[Simple ulcer of the ileocaecal region associated with thyroid cancer, report of a case].
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Adult↗
Biomedical subjects
S Tada
Publications and source records attributed to S Tada.
Low stringency hybridization study of the dopamine D4 receptor revealed D4-like mRNA distribution of the orphan seven-transmembrane receptor, APJ, in human brain.
We recently reported that the density of mRNA for the dopamine D4 receptor was extremely low in human cerebral cortex but unexpectedly higher in the corpus callosum and spinal cord both of which contain substantial white-matter area. Under low stringency conditions, Northern blot analysis using the D4 probe detected cross-hybridized mRNAs having a similar distributional profile to the D4 mRNA in human brain regions, suggesting the mRNA distributional profile is not peculiar to the D4 receptor. Homology screening revealed one of the mRNAs to be an orphan seven-transmembrane receptor, APJ, abundantly expressed in the corpus callosum and spinal cord. In porcine spinal cord the APJ mRNA was detected at a higher level in white-matter rather than in gray-matter area. These data suggest that a group of seven-transmembrane receptors, including the D4 and APJ receptor, is preferentially expressed in the white-matter area probably in non-neuronal glial cells.
Animals↗
YM-50001: a novel, potent and selective dopamine D4 receptor antagonist.
We investigated some in vitro pharmacological properties of a novel human dopamine D2-like receptor antagonist, YM-50001 [(R)-5-chloro-4-cyclopropylacarbonylamino-2-methoxy-N-[1-(3-methox ybenzyl)- 3-pyrrolidinyl]benzamide monooxalate]. Receptor binding studies revealed that YM-50001 had a potent affinity for human D4 receptors (Ki = 5.62 nM). YM-50001 displayed weak or negligible affinity for other neurotransmitter receptors including human D2 and D3 receptors. YM-50001 shifted the dopamine response curve on each human D2-like receptor subtype-mediated low-Km GTPase activity to the right. YM-50001 also exhibited good D4 selectivity with respect to D2-like receptor antagonism in the functional assay. These results indicate that YM-50001 is a novel, potent and selective D4 receptor antagonist.
Benzamides↗
Effect of indomethacin suppositories on rectal polyposis in patients with familial adenomatous polyposis.
BACKGROUND: Oral sulindac is known to reduce polyps in patients with familial adenomatous polyposis (FAP). The authors speculated that rectal administration of indomethacin would be effective therapy for adenomas in the rectal remnant of FAP. METHODS: Eight patients with FAP who had been treated by total colectomy with ileorectal anastomosis were administered an indomethacin suppository (50 mg) once or twice daily during a period of 4 or 8 weeks. The number of polyps at the same site within the rectum was counted under proctoscopy prior to, at the end of, and after the treatment. In four patients, proliferative activity of the rectal mucosa was assessed by immunohistochemical staining for MIB-1. RESULTS: In six of the eight patients who initially had ten or more polyps, the number of polyps decreased to fewer than five, whereas such a decrease could not be observed in the remaining two patients. In the six patients, the number of polyps increased after indomethacin was discontinued. The proliferative activity of the rectal mucosa was higher at the end of treatment than it was prior to indomethacin administration. CONCLUSIONS: Indomethacin suppositories may be effective in the management of rectal adenomatosis in patients with FAP.
Adenomatous Polyposis Coli↗
Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds.
In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory activity against apomorphine-induced climbing behavior in mice. The results indicate that D2, D3, and D4 receptors have different bulk tolerance (D4 > D3 > D2) for the substituent of the 4-amino group (R1) on the benzamide nuclei and that cyclopropyl-, cyclobutyl-, and cyclopentylcarbonyl groups likely possess adequate bulkiness with respect to D3 and D4 affinity and selectivity over D2 receptors in this series. The results also suggested that the N-substituent (R2) on the pyrrolidin-3-yl group performs an important role in expressing affinity for D2, D3, and D4 receptors and selectivity among the respective subtypes. One of the compounds, (S)-(+)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-[(cyclopropylcarbonyl+ ++) amino]-2-methoxybenzamide (5c) (YM-43611), showed high affinity for D3 and D4 receptors (Ki values of 21 and 2.1 nM, respectively) with 110-fold D4 selectivity and 10-fold D3 preference over D2 receptors and weak or negligible affinity for representative neurotransmitter receptors. Compound 5c displayed potent antipsychotic activity in inhibiting apomorphine-induced climbing behavior in mice (ED50 value, 0.32 mg/kg sc).
Animals↗
New method for evaluation of perigastric invasion of gastric cancer by right lateral position CT.
The purpose of this study was to evaluate usefulness of right lateral position CT in determining invasion of gastric cancer into adjacent organs. We assessed whether position shift, a change in the relative location of a gastric tumor and adjacent organs between the supine position and right lateral position CT, was a useful sign for absence of invasion into perigastric organs. In 37 patients with advanced gastric cancer with doubtful invasion into adjacent organs by conventional CT after 500 ml water oral intake, additive right lateral CT was performed. Of 24 cases of lesions in the gastric body, 16 had a position shift and no invasion into adjacent organs at surgery (T3), and 8 had no position shift and invasion (T4). The accuracy was 100%. Six gastric cardial and 7 pyloric tumors showed no position shift, and 3 cardial and 2 pyloric tumors were proved to be noninvasive (T3). The accuracy of cardial and pyloric tumor was 50 and 71%. We concluded that position shift may be useful in the diagnosis of invasion of adjacent organs by gastric cancer, limited to in cases with gastric body cancer.
Adult↗
Autoimmune hemolytic anemia in allergic granulomatous angitis (Churg-Strauss syndrome).
We describe a patient with allergic granulomatous angitis who developed autoimmune hemolytic anemia (AIHA). A 44-year-old male had been suffering from bronchial asthma. On admission, laboratory tests revealed the presence of severe eosinophilia (21,500/microliters), elevation of total immunoglobulin E (IgE), high lactic dehydrogenase (LDH) and low haptoglobin levels, in addition to moderate reticulocytosis. During admission, the patient showed almost simultaneous occurrence of vasculitis in the extremities, severe hemolysis and exacerbation of asthma in relation to the progression of eosinophilia. Both IgM and IgG autoantibodies were considered to be responsible for hemolysis. Interestingly, serum levels of interleukin-4 (IL-4) and IL-5 were increased in association with eosinophilia and increased IgE production. These findings suggest that the AIHA in this patient is mediated or enhanced at least partly by high IL-4 and IL-5 production. Although AIHA in this syndrome is very rare, it should be considered as a clinical manifestation.
Adult↗
Low levels of mRNA for dopamine D4 receptor in human cerebral cortex and striatum.
Significant densities of mRNA for the dopamine D4 receptor in cerebral cortex, particularly in frontal lobe, have been reported in rats and monkeys, supporting the D4 hypothesis in the pathology of schizophrenia. Using northern blot analysis and the competitive reverse transcription-polymerase chain reaction (RT-PCR) method, we determined the relative levels of D4 mRNA in human brain regions to clarify whether the cortical level is also higher in humans. Northern blot analysis revealed an unexpected profile of D4 mRNA in the brain. The detected mRNA size, 1.5 kb, was quite different from the 5.3 kb reported in human neuroblastoma SK-N-MC cells. Higher levels of D4 mRNA were detected not only in the mesolimbic system but also in the corpus callosum, spinal cord, medulla, and subthalamic nucleus. It was surprising that in the cerebral cortex regions as well as the striatum, D4 mRNA was hardly detected. The competitive RT-PCR revealed these relative densities to be at least three orders of magnitude lower than that of the striatal D2 receptor. Our results demonstrate a remarkable difference in cortical D4 mRNA density in humans compared with that in rats and monkeys. Furthermore, the mRNA distribution suggests that the higher density of D4-like binding sites reported recently in normal human striatum is not due to the D4 receptor.
Blotting, Northern↗
Cloning of variable regions of an antibody that reacts with the soluble fraction of human liver cells and its possible value in chronic liver disease.
A gene encoding the variable regions of the heavy and light chains of a mouse monoclonal antibody designated H2, which specifically reacts with human liver cells, was cloned into a phagemid vector. The clone of the variable region was designed to be expressed as a separate protein, the structure of which is the same as that of the mouse antibody. The cloned phage protein specifically reacted with anti-idiotypic antibodies produced in rabbits against the original mouse antibody, and this reaction was specifically blocked by the original antibody. The soluble protein, expressed as a fusion protein, was detected as a single 30-kd band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and specifically bound to an anti-H2 idiotypic antibody as determined by Western blot analysis. Sera of patients with various diseases were assayed for antibodies to anti-H2 by sandwich enzyme-linked immunosorbent assay (ELISA). Only sera from patients with chronic liver disease reacted strongly. This binding was specifically blocked by the cloned soluble protein. The nucleotide sequences of the variable regions were determined by the dideoxy chain-termination method, and the sequences were approximately 95% identical to those of other mouse immunoglobulins. These findings suggest that a human antibody with the same idiotype as a mouse monoclonal antibody that reacts with human liver cells, can be detected in patients with chronic liver disease, suggesting that autoimmunity may be partly responsible for these diseases.
Adult↗
Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18.
Rat Kupffer cell (KC)-mediated cytotoxicity against both the syngeneic hepatoma cell line AH70 and hepatocytes was evaluated by changes in mitochondrial function, and the possible role of ICAM-1/CD18 in the interaction between the cells was studied. Rhodamine 123 fluorescence, a marker of the mitochondrial membrane potential, decreased in AH70 cells after co-culture with CK, while that in hepatocytes was unchanged by co-culture. This decrease was blocked by anti-ICAM-1 anti-CD18 and the inhibition of nitric oxide synthesis. Cytometric studies demonstrated that ICAM-1 expression on AH70 cells increased after addition of IFN-gamma, IL-1beta, tumor necrosis factor (TNF)-alpha or KC, while in hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatment inhibited the increase in ICAM-1 expression and the decrease in rhodamine 123 fluorescence on AH70 cells after co-culture with KC. CD18 on KC was increased only after co-culture with AH70. TNF-alpha but not IFN-gamma was detected in the supernatant of co-culture between KC and AH70 cells, and this production was partially inhibited by anti-ICAM-1 and anti-CD18. The activity of inducible nitric oxide synthase in Kupffer cells and the levels of nitrites and nitrates in the co-culture supernatant increased over time, and this increase was attenuated either by addition of NO synthesis inhibitors, anti-ICAM-1 or anti-CD18. These results indicate that the rat KC causes mitochondrial dysfunction in cancer cells via the production of NO and cell-to-cell adhesion via ICAM-1/CD18 has an important role in this cytotoxic process.
Animals↗
Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.
Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA.
Amyloid↗
Case report: agranulocytosis induced by interferon-alpha therapy for chronic hepatitis C.
A 60-year-old woman presented with chronic active hepatitis C whose HCV-RNA genotype was II according to Okamoto's classification and serum HCV-RNA concentration was 10(4) copies/mL. Agranulocytosis was induced 13 days from the commencement of interferon (IFN)-alpha 2b (6 MU/day) therapy, so the IFN therapy was immediately discontinued. The agranulocytosis improved rapidly with the administration of a granulocyte colony stimulating factor (G-CSF). The possibility that IFN was associated with maturational arrest of myeloid progenitor cells was considered. During the course of 3 years of follow-up, her liver function has remained normal and serum HCV-RNA remains negative.
Agranulocytosis↗
In vitro pharmacological profile of YM-43611, a novel D2-like receptor antagonist with high affinity and selectivity for dopamine D3 and D4 receptors.
1. We investigated some neurochemical properties of a novel benzamide, YM-43611, [(S)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-cyclopropylcarbonylamino+ ++-2- methoxybenzamide] in comparison with putative D2-like receptor antagonists using both rat and human cloned dopamine D2-like receptors in vitro. 2. Receptor binding studies revealed that YM-43611 had appropriately potent affinities for both rat and human D2-like receptors, with moderate selectivity for D3 receptors and high selectivity for D4 receptors over D2 receptors (Ki values (nM) for rat receptors: D2, 165; D3, 35.5; D4, 1.85, and for human receptors: D2, 42.9; D3, 11.2; D4, 2.10). 3. YM-43611 displayed weak or negligible affinity for other neurotransmitter receptors, namely D1, D5, alpha(1), alpha(2), beta, 5-HT1A, 5-HT2A, 5-HT3, H1, M1 and M2 receptors. 4. Dopamine stimulated low-Km GTPase activity on membranes from Chinese hamster ovary (CHO) cells expressing the human D2-like receptor subtype. This response to dopamine of low-Km GTPase activity was inhibited by use of putative D2-like receptor antagonists. YM-43611 showed a moderate selectivity for D3 receptors (Ki = 45.5 nM) and a high selectivity for D4 receptors (Ki = 3.28 nM) over D2 receptors (Ki = 70.6 nM). 5. Dopamine inhibited forskolin-stimulated adenylate cyclase in intact CHO cells expressing the human D2-like receptor subtype. YM-43611 shifted the inhibition curve of dopamine on respective D2-like receptor subtype-mediated cyclic AMP formation to the right in a parallel fashion, showing a pA2 value of 7.42 (38.1 nM) for D2 receptors, a pKB value of 8.06 (8.68 nM) for D3 receptors, and a pA2 value of 8.42 (3.77 nM) for D4 receptors. 6. YM-43611 but not the other D2-like receptor antagonists exhibited good selectivity with respect to dual antagonism for D3 and D4 receptors in both receptor binding and functional assays. 7. These results indicate that YM-43611 is a novel D2-like receptor antagonist with high potency and selectivity for both D3 and D4 receptors. YM-43611 is therefore expected to be valuable in exploration of the physiological role of D3 and D4 receptors.
Animals↗
Classification of pulsating flow patterns in curved pipes.
The fully developed periodic laminar flow of incompressible Newtonian fluids through a pipe of circular cross section, which is coiled in a circle, was simulated numerically. The flow patterns are characterized by three parameters: the Womersley number Wo, the Dean number De, and the amplitude ratio beta. The effect of these parameters on the flow was studied in the range 2.19 < or = Wo < or = 50.00, 15.07 < or = De < or = 265.49 and 0.50 < or = beta < or = 2.00, with the curvature ratio delta fixed to be 0.05. The way the secondary flow evolved with increasing Womersley number and Dean number is explained. The secondary flow patterns are classified into three main groups: the viscosity-dominated type, the inertia-dominated type, and the convection-dominated type. It was found that when the amplitude ratio of the volumetric flow rate is equal to 1.0, four to six vortices of the secondary flow appear at high Dean numbers, and the Lyne-type flow patterns disappear at beta > or = 0.50.
Classification↗
Characterization of the properties of a human homologue of Escherichia coli RecQ from xeroderma pigmentosum group C and from HeLa cells.
We showed that DNA-dependent ATPase Q1 (DNA helicase Q1) from xeroderma pigmentosum complementation group C (XP-C) cells elutes from FPLC Mono Q column at higher concentrations of KCl than that from other human cells (35). We purified DNA helicase Q1 from XP-C and HeLa cells. The purified fractions of both cells contained a major polypeptide with a molecular mass of 73 kDa and had the same enzymatic properties, including salt- and temperature-sensitivity. Characterization using an anti-DNA helicase Q1 antibody indicated that this enzyme localized in the nuclei and was not modified by incorporating phosphate groups through phosphorylation and ADP-ribosylation. No interactions of DNA helicase Q1 with other proteins were indicated by immunoprecipitation of the helicase from crude extracts. No difference was observed in XP-C cells in intracellular localization of DNA helicase Q1, phosphorylation, and the interaction with other proteins as compared to HeLa cells.
Adenosine Triphosphatases↗
Digalactosyldiacylglycerol suppression of inhibition by sulfoquinovosyldiacylglycerol of alpha-glucosidase.
Digalactosyldiacylglycerol (DGDG) suppressed the inhibition by sulfoquinovosyldiacylglycerol (SQDG) of an alpha-glucosidase reaction. Suppressing was considered to be an apparent decrease in inhibitory activity of SQDG ascribed to direct interaction between SQDG and DGDG. This suppression was presumed to be caused by less access of SQDG to the enzyme because SQDG and DGDG formed mixed micelles.
Drug Interactions↗
Factors affecting prognosis of idiopathic interstitial pneumonia.
Idiopathic interstitial pneumonia (IIP) is a progressive and often fatal pulmonary disorder, and evaluating the prognosis of patients with IIP has never been sufficient. Accordingly, factors including clinical features, laboratory data, cellular components in bronchoalveolar lavage (BAL) fluid and response to corticosteroid therapy were analyzed in 35 patients with IIP whose median age of respiratory onset was 60 years (range; 37-77 years). Nineteen patients (54.3%) were in the active stage of IIP and 16 of them were treated with corticosteroids. Significant prognostic factors were the neutrophil percentage in BAL fluid, interstitial shadows on chest radiograph, pulmonary function, blood oxygen level, grade of dyspnea, and disease activity at the initial examination. Patients in the active stage showed higher proportions of neutrophils and eosinophils in BAL fluid than those in the non-active stage. Despite corticosteroid therapy, the survival of patients in the active stage was significantly shorter than those in the non-active stage. Fifty percent of the patients treated with corticosteroids were regarded as responders at 1 month after the initiation of therapy; however, there was no significant difference between responders and non-responders in terms of survival time. In conclusion, disease activity and neutrophils in BAL fluid may be important predictors of the prognosis of IIP.
Adrenal Cortex Hormones↗
Keio multicenter trial in high-dose interferon-alpha 2b treatment for chronic hepatitis C. Keio Interferon-alpha 2b Study Group.
The efficacy of two different high-dose treatment of IFN-alpha 2b was evaluated in this study. Serum hepatitis C virus (HCV) RNA levels were semi-quantified by simplified reverse transcription-polymerase chain reaction. Seventy-one patients with chronic hepatitis C received 10 million units of IFN-alpha 2b daily for 2 weeks or twice a week for 24 weeks. Alanine aminotransferase (ALT) levels overall normalized in 78.1% and 51.6% of the cases at the end of the therapy and 6 months after that, respectively. HCV RNA disappeared in 71.9% and 35.7% of the patients at the end of the therapy and 6 months after that, respectively. There was no significant difference between the 2 different regimes. The efficacy of the treatment was fair in cases in which the pretreatment level of the viral amount was low. The results of this study indicate that daily administration of IFN in the first 2 weeks during 6-month course does not increase the efficacy of the therapy in such a high-dose treatment regime.
Adult↗