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J Murata

Publications and source records attributed to J Murata.

At least 55 records · Page 3Linked to original sources

Augmented renal sympathetic nerve activity by central command during overground locomotion in decerebrate cats.

We examined whether the cerebrum is essential for producing the rapid autonomic adjustment at the onset of spontaneous overground locomotion. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR), and electromyogram of the forelimb triceps brachialis were measured when freely moving, decerebrate cats spontaneously produced overground locomotion, supporting body weight. Decerebration was performed at the level of the precollicular-premammillary body. RSNA increased 95 +/- 14 impulses/s (68 +/- 10% of baseline value) at the onset of spontaneous locomotion, which was followed by rises in MAP and HR (7 +/- 1 mmHg and 18 +/- 2 beats/min, respectively). Concomitantly with the MAP rise, RSNA declined toward control values and then increased again during the subsequent period of locomotion. The same rapid increase in RSNA at the onset of locomotion was observed after sinoaortic denervation and vagotomy. It is concluded that some central site(s), other than the cerebrum and the rostral part of the diencephalon, can generate the centrally induced autonomic adjustment at the onset of spontaneous overground locomotion, which is independent of arterial baroreceptor and vagal afferents.

Afferent Pathways↗

Synthesis of a biologically active fluorescent derivative of GM1, a main Ginseng saponin metabolite formed by intestinal bacteria.

A fluorescent derivative of GM1 [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], a main Ginseng saponin metabolite formed by intestinal bacteria, was obtained from the condensation of its trisnor-aldehyde derivative with dansyl hydrazine. The dansylated GM1 fluoresced strongly and showed almost the same properties as its parent compound in lipophilicity and biological activities, so this fluorescent compound might provide an insight into the mechanism of pharmacological activities of GM1.

Antineoplastic Agents↗

Microdialysis assessment of 5-fluorouracil release from thermosensitive magnetoliposomes induced by an electromagnetic field in tumor-bearing mice.

The current study was designed to evaluate the properties of thermosensitive magnetoliposomes (TMs), a new drug carrier proposed by the authors, in an electromagnetic field pertaining to their selective heating and drug release under an in vivo condition. TMs containing 5-fluorouracil (5-FU) were prepared by reverse-phase evaporation, injected into the tumor mass of B 16-BL6 melanoma in mice, and selectively heated by a 500-kHz electromagnetic field. The release profile of 5-FU from TMs was examined by using a microdialysis technique. The temperature of TMs in the tumor was effectively elevated to 42 degrees C and maintained at this temperature, overcoming the "cooling effect" of blood flow and surrounding tissues. The release kinetics of 5-FU from TMs was successfully analyzed by physiological modeling, which allows the prediction of intratumor drug concentrations during electromagnetic field exposure under various conditions. In conclusion, this study first demonstrated an in vivo evidence for the electromagnetic field-induced thermosensitive release of a drug from TMs in a tumor with the use of microdialysis.

Animals↗

Teratomas of the central nervous system: treatment considerations based on 34 cases.

OBJECT: The optimum clinical management of central nervous system (CNS) teratomas, particularly postsurgical adjuvant therapy, is still unclear, partly as a result of the tumors' low incidence. In this study the authors analyze 34 cases of CNS teratomas so that they may adequately indicate management of these lesions. METHODS: The median age of the 34 patients was 13 years. Twenty-seven patients treated between 1970 and 1991 were retrospectively reviewed. Four of these 27 patients died as a result of radical surgery; each of them had a teratoma involving the hypothalamus. After initial treatment, which included radiation therapy, 20 patients (48%) had died. In all seven cases of mature teratomas there was no recurrence. In two cases of immature teratomas in which there was complete surgical resection there was recurrence; however, salvage therapies were effective. Seven of eight patients with highly malignant teratomas died; for these patients salvage therapies, including repeated radiation and chemotherapy, failed. Seven patients who presented with CNS teratomas between 1992 and 1996 received adjuvant chemotherapy and radiation therapy according to a prospective study protocol. All seven patients were free from recurrence with a 70 to 100% Karnofsky Performance Scale score at a median follow-up period of 41 months. Patients with CNS teratomas rarely responded completely to chemotherapy or radiation therapy; an effective adjuvant therapy produced a partial response at best. CONCLUSIONS: Because teratomas show various responses to adjuvant therapy, a misdiagnosis of their histological subtype will lead to inadequate therapy. A diverse therapeutic protocol based on histological diagnosis is necessary to plan appropriate management. Treatment recommendations are discussed in detail in the article.

Adolescent↗

Inhibitory effect of vasoactive intestinal polypeptide (VIP) on experimental liver metastasis by murine colon 26-L5 carcinoma cells.

We previously reported that vasoactive intestinal polypeptide (VIP) significantly inhibited Matrigel invasion and haptotactic migration of murine colon 26-L5 carcinoma in vitro. To extend our study, we investigated the inhibitory mechanisms of VIP on Matrigel invasion of colon 26-L5 carcinoma, and the effect on metastatic properties of the tumor cells. VIP inhibited the invasion of the tumor cells in a concentration-dependent manner without affecting their growth, and achieved approximately 50% reduction at 10(-6) M. VIP also suppressed cell motility with a similar inhibition rate to the invasion assay. Time course study revealed that the motility was reduced by 40% when the tumor cells were preincubated with 10(-6) M VIP for 3 h. In contrast, 6-h pretreatment with 10(-6) M VIP caused the increased ability of the adhesion to both fibronectin and laminin with a 50% enhancement. A large amount of VIP1 receptor transcripts was expressed in the cells, whereas VIP2 receptor was undetectable, by RT-PCR and subsequent Southern blot hybridization. A specific antagonist for VIP1 receptor reversed the suppressed motility induced by VIP. Cryostat sections showed that the 3-h pretreatment of tumor cells with VIP caused the reduction of the arrest in the livers at 6 h after the tumor inoculation into a portal vein of mice. VIP could prevent the experimental liver metastasis of the tumor cells in a dose-dependent manner. The cells pretreated with 10(-6) M VIP for 3 h also showed the reduced ability of the liver metastasis. These results suggest that VIP could block the invasion and the metastasis of colon 26-L5 carcinoma through suppression of their motility.

Animals↗

[Application of percutaneous trans esophageal gastro-tubing (PTEG) in to home care for a patient with terminal stage of gastric cancer].

PURPOSE: Since 1994, we devised and have continued to develop a percutaneous trans esophageal gastro-tubing (PTEG) as an effective technique to drain gastrointestinal contents of critical patients suffering from gastric carcinoma. Here we report our satisfactory experience with a critical gastric cancer patient for whom we improved QOL by the application of the PTEG technique. The patient suffered from severe stenosis or obstruction of the digestive tract. This method was found to be effective enough to enable the patient to receive further medical care at home. CASE: The patient was a 36-year-old female who had far-advanced, inoperable gastric carcinoma. It was therefore decided to use the PTEG method. METHOD: The PTEG method was performed using a rupture-free balloon (RFB) catheter to drain the gastrointestinal contents. A reservoir-port for IVH use was embedded to control the patient's nutrition. A morphine hydrochloride suppository was then given for the pain. REMARK: PTEG was found to be effective, safe and simple; moreover, it is a less-invasive, intestine-maintaining method, which enabled the patient to continue receiving further medical treatment at home.

Adult↗

Nitric oxide as a carcinogen: analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide.

We have used a yeast p53 functional assay to study induction of mutations in the p53 tumor suppressor gene by nitric oxide and cytosine methylation. The yeast assay identifies only biologically important p53 mutations. p53 cDNA was treated with the nitric oxide donor sydnonimine, PCR-amplified and transfected into yeast. Sydnonimine produced a significant, dose-dependent increase in C:G-->A:T transversions. Many important p53 mutational hotspots are postulated to arise by deamination of methylCpG in tumors. We therefore examined nitric oxide induction of mutations in p53 cDNA methylated by PCR-mediated substitution of 5-methylcytosine for cytosine or by treatment with the SssI CpG methylase. Both methylation procedures increased the baseline mutation rate, and nitric oxide treatment produced a further increase in mutation yield. Sequence analysis showed that methylation alone led to C:G-->T:A transitions, whereas nitric oxide treatment simply produced more C:G-->A:T transversions. Thus the most important factor in C:G-->T:A transition at CpG sites identified in this experimental system is cytosine methylation, consistent with spontaneous conversion of 5-methylcytosine to thymine by deamination.

Carcinogens↗

Differential effect of intestinal neuropeptides on invasion and migration of colon carcinoma cells in vitro.

We investigated the effect of neuropeptides, which are vasoactive intestinal polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA), somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine-enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had no effect. Especially, VIP showed the most effective in inhibiting tumor invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was also observed in cell migration to fibronectin. VIP had no effect on the growth of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor. These results indicate that VIP, among the neuropeptides used, could inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial suppression of their motility, and the reduction was associated with an intracellular cAMP-mediated pathway.

Adenocarcinoma↗

Microglial cells induce cytotoxic effects toward colon carcinoma cells: measurement of tumor cytotoxicity with a gamma-glutamyl transpeptidase assay.

Activated macrophages have been shown to exert cytostatic and cytotoxic effects toward tumor cells via nitric oxide (NO) release. In the CNS, microglial cells are considered to be the main resident population of immune effector cells. In this study, cytotoxic activity of N11, an immortalized murine microglial cell line, toward rat progressive DHD/PROb and regressive DHD/REGb colon carcinoma cells was examined in parallel with NO production. Cytotoxicity was evaluated using a novel method, the gamma-glutamyl transpeptidase (gamma-GTP) assay, based on the fact that DHD tumor cells expressed high levels of gamma-GTP activity, while no gamma-GTP activity was found in cells of the monocyte/macrophage lineage. Results showed that activation of N11 cells by interferon-gamma plus either lipopolysaccharide or tumor necrosis factor-alpha induced high amounts of NO release and cytotoxic effects toward DHD/PROb as well as DHD/REGb cells. NO release by activated N11 cells was augmented by addition of tumor cell-conditioned medium. Both NO release by N11 cells and cytotoxicity were blocked by addition of N(G)-monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, suggesting that cytotoxicity was mediated by N11-derived NO. However, in the presence of L-NMA an increased production of interleukin-6 was also observed. In conclusion, in opposition to information obtained with brain-derived endothelial cells, brain-derived microglial cells did not differentiate between progressive and regressive clones of colon carcinoma cells. Our results point to a specific role for both endothelial and microglial cell types in the context of brain metastasis. Microglial cells can be cytotoxic for tumor cells, and this cytotoxicity is mediated by NO.

Animals↗

Effect of dimerization of the D-glucose analogue of muramyl dipeptide on stimulation of macrophage-like cells.

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) is the minimum required structure responsible for the immunoadjuvant activity of the bacterial cell wall. The D-glucose analogue of MDP (GADP) was reported to show a higher immunoadjuvant activity than MDP itself. Although the mechanism of activation by MDP and the existence of receptor against MDP are not clear, the patch formation and cluster formation of receptors are important steps on the signal transduction by such bioactive molecules. It is expected that the cluster effect such as antennary oligosaccharides reported by Lee et al. increased the affinity of ligand against receptor and accelerated the patch formation and cluster formation of receptors. In order to discuss the effect of multivalent-ligand formation of GADP on the activation of immunocompetent cells in more detail, we have synthesized GADP dimers combined through various lengths of alkyl and poly(ethylene glycol) (PEG) spacer groups as the simple models of multivalent-ligand molecule of GADP and evaluated their immunological enhancement activities in vitro. The GADP dimers showed a higher level stimulatory activities against macrophage-like cells than free GADP and monomeric GADP derivatives.

Acetylmuramyl-Alanyl-Isoglutamine↗

Resection of a recurrent parasagittal meningioma with cortical vein anastomosis: technical note.

BACKGROUND: Simpson Grade I resection of parasagittal meningiomas is not always feasible because of the involvement of the sagittal sinus and cortical veins. Complete resection requires reconstruction of the sagittal sinus and cortical veins. This report describes a surgical technique to preserve patency of the cortical veins. CASE REPORT: A recurrent parasagittal meningioma completely occupied the superior sagittal sinus and encased several large cortical veins. The tumor in the sagittal sinus was totally resected and the roof of the sinus was sutured. To avoid thrombotic cortical vein occlusion, two cortical veins encased by the meningioma were anastomosed end-to-end, regardless of their flow directions. The postsurgical course was uneventful and patency of the anastomosed veins was confirmed by postoperative angiography. CONCLUSIONS: End-to-end anastomosis of cortical veins was a useful surgical technique for radical resection of a parasagittal meningioma.

Adult↗

Characterization of a liver metastatic variant of murine colon 26 carcinoma cells.

Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.

Adenocarcinoma↗

Design of macromolecular biological response modifier by immobilizing of D-glucose analogue of muramyl dipeptide on carboxymethyl-dextran having mannose branches.

It is well known that muramyl dipeptide is a minimum required structure of bacterial peptidoglycan responsible for immunoadjuvant activity. Since mannose receptors exist on the surface of macrophages, polymers with branched mannose residues are expected to target moieties to macrophages. To achieve an efficient delivery of D-glucose analogue of muramyl dipeptide (GADP) via receptor-mediated endocytosis by mannose receptors on the surface of macrophages, GADP/carboxymethyl-dextran (CM-Dex)/Man conjugate was synthesized. Moreover, to study the effect of the introduction of mannose residues, we also synthesized GADP/CM-glucomannan (CM-GM) and GADP/CM-Dex conjugates. The immunological enhancement activities of their conjugates were evaluated by measurements of glucose consumption and beta-D-glucuronidase activity from macrophage-like cells. The GADP/CM-Dex/Man and GADP/CM-GM conjugates showed higher immunological enhancement activity than the GADP/CM-Dex conjugate. The immunological enhancement activity of GADP/CM-Dex/Man and GADP/CM-GM conjugates was decreased to the same level of immunological enhancement activity of GADP/CM-Dex conjugate under the presence of excess mannose. These results suggested that the introduction of mannose residues into GADP/CM-Dex conjugate could increase the affinity against macrophage and the immunological enhancement activity of GADP/CM-Dex conjugate itself.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Inhibitory effect of ketamine on depolarization-induced norepinephrine release in the rat ventral hippocampus investigated by in vivo microdialysis].

The release of norepinephrine (NE) in the ventral hippocampus was studied in rats with microdialysis method. The basal release of NE with perfusion of normal artificial cerebrospinal fluid (ACSF) was 1.58 +/- 0.37 x 20 microliters-1 sample. The NE concentration increased significantly with perfusion of high potassium (60 mM) ACSF indicating that depolarization-induced release was up to 5 times higher than the basic level. Ketamine (20 mg.kg-1 and 80 mg.kg-1 im) significantly inhibited the depolarization-induced increase of NE, but did not affect the basal release. Neither 5 mg.kg-1 im of ketamine nor MK-801 had any effect on the basic or the depolarization-induced release. These results suggest that the inhibitory effect of ketamine on the depolarization-induced NE release was not due to the NMDA channel blocking properties of ketamine.

Anesthetics, Intravenous↗

In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration.

The present study demonstrated in vivo and in vitro antimetastatic activities of a major intestinal bacterial metabolite M1 formed from protopanaxadiol saponins of ginseng (the root of Panax ginseng C. A. Meyer) in comparison with its whole standardized extract and ginsenosides Rb1, Rb2, and Rc. Although Ginseng extract (1 mg/mouse) and ginsenosides (0.5 mg/mouse) significantly inhibited lung metastasis produced by i.v. injection of B16-BL6 melanoma cells in syngeneic mice (27-61% of untreated control), they hardly inhibited the invasion and migration of B16-BL6 melanoma and HT1080 fibrosarcoma cells in vitro. However, the intestinal bacterial metabolite M1 inhibited lung metastasis of melanoma cells and in vitro tumor cell invasion and migration at nontoxic or marginally toxic concentrations. Additionally, pharmacokinetic studies of ginsenoside Rb1 and M1 after oral administration (2 mg/mouse) revealed that intact Rb1 was not detectable in serum for 24 h by HPLC analysis, whereas the level of M1 in the serum reached maximum at 8 h (8.5 +/- 0.4 micrograms/ml) after Rb1 administration and at 2 h (10.3 +/- 1.0 micrograms/ml) after M1 administration. These findings suggest that the in vivo antimetastatic effect by oral administration of ginsenosides is mediated by their metabolic component M1.

Administration, Oral↗

Alpha-melanocyte-stimulating hormone blocks invasion of reconstituted basement membrane (Matrigel) by murine B16 melanoma cells.

We have examined the effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on invasive ability of murine melanoma cell lines with different metastatic potential in a Matrigel invasion assay. alpha-MSH potently blocked the invasion of B16-BL6 cells with highly metastatic potential in a concentration-dependent manner, whereas it was less effective in inhibiting the invasion of weakly metastatic B16-F1 cells. Pretreatment of B16-BL6 cells with alpha-MSH resulted in a decrease of the adhesiveness to fibronectin and laminin substrates in a time-dependent fashion. As assessed by zymographic analysis, alpha-MSH partially inhibited the production of matrix metalloproteinase (MMP)-2 and -9 from both cell lines to a similar degree without affecting the degradative activity of these MMPs. alpha-MSH was more potent in inhibiting the migration of B16-BL6 cells towards both fibronectin- and laminin-coated substrates than that of B16-F1 cells. The growth and morphology of B16-BL6 cells were not changed after a 7-day incubation with alpha-MSH. The number of lung tumor colonies markedly decreased when B16-BL6 cells were coinjected intravenously with 10(-6) M alpha-MSH. However, alpha-MSH had no effect on the experimental lung metastases by B16-F1 cells. These results suggest that alpha-MSH suppressed the invasive and metastatic properties of B16 melanoma cells, and the degree of inhibition was associated with metastatic potential of B16 melanoma cells.

Animals↗

Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice.

The present study demonstrates that the transfection of B7-1 or its variant MB7-2 genes into MHC class I+ tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice. However, i.v. injection of the transfectants into T cell-deficient nude mice did not affect reduction of lung tumor colonies as compared with parental wild-type tumors, suggesting that such an inhibitory effect was closely associated with T cell-mediated responses. The reduced metastasis of B7+ tumor cells consequently led to the significant prolongation of survival. Expression of B7 on tumor cells did not influence the tumorigenicity in vivo and tumor cell invasion into basement membrane Matrigel in vitro. We also found that immunization of X-irradiated B7 transfectants was effective as a tumor vaccine for preventing lung metastasis caused by i.v. injection of B7- parental B16-BL6 cells but not against other syngeneic 3LL tumors. Thus, the B7-mediated anti-metastatic effect was tumor-specific. Vaccinations of irradiated B7+ tumor cells before and after surgical excision of the s.c. inoculated primary B7- tumors on day 21 achieved effectively the prevention of spontaneous lung metastasis. Our report that vaccination of irradiated B7+ tumor cells led to a therapeutic effect in an established tumor metastasis model clearly expands and confirms previous related observations.

Animals↗