Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 19 recordsLinked to original sources

PubMed1992

Inhibitory effect of an intracellular glutathione on delta 12-prostaglandin J2-induced protein syntheses in porcine aortic endothelial cells.

Delta 12-Prostaglandin (PG) J2 caused porcine aortic endothelial cells to synthesize a 31,000-dalton heme oxygenase and a 67,000-dalton protein (p67). Treatment of the cells with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted intracellular GSH, and enhanced the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2. In contrast, treatment with GSH increased the intracellular GSH level and reduced the induction. There was a reciprocal relationship between the level of intracellular GSH, and that of the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2. An increase in the intracellular GSH level caused an increase in the ethyl acetate-unextractable form of delta 12-PGJ2 in the cytosol, but suppressed the accumulation of delta 12-PGJ2 in the nuclei. Furthermore, GSH strongly inhibited the in vitro binding of delta 12-PGJ2 to isolated nuclei, which is N-ethylmaleimide sensitive. Moreover, the induction of heme oxygenase and p67 syntheses by the thiol-reactive agents arsenite and diethylmaleate was also inhibited by GSH treatment and enhanced by BSO treatment. These results demonstrate that intracellular GSH suppresses delta 12-PGJ2-induced heme oxygenase and p67 syntheses by inhibiting the binding of delta 12-PGJ2 to nuclei.

Animals↗

PubMed1992

Neurotransmitters in the vestibular commissural system of the cat.

The present study focused on the transmitters that control the vestibular neural activity and, in particular, that regulate commissural inhibition. Extracellular spikes of a single vestibular neuron were recorded in decerebrate cats. The seven barrels of the electrode, with the exception of the center barrel, were filled with transmitter candidates and their specific antagonists, while the center barrel was filled with 2 M NaCl for extracellular recording. After isolation of a type 1 neuron, chemicals were iontophoretically applied to examine their effects on its activity. The results were as follows: (1) GABA and glycine markedly decreased spontaneous firing of the neurons, while serotonin did not affect their activity. (2) Bicuculline abolished the inhibitory effects of GABA on the neurons. (3) Strychine abolished the effects of glycine. (4) Commissural inhibition induced by electrical stimulation of the contralateral labyrinth was not abolished by strychine but was abolished by bicuculline. We conclude that (1) vestibular type 1 neurons are controlled by GABAergic and glycinergic but not serotoninergic neurons, and (2) commissural inhibition is activated by the GABAA receptor, but not by the GABAB receptor.

Animals↗

PubMed1992

Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription.

Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of urea cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of urea cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.

Aging↗

PubMed1992

Abnormal expression of urea cycle enzyme genes in juvenile visceral steatosis (jvs) mice.

Juvenile visceral steatosis (jvs) mice from the C3H-H-2 degrees strain have markedly low levels of all the hepatic urea cycle enzymes (Imamura et al. (1990) FEBS Lett. 260, 119-121). The steady state levels of messenger RNA for the four urea cycle enzymes examined and also for albumin and serine dehydratase were severely reduced in the liver. The levels of mRNA for other liver-specific enzymes including aldolase B and phospho enol pyruvate carboxykinase did not vary significantly from normal littermates. As for extrahepatic expression of the urea cycle enzymes, only argininosuccinate synthetase in the kidney was decreased. Nuclear run-on experiments showed reduced transcription of the corresponding genes, which mostly accounts for the low mRNA levels. Furthermore, the time-course of mRNA accumulation from 5 days of age showed that the developmental induction of hepatic carbamyl phosphate synthetase and argininosuccinate synthetase mRNAs was strongly suppressed. These results suggest that jvs affects not only the regulation of the tissue-specific expression of the urea cycle enzymes but also the regulation of their developmental induction.

Animals↗

PubMed1992

Linkage, but not gene order, of homologous loci, including alpha-L-iduronidase (Idua), is conserved in the Huntington disease region of the mouse and human genomes.

alpha-L-iduronidase (IDUA), which when deficient causes mucopolysaccharidosis type I, is located near the Huntington disease locus (HD) on human Chromosome (Chr) 4p16.3, approximately 10(6) base pairs (bp) from the telomere. As part of our continuing efforts to define a detailed comparative map for this chromosomal segment in mice and humans, we have used an interspecific backcross between C57BL/6J and an inbred strain derived from Mus spretus to map Idua, the mouse homolog of IDUA. We also mapped the mouse homolog of D4S115, an anonymous locus approximately 250 kb proximal to IDUA. As expected, both Idua and D4S115h are located on the proximal portion of mouse Chr 5 near homologs for other loci on human Chr 4p. Comparison of gene order in mice and humans demonstrates, however, that a chromosomal rearrangement within this conserved synteny has occurred since divergence of lineages leading to mice and humans.

Animals↗

PubMed1992

SPECT demonstration of splenosis.

Splenosis is defined as the heterotopic autotransplantation of splenic tissue. The main cause of splenosis is splenic rupture following abdominal trauma, in which fragments of splenic tissue are seeded throughout the peritoneal cavity. Demonstration of splenosis by scintigraphy or CT imaging has been reported, but there is no previous report of simultaneous demonstration by SPECT and CT imaging. Autotransplantation of splenic tissue in the abdominal cavity forms a solid tumor-like image on CT and is difficult to differentiate from other abdominal masses. In such cases, SPECT demonstration of splenosis is very important for identification of its exact site. A case report of splenosis is presented, in which simultaneous demonstration by SPECT and CT was performed. This was confirmed at laparotomy for gastrectomy.

Abdominal Neoplasms↗

PubMed1992

Dissecting aneurysm of the posterior cerebral artery treated with proximal ligation.

A rare case of a dissecting aneurysm of the P3 segment of the right posterior cerebral artery is presented that seems to have occurred in association with mild head injury. The patient was treated surgically because of repeated intramural hemorrhage and enlargement of the aneurysm. Proximal ligation produced thrombosis of the aneurysm without resulting in infarction in the region of the posterior cerebral artery. The mechanisms of the dissection, diagnosis, and treatment are briefly discussed.

Adult↗

PubMed1992

Induction of heme oxygenase by delta 12-prostaglandin J2 in porcine aortic endothelial cells.

delta 12-Prostaglandin (PG)J2 stimulated the synthesis of a 31,000-dalton protein (termed p31) and the induction of cellular heme oxygenase activity in porcine aortic endothelial cells. A good correlation was observed between the time courses and dose dependencies of the induction of p31 synthesis and that of heme oxygenase activity by delta 12-PGJ2. Hemin, a known inducer of heme oxygenase, also induced p31 synthesis as well as heme oxygenase activity in the cells. On two-dimensional gel electrophoresis, p31 induced by delta 12-PGJ2 exhibited an isoelectric point of 5.4, which coincided exactly with that induced by hemin. These results indicate that the p31 induced by delta 12-PGJ2 in porcine aortic endothelial cells is heme oxygenase.

Animals↗

PubMed1992

DNA damaging activity of cadmium in Leydig cells, a target cell population for cadmium carcinogenesis in the rat testis.

To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H2O2 to induce DNA single strand breakage was evaluated in testicular Leydig cells using a simple and rapid DNA precipitation method. Effects of Cd, Fe, Zn and Ca on the oxidant-induced DNA damage and effects of reduced glutathione (GSH) on the genotoxicity caused by the peroxide and/or Fe were also assessed. H2O2 induced strong DNA single strand breakage. Cd alone did not exhibit such a genotoxicity nor did it enhance the peroxide-induced DNA damage. Ca and Fe(II) potentiated the oxidant-induced DNA single strand breakage, while Zn partially protected cells from the oxidative damage of DNA caused by the peroxide. GSH attenuated single strand breaks of DNA brought about by H2O2 and/or Fe. These results suggest that the initiation of carcinogenesis in the rat testis by Cd is triggered by active oxygen species such as H2O2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidant-mediated initiation is clearly a complicated event accomplished by multiple factors.

Animals↗

PubMed1992

Urinary calculi associated with solvent abuse.

We describe 3 cases of urinary calculi that developed during the course of long-term solvent abuse. The patients regularly sniffed a lacquer thinner (major component toluene) or a cement (xylene and cyclohexane) for 2 to 6 years before the development of urolithiasis. The occurrence of proteinuria and hematuria was closely related to solvent sniffing in 2 of the 3 patients. Regular, long-term solvent abuse must be included in the causes of urolithiasis, particularly in juveniles and young adults.

Adult↗

PubMed1992

Role of oxidative stress in single-dose, cadmium-induced testicular cancer.

Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population.

Animals↗

PubMed1992

Effects of thromboxane synthase inhibition on tumor necrosis factor-induced lung injury in sheep.

To examine the role of thromboxane (Tx) A2 in the pathogenesis of acute lung injury caused by tumor necrosis factor alpha (TNF), we tested the effects of OKY-046, a selective thromboxane synthase inhibitor, on pulmonary hemodynamics, lung lymph balance, circulating leukocytes, arterial blood gas analysis, and TxA2 (as TxB2) and prostacyclin (as 6-keto-prostaglandin F1 alpha) levels in plasma and lung lymph after TNF infusion in awake sheep. Infusion of human recombinant TNF (3.5 micrograms/kg) into a chronically instrumented awake sheep caused a transient increase in pulmonary arterial pressure (Ppa). The Ppa peaked within 15 min of the start of TNF infusion from 23.3 +/- 1.1 (SE) cmH2O of baseline to 42.3 +/- 2.3 cmH2O and then decreased toward baseline. The pulmonary hypertension was accompanied by transient hypoxemia, peripheral leukopenia, and the increases in TxB2 in plasma and lung lymph. These changes were followed by an increase in flow of protein-rich lung lymph, consistent with an increase in pulmonary microvascular permeability. OKY-046 significantly prevented the rises of Ppa and TxB2 concentrations in plasma and lung lymph during early phase after TNF infusion. OKY-046, however, did not attenuate the increase of lung lymph flow, transient hypoxemia, and leukopenia. From these data, and by comparison with our previous studies of OKY-046-pretreated sheep during endotoxemia, we conclude that TxA2 has an important role of the increase in the early pulmonary hypertension, but it is not related to the early hypoxemia, leukopenia, and lung lymph balances in TNF-induced lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Bioavailability of morphine in rabbits after rectal administration of suppository containing controlled release morphine tablet.

Two kinds of sustained release morphine suppositories have been prepared; one is an oleaginous base suppository (MSC) containing a controlled release morphine tablet (MST: MS Contin), and the other is a hollow-type suppository (MSCH) containing MST and morphine powder packed in its hollow space. In vitro release tests and in vivo rectal absorption experiments in rabbits were performed. The profiles of morphine release from MST and MSC in vitro were similar, and revealed that suppository bases had no effect on the release profile of morphine from the preparation. Morphine release from MSCH was rapid in the early phase, and then enclosed morphine was slowly and continuously released from MST. Phamacokinetics of morphine from the suppository were compared with the orally administered MST, and it was found that there was no difference in the maximum plasma concentration (Cmax) and the peak time (Tmax) between MSC and MST, but the mean residence time (MRT) of MSC was approximately three times longer than that of MST, and the extent of bioavailability (BA) of MSC was significantly larger than that of MST (71.6 +/- 14.2% and 11.9 +/- 4.0%, respectively). Cmax can be altered arbitrarily by changing the morphine content in the hollow space of MSCH. As in the case of MSC, the plasma concentration of morphine from MSCH was maintained. It is concluded from the above results that MSC is a satisfactory sustained release morphine suppository for the treatment of cancer pain, administering it twice a day, and that MSCH is effective due to its fast analgesic effect and sustained release nature not only for cancer pain but also for surgical operations.

Administration, Rectal↗

PubMed1992

Effect of l-menthol on the permeation of indomethacin, mannitol and cortisone through excised hairless mouse skin.

The effect of l-menthol on the skin permeability of mannitol, cortisone or indomethacin was examined by an in vitro penetration technique with hairless mouse skin. The donor solution was prepared with phosphate buffered saline, ethanol:buffered saline (20:80, v/v) or ethanol:buffered saline (20:80, v/v) containing 1% (w/v) l-menthol. Although ethanol showed little enhancing effect, l-menthol in an aqueous ethanol vehicle at pH 7.4 increased the permeability coefficients of mannitol and indomethacin by about 100 times that of the control (an aqueous vehicle) and increased that of cortisone by about 10 times. l-Menthol, however, scarcely enhanced the penetration of indomethacin at pH 3.0, the majority of the species being in unionized form. These results suggested that the menthol-ethanol-aqueous system enhanced skin permeability through a direct effect on the polar and/or lipid pathways, while the thermodynamic activity of the penetrant molecule in the delivery vehicle might also influence the effectiveness of the penetration enhancer.

Administration, Cutaneous↗

PubMed1992

[Studies on the baths with crude drug: the effects of Senkyu extract as skin penetration enhancer].

The effects of Senkyu (Cnidii Rhizoma and Ligustici chuanxiong Rhizoma) on the drug skin penetration were studied to clarify its effectivity as the baths. Ether and methanol extracts, and some essential oils of Senkyu (i.e. ligustilide, neocnidilide and butylidenephthalide) enhanced remarkably the skin penetration of benzoic acid. Furthermore, an appreciable correlation between the enhancing ratio and the skin/donor partition coefficient of benzoic acid was observed. These facts suggest that the constituents of Senkyu influence the skin penetration by enhancing the partition coefficient.

Animals↗

PubMed1992

Ganglioneuroblastoma with disseminated bone marrow infiltration in an adult.

Ganglioneuroblastoma is an extremely rare neoplasm of adults. We present a case of adrenal ganglioneuroblastoma in a 47-year-old female with disseminated bone marrow involvement. Bone marrow involvement was the major manifestation which determined the mortality of this patient. This case suggests that the diagnosis of bone marrow involvement should be carefully considered even in adult-onset ganglioneuroblastoma.

Adrenal Gland Neoplasms↗

PubMed1992

[Successful local adoptive immunotherapy for pleuritis carcinomatosa due to renal cell cancer. A case report].

A 54-year-old woman who had undergone radical nephrectomy for renal cell cancer nine months before was admitted to our hospital because of difficulty in breathing. X-ray films of the chest showed massive pleural effusion on the left side and cytological examination of the effusion revealed malignant cells which may have originated from renal cell cancer. Intrapleural instillations of interleukin-2 and of tumor infiltrating lymphocytes isolated from the pleural effusion were performed. After the initiation of the treatment, the pleural effusion decreased and malignant cells disappeared from the pleural fluid. Partial response defined by the criteria provided by the Japan Lung Cancer Society was achieved. No serious side effects were observed. This would be a useful treatment for pleuritis carcinomatosa by renal cell cancer.

Carcinoma, Renal Cell↗

PubMed1992

[A case of superior vena cava syndrome due to extensive venous thrombosis of an idiopathic nature].

A 37-year-old man was admitted with facial edema and right arm swelling. Venography, computed tomography and magnetic resonance imaging showed massive organizing thrombi in the superior vena cava and bilateral internal jugular as well as subclavian veins, and showed no mass lesions occluding the veins in the mediastinum. Angioscopy demonstrated a white thrombus at the entrance of the right subclavian vein. All results of blood coagulation tests were normal. The patient was diagnosed as having superior vena cava syndrome caused by idiopathic venous thrombosis. Anti-coagulant therapy with intravenous tissue plasminogen activator injection and continuous urokinase and heparin infusion into the thrombi through a catheter were not effective in lysing the thrombi. Collateral circulation gradually developed and his symptoms decreased. We decided to follow this patient on warfarin medication because of the difficulty in removing the thrombi surgically.

Adult↗