Search PubMed⌕ Search

Biomedical subjects

H Ohno

Publications and source records attributed to H Ohno.

At least 127 records · Page 7Linked to original sources
PubMed2000

Age-associated increase of basal corticosterone levels decreases ED2high, NF-kappaBhigh activated macrophages.

The proportion of cells with a high density of ED2 (ED2high cells) in peritoneal cells from old rats was significantly lower than that from young rats. The expression of major histocompatibility complex class II (MHC class II) molecules, the antigen presentation, production of interleukin (IL)-1beta and IL-6, and nuclear factor-kappaB activity in ED2high cells were markedly higher than those in cells with a low density of ED2 (ED2low cells), although no significant difference was observed in the expression of MHC class II molecules and the antigen presentation between ED2high cells from young and old rats. Meanwhile, basal corticosterone concentration in serum and glucocorticoid (GC) receptor mRNA expression in peritoneal cells increased significantly in old rats. The proportion of ED2high cells was increased by adrenalectomy in young rats. Furthermore, nuclear translocation of GC receptor was observed in ED2low cells, whereas GC receptor was detected in cytoplasmic extracts from ED2high cells. These results suggest that the decrease in functional ED2high macrophages with age results in the age-associated decline of immune responses, which is regulated, in part, by the basal GC concentration.

Adrenalectomy↗
PubMed2000

Risk factors for ischemic heart disease in an urban area of Japan: a case-control study in AMHTS.

OBJECTIVES: In Japan controversy exists as to whether or not the risk factors for ischemic heart disease (IHD) are the same as in western countries. We conducted a case-control study on IHD to clarify the risk factors in males in an urban area of Japan using our automated multiphasic health testing and services (AMHTS) system. METHOD: Cases were the clients who took the health check-up between January 1987 and July 1994 and had onset of IHD after the check-up. For each case five clients were selected as controls by conditional matching. The check-up data were compared between cases and controls 11 years, 6 years and just before the onset of the heart diseases. RESULTS: The statistically significant items were as follows: (1) Eleven years before the onset: Total cholesterol (T-Chol) for myocardial infarction (MI), and fasting blood sugar (FBS) for angina pectoris (AP). (2) Six years before the onset: T-Chol, electrocardiographic (ECG) findings and the complaint of palpitation or breathlessness for MI, and FBS and palpitation or breathlessness for AP. (3) Just before the onset: T-Chol, the complaint of chest pain, FBS, smoking index and hypertensive status for MI and palpitation or breathlessness, ECG findings, chest pain, systolic blood pressure and erythrocyte sedimentation rate at 60 minutes for AP. In conclusion, the risk factors for MI in males in an urban area of Japan are the same as in western countries. The most significant risk factor for AP in males in an urban area of Japan is fasting blood sugar.

Adult↗
PubMed2000

Serum extracellular superoxide dismutase in pediatric patients with various diseases as judged by an ELISA.

Extracellular superoxide dismutase (EC-SOD) concentration was measured in sera from 141 patients with 20 forms of infantile diseases including IDDM, SLE and epilepsy, 31 healthy children (controls), and 21 healthy young men by an enzyme-linked immunosorbent assay using a polyclonal antibody against human lung EC-SOD. Serum from patients with IDDM and fever of unknown origin had a significantly (p<0.05) lower concentration of EC-SOD than control serum. Part of sera from patients with the seven forms of diseases (SLE, viral infections, epilepsy, nephrosis, hyperthyroidism, hepatic disease, and Reye syndrome), on the other hand, had a greatly high concentration of EC-SOD, albeit not statistically significant. This SOD isoenzyme profile appears to be specific to each pediatric disease.

Adolescent↗
PubMed1999

Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcgamma receptors.

The generation of autoantibodies and deposition of immune complexes (ICs) in tissue play a primary role in autoimmune diseases. However, the IC-triggered response consists of complex mechanisms that make it difficult to identify the pathogenesis and develop specific therapy. We clarified here a sequential mechanism for the induction of hypersensitivity angiitis by analyzing the responsible Fc receptor (FcR), effector cells, and mediators in an animal model using FcR-deficient mice. In this model, rheumatoid factor-mediated skin vasculitis was induced in wild-type mice, whereas FcRgamma-deficient mice did not develop the vasculitis. Adoptive transfer of various FcR(+) cells into FcRgamma-deficient mice showed that mast cells but not macrophages derived from wild-type mice triggered skin vasculitis. Mast cells derived from either FcgammaRIII-deficient or tumor necrosis factor (TNF)-deficient mice did not possess the inducibility of skin vasculitis. These results indicate that triggering of vascular inflammation was induced by mast cells through IC binding on FcgammaRIII. TNF produced by such activated mast cells was mainly responsible for the pathogenesis of autoantibody-mediated vasculitis. These findings illustrate the clinical significance of mast cells, Fcgamma receptors, and TNF in IC-induced vasculitis syndrome.

Animals↗
PubMed1999

A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells.

Although polarized epithelial cells are well known to maintain distinct apical and basolateral plasma membrane domains, the mechanisms responsible for targeting membrane proteins to the apical or basolateral surfaces have remained elusive. We have identified a novel form of the AP-1 clathrin adaptor complex that contains as one of its subunits mu1B, an epithelial cell-specific homolog of the ubiquitously expressed mu1A. LLC-PK1 kidney epithelial cells do not express mu1B and missort many basolateral proteins to the apical surface. Stable expression of mu1B selectively restored basolateral targeting, improved the overall organization of LLC-PK1 monolayers, and had no effect on apical targeting. We conclude that basolateral sorting is mediated by an epithelial cell-specific version of the AP-1 complex containing mu1B.

Adaptor Protein Complex 1↗
PubMed1999

Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement delivers an inhibitory signal through the membrane-proximal region in the absence of the tyrosine motif in the cytoplasmic tail.

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif ((165)YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain-containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4-mediated suppression of T cell activation.

Abatacept↗
PubMed1999

Methylmercury level in umbilical cords from patients with congenital Minamata disease.

A total of 151 umbilical cords during the period from 1950 to 1969 were collected from the residents of the Minamata area (including 25 patients with congenital Minamata disease) for methylmercury (MeHg) analysis. When the MeHg discharge from the Chisso Company's Minamata factory into the Minamata Bay is compared with the incidence of congenital Minamata disease, the abrupt increase of the former in 1952 [Nishimura H. Chem. Today 1998;323:60-66] was found to precede that of the latter by approximately 2 years, thereby indicating that MeHg is the cause of the disaster. This was confirmed by the elevated levels of MeHg in the umbilical cords from residents of the Minamata area [from 0.35 +/- 0.30 (S.D.) ppm in 1952 to 0.96 +/- 0.75 ppm in 1955], the MeHg levels (1.60 +/- 1.00 ppm) in the cords from patients with congenital Minamata disease showing the highest values [P < 0.01 vs. acquired Minamata disease (0.72 +/- 0.65 ppm), mental retardation (0.74 +/- 0.64 ppm), other diseases (0.22 +/- 0.15 ppm), and no symptoms (0.28 +/- 0.20 ppm), respectively]. Thus, in order to fill a gap, which extends over a long period of time, in studies on environmental Hg pollution, umbilical cord samples were considered to be a useful tool.

Female↗
PubMed1999

Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

Alzheimer Disease↗
PubMed1999

Dependence of T cell antigen recognition on the dimensions of an accessory receptor-ligand complex.

The T cell antigen receptor (TCR) and its ligand peptide-major histocompatibility complex (MHC) are small (approximately 7 nm) compared with other abundant cell surface molecules such as integrins, CD43, and CD45 (23-50 nm). We have proposed that molecules at the T cell/antigen-presenting cell (APC) interface segregate according to size, with small "accessory" molecules (e.g., CD2, CD4, CD8, CD28, and CD154) contributing to the formation of a close-contact zone, within which the TCR engages peptide-MHC, and from which large molecules are excluded (Davis, S.J., and P.A. van der Merwe. 1996. Immunol. Today. 17:177-187). One prediction of this model is that increasing the size of these small accessory molecules will disrupt their function. Here, we test this prediction by varying the dimensions of the CD2 ligand, CD48, and examining how this affects T cell antigen recognition. Although the interaction of CD2 on T cells with wild-type or shortened forms of CD48 on APCs enhances T cell antigen recognition, the interaction of CD2 with elongated forms of CD48 is strongly inhibitory. Further experiments indicated that elongation of the CD2/CD48 complex inhibited TCR engagement of peptide-MHC, presumably by preventing the formation of sufficiently intimate contacts at the T cell/APC interface. These findings demonstrate the importance of small size in CD2/CD48 function, and support the hypothesis that T cell antigen recognition requires segregation of cell surface molecules according to size.

Animals↗
PubMed1999

Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells.

The apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct sets of integral membrane proteins. Biosynthetic targeting of proteins to the basolateral plasma membrane is mediated by cytosolic tail determinants, many of which resemble signals involved in the rapid endocytosis or lysosomal targeting. Since these signals are recognized by adaptor proteins, we hypothesized that there could be epithelial-specific adaptors involved in polarized sorting. Here, we report the identification of a novel member of the adaptor medium chain family, named mu1B, which is closely related to the previously described mu1A (79% amino acid sequence identity). Northern blotting and in situ hybridization analyses reveal the specific expression of mu1B mRNA in a subset of polarized epithelial and exocrine cells. Yeast two-hybrid analyses show that mu1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that mu1B may be involved in protein sorting events specific to polarized cells.

Adaptor Protein Complex 1↗
PubMed1999

Involvement of cysteinyl leukotrienes in biphasic increase of nasal airway resistance of antigen-induced rhinitis in guinea pigs.

We examined the effect of a specific cysteinyl leukotriene (LT) receptor antagonist, 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzopyran hemihydrate (pranlukast), on a novel model of allergic rhinitis induced by repeated intranasal ovalbumin challenge in actively sensitized guinea pigs. Repeated intranasal ovalbumin challenge caused a biphasic increase of nasal airway resistance, peaking 0.5 and 4 h after the final challenge. The early-phase response was accompanied by an increase in sneezing and nasal secretion, while that in the late phase was associated with edema and eosinophil infiltration of the nasal mucosa. Analysis of nasal lavage fluid showed that cysteinyl LTs increased in both phases. Pranlukast, when administered 1 h before every ovalbumin challenge, dose-dependently suppressed the increase of nasal airway resistance in the early- and late phase with evidence of histopathological improvements in the late phase. Pranlukast, however, failed to suppress sneezing and nasal secretion. We suggest that cysteinyl LTs play an important role in allergic rhinitis especially in the nasal obstruction due to edema of the nasal mucosa membrane.

Airway Resistance↗
PubMed1999

Monitoring of mercury pollution in Tanzania: relation between head hair mercury and health.

Through 1996 into 1997, a spot investigation on mercury contamination was conducted three times in Tanzania, especially around the Lake Victoria. A total of 150 goldminers, 103 fishermen and their families, and 19 residents of Mwanza City volunteered for the current study. A high total mercury level of 48.3 ppm (near to 50 ppm, a critical level of Minamata disease) and over in the head hair was observed in six goldminers (highest value, 953 ppm), four fishermen and their families (highest value, 416 ppm), and four Mwanza people (highest value, 474 ppm). With the exception of these 14 subjects, however, each mean total mercury level was well within the normal range (below 10 ppm). Out of the goldminers examined, 14 cases were diagnosed as a mild form of inorganic-mercury poisoning according to their clinical symptoms (such as polyneuropathy mercurialis, neuroasthemia, or tremor mercurialis) and the low ratio of methylmercury to total mercury, whereas neither inorganic-mercury poisoning nor methylmercury poisoning (Minamata disease) was noted in the fishermen and their families or in the Mwanza people. In addition, some subjects who showed a high total mercury level made habitual use of toilet soap containing much mercury. The findings obtained suggest that the mercury pollution in Tanzania is not very serious, however, it should be observed continuously.

Adolescent↗
PubMed1999

Human hepatitis B virus X protein augments the DNA binding of nuclear factor for IL-6 through its basic-leucine zipper domain.

The X gene product of human hepatitis B virus, HBx, transactivates the expression of viral and cellular genes through a wide variety of cis elements, including the nuclear factor for IL-6 (NF-IL6) binding sites, although HBx does not appear to bind DNA directly. We previously reported that HBx transactivated the interleukin 8 promoter through NF-kappaB binding site and C/EBP-like binding site (NF-IL6 binding site). In this study, the interactions were examined between NF-IL6 and HBx using recombinant proteins. In a DNA-protein binding assay, the formation of a specific complex between NF-IL6 and a DNA probe harboring an NF-IL6 binding site was increased by the addition of either the full or the C-terminal 104 amino acids of HBx. A direct protein-protein binding assay (far-Western blot) revealed the direct interaction between the C-terminal 104 amino acids of HBx and the basic region-leucine zipper domain of NF-IL6. These results indicate that HBx alters the DNA-binding affinity of NF-IL6 through the direct interaction between the C-terminal domain of HBx and the basic region-leucine zipper domain of NF-IL6.

Binding Sites↗
PubMed1999

Primary biliary cirrhosis associated with type A gastritis and chronic thyroiditis.

We report a patient with primary biliary cirrhosis (PBC) associated with type A gastritis, chronic thyroiditis, and iron deficiency anemia. The patient was a 45-year-old Japanese woman who was admitted to our hospital with severe microcytic and hypochromic anemia, abnormal results for liver function tests, and a diffuse goiter. The diagnosis of PBC (Scheuer's stage II) was confirmed by the presence of specific anti-mitochondrial antibody in high titers and histological examination showing chronic non-suppurative destructive cholangitis with bridging fibrosis. Additionally, marked atrophic mucosa throughout the body and fundus of the stomach was observed endoscopically, and there was positivity for intrinsic factor antibody, an extremely low ratio of serum pepsinogen A to C, and hypergastrinemia, indicating coexisting type A gastritis. The severe anemia was thought to be caused by failure of dietary iron absorption related to achlorhydria with this gastritis. However, the serum level of vitamin B12 was normal. She also had autoimmune thyroiditis. PBC is frequently associated with extrahepatic autoimmune diseases, including ductular lesions. However, the association of PBC with type A gastritis is quite rare, although the stomach is also an exocrine glandular structure. This particular case, in addition to previous reports, leads to a discussion of whether type A gastritis should be regarded as a possible, although uncommon, component disorder of so-called dry gland syndrome.

Anemia, Iron-Deficiency↗
PubMed1999

The long-term results of commissure plication annuloplasty for congenital mitral insufficiency.

BACKGROUND: Mitral valve repair in the pediatric population remains demanding because of a diversity of apparatus anomalies and the young age of the patients. METHODS: We reviewed our clinical results for mitral valve repairs for congenital mitral insufficiency. Forty-nine consecutive patients aged 2 months to 34 years (mean, 4.4 years) had mitral valve repair between June 1984 and December 1996. Forty-one patients (83.7%) had associated cardiac anomalies. The predominant pathologies for the regurgitations were chordal anomalies in 34 patients (69%), annular dilatation in 8 (16%), and leaflet anomalies in 7 (14%). Mitral valve repair included commissure plication annuloplasty in 43 patients (88%), modified DeVega in 11, cleft closure in 5, plication of the anterior leaflet in 3, triangular resection of the anterior leaflet in 2, chordal shortening in 1, and placement of artificial chordae in 1. Several combined techniques were required in 19 patients. RESULTS: There were no early or late deaths. The follow-up period was from 6 to 166 months (mean, 88.4 months). Forty-seven patients (95.9%) were in New York Heart Association class I. The long-term echocardiographic studies showed that 2 of 30 patients without reoperation had moderate regurgitation. The actuarial freedom from reoperation was 85.6% (95% confidence limits, 72.8%, 98.4%) at 13 years. Five patients (10.2%) required valve replacement from 13 days to 75 months after the valve repair. Two patients had cerebral ischemic events as a result of cardiomegaly and atrial fibrillation. CONCLUSIONS: Valve repair for congenital mitral insufficiency gave adequate results in combination with commissure plication annuloplasty and other techniques with excellent long-term functional status.

Adolescent↗