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Biomedical subjects

Y Kurihara

Publications and source records attributed to Y Kurihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in rheumatoid arthritis.

Infiltration of various types of leucocytes has been shown to play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Macrophage inflammatory protein-3 alpha (MIP-3 alpha) is a recently identified chemokine which is a selective chemoattractant for leucocytes such as memory T cells, naïve B cells and immature dendritic cells. In this study, we investigated the expression of MIP-3 alpha and its specific receptor CCR6 in the inflamed joints of patients with RA. Increased amounts of MIP-3 alpha were found by ELISA in synovial fluids (SF) of patients with RA. MIP-3 alpha was apparently detected in all synovial tissue specimens of RA patients (n = 6), but it could not be detected in that of osteoarthritis (OA) patients (n = 4). Expression of MIP-3 alpha was detected especially in the sublining layer, and infiltrating mononuclear cells in RA synovial tissue. Gene expression of MIP-3 alpha was also found in six out of 11 RA-synovial fluid cells by RT-PCR. Cultured synovial fibroblasts derived from either RA or OA patients were capable of producing MIP-3 alpha in response to IL-1 beta and TNFalpha in vitro. Furthermore, expression of CCR6 was found in infiltrating mononuclear cells in the cellular clusters and around the vessels of RA synovial tissue. These findings indicate that increased production of MIP-3 alpha may contribute to the selective recruitment of CCR6-expressing cells in RA.

Arthritis, Rheumatoid↗
PubMed2001

A new theory of phylogeny inference through construction of multidimensional vector space.

Here, a new theory of molecular phylogeny is developed in a multidimensional vector space (MVS). The molecular evolution is represented as a successive splitting of branch vectors in the MVS. The end points of these vectors are the extant species and indicate the specific directions reflected by their individual histories of evolution in the past. This representation makes it possible to infer the phylogeny (evolutionary histories) from the spatial positions of the end points. Search vectors are introduced to draw out the groups of species distributed around them. These groups are classified according to the nearby order of branches with them. A law of physics is applied to determine the species positions in the MVS. The species are regarded as the particles moving in time according to the equation of motion, finally falling into the lowest-energy state in spite of their randomly distributed initial condition. This falling into the ground state results in the construction of an MVS in which the relative distances between two particles are equal to the substitution distances. The species positions are obtained prior to the phylogeny inference. Therefore, as the number of species increases, the species vectors can be more specific in an MVS of a larger size, such that the vector analysis gives a more stable and reliable topology. The efficacy of the present method was examined by using computer simulations of molecular evolution in which all the branch- and end-point sequences of the trees are known in advance. In the phylogeny inference from the end points with 100 multiple data sets, the present method consistently reconstructed the correct topologies, in contrast to standard methods. In applications to 185 vertebrates in the alpha-hemoglobin, the vector analysis drew out the two lineage groups of birds and mammals. A core member of the mammalian radiation appeared at the base of the mammalian lineage. Squamates were isolated from the bird lineage to compose the outgroup, while the other living reptilians were directly coupled with birds without forming any sister groups. This result is in contrast to the morphological phylogeny and is also different from those of recent molecular analyses.

Amino Acid Sequence↗
PubMed2001

Evidence for the physiological and pathological roles of adrenomedullin from genetic engineering in mice.

Adrenomedullin (AM) has been implicated as having hypotensive as well as protective effects on organs and vessels against different kinds of injuries. To elucidate the in vivo pathophysiological roles of adrenomedullin, we established transgenic mice (AMTg) overexpressing adrenomedullin driven by preproendothelin-1 promoter and adrenomedullin knockout mice (AMKO). Blood pressure in AMTg was significantly lower than that in wild-type mice, and AMTg was significantly resistant to lipopolysaccharide-induced septic shock and vascular injuries. On the other hand, heterozygotes of AMKO, AM(+/-), were fully viable and hypertensive as compared with wild littermates. Mice homozygous for adrenomedullin null mutation (AM-/-) were embryonic lethal, and no embryos could survive beyond the midterm of gestation. Collectively, our findings indicate the indispensable role of adrenomedullin in circulatory homeostasis and the organ protection as well as the fetal morphogenesis and the maintenance of pregnancy.

Adrenomedullin↗
PubMed2001

Bronchiolitis obliterans with organizing pneumonia versus chronic eosinophilic pneumonia: high-resolution CT findings in 81 patients.

OBJECTIVE: The objective of this research was to compare high-resolution CT findings of bronchiolitis obliterans with organizing pneumonia (BOOP) with those of chronic eosinophilic pneumonia (CEP) and to determine whether high-resolution CT can differentiate the two. MATERIALS AND METHODS: We retrospectively reviewed high-resolution CT scans of 38 patients with BOOP and 43 patients with CEP. Without knowledge of the diagnosis, two radiologists evaluated the frequency and distribution of high-resolution CT findings in both groups of patients and made a diagnosis using a three-point scale of confidence. RESULTS: Nodules, nonseptal linear or reticular opacities, and bronchial dilatation were significantly more common in BOOP than in CEP (31.6% vs. 4.7%, p < 0.005; 44.7% vs. 9.3%, p < 0.001; and 57.9% vs. 25.6%, p < 0.005, respectively). Septal line thickening was more frequent in CEP than in BOOP (72.1% vs. 39.5%, p < 0.005). Peribronchial distribution of consolidation was more frequent in BOOP than in CEP (28.9% vs. 9.3%, p < 0.05). A correct diagnosis was made in 69.7% of cases, and the diagnostician was confident in 21.7%. Interobserver agreement was good (kappa = 0.6). CONCLUSION: Although several of the high-resolution CT findings of BOOP and CEP are different, these diseases are differentiated with confidence in only a small percentage of cases.

Adult↗
PubMed2001

Economic analysis of a filmless system based on the hospital information system.

A filmless system (FLS) based on a picture archiving and communication system (PACS) equipped with UNIX work- stations and a local area network (LAN) specialized for viewing radiographs has not been deemed acceptable, for reasons of economics. However, personal computers (PCs) have recently become more powerful, to the point where PCs approach UNIX workstations in terms of capabilities. As a result, a PC-based image viewing workstation (IVW) has sufficient functions for practical use. Diagnostic resolution is not equal to that of film, but is comparable. Since the hospital information system (HIS) includes many PC terminals connected by a LAN, the cost problem can be resolved by using these PC terminals as the IVWs. In order to investigate the practicability of this idea, two types of FLSs using HIS facilities were designed: one is a system based on the use of high-resolution cathode ray tubes (H-CRTs), and the other is based on the use of conventional CRTs and radiologist reports, minimizing the number of H-CRTs. The total costs of the two systems were analyzed. As a result, the former FLS was found to be about 15% more expensive than the latter, which was less expensive than a film-based system (FBS). However, whether the FLS is more profitable than the FBS from the viewpoint of hospital management strongly depends on the medical insurance system.

Costs and Cost Analysis↗
PubMed2001

[Anatomic and radiologic considerations of varied appearances of thoracic structures].

The purpose of this pictorial essay was to demonstrate normal chest anatomy and related pathologies on chest radiographs and chest CT images. It is important for the general practitioner to have a clear understanding of anatomy in order to avoid overestimating subtle radiologic findings and to be able to differentiate true pathological lesions. This pictorial essay includes various appearances of pleural fissures, companion shadows of the ribs, and minor structures of the chest walls and mediastinum.

Humans↗
PubMed2000

Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo.

Enhanced production of reactive oxygen species plays a role in myocardial injury following ischemia/reperfusion. Heme oxygenase-1 (HO-1) is a heme-catabolizing enzyme that is induced by and acts against oxidant-induced tissue injury. We examined whether HO-1 expression was regulated following ischemia and reperfusion in the rat heart. HO-1 expression increased as early as 24 h after reperfusion. Strong HO-1 expression was seen in monocytes/macrophages and myofibroblasts. Next, we examined whether the induction of HO-1 could ameliorate cardiac injury following ischemia/reperfusion. Intraperitoneal hemin injection (30 mg/kg/day) for 2 days prior to the operation resulted in an about 2.8-fold increase in HO-1 expression in the rat heart. Hemin treatment significantly decreased infarct area (6 +/- 2%) compared to the control (21 +/- 2%), which was reversed by the coadministration of an HO inhibitor in a dose-dependent manner. Our data suggest that induction of HO-1 can reduce the cardiac injury in vivo following ischemia/reperfusion.

Animals↗
PubMed2000

Hypotension and resistance to lipopolysaccharide-induced shock in transgenic mice overexpressing adrenomedullin in their vasculature.

BACKGROUND: Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. To determine the extent to which chronic AM overproduction affects circulatory physiology under normal and pathological conditions, we used a preproendothelin-1 promoter to establish transgenic mouse lines overexpressing AM in their vasculature. METHODS AND RESULTS: Transgenic mice overexpressing AM mainly in vascular endothelial and smooth muscle cells exhibited significantly lower blood pressure (BP) and higher plasma cGMP levels than their wild-type littermates. Blockade of NO synthase with N(G)-monomethyl-L-arginine elevated BP to a greater degree in AM transgenic mice, offsetting the BP difference between the 2 groups. Despite their lower basal BP, administration of bacterial lipopolysaccharide elicited smaller declines in BP and less severe organ damage in AM transgenic mice than in wild-type mice. Furthermore, the 24-hour survival rate after induction of lipopolysaccharide shock was significantly higher in the transgenic mice. CONCLUSIONS: A chronic increase in vascular AM production reduces BP at least in part via an NO-dependent pathway. In addition, smaller responses to LPS in transgenic mice suggest that AM is protective against the circulatory collapse, organ damage, and mortality characteristic of endotoxic shock.

Adrenomedullin↗
PubMed2000

Occurrence of serum M-protein species in Japanese patients older than 50 years based on relative mobility in cellulose acetate membrane electrophoresis.

We investigated the occurrence of serum M-protein species in 2,007 Japanese patients older than 50 years of age. All sera samples were analyzed by cellulose acetate membrane electrophoresis. The relative mobility of an M-protein band was calculated by dividing the migration distance of M protein by that of albumin. M proteins were found to be present in 71 of 2,007 cases (3.5%). Men 80-89 years old showed the highest occurrence of M proteins, 11.0%. The relative mobility of M-protein bands, especially the band of the IgA-type M protein, increased as the patient's age advanced. The patients had higher levels of the IgG-type M protein than healthy Japanese subjects. We found that the occurrence of M-protein species in Japanese patients increases with their age. The IgG-type M protein was most frequently expressed among other types. The mobility of the M protein was greater in older patients probably because of aging-related changes in the carbohydrate chain of immunoglobulins composing an M-protein molecule.

Aged↗
PubMed2000

Human glycine decarboxylase gene (GLDC) and its highly conserved processed pseudogene (psiGLDC): their structure and expression, and the identification of a large deletion in a family with nonketotic hyperglycinemia.

Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an in-born error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (psiGLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The psiGLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that psiGLDC is a processed pseudogene that arose from the GLDC transcript about 4-8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1-3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using psiGLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and psiGLDC should facilitate the molecular analysis of NKH.

Amino Acid Oxidoreductases↗
PubMed2000

Increase of intestinal calcium absorption and bone mineral density by heated algal ingredient (HAI) in rats.

Active absorbable calcium (AAACa) produced by adding HAI (heated algal ingredient) to oyster shell calcium (AACa) is quite efficiently absorbed from the intestine and can increase bone mineral density in elderly osteoporotic patients. HAI was produced by heating the seaweed Cystophyllum fusiforme under reduced pressure, extracting with 6N HCL, and partially neutralizing it. Butanol-ethanol extraction then yielded active HAI fraction A, corresponding to about 1% in weight. The active HAI fraction increased intestinal Ca absorption as shown by a dose-dependent increase of plasma Ca in young male parathyroidectomized rats maintained on a low-Ca diet by administration through a stomach tube with a constant dose of AACa. The action of the active fraction A to maintain bone mass was then tested in young male rats kept on a low-Ca diet for 2 weeks. Bone weight, trabecular bone density, and strength-strain index as indices of bone strength measured by peripheral computed tomography (pQCT) tended to increase when the active HAI fraction was given along with Ca. HAI increased intestinal Ca absorption and prevented the decrease of bone density in rats kept on a low-Ca diet.

Animals↗
PubMed2000

Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases.

Paraoxonase 1 (PON1) is proposed to have an anti-atherogenic action. Two polymorphisms at the PON1 (M/L55 and Q/R192) have been shown to be associated with coronary artery disease (CAD). This conclusion is not drawn universally, however, and specific ethnic characteristics may be important determinants in this association. Recently two homologues of PON1 - PON2 and PON3 - were identified and Sanghera et al. demonstrated C/S311 polymorphism at PON2 was associated with the risk of CAD. Within that context, we investigated the association between the aforementioned three polymorphisms and CAD and ischemic stroke in a Japanese population. The study population included 431 control subjects, 210 CAD patients, and 235 ischemic stroke patients. Genotype distributions and allele frequencies of M/L55 and C/S311 were similar among the control and patient groups, whereas the R192 allele frequency was significantly higher (P<0.001) in CAD (75%) and ischemic stroke (76%) patients than in control subjects (65%). When confounding influences of other risk factors were controlled for by multivariate analysis, R192 remained an independent risk determinant (additive model: OR (95% CI), P value CAD: 2.01 (1.45-2.79), 0.0001; ischemic stroke: 1.84 (1.34-2.52), 0.0002 (three genotypes into calculation)). Taken together, our data indicate that the Q/R192 is principally associated with both CAD and ischemic stroke in Japanese.

Aged↗
PubMed2000

NMR analysis of tertiary interactions in HDV ribozymes.

Three variants of minimized hepatitis delta virus (HDV) RNA ribozyme systems designed on the basis of the "pseudoknot" model were synthesized and their tertiary interactions were analyzed by NMR spectroscopy. Rz-1 is a cis-acting ribozyme system (the cleaved form, 56-mer) in which stem IV is deleted from the active domain of genomic HDV RNA. Rz-1 was uniformly labeled with stable isotopes, 13C and 15N. Rz-2 is a trans-acting ribozyme system (substrate: 8-mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme: 16-mer plus 35-mer). Rz-2 was partially labeled with stable isotopes in guanosine residues of enzyme 35mer. Rz-4 is a trans-acting ribozyme system (substrate: 8mer, the cytidine residue at the cleavage site is replaced by 2'-O-methylcytidine; enzyme 53mer) which was designed by Perrotta and Been. Rz-4 has the same sequence and an extra loop closing stem IV. From 2D-NOESY and 2D-HSQC (except for Rz-4) spectra, it was suggested each ribozyme forms "pseudoknot" type structure in solution. Additionally, it was found that G38 of Rz-1, G28 and G29 of Rz-2 and Rz-4 form base-pairs. These novel base-pairs are observed in the crystal structure of a modified genomic HDV RNA. From temperature change experiment of Rz-2, the imino proton signal of G28 disappeared at 50 degrees C earlier than the other corresponding signals. Upon MgCl2 titration of Rz-2, this signal showed the largest shift.

Base Sequence↗
PubMed2000

Role of endothelin-1 in stress response in the central nervous system.

Endothelin (ET)-1 is a 21-amino acid peptide that induces a variety of biological activities, including vasoconstriction and cell proliferation, and its likely involvement in cardiovascular and other diseases has recently led to broad clinical trials of ET receptor antagonists. ET-1 is widely distributed in the central nervous system (CNS), where it is thought to regulate hormone and neurotransmitter release. Here we show that CNS responses to emotional and physical stressors are differentially affected in heterozygous ET-1-knockout mice, which exhibited diminished aggressive and autonomic responses toward intruders (emotional stressors) but responded to restraint-induced (physical) stress more intensely than wild-type mice. This suggests differing roles of ET-1 in the central pathways mediating responses to different types of stress. Hypothalamic levels of ET-1 and the catecholamine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were both increased in wild-type mice subjected to intruder stress, whereas MHPG levels were not significantly affected in ET-1-knockout mice. Furthermore, immunohistochemical analysis showed that ET-1 and tyrosine hydroxylase, an enzyme in the catecholamine synthesis pathway, were colocalized within certain neurons of the hypothalamus and amygdala. Our findings suggest that ET-1 modulates central coordination of stress responses in close association with catecholamine metabolism.

Animals↗
PubMed2000

ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.

A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.

ADAM Proteins↗