[Thyroxine binding capacity (TBC)].
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Humans↗
Biomedical subjects
E Odagiri
Publications and source records attributed to E Odagiri.
[Neuron specific enolase (NSE)].
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Biomarkers, Tumor↗
Inhibin alpha, beta A subunit and activin type II receptor mRNAs are expressed in human brain tumors.
Inhibin and activin were initially isolated as regulators of pituitary or gonadal hormone and are now known to be growth factors belonging to the TGF-beta family with diverse influences on the differentiation and proliferation of various tissues. To investigate the role of inhibin and activin in human brain tumors, the expression of inhibin alpha, and beta A mRNA as well as activin type II receptor (ACTR II) mRNA were studied in various human brain tumors. The tumors were divided into the following 4 groups: 3 Rathke's cleft cysts and 2 craniopharyngiomas (group 1), 8 meningiomas (group 2), 8 malignant gliomas (group 3), and various other tumors including 1 each of germinoma, astrocytoma, hemangioblastoma, and osteochondroma as well as 2 malignant lymphomas and 2 metastatic squamous cell carcinomas (group 4). Immediately after resection, tumor tissues were homogenized in guanidine thyiocyanate to extract total RNA. PCR was then performed with reverse-transcribed cDNA and the respective amplification primers. DNA bands were obtained by agarose gel electrophoresis. Messenger RNA for the inhibin beta A subunit was demonstrated in all of the tissues studied. In contrast, inhibin alpha subunit mRNA was expressed in 60%, 50%, 75%, and 75% of the tumors in groups 1, 2, 3 and 4, respectively, whereas ACTR II mRNA was demonstrated in 20%, 37.5%, 62.5% and 50% of the tumors in each group. Coexpression of mRNAs for the inhibin alpha, and beta A subunits and ACTR II occurred in some brain tumors. The levels of inhibin alpha and ACTR II mRNA tended to be higher in the tumors with a higher grade of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Activin Receptors↗
Expression of inhibin alpha, and beta A subunit and activin type II receptor mRNAs in various human pituitary adenomas.
Inhibin and activin are known to be involved in the pituitary hormone secretion as well as proliferation of the pituitary. We studied the expression of inhibin alpha, and beta A subunit and activin type II receptor (ACTR 2) mRNAs in human pituitary adenomas to determine the significance of inhibin and activin in pituitary hormone secretion. Tumor tissues were homogenized immediately after resection in guanidinium thiocyanate to extract total RNA. PCR was performed with reversely transcripted cDNA and respective amplification primers. DNA bands obtained for inhibin alpha, beta A and ACTR 2 by agarose gel-electrophoresis were 367, 285, and 389 bp, respectively. Messenger RNAs for inhibin beta A were demonstrated in all of the pituitary tissues studied, namely in 3 GH, 2 ACTH, 6 PRL and 1 FSH producing adenomas and 17 non-functioning adenomas. Inhibin alpha mRNAs were detected in 10 of 12 functioning adenomas and 15 of 17 non-functioning adenomas. ACTR 2 mRNAs were found in 11 out of 17 non-functioning adenomas, but only found in 3 out of 12 functioning adenomas. These results suggested local production of activin, a homodimer of beta-subunits, and inhibin, a heterodimer of alpha and beta subunits, in most of the pituitary adenomas regardless of their hormone secretion. On the other hand, a significantly higher incidence of ACTR 2 in non-functioning adenomas than in functioning adenomas suggested that activin had its main site of action in non-functioning adenomas, which could be potential gonadotropinomas.
Activin Receptors↗
Reduction of telomeric length and c-erbB-2 gene amplification in human breast cancer, fibroadenoma, and gynecomastia. Relationship to histologic grade and clinical parameters.
BACKGROUND: Telomeric deletions contribute to genetic instability and may represent an important mechanism of carcinogenesis. Amplification of the c-erbB-2 gene has been demonstrated in breast carcinoma. The clinical significance of telomeric deletions and c-erbB-2 gene amplification therefore was studied in patients with breast disorders. METHODS: The Southern blot analysis was used to measure telomeric length as well as the c-erbB-2 gene amplification of breast carcinomas, adjacent normal breast tissues, fibroadenomas, and cases of gynecomastia. RESULTS: Significant reductions in telomeric length and concentration were observed in all breast tissues when compared to placental DNA. Mean telomeric lengths were lowest in carcinomas and fibroadenomas. There were no significant differences, however, in the telomeric lengths among tissues from patients with breast carcinomas, fibroadenomas, or gynecomastia. The degree of telomeric deletion correlated significantly with histologic grade and was most notable in Grade 3 (scirrhous) breast carcinoma. The extent of telomeric deletion reflects the histologic aggressiveness of breast carcinoma, and telomeric reduction already can be seen in the adjacent normal breast tissues from patients with breast cancer. c-erbB-2 gene amplification was observed in 26.8% of the patients with breast carcinoma. c-erbB-2 gene amplification was not observed, however, in patients with fibroadenomas or gynecomastia. The degree of telomeric deletion did not correlate with c-erbB-2 gene amplification, tumor size, clinical stage, steroid receptors, or prognosis. Telomeric length was shorter in lymph node-negative tumors than in lymph node-positive tumors. CONCLUSIONS: These findings indicate that a shorter telomere length reflects growth advantage in breast cancer tissue, and telomeric reduction may promote cancer progression.
Adult↗
Human plasma free activin and inhibin levels during the menstrual cycle.
The role of inhibin in gonadal function and reproduction has been confirmed by the measurement of plasma inhibin levels, but there has been no clinical data available on activin because of the lack of a good assay method. We measured plasma free activin levels during the normal menstrual cycle using a newly developed competitive protein binding assay with follistatin as the binding protein. Plasma inhibin levels were measured simultaneously using an alpha-subunit N-terminal fragment RIA with recombinant inhibin as the reference standard. Four normal women, aged 23-29 years, were investigated by obtaining plasma at 3-day intervals. Plasma inhibin levels showed some variation during the follicular phase, but a parallel rise in inhibin and progesterone was observed during the luteal phase. These findings confirmed those of previous studies. In contrast, plasma free activin levels did not show any substantial changes during the menstrual cycle. This study suggests that activin has no endocrine role in modulating the pituitary-gonadal axis during the normal menstrual cycle, while changes of inhibin reflect cyclic gonadal function and indicate an endocrine role for this protein in modulating gonadal activity.
Activins↗
Activin and inhibin secretion by cultured porcine granulosa cells is stimulated by FSH and LH.
Follistatin-free activin and inhibin levels were measured in the culture medium of porcine granulosa cells by a competitive protein binding assay and N-fragment RIA, respectively. Cultures were maintained for 6 days in MEM containing 10% fetal calf serum. FSH and HCG (1-1,000 IU/L) were added on day 2 to cultures containing 1 x 10(5) cells/ml and the medium was changed every 2 days. Granulosa cells secreted a large amount of progesterone, which indicated their luteinization. Activin and inhibin were both secreted throughout the 6 day culture period. Both of them increased equally in response to FSH and HCG in a dose-dependent manner on day 4, but their responses became discrepant on day 6, when the activin response decreased while the response of inhibin increased. This study demonstrated that cultured porcine granulosa cells secrete both activin and inhibin under the control of FSH and LH. The activin response was lost before that of inhibin, suggesting the role of activin at an earlier stage of luteinization.
Activins↗
Competitive protein binding assay for activin A/EDF using follistatin determination of activin levels in human plasma.
A sensitive and specific protein binding assay for activin A/EDF (activin) was developed using follistatin as a binding protein and [125I] labelled activin as a tracer. As 50% acetonitrile (CH3CN) separated free and follistatin-bound activin, plasma pretreated with an equal volume of CH3CN was used as the assay sample and B/F separation was also done with 50% CH3CN. The recovery of the assay was 85.0% and its sensitivity was 0.5 ng/ml. Crossreactivity with inhibin A was 1.8%. The mean plasma level of follistatin-free activin in normal subjects was 1.3 +/- 0.7%. (M +/- SD) ng/ml. Plasma free activin levels were generally elevated in patients with chronic renal failure or hematological diseases associated with anemia.
Activins↗
Effect of hemodialysis on the concentration of the seven tumor markers carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-related antigen, neuron-specific enolase, CA 125, CA 19-9 and CA 15-3 in uremic patients.
The incidence of the 7 tumor markers carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous cell carcinoma-related antigen (SCC), neuron-specific enolase (NSE), CA 125, CA 19-9 and CA 15-3 was studied before and after hemodialysis (HD) in 144 uremic patients who had no malignancies. Before HD, of all tumor markers, the mean concentration of SCC only exceeded the normal value. The positive rate was highest in SCC (95.1%), and that of CEA and NSE was 25.7 and 10.6%, respectively. However, AFP was within the normal range in all cases. Among CA antigens, the positive rate of CA 125 was 7.6%, of CA 19-9 was 6.3% and of CA 15-3 was 3.5%. After HD, the incidence as well as the mean concentration of all tumor markers increased. A parallel increment of total protein was observed after HD. The membrane filter used in HD appears to be insufficient to remove tumor marker proteins during HD. It is necessary to consider the clinical interpretation of elevated tumor markers in patients with uremia.
Antigens, Neoplasm↗
[A clinical evaluation of the CA 72-4 serum level as a possible tumor marker].
The level of CA 72-4 in serum has been measured in various diseases by an immunoradiometric assay using CA 72-4 RIA Kit for an evaluation of its clinical significance as a possible tumor marker. CA 72-4 showed a high positive rate in patients with ovarian and bile duct cancers. In contrast, the false positive rate was low in benign gynecological and digestive diseases. Serum CA 72-4 was found to be increased in patients with a mucinous cystadenocarcinoma and in other histological types in the early stages of an ovarian cancer. Further, the serum CA 72-4 level changed in parallel with the clinical course of the ovarian cancer. Therefore, our results suggest that measurement of CA 72-4 be combined with measurement of CA 125, so as to provide a better sensitivity and specificity in monitoring an ovarian cancer.
Antigens, Tumor-Associated, Carbohydrate↗
[Clinical evaluation of various tumor markers in pleural effusion and in the serum].
Various tumor markers and enzymes in the pleural effusion and serum have been measured in 47 patients with carcinoma and in 43 patients with benign disease, by means of a radioimmunoassay and biochemical methods. CEA in the pleural effusion showed a high specificity and sensitivity for the detection of the malignancy. In patients with a lung cancer, measurement of the NSE in the serum was more useful than in the pleural effusion. Further, both CA19-9 and SCC in the pleural effusion showed a high specificity in a differential diagnosis of cancer and benign diseases. On the other hand, CA 125, TPA and IAP in the pleural effusion and in the serum showed a high sensitivity, but a low specificity for diagnosing the malignancy. The levels of ADA were significantly higher in tuberculous pleural effusions than in carcinomatous effusions. Therefore, this suggests that measurement of the various tumor markers in both the pleural effusion and in the serum is useful in achieving a differential diagnosis of malignant and benign diseases.
Adenosine Deaminase↗
[Ovarian inhibin activity in rats with persistent estrus].
To investigate the significance of changes in ovarian inhibin in gonadal dysfunction with persistent estrus, female rats with persistent estrus were studied as animal model for polycystic ovaries (PCO). Newborn female Wistar rats treated with testosterone propionate s. c. (TP) and female rats raised under continuous light (LL) started at 9 weeks of age entered into continuous estrus 5 and 2 or 3 weeks after the treatment, respectively. Ovaries in both groups had many polycystic follicles Normal adult female rats with 4 day cycles were served as control. Ovarian inhibin content was measured by FSH suppressing activity of charcoal-treated ovarian homogenates using a rat anterior pituitary cell culture system. Blood samples were obtained at 11:00 a. m. and plasma levels of LH, FSH, PRL, estradiol (E2), progesterone (P) and testosterone were measured by RIA. Comparisons were made statistically between each experimental group and normal proestrus (PE). Both LH and FSH were similar to normal PE in TP LL, suggesting a lack of LH and FSH surges probably through hypothalamic dysfunction in TP and LL. Plasma PRL levels were variably elevated in both groups. Ovarian inhibin contents were comparably high to PE in both groups with parallel increases in plasma E2 and P. Plasma testosterone was elevated only in TP. In conclusion, female rats with persistent estrus induced by TP or LL exhibited polycystic ovarian changes similar to PCO. Increased inhibin content in TP and LL may reflect persistent follicular activity.
Animals↗
[Biochemical diagnosis of pheochromocytoma by determining normetanephrine and metanephrine concentrations in single voided urine].
Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.
Adrenal Gland Neoplasms↗
Testosterone restores testicular inhibin content in cryptorchid rats.
The effects of testosterone administration on testicular inhibin content and histology were studied in bilaterally cryptorchid rats, in which a marked decrease in testicular inhibin content had been observed. Mature male Wistar rats weighing approximately 300 g were made bilaterally cryptorchid by placing the testes in the abdominal cavity. Testosterone in oil, 0.1, 1.0 or 10 mg, was given i.m. each week. Testicular inhibin and testosterone content, histology and plasma LH, FSH and testosterone were studied 2 weeks later. Abnormally decreased testicular inhibin in cryptorchidism was restored toward normal by testosterone in a dose dependent manner in 2 weeks after surgery. Sertoli cell structure also recovered toward normal with increasing amount of testosterone. Decreased testicular testosterone content and Leydig cell atrophy were observed with suppressed plasma LH and FSH after testosterone. These results showed that the increased plasma concentration of testosterone had a stimulatory effect on the Sertoli cell function in cryptorchidism, in which compensated Leydig cell failure was demonstrated.
Animals↗
Studies on pituitary-gonadal function in patients with Cushing's syndrome.
Basal levels of sex steroids, and the responses of LH and FSH to LH-RH were studied in twenty-five female patients with Cushing's syndrome (17 Cushing's disease and 8 adrenocortical adenoma). Only two patients had a regular menstrual cycle. Amenorrhea or oligomenorrhea had been of long duration in the other cases except for three postmenopausal patients. In patients with Cushing's disease, basal estradiol was low or below normal in 86%. Progesterone was normal in 83%, but testosterone was high in half of the cases. The response of LH to LH-RH in patients with Cushing's disease was normal in 35%, low in 35% and high in 29% of the cases. FSH response to LH-RH was normal in 23.5%, low in 23.5% and high in 53%. In patients with adrenocortical adenoma, basal of estradiol was low or below normal, but progesterone and testosterone were normal in all cases. The response of LH and FSH to LH-RH in all patients with adrenocortical adenoma was higher than normal. In three postmenopausal women, a higher response of LH and FSH to LH-RH was seen in two cases and suppressed in one case. These data suggest that the main site of suppression of the gonadal axis in patients with adrenocortical adenoma is the gonad rather than the pituitary gland or hypothalamus, though the mechanism of hypogonadism in patients with Cushing's disease is heterogeneous.
Adolescent↗
Hypercortisolism and the resistance to dexamethasone suppression during gestation.
Maternal adrenocortical function was studied by measuring plasma cortisol and urinary free cortisol during gestation. Changes in suppressibility of pituitary-adrenocortical function were determined by dexamethasone administration. Urinary free cortisol as well as plasma cortisol increased during the course of gestation. The suppressibility by dexamethasone became less effective as pregnancy advanced. These results suggest that pregnant women have pituitary-adrenocortical hyperfunction and tissue refractoriness to glucocorticoid which increases during the course of gestation.
Adrenal Cortex↗
The changes in plasma cortisol and urinary free cortisol by an overnight dexamethasone suppression test in patients with Cushing's disease.
We studied the suppressibility of cortisol secretion in 15 patients with Cushing's disease by measuring morning plasma cortisol level as well as the 24-hour urinary free corisol (UFC) excretion following single doses of increasing amounts of dexamethasone (ranging from 0.5 to 32 mg) given at 11 p.m. The mean plasma cortisol level in patients with Cushing's disease was twice as high as in normal subjects, whereas the mean UFC in these patients was 6 times as high. Plasma cortisol in seven patients were suppressed by less than 4 mg of dexamethasone (in 2 cases, less than 0.5 mg; in 3 cases, less than 2 mg; and in 2 cases less than 4 mg). In these cases, basal plasma cortisol and UFC were less than 25 micrograms/dl and 350 micrograms/day, respectively. Among the other eight patients, plasma cortisol was partially suppressed in 5 cases and not suppressed in 3 cases by high doses of dexamethasone (16-32 mg). In these cases the basal plasma cortisol and UFC were more than 25 micrograms/dl and 350 micrograms/day, respectively. There was a significant correlation between the basal plasma cortisol and UFC (r = 0.687, p less than 0.01). These data suggest that the suppression by increasing amounts of dexamethasone in most cases with Cushing's disease was related to the severity of hypercortisolism.
Cushing Syndrome↗