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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 271 records · Page 15Linked to original sources
PubMed1994

Expression of neurotrophin genes in the brain of senescence-accelerated mouse (SAM) during postnatal development.

We compared the expression patterns of neurotrophin genes in the brain of senescence-accelerated mouse (SAMP8) which shows age-related impairment of learning behavior, with SAMR1 control which shows normal aging. By Northern blot analysis, NT-3 mRNA levels in the cortex were higher in SAMP8 than in SAMR1 mice during development, whereas in the midbrain, hippocampus and forebrain, NT-3 expression levels in SAMP8 were lower than those in SAMR1. At early stages, although NGF mRNA levels in SAMP8 were lower than those in SAMR1, BDNF mRNA levels were almost equivalent in both strains. By in situ hybridization analysis, NT-3 mRNA signals in the CA1 and CA2 regions in SAMP8 were shown to be reduced at early stages. However, BDNF mRNA signals were almost equivalent in both SAMR1 and SAMP8.

Aging↗
PubMed1994

res2+, a new member of the cdc10+/SWI4 family, controls the 'start' of mitotic and meiotic cycles in fission yeast.

In the fission yeast Schizosaccharomyces pombe, the cdc10+ and res1+ genes play a crucial role in the start of mitotic and meiotic cycles. They encode structurally related transcriptional complex proteins and regulate some S phase-specific genes. Here we report the identification of a new member of this family named as res2+. res2+ has been isolated as a multicopy suppressor of a res1- null mutant and specifies a 73 kDa protein, which has two copies of the Swi/ankyrin motif and shares the highest sequence and structure similarity with the Res1 protein. res2+ is largely redundant in function with res1+ and is required for the initiation of mitotic and premeiotic DNA synthesis, but has an additional role in meiotic division. Unlike res1+, res2+ is highly induced during conjugation and strongly depends on cdc10+ for its activity. We conclude that the fission yeast contains two functionally overlapping parallel 'start' systems, Res1-Cdc10 and Res2-Cdc10, the former of which plays a major role in mitotic cycle whereas the latter in meiotic cycle.

Amino Acid Sequence↗
PubMed1994

Analysis of risk factors for post-transfusion graft-versus-host disease in Japan. Japanese Red Cross PT-GVHD Study Group.

We distributed a questionnaire to highlight the effects of post transfusion graft-versus-host disease (PT-GVHD) and to elucidate the risk factors that would predispose people to the disease. The questionnaire described the pathogenesis and the clinical profiles of PT-GVHD and was distributed to doctors in Japan whose hospital conducted more than 1000 units of blood transfusions a year. Doctors were asked about their awareness and experience of PT-GVHD cases. Those who had seen cases of PT-GVHD were then asked to detail clinical course and laboratory data. Of the 14,083 doctors who replied to the first question, 47.4% did not realise that PT-GVHD could occur in immunocompetent hosts. From 304 cases where detailed information was supplied, 171 were considered clinically compatible with PT-GVHD. From these it seems that the risk factors linked to PT-GVHD are cardiovascular surgery, cancer, fresh and consanguineous blood transfusion, and being male. Patients with any of these factors should have some prophylactic therapy such as irradiation of blood before transfusion.

Adolescent↗
PubMed1994

Activation of human neutrophils by Arg-Gly-Asp-Ser immobilized on microspheres.

The adhesive interaction of cells with extracellular matrix components is essential for a variety of cellular functions, and is frequently mediated by a tetra peptide, Arg-Gly-Asp-Ser (RGDS), located within fibronectin and other proteins. In this study, the RGDS-mediated activation of polymorphonuclear leukocytes accompanied by phagocytosis was investigated using monodisperse polymeric microspheres carrying RGDS. The parent and Arg-Gly-Glu-Ser (RGES)-carrying microspheres, which have no adhesion activity, were employed as controls. The ingestion of microspheres into PMN was not enhanced by immobilizing RGDS. However, PMNs exhibited unique oxygen consumption and enhanced liberation of reactive oxygen when RGDS-carrying microspheres were phagocytosed. These PMN responses disappeared with the addition of soluble RGDS. Furthermore, cytochalasin D, which inhibits actin polymerization, showed a marked inhibitory effect on oxygen consumption in the RGDS-carrying microsphere system, as compared with those in other systems. These findings show that RGDS-carrying microspheres induced the biospecific activation of PMNs by the signal transduction via RGDS-integrin binding without alteration in the degree of phagocytosis.

Amino Acid Sequence↗
PubMed1994

HLA and atopic dermatitis with high serum IgE levels.

Patients with atopic dermatitis usually exhibit allergen-specific IgE antibodies against several environmental antigens. HLA restriction is presumed to be involved in the recognition of such antigens, but several previous reports have so far failed to find a significant association between atopic dermatitis and HLA antigens. In this study we examined 38 unrelated Japanese patients with severe atopic dermatitis and high serum IgE levels (greater than 800 U/ml). We investigated the serological HLA types and HLA class II alleles in this group of patients with atopic dermatitis. Frequencies of HLA-A24, A33, Cwblank, B44, DR13 and HLA-DRB1*1302, DQB1*0604, DPB1*0301 alleles were increased in the patients. In contrast, frequencies of HLA-Cw1, Bw6, DR4, DR53, and HLA-DQB1*0302 allele were decreased. However, none of these remained significant after p values were corrected. Further study on HLA association with atopic dermatitis through characterization of specific antigens or antigen epitopes is needed.

Adolescent↗
PubMed1994

Influence of the structure of support microspheres on leucocyte activation by RGDS-carrying microspheres.

A cell adhesive peptide, Arg-Gly-Asp-Ser (RGDS), enhances leucocyte response to stimuli when insolubilized or conjugated with proteins. In order to investigate the contribution of the microsphere structure to leucocyte response. RGDS was immobilized onto several polymeric microspheres. The respiratory burst of polymorphonuclear leucocytes (PMNs) contacting contacting microspheres was enhanced by RGDS in cases where it was immobilized on polystyrene and, more effectively, a positively charged one. This was not observed in polyacrylamide-based or negative-charged microsphere systems. These results demonstrate that the property of supports strongly affects the regulation of the PMN response via an adhesive interaction.

Amino Acid Sequence↗
PubMed1994

Swine as an allotransplantation model.

Because of their anatomical and physiological similarities to humans, pigs are well suited for solving technical problems associated with clinical transplantation. The availability of genetically defined strains of miniature swine is unique with this species, and has permitted the investigation, in a large animal model, of immunological and genetic aspects of allograft rejection, clinical manifestations associated with bone marrow transplantation, and the feasibility of various approaches for induction of transplantation tolerance. Immunological assays and various reagents are also available in order to pursue these studies.

Animals↗
PubMed1994

Application of hematopoietic progenitor assays for the estimation of hematotoxicity in rats.

In a study to employ progenitor-derived clonogenic assays of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid colony-forming units (CFU-E) for the assessment of chemically induced hematotoxicity in rats, we sought the appropriate culture medium for each assay. Then, the effect of cyclophosphamide or phenylhydrazine on bone marrow cells was examined in vivo and in vitro. Oral treatment of rats with 25 mg/kg of cyclophosphamide significantly decreased the number of CFU-GM, which was an earlier and more sensitive index than were other hematological parameters tested. Direct exposure of the culture to cyclophosphamide had little effect on CFU-GM production, but addition of sera from rats pretreated with cyclophosphamide strongly depressed their formation, which suggested that the active metabolites of cyclophosphamide produced in the body may play an important role in toxicity. Subcutaneous injection of rats with 40 mg/kg of phenylhydrazine produced a marked increase in CFU-E 6-24 hr after injection. Direct exposure of the culture to phenylhydrazine had severe cytotoxic effects, but addition of sera from rats receiving phenylhydrazine resulted in increased numbers of CFU-E, probably indicative of increases in endogenous erythropoietin in donor rats. These results demonstrate that the proper use of progenitor assays in the in vivo and in vitro studies may be a valuable tool for approaching the mechanism underlying hematotoxicity.

Animals↗
PubMed1994

Isolation and characterization of a 53 kDa major cell envelope protein antigen from Treponema denticola ATCC 35405.

A major cell envelope protein was purified from the cell envelope fraction of Treponema denticola ATCC 35405 by ion exchange chromatography after extraction with Zwittergent 3-14. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a relative molecular mass of 53 kDa for this protein with a pI of 6.3-6.8. Amino acid analysis revealed that this protein contained high proportions of hydrophobic amino acids (40.4%), and no cysteine could be detected. The N-terminus of the protein was blocked to Edman degradation. Rabbit antiserum raised against the purified 53 kDa protein reacted with the outer envelope of the T. denticola cell surface as confirmed by immunoelectron microscopy. This rabbit antiserum reacted with 4 of the 11 strains of treponemes tested in this study. Sera from 9 to 18 periodontitis patients reacted strongly with this 53 kDa cell envelope protein of T. denticola as determined by immunoblotting analysis.

Amino Acids↗
PubMed1994

Effects of dihydropyridine Ca blockers on the renal function in nephrotic spontaneously hypertensive rat (SHR).

An animal model having both hypertension and reduced renal function was produced by intraperitoneal injection of puromycin aminonucleoside (PAN) in spontaneously hypertensive rat (SHR). Using this model, two different dihydropyridine Ca blockers, CS-905 and nicardipine, were compared with regard to the relationship between hypotensive effects and changes in renal function in a conscious state. A single oral administration of CS-905 or nicardipine at doses of 3 or 10 mg/kg produced a dose-dependent decrease in blood pressure and an increase in heart rate. Glomerular filtration rate (GFR) was decreased only at 10 mg/kg. However, there was a substantial difference between the two drugs with respect to the relationship between blood pressure and GFR. The decrease of GFR by nicardipine was observed when blood pressure was at the lowest level, while GFR decreased by CS-905 returned to the initial level when blood pressure reached a nadir. Percent decrease of GFR by CS-905 was significantly less than that by nicardipine although both agents produced almost the same degree of peak hypotension. These results suggest the decrease in GFR by Ca blockers depends not only on the degree of hypotension but other factors as well, such as the rate of blood pressure lowering. Despite the hypotension, both agents produced a marked natriuresis. Since the natriuresis was not accompanied by an increase in GFR, it was assumed that the natriuretic effect of Ca blockers stemmed from their tubular effects rather than glomerular ones.

Animals↗
PubMed1994

Role of cytokine in the induction of adhesion molecules on cultured human gingival fibroblasts.

This study was undertaken in an effort to understand the role of cytokines on human gingival fibroblasts and T lymphocyte trafficking into inflamed gingival tissue. Using flow cytometry we examined gingival fibroblasts to determine the level of cell surface expression and the percentage of cells positive for intercellular adhesion molecule 1 (ICAM-1), the HLA-DR antigen, lymphocyte function-associated antigen 3 (LFA-3), and the CD44 molecule, which are involved in antigen presentation. The following cytokines were used: interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8. The levels of ICAM-1 expression were enhanced in a dose- and time-dependent manner by IL-1 beta, TNF-alpha, or IFN-gamma, but not by IL-6 or IL-8. HLA-DR surface expression was induced only by IFN-gamma in a dose- and time-dependent manner, but not by the other cytokines tested. In contrast, the expression of LFA-3 and the CD44 molecule could be detected without the stimulation of any cytokine, but the levels of their expression were not significantly changed by any cytokines. The enhanced ICAM-1 expression by cytokines was reduced in a time-dependent manner following the removal of cytokines from the reaction mixture, while IFN-gamma-induced HLA-DR expression was maintained even 7 days after the removal of IFN-gamma. These data support an interactive role for inflammatory cytokines and the expression of adhesion molecules on gingival fibroblasts in the pathogenesis of gingival inflammation in periodontal disease.

Antigen-Presenting Cells↗
PubMed1994

Serum c-erbB-2 in breast cancer patients.

The c-erbB-2 oncogene product in serum (serum c-erbB-2) was measured by an enzyme-immunoassay kit. The 12 U/ml cut-off level was estimated as the mean plus two standard deviations for 250 healthy women. With this cut-off level increased serum c-erbB-2 was found in 12.0% of primary breast cancer cases (n = 25), in 4.9% of non-recurrent breast cancer patients (n = 82), and in 31.4% of patients with recurrent breast cancer (n = 35). In patients with primary and recurrent breast cancer, whose sera were assayed concurrently for serum c-erbB-2, CEA and CA15-3, the positive rates of these markers were fairly similar. However, their combined use significantly increased the sensitivity as compared to the use of any one marker alone.

Adult↗
PubMed1994

Suppressive effect of cyclophosphamide on the progression of lethal graft-versus-host disease in mice--a therapeutic model of fatal post-transfusion GVHD.

In this paper, we examine in a murine system whether cyclophosphamide (CY) could prevent the development of fatal GVHD and furthermore whether it could be used to treat on-going GVHD. (C57BL/6xDBA/2)F1 (BDF1) mice were injected with spleen cells from B6 donors and their thoraces were opened to mimic cardiac operation. These mice lost body weight gradually and most of them died during 2-4 weeks post-transfusion. They showed splenomegaly, thymic atrophy and marked bone-marrow aplasia. When CY was administered at 100 mg kg-1 on days 0, 2, 7 and 9, all mice were relieved of GVHD and their organs were almost free of signs of GVHD. CY (100 mg kg-1) administered on days 7 and 9 also save mice from lethal GVHD. Moreover, CY administered at a dose of 20 mg kg-1 on days 9 and 11 when GVHD became apparent was also effective. These data suggest that CY might be used as a therapeutic agent for lethal post-transfusion GVHD.

Animals↗
PubMed1994

[Experimental techniques for developing new drugs acting on dementia (8)--Characteristics of behavioral disorders in senescence-accelerated mouse (SAMP8): possible animal model for dementia].

Experimental methods to assess age-related behavioral disorders such as impairments of learning and memory, emotional disorder and abnormality of circadian rhythms in senescence-accelerated mice (SAMP8), and the characteristics of the behavioral disorders are described. SAMP8 shows age-related impairments of learning and memory assessed by passive avoidance, two-way active avoidance and Morris water maze tasks, and the impairments are significant even at 2 months of age and become obvious with aging. Age-related emotional disorder is also observed in SAMP8 mice. SAMP8 mice exhibit age-related emotional changes as compared with the SAMR1 control; they show apparent increases in the number of entries into open arms and time spent on open arms in the elevated plus-maze test. In addition, punished drinking in SAMP8 is markedly increased in the water-drinking conflict test. It is implicated that the reduced anxiety-like behavior is closely related to learning impairments in the strain. Cholinergic drugs and a sustained formulation of thyrotropin-releasing hormone ameliorate impairments of learning behavior and the emotional disorder in SAMP8. Furthermore, SAMP8 shows an age-dependent abnormality of circadian rhythms of spontaneous motor activity (SMA) and ingestive behavior compared with the SAMR1 control, diurnal SMA and water intake in SAMP8 being higher than those of SAMR1. These findings suggest that the SAMP8 strain is a useful animal model for learning and memory impairments, emotional disorder and abnormality of circadian rhythms in patients with dementia.

Aging↗
PubMed1994

[Effects of succinylcholine on neuromuscular transmission during recovery from vecuronium].

Effects of succinylcholine (SCC), 1 mg.kg-1, given following incomplete recovery from muscle paralysis induced by vecuronium were investigated in 27 female patients undergoing elective surgery, which was performed under epidural anesthesia. Anesthesia was induced with thiamylal 5 mg.kg-1 followed by SCC to facilitate orotracheal intubation. Vecuronium bromide 0.08 mg.kg-1 was given and the lungs were ventilated with 67% N2O in O2 and 0.6% sevoflurane. Neuromuscular function was monitored by means of the induced EMG. The ulnar nerve was stimulated at the wrist. Supramaximal trains of four stimuli (2 Hz for 2 s: pulse width 0.2 ms) were administered every 20 s. The effect of SCC varied depending upon the degree of recovery from vecuronium. At the 25% recovery point, the response to SCC was biphasic, showing an initial reversal followed by an increase of the partial vecuronium block which recovered showing a fade phenomenon on train-of-four stimulation. At the 50% recovery point, an initial reversal was slight. Administered at 75% recovery from vecuronium, SCC produced total neuromuscular blockade without initial recovery. The overall duration of the SCC effect (time from the administration to 90% recovery) was 7-18 min. No prolonged paralysis from SCC occurred.

Adult↗