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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 199 records · Page 11Linked to original sources
PubMed1999

Tumor specific CTL therapy for advanced cancer and development for cancer vaccine.

BACKGROUND/AIMS: Advanced gastrointestinal (GI) cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of tumor specific cytotoxic T Lymphocyte (CTL) therapy as multidisciplinary treatment for patients with advanced cancer. METHODOLOGY: The enrolled advanced cancer patients had distant metastases derived from gastric cancer, colon cancer and bilio-pancreatic cancer. The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by various kinds of the activated killer cells. RESULTS: There was no severe toxicity, except fever and mild myelo-suppression. Six patients had complete response, and 18 patients had partial response out of 38 enrolled patients. The performance status was improved in responders (p<0.01); however, it was not changed in non-responders. Furthermore, the ratio of discharge of the responders was higher than that of non-responders. CONCLUSIONS: It was clarified that tumor-specific CTL therapy as multidisciplinary treatment is clinically valuable, especially in terms of quality of life. For developing the new strategy against cancer, CEA specific cancer vaccine trials have just started.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[A case report of emergent CABG after left main trunk occlusion as complication of direct PTCA].

A 38-years-old man was transferred to our hospital because of cardiogenic shock following acute left main trunk (LMT) occlusion as a complication of direct percutaneous transluminal coronary angioplasty (PTCA), and then underwent emergent coronary artery bypass grafting. We successed his life salvage, but he suffers from very severe heart failure following extensive myocardial infarction. Though acute LMT occlusion as a complication of PTCA is rare, a proper treatment has to be started as soon as possible if it occurs. We must make the systems of support for the emergencies among the surrounding hospitals.

Adult↗
PubMed1999

[Surgical treatment of ulcerative colitis].

Known indications in the surgical treatment of ulcerative colitis are acute severe attacks, intractability, and cancer prophylaxis. This study was performed to determine the optimum timing of operation in ulcerative colitis. Of 59 patients with intractability, 9(15%) had severe attacks and 6(10%) developed colorectal cancer. The mean duration of disease was 3.6 yr for 14 with severe attacks alone, 6 yr for 44 with intractability alone, 8.6 yr for 9 with both, and 16.5 yr for 16 with cancer prophylaxis. In this series, the operations for intractable disease were more likely to be delayed, and the longer these were delayed, the higher the rate was of pre- and postoperative complications.

Anal Canal↗
PubMed1999

[Proinsulin].

Explore the source record for details and available documents.

Diabetes Mellitus↗
PubMed1998

Expression cloning and functional characterization of human cDNA for ganglioside GM3 synthase.

Ganglioside GM3 is a major glycosphingolipid in the plasma membrane and is widely distributed in vertebrates. We describe here the isolation of a human cDNA whose protein product is responsible for the synthesis of GM3. The cloned cDNA spanned 2,359 base pairs, with an open reading frame encoding a protein of 362 amino acids with a predicted molecular mass of 41.7 kDa. The deduced primary structure shows features characteristic of the sialyltransferase family, including a type II transmembrane topology and the sialylmotifs L at the center and S at the C-terminal region. An amino acid substitution from aspartic acid to histidine was demonstrated at a position invariant in sialylmotif L of all the other sialyltransferases so far cloned. The best acceptor substrate for the gene product was lactosylceramide, and cells transfected with the cloned cDNA clearly exhibited de novo synthesis of GM3, with a measurable decrease in the precursor lactosylceramide. Despite the ubiquitous distribution of ganglioside GM3 in human tissues, a major 2.4-kilobase transcript of the gene was found in a tissue-specific manner, with predominant expression in brain, skeletal muscle, and testis, and very low expression in liver.

Amino Acid Sequence↗
PubMed1998

Effect of glucocorticoids on the mouse methionine adenosyltransferase A1 gene expression, which is regulated by two promoters.

The methionine adenosyltransferase A1 (MATA1) gene encodes the hepatic forms of the enzyme MAT I and III. To determine the molecular mechanisms that regulate MATA1 gene expression, we characterized promoters and the 5'-flanking sequence of MATA1. Transient expression assays demonstrated the presence of two promoters for the MATA1 gene. The p1 promoter is contained in the -57 to -2 nucleotide region, and gives rise to the P1 transcript initiated at +1. The p2 promoter is contained in the -248 to -146 nucleotide region. The -229 to -213 nucleotide region of the MATA1 gene, which contains an Ets-binding-site sequence, was necessary for p2 promoter activity. Sequence analysis of 5'-RACE products indicated that there was a transcript (P2) initiated at -156. The -107 to +145 nucleotide region is missing from the mature P2 transcript, which suggests that the -107 to +145 nucleotide sequence is an intron of the P2 transcript. The p2 promoter may give rise to the P2 transcript. The p1 promoter activity was increased by glucocorticoids, but the p2 promoter activity was not affected by glucocorticoids.

Adrenalectomy↗
PubMed1998

Proliferation and differentiation of human osteoblastic cells associated with differential activation of MAP kinases in response to epidermal growth factor, hypoxia, and mechanical stress in vitro.

In an attempt to elucidate the specificity of pathways from environmental stress to cellular outcome via mitogen activated protein kinases (MAPKs) activation, we examined the responsiveness of cultured human osteoblastic periodontal ligament (PDL) cells to epidermal growth factor (EGF), hypoxia, and mechanical stress, in terms of cell proliferation, differentiation, and associated activation of three different types of MAPK. Cell proliferation was promoted in the presence of 10ng/ml of EGF or in hypoxic conditions (5% O2), whereas it was inhibited by cyclic stretch (9% strain, 6 cycles/min), which was used as a model of mechanical stress. Conversely, the alkaline phosphatase activity, a marker for osteoblastic differentiation of the cells, was increased by cyclic stretch but decreased by EGF and hypoxia. The mitogenic response of PDL cells to EGF or hypoxia was associated with the selective phosphorylation and activation of extracellular-related kinase (ERK) 1/2, while phosphorylation and activation of c-Jun N-terminal kinase (JNK) was observed in mechanical stretch loaded cells. No such changes were seen in p38 protein. These findings suggested that stress-responsive changes in proliferation and osteoblastic differentiation of PDL cells are selectively mediated by ERK 1/2 and by JNK, respectively, and that a balance between these two pathways determines the cell fate.

Alkaline Phosphatase↗
PubMed1998

Development of GAP-43 mRNA in the macaque cerebral cortex.

To estimate the extent of axonal growth in various areas of the cerebral cortex, we measured the amount of GAP-43 mRNA in the cerebral cortex of developing macaque monkeys. In four areas, i.e., the prefrontal area (FD delta), the temporal association area (TE), the primary somatosensory area (PC), and the primary visual area (OC), the amount of GAP-43 mRNA was measured from the intermediate fetal period [embryonic day 120 (E120)] to the adult stage. In two other areas, i.e., the parietal association area (PG) and the secondary visual area (OB), the amount of GAP-43 mRNA was measured during the postnatal period. The amount of GAP-43 mRNA was highest at E120, decreased roughly exponentially, and approached the asymptote by postnatal day 70 (P70). The amount of GAP-43 mRNA was higher in the association areas (FD delta, TE, and PG) than in the primary sensory areas (PC and OC) during development and at the adult stage. These findings suggest that axonal growth in the cerebral cortex is most exuberant before or during the intermediate fetal period and approximately ends by P70. Furthermore, axonal growth is evidently more intensive in the association areas than in the primary sensory areas during the stage following the intermediate fetal period.

Aging↗
PubMed1998

High potassium-induced glutamate release in the cochlea: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate.

The time course of changes in perilymphatic glutamate release and their Ca2+-dependency were studied in the guinea pig cochlea during high K+-evoked depolarization. The glutamate concentration was analyzed continuously by an enzyme-linked fluorometric assay combined with microdialysis. Two peaks of glutamate increase were found in response to perfusion for 10 min. In the absence of Ca2+, the first peak was diminished, whereas the inhibition of the second peak was minimal.

Animals↗
PubMed1998

Toroidal coil counter-current chromatography. Achievement of high resolution by optimizing flow-rate, rotation speed, sample volume and tube length.

This paper deals with optimization of a new seal-free compact toroidal coil centrifuge to achieve high resolution in analytical counter-current chromatography (CCC). Toroidal coil CCC (hydrostatic motion) has advantages compared with high-speed CCC (efficiently mixing solution with planetary motion) in the separation of protein or easily emulsified samples. A toroidal coil separation column of 0.4 mm I.D. PTFE tubing was accommodated around the periphery of the cylindrical centrifuge bowl. Using a two-phase solvent system composed of chloroform-acetic acid-0.1 M hydrochloric acid (2:2:1, v/v/v) and a set of dinitrophenyl-amino acids as test samples, a series of experiments was performed with parameters such as the column length, sample volume, flow-rate, elution mode of the mobile phase and rotation speed. The highest efficiency, over 10,000 theoretical plates, was achieved with a 100 m long coiled tube and an 11 ml total capacity at a flow-rate of 0.01 ml/min at 800 rpm.

Amino Acids↗
PubMed1998

Development of guanine analyzer to measure activity of guanylate cyclase.

A previous analyzer of adenine compounds by high-performance liquid chromatography was converted for the determination of guanine, its nucleoside and nucleotides by a post-column fluorescence derivatization with phenylglyoxal (PGO) in place of bromoacetoaldehyde. The gel filtration column (Asahipak GS-320H) was used for separation by a mobile phase consisting of 25 mM sodium citrate buffered (pH 4.0)-150 mM NaCl solution and CH3CN (85:15, v/v) containing 15 mM PGO. The separated analytes reacted with flow through PGO in a reaction coil at 90 degrees C into fluorescent derivatives. Those derivatives were detected fluorimetrically, highly selective and quantitatively. The activity of soluble guanylate cyclase (sGC) in the neuroblastoma N1E-115 cell was measured by tracing the peak height of cGMP synthesized from substrate GTP using this guanine analyzer. The sensitivity of the present method was lower than the radioisotope method. However, our modified method was simpler, safer and quicker than the radioisotope method. Furthermore, this method could trace other guanine compounds simultaneously, allowing measurement of guanine metabolizing enzymatic activity. Therefore, it will be useful for screening of effectors on sGC.

Chromatography, Gel↗
PubMed1998

Toroidal coil counter-current chromatography study of the mass transfer rate of proteins in aqueous-aqueous polymer phase system.

The cause of excessive band broadening of protein samples in polymer phase partitioning by counter-current chromatography (CCC) was investigated. A simple rotary device was constructed to measure the mass transfer rates of five samples including potassium dichromate, methylene blue, lysozyme, ovalbumin and human serum albumin. The results indicated that the mass transfer rates of these samples are closely correlated with their molecular masses: the higher the molecular mass, the lower the mass transfer rate. These findings are also consistent with the partition efficiencies of these samples in the same solvent system by CCC. The beneficial effect of the Coriolis force demonstrated in protein separations by the toroidal coil centrifuge may be reasonably explained on the basis of the mass transfer resistance of protein molecules through the interface: we speculate that when the Coriolis force acts parallel to the effective coil segment it can produce large interfacial areas by dispersing the mobile phase into the stationary phase, thus accelerating the mass transfer rate of protein samples.

Chromatography, Liquid↗
PubMed1998

Membrane potential of mesenteric artery from carvedilol-treated spontaneously hypertensive rats.

The effects of chronic treatment of stroke-prone spontaneously hypertensive rats (SHRSP) with carvedilol, an antihypertensive agent which has both alpha- and beta-adrenoceptor-blocking actions, on membrane potential and relaxation of mesenteric resistant artery were studied. Five-week old SHRSP were treated with carvedilol for three months. At 16 weeks, the resting membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The magnitude of acetylcholine-induced hyperpolarization in arteries from carvedilol-treated SHRSP was not different from that of arteries from untreated SHRSP. In the presence of noradrenaline, the membrane potential of arteries from carvedilol-treated SHRSP was more negative than that of arteries from untreated SHRSP. The membrane potential of arteries from carvedilol-treated SHRSP in the presence of noradrenaline and acetylcholine was more negative than that of arteries from untreated SHRSP. The acetylcholine-induced relaxation in noradrenaline-precontracted preparations from carvedilol-treated SHRSP was greater than that in preparations from untreated SHRSP and was smaller than that in preparations from Wistar Kyoto rats. Scanning electronmicroscopy showed that carvedilol-treatment decreased the structural abnormalities of the endothelium of arteries from SHRSP. These results indicate that chronic carvedilol treatment made the membrane potential of smooth muscle more negative and improved endothelial function in the mesenteric artery of SHRSP, which may contribute to the antihypertensive effect of carvedilol.

Animals↗
PubMed1998

Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice.

Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal mice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.

Animals↗
PubMed1998

Gene expression of growth-associated proteins, GAP-43 and SCG10, in the hippocampal formation of the macaque monkey: nonradioactive in situ hybridization study.

We performed nonradioactive in situ hybridization histochemistry in the monkey hippocampal formation that includes the hippocampus, the subicular complex, and the entorhinal cortex to detect the expression of mRNA for two growth-associated proteins: GAP-43 and SCG10. Overall, the distribution patterns overlapped but were partially distinct. In the hippocampus, the intense hybridization signals for both GAP-43 and SCG10 mRNAs were observed in the pyramidal cell layer of Ammon's horn, especially in CA3 subfields. The intense hybridization signals were also observed in the stratum oriens of Ammon's horn and the polymorphic layer of the dentate gyrus. In the granule cell layer of the dentate gyrus, many GAP-43 mRNA-positive cells were observed, whereas a few positive cells with weak signals were observed for SCG10 mRNA. Throughout the subicular complex, the hybridization signals for both mRNAs were weak. In the entorhinal cortex, both mRNAs were abundant in the caudal field. These subregion-specific expression of the growth-associated proteins may reflect the functional specialization regarding plasticity in each region of the monkey hippocampal formation.

Animals↗
PubMed1998

Physiological mechanism-based analysis of dose-dependent gastrointestinal absorption of L-carnitine in rats.

We evaluated the dose-dependent (saturable) gastrointestinal absorption of L-carnitine, a lipid-lowering agent, in rats by a physiological mechanism-based approach to clarify its absorption characteristics and to examine the in vitro (in situ)-in vivo correlation in intestinal transport. The intestinal absorption rate constant (ka), which was estimated by the analysis of gastrointestinal disposition, decreased markedly from 0.1061 to 0.0042 min(-1) when the dose was increased from 0.05 micromol rat(-1) (low dose) to 100 micromol rat(-1) (high dose). The dose-dependence in ka was attributable to the saturability of intestinal transport that, in the perfused intestine, was similar to the saturability in ka. At the high dose, the apparent absorption rate constant (k'a) of 0.0021 min(-1), which was estimated by the analysis of plasma concentrations after oral administration, was an order of magnitude smaller than the gastric emptying rate constant (kg) of 0.059 min(-1) and comparable with the ka of 0.0042 min(-1), suggesting that the gastrointestinal absorption of L-carnitine is absorption-limited in the intestine. At the low dose, where intestinal L-carnitine absorption was far more efficient, the k'a of 0.0172 min(-1) was smaller than the ka of 0.1061 min(-1) and closer to the kg of 0.072 min(-1), suggesting that apparent absorption was retarded by gastric emptying which is less efficient than intestinal absorption. This shift in the rate-determining process with an increase in dose explains the less marked dose dependence in k'a compared with ka. The bioavailability decreased from 100 to 42% with an increase in dose. This could be accounted for quantitatively by a reduction in the fraction absorbed (F(a,oral)) due to a reduction in ka, assuming first-order absorption during the transit time of T(si) through the small intestine (F(a,oral) = 1 - exp(-ka x T(si))). Thus, using L-carnitine as a model, this study has successfully demonstrated that the saturability in gastrointestinal absorption can be correlated with the intestinal transport in a quantitative and mechanism-based manner. This should be of help not only for developing more efficient oral L-carnitine delivery strategies, taking advantage of in vitro (in situ) information about the intestinal transport mechanism, but also for establishing a more generally applicable in vitro (in situ)-in vivo correlation in gastrointestinal absorption.

Algorithms↗