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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 469 records · Page 26Linked to original sources
PubMed1995

Studies on antiulcer agents. III. Plausible mechanism of antisecretory action of ethyl 2[(1H-benzimadazol-2-yl)sulfinylmethyl]-4-dimethylamino- 5-pyrimidinecarboxylate, an H+/K(+)-ATPase inhibitor, based on its reaction with thiols.

To explore the mechanism of the gastric antisecretion activity of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]- 4-dimethylamino-5-pyrimidinecarboxylate (5), a potential H+/K(+)-ATPase inhibitor, in the acid compartment of parietal cells, its reaction with some alkylthiols in the presence of hydrochloric acid was investigated. Upon treatment with 2-mercaptoethanol under acidic conditions, 5 gave a characteristic 1:2 adduct, ethyl 4-[2-(2-hydroxyethyldithio)- 1-(2-hydroxyethylthio)ethylidenamino]pyrimido[1,2-a]benzimid azole-3- carboxylate (6), instead of providing a disulfide of type 3, 2-(2-alkyldithiomethylpyridino)benzimidazolide, the product predicted to be formed according to the reaction mechanism of common H+/K(+)-ATPase inhibitors, such as omeprazole or lansoprazole, with mercaptans. With a large excess of 2-mercaptoethanol, 5 provided 2-(2-hydroxyethylthio)-1H-benzimidazole (8) and ethyl 4-dimethylamino-2-(2-hydroxyethyldithio)-5-pyrimidinecarboxylat e (9) as well as 6. The transformation mechanisms and their implications are discussed.

Anti-Ulcer Agents↗
PubMed1995

Comparisons among feline herpesvirus type 1 isolates by immunoblot analysis.

Feline herpesvirus type 1 (FHV-1) isolated from cats suspected for feline viral rhinotracheitis could be divided into 3 genotypes (C7301, F2 and C7805 types) by digestion pattern with a restriction enzyme M1uI[16]. Variation of immunogenic products of 77 isolates were examined by immunoblot analysis using a polyvalent cat serum against C7301 strain, Japanese prototype strain of FHV-1. The result showed that a 36 kDa band was detected in 31 out of the 63 isolates belonging to C7301 type. However the band was not observed in the remaining 32 isolates of C7301 type and 14 isolates belonging to either F2 or C7805 type. In one isolate (91-58) of C7301 type, approximately 75 kDa band instead of 70 kDa band was observed, although the other bands were commonly observed in the remaining 76 isolates. From the results of the present and previous studies, FHV-1 field isolates could be divided into at least 4 groups and this grouping might be applicable for epidemiological studies of FHV-1 infection in the field.

Alphaherpesvirinae↗
PubMed1995

Construction of the recombinant feline herpesvirus type 1 deleted thymidine kinase gene.

We constructed a recombinant virus containing defined deletion within thymidine kinase (TK) gene from feline herpesvirus type 1 (FHV-1) C7301, which was isolated in Japan, by standard rescue procedures with thymidine arabinoside (araT) selection. The araT resistant recombinant virus was designated as C7301dlTK. Southern blot analysis, together with polymerase chain reaction, revealed a deletion with the expected size, based on agarose gel electrophoresis, of the TK gene region in the C7301dlTK. Growth kinetics of the C7301dlTK in CRFK cells was similar to that of ther parent C7301 that possesses TK activity. However, plaques produced by the C7301dlTK were significantly smaller than those of the parent virus. This report migth be applicable for the development of a new genetically engineered FHV-1 vaccine.

Animals↗
PubMed1995

Experimental infection of SPF piglets with porcine reproductive and respiratory syndrome (PRRS) viruses isolated from two farms.

Porcine reproductive and respiratory syndrome (PRRS) viruses were isolated from pig samples obtained from two farms characterized by an increased number of stillbirth and high mortality in new-born piglets (farm A), and respiratory distress with high mortality in weaning and growing pigs (farm B) in 1993, respectively. When primary specific pathogen-free piglets, 5-day-old or 13-day-old, were experimentally inoculated with the isolates, they showed clinical signs of depress, anorexia, pyrexia, diarrhea, sitting posture and periocular edema. Rate of the weight gain was reduced in the inoculated piglets compared with the non-inoculated pig. There were no apparent differences in clinical signs between the piglets inoculated with the virus samples derived from farms A and B. Microscopically, the most prominent changes observed in experimentally inoculated piglets were interstitial pneumonia, nonpurulent myocarditis and catarrhal lymphnoditis post inoculation day (PID) 28. Viruses were recovered from tissues collected from the inoculated piglets on PID 7 or 28. Furthermore, the viruses were continuously recovered from the sera from PID 7 to PID 28. Antibodies measured by indirect immunofluorescence assay to PRRS virus were first detected in sera on PID 14, and the antibody titer rose to 1:1280 on PID 28.

Animals↗
PubMed1995

[Detection of CD62P (GMP-140) on peripheral blood platelet membrane in various heart diseases].

The protein CD62P expressed on platelet surface membrane was measured by flow cytometry to evaluate its clinical significance. Whole blood contained 0.32% citrate from 64 patients with heart disease and 30 healthy adults were fixed with 0.1% paraformaldehyde. To 50 microliters of the fixed blood, 10 microliters of CD62 PE (Becton Dickinson) was added. After standing for 20 minutes at room temperature, the samples were washed and suspended in 1ml of PBS. Platelets were analyzed with Spectrum III (Ortho) flow cytometer. In healthy control, the percentage of platelets positive for anti-CD62P was 0.16 +/- 0.20 (mean +/- SD)%. Abnormal levels of CD62P were observed in 5 patients with unstable angina, 6 patients with acute myocardial infarction, 1 patient with old myocardial infarction, and 2 patients with mitral stenosis. These results show that activated platelets may play some roles in pathogenesis of heart disease though it is not fully clear yet.

Biomarkers↗
PubMed1995

Effects of parathyroidectomy on left ventricular mass in patients with hyperparathyroidism.

The effects of parathyroidectomy on left ventricular muscle volume and mechanical performance were evaluated echocardiographically in 24 patients with secondary hyperparathyroidism due to chronic renal failure and in 7 with primary hyperparathyroidism. Intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameters, shortening fraction, ejection fraction, and left ventricular mass index were measured by M mode recording by the parasternal short axis view prior to parathyroidectomy as baseline and repeated 12 months after parathyroidectomy. Serum basal carboxyterminal parathyroid hormone levels in patients with secondary hyperparathyroidism (34.4 +/- 13.7 ng/ml) were significantly higher than in those with primary hyperparathyroidism (3.4 +/- 5.1 ng/ml; p < 0.0001). At 12 months after parathyroidectomy, intraventricular septum and posterior wall thickness, left ventricular end-diastolic diameter and left ventricular mass index were reduced from 11.8 +/- 3.1 mm, 10.9 +/- 1.7 mm, 53.8 +/- 6.3 mm, 200.8 +/- 57.1 g/m2 to 10.0 +/- 2.1 mm (p < 0.05), 9.8 +/- 1.9 mm (p < 0.05), 50.7 +/- 7.2 mm (p < 0.05), 149.6 +/- 38.7 g/m2 (p < 0.0001), in patients with secondary hyperparathyroidism. In patients with primary hyperparathyroidism, all echocardiographic parameters remained in the normal range and did not show any significant changes before or after parathyroidectomy. From this study, parathyroid hormone at extremely high concentrations as seen in secondary hyperparathyroidism appears to be a cardiotoxic substance. Therefore, all patients with secondary hyperthyroidism should be examined by echocardiography and parathyroidectomy should be considered if myocardial hypertrophy is present.

Adult↗
PubMed1995

Involvement of dopamine, N-methyl-D-aspartate and sigma receptor mechanisms in methamphetamine-induced anticipatory activity rhythm in rats.

Daily injection of methamphetamine (MAP) increased the locomotor activity and produced the development of MAP-induced anticipatory activity on the next withdrawal day. Daily restricted feeding also causes a feeding-associated anticipatory activity rhythm. The importance of catecholaminergic neurons has been suggested in the manifestation of a feeding-associated corticosterone rhythm. In our study, we examined the role of dopaminergic neurons in the development of MAP-induced anticipatory activity. The development of MAP-induced anticipatory activity was blocked by coadministration of dopamine D2 receptor antagonists such as YM-09151-2 and sulpiride, the D1 receptor antagonist SCH23390 and haloperidol weak D1/D2 receptor antagonist, but not by clozapine. The anticipatory activity increase was reproduced by daily injection of the D2 receptor agonist quinpirole as well as moderately by the D1 receptor agonist SKF38393. Moreover, MAP-induced anticipation was blocked by coadministration of the N-methyl-D-aspartate receptor antagonist MK-801 or sigma ligands rimcazol and NE-100. Our results suggest that activation of the dopaminergic system, especially via D2 receptors may be required for the development of MAP-associated anticipatory activity increases and that N-methyl-D-aspartate receptors and sigma receptor mechanisms are also involved in the development of this behavior.

Animals↗
PubMed1995

[Cataract epidemiology survey in the three climatically different areas in Japan--prevalence of cataracts and types of lens opacification].

A cataract epidemiology study of 1,615 subjects from three climatically different places in Japan, village S in Hokkaido, town M in Noto and village Y in Okinawa, was conducted by one study group. Cataract diagnosis and grading of cataracts were objectively done with a photo-documentation system. The percentages of cataracts of over grade I classified by the Japanese Cooperative Cataract Epidemiology Study Group were 46.6%, 64.6% and 38.0% in village S, town M, and village Y, respectively. Those in their 50s, 60s, and 70s in the above places were 24.3%, 51.1% and 71.4% (village S), 38.4%, 65.3% and 84.6% (town M), and 25.2%, 42.9% and 65.4% (village Y), respectively. Cortical cataract was the most common, followed by nuclear and subcapsular types. Although the highest percentage of nuclear cataracts was seen in the subjects of village Y, subcapsular cataract was seen almost equally in the three areas. Lens transparency changes were evaluated by the light scattering intensities in the lens layers through photographed images. Intensity increased with ageing either linearly or exponentially.

Adult↗
PubMed1995

[Yearly changes and geographical distribution of allergic rhinitis morbidity estimated from records of the national health insurance].

The age-adjusted morbidity of allergic rhinitis (AR) in Ibaraki prefecture in May, estimated from data of national health insurance records, increased remarkably from 1980 to 1992 with varying yearly rates of increase. High AR morbidity years coincided with years of high Japanese cedar and cypress pollen counts, and moreover, an estimate equation of the morbidity using as explanatory variables, year and the yearly total count of pollen, accurately estimated AR morbidity. The AR morbidity varied with the size of the municipality. The AR morbidity of the town group and village group were about 80% and about 60% respectively of the city group in 1992. The map of the AR morbidity of each municipality showed that urbanized districts had higher morbidity than areas with cedar forests, which are supposedly sources of the cedar pollen. Continuous increase of morbidity of districts with much cedar forests terminated in 1986. Since then only the fluctuation of the morbidity corresponding to the pollen count was observed. The ratio of the morbidity of the years with much pollen to that of the years with little pollen was mapped. The map showed good agreement with the map of cedar forests. The results obtained above demonstrate the usefulness of the data of the national health insurance records.

Adolescent↗
PubMed1995

Brain activity of a rat reflects apparently the stimulation of acupuncture. A radioautography using 2-deoxyglucose.

To confirm a relationship between the central nervous system and the acupuncture, the response was examined in the rat brain using radioautography with tritiated 2-deoxyglucose, after stimulation of some acupoints. Eight groups, of a total of 27 rats were submitted to acupuncture at 6 different acupoints (Zusanli, Renzhong, Tianshu, Shenmen, Neiguan, Yongquan) and control, with or without electric pulses or with anesthesia respectively, prior to the injection with isotopic deoxyglucose. A hundred twenty cryosections were cut from a freshly frozen brain and exposed on single-coated X-ray films. The results showed that the acupuncture on the four acupoints of Zusanli, Tianshu, Shenmen and Neiguan enhanced the activity of the neocortex, the limbic cortex and the thalamic nuclei in comparison with the control group. The acupoints on Renzhong and Yongquan depressed the activity on the thalamic nuclei and the midbrain. The anesthesia with pentobarbital concealed the most activity on the whole area of the brain, which hardly responded to any stimulation of acupuncture. These results lead to the suggestion that the brain may reflect the signals by the stimulation of acupuncture and change the activity depending upon each acupoint.

Acupuncture Therapy↗
PubMed1995

[Relationship between daily high temperature and mortality in Kyushu, Japan].

We analyzed the relationship between daily high temperature and mortality in Kyushu, Japan, 1972-1990. Mortality rate was obtained by dividing the number of deaths in a certain daily high temperature category by person-days in the same category. The results were as follows: (1) With daily high temperature on the x-axis and mortality rate on the y-axis, the relationship between the two variables appeared to be V-shaped. The minimum mortality rate was observed at the 28 degrees C-33 degrees C level. (2) Among all deaths at 33+ degrees C level, the proportion of deaths from "excessive heat" never exceeded 0.4%. This suggested that heat stroke is not a major contributor to the V-shape formation. (3) The V-shape was observed even in 1990, suggesting that the rapid spread of air conditioners did not alter the relationship between daily high temperature and mortality rate. (4) For the 0-4 years age group, mortality was not temperature dependent. However, the 5-14 years age group showed high mortality rates at 33+ degrees C. This may be attributed to outdoor activities during summer. After 30 years of age, the overall mortality rates rose with age, with greater increases at lower ambient temperature levels. As a result, the 65+ years age group had the greatest temperature dependence. (5) Deaths from respiratory diseases, circulatory diseases, and senility were highly temperature dependent, whereas death from cancer was not temperature dependent. Deaths from digestive diseases, infectious diseases, and accidents showed moderate temperature dependence.

Adolescent↗
PubMed1995

[A study of effective administration of recombinant interferon-gamma in renal cell carcinoma regarding immunological influence on peripheral blood lymphocytes].

Immunological effect of recombinant interferon gamma (IFN-gamma) was studied in 18 cases of renal cell carcinoma. Sixteen of them were administered IFN-gamma as post-operative adjuvant therapy. Two of them were administered IFN-gamma for metastatic renal cell carcinoma. All of them were followed for at least 1 year. We divided the patients into two groups. One group subcutaneously received IFN-gamma every other day for 16 days, then 4 weeks later every week for one year (group A), and the other group, received alternate subcutaneous IFN-gamma every other day for 16 days and every week for 4 weeks (group B). For immunological testing, peripheral blood lymphocytes were obtained before treatment on day 1, 2 weeks later, 6 months later and 12 months later. The cells were tested for natural killer activity (NK), antibody dependent cellular cytotoxicity (ADCC), positive lymphocytes of CD3, CD4, CD8 and CD11b. Both ADCC and NK activity were increased after therapy, especially in group B. CD3, CD4 and CD8 positive lymphocytes were increased by means of IFN-gamma. On the other hand, CD11b-positive lymphocytes could not be elicited in group B. Tumor regression was observed in 2 cases of metastatic renal cell carcinomas. When clinical responses were observed, both ADCC and NK were elicited as compared with the pretreatment values. Our findings indicated that ADCC and NK could be elicited in group B.

Adult↗
PubMed1995

The effects of hemodialysis (HD) membranes on interleukin 1-beta (IL-1 beta) production from peripheral blood mononuclear cells (PBMC).

Dialysis-related symptoms are thought to be mediated by monocyte/macrophage-derived inflammatory cytokines, including interleukin 1-beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). We investigated the effect of hemodialysis (HD) membranes on IL-1 beta production using cultured peripheral blood mononuclear cells (PBMC). PBMC were stimulated with lipopolysaccharide (LPS) and the cell content and production of IL-1 beta were measured by ELISA. PBMC from a single healthy donor incubated with 5% of untreated plasma, and we found that HD patients plasma enhanced IL-1 beta production less than normal control plasma. The plasma obtained from the venous side of HD patients 15 minutes after starting a single HD (15-min HD plasma) did not enhance IL-1 beta production as much as the plasma from the arterial side, either before or upon completion of a single HD (pre-HD plasma, post-HD plasma). We studied IL-1 beta productivity when pre-HD plasma (arterial side) and 15-min HD plasma (venous side) were added to autologous PBMC. The IL-1 beta production by PBMC was less when the 15-min HD plasma was added to PBMC as compared to when the pre-HD plasma was added. This reduction tended to be greater when a dialyzer membrane used was a large-pore type made of regenerated cellulose (RC) or polymethylmetacrylate (PMMA) than with a small-pore RC membrane. After HD for 2 weeks using a small-pore RC membrane, the same HD patient was then treated with a large-pore RC membrane. The PBMC IL-1 beta production level decreased with the use of the large-pore RC as compared to the case with the small-pore RC membranes. The present study suggests that large-pore dialyzer membranes remove middle molecules and low molecular weight proteins which enhance IL-1 beta production, and that this production may be regulated by some mechanism unrelated to complement activation.

Biocompatible Materials↗
PubMed1995

Combination of anti-cell adhesive synthetic Arg-Gly-Asp-Ser analogue and anticancer drug doxorubicin heightens their original antimetastatic activities.

A new compound containing the cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide was synthesized, i.e. tetrahydrofurantetracarboxylic acid (THFTCA)-RGDS conjugate [THFTCA- (RGDS)3, FC-243], and the inhibitory effect of FC-243 on lung metastasis of B16-BL6 melanoma in mice was examined in combination with or without the anticancer agent doxorubicin (DOX). FC-243 showed an inhibitory effect on lung metastasis of melanoma cells in a dose-dependent manner. A mixture of THFTCA and RGDS peptide or THFTCA alone did not show any inhibitory effect on experimental lung metastasis as compared with FC-243 on a molar basis. RGDS peptide, however, required a higher dose to obtain a sufficient antimetastatic effect. Intermittent IV administration of FC-243 after the inoculation of B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with multiple administration of RGDS or untreated control. The in vitro tumor invasion study showed that FC-243 as well as RGDS+THFTCA on a molar basis resulted in similar inhibition of the invasion of B16-BL6 cells into reconstituted basement membrane Matrigel. Combined treatment with FC-243 and DOX significantly inhibited lung metastasis of melanoma as compared with either treatment alone or the untreated control. Administrations of FC-243 and DOX in combination substantially prolonged the survival time of mice. These results demonstrate that combination therapy of the anti-cell adhesive FC-243 and the anticancer agent DOX, i.e. antiadhesion therapy and chemotherapy, is a new approach that offers enhanced inhibitory effects on tumor metastasis and invasion.

Animals↗
PubMed1994

Transforming growth factor-beta 1 post-transcriptionally inhibits mouse growth hormone releasing factor secretion in placenta.

The aim of this study was to investigate whether TGF-beta 1 regulates mouse GHRF secretion by primary cultures of placental cells from day 12 of pregnancy. Ten ng/ml TGF-beta 1 significantly inhibited mouse GHRF secretion by the third day of culture. The lowest concentration of TGF-beta 1 that significantly inhibited mouse GHRF secretion was 1 ng/ml. The inhibitory effect of TGF-beta 1 on mouse GHRF secretion was completely eliminated by addition of an anti-TGF-beta 1 antibody. Steady-state levels of mouse GHRF mRNA as assessed by Northern analysis was not reduced by incubation of placental cells from day 12 of pregnancy with 10 ng/ml TGF-beta 1 for 5 days. Both placenta and decidua expressed TGF-beta 1 mRNA, and the level of TGF-beta 1 mRNA in decidua increased during gestation while the level of TGF-beta 1 mRNA was constant throughout gestation. These findings suggest that TGF-beta 1 is one of the potent regulators of mouse GHRF secretion and that TGF-beta 1 regulates mouse GHRF secretion in an autocrine or paracrine manner in the mouse placenta in vivo.

Animals↗
PubMed1994

Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds.

Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components. Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repair in the mouse, consistent with a role for syndecans in regulating cell proliferation and migration in response to these effectors. Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specificity for mesenchymal cells, and selectivity for syndecan-1 and -4. We have purified and synthesized a 4.8-kDa proline-rich protein from wound fluid that reproduces this induction of syndecan-1 and -4 in cultured cells. This peptide, identical to the antibacterial peptide PR-39, is released into the wound by the cellular infiltrate and induces syndecan expression at the same peptide concentrations that lyse bacteria. These results indicate that wounds contain a multifunctional protein that induces mammalian cells to express cell surface heparan sulfate proteoglycans as part of the wound repair process and that kills bacteria as part of a nonimmune defense mechanism.

3T3 Cells↗
PubMed1994

Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor.

Human MDA MB 231 cells were found to synthesize mostly the cell surface-associated precursor form of heparin-binding EGF-like growth factor (HB-EGF), a 27-kDa protein. Evidence for this form of HB-EGF included increased fluorescence intensity when cells were analyzed by flow cytometry using anti-HB-EGF antibodies, lack of HB-EGF in conditioned medium, and sensitivity to diphtheria toxin, for which HB-EGF is the receptor. Phorbol ester treatment of cells resulted, within 30 minutes, in loss of cell surface 27 kDA HB-EGF, lack of interaction with anti-HB-EGF antibodies, accumulation of active 21 kDa HB-EGF in conditioned medium, and the acquisition of diphtheria toxin resistance. It was concluded that cell surface-associated HB-EGF is the precursor of a bioactive growth factor, is biologically active as the receptor for diphtheria toxin, and is susceptible to rapid processing.

Diphtheria Toxin↗