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Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 217 records · Page 12Linked to original sources

Fibronectin promotes the proliferation of cytotoxic T lymphocytes generated from cancer patients.

We studied whether fibronectin (FN) enhances the activity of autologous tumour-reactive cytotoxic T lymphocytes (CTLs) generated from cancer patients. The proliferation of CTLs stimulated by immobilised anti-CD3 monoclonal antibody and interleukin 2 (IL-2) was enhanced three or four times by immobilised FN. whereas soluble FN did not alter the DNA synthesis of CTLs. Moreover, the cytotoxic activity of CTLs was augmented by FN stimulation against autologous tumour cells [4 h 51Cr release assay: FN(+) 16.7 +/- 4.7% vs FN (-) 11.8 +/- 3.1%; 16 h 51Cr release assay: FN(+) 24.8 +/- 4.7% vs FN (-) 16.5 +/- 5.7%, P<0.05]. The major cell surface phenotype of CTLs with FN was CD3+, CD4+ and CD25+ in 6 weeks' culture. Cytotoxicity against autologous tumour cells was inhibited by anti-HLA class I monoclonal antibody (MAb). The autologous tumour-killing activity of CTLs was suppressed by the elimination of CD4+ cells. Moreover, the cytokine production of CTLs was augmented by FN stimulation. Especially, the production of IL-2, interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly augmented by FN stimulation (P<0.05). Thus, CTLs generated by FN might have both killer and helper functions, since they could lyse autologous tumour cells and secrete various cytokines, including IL-2.

Adult↗

Protective effect of ubiquinone (coenzyme Q9) on ascites in broiler chickens.

1. The effect of ubiquinone (CoQ(9)) on ascites in broiler chickens was investigated. 2. The commercial broilers were divided into 2 groups of 100 birds each; CoQ(9) treated group and non-treated group. 3. The chickens were grown in a positive-pressured house with double high efficiency particulate air filtered intakes and exhaust, and thus were strictly isolated from infectious agents. 4. The chickens (15 to 21 d old) were exposed to cold stress in order to induce ascites. 5. The number of birds with ascites in the CoQ(9)-treated group was significantly lower than in the non-treated group. 6. Survival and production rates were better in the CoQ(9)-treated group than in the non-treated group.

Animal Feed↗

Involvement of nitric oxide and eicosanoids in platelet-activating factor-induced haemodynamic and haematological effects in dogs.

1. Platelet-activating factor (PAF) is a phospholipid mediator with potent cardiovascular and haematological actions. But its mechanisms of action in vivo have not been fully elucidated, probably due to difficulties arising from previous findings that the effects of PAF are largely mediated by the release of a variety of other autacoids. In the present study, the roles of nitric oxide and eicosanoids in the effects of PAF (0.01-0.25 microgram kg-1 i.v.) on systemic and pulmonary vasculatures and circulating blood cell count were pharmacologically evaluated in anaesthetized dogs. 2. Higher doses of PAF (> 0.1 microgram kg-1) produced a biphasic systemic hypotension. The first hypotension seen 30 s after the injection was accompanied by a decrease in systemic vascular resistance, thrombocytopenia and leukopenia, while the second hypotension seen 1-2 min after PAF was accompanied by a marked rise in pulmonary vascular resistance and decreases in aortic blood flow and cardiac contractility. Lower doses of PAF (0.01 - 0.05 microgram kg-1) caused only the first responses in a dose dependent manner. 3. Pretreatment with indomethacin inhibited the second responses to PAF without affecting the first responses. The thromboxane A2/prostaglandin H2 (TP)-receptor antagonist vapiprost blocked the PAF-induced rise in pulmonary vascular resistance. AA-861, a 5-lipoxygenase inhibitor, attenuated the PAF-induced cardiac depression. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester inhibited the PAF-induced early decrease in systemic vascular resistance. 4. All observed changes in haemodynamics and blood cell count after PAF were almost abolished by TCV-309, a PAF-receptor antagonist. 5. Reproducible hypotension and thrombocytopenia produced by a lower dose of PAF (0.05 microgram kg-1) were respectively attenuated and potentiated by pretreatment with NG-nitro-L-arginine, another nitric oxide synthase inhibitor. Administration of L-arginine reversed the effects of the nitric oxide synthase inhibitor. 6. These results indicate that PAF-receptor-mediated production of not only eicosanoids but also nitric oxide may contribute to the cardiovascular and haematological responses to PAF in the dog.

Animals↗

A quantitative analysis of testosterone action on FSH secretion from individual pituitary cells using the cell immunoblot assay.

We investigated the effects of testosterone on FSH secretion from male rat anterior pituitary cells in culture at the single cell level. Anterior pituitary cells cultured with or without 10 ng/ml testosterone for 72 h were mono-dispersed and subjected to cell immunoblot assays for FSH. Cell blots specific for FSH were quantified by means of a microscopic image analyzer. The number of FSH-secreting cells detected as immunoreactive cells blots on the transfer membrane represented 4.1% of total pituitary cells applied on the membrane. The amount of FSH secreted by single cells varied from < 20 to > 8,000 fg/cell/h. The number of FSH-secreting cells was not changed by the addition of 10 ng/ml testosterone into the culture medium. Testosterone administration increased the mean FSH secretion by 64% after 3 h incubation, resulting in a shift to the right in the frequency distribution of FSH secretion from single cells. The total amount of FSH, namely the sum of FSH secreted by each FSH-secreting cel, was increased by 92% by the addition of testosterone. However, mean amounts of FSH secretion by the top ten cells of the largest secretor subgroup (> 5 pg/cell/3 h) were not different between control and testosterone-treated groups. The present study analyzed, for the first time, FSH secretion from rat anterior pituitary cells at the single cell level. The results suggest that stimulation by testosterone of FSH secretion in vitro is not due to an increase in the number of FSH-secreting cells but to an increase in FSH secretion from each cell.

Animals↗

[Extirpation of total urinary tract as a final treatment for asynchronous multicentric urothelial cancer: a case report].

A 48-year-old male patient underwent transurethral resection (TUR) for solitary bladder tumor in January 1985. Pathological finding of the specimen was non-invasive transitional cell carcinoma (TCC) G2 > G1. Following the operation, prophylactic intravesical instillation of antitumor agents, intrapelvic irradiation, and hyperthermia were done for the recurrences. In June 1987, left renal pelvic tumor revealed, and nephroureterectomy was performed. Histological examination of renal pelvic tumor showed TCC G1. Five months later, multiple bladder tumors and right renal pelvic tumor were detected. A total cystectomy, partial nephrectomy and nephrostomy were performed in February and March 1988. Pathology of the bladder and right kidney were TCC G3. One month after these operations, tumors recurred in the rest of the right kidney. Complete remission was achieved after systemic chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). In January 1992, right renal pelvic tumor recurred again. After two cycles of M-VAC therapy, the rest of the right kidney was extirpated. Postoperative hemodialysis has been uneventful. He has lived without tumor recurrence for three years after the introduction of hemodialysis.

Antineoplastic Combined Chemotherapy Protocols↗

[Isolation rate of E. coli from surgical infections and their susceptibilities].

Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particularly against cefazolin are increasing year by year.

Anti-Bacterial Agents↗

Cerebral aneurysms: evaluation with three-dimensional CT angiography.

PURPOSE: To evaluate the usefulness of three-dimensional CT angiography (CTA), in which contrast material is used to create reformations of dynamic scans, in the diagnosis and the preoperative evaluation of cerebral aneurysms. METHODS: We used 3-D CTA to examine 65 patients with suspected or angiographically verified cerebral aneurysms. A blind study was performed to evaluate the diagnostic accuracy of 3-D CTA for cerebral aneurysms with the use of conventional angiography as the reference standard. RESULTS: In 50 patients, conventional angiography revealed 73 cerebral aneurysms ranging from 2 to 32 mm in maximum diameter. Three of the 73 cerebral aneurysms were located outside the imaging volume of 3-D CTA. The sensitivities of the two neuroradiologists for the remaining 70 aneurysms were 67% and 70%, respectively. Although 3-D CTA depicted cerebral aneurysms 5 mm or larger with good accuracy, it was less useful for the detection of smaller aneurysms. For the evaluation of giant aneurysms, this technique elucidated the relationships among the aneurysm, surrounding arteries, and neighboring bone structure. CONCLUSION: Three-dimensional CTA is useful for the diagnosis of cerebral aneurysms with diameters of 5 mm or more. This technique is especially useful in the preoperative evaluation of giant aneurysms.

Adult↗

Identification of actin as a substrate of ICE and an ICE-like protease and involvement of an ICE-like protease but not ICE in VP-16-induced U937 apoptosis.

Human leukemia U937 cells are induced to undergo apoptosis by several chemotherapeutic agents; however, the cellular components involved in the process have not yet been identified. We found that an actin-cleavage activity (ACA) was activated in the VP-16-treated U937 cytosolic fraction and 15K- and 30K-actin fragments were produced. This ACA was inhibited by inhibitors of interleukin-1 beta-converting enzyme (ICE)/ced-3 family proteases, such as Z-Asp-CH2-DCB, YVAD-CHO, TPCK, TLCK, and iodoacetamide. Differing from ICE, the ACA could not process pro-IL-1 beta to mature IL-1 beta. Although ICE can cleave actin in vitro, ICE activity was not activated in the VP-16 treated U937 cells. These results indicate that actin is a potential substrate of ICE and ICE-like proteases, and that VP-16 preferentially activate an ICE-like protease, but not ICE itself, in U937 cells.

Actins↗

Molecular and crystal structures of two 1,6-anhydro-beta-maltotriose derivatives.

Crystal structures of two 1,6-anhydro-beta-maltotriose derivatives, 1,6-anhydro-beta-maltotriose nonaacetate and 6"-bromo-6"-deoxy-1,6-anhydro-beta-maltotriose octaacetate, have been determined. Both structures are isomorphous and belong to the orthorhombic system, space group of P2(1)2(1)2(1), with cell dimensions of a = 15.659(3) A, b = 20.587(6) A, c = 13.023(2) A and a = 15.402(7) A, b = 19.737(8) A, c = 13.481(5) A, respectively. Each molecule has three alpha-(1-->4)-linked glucose units, and two of them have a typical 4C1 chair conformation, while the glucose unit with the 1,6-anhydro bridge has a 1C4 chair-envelope intermediate conformation. In spite of introducing the 1,6-anhydro bridge and acetyl groups, the conformations of the glycosidic linkages in these molecules are almost the same as those of other alpha-(1-->4)-linked oligosaccharides. Crystal structures are stabilized by hydrophobic interactions and by a weak intermolecular hydrogen bond of C-H. . .O.

Acetates↗

Amyloid beta peptide induces cytoplasmic accumulation of amyloid protein precursor via tau protein kinase I/glycogen synthase kinase-3 beta in rat hippocampal neurons.

Exogenous application of synthetic amyloid beta protein (A beta) is known to induce neurotoxic effects in rat hippocampal culture. We report here that A beta (25-35) induces accumulation of amyloid precursor protein (APP) derivatives in the cytoplasm of neurons. At the same time, the level of the secreted form of APP released into the culture medium decreases. Tau protein kinase I/glycogen synthase kinase-3 beta (TPK I/GSK-3 beta) antisense oligonucleotide blocked APP accumulation and prevented neuronal death. These results provide evidence that APP accumulation after A beta treatment is regulated by TPK I/GSK-3 beta. A beta neurotoxicity is probably mediated via phosphorylation of tau by TPK I/GSK-3 beta, resulting in an impairment of axonal transport, and cytoplasmic accumulation of APP.

Amyloid beta-Peptides↗

Retinoic acid induces gene expression of fibroblast growth factor-9 during induction of neuronal differentiation of mouse embryonal carcinoma P19 cells.

We have found that the gene expression of the ninth member of the fibroblast growth factor (FGF) family, FGF9 was induced during retinoic acid(RA)-induced neuronal differentiation of murine embryonal carcinoma P19 cells. We have reported here the nucleotide sequence of the mouse FGF9 cDNA. The murine cDNA showed 92.4% nucleotide sequence homology to the human FGF9 cDNA and 98.2% homology to that of rats. This mouse FGF9 cDNA encoded a polypeptide consisting of 208 amino acids with amino acid sequence identical to that of rats. Only one amino acid was replaced compared to the human homolog. The highly conserved sequence homology of FGF9 suggests its functional importance. FGF9 was originally isolated from a culture medium of a human glioma cell line as a growth-promoting factor for glial cells [5]. Upon induction of neuronal differentiation by forming cell aggregates with 10(-6) M RA, the gene expression of FGF9 was increased biphasically during the first 96 hours when cells were aggregating and from 168 hours to 192 hours followed by plating onto a tissue culture dish as glia-like cells proliferated. Neither undifferentiated P19 cells nor the cells aggregated without RA remaining undifferentiated expressed FGF9. This indicates that RA regulates the gene expression of FGF9 that may play an important role in neuronal differentiation in both early and late developmental process.

Amino Acid Sequence↗

Clinical significance of quantitative analysis of carcinoembryonic antigen assessed by flow cytometry in fresh human gastric cancer cells.

The expression of carcinoembryonic antigen(CEA) on tumor cells freshly excised from 51 patients with gastric cancer was studied using flow cytometry. The expression of CEA by flow cytometry was more quantitative than that by immunohistochemical staining. There was no relationship between the fluorescence intensity assessed by flow cytometry and serum CEA levels, except for patients with a high titer of serum CEA. The patients with high grade CEA expression on tumor cells by flow cytometry had poor prognoses, compared to patients with low CEA expression in undifferentiated gastric cancer. Thus, it is suggested that the quantitative CEA expression on tumor cells by flow cytometry could be a useful prognostic marker in postoperative gastric cancer patients.

Adenocarcinoma↗

Generation of CD4+ cytotoxic T lymphocytes stimulated by immobilized anti-CD3 monoclonal antibody and interleukin-2 in cancer patients.

The proliferation of autologous tumor-reactive cytotoxic T lymphocytes (CTL), induced by autologous mixed lymphocyte tumor-cell culture, was remarkably enhanced by activation with immobilized anti-CD3 monoclonal antibody (MAb) and interleukin-2 (IL-2), as compared with IL-2 alone. The activated CTL exhibited high cytotoxicity against autologous tumor cells. Cytotoxicity against autologous tumor cells was inhibited by anti-HLA-DR MAb. In negative selection with immunomagnetic beads, cytotoxicity against autologous tumor cells was inhibited by the elimination of CD4+ cells. The major cell-surface antigens of the activated CTL were CD3+, CD4+, CD25+, CD45RO+ and CD45RA-, suggesting helper T cells, and the activated CTL produced IL-2. It is concluded that the CTL activated by immobilized anti-CD3 MAb and IL-2 were CD4 cells that had both killer and helper functions. Our findings indicate that adoptive immunotherapy using these activated CTL would be effective in cancer patients.

Antibodies, Monoclonal↗

Novel antitumor indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11- dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4- c]carbazole-5,7(6H)-dione (NB-506): induction of topoisomerase I-mediated DNA cleavage and mechanisms of cell line-selective cytotoxicity.

A new indolocarbazole antitumor agent, NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H- indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione], enhanced the DNA cleavage catalyzed by HeLa S3 topoisomerase I at 0.01 microM but not the cleavage by topoisomerase II at 300 microM. It also caused single-strand DNA breakage in intact cells at 0.08 microM and more. Unlike the known topoisomerase I inhibitor camptothecin, NB-506 intercalated with DNA. However, the binding affinity to DNA and the inhibition against DNA polymerase alpha and RNA polymerase II were marginal compared with those of Adriamycin or actinomycin D. NB-506 inhibited the growth of various tumor cell lines at two micromoles or less, and its cytotoxicity was found to be cell line selective. This selective cytotoxicity of NB-506 was not fully explained by the differences in topoisomerase I activity in these cell lines, but there was some relationship between the amount of NB-506 accumulated in these cell lines and its cytotoxicity toward them. In conclusion, NB-506 is a potent topoisomerase I poison, acting selectively on tumor cell lines accumulating NB-506.

Animals↗

Localization of myogenin, c-fos, c-jun, and muscle-specific gene mRNAs in regenerating rat skeletal muscle.

It has been suggested that myogenin is an important factor for the differentiation of myoblasts and that its function in myogenesis is regulated by proto-oncogenes in in vitro experiments. We have characterized the spatial and temporal expression patterns of myogenin, c-fos, c-jun, and muscle creatine kinase mRNAs during the skeletal muscle regeneration process using in situ hybridization histochemistry. Myogenin transcripts are first detected in the myonuclei/nuclei of satellite cells at 6 h after induction of regeneration. Myogenin mRNA is expressed in desmin-positive myoblasts, yet no muscle creatine kinase mRNA is detected in this cell type. Both the muscle creatine kinase and myogenin mRNAs are expressed in the newly formed myotubes, but not at earlier stages. Transcripts for c-fos and c-jun mRNAs are expressed first in the myonuclei/nuclei of satellite cells at 3 h post-trauma. c-jun mRNA is expressed in both myoblasts and myotubes, while c-fos mRNA was not detected in these cells. These results suggest that myogenin plays important role in the regeneration of injured muscle and that c-jun and c-fos may have different roles in this process.

Animals↗