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Biomedical subjects

K Itakura

Publications and source records attributed to K Itakura.

At least 55 records · Page 3Linked to original sources
PubMed1992

[Biwasaki Leprosarium--a century of dedication].

Biwasaki Leprosarium, or Biwasaki Tairo Hospital, was established by Father Jean Marie Corre, a French Priest, in 1898. He was born in Brittany France, 1850. After being ordained to the priesthood, he came to Nagasaki, Kyushu, in 1876. He was just twenty six years old. He was greatly moved at the sight of the Hansenites and other sick people around the Honmyoji Temple in Kumamoto, Kyushu, which is one of the well-known temples in Japan. They were making a bare living by the charitable contributions of the pilgrims who visited the Temple, in those days. Fr. Corre moved from Nagasaki to Kumamoto. First, he built a church in Tetori, Kumamoto, and rented a house near the Honmyoji and began to look after the needs of the Hansenites. In 1896, he bought a large lot at Biwasaki in the Shimasaki area, Kumamoto, where is not far from Honmyoji. He remodeled some houses into the so-called sanatorium and started to accommodate those suffering from Hansen's disease. At the outset, he had the cooperation of nuns and church workers to look after the patients' needs. Furthermore, Fr. Corre appealed to Rome for the help and/or support in 1898 in order to expand this kind of project, and five nuns were dispatched in the following year from the Franciscan Missionaries of Mary in Rome. And since then the sisters have devoted themselves assiduously and faithfully to help the Hansenites as far as possible and they are still doing this. However, in 1963, a fire broke out from one of toilets and made a clear sweep of the whole building.(ABSTRACT TRUNCATED AT 250 WORDS)

Christianity↗
PubMed1991

Platelet factor 4 selectively inhibits binding of TGF-beta 1 to the type I TGF-beta 1 receptor.

A low molecular weight inhibitor of TGF-beta 1 binding was detected in partially purified human platelet extracts by using Hep 3B hepatoma cells in the binding assays. The inhibitory protein was purified to homogeneity and was identified as platelet factor 4 on the basis of its amino acid sequence. TGF-beta 1 binding to Hep 3B cells was almost completely inhibited by 100 nM concentrations of platelet factor 4, but TGF-beta 1 binding to NRK 49F fibroblasts was inhibited only slightly. Affinity cross-linking experiments revealed that these differences in the inhibition of TGF-beta 1 binding by platelet factor 4 were due to differences in the complements of TGF-beta 1 binding proteins present on these two cell types. In Hep 3B cells the majority of bound TGF-beta 1 was cross-linked to a complex which had an apparent molecular weight of 70 kDa. TGF-beta 1 binding to this protein was the most sensitive to inhibition by platelet factor 4. Based on its size and TGF-beta 1 binding properties, we believe this protein is the type I TGF-beta 1 receptor. Hep 3B cells also had a high-affinity TGF-beta 1 binding protein which appeared as an 80 kDa complex, and which we believe to be the type II TGF-beta 1 receptor. TGF-beta 1 binding to this protein was not inhibited by platelet factor 4. TGF-beta 1 was also cross-linked to complexes of higher molecular weights in Hep 3B cells, but it was not clear whether any of them represented the type III TGF-beta 1 receptor. In NRK 49F cells, the majority of bound TGF-beta 1 was cross-linked to a high molecular weight complex which probably represented the type III TGF-beta 1 receptor. NRK 49F cells also had type I TGF-beta 1 receptors and platelet factor 4 inhibited binding to these receptors in the NRK cells. Since the type I receptor contributed only a small percentage of total TGF-beta 1 binding, however, the overall effects of platelet factor 4 on TGF-beta 1 binding to NRK 49F cells were negligible. We were unable to demonstrate specific or saturable binding of platelet factor 4 to Hep 3B cells using either direct binding or affinity cross-linking assays. Thus, it is not clear whether platelet factor 4 inhibits TGF-beta 1 binding by competition for binding to the type I receptor. Modest concentrations of TGF-beta 1 reduced the adherence of Hep 3B cells to tissue culture dishes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Expression of rat microsomal epoxide hydrolase gene during liver chemical carcinogenesis.

A complementary DNA library was constructed from mRNA of rat liver induced by an initiating dose of a chemical carcinogen, diethylnitrosamine. Using a differential hybridization technique, a complementary DNA clone which is induced more than 10-fold by an acute single dose of diethylnitrosamine was identified. The DNA sequence of this clone was matched with rat microsomal epoxide hydrolase. This gene may be of great interest, since it was found to be highly expressed in neoplastic nodules and primary hepatocellular carcinomas induced by different carcinogenic regimes. The inducible high level expression of this gene becomes constitutive during the process of hepatocarcinogenesis. The gene was also found to be inducibly expressed during partial hepatectomy in a similar manner as a multidrug-resistant gene (mdr-I). No change in the transcriptional initiation site was observed in the gene expression between induced and uninduced rat livers. The 5' upstream region of the gene was characterized and some potential controlling elements for gene regulation, such as Sp-1, AP-2, and Hepatitis B virus enhancer, were found. Based on our own and published results, we hypothesize that the altered expression of this xenobiotic enzyme in nodules and cancer cells could be a result of constitutive internal stimuli which might be associated with cell growth.

Animals↗
PubMed1990

Formation of diastereoisomeric 3a-hydroxypyrroloindoles from a tryptophan residue analog mediated by iron (II)-EDTA and L-ascorbate.

Oxygenation of a tryptophan residue analog by ascorbate in the presence of catalytic amounts of iron(II) and ethylenediaminetetraacetic acid (EDTA) has been studied. Under physiological conditions, reaction of the tryptophan derivative (N-t-butoxycarbonyl-L-tryptophan) with Fe(II)-EDTA and ascorbate resulted mainly in the oxygenation of the indole moiety of the substrate. In this reaction, cis and trans diastereoisomeric alcohols 3a-hydroxy-1-t-butoxycarbonyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3- b]indoles have been successfully identified in the metal-catalyzed free radical oxidation of indole compounds. Hydroxylation at C-5 and C-6 and a ring opening reaction between C-2 and C-3 have also been confirmed. The reaction of Fe(II)-EDTA/ascorbate with the tryptophan derivative was apparently nonselective with regard to position and was significantly suppressed by the hydroxyl radical scavengers (mannitol and dimethylsulfoxide), suggesting the participation of the hydroxyl radical as the actual oxidizing species.

Ascorbic Acid↗
PubMed1990

Determination of a platelet activating factor antagonist (CV-3988): methodology and clinical application.

A high-performance liquid chromatographic method was developed for determination of the platelet activating factor antagonist CV-3988 in human plasma and urine. After development of a column extraction procedure without an internal standard, a more satisfactory organic extraction procedure was set up with amiodarone as internal standard. Linearity of the calibration curves was found in the range 0.0625-10 micrograms/ml CV-3988. Reproducibility was higher than 10% for the column extraction and lower than 10% for the organic extraction procedure. Recovery of CV-3988 from plasma averaged 81.7% for the column procedure and 40% for the organic extraction. Urine samples could be extracted only by the organic extraction procedure. The organic extraction procedure was applied to the determination of CV-3988 in plasma and urine samples after intravenous administration to normal volunteers.

Chromatography, High Pressure Liquid↗
PubMed1990

Identification of sequences responsible for positive and negative regulation by E1A in the promoter of H-2Kbm1 class I MHC gene.

The mechanism of transcriptional regulation of the H-2Kbm1 major histocompatibility complex (MHC) class I gene by adenovirus type 12 E1A (Ad12-E1A) was studied in transfected rat embryonal fibroblasts. Results of long-term expression of the chloramphenicol acetyl transferase (CAT) gene placed under the control of the 5'-flanking region of the mouse MHC class I gene. H-2Kbm1, and the results of nuclear run-on transcription assays, yield evidence for both positive and negative regulation of H-2Kbm1 by E1A gene product. Deletion studies in the H-2Kbm1 promoter region revealed that a proximal 58 bp upstream sequence (-194 to -136, relative to the cap site) and a distal 316 bp sequence (-1837 to -1521) respectively contribute to positive and negative regulation mediated by the E1A gene product. Both regulatory elements of MHC class I gene promoter region are responsible for the differential expression of the H-2Kbm1 gene in Ad12 transformed cells. A nuclear factor binding to the negative element has been detected only in extracts derived from cells expressing Ad12-E1A.

Adenovirus Early Proteins↗
PubMed1990

Application of long synthetic oligonucleotides for gene analysis: effect of probe length and stringency conditions on hybridization specificity.

Two different lengths of long unique synthetic oligonucleotide probes (37- and 48-mers) specific for human major histocompatibility complex (MHC) class II beta genes were synthesized. These oligonucleotides were utilized to examine factors influencing hybridization specificity. Both probe length and stringency of washing conditions were found to be crucial factors for sequence-specific hybridization.

Alleles↗
PubMed1989

TGF beta gene transcription in normal and neoplastic liver growth.

TGF beta is a potent, nontoxic inhibitor of mitogen-induced DNA synthesis in primary cultures of adult rat hepatocytes. Using a cDNA probe, we investigated TGF beta gene expression in quiescent, regenerating, and neoplastic liver, and several hepatoma lines by Northern gel analysis. We found that regenerating liver had increased TGF beta gene transcripts beginning at about 8 h, with a broad peak of 48-120 h and return to normal after 9 days. Separation of the regenerating liver into its constituent cell types, followed by RNA extraction and reprobing, revealed that increased TGF beta gene transcripts were confined to the enriched endothelial-cell population and not the hepatocytes. Increased hepatic TGF beta expression was also found in fetal liver and in rats immediately after birth. Elevated TGF beta mRNA levels were also found in primary cultures of oval cells and an established bile ductular cell line, as well as in carcinogen-altered liver epithelial cell lines. Transcripts were undetectable in normal human liver but were abundant in the human hepatoma lines Hep G2, Hep 3B, PLC/PRF/5, and SK-Hep-1. Elevated levels were also found in the normal rat liver-derived lines BRL-3A and clone 9 and the H4IIE rat hepatoma, but not in the HTC, MH1C1, and MH7777 rat hepatomas. The hepatocarcinogen diethylnitrosamine induced high transcript levels after single injections in a time- and dose-dependent manner. These results suggest that the liver may be a paracrine organ with respect to TGF beta gene expression, which can be induced by carcinogens and by growth stimulation.

Animals↗
PubMed1989

Disposition of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate, in the perfused rat liver.

The disposition of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), was studied in the single-pass perfused rat liver in order to clarify the effect of physico-chemical properties, such as molecular weight and electric charge, on the hepatic uptake of MMC-D. Six types of MMC-D were used: both cationic MMC-D (MMC-Dcat) and anionic MMC-D (MMC-Dan) conjugated with dextran with molecular weights of 10,000, 70,000, and 500,000. Outflow curves were analyzed using statistical moment theory. Remarkable hepatic uptake of MMC-Dcat was observed and the uptake amount increased with an increase in molecular weight (i.e., approximately 80% of the dose was taken up by the liver during a single passage of the conjugate with a molecular weight of 500,000). Intrinsic clearance (CLint,i) and apparent distribution volume (Vi) also increased as the molecular weight increased. On the other hand, almost 100% of applied MMC-Dan was recovered in the outflow regardless of molecular weight, with almost the same moment parameters as those of the vascular reference substance (VRS), 131I-labeled human serum albumin (HSA). In a repeated application, the uptake of MMC-Dcat decreased in a stepwise manner, suggesting a saturation in the hepatic uptake of MMC-Dcat, while the uptake of MMC-Dan was unchanged. The MMC-Dcat pretreatment also affected the uptake of Evans blue (EB) bound to bovine serum albumin (BSA). These results demonstrate that molecular weight and electric charge determine the hepatic disposition of macromolecular prodrugs.

Animals↗
PubMed1988

Characterization of rat skeletal muscle sarcolemmal insulin receptors and a sarcolemmal insulin binding inhibitor.

When insulin receptors of rat skeletal muscle sarcolemmal vesicles were solubilized with Triton X-100, the specific binding of 125I-labeled insulin increased by more than 10-fold over that seen in the intact vesicles. Partial purification of the skeletal muscle insulin receptors on wheat germ agglutinin affinity columns increased the total insulin binding activity by 7-fold and reduced the Kd for insulin binding from 1.92 to 0.20 nM, suggesting that an inhibitor of insulin binding was removed by this purification step. This was confirmed when the unbound fractions of the affinity column were dialyzed and reconstituted with the insulin receptors. The inhibitory activity in the sarcolemmal extract could not be accounted for by the presence of Triton X-100. The skeletal muscle inhibitor was more potent in inhibiting insulin binding to skeletal muscle insulin receptors than to liver or adipose receptors. The inhibitor was very effective in inhibiting insulin binding to wheat germ agglutinin-purified IM-9 receptors, but had negligible effects on insulin binding to intact IM-9 cells. The properties of the alpha and beta subunits of the skeletal muscle insulin receptors appear to be the same as those of insulin receptors of other tissues: cross-linking of 125I-labeled insulin to the receptor revealed a band of 130,000 daltons, and insulin stimulated the phosphorylation of bands of 90,000 and 95,000 daltons in the receptor preparation. The skeletal muscle insulin binding inhibitor elutes from molecular sieves in a major 160,000-dalton peak and minor 75,000-dalton peak. The binding inhibitor is not inactivated by heat, by mercaptoethanol, or by trypsin, pepsin, or proteinase K. Collectively, these data suggest that the inhibitor may be a small molecule that aggregates with itself, with larger proteins, or with detergent micelles.

Adipose Tissue↗
PubMed1988

Efficacy of a liposome preparation of anti-inflammatory steroid as an ocular drug-delivery system.

The efficacy of a liposome preparation on ocular steroid availability was investigated by both tracer studies and investigation of in vivo steroid uptake by the cornea. Dexamethasone and its ester derivatives were used as model drugs and aqueous suspensions of each served as control preparations. The liposome preparation containing dexamethasone valerate provided the highest ocular drug levels among the examined preparations. In the case of dexamethasone or dexamethasone palmitate, the liposomal form provided a lower drug level in comparison with the suspension. High esterase activity for dexamethasone valerate was observed in the corneal homogenate supernatant, and most of the steroid taken up after instillation of dexamethasone valerate was metabolized to free alcohol. The corneal dexamethasone level was almost proportional to the concentration of free dexamethasone valerate in the liposome preparation. Only the addition of stearylamine (SA) to the liposomal membrane had an added extra effect on the corneal absorption of dexamethasone valerate.

Animals↗
PubMed1988

Assessment of ocular irritability of liposome preparations.

Ocular irritability of neutral or positively charged liposomes were assessed by the Draize test, histological examination and the rabbit blinking test. The mean total score (MTS) of the Draize test showed a slight increase immediately following instillation of liposome preparations. However, it did not exceed the "practically nonirritating level", and the MTS rapidly became less than the "nonirritating level". No corneal histological alteration was observed by optical microscopy following 9 instillations of each liposome preparation. Although the neutral liposome preparation failed to increase the rabbit blinking count, the positively charged liposome preparation did so to a significant degree. The neutral liposome preparation was confirmed not to give rise to ocular irritation. However, the positively charged liposome preparation may cause pain or unpleasantness following instillation.

Animals↗
PubMed1988

Effects of Tween 80 and liposomes on the corneal permeability of anti-inflammatory steroids.

The effects of Tween 80 and liposomes on the corneal permeability of dexamethasone (DM) and dexamethasone valerate (DV) were investigated in vitro. A model based on diffusion theory could successfully be applied to analyzing the process by which DM penetrates the cornea from DM preparations. The penetration rate increased according to the concentration of free DM. Although the penetration rate was increased by pretreatment with Tween 80, it was not affected by pretreatment with liposomes. The steroid that penetrated through the cornea from DV preparations had been metabolized to DM. The transfer of DM across the cornea from DV preparations tended to slow down to some extent during the penetration process. Diffusion models were not applicable to this process, in contrast to the corneal penetration of DM from DM preparations. When liposome preparations of DV were applied, the penetration rate of DM across the cornea depended the concentration of free DV in these preparations. When DV aqueous preparations containing different concentrations of Tween 80 were applied, the penetration rate increased as the concentration of the surfactant was increased, even though the concentration of free DV in the suspensions was kept constant. These results suggest that the corneal permeability of anti-inflammatory steroids is not affected by liposomes, but is accelerated by Tween 80.

Animals↗