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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 523 records · Page 29Linked to original sources

MS-444, a new inhibitor of myosin light chain kinase from Micromonospora sp. KY7123.

A novel compound MS-444 was isolated from the culture broth of a bacterial strain KY7123. The strain was identified as Micromonospora sp. from its morphological and cultural characteristics. The compound inhibited the activity of purified smooth muscle myosin light chain kinase with an IC50 value of 10 microM. The production, isolation, physico-chemical properties and biological activities of MS-444 were described in this paper.

Animals↗

Relation between markers for viral hepatitis and clinical features of Japanese patients with hepatocellular carcinoma: possible role of alcohol in promoting carcinogenesis.

To assess the relationship between hepatitis virus markers and the clinical features of hepatocellular carcinoma (HCC), we measured markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in 88 Japanese patients with HCC. Twelve (14%) patients were HBsAg-positive and 67 (76%) were anti-HCV-positive (both c100-3 and c11/c7). HCV-RNA was detected in 8 (38%) of the 21 anti-HCV-negative patients by PCR, so that 75 patients (85%) were infected with HCV. Of the HBsAg-negative patients infected with HCV with no history of blood transfusion, the mean age of the alcoholics (consumption > 80 g ethanol daily for at least 10 years) was lower than that of the non-alcoholics (60 years vs. 65 years, P < 0.05). Among the HBsAg-negative and anti-HCV (or HCV-RNA)-positive patients with a history of blood transfusion, the mean interval between the time of blood transfusion and the diagnosis of HCC in the alcoholics was shorter (21 years) than that in the nonalcoholics (27 years), but the difference was not statistically significant. We conclude that infection by both HCV and HBV may play a role in the development of HCC, and that alcohol consumption may promote carcinogenesis.

Adult↗

[Effects of chronic ethanol intake on sugar chain structures of IgG in mice].

IgG is an N-glycosylated glycoprotein, and is secreted from B lymphocyte. Transferrin is also an N-glycosylated glycoprotein secreted from hepatic cell. We have investigated, by lectin-ELISA method, reactivities of sugar chain structures, which are Gal (beta 1, 4) GlcNAc, Fuc (alpha 1, 3 or 6) Gal, NeuAc (alpha 2, 6) Gal, galactose, poly mannoses and NeuAc (alpha 2, 3) Gal, in IgG or transferrin of ddY mice that were given ethanol solution for 3 weeks. In the investigation, we have found that the all reactivities of sugar chain structures in IgG and transferrin remarkably reduced. We have also found that Lewis-X (Gal (beta 1, 4) GlcNAc (3, 1 alpha Fuc)-), which is functional sugar chain structure in the IgG, was markedly reduced with dose-dependent manner. These findings indicate that ethanol decreases activities of glycotransferases in some cells which produce and secrete N-glycosylated glycoproteins. It has been reported that human erythrocyte has also N-glycosylated glycoproteins in the membrane, and its sialic acid and galactose are reduced after chronic ethanol intake. The past and present findings indicate that sugar chain structures of N-glycosylated glycoproteins in both serum and cell membranes are reduced after chronic ethanol intake. Though functions of sugar chain structures of N-glycosylated glycoproteins remain unclear, if functional structures like Lewis-X exist in N-glycosylated glycoproteins, the change of the sugar chain structures may have some relations to diseases occurring after chronic ethanol intake.

Alcoholism↗

[Severe hyperbilirubinemia after cisplatin-based chemotherapy].

Cisplatin is the most effective and widely used anti-cancer drug for ovarian cancer. We report 2 cases with severe hyperbilirubinemia after cisplatin-based chemotherapy. Case 1 was a 67-year-old woman with stage IV ovarian cancer. After operation, she had 2 courses of chemotherapy consisting of cisplatin (90 mg) and cyclophosphamide (550 mg). The regimen was changed to low-dose consecutive cisplatin (10 mg/day, day 1-day 5) because of her ileus and poor performance status. After 2 courses of cisplatin alone, her total bilirubin was elevated to 19.1 mg/dl. She died of respiratory distress. At autopsy, chronic cholangiolitis with intrahepatic bile stasis were noted. Case 2 was a 60-year-old woman with stage IIIc ovarian cancer. After operation she was treated with carboplatin (383 mg/day, day 1) and cisplatin (102 mg/day, day 3). One month after completing the first chemotherapy, her bilirubin elevated to 20.5 mg/dl. It took 3 months to normalize the serum bilirubin with steroid administration. During the second course using the same regimen as in the first course, the bilirubin elevated again. Cisplatin was suspected to be the drug inducing her hyperbilirubinemia. She was consecutively treated with carboplatin alone and the bilirubin did not elevate. Both cases had blood transfusion and intravenous hyperalimentation. It is difficult to disregard the effect of other drugs and therapy. In case 2, her bilirubin elevated repeatedly after cisplatin administration. Cisplatin may thus be the drug which induces the liver dysfunction.

Aged↗

Purification and characterization of a vegetative lytic enzyme responsible for liberation of daughter cells during the proliferation of Chlamydomonas reinhardtii.

A vegetative lytic enzyme (VLE) of Chlamydomonas reinhardtii mediates digestion of the cell walls of mother cells (sporangia) to allow release of daughter cells after miotic cell division in the vegetative cell cycle. This enzyme is secreted into the culture medium concurrently with the appearance of daughter cells in synchronized cultures. Using an assay that monitors digestion of the mother cell wall, we purified VLE by ion-exchange and gel-filtration chromatography from the medium of synchronized cultures. The purified enzyme was a basic glycoprotein with an apparent molecular mass of 120 kDa on gel filtration and 130 kDa on SDS-PAGE. Thus, VLE appeared to behave as a monomer. The enzyme acted specifically on the mother cell wall and was unable to digest the cell walls derived from single vegetative cells. The enzymatic activity was inhibited by PMSF, p-APMSF, TLCK, HgCl2, iodoacetate, EGTA, EDTA and 1, 10-phenanthroline. VLE cleaved several synthetic model peptides on the carboxyl side of a Lys or Arg residue, indicating that it is a protease that acts on protein in the mother cell wall in vivo to release the daughter cells.

Amino Acid Sequence↗

[CT-guided stereotactic operation for cerebellar abscess by the transtentorial hiatus approach: a case report].

We reported a case of cerebellar vermian abscess, well managed by CT-guided stereotactic aspiration and drainage via the transtentorial hiatus route. A 69-year-old man was admitted to our hospital because of acute deterioration of bronchiectasis. About one month later, he complained of headache and gait unsteadiness. CT scan revealed a multilocular abscess in the cerebellar vermis. Although conservative therapy with antibiotics was applied, the symptoms deteriorated and the lesion continued to grow. Aspiration and drainage were therefore performed for the main lesion by CT-guided stereotactic surgery via the transtentorial hiatus route. This was completed without complications. The postoperative course was good and the lesion had disappeared when enhanced CT was carried out about 2 months after the operation. We consider this stereotactic transtentorial hiatus operation to be an effective treatment for patients such as the present one with a superior vermian lesion and who is at risk due to a poor respiratory condition.

Aged↗

[Retinopathy and perinatal outcome in diabetic pregnancy].

Sixty patients with diabetes mellitus (DM) antedated pregnancy were enrolled; seven had proliferative retinopathy, 13 had simple retinopathy, and 40 were intact. Diet and/or insulin was prescribed to adjust their glucose control at fasting to < 100 mg/dl, as well as at 2 hours postprandial to < 120 mg/dl. Glycohemoglobin (Hemoglobin A1c) levels ranged between 5.4% and 6.4% in the third trimester in three groups. Incidences of pregnancy complications (toxemia, hydramnios, urinary tract infection and cesarean section) and neonatal complications (low Apgar score, hypoglycemia, jaundice, polycythemia, respiratory distress syndrome and anomaly) did not differ significantly with the grade of retinopathy. Compared with the intact group, the duration of DM was significantly longer in the retinopathy groups and the incidence of fetal distress was significantly higher in the proliferative retinopathy group. In ten of 60 patients (16.7%) the grade of retinopathy progressed during pregnancy. In four patients photocoagulation was performed for neovascularization, and proved to be effective. There was a tendency for those whose retinopathy progressed to the proliferative stage during pregnancy to have larger decreases in glycohemoglobin and for their retinopathy to worsen after delivery. With tight maternal glucose control and intensive fetal surveillance, we obtained good perinatal outcome in pregnancies with diabetic retinopathy, as compared to diabetic pregnancy without diabetic microangiopathy. Careful and frequent monitoring of retinal changes should be required during pregnancy and the postpartum period.

Adult↗

Endothelin ETA and ETB receptors facilitating parasympathetic neurotransmission in the rabbit trachea.

In the isolated rabbit trachea, electrical field stimulation (EFS) induced contraction that was inhibited by atropine or tetrodotoxin. Nonselective endothelin (ETA/ETB) receptor agonist, ET-1, relatively selective ETB receptor agonist, ET-3, and selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c (STXc), augmented the EFS-induced contraction by 2- to 3-fold with similar EC50 (0.4-1 nM). These agonists also showed direct contractile effect in the trachea. However, the threshold concentration of ET-1 (3 fM) to augment the electrical field stimulation-induced contraction was 100,000 times lower than that needed to directly stimulate smooth muscle. In contrast, these agonists did not augment the contraction induced by stimulation of muscarinic receptor by carbachol. An ETA receptor antagonist, BQ-123, was almost ineffective in antagonizing the effects of ET-1, ET-3 and STXc although if weakly antagonized the effects of IRL 1620. An ETB receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620 without changing the effect of STXc and antagonized the effects of only lower concentrations of ET-1. In the trachea in which the ETB receptor was desensitized by strong activation, IRL 1620 and STXc were ineffective and ET-3 showed only small effect at higher concentrations. In contrast, the ETB desensitization inhibited the effects of only lower concentrations of ET-1. The effect of ET-1 in the ETB-desensitized trachea was partially, but not fully, antagonized by BQ-123. A potent ETB antagonist, BQ-788, showed similar effects to the ETB desensitization. These results suggest that ET-1 enhances nervous acetylcholine release by simultaneously activating the ET-1-selective ETA receptor and the isopeptide-nonselective ETB receptor (ETB1 subtype that is sensitive to both RES-701-1 and BQ-788 and the ETB2 subtype that is sensitive only to BQ-788).

Acetylcholine↗

[The perinatal risk factors of periventricular leukomalacia (PVL) in premature infants].

Periventricular leukomalacia (PVL) has recently been recognized as an important risk factor in neurological impairment of the premature infant. We studied 29 PVL cases concerning perinatal risk factors retrospectively comparing them with a non-PVL matched control group. Variable decelerations were more frequently observed with statistical significance in the PVL group in the intrapartum period. There was no significant difference between the two groups in the appearance of late deceleration. A lower incidence of RDS, a higher incidence of low Apgar score, a longer period of ventilation and oxygen inhalation and a more persistent presence of apneic spells were documented in the PVL group with statistical significance. Our study suggests the significance of variable deceleration as a risk factor in the occurrence of PVL in premature infants as well as other previously documented risk factors.

Apgar Score↗

Capillaries with fenestrae in the rat soleus muscle after experimental limb immobilization.

Capillaries in the rat soleus muscle were examined by electron microscopy 4 weeks after limb immobilization and compared to those in untreated muscle. Immobilized muscles showed degenerative changes such as dissolution of sarcomeres, vacuoles, and a small increase in connective tissues, including collagen fibers, around muscle fibers. Eight percent of the capillaries in these muscles were found to have fenestrae. The non-nuclear portions of the endothelial cells were extremely thin and were perforated by several fenestrae which were bridged by a single-layered diaphragm. The untreated muscles contained only continuous capillaries. These findings suggest that the occurrence of capillaries with fenestrae in the immobilized muscle may be a result of structural changes in the muscle.

Animals↗

Effects of a novel N-methyl-D-aspartate (NMDA) receptor antagonist, 3,3'-dimethyl-3,4,3',4'-tetrahydro-6,8,6',8'-tetramethoxy-[10,10' -bi-2- oxanthracene]-4,9,9'-(1H,1'H)-triol 4-acetate (ES-242-1), on NMDA-induced increases of intracellular Ca2+ concentration in cultured hippocampal neurons.

The effects of a novel N-methyl-D-aspartate (NMDA) receptor antagonist, ES-242-1 (3,3'-dimethyl-3,4,3',4'-tetrahydro-6,8,6',8'-tetramethoxy-[10,10' - bi-2-oxanthracene]-4,9,9'-(1H,1'H)-triol 4-acetate), on NMDA-induced increases of intracellular Ca2+ concentration in cultured hippocampal neurons were examined. ES-242-1 selectively blocked the NMDA-induced increase in intracellular free Ca2+ concentration ([Ca2+]i), but not the [Ca2+]i increase stimulated by quisqualate or kainate. The effect of ES-242-1 appeared in the slow development of a blockade of [Ca2+]i (half blocking time: 90 sec) when 100 microM NMDA was applied with 10 microM ES-242-1, whereas the initial [Ca2+]i rise was attenuated by 10 microM ES-242-1 when the latter was applied with a lower concentration of NMDA (10 microM). This is consistent with a previous observation that ES-242-1 binds to both the transmitter recognition site and the channel domain. The blockade by ES-242-1 was reversed by washing. In contrast, the blockade by MK-801 was not relieved easily by washing. These results suggest that ES-242-1 blocks the NMDA-induced [Ca2+]i increase due to a combination of two well-recognized mechanisms, which are different from that of MK-801, at the NMDA receptor.

Animals↗

Transposition of Tnr1 in rice genomes to 5'-PuTAPy-3' sites, duplicating the TA sequence.

Tnr1 is a repetitive sequence in rice with several features characteristic of a transposable DNA element. Its copy number was estimated to be about 3500 per haploid genome by slot-blot hybridization. We have isolated six members of Tnr1 located at different loci by PCR (polymerase chain reaction) and determined their nucleotide sequences. The Tnr1 elements were similar in size and highly homologous (about 85%) to the Tnr1 sequence identified first in the Waxy gene in Oryza glaberrima. A consensus sequence of 235 bp could be derived from the nucleotide sequences of all the Tnr1 members. The consensus sequence showed that base substitutions occurred frequently in Tnr1 by transition, and that Tnr1 has terminal inverted repeat sequences of 75 bp. Almost all the chromosomal sequences that flank the Tnr1 members were 5'-PuTA-3' and 5'-TAPy-3', indicating that Tnr1 transposed to 5'-PuTAPy-3' sites, duplicating the TA sequence. PCR-amplified fragments from some rice species did not contain the Tnr1 members at corresponding loci. Comparison of nucleotide sequences of the fragments with or without a Tnr1 member confirmed preferential transposition of Tnr1 to 5'-PuTAPy-3' sites, duplicating the TA sequence. One amplified sequence suggested that imprecise excision had occurred to remove a DNA segment containing a Tnr1 member and its neighboring sequences at the Waxy locus of rice species with genome types other than AA. We also present data that may suggest that Tnr1 is a defective form of an autonomous transposable element.

Adenine Nucleotides↗

Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) and cytotoxic agents in mice.

The antitumor effect of the novel angiogenesis inhibitor O-(Chloroacetyl-carbamoyl) fumagillol, TNP-470 (TNP, s.c.), a synthetic analogue of fumagillin, was studied in combination with cytotoxic agents--mitomycin C (MMC, i.p.), Adriamycin (i.p.), cisplatin (i.p.), and 5-fluorouracil (i.p.), using B16BL6 melanoma (B16 M) and Lewis lung carcinoma in C57BL/6 mice. When the mice were treated on days 3 and 5, addition of MMC (total dose, 5 mg/kg) or 5-fluorouracil (140 mg/kg) to TNP (150 mg/kg) maximally reduced s.c. B16 M volume from 60 to 15% or from 68 to 40% of control, respectively, and addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. Lewis lung carcinoma volume from 75 to 62% of control (P < 0.02, compared to the corresponding single drug treatments). During treatment on days 3, 5, 7, 9, and 11, addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. B16 M volume from 43 to 6% of control and reduced the number of pulmonary metastasis of i.v. B16 M from 26 to 5% of control (P < 0.001). For established tumors (> 5 mm in maximal diameter), addition of MMC (12-14 mg/kg), Adriamycin (15-17.5 mg/kg), or cisplatin (4 mg/kg, by one shot) to TNP (120-140 mg/kg) with a 6-7 fractionated dosing schedule reduced s.c. B16 M volume from 50 to 20, 24, or 31% of control and reduced s.c. Lewis lung carcinoma volume from 52 to 34, 27, or 34% of control, respectively (P < 0.02). The effect of combination therapy was additive and dose-dependent, and the earlier fractionated dosing schedule exerted more enhanced antitumor effects. TNP reduced the body weight by approximately 10% of control at maximum, but this toxicity was reversible and was not affected by addition of the cytotoxic agents. The results suggest that the combination of angiogenesis inhibitor TNP and standard cytotoxic agents can be a beneficial addition to the treatment of solid tumors.

Animals↗

Endothelin ETB receptor antagonist, RES-701-1: effects on isolated blood vessels and small intestine.

RES-701-1 (cyclic (Gly1-Asp9)(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe- Phe-Asn-Tyr-Tyr-Trp)), a peptide isolated from Streptomyces sp., has been reported to inhibit the endothelin ETB receptor. We examined the effects of this peptide on the blood vessels and the small intestine. In isolated rat aorta without endothelium, 10 microM RES-701-1 did not affect the resting tone, nor did it attenuate the contractions induced by endothelin-1, endothelin-3 or norepinephrine. In the aorta with endothelium, 3 microM RES-701-1 shifted the concentration-response curves for the contractile effects of endothelin-1 and endothelin-3 to the left. Removal of endothelium showed a similar effect to 3 microM RES-701-1. In the norepinephrine-stimulated aorta, endothelium-dependent relaxation induced by endothelin-3 was antagonized by 0.3-10 microM RES-701-1 in a concentration-dependent manner. In the guinea pig ileum stimulated by carbachol, endothelin-3 induced a transient relaxation followed by sustained relaxation. RES-101-1 (3 microM) selectively inhibited the transient relaxation. Since it has been shown that the contractile effects of endothelins in the aorta are mediated by the endothelin ETA receptor whereas the endothelium-dependent relaxation and the ileal relaxation are mediated by the endothelin ETB receptor, it is suggested that RES-701-1 is a selective antagonist against the endothelin ETB receptor.

Amino Acid Sequence↗

The tissue distribution of mRNAs for the PACE4 isoforms, kexin-like processing protease: PACE4C and PACE4D mRNAs are major transcripts among PACE4 isoforms.

In the previous study [Biochem. Biophys. Res. Commun. (1994) 200, 943-950] we identified two novel cDNAs (PACE4C and PACE4D) encoding human Kexin-like protease, the PACE4 isoforms. In this study, we examined the expression of PACE4 isoform transcripts in various rat tissues. To detect very low levels and to distinguish among these isoforms, we used the reverse transcriptase-polymerase chain reaction (RT-PCR). PACE4C and PACE4D transcripts were detected in most tissues like PACE4A transcripts, however their tissue distribution profiles and the extent of expression differ. PACE4C and PACE4D transcripts are expressed at a much higher level than PACE4A transcript. These results indicate that PACE4C and PACE4D mRNAs are major transcripts of PACE4.

Animals↗