Search PubMed⌕ Search

Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 289 records · Page 16Linked to original sources

Effects of influenza A virus on lectin-binding patterns in murine nasopharyngeal mucosa and on bacterial colonization.

To clarify the role of viral infection in otitis media, we intranasally inoculated mice with influenza A virus and examined histologic changes in the nasopharyngeal mucosa using a battery of lectins. Additionally, live Haemophilus influenzae or Streptococcus pneumoniae was injected into the nasopharynx after virus inoculation, and the clearance of bacteria from the nasopharynx was examined. Staining of the mucous blanket and epithelial cell surfaces in the nasopharynx with peanut agglutinin, succinyl wheat-germ agglutinin, and Bandeiraea simplicifolia agglutinin was significantly enhanced with intranasal virus inoculation when compared with that in control animals. The nasopharynx was moderately stained with Maachia amurensis agglutinin and wheat-germ agglutinin in control animals, and the staining was enhanced after virus inoculation. These findings were most remarkable 5 and 9 days after virus inoculation. The numbers of bacteria cultured from the nasopharynx were significantly increased when bacteria were injected 5 days after virus inoculation. These results suggest that an alteration in the glycoconjugate structure lining the nasopharyngeal mucosa caused by the influenza virus might be associated with the reduction in bacterial clearance.

Animals↗

Growth reduction of the Japanese black pine corresponding to an air pollution episode.

Changes of tree-ring widths of Japanese black pine (Pinus thunbergii Parl.) trees growing in air-polluted and unpolluted areas were analyzed. In the stand close to an industrial complex, a large reduction in the series of tree-ring index (TRI), which were computed by removing endogenous effects from the measured series, appeared from the 1960s to 1970s. This reduction in radial tree growth was not explained by the climatic response model calibrated for a pre-pollution period. TRI changes corresponding with changes in concentrations of sulfur dioxide (SO(2)), and a significant negative correlation between the TRI and SO(2) concentration were found in the polluted area. Reduction in tree-ring growth was not seen in the unpolluted area. These results indicate that the past reduction in the growth of Japanese black pine trees growing in an industrial area was mainly caused by SO(2).

Journal Article↗

Association of a T-cell receptor constant alpha chain gene polymorphism with progression of IgA nephropathy in Japanese patients.

Immunogenetic studies have suggested the role of the T-cell receptor (TCR) in the development of immune-mediated diseases. We investigated whether a genetic polymorphism in the TCR constant alpha (Calpha) chain region might modify the susceptibility or progression of immunoglobulin A (IgA) nephropathy. The TCR Calpha chain genotype was studied in 213 Japanese patients with IgA nephropathy and 73 individuals from the general population. A polymerase chain reaction-based TaqI restriction fragment length polymorphism assay (TaqI RFLP) was applied on the 5' flanking region of the TCR Calpha first exon. The TaqI-undigested (t) and TaqI-digested (T) alleles showed similar genotype distributions between the patients with IgA nephropathy and controls (tt:Tt:TT = 16.9%:46.5%:36.6% in IgA nephropathy v 9.6%:58.9%:31.5% in controls; chi(2) = 1.9; P = not significant). To further investigate the role of TCR Calpha chain gene polymorphism in renal prognosis, we analyzed those patients with IgA nephropathy in whom renal status had been monitored for a period of more than 3 years (n = 182). According to outcome, two groups were formed. The stable (S) group included 98 patients with renal function that remained unchanged during an average follow-up of 10.7 +/- 0.4 (SE) years. The progressive (P) group (n = 84) included patients with progressively declining renal function, with an average follow-up of 11.9 +/- 0.5 years. The genotype distributions of the TCR Calpha chain gene polymorphisms between these two groups differed significantly (tt:Tt:TT = 25.5%:40.8%:33.7% in S v 10.7%:44.1%:45.2% in P; chi(2) = 7.0; P < 0.05). The frequency of the T allele was greater in the P group (67.3% in P v 54.1% in S; chi(2) = 6.6; P = 0.01). The TT or Tt genotypes were more commonly observed in patients from the P group (89.3% of T allele carriers in P v 74.5% in S; chi(2) = 6.5; P = 0.01). It appeared the T allele might foreshadow a poor renal prognosis, conferring a potential risk for developing renal failure with time (odds ratio, 2.7; confidence interval, 1.2 to 6.0; P < 0.05). In summary, TCR Calpha chain genetic variability was associated with loss of renal function over time in patients with IgA nephropathy. In conclusion, the TCR Calpha chain polymorphism might prove helpful to predict progression to chronic renal failure in Japanese patients with IgA nephropathy.

Adult↗

The influence of pneumococcal otitis media on the cochlear lateral wall.

The cochlear influence of otitis media was investigated in order to identify damaged regions causing cochlear malfunction. BALB/c mice were challenged with viable Streptococcus pneumoniae into the middle ear cavity and were killed 1 day to 1 month later for immunohistochemical analysis. Otitis media was induced in all of the animals, and some showed inflammatory cells in the cochlea. Although other changes were not obvious by hematoxylin and eosin staining, immunohistochemistry showed the presence of fibrinogen in the cochlea, mainly in the lower portion of the spiral ligament and in the spiral limbus. Immunostaining for connexin 26 was decreased in the spiral ligament, accompanied by marked fibrinogen staining. Immunostaining for sodium-potassium-adenosine triphosphatase in the stria vascularis and in the type II fibrocytes of the spiral ligament was not affected obviously. The presence of fibrinogen in the cochlea suggests disruption of the blood-labyrinth barrier caused by the middle ear inflammation. Changes in connexin 26 staining suggest the possibility that the spiral ligament could be among the regions responsible for the cochlear malfunction.

Animals↗

Biphasic effects of zonisamide on serotonergic system in rat hippocampus.

To study the mechanisms of antiepileptic action of zonisamide (ZNS), we determined the effects of ZNS on extracellular, total levels and re-uptake activity of serotonin (5-HT) in rat striatum and hippocampus. After acute administrations, plasma ZNS concentrations associated with anticonvulsive action (effective concentrations) increased the total levels of 5-HT, its metabolise (5-hydroxyindoleacetic acid: 5-HIAA) and precursor (5-hydroxytryptophan: 5-HTP). After chronic administration of ZNS, effective plasma concentrations also increased the extracellular and total levels of 5-HT, 5-HIAA, and 5-HTP. On the other hand, after both acute and chronic administrations of ZNS, a supra-effective ZNS concentration either decreased or did not affect the total levels of these substances. Therefore, the stimulatory effects of ZNS on the 5-HT system were reduced by an increase in ZNS concentration to supra-effective concentrations. ZNS concentrations of 30-1000 microM did not affect hippocampal 5HT re uptake activity in vitro. These results suggest that ZNS has biphasic effects on the 5-HT system, in that effective concentrations of ZNS enhance and supra-effective concentrations of ZNS reduce the function of the 5-HT system. These biphasic effects of ZNS on the 5-HT system may be involved in the mechanisms of action of the antiepileptic and psychotropic effects, and side effects of ZNS.

5-Hydroxytryptophan↗

Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis.

The activation of STAT3 by the cytokine receptor gp130 is required for both the G1 to S cell cycle transition and antiapoptosis. We found that Pim-1 and Pim-2 are targets for the gp130-mediated STAT3 signal. Expression of a kinase-defective Pim-1 mutant attenuated gp130-mediated cell proliferation. Constitutive expression of Pim-1 together with c-myc, another STAT3 target, fully compensated for loss of the STAT3-mediated cell cycle progression, antiapoptosis, and bcl-2 expression. We also identified valosine-containing protein (VCP) as a target gene for the Pim-1-mediated signal. Expression of a mutant VCP led cells to undergo apoptosis. These results indicate that Pim-family proteins play crucial roles in gp130-mediated cell proliferation and explain the synergy between Pim and c-Myc proteins in cell proliferation and lymphomagenesis.

Adenosine Triphosphatases↗

Comparison of endoscopic features of early-stage squamous cell lung cancer and histological findings.

Seventy cases with early-stage central-type squamous cell carcinoma were treated surgically between 1984 and 1993 in seven participating institutes. We classified endoscopic features of early-stage central-type squamous cell carcinoma into three types (hypertrophic type, nodular type and polypoid type). After surgery we investigated the relationship between endoscopic features and both the area of superficial extent and depth of carcinoma invasion based on histopathological investigations of the surgical specimens. In 66.7% of the hypertrophic type lesions cancer cells did not invade into the cartilaginous layer, and only 4.8% of this type showed tumour invasion beyond the bronchial cartilage. On the other hand, a few nodular and polypoid type cases showed in-situ carcinoma or carcinoma with invasion from the subepithelial layer to the muscle layer, and in approximately 20% the these types we observed carcinoma invasion beyond the cartilaginous layer, which was not suitable for photodynamic therapy. Also, concerning the greatest dimension 24 out of 35 lesions (68.6%) less than 10 mm in the greatest dimension were evaluated as either in-situ carcinoma or micro-invasive tumour within the muscle layer. The endoscopic features can provide a basis for the determination of therapeutic strategy in early-stage central-type lung cancer.

Aged↗

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

Animals↗

Lymphocyte-sensitivity to glucocorticoid correlates with the sensitivity to cyclosporin A and tacrolimus in chronic renal failure patients.

AIMS: Association between lymphocyte-sensitivity to immunosuppressants in transplant recipients in vitro and clinical outcomes has been demonstrated. In general, renal transplant recipients are treated with a combination of immunosuppressants such as either glucocorticoid/cyclosporin A (CsA) or glucocorticoid/tacrolimus (FK506) but the pharmacological complementarity of these drugs is still controversial. We examined relationships between the lymphocyte-sensitivities to these immunosuppressants. METHODS: We examined lymphocyte-sensitivities to prednisolone (PSL), CsA, and FK506 in vitro in a total of 190 chronic renal failure (CRF) patients and 140 healthy subjects. The lymphocyte-sensitivity was evaluated from the IC50 value against mitogen-stimulated lymphocyte-blastogenesis in vitro. RESULTS: Statistically significant correlations of the IC50 values in CRF patients between the following pairs of drugs were observed: PSL and CsA (P<0.0001; n=129, r=0.419), PSL and FK506 (P<0.001; n=54, r=0. 441), and CsA and FK506 (P<0.0001; n=45, r=0.608). Similar correlations were also observed in lymphocytes from healthy subjects. The population of CRF patients who exhibited high IC50 values (low sensitivities) to PSL and FK506 was significantly larger than that of healthy subjects (P<0.05). CONCLUSIONS: Patients who showed low lymphocyte-sensitivity to either of the drugs also may exhibit low sensitivity to the others, and thus they may have a high risk of unsatisfactory outcome under combination therapy after renal transplantation. To overcome this risk, the selection of immunosuppressants is recommended to be restricted according to individual lymphocyte-sensitivities to these drugs in vitro, or alternatively, by addition of other drugs with different mechanisms for immunosuppression.

Adult↗

Osteitis fibrosa cystica generalizata with adult T-cell leukaemia: a case report.

We report on a 62-year-old female initially suffering from extreme pain in both her lower extremities. Plain radiographs revealed multiple osteolytic lesions. Laboratory analyses indicated high levels of serum calcium and parathyroid hormone related protein (PTHrP) and detected HTLV-1 antibody. Histological examination of biopsied specimens which were obtained from osteolytic lesions indicated osteitis fibrosa cystica (OFC) without tumour cells. After the initial biopsy, a subcutaneous mass developed in the left thigh. Microsections of the biopsied mass disclosed adult T-cell leukaemia (ATL) neoplastic cells. Immunohistochemical findings revealed that PTHrP secreted from ATL neoplastic cells induced the OFC.

Female↗

Non-invasive quantitative detection and applications of non-toxic, S65T-type green fluorescent protein in living plants.

Green fluorescent protein (GFP) has emerged as a powerful new tool in a variety of organisms. An engineered sGFP(S65T) sequence containing optimized codons of highly expressed eukaryotic proteins has provided up to 100-fold brighter fluorescence signals than the original jellyfish GFP sequence in plant and mammalian cells. It would be useful to establish a non-invasive, quantitative detection system which is optimized for S65T-type GFP, one of the brightest chromophore mutants among the various GFPs. We demonstrate here that highly fluorescent transgenic Arabidopsis can be generated, and the fluorescence intensity of whole plants can be measured under non-disruptive, sterile conditions using a quantitative fluorescent imaging system with blue laser excitation. Homozygous plants can be distinguished from heterozygous plants and fully fertile progenies can be obtained from the analyzed plants. In the case of cultured tobacco cells, GFP-positive cells can be quantitatively distinguished from non-transformed cells under non-selective conditions. This system will be useful in applications such as mutant screening, analysis of whole-body phenomena, including gene silencing and quantitative assessments of colonies from microorganisms to cultured eukaryotic cells. To facilitate the elucidation of protein targeting and organelle biogenesis in planta, we also generated transgenic Arabidopsis that stably express the plastid- or mitochondria-targeted sGFP(S65T). Etioplasts in dark-grown cotyledons and mitochondria in dry seed embryos could be visualized for the first time in transgenic Arabidopsis plants under normal growing conditions.

Arabidopsis↗

Multicenter study on the effects of day care therapy on schizophrenia: a comparison of day care patients with outpatients.

The effects of day care therapy for a period of 6 months upon patients with schizophrenia were studied through comparison with schizophrenia outpatients at four facilities in Japan. The clinical features of the 31 day care patients and 30 outpatients were evaluated by the hospital staff using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment Scale (GAS), and by the patients' close relatives using the Katz Adjustment Scale (KAS) before and after 6 months of treatment. Day care patients showed a significant decrease in the general pathological score of PANSS and GAS, but outpatients did not show any comparable improvement. As for KAS scores, similar improvement was observed for both the day care patients and outpatients After 6 months, 43% of the day care patients improved on the post-/pre- PANSS total scores ratio, as against only 13% of the outpatients. In addition, 13% of the outpatients were readmitted due to an exacerbation of their symptoms, whereas all day care patients were able to remain at home for 6 months. This study clearly demonstrated that day care therapy for patients with schizophrenia was more effective than the usual outpatients treatment setting. Further therapeutic efforts (e.g. psycho-education) in day care therapy are needed in order to improve family member's evaluation of the patient.

Adult↗

Lipoprotein abnormalities in diabetic nephropathy.

BACKGROUND: The risk of death from coronary heart disease (CHD) is substantially increased in diabetic nephropathy compared with normal subjects or diabetes without nephropathy. I tried to define abnormal plasma lipoproteins profiles contributing to the increased CHD risk in diabetic nephropathy. This study included: middle-aged to older type 2 diabetic patients with normoalbuminuria, microalbuminuria, and overt albuminuria; nondiabetic patients with primary renal disease; and normal control subjects. RESULTS: Triglyceride (TG) levels were significantly increased in type 2 diabetic patients with microalbuminuria and overt proteinuria. Glycemic control or insulin resistance were not associated with TG levels. Intermediate-density lipoprotein (IDL) and remnant-like particle (RLP) cholesterol in type 2 diabetics were significantly elevated in patients with overt nephropathy. Hepatic TG lipase (HTGL) was significantly decreased in diabetic nephropathy, and their higher IDL levels were inversely related to decreased HTGL. Low-density lipoprotein (LDL) size was significantly smaller in diabetic nephropathy compared with nondiabetics with kidney disease. The TG response after the oral fat load was significantly greater in diabetic nephropathy, and the LDL size was inversely associated with the magnitude of postprandial lipemia. Microalbuminuric diabetic patients had a lower lipoprotein lipase (LPL) mass and a higher von Willebrand factor (vWF), an indicator of endothelial cell damage, than normoalbuminuric patients. The LPL mass was inversely associated with vWF, suggesting that widespread endothelial cell damage results in a reduction in LPL bound to endothelium in diabetic subjects with microalbuminuria. CONCLUSIONS: Plasma lipoprotein profiles become more atherogenic in patients with diabetic nephropathy, including the subclinical stage, compared with diabetics without nephropathy or those with nondiabetic kidney disease.

Diabetes Mellitus, Type 2↗

Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients.

BACKGROUND: It has been reported that remnant lipoproteins and small, dense low-density lipoproteins (LDLs) are risk factors for cardiovascular disease. To determine whether these risk factors are present in hemodialysis (HD) patients who are suffering from a high incidence of atherosclerotic vascular disease, we measured concentrations of remnant lipoproteins and LDL particle diameter in HD patients and compared these with controls. We also measured lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) that play important roles in the generation of remnant lipoproteins and small, dense LDL, and we correlated these changes with plasma lipoprotein abnormalities in HD patients. METHODS: Lipoproteins were separated by ultracentrifugation. Apoprotein B in very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) fractions were measured by a sensitive enzyme-linked immunosorbent assay method. The average LDL particle diameter was measured by gradient gel electrophoresis. RESULTS: Plasma triglyceride, total cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations were comparable between HD patients and controls, whereas LDL cholesterol was significantly lower in HD patients. The average LDL particle diameter was not significantly different between HD patients and controls. LDL particle diameter was inversely related to plasma triglyceride concentrations in all of the subjects. VLDL triglyceride, VLDL cholesterol, and VLDL apoprotein B were comparable between HD patients and controls. IDL triglyceride, IDL cholesterol, and IDL apoprotein B concentrations were all significantly increased in HD patients compared with those in controls. LPL mass was not altered, but HTGL activity was significantly decreased in HD patients. The HTGL activity was inversely related to IDL concentrations. CONCLUSIONS: These results suggest that a prominent characteristic of lipoprotein abnormalities in HD patients is a marked increase in IDL particle number. In addition, small, dense LDL is not associated with uremic dyslipidemia. Because HTGLs promote the conversion from IDL to LDL and the generation of lipid-poor LDL, a decrease in HTGL activity may contribute to the accumulation of IDL particle and may prevent small, dense LDL formation in HD patients.

Case-Control Studies↗

Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles.

Diesel exhaust particles (DEP), an environmental pollutant, are known to induce lung cancer in experimental animals. To clarify whether reactive oxygen species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enzyme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response to ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP. The 8-OH-Gua repair activities in the DEP-treated groups decreased during the period from 2 h to 2 days following DEP exposure and then recovered to the level of the control group at 5 days after exposure. OGG1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after administration. In conclusion, the 8-OH-Gua level in rat lung DNA increases markedly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis.

Animals↗

CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5.

The CD9 molecule is a 24-27 kDa cell surface glycoprotein, which may be related to Schwann cell migration and adhesion. In this study, we examined the expression of CD9 in human extravillous trophoblasts, which invade into the endometrium during implantation and placentation. CD9 was detected immunohistochemically on the extravillous trophoblasts in the cell columns of first trimester placentae, but not on villous trophoblasts. In the second and third trimester, CD9 was highly expressed on the extravillous trophoblasts in the basal plate of placentae, and in the chorion laeve in the fetal membrane of term placentae. The molecular mass of CD9 in the chorion laeve was shown to be 27 kDa by Western blotting. The mRNA of CD9 was also detected in the chorion laeve by reverse transcription-polymerase chain reaction (RT-PCR). Proteins were purified from chorion laeve by affinity chromatography with anti-integrin alpha3 and alpha5 monoclonal antibodies and Western blotting, revealed that CD9 was associated with both integrins. These findings indicate that CD9 is a differentiation-related molecule present in the extravillous trophoblasts. Since it is associated with integrin alpha5 which has been proposed to regulate trophoblast invasion, CD9 may be implicated in trophoblast invasion at the feto-maternal interface.

Antigens, CD↗

CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells.

The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion.

Antibodies, Monoclonal↗

CD9 is expressed on the cell surface of human granulosa cells and associated with integrin alpha6beta1.

The CD9 molecule is a 24-27 kDa cell surface glycoprotein which is reported to be involved in cell adhesion and migration. Recently, CD9 was shown to be associated with beta1-related integrins. We have previously found that integrin alpha6beta1 is expressed on human granulosa cells (GC) and regulates luteinization of GC in concert with its ligand laminin. In this study, we examined the expression of CD9 in human ovary and the relationship between CD9 and integrin alpha6beta1 in GC. By immunohistochemistry, CD9 was detected on GC in a small antral follicle of <1 mm in diameter. In growing follicles, CD9 was moderately expressed on both GC and theca interna cells (TI). The expression intensity of CD9 on GC increased in preovulatory follicles. In the early luteal phase, CD9 was expressed in both luteinizing GC and TI. The expression intensity on large luteal cells decreased in the mid-luteal phase. In the corpus luteum (CL) of pregnancy, CD9 continued to be expressed on large luteal cells, but not on small luteal cells. By flow cytometry, CD9 was detected on the cell surface in approximately 90% of the isolated GC from patients undergoing in vitro fertilization. The molecular weight of CD9 in the isolated GC was shown to be 26.5 kDa by Western blotting. CD9 mRNA was also detected in the isolated GC and CL by reverse transcription-polymerase chain reaction (RT-PCR). The proteins purified from GC by immunoaffinity chromatography using anti-integrin alpha6 monoclonal antibodies were shown by Western blotting to include CD9 as well as integrin beta1. These findings suggest that CD9 is a differentiation-related molecule of GC and TI and that it is associated with integrin alpha6beta1 on the cell surface of GC, suggesting that CD9 is implicated in the function of human GC in cooperation with integrin alpha6beta1.

Adult↗