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Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 379 records · Page 21Linked to original sources

The response to epidermal growth factor of human maxillary tumor cells in terms of tumor growth, invasion and expression of proteinase inhibitors.

Three cancer cell lines, IMC-2, IMC-3 and IMC-4, were established from a single tumor of a patient with maxillary cancer. We examined responses to epidermal growth factor (EGF) of these 3 cell lines with regard to cell growth and tumor invasion. The growth rate of IMC-2 in nude mice was markedly faster than that of the IMC-3 and IMC-4 cell lines. Assay for invasion through fibrin gels showed significantly enhanced invasive capacity of IMC-2 cells in response to EGF, but no change for IMC-3 and IMC-4 cells. We examined response to EGF of IMC-2 cells with regard to expression of a growth-related oncogene (c-fos), proteinases and their inhibitors. Expression of c-fos was transiently increased in IMC-2 cells at rates comparable to those seen in the 2 other lines in the presence of EGF. There was no apparent effect of EGF on the expression of urokinase-type plasminogen activator and 72-kDa type-IV collagenase in IMC-2 cells. In contrast, EGF specifically enhanced the expression of plasminogen activator inhibitor-I (PAI-I) and tissue inhibitor of metalloproteinases-I (TIMP-I) in IMC-2 cells. Our data suggest that proteinase inhibitors or other related factors may play an important role in tumor growth and invasion in response to EGF.

Animals↗

A study on peroxidative damage of the porcine intestinal brush-border membranes using a fluorogenic thiol reagent, N-(1-pyrene)maleimide.

To examine the effects of lipid peroxidation on the protein conformation in the porcine intestinal brush-border membranes, a fluorogenic thiol reagent, N-(1-pyrene)maleimide (NPM) was employed. By treatment of NPM-labeled membranes with 100 microM ascorbic acid/10 microM Fe2+ in the presence of various concentrations of tert-butyl hydroperoxide (t-BuOOH), the fluorescence intensity of the complex decreased with the formation of conjugated diene, depending on the hydroperoxide concentration. The temperature dependence profile of the fluorescence intensity of NPM-labeled control membranes showed a thermal transition of the NPM fluorescence at 27-28 degrees C. The transition phenomenon of the NPM fluorescence in the membranes around this temperature disappeared by treatment of the labeled membranes with 100 microM ascorbic acid/10 microM Fe2+/0.6 mM t-BuOOH. The difference in response of the fluorescence characteristics of the bound NPM for temperature variation between the control and peroxidized membranes was also observed in the quenching efficiency with acrylamide. Measurement of the fluorescence polarization revealed that the harmonic mean of the rotational relaxation times of the bound NPM molecules to the membrane proteins increased from 1.96 to 4.93 microseconds by lipid peroxidation of the membranes. This indicates that the movement of the region containing NPM-labeled SH groups in the membrane proteins is restricted by lipid peroxidation. Treatment of NPM-labeled peroxidized membranes with sodium dodecyl sulfate (SDS) resulted in a restoration of the intensity of the NPM fluorescence to the level of the control ones. In addition, the temperature dependence profile of the fluorescence intensity of NPM-labeled peroxidized membranes in the presence of SDS also showed an appearance of a transition phenomenon around 30 degrees C. The result of SDS-polyacrylamide gel electrophoresis of the peroxidized membranes revealed that high-molecular-weight aggregates of the membrane proteins were not formed by lipid peroxidation. On the basis of these results, changes in the environmental properties around NPM-labeled SH groups in the membrane proteins by lipid peroxidation are discussed.

Animals↗

Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance.

Aged↗

A phase I study of chronic daily dosing of oral etoposide in combination with cisplatin for patients with advanced cancer.

A dose escalation study of daily oral etoposide and cisplatin was carried out on 22 patients with advanced cancer using starting doses of 20 mg/m2/d of etoposide given orally for 21 days and 80 mg/m2 of cisplatin given intravenously (IV) on day 1. A total of 40 courses were given. Myelosuppression was the major dose-limiting toxicity, with a maximum tolerated dose of 50 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. Doses of 40 mg/m2/d of etoposide for 21 days plus 80 mg/m2 of cisplatin for 1 day in four of eight courses (50%) were associated with Grade 3 or worse leukopenia that occurred between days 18 and 26. However, no Grade 3 or worse thrombocytopenia occurred at this dose level. Nausea and vomiting occurred in most patients at each dose level but were mild and could be controlled by antiemetics. Alopecia also occurred frequently. Significant mucositis (Grade 4) occurred in one patient, but no other toxicities were observed. Four partial responses that lasted from 1.3 to 5.8+ months were observed in patients with cervical (one patient), small cell lung (one patient), and squamous cell lung cancer (two patients); one of them had been heavily pretreated with platin analogue-containing regimens. The recommended doses for Phase II studies on this schedule are 40 mg/m2/d of oral etoposide for 21 days plus 80 mg/m2 of IV cisplatin on day 1. A combination regimen on this schedule seems particularly effective in patients with etoposide-sensitive malignancies.

Adult↗

Spindle cell carcinoma of the lung. A clinicopathologic study of three cases.

Two cases of monophasic spindle cell carcinomas and one case of adenosquamous carcinoma with the spindle cell component located in the lower respiratory tract are presented. In the biphasic tumor, areas of transition from carcinoma to sarcomatous spindle cells were clearly found. The two monophasic tumors and the spindle cell component of the biphasic tumor were histologically characterized by sheets of spindle cells. However, by electron microscopic and immunohistochemical study, several features of squamous epithelial differentiation were found in the spindle cell areas of all cases. Keratin and vimentin were, in various degrees, coexpressed in all the cases. Therefore, it is supposed that the spindle cell component displays a spectrum of phenotypes originating from squamous cell carcinoma, and monophasic spindle cell carcinoma is considered as a kind of the extreme phenotype of squamous cell carcinoma pretending mesenchymal differentiation.

Adenocarcinoma↗

Fluorescence characteristics of peroxidation products in porcine intestinal brush-border membranes.

Treatment of the porcine intestinal brush-border membranes with 100 microM ascorbic acid and 10 microM Fe2+ in the presence of various concentrations of tert-butyl hydroperoxide (t-BuOOH) resulted in a marked fluorescence development at 430 nm, depending on the hydroperoxide concentration. This fluorescence formation was closely related to lipid peroxidation of the membranes as assessed by formation of conjugated diene. However there is no linear relation between thiobarbituric acid-reactive substances (TBARS) and fluorescence formation. On the other hand, fluorescence formation in the membranes by treatment with ascorbic acid/Fe2+ or t-BuOOH alone was negligible. The results with antioxidants and radical scavengers suggest that ascorbic acid/Fe2+/t-BuOOH-induced lipid peroxidation of the membranes is mainly due to t-butoxyl and/or t-butyl peroxy radicals. Most TBARS produced during the peroxidation reaction were released from the membranes, but fluorescent products remained in the membrane components. The fluorescence properties of products formed by lipid peroxidation of the membranes were compared with those of products derived from the interaction of malondialdehyde (MDA) or acetaldehyde with the membranes. The fluorescence products in the acetaldehyde-modified membranes also exhibited the emission maximum at 430 nm, while the emission maximum of MDA-modified membranes was 470 nm. The fluorescence intensity of MDA-modified membranes was markedly decreased by treatment with 10 mM NaBH4 but that of the peroxidized or acetaldehyde-modified membranes was enhanced by about two-fold with the treatment. In addition, a pH dependence profile revealed that the fluorescence intensity of the peroxidized or acetaldehyde-modified membranes decreases with increasing pH of the medium, whereas that of MDA-modified ones did not change over the pH range from 5.4 to 8.0. On the basis of these results, the fluorescence properties of products formed in the intestinal brush-border membranes by lipid peroxidation are discussed.

Animals↗

1-Hydroxyethylidene-1,1-bisphosphonate decreases the postovariectomy enhanced interleukin 1 secretion from peritoneal macrophages in adult rats.

Bisphosphonates are potent inhibitors of bone resorption. In previous studies, we have shown that ovariectomy accelerates bone resorption and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) inhibits ovariectomy-accelerated bone resorption in female Wistar adult rats. As interleukin 1 (IL-1) stimulates bone resorption in vitro and in vivo, we have investigated the effects of ovariectomy and HEBP administered in vivo on IL-1 secretion from peritoneal macrophages in adult rats. Ovariectomy or sham surgery were performed in female Wistar rats at 40 weeks of age. Ovariectomized and sham-operated rats were administered with HEBP (10 mg) or saline, 10 times in total, from 43 to 46 weeks of age. Paraffin oil-induced peritoneal macrophages at 46 weeks of age were cultured for 24 hours. Lipopolysaccharide (LPS)-stimulated peritoneal macrophages from ovariectomized rats secreted more IL-1 than sham-operated rats. HEBP decreased LPS-stimulated IL-1 secretion from peritoneal macrophages in ovariectomized rats, but not in sham-operated rats. In vivo administration of HEBP decreased IL-1 secretion only in postovariectomy hyperresorptive states. These results suggest that alterations in LPS-stimulated IL-1 secretion from oil-induced peritoneal macrophages may be responsible, at least in part, for the postovariectomy acceleration in bone resorption and its inhibition by HEBP.

Analysis of Variance↗

Altered localization of antigen recognized by proteinuria-inducing monoclonal antibody in experimental nephrosis.

Change in the localization of the antigen recognized by the proteinuria-inducing monoclonal antibody (MA) 5-1-6 in experimental nephrosis was studied by indirect and biotin-avidin immunofluorescence, and immunoperoxidase at light and electron microscopical levels. The proteinuric state was induced by the administration of the aminonucleoside of puromycin (PAN) or adriamycin. The antigen decreased in quantity and/or its distribution changed with an increase in the amount of protein excreted in both experimental models. Recovery from the alterations observed during the development and proteinuria appeared to occur when PAN-induced proteinuria subsided. This antigenic molecule may thus be essential for maintaining the normal permselectivity of glomerular capillary walls.

Animals↗

Oxygen-radical-mediated lipid peroxidation and inhibition of ADP-induced platelet aggregation.

The effects of lipid peroxidation on ADP-induced aggregation of washed rat platelets were examined using a oxygen-radical-generating system consisting of H2O2 and ferrous ion. Lipid peroxidation was assessed by measurement of thiobarbituric acid-reactive substances (TBARS). Incubation of the platelets with various concentrations of H2O2 (2-10 mM) in the presence of 10 microM Fe2+ resulted in a decrease of the aggregating capacity and an increase of TBARS value, depending on the concentrations of H2O2. Addition of catalase (0.1 mg/ml) to the incubation medium containing 10 microM Fe2+ and 10 mM H2O2 effectively protected the aggregating capacity, but superoxide dismutase (0.1 mg/ml) did not protect H2O2/Fe(2+)-induced inhibition of the platelet aggregation. The results of kinetic studies on the platelet aggregation with varying ADP and Ca2+ concentrations suggested that treatment of the platelets with H2O2/Fe2+ causes decreases in the binding affinities of ADP and Ca2+ for the platelets. On the basis of these results, change in the aggregating capacity of the platelets by treatment with H2O2/Fe2+ is discussed in relation to lipid peroxidation.

Adenosine Diphosphate↗

Transient massive proteinuria associated with Mycoplasma pneumoniae infection.

A 5-year-old girl presented with Mycoplasma pneumoniae infection, which was associated with eyelid edema and massive proteinuria. Her clinical manifestations were similar to those of nephrotic syndrome, except for the absence of hypoproteinemia. Light microscopy of renal biopsy tissue showed minor glomerular abnormalities, with no tubulointerstitial changes. Electron microscopy showed sparse fusion of the foot processes, regular nonthickened glomerular basement membrane, and no electron-dense deposits. Immunofluorescent staining of the glomeruli for immunoglobulins (IgG, IgA, IgM) and complement (C3, C4) was negative. Mycoplasma antigen was not detected by indirect immunofluorescence. These findings suggest a causal relationship between M pneumoniae infection and transient renal injury.

Child, Preschool↗

Organ-specific occurrence and expression of the isoforms of nonspecific lipid transfer protein in castor bean seedlings, and molecular cloning of a full-length cDNA for a cotyledon-specific isoform.

Four kinds of nonspecific lipid transfer proteins (nsLTP) were purified from different organs of castor bean (Ricinus communis L.) seedlings. Amino acid compositions and amino-terminal sequences of the four nsLTPs were determined and compared with those of castor bean isoforms, nsLTP-A, -B, and -C, previously reported [Takishima et al. (1986) Biochim. Biophys. Acta 870, 248-255; Takishima et al. (1988) Eur. J. Biochem. 177, 241-249]. Two isoforms from the cotyledons were identified as nsLTP-A and -C, one isoform from the endosperms as nsLTP-B, and the other was a new isoform from the axes. This new isoform was named nsLTP-D and its amino acid sequence was determined. These results demonstrated organ-specific occurrence of the nsLTP isoforms in castor bean seedlings. The isoforms nsLTP-A, -B, -C, and -D showed similar transfer activity not only for phosphatidylcholine and phosphatidylethanolamine but also for monogalactosyldiacylglycerol, although the homology among their amino acid sequences ranged from 70 to 30%. Two cDNA clones (pnsLTP-C and pnsLTP-D) for nsLTPs of castor bean seedlings were isolated and sequenced. pnsLTP-C was the cDNA clone for nsLTP-C expressed in the cotyledons, and pnsLTP-D was that for nsLTP-D in the axis. A coupled in vitro transcription-translation analysis of both cDNA clones revealed that pnsLTP-C encodes the full-length of nsLTP-C precursor (pro-nsLTP-C), while pnsLTP-D encodes a part of nsLTP-D precursor. PronsLTP-C contained a 24-amino acid pre-sequence preceding the mature nsLTP-C (92 amino acids).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Redevelopment of small-cell lung cancer nine years after the start of therapy. A case report and review of the literature.

Most patients with small-cell lung cancer usually relapse within 1 to 2 years. Relapses after a 5-year disease-free interval occur extremely rarely. This report describes a patient with limited-stage small-cell lung cancer who had achieved a complete response to combination chemotherapy followed by chest irradiation but developed small-cell lung cancer 9.4 years after the beginning of therapy. Small-cell lung cancer recurred in the same side of the lung, in the mediastinal nodes, and in the liver. The pattern of development of small-cell lung cancer suggests that the patient had a relapse rather than a metachronous lung cancer. To our knowledge, this is the second-latest relapse of small-cell lung cancer in the literature.

Aged↗

Cervical esophageal motility: evaluation with US in progressive systemic sclerosis.

High-resolution ultrasound (US) showed that initial peristalsis propelled ingested soda smoothly and rapidly in 20 volunteers without symptoms who met both manometric and radionuclide esophageal scintigraphic (RES) criteria for normal motility. Twenty-eight patients with progressive systemic sclerosis were classified according to results of RES as follows: group 1, normal esophageal motility (three patients [11%]); group 2, hypomotility of the esophagus, excluding the cervical esophagus (18 patients [64%]); and group 3, hypomotility of the cervical esophagus (seven patients [25%]). In the seven patients of group 3, US demonstrated that an incomplete peristalsis sequence or a feeble peristalsis propelled the soda in a slow and/or to-and-fro motion with low velocities. In the other 21 patients (75%), the soda passed through the esophagus smoothly and rapidly. Retention of soda in the cervical esophagus was not limited to patients with hypomotility of the cervical esophagus. It is concluded that US is useful in evaluation of cervical esophageal motility.

Adult↗

A randomized trial in inoperable non-small-cell lung cancer: vindesine and cisplatin versus mitomycin, vindesine, and cisplatin versus etoposide and cisplatin alternating with vindesine and mitomycin.

Patients with inoperable non-small-cell lung cancer (NSCLC) were randomly assigned to receive one of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine, and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). In 199 assessable patients, the response rates were VP, 33%; MVP, 43%; and EP/VM, 19%. The addition of mitomycin to the VP regimen did not significantly improve the response rate. The response rate was significantly lower with the EP/VM regimen than with the MVP regimen (P less than .01). The median survival times were VP, 50 weeks; MVP, 42 weeks; and EP/VM, 40 weeks. These differences were not significant. Grade III or IV thrombocytopenia was significantly greater (P less than .01) in MVP patients (22%) than in the VP (5%). Other toxicities were similar in the three groups. Analyses of prognostic factors showed that treatment with MVP, sex, and histologic classification (squamous cell carcinoma) were predictive of improved response. Important factors for improved survival, according to the Cox regression analysis, were the stage of disease, performance status, sex, weight loss before diagnosis, and hemoglobin concentration.

Adult↗

Changes in surface charge density of lecithin liposomes by lipid peroxidation. A fluorescence study with 8-anilino-1-naphthalenesulfonate.

Treatment of lecithin liposomes with 100 microM ascorbic acid and 10 microM ferrous ion resulted in the formation of fluorescent products exhibiting an emission maximum at 430 nm and a decrease in the fluorescence intensity of 8-anilino-1-naphthalenesulfonate (ANS) bound to the liposomes without change in the emission maximum. The degree of ascorbic acid/Fe(2+)-induced decrease in the ANS fluorescence was dependent on the extent of fluorescent product formation. The results of kinetic studies on ANS-binding to the liposomes showed that treatment of the liposomes with ascorbic acid/Fe2+ causes an increase of the apparent dissociation constant (Kd) of ANS-liposome complex. This indicates that lipid peroxidation of the liposomes by treatment with ascorbic acid/Fe2+ decreases the binding affinity of ANS to the liposomes. In addition, it was also found that there is a good correlation between degrees of the Kd value and the formation of fluorescent products. The fluorescence properties, i.e. emission maximum and response of the fluorescence intensity for borohydride reduction, of the products formed by lipid peroxidation of the liposomes were similar to those derived from modification of the liposomes with monofunctional aldehydes such as acetaldehyde and heptaldehyde. From these results, it is suggested that the decrease of ANS-binding affinity to the liposomes by treatment with ascorbic acid/Fe2+ may be due to changes in the surface charge density of the liposomes relating to the formation of fluorescent products.

Anilino Naphthalenesulfonates↗

Antioxidant effect of vitamin K homologues on ascorbic acid/Fe(2+)-induced lipid peroxidation of lecithin liposomes.

The effects of vitamin K homologues (K1, K2 and K3) on lipid peroxidation of lecithin liposomes induced by ascorbic acid and ferrous ion were examined. Ubiquinone-10 (UQ-10) was used as a reference in evaluation of the effectiveness of these vitamins. The lipid peroxidation was assessed by measurements of thiobarbituric acid-reactive substance (TBARS) and conjugated diene formation during the reaction. Among them, vitamins K1 and K2 inhibited the lipid peroxidation, as did UQ-10, with the order of effectiveness: UQ-10 greater than K2 greater than K1. By contrast, vitamin K3 had no inhibitory effect on ascorbic acid/Fe(2+)-induced lipid peroxidation of the liposomes. The inhibitory effect of vitamins K1 and K2 appeared only when these vitamins were incorporated into the liposomes by sonication. Simple mixing of the liposomes with these vitamins or with UQ-10 did not inhibit peroxidation of the liposomes even at high concentrations. From measurements of nitroblue tetrazolium reduction and p-nitrosodimethylaniline bleaching of vitamin K1- or K2-incorporated liposomes in the presence of ascorbic acid/Fe2+, it was found that these vitamins prevent the formation of hydroxyl radicals, not superoxide anions, during the peroxidation reaction. However, the degree of ascorbic acid/Fe(2+)-induced TBARS formation of the liposomes was not inhibited by the addition of mannitol to the reaction mixture. From these results, it is suggested that the inhibitory effect of these vitamins is mainly involved in termination of radical-chain reaction. Experimental results using several radical scavengers and/or antioxidants supported this interpretation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidants↗

Arteriovenous malformations of the kidneys: diagnosis and follow-up with color Doppler sonography in six patients.

We performed color Doppler sonography in six patients with arteriovenous malformations of the kidneys. The diagnosis was established by angiography in all patients. Color Doppler sonograms were obtained at a large Doppler frequency-shift range (55 cm/sec of maximal average flow velocity at zero Doppler angle) to depict high-velocity blood flow in the malformation. In all patients, the malformations were seen as focal areas of flow, portrayed as a mixing of lighter colors. These were reflected by a rapid flow rate and marked tortuosity of the vessels. The sonograms showed a small peripheral malformation that was indistinct on selective renal angiography. However, flow in normal vessels grouped in the hilum obscured lighter-color flow of a small central malformation. In three patients who had total or partial ablation of the malformations with alcohol, follow-up color Doppler sonograms showed that the focal areas of flow, represented as mixing of lighter colors, disappeared or became smaller. This study shows that color Doppler sonography is a useful noninvasive procedure for diagnosing arteriovenous malformations of the kidney.

Adult↗

All eight possible mono-beta-D-glucosides of validoxylamine A. I. Preparation and structure determination.

Validamycin A is the major and most active compound among the validamycin complex. Since the site of beta-glucosidic attachment to validoxylamine A (1) was expected to affect the activity against the pathogenic fungus, Rhizoctonia solani, all eight possible mono-beta-D-glucosides of 1 were prepared. 2-O-, 4-O-, 4'-O-, and 7'-O-beta-D-glucopyranosylvalidoxylamine A (2, 4, 6 and 9, respectively) were prepared by microbial beta-glycosylation of 1 with strains of Rhodotorula sp. 7-O- and 6'-O-beta-D-glucopyranosylvalidoxylamine A (5a and 8a, respectively) were prepared semisynthetically through microbial formation of 7-O-beta-D-glucopyranosylvalidamine (10), oxidation of the primary amine of 10 to a ketone, and coupling of the ketone derivative with valienamine, and through microbial formation of 6-O-beta-D-glucopyranosylvalienamine (11), and coupling of 11 with (2R)-(2,4/3,5)-2,3,4-trihydroxy-5-hydroxymethylcyclohexanone (12), respectively. 3-O- and 5'-O-beta-D-glucopyranosylvalidoxylamine A (3a and 7a, respectively) were chemically synthesized.

Antifungal Agents↗