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Biomedical subjects

M Kishi

Publications and source records attributed to M Kishi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Role of neutrophils in xanthine/xanthine oxidase-induced oxidant injury in isolated rabbit lungs.

Reactive oxygen species have been shown to play an important role in the pathogenesis of lung injury. This study was designed to clarify the role of intrapulmonary neutrophils in the development of xanthine/xanthine oxidase (X/XO)-induced lung injury in isolated buffer-perfused rabbit lungs. We measured microvascular fluid filtration coefficient (K(f)) and wet-to-dry weight ratio to assess lung injury. X/XO induced a significant increase in K(f) and wet-to-dry weight ratio in neutrophil-replete lungs, whereas the lung injury was attenuated in neutrophil-depleted lungs. A neutrophil elastase inhibitor, ONO-5046, also attenuated the lung injury. In addition, X/XO induced a transient pulmonary arterial pressure (P(pa)) increase. The thromboxane inhibitor OKY-046 attenuated the P(pa) increase but did not alter the increase in permeability. Neutrophil depletion reduced the K(f) increase but had no effect on the P(pa) increase. These results suggest that intrapulmonary neutrophils activated by X/XO play a major role in development of the lung injury, that neutrophil elastase is involved in the injury, and that the X/XO-induced vasoconstriction is independent of intrapulmonary neutrophils.

Animals↗
PubMed1999

Regulation of the mouse preprothyrotropin-releasing hormone gene by retinoic acid receptor.

Retinoic acid (RA) has been reported to inhibit the secretion and synthesis of the pituitary TSH in vivo and in vitro. However, little is known about the influence of RA on the expression of the prepro-TRH gene. We therefore investigated whether the promoter activity of the mouse TRH gene is directly regulated by RA using a transient transfection assay into CV-1 cells. In the absence of cotransfected RA receptor (RAR), all-trans-RA did not affect the promoter activity. In contrast, the cotransfected RARalpha significantly stimulated promoter activity in the absence of ligand, and all-trans-RA reversed basal promoter activation. The cotransfected thyroid hormone receptor-beta (TRbeta), but not 9-cis-RA receptor (RXR), had an additive effect on the RAR-dependent stimulation. TR and RAR can similarly interact with the corepressor proteins, and the cotransfected nuclear receptor corepressor (N-CoR) has been demonstrated to augment the transcriptional stimulation of the TRH gene by unliganded TR. As observed with TR, the coexpression of a N-CoR variant significantly enhanced the ligand-independent stimulation by RAR. A mutant RAR (RAR403) lacking the C-terminal activation function-2 (AF-2) activation domain that was essential for ligand-induced corepressor release constitutively stimulated the promoter activity. The constitutive stimulation by RAR403 was augmented by the cotransfected N-CoR variant. A deletion analysis of the 5'-flanking region of the TRH gene revealed that the minimal promoter region for the regulation by RAR was -83 to +53, with a consensus half-site motif for the thyroid hormone response element at -57. In contrast to the strong binding of TR to the thyroid hormone response element half-site in gel retardation assays, no binding of RAR homodimer, RAR/ RXR heterodimer, or RAR/TR heterodimer was observed to the minimal promoter region. These results collectively suggest that RAR without heterodimerization with RXR and TR regulates transcription of the mouse TRH gene in cooperation with the corepressor, and that the DNA binding of RAR appeared to be unnecessary for regulation of the TRH gene promoter.

Animals↗
PubMed1999

p120 acts as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers.

p120 was originally isolated as a novel nuclear co-activator for thyroid hormone receptor. In this study, we characterized its interaction and transactivation of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 9-cis-retinoic acid receptor (RXR) heterodimers. Transient transfection study revealed that p120 enhanced the transcriptional activation of PPARgamma/RXR induced by PPARgamma- or RXR-specific ligands. In the glutathione-S-transferase pull-down assay, while steroid receptor coactivator-1 showed apparent interactions with both RXR and PPARgamma, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPARgamma even in the presence of thiazolidinediones. The yeast two-hybrid analysis showed no interaction of p120 with PPARgamma under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPARgamma/RXR/p120 complex formation only in the presence of 9-cis-RA. Furthermore, the yeast three-hybrid assay clearly revealed a significant interaction between p120 and PPARgamma via RXR of PPARgamma/RXR heterodimer only in the presence of 9-cis-RA. These findings indicate that p120 acts as a specific co-activator for the RXR of PPARgamma/RXR heterodimer in a 9-cis-RA-dependent manner.

Adipose Tissue↗
PubMed1999

Synergistic effect of naphthoquinones on the mutagenicity of nitroarene.

Nitro reduction is a critical step in the mutagenic activation of nitroarene. Nitroarene and quinone are known to be reduced by common enzymes, and thus, naphthoquinone (NQ) was studied for its effects on the mutagenicity of nitroarene in the Ames test using Salmonella typhimurium TA98 without S9. The mutagenicity of 1,3-dinitropyrene in TA98 was found to increase 9- and 6-fold as much in the presence of 70 nmol/plate of 2-methyl-1,4-NQ and 2-hydroxy-1,4-NQ, respectively. Mutagenicity also became greater in 1,3,5-trinitronaphthalene, 1-nitropyrene and 3-nitrofluoranthene. Seventy nmol/plate of 2-methyl-1,4-NQ increased the mutagenicity of 1-nitropyrene by 10.5-fold as much.

Drug Synergism↗
PubMed1999

Enhancing effect of dietary vinegar on the intestinal absorption of calcium in ovariectomized rats.

We studied the effect of dietary vinegar on calcium absorption by using ovariectomized rats fed on a low-calcium diet. The apparent absorption of calcium was higher when the rats were fed on a diet containing 1.6% vinegar for 32 days than when fed on a diet without vinegar (P < 0.05). The calcium content in the femur of the rats given diets containing 0.4% and 1.6% vinegar were also higher (P < 0.05). The serum parathyroid hormone level was lower and the crypt depth of the duodenum thicker in the rats fed on a diet containing 1.6% vinegar (P < 0.05). These results suggest that dietary vinegar enhanced intestinal calcium absorption by improving calcium solubility and by the trophic effect of the acetic acid contained in vinegar, which would reduce the bone turnover caused by ovariectomy and be helpful in preventing osteoporosis.

Acetic Acid↗
PubMed1999

[Disappearance of Mallory bodies in the liver of autopsy cases with a history of heavy drinking].

Mallory bodies, the intra-cytoplasmic inclusions in hepatocytes, are thought to be a pathognomonic feature of alcoholic liver disease, particularly of alcoholic hepatitis. The presence of Mallory bodies is considered as a reflection of serious illness in alcoholic liver disease. Mallory bodies are thought to disappear relatively rapidly with the use of therapeutic agents after giving up alcohol drinking. However, histological vicissitudes of Mallory bodies have not been studied extensively. In the present study, 19 autopsied cases with a history of heavy drinking were clinicopathologically evaluated. All patients were admitted to our hospital, and stopped alcohol drinking. These period of non-drinking ranged from one day to 150 days (group A: 1-7 days, group B: 8-30 days, group C: 31-150 days). Histological evaluation was performed by hematoxylin and eosin staining, Luxol Fast blue staining and chromotrope aniline blue staining of formalin-fixed paraffin-embedded liver sections. Hepatocytes including Mallory bodies were counted. The incidence of Mallory body formation was as follows: Group A (50%), group B (100%), and group C (100%) respectively. Average count of Mallory bodies: Group A (12.3/10 fields), group B (141.4/10 fields), and group C (188.3/10 fields). Fatty change was more significant in group A than in group B or C, and bile stasis was more significant in group B or C than in group A. These findings suggest that Mallory bodies may remain for several months after giving up drinking.

Adult↗
PubMed1999

Mechanisms of action of OPC-28326, a selective hindlimb vasodilator.

The unique cardiovascular profile of OPC-28326 [4-(N-methyl-2-phenylethylamino)-1-(3, 5-dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride monohydrate] provides insight into basic mechanisms of this new drug as determined by experiments in dogs and rats. In anesthetized open-chest dogs, an i.v. administration of a low dose (0.3 and 1.0 microg/kg) of OPC-28326 selectively increased femoral artery blood flow with only minimal action on systemic blood pressure, heart rate and coronary, carotid, vertebral, renal, and mesenteric blood flows. Biochemical study suggests that OPC-28326 had no effect on phosphodiesterase-3 and -5. OPC-28326 dose-dependently inhibited phenylephrine-induced increases in blood pressure in spinally anesthetized dogs. The potency of OPC-28326 was, however, about 180 times lower than that of prazosin. Although binding studies have revealed an affinity of OPC-28326 to serotonin 5-HT(2) receptors, the drug is without effect, except at very high concentrations, on serotonin-induced contraction in an isolated canine femoral artery preparation. The potency of OPC-28326 on the increase in femoral artery blood flow was about 14 times higher than that of prazosin but was at about the same level as that obtained with yohimbine in canine autoperfused femoral artery preparations. In perfused rat hindlimb preparations, OPC-28326 inhibited the decrease in perfusion flow induced by brimonidine, a selective alpha(2)-adrenoceptor agonist. The potency of OPC-28326 was at least 10 times less than that of yohimbine. Taken together, the results show that at low doses, OPC-28326 selectively exerts a potent vasodilating effect on the femoral arterial bed, in part due to an alpha(2)-adrenoceptor-blocking activity.

Adrenergic Antagonists↗
PubMed1998

A novel homeobox gene, dharma, can induce the organizer in a non-cell-autonomous manner.

The formation of Spemann organizer is one of the most important steps in dorsoventral axis determination in vertebrate development. However, whether the organizer forms autonomously or is induced non-cell-autonomously is controversial. In this report we have isolated a novel zebrafish homeobox gene, dharma, capable of inducing the organizer ectopically. The expression of dharma was first detected in several blastomeres at one side of the margin soon after the mid-blastula transition and continued in the dorsal side of the yolk syncytial layer (YSL) under the embryonic shield, the zebrafish organizer, until the onset of gastrulation. Furthermore, dharma expressed in the YSL induced the organizer in a non-cell-autonomous manner. These results provided the first identification of a zygotic gene to be implicated in the formation of an organizer-inducing center.

Amino Acid Sequence↗
PubMed1998

Nonadrenergic, noncholinergic relaxation mediated by nitric oxide with concomitant change in Ca2+ level in rectal circular muscle of rats.

The mediators of nonadrenergic, noncholinergic (NANC) relaxation of the circular muscle of rat rectum were examined in vitro. In the circular muscle of rat rectum, NG-nitro-L-arginine (L-NOARG) at 10 microM did not affect electrical field stimulation-induced relaxation but at 100 microM it inhibited electrical field stimulation-induced relaxation by about 75% and 1-mM L-arginine reversed the inhibition. Exogenous nitric oxide (NO) (1-10 microM) concentration dependently relaxed the circular muscle. Electrical field stimulation increased the cyclic GMP content of the circular muscle to about twice its resting level. L-NOARG, even at 10 microM, completely inhibited the electrical field stimulation-induced elevation of cyclic GMP content. However, L-arginine at 1 mM did not reverse the inhibition in cyclic GMP content. Inhibitory junction potentials (i.j.ps) induced by electrical field stimulation in the circular muscle cells were not affected by L-NOARG, 100 microM. Apamin ( < or = microM) did not affect the electrical field stimulation-induced relaxation, but almost completely inhibited electrical field stimulation-induced i.j.ps. NO (0.3-10 microM) induced relaxation of the circular muscle with a concomitant decrease in intracellular Ca2+ level ([Ca2+]i). Abundant immunoreactivity of NO synthase was found in the circular muscle layer, in addition to myenteric and submucosal plexus. The results suggest that NO induces NANC relaxation with a concomitant change in [Ca2+]i in the circular muscle of rat rectum. However, the involvement of changes in cyclic GMP level and in membrane potentials in the mechanism was not shown in the present experimental conditions.

Animals↗
PubMed1998

Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein.

The Borna disease virus (BDV) replicates in the nucleus. The viral p40 protein (N), which is found abundantly in the nucleus in BDV-infected cells, may play an important role in virus replication. To analyze the amino acid residues involved in the nuclear targeting of BDV N, a series of eukaryotic expression plasmids encoding deletion mutants of N was constructed and transfected into COS-7 cells. In indirect immunofluorescence assays with a rabbit anti-BDV N antiserum, wild-type N was located in the nucleus of transfected cells in the absence of other viral constituents. In contrast, mutants lacking the 13 NH2-terminal amino acid residues 1MPPKRRLVDDADA13 in common gave a cytoplasmic localization pattern. Similarly, a mutant with substitution of 4KRR6 by 4NSG6 was retained in the cytoplasm. Furthermore, a nonapeptide, 3PKRRLVDDA11, derived from the NH2-terminal region of N conferred nuclear targeting activity to beta-galactosidase, which normally resides in the cytoplasm. Thus, we have identified the nuclear targeting signal of the BDV N and narrowed it to the NH2-terminal region where 4KRR6 basic amino acid residues are located.

Animals↗
PubMed1998

SoxD: an essential mediator of induction of anterior neural tissues in Xenopus embryos.

Vertebrate neurogenesis is initiated by the organizer factors that inhibit antineuralizing activities of bone morphogenetic proteins (BMPs) in the ectoderm. Here, we report a candidate mediator of neuralization, SoxD. Expression of SoxD starts at late blastula stages widely in the prospective ectoderm and becomes restricted to the dorsal ectoderm by mid-gastrula stages. SoxD expression is enhanced by the neural inducer Chordin and is suppressed by BMP4 and its downstream genes. Microinjection of SoxD mRNA causes ectopic formation of neural tissues in vivo and induces neural and neuronal markers in the isolated animal cap. Injection of a dominant-negative form of SoxD mRNA can block neuralization of ectoderm caused by attenuation of BMP signals and can strongly suppress formation of anterior neural tissues in vivo. These data show that SoxD functions as an essential mediator of downstream signaling of neural induction.

Amino Acid Sequence↗
PubMed1998

A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome inherited as an autosomal dominant trait. Various heterozygous germline mutations of the responsible gene, MEN1, have been identified within its exons in many, but not all, affected individuals. We here demonstrate, by DNA polymorphism analysis and gene dosage analysis with polymerase chain reaction (PCR), a large heterozygous germline MEN1 deletion in a kindred with MEN1, in whom no mutation could be detected in the PCR-amplified exons. The deletion spanned an at least 7 kb region containing the entire MEN1 gene. These findings indicate that a large germline deletion of the MEN1 gene, which escapes detection in PCR-based sequence analysis, should be considered as a potential cause of MEN1.

Chromosome Deletion↗
PubMed1998

Two proline-rich nuclear localization signals in the amino- and carboxyl-terminal regions of the Borna disease virus phosphoprotein.

Borna disease virus (BDV) uses a unique strategy of replication and transcription which takes place in the nucleus, unlike other known, nonsegmented, negative-stranded RNA viruses of animal origin. In this process, viral constituents necessary for replication must be transported to the nucleus from the cytoplasm. We report here the evidence that BDV P protein, which may play an important role in viral replication and transcription, is transported into the nucleus in the absence of other viral constituents. This transportation is accomplished by its own nuclear localization signals (NLSs), which are present in both N-terminal (29PRPRKIPR36) and C-terminal (181PPRIYPQLPSAPT193) regions of the protein. These two NLSs can function independently and both have several Pro residues as key amino acids.

Amino Acid Sequence↗
PubMed1998

Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia.

Leukocytes have been shown to contribute to ischemia-reperfusion injury in skeletal muscle. Pentoxifylline (PTXF), a xanthine-derived phosphodiesterase inhibitor, has received recent attention because of its action on leukocytes. To clarify the effects of PTXF in reperfusion injury, we measured the resting transmembrane potential difference (Em) and evaluated postcapillary venule microcirculation using intravital microscopy in rat skeletal muscle during ischemia and reperfusion. The infrarenal aorta was clamped for 90 min and then reperfused for 60 min. Persistent depolarization of the resting Em was observed in an ischemia-reperfusion (IR) group and was significantly repolarized in a PTXF group during the reperfusion period. The tissue water content was significantly reduced in the PTXF group, although no difference was noted in the tissue lactate content. Flowing erythrocyte velocity and wall shear rate in the PTXF group were significantly higher than in the IR group during the reperfusion period but without significant differences in vessel diameter and hemoglobin oxygenation. Blood flow measured by laser-Doppler flowmeter was also significantly improved in the PTXF group. Furthermore, the adherent leukocyte count was significantly reduced in the PTXF group during this same period. These results indicate that PTXF attenuated reperfusion-associated membrane injury and tissue edema and that PTXF suppressed leukocyte adhesion and improved hindlimb blood flow during the reperfusion period.

Animals↗
PubMed1998

Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction.

In a differential screen for downstream genes of the neural inducers, we identified two extremely early neural genes induced by Chordin and suppressed by BMP-4: Zic-related-1 (Zic-r1), a zinc finger factor related to the Drosophila pair-rule gene odd-paired, and Sox-2, a Sry-related HMG factor. Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation, following the onset of Chordin expression and preceding that of Neurogenin (Xngnr-1). Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. In contrast, Sox-2 alone is not sufficient to cause neural differentiation, but can work synergistically with FGF signaling to initiate neural induction. Thus, Zic-r1 acts in the pathway bridging the neural inducer with the downstream proneural genes, while Sox-2 makes the ectoderm responsive to extracellular signals, demonstrating that the early phase of neural induction involves simultaneous activation of multiple functions.

Animals↗
PubMed1998

A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial Golgi cisternae.

Small GTP-binding proteins of the Rab family play important roles at defined steps of vesicular transport in protein secretion and the endocytosis pathway. In mammals, more than 30 proteins belonging to the Rab family have been reported to date. We report here the molecular cloning and characterization of a novel Rab protein, Rab33B. The amino acid sequence of Rab33B shows 55.3% identity to the Rab33A protein (previously called S10), and these two proteins share unique amino acid sequences at the effector domain. The genomic organization of rab33B was the same as rab33A: it consists of two exons. Thus, these two proteins make a subclass within the Rab family. Northern blot analysis showed that rab33B is expressed ubiquitously in mouse tissues, in contrast to rab33A whose expression is restricted to the brain and the immune system. A 26 kDa protein was detected by western blotting using a Rab33B-specific monoclonal antibody. Using immunofluorescence studies, Rab33B was shown to co-localize with (alpha)-mannosidase II, a Golgi-specific marker. Immunoelectron microscopy analysis further defined the localization of Rab33B to the medial Golgi cisternae. These results suggest Rab33B plays a role in intra-Golgi transport.

Animals↗
PubMed1998

Timing of completion of the first meiotic division in bovine oocytes after maintenance of meiotic arrest with cycloheximide and their subsequent development.

This study examined the timing of completion of meiosis I of bovine oocytes in which meiotic resumption had been inhibited by cycloheximide (CHX), and also determined the optimum interval of maturation in culture for subsequent fertilization and development. Most oocytes treated with CHX reached metaphase II at 16 hr in the maturation culture, while control oocytes did at 20 hr. CHX-treated oocytes cultured for 16 hr were normally fertilized but failed to develop into blastocysts. Maturation in culture for 20 hr resulted in comparable development for control oocytes. The results indicate that nuclear maturation of CHX-treated oocytes was completed 4 hr faster than for control oocytes, however the same interval of maturation as that of control oocytes is necessary for subsequent development to blastocysts.

Animals↗