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Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 199 records · Page 11Linked to original sources
PubMed1997

Increased production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells in undialyzed chronic renal failure.

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.

Adult↗
PubMed1997

Assessment of UDP-galactosyl-transferase activity in gastric mucosa of patients with chronic liver disease using an enzyme-linked peanut agglutinin binding assay.

Gastric mucin plays an important role in protecting mucosa from irritants such as acids and pepsin, and UDP-galactosyltransferase is a key enzyme in mucin synthesis. In order to study the synthesis of gastric mucin in patients with chronic liver disease, we developed a new assay using a peanut agglutinin lectin to measure this enzyme in human gastric mucosa obtained by endoscopic biopsy. Enzyme activity correlated well with that determined with a previous method using radiolabeled galactose. The enzyme activity in gastric mucosa of cirrhotic patients was significantly lower than in patients with chronic hepatitis or in normal controls and correlated with the amount of mucin in surface epithelial cells. Our findings suggest that the synthesis of gastric mucin is impaired in patients with liver cirrhosis.

Adult↗
PubMed1997

Visualization of central stellate fibrosis in hyaline vascular type Castleman's disease.

Hyaline vascular type Castleman's disease (HVCD) is a benign cause of lymph node hypertrophy which radiologically resembles tumours such as paraganglioma and lymphoma. However, a distinguishing pathological characteristic of HVCD is the presence of central stellate fibrosis. Since conventional CT and MRI scans failed to differentiate areas of fibrosis, three-phase dynamic CT was performed on a patient who was thought to have HVCD. The images showed central fibrosis and consequently the correct pre-operative diagnosis of HVCD was made.

Adult↗
PubMed1997

Effects of angiotensin AT1 receptor antagonist on volume overload-induced cardiac gene expression in rats.

The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin AT1 receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin AT1 receptor antagonist, CS-866 (10 mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10 mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Ca(2+)-ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Ca(2+)-ATPase expression. Unlike the left ventricle, the significant downregulation of alpha-myosin heavy chain and transforming growth factor-beta 3 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-beta 3. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that AT1 receptor partially contributed to volume overload-induced changes in cardiac gene expression and that AT1 receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy.

Actins↗
PubMed1997

Geranylgeranylacetone and cetraxate hydrochloride increase UDP-galactosyltransferase activity in rat gastric mucosa.

UDP-galactosyltransferase (UDP-Gal-T) is a key enzyme in the synthesis of mucus glycoprotein which plays an important role in gastric mucosal defensive mechanisms. Analysis of gastric UDP-Gal-T activity should clarify the mechanisms of the action of antiulcer drugs regarding gastric defensive factors. Here, we examined UDP-Gal-T activity in rat gastric mucosa treated with the antiulcer drugs geranylgeranylacetone (GGA) and cetraxate hydrochloride (CET). The effects of coadministration of indomethacin and exogenous administration of prostaglandins (PGs) were also studied. GGA and CET significantly increased UDP-Gal-T activity, and coadministration of indomethacin inhibited the increase of enzyme activity. UDP-Gal-T activity level with GGA was significantly higher than the control level, even in the presence of indomethacin. With CET, however, this was not the case. Among PGs, PGE1 significantly increased enzyme activity. Concomitant administration of PGE1 and GGA or CET increased UDP-Gal-T activity even with indomethacin to the levels achieved when these antiulcer drugs were administered without indomethacin. Our findings suggest that GGA and CET exert antiulcer effects by increasing mucus glycoprotein synthesis and that endogenous PG synthesis may be involved in this process. However, mechanisms not mediated by endogenous PGs may also exist in the stimulatory action of GGA on UDP-Gal-T activity.

Animals↗
PubMed1997

Enzyme immunoassay of glioma cell tenascin secretion and augmentation by tumor necrosis factor-alpha.

Expression of tenascin, an extracellular matrix glycoprotein, was measured in glioma cell lines using a newly established enzyme immunoassay. Secreted tenascin was found at concentrations greater than 800 ng/ml in eight of 14 glioma, three small cell lung carcinoma, two melanoma, and one sarcoma cell lines. The remaining six glioma and other carcinoma cell lines, and cell lines originating from normal tissues demonstrated low levels or no secretion into the supernatant. The glioma cell line, U-251-MG nu/nu, which has almost 100% transplantability in nude mice, had the highest expression level of tenascin among the glioma cell lines examined. Even low secretor glioma cell lines released high concentrations of tenascin, detectable by assaying the NP-40 solubilized cell lysates. Flow cytometric analysis revealed that tenascin was located on both the cell surface and primarily in the cytoplasm of glioma cells. When the glioma cell lines were exposed to tumor necrosis factor-alpha (TNF-alpha), levels of secreted tenascin increased between 36% and 380%, whereas transforming growth factor-beta induced only minimal changes. These results suggest that glioma cell lines may be classified according to the degree of tenascin secretion/expression: high secretor type, low secretor type, and non-expressing type. The increase in tenascin secretion by TNF-alpha suggests that the expression of tenascin in glioma growth and development may be mediated through a cytokine network.

Animals↗
PubMed1997

Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha.

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.

Animals↗
PubMed1997

[The meaning and structure of cancer survivors' perception of their health].

The purpose of this study is to examine the meaning and structure of cancer survivors' perception of their health. An ethnographic approach is used in an inductive analysis of survivors' behavior. Thirty cancer survivors were examined through interviews and participant observation (participant observation was conducted in their own homes, offices, outpatient departments, or at the meetings of survivors' self-help groups). The cancer survivors' perceptions of their health, described in their own words, are categorized in 17 "folk domains of concepts". Among them, category A, "kekkyoku-wa-jibun-da (After all, there is nobody but me)" was selected as the tentative theme: the remaining domains were reorganized by their relationship with this theme domain. Through this study, it was found that the theme domain plays an important role when a cancer survivor struggles for survival and arrives at a state in which extraordinary circumstances brought about by cancer do not bother him any longer. This findings indicates that sound recovery from cancer can be achieved through harmony between a cancer survivor's self and his daily life. This also suggests that help should be provided to cancer survivors to contribute to stable surroundings that enable them to establish a sound self concept.

Adaptation, Psychological↗
PubMed1997

[The changes of regional cerebral blood flow and oxygen metabolism following ventricular puncture].

In seven patients who underwent ventricular puncture as a procedure for either continuous ventricular drainage or ventriculoperitoneal shunt between April 1983 and December 1988, the changes between pre- and postoperative regional cerebral blood flow (rCFB) and the regional cerebral metabolic rate of oxygen (rCMRO2) around the regions along the tract of puncture were evaluated. In each patients, rCBF and rCMRO2 were measured using Positron Emission Tomography (PET) by the steady state method. The regions of interest (ROIs) with diameters of 2cm were set as follows: The gray matter (PSG) and white matter (PSW) along the tract of the puncture, the same regions on the opposite side (OSG and OSW) and the bilateral motor cortex (PSM and OSM) as control. All changes, as well as lateralities at each region were studied. In 4 of 7 patients long term follow up PET studies (mean = 657 days after the procedure) were performed. After the procedure values of rCBF significantly increased in OSG and OSW (p < 0.05) and tended to increase in PSG and PSW. But compared with OSG and OSW, the degree of increase in PSG and PSW were suppressed. In the motor cortex evident changes were not recognized. Lateralities between PSG and OSG and those between PSW and OSW tended to increase after procedure. In long term follow up studies the values further increased in all regions including PSG and PSW and lateralities tended to decrease, but suppression of improvement around the puncture site was prolonged. The changes of rCMRO2 had the same tendency but it was not significant. The rCBF and rCMRO2 generally increased following the procedure accompanying ventricular puncture. Perhaps this was because of adjustment of increased intracranial pressure or cerebrospinal fluid circulation. But the degree of improvement around the puncture site was suppressed. Minor brain injury caused by the procedure was considered to be the cause of reduction of improvement of cerebral blood flow and cerebral oxygen metabolism.

Aged↗
PubMed1997

[Visually-guided discrimination and preference of sexuality in female macaque monkeys].

Visual information about face and body including facial expression and bodily behavioral patterns has been known to play an important role in social and emotional communication in monkeys. Its involvement in sexual activity has also been demonstrated in male monkeys but it is poorly understood in female monkeys. In the present study, visually-guided discrimination and preference of sexuality were investigated in female macaque monkeys performing operant bar-press tasks in an experimental cage which had a transparent panel facing a display. In the sex discrimination task, two rhesus monkeys (Macaca mulatta) were trained to discriminate sex of a monkey shown in a picture which was randomly selected from six photographs (three males and three females) and was presented on the display. The monkey pressed a right or left bar for male or female monkey, respectively, to get water as a reward. Under this discrimination task, the monkeys could discriminate the sexes of monkeys shown in newly presented pictures. When choice bars were reversed, correct responses significantly decreased below chance level. In the sex preference task, three rhesus monkeys and three Japanese monkeys (M. juscata) were used. The monkeys voluntarily pressed the bar to watch the video movie showing either male or female rhesus monkeys. The movies were presented as long as the subject kept pressing the bar. The same movie was continued when the monkey pressed the bar again within 10s after the previous release of the bar, while it was changed to the other when 10s passed after the subject released the bar. The total duration of the responses in daily sessions was measured. In this visual preference task, four out of six monkeys showed sex preference. Three adult Japanese monkeys (6-8 y) pressed the bar to watch the video movie of male monkeys which was taken in breeding season with longer duration than that of female monkeys taken in the same season. The other two adult rhesus monkeys (7 8 y) did not show the sexual preference. The one remaining youngest rhesus monkey (5 y) preferred to watch the female movie which was taken in non-breeding season. The visual preference was observed not only in winter but also in summer when tested. The present results suggest that visual information alone is sufficient to discriminate sex and produce sex preference in some female monkeys. The seasonal changes in visual appearance of objects seem to be more determinant factors for the preference than the endogenous factors of subjects.

Animals↗
PubMed1997

[The influence of anti-interferon-alpha 2a antibodies in initial daily four-week interferon-alpha 2a therapy for chronic hepatitis C].

Thirty-two patients with chronic active hepatitis C were initially treated with 9 million units of interferon (IFN)-alpha 2a daily for 4 weeks and then thrice weekly for 20 weeks. The incidence of development and influence on clinical effectiveness of anti-IFN alpha 2a neutralizing antibodies measured by bioassay were investigated. Thirteen (41%) of the 32 patients developed antibodies, 4 (12.5%) of whom exhibited a high titer of 128 NU or greater. There was a significant difference (p < 0.05) between responders and non-responders in the low viral load group (less than 10(5) copies/50 microliters) in the incidence of antibody development, with antibodies present in 2 of the 9 responders (22%) and 5 of the 7 non-responders (71%). There was also a significant difference between the antibody-negative and antibody-positive patients in circulating HCV-RNA, 2-5AS activity and average ALT levels at the latter half of treatment. In addition, 2-5AS activity was significantly lower (p < 0.05) at completion of treatment in the high antibody titer group (128 NU or greater) than in the low antibody titer group. These results indicate that the development of anti-IFN neutralizing antibodies had a definite influence on the clinical course of IFN treatment for chronic hepatitis C.

Adult↗
PubMed1997

[Gene therapy for brain tumors].

Patients with glioma(which constitute 33% of all brain tumor cases) still have a poor prognosis, especially in the case of malignant(anaplastic astrocytoma and glioblastoma). This poor prognosis is related to the fact that malignant glioma cells aggressively infiltrate into normal brain tissues, making total removal of the tumor impossible. The median survival time of glioblastoma patients is less than 2 years, despite multimodality treatment with extensive surgical resection and adjuvant therapies using radiation and immunochemotherapy. In order to overcome this formidable neoplasm, the effectiveness of molecular neurosurgery using gene therapy has been investigated since 1992. In this paper, the current state of gene therapy for malignant brain tumors are described, and the future direction of this fascinating approach is discussed.

Brain Neoplasms↗
PubMed1997

[Therapeutic strategy and clinical outcome in congenital diaphragmatic hernia].

Congenital diaphragmatic hernia (CDH) continues to carry a high mortality rate 40%-60% mainly due to severe pulmonary hypoplasia. At our institute, thirty-seven neonates were treated for CDH diagnosed within the first 24 hours of life. Eleven of thirty-seven patients died and the mortality rate was 30%. Deaths in ten patients were due to severe pulmonary hypoplasia. The other one patient died from barotrauma at three months of age. All twenty-six patients who responded to ventilatory management and pharmacological therapies underwent surgical repair of CDH and all except one survived. Eight of eleven patients who did not respond to treatment also underwent surgery, but all died. These cases were all treated fufore ECMO introduction. Two of the other three in whom ECMO support was instituted died postoperatively. Among the parameters PH < 7, PaO2 < 60, PaCO2 > 60, AaDO2 > or = 600 and OI > or = 40 recorded on admission and examined retrospectively, OI > or = 40 was the most reliable as a predictor for poor outcome (sensitivity: 100%, specificity: 81%) and probably entry criteria for ECMO. The mean lung/body weight ratio of nonsurviving neonatal cases was as low as 0.49 +/- 0.18% while at least 1% is the critical value for survival. To salvage the CDH patient with severe pulmonary hypoplasia, surgical intervention before birth is inevitably necessary based on accurate prenatal diagnosis and established surgical techniques.

Animals↗
PubMed1996

Effects of gemfibrozil administration on very low density lipoprotein receptor mRNA levels in rabbits.

To elucidate the regulation of very low density lipoprotein (VLDL) receptor gene expression, we administered to rabbits for 14 days gemfibrozil, a fabric acid derivative and a lipid lowering drug that is also included among peroxisome proliferators. VLDL receptor mRNA levels were examined by Northern blot analysis. The VLDL receptor mRNA levels in retroperitoneal adipose tissue and in gastrocnemius muscle were increased 6.9-fold and 3.7-fold, respectively, with gemfibrozil treatment, but no marked changes were observed in the heart, the organ in which VLDL receptor is most highly expressed. In the liver, VLDL receptor mRNA was not detected either before or after gemfibrozil administration. Lipoprotein lipase (LPL) and long-chain acyl coenzyme A synthetase (ACS) mRNA levels were also increased in parallel in adipose tissue. The enhanced expression of VLDL receptor mRNA may contribute to the increase of triglyceride-rich lipoprotein catabolism in peripheral tissues such as adipose tissue and muscles.

Adipose Tissue↗
PubMed1996

Differences in inducibility of CYP1A1-mRNA by benzimidazole compounds between human and mouse cells: evidences of a human-specific signal transduction pathway for CYP1A1 induction.

Three benzimidazole compounds, omeprazole (OP), thiabendazole (TBZ), and lansoprazole (LP), were compared with respect to the induction of CYP1A1-mRNA in human hepatoma cells, HepG2. OP was the most potent inducer among the three compounds, but LP was found to be a weak inducer. Induction by TBZ was at an intermediate level. None of these compounds induced CYP1A1-mRNA in a mouse hepatoma cell line, Hepa-1. The transient expression of mouse Cyp1a1-CAT gene into HepG2 cells showed that OP treatment of the transfectants induced CAT activity to the same degree as 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment. Therefore, the cellular factors in human cells were able to work on the mouse regulatory element. The expression of human aryl hydrocarbon (Ah) receptor in the mouse Hepa-1 mutant cell line cl-19, which is defective in Ah receptor, did not increase the induction level of CYP1A1-mRNA by OP treatment. When the cultured medium of HepG2 cells in the presence of OP was added to the mouse Hepa-1 cell culture medium, CYP1A1-mRNA was not induced in Hepa-1 cells. It is thus concluded that metabolites of OP in human cells are not the ligands for the human Ah receptor. Therefore, in human cells, but not mouse cells, there must be an OP-sensitive activation factor for the human Ah receptor.

2-Pyridinylmethylsulfinylbenzimidazoles↗