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Biomedical subjects

M Horimoto

Publications and source records attributed to M Horimoto.

At least 91 records · Page 5Linked to original sources

Maternally derived antibodies to Japanese encephalitis virus in cattle.

Serum samples were collected from 55 pairs of calves that had not passed the first summer and their dams reared in Kagoshima from 1983 through 1985. They were investigated for the HI antibody to Japanese encephalitis virus (JEV) in calves and for the correlation of antibody levels between calves and their dams. The maternally derived antibody was detected in 35 of 55 calves (63.6%), showing the mean antibody titer of 12.4. A significant negative correlation (p less than 0.01) was noted between the age of calve and titer of passively acquired antibodies. The regression equation suggested that the maternal antibody disappeared from the calf serum at about 3 months of age. On the other hand, 37 of 55 dams (67.3%) were positive for HI antibody to JEV, and the mean titer of the antibody was 12.7. There was a significant correlation (p less than 0.01) in serum antibody titers between dams and their calves.

Age Factors↗

Synergistic effect of thyroid hormone and thyrotropin on iodothyronine 5'-deiodinase in FRTL-5 rat thyroid cells.

The effects of T3 and T4 on the iodothyronine 5'-deiodinase (5'-D) activity in FRTL-5 rat thyroid cells were investigated. T3 and T4 stimulated the 5'-D activity in a dose-dependent manner. Kinetic studies showed that the stimulation of the 5'-D by T3 was associated with an increase in maximum velocity (Vmax) in [11.9 +/- 0.2 (mean +/- SE) and 25.4 +/- 0.9 pmol I-released/mg protein.min, respectively, in control and cultured with 10(-9) M T3 for four days] but without a change in apparent Michaelis-Menten constant (Km) (94.8 +/- 5.3 nM and 105.4 +/- 12.1 nM, respectively). Furthermore, cycloheximide (5 microM) completely abolished the stimulatory effect of T3 on the 5'-D activity. T3 and T4 also enhanced the 5'-D activity stimulated by TSH in a dose-dependent manner. Kinetic studies showed that the stimulatory effect of T3 on the 5'-D stimulated by TSH was again associated with an increase in Vmax (86.0 +/- 4.0 and 166.5 +/- 1.9 pmol I- released/mg protein.min, respectively, cultured with 0.3 U/liter TSH and cultured with TSH plus 10(-9) M T3 for four days) without a change in apparent Km (114.0 +/- 7.4 nM and 111.6 +/- 12.5 nM, respectively). Cycloheximide (5 microM) completely abolished the stimulatory effect of TSH plus T3 on the 5'-D activity. There were no significant differences observed between cells cultured with TSH and with TSH plus T3 in either the intra- or extracellular cAMP contents. Furthermore, T3 enhanced the 5'-D activity stimulated by (Bu)2 cAMP. These results strongly suggest that T3 or T4 was synergistic with TSH in stimulating the 5'-D activity in FRTL-5 cells, and that cAMP production would be an important component of the synergism.

Animals↗

Graves' immunoglobulin G stimulates iodothyronine 5'-deiodinating activity in FRTL-5 rat thyroid cells.

To elucidate the effect of Graves' immunoglobulin G (IgG) on iodothyronine deiodination in the thyroid, we examined the characteristics of iodothyronine 5'-deiodinating (I-5'-D) activity in FRTL-5 rat thyroid cells and the effect of Graves' IgG on its activity. FRTL-5 cells were sonicated and incubated with 0.5 mumol/L rT3 with a tracer amount of [125I]rT3 in 0.1 mol/L phosphate buffer containing 1 mmol/L EDTA and 0.5 mmol/L dithiothreitol. The released 125I- was separated by Dowex-50WX2 column and counted. The amount of I- released was tissue, incubation time, temperature, and pH dependent, strongly suggesting that the reaction is enzymatic. The activity was completely inhibited by propylthiouracil. The Km value for rT3 was approximately 0.32 microM when analyzed by Lineweaver-Burk plot. TSH, dibutyl cAMP, and Graves' IgG induced I-5'-D activity in a dose-dependent manner. However, cycloheximide (5 mumol/L) abolished the stimulating effects of these agents on I-5'-D activity. These results suggest that TSH, dibutyl cAMP, and Graves' IgG induced I-5'-D activity through the synthesis of new enzyme protein. A significant positive correlation between thyroid-stimulating antibody activity assayed by measuring cAMP production using FRTL-5 cells and I-5'-D activity induced by the Graves' IgG in 10 patients with untreated Graves' disease was observed (r = 0.79; P less than 0.01). The present findings suggest that type I iodothyronine 5'-deiodinase exists in FRTL-5 rat thyroid cells and that Graves' IgG as well as TSH stimulate the activity at least in part by activating adenylate cyclase.

Animals↗

Meteorological factors involved in Japanese encephalitis virus infection in cattle.

From 1982 to 1987 a total of 4,371 dairy cattle in Saitama Prefecture, were examined for levels of hemagglutination inhibition (HI) antibody to Japanese encephalitis virus (JEV) and the correlation with meteorological factors and an antibody positive rate was studied. Positivity rates of HI antibody from July to October each year (Yi) ranged from 58.8 to 88.0% with a considerable annual variation. Simple regression analysis of Yi with the comparative meteorological value (Xi) was determined from mean temperatures (Ti, j-1), rainfalls (Ri, j-1) for 10-day-periods each, and the number of days showing 25 degrees C or above (ti, j-1) from June to September, which yielded a correlation coefficient of 0.8147 (p less than 0.05) and an equation for estimated HI antibody positivity rate: Yi = -0.04Xi+79.9 (p less than 0.05). Multiple regression analysis with the power values of three meteorological parameters as independent variables and Yi as the dependent variable, showed a multiple correlation coefficient of 0.987 (p less than 0.05) and a multiple regression equation: Yi = -3991T1/13-0.0035R-12+1978t1/9+4187 (p less than 0.05), giving estimated positivity rates almost equal to the values from the observations. Therefore, a predictive equation was formulated reflecting positive and negative correlations of sero-positivity with the temperature and the precipitation, respectively.

Animals↗

A sensitive and practical bioassay for thyrotropin (TSH): comparison of the bioactivity of TSH in normal subjects and in patients with primary hypothyroidism.

To study the possible correlation between the bioactivity ratios of the serum TSH and serum thyroid hormone concentrations in patients with primary hypothyroidism, the bioactivity of TSH in these patients was determined by means of a sensitive and practical bioassay and the results were compared to those in normal subjects. Sample sera were obtained from 11 patients with primary hypothyroidism and 9 normal subjects. TSH was extracted from the serum with anti-human TSH monoclonal antibody-coated tubes. The bioassay for TSH was performed by measuring the amount of cAMP released into the medium from cultured FRTL-5 cells incubated with the TSH extract. Linear relations were found between the serum TSH values, measured by the immunoassay, and the bioactivity of the TSH, measured by the present assay, in normal subjects (y = 1.13 x-0.3, r = 0.89, p less than 0.01) and in patients with primary hypothyroidism (y = 0.90 x + 0.7, r = 0.93, p less than 0.01). Moreover, the regression line in patients with primary hypothyroidism was not significantly different from that in normal subjects based on the analysis of covariance. The present findings suggest that the bioactivity of TSH is consistent with the immunoreactivity of TSH in patients with primary hypothyroidism as well as in normal subjects.

Adult↗

Human chorionic gonadotropin promotes thyroid growth via thyrotropin receptors in FRTL-5 cells.

To ascertain the presence of thyroid growth-promoting activity (TGA) in the sera of pregnant women, we measured TGA in the sera of pregnant women by means of a bioassay based on [3H]-thymidine [( 3H]Tdr) incorporation in cultured rat FRTL-5 thyroid cells. Furthermore, to elucidate the mechanisms of human chorionic gonadotropin (hCG) in promoting the thyroid growth, we evaluated the effects of blocking type TSH receptor antibody (blocking IgGs) from patients with primary hypothyroidism on the activity of hCG. After the PEG-pretreated serum or the serum plus blocking IgGs was incubated for 72 h at 37 degrees C with FRTL-5 cells and [3H] Tdr, [3H] Tdr incorporated in the cells was counted. Although 9 normal pregnant women had normal TGA, two patients with hydatidiform mole, whose hCG levels were 966,500 and 497,100 IU/L, had positive TGA, but the activity showed normal when analyzed with the addition of a blocking IgG. hCG also showed a dose-dependent increase in [3H]Tdr incorporation, and it was inhibited by the addition of blocking IgGs. Furthermore, the inhibition of hCG-induced [3H]Tdr incorporation by 16 blocking IgGs correlated with their TBII and the inhibition activity of hCG-induced cAMP accumulation. Analysis by the Lineweaver-Burk plots of dose response curves of TSH- and hCG-induced [3H]Tdr incorporation showed the same inhibition pattern as with the addition of the same blocking IgGs. In conclusion, 1) hCG-related TGA exists in the sera of some patients with hydatidiform mole; and 2) hCG and the sera of some patients with hydatidiform mole promote thyroid growth, at least in a part, via TSH-receptors in FRTL-5 cells.

Adolescent↗

Thyroid-stimulating activity of human chorionic gonadotropin in sera of normal pregnant women.

To ascertain the thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the adenylate cyclase activation in the cultured FRTL-5 cells by extracted hCG from 7 normal pregnant women. hCG was extracted from the sera using anti-hCG-beta subunit monoclonal antibody-coated microwells, eluted with 2 mol/l guanidine-HCl, and reconstituted with hypotonic Hanks' solution. FRTL-5 cells were precultured in 5H medium, incubated for 2 h with the serum extracts, and the cAMP released into the medium was measured. hCG levels in serum extracts ranged from 1100 to 6800 IU/l; values corresponded to 1.4-19.8% compared with those in the original serum samples. Addition of the extracts to FRTL-5 cells resulted in significant increases in the cAMP accumulation, ranging from 9.8 to 59.0 nmol/l. cAMP levels were also increased in a dose-dependent manner by adding purified hCG as well as crude hCG and hTSH to FRTL-5 cells. These findings suggest that the thyroid gland of normal pregnant women may actually be stimulated by hCG itself.

Adult↗

[Hypertrophic obstructive cardiomyopathy in the right ventricle presenting in the elderly woman: a case report].

A 69-year-old woman was admitted to the hospital for evaluation of a cardiac murmur, which had been indicated at her childhood. On physical examination, a systolic ejection murmur was heard on the lower left sternal border. Chest roentgenogram revealed a cardiomegaly. Echocardiography and MRI showed a thickening of the interventricular septum and the right ventricular (RV) free wall, which obstructed the RV body. At cardiac catheterization, a systolic pressure gradient of 100 mmHg was shown between the RV outflow tract and the apex. There was no pressure gradient in the left ventricle (LV). RV angiocardiograms disclosed a severe obstruction of the RV body, while LV angiocardiograms showed a slight enlargement of the LV with a diffuse hypokinesis of its wall. Myocardial biopsy of both ventricles revealed a bizarre hypertrophy of myocytes and disorganization. The histological findings were more conspicuous in the RV. Based on these findings, this case was diagnosed as hypertrophic obstructive cardiomyopathy (HOCM) in the RV. HOCM in the RV presenting in the elderly, is extremely rare. Our case is also characterized by a concomitant LV involvement, which demonstrated the slightly enlarged LV and the diffuse hypokinesis of its wall.

Age Factors↗

[Japanese encephalitis virus infection in cattle: a serological survey in Saitama and Kagoshima Prefectures].

Serum samples were collected from a total of 1,306 and 536 cattle raised in Saitama and Kagoshima Prefectures, respectively, during a period from 1982 to 1984. Their antibody titers against Japanese encephalitis virus (JEV) were determined by the hemagglutination-inhibition test. Antibody prevalences were 65.5% (856/1306) and 68.8% (369/536) in Saitama and Kagoshima Prefectures, respectively. In both prefectures, there was a rapid increase in positive rate and mean titer in summer. Afterwards, there was a gradual decrease in both rate and titer in Saitama Prefecture in winter. In Kagoshima Prefecture, however, the rate and titer did not so markedly decrease in winter, but remained high in December. The rate of positive reactors to JEV in Kagoshima Prefecture increased gradually from 29.4% (1 year old) to 74.5% (4 years old) with advance in age. This rate in each age group remained almost at the same level ranging from 64.0% to 82.8% in Saitama Prefecture.

Age Factors↗

Thyroid-stimulating activity in sera of normal pregnant women.

To evaluate the effect of a thyroid stimulator on thyroid function in the sera of normal pregnant women, we measured thyroid-stimulating activity (TSA) using a highly sensitive bioassay based on cAMP accumulation in cultured rat FRTL-5 thyroid cells. Serum was pretreated with 10% polyethylene glycol (PEG), and the supernatant (PEG-pretreated serum) was then used in the following studies. FRTL-5 cells were preincubated in 5H medium and incubated for 2 h with PEG pretreated serum, and cAMP was measured. All 11 patients with untreated hyperthyroid Graves' disease with strongly positive thyroid-stimulating antibody activity had normal TSA, because only 5.6% of their immunoglobulin G was recovered in the PEG-pretreated serum. In 32 normal pregnant women, 29 (91%) had positive TSA. Their TSA showed statistically significant positive correlations with serum hCG and free T4 levels, and a negative correlation with serum TSH levels. Moreover, when hCG was absorbed from sera by incubation with the solid phase anti-HCG monoclonal antibody, a significant positive correlation was observed between the rate of decrease in hCG and that in TSA. In conclusion, 1) TSA exists in the sera of normal pregnant women, which reflects hCG itself; and 2) thyroid glands of normal pregnant women may be stimulated by TSA to induce a slight suppression of TSH but not sufficient to induce overt hyperthyroidism.

Adult↗

Histological evidence of left ventricular involvement in arrhythmogenic right ventricular dysplasia.

A 40-year-old female with arrhythmogenic right ventricular dysplasia (ARVD) demonstrated a reduced motion of the left ventricular (LV) apex. Specimens of LV free wall, obtained by endomyocardial biopsy, histologically revealed prominent interstitial fibrosis with sparse distribution of myocytes. The myocytes were hypertrophic and disrupted with loss of myofibrils. This is a case of ARVD, where LV involvement was histologically verified.

Adipose Tissue↗

Activity of thyroid stimulating antibody and thyroid stimulation blocking antibody determined by radioiodine uptake into FRTL-5 cells.

To investigate the pathophysiology of patients with autoimmune thyroid diseases, we measured serum thyroid stimulating antibody (TSAb) activity and thyroid stimulation blocking antibody (TSBAb) activity by determining the radioiodine (125I) uptake into FRTL-5 cells. FRTL-5 cells were pre-incubated for seven days with 5H medium and then incubated for 48 hours with patients' crude IgG prepared by polyethylene glycol precipitation. In order to measure TSBAb, 10 microU/ml TSH was also added. 125I was added one hour before the end of the 48 hour incubation period. After the incubation, the medium was aspirated, and the radioactivity in the cells was counted. In patients with untreated hyperthyroid Graves' disease, TSAb was detectable in 18 of 20 patients, the detectability being 90%, and activity showed a statistically significant positive correlation with TSAb activity determined by c-AMP accumulation. Out of 41 patients with hypothyroidism, TSBAb determined by 125I uptake was positive in six cases, the detectability being 14.6%. The inhibition of 125I uptake by one of these six IgGs was suggested to be at the TSH receptor level because it inhibited TSH induced c-AMP accumulation and showed positive thyrotropin binding inhibitor immunoglobulin (TBI I) activity, but did not inhibit the forskolin- and (Bu)2cAMP-induced 125I uptake. Inhibition of another IgG was suggested at the post-receptor level because it did not inhibit TSH induced cAMP accumulation and showed negative TBI I activity, but inhibited forskolin- and (Bu)2cAMP-induced 125I uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A sensitive and practical bioassay for thyrotropin using cultured FRTL-5 cells: assessment of bioactivity for serum TSH in patients with chronic renal failure.

A sensitive bioassay for TSH employing a practical extraction method was developed, and the bioactivities in patients with chronic renal failure receiving hemodialysis were compared with those in normal subjects. Serum samples were obtained from 12 normal subjects and 12 patients with chronic renal failure receiving hemodialysis. TSH was extracted from the serum using anti-human TSH monoclonal antibody coated tubes, followed by elution with 2.0 mol/l guanidine-HC1 solution (pH 3.2). After the eluate had been dialyzed against phosphate buffered saline (pH 7.4) and again against TRIS-HC1 solution (pH 7.4) and then lyophilized, it was reconstituted with hypotonic Hanks' solution. Bioassay for TSH was performed by measuring the levels of cAMP released into the medium from cultured FRTL-5 cells incubated with the extract. The mean immunoreactive recovery rates of TSH from the serum in normal subjects and patients with chronic renal failure were about 42% (+/- 6) and 40% (+/- 2), respectively. The present bioassay was sufficiently sensitive to detect a serum TSH level of 1.0 mU/l when 3.0 ml of serum was used. Extracts from standard sera at concentrations ranging from 1.0 to 10 mU/l added to the culture medium caused significant linear increases in cAMP production. Based on analysis of covariance the regression line between the immunoreactivities and bioactivities of serum TSH in patients with chronic renal failure (y = 0.90x + 0.3, r = 0.92) was not significantly different from that in normal subjects (y = 1.04x + 0.1, r = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Studies on the pituitary and thyroid function in patients with nonthyroid illnesses].

Serum thyroid hormone and TSH concentrations were determined in patients with nonthyroidal illnesses (NTI) including 26 patients with chronic renal failure on hemodialysis, 15 patients with end-stage malignancy and 21 normal controls. Serum TSH levels were measured by a highly sensitive immunoradiometric assay Kit (RIA-gnost hTSH) and free-T4 levels were determined not only by both back-titration method and T4 derivative method, but also by magnesium precipitation method using equilibrium dialysis. TSH levels in normal controls ranged from 0.6 to 2.4 microU/ml. In 40 of 41 patients with NTI, serum T3 levels were less than 100 ng/dl, and 37 patients had diminished T3 levels, as compared with those in normal controls. Moreover, serum T4 levels were also diminished in 19 patients with NTI, and T4 levels related significantly to serum TBG levels in all patients with NTI (r = +0.76, p less than 0.01), suggesting that the diminution of T4 levels in patients with NTI can be explained partly by decreased TBG levels. However, it was remarkable that free T4 levels in serum, determined by RIA kits, were decreased in approximately half of the patients with NTI. Free T4 levels by the magnesium precipitation method were still lower in these patients when compared with those in normal controls. Serum TSH levels in patients with NTI showed a wide scattering from below to above the normal range, and the mean value was not significantly different from that in normal controls. No significant relations were found between TSH levels and T4, T3, or free T4 levels in patients with NTI.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic Nephropathies↗

Relationship among thyrotropin (TSH), thyroid stimulating immunoglobulins, and results of triiodothyronine (T3) suppression test in patients with Graves' disease.

To investigate the relationship between TSH and abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease in whom normal thyroid hormone levels in the serum were maintained by antithyroid drug therapy and in patients with euthyroid Graves' disease, determinations were made of the TSH concentration, action of thyroid stimulating immunoglobulins (TSAb and TBII), and T3 suppression. Out of thirty-three patients with hyperthyroid Graves' disease, twelve patients with subnormal TSH levels were all non-suppressible according to the T3 suppression test results and the detectability of TSAb and/or TBII was as high as 75%. In three out of five patients with euthyroid Graves' disease, the serum TSH level was subnormal. All three showed non-suppressibility in the T3 suppression test and positive action of either TSAb or TBII. One of them became clinically thyrotoxic when the TSAb activity was further increased and TBII became positive, and was therefore diagnosed as having hyperthyroid Graves' disease. The present findings suggest that there are still abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease who have low TSH, even if their thyroid hormone concentrations remain normal. Moreover, it is likely that some of the patients with euthyroid Graves' disease are actually in a state of subclinical hyperthyroidism because of the presence of abnormal thyroid stimulator(s).

Adolescent↗