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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 451 records · Page 25Linked to original sources
PubMed1995

Attenuating effect of arecoline and physostigmine on an impairment of mealtime-associated activity rhythm in old rats.

In the present study, we examined whether cholinergic drugs such as arecoline and physostigmine attenuated an impairment of time perception presented by daily scheduled feeding in aged rats. When feeding was restricted to a single meal at a fixed time of day (13:00-17:00) for 6 successive days, young rats exhibited intense locomotor activity from 1-3 h before feeding time. Intense locomotor activity was observed between 12:00-17:00 in young animals even on the fasting day (on day 7) (mealtime-associated activity). However, this mealtime-associated activity was impaired in old rats. Daily injection of arecoline (10 mg/kg) or physostigmine (0.1 and 0.2 mg/kg) at 17:00 for 6 successive days attenuated the impairment of mealtime-associated activity on the fasting day in a dose-dependent manner in old rats, whereas daily treatment with D-glucose (100 or 2000 mg/kg) did not. The results of the present study suggest that cholinergic drugs attenuate the impairment of the manifestation of mealtime-associated anticipatory activity related to 'temporal learning' in old rats.

Activity Cycles↗
PubMed1995

Attenuating effect of bifemelane on an impairment of mealtime-associated activity rhythm in aged and MK-801-treated rats.

In the present experiment, we examined the attenuating effect of bifemelane hydrochloride (BF), 4-(o-benzyl phenoxy)-N-methylbutylamine hydrochloride, on the impairment of time perception caused by daily scheduled feeding using aged and MK-801-treated rats. When feeding was restricted to a single meal at a fixed time of day (1300-1700 h) for six successive days, young rats exhibited intense locomotor activity 1-3 h before feeding time. Intense locomotor activity was observed for 1200-1700 h even on the fasting day (day 7; mealtime-associated activity). Mealtime-associated activity was impaired in 24-mo-old rats and also in N-methyl-D-aspartate receptor antagonist, MK-801-treated rats. Daily injections of bifemelane at 1700 h for six successive days significantly attenuated the impairment of mealtime-associated activity on the seventh day in a dose-dependent manner in aged rats. In addition, cotreatment of MK-801 with bifemelane blocked the MK-801-induced impairment of mealtime-associated activity. The present study suggests that bifemelane has an enhancing effect on learning and memory performance, such as spatial and temporal perception.

Aging↗
PubMed1995

Expression of Marek's disease virus (MDV) serotype 2 gene which has partial homology with MDV serotype 1 pp38 gene.

We constructed the recombinant baculovirus expressing the gene of non-pathogenic Marek's disease virus (MDV) serotype 2 (MDV2) which encodes a polypeptide with partial homology to MDV serotype 1 (MDV1) pp38, an antigen associated with transformed cells. The recombinant MDV2 protein was detected as a band of 32 kDa in immunoblot analysis with MDV2-infected chicken serum. Mouse serum against insect Spodoptera frugiperda cells infected with the recombinant baculovirus immunoprecipitated a 38 kDa molecule from the lysate of MDV2-infected chicken embryo fibroblasts (CEFs) but did not immunoprecipitate the MDV1 pp38 from the lysate of MDV1-infected CEFs. This result indicates that the recombinant MDV2 protein has no epitopes shared with the MDV1 pp38.

Animals↗
PubMed1995

Preparation of monoclonal antibodies against Marek's disease virus serotype 1 glycoprotein D expressed by a recombinant baculovirus.

A recombinant baculovirus, the genome of which contains DNA encoding Marek's disease virus serotype 1 (MDV1) homolog of glycoprotein D (gD) of herpes simplex virus under the polyhedrin promoter was constructed and designated rAcMDV1gD. Five monoclonal antibodies (MAbs) which recognize the MDV1 homolog of gD (MDV1 gD) in Spodoptera frugiperda cells infected with rAcMDV1gD were prepared. The MAbs reacted with proteins ranging from 52 to 49 kDa in rAcMDV1gD-infected cell lysates by immunoblot analysis. These molecular weights were coincident with molecular weights predicted from the open reading frame of MDV1 gD. By ELISA additivity test, the 5 MAbs were divided into 3 groups which seemed to recognize 3 different epitopes. In addition, all of the 5 MAbs were reactive with chick embryo fibroblasts (CEFs) expressing MDV1 gD. The MAbs are considered to be useful to study the role of MDV1 gD in MDV1 infection.

Animals↗
PubMed1995

Immunocytochemical location and hormonal control of androgen receptors in lacrimal tissues of the female MRL/Mp-lpr/lpr mouse model of Sjögren's syndrome.

Androgen therapy suppresses lymphocyte infiltration in, and improves the functional activity of, lacrimal glands in a female mouse model (MRL/Mp-lpr/lpr [MRL/lpr]) of Sjögren's syndrome. To extend these findings, the current investigation was designed to identify the cellular target(s) within lacrimal tissue that may mediate this androgen effect. In addition, we explored the endocrine regulation of androgen receptors in autoimmune lacrimal glands. Adult, female MRL/lpr mice were exposed systemically to vehicle, steroid hormones or immunosuppressive agents for varying time intervals after the onset of disease. Immediately before or after treatment, lacrimal glands were obtained and processed to determine the cellular distribution and nuclear density of androgen receptors by immunoperoxidase and image analysis techniques. Our findings demonstrated that: (1) androgen receptors exist almost exclusively within nuclei of acinar and ductal epithelial cells in lacrimal tissue of MRL/lpr mice; (2) androgen receptors are not detectable in the extensive lymphocytic populations that infiltrate the gland; (3) testosterone administration induces a significant increase in the number of androgen receptor-containing cells in, as well as the density of androgen receptors in epithelial cell nuclei of, lacrimal tissue; (4) hormone action is steroid-specific: administration of androgen analogues, but not estrogens, glucocorticoids or cyclophosphamide, stimulate the accumulation of androgen receptors; and (5) androgen receptor density is significantly reduced following the withdrawal of androgen therapy. These results show that epithelial cells, but not lymphocytes, are the androgen target cells in lacrimal tissue, and suggest that these cells may mediate the androgen-related immunosuppression and functional enhancement in lacrimal glands of autoimmune female mice. Our findings also demonstrate that androgens increase the expression of their own receptors in MRL/lpr lacrimal tissue.

Animals↗
PubMed1995

Expression and identification of the feline herpesvirus type 1 glycoprotein B (gp143/108).

The gene for feline herpesvirus type 1 (FHV-1) glycoprotein B (gB) has been cloned into an expression vector, pRVSVneo, containing the long terminal repeat of Rous sarcoma virus and polyadenylation signal of SV40. This expression vector containing FHV-1 gB gene, pRVSVgBneo, was transfected into Crandell feline kidney (CRFK) cells which are susceptible to FHV-1 infection. By indirect immunofluorescence analysis, the expressed gB was recognized with a panel of monoclonal antibodies (MAbs) against FHV-1 gp143/108. Immunoprecipitation analysis using a MAb 34H12 showed that molecular weights of the gB were 143 and 108 kDa under non-denaturing conditions that 108, 70, 64, and 58 kDa under denaturing conditions. The molecular weights were similar to those of the gB expressed in FHV-1-infected CRFK cells. In addition, when plasmid DNAs were injected into mice to obtain gB-monospecific serum, the pooled serum from mice inoculated with pRVSVgBneo, but not with pRVSVgDneo or pRVSVneo, recognized the FHV-1 gB polypeptides.

Animals↗
PubMed1995

A function of Ly-5 (CD-45) in the generation of lymphokine-activated killer cells defined by Ly-5 anti-sense oligodeoxyribonucleotides and Ly-5 monoclonal antibody.

The unique feature of the Ly-5 system is that it is a major cell surface glycoprotein, representing up to 10% of the total cell surface complement, confined to the hematopoietic cells as a family of isoforms generated by alternative splicing of a single Ly-5 gene. The cytoplasmic domain of Ly-5 has protein tyrosine phosphatase activity suggesting that Ly-5 is involved in signal transduction. We used Ly-5 anti-sense oligodeoxyribonucleotides (oligo) and Ly-5 monoclonal antibody (mAb) to study the functional role of Ly-5 in the concanavalin A mitogenesis response by spleen cells, as well as in the generation of lymphokine-activated killer cells and the proliferative response by spleen cells induced by recombinant human interleukin-2 (rhIL-2). Our results indicate that the Ly-5 mAb could enhance these activities whereas the anti-sense oligo was inhibitory. These data clearly suggest that Ly-5 is involved in the IL-2 and IL-2 receptor responsive circuit.

Animals↗
PubMed1995

Maintaining low concentrations of plasma beta 2-microglobulin through continuous slow haemofiltration.

As a first step in the development of a future wearable artificial kidney, we conducted three forms of treatment with continuous haemofiltration (CHF) on a group of 10 patients in an attempt to determine what plasma values of small molecules and beta 2-microglobulin (beta 2-M) could be maintained. In the first system, one ordinary 4-h haemodialysis, followed by 7-day CHF with 51 exchange per day, was repeated. The second system consisted of CHF with 51 exchange/day and thrice weekly slow nocturnal dialysis. The third system used CHF with 101 exchange per day. The first, second and third systems were used with three, four and four patients, respectively, for at least 4 weeks each. PAN-DX and FH-66 haemofilters were used eight and three times, respectively, with continuous infusion of heparin at 500-700 units/h. In the first system, the pre-CHF plasma beta 2-M was 45.5 +/- 3.1 mg/l, against a much lower 18.8 +/- 1.0 mg/l 4 weeks later. With the second system, this decrease was from 43.5 +/- 5.7 mg/l to 18.1 +/- 1.1 mg/l with 4 weeks treatment, and from 44.7 +/- 3.4 mg/l to 18.1 +/- 1.4 mg/l with 3 weeks treatment. Pre-haemodialysis treatment levels of urea nitrogen, plasma creatinine and uric acid in the first system were greater than ordinary pre-haemodialysis levels. On the second system, these were kept at -54 +/- 8.3%, -52.2 +/- 6.7% and -47.6 +/- 4.4% of the ordinary pre-haemodialysis levels, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Isolation and characterization of heparin-binding growth factors in human leiomyomas and normal myometrium.

Uterine leiomyomas (fibroids) are benign, smooth muscle cell (SMC) tumors of the myometrium containing abundant extracellular matrix (ECM). Heparin-binding growth factors present in leiomyoma and normal myometrial fresh tissue were isolated using heparin-affinity fast protein liquid chromatography. Purification of these growth factors was monitored by the stimulation of [3H]thymidine incorporation into BALBc-3T3 cells and myometrial SMC. Western blot analysis confirmed that two consistent peaks of growth factor activity (eluting at 0.5 M NaCl and 1.7 M NaCl) were platelet-derived growth factor (PDGF), 31 kDa, and basic fibroblast growth factor (bFGF), 18 kDa, respectively. Northern blot analysis of leiomyoma and myometrial tissue revealed three RNA transcripts (2.8, 2.3, and 1.9 kb) for PDGF-A chain, one RNA transcript (4.0 kb) for PDGF-B chain, and two RNA transcripts (3.7 and 3.5 kb) for bFGF. RNase protection assay showed elevated expression of the bFGF mRNA transcript in leiomyomas in 3 out of 5 patients. Immunoperoxidase staining of paraffin-embedded tissue showed that PDGF was predominantly intracellular in both vascular and myometrial SMC. Basic FGF, by contrast, was found primarily bound to the ECM of myometrium and fibroids. Leiomyomas showed much stronger staining for bFGF due to the large areas of ECM in these tumors. A third mitogenic peak eluting at 1.1 M NaCl was also seen in both myometrial and leiomyoma tissue. This peak was not definitively identified by Western blotting. However, Northern analysis for heparin binding-epidermal growth factor (HBEGF), which also elutes at 1.1 M NaCl, detected one RNA transcript for HBEGF (2.5 kb) in normal myometrium but little or no expression in the corresponding leiomyoma tissue. Immunoperoxidase staining showed that HBEGF was a cell-membrane-associated protein in both normal myometrial and leiomyoma SMC with more intense staining in normal myometrium. These results show that both leiomyomas and myometrium synthesize a number of heparin-binding growth factors. The enhanced growth of leiomyomas may be due, in part, to the presence of large quantities of bFGF that are stored in the ECM of these tumors. In addition, the level of HBEGF mRNA declines during the transformation of myometrial SMC into leiomyomas.

Animals↗
PubMed1995

Can the risk for acute cardiac events in acute coronary syndrome be indicated by platelet membrane activation marker P-selectin?

BACKGROUND: P-selectin, an adhesion molecule of the selectin family, is expressed on the surface of activated thrombocytes by thrombin. The aim of the present study was to assess the predictive value of P-selectin (estimated by flow cytometric assay) for acute cardiac events in acute coronary syndrome. METHODS: The study consisted of 48 patients with acute coronary syndrome and 30 healthy control subjects. After immediate fixation with 1% paraformaldehyde, 50 microliters of this aliquot was incubated with phycoerythrin-CD62-related antigen, and then measured by flow cytometry. The short-term clinical course of the patients was compared with their P-selectin values. RESULTS: The average P-selectin values in the 30 healthy volunteers was 0.11 +/- 0.20% (range, 0.0-0.5%). Significant differences were observed between acute cardiac events in patients with unstable angina and high P-selectin values and those with normal P-selectin values (chi 2 = 4.3; P < 0.05). Moreover, the angina patients who experienced acute cardiac events had significantly elevated P-selectin values (2.1 +/- 2.3%) compared with patients who did not experience acute cardiac events (0.3 +/- 0.4%, P < 0.05). The P-selectin values were elevated in seven out of 24 patients who suffered acute myocardial infarction. Seven of the 14 patients with acute coronary syndromes and high P-selectin values required urgent percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), or both, otherwise they developed extension of the infarction. However, only five of the 34 patients with normal P-selectin values required urgent PTCA or CABG. Significant differences were observed in acute cardiac events between the high P-selectin and normal P-selectin groups (chi 2 = 4.8, P < 0.05). CONCLUSION: High P-selectin values indicate activation of platelets and the risk of acute cardiac events in patients with acute coronary syndrome.

Blood Platelets↗
PubMed1995

Dual pathways of tubular morphogenesis of vascular endothelial cells by human glioma cells: vascular endothelial growth factor/basic fibroblast growth factor and interleukin-8.

In this study, we examined whether human glioma cells are angiogenic in a model using human microvascular endothelial cells, and also which factor is responsible for the glioma-dependent angiogenesis. Tubular morphogenesis in type I collagen gel by human microvascular endothelial cells was stimulated in the presence of 10 and 100 ng/ml of vascular endothelial growth factor (VEGF), 10 ng/ml basic fibroblast growth factor (bFGF) and 10 ng/ml of interleukin-8 (IL-8). Tube formation of the microvascular endothelial cells was assayed in the glioma cell lines IN157 and IN301, co-cultured using the double chamber method. IN301 cells had much higher levels of VEGF, bFGF and transforming growth factor-beta mRNA than IN157 cells, whereas the two had similar levels of transforming growth factor-alpha mRNA. By contrast, IN157 cells had much higher levels of IL-8 mRNA than IN301 cells. IN301-dependent tubular morphogenesis was inhibited by anti-VEGF or anti-bFGF antibody, and the inhibition was almost complete when anti-VEGF and anti-bFGF antibodies were present. On the other hand, IN157-dependent tubular morphogenesis was inhibited by anti-IL-8 antibody, but not by anti-VEGF or anti-bFGF antibodies. These findings demonstrated dual paracrine controls of tumor angiogenesis by human glioma cells. One is mediated through VEGF and/or bFGF, and the other, through IL-8.

Astrocytoma↗
PubMed1995

Sequence analysis of the germ-line VH gene corresponding to a nephritogenic antibody in MRL/lpr lupus mice.

In order to investigate the genetic origin of nephritogenic antibodies in MRL/Mp-lpr/lpr (MRL/lpr) lupus mice, we isolated the germ-line heavy chain variable region (VH) gene corresponding to the nephritogenic antibody, B1, derived from an unmanipulated MRL/lpr mouse. Injection of this antibody into C.B-17/Icr-scid/scid mice resulted in the generation of wire loop-like glomerular lesions resembling those of lupus nephritis. Nucleotide sequences of this germ-line VH gene showed no replacement mutation in the VH region of the B1 antibody. Furthermore, this gene was identical to that found in the C3H/HeJ-lpr/lpr strain of mice. Our results suggest that germ-line VH genes can encode nephritogenic antibodies without somatic mutation, even in a mouse strain not prone to lupus.

Animals↗
PubMed1995

Comparison of behavioural effects of repeated treatment with methamphetamine plus scopolamine and methamphetamine alone on behavioural sensitization and conditioned response.

We investigated how repeated treatments with methamphetamine (4.0 mg kg-1, i.p.) plus scopolamine (0.5 mg kg-1, i.p.) and methamphetamine alone effected behavioural sensitization and conditioned response in rats. Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of focused stereotyped behaviour than repeated methamphetamine treatment. Stereotyped behaviour induced by methamphetamine plus scopolamine was reproduced by challenge injections of methamphetamine plus scopolamine, methamphetamine, and to a lesser extent by scopolamine challenges. The methamphetamine plus scopolamine-sensitized rats were conditioned to a low frequency tone (300 Hz, 100 dB) associated with the drug state. They exhibited a conditioned response to pairings of the tone (conditioned stimulus) and placebo injections. However, they did not respond to the tone alone or the placebo injections alone. The methamphetamine-sensitized rats failed to demonstrate any conditioning; only the repeated methamphetamine plus scopolamine treatment induced sensitization to the drug-associated tone. Pairings of exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for conditioning to the tone associated with the drug state. We conclude that behavioural sensitization may operate via a reciprocal balance between the dopaminergic and cholinergic inhibitory systems, in favour of a dopaminergic dominance. Conditioning to the drug-associated tone may be mediated via a reciprocal balance between the two transmitter systems.

Animals↗
PubMed1995

Restriction endonuclease analysis of field isolates of feline herpesvirus type 1 and identification of heterogeneous regions.

The genomic heterogeneity of 78 isolates of feline herpesvirus type 1 (FHV-1) recently isolated from cats suspected to have feline viral rhinotracheitis was analyzed by examining the digestion patterns found with restriction endonuclease MluI. The FHV-1 field isolates were classified into at least three genotypes, namely, the C7301, F2 (an attenuated vaccine strain), and C7805 types. The C7301 type seems to be a major type, since 64 of the 78 isolates belonged to this type. Eight and six isolates belonged to the F2 and C7805 types, respectively. Compared with the C7301 type, the heterogeneous region of the F2 type was localized to a 4.3-kbp EcoRI fragment within the US segment and the heterogeneous region of the C7805 type was localized to a 5.5-kbp XbaI fragment within the UL segment. Northern (RNA) blot analysis revealed no differences in the products transcribed from these regions. In addition, nucleotide sequence analysis showed that the MluI sites not found in the F2 and C7805 types were located in the regions homologous to the herpes simplex virus type 1 gI and UL5 genes, respectively.

Animals↗
PubMed1995

Sodium hyaluronate eyedrops in the treatment of dry eyes.

BACKGROUND: Several studies in the past have attempted to demonstrate the efficacy of sodium hyaluronate in the treatment of dry eyes. However, results have been conflicting and a definite conclusion has not yet been reached. This study recruited a larger group of patients and has incorporated for the first time both fluorescein and rose bengal staining in the evaluation of the epithelium. METHODS: Eighteen albino rabbit corneas were used in a basic animal study to demonstrate the efficacy of sodium hyaluronate by comparing the effects on the rate of epithelial healing. The optimal concentration to be used in the clinical trial was determined from the results of the basic study. In the clinical study 104 patients with dry eye syndrome were enrolled in a double masked controlled clinical trial. Patients received sodium hyaluronate drops in one eye and control medication in the other eye for 4 weeks. Grading of subjective symptoms and clinical examinations were performed at 2 and 4 weeks. RESULTS: In the animal study sodium hyaluronate at concentrations of 0.1% and 0.5% significantly accelerated the recovery time of iodine vapour induced corneal erosions (p < 0.01). In the clinical study no statistical significance was observed in the improvement of subjective symptoms or rose bengal staining, while fluorescein scores significantly improved in eyes receiving sodium hyaluronate (p = 0.0001) at 4 weeks. CONCLUSION: Sodium hyaluronate drops applied in six daily doses could not be demonstrated to offer advantages over conventional tear supplies in the improvement of subjective symptoms, but may play a role in maintaining a healthy corneal epithelium.

Animals↗
PubMed1995

Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer.

The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL-1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta.

Animals↗