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R Demura

Publications and source records attributed to R Demura.

At least 37 records · Page 2Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

[Radioimmunoassay of synthetic steroid hormones].

The problem and recent progress of radioimmunoassay for various kinds of synthetic steroid hormones are reviewed. The specificity and sensitivity depend mostly on the position of synthetic antigen (hemisuccinate or oxime). Using good antibodies, a direct radioimmunoassay without extraction procedures of samples is available. A simplified method is required for the monitoring of synthetic steroids to know the effects and side effects.

Betamethasone↗
PubMed1994

[Thyroid function in patients with anorexia nervosa and depression].

Thyroid hormone levels were measured in 21 patients with anorexia nervosa, 15 patients with depression and 16 patients with severe depression and were compared with those in 53 normal subjects. In anorexia nervosa and severe depressed patients, serum T3, T4, fT3, fT4 and T3/T4 ratio showed significantly lower values than those in normal subjects. However there was no difference between depressed patients and normal subjects. The serum TSH levels were within normal range in all of the studied subjects. Thus, thyroid hormone levels in severe depressed patients were similar to those in anorexia nervosa and the changes were inversely related to disease conditions. The supplementation of thyroid hormones to antidepressant relieved clinical symptoms in some of the severe depressed patients. These results suggested that the changes in thyroid hormone levels in anorexia nervosa and severe depression were mainly due to impaired conversion of T4 to T3 by increased cortisol secretion through emotional stress.

Adult↗
PubMed1994

[Clinical study of serum ErbB-2 protein using sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken')].

Sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken') was developed to determine the levels of c-erbB-2 oncogene product (ErbB-2 protein) in human sera, and a clinical investigation was carried out to evaluate this novel oncogene product. The mean serum concentration of the ErbB-2 protein determined from 364 donors was 4.0 +/- 0.69 ng/ml (mean +/- SD) for females and 4.5 +/- 0.96 ng/ml for males. Cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positivities of serum ErbB-2 protein in patients with breast carcinoma were 13.0% for primary cases and 47.9% for recurrent cases. Patients with hepatic disorders also had positive serum ErbB-2 protein levels, ie, 43.8% (7/16) for hepatocellular carcinoma and 28.9% (11/38) for hepatitis and liver cirrhosis, although the increase was slight and barely exceeded 10 ng/ml. In comparison with the levels of other tumor markers, such as CEA, CA 15-3 and NCC-ST 439, the serum ErbB-2 level was shown to have poor correlations, and was thus assumed to be useful for combination with those tumor markers. In serial determinations of serum ErbB-2 protein in two patients with recurrent breast carcinoma, the antigen increased preceding the increases in the other tumor markers, thereby also showing usefulness as a monitoring marker for breast carcinoma. In conclusion, these results indicated that ErbB-2 measurement improves the assessment of breast cancer in combination with other tumor markers and is useful as a tool for monitoring the clinical condition and the response for treatment in breast cancer.

Aged↗
PubMed1994

[Clinical evaluation of serum ErbB-2 protein using enzyme immuno assay (ErbB-2 EIA [Nichirei])].

The levels of ErbB-2 protein in serum samples from patients with breast cancer, other various malignant tumors, and benign diseases were determined using the sandwich EIA for clinical evaluation. In 364 healthy blood donors, cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positive rate of primary breast cancer was 13.0% (24/185) and that of recurrent breast cancer was 51.2% (62/121). No significant correlation was found between serum levels of ErbB-2 protein and other tumor markers, such as CEA, CA 15-3, and ST 439. Measurement of ErbB-2 protein in combination with these tumor markers showed increased sensitivities. The positive rates and levels of ErbB-2 protein in sera of patients with metastasis to multiple organs were significantly higher than those in patients with metastasis to only a single organ. In postoperative follow-up of two patients with recurrent breast cancer, the levels of ErbB-2 exceeded its cut-off value a few months earlier than did the other tumor markers. These results indicate that the measurement of the ErbB-2 protein in serum is useful for the diagnosis and a monitoring the relapse of breast carcinoma.

Biomarkers, Tumor↗
PubMed1994

[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")].

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.

Antibodies, Monoclonal↗
PubMed1994

[Changes of thyroid hormone levels during ACTH therapy in epileptic children].

To investigate the effect of ACTH on thyroid function, thyroid hormone levels were measured in twelve patients with epileptic children who were treated with ACTH. One week after daily administration of ACTH, serum T3, T4, TSH, thyroglobulin and T3/T4 ratio showed significantly lower values compared with those of pretreatment values (p < 0.001-p < 0.05). Thyroid hormone levels respectively showed negative correlation with cortisol levels before and one week after ACTH treatment respectively. Tapering of ACTH brought a rapid recovery of T3, T4, TSH and thyroglobulin levels with concomitant return of plasma cortisol levels to the normal range. These results suggested that excess ACTH suppressed thyroid hormone secretion mainly through a decreased TSH secretion and a peripheral conversion of T4 to T3 by increased cortisol levels.

Adrenocorticotropic Hormone↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

[Maternal and cord blood thyroid hormones in Graves' disease and fetal states].

Serum concentrations of thyroid hormones (T3, T4, fT3 and fT4), TSH and TRAb in 14 mothers with Graves' disease at 1-4 weeks before delivery were comparably studied with cord blood hormone levels and various fetal states. Twelve mothers were on anti-thyroid drugs and 2 were drug-free, with 8 being euthyroid and 6 being hyperthyroid. Serum concentrations of T3, T4 and fT3 in cord blood were all the same regardless of maternal thyroidal function. Though cord blood TRAb levels correlated with maternal levels, cord fT4 levels were low in those who given antithyroid drugs. TSH levels in cord blood were low in Cesarean section delivery and babies with low birth weight. Birth weight and gestational weeks were both inversely correlated with maternal T4, fT4, fT3 and TRAb concentrations. Thus, maternal hormone levels at late stage of pregnancy in Graves' disease could be useful indices for perinatal risk.

Adult↗
PubMed1993

[Recent progress in the diagnosis and treatment of hypopituitarism].

Measurement of basal pituitary hormone levels by IRMA made it possible to suspect even hypopituitarism because of the high sensitivity and specificity. Clinical application of TRH, LH-RH, CRF and GRF made it easier to diagnose pituitary reserves of individual pituitary hormones directly. Comparisons of GH or ACTH responses to ITT with those to CRF or GRF are especially useful for a differentiation of hypothalamic and pituitary lesions. A search for gene abnormality by various techniques may be necessary for a diagnosis of the nature of pituitary tumor as a cause of hypopituitarism. Replacement of growth hormone to adult GH deficiency is the greatest concern for future with a variety of dispute. Determination of plasma pituitary hormone levels is a good marker for a titration of a dosage of corticosteroid or thyroid hormone replacement.

Bromocriptine↗
PubMed1992

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↗
PubMed1992

Effect of LHRH on plasma 7B2 in patients with gonadotropin-producing pituitary adenomas.

Plasma immunoreactive (IR)-7B2 was measured in four patients with gonadotropin-producing pituitary adenomas. The basal level of plasma IR-7B2 was elevated in one of the four patients. Hyperresponse of plasma IR-7B2 to LHRH or LHRH/TRH was noted in two patients tested. 7B2 was positively stained in a paraffin-embedded section of gonadotropin-producing pituitary adenoma obtained at surgery. These findings suggest that 7B2 is produced in gonadotropin-producing pituitary adenomas and secreted into the blood stream under certain conditions. 7B2 may be a useful marker for gonadotropin-producing pituitary adenomas.

Adenoma↗
PubMed1992

Endothelin-3 immunoreactivity in gonadotrophs of the human anterior pituitary.

Endothelin (ET), originally discovered in vascular endothelial cells, has also been demonstrated in nonvascular tissues. The present study was undertaken to elucidate the presence of ET in the human pituitary. The avidin-biotin complex method with antiserum to ET-1 (and ET-2) or ET-3 was used to identify ET in human pituitaries obtained by autopsy. ET-3 immunoreactivity was found in the cytoplasm of large ovoid cells of the anterior pituitary. Using the double staining method, the cells containing ET-3 immunoreactivity were differentiated from cells containing ACTH, TSH beta, GH, PRL, and protein S-100. By staining with anti-LH beta antiserum in adjacent sections and using the double staining method, the cells were identified as gonadotrophs. No staining was observed in the posterior pituitary. In addition, no ET-1 (and ET-2) immunoreactivity was detected. The specific localization of ET-3 immunoreactivity in the gonadotrophs of the human pituitary suggests a possible role of ET-3 in the regulation of anterior pituitary function.

Adolescent↗
PubMed1992

A patient with a prolactinoma associated with an aldosterone producing adrenal adenoma: differences in dopaminergic regulation of PRL and aldosterone secretion.

A patient with a rare combination of prolactinoma and aldosterone producing adrenal adenoma (APA) was reported in relation to studies concerning dopaminergic regulation of PRL and aldosterone secretion. The patient is a 38-year-old female with plasma PRL and aldosterone concentrations (PAC) of 563 ng/ml and 54 ng/dl, respectively. A bolus of 10 mg of metoclopramide significantly increased plasma PRL in 6 normal subjects and in 4 patients with APA, whereas the responses were blunted in 7 patients with prolactinoma and in our patient. The response of aldosterone to metoclopramide was less than that of PRL, but similar in all studied subjects, indicating that the dopaminergic inhibition of aldosterone secretion is less than that of PRL in normal subjects and did not change in patients with APA or prolactinoma. Oral administration of 2.5 mg of bromocriptine suppressed plasma PRL significantly in all the subjects studied, but did not produce any consistent changes in PAC. Discrepancies in the response of PRL and aldosterone to metoclopramide and to bromocriptine suggest a difference in the dopaminergic regulation of PRL and aldosterone secretion in both normal subjects and patients with prolactinoma and APA. It is unlikely that reduced dopaminergic inhibition is the basis for hypersecretion of PRL and aldosterone in our patient.

Adenoma↗