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Biomedical subjects

N Moriyama

Publications and source records attributed to N Moriyama.

At least 37 records · Page 2Linked to original sources

Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na(+)-HCO(3)(-) cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na(+)-HCO(3)-cotransport activity has not been detected in mammalian lens epithelia, cell pH (pH(i)) measurements revealed the presence of Cl(-)-independent, electrogenic Na(+)-HCO(3)-cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pH(i) recovery from acid load in the presence of HCO(3)(-)/CO(2) was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO(3)-transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Estimating pulmonary capillary wedge pressures using Doppler variables of early diastolic left ventricular inflow.

The present study was performed to determine whether a multilineal regression model based on the early diastolic transmitral flow peak velocity (E) and the propagation velocity of early diastolic inflow (PV) could estimate the pulmonary capillary wedge pressure (PCWP). PCWP and Doppler variables were simultaneously recorded in 30 patients. PCWP was estimated by multilinear regression analysis using E and PV. The predictive accuracy of the equation obtained from the analysis was tested prospectively in a separate group of 65 patients divided into 3 groups: left ventricular (LV) systolic dysfunction (Group A), LV hypertrophy (Group B), and preserved systolic function without hypertrophy (Group C). The initial results obtained in groups B and C, respectively, were: r=0.77; r=0.81. These results indicate that a multilinear regression model based on E and PV is a noninvasive method of accurately estimating PCWP in a variety of cardiac disease states.

Adult↗

Targeted transarterial oily chemoembolization for small foci of hepatocellular carcinoma using a unified helical CT and angiography system: analysis of factors affecting local recurrence and survival rates.

OBJECTIVE: We assessed the local recurrence rate after a single targeted transarterial oily chemoembolization for small hepatocellular carcinoma with the unified helical CT and angiography system and analyzed the factors affecting the local recurrence rate and survival rate with Cox proportional hazards model. MATERIALS AND METHODS: For 54 consecutive patients with 71 small hepatocellular carcinomas (< or = 5 cm) with no more than two associated lesions, targeted oily chemoembolization was performed with an emulsion of doxorubicin hydrochloride mixed with iodized oil or a suspension of zinostatin stimalamer followed by gelatin sponge particles. When local recurrence or a new lesion appeared, follow-up targeted oily chemoembolization was performed. RESULTS: For 52 of 71 lesions, the catheterization to a subsegmental or more distal feeding artery could be performed. Local recurrence was recognized in 33.2% at 1 year and 37.8% at 2 and 3 years. The significant factors that affected local recurrence were tumor size (p = 0.005) and degree of deposition of iodized oil within the lesion (p = 0.049). The survival rates at 1, 2, and 3 years were 93.3%, 77.1%, and 77.1%, respectively. The significant factors affecting survival rate were tumor thrombus in large vessels (p = 0.0001), appearing after the first chemoembolization, and maximum tumor size (p = 0.022). CONCLUSION: Single targeted transarterial oily chemoembolization with the unified helical CT and angiography system had a low local recurrence rate for small hepatocellular carcinoma, and follow-up embolization resulted in a good survival rate. Tumor size along with degree of intratumoral iodized oil deposition and tumor thrombus along with maximum tumor size were significant factors affecting local recurrence and survival rate, respectively.

Aged↗

[Evaluation of computer-assisted diagnosis of small pulmonary nodules using contrast-enhanced dynamic helical CT].

Dynamic helical computed tomography(DH-CT) was performed to examine 45 lesions(23 lung cancers, 2 pulmonary metastasis, and 20 benign nodules) as an application of computer-assisted qualitative analysis of small pulmonary nodules. Based on the three-dimensional(3D) CT image data, the internal structure of the nodule was assessed quantitatively and temporal changes were evaluated. The entire lesion was examined by helical scanning with a beam width of 2 mm(pitch of 1) before contrast enhancement and 2 and 4 minutes after contrast enhancement. Using the digital CT data, the pixels inside the nodules were quantified based on a combination of CT values and 3D curvature in order to differentiate between benign(BN) and malignant nodules (MN). (The numeral score abovementioned was calculated.) The average scores for BN 2 and 4 minutes were -5.72 and -12.8, respectively, and those for MN were 5.51 and 12.0, respectively(p < 0.01). Assuming that a score of 0 or higher indicates a MN based on the CT data 4 minutes. In conclusion, 3D computer-assisted analysis of the internal structure of small pulmonary nodules using contrast-enhanced DH-CT was found to be effective for differentiating between benign and malignant nodules.

Adult↗

Computed tomography screening for lung carcinoma in Japan.

BACKGROUND: In Japan, lung carcinoma is the leading cause of cancer-related deaths. Adenocarcinoma accounts for roughly half of all lung carcinomas. Earlier detection of lung carcinoma is expected to reduce mortality rates. Computed tomography (CT) provides higher contrast resolution and greater visualization of chest compartments that are difficult to view with chest radiography, such as the mediastinum. CT further permits the detection of minute peripheral nodules. At present, several institutions and research groups are evaluating the utility of low dose spiral CT for lung carcinoma screening. METHODS: From September 1993 to December 1998, 1669 individuals underwent a biannual screening program for lung carcinoma. The program included posteroanterior radiograph, sputum cytology, and low dose spiral CT at a for-profit organization: The Anti-Lung Cancer Association (ALCA). A total of 9993 examinations were carried out. The low dose spiral CT parameters used were 120 kvP, 50 mA, 10-mm collimation, and 2:1 pitch. RESULTS: Peripheral lung carcinoma was detected in 31 of 9993 examinations (0.3%). Of the 31 cases, 24 tumors (77%) were detected by low dose spiral CT but were not visible on standard chest radiography. Twenty-two of the 24 tumors were Stage IA (T1N0M0, according to staging system revised in 1997). CONCLUSIONS: Low dose spiral CT shows promise for lung carcinoma screening. The effectiveness of the technique for the detection of minute lung lesions remains to be established. Routine use of the technique will require resolution of several issues. These issues include the establishment of CT diagnostic criteria, the development of a diagnostic support system, the establishment of methods for definite diagnosis, and assessments of efficacy.

Humans↗

Pilot study on sentinel node biopsy in breast cancer.

BACKGROUND AND OBJECTIVES: Sentinel node biopsy (SNB) in breast cancer using indigo carmine was started in January 1998, and this method has proved feasible and reliable. From our initial experience, sentinel lymph nodes (SLNs) were identified in 65 of 88 cases of breast cancer (74%). METHODS: Lymphatic mapping in breast cancer was assessed using radionuclide, technetium-99m human serum albumin or technetium-99m tin colloid. A pilot study on SNB with dye or a combined method was performed between August 1998 and January 1999. RESULTS: SLNs were identified in 55 of 59 cases (93%). False-negative SLNs were found in 2 cases. The sensitivity and accuracy in all cases were 92% and 96%. SLNs in 52 cases were also diagnosed by immediate frozen sectioning. The sensitivity and accuracy were 89% and 96%. CONCLUSIONS: SNB in the combined method was the best way to identify SLNs in breast cancer.

Axilla↗

Differentially expressed mRNAs in androgen-independent but not androgen-dependent Shionogi carcinoma.

UNLABELLED: Recently, a new and highly effective method termed suppressive subtractive hybridization (SSH) has been introduced to clone differentially expressed mRNAs. Genes expressed in androgen-independent but not in androgen-dependent tumors, and vice versa, are obviously significant to delineate the mechanisms of androgen dependency/independency of these tumors. Mouse mammary cancer (Shionogi carcinoma-115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. METHODS: We cloned androgen-independent and androgen-dependent Shionogi carcinoma-115 specific mRNAs by the SSH method. Cloned sequences were compared with known sequences using NCBI BLAST across the Internet. Two clones were positive for cDNA insert when androgen-independent cDNA was used as tester cDNA, while no clones were positive using the androgen-dependent tester cDNA. One of the former was mouse protein kinase C beta-II while the other was a new DNA sequence. Mouse protein kinase C beta-II mRNA and the new mRNA were shown to be differentially expressed by RT-PCR analysis in androgen-independent but not androgen-dependent Shionogi carcinoma. Two mRNA species differentially expressed in androgen-independent but not androgen-dependent Shionogi carcinoma were cloned by the SSH method. The significance of these mRNAs for androgen-dependency/independency of Shionogi carcinoma should be explained in future studies.

Androgens↗

Distribution of alpha1-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular contraction in human renal artery.

This study was intended to quantify the amounts of the alpha1-adrenoceptor subtype mRNAs in human renal artery and to demonstrate the distribution of receptor subtypes responsible for the contraction of the renal artery. RNase protection assay showed that the mean amount of alpha1a mRNA was much greater than that of alpha1b or alpha1d mRNAs in both the main and branch renal arteries. However, the abundance of alpha1a mRNA in human renal artery was much less than in our previous data in the prostate. In situ hybridization showed that all alpha1 subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the branch artery. However, the intensity of signals for alpha1d and alpha1b antisense RNAs probes was lower than that for the alpha1a antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an alpha1A/L-adrenoceptor selective antagonist, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction, and prazosin showed relatively low affinity with a pA2 value of 8.8. These data suggest that the alpha1A/L-adrenoceptor mediates primarily those responses to noradrenaline in this artery. The other alpha1-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.

Adrenergic alpha-Antagonists↗

Immunochemical analysis of a photoreceptor protein using anti-IP3 receptor antibody in the unicellular organism, Blepharisma.

The blepharismin-200 kD protein complex of the ciliated protozoan Blepharisma is a novel type of photosensor responsible for the step-up photophobic response of the cell. In immunoblotting assays, the 200 kD protein is weakly cross-reacted with anti-inositol triphosphate receptor antibody (anti-IP3 R antibody). Indirect immunofluorescence assays show that the pigment granules in which the blepharismin-200 kD protein complex is localized are labelled by anti-IP3 R antibody. When the anti-IP3 R antibody or antisense oligonucleotide for IP3 receptor is introduced into the living cells of Blepharisma, both the photosensitivity of the cells and content of blepharismin-200 kD protein are reduced. The results suggest that the photoreceptor 200 kD protein is possibly an IP3 receptor-like protein.

Amino Acid Sequence↗

Contractile properties of urethral smooth muscles of young and aged female dogs: morphological and pharmacological aspects.

BACKGROUND: Alpha1-adrenoceptors are highly concentrated in the urethral smooth muscles and may play an important role in the contraction of this area. However, detailed examinations of age-related changes of the properties of urethral smooth muscle have rarely been undertaken. METHODS: The contractile properties of urethras from young non-parous and old parous female beagles were determined with a urethral function study, macroscopic autoradiography for urethras using [3H]-labeled tamsulosin and morphometry of the urethral muscles. RESULTS: The antagonistic effect (pA2) of prazosin for norepinephrine was 7.76+/-0.13 in young dogs and 7.62+/-0.06 in aged dogs. The specific binding of [3H]-tamsulosin (a relatively selective alpha1A-adrenoceptor antagonist) was recognized diffusely in proximal urethras with in vitro autoradiography. The density of binding in smooth muscles was approximately 60 and 40% in circular longitudinal layers, respectively, for both dogs. CONCLUSIONS: The female canine urethra had alpha1A, and alpha1L-adrenoceptors. No age-related changes were seen in the function of the proximal urethra, distribution of alpha1-adrenoceptor binding sites and smooth muscle densities.

Adrenergic alpha-Agonists↗

Neutrophil chemoattractant 2 beta regulates expression of the Reg gene in injured gastric mucosa in rats.

BACKGROUND & AIMS: Regenerating (Reg) protein has a trophic effect on gastric mucosal cells. We have shown that Reg gene expression is increased in enterochromaffin-like (ECL) cells during the healing of damaged gastric mucosa around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage. METHODS: Time course changes of the expression of genes for various proinflammatory cytokines and Reg were investigated after induction of gastric mucosal lesions in rats. The direct effect of proinflammatory cytokines on Reg gene expression and Reg protein production were investigated in vitro using counterflow elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain reaction. Reg gene expression was also investigated in rats treated by the neutralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 beta). RESULTS: During healing, the gene expression of several proinflammatory cytokines and Reg was markedly augmented. Among the proinflammatory cytokines, CINC-2 beta is the only cytokine in which augmented expression preceded the increase of Reg gene expression. In rats treated with CINC-2 beta neutralizing antibody, the augmentation of Reg gene expression was significantly inhibited. When ECL cells were incubated with these proinflammatory cytokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg protein in ECL cells. CXCR-2 was identified in isolated ECL cells. CONCLUSIONS: CINC-2 beta, expressed in damaged gastric mucosa, stimulates the production of Reg protein in ECL cells via CXCR-2 and may be involved in the accelerated healing of injured gastric mucosa.

Animals↗

Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists.

Peroxisome proliferator-activated receptor (PPAR) gamma is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPARgamma activation induces growth inhibition in these cells. PPARgamma expression in human gastric cancer cells, however, has not been fully investigated. We report the PPARgamma expression in human gastric cancer, and the effect of PPARgamma ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPARgamma protein in surgically resected specimens from well differentiated, moderately differentiated and poorly differentiated adenocarcinoma. We used reverse transcription-polymerase chain reaction and Northern and Western blot analyses to demonstrate PPARgamma expression in four human gastric cancer cell lines. PPARgamma agonists (troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J2) showed dose-dependent inhibitory effects on the proliferation of the gastric cancer cells, and their effect was augmented by the simultaneous addition of 9- cis retinoic acid, a ligand of RXRalpha. Flow cytometry demonstrated G1 cell cycle arrest and a significant increase of annexin V-positive cells after treatment with troglitazone. These results suggest that induction of apoptosis together with G1 cell cycle arrest may be one of the mechanisms of the antiproliferative effect of PPARgamma activation in human gastric cancer cells.

Apoptosis↗

Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric mucosa.

Prostaglandin E2 (PGE2) plays an important role in the regulation of gastric mucus secretion. We have previously shown that the prostaglandin EP4 receptor (EP4) gene is abundantly expressed in gastric mucus-producing cells. Furthermore, we have shown that EP4 is present in a rat normal gastric mucosal cell line (RGM1) and that PGE2 increases mucus secretion from these cells via EP4. Rebamipide, an anti-gastric ulcer agent, has been reported to promote gastric PGE2 production and mucus secretion. However, it is unclear whether rebamipide influences mucus secretion by altering expression of the EP4 gene. Therefore, we tested the effect of rebamipide on EP4 gene expression in the gastric mucosa. Seven-week-old Wistar rats received oral rebamipide (100 mg/kg) with and without water-immersion restraint stress (WRS). All rats were killed, and their gastric tissues were used to investigate the expression of mRNA for EP4 and cyclooxygenase types 1 and 2. The thickness of the gastric mucus layer was also measured. The effect of rebamipide on EP4 gene expression and PGE2 production in RGM1 cells was also investigated in vitro. Furthermore, the effect of PGE2 on cyclic adenosine monophosphate (cAMP) production by RGM1 cells with or without rebamipide was studied. Oral rebami-pide significantly increased EP4 gene expression in the gastric antrum but not in the corpus after WRS. Furthermore, it increased surface mucus thickness and suppressed ulcer formation in the gastric mucosa after WRS. In vitro, rebamipide significantly augmented EP4 gene expression in RGM1 cells, and PGE2 significantly increased the cAMP production by RGM1 cells incubated with rebamipide. Rebamipide promotes EP4 gene expression and may consequently increase the gastric mucus secretion via EP4 receptors in the rat antral mucosa.

Alanine↗

Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. The Prostate Cancer Study Group.

BACKGROUND: The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. METHODS: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. RESULTS: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p<0.05). Group II showed a longer progression-free survival (p <0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. CONCLUSIONS: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

Aged↗

Highly enhanced hepatic masses seen on CT during arterial portography: early hepatocellular carcinoma and adenomatous hyperplasia.

BACKGROUND: To describe computed tomographic (CT) features of highly enhanced hepatic masses as seen on CT during arterial portography (CTAP) and to survey the varieties of hepatic lesions associated with such findings. METHODS: CTAP files for 400 patients were reviewed, on the basis of which six patients with highly enhanced hepatic masses were selected. These six patients also subsequently underwent CT during hepatic arteriography (CTHA) on the same day. All the patients had chronic liver damage, which was cirrhotic in five cases. Five had a current diagnosis and one had a history of hepatocellular carcinoma (HCC). RESULTS: Solitary highly enhanced masses were observed on CTAP in three patients, three masses were seen in one patient and multiple (10-12) masses in the other two patients. All the CTAP-enhanced masses except one were round in shape and homogeneous in attenuation. The size of the mass ranged from 6 to 25 mm in diameter. In all except two nodules in one patient, the masses were hypoattenuated on CTHA. On histopathological examination of five nodules in three patients, the nodular lesions were consistent with so-called early HCC (well-differentiated HCC of Edmondson I) in four nodules and adenomatous hyperplasia in the other nodule. CONCLUSIONS: Highly enhanced hepatic masses relative to the surrounding liver parenchyma have been sporadically noted on CTAP, especially in patients with liver cirrhosis. When present, such nodules are typically hypoattenuated on CTHA and histological features are consistent with early HCC and adenomatous hyperplasia.

Adenoma↗