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Biomedical subjects

M Nagata

Publications and source records attributed to M Nagata.

At least 181 records · Page 10Linked to original sources

Surface expression and release of soluble forms of CD8 and CD23 in CD40- and IL-4-activated mononuclear cells from patients with Graves' disease (GD).

We investigated the effect of T cell-dependent B cell activation on the surface expression and release of the soluble forms of CD8 and CD23 by peripheral blood mononuclear cells (PBMC) obtained from patients with GD, versus patients with Hashimoto's thyroiditis, and normal controls. Incubating the PBMC with anti-CD40 MoAbs and IL-4 increased the soluble CD23 levels in cells from all three groups. An increase in the number of CD23+ cells was observed in the PBMC from the patients with GD, but not in PBMC from Hashimoto's thyroiditis or controls. Less soluble CD8 was released from anti-CD40 antibody and IL-4-stimulated PBMC obtained from patients with GD relative to those from the controls. In addition, the number of CD8+ cells was significantly reduced in stimulated PBMC from the GD patients relative to those from controls. Incubation of PBMC with anti-CD40 antibody plus IL-4 did not affect the proportions of CD4+, CD20+, Fas+ CD4+, and Fas+ CD8+ cells. The addition of T3 to cultured PBMC from controls did not reproduce the changes in CD23+ and CD8+ cells noted in the samples froin GD patients. Thus, T cell-dependent B cell activation, mediated by a CD40 pathway, may reduce the number of CD8+ cells, causing exacerbation of GD.

Adult↗

Effects of thyroid hormone on catecholamine and its metabolite concentrations in rat cardiac muscle and cerebral cortex.

Clinical and experimental data suggest that thyroid hormone affects the actions of catecholamine (CA). However, the serum or tissue levels of CA during thyroid disorders have not been well defined. Accordingly, we investigated the levels of CA and their metabolites in the cardiac muscle, the cerebral cortex, and the plasma of rats with hyperthyroidism and hypothyroidism versus euthyroid animals. The Neurochem analyzer system (ESA, Inc., Bedford, MA) was used in such determinations. The cardiac muscles of hyperthyroid rats exhibited a 16% decrease in the levels of 1-dopa, 3-methoxytyramine (3-MT) and homovanillic acid (HVA) as compared with those in euthyroid rats. The levels of norepinephrine (NE) in cardiac muscle of these rats increased significantly (5.2-fold) relative to the levels in euthyroid rats. NE was undetectable in the cardiac muscles of the hypothyroid rats. Epinephrine (E) and dopamine (DA) were not detected in the cardiac muscles of the rats with either thyroid disorder. Levels of E and 3,4-dihydroxymandelic acid (DOPEG) were detected only in the cerebral cortex of hyperthyroid rats. The cerebral cortex levels of 3-methyoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), metanephrine (MN), and homovanillic acid (HVA) were all significantly increased in the hyperthyroid versus the euthyroid rats. The cerebral cortex levels of DA, NE, normetanephrine (NMN), and VMA in the hyperthyroid rats all showed a significant decrease. Levels of NE, NMN, and DOPAC in the cerebral cortex increased significantly in the hypothyroid rats. The level of VMA was undetectable in cerebral cortex of such animals. Data from studies on cardiac muscle and cerebral cortex indicate that the changes in CA and CA metabolites are responsible in part for the cardiovascular and the central nervous system symptoms observed in hyperthyroidism and hypothyroidism.

Animals↗

Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders.

To clarify the different roles of free radical scavenging systems in various thyroid disorders, we measured the levels of alpha-, beta-, and gamma-tocopherols and coenzyme Q in the thyroid tissues of patients with thyroid tumors and Graves' disease using high-performance liquid chromatography. The levels of alpha-tocopherols and gamma-tocopherols in the thyroid tissue of patients with papillary carcinoma and the level of gamma-tocopherol in the thyroid tissue of patients with malignant lymphoma were elevated compared with those in normal thyroid tissues. The level of coenzyme Q was reduced in the thyroid tissue of patients with Graves' disease and follicular and papillary thyroid carcinomas. These findings imply that vitamin E and coenzyme Q as scavengers play some role in thyroid follicular cell hyperfunction or dysfunction.

Graves Disease↗

Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with propylthiouracil therapy.

A teenage girl with crescentic glomerulonephritis had antineutrophil cytoplasmic antibody (ANCA) detected after she had received propylthiouracil (PTU) for hyperthyroidism without cutaneous vasculitis. ANCA was detected on admission; renal biopsy showed crescentic glomerulonephritis with focal necrotizing glomerulonephritis but no immune deposits. Administration of steroid and decreasing the dose of PTU produced a good clinical response and the ANCA disappeared. It was concluded that ANCA is closely related to the pathogenesis of crescentic glomerulonephritis and that treatment with PTU appeared to induce ANCA.

Adolescent↗

Oral tolerance is not influenced by oral application of oil-emulsified proteins.

A 2-week program of feeding protein antigens as an oil-in-water emulsion to naive mice elicited a significant serum IgG antibody response, whereas their aqueous preparations did not at all. The unresponsive immune state that had been developed after feeding aqueous antigen was not disturbed by subsequent oral challenge with the same antigen in the presence of oil. These results suggest that the principle of oral tolerance is a feasible strategy for prophylaxis of hypersensitization to protein antigens, where protein tolerogens, in this case, are to be given without any additives at their first introduction.

Administration, Oral↗

Effect of immunotherapy on the production of eosinophil adhesion-inducing activity from mononuclear cells in house-dust-mite-sensitive bronchial asthma.

An initial step of eosinophil (EOS) accumulation in the sites of allergic inflammation is the adhesion to endothelial cells. There is increasing evidence that immunotherapy (IT) modulates the production of cytokines from mononuclear cells and hence attenuates allergic inflammation. To examine whether IT modifies the production of factor(s) which induce EOS adhesion, peripheral blood mononuclear cells (PBMC) from house-dust-mite-sensitive asthmatics treated with or without IT were cultured for 96 h in the presence or absence of 1/microg/ml Dermatophagoides farinae antigen. EOS were isolated from the peripheral blood of healthy subjects. EOS adhesion-inducing activity (EAIA) in the PBMC culture supernatants was examined by the ability to modify EOS adhesion to paraformaldehyde-fixed human umbilical vein endothelial cells (HUVEC) which were stimulated with IL-4 plus TNF-alpha. In asthmatics without IT, the addition of D. farinae antigen significantly promoted the production of EAIA from PBMC (EOS adhesion: 22.4+/-13.1% by medium control vs. 30.5+/-18.9% by D. farinae, n=10, p=0.023). This enhancing effect was blocked by an anti-beta2-integrin antibody. In contrast, the addition of D. farinae did not modulate EAIA production from PBMC in asthmatics treated with IT (23.1+/-10.3% vs. 21.5+/-12.3%, n=10, p=NS). These results suggest that IT induces the inhibition of antigen-dependent production of EAIA from PBMC. This may contribute to the inhibitory effect of IT on eosinophil recruitment in allergic inflammation.

Animals↗

Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1 activation of eosinophil function.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.

Adult↗

Immunohistochemical diagnosis of a Merkel cell tumor in a dog.

We examined the clinical and immunohistochemical features of a Merkel (neuroendocrine) cell tumor on the skin between the eyes of a 12-year-old male Yorkshire Terrier dog. The tumor was characterized by locally expansive dermal nodules composed of solid nests or clusters of epithelioid cells surrounded by fine fibrous stroma. Basal cell epithelioma, Merkel cell tumor, and extramedullary plasmacytoma were also considered as diagnoses. Because the cytoplasm of the tumor cells stained positively for cytokeratin and chromogranin A but not for immunoglobulins, the tumor was diagnosed as a Merkel cell tumor. An electron-microscopic study of a tissue specimen revealed electron-dense granules approximately 200 nm in diameter. These granules were irregularly dispersed throughout the cytoplasm of the tumor cells, which would be expected in neuroendocrine cells. Twelve months after resection, a 0.8-cm-diameter tumor recurred at the original site. However, further follow-up of 22 months revealed no evidence of additional tumor growth, invasion, or metastasis, so we concluded that this tumor was benign.

Animals↗

Determination of urinary and serum pentosidine and its application to elder patients.

Pentosidine, a fluorescent cross-linking compound, accumulates in extracellular matrix, especially in the collagen, and is formed by the nonenzymatic process of advanced Maillard reaction. We developed a method of determination of pentosidine and tried to examine its level in urine and serum of elder patients. The method, which involves the hydrolysis of samples, pretreatment using a CF-11 cellulose column and HPLC quantification, resulted in a high recovery (94.3%) of pentosidine with low coefficient of variation (8-10%) of total analysis. Serum and urinary levels of pentosidine in control subjects gradually increased with age. Elder patients with cerebral infarction showed higher levels of serum and urinary pentosidine as compared with those with senile dementia and other geriatric disorders. These results suggest that serious damage to systemic vascular tissues has already occurred in these patients due to glycation.

Adult↗

The correlation between coronary stenosis index and flow-mediated dilation of the brachial artery.

We examined the relationship between flow-mediated dilation (FMD) of the brachial artery and the extent and severity of coronary artery disease (CAD). Using high-resolution ultrasonography, we measured FMD and nitroglycerin-induced brachial artery dilation. We studied 121 patients (77 men, 44 women; mean age 64+/-11 years, range 25-79 years) who underwent coronary arteriography. The extent and severity of CAD were assessed by the coronary stenosis index (CSI). The adjusted FMD correlated inversely with CSI (rs=-0.63, p<0.0001). Multivariate analysis demonstrated that the adjusted FMD was an independent predictor of CSI. The adjusted FMD was 10.2+/-4.8% in patients without CAD (n=32), 7.7+/-6.0% in patients with single-vessel disease (n=31), 5.2+/-5.5% in patients with double-vessel disease (n=29), and 2.0+/-3.9% in patients with triple-vessel disease (n=29). The adjusted FMD was significantly lower in the double- (p<0.01) and triple-vessel (p<0.0001) disease groups than in patients without CAD. The adjusted FMD was significantly lower in the triple-vessel disease group than in the single-vessel disease group (p<0.001). Based on our results, as coronary atherosclerosis becomes more severe, the adjusted brachial artery FMD becomes more severely impaired.

Adult↗

Suppressive effects of antihistaminic and/or anti-PAF agents on passive anaphylactic shock in mice sensitized with allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum.

For the immunopharmacological characterization of murine passive anaphylactic shock, the effects of antihistaminics and/or anti-platelet-activating factor (anti-PAF) agents were studied on the shock mediated by allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum. IgE antibody-mediated shock was strongly suppressed by cyproheptadine (10 mg/kg, ip) in every strain regardless of the age and sex of the mice and the presence or absence of a shock potentiator. As far as tested with CTS, DS, and B6D2F1 mice, IgE antibody-mediated shock was also suppressed by the other two antihistamines, triprolidine (10 mg/kg, ip) and oxatomide (100 mg/kg, po). This type of shock was not suppressed by an anti-PAF agent, CV-6209 (3.3 mg/kg, iv), when tested on aged CTS mice given no shock potentiator and young DS mice given a potentiator such as Bordetella pertussis organisms or DL-propranolol. IgG1 antibody-mediated shock was also suppressed by cyproheptadine in general except for CTS mice. Suppression in the DL-propranolol-treated DS and C3H/He mice was not very marked on sensitization with undiluted or slightly diluted IgG1 ascites but quite striking on sensitization with properly diluted ascites. In contrast with the effect of cyproheptadine, suppression by CV-6209 was obvious in aged CTS mice but not in young DL-propranolol-treated DS mice. The shock in DL-propranolol-treated DS mice sensitized with undiluted or slightly diluted ascites was completely abolished by the combined use of these two agents. These results suggest that histamine and/or PAF play a major role in IgE antibody- and IgG1 antibody-mediated shock. However, so far as tested in young DS mice, the shock mediated by hyperimmune serum differed in drug susceptibility from that mediated by the monoclonal antibodies. In the absence of shock potentiators, prevention was produced by cyproheptadine in the males which had been sensitized with the 1:4 or 1:8 dilution of the immune serum. In the presence of DL-propranolol, prevention was not produced even by the combined treatment with cyproheptadine and CV-6209. Therefore, it is likely that some mediators other than histamine and PAF, whose release is triggered by antibody isotypes other than IgE and IgG1, play a greater role for the shock mediated by hyperimmune serum than for the shock mediated by IgE or IgG1 antibody, especially in the presence of shock potentiators.

Anaphylaxis↗

Recurrent malignant proliferating trichilemmal tumour: local management with ethanol injection.

We report a 59-year-old woman who exhibited a recurrent malignant proliferating trichilemmal tumour on the scalp for 1 5 years. The tumour was recalcitrant to conventional treatments such as chemotherapy, radiation or hyperthermia and we performed intratumoral ethanol injection as an alternative means of reducing tumour mass and obtaining haemostasis. Biopsy specimens obtained after the ethanol injection revealed oedema, haemorrhage in the dermis and degeneration of the tumour cells, showing vacuolization with pyknotic nuclei. For cases of recurrent skin tumours and for patients in poor clinical condition, intratumoral ethanol injection is likely to be a therapeutic alternative to surgery or other conventional treatments.

Anemia↗

[A qualitative analytical method for nonpermitted food colors by HPLC].

The Ministry of Health and Welfare has been proposed an analytical method for food colors by HPLC. Conditions in the method and modified conditions of the proposed method were applied for permitted and nonpermitted food colors, and relative retention times were obtained. The relative retention times would be a clue of the confirmation of these nonpermitted colors by other method.

Chromatography, High Pressure Liquid↗

[A clinical evaluation of clustered immunotherapy in house-dust-mite-sensitive adult bronchial asthma].

Clustered immunotherapy (C-IT) using house-dust (HD) antigen was performed in eight HD-mite-sensitive adult bronchial asthmatics. Six mg of mequitazine was given 2 hours before each visit. For each visit, injections of antigen were performed four times with an hour interval. Either 0.1 ml of 10-fold concentration of the HD or a final dose at the end of the fifth week was determined as a maintenance dose. All cases have reached to ten-fold concentration of the HD antigen within 5 weeks and been able to introduce maintenance therapy without any systemic reaction. Following C-IT, a rapid increase in morning peak expiratory flow rate was observed which is followed by decrease in clinical scores. Furthermore, an increase in mite-specific IgG4 antibody and a decrease in peripheral blood eosinophils were observed 16 weeks following C-IT. These results suggest that C-IT using HD antigen can be performed safely and securely and provides rapid immunological responses as well as clinical benefit in HD-mite-sensitive adult asthmatics.

Adolescent↗

Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells.

By means of the differential display method, we isolated a novel human gene that is expressed specifically in pancreas. The cDNA, designated "pancpin," contained an open reading frame of 1,215 nucleotides encoding a 405 amino acid protein, showing a high degree of similarity to serine protease inhibitors belonging to the serpin superfamily. To investigate its possible role in pancreatic carcinogenesis, we looked for genetic alterations of this gene in pancreatic cancer cell lines and primary pancreatic cancer tissues. Expression of pancpin was barely detectable in any of the four pancreatic cancer cell lines examined, and very weak also in 10 of 13 pancreatic cancer tissues. A somatic missense mutation at codon 221 was found in two of 16 primary pancreatic cancers. These findings indicate that down-regulation of pancpin expression may play a significant role in development or progression of pancreatic cancer.

Amino Acid Sequence↗