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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 55 records · Page 3Linked to original sources
PubMed2002

A useful approach to the differential diagnosis of small polypoid lesions of the gallbladder, utilizing an endoscopic ultrasound scoring system.

BACKGROUND AND STUDY AIMS: The purpose of this study was to assess the accuracy of endoscopic ultrasonography (EUS) in making a differential diagnosis of small (< or = 20 mm in diameter) polypoid lesions of the gallbladder, and to construct an EUS scoring system. PATIENTS AND METHODS: The EUS findings were retrospectively analyzed in 70 surgical cases of small polypoid lesions classified into two groups: neoplastic (adenocarcinoma in 11, and adenoma in 7), and non-neoplastic (cholesterol polyp in 44, inflammatory polyp in 7 and fibrous polyp in 1). The EUS variables were the maximum diameter and height/width ratio of the largest polyps, echo level, internal echo pattern, surface patterns, number and shape of polyps, presence of hyperechoic spotting, complication of gallbladder stones. The EUS data were used for the construction of an EUS scoring system to ascertain the risk of neoplasia. RESULTS: Three EUS variables, i. e. tumor maximum size, internal echo pattern, and hyperechoic spotting were statistically significant according to multivariate analysis using stepwise logistic regression models (P < 0.01, P < 0.05, and P < 0.01, respectively). The total EUS score based on the coefficient of multivariate analysis was as follows: (maximum diameter in mm) + (internal echo pattern score; where heterogeneous = 4, homogeneous = 0) + (hyperechoic spot[s] score; where presence = - 5, absence = 0). According to our EUS scoring system, the sensitivity, specificity, and accuracy for the risk of neoplastic polyps with scores of 12 or higher were 77.8 %, 82.7 % and 82.9 %, respectively. CONCLUSIONS: The EUS scoring system will be a useful means of differentiating between neoplastic and non-neoplastic polyps of the gallbladder.

Adenocarcinoma↗
PubMed2002

Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids.

BACKGROUND AND AIMS: Mucus released from goblet cells is important in intestinal mucosal defence, and mucin glycoproteins are thought to be major components of mucus. Recently, we identified and cloned another component of human colonic mucus, IgG Fc binding protein (Fc gamma BP). Fc gamma BP is immunologically distinct from known Fc gamma receptors and its structure contains repeated cysteine rich unit sequences resembling those present in mucins. In this work, we assessed the tissue distribution of Fc gamma BP, its binding activity in various body fluids, and its ability to inhibit complement mediated haemolysis. METHODS: Immunohistochemical localisation of Fc gamma BP, using monoclonal antibodies against Fc gamma BP (K9 or K17) and labelled IgG, was conducted in various mucin producing tissues: colon, small intestine, stomach, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, conjunctiva, and cervix uteri. The binding activity of Fc gamma BP in mucus extracted from colon, gastric juice, bile, nasal discharges, saliva, sputum, and tears was also examined by immunodotblot and immunoprecipitation using these monoclonal antibodies. Inhibition of complement mediated haemolysis by Fc gamma BP was investigated using sheep red blood cells (SRBC) and anti-SRBC IgG. RESULTS: The immunohistochemical study revealed that mucin secreting cells in the colon, small intestine, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, and cervix uteri contained Fc gamma BP, and immunodotblot and immunoprecipitation analysis using IgG and monoclonal antibodies demonstrated that the fluids secreted by these cells were capable of binding IgG. Mucin producing cells of the conjunctiva did not express Fc gamma BP molecules or bind to IgG. The surface mucus cells in the stomach were variably positive for Fc gamma BP. Perhaps because of proteolytic degradation, Fc gamma BP in gut lavage fluid did not have IgG binding activity, although this activity was present in the mucus covering the colon. Fc gamma BP suppressed complement mediated haemolysis of SRBC. CONCLUSIONS: Fc gamma BP is widely expressed on mucosal surfaces and in external secretions. It is functionally intact in several fluids. These findings lend support to the concept that Fc gamma BP is an important component of mucosal immunological defences.

Animals↗
PubMed2002

[Surgical treatment of cardiovascular manifestations of Marfan syndrome].

The present study determines the effect of surgical treatment of cardiovascular manifestations of Marfan syndrome in 72 patients by 114 operations, during 34-year period. This therapy resulted in aortic root repair, aortic arch replacement, or both in 78, mitral valve repair in 9, descending thoracic aortic replacement in 14, thoracoabdominal aortic replacement in 10, and abdominal aortic replacement in 6, including total aortic replacement in 4 and nearly total aortic replacement in 4 patients. Fusiform aneurysms were present in the the ascending aorta in 37, the aortic arch in 2, the thoracoabdominal aorta in 2, and the abdominal aorta in 6 patients. Aortic dissection occurred in 40 (55.6%), including type A aortic dissection in 29 patients. Aortic root repair included separate valve-graft in 8, Bentall composite valve-graft in 25, composite valve-graft with button technique in 26, composite valve-graft with interposition graft technique in 10, and valve sparing procedure in 5 patients. The overall early (30-day) mortality was 7.9%. The early survival was 75% in separate valve-graft procedure and 99.2% in composite valve-graft procedure. Late coronary dehiscence did not occur in the patients with Bentall technique in which the reattachments of coronary ostia were performed in 2 layers, but occurred in 50% of patients with the coronary anastomoses in 1 layer. Aortic valve regurgitation relapsed in 2 of the 5 patients with valve sparing procedure. Event free rate for the patients with composite valve-graft using button technique was 81.1% at 10 years. There were 14 late deaths; dissection or rupture of the residual aorta, composite graft endocarditis and cardiac failure were the principle causes of late deaths. In conclusion, Marfan patients with cardiovascular diseases can undergo surgical treatment with a low operative risk and low morbidity. Although late endocarditis remains a serious problem, we believe that Marfan syndrome is a contraindication for valve sparing procedure. Because of the potential for late dissection or aneurysm in other areas of the aorta, patients with Marfan syndrome should have serial computed tomographic scans indefinitely.

Adolescent↗
PubMed2001

Effects of aging on 5-HT(1A) receptors and their functional response to 5-HT(1a) agonist in the living brain: PET study with [carbonyl-(11)C]WAY-100635 in conscious monkeys.

Age-related changes in the serotonin 5-HT(1A) receptors in the living brains of conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) were evaluated by [carbonyl-(11)C]WAY-100635 and high-resolution positron emission tomography (PET). The regional distribution pattern of [carbonyl-(11)C]WAY-100635 at 60-91 min postinjection was the highest in the cingulate gyrus and hippocampus, high in the frontal and temporal cortices, lower in the occipital cortex, striatum, thalamus, and raphe nuclei, and lowest in the cerebellum in both young and aged monkeys. Graphical Logan plot analysis with metabolite-corrected plasma radioactivity as an input function into the brain was applied to evaluate 5-HT(1A) receptor binding in vivo. Significant age-related decreases in 5-HT(1A) receptor binding were observed only in the frontal and temporal cortices. In the hippocampus, although 5-HT(1A) receptor binding indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the 5-HT(1A) receptor agonist 8-OH-DPAT was administered intravenously at a dose of 0.1, 0.3, or 1 mg/kg 30 min after tracer injection, binding of [carbonyl-(11)C]WAY-100635 was displaced in both age groups in a dose-dependent manner. However, the degree of displacement was more marked in young than in aged monkeys. These observations demonstrated the usefulness of [carbonyl-(11)C]WAY-100635 as an indicator of the age-related changes in cortical 5-HT(1A) receptors measured noninvasively by PET. In addition, these observations suggested that the age-related impairment of 5-HT(1A) receptor responses to 8-OH-DPAT might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Ketamine alters the availability of striatal dopamine transporter as measured by [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the monkey brain.

The effects of ketamine anesthesia on the binding of [(11)C]-labeled cocaine analogs, [(11)C]beta-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) and [(11)C]beta-CIT-FE (N-(2-fluoroethyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane), to the striatal dopamine transporter (DAT) were evaluated in the monkey brain using positron emission tomography (PET). We sequentially measured the kinetics of these labeled compounds in the brains of five young-adult male rhesus monkeys (Macaca mulatta) in the conscious state, followed by those under ketamine anesthesia with continuous infusion (3 and 10 mg/kg/h). After intravenous injection, [(11)C]beta-CFT and [(11)C]beta-CIT-FE were predominantly accumulated in the striatum in both conscious and ketamine-anesthetized states. In the conscious state, the striatal uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE continuously increased with time up to 91 min after injection. Continuous infusion of ketamine-induced higher levels of uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE into the brain in a dose-dependent manner as compared with conscious state, and kinetic analysis with metabolite-corrected arterial input function indicated that the binding potentials (BP = k(3)/k(4)) of both compounds were elevated by ketamine. Not only [(11)C]beta-CIT-FE but also [(11)C]beta-CFT reached the equilibrium state of specific binding in the striatum within 40-50 min after injection. The present results demonstrated that ketamine significantly alters the DAT availability as measured with [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the brain.

Anesthetics, Dissociative↗
PubMed2001

Facilitation of dopaminergic neural transmission does not affect [(11)C]SCH23390 binding to the striatal D(1) dopamine receptors, but the facilitation enhances phosphodiesterase type-IV activity through D(1) receptors: PET studies in the conscious monkey brain.

The present study evaluated the effects of methamphetamine and scopolamine on the striatal dopamine D(1) receptor binding, measured by [(11)C]SCH23390, and D(1) receptor-coupled cAMP messenger system, determined as phosphodiesterase type-IV (PDE-IV) activity, were evaluated in the brains of conscious monkeys using positron emission tomography (PET) with microdialysis. When methamphetamine (0.1, 0.3, and 1 mg/kg) or scopolamine (0.01, 0.03, and 0.1 mg/kg) was systemically administered, [(11)C]SCH23390 binding to D(1) receptors was not affected. With administration of methamphetamine, the striatal PDE-IV activity, as measured with R-[(11)C]rolipram (active form) and S-[(11)C]rolipram (inactive form), was dose-dependently facilitated with enhanced dopamine level in the striatal ECF. Administration of scopolamine also induced facilitated PDE-IV activity without any apparent changes in the ECF dopamine. These facilitations of PDE-IV activity were abolished by preadministration of SCH23390, but not by raclopride. These results demonstrate that, as evaluated by PDE-IV activity, the inhibition of muscarinic cholinergic receptors actually facilitated dopamine neuronal signal transduction through D(1) receptors, as observed previously on D(2) receptors with no apparent increase in the striatal ECF dopamine level, but the enhanced dopamine transmission could not detected by [(11)C]SCH23390.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Congenital glaucoma and Silver-Russell phenotype associated with partial trisomy 7q and monosomy 15q.

We report on a 28-year-old man with trisomy 7q34-qter and monosomy 15q26.3-qter caused by a paternal balanced chromosomal translocation, t(7;15)(q34;q26.3). He had bilateral congenital glaucoma (buphthalmos), as well as typical manifestations of partial trisomy 7q. To our knowledge, this is the second description of a possible relation between congenital glaucoma and 7q trisomy. He also had some Silver-Russell syndrome features, such as short stature of prenatal onset, a characteristic triangular face, clinodactyly of the fifth fingers, and body asymmetry. Fluorescence in situ hybridization analysis on his chromosomes revealed that one copy of the insulin-like growth factor 1 receptor gene (IGF1R) at 15q25-q26 was deleted, suggesting a possible role of IGF1R in the SRS phenotype.

Abnormalities, Multiple↗
PubMed2001

Detection of Fcgamma binding protein antigen in human sera and its relation with autoimmune diseases.

Intestinal goblet cells of patients with ulcerative colitis and Crohn's disease highly express a binding protein of the Fc portion of IgG (FcgammaBP), which is entirely different from the Fcgamma receptors I,II, and III on neutrophils and macrophages. In this study, we proved the qualitative existence of FcgammaBP antigen in the sera of patients with rheumatoid arthritis and systemic lupus erythematosus, and, further, established a highly sensitive and quantitatively reproducible assay for FcgammaBP antigen in order to prevent the cross-reactivity of FcgammaBP with von Willebrand factor which has about 30% homology. This assay revealed a higher level of FcgammaBP antigen in the blood stream of patients with autoimmune diseases, especially progressive systemic sclerosis. This would suggest that abnormal production of autoantibodies reflects increased generation of FcgammaBP in goblet cells and its secretion into the circulation by an unknown mechanism.

Animals↗
PubMed2001

Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene.

NR-binding SET-domain-containing protein (NSD1) is a mouse nuclear protein containing su(var)3-9, enhancer-of-zeste, trithorax (SET), proline-tryptophan-tryptophan-proline (PWWP) and plant homeodomain protein (PHD)-finger domains (Huang et al., EMBO J. 17 (1998) 3398). This protein also has two other distinct nuclear receptor (NR)-interaction domains, called NID(-L) and NID(+L), and acts as both a NR corepressor and a coactivator by interacting directly with the ligand-binding domain of several NRs. Thus, NSD1 is a bifunctional, transcriptional, intermediary factor. We isolated the human homologue (NSD1) of the mouse NSD1 gene (Nsd1), mapped it to human chromosome 5q35, and characterized its genomic structure. NSD1 consists of at least 23 exons. Its cDNA is 8552 bp long, has an 8088 bp open reading frame, contains at least six functional domains (SET, PWWP-I, PWWP-II, PHD-I, PHD-II, and PHD-III) and ten putative nuclear localization signals, and encodes 2696 amino acids. NSD1 shows 86% identity with the mouse Nsd1 at the nucleotide level, and 83% at the amino acid level. NSD1 is expressed in the fetal/adult brain, kidney, skeletal muscle, spleen, and the thymus, and faintly in the lung. Two different transcripts (9.0 and 10.0 kb) were consistently observed in various fetal and adult tissues examined. These findings favor the character of NSD1 as a nucleus-localized, basic transcriptional factor and also a bifunctional transcriptional regulator, such as that of the mouse Nsd1. It remains to be investigated whether mutations of NSD1 lead to a specific phenotype in man.

Amino Acid Sequence↗
PubMed2001

Age-related changes in muscarinic cholinergic receptors in the living brain: a PET study using N-[11C]methyl-4-piperidyl benzilate combined with cerebral blood flow measurement in conscious monkeys.

The effects of changes in regional cerebral blood flow (rCBF) with aging on muscarinic cholinergic receptor binding were evaluated with [15O]H(2)O and N-[11C]methyl-4-piperidyl benzilate (4-MPB) in the living brains of young (5.9+/-1.8 years old) and aged (19.0+/-3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo with [11C]4-MPB, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and graphical Patlak plot analysis was applied. In addition, two-compartment model analysis using the radioactivity curve in the cerebellum as an input function (reference analysis) was also applied to determine the distribution volume (DV=K(1)/k(2)') for [11C]4-MPB. With metabolite-corrected arterial input, Patlak plot analysis of [11C]4-MPB indicated a regionally specific decrease in muscarinic cholinergic receptor binding in vivo in the frontal and temporal cortices as well as the striatum in aged compared with young animals, showing no correlation with the degree of reduced rCBF. In contrast, on the reference analysis with cerebellar input of [11C]4-MPB, all regions assayed except the pons showed a significant age-related decrease of DV, and the degree of reduction of DV was correlated with that of rCBF. These results demonstrated the usefulness of kinetic analysis of [11C]4-MPB with metabolite-corrected arterial input, not with reference region's input, as an indicator of the aging process of cortical muscarinic cholinergic receptors in vivo measured by PET with less blood flow dependency.

Acetylcholine↗
PubMed2001

Synthesis and redox behavior of azulene-substituted benzene derivatives and (eta(5)-cyclopentadienyl)[tetra- and di(6-azulenyl)cyclobutadiene]cobalt complexes.

1,2-Di(6-azulenyl)tetraphenylbenzenes and (6-azulenyl)pentaphenylbenzenes were synthesized by Diels-Alder reactions of di(6-azulenyl)acetylenes and 6-(phenylethynyl)azulenes with tetraphenylcyclopentadienone. Cobalt-mediated cyclooligomerization of mono- and di(6-azulenyl)acetylenes afforded 1,3,5- and 1,2,4-tri(6-azulenyl)benzene derivatives together with (eta(5)-cyclopentadienyl)[tetra- and di(6-azulenyl)cyclobutadiene]cobalt complexes. The redox behavior of these novel (6-azulenyl)benzene derivatives and [tetra- and di(6-azulenyl)cyclobutadiene]cobalt complexes was examined by cyclic voltammetry (CV). Mono(6-azulenyl)benzenes exhibited a reduction wave upon CV. In contrast, 1,2-di(6-azulenyl)benzenes showed a two-step reduction wave at the similar potential region upon CV, which revealed the formation of a dianion stabilized by 6-azulenyl substituents under electrochemical reduction conditions. Three 6-azulenyl substituents on benzene in a 1,2,4 relationship also increased electron-accepting properties because of the formation of a closed-shell dianionic structure, whereas 1,3,5-tri(6-azulenyl)benzenes were reduced stepwise.

Journal Article↗
PubMed2001

Solid-Phase synthesis of a library constructed of aromatic phosphate, long alkyl chains and tryptophane components, and identification of potent dipeptide telomerase inhibitors.

Telomerase inhibitors are expected as a new candidate of therapeutic agents for cancer. Recently, we have found novel inhibitors based on the bisindole skeleton. In this study, solid-phase synthesis was applied to construct a library of inhibitors having aromatic phosphate, long alkyl chain and tryptophane components, from which a D,D-ditryptophane derivative has been identified as a new potent telomerase inhibitor with IC(50) values of 0.3 microM. A hypothetical binding model for the new inhibitors has been proposed based on the structure-activity relationship.

Dipeptides↗
PubMed2001

Genetic susceptibility and environmental estrogen-like compounds.

Environmental chemicals with estrogenic activities have been suggested to be able to interact with the endocrine system. Endogenous estrogen is synthesized in the ovarian theca cells of premenopausal women or in the stromal adipose cells of the breast of postmenopausal women and minor quantities in peripheral tissue. These cells, as well as breast tissue, express all the necessary enzymes for this synthesis, CYP17, CYP11a, CYP19, 17-beta-hydroxysteroid hydrogenase, steroid sulfatase as well as enzymes further hydroxylating estradiol, such as CYP1A1, CYP3A4, CYP1B1, catechol-o-methyltransferase (COMT). Polymorphisms in these enzymes may have a possible role in the link between environmental estrogens and hormone-like substances and the interindividual risk of breast cancer.

Aromatase↗
PubMed2001

Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide.

BACKGROUND: Excessive production of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is critically involved in endotoxin (ET)-induced hypotension. Tumor necrosis factor-alpha (TNF-alpha) plays an important role in induction of iNOS. Because activated protein C (APC), a physiological anticoagulant, inhibits TNF-alpha production, it might prevent hypotension by inhibiting excessive production of NO. In this study, we examined this possibility using a rat model of septic shock. METHODS AND RESULTS: Intravenous administration of APC prevented both ET-induced hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-). The hypotension was also inhibited when APC was administered 30 minutes after ET administration. APC inhibited the increases in lung levels of iNOS activity by inhibiting expression of iNOS mRNA in animals given ET. APC significantly inhibited the increases in lung tissue levels of TNF-alpha and expression of TNF-alpha mRNA in animals given ET. Neither DEGR-F.Xa, a selective inhibitor of thrombin generation, nor DIP-APC, an active site-blocked APC, showed any effect on these ET-induced changes. Both inhibition of TNF-alpha production by leukocytopenia and treatment with anti-rat TNF-alpha antibody produced effects similar to those induced by APC. Aminoguanidine, a selective inhibitor of iNOS, inhibited both the hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(-) in this animal model. CONCLUSIONS: These observations strongly suggest that APC inhibits iNOS induction by decreasing TNF-alpha production, leading to the prevention of ET-induced hypotension. Furthermore, such effects of APC were not dependent on its anticoagulant effects but rather on its serine protease activity.

Amino Acid Chloromethyl Ketones↗