Search PubMed⌕ Search

Biomedical subjects

T Koide

Publications and source records attributed to T Koide.

At least 163 records · Page 9Linked to original sources

Antioxidant, gallic acid, induces apoptosis in HL-60RG cells.

Gallic acid, a naturally occurring plant phenol with antioxidative activity, was found to induce cell death in promyelocytic leukemia HL-60RG cells, although many antioxidants are well known to protect the cell from oxidative stress. Morphological and biochemical studies indicated that the gallic acid-induced cell death is apoptosis. Flow cytometric analysis revealed that the apoptosis was not triggered at a specific phase of the cell cycle and that 2 h exposure of gallic acid to HL-60RG cells was enough to induce apoptosis. The inhibitory assay suggested that gallic acid-induced cell death was mediated by reactive oxygen species such as hydrogen peroxide, superoxide anion in addition to Ca2+ ion, calmodulin-dependent enzymes. Structure-activity analysis suggests that gallic acid induces apoptosis in HL-60RG cells, depending on its distinctive feature derived from the structure but not on its antioxidative activity.

Animals↗

ATP- and antizyme-dependent endoproteolysis of ornithine decarboxylase to oligopeptides by the 26 S proteasome.

Previously we reported that ornithine decarboxylase (ODC) is degraded ATP-dependently by the 26 S proteasome in the presence of antizyme (AZ), an ODC inhibitor (Murakami, Y., Matsufuji, S., Kameji, T., Hayashi, S., Igarashi, K., Tamura, T., Tanaka, K., and Ichihara, A. (1992) Nature 360, 597-599). Here we examined the cleavage of ODC by the 26 S proteasome. When ODC purified from ODC-overproducing cells was incubated with the 26 S proteasome and with AZ fused with maltose-binding protein (MBP) in the presence of ATP, ODC was degraded specifically without appreciable breakdown of MBP-AZ. The major degradation products of ODC, which were separated by high performance liquid chromatography on a reverse-phase column, were identified by N-terminal amino acid sequencing. The 26 S proteasome generated a variety of short peptides of 5-11 amino acid residues derived from regions throughout the ODC sequence. No detectable amounts of free amino acid residues were produced, indicating endoproteolytic degradation of ODC by the 26 S proteasome. Their major sites for cleavage of ODC by the 26 S proteasome were on the carboxyl sides of neutral/hydrophobic amino acid residues, but a few were on those of acidic or basic amino acid residues. These results demonstrate that the 26 S proteasome causes exhaustive endoproteolysis of the naturally occurring short-lived protein ODC in a multicatalytic and ATP-dependent manner.

Adenosine Triphosphate↗

Effects of protein kinase C activators on Na, K-ATPase activity in rat brain microvessels.

In order to study the possible role of C kinase (PKC) on sodium pump of cerebral vessels, we used diacylglycerol (diC8: sn-1,2-dioctanoylglycerol) and phorbol esters (PMA: phorbol 12-myristate 13-acetate; PDA: phorbol 12,13-diacetate; 4 alpha-P: 4-alpha phorbol) as PKC activators, and examined their effects on Na,K-ATPase activity in rat brain microvessels (MVs). Rats were divided into non-treated (control; n = 9), four-vessel occlusion (4VO; 30-30 minutes ischemia and recirculation, n = 5), and middle cerebral artery occlusion (MCAO, n = 3) groups. MVs were passed through nylon meshes and were obtained by ultracentrifuge at 58000 g. Na,K-ATPase activity in MVs was determined by the phosphomolybdate method. DiC8 enhanced Na,K-ATPase activity at 10(-4) M in the control group, the 4VO group and the contralateral hemispheres of the MCAO group (139% +/- 0.06, 135% +/- 0.2, 133% +/- 0.18, mean +/- SE, p < 0.05, p < 0.01, Wilcoxon rank sum) respectively, but had no effects on MVs in the ipsilateral hemispheres of MCAO group (74% +/- 0.04). This activation by diC8 was inhibited by PKC inhibitors, staurosporine (3 x 10(8) M) and H7 (10(-6) M) in the control MVs. By contrast, PMA suppressed Na, K-ATPase at 10(-5) M in the control group (-25% +/- 0.07), but it tended to activate Na,K-ATPase activity in the ipsilateral hemispheres of the MCAO groups (33% +/- 0.09). PDA and 4 alpha-P did not have any consistent effects at the concentration examined. The cause of difference between the effects of diC8 and PMA is unclear at present, but it may stem from the mode of lipid-membrane interaction in these agents and the difference in the condition of cells as well.

Animals↗

Prognosis after hepatic resection in patients with hepatocellular carcinoma, estimated on the basis of the morphometric indices.

To determine whether the morphometric indices of hepatocellular carcinoma (HCC) correlated with the prognoses, the microscopic morphometric values for 84 HCC cases treated by hepatic resection were studied using an image analyzer in relation to the survival rate and the gross classification. The mean survival time (MST) was 58 months in cases with a nucleocytoplasmic area ratio (N/C) of less than 0.28; this was significantly longer than the 38-month MST in cases with an N/C of more than 0.28 (P < 0.05). In stage III disease, the MST for cases with an N/C of less than 0.28 was 63 months, which was significantly longer than the MST of 13 months for cases with an N/C of more than 0.28. After relatively noncurative hepatic resection, the MST for cases with an N/C of less than 0.28 was 49 months, and this was significantly longer than the MST of 8 months for cases with an N/C of more than 0.28. The MST was 71 months for cases with a coefficient of variance of the nuclear form factor (NCV) of less than 5.5%, which was significantly longer than the MST of 33 months for cases with an NCV of more than 5.5% (P < 0.05). In stage III disease, the MST was 69 months for cases with an NCV of less than 5.5%, and this was significantly longer than the MST of 29 months for cases with an NCV of more than 5.5% (P < 0.05). In cases with an N/C of less than 0.28, 18% had vascular invasion and 38% had intrahepatic metastases, whereas in those with an N/C of more than 0.28, 62% had vascular invasion and 67% had intrahepatic metastases (P < 0.01, P < 0.05). Based on the results of these morphometric studies on HCC cases treated by hepatic resection, N/C and NCV may be useful as prognostic factors.

Carcinoma, Hepatocellular↗

Insulin-binding sites in the mouse deferent duct.

In vivo light microscopic autoradiography was used to demonstrate the presence of specific insulin-binding sites in the mouse deferent duct three min after intravenous injection of 125I-insulin with or without excess of unlabeled insulin. The studies showed high specific insulin binding in the endothelial cells of capillaries and certain fibroblasts of the lamina propria. In the epithelium, although the tall columnar cells were free of specific insulin binding, the basal cells had relatively high specific insulin binding. Because the deferent duct has been considered to exert certain effects on sperms, the presence of high specific insulin binding at these sites may provide further support for this concept.

Animals↗

Hepatitis C virus serotype II responds more favorably to interferon-alpha therapy.

To determine whether serological typing of hepatitis C virus correlated with the response to interferon-alpha therapy, hepatitis C virus serotypes were determined by subtype-specific antibody to NS4 polypeptide by enzyme-linked immunosorbent assay in 55 Japanese patients with chronic active hepatitis C who subsequently received recombinant interferon-alpha 2a therapy. Response to interferon-alpha was defined as complete and sustained (n = 12), complete response followed by relapse (n = 26), and no response (n = 17). There was no difference in the clinical biochemical parameters between these patients groups. However, a higher proportion (50.0%) of patients with hepatitis C virus serotype II showed complete and sustained response to interferon-alpha, compared to serotype I (11.1%, p < 0.01). These data indicate that this simple hepatitis C virus serotyping assay is a useful predictor of response to interferon-alpha therapy in patients with chronic hepatitis C virus infection.

Adult↗

Amino acid sequence of porcine antithrombin III.

Antithrombin III (ATIII) is a member of the serine protease inhibitor (serpin) family. As a step towards a better understanding of the heparin-binding mechanism of mammalian ATIIIs, the amino acid sequence of porcine ATIII was established by sequence analysis of the peptides derived from cyanogen bromide cleavage and enzymatic digestion with lysyl endopeptidase, V8 protease, and trypsin. Porcine ATIII was found to consist of 431 amino acid residues, with a calculated molecular weight of 48,930 without carbohydrate. Its molecular weight with 16.4% carbohydrate was estimated as 56,955, which is in good agreement with the value determined by SDS-PAGE. Porcine ATIII showed high sequence similarity to other mammalian ATIIIs, including the reactive site, heparin-binding basic amino acid residues, and disulfide bonds. The most notable feature of porcine ATIII was that it possesses only three carbohydrate chains, at Asn136, 156, and 193, whereas other mammalian ATIIIs have four, additional chain being at Asn97; this is replaced by Asp in porcine ATIII. In the case of human ATIII, the chains are at Asn96, 135, 155, and 192. The heparin-binding affinities of human and porcine ATIIIs were compared using an immobilized heparin column. Porcine ATIII eluted from the column with a peak at an NaCl concentration of 924 mM while human ATIII eluted at 838 mM NaCl. Neuraminidase treatment of each ATIII enhanced the heparin-affinity to the same extent. These results suggest that in spite of the high degree of amino acid sequence identity between porcine and human ATIIIs (91% identical), porcine ATIII has a higher heparin-binding affinity than human, because it lacks a carbohydrate chain at Asp97.

Amino Acid Sequence↗

Topical treatment of resistant warts with glutaraldehyde.

UNLABELLED: Therapy with glutaraldehyde (GA) was used to treat twenty-five patients with selectively resistant warts. The patients were categorized as having one or more of the following conditions: 1) the location of the warts was either periungual, palmar or plantar, 2) the age of the patient was five years or younger, 3) the number of warts was two or more. RESULTS: Eighteen (72%) out of twenty-five cases were cured, and the other seven (28%) were not. The individual cure rates of the three conditions above were 80%, 60%, and 68.5% respectively. Pigmentary changes occurred immediately after the initial topical application of glutaraldehyde, and the surface of the verruca hardened. Soon afterwards some debris began to drop off of the verruca tissue little by little, and final healing was completed by less than twelve weeks without disagreeable marks. This therapy was found to be extremely useful, not only because the cure rate was high, but the following advantages were also noted: 1) no pain or pruritus, 2) no evidence of scarring or permanent pigmentary change, 3) good penetration in any location, 4) no need for special instruments or reagents except the solution, and 5) no special technique required (possible home treatment). This therapy is superior to cryotherapy (CT) in that it is useful for warts on any location, regardless of the number of lesions, and it is good for young children, although the cure rates for CT and GA are almost equal.

Administration, Topical↗

Infantile granulomatous urachal abscess with acute localized peritonitis and appendicitis.

Infected urachal remnants in early childhood are occasionally seen. However, intraperitoneal penetration of an infected urachal remnant, resulting in acute peritonitis, is rare. We report a case of infantile granulomatous urachal abscess extending into the peritoneum and appendix. The diagnosis and treatment of urachal abscess in childhood are discussed.

Abscess↗

Light microscopical immunohistochemical study on parathyroid adenoma in primary hyperparathyroidism.

Fifteen adenomatous parathyroid glands obtained from 15 patients with primary hyperparathyroidism were examined both pathologically and immunohistochemically and connected with the clinical data for each patient. Four consecutive sections of the largest section surface of each resected adenomatous parathyroid gland were utilized for 4 kinds of stains, that is, hematoxylin-eosin, Grimelius and the immunohistochemical stains for parathyroid hormone (PTH) and chromogranin A. The results were as follows: (1) The large adenomatous parathyroid glands showed strong reactions to PTH as well as chromogranin A and Grimelius. On the other hand, the parathyroid adenoma obtained from a 9-year-old boy with hypercalcemic crisis showed almost no stain-positive cells for both PTH and chromogranin A. It is assumed that the former phenomenon reflects a substantial storage of secretory granules, while the latter reflects exhaustion of these granules. (2) The normal parathyroid cells in the neoplastic parathyroid glands generally showed stronger reactions to PTH and chromogranin A than neoplastic parathyroid cells. This suggests that normal cells in the neoplastic parathyroid glands may have their release of PTH rather than its synthesis suppressed, and also might support the hypothesis of some authors that chromogranin A or SP-I might contribute to stabilization of PTH or the secretory vesicle.

Adenoma↗

Paratesticular myxoma.

We report a case of paratesticular myxoma. These tumors, which arise from mesenchymal tissues, occur in a variety of sites, the most common being subcutaneous tissues and skeletal muscles but they rarely have been reported to originate in the paratesticular region. The differential diagnosis of other mesenchymal neoplasms of the paratesticular area is discussed.

Diagnosis, Differential↗

Molecular parameters for the anti-human immunodeficiency virus activity of T22 ([Tyr5,12, Lys7]-polyphemusin II).

T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human immunodeficiency virus (HIV) activity and exert its effects on a virus-cell fusion process. In the present study, the all-D enantiomer of T22 and its related compounds were synthesized to examine the molecular parameters required for the interaction of T22 with membrane components of cells or viruses in order to exert this anti-HIV activity. The anti-HIV activity of these analogs was investigated in comparison with their membrane permeability with aspect to large unilamellar vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV activity compared with T22, whereas they both showed the same membrane permeability. No positive correlation between anti-HIV activity and membrane permeability was observed. These results suggest that the anti-HIV activity of T22 is mediated through the interaction with chiral component(s) of the cell or virus.

Amino Acid Sequence↗

Protective effect of FR115427 against ischemic hippocampal damage in gerbils.

Excitatory amino acids and their receptors have been postulated to be involved in mediating ischemic neuronal damage. We occluded the bilateral carotid arteries for 5 min in gerbils to examine the effect of FR115427, a novel N-methyl-D-aspartate (NMDA) antagonist, on ischemic neuronal damage. FR115427 prevented hippocampal CA1 cell damage at a dose of 10 mg/kg and reduced spontaneous locomotor hyperactivity in gerbils after the development of ischemia at a dose of 32 mg/kg. The effective doses of MK801 were 3.2 mg/kg for preventing hippocampal CA1 cell damage and 1 mg/kg for reducing spontaneous locomotor hyperactivity. Moreover, we monitored the changes in body temperature of ischemic gerbils for 24 hr. The body temperature of ischemic gerbils significantly increased 1 hr after reperfusion. The pretreatment with FR115427 or MK801 prevented the hyperthermia provoked 1 hr after reperfusion in ischemic gerbils. In addition, the hypothermia was developed in gerbils treated with MK801 24 hr after reperfusion. However, FR115427 did not show hypothermia at any time. These results indicate that FR115427 has a protective effect against ischemic hippocampal CA1 cell damage after systemic administration, and this protective effect appears to be due to anti-NMDA activity.

Animals↗

Fluorine uptake and crystallinity of dentin treated with glass ionomer cement containing tannin-fluoride preparation.

We investigated the fluorine uptake in various layers of bovine dentin treated with glass ionomer cement (GIC) where a tannin-fluoride preparation (HY agent) was incorporated in the cement powder at ratios of 0% (HY0), 1.5% (HY1.5), 5% (HY5), and 10% (HY10) by weight. The crystallinity of the dentin treated with the HY0 and HY10 cements was also investigated. The higher the ratio of incorporated HY agent, the deeper the penetration of fluorine in the dentin, and the greater the amount of fluorine taken up that bonded with the apatite. Compared with total fluorine uptake, more time is needed for fluorine to form a stable bond with apatite. It is also suggested that the crystallinity of dentin is enhanced when exposed to GIC containing the HY agent.

Animals↗

A narrow therapeutical window of a nitric oxide synthase inhibitor against transient ischemic brain injury.

N omega-nitro-L-arginine (0.3-10 mg/kg), a nitric oxide (NO) synthase inhibitor, was administered i.p. to gerbils subjected to 10 min of carotid artery occlusion seven times at 5 min, 3, 6, 24, 48, 72 and 96 h after recirculation. Histopathological examination of the brains obtained 6 days after reflow disclosed that N omega-nitro-L-arginine possesses an ability to mitigate neuronal necrosis in the CA1 subfield of the hippocampus with an optimal dosage of 3 mg/kg. These results strongly suggest that NO synthase activation is at least partly involved in the pathogenetic cellular mechanisms underlying selective neuronal necrosis following cerebral ischemia.

Amino Acid Oxidoreductases↗

Heparin sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization.

The nature of the soluble stone matrix and its possible role in urinary stone formation was studied. For this purpose we performed two-dimensional cellulose acetate membrane electrophoresis of the glycosaminoglycans (GAGs) which were contained in the soluble stone matrix, substances adsorbed onto calcium oxalate crystals in vitro (crystal surface binding substances, CSBS) and urinary macromolecules (UMMs). The main GAG in the soluble stone matrix and CSBS was found to be heparan sulfate, whereas the UMMs contained various GAGs usually seen in urine. An inhibition assay showed the soluble stone matrix to have the strongest inhibitory activity among these macromolecular substances when inhibitory activity was expressed in terms of uronic acid concentration. It is suggested that the main GAG in the soluble stone matrix consists of heparan sulfate, which has a strong inhibitory activity on calcium oxalate crystal growth and aggregation and constitutes part of the CSBS.

Adult↗