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H Iijima

Publications and source records attributed to H Iijima.

At least 19 recordsLinked to original sources
PubMed2004

Allelic losses on chromosome 3p are accumulated in relation to morphological changes of lung adenocarcinoma.

We performed allelotyping analysis at nine regions on chromosome 3p using 56 microdissected samples from 23 primary lung adenocarcinomas to examine the process of progression within individual lung adenocarcinoma with various grades of differentiation. Identical allelic patterns among various grades of differentiation were found in eight cases. Accumulation of allelic losses from high to lower differentiated portions was found in seven cases and accumulation of allelic losses from low to higher differentiated portions was found in five cases. Various allelic patterns among various grades of differentiation were found in three cases. These results suggested that allelic losses on 3p play an important role in morphological changes of lung adenocarcinomas. We also investigated the relationship between allelic losses on 3p and histological subtypes of lung adenocarcinoma. The frequencies of allelic losses at 3p14.2 and telomeric region of 3p21.3 were higher in papillary type tumour (nine out of 14, 64% and 11 out of 15, 73%) than in bronchioloalveolar carcinoma-type tumour (one out of 8, 13%; P=0.031 and four out of 12, 33%; P = 0.057). These results indicated that allelic losses at 3p14.2 and telomeric region of 3p21.3 are related to pattern of the proliferation of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Dihydrothymine lesion in X-irradiated DNA: characterization at the molecular level and detection in cells.

PURPOSE: To study the formation of the dihydrothymine lesion produced in DNA by ionizing radiation in an anaerobic environment. MATERIALS AND METHODS: The dihydrothymine lesion, along with other lesions, was isolated from an X-irradiated aqueous solution of the dinucleoside monophosphate d(TpA) and analysed by correlated two-dimensional nuclear magnetic resonance spectroscopy. The dihydrothymine lesion was obtained by enzymatic digestion of irradiated DNA in the form of modified dinucleoside monophosphates, d(T(d)A), where T(d) stands for dihydrothymidine. Liquid chromatography-tandem mass spectrometry was used to detect the lesion in the DNA of X-irradiated mouse fibroblast cells. RESULTS: The modified dinucleoside monophosphate, d(T(d)pA), fragments by two pathways so that altogether the lesion could be detected using two different sets of tandem mass spectrometry (precursor ion mass/daughter ion mass) values. CONCLUSION: The dihydrothymine lesion is a significant lesion in cells exposed to ionizing radiation in an anaerobic environment.

Animals↗
PubMed2003

Disposition of a synthetic analogue of lipid A (E5564) in rats.

1. E5564, a lipid A analogue that potently antagonises lipopolysaccharide, is being developed to treat sepsis caused by Gram-negative bacterial infections. The pharmacokinetic profile of E5564 is independent of dose between 0.1 and 1 mg kg(-1). The distribution volume of E5564 is slightly larger than the total plasma volume, and the terminal elimination half-life is about 5 h. 2. Following (14)C-E5564 administration (0.5 mg kg(-1)), radioactivity rapidly accumulates in the liver and spleen. The half-life of E5564 in the liver is 5.1 h, which is similar to that in the plasma. At 48 weeks after dosing, 35.27% of the administered radioactivity was still present in the liver. Cumulative urinary and faecal excretion of radioactivity for up to 48 weeks after administration were 3.86 and 67.17% of the dose, respectively. 3. The results of mass spectroscopy and nuclear magnetic resonance analysis reveal that the main hepatic metabolite is di-dephosphorylated E5564. The half-life of di-dephosphorylated E5564 in the liver is 87.4 days, which is similar to that for the hepatic radioactivity. 4. The results indicate that E5564 is rapidly taken up by the liver, is metabolized via dephosphorylation pathways to form dephosphorylated E5564 and is mainly excreted in the faeces.

Animals↗
PubMed2002

The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease.

The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet-deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.

Adult↗
PubMed2001

Eosinophil peroxidase mediates protein nitration in allergic airway inflammation in mice.

The eosinophilic inflammatory response in asthma is associated with protein nitration, detected as immunostaining for 3-nitrotyrosine (3NT). As the presence of 3NT is strongly correlated with upregulation of the inducible form of nitric oxide synthase (NOS II), it has been hypothesized that 3NT formation results from the action of peroxynitrite (ONOO-), a highly reactive NO derivative produced from the reaction of molecular NO and O2-. However, recent observations have suggested that the action of peroxidases, including eosinophil peroxidase (EPO), may be responsible for protein nitration. In this study, we used murine models of allergic asthma to address the relative contribution of EPO and NOS II to protein nitration. We studied EPO-deficient New Zealand White (NZW) mice, which were sensitized and challenged intranasally with ovalbumin (OVA). Despite comparable levels of eosinophilia, NO, and superoxide production, NZW mice exhibited markedly decreased 3NT staining around the airways after OVA challenge when compared with two other strains (A/J and C57BL/6J). Immunocytochemical analysis of bronchoalveolar lavage (BAL) cells and lung sections suggested that 3NT staining was largely confined to eosinophils. This was confirmed by Western Blot analysis of proteins from different subsets of BAL cells that demonstrated a marked decrease in 3NT formation in eosinophils from NZW mice. These results contrast with those obtained in OVA-sensitized and -challenged NOS II deficient mice, which despite decreased NO production, exhibited similar 3NT staining in the airways after OVA challenge as in wild-type control mice. In this model, protein nitration was thus not a function of NO production by NOS II. We conclude that in the mouse, 3NT formation after specific allergen challenge is dependent on EPO activity, particularly in eosinophils themselves. In contrast, 3NT formation is not driven by upregulation of NOS II expression in this model and does not appear to depend on increases in the level of NO production.

Animals↗
PubMed2001

Site-dependent effect of O-glycosylation on the conformation and biological activity of calcitonin.

We synthesized seven O-glycosylated calcitonin derivatives, each with a single GalNAc residue attached to either Ser or Thr, and studied their three-dimensional structure and biological activity to examine site-dependent effects of O-glycosylation. The CD spectra in an aqueous trifluoroethanol solution showed that the GalNAc attachment at Thr6 or Thr21 reduced the helical content of calcitonin, indicating that the O-glycosylated residue functions as a stronger helix breaker than the original amino acid residue. Only the GalNAc attachment at Ser2 or Thr21 retained the hypocalcemic activity of calcitonin. This result corresponded well to that of the calcitonin-receptor binding assay. The GalNAc attachment other than Ser2 or Thr21 perturbed the interaction with the receptor, resulting in the loss of the hypocalcemic activity. The biodistribution did not change much among the seven derivatives, but some site dependency could also be observed. Thus, we can conclude that the O-glycosylation affects both the conformation and biological activity in a site-dependent manner.

Acetylgalactosamine↗
PubMed2001

Natural killer cell tumoricidal activity and deterioration of lung tumor metastasis in silicotic mice and stressed silicotic mice.

Aim of this study is to explore the role of splenic NK cells in the lung metastasis in the silicotic mice. The number of metastatic foci increased 1.5-fold and 1.8-fold in the silicotic and stressed silicotic mice compared with the control mice. Treatment with an immunomodulator reduced the rate of tumor metastasis in silicotic mice with or without stresses, while their NK cell activity was normalized. Decrease of NK cell activity on the day of tumor inoculation but not on the post-inoculation days seems to be a major factor for predicting the extent of tumor metastasis in the silicotic and stressed silicotic mice.

Adjuvants, Immunologic↗
PubMed2001

Homeobox protein Hex induces SMemb/nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element.

Recent studies have shown that the homeobox gene Hex plays an important role in inducing differentiation of vascular endothelial cells. In this study, we examined the expression of Hex in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Immunohistochemistry showed a marked induction of Hex protein in neointimal VSMCs after balloon injury in rat aorta. Western and reverse transcriptase-polymerase chain reaction analyses demonstrated that Hex was abundantly expressed in cultured VSMCs, whereas it was undetectable in other cell types or in normal aorta. The expression pattern of Hex was similar to that of SMemb/NMHC-B, a nonmuscle isoform of myosin heavy chain that we have previously reported to be a molecular marker of dedifferentiated VSMCs. We next examined the role of Hex in SMemb gene transcription. Promoter analysis demonstrated that the sequence identical to consensus cAMP-responsive element (CRE) located at -481 of the SMemb promoter was critical for Hex responsiveness. Mutant Hex expression vector, which lacks the homeodomain, failed to stimulate SMemb gene transcription, suggesting the requirement of the homeodomain for its transactivation. Elecrophoretic mobility shift assay showed that Hex binds to a consensus binding sequence for homeobox proteins, but not to CRE. Cotransfection of protein kinase A expression vector increased the ability of Hex to stimulate SMemb promoter activity in a CRE-dependent manner. Overexpression of CRE binding protein (CREB), but not Mut-CREB which contains mutation at Ser133, strongly activated Hex-induced SMemb promoter activity. These results suggest that Hex mediates transcriptional induction of the SMemb/NMHC-B gene via its homeodomain, and Hex can function as a transcriptional modulator of CRE-dependent transcription in VSMCs.

3T3 Cells↗
PubMed2001

Functioning adrenal black adenoma with pulmonary and cutaneous cryptococcosis: a case report and review of English literature.

A 53-year-old woman experienced progressive general weakness and lumbago in the 2 years prior to a physical examination which disclosed cushingoid manifestations and a skin ulcer on the back of her right knee joint. Her plasma cortisol concentration ranged from 24.7 to 31.1 microg/dl, with an ACTH level <5 pg/ml. Urinary excretions of 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) were 20.5 mg/day and 5.1 mg/day, respectively, and urinary cortisol was also increased (421 microg/day). Cortisol was not suppressed after the administration of 8 mg dexamethasone. Abdominal ultrasound sonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI) studies demonstrated a left adrenal tumor and further, a chest X-ray examination showed a cavitary lesion containing a fungus ball-like mass in the left lower lung field. The serum cryptococcal antigen titer was positive at 1:128 and a bronchoalveolar lavage fluid culture yielded a growth of Cryptococcus neoformans. A biopsy specimen of the skin ulcer also suggested cryptococcosis. As a result, a left adrenectomy was performed, and the excised specimen was shown to be an adenoma consisting of compact cells with abundant pigmentation (black adenoma). A diagnosis of functioning black adenoma of the adrenal gland, complicated with pulmonary and cutaneous cryptococcosis was made.

Adrenal Gland Neoplasms↗
PubMed2001

A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein.

The myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene was identified as a gene that caused open angle glaucoma (OAG). Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for the MYOC/TIGR gene in 120 unrelated Japanese OAG patients with increased intraocular pressure (IOP), 116 unrelated OAG patients without increased IOP, and 106 unrelated control subjects without glaucoma. An Arg158Gln sequence change in the leucine zipper-like motif (LZM) region in the myosin-homology domain was found in 2 OAG patients with or without increased IOP, and in a 56-year-old control subject without glaucoma. This is the first report of missense sequence change in the LZM region of the MYOC/TIGR protein in subjects showing various phenotypes, including a control subject. These findings suggest that Arg158Gln in the LZM region is probably a rare nondisease-causing polymorphism, despite its important role in this region, because it was found in a control subject, although Arg158Gln was previously reported as a probable disease-causing mutation.

Adult↗
PubMed2001

Perimetric sensitivity and retinal thickness in eyes with macular edema resulting from branch retinal vein occlusion.

PURPOSE: To document and study the relationship between perimetric sensitivity and retinal thickness at the foveal and parafoveal points in eyes with macular edema associated with branch retinal vein occlusion. METHODS: A prospective study was performed using the central 10-2 Humphrey perimetry program and optical coherence tomography. Seventeen eyes with branch retinal vein occlusion were eligible showing macular edema without macular nonperfusion or massive retinal hemorrhage. RESULTS: The sensitivity and retinal thickness were significantly correlated at the fovea (r = -0.629, P =.006) as well as 1 (r = -0.656, P <.0001) and 3 (r = -0.885, P <.0001) degrees apart from the fovea. The visual acuity that is expressed as a logarithm of the minimum angle of resolution (LogMAR) also correlated with retinal thickness (r = 0.591, P =.011). CONCLUSION: The increased retinal thickness resulting from macular edema is closely correlated with retinal sensitivity as measured by automated static perimetry both at the fovea and parafovea. Measuring the retinal thickness using optical coherence tomography may be useful in monitoring macular edema in eyes with branch retinal vein occlusion.

Adult↗
PubMed2001

Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy.

PURPOSE: To document the findings of optical coherence tomography in eyes with tractional macular elevation associated with proliferative diabetic retinopathy, paying special attention to differentiating between tractional retinal detachment and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively reviewed images of optical coherence tomography obtained from 17 consecutive eyes (17 patients) with proliferative diabetic retinopathy without vitreous opacity and showing tractional macular elevation with or without foveal involvement. RESULTS: Tractional retinal detachment and retinoschisis could be differentiated in the cross-sectional images of optical coherence tomography. Retinoschisis with or without associated retinal detachment was observed in 16 of 17 eyes (94%), whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes showed both findings of retinal detachment and retinoschisis. CONCLUSIONS: Optical coherence tomography is useful for distinguishing tractional retinoschisis from retinal detachment in eyes with proliferative diabetic retinopathy and macular elevation. Tractional retinoschisis with or without retinal detachment is the most frequent pattern of tractional macular elevation in eyes with proliferative diabetic retinopathy.

Adult↗
PubMed2001

Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy.

PURPOSE: To document the findings of optical coherence tomography in eyes with tractional macular elevation associated with proliferative diabetic retinopathy, paying special attention to differentiating between tractional retinal detachment and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively reviewed images of optical coherence tomography obtained from 17 consecutive eyes (17 patients) with proliferative diabetic retinopathy without vitreous opacity and showing tractional macular elevation with or without foveal involvement. RESULTS: Tractional retinal detachment and retinoschisis could be differentiated in the cross-sectional images of optical coherence tomography. Retinoschisis with or without associated retinal detachment was observed in 16 of 17 eyes (94%), whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes showed both findings of retinal detachment and retinoschisis. CONCLUSIONS: Optical coherence tomography is useful for distinguishing tractional retinoschisis from retinal detachment in eyes with proliferative diabetic retinopathy and macular elevation. Tractional retinoschisis with or without retinal detachment is the most frequent pattern of tractional macular elevation in eyes with proliferative diabetic retinopathy.

Adult↗
PubMed2001

Intravitreal phacoemulsification with pars plana vitrectomy and posterior chamber intraocular lens suture fixation for dislocated crystalline lenses.

This technique to manage a dislocated crystalline lens comprises intravitreal phacoemulsification with transscleral suture fixation of a posterior chamber intraocular lens (IOL). The dislocated lens in the vitreous cavity is removed using a standard phaco handpiece with the assistance of a fiber-optic light pipe. Then, the IOL is implanted. The technique was used in 10 eyes of 8 patients with lens luxation or subluxation. The postoperative best corrected visual acuity was 20/25 or better except in 1 eye, and no serious complications were observed. Increased intraocular pressure before surgery in 4 eyes was normalized in 3 eyes.

Aged↗
PubMed2001

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open-angle glaucoma.

The myocilin gene was identified as a gene (MYOC) that caused primary open-angle glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the myocilin gene mutation was previously reported, no study using large numbers of patients with NTG has been reported. Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping the myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and nineteen patients with POAG and 100 control subjects without glaucoma were studied as reference subjects. Five amino acid sequence changes of the myocilin were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese, Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it was reported in Chinese. Although some Japanese patients with NTG had sequence changes of the myocilin gene, there were no apparent specific mutations in patients with NTG.

Adolescent↗
PubMed2001

Dual action of nitric oxide on purely isolated retinal ganglion cells.

PURPOSE: The role of nitric oxide (NO) in the survival of retinal ganglion cells (RGCs) was investigated. METHODS: RGCs were purely isolated from postnatal Sprague-Dawley rats by 2-step panning and were cultured in chemically defined serum free medium. An NO releaser, S-nitroso-N-acetylpenicillamine (SNAP: 500 microM, 250 microM, 100 microM, 10 microM, 1 microM, 100 nM, and 10 nM), an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO: 100 microM, 33 microM, 10 microM, 1 microM), mixture of 100 microM SNAP and 33 microM c-PTIO, N(G)-nitro-L-arginine methyl ester (L-NAME: 10 mM, 5 mM, 500 microM, 100 microM or 10 microM), or their vehicles were added to the medium of pure RGC culture for 48 hr. Survival rates of small and large RGCs were determined separately by flow cytometry. RESULTS: At > or = 100 microM, SNAP significantly reduced RGC survival in a concentration dependent manner. At < or = 41 microM, SNAP significantly increased survival, particularly of large RGCs. c-PTIO and L-NAME reduced the survival rates concentration-dependently. A mixture of 100 microM SNAP and 33 microM c-PTIO significantly improved RGC survival compared with when they were added on their own. CONCLUSIONS: These results indicate that NO exhibits neuroprotective and neurotoxic actions on RGCs and that low concentrations of NO may be beneficial for the survival of neonatal RGCs in vitro.

Animals↗
PubMed2001

Crucial amino acid residues of mouse CD1d for glycolipid ligand presentation to V(alpha)14 NKT cells.

A novel lymphocyte, NKT cells bearing an invariant V(alpha)14 antigen receptor, specifically recognizes alpha-galactosylceramide (alpha-GalCer) exclusively presented by mouse CD1d (mCD1d). However, the precise molecular interaction remains unclear. For the basis of functional analyses, a docking model of alpha-GalCer with the crystal structure of mCD1d was constructed. Possible residues involved in the alpha-GalCer--mCD1d interaction were found to be Arg79, Glu83 and Asp80 for carbohydrate recognition, and Asp153 for interaction with the amide group on the fatty acyl chain. The alpha-GalCer-presenting ability of various transfectants expressing mutant mCD1d was completely abrogated if a single amino acid mutation was induced at positions 79, 80, 83 or 153, suggesting that the polar amino acids above the F' pocket are crucial for alpha-GalCer presentation to activate V(alpha)14 NKT cells. The possibility that Glu83 is a contact site for the NKT cell receptor is also discussed.

Amino Acids↗