Search PubMed⌕ Search

Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 487 records · Page 27Linked to original sources
PubMed1999

Cytogenetic alterations in pituitary adenomas detected by comparative genomic hybridization.

Pituitary adenomas are benign monoclonal tumors that are either hormonally functional or nonfunctional. Although their histologic and immunocytologic characteristics have been studied extensively, cytogenetic studies are scarce. We have investigated the cytogenetic alterations and DNA ploidy patterns of 12 sporadic pituitary adenomas, including 2 growth-hormone-secreting tumors, 1 prolactinoma, and 9 nonfunctional adenomas, by comparative genomic hybridization (CGH) and laser scanning cytometry (LSC). CGH revealed that the mean number of sites of copy gain was significantly higher in functioning adenomas than in nonfunctioning tumors (P < 0.01). The most frequent change detected was loss of 13q (5 cases), with a minimal common overlapping region at 13q14. These findings suggest that a putative tumor suppressor gene on 13q14 may play an important role in the development of pituitary adenomas. DNA aneuploidy was detected by LSC in 3 of the 12 cases. The DNA aneuploid adenomas showed cytogenetic changes more frequently than did the DNA diploid tumors (P < 0.02).

Adenoma↗
PubMed1999

Noggin and bone morphogenetic protein-4 coordinately regulate the progression of chondrogenic differentiation in mouse clonal EC cells, ATDC5.

Here we report the gene expression and regulation and the function of noggin in clonal mouse chondrogenic EC cells, ATDC5. In ATDC5 cells, the expression of Noggin mRNA increased in parallel with the progression of chondrogenic differentiation. The treatment with conditioned medium of noggin-transfected COS-7 cells decreased the levels of type II and type X collagen gene transcripts of differentiated ATDC5 cells in a dose-dependent manner, and this inhibitory action was reversed by exogenously administered BMP-4 in a dose-dependent manner. The steady-state level of noggin gene transcripts was markedly upregulated by exogenously administered BMP-4 in time- and dose-dependent manners. Furthermore, this stimulatory effect of BMP-4 was attenuated by treatment with actinomycin D, but not with cycloheximide. These results indicate that noggin and BMP-4 coordinately regulate the progression of chondrogenic differentiation in ATDC5 cells.

Animals↗
PubMed1999

Evidence for the collateral innervation of the esophagus and the heart from neurons in the compact formation of the nucleus ambiguus of the rat.

We investigated whether the heart receives collateral projections from the neurons which innervate the esophagus with a retrograde double-labeling method using two fluorescent tracers. Following injections of True Blue (TB) into the esophagus and Diamidino Yellow (DY) into the heart, about 21.9% of the labeled esophageal motoneurons in the compact formation of the nucleus ambiguus (AmC) were retrogradely double labeled. No single-labeled cardiac motoneurons were found in the AmC. The present results provide anatomical substrates for the esophagocardiac reflex.

Amidines↗
PubMed1999

Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma.

BACKGROUND: Interleukin (IL)-6 plays a central role as a differentiation and growth factor of tumor cells. It may be hypothesized that increased serum IL-6 derives from the tumor tissue, and that serum IL-6 levels consequently reflect the biologic characteristics of the tumor. The authors investigated the association between the serum levels of IL-6 in colorectal carcinoma patients and the biologic characteristics of the tumor as well as clinicopathologic status of the patients. METHODS: Serum and tissue levels of IL-6 in 70 patients were determined using an immunoradiometric assay. Expression of IL-6 and IL-6 receptor were evaluated immunohistochemically. The proliferative activity of the tumor was assessed by nuclear Ki-67 labeling index. RESULTS: The concentration of serum IL-6 in the patients was significantly higher than that in normal controls. The tissue concentration of IL-6 in tumor tissue was significantly higher than that in normal mucosa, and was correlated strongly with the serum IL-6 concentration. The serum IL-6 concentration was correlated with clinicopathologic parameters, including liver metastases and tumor size, and with proliferative activity of the tumor as assessed by the Ki-67 labeling index. In the patients with Stage I or II tumors, the preoperative serum IL-6 concentration was reduced significantly 3 months after surgery. Immunohistochemically, tumor tissues that expressed IL-6 immunoreactivity had a higher incidence of expression of IL-6 receptor immunoreactivity. CONCLUSIONS. Serum IL-6 concentration reflects IL-6 concentration in the tumor component and may reflect the proliferative activity of the tumor in patients with colorectal carcinoma.

Adult↗
PubMed1999

Late retinal complications of radiation therapy for nasal and paranasal malignancies: relationship between irradiated-dose area and severity.

PURPOSE: Radiation-induced cataract, once a notorious ocular complication of radiation therapy, is no longer considered a severe complication, because visual acuity can be restored by surgical treatment without significant complications. Late retinal complications of retinopathy and glaucoma, for which there is no effective method of treatment, have become serious complications of radiotherapy of the head and neck. We retrospectively investigated the risk of late retinal complications of radiotherapy for nasal and paranasal malignancies according to the radiation dose and area of the retina irradiated. METHODS AND MATERIALS: Between October 1982 and May 1996, 43 eyes of 25 patients were exposed to fractionated external-beam irradiation for treatment of advanced nasal and paranasal cancer. None of the patients had tumor invasion into the eyes. The patients were followed ophthalmologically for a minimum of 2 years (range 2.0-11, mean 4.5, median 3.3). The radiation dose and area of the retina irradiated were estimated from the dose distribution figures calculated using the portal films and CT scan. RESULTS: Major late adverse effects of radiotherapy were observed in the retina in 9 of 43 eyes (in 8/25 patients). Radiation retinopathy was observed in 7 eyes, and the cumulative incidence was 25%. The median interval before the onset of symptoms attributable to retinopathy was 32 months (range 16-60). Neovascular glaucoma developed in 3 of the 43 eyes, with a cumulative incidence of 7%. The median period to the onset of symptoms attributable to glaucoma was 22 months (range 16-26). Obstruction of the central retinal artery was observed in 1 eye. The irradiation doses to the retinas that developed late complications ranged between 54-75 Gy (mean 61, median 61). No patients who received less than 50 Gy developed retinal complications. The retina in 21 eyes was exposed to a dose of 50 Gy or more. In 13 of the 21 eyes, 60% or more of the retina was irradiated, and 8 of the eyes (62%) in this group (> or = 50 Gy, > or = 60%) developed severe retinal complications, whereas such complications only developed in 1 of the 8 eyes (13%) in the other group (> or = 50 Gy, > or = 60%). The results suggest that the radiation dose and area irradiated are the most important factors in the development of severe complications. CONCLUSION: Radiation-induced retinopathy and glaucoma are more serious late complications than cataracts, which are easily treated with surgery. We investigated the risk of late retinal complications of radiotherapy, and our findings suggested that the radiation dose and area irradiated are the most important factors in the development of severe complications. We recommend that the radiation dose and area of the retina irradiated be minimized in patients at risk of eye complications, and the patients should be closely followed by periodic ophthalmologic testing after treatment.

Adult↗
PubMed1999

Indian hedgehog in the late-phase differentiation in mouse chondrogenic EC cells, ATDC5: upregulation of type X collagen and osteoprotegerin ligand mRNAs.

Endochondral bone formation includes a cascade of cellular events such as proliferation, maturation, hypertrophic conversion and calcification of chondrocytes and the cartilage replacement by bone. During these processes, hypertrophic conversion and calcification of chondrocytes (the late-phase differentiation) is a crucial process of chondrogenic differentiation. Indian hedgehog (Ihh), a secreted protein expressed in early hypertrophic chondrocytes, is thought to be involved in regulation of hypertrophic conversion via a feedback loop through the perichondrium. In the present study, we showed by Northern analysis and in situ hybridization that Smoothened (Smo), a key component in hedgehog signal transduction, was expressed in chondrocytes in both adult mice and mouse embryos at 16 days post-coitum in vivo, suggesting that Ihh directly acts on chondrocytes. We previously reported that Ihh, Patched and Smo were all expressed in differentiated ATDC5 cells. Exogenously administered mouse recombinant N-terminal protein of Ihh (mrIhh-N) upregulated the gene expression of type X collagen, a phenotypic marker of hypertrophic chondrocytes, as well as osteoprotegerin ligand (OPGL), a potent stimulator of osteoclastogenesis and osteoclast activity, while it did not modulate the expression of Ihh itself, bone morphogenetic protein (BMP)-4, BMP-6, transforming growth factor (TGF)-beta1 and TGF-beta2 in differentiated ATDC5 cells. Moreover, when added to the osteoclast cultures, mrIhh-N markedly stimulated the formation of resorption pits on dentine slices. Our data support the hypothesis that Ihh stimulated the late-phase chondrogenic differentiation in differentiated ATDC5 cells and upregulated the gene expression of OPGL in these cells.

Alveolar Bone Loss↗
PubMed1999

Ras proteins induce senescence by altering the intracellular levels of reactive oxygen species.

Human diploid fibroblasts eventually lose the capacity to replicate in culture and enter a viable but nonproliferative state of senescence. Recently, it has been demonstrated that retroviral-mediated gene transfer into primary fibroblasts of an activated ras gene (V12ras) rapidly accelerates development of the senescent phenotype. Using this in vitro system, we have sought to define the mediators of Ras-induced senescence. We demonstrate that expression of V12Ras results in an increase in intracellular and in particular, mitochondrial reactive oxygen species. The ability of V12Ras to induce growth arrest and senescence is shown to be partially inhibited by coexpression of an activated rac1 gene. A more dramatic rescue of V12Ras-expressing cells is demonstrated when the cells are placed in a low oxygen environment, a condition in which reactive oxygen species production is inhibited. In addition, in a 1% oxygen environment, Ras is unable to trigger an increase in the level of the cyclin-dependent kinase inhibitor p21 or to activate the senescent program. Under normoxic (20% O2) conditions, the V12Ras senescent phenotype is demonstrated to be unaffected by scavengers of superoxide but rescued by scavengers of hydrogen peroxide. These results suggest that in normal diploid cells, Ras proteins regulate oxidant production and that a rise in intracellular H2O2 represents a critical signal mediating replicative senescence.

Apoptosis↗
PubMed1999

AlphaB-crystallin in the rat lens is phosphorylated at an early post-natal age.

We determined the developmental changes in the phosphorylation state of alphaB-crystallin in lenses from rats at various post-natal ages by isoelectric focusing gel electrophoresis or sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a subsequent Western blot analysis of extracts of lenses using antibodies that recognized the carboxy-terminal sequence or each of the three phosphorylated serine residues (Ser-19, Ser-45 and Ser-59) in alphaB-crystallin. Phosphorylated forms of alphaB-crystallin were barely detected at birth but they became detectable at 3 weeks of age and reached plateau levels at 8 weeks of age. The phosphorylation of alphaB-crystallin at Ser-45 was observed preferentially. The active form of p44/42 MAP kinase, which is responsible for the phosphorylation of Ser-45 in alphaB-crystallin, also increased in a development-dependent manner. Thus we found that the developmental increase of the phosphorylation at Ser-45 of alphaB-crystallin in the rat lens was due to the developmental activation of p44/42 MAP kinase.

Animals↗
PubMed1999

Nitric oxide induces apoptotic death of cardiomyocytes via a cyclic-GMP-dependent pathway.

Recently, we have reported that excess amounts of nitric oxide (NO) produced by inducible NO synthase are involved in the development of myocardial damage in rats with induced myocarditis. However, there remain many problems to be solved concerning its mechanism of action. In this study, we examined whether NO induces apoptotic cell death in cardiomyocytes. Cultured neonatal rat cardiomyocytes were exposed to S-nitroso-N-acetylpenicillamine (SNAP) and (+/-)-E-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamine (NOR 3), as NO donors, or 8-bromo-cyclic GMP (cGMP), an analog of cGMP which functions as a second messenger in cells stimulated by NO. DNA fragmentation was confirmed by electron microscopy, by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method, and by agarose gel electrophoresis. Exogenously supplied SNAP or NOR 3 induced cardiomyocyte apoptosis in a dose- and time-dependent manner. Cardiomyocytes exposed to SNAP displayed typical features of apoptosis as demonstrated by electron microscopy. Treatment of the cells with 8-bromo-cGMP also induced apoptosis. In cardiomyocytes, SNAP-induced apoptosis was completely blocked by a PKG inhibitor (KT5823) and by a soluble guanylate cyclase inhibitor (ODQ) and was suppressed by hemoglobin and was completely blocked by ZVAD-FMK, a caspase inhibitor. These results show that NO-mediated apoptosis of cardiomyocytes is cGMP dependent and that caspases are involved in this process.

Animals↗
PubMed1999

Cloning of a novel gene specifically expressed in clonal mouse chondroprogenitor-like EC cells, ATDC5.

We cloned a full-length cDNA encoding a novel mouse protein, A-C2, by differential display method using mouse embryonic fibroblast C3H10T1/2 cells and mouse chondroprogenitor-like EC cells, ATDC5. The deduced amino acid sequence of A-C2 consisted of 106 amino acids with no significant homology to the sequences previously reported. Northern blot analysis showed two major bands of 2.1 and 1.8 kb sizes. Expression of A-C2 mRNA was exclusive to ATDC5 cells at their undifferentiated stage. None of ATDC5 cells at their differentiated stage and adult mice tissues examined expressed A-C2 gene.

Amino Acid Sequence↗
PubMed1999

Stimulation of ultraviolet-induced apoptosis of human fibroblast UVr-1 cells by tyrosine kinase inhibitors.

Damnacanthal is an anthraquinone compound isolated from the root of Morinda citrifolia and was reported to have a potent inhibitory activity towards tyrosine kinases such as Lck, Src, Lyn and EGF receptor. In the present study, we have examined the effects of damnacanthal on ultraviolet ray-induced apoptosis in ultraviolet-resistant human UVr-1 cells. When the cells were treated with damnacanthal prior to ultraviolet irradiation, DNA fragmentation was more pronounced as compared to the case of ultraviolet irradiation alone. The other tyrosine kinase inhibitors, herbimycin A and genistein, also caused similar effects on ultraviolet-induced apoptosis but to a lesser extent. Serine/threonine kinase inhibitors, K252a, staurosporine and GF109203X, rather suppressed the ultraviolet-induced DNA cleavage. Immunoblot analysis showed that pretreatment with damnacanthal followed by ultraviolet irradiation increased the levels of phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases. However, the other tyrosine kinase inhibitors did not increase the phosphorylation of extracellular signal-regulated kinases but stimulated phosphorylation of stress-activated protein kinases. Consequently, the ultraviolet-induced concurrent increase in both phosphorylated extracellular signal-regulated kinases and stress-activated protein kinases after pretreatment with damnacanthal might be characteristically related to the stimulatory effect of damnacanthal on ultraviolet-induced apoptosis.

Anthraquinones↗
PubMed1999

N-acetyltransferase 1 genetic polymorphism influences the risk of prostate cancer development.

The potential involvement of N-acetyltransferase 1 (NAT1) genetic polymorphisms in prostate cancer (PCa) patients was analyzed in 101 patients with PCa and 97 controls with no incidental malignancy. Identification of NAT1*10, the variant allele associated with the rapid acetylator phenotype was by allele-specific polymerase chain reaction (PCR). When the NAT1*10 heterozygote and other genotypes without NAT1*10 allele were considered as low risk genotypes, NAT1*10/NAT1*10 had a significantly higher risk of PCa (OR = 2.4, 95% CI; 1.0-5.6). If our preliminary results can be confirmed in a larger population, it may be a useful marker for PCa risk.

Alleles↗
PubMed1999

Vasopressin stimulates the induction of heat shock protein 27 and alphaB-crystallin via protein kinase C activation in vascular smooth muscle cells.

In the present study, we examined the effect of vasopressin on the induction of the low-molecular-weight heat shock proteins heat shock protein 27 (HSP27) and alphaB-crystallin in an aortic smooth muscle cell line, A10 cells. Vasopressin induced a time-dependent accumulation of HSP27 and alphaB-crystallin. The stimulatory effects of vasopressin were dose-dependent over the range 0.1 nmol/L to 0.1 micromol/L. The EC50 values for vasopressin were 2 (HSP27) and 4 nmol/L (alphaB-crystallin). Vasopressin induced increases in the levels of the mRNAs for HSP27 and alphaB-crystallin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, induced an accumulation of HSP27 (EC50, 20 nmol/L) and alphaB-crystallin (EC50, 2 nmol/L). In contrast, 4alpha-phorbol 12,13-didecanoate, a non-PKC-activating phorbol ester, had no such effect. Staurosporine and calphostin C, inhibitors of PKC, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin as well as that induced by TPA. BAPTA/AM and TMB-8, inhibitors of intracellular Ca2+ mobilization, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin. These results strongly suggest that vasopressin stimulates the induction of HSP27 and alphaB-crystallin via PKC activation in vascular smooth muscle cells and that this effect of vasopressin is dependent on intracellular Ca2+ mobilization.

Animals↗
PubMed1999

Pyrazolopyridine derivatives act as competitive antagonists of brain adenosine A1 receptors: [35S]GTPgammaS binding studies.

The effects of adenosine receptor ligands and three novel pyrazolopyridine derivatives on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding to rat cerebral cortical membranes were examined. [35S]GTPgammaS binding was stimulated in a concentration dependent manner by several adenosine receptor agonists. The adenosine A2a receptor selective agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), was ineffective confirming specificity for adenosine A1 receptor activation. 2-Chloro-N6-cyclopentyladenosine (CCPA; 10(-7) M)-stimulated [35S]GTPgammaS binding was inhibited by xanthine and pyrazolopyridine based adenosine receptor antagonists. The concentration-response curve for CCPA-stimulated [35S]GTPgammaS binding was shifted to the right with increasing concentrations of antagonist without significant changes in maximal response. Schild analyses determined pK(B) values of 8.97, 8.88, 8.21, 8.16, 7.79 and 7.65 for 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), (R)-1-[(E)-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl) acryloyl]-2-piperidine ethanol (FK453), 6-oxo-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl)-1(6H)-pyridazinebutyric+ ++ acid (FK838), 9-chloro-2-(2-furyl)[1,2,4]triazolo-[1,5c]quinazolin-5-amine (CGS 15943), 8-cyclopentyl-1,3-methylxanthine (CPT) and (R)-1-[(E)-3-(2-phenylpyrazolo[1,5a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352), respectively. Schild slopes were close to unity, confirming that these novel pyrazolopyridine derivatives act as competitive antagonists at rat brain adenosine A1 receptors.

Adenosine↗
PubMed1999

Antecedent angina pectoris as a predictor of better functional and clinical outcomes in patients with an inferior wall acute myocardial infarction.

We examined whether angina pectoris (AP) occurring shortly before the onset of acute myocardial infarction (AMI) can render the right ventricle and the conducting tissue resistant to ischemia in 75 patients with an inferior wall AMI. Each patient had total occlusion in the proximal right coronary artery and underwent successful coronary angioplasty < or =24 hours from the onset. We divided patients into 2 groups based on presence or absence of antecedent AP < or =24 hours before the system onset: group 1 (absent) = 57 patients; group 2 (present) = 18 patients. Collateral circulation was more frequently observed in group 2 than in group 1 (group 1 vs 2, 28% vs 61%, p <0.01). Elevation in ST segment > or =1 mm in lead V4R, hemodynamic right ventricular dysfunction, and frequency of high-degree heart block were more frequent in group 1 than in group 2 (75% vs 44%, 79% vs 39%, 53% vs 11%, p <0.05, respectively). Multivariate analysis demonstrated that antecedent AP is the only factor related to these complications. Thus, episodes of AP occurring shortly before onset may restrain development of ischemic damage of the right ventricle and conducting tissue, and are associated with better clinical and functional outcomes among patients with an inferior wall AMI.

Acute Disease↗
PubMed1999

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Aged↗
PubMed1999

Variables affecting the transduction efficiency of adenovirus vectors in bovine aortic endothelial cells.

Features and kinetics of Adenovirus (Ad)-mediated gene transfer to endothelial cells (EC) are not ultimately determined. We tested variables pertinent to the efficiency of Ad-mediated gene transfer to bovine aortic endothelial cells (BAEC) including: (1) Ad-vectors with different promoters, (2) kinetics of transduction efficiency of LacZ gene to BAEC, (3) the concentration and volume of vector-containing medium, (4) the period of incubation time of Ad vectors with BAEC, (5) the duration of transgene expression. An Ad5-LacZ vector with a cytomegalovirus (CMV) promoter transduced the LacZ gene to the cells more efficiently than vectors with the Rous sarcoma virus (RSV) promoter. However, both vectors exhibited a dose-dependent relationship between the vector multiplicity of infection (moi) and the percentage of LacZ-expressing cells. The higher moi of both vectors achieved nearly 100% of transduction efficiency in cultured BAEC. Although the Ad-CMV-LacZ vector better transduced the LacZ gene to BAEC than Ad-RSV-LacZ, a long period of vector exposure to BAEC could overcome the slightly difference in transduction efficiency between the two vectors. These results indicate that both Ad vectors are efficient for gene transfer to endothelial cells, and higher moi of vectors or a longer period exposure of vectors to EC can facilitate efficient transduction of foreign gene into EC in culture.

Adenoviridae↗