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Biomedical subjects

H Fukazawa

Publications and source records attributed to H Fukazawa.

At least 145 records · Page 8Linked to original sources
PubMed1985

A novel tumor-associated molecular species of 5'-nucleotide phosphodiesterase.

5'-Nucleotide phosphodiesterase (5'-NPDase) was partially purified from plasma membranes of murine lymphoma L5178Y. The enzyme was inactivated by N-ethylmaleimide and Zn2+, but stabilized by dithiothreitol, suggesting that it is an SH enzyme. The enzyme, Km 1.54 mM, pI 5.8 and MW 23k, differs from liver 5'-NPDase in MW, Km and sensitivity to some inhibitors. On the contrary, 5'-NPDase, derived from normal mouse organs, is similar to the liver enzyme. The results suggest that tumor cells possess a novel molecular species of 5'-NPDase.

Animals↗
PubMed1985

[The relationship between serum IAP and peripheral K cells in patients with subacute thyroiditis].

In a previous study, we showed that the percentage of peripheral K cells of patients with subacute thyroiditis (SAT), determined by a plaque-forming cell technique, was significantly lower than that of normal controls, and that ther sera from SAT significantly inhibited the activity of K cells in normal lymphocytes, suggesting that in the sera of SAT there is some factor which inhibits K cell activity. In this study, we investigated the relationship between K cells and the serum immunosuppressive acidic protein (IAP), the sex difference in percentage of K cells, and the absolute count of K cells in patients with SAT. In normal controls, there was a sex difference in the percentage of K cells in total lymphocytes; the percentage was significantly lower in women (mean +/- S.D., 5.0 +/- 2.0%; n = 12; p less than 0.01) than in men (8.4 +/- 2.9%; n = 20). However, there was no sex difference in the absolute count of peripheral K cells. In the acute phase of SAT, the percentages of K cells wee 2.4 +/- 1.8%; 2.4 +/- 1.9% and 2.7 +/- 1.0% in 19 patients, 16 females and 3 males, respectively, which were significantly lower than 6.8 +/- 3.0%, 5.0 +/- 2.0% and 8.4 +/- 2.9% in 25 controls, 12 females and 13 males, respectively. The absolute counts of K cells in the acute phase of SAT were 56 +/- 45/mm3 and 58 +/- 48/mm3 in 13 patients including 11 females, respectively, which were significantly lower than 165 +/- 63/mm3 and 153 +/- 73/mm3 in 12 patients including 5 female controls, respectively. It was observed that serum IAP values in SAT were correlated negatively with the percentage of K cells and positively with the inhibition rate of SAT sera on K cells from normal subjects. Moreover, purified IAP showed a dose-related inhibition on the K cells from the control subjects. These results suggest that IAP in the sera of SAT seems to be one of the factors which inhibits the activity of K cells.

Adult↗
PubMed1985

[An epidemiological study of subacute thyroiditis in northern Japan].

It is difficult to study subacute thyroiditis epidemiologically since it occurs sporadically and infrequently. Information about 1,127 cases (108 males, 1,019 females, from 1967 to 1982) of subacute thyroiditis in northern Japan was obtained through a questionnaire. It was found that the usual age for the disease was forty, that females predominated in a ratio of 10.6:1, and that the prevalent month was July. In clinical features, the frequencies of the inflammatory symptoms were high in the acute phase of the disease, and the frequencies of hyperthyroid symptoms increased with the progress of the disease. According to the course of the disease (days after the onset without treatment), the patients were divided into seven subgroups, such as 1 approximately 7 days, 8 approximately 14 days, 15 approximately 21 days, 22 approximately 28 days, 29 approximately 42 days, 43 approximately 56 days and over 57 days, respectively. Compared with the 1 approximately 7 days group, the erythrocyte sedimentation rate, serum T4 and T3 concentrations in the 15 approximately 21 days group showed a significant increase from 64 +/- 35 to 75 +/- 30 mm/h (p less than 0.001), 14.6 +/- 5.5 to 17.6 +/- 5.6 micrograms/100 ml (p less than 0.001) and 218 +/- 124 to 263 +/- 109 ng/100 ml (p less than 0.05), respectively, but the BMR showed as insignificant increase from 20 +/- 15 to 24 +/- 14%. The 24-hr 131I-thyroid uptake and resin sponge uptake (RSU) in the 21 approximately 28 days group were 1.2 +/- 1.5% and 35.1 +/- 6.7%, respectively; the former was significantly lower (p less than 0.02) and the latter was insignificantly higher than the values (2.0 +/- 2.6% and 33.9 +/- 7.9%, respectively) in the 1 approximately 7 days group. The recovery time in the steroid-treated group was 57.2 +/- 47.6 days, which showed a statistically insignificant difference from 64.8 +/- 50.5 days of the sodium salicylate-treated group. But the recovery time of 78.2 +/- 64.9 days in other anti-inflammatory drug-treated groups was significantly longer than that of the steroid and sodium salicylate-treated groups (p less than 0.001 and p less than 0.05). Among 9 viral diseases, such as measles, varicella, erythema infection, hand-foot and mouth disease, rubella, mumps, influenza, epidemic keratoconjunctivitis and acute hemorrhagic conjunctivitis observed in northern Japan and Miyagi prefecture in the past 4 years, mumps, hand-foot and mouth disease and epidemic keratoconjunctivitis were prevalent in summer.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1985

Human placental thyroxine inner ring monodeiodinase in complicated pregnancy.

Production of rT3 from T4 in the placenta were measured in four patients with induced abortion, in three patients with spontaneous abortion, in 19 patients with various complications of pregnancy including Graves' disease, and in 18 normal pregnancies. The placentas, obtained at delivery, were homogenized and centrifuged at 800 X g. Supernatants (1 mg protein) were incubated with 1 microgram of stable T4 and 50 mmol/L dithiothreitol at 37 degrees C for 60 minutes. The generated rT3 was measured by radioimmunoassay (RIA). In patients who delivered at 38 to 41 weeks with complicated pregnancy, the net placental rT3 production from T4 was 7.3 +/- 2.5 ng/tube, which was not significantly different from that obtained in normal pregnancy (8.5 +/- 2.4) at an equivalent gestational age. In patients with abortions, the net placental rT3 generation from T4 was very high, and there was a significant negative correlation between the net placental rT3 production from T4 and gestational age. These results indicate that the net placental rT3 production from T4 is not affected by complications of pregnancy, but shows a significant change with the progress of gestation.

Abortion, Induced↗
PubMed1985

Determination of free triiodothyronine in serum: comparison of radioimmunoassay with equilibrium dialysis method.

In normal volunteers, serum free triiodothyronine (FT3) concentrations determined by Immophase FT3 RIA kit, Amerlex FT3 RIA kit and equilibrium dialysis methods (absolute FT3, AFT3: product of total T3 and percent FT3) were 4.03 +/- 0.65, 3.69 +/- 0.58 and 3.22 +/- 0.65 pg/ml (mean +/- S.D.), respectively. The normal free triiodothyronine index (FT3I) was 38.4 +/- 6.5. In patients with hyper-and hypothyroidism, the FT3 values measured by these methods were clearly abnormal. In patients with decreased thyroxine binding-globulin, the mean FT3 concentrations determined by these methods were not significantly different from the normal. However, the mean FT3I was significantly lower than normal. In pregnant women at delivery, Amerlex FT3 values were subnormal in 7 of 9 subjects. All of these samples except one were within the normal range when evaluated by Immophase FT3 and AFT3, although their mean values were significantly lower than the mean of normal. On the other hand, the mean FT3I was not significantly different from the mean of normal. The correlations between FT3 were all statistically significant. In a clinically euthyroid patient who had chronic thyroiditis and who was shown to have anti-T3 antibody in her serum, Immophase FT3 and Amerlex FT3 values were above the high standards. However, AFT3, calculated by multiplying total T3 (determined after ethanol extraction) by percent FT3 was normal. In conclusion, the evaluation of FT3 by these radioimmunoassay methods proved clinically useful, when appropriate limitations are considered.

Dialysis↗
PubMed1985

Effect of carteolol, indenolol and metoprolol on the thyroid hormone of hyperthyroid patients.

Thirty-four hyperthyroid patients were divided into four groups: placebo, carteolol (20 mg/day), indenolol (60 mg/day) and metoprolol (120 mg/day) groups. The heart rate was determined before and two weeks after the treatment with each drug. Serum levels of T4, T3 and rT3 were measured before, and one and two weeks after the treatment. Both indenolol and metoprolol significantly reduced the heart rate (p less than 0.01 and p less than 0.05, respectively), whereas carteolol was ineffective. Carteolol significantly decreased T4 from 23.4 +/- 4.4 micrograms/100 ml to 20.1 +/- 3.2 micrograms/100 ml (p less than 0.01) in one week and to 20.0 +/- 3.7 micrograms/100 ml (p less than 0.01) in two weeks. T3 and rT3 were also decreased significantly (p less than 0.05 and p less than 0.01, respectively) two weeks after the treatment with carteolol. After two weeks of indenolol treatment, T4 was decreased significantly from 26.2 +/- 8.5 micrograms/100 ml to 23.9 +/- 8.2 micrograms/100 ml (p less than 0.05) and T3 from 789 +/- 391 ng/100 ml to 592 +/- 340 ng/100 ml (p less than 0.02). Metoprolol had no effect on serum thyroid hormone levels. The decrease in the serum level of thyroid hormones by carteolol and indenolol but not by metoprolol in patients with hyperthyroidism would be due to the blockade of beta 2-adrenoreceptors concerning with thyroid hormone secretion.

Adrenergic beta-Antagonists↗
PubMed1985

Studies on antineoplastic activity of naphthomycin, a naphthalenic ansamycin, and its mode of action.

An antibiotic, identical with naphthomycin, was isolated from a soil Streptomyces. The antibiotic displayed significant therapeutic activity by ip administration against murine tumors: Ehrlich carcinoma and IMC carcinoma implanted ip. The maximum increase of life-span was more than 169% in Ehrlich carcinoma, and 128% in IMC carcinoma. The antibiotic exhibited a potent cytotoxicity against murine leukemic cells: P388, L1210, and L5178Y. IC50 was 0.4-1.3 microgram/ml in culture. The activity of naphthomycin was reversed by SH compounds: 2-mercaptoethanol, dithiothreitol, and glutathione. DNA and RNA syntheses were more markedly inhibited by naphthomycin than protein synthesis in L5178Y cells. Approximately 50% inhibition of nucleic acid syntheses was observed at an antibiotic concentration of 2 micrograms/ml. Naphthomycin blocked alkaline phosphodiesterase obtained from L5178Y cells: IC50 was ca. 7.6 micrograms/ml. The antibiotic neither caused metaphase arrest nor prevented tubulin polymerization. The results suggest that the mechanism of cytotoxicity of naphthomycin is the inhibition of various SH enzymes, particularly those involved in nucleic acid biosynthesis. The mode of action is unique in the ansamycin group of antibiotics.

Animals↗
PubMed1984

[Changes in antimicrosomal antibody, serum thyroglobulin and thyrotropin binding inhibitor immunoglobulin in a patient with silent thyroiditis who experienced four thyrotoxic episodes].

Serial changes of thyroid hormones, TSH, anti-thyroidal antibodies, serum Tg and TBII were studied in a patient with silent thyroiditis who experienced four episodes of transient thyrotoxicosis in a follow-up period of five years. The titers of MCHA were high in the thyrotoxic episodes and further increased in the following hypothyroid phases. In the euthyroid phase it became lower. The serum level of Tg was normal or moderated elevated in the thyrotoxic episodes, and it further elevated in the hypothyroid phase. Surgical biopsy, performed in the euthyroid phase about one year after the forth thyrotoxic episode, revealed the findings of Hashimoto's disease. Two different types of transient thyrotoxic episode, one with positive TBII and high uptake and the other with negative TBII and low uptake, were observed in the same patient with silent thyroiditis. In the beginning of the clinical course, the patient showed positive TBII, high 131I-uptake (77%) in the second episode of thyrotoxicosis, no response of TSH to TRH administration and absence of T3-suppressibility. The value of TBII gradually became normal and was negative at the forth episode of thyrotoxicosis when 131I-uptake was low (1.3%). After this last episode, TSH response to TRH administration was normal in euthyroid phase and augmented in hypothyroid phase. The presence of transient positive TBII and of histological changes of Hashimoto's disease was suggestive of the close relationship between Graves' and Hashimoto's diseases.

Antibodies↗
PubMed1984

[Peripheral K lymphocytes in patients with subacute thyroiditis].

In a previous study, we showed that immunosuppressive acidic protein (IAP) was markedly increased in the acute phase in patients with subacute thyroiditis (SAT). In order to investigate the immunological abnormalities in SAT, peripheral K lymphocytes in SAT and hyperthyroidism were measured by the plaque-forming technique using sheep-red-blood cells as a target. The effect of the patients' serum on K-cells in normal lymphocytes was also investigated. The percentages of K-cells in 5 patients with SAT in the acute and recovery phases were 2.3 +/- 1.9 (mean +/- S.D.) and 5.3 +/- 2.2%, respectively. The former was significantly lower than the latter (p less than 0.05). Furthermore, the value in the acute phase showed a significant decrease against that of the normal controls (7.3 +/- 3.4, n = 14, p less than 0.01). The percentage of K-cells in 16 patients with hyperthyroidism was 2.8 +/- 2.2%, which was also significantly lower than that of the normal controls (p less than 0.05). The degree of inhibition of K-cells in normal lymphocytes by sera from 12 SAT in the acute and recovery phases was 69 +/- 21% and 35 +/- 22%, respectively, which was significantly higher (p less than 0.01 and p less than 0.05, respectively) than that in 12 normal sera (15 +/- 20%). Furthermore, the inhibition was markedly higher in the acute phase than in the recovery (p less than 0.01). The sera from 10 patients with hyperthyroidism also inhibited K-cells of normal lymphocytes (p less than 0.01). It was suggested that in the sera of SAT and hyperthyroidism there is some factor which inhibits K-cells.

Adolescent↗
PubMed1984

Purification and characterization of C-S lyase from Fusobacterium varium. A C-S cleavage enzyme of cysteine conjugates and some S-containing amino acids.

An enzyme responsible for the carbon-sulfur bond cleavage of various S-aryl, S-aralkyl, and S-alkyl cysteines has been purified about 270-fold from Fusobacterium varium. Incubation of a cysteine conjugate of p-bromobenzene with the enzyme yielded equimolar amounts of p-bromobenzenethiol, pyruvic acid, and ammonia, indicating that the carbon-sulfur bond cleavage proceeds via an alpha, beta-elimination reaction. The enzyme activity was inhibited either by hydroxylamine or KCN and stabilized by pyridoxal phosphate, which probably acted as cofactor. The broad substrate spectrum of this enzyme suggested an important role of the intestinal microflora in the in vivo formation of methylthio-containing metabolites of various xenobiotics.

Chromatography, DEAE-Cellulose↗
PubMed1984

[Free thyroxine estimation for screening of hyper- and hypothyroidism in an adult population].

Serum free thyroxine (FT4) was determined in 1,114 adults (male 239, female 875) in a periodic health evaluation in 1980 to detect unsuspected thyroid dysfunction, especially hyper- and hypothyroidism. The participants were dwelling in two towns of Miyagi prefecture. Beside FT4, serum T4 and T3 were also determined by radioimmunoassay. If thyroid dysfunction was suspected, further detailed examinations such as TRH-test (500 micrograms i.v.), radioimmunologic determinations of serum TSH and TBG, resin-sponge T3-uptake, 24-hr thyroid radioiodine 131I-uptake, radioiodine thyroid scan and anti-thyroid antibodies were performed. There were 3 patients with hyperthyroidism (0.27%), 4 with hypothyroidism (0.36%), 3 taking thyroid medication (2; Hashimoto's disease, 1; goiter), 3 on estrogen administration, 4 with Hashimoto's disease and 1 with goiter. Excluding these 18 patients, FT4, T4 and T3 values in 1,096 euthyroid subjects, 236 males and 860 females, were 1.1 +/- 0.3 (mean +/- S.D.), 1.1 +/- 0.3 and 1.0 +/- 0.3 ng/100 ml, 8.9 +/- 1.5, 8.8 +/- 1.6 and 9.0 +/- 1.5 micrograms/100 ml, and 122 +/- 33, 125 +/- 26 and 122 +/- 35 ng/100 ml, respectively. Serum FT4, T4 and T3 showed the distribution of logarithmic normal probability. The 95% normal range for free T4 was 0.60 to 1.80 ng/100 ml, total T4 6.0 to 11.8 micrograms/100 ml, and T3 84 to 176 ng/100 ml, respectively. Out of 1,114 subjects examined, the cases to be reexamined for the higher serum concentration than normal were 26 in FT4, 35 in T4 and 27 in T3, respectively. And the cases for lower values were 28 in FT4, 31 in T4 and 24 in T3, respectively. Serum FT4 values in the subjects during the administration of estrogens were within the normal range. FT4 and T4 were low in four patients with hypothyroidism, but two of them showed normal T3 values. Determinations of serum FT4, total T4 and total T3 were all useful for the screening of hyperthyroidism. But serum FT4 was the most reliable of the three. Determination of either serum FT4 or total T4 was suitable for the screening of hypothyroidism, but serum total T3 measurement did not cover all patients with hypothyroidism.

Adult↗
PubMed1984

Changes in thyroxine monodeiodination in rat liver, kidney and placenta during pregnancy.

Monodeiodination of thyroxine (T4) was studied in the liver, kidney and placenta of pregnant rats. Age matched female non-pregnant and pregnant Sprague-Dawley rats on the 7th, 14th, 17th and 21st days of gestation were used. The 800 X g supernatants of tissue homogenates (protein 1 mg/tube) were incubated with 1 microgram of stable T4 in the presence of 5 mM dithiothreitol (DTT) at 37 degrees C for 60 min at pH 7.5. Net triiodothyronine (T3) generation from T4 in rat liver homogenates on the 7th day of gestation was significantly lower than that in the non-pregnant rat. Thereafter it increased, but values on the 14th, 17th and 21st days of gestation were not significantly different from those obtained in the non-pregnant rat. Net renal T3 generation from T4 on the 14th day was significantly lower than that in the non-pregnant rat. It was increased thereafter and the values at the 17th and 21st days of gestation were not significantly different from those in the non-pregnant rat. Net reverse T3 (rT3) generation from T4 in the placenta rose from the 14th to the 17th day and then dropped by the 21st day and the value at the 17th day was significantly higher than those at the 14th and 21st days of gestation. These results indicate that 1) both T4 outer-ring monodeiodination in the pregnant rat liver and kidney, and T4 inner-ring monodeiodination in the placenta show significant variation with the progress of gestation; 2) the time course of the T4 outer-ring monodeiodination in pregnant rat liver and kidney is completely different from T4 inner-ring monodeiodination in the placenta.

Animals↗
PubMed1984

Monodeiodination of thyroxine in the maternal and fetal dog kidneys and placenta.

We studied the monodeiodinating activities of the dog placenta and the pregnant dog kidney and compared them with those of the non-pregnant dog kidney and fetal kidney. Each tissue was homogenized in 50 mM Tris/HC1 buffer, pH 7.5. The homogenate (1 mg protein) was incubated with 1 microgram of T4 at 37 degrees C in the air for 15 min or 60 min in the presence of 5 mM DTT. The T3 and reverse T3 generated in the reaction mixture were extracted into cold ethanol and then measured by RIA. Sulfhydryl group content in each tissue was determined. The characteristics of monodeiodinating activity of the dog placenta were in good concordance with those of the rat and human placentas. Net reverse T3 production in the dog placenta was 1.4-13.2 (6.1 +/- 5.3, mean +/- S.D.) ng/mg protein/micrograms T4/60 min but net T3 production was negligible. Although it seemed that the T3 production/reverse T3 production ratio in the pregnant dog kidney was lower than that in the non-pregnant dog kidney, there was no statistical significance. It is conceivable that the characteristics of deiodination in the placenta are tissue specific, independent of the changes in internal conditions induced by pregnancy. In the fetal dog kidney homogenate, T3 and reverse T3 were metabolized only minimally and productions of T3 and reverse T3 were also very low. An increase in DTT concentration up to 100 mM had no effect on the production rates of these triiodothyronines . Total and non-protein SH group contents in the fetal dog kidney homogenate were about the half of those in the maternal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Enhanced prolactin secretion in patients with primary hypothyroidism during thyroid replacement.

Thyroid hormones are known to exert some influence on prolactin (PRL) secretion indirectly via the hypothalamic dopaminergic system and directly at the level of pituitary gland. In order to study the effect of thyroid hormones on the activity of hypothalamic dopamine neurons, lactotrophs and thyrotrophs, we administered increasing doses of thyroid hormones to patients with primary hypothyroidism, and examined the changes of basal PRL, TSH and PRL responses to a dopamine receptor blocker (sulpiride). Among 24 patients with primary hypothyroidism, hyperprolactinemia was observed in 10 cases (18.0-236 ng/ml, mean +/- S.E. 58.6 +/- 20.0 ng/ml), while elevated TSH levels were observed in all of them (6.6-972 microU/ml, mean +/- S.E. 231.4 +/- 53.9 microU/ml). There was a significant negative relationship between plasma T3 or T4 levels and basal plasma TSH levels (p less than 0.05), whereas a poor correlation was observed between the thyroid hormones and basal plasma PRL levels (r = -0.25, p greater than 0.05). Following the administration of gradually increasing doses of thyroid hormones, plasma PRL showed paradoxical and transient increases, while plasma TSH decreased steadily. Plasma PRL response to sulpiride also became exaggerated during the treatment. The elevated basal PRL level and the enhanced response to sulpiride turned to be within the normal range when the patients became euthyroid by treatment. These results may indicate that thyroid hormones stimulate not only hypothalamic dopaminergic activity, but also the lactotroph activity in a long term hypothyroid state. Regarding the paradoxical elevation of basal PRL, one can postulate that the activation of lactotroph by a small dose of thyroid hormone may be able to overcome the hypothalamic dopaminergic inhibition.

Adult↗
PubMed1984

Metabolism of tenoxicam in rats.

The structures of six metabolites of tenoxicam in rats (2 mg/kg, orally), elucidated by physicochemical analyses or the reverse-isotope dilution method, were 5'-hydroxytenoxicam (5% dose), 3-(methylsulphamoyl)-2-thiophenecarboxylic acid (9% dose), and the C-7 or C-8 O-glucuronide of tenoxicam (30% dose). The mechanism of formation of N-methylthiophenesulphimide, a possible precursor of 3-(methylsulphamoyl)-2-thiophenecarboxylic acid from tenoxicam, is discussed.

Animals↗