Search PubMed⌕ Search

Biomedical subjects

M Tamura

Publications and source records attributed to M Tamura.

At least 631 records · Page 35Linked to original sources

Recombinant human granulocyte colony-stimulating factor inhibits the metastasis of hematogenous and non-hematogenous tumors in mice.

We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.

Animals↗

REM sleep-associated hemoglobin oxygenation in the monkey forebrain studied using near-infrared spectrophotometry.

The oxygenation state of hemoglobin (Hb) in the monkey forebrain was monitored continuously throughout nocturnal sleep using a near-infrared spectrophotometric technique. During rapid eye movement (REM) sleep, an increase in oxygenated Hb occurred concomitantly with a decrease in deoxygenated Hb, while no significant changes in Hb oxygenation were observed during slow wave sleep (SWS). A gradual increase in total Hb content was also observed to occur during each REM sleep episode but not during SWS.

Animals↗

A possible mechanism of mitochondrial dysfunction during cerebral ischemia: inhibition of mitochondrial respiration activity by arachidonic acid.

The dramatic increase in the arachidonic acid (AA) level in the brain is a well-known molecular event during cerebral ischemia. As mitochondria are known to be one possible site of the cell damage, the effects of AA on the respiratory activity of rat brain mitochondria were investigated in vitro using an oxygen electrode. In NAD-linked respiration, respiratory control ratio was decreased significantly by AA, with an IC50 of 6.0 microM. AA had the dual effect on mitochondrial respiration, a decrease in state 3 and uncoupled state and an increase in state 4 (i.e., uncoupling) as reported by Hillered and Chan (J. Neurosci. Res. 19, 94-100, 1988). Furthermore, we found that other unsaturated long-chain free fatty acids (C18:1-C18:3, C20:1-C20:5) also showed such a dual effect. Cyclooxygenase metabolites of AA such as prostaglandins (D2, E2, F2 alpha, E1) and thromboxane B2, and lipoxygenase metabolites such as leukotrienes (D4, B4) and 5- or 12-hydroperoxyeicosatetraenoic acid had no significant effect. The inhibition of the uncoupled state by AA was more marked in NAD-linked than that in FAD-linked respiration, while the degree of uncoupling by AA were the same in both respirations. In spectrophotometrical measurement, the reduction of cytochromes and flavo-protein was markedly inhibited by AA in NAD-linked respiration, but not in the FAD-linked one. In addition, the activity of cytochrome c oxidase was scarcely inhibited by AA. These data suggest that AA itself, not its metabolites, may inhibit mitochondrial ATP production during brain ischemia and that AA may act on the site(s) closely related to NAD-linked respiration, but not the FAD-linked one, in addition to its uncoupling effect.

Animals↗

Three-dimensional observations on microvascular growth in rat glioma using a vascular casting method.

The microvascular growth of ethylnitrosourea-induced rat glioma was observed using vascular casting and scanning electron microscopy (SEM). Light microscopy showed central necrosis and marginal invasive tumor cell growth with increased vascularity, and suggested that adopted pre-existing circulation was dominant in the inoculated brain tumors. In SEM, numerous buds or nodular protrusions and a few large and tortuous vessels along the tumor margin were seen at the early stage. In the intermediate stage, microaneurysms, buds with septum formation and anastomotic arches appeared, and these tumor vessels became more tortuous and larger, and extended as the tumor grew. Several "potato-shaped" huge vessels and linear nodular large vessels also appeared. In the late stage, glomeruli appeared and potato-shaped huge vessels increased in number. The neovascularization and microvascular growth of the tumors was characterized by three patterns: (a) growth of the parent vessels forming buds, (b) vascular growth in a meshwork formation producing glomeruli, and (c) vascular enlargement without a definite pattern creating potato-shaped huge vessels. The tumor vessels gradually lost their natural three-dimensional structure.

Animals↗

Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart.

The effects of increased free fatty acid (FFA) levels on ventricular arrhythmias remain controversial. Using ventricular fibrillation threshold (VFT), we examined the relationship between FFA levels and ventricular arrhythmias. Isolated rat hearts were perfused with palmitate bound to either albumin or fatty acid binding protein (FABP) by Langendorf's method. The VFT was determined by electrical stimulation. Perfusion with 0.12 mM albumin alone, 0.12 mM palmitate bound to 0.12 mM albumin, and 0.36 mM palmitate bound to 0.12 mM albumin did not lower the VFT significantly. However, 0.60 mM palmitate bound to 0.12 mM albumin lowered VFT from 2.19 +/- 0.20 mA to 1.56 +/- 0.13 mA. The perfusion of 0.36 mM palmitate bound to 0.12 mM FABP lowered the VFT from 2.05 +/- to 0.19 mA to 1.47 +/- 0.23 mA, but 0.12 mM FABP alone did not affect the VFT. Perfusion with 0.36 mM palmitate bound to 0.12 mM FABP caused the VFT to fall more than perfusion with 0.36 mM palmitate bound to 0.12 mM albumin. Then the effects of verapamil perfusion or a low concentration of perfusate Ca2+ on VFT were examined. VFT was determined by electrical stimulation. Palmitate (0.6 mM) bound to 0.12 mM albumin lowered VFT. Verapamil 10(-7) M perfusion and a low concentration of Ca2+ (Ca2+ 1.67 mM) suppressed the FFA-induced fall of VFT. These results suggested that the arrhythmogenic action of FFA was related to Ca2+ overload in myocardial cells.

Albumins↗

Bidirectional cavopulmonary anastomosis using vertical vein for right isomerism, pulmonary atresia, and TAPVR.

An 8-year-old girl who was diagnosed as having right atrial isomerism, pulmonary atresia, butterfly-shaped juxtaductal pulmonary arterial stenosis, total anomalous pulmonary venous return of the supracardiac type, regurgitant common atrioventricular valve, and univentricular heart of the right ventricular type underwent bilateral, bidirectional cavopulmonary anastomosis using a vertical vein and anastomosis between the common pulmonary venous trunk and atrium. The surgical procedure in this patient is described.

Anastomosis, Surgical↗

Antibodies to HA and NA augment uptake of influenza A viruses into cells via Fc receptor entry.

The hemagglutinin (HA) and neuraminidase (NA) of influenza A viruses induce antibodies which augment the uptake of influenza A virus by antigen presenting cells via Fc receptor entry. Antibody-dependent enhancement of uptake of virus by cells was mediated by Fc receptors because F(ab')2 preparations of lgG mixed with virus did not enhance virus uptake. The enhanced infection was measured using a fluorescent focus assay and was confirmed by dot-blot hybridization analysis. A 25-fold increase in the number of cells containing influenza antigens was detected when virus was mixed with subneutralizing concentrations of immune serum to the homologous virus before adding to neuraminidase-treated cells. Infection was also augmented using reassortant viruses which shared only the HA or the NA of the virus used to induce antibodies. Specific antisera to purified HA or NA also enhanced virus uptake. These results indicate that both the HA and the NA induce antibodies that enhance uptake of virus by Fc receptor bearing cells. In addition we determined that the drift of neutralizing antigens occurred more quickly than the drift of infection-enhancing antigens during the evolution of virus strains of the H3 subtype. The increase in the number of antigen presenting cells as a result of uptake of virus complexed with cross-reactive enhancing antibodies may affect the T cell responses to influenza infection.

Animals↗

Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer's lung, ventilation pneumonitis, and bird fancier's lung: report of a nationwide epidemiologic study in Japan.

We performed a nationwide epidemiologic study of hypersensitivity pneumonitis (HP) in Japan by questionnaire and found that 835 cases of HP were recognized during the 1980s; 74.4% were summer-type HP, 8.1% farmer's lung, 4.3% ventilation pneumonitis, 4.1% bird fancier's lung, 2.3% other types, such as chemical worker's lung, and 6.8% of unknown causative agent. It was found that the CD4/CD8 ratios of bronchoalveolar lavage (BAL) lymphocytes were significantly different with the type of disease. The ratio was 0.6 +/- 0.1 (mean +/- SEM) in summer-type HP (N = 271), 4.4 +/- 0.7 in farmer's lung (N = 22), 1.6 +/- 0.3 in ventilation pneumonitis (N = 19), and 2.0 +/- 0.5 in bird fancier's lung (N = 19). In farmer's lung, the CD4/CD8 ratio in smokers was 6.2 +/- 1.9 (N = 6) in contrast with 3.4 +/- 0.7 for nonsmokers (N = 16) (p less than 0.05). It has been generally considered that the phenotypes of BAL lymphocytes in patients with HP are predominately CD8 cells. Our present results, however, indicate that the phenotypes of BAL lymphocytes vary with the type of HP, probably depending on factors such as causative agent, smoking, or staging of the disease.

Age Factors↗

Protective effects of Healon and Occucoat against air bubble endothelial damage during ultrasonic agitation of the anterior chamber.

An important aspect of any new viscoelastic substance is the corneal endothelial protection. We compared the protective effects of sodium hyaluronate (Healon) and hydroxypropylmethylcellulose (Occucoat) by introducing a controlled volume of air bubbles into the anterior chamber of human eye bank eyes during ultrasonic agitation of the anterior chamber. Eight eyes received Healon and 11 eyes received Occucoat. Damage to endothelial cells in the central cornea was quantified by vital staining. Endothelial damage averaged 4.5% in eyes in which no viscoelastic was used (positive control); damage was 0.4% in eyes in which a viscoelastic was injected but no air bubbles were introduced (negative control). We found that endothelial damage averaged 4.25% in specimens that received air plus Healon and 1.4% in specimens that received air plus Occucoat. Occucoat appeared to have somewhat better protective effects than Healon against air bubble damage to the corneal endothelium during ultrasonic agitation of the anterior chamber.

Air↗

Quantitative analysis of the hemoglobin oxygenation state of rat brain in vivo by picosecond time-resolved spectrophotometry.

Through the use of a picosecond laser pulse of near-infrared light at 1,064 nm, the temporal profile of the transmitted light through the anesthetized rat head has been investigated. The light intensity at a certain time after the input pulse was exponentially attenuated by the hemoglobin concentration with hematocrit values from 1.5 to 50%, although the transmitted pulse broadened markedly due to scattering by the cerebral tissue. The optical pathlength, which is required for quantitation of the absolute absorbance change, was directly determined, by the time of flight measurement of the light pulses, as the product of the velocity of light in tissue and time. The mean concentration of hemoglobin in the brain could be determined quantitatively by the use of this pathlength. The oxygen saturation of venous blood determined by our time of flight measurement was very close to that in the internal jugular vein determined directly with a gas analyzer. Thus, the picosecond laser technique is useful for quantifying the blood oxygenation in tissues.

Animals↗

Acceleration of the hemopoietic reconstitution in mice undergoing bone marrow transplantation by recombinant human granulocyte colony-stimulating factor.

We have investigated the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on hemopoietic reconstitution after bone marrow transplantation (BMT) following lethal irradiation in mice. Mice received a daily administration of 10 micrograms/kg rG-CSF or control vehicle one through 21 days after BMT. Spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg), and erythroid burst-forming units (BFU-E) increased in both bone marrow and spleen of the rG-CSF-treated mice as compared with the control. This increase was evident during the administration period. In spite of the increase in the progenitor cells in bone marrow and spleen, only a recovery of neutrophils was accelerated in peripheral blood. Thus rG-CSF accelerated granulopoietic recovery in the BMT mice, with an enhanced recovery of the stem cells and the progenitors for erythrocytes and megakaryocytes. These results indicate the potential clinical usefulness of rG-CSF in the treatment of patients undergoing BMT.

Animals↗

Mechanism of protective effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on Pseudomonas infection.

Decrease in resistance to systemic Pseudomonas infection in cyclophosphamide (CPA)-induced neutropenic mice was prevented by injections of recombinant human granulocyte colony-stimulating factor (rG-CSF). In order to explore mechanism of the prevention of CPA-induced decrease in the anti-infectious resistance by rG-CSF, CPA-treated and then rG-CSF-injected mice were inoculated i.p. with P. aeruginosa, and growth of the infecting bacteria and infiltration of leukocytes in the peritoneal cavity were determined. In the mice who had received 4 daily s.c. injections of rG-CSF from the day after CPA-injection, a large number of neutrophils were mobilized into the peritoneal cavity in response to the bacterial inoculation and growth of the infecting Pseudomonas in the cavity was markedly inhibited, whereas in CPA-induced neutropenic mice few neutrophils were mobilized and the infecting bacteria proliferated vigorously in the peritoneal cavity. These results suggest that administration of rG-CSF prevents CPA-induced neutropenia and neutrophils circulating at normal level in the number are normally mobilized into the peritoneal cavity in response to Pseudomonas inoculation, and that the mobilized neutrophils inhibit proliferation of the infecting Pseudomonas.

Animals↗

Forty year review of bacterial endocarditis in infants and children.

From 1950 through 1989 at Tokyo University's Department of Pediatrics, 25 children were treated for bacterial endocarditis. Twenty-two of these patients had previously been diagnosed as suffering from congenital heart disease. Twenty one of the 25 patients had positive blood cultures. Streptococcus viridans was the most common organism isolated, although the incidence of Streptococcus viridans infection has decreased in the last 20 years. In present series only a few post-surgical cases with congenital heart disease occurred. There were three deaths which all occurred prior to 1965.

Adolescent↗

Experimental labyrinthitis in guinea pigs caused by a hantavirus.

Hantavirus-induced acute viral infection of the inner ear of guinea pigs is reported. Guinea pigs were inoculated directly into the inner ear through the round window, or intraperitoneally with hantavirus (B-1 strain), and the cochlea was examined using an immunohistochemical technique for the localization of viral antigens. Virus-specific antigens were detected prominently in the stria vascularis and to a lesser degree in other inner ear structures of the infected guinea pigs. The morphological changes in the inner ear structures of these guinea pigs were observed. Virus was isolated from the blood of some infected guinea pigs. These data suggest that hantavirus can infect the inner ear of the guinea pig via viremia. The effect of immunosuppression by ciclosporin A or cyclophosphamide is discussed.

Acute Disease↗