Search PubMed⌕ Search

Biomedical subjects

T Fukuhara

Publications and source records attributed to T Fukuhara.

At least 91 records · Page 5Linked to original sources

Continuously applied compressive pressure induces bone resorption by a mechanism involving prostaglandin E2 synthesis.

In previous research, we devised a specific culture chamber to examine the effect of continuously applied compressive pressure (CCP) on bone formation and resorption. The chamber was infused with compressed mixed gases with different O2 and CO2 composition to maintain the pO2, pCO2, and pH in the culture medium under pressures of +0.5 atm (1.5 atm total) to +2.0 atm (3.0 atm total) at the same levels as those at the ordinary pressure (1 atm). Using the specific culture chamber, we demonstrated that CCP greatly suppressed the differentiation of mouse osteoblast-like MC3T3-E1 cells. The inhibition by CCP appeared to be mediated by prostaglandin E2 (PGE2). In the present study, we examined the effect of CCP on osteoclastic bone resorption. CCP treatment of mouse bone marrow culture markedly increased both the PGE2 production and the number of tartrate-resistant acid phosphatase (TRACP)-positive mononuclear cells (possibly precursors of multinucleated osteoclasts). An autoradiographic study using [125I]-salmon calcitonin showed clearly that those TRACP-positive cells had calcitonin receptors. The CCP effect was the greatest at +1.0 atm (2.0 atm total). Isobutylmethylxanthine potentiated the production of TRACP-positive cells induced by CCP. Adding indomethacin completely inhibited both the TRACP-positive cell formation and the PGE2 production induced by CCP. CCP also increased the release of 45Ca from prelabeled mouse calvaria during later stages (2-6 days) of the 6-day culture period. CCP markedly increased PGE2 but not interleukin 1 in the culture media of mouse calvaria. These results indicate that, besides inhibiting osteoblast differentiation, CCP stimulates bone resorption by generating new osteoclasts through a mechanism involving PGE2 production.

Acid Phosphatase↗

Permeability of small coronary arteries and myocardial injury in hypertensive diabetic rats.

Damage to the coronary artery and myocardium is known to be more marked when hypertension is complicated by diabetes than when either is present alone. The reason is not clear, but one possible factor is vascular permeability. Therefore, we investigated vascular permeability using sodium fluorescein of 70 mg/kg body weight, in 12-week-old streptozotocin-induced diabetic spontaneously hypertensive rats. Non-diabetic spontaneously hypertensive rats, diabetic rats with normal blood pressure, and non-diabetic rats with normal blood pressure of the same age were used as controls and treated similarly. H-E and Azan staining were used to examine vascular abnormality and mycoardial damage. The diabetic spontaneously hypertensive rats showed marked sodium fluorescein in the coronary artery wall and surrounding area, demonstrating greater vascular permeability than non-diabetic spontaneously hypertensive rats, diabetic and non-diabetic normotensive rats. Heart weights and diameters of myocytes were smaller in the diabetic than in the non-diabetic spontaneously hypertensive rats. Diabetic spontaneously hypertensive rats also exhibited marked perivascular fibrosis and focal necrosis. Thus, increased vascular permeability may play a role in vascular and myocardial changes in diabetic spontaneously hypertensive rats.

Animals↗

In vivo administration of cytokine in allogeneic bone marrow chimeras.

When we analyzed the in vivo efficacy of cytokine administration in murine allogeneic bone marrow chimeras, mitogen-induced responses to ConA, PHA, LPS, or PWM were increased by the in vivo administration of human recombinant granulocyte colony-stimulating factor (rG-CSF), human recombinant interleukin 2 (rIL-2), or WEHI-3B conditioned medium (CM). Furthermore, we found increased alloreactive mixed lymphocyte reactions (MLRs) against donor and/or host type alloantigens in spleen cells from (BALB/c----C3H/He) chimeras, although cytotoxic activity against BALB/c or C3H/He target cells was not detected in spleen cells from these chimeras. Since no significant increase of T cells or Ia positive cells was observed, some functional activation, rather than changes in the cell count, appeared to relate to increase immunoreactivity. An increased IL-2 production in spleen cells from chimeras injected with cytokine was observed shortly after the cessation of cytokine administration. Thereafter, an IL-2 production in these chimeras decreased around 45 days after bone marrow transplantation and then recovered nearly to the control level. An increased IL-2 responsiveness was also observed in spleen cells from these chimeras. These findings suggest that the in vivo administration of rG-CSF as well as rIL-2 or WEHI-3B CM (IL-3) can modulate the immunoreactivity in chimeras via the network of immune systems.

Animals↗

Electric fields stimulate DNA synthesis of mouse osteoblast-like cells (MC3T3-E1) by a mechanism involving calcium ions.

A cell culture system was designed to study the effect of an electric field on bone cells. This system subjected cultured bone cells to a series of high-voltage pulses at varying amplitudes of electric field without changing the ion concentrations of the culture medium. When mouse osteoblast-like cells (MC3T3-E1) were stimulated for 5 min to 20 hr by an electric field (3.19 kV/m, 3 msec, 10 Hz pulses), DNA synthesis was greatly increased. The stimulation occurred only during the growth phase. The electric field also increased incorporation of 45Ca into the cells, but it did not stimulate cAMP production. Adding calcium ionophore A23187 stimulated both 45Ca uptake and DNA synthesis, but dibutyryl cAMP did not stimulate either of them. These results suggest that the electric field stimulates the DNA synthesis of growing osteoblasts by a mechanism involving calcium ions.

Animals↗

Congestive heart failure associated with diabetes mellitus.

A case of typical congestive heart failure associated with diabetes mellitus is reported. The case was diagnosed on the basis of biopsy findings such as basal laminar thickness and of angiographically normal coronary arteries. The therapy, including insulin, resulted in normalization of electrocardiographic abnormalities and improvement of myocardial contractility.

Aged↗

[Allogeneic bone marrow transplantation after the treatment of alpha-IFN and high-dose SNMC in two cases of acute myeloblastic leukemia with post-transfusional non-A, non-B hepatitis].

Two patients of acute myeloblastic leukemia (M2) with post-transfusional hepatitis (non-A, non-B) were treated with alpha-IFN and high-dose SNMC before allogeneic bone marrow transplantation. Bone marrow transplantation from HLA identical and MLR negative sibling donor was carried out when their hepatic functions were almost normalized. In the early phase after bone marrow transplantation, the hepatic function in both two cases has been stable, thus indicating that this treatment should be tried for reducing hepatic dysfunction and for safety bone marrow transplantation.

Adult↗

[Polycythemia vera with an inhibitor against factor XII].

A case of polycythemia vera with an inhibitor against factor XII was reported. A 60-year-old female was admitted to Hokkaido University School Hospital because of erythrocytosis and hepatosplenomegaly. The hemoglobin was 22.5 g/dl and white cell count was 9,500/microliters without immature cells. The platelet count was 484,000/microliters. Bone marrow specimens showed marked hypercellularity. Philadelphia chromosome was not found on chromosome analysis. She was diagnosed as polycythemia vera according to the criteria of polycythemia Vera Study Group. Activity of factor XII was found to be decreased on the initial examination, but she had no personal and familial history of bleeding. In order to clarify the cause of decreased activity of factor XII, her plasma was mixed with normal plasma, and then examined PTT using factor XII deficient plasma. Her plasma mixed with equivalent normal plasma did not show the correction of prolonged PTT. It was suggested that an inhibitor of her plasma was included in the IgG fraction using gel chromatography. The patient was treated with phlebotomy and administration of N4-palmitoyl (1- -D-arabinofurasyl) cytosine (derivative of cytosine arabinoside; PLAC) 200 mg/day and Busulfan (1 mg/day). Factor XII was not corrected by phlebotomy, but corrected gradually by administration of PLAC and Busulfan.

Factor XII↗

[Hypertrophic cardiomyopathy--examination findings, family histories and results of close examinations of a family in two autopsied cases].

A 55-year-old woman, who died immediately after getting an intramuscular injection of lincomycin for treatment of a cold, and a 14-year-old boy, who died suddenly while practicing soccer, were autopsied respectively and their disease was diagnosed as hypertrophic cardiomyopathy by characteristic pathological findings. Each family history was investigated. Especially, the latter case showed clearly a family line of hypertrophic cardiomyopathy. At the request of the family, his elder brother and mother were examined closely at the University Hospital. Their illness was diagnosed accurately as hypertrophic cardiomyopathy from their findings of electrocardiograms, echocardiograms and endomyocardial biopsies. They are now taking medications and guidances of a doctor as to physical activity and way of life as outpatients at the University Hospital.

Adolescent↗

Clinicopharmacological studies of a newly synthesized cardiotonic agent (TA-064) in patients with congestive heart failure.

In animal experiments, a new inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenetyl)amino] ethanol, designated TA-064 was found to possess a more positive inotropic than chronotropic action. Its effectiveness and lack of significant toxicity make it beneficial for clinical use as a cardiotonic in human heart failure. The effects of TA-064 were investigated in patients with various types of heart disease (n = 29). Cardiac output increased, left ventricular end-systolic dimension decreased, and left ventricular fractional shortening increased for 15 minutes after a single intravenous dose (1 mg). The plasma level of TA-064 at the cessation of infusion was 61.1 +/- 49.6 ng/ml and thereafter declined biexponentially. After a single oral dose (10 mg), TA-064 appeared in the plasma at 30 minutes and reached its peak levels of 13.7 +/- 5.6 ng/ml at 60 minutes. Seven hours later, the plasma level was 5.9 +/- 3.1 ng/ml which was considered to be within the effective range according to the results after intravenous administration. In conclusion, minimal effective plasma levels of TA-064 are obtained by oral administration of 10 mg three times a day.

Administration, Oral↗

Myocarditis with multinucleated giant cells detected in biopsy specimens.

A 42-year-old woman was transferred to our hospital for evaluation of bradycardia with a complete atrioventricular block. Her pulse was 41 regular beats/min with blood pressure 166/92 mmHg. There were no skin lesions, edema, or lymphadenopathy. The white blood cell count was 6300/mm3. The serum glutamic oxaloacetic transaminase was 21 IU and creatine phosphokinase was 34 IU. C-reactive protein was negative. The level of serum angiotensin converting enzyme was slightly increased at 25.8 IU/l/37.0 degrees C (normal range: 7-24.0). Chest radiography showed congestive heart failure with a cardiothoracic ratio of 54%. There was no bilateral lymphadenopathy or fibrous changes during her clinical course. The coronary arteries were completely normal angiographically. Left ventriculograms revealed slight hypokinesis and dilatation (end-diastolic volume index of 112 ml/m2, ejection fraction of 53%). Left ventricular end-diastolic pressure was slightly abnormal at 16 mmHg. Two right and two left ventricular endomyocardial biopsies were performed. Right ventricular biopsy demonstrated edematous tissue and a slight mononuclear cell infiltration with little fibrosis. Left ventricular specimens showed an extensive area of fibrosis, with large, multinucleated giant cells with an asteroid body and chronic inflammation without epithelioid cells. The less affected areas of another specimen showed mild interstitial fibrosis and degenerative myocytes with vacuolation, and some multinucleated myocytes without an asteroid body were present. This case was diagnosed as cardiac sarcoidosis rather than idiopathic giant cell myocarditis. The patient has been implanted with a permanent pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Non-specific suppressor cells in murine bone marrow chimeras: their possible role in GVHD-associated immunodeficiency.

Suppressor cells against several mitogen-induced responses were detected in the spleen of murine bone marrow chimeras, regardless of intravenous (i.v.) or intrasplenic (i.s.) bone marrow transplantation (BMT). According to the time-course of the suppressor activity against Con A, PHA, and PWM, they were readily detected at 11-21 days after BMT and thereafter, either gradually decreased or remained at a plateau level. In contrast, the suppressor activity against the LPS-stimulated response increased at 39-52 days as compared to 24-34 days after BMT. Characterization studies of suppressor cells early (11-21 days) after BMT revealed that those in the i.v. and i.s. chimeras were composed of host-derived plastic dish adherent and/or anti-Thy 1.2 antibody-insensitive spleen cells in general. On the contrary, those in the i.v. and i.s. chimeras that possessed severer GVHD were mainly composed of host-derived plastic dish non-adherent spleen cells. Since the suppressor activity was higher in chimeras with severe graft-versus-host disease (GVHD) than in conventional chimeras, suppressor cells against the mitogen-induced responses may be related to the immunodeficiency associated with GVHD. Particularly, plastic dish non-adherent suppressor cells may closely relate to GVHD-associated immunodeficiency as compared with plastic dish adherent suppressor cells.

Animals↗

Suppressor activity in the supernatant of T cell clones derived from chimeric mouse spleen cells.

The supernatant from cultures of T cell clones derived from (BALB/c----C3H/He) chimeras suppresses BALB/c anti-C3H/He or BALB/c anti-C57BL/6 MLRs. When we studied the alloantigen specificity of the suppressor activity in culture supernatant, we observed three types of the suppressor activity (i.e., the suppressor activity against BALB/c anti-C3H/He MLR, against BALB/c anti-C57BL/6 MLR, and against both MLRs) on day 3 after stimulation of the T cell clones with 20% crude IL2 and feeder cells. Since the alloantigen specificity fluctuated somewhat with time, we considered that a time-course study was needed to determine it correctly. We thought it unlikely that any IFN-gamma or PGE2 in the culture supernatant of the T cell clones would have mediated the suppression. Our results suggest that alloantigen specific and non-specific suppressor T cells exist in bone marrow chimeras. The former appears to play an important role in inducing and maintaining transplantation tolerance, while the latter seems to have a rather harmful effect upon chimeras.

Animals↗