI-eliciting antigen.

Animals↗
PubMed1994

Phase I study of irinotecan and cisplatin with granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer.

PURPOSE: Since leukopenia was one of the dose-limiting toxicities of the combination of irinotecan (CPT-11) and cisplatin in a previous trial, we conducted a phase I trial to investigate whether support with recombinant human granulocyte colony-stimulating factor (rhG-CSF) would permit further intensification of the CPT-11 dose in combination with a fixed cisplatin dose. PATIENTS AND METHODS: Twenty previously untreated patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) were treated with CPT-11 on days 1, 8, and 15 in combination with cisplatin 80 mg/m2 intravenously on day 1. In addition, rhG-CSF (2 micrograms/kg/d) was administered on days 4 to 21, except on the days of CPT-11 treatment. The starting dose of CPT-11 was 70 mg/m2, and the CPT-11 dose was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS: Diarrhea was the dose-limiting toxicity at 90 mg/m2. Two of six patients experienced either grade 3 or 4 diarrhea or grade 3 leukopenia during the first course of therapy at this dose level. Modest escalation of the CPT-11 dose from 80 to 90 mg/m2 resulted in a marked increase in the plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38). Occurrence of diarrhea was well correlated with the peak plasma concentration (Cmax) of SN-38 (P = .035). There were 10 partial responses (50%) among 20 patients. CONCLUSION: The recommended dose for phase II studies is 80 mg/m2 of CPT-11, and 80 mg/m2 of cisplatin plus rhG-CSF. With the use of rhG-CSF, the CPT-11 dose can be increased 33% above that in the original regimen (60 mg/m2 of CPT-11 and 80 mg/m2 of cisplatin).

Adult↗
PubMed1994

Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer.

PURPOSE: For patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC), radiotherapy (RT) has been used conventionally for many years. Few prospective trials have determined the role of RT. Recently, chemotherapy (CT) has been shown to produce excellent responses in regionally advanced disease. We therefore conducted a randomized trial using cisplatin (P)-based CT regimens with or without thoracic irradiation. PATIENTS AND METHODS: We randomly assigned 92 patients with locally advanced NSCLC to receive one of three arms of P-based combination chemotherapy: vindesine (V) plus P, mitomycin (M) plus V plus P, or etoposide (E) plus P alternating with V plus M. After two cycles of CT, patients were reevaluated and those with stage III were again randomized to receive RT or not. RT consisted of 50 to 60 Gy in 5 to 6 weeks; 2 Gy was delivered once daily in conventional fractions. RESULTS: Sixty-three patients were included in the second randomization. The patients in the CT/RT group (n = 32) and CT-alone group (n = 31) were comparable in terms of age, sex, performance status, histologic features, stage of disease, and induction CT regimen. The median durations of survival were similar for the two groups (461 days in CT/RT group and 447 days in CT-alone group). The survival rate in the CT/RT group was 58% at 1 year, 36% at 2 years, and 29% at 3 years, as compared with 66%, 9%, and 3% at 1, 2, and 3 years, respectively, in the CT-alone group. One patient in the CT/RT group died of pneumonitis, but there were no CT-related deaths. CONCLUSION: In locally advanced NSCLC, P-based combination CT followed by chest irradiation significantly increases the number of long-term survivors as compared with CT alone. RT to bulky disease in the thorax is thus an important part of combined modality therapy, and a necessary part of further studies in locally advanced disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase I and pharmacologic study of irinotecan and etoposide with recombinant human granulocyte colony-stimulating factor support for advanced lung cancer.

PURPOSE: We conducted a phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) support because of the overlapping neutrophil toxicity of both drugs. The aim was to determine the maximum-tolerated dose of CPT-11 combined with a fixed dose of etoposide in patients with advanced lung cancer, as well as the dose-limiting toxicities of this combination. PATIENTS AND METHODS: Twenty-five patients with stage III or IV lung cancer, 15 (60%) with prior chemotherapy, were treated at 4-week intervals using CPT-11 (90-minute intravenous infusion on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3). In addition, rhG-CSF (2 micrograms/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. The starting dose of CPT-11 was 60 mg/m2, and it was escalated in 10-mg/m2 increments until the maximum-tolerated dose was reached. RESULTS: The maximum-tolerated dose of CPT-11 was 90 mg/m2, since two of the three patients developed grade 3 to 4 leukopenia or grade 3 to 4 diarrhea during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the dose-limiting toxicities, while thrombocytopenia was only a moderate problem. Elimination of CPT-11 was biphasic, with a mean +/- SD beta half-life of 18.17 +/- 9.09 hours. The mean terminal half-life of 7-ethyl-10-hydroxycamptothecin (SN-38; the major metabolite of CPT-11) was 43.40 +/- 37.84 hours. There was one complete response (5%) and eight partial responses (38%) among 21 assessable patients, for an overall response rate of 43%. The response rates for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) were 58% (seven of 12 patients) and 22% (two of nine patients), respectively. CONCLUSION: The combination of CPT-11 and etoposide with rhG-CSF support seems to be active against lung cancer, especially SCLC, with acceptable toxicity. The recommended dose for phase II studies in previously untreated patients is 80 mg/m2 of CPT-11 (days 1, 8, and 15) and 80 mg/m2 of etoposide (days 1 to 3) plus 2 micrograms/kg of rhG-CSF (days 4 to 21, except when CPT-11 is given). In addition, 70 mg/m2 of CPT-11 appears to be the appropriate dose for previously treated patients receiving this regimen.

Adult↗
PubMed1994

Specificity of riboflavin molecular groups for riboflavin binding to rat small intestinal brush border membrane.

The binding of riboflavin to rat small intestinal brush border membrane at equilibrium was formerly shown to have a saturable, specific component, prevailing at the intraluminal physiological concentrations of the vitamin. In this study, the specificity of riboflavin binding to rat small intestinal brush border vesicles was further investigated using structural analogues of riboflavin. The vesicles, prepared by Ca(2+)-precipitation, were incubated at 25 degrees C, for 20 min, in the presence of [3H]-riboflavin at physiological intraluminal concentrations for rat, and each analogue, at appropriate concentrations. Three groups of analogues were used, that were derived from the riboflavin molecule by modifying one of the following positions: the ribityl side chain, position 3, and position 8 of the isoalloxazine moiety. Group specificity was assessed by determining the inhibition potency of each analogue on the saturable component of riboflavin binding to the vesicles. Inhibition constants were calculated, according to Dixon, for lumiflavin, lumichrome, and for analogues substituted at position 8. Specific riboflavin binding was inhibited competitively by most of the analogues used. Substitutions at the ribityl side chain or at position 3 of the isoalloxazine moiety reduced the inhibition power. Substitutions at position 8 enhanced the inhibition power in direct proportion to the bulk of the substituents. We conclude that the ribityl side-chain and the NH group at position 3 are essential for recognition by the specific binding sites, whereas the methyl group at position 8 is important but not essential. The analogues that bind to specific membrane sites for riboflavin share specificity requirements with many riboflavin binding proteins, and are also good substrates for the intracellular phosphorylating enzyme flavokinase. Thus, the riboflavin-binding component in the membrane is likely to be a protein with high specificity. Cellular internalization of the membrane bound vitamin is probably achieved by phosphorylation of the vitamin bound to the inner side of the membrane.

Animals↗
PubMed1994

[On the localization of the binding site(s) of antibodies against TSH receptor using synthetic peptides].

In order to elucidate autoimmune B-cell recognition sites of human thyrotropin receptor (TSHR), nine overlapping synthetic peptides (residues 12-30, 24-44, 151-175, 171-195, 308-328, 324-344, 339-364, 359-380, and 375-399) were synthesized and biological activities of antibodies against each of the peptide were examined. It was shown that antibodies against TSHR 12-30, 24-44, 151-175, 171-195, 324-344, and 359-380 had thyroid stimulating antibody activity (TSAb), whereas antibodies against 339-364, 359-380, and 375-399 had thyroid stimulation blocking activity (TSBAb). From these results it was concluded that epitopes where TSH receptor antibodies with TSAb and TSBAb activities are bound are widely located in N-terminal, mid portion, and C-terminal regions.

Animals↗
PubMed1994

[Significance of phrenic nerve block in the anesthetic management of laparoscopic cholecystectomy].

The significance of phrenic nerve block was studied in the anesthetic management of laparoscopic cholecystectomy. Right phrenic nerve block with 1% mepivacaine 10 ml was performed after the patients were epidurally catheterized and anesthetized with isoflurane and nitrous oxide in oxygen. Intraoperative anesthetic requirement and postoperative shoulder pain incidence in patients with this block were compared with those in patients without block. Addition of the phrenic nerve block to general and epidural anesthesia did not reduce the intraoperative dosage of isoflurane, but it significantly prevented occurrence of postoperative right shoulder pain. It is known that phrenic nerve contains sensory element and that laparoscopic procedures of gall bladder elicit noxious stimuli which cannot be blocked by ordinary epidural anesthesia for abdominal surgery. Also, shoulder pain is said to be phrenic nerve-mediated referred pain. Our study suggests that blockade of these stimuli is effective in preventing postoperative event rather than intraoperative.

Adult↗
PubMed1994

Intermittent outpatient based ECUM. A case report.

Extracorporeal Ultrafiltration Method (ECUM) could be used in patients with refractory congestive heart failure (CHF). We have encountered a 56-year-old woman with refractory congestive heart failure (CHF) (NYHA II-III) due to coronary artery disease, complicated by moderately advanced diabetic nephropathy (Cr = 2.4 mg/dl). Due to the non-responsiveness to medical treatments, she has begun receiving the intermittent ECUM once or twice a week on an outpatient basis. ECUM effectively reduced cardiac preload and temporarily relieved her intractable respiratory distress. Based on our present clinical experience, we propose that one could consider an outpatient based intermittent ECUM as one of the useful therapeutic modalities to ameliorate refractory CHF.

Female↗
PubMed1994

[Clinical results of breast conservation therapy; a radiotherapeutical viewpoint].

Between November 1987 and March 1993, 244 breasts in 243 patients underwent breast conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin--positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including beam angle and the head rotation angle. During follow-up for 2-66 months (median, 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 patients (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has occurred. The cumulative survival rate and the disease--free survival rate at five years were 95.2% and 91.8%, respectively. These promising clinical results of breast conservation therapy encourage further clinical trials.

Breast Neoplasms↗
PubMed1993

Stimulation of Fe(2+)-induced lipid peroxidation in phosphatidylcholine liposomes by aluminium ions at physiological pH.

The effects of aluminium ions on Fe(2+)-induced lipid peroxidation in egg yolk phosphatidylcholine liposomes were examined under various conditions. The degree of Fe(2+)-induced lipid peroxidation of the liposomes was dependent on pH of the reaction mixture: pH 5.0 > pH 7.4. However, Fe2+ did not induce lipid peroxidation in the liposomes at pH 9.0. The addition of AlCl3 to the liposomal suspension resulted in a marked stimulation of Fe(2+)-induced liposomal peroxidation at pH 7.4, depending on the concentration of AlCl3. On the other hand, Fe3+, Cu2+, Pb2+, Cd2+ and Cr6+ did not induce lipid peroxidation in the liposomes at pH 7.4 regardless of the presence and absence of AlCl3. Fe3+ enhanced Fe(2+)-induced liposomal peroxidation at pH 7.4 but is unrelated to the stimulatory effect of AlCl3. In the absence of AlCl3, Fe(2+)-induced liposomal peroxidation was observed after a lag phase of about 15 min. The lag phase of the reaction was shortened by the addition of AlCl3 in a dose-dependent fashion. The shortening of the lag phase was also observed by the decrease of Fe2+ concentration or by the co-presence of Fe3+ in the reaction mixture. In addition, it was found that AlCl3 stimulates Fe2+ disappearance and Fe3+ formation. The addition of AlCl3 to the liposomal suspension at pH 7.4 resulted in a marked increase of the turbidity of the suspension. On the other hand, the turbidity of the liposomal suspension at pH 5.0 did not change by the addition of AlCl3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Chloride↗
PubMed1993

Inhibition of mitogen-induced proliferation of spleen lymphocytes is correlated with the induction of cell-mediated immunity in Salmonella infection in mice.

The proliferation of murine spleen cells stimulated by a T-cell mitogen such as phytohemagglutinin (PHA) or concanavalin A (ConA) was significantly suppressed when the mice were immunized with either the viable cells or the sonicate of Salmonella typhimurium but not of Escherichia coli. The suppression of T-cell proliferation caused by the sonicate of S. typhimurium was completely restored by addition of phorbol 12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC). Western blots using anti-phosphotyrosine antibodies showed that the mitogen-induced tyrosine phosphorylation of 120-, 106-, 94-, 76-, 68- and 57-kDa proteins in murine splenic T-cells was inhibited in the mice immunized with the viable cells but not the sonicate of S. typhimurium. These results suggest that the inhibition caused by the sonicate involves suppression of PKC activity, whilst that produced by viable cells involves down-regulation of tyrosine phosphorylation, and both inhibitions correlate with the induction of cell-mediated immunity in mice, as evidenced by the induction of delayed-type hypersensitivity reactions.

Animals↗