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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 559 records · Page 31Linked to original sources

Expression of glutamate transporters in cultured glial cells.

Expression of mRNAs for glutamate transporter (GLT-1) and glutamate aspartate transporter (GLAST) was investigated in three different types of purified glial cells by the reverse transcriptase-polymerase chain reaction (RT-PCR). Cultured astrocytes, oligodendrocytes, and microglia expressed mRNAs for GLAST and GLT-1; mRNA for GLAST was expressed more prominently than that for GLT-1 in astrocytes. Oligodendrocytes and microglia expressed mRNAs for both GLT-1 and GLAST equally, but the expression in microglia was not prominent, suggesting glutamate uptake is not essential in microglia. In astrocytes cultured from different brain regions, GLAST mRNA was equally expressed. GLT-1 mRNA was also detected in these astrocytes, but the expression level was lower than that of GLAST.

ATP-Binding Cassette Transporters↗

cDNA cloning of a thromboxane A2 receptor from rat astrocytes.

A cDNA clone for rat thromboxane (TX) A2 receptor was obtained from cultured astrocytes. The cDNA encodes a protein of 341 amino acids with seven putative transmembrane domains. The receptor is homologous with mouse and human TXA2 receptors at 92.7% and 71.8%, respectively. Expression of messenger RNA for the receptor was examined by reverse transcriptase-polymerase chain reaction, showing ubiquitous expression in brain glial cells such as astrocytes, oligodendrocytes and microglia.

Amino Acid Sequence↗

Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantation. The IgE allotype is an important marker of graft-versus-host disease.

Induction of a graft-vs-host reaction in irradiated (BALB/c X C57BL/6)F1 mice (CBF1 mice) with bone marrow cells (BMC) plus spleen cells of BALB/c mice leads to bone marrow transplantation--GVHD (BMT-GVHD). BMT-GVHD is characterized by liver disease, splenomegaly, and hypergammopathy. In addition, we found that increased serum IgE and IgG1 levels were correlated with BMT-GVHD such as liver disease and splenomegaly. The allotype of increased IgE levels in BMT-GVHD was IgEa of donor origin, not IgEb of host origin. We also found that in the thymus of murine BMT-GVHD, the CD4+ CD8+ double-positive T cells were decreased, but the CD4+ CD8- or CD4- CD8+ single-positive T cells were increased. Interestingly, double-positive T cells appeared in the spleen, suggesting that abnormal T cell differentiation existed in murine BMT-GVHD. When the recipients were treated with anti-IL-4 Ab (11B11), the increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell differentiation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of allogeneic effects, and 11B11 prevents immunodysfunction including T cell differentiation in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.

Animals↗

Fetus-specific CYP3A7 and adult-specific CYP3A4 expressed in Chinese hamster CHL cells have similar capacity to activate carcinogenic mycotoxins.

To assess whether CYP3A4 and CYP3A7 have a similar capacity to activate carcinogenic mycotoxins, we established cell lines stably expressing human CYP3A4 and CYP3A7, which are adult- and fetal-specific forms of cytochrome P450 in human livers, respectively. Each cDNA was introduced into CR-119 cells which had been established by introducing guinea pig NADPH-cytochrome P450 reductase cDNA into Chinese hamster lung cells. The cell lines (4-line and 7-line) stably expressed the mRNA and the protein corresponding to CYP3A4 and CYP3A7, respectively. The concentration-response for aflatoxin B1 (AFB1) cytotoxicity in 4-line and 7-line, respectively, was compared. 4-10 and 7-40 cells were approximately 17- and 20 times more sensitive to AFB1 than the parental CR-119 cells, respectively. In addition, the sensitivities to AFB1 of both 4-10 and 7-40 cells were enhanced approximately seven times by the addition of 10 microM alpha-naphthoflavone, a known activator of CYP3A enzyme, while the sensitivities were suppressed approximately four times by the addition of 100 microM troleandomycin, which forms a metabolite intermediate complex with CYP3A enzyme. Moreover, both cell lines showed approximately 10 and 2 times higher sensitivity to sterigmatocystin and aflatoxin G1 than CR-119 cells, respectively. These results indicate that CYP3A4 and CYP3A7 have essentially similar capacities to activate AFB1, sterigmatocystin, and aflatoxin G1 to produce toxic metabolites.

Adult↗

Enalapril improves heart failure induced by monocrotaline without reducing pulmonary hypertension in rats: roles of preserved myocardial creatine kinase and lactate dehydrogenase isoenzymes.

We investigated the redistribution of myocardial isoenzymes of creatine kinase (CK) and lactate dehydrogenase (LD) in rats with right heart failure induced by monocrotaline and assessed the effect of enalapril, an angiotensin converting enzyme inhibitor. Wistar rats were divided into four groups: (1) control (n = 20), (2) control + enalapril (25 mg/kg/day) (n = 22), (3) monocrotaline (50 mg/kg) (n = 45), (4) monocrotaline (50 mg/kg) + enalapril (25 mg/kg/day) (n = 32). After 4 weeks, the monocrotaline group developed severe pulmonary hypertension and right ventricular hypertrophy with marked decrease in myocardial norepinephrine and increase in both plasma atrial natriuretic peptide and mortality rate (33.3%). The marked decrease in both MM and mitochondrial CK ('creatine shuttle') and the relatively constant BB and MB CK caused the net depression of total CK. The depression of LD1 (aerobic LD) was remarkable compared with the relatively constant total LD. In the monocrotaline+enalapril group, mortality rate (9.4%), cardiac hypertrophy and plasma atrial natriuretic peptide were all significantly reduced and myocardial norepinephrine recovered although pulmonary hypertension was not improved at all. However, myocardial total, MM and mitochondrial CK and LD1 activities were all recovered completely or partially in this group. Thus, enalapril reduced cardiac hypertrophy and failure and improved the prognosis in this model of pulmonary hypertension. This beneficial effect of enalapril was not associated with pulmonary vasodepression but with the inhibition of myocardial isoenzyme redistribution of CK and LD, i.e. the preservation of 'creatine shuttle' and aerobic LD.

Animals↗

Constitutive activation of the Fas ligand gene in mouse lymphoproliferative disorders.

Mice homozygous for lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) develop lymphadenopathy and splenomegaly and suffer from autoimmune disease. The lpr mice have a defect in a cell-surface receptor, Fas, that mediates apoptosis, while gld mice have a mutation in the Fas ligand (FasL). Northern hybridization with the FasL cDNA as probe indicated that the cells accumulating in lpr and gld mice abundantly express the FasL mRNA without stimulation. By means of in situ hybridization and immunohistochemistry, we identified the cells expressing the FasL mRNA as CD4-CD8- double negative T cells. The T cells from lpr mice were specifically cytotoxic against Fas-expressing cells. Since FasL is normally expressed in activated mature T cells these results indicate that the double negative T cells accumulating in lpr and gld mice are activated once, and support the notion that the Fas/FasL system is involved in activation-induced suicide of T cells. Furthermore, the graft-versus host disease caused by transfer of lpr bone marrow to wild-type mice can be explained by the constitutive expression of the FasL in lpr-derived T cells.

Animals↗

Mild emphysema: a novel method using formalin-fixed lungs for computed tomography and pathological analyses.

We evaluated a novel method of computed tomography (CT) analysis using formalin-fixed lungs of autopsy cases with mild emphysema. Eight formalin-inflated lungs (FILs) obtained at autopsy were examined using CT after draining off the formalin and air inflation with an air pump, and subjected to pathological study including pathological scoring of emphysema and microscopic image analysis (MIA). Satisfactory CT examination was carried out within 5 h of lung fixation. The mean alveolar area determined by MIA correlated highly with the lung volume (r = 0.845) and CT score (r = 0.722). This method is simple compared with conventional polyethylene glycol fixation for CT and enables CT examination of resected lungs without anxiety about biohazards, Mild emphysema can be detected by MIA.

Aged↗

Portal vein reconstruction using an internal jugular vein as a graft: report of a case.

We report the case of a 41-year-old man with pancreatic carcinoma invading the portal vein who was successfully treated by portal vein resection combined with pancreatoduodenectomy and reconstruction using an autointernal jugular vein. The internal jugular vein is an ideal graft for portal vein replacement because it has sufficient length, a well-matched diameter, and there is no venous insufficiency after unilateral resection. Nevertheless, this is the first report of portal vein reconstruction using the internal jugular vein as a graft.

Adenocarcinoma↗

Approach through the temporal horn of the lateral ventricle for clipping of large dorsal type basilar bifurcation aneurysms.

The authors describe an approach through the temporal horn of the lateral ventricle which proved to be useful for clipping of a large dorsal type basilar bifurcation aneurysms. It facilitates the preservation of the perforating arteries behind the aneurysm, because it gives sufficient working space to move the aneurysm dome. Furthermore this approach avoids many of the disadvantages of other approaches, especially the risk of iatrogenic injuries of the Sylvian or Labe's vein.

Aneurysm, Ruptured↗

Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced by HIV-1 gp120.

Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play a central role in inducing immunoregulatory disorders after HIV infection. The apoptotic death of normal human peripheral blood mononuclear cells was induced by priming with gp120 followed by stimulation with an anti-T cell receptor (TCR) antibody. Tumor necrosis factor-alpha produced by gp120-binding macrophages may be important to induce this cell death. Treatment of gp120-primed cells with an immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death, and this blocking effect of FK506 was concentration dependent. FK506 did not have any influence on cell growth and viability over the range of concentrations tested. These findings suggest that FK506 is a potentially useful drug in delaying the onset of AIDS after HIV infection.

Antiviral Agents↗

Molecular cloning and sequence determination of the peplomer protein gene of feline infectious peritonitis virus type I.

cDNA clones spanning the entire region of the peplomer (S) gene of feline infectious peritonitis virus (FIPV) type I strain KU-2 were obtained and their complete nucleotide sequences were determined. A long open reading frame (ORF) encoding 1464 amino acid residues was found in the gene, which was 12 residues longer than the ORF of the FIPV type II strain 79-1146. The sequences of FIPV type I and mainly -tPV type II were compared. The homologies at the N- (amino acid residues 1-693) and C- (residues 694-1464) terminal halves were 29.8 and 60.7%, respectively. This was much lower than that between FIPV type II and other antigenically related coronaviruses, such as transmissible gastroenteritis virus of swine and canine coronavirus. This supported the serological relatedness of the viruses and confirmed that the peplomer protein of FIPV type I has distinct structural features that differ from those of antigenically related viruses.

Amino Acid Sequence↗

Direct approach to intracranial vertebral arteriovenous fistula. Case report.

A case of intracranial vertebral arteriovenous fistula is reported. The treatment of choice for this particular vascular malformation is controversial because of the difficulty of management of the intracranial portion of the lesion. We here report a case treated successfully by direct surgery. Its anatomical delineation and operative approach are discussed.

Adult↗

Abnormal arachidonate distribution in low-density lipoprotein and thoracic aorta in hyperinsulinemia.

The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension (20 U/kg) for 12 weeks. After this period, body mass and food consumption did not differ significantly between control and insulin-treated animals. Daily insulin injection significantly increased urinary excretion of epinephrine and decreased urinary excretion of norepinephrine and dopamine, but had no significant effect on blood pressure or heart rate. Although insulin decreased plasma triglyceride concentration by 44% (P < .01), the triglyceride to protein ratio in plasma low-density lipoprotein (LDL) was increased by 34% (P < .05) in insulin-treated rats; the cholesterol to protein and triglyceride to protein ratios remained unaffected, indicating a change in the quality of the LDL particle. Insulin also increased the percentage of arachidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contrast, cholesteryl esters and triglycerides in the thoracic aorta were significantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and decreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmitoleic acid (16:1) and decreased the percentages of saturated fatty acids and n-6 fatty acids in aortic cholesteryl esters. These results indicate that insulin induced deposition of cholesteryl esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data further suggest that the development of atherosclerosis in response to hyperinsulinemia may be associated with arachidonate-rich triglycerides in LDL.

Animals↗

Expression of CYP3A7, a human fetus-specific cytochrome P450, in cultured cells and in the hepatocytes of p53-knockout mice.

CYP3A7 is a major form of cytochrome P450 in human fetal livers. To elucidate toxicological significance of CYP3A7 in fetal livers, CYP3A7 cDNA was introduced into Chinese hamster lung (CHL) cells. Transformants carrying the CYP3A7 gene were more sensitive to mycotoxins than parental CHL cells. In additional studies, we established a hepatocyte cell line from CYP3A7-transgenic/p53-knockout mice. In hepatocyte cells from CYP3A7-transgenic/p53-knockout mice, CYP3A7 mRNA was expressed and the catalytic activity of CYP3A7 protein was detected. The cells are expected to show cytotoxicity to mycotoxins and teratogens. These cell lines provide a valuable panel for studying the fetal toxicities of chemicals in humans.

Animals↗

Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease.

We observed the sequential changes in serum thyroid hormones and thyroid-stimulating hormone receptor antibodies in an infant born at 30 weeks of gestation to a mother with florid Graves disease. Transient central hypothyroidism caused by pituitary suppression was observed after the resolution of peripheral thyrotoxicosis induced by thyroid-stimulating antibody. Central hypothyroidism became overt when the suppression of the pituitary gland after fetal thyrotoxicosis was combined with weak activity of thyroid-stimulating antibody after birth.

Adult↗