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Biomedical subjects

K Nishijima

Publications and source records attributed to K Nishijima.

At least 73 records · Page 4Linked to original sources

Anti-IL-10 antibody enhances the proliferation of CD8+ T cell clones: autoregulatory role of murine IL-10 in CD8+ T cells.

All CD8+ T cell clones used in this study secreted IL-10, and their proliferation was inhibited by exogenous IL-10. This study addresses the question of whether IL-10 produced by responding T cell clones would inhibit proliferation of the secreting T cells themselves. Anti-IL-10 antibodies enhanced the proliferative response of the CD8+ T cell clones, the enhancing effect appearing in the late period of proliferation. However, the proliferation of both CD4+ Th1 and Th2 clones was not affected by anti-IL-10 throughout the culture. In addition to that of the cloned T cells, the proliferative response of a primary culture of CD8+ T cells was enhanced by the anti-IL-10 antibody. This is the first report on a lymphokine which has an autoregulatory role in inhibiting T cell proliferation.

Animals↗

Activation via TCR or IL-2 receptor of a CD8+ suppressor T cell clone: effect on IL-10 production and on proliferation of the suppressor T cell.

In a previous study, we established CD8+ suppressor T cell (Ts) clone 13G2 which produced the suppressive lymphokine, interleukin-10 (IL-10). In this study, we examined what physiological activator could induce both production of IL-10 from 13G2 and the proliferation of 13G2. Both the antigenic stimulation mimicked by the anti-CD3 antibody and the T cell growth factor interleukin-2 (IL-2) induced IL-10 production from the 13G2 clone equally well. 13G2 cells proliferated remarkably with IL-2 stimulation, while anti-CD3 only slightly induced proliferation of the clone. 13G2 cells also produced IL-10 in the presence of hydroxyurea which blocked transit of cells from G1 to S phase. However, cycloheximide blocked the production of IL-10 from the Ts clone. The study demonstrates that both the anti-CD3 antibody and IL-2 induced IL-10 synthesis of the Ts clone equally well, and the proliferative response of Ts cells was induced more by IL-2 than by anti-CD3. IL-2 proved to be a good stimulator for Ts cells to produce suppressive lymphokine and to multiply their population.

Animals↗

Immunohistochemical demonstration of tenascin and fibronectin in odontogenic tumours and human fetal tooth germs.

The distribution of tenascin and fibronectin (plasma fibronectin) was studied immunohistochemically in ameloblastomas, ameloblastic fibromas and ameloblastic carcinomas, as well as in tooth germs using monoclonal antibodies. Tenascin is an extracellular matrix molecule that was shown to be enriched in the embryonic mesenchyme surrounding the budding epithelium in various organs, including the tooth. Tenascin was strongly expressed in the basement membrane zone of the ameloblastomas and in the early tooth germ and the dental lamina, but not in the dental follicle. The expression of tenascin in the ameloblastic fibroma was seen in the basement membrane of the epithelial islands throughout the stromal tissues. There were clear differences in fibronectin expression in the follicular ameloblastoma and ameloblastic carcinoma. The results suggest that tenascin and fibronectin are involved in epithelial mesenchymal interactions of the tooth germ and in odontogenic tumours.

Ameloblastoma↗

Preferential stimulation of extracellular release of dopamine in rat frontal cortex to striatum following competitive inhibition of the N-methyl-D-aspartate receptor.

Using a brain microdialysis technique, we have shown in the rat that local infusion of a selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755), into the medial frontal cortex via dialysis tubing caused a concentration-related increase in the extracellular release of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the cortical region. Coinfusion of a sodium channel blocker, tetrodotoxin, completely inhibited the ability of the NMDA antagonist to augment frontal dopamine metabolism. These findings suggest that dopamine neurons projecting to the frontal cortex might be under a tonic transsynaptic inhibition exerted by excitatory amino acid neurotransmission via the NMDA receptor at the level of dopamine terminal fields.

3,4-Dihydroxyphenylacetic Acid↗

[A case of hepatoblastoma using intraarterial hepatic chemotherapy with THP-ADR].

The patient was a 2-year-old who was admitted with the diagnosis of liver tumor. The diagnosis at admission was stage III A hepatoblastoma complicated with tumor thrombosis of portal vein. Soon after the admission, the patient's general condition became deteriorated with increased ascites and severer jaundice. As the patient was considered to be in oncogenic emergency, chemotherapy with systemic administration of ADR and CDDP was started. Despite decreases in tumor marker and tumor shrinkage on imaging examinations, tachycardia and arrythmia occurred from the end of the second course of chemotherapy, suggesting ADR-induced cardiomyopathy, when the systemic administration of ADR was switched to less cardiotoxic hepatic arterial infusion of THP-ADR. Following 13 courses of intra-arterial infusion with the total dose of THP-ADR of 200 mg/m2, the tumor was found to have reduced markably in size and thus surgical resection of the tumor was performed. Our experience of this case indicates that, considering the pharmacokinetics and side effects, THP-ADR should be a very effective anti-tumor agent for intra-arterial hepatic infusion. The patient died 10 months after surgery because of multiple metastases into the brain and lungs.

Antibiotics, Antineoplastic↗

Loop and distal actions of a novel diuretic, M17055.

We investigated the mechanism of action of a novel 'high ceiling' diuretic, M17055, in in vivo clearance studies with anesthetized dogs during water diuresis and in vitro microperfusion studies of isolated rabbit renal tubules. In the clearance study, intravenous infusion of M17055 (1 mg/kg per h) decreased free water clearance and increased urinary excretion of Na+ and Cl- to a greater extent than did a maximum dose of furosemide (30 mg/kg per h). With the maximum dose of furosemide, an additional dose of M17055 or hydrochlorothiazide resulted in additional suppression of free water clearance. These results indicate that M17055 has some additional mechanisms of action in the distal nephron. In isolated rabbit cortical thick ascending limb of Henle's loop, M17055 applied to the lumen decreased the lumen positive transepithelial voltage at concentrations over 10(-6) M and suppressed the lumen-to-bath 36Cl- flux at 10(-5) M. In the connecting tubule, M17055 added to the lumen suppressed lumen negative transepithelial voltage in a concentration-dependent manner in a range from 10(-4) to 10(-3) M. The effect of M17055 on transepithelial voltage was also observed in the distal convoluted tubule and cortical collecting duct. Moreover, 10(-3) M of M17055 in the lumen significantly decreased the lumen-to-bath 22Na+ flux in the cortical collecting duct. From these observations, it appears that M17055 acts not only on the thick ascending limb of Henle's loop but also on the distal segments via inhibition of electrogenic Na+ transport.

Animals↗

Recommendation for an exercise prescription to prevent coronary heart disease.

Healthy male and female adults who visited the Japanese Red Cross Health Care Center were undertaken to the study of hematological examination, blood chemistry, electrocardiography and exercise loading test by bicycle ergometer. We attempted to evaluate the medical check up system for decision making of exercise prescription and useful exercise test to prevent coronary heart disease (CHD).

Adult↗

Cooperative activation of Chox-4 homeobox genes by factors from the polarizing region and the apical ridge in chick limb morphogenesis.

When a mouse zone of polarizing activity (ZPA) at the posterior margin of the limb bud was grafted at the anterior margin of the chick limb bud, we found that expression of the chick homeobox genes, Chox-4.7 and -4.8, was induced prior to the formation of chick extra digits. The induction was observed in the restricted domain close to both grafted mouse ZPA and the chick apical ectodermal ridge (AER). When the posterior half of the AER was removed, the normal expression was diminished in the posterodistal region. Thus, it is likely that at least two distinct factors, one from the ZPA and the other from the AER, provide positional information to induce cooperatively the sequential expression of the Chox-4 genes.

Animals↗

A novel quinolinone diuretic, M12285, and its activation mechanism through sulfate conjugation.

The diuretic activity of a quinolinone oxime diuretic, M12285, was examined after renal arterial, i.v. and portal injection in rats. M12285 injected into the renal artery at a dose of 1 mg/kg caused no diuretic effect, whereas i.v. and portal injections induced marked diuresis dose dependently. The minimum effective dose with portal injection was lower (1 mg/kg) than that with i.v. injection (3 mg/kg) and the start of the effect was faster with portal injection. These results indicated that some metabolic modification in the liver is necessary for the diuretic activity to appear. Accordingly, we performed in situ rat liver perfusion with M12285 and obtained several metabolites. Renal arterial injection of each fractionated metabolite of M12285 revealed that all the diuretic activity derived from one of these metabolites. From IR and 1H-nuclear magnetic resonance (1HNMR) measurements, the chemical structure of this active metabolite was assumed to be a sulfate-conjugated form of M12285 at the oxime moiety. Based on this tentative chemical structure, we synthesized the oxime sulfate of M12285 (potassium salt, M17000) and confirmed the identity of IR and 1HNMR spectra. Administration of M17000 into the renal artery induced apparent diuresis in a dose-dependent manner in both rats and dogs. These results indicate that the oxime sulfate of M12285 is responsible for the diuretic activity of M12285. Therefore, we synthesized several derivatives of M17000 and confirmed their possible therapeutic value as a novel family of diuretics, namely quinolinone oxime sulfonic acids.

Animals↗

An experimental study of the osteogenicity of free periosteal allografts with cyclosporine A administration.

Free tibial periosteum was grafted onto the dorsum (m. cutaneous trunci) of Sprague-Dawley rats to examine its osteogenic potential. The animals were divided into 3 groups based on type of: A. autogenous periosteum, B. allogeneic periosteum and C. allogeneic periosteum, and treated with cyclosporine A immunosuppression. The osteogenic response was evaluated radiologically and histologically. This study indicates that in this model periosteal allografts with immunosuppression of the recipient result in osteogenesis. Clinical application of the technique will only be possible if immunosuppressive methods with minimal morbidity are developed so that they can be used for prolonged periods.

Animals↗

Responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in multiple myeloma.

The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was investigated in vitro in 21 patients with multiple myeloma to assess the clinical usefulness of rh-Ep in this disease. CFU-E and BFU-E assays were performed by methylcellulose culture methods. The myeloma patients were divided into two groups according to the percentage of plasma cells in the bone marrow (over 50% and under 50%). Among the patients with few plasma cells, some revealed normal CFU-E and BFU-E growth at 2 units of rh-Ep, and no further increase was observed even with an increasing dose of rh-Ep. Among the other patients, more than half demonstrated a good response to rh-Ep. Among the patients with a high percentage of plasma cells, some revealed no response to rh-Ep, but there were patients with a high percentage of plasma cells in the bone marrow who had a good response to rh-Ep. High doses of rh-Ep may be clinically effective in some patients with multiple myeloma independently of the level of plasma cells in the bone marrow.

Aged↗

Strong influence of the processing of the antigen on negative effects on T cell activation by regions outside the determinant area of bovine alpha s1-casein.

alpha s1-Casein can elicit a proliferative response in responding T cell clone 3D20 cells (specific for I-Ab plus fragment 136-151), even when using fixed splenic antigen-presenting cells (APC) not carrying antigen processing ability. The order of potency of each tested antigen for fixed APC was the determinant peptide (136-151) > the long peptide (136-195) > the intact protein (199 residues), indicating that regions outside the determinant area negatively affected the stimulatory potency of the antigens. On the other hand, the order for normal splenic APC was the short peptide > the intact protein > the long peptide. This shows that negative effects by regions outside the determinant area were strongly influenced by the antigen processing.

Adjuvants, Immunologic↗

Pharmacological properties of the novel highly potent diuretic 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt.

7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt (M17055, CAS 114417-20-8) showed potent diuretic and saluretic effects dose-dependently, in rats (p.o.), mice (p.o.) and dogs (i.v.), at doses of 0.1-100 mg/kg, 0.3-100 mg/kg and 0.01-30 mg/kg, respectively. The efficacy of M17055 for diuresis, natriuresis and chloruresis was much higher than that of hydrochlorothiazide and almost the same as that of furosemide. These results indicate that this compound may be classified as a "high ceiling diuretic". The potencies of M17055 for natriuresis in rats (p.o.), mice (p.o.) and dogs (i.v.) calculated with ED50 values were 38, 34 and 24 times, respectively, more potent than those of furosemide. Urinary excretions of sodium, chloride and potassium increased in parallel with urinary volume with the administration of M17055 or furosemide, whereas an apparent dissociation with urinary calcium and sodium excretion was observed with M17055 alone. In rats, the increase of urinary calcium excretion with M17055 was significantly lower than that with furosemide under comparable conditions of natriuresis. Moreover, in mice, M17055 decreased urinary calcium excretion at doses with low effectiveness. In clearance studies using anesthetized dogs, M17055 suppressed negative free water clearance (CH2O) under saline loaded conditions, and it decreased positive CH2O under water diuretic conditions. These changes in the effects on CH2O induced by M17055 resemble those of loop diuretics. However, M17055 could not shift negative CH2O to positive, while furosemide was able to do so. Moreover, positive CH2O decreased to nearly zero with M17055, while urine remained dilute with furosemide even at 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[A case of pulmonary fibrosis in which inhibition of pulmonary vasoconstriction was detected using DSA pulmonary wedge angiography].

A 65-year-old man was admitted to our hospital complaining of productive cough and dyspnea on exertion. X-ray films and CT scan of the chest disclosed diffuse reticular shadows, especially in the bilateral lower lung fields. Blood gas analysis showed severe hypoxemia. Pulmonary function test disclosed severe restrictive pattern. From these findings, the patient was thought to have pulmonary fibrosis. Right heart catheterization showed pulmonary hypertension. To evaluate the pulmonary vascular bed, we performed DSA pulmonary wedge angiography. The pulmonary capillary phase stained homogeneously in normal subjects. However, in the present case, filling of the right pulmonary A9 was incomplete and capillary bed staining was decreased under room air condition. After breathing 5 L/min oxygen for 20 min., the A9 was filled well and capillary bed staining was increased. We consider that this change was induced by inhibition of hypoxic pulmonary vasoconstriction (HPV) by oxygen. DSA pulmonary wedge angiography was useful for visual evaluation of HPV.

Aged↗