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Biomedical subjects

K Shizume

Publications and source records attributed to K Shizume.

At least 217 records · Page 12Linked to original sources
PubMed1986

Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly.

The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly.

Acromegaly↗
PubMed1986

Radioimmunoassay for insulin-like growth factor I (IGF-I) using biosynthetic IGF-I.

We produced antiserum to insulin-like growth factor I (IGF-I), and developed a specific and sensitive radioimmunoassay (RIA) for IGF-I using the biosynthetic IGF-I. This antiserum to IGF-I was specific for IGF-I; no cross-reactivities with multiplication stimulating activity, porcine insulin or human growth hormone (hGH) were detected. The sensitivity was 10-25 pg/tube with 50% displacement at 125 pg/tube. The intra- and inter-assay coefficients of variation for IGF-I were 5.4 and 9.7%, respectively. The plasma IGF-I levels as determined by RIA in normal adults (N = 46), patients with active acromegaly (N = 31), and pituitary dwarfs (N = 31) were 21.6 +/- 1.0, 157.3 +/- 17.0, and 2.5 +/- 0.3 ng/ml (Mean +/- SEM), respectively, indicating the levels were GH-dependent. The plasma IGF-I levels were significantly increased from 2.2 +/- 0.2 to 26.5 +/- 3.2 ng/ml after hGH administrations for three consecutive days in five pituitary dwarfs. The IGF-I levels were low in patients with hypothyroidism and liver cirrhosis, but were normal in patients with chronic renal failure. These data confirm previous reports and this radioimmunoassay proves useful in evaluating plasma IGF-I levels.

Acromegaly↗
PubMed1986

Characterization of immunoreactive corticotropin and corticotropin-releasing factor in human adrenal and ovarian tumours.

The distribution of immunoreactive ACTH (I-ACTH) and corticotropin-releasing factor (I-CRF) in the human adrenal was determined and these peptides were indentified in adrenocortical adenomas from patients with primary aldosteronism. Cushing's syndrome, and ovarian tumours and compared with the results in phaeochromocytomas. I-ACTH and I-CRF, mainly localized in the adrenal medulla from patients without endocrine disorders, showed a good correlation with the epinephrine concentrations. I-ACTH and I-CRF were present in all the above-mentioned tumours. Gel filtration of I-ACTH and I-CRF from these tumours showed the presence of large molecular weight forms of these peptides as well as authentic peptides. The trypsinization study of I-CRF from phaeochromocytoma suggested that such large molecular weight forms were the precursors of authentic CRF. High performance liquid chromatography showed I-CRF in these tumours to be similar to hypothalamic CRF. Phaeochromocytoma tissue slices incorporated [3H]leucine into ACTH and CRF. These findings raised the possibility that I-ACTH and I-CRF are synthesized and processed in phaeochromocytoma.

Adenoma↗
PubMed1986

Treatment of Turner's syndrome with methionyl human growth hormone for six months.

Twenty patients with Turner's syndrome were treated with methionyl human growth hormone (met-hGH) produced by recombinant DNA technology. Plasma non-esterified fatty acid (NEFA) (mean +/- SEM) increased significantly from 0.52 +/- 0.06 to 1.30 +/- 0.09 mEq/l at 4 h after the first administration of 4 IU of met-hGH (P less than 0.001). Basal plasma somatomedin C (SM) levels were within the normal range; however, they increased significantly at 24 h after the first three daily injections of 4 IU of met-hGH (basal, 0.92 +/- 0.14; 24 h, 1.39 +/- 0.16; 48 h, 1.68 +/- 0.19; 72 h, 1.91 +/- 0.22 U/ml; P less than 0.001). For long-term treatment, the patients were given 16 IU of met-hGH per week for 6 months. The height increase during treatment was greater in 16 patients, but smaller in 4 than before treatment. The heights increased between 1.4 and 3.7 cm during 6 months of treatment, which corresponds to between 2.8 and 7.4 cm/year. The mean increase of 5.7 +/- 0.4 cm/year was greater than the pretreatment value of 3.7 +/- 0.2 cm/year (P less than 0.001). There was a positive correlation between growth rate and maximum increase in SM (r = 0.51, P less than 0.05). Antibody against hGH appeared in 3 patients after 2 months; 10 of the 20 patients had antibody after 6 months of treatment. However, the antibody did not suppress the growth effect of met-hGH. Otherwise there were no significant changes in physical, blood, or urine examinations. These results indicate that hGH treatment is useful for the acceleration of growth velocity in patients with Turner's syndrome.

Adolescent↗
PubMed1986

Long-term treatment of idiopathic hyperaldosteronism using trilostane.

Three patients with idiopathic hyperaldosteronism were continuously treated with trilostane, a competitive inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH) (3 to 4 2/3 years). Trilostane, in conjunction with antihypertensive drugs, effectively decreased plasma aldosterone levels and improved hyperaldosteronism symptoms without undesirable side effects. Trilostane continued to be effective even when treatment was continuous. Rapid ACTH testing (iv bolus of 0.25 mg alpha 1-24 ACTH) was done on the day without trilostane after long-term treatment, and plasma levels of aldosterone and cortisol were compared to those obtained during a pre-treatment period. Results suggest that the inhibitory effect of trilostane on steroid biosynthesis rapidly disappears following discontinuance of trilostane administration even after long-term treatment, and that continuous treatment causes no significant or irreversible change in steroid biosynthesis. These results suggest that trilostane is a safe, feasible therapeutic agent for long-term treatment of idiopathic hyperaldosteronism.

Adrenocorticotropic Hormone↗
PubMed1985

Identification and initial characterization of transforming growth factor-like mitogen(s) in human anterior pituitary.

Transforming growth factor (TGFs) are a family of peptide(s) defined by their ability to induce anchorage-independent growth of non-neoplastic indicator cells in soft agar. We found that acid-ethanol extracts of human anterior pituitary tissues were able to stimulate colony growth of normal rat kidney fibroblasts in soft agar. When subjected to gel-filtration on a column of Bio-Gel P-60 in 1 M acetic acid, the majority of TGF activity eluted in fractions corresponding to an apparent mol wt 15,000. The activity was heat- and acid-stable, but was inactivated by treatment with trypsin and dithiothreitol. Pituitary TGF-like materials did not compete with epidermal growth factor (EGF) for receptor binding and did not require EGF for colony-forming activity. Thus, human pituitary TGF was not like type alpha or type beta TGF.

Binding, Competitive↗
PubMed1985

Antisera to atrial natriuretic factor reduces urinary sodium excretion and increases plasma renin activity in rats.

Although the presence of atrial natriuretic factor in the blood has been demonstrated by radioimmunoassay, its biological activity and physiological significance has not been elucidated. Using specific antiserum against atrial natriuretic factor, we investigated the effect of passive immunization in rats. A significant reduction of urine output and urinary sodium excretion lasted for about 30 min after intravenous administration of antiserum. The effects were more pronounced in rats pretreated with deoxycorticosterone acetate and saline. Plasma renin activity was increased after the administration of antiserum. No significant effects on the urinary sodium excretion was observed following injection of normal rabbit serum. The results of this study provide evidence indicating that endogenous atrial natriuretic factor plays an important role in the regulation of urinary water and sodium excretion and plasma renin activity.

Aldosterone↗
PubMed1985

Atrial natriuretic factor inhibits vasopressin secretion from rat posterior pituitary.

The effects of synthetic atrial natriuretic factor (ANF) were studied in superfused rat posterior pituitary gland. ANF (10(-6)M, 10(-10)M) significantly inhibited basal as well as KC1 (50 mM) or angiotensin II-stimulated immunoreactive arginine vasopressin secretion. The magnitude of inhibition was greater at 10(-6)M than at 10(-10)M. ANF also decreased cAMP secretion and increased cGMP secretion from the posterior pituitary. These results suggest that ANF directly acts on the posterior pituitary to inhibit arginine vasopressin secretion and that this effect is, at least, partly mediated by the changes in cyclic nucleotide production.

Angiotensin II↗
PubMed1985

In vitro study of immunoreactive corticotropin-releasing factor release from the rat hypothalamus.

Immunoreactive corticotropin-releasing factor (I-CRF) release from rat hypothalami was studied in vitro utilizing a perifusion of rat hypothalami and a rat CRF RIA. Basal release of I-CRF from the hypothalamus of adrenalectomized or hypophysectomized rats was higher than in that of normal rats. K+-induced I-CRF release was completely suppressed by omission of Ca++ from the medium. Dexamethasone suppressed I-CRF release from hypothalami, but not from median eminence (ME). C-AMP and angiotensin II had mild stimulatory effects on I-CRF release. These results suggest that 1) the feedback mechanism acts mainly on a higher level than ME, and 2) c-AMP and angiotensin II may be involved in CRF-releasing mechanism(s).

Adrenalectomy↗
PubMed1985

Rat atrial natriuretic polypeptide stimulation of adrenal zona glomerulosa cell growth.

Rat atrial natriuretic polypeptide (rANP) was found to stimulate [3H] thymidine incorporation into the DNA of bovine adrenal glomerulosa cells in a primary culture in a dose-dependent manner. The minimum effective dose was a very low concentration (10(-12) M of ANP), suggesting that ANP had a physiological effect. These findings are the first indication that ANP possesses growth-stimulating activity with regard to adrenal zona glomerulosa cells.

Adrenal Cortex↗
PubMed1985

The satiety effect of growth hormone-releasing factor in rats.

The effect of growth hormone-releasing factor (GRF) on feeding behavior in rats was examined. Starvation-induced feeding was suppressed by intraventricular administration of 1 nmol and 4 nmol of synthetic human GRF (hGRF). Food intake was not affected when the peptide was administered by intraperitoneal injection. Furthermore, centrally administered hGRF also suppressed feeding in hypophysectomized rats. These results suggest that GRF suppression of food intake is mediated through the central nervous system independent of its effect on pituitary growth hormone secretion.

Animals↗
PubMed1985

[A simple and highly sensitive radioimmunoassay for 8-arginine vasopressin in human plasma using a reversed-phase C18 silica column].

A highly sensitive and simple radioimmunoassay for the measurement of 8-arginine vasopressin (AVP) in human plasma has been developed. The dose response curve ranges from 0.025 to 8 pg/tube. This simple extraction technique employing an ODS C18 column recovered 87.1 +/- 10.4 (mean +/- SD)% of AVP in the range of 1-10 pg/ml added to 0.5 ml plasma. Determination of AVP in each fraction of plasma, which was gel-filtrated through a Sephadex G25 (1 X 25 cm), revealed that the fraction of plasma AVP was superimposed on that of authentic AVP, and interference of non-specific substances was completely eliminated by an ODS C18 column. Using the assay, 13 of 16 patients with diabetes insipidus (DI) showed plasma AVP concentrations ranging from 0.03 to 0.21 pg/ml, and the other 3 patients had less than 0.03 pg/ml. The AVP concentrations of DI were clearly distinguished from those obtained in normal subjects (0.30-4.20 pg/ml, n = 65). The within and between assay variability was about 10% each. Plasma AVP concentrations (mean +/- SD) of normal subjects (n = 6) standing, sitting, and supine after an overnight of fluid deprivation were 2.41 +/- 1.15, 1.95 +/- 0.85 and 0.97 +/- 0.48 pg/ml (30 min after) respectively. Plasma AVP concentrations of normal subjects (n = 6) after water load (20 ml/kg wt) were clearly reduced from 1.89 +/- 1.00 (before) to 0.42 +/- 0.21 (standing for 60 min) and also from 0.89 +/- 0.41 to 0.40 +/- 0.22 pg/ml (supine for 60 min).

Adult↗
PubMed1985

Graves' disease with neutropenia and marked splenomegaly: autoimmune neutropenia due to propylthiouracil.

A 38-year-old man with Graves' disease taking propylthiouracil (PTU) for 6 years developed neutropenia and marked splenomegaly. After subtotal thyroidectomy with discontinuance of PTU the patient remained asymptomatic for the last two and half years. The serum obtained during the period of neutropenia demonstrated opsonic activity to neutrophils of the patient as well as of normal volunteers. This opsonic antineutrophil activity was located in the IgG fraction of the serum. Furthermore, PTU at the concentration (0.1-1.0 micrograms/ml) attainable in the patient's serum significantly stimulated [3H] thymidine incorporation in the patient's lymphocytes. These findings indicate that the patient developed autoimmune neutropenia by producing opsonic antineutrophil antibodies in association with the PTU therapy.

Adult↗
PubMed1985

Renotropic stimulation of DNA synthesis of proximal tubules and endothelial cells in the outer medulla.

We explored the effects of ovine pituitary-derived renotropin on renal DNA synthesis in castrated hypophysectomized mice. Administration of the preparation at a dose of 47 micrograms for 5 days was followed by significant increases in renal DNA (134% of controls), and in kidney dry weight, protein and RNA. A time course study showed that [3H]-thymidine incorporation into renal DNA peaked at 8-10 h after one injection (60 micrograms) 1.9 times higher than in controls. Autoradiographic studies indicated that labeling indices increased significantly in proximal tubules (17 times) and endothelial cells (4 times) in the outer renal medulla of treated mice compared to controls. Nuclear areas in these cells also increased significantly. Our studies demonstrated a time course of new DNA synthesis stimulated by a renotropin and identified renotropin target cells.

Animals↗
PubMed1985

Immunoreactive corticotropin-releasing factor in human plasma.

Plasma immunoreactive corticotropin-releasing factor (I-CRF) levels were determined by using a human CRF radioimmunoassay and an immunoaffinity procedure. The basal plasma I-CRF level in normal subjects was 6 +/- 0.5 pg/ml (mean +/- SD). We found that most plasma I-CRF levels were affected by stress, negative feedback, and circadian rhythm. Basal I-CRF levels were high in patients with Addison's disease, Nelson's syndrome, hypopituitarism stemming from pituitary macroadenoma, and CRF- and adrenocorticotropic hormone-producing tumors. A very low, but significant, amount of I-CRF was detected (1-3 pg/ml) in patients with Cushing's syndrome, in corticosteroid-treated patients, and in a patient with hypothalamic hypopituitarism. These results suggest that a major component of plasma I-CRF is of hypothalamic origin, however, other extrahypothalamic tissues cannot be ruled out as a minor source of plasma I-CRF.

Adrenal Gland Diseases↗
PubMed1985

Stimulation of renal deoxyribonucleic acid synthesis by a pituitary-derived renotropin and its inhibition by testosterone and thyroxine.

Kidney slices were obtained from castrated-hypophysectomized male rats treated with a single injection of several different gonadotropin preparations (two ovine LH fractions, one bovine LH fraction, and one hCG fraction) or vehicle, then incubated in a buffer containing [3H]thymidine. Only one of the above, an ovine LH preparation, increased [3H]thymidine incorporation into renal DNA, with a peak occurring 8-10 h after injection and therefore termed renotropin. However, in hypophysectomized rats with intact testes, such an effect was not observed. Furthermore, while testosterone propionate alone did not alter basal incorporation in castrated-hypophysectomized rats, it abolished the incorporation that was stimulated by renotropin. These results suggest that androgens, whether of testicular origin or exogenously administered, suppress the increased incorporation of [3H]thymidine stimulated by renotropin. This antagonistic effect of androgen was also observed with T4, but to a lesser degree. Our findings confirm the presence of renotropin, which could not be attributed to other known pituitary hormones, and suggest that there is a complex interaction between this factor and two other renal growth-promoting hormones, testosterone and T4.

Animals↗