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Biomedical subjects

N Inoue

Publications and source records attributed to N Inoue.

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

Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells.

A major determinant of the level of cellular superoxide anion (O2-.) is the dismutation of O2-. to hydrogen peroxide by the enzyme superoxide dismutase (SOD). Three forms of SOD exist, but in endothelial cells, the major form outside of the mitochondria is the cytosolic copper/zinc-containing superoxide dismutase (Cu/Zn SOD). Since fluid shear stress is an important determinant of the function and structure of endothelial cells in vivo, we examined the effect of laminar shear stress on the expression of Cu/Zn SOD in cultured human aortic endothelial cells. Laminar shear stress of 0.6 to 15 dyne/cm2 increased Cu/Zn SOD mRNA in a time- and dose-dependent manner in human aortic endothelial cells. Shear stress also increased both Cu/Zn SOD protein content and the enzyme activity. Nuclear runon assays showed that nuclei from human aortic endothelial cells exposed to laminar shear stress had a 1.6-fold greater transcriptional activity of the Cu/Zn SOD gene compared with cells not exposed to shear, indicating that an increase in Cu/Zn SOD mRNA induced by laminar shear stress is at least in part mediated by increased transcription. In contrast, shear stress had no effect on Cu/Zn SOD mRNA levels in human aortic smooth muscle cells. These findings show that physiological levels of shear stress increase expression of Cu/Zn SOD in the endothelium. This adaptation to shear stress might augment the effect of locally produced NO. and thereby promote the antiatherogenic and anti-inflammatory properties of the endothelial cell.

Aorta↗
PubMed1996

Effect of mizoribine on effector T cell-mediated immune responses in mice.

T cells play a principal role in cellular immunity and govern the regulatory mechanism in humoral immunity. Therefore, T cells play a key role as either effectors or regulators in the immune network. Mizoribine (MZR), an immunosuppressive agent, suppresses both humoral and cellular immunity by acting on both T cells and B cells. In this study, we examined the effect of MZR on various effector T cell-mediated immune responses in mice. MZR prolonged skin graft survival and suppressed a localized graft-versus-host reaction (GvHR) and sheep red blood cell (SRBC)-induced delayed-type hypersensitivity (DTH) reaction. In a collagen-induced arthritic mice model, MZR reduced the arthritic index and the swelling of the hind limbs. Furthermore, MZR suppressed both bone damage and histopathological changes in the hind limbs. Interestingly, MZR markedly suppressed the DTH reaction to type II collagen (CII) but had no effect on anti-CII antibody levels in this arthritic model. In these models, effector T cells such as cytotoxic T lymphocyte (CTL) and TDTH cell play an important part in the development of these reactions. It is suggested that MZR inhibited these reactions via the inhibition of the effector T cell-mediated immune response. Therefore, it is also suggested that the suppressive effect of MZR on clinical rejection and autoimmune disease is based on its suppression of the effector T cell-mediated immune response, that is cellular immunity, in addition to humoral immunity.

Animals↗
PubMed1996

Modulation of endothelial cell nitric oxide synthase expression.

The 5' promoter region of endothelial cell nitric oxide synthase (ecNOS) gene has several features which are compatible with a constitutively expressed, so called "housekeeping" gene. These include absence of a TATA box and the presence of Sp1 binding sites situated near the transcription start site. The promoter also contains sequences which suggest that it may be regulated by a variety of transcription factor-mediated signals. Studies of cultured endothelial cells show that ecNOS expression is modulated by shear stress, transforming growth factor beta, inhibition of protein kinase C, and the state of proliferation. These experiments indicate that although the ecNOS is a "constitutively expressed" gene, its content in the endothelium is subject to modest degrees of regulation which may have important physiological and pathophysiological implications.

Animals↗
PubMed1996

Possible involvement of the total amount of morphine infused in the development of acute morphine dependence in rats.

The severity of naloxone-precipitated withdrawal in rats infused intravenously with morphine at the rates of 2.5, 5 and 10 mg/kg/hr over various time periods was investigated. Plasma morphine concentration reached a constant and rate-dependent level at 1 hr after the start of morphine infusion, and this level was maintained until the termination of infusion. Naloxone (2.0 mg/kg, s.c.) was challenged 18 hr after infusion was stopped, and the withdrawal was evaluated by plasma corticosterone (PCS) increase, diarrhea and body weight loss. The incidence of naloxone-precipitated withdrawal signs was related to both the infusion rate and duration of morphine infusion. The duration of morphine infusion (ET50) needed to elicit naloxone-precipitated PCS increase and diarrhea in 50% of the rats was inversely related to the morphine infusion rates, but the total amount of infused morphine (EA50) that elicited naloxone-precipitated withdrawals in 50% of rats was the same at all infusion rates. These results suggest that the total amount of morphine infused may play an important role in the development of acute physical dependence on morphine rendered by continuous intravenous morphine infusion for 1-8 hr.

Acute Disease↗
PubMed1996

Chronic toxicity of indium arsenide and indium phosphide to the lungs of hamsters.

Chronic toxicity of indium arsenide (InAs) and indium phosphide (InP) was studied in male Syrian golden hamsters which received InAs or InP particles containing a total dose of 7.5 mg of arsenic or phosphorus by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total life span, the cumulative body weight gain of hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the InP group when compared with that in the control group. Concerning the histopathological findings of the lung, the incidence rates of proteinosis-like lesions, alveolar or bronchiolar cell hyperplasia, pneumonia, emphysema and metaplastic ossification observed in the InAs or InP group were significantly higher than those observed in the control group. From these results, it would seem that InAs and InP produced severe damage to the lungs of hamsters.

Animals↗
PubMed1996

Alterations of hepatic drug metabolising system due to dimethylformamide (DMF).

The effect of repeated exposures to N, N-dimethylformamide (DMF) on the liver and the hepatic microsomal monooxygenase system and glutathione metabolizing enzymes were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 1.0 ml/kg body weight (950 mg/kg), 3 times a week for 2 weeks. The gain in the body weight in the DMF group were suppressed compared with the control group at 2 week. The relative weight of the liver, spleen and kidney also appeared to increase in the DMF group as same as in the control group. Hematological examinations showed no changes. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) did not change in the DMF group. Hepatic microsomal protein and cytochrome P-450 did significantly decrease by 30% and 38%, respectively, while there was no change in cytochrome b5, NADPH-cytochrome c reductase and NADH-ferricyanide reductase. Glutathione peroxidase (GPx) activity was not affected by DMF administration, while glutathione reductase (GR) and glutathione S-transferase, (GST) activity were significantly increased by 16% and 64%, respectively. These results indicate that DMF alters tke hepatic drug metabolizing system without significant increase of the serum transaminase levels. These findings may contribute to elucidate the mechanism of DMF hepatotoxicity.

Animals↗
PubMed1996

Development of a canine chemotherapeutic model with ifosfamide.

The purpose of this study was to develop a canine experimental model for neoadjuvant chemotherapy of primary bone tumors with ifosfamide, which is safe and clinically relevant for use in human beings with bone tumors. Our study was divided into two steps, each with four dogs. In the first step ifosfamide was administered for 4 consecutive days in three cycles with 3-week intervals between each cycle. For this first step a daily dosage of 300 mg/m2 of body surface resulted in only moderate leukopenia, whereas a daily dosage of 450 mg/m2 caused severe leukopenia. Therefore, to determine the maximal dose tolerable and to verify the results from step 1, we administered the higher daily dosage of 450 mg/m2 in step 2 for four successive cycles with 3-week intervals. In each step one dog died acutely after the first cycle of chemotherapy. In addition during step 2 one dog died of overwhelming sepsis after the second cycle of ifosfamide. The remaining five dogs survived without other appreciable laboratory abnormalities. Neither hematuria nor proteinuria was observed throughout the course of study, and relevant findings were not observed at autopsy. We determined that 450 mg/m2 was the maximal tolerated dosage of ifosfamide for our regimen, with the dose-limiting factor being myelosuppression, specifically leukopenia. Using this canine model, we can estimate the effect of ifosfamide on bone graft incorporations and the fixation of biologic prostheses that is clinically the most important aspect of limb salvage surgery.

Animals↗
PubMed1996

[Immunoglobulin heavy chain variable region(VH) genes in B cell clones producing anti-colon antibodies in ulcerative colitis].

We have established anti-colon antibodies producing B cell clones from the patient with ulcerative colitis, and analyzed the immunoglobulin heavy chain variable region (VH) gene segments of these clones using RT-PCR with VH family specific primers. VH3 family was used by all ten clones from ulcerative colitis that produced anti-colon antibodies, while various VH gene families were used by eight clones from normal controls. By nucleotide sequence analysis, two LPL clones were thought to be derived from a germ line gene segment, VH26. However, other three PBL clones were derived from 22-2B, 9-1 and 1.9-III, respectively. These results suggest the heterogeneity of the colonic antigens that autoantibodies in ulcerative colitis recognize.

Antibody-Producing Cells↗
PubMed1996

[Intraventricular arachnoid cyst--on the origin of intraventricular arachnoid cysts].

Arachnoid cysts very rarely occur within the ventricular system, where no arachnoid tissue exists. We present three cases of intraventricular arachnoid cyst with special reference to its origin. The first patient was a 5-year-old boy who complained of headaches and enlargement of his head. A CT scan revealed obstructive hydrocephalus and a large cystic lesion in the right lateral ventricle. The symptoms resolved after fenestration of the cyst and cystoperitoneal shunt. The second patient was a 49-year-old woman who complained of headache and numbness in her left upper extremity. A CT scan and MRI revealed a large cyst in the trigone of the right lateral ventricle. Fenestration of the cyst wall and cystoperitoneal shunt were performed relieving her complaints. The third patient was a 42-year-old man who complained of frequent seizures and dizziness. A CT scan and MRI demonstrated a moderate size cystic mass in the inferior horn of the right lateral ventricle. The symptoms were improved by partial resection of the cyst wall. Immunohistochemical studies and light microscopy confirmed that the cyst walls were composed of arachnoid membrane, implying that the cysts were arachnoid cysts. CT and MRI in these three cases showed widening of the choroidal fissure bordering the cyst wall, occasionally involving a part of the protruding cyst wall. On enhanced CT and MRI, the choroid plexus in the trigone of ipsilateral lateral ventricle was displaced anterolaterally, implying that the cysts had grown from outside the choroid plexus. Postoperative MRI demonstrated the shrunken cyst wall attached to the choroidal fissure. The surgical findings in case 3 also showed that the cyst wall was attached firmly to the choroid plexus. These findings appeared to indicate that the intraventricular arachnoid cyst originated from the arachnoid layer drawn into the choroidal fissure with choroidal vascular mesenchyme.

Adult↗
PubMed1995

Analysis of cis-acting regions upstream of the rat Na+/K(+)-ATPase alpha 1 subunit gene by in vivo footprinting.

By means of in vivo footprinting, we examined the putative cis-acting DNA elements located between -50 and -122 of rat Na+/K(+)-ATPase alpha 1 subunit gene ATP1A1. Proximal and distal GC box sequences and a consensus sequence for the active transcription factor (ATF) were protected for all the tissues examined (kidney, brain and liver). Putative cooperation between two binding factors on the ATF site and the proximal GC box was observed. The overall in vivo footprinting profiles of the three tissues did not exhibit any marked differences that could account for the variation in the extent of tissue-specific transcription. The alpha 1 regulatory element (ARE) found by Suzuki-Yagawa et al. does not appear to be an element responsible for tissue-specific regulation of the gene.

Animals↗
PubMed1995

Structure and chromosomal localization of the GPI-anchor synthesis gene PIGF and its pseudogene psi PIGF.

Posttranslational modification by the GPI glycolipid anchor is essential for the surface expression of many membrane proteins. Defect of GPI biosynthesis due to somatic mutation in the hematopoietic stem cell is the basis for an acquired genetic disease, paroxysmal nocturnal hemoglobinuria (PNH). Previously, an X-linked gene PIGA (phosphatidylinositol glycan class A), which participates in the first step of the biosynthesis, was shown to be mutated in abnormal cells from all 60 patients with PNH. The cDNA of another GPI synthesis gene PIGF was previously cloned, but it is not involved in pathogenesis of PNH. In the present study, we have analyzed PIGF genomic clones. The PIGF gene contained six exons spanning about 40 kb and was located to the short arm of chromosome 2 at 2p16-p21. The frequency of mutations on both alleles of PIGF should be much lower than that of mutation in the X-linked PIGA, accounting for a lack of involvement of PIGF in PNH. We also identified the processed pseudogene of PIGF (psi PIGF) and mapped it to 5q35.

Base Sequence↗
PubMed1995

Reduction of masseter muscle activity in bottle-fed babies.

Our previous studies suggested that there are significant differences in the growth of the jaw and in muscle activity between breast- and bottle-fed infants. To confirm these differences quantitatively, myoelectric activities of the masseter muscles of bottle-fed babies were studied. Twelve bottle-fed babies, as well as 12 breast-fed babies as a control group, were examined electromyographically during bottle or breast feeds. The duration time of sucking bursts, interval time, cycle time, 0-to-peak amplitude, integrated amplitude of bursts, and integrated amplitude/duration time were measured and the number of bursts over 30 microV was counted. All differences of means were significant by t-test. The masseter muscle activity in bottle-fed babies is significantly reduced. Our results are contrary to previous papers in which almost the same sucking actions in both breast and bottle feeding were reported. The reason why previous researchers thought that the sucking patterns in breast- and bottle-fed babies are essentially the same is considered, and the implications of the differences for dental health are discussed.

Bottle Feeding↗
PubMed1995

An assay method for nitric oxide synthase in crude samples by determining product NADP.

An assay method for nitric oxide synthase (NOS) was developed based on fluorometric or enzymatic determination of NADP+. An aliquot (< or = 2 microliters) of crude enzyme sample, homogenate or supernatant of rat cerebellum, was added to a reaction mixture containing arginine, NADPH, and O2 and incubated at 25 degrees C for 30 min. A strongly fluorescent substance was formed from a product, NADP+, and measured (fluorometric assay). When rat cerebellar layers were assayed, freeze-dried sections of layers (0.2 to 2 micrograms dry wt) were added directly into 1.24 microliters of NOS reaction mixture and the total NADP+ formed in picomole amounts was specifically amplified up to 4000-fold and determined, using an enzymatic NADP cycling amplification reaction (enzymatic-cycling assay). NOS activity was calculated as the difference in NADP+-forming activity in the absence and presence in the reaction mixture of NG-nitro-L-arginine, a specific inhibitor of NOS. Enzymatic activity was analyzed in rat cerebellar supernatants by two procedures. With supernatants (and purified macrophage NOS), the ratio between the specific activities on a protein basis using the present NADP+ formation assay and using [3H]citrulline formation from [3H]arginine as substrate was 2. The distribution of NOS activity was shown between the particulate and supernatant fractions of rat cerebellum. The molecular and granular layers of rat cerebellum contained similar NOS activities, while the activity in the white matter was negligibly low. NOS distribution is also reported among rat organs.

Animals↗
PubMed1995

Effects of creatine and beta-guanidinopropionic acid on the growth of Ehrlich ascites tumor cells: i.p. injection and culture study.

Growth of Ehrlich ascites tumor (EAT) cells in the abdominal space of mice or in cell culture was studied in response to i.p. injection or addition, respectively, of creatine or creatine analogue beta-guanidinopropionic acid (beta-GPA). The increase in body weight of the mice due to cancer growth was less in the beta-GPA-injected than in the creatine- or sham-injected group. The volume of abdominal ascites and total cell counts at 11th day after implantation of EAT cells was significantly less in the beta-GPA than in the other groups. The proliferation rate of EAT cells in the beta-GPA group was 27% and 35% of the creatine- and sham-injected groups, respectively. Supplementation of creatine tended to enhance the growth of EAT cells. The creatine concentration in ascites fluid was approximately 4-times greater than in blood plasma of sham-injected control mice. But the creatine content in EAT cells was significantly reduced to approximately 50% in response to beta-GPA injection. Cell culture without creatine caused a significant decrease in viability. The viability was improved, however, by addition of either creatine or serum into the medium. By contrast, it was not significantly increased by addition of serum alone which caused only a minor elevation of the creatine level (23 microM). It is suggested that EAT cell growth is inhibited by lowering the availability of creatine in association with some unknown factors in serum or ascites fluid.

Abdomen↗
PubMed1995

Change of phosphotyrosine immunoreactivity on microglia in the rat substantia nigra following striatal ischemic injury.

Using immunohistochemistry, we investigated changes in phosphotyrosine (P-Tyr) immunoreactivity on the microglia of the rat substantia nigra (SN) following striatal ischemic injury produced by transient middle cerebral artery (MCA) occlusion. Anterograde axonal degeneration in the SN due to striatal ischemic injury was detected by depletion of calcineurin immunoreactivity in that region from 1 day after operation. From 3 days to 1 month (the longest period examined in this study) after MCA occlusion, there was a significant increase in P-Tyr immunoreactivity in the SN ipsilateral to the MCA occlusion. Also, light microscopic observation showed that the microglia exhibited an increased immunoreactivity for P-Tyr and characteristic morphological changes in the ipsilateral SN. The present results indicate that a signal transducing cascade(s) associated with tyrosine phosphorylation may be involved in the activation of the microglia in the SN responding to anterograde degeneration of the striatonigral pathway.

Animals↗
PubMed1995

The endothelial cell nitric oxide synthase: is it really constitutively expressed?

During the past two years, the enzyme responsible for production of endothelium-derived nitric oxide, the endothelial cell NO synthase (ecNOS) has been cloned and the gene encoding this enzyme isolated, cloned and its structure characterized. This research has provided direction for a variety of studies of regulation of the ecNOS. Several features of the ecNOS are compatible with a constitutively expressed, poorly regulated gene, including absence of a TATA box and numerous SP-1 sites. The promoter also contains a number of putative binding domains which suggest that it may be regulated by a variety of transcription factor mediated signals. In this review we will discuss evidence to support the concept that the ecNOS is a constitutively expressed gene subject to a modest degree of regulation by important physiological influences.

Amino Acid Oxidoreductases↗