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Biomedical subjects

A Kuwayama

Publications and source records attributed to A Kuwayama.

At least 73 records · Page 4Linked to original sources

Concomitant secretion of adrenocorticotropin, beta-endorphin, and gamma-melanotropin from perfused pituitary tumor cells of Cushing's disease: effects of lysine vasopressin, rat median eminence extracts, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone.

Regulation of secretion of ACTH-, beta-endorphin-, and gamma-melanotropin-like immunoreactivities (ACTH-LI, beta-EP-LI, and gamma-MSH-LI, respectively) was studied by using a perfused Sephadex column containing dispersed pituitary tumor cells obtained from three patients with Cushing's disease. Serial dilution of the perfusion medium gave lines parallel to the standard curve in each RIA for ACTH, beta-EP and gamma-MSH, suggesting that immunoreactive materials in the medium are immunologically indistinguishable from the authentic peptides. Gel exclusion chromatography of the medium revealed the existence of ACTH, beta-lipotropin (beta-LPH), beta-EP, and their possible precursor protein. gamma-MSH-LI consists of a major peak of big gamma-MSH eluted near the elution position of beta-LPH, suggesting the entire or nearly entire N-terminal portion of the precursor molecule. The addition of lysine vasopressin and rat median eminence extracts (MEE) to the perfusion system concomitantly enhanced the release of ACTH-LI, beta-EP-LI, and gamma-MSH-LI, although the dose-response relationship was clear-cut only in the case of MEE. TRH and LRH also elicited the concomitant release of these peptides in one patient, in whom combined administration of TRH and LRH significantly augmented plasma cortisol levels when studied preoperatively. The molar ratio of ACTH-LI to beta-EP-LI was approximately 1.0, whereas gamma-MSH-LI was about one fourth of ACTH-LI when compared on a weight basis. These results indicate that 1) ACTH-producing human pituitary adenomas concomitantly secrete ACTH, beta-LPH, beta-EP, and big gamma-MSH, and 2) lysine vasopressin, MEE, TRH, and LRH act directly on pituitary cells to stimulate the release of these peptides.

Adenoma↗

Anterior pituitary function after transsphenoidal selective adenomectomy in patients with Cushing's disease.

The anterior pituitary function in 25 patients with Cushing's disease was assessed before and after transsphenoidal adenomectomy. Pituitary adenoma was detected and removed in 24 cases, resulting in clinical remission in 22. Postoperative hypoadrenocorticism was observed in all of the cases with remission, necessitating substitution of glucocorticoid. One case had a recurrence after a year in remission. Plasma ACTH and cortisol rapidly decreased after surgery and remained at subnormal levels. However, diurnal rhythmicity of ACTH and cortisol appeared in 5 of 9 cases within 6 months after surgery and exhibited normal suppressibility in response to low dose dexamethasone. The impaired ACTH response to hypoglycemia was restored after surgery. The GH response to hypoglycemia and the TSH response to TRH were improved by correction of hypercorticism and became evident over time. These results suggest that preoperative impairment of anterior pituitary hormone secretion is secondary to hyperadrenocorticism and that ACTH hypersecretion by a primary pituitary adenoma is the primary etiology in Cushing's disease. We conclude that transphenoidal pituitary exploration should be considered as a first choice of treatment of Cushing's disease because of its high clinical remission rate in association with normalization of other endocrine functions.

Adenoma↗

Follow-up study on treatment in 27 patients with Cushing's disease: adrenalectomy, transsphenoidal adenomectomy and medical treatment.

27 patients with Cushing's disease were treated over a period of 18 years at the Departments of Medicine and Surgery, Nagoya University School of Medicine and the following results were obtained. 1) Adrenalectomy. 21 of 27 patients with Cushing's disease underwent adrenalectomy. 19 patients had total bilateral adrenalectomy and 2 patients unilateral adrenalectomy. 4 patients died, the cause of death not being related directly to adrenalectomy. 9 of 15 bilaterally adrenalectomized patients had hyperpigmentation even though they had been given substitution therapy with cortisol 20-30 mg daily. They had elevated plasma ACTH levels, which were not completely suppressed by 2 mg of dexamethasone or 2.5 mg of bromocriptine per day. 2) Adenomectomy, 5 patients had adenomectomy via the transsphenoidal approach. 3 patients were cured but one of them has required postoperative substitution therapy with cortisol for hypopituitarism for one year until today. 2 of 5 adenomectomized patients had a recurrence of Cushing's syndrome after remission for 6-8 months. One of these recurrent cases has been subsequently treated successfully with bromocriptine, a dopaminergic drug. 3) Medical treatment. 2.5 mg per day of bromocriptine has been effective in 2 patients without a pituitary adenoma and ineffective in the other 4 patients with a pituitary adenoma. 24 mg per day of cyproheptadine, an antiserotoninergic drug was not effective in any of the 4 patients with a pituitary adenoma.

Adenoma↗

Morphofunctional study of pituitary adenomas with acromegaly by immunoperoxidase technique and electron microscopy.

In attempting to establish a functional classification of acidophilic adenomas of the pituitary gland, immunoperoxidase staining techniques specific for growth hormone (GH), prolactin (PRL), and luteinizing hormone (LH) were carried out. Surgically removed specimens from 24 acromegalic patients were studied. The pathologic observations were then compared with the basal plasma levels of each of the hormones. The existence of GH was demonstrated in all patients. Immunohistologically, GH-secreting adenomas could be subdivided into three types: Type I had the highest plasma-GH level (average 121 ng/ml), while the average plasma-GH levels of types II and III were 103 ng/ml and 73 ng/ml, respectively. This result suggested that the serum-GH level may correlate with the GH cell population in a tumor. In 13 of the acromegalic patients, immunoenzyme methods were utilized in order to identify prolactin cells. No clear correlation between serum-PRL levels and the distribution of PRL cells could be demonstrated. A few immunoreactive LH cells were found in 13 patients. These LH cells may be a mixture of normal cells, based on our clinical finding.

Acromegaly↗

Immunoreactive beta-endorphin and adrenocorticotropin in human cerebrospinal fluid.

To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushing's disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelson's syndrome, Cushing's syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions.

Acromegaly↗

[An endocrinological study of hyperprolactinemia and its treatment (author's transl)].

Twenty-six cases of women with pituitary adenoma and seven cases of women with functional hyperprolactinemia were studied to evaluate the effects of neurosurgery and Bromocriptine treatment. In the patients with pituitary adenoma, the mean serum PRL level was significantly higher than that in the functional cases. Among the patients with pituitary adenoma, the serum PRL levels were roughly correlated to the size of the tumors. Basal serum LH, FSH and 17 beta-estradiol levels were lower in the patients with pituitary macroadenoma than in those with microadenoma. Neurosurgery was performed on fourteen patients of pituitary adenoma. Of ten cases with visual disturbance, it was necessary to use Bromocriptine to reduce the serum PRL to the normal level after operation. In the treatment of sixteen patients with microadenoma, Bromocriptine alone was used for eight of them and surgery was performed on four. As a result, there was a significant lowering of the serum PRL level and induction of regular menses in ten patients. Regular menses were induced by means of Bromocriptine treatment in all of the patients with functional hyperprolactinemia. Our data indicate that neurosurgery, either selective or combined with Bromocriptine, can normalize PRL levels and induce regular menses in patients with hyperprolactinemia.

Adenoma↗

[Measurement of methionine-enkephalin-like substance in CSF from normal subjects and patients with pituitary adenoma (author's transl)].

Methionine-enkephalin-like substance was measured in CSF by the radioreceptor-assay established by Furui et al. Samples were obtained from preoperative 20 cases, in which were included 11 cases of pituitary adenoma, 3 cases of craniopharyngioma, 2 cases of pseudtumor cerebri and 4 normal cases, by lumbar puncture. Also postoperative measurement of this substance and pre- and postoperative measurement of ACTH in plasma were performed in 5 cases of Cushing's disease. Five ml of CSF was chromatograpied on two successive columns, lyophilized and assayed for opiate receptor affinity against 3H-dihydromorphine. Measured values were expressed as methionine-enkaphalin equivalents using the displacement curve run in parellel. Methionine-enkephalin-like substance level ranged from less than 0.5 to 20.0 pmoles/ml in all cases and mean value was 2.6 pmoles/ml (+/- 1.0 S.E.) in normal subjects. In Cushing's disease the level was not elevated preoperatively (2.1 +/- 0.3) and did not significantly decrease postoperatively (1.6 +/- 0.4 pmoles/ml) in contrast to the decrease of ACTH in plasma. It is suggested that methionine-enkephalin-like substance in CSF is not derived from ACTH producing cells of pituitary gland. One case of craniopharyngioma showed very high value. This case revealed diabetes insipidus at sampling. The possibility of participation of methionine-enkephalin in secretion of antidiuretic hormone was discussed.

Adenoma↗

[The correlationship between basal prolactin levels and the suppressive effect of CB-154 or L-DOPA on GH release in acromegalic patients (author's transl)].

It has been reported that the plasma growth hormone (GH) and prolactin (PRL) levels in acromegalic patients were suppressed after intensive administration of dopaminergic drugs, but we found that the plasma GH levels in some acromegalic patients were not suppressed. Plasma GH and PRL levels after a single oral administration of CB-154 (2.5mg) and L-DOPA (1g) were measured in 18 active acromegalic patients with and without galactorrhea. 1. The mean plasma GH levels after the administration were clearly suppressed in 8 patients with galactorrhea, while they were not suppressed in 10 patients without galactorrhea. These drugs were more effective in suppressing plasma GH levels in acromegalic patients with galactorrhea and hyperprolactinemia. 2. We calculated the responsiveness of the plasma GH level as follows: GH responsiveness (%) = (mean plasma GH level after the administration of CB-154 or L-DOPA)/ (basal GH level) x 100. The basal plasma PRL levels were inversely correlated with GH responsiveness (CB-154: r=-0.690, p less than 0.01. L-DOPA: r=-0.541, p less than 0.05). It was found that the effect of dopaminergic drugs on plasma GH levels was closely correlated with basal PRL levels in acromegalic patients. This implies that the chronic administration of CB-154 may be effective in acromegalic patients with galactorrhea and hyperprolactinemia.

Acromegaly↗