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Biomedical subjects

H Tamura

Publications and source records attributed to H Tamura.

At least 217 records · Page 12Linked to original sources

The mechanism of lactitol (NS-4) in inducing adrenomedullary proliferative lesion in rats.

We used 13-week repeated oral administration of lactitol as part of a study to clarify the mechanism by which lactitol induces the proliferation of adrenomedullary chromaffin cells. There was a marked increase in urinary calcium (Ca) excretion even though the lactitol administration had no effect on the blood Ca level. A tendency for an increase in adrenal venous blood epinephrine (EPI) and norepinephrine (NE) concentrations was seen. Organ weight measurement of adrenal glands revealed a tendency for an increase in absolute weight and a significant increase in relative weight. Morphometric analysis of adrenomedullary chromaffin cells showed a tendency for an increased total cell volume and a decreased numerical density; but, there was no conspicuous change in the total cell number. Determinations of the anti-bromodeoxyuridine (BrdU) and antiproliferative cell nuclear antigen (PCNA) antibody-positive cell counts showed a tendency for an increased proliferation rate for adrenomedullary chromaffin cells. Electron microscopy showed a slight increase in the number of Golgi apparatuses in these cells. Because the marked increase in urinary Ca excretion was concomitant with morphological changes that suggested the hyperfunction of chromaffin cells in the adrenal medulla and a tendency for an increased cell proliferation rate, we assume that persistent hyperfunction of the adrenomedullary chromaffin cells, which was mediated by enhanced Ca absorption from the intestinal tract, may have induced proliferative lesion.

Adrenal Medulla↗

[Mutagenicity studies of montirelin hydrate (NS-3)].

Montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was examined for mutagenicity in the reverse mutation test, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at dose range of 156.25-5,000 micrograms/plate using Salmonella typhimurium strains, TA1535, TA100, TA1537, and TA98, and Escherichia coli WP2uvrA. The drug did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S-9mix). The chromosome aberration test was carried out at dose range of 300-4,800 micrograms/ml using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosomal aberrations were observed with or without metabolic activations. The micronucleus test was conducted in the bone marrow cells of Slc:ddY male mice. Mice were given the drug by a single intraperitoneal administration at doses of 0, 250, 500, 1,000, and 2,000 mg/kg. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that montirelin hydrate has no mutagenic activity in vitro or in vivo.

Animals↗

Opaque eyes developed in transgenic mice with T-cell receptor delta gene.

PURPOSE: During the generation of transgenic mice (TGs) introduced with mouse T-cell receptor delta (TCR delta) gene, the authors found a TG line with corneal opacity that coincided with the presence of the transgene. The authors investigated the pathogenesis and molecular mechanisms of this corneal opacity in this line. METHODS: The pathologic features and pathogenesis of the corneal opacity in TGs were examined histologically using transmission and scanning electron microscopy, as well as light microscopy. DNA and RNA blot analyses were performed to examine the copy number and the expression of the transgenes, respectively. RESULTS: Histologically, edema of the corneal epithelium and adhesion of the iris to the cornea were observed in adult TGs. In the developmental analysis, the authors first observed relative hypoplasia of the ciliary body on day 18 of gestation and dysgenesis of the anterior chamber angle from postnatal day 2. Corneal opacity was observed from postnatal day 8, coinciding with the histologic vesicular change of the epithelium. No inflammation was observed through its life. In the sublines that have different copy numbers of the transgene, the occurrence of the opacity depended on the copy number of the transgene. Expression of the transgene in the thymus was consistent with the number of the introduced transgene. CONCLUSION: In a TCR delta TG line, the overexpression of transgenes coincided with abnormal development of the ocular anterior segment and the corneal opacity. Pathogenesis is described, and possible molecular mechanisms are discussed.

Animals↗

Late-onset renal dysfunction in a patient with non-Hodgkin's lymphoma following an autologous bone marrow transplantation.

Various types of glomerulonephropathy have been reported in patients with malignant lymphoma. The present report describes a 21-year-old man with non-Hodgkin's lymphoma who developed renal insufficiency 4 months after undergoing autologous bone marrow transplantation without combined total body irradiation treatment. At the presentation of renal dysfunction, the malignant lymphoma had been in complete remission. A renal biopsy specimen revealed glomerular changes resembling those seen in patients with hemolytic uremic syndrome. However, hematologic examinations exhibited no evidence of thrombocytopenia or thrombotic microangiopathy, such as red cell fragmentations on the peripheral blood smear. Although the etiology of this nephropathy remains unclear, the chemotherapeutic agents administered in conditioning regimens for bone marrow transplantation were suspected of contributing to the renal insufficiency. Methylprednisolone pulse therapy appeared to be effective in arresting progression of the nephropathy. This case indicates that renal function should be monitored carefully in patients with malignant lymphoma after bone marrow transplantation, even if such patients lack the signs or symptoms of thrombotic microangiopathy.

Adult↗

[Treatment with percutaneous transluminal balloon venoplasty for superior vena cava syndrome after permanent pacemaker implantation].

Superior vena cava (SVC) syndrome after transvenous implantation of a permanent pacemaker is relatively uncommon. We present a woman whose neck and face became swollen two years after implantation of a two-chamber pacemaker. Computed tomography and digital subtraction angiography revealed severe SVC stenosis. Percutaneous transluminal venoplasty (PTV) was performed to relieve the stenosis. PTV was effective to improve the swelling of her neck and face. PTV seems to be a good method to relieve SVC stenosis after implantation of a pacemaker.

Adult↗

Role of the domain-domain interaction in the construction of the antigen combining site. A comparative study by 1H-15N shift correlation NMR spectroscopy of the Fv and Fab fragments of anti-dansyl mouse monoclonal antibody.

A comparative NMR structural study of anti-dansyl Fv and Fab fragments is reported. Both of these antigen binding fragments have been prepared using antibodies that originate from the identical anti-dansyl switch variant cell lines. It has been confirmed that the Fv and Fab fragments possess the identical binding property. The antigen binding fragment analogs labeled with 15N of the main chain amide group of the aromatic residues (His, Phe, Trp, and Tyr) were used. The chemical shift and hydrogen-deuterium exchange rate of the amide protons are compared for the Fv and Fab fragments. On the basis of the NMR data obtained, we have concluded that (1) the structural change induced in the VH domain upon antigen binding significantly affects the dynamical structure of the VL domain and (2) the existence of the constant regions affects the fluctuation of the VL domain, increasing the thermal stability of the variable region.

Amides↗

Mutational analysis of the COOH-terminal hydrophobic domain of bovine liver 5'-nucleotidase as a signal for glycosylphosphatidylinositol (GPI) anchor attachment.

In order to address the minimum domain of the COOH-terminal hydrophobic region responsible for GPI modification of bovine liver 5'-nucleotidase, we constructed a series of the deletion mutants of the COOH-terminus and expressed them in COS cells. Cells transfected by the deletion mutant of 6 amino acids (-IIILYQ) from the hydrophobic domain (-FSLIFLSVLAVIII-LYQ) did not show any elevation of cell surface-associated 5'-nucleotidase activity, whereas the 2 (-YQ) or 4 (-ILYQ) amino acid deletion mutant retained the bovine liver-derived activity on the cell surface as a GPI-anchored protein. Loss of half the hydrophobic domain (6 or 8 amino acids) resulted in accumulation of the activity in the cell. On the other hand, deletion of the whole hydrophobic domain (17 amino acids) or the entire cleaved-off domain (25 amino acids) made the product secreted into the medium. In conclusion, the hydrophobicity of 13 amino acids in length was enough for the GPI modification of the bovine liver 5'-nucleotidase.

5'-Nucleotidase↗

The novel mAb QR6.6 detects a surface molecule on immature thymocytes and inhibits their proliferation on thymic epithelial cells.

We previously reported that the nude mouse-derived splenic T cell clone N-9F exhibits a proliferative response when cultured on thymic stromal cells. This N-9F proliferation is mediated by direct cell-to-cell interactions between T and thymic stromal cells. A thymic epithelial cell clone, SL10.3, also supports N-9F growth. To identify the molecule involved in T cell development in the thymus, we established mAb specific to the N-9F clone. One of these mAb, QR6.6, was found to inhibit the N-9F proliferative response on SL10.3. QR6.6-positive cells were detected in thymus but not in other lymphoid organs such as bone marrow, lymph nodes, or spleen. QR6.6-positive cells accounted for 3 to 5% of the cells in adult thymuses whereas higher percentages were found in neonatal (10-20%) and fetal thymuses (70% at E17 and 10-20% at E15). The positive cells were primarily CD4-8- thymocytes in fetuses and CD4-8- to CD4+8+ thymocytes in adults. The QR6.6 mAb precipitates a 100 kDa molecule from the N-9F clone. The addition of the mAb to fetal thymus organ culture reduces the recovery of cells at culture day 4. It was also found that the mAb inhibits fetal thymocyte proliferation on the SL10.3 thymic epithelial cell line. These results suggest that the 100 kDa molecule detected by the QR6.6 mAb may play a crucial role in the early stage of thymocyte development.

Animals↗

Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria.

To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode's solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement transducer. Perfusate potassium concentrations were increased from 5.4 mmol.L-1 to either 8.1 mmol.L-1 or 10.8 mmol.L-1 by adding KCl to the standard Tyrode's solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate. In standard Tyrode's solution (potassium 5.4 mmol.L-1, pH 7.4), halothane 0.5-2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of halothane for 50% inhibition of contractile force (IC50) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium- or pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas 1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis (pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Inhibition of NGF-induced neurite outgrowth of PC12 cells by Bacillus cereus sphingomyelinase, a bacterial hemolysin.

Sphingomyelinase of Bacillus cereus, a bacterial hemolysin, reduced nerve growth factor (NGF)-induced neurite outgrowth of PC12 cells in a dose-dependent manner. At 200 mU/ml, sphingomyelinase repressed half the neurite outgrowth of the cells at 250 ng/ml NGF. The c-fos superinduction, one of the early responses induced by NGF, was not influenced by this treatment, suggesting that the repression by sphingomyelinase occurred via a protein kinase C-independent pathway.

Animals↗

Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes.

The plasma soluble interleukin 2 receptor (sIL-2R) level and its relationships with haematologic and immunologic data were examined in 40 patients with myelodysplastic syndromes (MDS). The plasma sIL-2R level was significantly higher in the high-risk MDS group (refractory anaemia with excess blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia) than in the low-risk MDS group (refractory anaemia (RA) and RA with ringed sideroblasts) or in normal subjects, although there was considerable variation in the plasma sIL-2R level within each MDS group. The plasma sIL-2R level correlated positively with the bone marrow cellularity and bone marrow blast mass, but not with the absolute number of CD25+ lymphocytes. This may support the idea that plasma sIL-2R is derived from malignant MDS cells in the bone marrow. The plasma sIL-2R level correlated negatively with the absolute numbers of the CD8+, CD3-CD16+, and CD3-CD56+ cell populations in freshly isolated lymphocytes, the percentage of CD3-CD56+ cells in lymphokine (interleukin 2)-activated killer (LAK) cells, and the cytotoxicity of LAK cells. We conclude that MDS patients having a high plasma sIL-2R level often have a defect in natural killer and CD8+ T-cells.

Adult↗

Diagnostic and prognostic significance of plasma endotoxin determination in febrile patients with haematological malignancies.

We evaluated the clinical utility of a new endotoxin-specific chromogenic limulus test in febrile patients with haematological malignancies. The specificity is assured by the removal of factor G, which is sensitive to (1-->3)-beta-D-glucan, from horseshoe crab amoebocyte lysate. The sensitivity and specificity of the test to systemic gram-negative bacterial infections were 69.7 and 96.3%, respectively. Meanwhile, gram-negative bacteria grew in only 39.7% of endotoxaemic samples. Thus, it seems appropriate to consider gram-negative bacteraemia and endotoxaemia as different entities. Endotoxaemia was significantly associated with septic shock and infectious death, especially in patients with neutropenia. The new test, the results of which are available within 3 h, should help physicians to recognise this ominous sign early and to initiate a prompt countermeasure to endotoxaemia.

Age Factors↗