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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 109 records · Page 6Linked to original sources
PubMed2001

[Antitumor effect of the plant alkaloid preparation, cepharanthin].

The antitumor effect of cepharanthin (CR), a biscoclaurine alkaloid, was examined as to its direct action on tumor cells and inhibitory action on angiogenesis in tumors. The effect of CR on in vitro invasion by murine RL-[symbol: see text] 1 leukemia cells and Colon 26 tumor cells was studied using a biocoat matrigel invasion chamber. One hundred micrograms/ml of CR inhibited tumor cell invasion. Early induction of apoptosis was assayed by the binding of annexin V and phosphatidylserine (PS) in the cellular membrane CR (10 and 100 micrograms/ml) induced apoptosis in human Daudi and Raji B lymphoblastoid cells. Treatment with CR (1 and 10 micrograms/ml) also inhibited the in vitro growth of Daudi and Raji cells. Ten micrograms/ml of CR also inhibited the growth of human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC). These results indicate that CR has diversified antitumor functions, i.e., an enhancement of a sequential immune mechanism, a direct cytotoxic effect and inhibitory action of angiogenesis in tumors.

Alkaloids↗
PubMed2001

[Tumor angiogenesis and tumor angiogenesis inhibitors].

It is important to survey the molecular targets which are involved in tumor angiogenesis for the development of antiangiogenic agents as one of the cancer therapy. This article is meant to review the recent molecular targets of tumor angiogenesis and the molecular mechanism of antiangiogenic agents in human clinical trials.

Angiogenesis Inhibitors↗
PubMed2001

High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas.

We used suppression subtractive hybridization to identify highly expressed genes in the cancerous region of human renal cell carcinoma (RCC) compared with noncancerous tissue. Nine genes were identified to show increased expression in the cancerous region compared with the noncancerous region. The nine genes included thymosin beta4, secreted protein acidic and rich in cysteine (SPARC), Cap43, ceruloplasmin, serum amyloid A, osteopontin, heat shock protein 90 (HSP90), LOT1, and casein kinase I. Of these 9 genes, in situ hybridization with 10 clinical samples consistently showed a strong expression of Cap43 mRNA in infiltrating macrophages in RCCs, but not in cancer cells proliferating in an alveolar pattern. However, Cap43 mRNA was also apparently detected in epithelial cells of the renal proximal tubuli in noncancerous tissue. The higher expression of the Cap43 gene in the cancerous region of RCCs appears to depend on macrophage infiltration. Moreover, treatment with phorbol ester resulted in enhanced expression of the Cap43 gene in human monocytic cells in vitro. The expression of the Cap43 gene in infiltrating macrophages is discussed in association with the differentiated or activated status of monocyte/macrophage.

Adult↗
PubMed2001

[Usefulness of chemotherapy with CPT-11 in clinic for three colorectal cancer in terminal stage].

In our clinic we performed chemotherapy with CPT-11 in three cases of non-resectable advanced colorectal cancer, including two cases of multiple liver metastasis and one case of multiple lung metastasis, and obtained various alleviating effects. Heretofore two factors. 1. direct effect and 2. longevity effects, have been focused on when evaluating the effect of various chemotherapy regimens. However, the symptoms of these patients were alleviated by the chemotherapy without obtaining either of the two effects. Furthermore, their performance statuses were improved. It is therefore sufficiently beneficial for patients in the terminal stage to undergo the chemotherapy. The patient in the terminal stage should be taken care of in the clinic rather than in the hospital. At present, safe and effective therapies on an ambulant basis have not been established. It will now be necessary for us to evaluate the many accumulated cases. It is conceivable that chemotherapy with CPT-11 in the clinic would be extremely useful for patients in the terminal stage for the purpose of improving the QOL, if the dose and administration interval of CPT-11 are given sufficient attention.

Ambulatory Care↗
PubMed2001

[Intravenous leiomyomatosis with cardiac extension in an elderly woman: report of a case].

Intravenous leiomyomatosis is a histologically benign smooth-muscle tumor arising from either a uterine myoma or the wall of a uterine vessel with extension into veins. We describe a 71-year-old woman with a prior history of subtotal hysterectomy for uterine myoma years earlier who presented with palpitation. Echocardiographic examination revealed an intracardiac mass protruding into the right ventricle during diastole. The caval tumor could be traced to the right renal vein by magnetic resonance image. She was operated on for intracardiac and intracaval leiomyomatosis. The intracaval tumor proved to be not totally resectable. Presence of smooth muscle was confirmed by smooth muscle actin and desmin positive cells in the tumor. Tumor cells also proved to possess estrogen receptors. The patient has been closely followed-up with antiestrogen therapy.

Aged↗
PubMed2001

Lack of association between hepatocyte nuclear factor-1beta gene and common forms of type 2 diabetes in the Japanese population.

Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). We studied the contribution of the HNF-1beta gene to susceptibility to common forms of Type 2 diabetes in the genetically homogeneous Japanese population, by investigating the allelic association of Type 2 diabetes with two markers in the HNF-1beta region. The frequency of a nonsense mutation, R177X, which was previously reported in a Japanese family, was also studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using a mismatch primer. A total of 200 subjects were studied. There was no significant difference in allele frequencies of either of the two polymorphisms studied between patients with Type 2 diabetes and control subjects, or between subgroups of patients subdivided by the presence of mild or severe diabetic nephropathy. None of the subjects studied had R177X mutation, giving a frequency of less than 1.1% in common forms of Type 2 diabetes in Japan. These results suggest that mutations in the HNF-1beta gene derived from a limited number of founders are not a major cause of common forms of Type 2 diabetes, even in the genetically homogeneous Japanese population.

Adult↗
PubMed2001

[Evaluation of patients who received treatment (procedures) that involved minor surgical techniques at home].

We retrospectively examined the clinical records of 24 patients who underwent minor surgery under local anesthesia among 207 who were taken care of at home by our staff, from December 1986 to March 2001. There were 17 men and 7 women. Their mean age was 74 years and the range was 50 to 92 years old. The treatment consisted of central vein catheterization in 14 patients, skin suture in 6, subcutaneous implantation of port establishment and epidural catheterization in 3 patients each, treatment of anus, thorax centesis, skin tumor resection, and treatment of bed sores 2 patients each, wash of thorax, ovarian cyst centesis, and transcutaneous trachocentesis 1 patient each. A relationship of trust with the patient and the family and informed consent were thought as the most important aspects regarding treatment involving minor surgery provided at home.

Aged↗
PubMed2000

Glycosylation effect on membrane domain (GEM) involved in cell adhesion and motility: a preliminary note on functional alpha3, alpha5-CD82 glycosylation complex in ldlD 14 cells.

Laminin (LN)- or fibronectin (FN)-dependent adhesion in Krieger's ldlD 14 (D14) cells is enhanced significantly in the presence vs absence, of galactose (Gal), whereas LN- or FN-induced haptotactic cell motility is barely affected unless cells express CD82 by its gene transfection (cells termed D14/CD82). The effect of CD82 on LN- or FN-induced motility is based on its ability to associate with alpha3 or alpha5 integrin to form a complex associated with a low-density lipid membrane domain (termed GEM or GSD). Complex formation is greatly affected by N-glycosylation of both integrin and CD82, as well as by concurrent GM3 ganglioside synthesis. The effect of glycosylation on alpha5-CD82 complex was also studied in D14 cells expressing mutant CD82, defective in all three N-glycosylation sites. LN-induced motility was greatly inhibited, whereas FN-induced motility was enhanced, with complete N-glycosylation in D14/CD82 cells in Gal-added medium, whereby alpha5-CD82 complex formation did not occur or occurred at a minimal level. Both LN- and FN-induced motility were inhibited when N-glycosylation was impaired, or N-glycosylation of CD82 was deleted, whereby alpha5-CD82 complex formation occurred strongly. Thus, glycosylation profoundly affects interaction of integrin with CD82, leading to significant inhibition or promotion of cell motility.

Animals↗
PubMed2000

Angiostatin generation by cathepsin D secreted by human prostate carcinoma cells.

Angiostatin, a potent endogenous inhibitor of angiogenesis, is generated by cancer-mediated proteolysis of plasminogen. The culture medium of human prostate carcinoma cells, when incubated with plasminogen at a variety of pH values, generated angiostatic peptides and miniplasminogen. The enzyme(s) responsible for this reaction was purified and identified as procathepsin D. The purified procathepsin D, as well as cathepsin D, generated two angiostatic peptides having the same NH(2)-terminal amino acid sequences and comprising kringles 1-4 of plasminogen in the pH range of 3.0-6.8, most strongly at pH 4.0 in vitro. This reaction required the concomitant conversion of procathepsin D to catalytically active pseudocathepsin D. The conversion of pseudocathepsin D to the mature cathepsin D was not observed by the prolonged incubation. The affinity-purified angiostatic peptides inhibited angiogenesis both in vitro and in vivo. Importantly, procathepsin D secreted by human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that by human prostate carcinoma cells. Since deglycosylated procathepsin D from both prostate and breast carcinoma cells exhibited a similar low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in carbohydrate structures of procathepsin D molecules between the two cell types. The seminal vesicle fluid from patients with prostate carcinoma contained the mature cathepsin D and procathepsin D, but not pseudocathepsin D, suggesting that pseudocathepsin D is not a normal intermediate of procathepsin D processing in vivo. The present study provides evidence for the first time that cathepsin D secreted by human prostate carcinoma cells is responsible for angiostatin generation, thereby causing the prevention of tumor growth and angiogenesis-dependent growth of metastases.

Angiostatins↗
PubMed2000

Ultrastructure of the capillary pericytes and the expression of smooth muscle alpha-actin and desmin in the snake infrared sensory organs.

The infrared sensory membranes of pit organs of pit vipers have an extremely rich capillary vasculature that forms many vascular loops, each serving a small number of infrared nerve terminals. We clarified the ultrastructure of capillary pericytes in the pit membranes by scanning and transmission electron microscopy, and examined the immunoreactivity in their cytoplasm to two contractile proteins: smooth muscle alpha-actin (SM alpha-actin) and desmin. The capillary pericytes had two major cytoplasmic processes: thickened primary processes that radiate to embrace the endothelial tube and flattened secondary processes that are distributed widely on the endothelium. Coexpression of SM alpha-actin and desmin was observed in the pericytes of entire capillary segments, and SM alpha-actin was characterized by prominent filament bundles directed mainly at right angles to the capillary long axis. This expression pattern was different from that of capillary pericytes of the scales, where SM alpha-actin was expressed diffusely in the cytoplasm. In a series of electron microscopic sections, we often observed the pericyte processes depressing the endothelial wall. We also observed a close relationship of the pericytes with inter-endothelial cell junctions, and pericyte processes connected with the endothelial cells via gap junctions. From these findings, we surmised that capillary pericytes in the pit membrane have a close functional relationship with the endothelium, and through their contractile and relaxing activity regulate capillary bloodflow to stabilize production of infrared nerve impulses.

Actins↗
PubMed2000

Stimulatory function of gp49A, a murine Ig-like receptor, in rat basophilic leukemia cells.

Murine gp49, a 49-kDa type I transmembrane glycoprotein, is a member of the Ig-like receptors expressed on the surface of cells involved in natural immunity such as mast cells, NK cells, and macrophages. The two major subtypes, gp49A and gp49B, are encoded by two different genes adjacent to each other. gp49B contains an immunoreceptor tyrosine-based inhibitory motif in its cytoplasmic region and is known to function as an inhibitory molecule. In contrast, gp49A does not harbor any specific motif for signal transduction, nor has its physiological role been determined. Here we report on the stimulatory nature of gp49A by analyzing biochemical characteristics of chimeric molecules consisting of an ectodomain of Fc receptor and a C-terminal half of gp49A, namely the pretransmembrane, transmembrane, and cytoplasmic portions, expressed on the rat basophilic leukemia mast cell line. Cross-linking of the chimeric receptors evoked cytoplasmic calcium mobilization, PGD(2) release, and transcription of IL-3 and IL-4 genes, but did not elicit degranulation of the cells. The chimeric molecule could be expressed as a singlet and a homodimeric form on the cell surface. A pretransmembrane cysteine residue of gp49A was necessary for dimer formation. Dimerization was be necessary for their incorporation into glycolipid-enriched membrane fraction (GEM) upon cross-linking stimuli. The calcium mobilization response was inhibited by treatment of cells with methyl-beta-cyclodextrin, an inhibitor of GEM formation. Together with these results, it was strongly suggested that gp49A could be expressed as a homodimer and elicit activation signals that lead to calcium mobilization, eicosanoid production, and cytokine gene transcription through its incorporation into GEM.

Animals↗
PubMed2000

On-line automated high-performance liquid chromatographic determination of total riboflavin phosphates using immobilized acid phosphatase as a pre-column reactor.

An automated chromatographic detection system for the determination of total riboflavin phosphates using immobilized sweet potato acid phosphatase as a pre-column reactor is reported on. An immobilized enzyme reactor, incorporated in the on-line analytical system, hydrolysed riboflavin phosphates to riboflavin, and then lipophilic riboflavin was concentrated at the top of an ODS trap column. Enzymatically hydrolysed riboflavin was back-eluted from the trap column using a mobile phase containing methanol, and then subsequently chromatographed on an ODS analytical column. The effluents were monitored by UV absorption at 280 nm. The calibration graph for total riboflavin phosphates, determined by this method, was linear over the range 0.5-500 nmol/ml, with a correlation coefficient of 0.9999. The detection limit at a signal-to-noise ratio of 3 was 25 pmol/ml. The average conversion rate of riboflavin phosphates to riboflavin was estimated at 97%. The relative standard deviations of the intra- and inter-assay precision were 1.2 and 2.6%, respectively.

Acid Phosphatase↗
PubMed2000

The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13.

IL-13 is a multifunctional lymphokine sharing a number of biological properties with IL-4. We previously observed that IL-4 shows angiogenic activities in vitro as well as in vivo. In this study we examined the effect of IL-13 on angiogenesis in vitro and in vivo and also the underlying mechanisms. Human IL-13 significantly stimulated the formation of tube-like structures in collagen gels by human microvascular endothelial cells and bovine aortic endothelial cells by about 3-fold over the controls in the absence of the cytokines. Administration of murine IL-13 led to neovascularization when implanted in the rat cornea. Coadministration of neutralizing mAb to the IL-4R inhibited both tubular morphogenesis in vitro and activation of STAT6 induced by IL-4 or IL-13. Both IL-4 and IL-13 markedly increased mRNA levels of VCAM-1 in vascular endothelial cells, and the production of the soluble form of VCAM-1 was also stimulated in response to IL-4 or IL-13. Administration of anti-VCAM-1 Ab in vitro blocked tubular morphogenesis induced by IL-4 and IL-13. Angiogenesis induced in vivo in rat cornea by IL-4 and IL-13 was also inhibited by Ab against the rat alpha4 integrin subunit. These findings suggest that angiogenesis dependent on IL-4 and IL-13 is mainly mediated through a soluble VCAM-1/alpha4 integrin pathway.

Animals↗
PubMed2000

A fusion inhibitor (FP-21399) for the treatment of human immunodeficiency virus infection: a phase I study.

FP-21399 is a bis(disulfonaphthalene) derivative that prevents human immunodeficiency virus (HIV) infection of uninfected cells by blocking entry of the virus. FP-21399 shows an affinity for lymph nodes. In this phase I study, FP-21399 was administered intravenously over 1 h as a single dose (0.9, 1.7, 2.8, and 4.2 mg/kg) or as a once-weekly infusion (1, 2, and 3 mg/kg) for 4 consecutive weeks to 34 HIV-1 infected patients with CD4(+) cell counts of 50-400 cells/microL. Concomitant antiretroviral therapy was permitted but not required. The most frequent adverse events involved the transient, dose-dependent appearance of drug- or metabolite-related color in the urine and skin. Plasma drug levels were linear with dose. The drug was cleared, with an elimination half-life of 4 h and a terminal half-life of 1.5-2 days; the terminal half-life represented redistribution and clearance from tissues. FP-21399 administered weekly for 4 weeks was well tolerated. Further studies are necessary to define the role of this fusion inhibitor in the treatment of HIV infection.

Adult↗
PubMed2000

Tumor thickness is a histopathologic predictive parameter of tumor metastasis and prognosis in patients with Dukes stage C ulcerative-type colorectal carcinoma. A two-hospital-based study.

BACKGROUND: Metastasis to the liver or lymph nodes is an important prognostic factor in patients with colorectal carcinoma. The purpose of the current study was to estimate the power of tumor thickness in predicting metachronous liver metastasis (MLM), lymph node metastasis (LNM), or overall survival (OS) in patients at two hospitals (the National Cancer Center Hospital [NCCH] and the National Cancer Center Hospital East [NCCHE]) to confirm the reproducibility of the study. METHODS: The subjects of this study were 74 and 186 consecutive patients with ulcerative-type colorectal carcinoma treated at the NCCH and NCCHE, respectively. Tumor thickness was measured in three areas: 1) the marginal elevated area (MEA), 2) the central depressed area (CDA), and 3) the most thickened area (MTA). Studies were performed with well known histologic parameters to compare the predictive power of tumor thickness on MLM, LNM, and OS using the Cox proportional hazards regression model or analysis of variance. RESULTS: A significant correlation between tumor thickness and MLM was observed only in the CDA in the NCCH patients (P = 0.005). The authors applied a tumor thickness cutoff value in the CDA of 10 mm (</= 10 mm and > 10 mm) for further study. Multivariate analyses demonstrated that a tumor CDA thickness > 10 mm was associated significantly with MLM, multiple LNMs, and OS in NCCH patients with Dukes Stage C disease (P = 0.002, P = 0.023, and P = 0.002, respectively). A significant predictive power for tumor CDA thickness for MLM, multiple LNMs, and OS was confirmed by multivariate analysis in NCCHE patients with Dukes Stage C disease (P = 0.008, P = 0.021, and P = 0.010, respectively). CONCLUSIONS: The CDA thickness of the tumor was found to be a useful predictive parameter for MLM, multiple LNMs, and OS in patients with Dukes Stage C ulcerative-type colorectal carcinoma who were being treated in two independent hospitals.

Aged↗
PubMed2000

Neurotoxic effect of high dose methamphetamine administration on the hippocampal formation of adult mice: morphometric study using image analyzer.

The volume of the hippocampal formation was measured after repeated methamphetamine (MAP) administration. MAP (30 mg/kg, i.p.) or an equivalent volume of saline (SAL) was administered once daily for 5 days to adult male BALB/c mice. The animals were perfused 7 days after the last injection, and brain sections were stained with cresyl violet and studied with a computer-assisted image analyzer. The volume of the molecular layer at the ventral position of the dentate gyrus of MAP-treated animals was significantly decreased (77% of control, p < 0.001). In contrast, the volumes of the molecular layers at the dorsal and midseptal positions of the dentate gyrus did not change after MAP administration. Similarly, repeated MAP treatment did not affect the volumes of the granular layer and hilus at the dorsal, midseptal or ventral positions of the dentate gyrus. The present results are the first to document a persistent neurotoxic effect of high dose MAP administration on the hippocampal volume of adult mice.

Animals↗