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Biomedical subjects

N Itoh

Publications and source records attributed to N Itoh.

At least 55 records · Page 3Linked to original sources

Bacterial Infection in the Conjunctiva of Patients with Adenoviral Conjunctivitis.

Purpose: We evaluate the microbiological features of mixed infection in adenovirus-infected conjunctiva.Subjects: Isolation of bacteria was performed in 82 samples of adenoviral conjunctivitis at six eye clinics in Japan.Methods: For microbiological diagnosis, we performed immunochromatography (IC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for detection and serotyping of adenovirus, and PCR for detection of herpes simplex virus (HSV) and Chlamydia trachomatis antigens out of 82 samples with adenoviral conjunctivitis.Results: Pathogenic bacteria were isolated in 6 samples out of 82. Out of these 6 cases, 5 samples were gram-negative rods and most of them were Flavobacterium meningosepticum (4 samples). Adenovirus type 8 was isolated from all these mixed infection cases. However, HSV-1 and Chlamydia trachomatis were not found.Conclusions: From these results, it is suggested that gram-negative rods, especially F. meningosepticum, are the most common bacteria causing mixed bacterial infection in adenoviral conjunctivitis.

Journal Article↗

Physiological function of bromoperoxidase in the red marine alga, Corallina pilulifera: production of bromoform as an allelochemical and the simultaneous elimination of hydrogen peroxide.

The physiological function of vanadium-bromoperoxidase (BPO) in the marine red alga, Corallina pilulifera, has been characterized from the viewpoint of allelochemical formation. The algae emit bromoform (CHBr3) depending on the enzyme activity level in vivo (Itoh, N., Shinya, M., 1994. Seasonal evolution of bromomethanes from coralline algae and its effect on atmospheric ozone. Marine Chemistry 45, 95-103). We demonstrated that bromoform produced by C. pilulifera played an important role in eliminating epiphytic organisms, especially microalgae on the surface. Such data suggest a strong relationship between the coralline algae and the coralline flat (deforested area in the marine environment: called isoyake in Japanese). Lithophyllum yessoense, the main inhabitant of coralline flats in Japan, produced a lower level of CHBr3 than C. pilulifera, and showed BPO activity. On the other hand, the seasonal change of BPO activity in C. pilulifera in vivo was in proportion to superoxide dismutase (SOD) activity and in inverse proportion to catalase activity. The phenomenon implies that BPO could be a potential substitute for catalase, because the enzyme catalyzes an efficient Br(-)-dependent catalase reaction.

Benzopyrans↗

Symptomatic and urodynamic improvement by oral distigmine bromide in poor voiders after transurethral resection of the prostate.

UNLABELLED: OBJECTIVESz: To study the clinical and urodynamic effects of oral distigmine bromide (distigmine) by using pressure-flow studies in patients who were persistently poor voiders after transurethral resection of the prostate. METHODS: The study included 14 poor voiders after transurethral resection of the prostate who were 50 years old or older. Their poor voiding conditions were characterized by a mean International Prostate Symptom Score of 18.9 or a mean quality-of-life index of 4.6 and a mean maximum flow rate of 8.9 mL/s. All patients underwent symptomatic and urodynamic investigations before and after 4 weeks of daily treatment with 15 mg oral distigmine. RESULTS: In the baseline pressure-flow studies, all patients had weak detrusor contractility as demonstrated by Schäfer's diagram and the maximum Watts factor but did not have bladder outlet obstruction. They had symptomatic improvements after oral distigmine treatment, with the International Prostate Symptom Score reduced to a mean of less than 10 and the quality-of-life index reduced to a mean of less than 3. In the urodynamic investigations, the maximum flow rate improved significantly to a mean of more than 12 mL/s in parallel with a significant increase in the maximum Watts factor. Detrusor contractility according to Schäfer's diagram also tended to improve after oral distigmine treatment. However, no significant changes were found in any of the parameters of bladder outlet obstruction. CONCLUSIONS: Poor voiders after transurethral resection of the prostate who have weak detrusor contractility without bladder outlet obstruction may benefit clinically from treatment with distigmine because of its efficacy in increasing detrusor contractility without enhancing bladder outlet obstruction.

Administration, Oral↗

Risk factors for multiple intravesical recurrences of superficial bladder cancer.

OBJECTIVES: To elucidate the risk factors for a second or third intravesical recurrence in patients with superficial bladder cancer. METHODS: Of 84 consecutive patients newly diagnosed as having superficial bladder cancer in Sapporo Medical University Hospital, 30 patients who had at least one recurrent superficial bladder cancer and were followed up for more than 3 years were included in this study. Multivariate analysis by Cox's proportional hazards model was used to determine which clinical and pathologic variables significantly affected the second and third recurrences. Stepwise regression analysis was used to determine which clinical and pathologic variables significantly affected multiple recurrences of bladder cancer. RESULTS: The 1, 2, and 5-year recurrence-free rates as determined by the Kaplan-Meier method were 66.1%, 43.8%, and 29.8% for a second recurrence and 67.4%, 61.8%, and 39.2% for a third recurrence, respectively. Multivariate analysis revealed that only the interval between the initial transurethral resection of the bladder cancer and the first recurrence was a significant and independent factor affecting the second recurrence. In the study of the third recurrence, the interval between the first and second recurrences was the only definite risk factor for the third one. When multiple recurrences were considered, stepwise regression analysis revealed that a time of 6 months or less from the initial transurethral resection until the first recurrence was a significant factor that affected the total frequency of bladder cancer recurrence (R(2) = 0.220, P = 0.0078). CONCLUSIONS: The results of our study indicate that patients will have the potential for frequent recurrences if they have the disease with recurrence after a short interval. This result may contribute to the selection of patients with superficial bladder cancer to receive aggressive adjuvant treatments to prevent frequent recurrences.

Adult↗

Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth and morphogenesis.

Experimental evidence is rapidly emerging that the coupling of positive regulatory signals with the induction of negative feedback modulators is a mechanism of fine regulation in development. Studies in Drosophila and chick have shown that members of the SPROUTY family are inducible negative regulators of growth factors that act through tyrosine kinase receptors. We and others have shown that Fibroblast Growth Factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis. Herein, we provide direct evidence that mSprouty2 is dynamically expressed in the peripheral endoderm in embryonic lung and is downregulated in the clefts between new branches at E12.5. We found that mSprouty2 was expressed in a domain restricted in time and space, adjacent to that of Fgf10 in the peripheral mesenchyme. By E14.5, Fgf10 expression was restricted to a narrow domain of mesenchyme along the extreme edges of the individual lung lobes, whereas mSprouty2 was most highly expressed in the subjacent epithelial terminal buds. FGF10 beads upregulated the expression of mSprouty2 in adjacent epithelium in embryonic lung explant culture. Lung cultures treated with exogenous FGF10 showed greater branching and higher levels of mSpry2 mRNA. Conversely, Fgf10 antisense oligonucleotides reduced branching and decreased mSpry2 mRNA levels. However, treatment with exogenous FGF10 or antisense Fgf10 did not change Shh and FgfR2 mRNA levels in the lungs. We investigated Sprouty2 function during lung development by two different but complementary approaches. The targeted overexpression of mSprouty2 in the peripheral lung epithelium in vivo, using the Surfactant Protein C promoter, resulted in a low level of branching, lung lobe edges abnormal in appearance and the inhibition of epithelial proliferation. Transient high-level overexpression of mSpry2 throughout the pulmonary epithelium by intra-tracheal adenovirus microinjection also resulted in a low level of branching. These results indicate for the first time that mSPROUTY2 functions as a negative regulator of embryonic lung morphogenesis and growth.

Adenoviridae↗

Growth rates of primary and metastatic lesions of renal cell carcinoma.

BACKGROUND: The natural history and growth rate of renal cell carcinoma (RCC) have not yet been determined. The growth rates of primary lesions in incidentally found RCC were compared with those of metastatic lesions. METHODS: Sixteen patients who did not receive immediate surgical treatment for renal solid masses that were later proven to be RCC were reviewed retrospectively. All primary lesions of the 16 patients were found incidentally. For comparison, metastatic lesions were evaluated in another 16 patients with RCC. Of these, 11 underwent surgical treatment for the primary lesions. RESULTS: The growth rates of primary and metastatic lesions of RCC varied. They ranged from 0.10 to 1.35 cm/year for primary lesions and from 0.08 to 7.87 cm/year for metastatic lesions. The growth rate of primary lesions of incidentally found RCC was lower than that of metastatic lesions (P = 0.0159). The initial tumor diameter and pathological grade did not affect the growth rate of the primary lesion of incidentally found RCC. However, a close correlation was found between the growth rate of metastatic lesions and the pathological grade of the primary lesion in patients with metastasis. CONCLUSIONS: The growth rate of incidentally found RCC varied. Some patients with the disease may be candidates for 'watchful waiting' when an immediate surgical treatment is not indicated, but they should be selected with great caution.

Adrenal Gland Neoplasms↗

The correlation between penile tumescence measured by the erectometer and penile rigidity by the RigiScan.

BACKGROUND: The goal of this study was to evaluate the correlation between increments of penile tumescence and penile rigidity measured by the erectometer and the RigiScan, respectively. METHODS: Nocturnal penile tumescence (NPT) was measured in 25 volunteers (mean age, 49.5 years). The erectometer and the RigiScan were used simultaneously for a total of 47 nights. We studied the correlation between maximum penile circumferential changes determined by the erectometer and penile rigidity patterns measured by the RigiScan. RESULTS: Maximum circumferential changes during NPT measured by the erectometer were well correlated to those determined by the RigiScan (correlation coefficient, 0.719). In addition, penile circumferential changes measured by the erectometer corresponded well to the penile rigidity pattern determined by the RigiScan (P=0.0001). Specifically, maximum penile circumferential changes of more than 30 mm and less than 10 mm had 70% positive predictive value and 100% negative predictive value for predicting the normal rigidity pattern, respectively. CONCLUSIONS: Penile circumferential changes measured by the erectometer were well correlated to penile rigidity measured by the RigiScan, particularly when the increments were larger than 30 mm or less than 10 mm. These results suggested that the erectometer was a useful tool to estimate the penile rigidity patterns of the RigiScan.

Adult↗

Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1.

The regulation of intracellular ascorbic acid (AsA) levels may be under the control of an AsA-specific membrane transporter. The present study investigates AsA uptake and expression of Na-dependent vitamin C transporter (SVCT) mRNA in the mouse osteoblastic cell line, MC3T3-E1. Among eight compounds tested, dexamethasone (Dex) all-trans retinoic acid, transforming growth factor beta, prostaglandin E2 and transferrin significantly and respectively) stimulated the update of AsA into MC3T3-E1 cells. Among these five, Dex was the most active, inducing mSVCT2 mRNA and the uptake of AsA in a time- and concentration-dependant manner. Dex did not induce mSVCT1 mRNA. These results suggest that the Dex-induced stimulation of AsA incorporation into osteoblastic cells is mediated by the induction of mSVCT2. Since Dex reduced alkaline phosphatase activity in MC3T3-E1 cells in our culture conditions, Dex-induced stimulation of AsA incorporation might not be the result of differentiation. Hormone-regulated changes of SVCT expression may have an important role in cell functions.

Alkaline Phosphatase↗

Prevalence of Giardia lamblia infection in household dogs.

A total of 1035 household dogs were examined for the presence of Giardia lamblia (G. lamblia) in their feces. Fecal samples from 151 (14.6%) of the dogs were positive for Giardia. The protozoan was more often detected in soft feces (26.4%) than in normal (10.0%) or diarrheic feces (13.7%) (p < 0.001 and p < 0.01, respectively). The forms of the organisms obtained from the 151 dogs were cysts (77.5%), trophozoites (9.9%), or both cysts and trophozoites (12.6%). Dogs kept indoors had a higher prevalence (18.5%) of Giardia than dogs kept outdoors (4.8%) (p < 0.001). Giardia infection was also more prevalent in 1-6 months old puppies (21.7%) compared to other groups (2.4%-7.5%) (p < 0.001). The prevalence of Giardia in dogs originally purchased from pet shops or breeding kennels was extremely high (21.5%) compared to that of dogs from individual households (4.3%) (p < 0.001). With regard to human public health, the high infection rate of Giardia in puppies and dogs kept indoors is a serious problem because G. lamblia in infected dogs may have zoonotic potential. No reports of human giardiasis transmitted from dogs have been made. However, the results of this study suggest that the risk of Giardia transmission from household dogs to humans is not negligible. Pet owners should be taught appropriate hygiene measures to prevent Giardia transmission from dogs to humans.

Animals↗

Eubacterial diterpene cyclase genes essential for production of the isoprenoid antibiotic terpentecin.

A gene cluster containing the mevalonate pathway genes (open reading frame 2 [ORF2] to ORF7) for the formation of isopentenyl diphosphate and a geranylgeranyl diphosphate (GGDP) synthase gene (ORF1) had previously been cloned from Streptomyces griseolosporeus strain MF730-N6, a diterpenoid antibiotic, terpentecin (TP) producer (Y. Hamano, T. Dairi, M. Yamamoto, T. Kawasaki, K Kaneda, T. Kuzuyama, N. Itoh, and H. Seto, Biosci. Biotech. Biochem. 65:1627-1635, 2001). Sequence analysis in the upstream region of the cluster revealed seven new ORFs, ORF8 to ORF14, which were suggested to encode TP biosynthetic genes. We constructed two mutants, in which ORF11 and ORF12, which encode a protein showing similarities to eukaryotic diterpene cyclases (DCs) and a eubacterial pentalenene synthase, respectively, were inactivated by gene disruptions. The mutants produced no TP, confirming that these cyclase genes are essential for the production of TP. The two cyclase genes were also expressed in Streptomyces lividans together with the GGDP synthase gene under the control of the ermE* constitutive promoter. The transformant produced a novel cyclic diterpenoid, ent-clerod-3,13(16),14-triene (terpentetriene), which has the same basic skeleton as TP. The two enzymes, each of which was overproduced in Escherichia coli and purified to homogeneity, converted GGDP into terpentetriene. To the best of our knowledge, this is the first report of a eubacterial DC.

Amino Acid Sequence↗

Involvement of IQGAP1, an effector of Rac1 and Cdc42 GTPases, in cell-cell dissociation during cell scattering.

We have previously proposed that IQGAP1, an effector of Rac1 and Cdc42, negatively regulates cadherin-mediated cell-cell adhesion by interacting with beta-catenin and by causing the dissociation of alpha-catenin from cadherin-beta-catenin-alpha-catenin complexes and that activated Rac1 and Cdc42 positively regulate cadherin-mediated cell-cell adhesion by inhibiting the interaction of IQGAP1 with beta-catenin. However, it remains to be clarified in which physiological processes the Rac1-Cdc42-IQGAP1 system is involved. We here examined whether the Rac1-IQGAP1 system is involved in the cell-cell dissociation of Madin-Darby canine kidney II cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hepatocyte growth factor (HGF)-induced cell scattering. By using enhanced green fluorescent protein (EGFP)-tagged alpha-catenin, we found that EGFP-alpha-catenin decreased prior to cell-cell dissociation during cell scattering. We also found that the Rac1-GTP level decreased after stimulation with TPA and that the Rac1-IQGAP1 complexes decreased, while the IQGAP1-beta-catenin complexes increased during action of TPA. Constitutively active Rac1 and IQGAP1 carboxyl terminus, a putative dominant-negative mutant of IQGAP1, inhibited the disappearance of alpha-catenin from sites of cell-cell contact induced by TPA. Taken together, these results indicate that alpha-catenin is delocalized from cell-cell contact sites prior to cell-cell dissociation induced by TPA or HGF and suggest that the Rac1-IQGAP1 system is involved in cell-cell dissociation through alpha-catenin relocalization.

Animals↗

FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo.

Transgenic mice in which fibroblast growth factor (FGF)-10 was expressed in the lungs of fetal and postnatal mice were generated with a doxycycline-inducible system controlled by surfactant protein (SP) C or Clara cell secretory protein (CCSP) promoter elements. Expression of FGF-10 mRNA in the fetal lung caused adenomatous malformations, perturbed branching morphogenesis, and caused respiratory failure at birth. When expressed after birth, FGF-10 caused multifocal pulmonary tumors. FGF-10-induced tumors were highly differentiated papillary and lepidic pulmonary adenomas. Epithelial cells lining the tumors stained intensely for thyroid transcription factor (TTF)-1 and SP-C but not CCSP, indicating that FGF-10 enhanced differentiation of cells to a peripheral alveolar type II cell phenotype. Withdrawal from doxycycline caused rapid regression of the tumors associated with rapid loss of the differentiation markers TTF-1, SP-B, and proSP-C. FGF-10 disrupted lung morphogenesis and induced multifocal pulmonary tumors in vivo and caused reversible type II cell differentiation of the respiratory epithelium.

Adenoma↗

The Na(+)/H(+) exchanger SM-20220 attenuates ischemic injury in in vitro and in vivo models.

The aim of this study is to clarify whether the activation of a Na(+)/H(+) exchanger (NHE) is tightly concerned with neuronal and glial cell injury induced by ischemia using a selective NHE inhibitor, SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate). Two hours of hypoxia followed by 24 h of reoxygenation induced lactate dehydrogenase (LDH) release, a marker of cell membrane damage, in cultured neurons and glia derived from rats. SM-20220 significantly reduced LDH release in both cells in a concentration-dependent manner, and this effect was statistically significant at concentrations of more than 10(-8) mol/l for neurons and 10(-7) mol/l for glia. A standard NHE inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride, also reduced LDH release in neurons at concentrations of more than 10(-7) mol/l. In a rat transient middle cerebral artery occlusion model, intravenous infusion of SM-20220 reduced cerebral infarction when the serum concentration of SM- 20220 was maintained at about 10(-7) mol/l. These results suggest that the activation of the NHE plays an important role in ischemic neuronal and glial cell injury, and NHE inhibitor may have good therapeutic value for the treatment of ischemic stroke.

Amides↗

Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis.

The importance of mesenchymal-epithelial interactions for the proper development of the pancreas has been acknowledged since the early 1960s, even though the molecule(s) mediating this process have remained unknown. We demonstrate here that Fgf10, a member of the fibroblast growth factor family (FGFs), plays an essential role in this process. We show that Fgf10 is expressed in the mesenchyme directly adjacent to the early dorsal and ventral pancreatic epithelial buds. In Fgf10(-/-) mouse embryos, the evagination of the epithelium and the initial formation of the dorsal and ventral buds appear normal. However, the subsequent growth, differentiation and branching morphogenesis of the pancreatic epithelium are arrested; this is primarily due to a dramatic reduction in the proliferation of the epithelial progenitor cells marked by the production of the homeobox protein PDX1. Furthermore, FGF10 restores the population of PDX1-positive cells in organ cultures derived from Fgf10(-/-) embryos. These results indicate that Fgf10 signalling is required for the normal development of the pancreas and should prove useful in devising methods to expand pancreatic progenitor cells.

Animals↗

Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell-cell adhesion sites.

Rac1, a member of the Rho family small GTPases, regulates E-cadherin-mediated cell-cell adhesion. However, it remains to be clarified how the localization and activation of Rac1 are regulated at sites of cell-cell contact. Here, using enhanced green fluorescence protein (EGFP)-tagged Rac1, we demonstrate that EGFP-Rac1 is colocalized with E-cadherin at sites of cell-cell contact and translocates to the cytosol during disruption of E-cadherin-mediated cell-cell adhesion by Ca(2+) chelation. Re-establishment of cell-cell adhesion by restoration of Ca(2)(+) caused EGFP-Rac1 to become relocalized, together with E-cadherin, at sites of cell-cell contact. Engagement of E-cadherin to the apical membrane by anti-E-cadherin antibody (ECCD-2) recruited EGFP-Rac1. We also investigated whether E-cadherin-mediated cell-cell adhesion induced Rac1 activation by measuring the amounts of GTP-bound Rac1 based on its specific binding to the Cdc42/Rac1 interactive binding region of p21-activated kinase. The formation of E-cadherin-mediated cell-cell adhesion induced Rac1 activation. This activation was inhibited by treatment of cells with a neutralizing antibody (DECMA-1) against E-cadherin, or with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase). IQGAP1, an effector of Rac1, and EGFP-Rac1 behaved in a similar manner during the formation of E-cadherin-mediated cell-cell adhesion. Rac1 activation was also confirmed by measuring the amounts of coimmunoprecipitated Rac1 with IQGAP1 during the establishment of cell-cell adhesion. Taken together, these results suggest that Rac1 is recruited at sites of E-cadherin-mediated cell-cell adhesion and then activated, possibly through PI 3-kinase.

Androstadienes↗