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Biomedical subjects

F Kurimoto

Publications and source records attributed to F Kurimoto.

At least 37 records · Page 2Linked to original sources

Cord-blood-derived human cultured mast cells produce interleukin 13 in the presence of stem cell factor.

BACKGROUND: Mast cells have been regarded as a potential source of cytokines. Although the human mast cell line HMC-1 and human lung mast cells have been shown to produce interleukin (IL) 13, it still remains uncertain whether cord-blood-derived human cultured mast cells produce IL-13. METHODS: Human cultured mast cells were raised from cord blood cells in the presence of stem cell factor (SCF) and IL-6. Levels of IL-13 mRNA were examined by a semiquantitative reverse transcriptase-polymerase chain reaction. IL-13 levels in the supernatants were measured with an enzyme-linked immunosorbent assay. RESULTS: When the IgE-sensitized cultured mast cells were activated with anti-IgE, mRNA for IL-13 was amplified with a peak at 3 h after the stimulation. IL-13 was not detected in the supernatants of the activated mast cells in the absence of SCF, whereas the mast cells secreted significant amounts of IL-13 after the stimulation in the presence of SCF. Calcium ionophore A23187 also stimulated the mast cells to release IL-13 into the supernatant in the presence of SCF. CONCLUSIONS: These observations suggest that human mast cells can produce IL-13 under the condition with SCF. The cord-blood-derived human cultured mast cells will help in studying the functional properties of human mast cells in allergic diseases.

Calcimycin↗

Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in patients with anorexia nervosa.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. To study the role of TNF-alpha on the pathophysiology of anorexia nervosa and its complications, plasma concentrations of TNF-alpha, 2 soluble TNF receptors (sTNF-RI and sTNF-RII), and leptin were measured in 20 female patients with anorexia nervosa (AN) and 20 age-matched normal women (N). Plasma TNF-alpha concentrations in AN were significantly higher than those in N (4.1 +/- 0.6 pg/mL vs. 1.6 +/- 0.1 pg/mL; P < 0.01). Although no significant difference was observed in plasma sTNF-RI concentrations between the two groups, plasma sTNF-RII concentrations in AN were significantly higher than those in N (2094.0 +/- 138.5 pg/mL vs. 1569.5 +/- 84.0 pg/mL; P < 0.01). Plasma concentrations of TNF-alpha and sTNF-RII after treatment of 8 anorectic patients were not different from those before treatment, although body fat mass and plasma leptin concentrations significantly increased after treatment. Plasma TNF-alpha concentrations were not related to body fat mass in anorectic patients. These results suggest that the adipose tissue may not be the immediate source of TNF-alpha in anorectic patients and that TNF-alpha may contribute to the pathophysiology of immunological and metabolic abnormalities in anorexia nervosa.

Adult↗

Combination of automatic HPLC-RIA method for determination of estrone and estradiol in serum.

We developed a highly sensitive assay for estrone and 17 beta-estradiol in serum. Estrone and 17 beta-estradiol, obtained by solid-phase extraction using a Sep pak tC18 cartridge, were purified by high-performance liquid chromatography (HPLC). Quantitation of estrone and 17 beta-estradiol were carried out by radioimmunoassay. Not insignificantly, this automatic system of extraction and HPLC succeeded in analyzing 80 samples a week. Intra-assay coefficients of variation (CV) for estrone and 17 beta-estradiol ranged from 19.5 to 28.7%, and from 8.5 to 13.7%, respectively. The minimum detectable dose for estrone and 17 beta-estradiol were 1.04 pg/ml and 0.64 pg/ml, respectively. The serum levels of 17 beta-estradiol using our method strongly correlated with those by Gas chromatography mass spectrometry (GC-MS). The serum levels of estrone and 17 beta-estradiol in 154 peri- and postmenopausal women were estimated to be between 15 and 27 pg/ml and between 3.5 and 24.0 pg/ml, respectively, while the serum level of 17 beta-estradiol in postmenopausal women, in particular, was estimated to be from 3.5 to 6.3 pg/ml. For postmenopausal women who suffered from vasomotor symptoms, the mean levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with daily 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) were 135.0 and 21.3 pg/ml at 12 months, respectively. On the other hand, levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with CEE and MPA every other day, were 73.4 and 15.3 pg/ml, respectively. These highly sensitive assays for estrone and 17 beta-estradiol are useful in measuring low levels of estrogen in postmenopausal women, and monitoring estrogen levels in women receiving CEE as hormone replacement therapy.

Adult↗

Contribution of the T cell receptor BJ gene to recognition of the P91A tumor antigen in DBA/2 mice.

To understand specific immune responses against a tumor, it is important to characterize T cells that recognize the tumor antigen. The mouse P91A antigen is one of the well-defined tumor antigens that is expressed on the P911 cell line, and T cells responding to the antigen in DBA/2 mice were reported to be restricted to BV8S2/S3 families in their T cell receptor (TCR) BV gene usage. We have further characterized the P91A-responding T cells in DBA/2 mice, focusing on TCR BJ gene usage and using the polymerase chain reaction/enzyme-linked immunosorbent assay and DNA sequencing studies of their third complementarity-determining (CDR3) regions. As a result, T cells with cytotoxic activity to the P91A antigen, induced from murine spleen cells both in vivo and in vitro, showed predominant use of the BJ2S1 gene segment in both BV8S2 and BV8S3 T cells compared to unmanipulated murine spleen cells. Sequencing studies of the CDR3 regions in the BV8S3 T cells revealed clonal expansion of T cells with the BV8S3-BJ2S1 combination in two of three DBA/2 mice tested. In the remaining mouse, clonal expansion was not detected despite predominant use of the BJ2S1 segment by these T cells. These data suggest that P91A-recognizing T cells would predominantly use the BV8S2/S3-BJ2S1 combination. Analysis of T cells with these TCR BV-BJ gene combinations may contribute to the evaluation, monitoring and development of a T-cell-mediated immunotherapeutic strategy.

Animals↗

Insulin-like growth factors - insulin-like growth factor binding protein axis and diabetic control in insulin-dependent diabetes mellitus.

There is some evidence that insulin-like growth factors (IGFs) and/or IGF binding proteins (IGFBPs) (IGF-IGFBP axis) may be involved in glucose metabolism. The purpose of this study was to investigate the relationship between the IGF-IGFBP axis and diabetic control in subjects with insulin-dependent diabetes mellitus (IDDM). Thirty-nine subjects with IDDM without major complications (age: 5.8-30.3 years, 13 males and 26 females) participated in this study. In all subjects, the free form of IGF-I (free IGF-I), the total IGF-I (total IGF-I: free plus complexed form of IGF-I) and IGFBP-3 in serum or plasma were measured. The Z-scores of free IGF-I, total IGF-I, and IGFBP-3 were calculated. In 18 young adults with IDDM (age 18.0-30.3 years, 5 males and 13 females), IGFBP-1 in serum was also measured. In all subjects, the diabetic control parameters such as blood glucose (BS) (momentary control), 1,5-anhydro-D-glucitol (1,5 AG) (Ultrashort-term), fructosamine (short term), and glycosylated hemoglobin (HbA1) (long-term) were measured. None of the Z scores for free IGF-I, total IGF-I or IGFBP-3 had a significant correlation with BS. In young adults, IGFBP-I was correlated with BS (r=0.57, P<0.005). None of the Z scores for free IGF-I, total IGF-I or IGFBP-3 had a significant correlation with 1,5 AG, fructosamine or HbA1. In young adults, IGFBP-1 did not correlate with 1,5 AG, fructosamine or HbA1. These data suggested that the IGF-IGFBP axis did not reflect diabetic control in subjects with IDDM under treatment.

Adolescent↗

Plasma level of basic fibroblast growth factor increases with progression of chronic liver disease.

Basic fibroblast growth factor (FGF) is thought to be involved in carcinogenesis and, to clarify its clinical significance, the study of its blood level in cancer patients is important. Plasma levels of basic FGF are reported to be elevated in some cancers. However, little is known of basic FGF levels in plasma in hepatocellular carcinoma (HCC). In this study, we measured basic FGF plasma levels in patients with chronic liver disease and compared the levels in chronic hepatitis (CH), liver cirrhosis (LC), and HCC. We also examined whether these levels were related to serum levels of asparate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, total bilirubin, total protein, and albumin, and to the indocyanine green test (i.e., liver function tests) and to type III procollagen. 7S domain of IV type collagen, and hyaluronic acid (i.e., markers of liver fibrosis). Levels of basic FGF, determined by a quantitative "sandwich" enzyme immunoassay, were significantly elevated with the progression of liver disease; being 3.67 +/- 2.37 (mean +/- SD). 7.78 +/- 6.61, and 12.37 +/- 7.67 pg/ml in the CH, LC, and HCC groups, respectively. FGF levels were elevated to a greater extent in the HCC patients than in the CH (P < 0.0001) and LC patients (P = 0.0117). Levels were higher in LC than in CH (P = 0.0204). None of the liver function test findings or levels of markers of liver fibrosis were correlated with levels of basic FGF. These results suggest that circulating basic FGF could serve as a new indicator of the progression of chronic liver disease. The extremely elevated plasma of level basic FGF in the HCC group suggests that basic FGF may be related to the development of HCC.

Biomarkers↗

Heterogeneity of mast cells in mastocytosis and inhibitory effect of ketotifen and ranitidine on indolent systemic mastocytosis.

BACKGROUND: Mastocytosis is a disorder of mast cell proliferation that occurs in both cutaneous and systemic forms. The most frequent site is the skin. OBJECTIVE: The mast cell subtype of two patients with mastocytosis was investigated. METHODS: Immunohistochemical studies were performed on the skin or gastric mucosa or both of the two patients. Blood and urine levels of various mediators were measured for one patient. RESULTS: Mast cells containing tryptase and chymase were the only type seen in the skin lesions of an 11-month-old boy with urticaria pigmentosa. Mast cells containing tryptase were predominant in lesions of the skin and gastric mucosa of a 41-year-old man with indolent systemic mastocytosis. However, mast cells containing tryptase and chymase were predominant in the nonlesional and the normal skin of this patient. Tryptase-positive cells were more numerous in lesional skin than nonlesional skin and normal skin. Elevated blood and urine levels of various mediators were decreased by means of combination therapy with ketotifen and ranitidine. CONCLUSION: In indolent systemic mastocytosis, mast cell dynamics involve only cells containing tryptase. Release of mediators from mast cells may be inhibited by means of combination therapy with histamine H1 and H2 receptor antagonists.

Adult↗

Elevation of the plasma level of RANTES during asthma attacks.

BACKGROUND: RANTES is considered to play an important role in various immune and allergic disorders since it is a potent chemoattractant for inflammatory cells such as eosinophils, memory T cells, and monocytes. OBJECTIVE: To investigate the possible role of RANTES in the pathogenesis of bronchial asthma. METHODS: The plasma level of RANTES was measured in 12 asthma patients and 15 normal controls by a sandwich enzyme-linked immunosorbent assay. RESULTS: In the patients with asthma, the plasma RANTES level was significantly elevated during acute attacks compared to that in the controls. In addition, it was higher than that during the asymptomatic state in the same patients. Plasma beta-thromboglobulin levels were also elevated in asthma patients during acute attacks and showed a correlation with the RANTES level. CONCLUSION: These findings suggest a role for RANTES in the pathogenesis of asthma and a possible role for platelets in RANTES release in asthma.

Adult↗

Gelatin-specific humoral and cellular immune responses in children with immediate- and nonimmediate-type reactions to live measles, mumps, rubella, and varicella vaccines.

BACKGROUND: This study was designed to investigate the development of both cellular and humoral immune responses to gelatin in patients with vaccine-related immediate and nonimmediate reactions. Our purpose was to define the nature of the responses in the different clinical states. METHODS: Six patients with immediate reactions and 21 patients with nonimmediate reactions after inoculation of various live vaccines were studied. Measurement of gelatin-specific IgE was performed in all subjects. Gelatin-specific T-cell responses detected by an in vitro lymphocyte proliferation assay and by an assay for IL-2 responsiveness were investigated to compare the immune response in patients with the two types of reaction. RESULTS: All six patients with immediate reactions had IgE responses to gelatin, whereas none of the 21 patients with nonimmediate reactions had any anti-gelatin IgE. All of the six patients with immediate reactions and 17 of the 21 patients with nonimmediate reactions exhibited positive T-lymphocyte responses specific to gelatin. CONCLUSIONS: Immediate and nonimmediate reactions are caused by different types of allergy to gelatin, and cell-mediated immunity to gelatin may play an important role in the pathogenesis of nonimmediate reactions.

Antibodies, Viral↗

Sulfidoleukotriene release test (CAST) in hypersensitivity to nonsteroidal anti-inflammatory drugs.

There is a great need to develop a method for making an accurate and reliable in vitro diagnosis of adverse hypersensitivity reactions to drugs. We measured the amount of sulfidoleukotriene (sLT) released from the peripheral blood leukocytes obtained from 25 patients who developed hypersensitivity reactions following the administration of nonsteroidal anti-inflammatory drugs (NSAIDs); 12 patients demonstrated reactions to Voltaren, 8 patients to Bufferin, and 5 patients to Sedes G. The stimulation index, the ratio of the amounts of sLT (pg/ml) incubated with and without drugs, was considerably higher in the patients than in the controls, which consisted of 5 nonallergic healthy subjects. The sensitivity of the CAST (cellular antigen stimulation test) was evaluated to range from 62.5 to 80%, while the specificity was 70-100%. The CAST may thus be useful as a novel in vitro test system in order to screen for possible hypersensitive reactions to NSAIDs with both reliability and safety.

Adult↗

Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer.

In human endometrium insulin-like growth factor binding protein (IGFBP)-1 inhibits the mitogenic action of insulin-like growth factor (IGF)-I by inhibiting the binding of IGF-I to its receptor. Our purpose was to compare circulating levels of IGF-I and IGFBP-1 in women with and without endometrial cancer. We assessed circulating levels of IGF-I and IGFBP-1 and IGFBP-3 in 23 patients with endometrial cancer, 11 patients with uterine cervical cancer and 27 healthy control women. The mean circulating level of IGF-I decreased significantly following menopause but was not correlated with age in the control group. The body mass index was significantly higher in the endometrial cancer group than in the control group. Analysis of covariance showed that even after the data were adjusted to eliminate the influence of the body mass index, the circulating IGF-I concentration was higher in postmenopausal endometrial cancer patients than in postmenopausal control subjects. The mean circulating level of IGFBP-1 was significantly lower in postmenopausal cancer patients than in postmenopausal control subjects. There were no significant differences in the serum levels of IGF-I and IGFBP-1 in the patients with cervical cancer and the control group. In conclusion, an increased circulating concentration of IGF-I and a decreased circulating concentration of IGFBP-1 are associated with endometrial cancer especially in postmenopausal women.

Adult↗

Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women.

The present study was performed to examine the effect of natural menopause on serum levels of IGF-I, IGF-binding protein (IGFBP)-2 and -3 as well as on bone mass and lipid metabolism in perimenopausal women. One hundred and twenty-one healthy Japanese women, who were 45-55 years old, were studied (71 premenopausal and 50 postmenopausal women 1-9 years after menopause). Bone mineral density (BMD) was measured at the middle third of the radius by using dual energy X-ray absorptiometry. Serum levels of IGF-I, but not those of IGFBP-2 or -3, were significantly reduced in the postmenopausal group compared with the premenopausal group. One year after menopause, serum IGF-I levels were significantly lower, and the biochemical markers of bone turnover, such as serum total alkaline phosphatase level and urinary calcium to creatinine ratio, were significantly higher than the premenopausal levels. Serum levels of IGF-I, but not those of IGFBP-2 or -3, were positively correlated with BMD. Serum levels of IGFBP-2, but not those of IGF-I or IGFBP-3, were negatively correlated with body mass index and body weight. Finally, serum levels of IGFBP-3, but not those of IGF-I, were positively correlated with serum levels of total cholesterol and triglyceride. The present findings suggest that a rapid decrease in serum IGF-I levels after menopause might be partly involved in bone loss following gonadal failure and that IGFBP-2 and -3 might be related to the regulation of body mass and lipid metabolism during perimenopause respectively, although the mechanisms remain unknown.

Bone Density↗

[Determination of intratumoral estrone (E1) and estradiol (E2) in primary breast cancer tissues by sensitive HPLC-RIA].

The alternation of intratumoral estrogen metabolism has been indicated in breast cancer tissues. We determined the intratumoral concentrations of estrone (E1) and estradiol (E2) by a sensitive HPLC-radioimmunoassay (RIA) and analyzed its clinical significance in 74 primary breast cancer tissues. The average intratumoral concentrations of E1 were 48.6 + 7.3 pg/g w.w and 80.6 + 43.2 pg/g w.w in pre- and post-menopausal patients, respectively. The E2 concentrations were 168.7 + 36.8 pg/g w.w and 104.7 + 23.6 pg/g in pre- and post-menopausal patients, respectively. The background analysis demonstrated that intratumoral E2 levels were significantly higher in estrogen receptor (ER) positive tumors compared to ER negative tumors (p < 0.01). A significant correlation was also found between intratumoral E2 concentrations and progesterone receptor (PgR) status, indicating that E2 synthesis is frequently upregulated in hormone dependent tumors. These findings are important for studying the hormonal microcircumstances of Japanese breast cancer patients and also for considering the indication for clinical treatment using aromatase inhibitors.

Adult↗

[Lymphocytic interstitial pneumonia associated with Sjögren's syndrome and mediastinal lymphadenopathy: diagnosis by open-lung biopsy].

A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sjögren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.

Biopsy↗

Effects of interferon-gamma on cell differentiation and cytokine production of a human monoblast cell line, U937.

The U937 cell, a human monoblast cell line, has been used as a model to study the function of human monocytes. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production, cell surface antigens, and cytokine production of U937 cells. IFN-gamma treatment enhanced O2- production of fMLP or PMA-stimulated U937 cells. IFN-gamma increased the ratio of CD23 and CD11b positive cells. The fluorescence intensity of CD14 and CD25 was enhanced by IFN-gamma treatment. U937 cells produced IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha by lipopolysaccharide (LPS) stimulation. IFN-gamma treatment enhanced TNF-alpha production, but decreased IL-6 production. These results suggest that IFN-gamma differentiates U937 cells to monocyte-like cells and it regulates the production systems of IL-6 and TNF-alpha separately in U937 cells.

Antigens↗

Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes.

Although evidence indicates that dehydroepiandrosterone (DHEA) exerts direct physiological effects, its mechanism of action remains unknown. DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line, PEER, revealing that a single class of high-affinity binding sites for DHEA (dissociation constant = 7.4 +/- 0.53 nmol/L, mean +/- SE, n = 4) was greatly increased when treated with DHEA, phorbol-12-myristate-13-acetate, and the Ca2+ ionophore A23187. Bound [3H]DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone, but not effectively by other steroids, including DHEA sulfate. These results not only indicate the existence of a DHEA receptor, but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation.

Binding Sites↗