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Biomedical subjects

I Morimoto

Publications and source records attributed to I Morimoto.

At least 109 records · Page 6Linked to original sources
PubMed1987

Inhibitory effect of interferon-gamma on the response of human thyrocytes to thyrotropin (TSH) stimulation: relationship between the response to TSH and the expression of DR antigen.

Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.

Bucladesine↗
PubMed1987

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone pulse therapy.

This preliminary study was undertaken to investigate the efficacy of high-dose iv methylprednisolone pulse therapy in 5 patients with Graves' ophthalmopathy. One gram of methylprednisolone sodium succinate was given iv daily for 3 successive days. The 3-day infusion was repeated 3 to 7 times at intervals of 1 week; total duration of pulse therapy was 3 to 7 weeks. The clinical improvement of eye involvements by pulse therapy was assessed immediately after the last pulse therapy. The clinical assessment of the effect of pulse therapy for Graves' ophthalmopathy showed a good response in 3 patients, a fair response in one, and no response in one. However, in one patient, who was judged to show no response, complete improvement of the enlarged extraocular muscle was observed on orbital computed tomography. Moreover, two patients, who have been followed without any other therapies, showed no relapse of eye involvements for 32 and 10 months, respectively. Although it is impossible to determine whether pulse therapy is more effective than other immunosuppressive therapies, the results of this preliminary study suggest that pulse therapy may be a good immunosuppressive therapy for Graves' ophthalmopathy too. Controlled studies are desired.

Adult↗
PubMed1987

Serum TSH, thyroglobulin, and thyroidal disorders in atomic bomb survivors exposed in youth: 30-year follow-up study.

Follow-up examinations to determine the frequency of thyroidal disorders were conducted by the Radiation Effects Research Foundation (RERF) on individuals in Hiroshima and Nagasaki who were less than 20 yr of age at the time of exposure to the atomic bomb. Concentrations of serum thyroid stimulating hormone (TSH), thyroglobulin (TG), and anti-TG antibody 30 yr after exposure were also determined. Nontoxic uninodular goiter was found in 13 cases of the 100 + rad exposed group (n = 477) and in three cases of the nonexposed group (n = 501). The prevalence in the 100+ rad exposed group was significantly higher (chi-squared = 6.584, p less than 0.01). Thyroid cancer was found in eight exposed cases, all of whom were in the 100+ rad group, and the prevalence was significantly greater (chi-squared = 7.919, p less than 0.01). Regardless of the presence or absence of thyroid disorders, serum TSH and TG levels were not statistically different between the 100 rad + exposed and nonexposed groups. Although hypothyroidism was found in 23 of the total cases, there was no correlation between its development and exposure to ionizing irradiation.

Adolescent↗
PubMed1986

[Free testosterone index: comparison with plasma free testosterone].

Blood-free testosterone indices were measured among 28 normal men (age; 24-48 yrs.), 20 normal women (20-36 yrs.), 18 pregnant women (22-31 yrs.), 17 males with hypogonadism (23-56 yrs.), 17 males with chronic hepatitis (20-42 yrs.), 24 males with liver cirrhosis (29-68 yrs.), 34 males with hyperthyroidism (20-42 yrs.) and 7 hirsute women (18-31 yrs.), and these were compared with the plasma concentrations of free testosterone. The testosterone index was obtained by multiplying the plasma concentration of testosterone by the percent of sex hormone-binding globulin (SHBG), non-bound testosterone precipitated by dextran-coated charcoal. A significant increase of plasma testosterone was observed in patients with chronic hepatitis (p less than 0.001) and hyperthyroidism (p less than 0.001) as compared with normal men and was also observed in pregnant (p less than 0.01) and hirsute women (p less than 0.01) as compared with normal women. The close negative correlation between plasma levels of testosterone and the percent of SHBG non-bound testosterone (r = -0.87, n = 79, p less than 0.001) was observed among normal men, male patients with chronic hepatitis and hyperthyroidism. The sex hormone binding capacity was increased from two to three fold in patients with chronic hepatitis and hyperthyroidism. The patients with compensated liver cirrhosis had increased plasma testosterone and a decreased percent of SHBG non-bound testosterone, and those with decompensated liver cirrhosis had decreased plasma testosterone and a normal percent of SHBG non-bound testosterone. The plasma concentration of free testosterone was normal in patients with chronic hepatitis and hyperthyroidism. It decreased in pregnancy (p less than 0.01) and increased in hirsute women (p less than 0.01). The blood free testosterone index was slightly high in one third of the patients with chronic hepatitis and hyperthyroidism as compared with that in normal men. However, a close correlation of the percent of SHBG non-bound testosterone and fractional free testosterone (%) measured by equilibrium dialysis (gamma = 0.82, p less than 0.001) was obtained in all subjects (n = 170). These data suggest that the blood free testosterone index parallels the plasma concentration of free testosterone and is useful to evaluate the status of androgenicity.

Adult↗
PubMed1986

Kinetic study of immunoreactive human thyroglobulin.

Thyroglobulin (Tg) can be detected in the circulation of normal subjects. Serum Tg is increased in patients with various thyroidal disorders including Graves' disease; however, little is known about Tg metabolism. Therefore, a kinetic study of human Tg was carried out in 13 normal men, 19-28 yr old, and 6 untreated hyperthyroid patients with Graves' disease, 3 men (22 to 25 yr old), and 3 women (21 to 63 yr old). Ten milligrams of Tg were injected as a bolus dose. Blood samples were collected before and 10 min, and 2, 4, 6, 8, 12 h and every 12 h up to 72 h after injection. Concentrations of serum Tg were measured by an RIA method developed in our laboratory. Anti-Tg antibody was not detected in any subject. Various indices of this kinetic study were calculated using single compartmental analysis. In 13 normal subjects, the mean serum concentrations of Tg were 17 +/- 12.6 (SD) ng/ml; mean half-life was 29.6 +/- 2.8 h; distribution volume was 11,210 +/- 3,076 ml/60 kg body weight; fractional decay was 2.40 +/- 0.22%/h; MCR was 268.9 +/- 87.8 ml/h X 60 kg; and release rate was 100.3 +/- 50.2 micrograms/day X 60 kg. Serum concentrations of Tg were increased in four of the six untreated hyperthyroid patients with Graves' disease. Their Tg half-lives and MCR were within the normal range. In the two patients who had normal serum concentrations of Tg, the Tg half-lives were shorter and MCR were greater than in normal subjects. The release rates of Tg were increased in all six of these patients. In summary, in hyperthyroid patients, Tg release is significantly greater than normal, whereas Tg metabolism is similar to that in normal subjects.

Adult↗
PubMed1986

Stimulation of thyroid adenylate cyclase activity by sera from patients with non-thyroidal illness.

We have previously shown that sera from many hypothyroid patients stimulated adenylate cyclase activity as measured by serum bioactive TSH concentrations produced by FRTL-5 cell line. This TSH-stimulating activity did not correlate with serum immunoreactive TSH. IgG fractions of these sera did not stimulate FRTL-5 cells. The present study was, therefore, undertaken to investigate the thyroid stimulating activity of sera from patients with non-thyroidal illness. Studies were performed in 36 patients with various non-thyroidal illness. In these patients, serum concentrations of T4, free thyroxine, T3, and TSH were determined. In addition, sera were incubated with FRTL-5 cells or porcine thyroid cells in primary culture in the presence of 0.4 mM MIBX, and medium cAMP concentrations were determined by radioimmunoassay. Sera obtained from some patients with various non-thyroidal illness increased cAMP concentrations in culture media of FRTL-5 cells as well as that of porcine thyroid cells. The thyroid stimulating effects of sera were not disease specific and significantly correlated inversely with serum T3 and T4 concentrations. Serum TSH concentrations in these patients were within the normal range even by the newly developed ultrasensitive assay. Although the nature of substance(s) present in sera of patients with low T3 syndrome which stimulates thyroid adenylate cyclase is not entirely known, it is conceivable that there exist mechanisms independent of TSH to compensate the decreased serum T3 levels in low T3 syndrome.

Adenylyl Cyclases↗
PubMed1986

Pregnancy and penicillamine treatment in a patient with Wilson's disease.

A 22-year-old female with Wilson's disease became pregnant and subsequently delivered a normal infant. At the age of 17 the patient presented evidence of liver cirrhosis and was diagnosed as having Wilson's disease. A regimen of d-penicillamine was started at this time and continued, although irregularly for the 10 months prior to her 9th week of pregnancy. At the 14th week of pregnancy she was started on 500 mg of D-penicillamine a day. She was stable during the remainder of her pregnancy and after delivery. Fetal development was normal and a normal infant was delivered at 35 weeks. It is suggested that pregnancy is not contraindicated in well treated Wilson's disease, and that a regimen of D-penicillamine during pregnancy can control the illness without harming the fetus.

Adult↗
PubMed1986

Determination of the volume of the thyroid gland by a high resolutional ultrasonic scanner.

We developed a new ultrasonic scanner for the thyroid and, in this study, the estimated volumes of the thyroids by this scanner were compared with the weights of those obtained at operation. In this ultrasonic scanner, an annular array transducer was employed instead of the conventional single element concave transducer. The distance of the focused area by this transducer was as long as 5 cm compared to 1 cm by the conventional transducer; therefore, the image obtained by the new scanner was so clear that it was not difficult to draw accurately the outlines of the thyroids. The volumes of the thyroids were calculated by a computerized digitizer. The estimated volumes of the thyroids by the ultrasonic scanner were closely correlated with their weights calculated by adding the actual weights of the thyroids removed to the estimates of the thyroids left at operation. Their correlation coefficients were as high as 0.99. This suggests that this new ultrasonic scanner is very useful in the determination of the volumes of the thyroids, since the measurement is very accurate, simple, and reproducible.

Adenoma↗
PubMed1984

[Dihydrotestosterone formation (5 alpha-reductase activity) in cultured human skin fibroblasts].

Testosterone secreted from the testis is converted to dihydrotestosterone (DHT) in target tissues by 5 alpha-reductase and DHT exerts its action on the nucleus. Since skin is one of the target tissues of androgen we established a system for culturing human skin fibroblasts, and we investigated the conversion of testosterone to DHT in genital and nongenital skin fibroblasts obtained from males as well as from females. In our system, fibroblasts were incubated with 0.1 microM 1, 2-3H testosterone, and labeled metabolites were separated by thin layer chromatography. DHT formation was linear for 6 hours and the rate of DHT formation correlated with the growth phase of the fibroblasts. In the course of serial subculture, DHT formation did not change between the 3rd and 10th subculture in four cell strains. DHT formation in nongenital skin fibroblasts did not differ significantly between males and females. Fibroblasts obtained from male genital skin produced significantly greater amounts of DHT than those from male or female nongenital skin. Furthermore, DHT formation in genital skin fibroblasts did not differ between normal males and hypogonadal males. These data suggest that genital skin is the target tissue where testosterone strongly converts to DHT and the difference of male secondary sexual characteristic appearance between males and females may not depend on the sensitivity of the target tissues to androgen but on the secretion rate of androgen.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1984

[The measurement of dializable free testosterone].

Non-protein bound testosterone is considered to represent an active androgen in blood, and it reflects in androgenicity. We measured the dializable free testosterone (AFT) in various disorders. The values of plasma testosterone (T), fractional free testosterone (%FT) and AFT were 560 +/- 151 (mean +/- SD) ng/dl 1.9 +/- 0.4% and 10.7 +/- 3.3 ng/dl in normal males (n = 43, aged 25-58), 51 +/- 12 ng/dl, 1.2 +/- 0.3% and 0.6 +/- 0.2 ng/dl in normal females (n = 30, aged 21-41), and 63 +/- 26 ng/dl, 0.6 +/- 0.3% and 0.4 +/- 0.2 ng/dl in pregnancy (n = 20, second and third trimester), respectively. Those values in normal females and pregnancy were significantly lower than those in normal males (p less than 0.001). In male, the concentrations of T and AFT in patients with primary (n = 43, aged 18-50) and secondary hypogonadism (n = 16, aged 22-66) were significantly decreased (p less than 0.001 vs normal males), respectively. The plasma concentration of total testosterone (T) was increased 1032 +/- 269 ng/dl in chronic hepatitis (p less than 0.001) (n = 21, aged 28-52) and 1455 +/- 366 ng/dl in hyperthyroidism (p less than 0.001) (n = 44, aged, 18-52). However, %FT in those disorders was significantly decreased 1.2 +/- 0.3% in chronic hepatitis (p less than 0.001) and 0.8 +/- 0.3% in hyperthyroidism (p less than 0.001), and plasma levels of AFT in both disorders were not different as compared with that in normal males.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1983

Mutagenic activities of gentisin and isogentisin from Gentianae radix (Gentianaceae).

The mutagenic activities of 2 hydroxyxanthones, gentisin and isogentisin, obtained from the methanol extract of Gentianae radix (Gentianaceae) were investigated. The methanol extract of Gentianae radix, which showed mutagenicity in the Ames test in Salmonella typhimurium strain TA100 with S9 mix, was fractionated by column chromatography on Sephadex LH-20, and the fractions were purified by preparative TLC and column chromatography on polyamide. 2 mutagenic materials thus obtained, S1 and S2, each gave a single band on TLC. Identification of S1 and S2 was accomplished by comparing the analytical (mps, elementary analyses) and spectral (UV, IR, mass, NMR) results for S1 and S2 with literature data for gentisin and isogentisin. At doses below 10 micrograms, S1 (gentisin) and S2 (isogentisin) had similar specific mutagenic activities. At doses of over 10 to 50 micrograms, the mutagenic activities of S2 and S1 were 19.1 and 6.94 revertants per microgram respectively. This much lower activity of S1 than S2 may be a result of its poor solubility owing to the presence of the OMe group at C-3. The combined yield of S1 and S2 was about 76 mg (40 mg as S1 and 36 mg as S2), which accounted for 76% of the content of mutagenic compounds (100 mg) estimated roughly from the total mutagenic activity in the extract of the starting materials (100 g).

Animals↗
PubMed1983

An autopsy case of 17 alpha-hydroxylase deficiency with malignant hypertension.

This is the first autopsy case of male 17 alpha-hydroxylase deficiency with malignant hypertension. The subject had hypertension, hypokalemic alkalosis, and pseudohermaphroditism. At age 21, 17 alpha-hydroxylase deficiency was diagnosed by low urinary excretion of 17-hydroxysteroids, low secretion rate of cortisol, and low plasma testosterone level in association with high urinary excretion of pregnanediol and high plasma progesterone and corticosterone. Urinary excretion of aldosterone and PRA were suppressed, and plasma ACTH was elevated. Hypertension and hypokalemic alkalosis were normalized with dexamethasone therapy. After missing 5 yr of follow-up, malignant hypertension developed, and PRA and aldosterone were elevated. Histological examination revealed some characteristic arteriolar lesions as in malignant nephrosclerosis. Juxtaglomerular hyperplasia and an increase of renin granules were observed, which reflected high PRA. Abnormal histological findings of endocrine organs were observed in the breast, the pituitary gland, the adrenal glands, and the testis.

Adrenal Hyperplasia, Congenital↗