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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 289 records · Page 16Linked to original sources
PubMed1999

Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion.

This study describes the pharmacologic profile of a new Na+/H(+)-exchange inhibitor, FR183998, in anesthetized rats. FR183998 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes with median inhibitory (IC50) value of 0.3 nM. Treatment with FR183998 (0.01-0.32 mg/kg, i.v.) reduced or completely abolished ventricular fibrillation and mortality induced by 5-min ischemia followed by reperfusion, when it was administered not only 5 min before ischemia but also 1 min before reperfusion. Myocardial infarct size induced by 30-min ischemia and 60-min reperfusion was reduced significantly in a dose-dependent manner by FR183998 (0.1-1.0 mg/kg, i.v.) when the drug was administered preischemically or at an early phase of ischemia. The ventricular tachycardia and the ventricular fibrillation observed during the ischemic period also were suppressed significantly. These results indicate that FR183998 has a strong inhibitory effect on Na+/H+ exchange and suggest that treatment with FR183998 either before or immediately after the onset of ischemia can prevent the occurrence of arrhythmias and myocardial cell necrosis in situations of ischemia and reperfusion.

Anesthesia↗
PubMed1999

Clinicopathological features of superficial depressed-type colorectal neoplastic lesions.

OBJECTIVE: We performed this study to analyze the endoscopic findings, dissecting microscopic features, and p53 immunostaining in superficial depressed-type (depressed) colorectal neoplastic lesions. METHODS: Dissecting stereomicroscopy was used to ascertain the size and pit pattern of lesions removed by endoscopic snare polypectomy. Immunohistochemical staining of p53 was performed with an antigen retrieval system using a monoclonal antibody to p53. RESULTS: All depressed neoplastic lesions (submucosal carcinoma, n = 6; high-grade dysplasia, n = 14; and adenoma, n = 30) were small (< 1 cm in diameter) and were detected as a depression with or without a marginal elevation on colonoscopic examination. In the dissecting microscopic study, submucosal carcinomas and lesions of high-grade dysplasia almost exclusively showed irregular small pits, with the exception of four malignant lesions with moderate submucosal invasion in which the pit structure was absent. In contrast, adenomas had either regular small (29/30 lesions) or oval pits (1/30 lesions). Rates of p53 positivity were 100%, 64%, and 7% in depressed submucosal carcinomas, lesions of high-grade dysplasia, and adenomas, respectively, thus the prevalence of p53 positivity was significantly higher in the former two groups than in the adenoma group. CONCLUSIONS: The high frequency of invasive carcinoma and high-grade dysplasia found in depressed colorectal neoplastic tumors, despite their small size, indicates that these lesions may be a subtype of colorectal tumor with more aggressive malignant potential at an earlier stage.

Adenoma↗
PubMed1999

[Enterococcus gallinarum septicemia in a patient with acute myeloid leukemia].

A 62-year-old male was admitted with complaints of fever and body weight loss. The patient was diagnosed as acute myeloid leukemia (M1) and chemotherapy was started. About 80 days after admission, the patient developed diarrhea with high fever. And E. gallinarum was isolated from the blood culture. We carried out PCR using primers for vanA, vanB and vanC in our E. gallinarum, and showed the existence of the vanC1. This organism should be considered as one of the possible pathogenes in the infectious complications of the immuno-compromized patient.

Bacteremia↗
PubMed1999

[Clinical evaluation of anaerobic infections in patients with bronchopulmonary infections diagnosed by transtracheal aspiration].

We evaluated the clinical and bacteriologic features in the patients with bronchopulmonary infections isolated anaerobes from transtracheal aspirates between April 1990 and March 1998. Some anaerobe was isolated in 42 (10.9%) in 387 patients whom we performed transtracheal aspiration (TTA), in 42 (15.7%) of 268 in whom some organism was isolated from TTA, or in 42 (16.3%) of 257 patients in whom some bacterium excluding acid-fast bacteria, fungi or mycoplasma from TTA. The isolation rate of anaerobic bacteria was 93.3% in the patients with lung abscess, 22.7% in the patients with nosocomial pneumonia, 19.4% in the patients with community-acquired pneumonia, 26.7% in the patients with acute exacerbation of chronic lower respiratory tract infection (CLRTI), 1.6% in the patients with persistent infection of CLRTI, and 3.0% in the patients with acute bronchitis, respectively. The major anaerobes, isolated from TTA, were Peptostreptococcus micros and Prevotella melaninogenica. The aerobic bacteria were isolated with anaerobic bacteria in 32 of 42 patients at the same time. The quantitive grade of colonial growth of anaerobes was equal to or more than aerobes in the patients with lung abscess and pneumonia. We mostly administrated 3rd generation cephems or carbapenems with or without clindamycin for the treatment of anaerobic infections. Forty-one of 42 patients were cured only by the therapy of antimicrobial agents, but pneumonia patient with lung cancer died in spite of adequate antimicrobial therapy. These results suggest that the anaerobic infections are important in the bronchopulmonary infections.

Bacteria, Anaerobic↗
PubMed1999

Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease.

OBJECTIVE: Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS: An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a chi2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study. RESULTS: The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0. 63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E epsilon4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31). CONCLUSIONS: These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.

Adult↗
PubMed1999

Failure to confirm a synergistic effect between the K-variant of the butyrylcholinesterase gene and the epsilon4 allele of the apolipoprotein gene in Japanese patients with Alzheimer's disease.

To confirm a synergistic effect between the polymorphic K variant of the butyrylcholinesterase (BChE-K) gene and the epsilon4 allele of the apolipoprotein E (APOE) gene in Alzheimer's disease, the frequency of the BChE-K allele was re-examined in a large series of Japanese patients with Alzheimer's disease and controls. Two hundred and three patients with Alzheimer's disease and 288 age and sex matched controls were genotyped by polymerase chain reaction and restriction fragment length polymorphism for BChE-K and APOE. No changes were found in the frequency of BChE-K, either in the Alzheimer's disease group as a whole (0.17 v 0.14; p=0.36) or in early (0.16 v 0.16; p=0.98) or late (0.17 v 0.13; p=0.24) onset patients compared with age matched controls. The study failed to confirm the findings of a previous study which found a significantly higher incidence of BChE-K in patients with Alzheimer's disease with APOE epsilon4 allele than in controls. In the Japanese population studied here, there was no association between BChE-K and Alzheimer's disease, nor an interaction between BChE-K and APOE epsilon4 allele.

Aged↗
PubMed1999

Leiomyomas in uterine remnants associated with vaginal agenesis.

A premenopausal woman with vaginal agenesis underwent surgery for leiomyomas in rudimentary uterine horns. Immunohistochemical study of surgical specimens revealed that progesterone receptors are distributed in the nuclei of a majority of the leiomyoma cells and in the nuclei of a minority of the myometrial cells. Estrogen receptors are not detected in the surgical specimens.

Cell Nucleus↗
PubMed1999

Highly aggressive behavior and poor prognosis of small-cell carcinoma in the alimentary tract: flow-cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen.

The purpose of this study was to determine the clinical course, and effects of the histopathologic characteristics of specific tumors, including DNA contents and immunohistochemical aspects, in patients with small-cell carcinoma of the alimentary tract. Medical records of 14 patients who presented with small-cell carcinoma of the alimentary tract were retrospectively reviewed. Primary tumors were studied by immunohistochemical and flow cytometric analyses. Of these 14 small-cell carcinomas, 4 were esophageal, 8 gastric, and 2 colonic tumors. DNA aneuploidy was observed in 8 tumors. Staining for the p53 product was positive in 57.1% of all the tumors. The average proliferating cell nuclear antigen (PCNA) labeling rate (LR) was 72.4 +/- 11.6%. The average PCNA LR was significantly higher for the p53-positive group (p < 0.05). The estimated median survival was 253 days for all patients. Noncurative resection was associated with a significantly less favorable prognosis (p < 0.01). Distant metastases were observed in 13 of 14 patients. A higher PCNA LR of small-cell carcinoma may be an unfavorable characteristic of biological behavior. The patients with disseminated disease should undergo a symptomatically palliative operation combined with chemotherapy.

Adult↗
PubMed1999

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Aged↗
PubMed1999

Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 2. Condensed heterocyclic derivatives.

A novel series of platelet receptor glycoprotein (Gp) IIb/IIIa antagonists with condensed heterocycles as their basic core was synthesized. In an in vitro assay, trans-4-(5-amidinobenzofuran-2-carboxamido)cyclohexyloxyacetic+ ++ acid 17e and trans-3-[4-(5-amidinobenzofuran-2- carboxamido)cyclohexyl]propionic acid 17f produced marked inhibitions with IC50 values of 0.018 and 0.006 microM, respectively in a human platelet adenosin-5'-diphospate (ADP)-induced aggregation assay; they also exhibited a wide spectrum of inhibition toward major aggregation agonists (ADP, collagen, thrombin, PMA (tumor promoter) and arachidonic acid). These compounds were > 2-3 orders of magnitude more effective in inhibiting platelet aggregation than human umbilical vein endothelial cell (HUVEC) binding. The oral administration of 10 mg/kg of either 17e and 17f to guinea pig, resulted in a 60% inhibition of ex vivo platelet aggregation after 5 h. Oral administration of ethyl trans-4-(5-amidinoben-zofuran-2- carboxamido)cyclohexyloxyacetate 18e (10 mg/kg) resulted in 80% inhibition of platelet aggregation in dogs for 6 h after oral administration with a return to baseline by 24 h. Ethyl trans-3-[4-(5-amidinobenzofuran-2-carboxamido)cyclohexyl]propionat e 18f (AR0598) produced 80% inhibition for 5 h after oral administration. Prodrug 18e showed a good profile in dogs with a long duration of action. 18e (AR0510) was selected as suitable clinical candidate for development as an orally active antithrombotic agent.

Adenosine Diphosphate↗
PubMed1999

Synthesis and muscarinic activity of novel aniline derivatives with a 1-azabicyclo[3.3.0]octane moiety.

In order to develop drugs effective against Alzheimer's disease, we synthesized a series of aniline derivatives having a characteristic cyclic amine, 1-azabicyclo[3.3.0]octane ring, and evaluated their binding affinity for the central muscarinic cholinergic receptor. Among these compounds which showed high affinity to the M1 receptor, N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline (9f fumarate, SK-946) showed the highest affinity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced dementia mice. Some anilines with a 1-azabicyclo[3.3.1]nonane ring were also synthesized by the ring expansion of the 1-azabicyclo[3.3.0]octane ring, and showed a high affinity for the central muscarinic cholinergic receptor.

Aniline Compounds↗
PubMed1999

Low dose synthetic human atrial natriuretic peptide infusion in a patient with mitral stenosis and severe pulmonary hypertension.

The present report concerns a case of very low plasma levels of atrial natriuretic peptide (ANP) accompanying severe pulmonary hypertension due to mitral stenosis. There was remarkable fibrosis in the atrium and ANP secretion may have been insufficient. Low-dose infusion (0.025 microg kg(-1) min(-1)) of synthetic human alpha-ANP infusion was very effective in improving the pulmonary hypertension.

Atrial Natriuretic Factor↗
PubMed1999

Protective effect of FR168888, a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in rats: in comparison with other cardioprotective compounds.

We have studied the effects of FR168888 (5-hydroxymethyl-3-(pyrrol-1-yl)benzoylguanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in anesthetized rats and compared them with those of other cardioprotective compounds. FR168888 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes acidified with Na+-propionate with a Ki value of 6.4 nM. Pretreatment with FR168888 (0.032-0.32 mg/kg, i.v.) reduced or completely abolished the ventricular fibrillation (VF) induced by reperfusion after 5 min of regional ischemia, while lidocaine, a class I antiarrhythmic agent, showed less effect against VF as compared with FR168888. The size of myocardial infarction induced by 60-min ischemia and 60-min reperfusion was attenuated by FR168888 dose-dependently (1.0-10 mg/kg, i.v.), and ventricular tachycardia and VF were significantly reduced during the ischemic period. In contrast, propranolol and diltiazem did not show such protective effects on myocardial infarct size. In addition, FR168888 did not change hemodynamic parameters in rats. These results indicate that FR168888 has a strong inhibitory effect on Na+/H+ exchange and that treatment with FR168888 can protect the heart from arrhythmia and myocardial cell death in ischemic and reperfused situations.

Anesthesia↗
PubMed1999

Purification and characterization of beta-1,3-xylanase from a marine bacterium, Vibrio sp. XY-214.

beta-1,3-Xylanase was purified to gel electrophoretic homogeneity and 83-fold from a cell-free culture fluid of Vibrio sp. XY-214 by ammonium sulfate precipitation and successive chromatographies. The enzyme had a pl of 3.6 and a molecular mass of 52 kDa. The enzyme had the highest level of activity at pH 7.0 and 37 degrees C. The enzyme activity was completely inhibited by Cu2+, Hg2+, and N-bromosuccinimide. The enzyme hydrolyzed beta-1,3-xylan to produce mainly xylotriose and xylobiose but did not act on xylobiose, p-nitrophenyl-beta-D-xyloside, beta-1,4-xylan, beta-1,3-glucan, or carboxymethyl cellulose.

Amino Acid Sequence↗
PubMed1999

Analysis of the N-terminal polypeptide of the capsid precursor protein and the ORF3 product of feline calicivirus.

The N-terminal unique polypeptide region of the capsid precursor protein of feline calicivirus (FCV) and the protein encoded by ORF3 of FCV were expressed as fusion proteins with glutathione S-transferase to analyze the expressed products in FCV-infected cells. Immunoblot analysis using a serum from a cat experimentally infected with FCV indicated relatively high immunogenicity of the N-terminal polypeptide in FCV-infected cats, as compared with the ORF3 protein. Specific antisera were prepared by immunization to mice with the fused proteins and used in immunoblot analysis. A 14 kD product corresponding to the N-terminal polypeptide and a 10 kD polypeptide of the ORF3 product were identified in the FCV-infected cells but not detected in the purified particles. No neutralization activity against FCV was detected in these antisera. The proteins identified as polypeptides of 14 kD and 10 kD in this study may have functions as non-structural proteins.

Animals↗
PubMed1999

Analysis of porcine cytomegalovirus DNA polymerase by consensus primer PCR.

We used a consensus primer PCR method to amplify a region of herpesviral DNA-directed DNA polymerase gene using degenerate primers for initial characterization of the porcine cytomegalovirus (PCMV) genome. The sequence of the PCR product from PCMV DNA template and its alignment with other herpesvirus DNA polymerase counterparts showed that both conserved amino acid residues and conservative amino acid substitutions are in parallel. Phylogenetic analysis revealed that PCMV should be included in the clade comprising human herpesvirus 6 and 7, rather than human and mouse cytomegaloviruses, in Betaherpesvirus subfamily.

Amino Acid Sequence↗
PubMed1999

Expression of bovine cytokines in Escherichia coli.

Glutathione S-transferase fusion proteins of bovine interleukin-2 (IL-2), IL-4, IL-6 and interferon-gamma (IFN-gamma) were expressed in Escherichia coli. Complementary DNA (cDNA) for open reading frame of each cytokine without signal peptide encoding region was amplified by reverse transcriptional polymerase chain reaction method and was subcloned into pGEX-5X-1. In result, IL-6 and IFN-gamma fusion proteins in bacteria were soluble, but IL-2 and IL-4 fusion proteins were insoluble. The insoluble IL-2 fusion protein successfully refolded by urea became soluble. The recombinant IL-2, IL-6 and IFN-gamma could be obtained by the batch method using Glutathione Sepharose 4B and Factor Xa digestion, which may be useful for preparation of antisera as antigens and functional studies.

Animals↗