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Biomedical subjects

H Miyazaki

Publications and source records attributed to H Miyazaki.

At least 307 records · Page 17Linked to original sources
PubMed1996

Soluble complement receptor type 1 inhibited the systemic organ injury caused by acid instillation into a lung.

BACKGROUND: Acid aspiration into one lung causes contralateral lung injury and systemic organ injury; this injury is thought to be mediated by the sequestration of activated neutrophils. Recombinant human soluble complement receptor 1 (sCR1) inhibits both the classical and alternative complement pathways; this study investigated the role of the complement system in unilateral acid lung injury by measuring the effects of administering sCR1 before or immediately after acid instillation. METHODS: Anesthetized rats (n = 18 in each group) underwent tracheostomy and insertion of a cannula into the anterior segment of the left lung. Then either 0.1 ml 0.1 N hydrochloric acid (HCl group) or 0.1 ml pH 7.4 phosphate buffered-saline (PBS group) was instilled. Fifteen minutes before (pre-sCR1 group) or 15 min after (post-sCR1 group) the acid was instilled, 10 mg/kg sCR1 was administered intravenously. Four hours after the acid instillation, rats were killed. In an additional 4 rats in each group, blood and bronchoalveolar lavage fluids obtained 1 h after the instillation of either acid or PBS were analyzed for tumor necrosis factor-alpha activity. RESULTS: The instillation of acid led to an increased wet-to-dry ratio of 5.2 +/- 0.1 in the acid-instilled lungs compared with their contralateral lungs (4.7 +/- 0.06). These values were greater than the values of 4.6 +/- 0.2 and 4.5 +/- 0.03 in the PBS-instilled lungs and their contralateral lungs, respectively (P < 0.05). The administration of sCR1 before or immediately after the instillation of acid did not attenuate the increase in the wet-to-dry ratio of the acid-instilled lungs. However, the small but consistent increase in the wet-to-dry ratio of the contralateral lungs was attenuated by the sCR1 infusions (P < 0.05). The instillation of acid increased the protein concentration in the bronchoalveolar lavage fluids from the injured lungs (1,000 +/- 206 micrograms/ml) compared with the protein concentration measured in the bronchoalveolar lavage fluids from their contralateral lungs (254 +/- 55 micrograms/ml). The administration of sCR1 before or immediately after the instillation of acid did not decrease the protein concentration in the bronchoalveolar lavage fluids from the acid-instilled lungs. The myeloperoxidase activity was increased in the acid-instilled lung, in their contralateral lung, and in the small intestines of the animals. The infusions of sCR1 before or immediately after the administration of acid led to significant decreases in the myeloperoxidase activities measured in the lungs and the intestines of the treated animals. Plasma tumor necrosis factor-alpha activity was only increased (2.7 +/- 1.1 U/ml) in the animals that had received acid instillations. The infusions of sCR1, administered either before or immediately after the acid instillations, significantly decreased the measured tumor necrosis factor-alpha activity in the plasma (0.5 +/- 0.6 and 1.0 +/- 0.7 U/ml, respectively). CONCLUSIONS: The results suggest that the complement system plays an important role in the pathogenesis of the injury of the contralateral lung and of the small intestine after unilateral instillation of acid to the lung. Further investigation is warranted to determine the clinical utility of antiinflammatory agents in acid-induced lung injury.

Acids↗
PubMed1996

Synergistic effects of erythropoietin and interleukin-6 on the in vitro proplatelet process formation of rat megakaryocytes.

The recombinant hemopoietic factors of megakaryocyte potentiator (MEG-POT) were studied to compare their activity in stimulating proplatelet process formation (PPF) with thrombopoietin (TPO, c-MpI ligand). For the assay, a highly enriched (> 95%) population of more than 90% viable megakaryocytes was isolated from rat bone marrow using the immunomagnetic beads method and cultured with fetal calf serum (FCS) or in a serum-free condition. Megakaryocytes developing slender beaded cytoplasmic processes (proplatelet processes) were observed on both inverted phase contract microscopy and scanning electron microscopy. A large number of proplatelet process clusters were dose-dependently formed with the addition of varying doses of recombinant erythropoietin (rEpo) and interleukin-6 (rIL-6) as well as TPO. Epo and IL-6 were demonstrated to act synergistically solely at low doses in the development of PPF (P < 0.05). Other recombinant factors such as IL-11, leukemia inhibitory factor (LIF) and erythroid differentiation factor (EDF) appeared weak or ineffective. From these in vitro observations, it was suggested that a synergism of Epo and IL-6 might play a significant role in the terminal stage of megakaryocyte maturation leading to platelet release.

Animals↗
PubMed1996

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat.

In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/ macrophage population contributes to liver damage.

Alanine Transaminase↗
PubMed1996

Changes in caries prevalence in Japan.

In Japan, the mean DMFT at 12 years of age increased from 2.8 in 1957 to 5.9 in 1975. From the 1981 survey (DMFT = 5.43), conversely, the mean DMFT decreased and reached 3.64 in 1993. The increase in caries prevalence can, without doubt, be explained by an increment of sugar consumption, since the intake of sugar increased after World War II and exceeded 18.25 kg/year (50 g/day) in 1965 and reached a maximum value (29.3 kg/year) in 1973 in Japan. On the other hand, the reason why the DMFT has decreased since 1981 is not clear. In many industrialized countries, a caries reduction has been achieved with acceptable fluoride exposure, although sugar consumption was still at a high level. However, fluoride usage was still limited during the last 2 decades in Japan. There is no community where fluoridated drinking water has been supplied since 1972. Fluoride tablet use was also discontinued for children in the 1970s. Fluoride mouthrinsing programs were available for only 1% of school children in 1992. Moreover, the market share of fluoridated dentifrices stayed at 10% until 1986 and became 30% only in 1988. An excellent correlation (r = 0.91; P < 0.01) is observed between the DMFT in 12-year-olds and per capita sugar consumption per year between 1957 and 1987 in Japan.

Adolescent↗
PubMed1996

Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of antibiotics in this model.

The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.

Animals↗
PubMed1996

Exercise-induced change in beta-adrenergic receptor number in lymphocytes from trained and untrained men.

This study was undertaken to clarify whether beta-adrenergic receptor (beta-AR) translocation from intracellular sites to the cell surface contributes to an increase in the number of beta-AR in lymphocytes from trained and untrained men after exercise. Nine trained and 9 untrained subjects performed exercise on a bicycle ergometer until exhaustion. The number of beta-AR in the cell surface (beta-AR(surface)) and intracellular sites (beta-AR(intra)) was determined at rest and after maximal exercise by measuring the binding of the radioligand 125I-iodocyanopindolol in the presence or absence of hydrophilic (CGP-12177A) or lipophilic (propranolol) unlabeled ligands. The number of beta-AR(surface) increased after exercise from 1,524.4 +/- 321.4 to 3,432.6 +/- 503.3 sites/cell (p < 0.01), whereas that of beta-AR(intra) decreased from 356.2 +/- 85.7 to 190.3 +/- 60.2 sites/cell (p < 0.05). The isoproterenol-stimulated cAMP production per 1 x 10(6) lymphocytes after exercise was significantly higher than that at rest. However, the cAMP production per single beta-AR(surface) tended to be lower after exercise. No differences between the trained and untrained subjects were found in beta-AR numbers or intracellular cAMP levels. These findings demonstrate that maximal exercise induces the translocation of beta-AR from intracellular sites to the cell surface in human lymphocytes. However, this translocation accounts for only 10% of the increase in total cellular beta-AR, suggesting that other mechanisms are predominant and contribute substantially to the increase in beta-AR(surface).

Adult↗
PubMed1996

Proximal ligation of large distal posterior inferior cerebellar artery aneurysm.

A 41-year-old male presented with vertigo, nausea, and vomiting suggesting a space-occupying lesion of the posterior fossa. Computed tomography (CT) and left vertebral angiography revealed a large distal posterior inferior cerebellar artery (PICA) aneurysm. Operation revealed the fusiform aneurysm was partially embedded in the medulla, preventing neck clipping or trapping of the aneurysm. Therefore, proximal ligation of the PICA was performed. The symptoms caused by the mass effect improved, and the aneurysm was not visualized by CT or angiography. Ligation of the PICA proximal to the choroidal point is not necessarily safe. In our case, ligation was distal to the tonsillomedullary segment from which the perforating arteries mainly arose, so the postoperative course was good without new neurological deficits. Proximal ligation is an effective treatment for distal PICA aneurysms manifesting as mass effect if other interventions are not possible.

Adult↗
PubMed1996

Intermolecular interactions of antimicrobial fluoroquinolones with purified rat liver CYP1A2 studied by proton nuclear magnetic resonance spectroscopy.

1. Binding and inhibition of antimicrobial fluoroquinolones towards liver CYP1A2 purified from 3-methylcholanthrene-treated rats were investigated using proton nuclear magnetic resonance (nmr) and phenacetin metabolism. 2. The proton nmr longitudinal relaxation rate study indicated that the paramagnetic effects of the haem iron of CYP1A2 were observed in protons of enoxacin with a 1,8-naphthyridine skeleton and its 4'-nitrogen atom on the 7-piperazine ring probably participated in specific binding to the haem iron. These data suggest a facile accessibility and strong binding of enoxacin to the active site of the enzyme. On the contrary, the binding region of norfloxacin with a quinoline skeleton could not be specified, and an 8-fluorinated derivative (AT-3970) had much lower paramagnetic effects and no specific binding region. 3. In a reconstituted CYP1A2 system, enoxacin exhibited the most potent inhibition of phenacetin O-deethylation. The metabolism was less inhibited by norfloxacin, and AT-3970 had a weak inhibitory activity. 4. The binding ability of the fluoroquinolones to the CYP1A2 active site is likely to determine their inhibitory activity against phenacetin metabolism.

Animals↗
PubMed1996

Molecular structure of the mouse amelogenin genomic DNA.

A genomic DNA clone (14.5 kbp) for amelogenin, a tooth enamel specific protein, has been isolated from a mouse genomic library. The nucleotide structure of this DNA was determined by the polymerase chain reaction and sequence analysis. The result indicated that the cloned DNA contained all the exons in addition to approximately 5.5 kbp of upstream sequence.

Amelogenin↗
PubMed1996

DMI-2 and DMI-3, DNA methyltransferase inhibitors produced by Streptomyces sp. strain no. 560.

Streptomyces sp. strain No. 560 produces several types of DNA methyltransferase inhibitors in the culture filtrate. Two of them, DMI-2 and DMI-3, were distinguished from the previously reported DMI-1 by their inhibitory spectrum and inhibition characteristics against DNA methyltransferase. The molecular weights of DMI-2 and DMI-3 were 854 and 435, respectively. The structure of DMI-2 was determined to be 4"'R,6aR,10S,10aS-8-acetyl-6a, 10a-dihydroxy-2-methoxy-12-methyl-10-[4'-[3"-hydroxy-3",5"-dimethyl-4" (Z-2"',4"'-dimethyl-2"'-heptenoyloxy) tetrahydropyran-1"-yloxy]-5'-methylcyclohexan-1'-yloxy ]-1,4,6, 7,9-pentaoxo-1,4,6,6a,7,8,9,10,10a,11-decahydronaphthacene. The chemical structure of DMI-2 was established as a tautomer of dutomycin which is an antitumor antibiotic produced by Streptomyces sp. 1725. DMI-2 and DMI-3 showed strong inhibition against N6-methyladenine-DNA methyltransferase (M. Eco RI). DMI-2 inhibited M. Eco RI in a competitive manner with respect to plasmid pUC19 used as DNA substrate and in an uncompetitive manner with respect to S-adenosylmethionine (SAM) used as methyl donor. DMI-3 inhibited M. Eco RI in a competitive manner with respect to plasmid pUC19 and SAM. The inhibitory activities of both inhibitors depended upon the pH and temperature in the assay media.

DNA Methylation↗
PubMed1996

Coexpression of thrombopoietin and c-mpl genes in human acute myeloblastic leukemia cells.

Thrombopoietin (TPO) is a recently identified hematopoietic growth factor that is essential for the growth and development of megakaryocytes. We have previously shown that TPO induces proliferation of acute myeloblastic leukemia (AML) cells in vitro. In this study, we have examined the expression of TPO and its receptor c-mpl in a series of AML cases and human leukemia cell lines. The mRNA transcripts of TPO were detectable in 18 of 50 AML cases and in some myeloid leukemia cell lines (HEL, M07E and CMK) by means of reverse transcriptase polymerase chain reaction (RT-PCR). In addition, TPO transcripts were coexpressed with c-mpl transcripts in 10 of 50 AML cases and in HEL, M07E and CMK cells. With regard to the French-American-British (FAB) classification, coexpression OF TPO and c-mpl was observed with high frequency in AML cases of M7-type. Despite the TPO expression in a substantial fraction of leukemia cells, biological activity of TPO was not found in the conditioned medium that was obtained from cultivation of TPO mRNA-positive leukemia cells. These results suggest that TPO may not commonly participate in the abnormal growth of AML cells as an extracellular autocrine growth factor.

Base Sequence↗
PubMed1996

[Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families].

Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families were described. All cases were clinically manifested by jaundice and splenomegaly. Hemolysis was evident from indirect hyperbilrubinemia, reticulocytosis and decrement of serum haptoglobin. Red blood cells showed morphological abnormalities such as poikylocytosis, anisocytosis and target cells on blood smears. Both direct and indirect Coombs' tests were negative. Ham test, sugar water test and hemoglobin electrophoresis showed no abnormalities. Osmotic fragility test showed decreased membrane fragility. Lipid analysis of red cell membrane showed increment of phosphatidylcholine content and decrement of sphingomyelin content, although plasma lipids were essentially normal. Influx and efflux of sodium through the red cell membrane were both increased. Splenectomy was performed without effect on one patient and the mother of other patients.

Adult↗
PubMed1996

GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin.

The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development.

Animals↗
PubMed1996

[A case report of germinoma with syncytiotrophoblastic giant cells (STGC) in the basal ganglia].

We report a case of germinoma with syncytiotrophoblastic giant cells (STGC) in the basal ganglia which was encountered at the Department of Neurosurgery, Hiratsuka City Hospital, Kanagawa, Japan. A 9-year-old boy was admitted to our hospital on September 13th, 1993 because of left hemiparesis and precocious puberty. Endocrinological examination revealed a high serum level of human chorionic gonadotropin (HCG) (290 mIU/ml) and beta-subunit human chorionic gonadotropin (HCG-beta) (1.3 ng/ml). Plain CT scan showed an irregularly-defined mass lesion in the right basal ganglia, which had several low density spots and was inhomogeneously enhanced on contrast CT scan. The tumor developed from the right putamen to the thalamus and showed a tendency towards involvement of the hypothalamic region on MR imaging. We performed a right front-temporal craniotomy on 29th September, 1993, and a piece of the tumor was removed. It was histologically diagnosed to be germinoma with STGC. We treated the patient with carboplatin and etoposide (CBDCA 200 mg/m2day1, VP-16 60 mg/m2day1-5) chemotherapy and radiotherapy (local 30 Gy) after surgery. Postoperative course was good without recurrent signs. He is now in good health and going to elementary school without neurological deficit. There are very few reports of germinoma with STGC arising in the basal ganglia. We provide a new treatment of germinoma with STGC, chemotherapy and radiotherapy after surgery.

Basal Ganglia Diseases↗
PubMed1996

[Treatment results for unselected patients with acute myelogenous leukemia. During a 10-year period, August 1984 to July 1994].

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Adolescent↗
PubMed1996

Rapid progression of flat warts in a patient with malignant lymphoma after PBSCT.

A 51-year-old man with non-Hodgkin's lymphoma in his third remission received autologous PBSCT. He had had a couple of flat warts on his right hand since admission, which showed no progression during conventional dose chemotherapy. On day 15 of PBSCT, however, the warts began to develop and spread to his forehead, face, neck and arms over several days. The diagnosis of flat warts was made and human papilloma virus type 3 was detected by PCR analysis. Severe immunosuppression associated with PBSCT may have caused this rapid and disseminated growth of flat warts.

Hematopoietic Stem Cell Transplantation↗