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Biomedical subjects

Y Kurihara

Publications and source records attributed to Y Kurihara.

At least 73 records · Page 4Linked to original sources
PubMed1999

Responses of blood pressure and catecholamine metabolism to high salt loading in endothelin-1 knockout mice.

The molecular mechanism responsible for salt sensitivity is poorly understood. Mice heterozygous for the null mutation of the endothelin-1 (ET-1) gene, Edn1, may be a potential tool for studying this mechanism, because they have elevated blood pressure and disturbances in central sympathetic nerve regulation. In the present study, we used this mouse model to examine the degree to which ET-1 contributes to the responses of blood pressure and catecholamine metabolism to high salt loading. Male Edn1+/- heterozygous mice and Edn1+/+ wild-type littermates were given either a high salt (8%) or a normal salt (0.7%) diet for 4 wk. During the normal diet, renal ET-1 levels in Edn1+/- mice were approximately 50% lower than ET-1 levels in wild-type mice, whereas the high salt diet decreased renal ET-1 levels by about 50% in both Edn1+/- and wild-type mice. The high salt diet significantly increased urinary sodium excretion and fractional excretion of sodium (FENa) but did not affect circulating plasma volume, serum electrolytes, creatinine clearance, or systemic blood pressure. In addition, urinary norepinephrine and normetanephrine excretion were significantly increased, indicating that salt loading can increase sympathetic nerve activity in normal mice. These responses to salt loading did not differ between Edn1+/- mice and their wild-type littermates. We conclude that physiological changes in ET-1 production do not affect the responses of blood pressure and catecholamine metabolism to salt loading, although the renal ET-1 content is decreased by salt loading.

Animals↗
PubMed1999

[Time-resolved three-dimensional contrast-enhanced MR angiography of the carotid artery].

Contrast-enhanced MR angiography (ceMRA) allows practical carotid arteriography without venous enhancement. However, it requires some intricate preparation such as a test bolus of the contrast agent or determination of the tracking volume even in the automatic triggering Smartprep system. The purpose of this study was to obtain carotid ceMRA without any preparation by means of a repeated multiple ultrashort three-dimensional MRA sequence (e3d56), i.e., time-resolved MRA (trMRA). Twenty-three patients underwent sagittal trMRA using a 1.0-Tesla superconducting unit. Multiple projection angiograms are acquired in three contiguous phases with a time resolution of 6 seconds per slab, including 10 partitions, after a bolus injection of 10 ml of Gd-DTPA followed by 20 ml of saline at 2 ml/sec. In all patients, the signal from the arteries could be separated from that of the veins in at least one phase. Carotid trMRA with 6-sec temporal resolution is a reliable technique for selective arteriography, avoiding the necessity of timing the contrast agent bolus.

Adult↗
PubMed1999

Endothelin and neural crest development.

A series of gene targeting research have revealed novel roles of endothelins (ETs), peptides with potent vasoconstrictive and proliferative activities, in neural crest development in mammals. The phenotype of mice lacking the ET-1/ET-A receptor-mediated signalling affects cranial/cardiac neural crest-derived structures including the branchial arches and great vessels, and is highly similar to a set of the phenotypes of the avian neural crest ablation model. In contrast, mice lacking the ET-3/ET-B receptor-mediated signalling have defects in enteric neurons and melanocytes derived from trunk/vagal neural crest, resulting in megacolon and coat color spotting. Thus, both distinct pathways of the ET system seem to participate in the normal development of different neural crest lineages. Moreover, mutations in the human ET-3 and ET-B receptor genes have been identified in patients with Hirschsprung disease. As for the mechanisms involving the ET system in neural crest development, HANDs and Goosecoid, transcriptional factors essential for embryogenesis, have been suggested as key molecules downstream to the ET-mediated signalling in cranial/cardiac neural crest.

Animals↗
PubMed1999

Problems regarding the integration of medical images into the total hospital information system.

Since 1989, the integration of medical images into the total hospital information system (HIS) has been investigated and developed at Kochi Medical School. The basic concept of the integration is that, in the same way they can view text based data, doctors can retrieve and view images using the PC terminals of the total HIS. The possibility of utilizing the PC terminals of the total HIS as image viewing stations was investigated. A test run was performed in the period from October 1995 to July 1997. The test run revealed that fast image access is crucial in order for the system to be useful for doctors. After making various improvements, the final system became well used in the clinical practice. However, in order to progress to the film-less stage, the final system still has three problems that must be solved: quality of the image display, operation of multi-exams, and quality assurance of the digital image.

Computer Systems↗
PubMed1998

Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice.

Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal and ET-1 deficient mice. RSNA was successfully recorded in urethane-anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1 deficient mice (105+/-2 mmHg and 9.71+/-1.49 muVs, n=20) were significantly higher than those in wild-type mice (96+/-2 mmHg and 5. 07+/-0.70 muVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different between ET-1 deficient (73.4+/-9.4%) and wild-type mice (91.2+/-12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8+/-3.6 vs. 39.1+/-5.2% at 10% CO2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.

Animals↗
PubMed1998

Simulated increase of hurricane intensities in a CO2-warmed climate

Hurricanes can inflict catastrophic property damage and loss of human life. Thus, it is important to determine how the character of these powerful storms could change in response to greenhouse gas-induced global warming. The impact of climate warming on hurricane intensities was investigated with a regional, high-resolution, hurricane prediction model. In a case study, 51 western Pacific storm cases under present-day climate conditions were compared with 51 storm cases under high-CO2 conditions. More idealized experiments were also performed. The large-scale initial conditions were derived from a global climate model. For a sea surface temperature warming of about 2.2 degrees C, the simulations yielded hurricanes that were more intense by 3 to 7 meters per second (5 to 12 percent) for wind speed and 7 to 20 millibars for central surface pressure.

Journal Article↗
PubMed1998

Sweet and sweetness-inducing activities of new triterpene glycosides, strogins.

In a previous study we isolated homologues of new oleanane-type triterpene glycosides from leaves of Staurogyne merguensis Kuntze and named them strogins. Strogins themselves have a sweet taste (sweet activity), which diminishes in a few minutes. Subsequent application of cold water to the mouth then elicits a sweet taste (sweetness-inducing activity). In the present study we systematically examined the properties of the sweet and sweetness-inducing activities of strogins. Strogins 1, 2 and 4 had both the sweet and sweetness-inducing activities, while strogins 3 and 5 had no activities. The sweetness-inducing activity in response to cold water lasted for 1 h for strogin 2 and 2 h for strogins 1 and 4. The sweetness-inducing activity was immediately diminished by application of gamma-cyclodextrin to the mouth after strogins were held in the mouth. It seems that the strogins were adsorbed on the gustatory receptor membranes and eliminated by inclusion activity of gamma-cyclodextrin. The structure of strogin resembles that of gymnemic acid, which has antisweet activity. There was competition between strogin 1 and gymnemic acid; treatment of the tongue with strogin 1 before application of Gymnema extract to the mouth reduced the antisweet activity. While the sweetness-inducing activity of curculin in response to water was suppressed by the presence of divalent cations such as Ca2+ or Mg2+, that of strogin was not suppressed by the divalent cations. The changes in the inactive complex between strogin and the sweet receptor site in the adaptation state into the active complex induced by cold stimulation were discussed.

Cations, Divalent↗
PubMed1998

Upregulation of endothelin-1 and adrenomedullin gene expression in the mouse endotoxin shock model.

Septic shock is a life-threatening disorder caused by lipopolysaccharide (LPS) and other bacterial products. Accumulating evidence indicates a role for vasoactive substances and cytokines in this disease process. In this study we examined the effect of LPS on the gene expression of endothelin-1 (ET-1) and adrenomedullin (AM), two major vasoactive peptides predominantly produced by vascular endothelial cells, to investigate their role in the pathophysiology of septic shock. LPS induced ET-1 and AM gene expression in the heart, lung, kidney, liver, and aorta within 6 h. In the liver, whereas basal ET-1 and AM mRNA were hardly detectable, ET-1 and AM gene expression and peptide production were markedly increased by LPS. This LPS-induced upregulation of ET-1 and AM expression is greatly potentiated by D-galactosamine (D-GalN), although D-GalN alone could not induce ET-1 and AM gene expression. These results, together with the previous findings that liver injury induced by LPS and D-GalN is mainly mediated by tumor necrosis factor-alpha (TNF-alpha), suggest that the LPS-cytokine pathway may cause upregulation of ET-1 and AM production, leading to dysregulation of systemic and regional vascular tone.

Adrenomedullin↗
PubMed1998

Systemic and renal response to salt loading in endothelin-1 knockout mice.

Endothelin-1 (ET-1) knockout mice demonstrate elevated blood pressure, which may be associated with disturbance in central cardiorespiratory regulation. In this study we examined responses to salt loading in ET-1 knockout mice to investigate whether ET-1 is involved in the pathophysiology of salt-sensitive hypertension. Male Edn1+/- heterozygous mice and their wild-type littermates were fed either a high NaCl (8%) or a normal (0.2%) diet for 4 weeks. Systemic blood pressure and tissue ET-1 levels were measured as well as several parameters relating to sodium handling and volume homeostasis. On normal diet, renal ET-1 levels of Edn1+/- mice were about 50% of those of wild-type mice. A high-salt diet caused a significant decrease in renal ET-1 levels by about 50% in both groups. Urine volume, urinary sodium excretion, and FENa in mice on the 8% NaCl diet were significantly higher than those in mice on the 0.2% NaCl diet, whereas there were no differences in circulating plasma volume, serum electrocytes, and creatinine clearance. These responses were similar in Edn1+/- and wild-type mice. Although systemic blood pressure was significantly higher in Edn1+/- mice than in the wild-type, the effect of salt loading on blood pressure was not significant in either Edn1+/- or wild-type mice. We conclude that changes in ET-1 production within a physiologic range do not affect salt sensitivity, although renal ET-1 content is decreased by salt loading.

Animals↗
PubMed1998

Computed tomography measurements of overinflation in chronic obstructive pulmonary disease: evaluation of various radiographic signs.

Using computed tomography (CT), the authors determined significant signs of overinflation. Both the pulmonary function tests (PFT) and CT of 74 patients who underwent thoracic surgery for lung cancer (44 with normal lung function, 30 with chronic obstructive pulmonary disease) were reviewed. The following were correlated with forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC): tracheal index (transverse/anteroposterior diameter), sterno-aortic distance, thoracic cage ratios (anteroposterior/transverse diameters) at the tracheal carina (TC1) and 5 cm below (TC2); and depth of the azygoesophageal recess and the presence of intercostal lung bulging (ILB). Significant correlations were observed between FEV1/FVC and tracheal index (r = 0.578, p < 0.0001), TC1 (r = -0.523, p < 0.0001), TC2 (r = -0.533, p < 0.0001), and ILB (r = -0.462, p < 0.0001). Correlations were significant but weak between FEV1/FVC and sterno-aortic distance (r = -0.351, p = 0.0027) and depth of the azygoesophageal recess (r = -0.308, p = 0.0085). Reduced tracheal index and increased anteroposterior diameter of the thoracic cage correlated most significantly with a pulmonary function index of chronic airway obstruction.

Adult↗
PubMed1998

Dental caries susceptibility in mice is closely linked to the H-2 region on chromosome 17.

The generation of dental caries in humans is thought to be regulated by many intrinsic and social factors. In this study, we examined the effect of MHC on susceptibility to dental caries in mice. The mean carious score of BALB.K/Ola, a H-2 congenic strain in which the H-2 region derived from C3H/HeJ (H-2(k/k)) is introduced into BALB/cJ (H-2(d/d)), was markedly reduced as compared with that of its recipient strain (BALB/cJ). Mating experiments confirmed a strong genetic linkage between H-2 haplotype and caries susceptibility. These results demonstrate that one of the genetic factors of the susceptibility in the mouse is mapped within the H-2 region. This finding of a host genetic factor influencing the generation of dental caries will help in developing clinical preventive strategies.

Animals↗
PubMed1998

Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese.

Hyperhomocyst(e)inemia has been identified as an independent risk factor for atherosclerotic and thromboembolic diseases such as coronary artery disease, cerebral artery disease, and venous thrombosis. Recently, the alanine/valine (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes that catalyzes the remethylation of homocysteine, was reported. The VV genotype is correlated with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis of cerebral infarction of all study patients was confirmed by CT of the brain. The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. In 256 stroke patients and 325 control subjects, the frequencies of the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared with the AA genotype. Both of these effects were statistically significant (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in particular, the allele frequency of the V mutation was 0.56, and the association between the V allele and stroke was highly significant. Plasma homocyst(e)ine levels were significantly higher in patients with the VV genotype than in patients with the AA or AV genotype, especially those with low plasma folate levels. The V allele of the MTHFR gene was significantly associated with cerebral infarction in an elderly Japanese population in a codominant manner. The VV genotype may contribute to risk for ischemic stroke through a predisposition to increased plasma homocyst(e)ine levels, and dietary folate supplementation may be of benefit, particularly to patients with this genotype.

Aged↗
PubMed1998

Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1.

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 RL). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET-1(+/-) heterozygous mice as compared with ET-1(+/+) wild-type mice (EC200 RL: 1.8 +/- 0.1 versus 21.6 +/- 5.6 mg/ml, p < 0.002). Pretreatment with the nitric oxide (NO) synthase inhibitor Ng-monomethyl-L-arginine (L-NMMA) significantly enhanced methacholine responsiveness in ET-1(+/+) wild-type mice, but not in ET-1(+/-) heterozygous mice. Meanwhile, there was no difference between ET-1(+/-) heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology.

Airway Resistance↗
PubMed1998

Detection of antigens by immunofluorescence on ultrathin cryosections of skin.

Cryoultramicrotomy was originally established to provide ultrathin cryosections as substrates for on-section immunolabeling in immunoelectron microscopy. Recently, we recognized that ultrathin cryosections of skin (0.2 micrometer thick) could serve as substrates for immunofluorescence (IF) with excellent resolution. To assess the advantages and the limitations of IF on ultrathin cryosections, we compared the labeling of IF on 0.2-micrometer ultrathin cryosections of skin with those of routine IF on 6-micrometer cryostat sections, confocal laser scanning microscopy (LSM), and immunogold electron microscopy using several markers of keratinocyte cell surface and basement membrane zone molecules. IF on ultrathin cryosections clearly demonstrated a lack of bullous pemphigoid antigens beneath the melanocytes, desmosomal antigens as discontinuous dot-like labeling, and nondesmosomal plasma membrane antigen as a ladder-like pattern. IF on ultrathin cryosections provided convincing images with higher resolution than confocal LSM, which corresponded well to those of immunogold electron microscopy. IF on ultrathin cryosections had superior resolution compared to routine IF or confocal LSM and should serve as a powerful tool in future studies for the analysis of skin antigens. (J Histochem Cytochem 46:1455-1460, 1998)

Antigens, CD↗
PubMed1998

A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme.

Numerous human syndromes are the result of abnormal cranial neural crest development. One group of such defects, referred to as CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, associated with chromosome 22 microdeletion) syndrome, exhibit craniofacial and cardiac defects resulting from abnormal development of the third and fourth neural crest-derived branchial arches and branchial arch arteries. Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) signaling peptide, have a phenotype similar to CATCH-22 syndrome with aortic arch defects and craniofacial abnormalities. Here we show that the basic helix-loop-helix transcription factor, dHAND, is expressed in the mesenchyme underlying the branchial arch epithelium. Further, dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos. In mice homozygous null for the dHAND gene, the first and second arches are hypoplastic secondary to programmed cell death and the third and fourth arches fail to form. Molecular analysis revealed that most markers of the neural-crest-derived components of the branchial arch are expressed in dHAND-null embryos, suggesting normal migration of neural crest cells. However, expression of the homeobox gene, Msx1, was undetectable in the mesenchyme of dHAND-null branchial arches but unaffected in the limb bud, consistent with the separable regulatory elements of Msx1 previously described. Together, these data suggest a model in which epithelial secretion of ET-1 stimulates mesenchymal expression of dHAND, which regulates Msx1 expression in the growing, distal branchial arch. Complete disruption of this molecular pathway results in growth failure of the branchial arches from apoptosis, while partial disruption leads to defects of branchial arch derivatives, similar to those seen in CATCH-22 syndrome.

Animals↗
PubMed1998

Gene expression of bone matrix proteins and endothelin receptors in endothelin-1-deficient mice revealed by in situ hybridization.

Endothelin-1 (ET-1) was first found as a vasoconstrictor protein excreted by vascular endothelial cells, but recently ET-1 has been considered to have widespread functions that include regulation of osteochondrogenic metabolism. We analyzed sections of head regions in ET-1 knockout mice that are known to have abnormalities in pharyngeal arch-derived tissues and found that there was severe hypoplasia in facial bones. The hypoplasia suggests that the matrix mineralization system of facial bones is disrupted in ET-1-/- homozygous mice. To elucidate whether osteogenic cells in facial bones are the targets for ET-1 and whether expression of bone matrix genes are modulated by ET-1, we examined gene expression of ET-1 receptors, ETA and ETB, and that of the bone matrix proteins, osteonectin (ON) and osteopontin (OP), both in the head regions of ET-1+/- heterozygous and ET-1-/- homozygous mice by means of in situ hybridization. Different patterns of expression between ETA and ETB mRNAs were observed in both groups. In 18.5 days post coitus fetuses, ETA mRNA was most strongly expressed in osteogenic cells along craniofacial bones, but ETB mRNA was most strongly expressed in trunks of trigeminal nerve. This finding suggests that ET-1 may modulate osteogenic cells through ETA receptor but not through ETB receptor. The expression patterns of ETA, OP, and ON mRNAs were distinct between the two groups. In the lower jaw of ET-1+/- heterozygous mice, the ETA, ON, and OP mRNA positive cells were scattered in the inner and outer regions of the thick bone matrix, but in ET-1-/- homozygous mice, cells containing those mRNAs were located close to each other at the surface of thin bone matrix. However, cellular expression of ON and OP mRNAs in osteogenic cells of ET-1-/- homozygous mice was not suppressed as compared with ET-1+/- heterozygous mice. We conclude that ET-1 may regulate proliferation and migration of osteogenic cells in the maxillofacial region, rather than modulating the expression level of ON and OP mRNAs.

Animals↗