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Biomedical subjects

K Matsuda

Publications and source records attributed to K Matsuda.

At least 397 records · Page 22Linked to original sources

Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system. I. ACh and L-dopa.

To characterize neuronal phenotypes, aminergic neurotransmitters, i.e. acetylcholine (ACh), catecholamine (CA)s and other biogenic amines (serotonin, octopamine), were surveyed in 10 colonial clones from one cell line of Drosophila larval CNS using HPLC-ECD system. ACh, which is a neurotransmitter in Drosophila, was found in 7 out of 10 clones. CAs, their metabolites, and other amines were not detected in any clones. However, all the 10 clones expressed L-dopa, a precursor of CAs. Consequently, seven clones expressed ACh and L-dopa. L-dopa as a novel neurotransmitter candidate was discussed.

Acetylcholine↗

Expression of alpha-1,3 linkage-containing oligomannosyl residues in a cell-wall mannan of Candida tropicalis grown in yeast extract-Sabouraud liquid medium under acidic conditions.

We investigated the cell-wall mannan obtained from Candida tropicalis IFO 1647 strain cells grown in yeast extract-Sabouraud medium at pH 3.0 by two-dimensional homonuclear Hartmann-Hahn spectroscopy. The results indicate that the phosphate group and the side chains containing a beta-1,2-linked mannopyranose unit decreased compared to those of mannan from cells grown under conventional conditions (pH 5.9) with concomitant expression of alpha-1,3 linkage-containing oligomannosyl side chains. The results of acetolysis of these mannans indicated that the presence of alpha-1,3-linked mannopyranose unit existed in side chains corresponding to pentaose and hexaose, Manp alpha 1-3 Manp alpha 1-2Manp alpha 1-2 Manp alpha 1-2Man, and Manp alpha 1-2Manp alpha 1-3Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man, in the mannan from cells grown at pH 3.0.

Candida↗

Developmental regulation of rat serine dehydratase gene expression: evidence for the presence of a repressor in fetal hepatocytes.

To determine why the rat serine dehydratase gene becomes transcriptionally activated just after birth, we examined the interactions of DNA binding proteins of fetal and adult rat livers with the serine dehydratase gene promoter by DNase I protection analysis and gel mobility shift assay. Several binding regions of nuclear proteins were found to be common to fetal and adult livers and interaction of factors with the characteristics of Sp1 or NF-Y was suggested. Two additional regions, named regions B and I, were specific to fetal liver. These regions contain GATA-like sequences and competition experiments by gel mobility shift assay suggested that the fetal liver-enriched factor binds to the GATA-like sequences. The function of the regions B and I in transcription regulation was investigated in fetal and adult hepatocytes by transient DNA transfer experiments with serine dehydratase-chloramphenicol acetyltransferase fusions. These experiments showed that these regions functioned as negative cis-acting elements in fetal hepatocytes, but not in adult hepatocytes.

Animals↗

Molecular cloning of a human transmembrane-type protein tyrosine phosphatase and its expression in gastrointestinal cancers.

To determine the expression of various protein-tyrosine phosphatases (PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains were amplified by reverse transcriptase polymerase chain reaction from KATO-III cell mRNA and sequenced. Among 72 polymerase chain reaction clones, one of the cDNA sequences encoded a novel potential PTP (stomach cancer-associated PTP, SAP-1). The full length (3.9 kilobases) of the SAP-1 cDNA was further isolated from the KATO-III cell cDNA library and the WiDr cell cDNA library. The predicted amino acid sequence of the SAP-1 cDNA showed that mature SAP-1 consisted of 1093 amino acids and a transmembrane-type PTP, which possessed a single PTP-conserved domain in the cytoplasmic region. The extracellular region of SAP-1 consisted of eight fibronectin type III-like structure repeats and contained multiple N-glycosylation sites. These data suggest that SAP-1 is structurally similar to HPTP beta and that SAP-1 and HPTP beta represent a subfamily of transmembrane-type PTPs. SAP-1 was mainly expressed in brain and liver and at a lower level in heart and stomach as a 4.2-kilobase mRNA, but it was not detected in pancreas or colon. In contrast, among cancer cell lines tested, SAP-1 was highly expressed in pancreatic and colorectal cancer cells. The bacterially expressed SAP-1 fusion protein had tyrosine-specific phosphatase activity. Immunoblotting with anti-SAP-1 antibody showed that SAP-1 is a 200-kDa protein. In addition, transient transfection of SAP-1 cDNA to COS cells resulted in the predominant expression of a 200-kDa protein recognized by anti-SAP-1 antibody. SAP-1 is mapped to chromosome 19 region q13.4 and might be related to carcinoembryonic antigen mapped to 19q13.2.

Amino Acid Sequence↗

ACAT inhibitors as antiatherosclerotic agents: compounds and mechanisms.

Atherosclerosis is a major death cause in western industrialized countries. A diagnosing system, medical prevention, and treatment of atherosclerosis is not sufficient so far. A direct acting antiatherosclerotic agent is eagerly waited. ACAT inhibitor approach could provide such an agent. In the formation of atherosclerosis, cholesteryl esters, which are the lipids which accumulate in atheromatous plaques by an aid of macrophages and smooth muscle cells, forming foam cells, may play an important role. ACAT enzyme is responsible for the acylation of cholesterol to cholesteryl esters, a transformation which can be essential in not only cholesteryl esters accumulation at arterial walls but also the absorption of cholesterol in the intestine and the excretion of cholesterol in the liver. From these points, ACAT inhibitors might work against atherosclerosis in three different ways: first, cholesteryl ester accumulation inhibition at arterial walls could be a direct antiatherosclerotic effect; second, cholesterol absorption inhibition at the intestine; and third, cholesterol excretion acceleration at the liver, while the later two effects would result in a reduction of blood cholesterol level--a major risk factor of atherosclerosis. Taking account of this discussion, the ACAT inhibitors would be potent antiatherosclerotic agents. Medicinal research has been contributing full strength to produce an ultimate compound. These efforts should provide a drug which will be useful to patients.

Arteriosclerosis↗

Fas-mediated apoptosis in primary cultured mouse hepatocytes.

The Fas antigen is a member of the tumor necrosis factor/nerve growth factor receptor family and is expressed in tissues such as the thymus, liver, and ovary. Agonistic anti-Fas antibodies have cytolytic activity against cell lines expressing the Fas antigen. In this study, we show that anti-Fas antibody can induce the death of mouse hepatocytes in primary culture. Cell death via apoptosis was evidenced by the fact that the dying cells displayed DNA fragmentation, extensive surface bleb formation, and chromatin condensation. Anti-Fas antibody alone induced apoptosis in less than 20% of the cultured hepatocytes, whereas all cells were killed within 24 h by anti-Fas antibody in the presence of actinomycin D, cycloheximide, or protein kinase C (PKC) inhibitors such as H-7 and HA1004. These results indicate that the Fas antigen expressed in mouse hepatocytes functionally transduces the apoptotic signal and suggest that cultured mouse hepatocytes express protective proteins against apoptosis and that phosphorylation by PKC is also involved in protection of the hepatocytes from Fas-mediated apoptosis.

Animals↗

Hormonal control of response to and secretion of sex attractants in Japanese newts.

Hormonal control of sexual chemoattraction in the newt, Cynops pyrrhogaster, was investigated by a water preference test. Sexually inert newts injected with prolactin (PRL) and human chorionic gonadotropin (HCG) in combination preferred the water in which newts of the opposite sex had been kept, whereas saline-injected specimens did not. This indicates that PRL and HCG enhance the response of the newts to attractant(s) secreted by the opposite sex. The water in which PRL plus HCG-treated newts had been kept attracted the opposite sex more intensely than the water in which PRL-, HCG-, or saline-injected newts had been kept. In castrated males, PRL plus testosterone propionate (TP), and in ovariectomized females, PRL plus estradiol induced the secretion of substance(s) that attracted newts of the opposite sex. Removal of the abdominal gland of the cloaca in the male or the oviduct in the female attenuated the attracting activity of the water in which they were kept. Involvement of PRL and gonadal steroids in the secretion of sex attractants by the male abdominal gland and female oviduct was suggested.

Animals↗

Effect of maternal antibody on IgA antibody response in nasopharyngeal secretion in infants and children during primary respiratory syncytial virus infection.

The IgA antibody response to respiratory syncytial virus (RSV) was determined in nasopharyngeal secretions (NPS) of 22 infants and children infected with RSV group A strains, employing an ELISA. The antibody activity observed during the convalescent phase against whole virus, fusion glycoprotein (F) and large glycoprotein (G) was examined in young infants (under 6 months) and compared with that of older individuals (6 to 16 months). Both groups showed similar degrees of IgA antibody activity to whole virus in NPS; however, older individuals showed a significantly higher activity of IgA F antibody than that of IgA G antibody in the NPS. On the other hand, in the NPS of young infants, IgA F antibody was somewhat suppressed and IgA G antibody activity predominated over that of IgA F. Pre-existing (maternal) serum IgG anti-RSV F antibody activity was higher than that of antibody to G. A significant reverse correlation was observed between the activity of pre-existing serum IgG F antibody and NPS IgA F antibody in the convalescent phase after primary infection with RSV. These observations suggest that maternally derived RSV IgG antibody, which contains abundant anti-F activity, may suppress the development of IgA F antibody response at infection sites in the respiratory tract in young infants during primary RSV infection. These changes may be related to the severity of acute infection and longer convalescence often observed in young infants during RSV infection.

Aging↗

Hyperthermic isolated limb perfusion with intra-arterial administration of carboplatin and/or interferon-beta for the treatment of malignant melanoma of the leg.

Our experiences of hyperthermic isolated limb perfusion with administration of carboplatin, interferon-beta or a combination of both are reported. Administration of high doses of these reagents was well tolerated by patients with melanoma without severe complications after the treatment. A total of 8 patients underwent this therapeutic modality. Remarkable clinical improvement was seen in the first patient, who was in Stage III at the time of the perfusion. Histopathological findings indicated severe damage to the melanoma cells after the operation. Prophylactic hyperthermic perfusion was performed in 6 other patients with Stage II-III melanoma of the lower limb. None of them have shown any signs of recurrence 1-10 months later. The activities of natural killer cells or T lymphocytes appeared to be increased when the perfusion was carried out with concomitant administration of both carboplatin and interferon-beta. These results suggest that hyperthermic isolated limb perfusion with carboplatin and/or interferon beta administration is effective in patients with advanced stage melanoma.

Adult↗

Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. There have been several clinical reports of acute myocardial infarctions occurring in young male athletes abusing anabolic steroids. The effects of treatment of male Guinea pigs with testosterone on the responses to U46619, a TXA2 receptor agonist, in the isolated perfused heart were determined. The maximum pressor responses of the isolated perfused Guinea pig heart to U46619 were significantly (P < 0.05) greater in the Guinea pigs treated with testosterone compared to the controls. These results indicate that testosterone can enhance coronary artery vascular reactivity to TXA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Improvement of quality-of-life following resective surgery for temporal lobe epilepsy: results of patient and family assessments.

In order to evaluate the quality-of-life (QOL) of epilepsy surgery patients, we surveyed patients' degree of life satisfaction and their families' degree of satisfaction with patient's status in a range of domains both pre- and post-operatively. Of 100 patient-family sets of surveys that were mailed out, 93 were completed and returned from patients and 91 from their families. All patients surveyed had temporal lobe epilepsy and had been followed for longer than 2 years after resective surgery. Patients and their families rated overall QOL as having markedly improved following surgery. However, they rated social domains of QOL, including role activities, financial status, and social and family relationships as having improved relatively little. Despite freedom from seizures, a few patients' families were dissatisfied with the patients' post-operative status, primarily for psychosocial reasons. Patients operated on at a later age reported little gains in life satisfaction following surgery. This study supports the conclusion that surgical intervention should occur before patients are subjected to the psychological conflicts and social handicaps associated with chronic intractable epilepsy.

Adaptation, Psychological↗

Effects of ZCR-2060 on allergic airway inflammation and cell activation in guinea-pigs.

The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg-1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10(-6)-10(-4) M) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10(-6)-10(-4) M). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.

Animals↗

Respiratory syncytial virus group-specific antibody response in nasopharyngeal secretions from infants and children after primary infection.

Respiratory syncytial virus (RSV) group-specific immunoglobulin A (IgA) and IgG enzyme-linked immunosorbent assay antibody and neutralizing antibody responses were determined for nasopharyngeal secretions (NPS) from 27 infants and children (6 to 18 months of age) undergoing primary infection with RSV group A or B strain. IgA and IgG antibody responses against RSV envelope glycoproteins (fusion [F] and large [G] glycoprotein) in NPS were also analyzed. Most subjects examined developed moderate levels of NPS IgA and IgG antibodies and neutralizing antibody activity to both group A and B strains in convalescent phase; however, the levels of antibodies to homologous strains were significantly higher than to the heterologous strains. Patients infected with group A developed antibodies in both F and G glycoproteins of A2 strains (group A). Patients infected with group B developed levels of antibody activity to F glycoprotein of A2 strain similar to those of patients infected with group A. However, these subjects developed little or no antibody response to G glycoprotein of A2 strain. These data suggest that the IgA and IgG antibody responses to G glycoprotein in the respiratory tract are group specific. It is suggested that lack of antibody response to the G glycoprotein of the heterologous group in the respiratory tract may determine the outcome of reinfection with other RSV strains.

Antibodies, Viral↗

Structure of cell wall mannan of Candida kefyr IFO 0586.

We conducted a structural analysis of the antigenic cell wall mannoprotein (mannan) isolated from Candida kefyr (formerly Candida pseudotropicalis) IFO 0586. The result of two-dimensional homonuclear Hartmann-Hahn analysis of this mannan indicates that the molecule is constructed from alpha-1,2- and alpha-1,6-linked mannopyranose residues. Upon alkali treatment (beta-elimination reaction), this mannan released two alpha-1,2-linked mannooligosaccharides, biose and triose. The structure of the alkali-stable mannan (outer chain) moiety was investigated by acetolysis. The structures of the resultant oligosaccharides, biose and triose, from the outer chain moiety were found to be the same as those of the alkali-released ones. Further, the treatment of the parent mannan with an Arthrobacter GJM-1 exo-alpha-mannosidase gave a linear mannan consisting solely of alpha-1,6-linked mannopyranose residues. These results indicate that the mannan forms the long backbone of the alpha-1,6 linkage, with a large number of short alpha-1,2-linked oligomannosyl side chains forming a comblike structure. Moreover, we investigated the serological properties of this mannan by performing an inhibition assay of a slide agglutination reaction with mannooligosaccharides and polyclonal factor sera (Candida Check; Iatron). The result indicates that the factor 1 serum preferentially recognizes the alpha-1,2-linked oligomannosyl side chains in this mannan. On the other hand, the fact that the mannan does not contain an antigenic determinant(s) corresponding to factor 8 suggests that the epitope(s) of this factor resides in other molecules on the cell surface of this strain.

Candida↗

Structures of cell wall mannans of pathogenic Candida tropicalis IFO 0199 and IFO 1647 yeast strains.

We conducted a structural analysis of the cell wall mannans isolated from two Candida tropicalis strains, IFO 0199 and IFO 1647, exhibiting strong agglutinabilities against anti-Candida factor sera 5 and 6. The products released from these mannans by acid treatment were identified as the oligosaccharides, from biose to pentaose, consisting solely of beta-1,2-linked mannopyranose units corresponding to common epitopes of Candida albicans serotypes A and B (factor 5). Mild acetolysis of acid- and alkali-treated mannans produced large amounts of hexaose and heptaose, Man rho beta 1-2Man rho beta 1-2Man rho alpha 1-2Man rho alpha 1-2Man rho alpha 1-2Man and Man rho beta 1-2Man rho beta 1-2Man rho beta 1-2Man rho alpha 1-2 Man rho alpha 1-2Man, corresponding to the C. albicans serotype A-specific epitopes (factor 6). However, the homologous pentaose, Man rho beta 1-2Man rho alpha 1-2 Man, was not generated by this procedure. The oligosaccharides (biose to hexaose) obtained from the mannans by conventional acetolysis were composed exclusively of alpha-1,2-linked mannopyranose units. Therefore, the mannans of C. tropicalis IFO 0199 and IFO 1647 do not have the alpha-1,3-linked mannopyranose units previously observed in the mannans of C. albicans and Candida stellatoidea. The results of this study and previous findings indicate that the similarity of the antigenicities of three Candida species, C. albicans serotype A, C. stellatoidea type II, and C. tropicalis, reside in the beta-1,2 and alpha-1,2 linkages containing oligomannosyl side chain (factor 6) in the cell wall mannan.

Agglutination Tests↗

Testosterone increases thromboxane A2 receptor density and responsiveness in rat aortas and platelets.

Testosterone has been implicated as a risk factor for cardiovascular diseases. Thromboxane (Tx) A2 is an important pathophysiological mediator for thrombotic vascular diseases. This study investigated the effects of testosterone on platelet and vascular TxA2 receptors. Male rats were treated with either testosterone cypionate for 2 wk, sham operated, castrated, or castrated and treated with testosterone cypionate for 2 wk. Treatment of intact rats with testosterone significantly (P < 0.001) increased the TxA2 receptor density in platelets from 25.4 +/- 3.2 to 42.9 +/- 4.2 fmol/mg protein (P < 0.005, n = 17) and in aortic membranes from 48.7 +/- 1.7 to 86.1 +/- 6.1 fmol/mg protein, n = 9. The threshold concentration of the TxA2 mimetic, [1S-(1 alpha, 2 beta(5Z),3 alpha(1E,3R*)4 alpha)]-7-[3-(3-hydroxy-4- (4'-iodophenoxy)-1-butenyl)-7-oxabicyclo[2.21]heptan-2-yl]-5 -heptenoic acid (I-BOP), to induce platelet aggregation was significantly (P < 0.01) decreased from 0.45 +/- 0.16 nM, n = 7, in the control rats to 0.07 +/- 0.01 nM, n = 13, in the testosterone-treated rats. Testosterone treatment resulted in a significantly (P < 0.05) greater maximum aortic contractile response to the TxA2 mimetic, U-46619, compared with intact rats. Castration resulted in a significant (P < 0.01) decrease in aortic TxA2 receptor density from 51.7 +/- 3.7 to 27.3 +/- 5.3 fmol/mg protein, which was significantly reversed by testosterone treatment (89.2 +/- 7.1 fmol/mg protein; n = 4). Castration resulted in a significantly (P < 0.05) lower maximal aortic contractile response that was reversed by treatment with testosterone. Castration did not significantly change platelet TxA2 receptor density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibitory effects of sialic acid- or N-acetylglucosamine-specific lectins on histamine release induced by compound 48/80, bradykinin and a polyethylenimine in rat peritoneal mast cells.

The effects of seven lectins with various sugar-specificities on histamine release from rat peritoneal mast cells induced by non-immunologic stimuli were studied. The non-immunologic stimuli used were three basic secretagogues, compound 48/80, bradykinin and PEI6 (polyethylenimine with a molecular weight of 600). In this study, we observed inhibition of the histamine release by Macckia amurensis mitogen and Solanum tuberosum agglutinin (100 micrograms/ml at 37 degrees C for 10 min), which are specific for sialic acid-alpha 2,3-N-acetyl galactosamine (Sia alpha 2,3GalNAc) and N-acetyl glucosamine (GlcNAc) oligomers, respectively. The effects of Phytolacca americana mitogen and Sambucus sieboldiana agglutinin were different. Three lectins specific for mucin type oligosaccharides inhibited the histamine release induced by compound 48/80 but not that induced by bradykinin or PEI6. Since bradykinin and PEI6 additively enhanced the histamine release induced by compound 48/80, they partially shared the same signalling pathways. Glycoproteins with bisecting GlcNAc and Sia residues, as described previously (Jpn. J. Pharmacol. 57, 79-90, 1991), seemed to be one of the action sites for compound 48/80, bradykinin and PEI6. In addition to the direct activation of the pertussis toxin-sensitive G proteins, we propose another mechanism of non-immunologic stimuli via specific glycoproteins on rat peritoneal mast cells. The apparent sugar residues involved were asparagine-linked oligosaccharides with Sia (especially Sia alpha 2,3Gal), GlcNAc oligomers and/or bisecting GlcNAc.

Acetylglucosamine↗

Datura stramonium agglutinin released histamine from rat peritoneal mast cells that was inhibited by pertussis toxin, haptenic sugar and N-acetylglucosamine-specific lectins: involvement of glycoproteins with N-acetylglucosamine residues.

The N-acetyl glucosamine (GlcNAc)-specific lectin Datura stramonium agglutinin (DSA) rapidly and sugar-specifically released histamine from rat peritoneal mast cells, and pertussis toxin (IAP) inhibited it, suggesting that DSA activated mast cells via an IAP-sensitive G protein pathway. The additive effects of DSA and basic secretagogues such as compound 48/80 that activate IAP-sensitive G protein directly suggest that they shared the same mechanism of action including involvement of the IAP-sensitive G protein. Using lectin-blotting, blots of the corresponding glycoproteins detected by DSA diminished by haptenic sugar or pretreatment of the cells with N-glycosidase F, suggesting that the binding of DSA was responsible for the mast cell activation. The other GlcNAc-specific lectins such as Phytolacca americana mitogen, Solanum tuberosum agglutinin and wheat germ agglutinin (WGA) inhibited the histamine release induced by DSA, suggesting that these lectins were antagonists, but DSA was an agonist. Sialic acid-specific Macckia amurensis mitogen (MAM) inhibited the histamine release, and neuraminidase-treatment decreased mast cell activation induced by DSA. At least four mast cell glycoproteins that have affinity to DSA, WGA and MAM and are sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be binding sites coupled to histamine release including the IAP-sensitive G protein pathway. DSA is a useful tool for studying signal transduction of mast cells including the involvement of the IAP-sensitive G protein.

Acetylglucosamine↗