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Biomedical subjects

K Nonaka

Publications and source records attributed to K Nonaka.

At least 145 records · Page 8Linked to original sources

Inhibitory effect of FK506 on intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells.

The effect of FK506, an immunosuppressive agent, on phytohemagglutinin (PHA) or interferon gamma (IFN gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured human thyroid cells from patients with Graves' disease was investigated. Primary cultured thyroid cells were incubated for three days with IFN gamma (10 to 800 U/ml) or PHA (1 to 50 micrograms/ml) in the presence of FK506. The surface expression of ICAM-1 was measured by flow cytometry. In some experiments, polyclonal anti-IFN gamma antibody was added to the culture to determine whether ICAM-1 expression was blocked. FK506 inhibited the PHA-induced ICAM-1 expression in thyroid cells, but not the induction by IFN gamma. PHA-induced ICAM-1 expression was not inhibited by the polyclonal anti-IFN gamma antibody. FK506 did not affect the proliferation of thyroid cells. This data indicates that the inhibitory effect of FK506 on ICAM-1 expression in primary cultured thyroid cells may be due to actions on infiltrating lymphocytes in the thyroid gland. Further studies are necessary to elucidate whether the inhibition of ICAM-1 by FK506 results in the suppression of autoimmune reactions in the thyroid gland.

Cells, Cultured↗

[Surgical management of coronary artery fistula with tricuspid stenosis in a three-month-old infant].

This is a case report of a 3-month-old infant who had been suffering from progression of cardiac failure. Two dimensional echo-cardiography revealed a fistula between the right coronary artery to the right heart. He was operated upon using extracorporeal circulation. Symbas procedure was carried out to close the fistula. Upon opening the right atrium, there noted tricuspid stenosis (TS). Then, ASD was created to reduce the right atrial pressure to prevent right heart failure secondary to TS. He is doing well postoperatively.

Arteriovenous Fistula↗

Recent fertility decline in Dariusleut Hutterites: an extension of Eaton and Mayer's Hutterite fertility study.

A church book that has been routinely updated by the Dariusleut Hutterites enabled us to update some fertility tables presented by Eaton and Mayer in the 1950s. The age-specific (nuptial) fertility rates and the total fertility rates (TFRs) were calculated for every 5-year period from 1901-1905 to 1981-1985. Our calculations for Dariusleut, one of the three sects of the Hutterites, gave slightly lower age-specific nuptial fertility rates before 1951 compared with the figures given by Eaton and Mayer (1953) for all Hutterites in the corresponding time periods. The recent decline in Hutterite fertility, especially at higher maternal ages, was confirmed in this study. The TFR, given as a sum of 5-year-grouped age-specific nuptial fertility rates from 15 to 49 years of maternal age, was higher (8.80-9.83) in the years 1946-1965, but it declined to 8.13 in 1966-1970, to 7.22 in 1971-1975, to 6.39 in 1976-1980, and to 6.29 in 1981-1985. For the age groups 35-39 years and older the age-specific nuptial fertility rate in 1981-1985 decreased by more than 50% compared with the rate during the peak period of 1951-1955. The probability of a married woman having a live birth at each age from 15 to 49 years still peaked around the twentieth year of life, as found by Eaton and Mayer (1953), but it decreased more rapidly from the late twenties among the recently married women, most evidently in their thirties.

Adolescent↗

Trends in cohort fertility of the Dariusleut Hutterite population.

A church book containing vital information on Dariusleut Hutterite families enabled us to trace the life course of individual women. We conducted a retrospective cohort study on the women born in the Dariusleut sect for the period 1901-1965, focusing on their marriage and reproductive histories. The subjects were grouped into 5-year birth cohorts from 1901-1905 to 1961-1965. The marital age-specific fertility rate (MASFR) increased from the 1901-1905 cohort to the 1926-1930 cohort and then began to decrease, particularly at the ages of 30-39 years. The initial increase in MASFR was not reflected directly in the cohort mean of the total number of children per woman because of a concurrent delay in age at marriage. Marriage delay, however, could not explain the drastic decrease, which started in the 1931-35 cohort, in the total number of children per woman; the decrease in MASFR at the ages of 30 years and older was considered a major reason for the recent changes in Hutterite fertility. The causes of the recent fertility decrease of Hutterites at higher ages remain to be investigated.

Adult↗

[Mitral valve replacement and closure of atrial septal defect in the case associated with Marfan syndrome].

This is a case report of 8-years-old boy, who was diagnosed mitral regurgitation, secundum type of atrial septal defect and annulo-aortic ectasia in association with Marfan syndrome. His diagnosis was confirmed at the age of 6 years when cardiac catheterization was carried out. Atrial septal defect was closed using PTFE patch (0.2 mm in thickness). His diseased mitral valve was replaced with CarboMedics prosthesis 27 mm in diameter. Because of intact aortic valvular function, we left the ectatic aorta alone at present time for future procedure. His postoperative course was uneventful. He is active and doing well at present and has been followed-up at the outpatient clinic routinely. He might be having to require AVR and graft implantation for ectatic ascending aorta.

Child↗

[Acute erythroblastic leukemia presenting as FAB M6 with surface marker positive for megakaryocytic and erythroid: report of a case].

A fifty five-year-old male presenting as FAB M6 had blasts that were positive both for erythroblastic and megakaryocytic surface makers, i.e., carbonic anhydrase I, CD36 and CD41. HLA-DR and cD71 were also positive. In a very small portion, CD33 and glycophorin A were also positive. By Giemsa staining, these blasts were relatively large and had basophilic cytoplasm. By electroscopic study, PPO was negative and showed ferritin particles, theta granules and iron containing mitochondria in cytoplasm. Chromosome analysis revealed major karyotypic abnormality (MAKA). After initial treatment with blood transfusion, prednisolone and exymetholone, CD41b increased in positive ratio. Trial of remission induction with BHAC-DMP failed and patient died in 5 months.

Antigens, CD↗

Nitric oxide and nitric oxide synthase mRNA induction in mouse islet cells by interferon-gamma plus tumor necrosis factor-alpha.

It has been shown that nitric oxide (NO) is involved in islet cell damage induced by interleukin-1 (IL-1). Here we show that interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) synergistically induced NO production and inducible NO synthase (iNOS) mRNA expression in mouse islet cells. Cycloheximide (CXH) did not prevent the iNOS mRNA expressions. The combination of IFN-gamma and TNF-alpha, which is highly cytotoxic to mouse islet cells, failed to destruct islet cells in the absence of L-arginine or in the presence of NG-monomethyl-L-arginine (NMMA). These observations suggest that NO is a primary effector in islet cell damage caused by IFN-gamma plus TNF-alpha.

Amino Acid Oxidoreductases↗

Interleukin-1 induction of tumor necrosis factor-alpha mRNA and bioactive tumor necrosis factor-alpha in a pancreatic beta-cell line by a mechanism requiring no de novo protein synthesis.

Interleukin-1 (IL-1) has been implicated as an effector in insulitis of Type 1 (insulin-dependent) diabetes. Exposure of a beta-cell line (beta TC1) to IL-1 beta resulted in an increase of preproinsulin mRNA at 0.5 h followed by a gradual decrease. Tumor necrosis factor-alpha (TNF-alpha) mRNA expression by beta TC1 cells was demonstrated 1-3 h after the addition of IL-1 beta. TNF bioactivity was detected in homogenates of beta TC1 cells exposed to IL-1. The supplementation of cycloheximide (CHX) together with IL-1 beta resulted in the superinduction of TNF-alpha mRNA, suggesting that de novo protein synthesis is not required in IL-1-induced TNF-alpha mRNA expression. Endogenous TNF-alpha of beta-cells may be involved in the islet lesion of type 1 diabetes.

Actins↗

Low twinning rate and seasonal effects on twinning in a fertile population, the Hutterites.

This paper analyzes from the mid 18th century to 1987 the birth records of the "Dariusleut," one of the three subgroups of the Hutterite population. The aim of this study is to describe several aspects of the twinning rate in a fertile population. The overall rate of twinning was 0.90%: 103 twins among all 11,492 maternities. The rate peaked at the 7th birth order and at the maternal age of 40 years and over. Until the mid 19th century when the Hutterites lived in Russia, the twinning rate was higher (1.5%), and it decreased during the migration period in the second half of the 19th century (0.7%). After the group had settled in the USA and Canada, the population maintained a twinning rate of 1.0% until 1965. After 1965 the rate decreased to 0.7%, partly due to a decline in fertility among women aged 30 years and over. There was a significant seasonal variation: the twinning rate decreased to 0.5% in May-July compared to 1.2% for the other three seasons during the years up to 1965 (P < 0.01), while more recent mothers did not show such a seasonal variation. The incidence of twin births in this population seems to have been influenced by environmental factors, which would change their effect seasonally and secularly.

Adult↗

Intravenous methylprednisolone pulse therapy for Graves' ophthalmopathy.

To investigate the efficacy of intravenous methylprednisolone pulse therapy on Graves' ophthalmopathy (GO), fifteen patients with severe GO were treated with large dose intravenous methylprednisolone (at a daily dosage of 1 g for 3 successive days). This treatment was repeated 3-5 times for 3-5 weeks. They were monitored before, 2 weeks after and 6 months after therapy by ophthalmological assessment, orbital magnetic resonance imaging (MRI), and by measuring serum antibodies to rat eye muscle (EMAB) in an enzyme linked immunosorbent assay and peripheral blood lymphocyte subsets by flow cytometry. Diplopia and periorbital edema markedly improved after treatment in 9 patients. Mean proptosis values and intraocular pressure measurements significantly decreased after pulse therapy. In 12 patients enlarged eye muscles significantly reduced in size after treatment, as determined by MRI. The overall ophthalmopathy index was improved from 4.8 +/- 2.4 to 2.5 +/- 1.6 at the end of pulse therapy (P < 0.01) and 2.4 +/- 1.5 six months after therapy (P < 0.01). Serum EMAB were detected in 8 out of 10 patients tested and their level significantly decreased after pulse therapy (from 3.3 +/- 1.4 to 2.5 +/- 1.2, P < 0.01). A significant increase in peripheral blood CD4+CD45RA+ cells was observed after pulse therapy. Increased numbers of CD11-CD8+ cells and decreased numbers of CD11+CD8++ cells were found prior to treatment and were normalized after pulse therapy. Our study indicates that methylprednisolone pulse therapy can be considered as a choice for the treatment of GO. The improvement in eye muscle involvement in these patients may be due to the effects of infused methylprednisolone on both humoral and cellular immune functions.

Adult↗

Effects of free radical scavengers on cytokine actions on islet cells.

We investigated the effect of free radical scavengers on the actions of cytokines on islet cells. Interferon-gamma and tumor necrosis factor-alpha reduced the nicotinamide adenine dinucleotide content of mouse islet cells; the combination of interferon-gamma (4 x 10(5) U/l) and tumor necrosis factor-alpha (4 x 10(5) U/l) caused nicotinamide adenine dinucleotide reduction by approximately 40%. Dimethyl urea and dimethyl sulfoxide prevented the decrease, whereas superoxide dismutase, catalase, and mannitol were not effective. Dimethyl urea and dimethyl sulfoxide protected islet cells from the synergistic cytotoxic action of interferon-gamma and tumor necrosis factor-alpha. Major histocompatibility complex class II antigen induction by interferon-gamma and tumor necrosis factor-alpha was also inhibited by dimethyl urea and dimethyl sulfoxide, but not by superoxide dismutase, catalase and mannitol. Since superoxide dismutase of a membrane-penetrable form attenuated the class II antigen induction, the inefficiency of superoxide dismutase, catalase and mannitol may be attributable to their inability to penetrate islet cells. These results suggest that the intracellular generation of free oxygen radicals is involved in islet cell cytotoxicity and class II molecule expression by interferon-gamma and tumor necrosis factor-alpha, and that nicotinamide adenine dinucleotide reduction may be associated with islet cell dysfunction caused by the cytokines.

Animals↗

FK506 inhibits phytohemagglutinin-, but not interferon-gamma-, induced HLA-DR antigen expression and accessory cell function on primary cultured human thyroid cells.

We investigated the effects of FK506, a novel immunosuppressive agent, on the phytohemagglutinin (PHA) or interferon-gamma (IFN-gamma)-induced expression of HLA-DR antigen, accessory cell function and proliferation of primary cultured human thyroid cells. Primary cultured thyroid cells from patients with Graves' disease were incubated for 3 days with PHA in concentrations in the range 1-50 mg/l or with 200 kU/l of IFN-gamma, in the presence or absence of FK506. The surface expression of HLA-DR antigen was measured by flow cytometry. Accessory cell function of thyroid cells was assessed by the incorporation of [3H]thymidine to T cells in the presence of 0.1-1.0 micrograms/l staphylococcus enterotoxin B (SEB). The proliferation of thyroid cells was determined from [3H]thymidine incorporation assays. FK506 inhibited the induction of HLA-DR antigen expression by PHA on thyroid cells in a dose-dependent manner, but did not inhibit that by IFN-gamma. Polyclonal anti-IFN-gamma antibody partly inhibited the PHA-induced HLA-DR antigen expression on thyroid cells. Phytohemagglutinin enhanced the SEB-mediated accessory cell function of thyroid cells. FK506 inhibited the accessory cell function induced by PHA. FK506 alone did not directly affect the thyroid cell proliferation, although it ameliorated the thyroid cell growth suppressed by PHA. Our data suggest that FK506 suppresses the HLA-DR antigen expression induced by PHA and the subsequent accessory cell function on thyroid cells via the inhibition of T lymphocytes present in the primary culture.

Antigen-Presenting Cells↗

[The effect of four recipient strains on intra-uterine growth in mice--birth weight].

The embryo transfer technique is a very powerful tool for detecting intra-uterine effects of dams on prenatal growth of embryos. Embryos of DDD strain were transferred to a recipient of the same strain. Litter size, gestation period and birth weight of newborn offspring were measured. To examine the effect of embryo transfer on the prenatal growth of embryos, these results were compared with those of newborn DDD strain of mice that had developed from non-transferred embryos. Embryos of DDD strain were transferred to four strains of recipients (DDD/Qdj, C3H/Qdj, C57BL/Qdj and DBA/1J Sea). Litter size, gestation period and birth weight of newborn offspring were measured. The four strains of recipients were compared to examine the effect of recipient strain on the prenatal growth of the embryos. The results were as follows. 1. There was no gender difference in birth weight of offspring. 2. A negative correlation (partial regression coefficients: -0.024, P < 0.001 in the transfer and non-transfer groups, and -0.058, P < 0.001, in the four strains of recipients) was observed between litter size and birth weight of newborn offspring, while a positive correlation (partial regression coefficients: 0.068, P < 0.001 in the transfer and non-transfer groups, and 0.071, P < 0.001 in the four strains of recipients) was observed between gestation period and birth weight of newborn offspring. 3. Embryo transfer might affect the intra-uterine growth of transferred embryos. 4. The four different strains of recipients might contribute unequally to the prenatal growth of transferred embryos because of their different intra-uterine conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of the carbohydrate composition of a low-protein meal on the postprandial responses of plasma glucose and insulin in diabetic patients.

We determined whether, in 15 diabetic patients, a conventional low-protein diet containing a high proportion of mono- and disaccharides would lead to a deterioration of postprandial glucose metabolism. Three different test meals were given on 3 different days. We found that a high proportion of simple carbohydrates, when consumed as a low-protein meal, aggravated the postprandial hyperglycemia in diabetic patients. The substitution of complex carbohydrates for simple sugars in the meal suppressed postprandial hyperglycemia in diabetic patients.

Adult↗

Pancreatic beta-cell-selective production of tumor necrosis factor-alpha induced by interleukin-1.

Cytokines have been regarded as effector molecules responsible for beta-cell death and major histocompatibility complex hyperexpression in endocrine pancreas of type I diabetes. However, the mechanism that results in beta-cell-selective destruction has not been elucidated. We demonstrated in this study, using cell lines of transformed mouse beta-cells and alpha-cells, that only pancreatic beta-cells but not alpha-cells produced tumor necrosis factor-alpha when exposed to interleukin-1 beta. Northern blot analysis confirmed the beta-cell-selective expression of tumor necrosis factor-alpha mRNA. Interleukin-1 beta also provoked tumor necrosis factor-alpha mRNA expression in vitro by normal mouse islet cells. Because tumor necrosis factor-alpha has been shown to potentiate beta-cell cytotoxicity of interleukin-1 and interferon-gamma, tumor necrosis factor-alpha produced in situ by beta-cells might be self-destructive. In fact, a low dose of interleukin-1 beta in combination with a low dose of interferon-gamma preferentially injured beta-cells. Hence endogenous tumor necrosis factor-alpha production by beta-cells may be involved in beta-cell-selective destruction in type 1 diabetes.

Animals↗

Inhibitory effects of nicotinamide on intercellular adhesion molecule-1 expression on cultured human thyroid cells.

We investigated the effects of nicotinamide and 3-aminobenzamide (3-AB), inhibitors of poly (ADP ribose) synthetase, on phytohaemagglutinin (PHA)- or interferon-gamma (IFN-gamma)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured thyroid cells from patients with Graves' disease. Primary cultured thyroid cells were incubated for 3 days with IFN-gamma (10-800 U/ml) or PHA (1-50 micrograms/ml) in the presence of nicotinamide, 3-AB, superoxide dismutase or catalase. The surface expression of ICAM-1 was measured by flow cytometry. Nicotinamide and 3-AB dose-dependently inhibited the induction of ICAM-1 expression by IFN-gamma or PHA on thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of ICAM-1 on thyroid cells. Our data suggest that the mechanism of the suppression of ICAM-1 expression on thyroid cells by nicotinamide is not likely to be due to the free radical scavenging. Further studies are indicated to elucidate whether the inhibition of ICAM-1 by these drugs may result in the suppression of autoimmune reaction in the thyroid gland.

Antigens, CD↗