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Biomedical subjects

S Akimoto

Publications and source records attributed to S Akimoto.

At least 91 records · Page 5Linked to original sources
PubMed1996

Formation of focal adhesion and spreading of polarized human colon cancer cells in association with tyrosine phosphorylation of paxillin in response to phorbol ester.

Regulation of cell adhesion systems is involved in both normal development and the invasive behavior of carcinomas. We examined alterations of cell morphology and adhesion molecules in response to phorbol ester treatment of the SW1116 colon cancer cell line, which forms well-organized dome-like tubular structures in culture. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced rapid spreading of cancer-cell colonies through formation of focal adhesion and disappearance of adherens junctions. Immunologic analyses demonstrated that tyrosine-phosphorylated proteins were concentrated at focal adhesions, and that tyrosine phosphorylation of two proteins, paxillin and an unidentified 130-kd protein, was significantly increased. Tyrosine phosphorylation of paxillin was detectable within 15 min after TPA treatment, when only lamellipodia had extended from the colony, and in cells treated with blocking antibodies against integrins beta 1 and beta 5, which strongly inhibited spreading and disorganization while preserving adherens junctions. The level of paxillin phosphorylation correlated well with the degree of morphologic change induced by low-dose TPA, and the dephosphorylation occurred before reversion of morphology upon removal of TPA. These findings suggest that the TPA signal was transduced to the tyrosine phosphorylation of paxillin strongly associated with formation of focal adhesion, and that this in turn induced dysfunction of the cadherin system and caused spreading and disorganization of the tubular structure. The mechanism responsible for disruption of the cadherin system at adherens junctions was not clear, but the transition of beta-catenin into nuclei corresponded to the disappearance of its signal along areas of cell-cell contact. This SW1116 model provides a good system for studying the molecules involved in transient regulation and crosstalk between the cell-cell and cell-substratum adhesion systems, which may explain the mechanism of invasion of well-differentiated human carcinomas.

Antibodies, Monoclonal↗
PubMed1996

[Prognostic factors in stage D2 prostate cancer: results of univariate and multivariate analyses].

To evaluate prognostic factors in stage D2 prostate cancer, 235 patients who had been treated with endocrine therapy were investigated. With univariate analysis, performance status, hemoglobin concentration, serum alkaline phosphatase, LDH, histological grade, extent of disease (EOD), and response of tumor markers at 3 months were shown to be significant prognostic factors. To compare these 7 factors, multivariate analyses was performed in 196 cases. Cox proportional hazard model demonstrated that LDH, followed by response of tumor markers at 3 months, histological grade, and EOD were significant for predicting prognosis. We concluded that the patients whose serum LDH was above the normal range and/or whose tumor markers were not or had not been normalized 3 months after the onset of endocrine therapy were in the high risk group, and should be given more aggressive treatment.

Aged↗
PubMed1996

Antineutrophil cytoplasmic autoantibodies in patients with systemic sclerosis.

Perinuclear type of antineutrophil cytoplasmic antibodies (p-ANCA) have been found in patients with periarteritis nodosa, Churg-Strauss arteritis, or pauci-immune idiopathic crescentic glomerulonephritis. Recently, the association of p-ANCA and normotensive renal failure, in patients with systemic sclerosis (SSc), was reported. We have studied the incidence of p-ANCA in patients with SSc and have investigated its relationship to clinical and laboratory findings. Sera from 77 patients with SSc were examined by the indirect immunofluorescence (IIF) test, employing an ethanol-fixed human neutrophil and enzyme-linked immunosorbent assay, using purified myeloperoxidase (MPO) as an antigen (MPO-ELISA). The sera from seven patients (9.1%) were p-ANCA positive, by both IIF and MPO-ELISA. One patient died from systemic necrotizing angiitis but the remaining six patients have shown no symptoms of systemic vasculitis or of renal involvement. There was a tendency for patients positive for p-ANCA (anti-MPO antibody) to also be positive for other autoantibodies, such as anti-Sc1-70 antibody, anti-centromere antibody, anti-microsome antibody, anti-thyroglobulin antibody and rheumatoid factor. Although the incidence of p-ANCA (anti-MPO antibody) is low in patients with SSc, and its clinical significance in SSc needs further investigations, this could be a serological marker for certain symptoms in SSc.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.

Adenocarcinoma↗
PubMed1996

[Mass screening for prostate cancer in Japan].

Since 1975 mass screening for prostate cancer has been performed in Japan. The Prostate Research Foundation has analysed the data every year that collected from all institutes performing a mass screening. Up to 1993, 67, 225 subjects were examined. The detection rate of prostate cancer was 0.69%. Approximately half of the cancer were stage B, and the subjects who have metastatic stage were only 20% and the pattern of stage seemed to be different from that of patients who visited hospitals. In Chiba prefecture the subjects lived in a district of south Boso peninsula received a mass screening for prostate cancer with total of 1,964 men from 1985, and 17 cancers were diagnosed (0.87%). The distribution of prostate-specific antigen (PSA) assayed with Tandem-R kit was examined using the stocked sera (n = 976) of the screening for prostate cancer in Chiba prefecture. The percentage of 0.05-4.0 ng/ml, 4.1-9.9 ng/ml, over than 10.0 ng/ml of the PSA, were 89.6%, 7.0%, 3.4%, respectively. This distribution is approximately as same as the previous reports by the United States and Canada.

Age Factors↗
PubMed1995

c-erbB-2 gene product directly associates with beta-catenin and plakoglobin.

Association of the c-erbB-2 oncogene product with the cadherin-catenin complex has been demonstrated in human cancer cell lines. Although beta-catenin and plakoglobin have been proven to be crucial for the association, no previous study has shown whether the interactions are direct or indirect. In the present study, the c-erbB-2 gene product was shown by far-Western blotting analysis to associate directly with both beta-catenin and plakoglobin through its cytoplasmic domain core region, which showed extensive homology with epidermal growth factor receptor. These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers.

Adenocarcinoma↗
PubMed1995

Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate.

OBJECTIVES: A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. METHODS: Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. RESULTS: Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. CONCLUSIONS: Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

Aged↗
PubMed1995

Molecular cloning of the leuB gene from Bacteroides fragilis by functional complementation in Escherichia coli.

Clones containing the Bacteroides fragilis leuB-complementing gene were isolated by screening of a B. fragilis genomic library constructed in Escherichia coli. One recombinant clone, designated pOT865, with the smallest DNA insert (4.5 kb) could complement three independent leuB mutations in E. coli and the leuB-complementing determinant in pOT865 was localized to a region of 1.5-kb DNA. The results of Southern blot analysis suggested that a single copy of the cloned gene was present in the B. fragilis genome. The cloned fragment appeared to contain a sequence that could function as promoter in E. coli and direct the synthesis of a 42-kDa protein. These results suggest that the cloned segment contains the structural gene for beta-isopropylmalate dehydrogenase (leuB).

3-Isopropylmalate Dehydrogenase↗
PubMed1995

Nucleotide sequence of the gene encoding beta-isopropylmalate dehydrogenase (leuB) from Bacteroides fragilis.

The complete nucleotide sequence of the gene (leuB) coding for beta-isopropylmalate dehydrogenase of Bacteroides fragilis was determined. An open reading frame of 1,061 nucleotides was detected that could encode a polypeptide of 353 amino acid residues with a calculated molecular mass of 39,179 Da. The deduced amino acid sequence of the beta-isopropylmalate dehydrogenase from B. fragilis showed substantial sequence similarity with the beta-isopropylmalate dehydrogenases from other bacteria.

3-Isopropylmalate Dehydrogenase↗
PubMed1995

Purification and characterization of a fibrinogen-degrading protease in Bacteroides fragilis strain YCH46.

A novel fibrinogenolytic protease was purified from Bacteroides fragilis strain YCH46. The protease was extracted from cells by ultrasonic treatment and was purified 425-fold with a recovery of 2.1% by sequential procedures using azocasein as a substrate. The purified protease showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an estimated molecular weight of 100 kDa, which was consistent with the value obtained by gel filtration, indicating a monomeric native structure. Its optimal pH, Km, and Vmax for azocasein were 7.5, 0.2%, and 286 U/min/mg, respectively. The protease activity was completely inhibited by addition of 1 mM Hg2+, Cu2+, Zn2+, diisopropyl fluorophosphate, N-ethylmaleimide or p-chloromercuribenzoate but not by the inhibitors of metalloprotease or aspartic protease, suggesting that the enzyme is a serine-thiol-like protease. The protease hydrolyzed azocasein, casein, fibrinogen, gelatin, and azocoll, but not bovine serum albumin, ovalbumin, fibrin, fibronectin, immunoglobulins, transferrin, hemoglobin or types I, III, and IV collagen. The enzyme also hydrolyzed the chromogenic substrates alanyl-alanine p-nitroanilide, L-valyl-alanine p-nitroanilide, alanyl-alanyl-valyl-alanine p-nitroanilide, and glycyl-proline p-nitroanilide, but was inert toward L-alanine p-nitroanilide, alanyl-alanyl-alanine p-nitroanilide, and N-alpha-benzoyl-DL-arginine p-nitroanilide. The protease completely hydrolyzed the alpha-chain of fibrinogen at 37 C within 10 hr and at the same time the time required for clotting of protease-treated fibrinogen by thrombin was prolonged. The fibrinogenolytic activity of a crude extract of B. fragilis was stronger than that of other species of the Bacteroides fragilis group tested: B. ovatus, B. distasonis, B. eggerthii, B. uniformis, and B. thetaiotaomicron. These results suggest that the fibrinogenolytic protease is an important biological factor in Bacteroides infection.

Amino Acid Sequence↗
PubMed1995

Microsatellite instability and other molecular abnormalities in human prostate cancer.

Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple genetic loci may result from mismatch repair errors, and occurs in hereditary nonpolyposis colorectal carcinoma and certain sporadic cancers. To examine microsatellite instability during the pathogenesis of human prostate cancer, we screened 48 prostate cancer cases (20 stage B, 10 stage C and 18 endocrine therapy-resistant cancer-death cases) for replication error at 17 microsatellite marker loci on 9 chromosomes. Microsatellite instabilities were found in 7 of 48 cases (14.6%), and all 7 cases showing the instability were poorly differentiated adenocarcinomas. Moreover, microsatellite instabilities were more frequently observed in cancer-death cases (6/18, 33%) than in stage B + C cases (1/30, 3.3%). These data suggest that microsatellite instability is an important genetic change related to the progression of a subset of human prostate cancer cases. It is suggested to be associated with extensive, concurrent molecular changes including androgen receptor gene mutations, as well as frequent loss of heterozygosity at chromosomal regions 8p, 10q, and 16q.

Adenocarcinoma↗
PubMed1995

Disease progression in stage A prostate cancer.

To study the disease progression in stage A prostate cancer, 212 patients with stage A from a group of 3370 patients who underwent transurethral resection of the prostate, or subcapsular prostatectomy during the period 1972-1991 were followed. The stage A cases were subdivided into 103 A1 patients and 109 A2 patients and their subsequent course was followed for an average of 41.7 months (6-174 months). Progression to clinical cancer was found in 12 patients, 2 from A1 and 10 from A2 groups. This progression was evident 40.5 months (14-130 months) after prostatectomy. Eight (67%) of these cases responded to endocrine therapy. The rate of expression of ras p21, and the number of argyrophilic nucleolar organizer regions in stage A cancer cells were greater in progressing than in non-progressing cases. These results indicate that stage A cancer with progression arises mainly from the A2 subgroup and exhibits a distinctly proliferative potential even at small foci.

Adult↗
PubMed1995

Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine conjugate beta-lyase purified from Peptostreptococcus magnus.

To determine the role of cysteine conjugate beta-lyase (beta-lyase) in the metabolism of mutagenic nitropolycyclic aromatic hydrocarbons, we determined the effect of beta-lyase on the mutagenicities and DNA binding of cysteine conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), which are detoxified metabolites of the mutagenic compound 1-nitropyrene. We purified beta-lyase from Peptostreptococcus magnus GAI0663, since P. magnus is one of the constituents of the intestinal microflora and exhibits high levels of degrading activity with cysteine conjugates of 1-nitropyrene oxides (1-NP oxide-Cys). The activity of purified beta-lyase was optimal at pH 7.5 to 8.0, was completely inhibited by aminooxyacetic acid and hydroxylamine, and was eliminated by heating the enzyme at 55 degrees C for 5 min. The molecular weight of beta-lyase was 150,000, as determined by fast protein liquid chromatography. S-Arylcysteine conjugates were good substrates for this enzyme. As determined by the Salmonella mutagenicity test, 5 ng of beta-lyase protein increased the mutagenicity of the cysteine conjugate of 1-NP 9,10-oxide (10 nmol per plate) 4.5-fold in Salmonella typhimurium TA98 and 4.1-fold in strain TA100. However, beta-lyase had little effect on the cysteine conjugate of 1-NP 4,5-oxide (10 nmol per plate). Both conjugates exhibited only low levels of mutagenicity with nitroreductase-deficient strain TA98NR. In vitro binding of 1-NP oxide-Cys to calf thymus DNA was increased by adding purified beta-lyase or xanthine oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Tumor marker doubling time in patients with prostate cancer: determination of prostate-specific antigen and prostatic acid phosphatase doubling time.

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

Acid Phosphatase↗
PubMed1995

[Usefulness of hyper sensitive PSA assay kits for determination on low range of prostate specific antigen in prostate cancer].

Prostate specific antigen (PSA) levels after total prostatectomy or radiation therapy to localized prostate cancer and also during endocrine therapy are within normal range. Therefore, it is necessary to use hyper sensitive PSA assay kits for early detection of relapse. The present study was undertaken to evaluate two hyper sensitive assay kits (Delfia kit, lower limit 0.1 ng/ml, Kabi Pharmacia Diagnostics Co. and Markit M kit, 0.5 ng/ml, Dainippon Pharmaceutical Co.) and to compare them with conventional PSA kit (Eiken Chemical Co., 1.0 ng/ml). Total of 291 sera were examined: patients consisted of 10 total prostatectomy+endocrine therapy, 9 radiation therapy+endocrine therapy, 5 radiation therapy alone and 44 endocrine therapy alone. Values of endocrine therapy alone were divided into two groups according to duration after start of treatment; more or less than 5 years. The following results were obtained. 1. In non-relapse patients after total prostatectomy+endocrine therapy and radiation+endocrine therapy, PSA showed under lower limit with hyper sensitive kit. On the contrary, conventional kit indicated more than 1.0 ng/ml. 2. Radiation therapy alone kept PSA in detectable range with hyper sensitive kit in spite of no sign of relapse. 3. In non-relapsed patients under endocrine therapy alone, long duration (more than 5 years after start of treatment) decreased PSA in non detectable values with hyper sensitive kits. In this case, conventional kit still showed PSA as more than 1 ng/ml. 4. Doubling time at relapse was estimated similar with Delfia kit and Markit M kit, and much longer with conventional kit. It is concluded that hyper sensitive kit is more useful to manage patients after therapy than conventional kit.

Aged↗
PubMed1995

[Usefulness of fine needle aspiration cytology in the diagnosis of prostate cancer].

The efficacy of aspiration cytology, using Franzen method and echo-guided aspiration for prostate cancer was examined to 102 patients under saddle-block anesthesia in urological clinic of Chiba University Hospital. Between 1990 and 1993, 77 cases out of 102 patients were diagnosed histologically as prostate cancer by needle biopsy and 90% of them were coincidental with findings of aspiration cytology. Looking at histological grades, well differenciated cancer was shown to yield low positivity compared with moderately and poorly differentiated cancer. Positive rate showed similar when grade of specimens from needle biopsy was classified with Gleason pattern. Neither T category nor method of aspiration between Franzen and echo-guided methods influenced positive rate of aspiration cytology. On aspiration cytology, its grading revealed 60% of coincidence with that obtained by histological method. When counting more than 300 scattered cells, 90% of coincidence was achieved with histological grading. It is concluded that aspiration cytology is efficient for diagnosis of prostate cancer.

Biopsy, Needle↗