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Biomedical subjects

K Shizume

Publications and source records attributed to K Shizume.

At least 145 records · Page 8Linked to original sources
PubMed1988

Twenty-four hour plasma GH, FSH and LH profiles in patients with Turner's syndrome.

We studied the plasma GH profiles in 6 patients with Turner's syndrome and 6 normal girls of short stature by sampling every 20 min for 24 hours. We observed episodic secretion of GH in these subjects. The mean plasma 24 h GH level in patients with Turner's syndrome was 3.6 +/- 1.4 (SD) ng/ml which was significantly lower than that of normal short girls (7.1 +/- 2.2 ng/ml, p less than 0.01). The GH secretion during both nighttime and daytime was decreased in the patients with Turner's syndrome, however the number of pulses did not differ significantly. There were no correlations between the mean plasma 24 h GH level on one hand and peak GH level obtained after GH provocative test and plasma somatomedin C on the other. Plasma FSH and LH levels were also measured in 4 patients with Turner's syndrome. Both levels were elevated and there observed no clear pulsatile secretion of FSH, but, some pulsatile secretion of LH was observed in two patients. These data indicate that patients with Turner's syndrome have decreased endogenous GH secretion, even though they show normal GH responses to GH provocative tests.

Adolescent↗
PubMed1988

Human growth hormone-releasing hormone (hGH-RH; hGRF) treatment of four patients with GH deficiency.

Four patients with GH deficiency aged 6-14 years old were treated with hGRF for 6 months. Before the treatment maximal plasma GH responses to 50 micrograms iv hGRF administration were 48.6, 12.1, 24.3 and 13.0 ng/ml, respectively. Human GRF was administered at a dosage of 50-100 micrograms twice a day subcutaneously. In two patients, the growth rate was increased from 2.4 and 2.0 cm/year to 8.2 and 9.8 cm/year, respectively. In the other two patients, the growth rate did not change with hGRF treatment. Plasma somatomedin C levels increased in one patient but did not change in the other three. Antibody to hGRF was observed in two patients during the treatment, but the presence of antibody did not affect the growth rate.

Adolescent↗
PubMed1988

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↗
PubMed1988

The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells.

The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10(-6) mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.

Animals↗
PubMed1988

3,3',5'-Triiodothyronine inhibits ontogenetic development of iodothyronine-5'-deiodinase in the liver of the neonatal mouse.

To elucidate the effect of rT3 on iodothyronine-5'-deiodinating activity (I-5'-DA) in the liver of neonatal mice, rT3 was injected sc on the 5-8th day after birth and I-5'-DA in the liver was determined. A single injection of rT3 (0.01-1 microgram/g) inhibited the ontogenetically developing I-5'-DA in a dose- and time-dependent manner. The inhibitory effect was reversible and specific for I-5'-DA. Lineweaver-Burk analysis revealed that the time- and dose-dependent decrease in the enzyme activity was due to a decrease in Vmax with no alteration in Km values (5 x 10(-8) mol/l). The maximal inhibitory effect was observed at a dose of 1 microgram rT3/g, whereas the inhibitory effect was diminished at greater doses (4-10 micrograms/g), probably owing to a contamination with T4 of the rT3 preparation administered. Furthermore, consistent with our previous in vitro findings, rT3 inhibited the I-5'-DA induced by T3 in the liver of neonatal mice. These findings suggest that rT3 inhibited I-5'-DA in the liver of neonatal mice by decreasing the amount of enzyme available to the substrate and that rT3 also elicited an antagonistic effect against T3 in the induction of I-5'-DA in vivo.

Animals↗
PubMed1988

Immunohistochemical localization of atrial natriuretic peptide binding sites in juxtaglomerular cells and vascular walls of rat kidney.

Since the kidney is one of the major sites of action for atrial natriuretic peptide (ANP) and immunoreactive ANP has been detected in tissue extract by radioimmunoassay, we have applied the immunohistochemical technique by using the avidin-biotin complex method to investigate ANP binding sites in the rat kidney. Although no immunostaining was observed in the kidney of control rats, immunoreactive ANP was present in the juxtaglomerular cells, the vascular walls of interlobular arteries, arcuate arteries, arterioles including vas afferens and vas efferens, and the medullary peritubular capillary of ANP-pretreated rats. In contrast, no tubular structure was stained. These results suggest that ANP may affect renin secretion via its direct action on the juxtaglomerular cells and that it predominantly induces natriuresis by its effects on renal hemodynamics.

Animals↗
PubMed1988

Effects of glycosylation inhibitors on human growth hormone receptor in cultured human lymphocytes.

IM-9 cultured human lymphocytes were treated with N-linked glycosylation inhibitors, N-linked oligosaccharide processing inhibitors, or neuraminidase to study the effect of glycosylation modification on human growth hormone binding and molecular weight of surface hGH receptor. One mg/l tunicamycin and 20 mmol/l glucosamine decreased 125I-hGH binding to the cells to 46.3 +/- 2.4% (mean +/- SEM) and 21.9 +/- 0.2% of the controls, respectively. The hGH binding was 33.0 +/- 18.4% of the control value in the cells treated with monensin. The inhibition of binding was due to a decrease in the hGH receptor number without any affinity changes in these cells. Neither 1 mg/l swainsonine nor 100 mg/l castanospermine had any effect on the hGH binding. On the other hand, 125I-hGH binding to neuraminidase-treated cells was significantly enhanced with accompanying affinity changes. When 125I-hGH was cross-linked to IM-9 cells, there were no differences in the molecular weight of hGH receptor complexes (140 K) between untreated cells and cells treated with tunicamycin, glucosamine, monensin, or castanospermine. However, the 128 K hGH-receptor complex appeared in swainsonine-treated cells; this complex was sensitive to endoglycosidase H. These data show that the altered carbohydrate moiety changed hGH binding and the size of surface hGH receptor and suggest that glycosylation of receptor is important for the binding of hGH and for its physiological action.

Alkaloids↗
PubMed1988

Withdrawal of endogenous somatostatin induces secretion of growth hormone-releasing factor in rats.

Secretion of GH occurs in episodic bursts under the dual control of two hypothalamic peptides, GH-releasing factor (GRF) and GH-inhibiting factor (somatostatin, SRIF). Recent studies in rats suggest that episodic GH secretion is generated by the periodic release of GRF, which is associated with the simultaneous withdrawal of SRIF secretion. To test the possibility that GRF discharge is functionally coupled with the withdrawal of SRIF, we investigated whether acute withdrawal of SRIF can induce GRF release by the rat hypothalamus using highly specific antisera against SRIF and rat GRF. In conscious unrestrained rats, i.v. administration of SRIF antiserum at the period of the GH trough induced a rapid onset of the GH secretory surge with a peak value of 309 +/- 67 micrograms/l (mean +/- S.E.M.) 30 min after injection. Pretreatment with antiserum to rat GRF resulted in a approximately 83% suppression of the GH surge induced by SRIF antiserum without affecting the trough GH values. GRF antiserum also significantly inhibited the spontaneous GH surge. In urethane-anaesthetized rats, as in conscious rats, an acute phasic GH release was caused by SRIF antiserum despite the interference of anaesthesia with spontaneous GH secretion. A further surge-like GH secretion was not restored during the next several hours, however, with the GH secretory profile being characterized by a tonic increase in the baseline levels of GH. In the anaesthetized rat antiserum to rat GRF, having no effect on basal GH levels, similarly inhibited by approximately 66% the acute GH surge induced by SRIF antiserum and decreased by about 30% the later sustained rise in GH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Phorbol ester pretreatment attenuates the growth hormone (GH) response to GH-releasing factor in cultured rat pituitary cells.

The effect of phorbol ester pretreatment on rat (r) GH release induced by GH-releasing factor (GRF) or 8-bromo-cyclic (c)AMP was investigated using rat pituitary cells cultured in monolayers. Pretreatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 h significantly suppressed the rGH release induced by GRF, but not that by 8-bromo-cAMP 20 h later; this suppressive effect of TPA was concentration-dependent from 8 to 160 nmol/l, and complete suppression was observed after pretreatment with 80-160 nmol TPA/l. Production of cAMP by pituitary cells stimulated with GRF was similarly attenuated in TPA-pretreated cells. The rGH responsiveness to GRF of these cells was fully recovered on prolonged culture (40 h), suggesting that the inhibitory effect of TPA is reversible. In contrast, pretreatment with GRF (5 nmol/l) resulted in suppression of the rGH response to subsequent exposure to GRF (5 nmol/l) or 8-bromo-cAMP (10 mmol/l), but not to TPA. These observations suggest that pretreatment with TPA modifies the rGH response to GRF at steps before the formation of cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Stimulation of alkaline phosphatase activity by thyroid hormone in mouse osteoblast-like cells (MC3T3-E1): a possible mechanism of hyperalkaline phosphatasia in hyperthyroidism.

In order to elucidate the mechanism of increased alkaline phosphatase (AI-P) activity of bone origin in serum of patients with hyperthyroidism, the effects of thyroid hormone on mouse osteoblast-like cells (MC3T3-E1) were studied in vitro. Triiodo-L-thyronine (T3) and thyroxine (T4) produced a dose-dependent increase in AI-P activity in the cells at minimum concentrations of 10(-10)M T3 (free T3, 5 x 10(-12) M) and 10(-8) M T4 (free T4, 8 x 10(-11) M), respectively. Scatchard analysis revealed that MC3T3-E1 cells contained nuclear binding sites specific for T3 with an apparent Kd of 120 pM (maximum number of binding sites, approximately 2500 per cell). When cells were cultured with T3 in alpha-minimal essential medium (alpha-MEM) for a prolonged period, AI-P activity also became detectable in the conditioned medium. In contrast to rat osteosarcoma cells (ROS 17/2.8), MC3T3-E1 cell growth was inhibited by T4 in a concentration-dependent manner. These findings suggest that thyroid hormone inhibits proliferation and stimulates differentiation of mouse osteoblast-like cells. Since T3 and T4 stimulate AI-P activity not only in the cells but also in the medium, we speculate that the hyper-alkaline phosphatasia frequently seen in patients with hyperthyroid Graves' disease is partly due to a direct effect of thyroid hormone on osteoblasts or osteoblast-like cells.

Alkaline Phosphatase↗
PubMed1988

Urinary IGF-I measurement and its clinical application.

Immunoreactive and receptor-reactive IGF-I was found to be present in human urine; 30% of the IGF-I immunoreactivity in urine was in its free form and the remainder was a high molecular weight form (approximately 40,000 MW). Urinary IGF-I was quantified by radioimmunoassay after extraction by Sep-Pak C18 cartridge, a method that measures only the free form of IGF-I. Daily (24-hour) urinary IGF-I excretion was measured in 3 hypopituitary children and 16 short normal children. The IGF-I level in the 24-hour urine samples correlated with the plasma IGF-I level and the mean 24-hour plasma GH concentration. The mean 24-hour plasma GH concentration, however, correlated better with the GH level in the 24-hour urine samples and the plasma IGF-I level than with the urinary IGF-I value. The mean IGF-I levels in single urine samples from normal subjects lay between those from patients with acromegaly (which were high) and those from patients with hypopituitarism (which were low). There were overlaps, however, in individual values between the normal and hypopituitary patients. These data indicate that urinary IGF-I values are altered by the GH secretion state, though the clinical application of urinary IGF-I measurement may be limited.

Acromegaly↗
PubMed1988

Treatment of hypopituitarism with recombinant somatropin for 1 year.

Twenty-five hypopituitary patients were treated with recombinant somatropin for 1 year at a dosage of 0.5 IU/kg/week. In previously untreated patients (n = 16), heights increased by between 4.5 and 10.2 cm, with a mean height velocity of 7.7 +/- 1.8 cm/year (mean +/- SD). In previously treated patients (n = 9), heights increased by between 3.9 and 7.6 cm, with a mean height velocity of 5.8 +/- 1.0 cm/year, similar to that observed during previous treatment with pituitary GH. Anti-GH antibodies were observed in two patients at a low titre. The antibodies disappeared in one patient during the treatment. These data indicate that recombinant somatropin has a growth promoting effect and low immunogenicity.

Adolescent↗
PubMed1987

Production of interleukin 1 alpha-like factor and colony-stimulating factor by a squamous cell carcinoma of the thyroid (T3M-5) derived from a patient with hypercalcemia and leukocytosis.

In order to elucidate the pathogenesis of humoral hypercalcemia and leukocytosis in a 71-year-old patient with squamous cell carcinoma of the thyroid, bone-resorbing activity (BRA) and colony-stimulating activity in the conditioned medium of T3M-5 cells, a clonal cell line established from the tumor, were studied. Gel chromatography of the concentrated conditioned medium revealed respective single peaks of colony-stimulating activity (Mr approximately 27,000) and BRA (Mr 15,000-20,000). BRA did not elicit parathyroid-hormone-like activity but greatly enhanced phytohemagglutinin-induced thymocyte proliferation. This interleukin 1 (IL-1)-like activity exactly coeluted with BRA upon gel chromatography, DEAE-Sepharose ion-exchange chromatography, and isoelectric focusing (pI, 4.7-5.2). BRA was partially inhibited by indomethacin and hydrocortisone, and completely inhibited by anti-IL-1 alpha antiserum, whereas anti-IL-1 beta antiserum had no effect. Furthermore, transplantation of T3M-5 cells into nude mice caused marked hypercalcemia as well as leukocytosis. These findings suggested that excessive production of colony-stimulating factor and IL-1 alpha-like factor by the squamous cell carcinoma was responsible for leukocytosis and hypercalcemia, respectively, in the tumor-bearing nude mice and in the patient. Since several similar cases have been reported in Japan, the syndrome of leukocytosis and hypercalcemia associated with certain solid tumors may constitute a new paraneoplastic syndrome.

Aged↗
PubMed1987

Effects of tumor promoters (mezerein, teleocidin and palytoxin) on growth hormone secretion from rat anterior pituitary cells cultured in monolayer.

The effects of compounds with tumor promoting activity (mezerein, teleocidin and palytoxin) on rat growth hormone (rGH) release was compared to that of TPA (12-O-tetradecanoyl phorbol-13-acetate). Mezerein and teleocidin both of which are activators of protein kinase C (TPA type tumor promoter), elicited rGH release about 3.5 to 4 fold above control values. The ED 50 was 16 nM for mezerein, 1.1 nM for teleocidin and 1.5 nM for TPA. In contrast to mezerein or teleocidin, a non-TPA type tumor promoter (palytoxin) which does not activate protein kinase C failed to stimulate rGH release. These observations suggest that the activation of protein kinase C is essential in the release of rGH induced by the tumor promoters.

Acrylamides↗
PubMed1987

Coronary hemodynamics and cardiac beating modulate atrial natriuretic factor release from isolated Langendorff-perfused rat hearts.

The role of coronary hemodynamics and cardiac beating on atrial natriuretic factor (ANF) release was studied in the isolated Langendorff-perfused rat heart. ANF release was measured by radioimmunoassay. When the coronary flow rate was changed, ANF release decreased or increased in a flow-dependent manner. When the perfusion pressure was changed, ANF release also increased or decreased, respectively, with concomitant changes in coronary flow rate. Furthermore, perfusion with 50 mM potassium chloride showed immediate cardiac arrest and a decrease of ANF release to an undetectable level with a significant decrease in coronary flow. However, low but readily detectable amounts of ANF were released when coronary flow rate was maintained. These results may suggest that coronary hemodynamics and cardiac beating could be factors modulating ANF secretion from the atrium.

Animals↗
PubMed1987

Tumor necrosis factor type alpha (cachectin) stimulates mouse osteoblast-like cells (MC3T3-E1) to produce macrophage-colony stimulating activity and prostaglandin E2.

To elucidate the mechanism of tumor necrosis factor alpha (TNF-alpha)-induced bone resorption, the effects of recombinant human TNF-alpha on mouse osteoblast-like cells (MC3T3-E1) were studied. TNF-alpha stimulated MC3T3-E1 cells to produce prostaglandin E2 (PGE2) and macrophage colony stimulating activity (M-CSA) in a dose-dependent manner. TNF decreased alkaline phosphatase (AL-P) activity of MC3T3-E1 cells. These TNF effects were observed at 1 ng/ml (approximately 6 X 10(-11)M). The inhibitory effect on AL-P activity was reversible and the cell growth of MC3T3-E1 cells was only slightly affected by TNF. These findings suggest that both PGE2 and M-CSA stimulated by TNF-alpha are possibly involved in osteoblast-mediated osteoclastic bone resorption, whereas inhibition of AL-P activity may lead to a decrease in bone formation.

Animals↗
PubMed1987

Inhibitory effect of norepinephrine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro.

Effects of catecholamines on immunoreactive corticotropin-releasing factor (I-CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Norepinephrine had a potent inhibitory effect on I-CRF release in a dose-dependent manner at 0.1 nM-1 microM concentrations, but dopamine did not. This inhibitory effect of norepinephrine was completely blocked by propranolol, but only partially blocked by phentolamine. Isoproterenol also had a potent inhibitory effect at 0.01-100 nM concentrations, and a high dose of phenylephrine (10 nM) inhibited I-CRF release. Clonidine did not influence I-CRF release. These results suggest that norepinephrine inhibits I-CRF release mainly through the beta-adrenergic receptor and partially through the alpha 1-receptor.

Adrenergic Agonists↗