Biomedical subjects

N Hizuka

Publications and source records attributed to N Hizuka.

At least 73 records · Page 4Linked 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

Treatment of acromegaly with long acting somatostatin analogue SMS 201-995.

Ten acromegalic patients were treated with the somatostatin analogue SMS 201-995 (SMS) for 3-38 weeks in various doses and by different administration routines (thrice daily or multiple sc injection). Plasma GH daily profiles, plasma IGF-I, urinary GH, serum TSH, IRI and fasting blood glucose (FBG) concentrations were measured before and during SMS treatment. Plasma GH rapidly decreased within one hour in all patients and was suppressed for at least 4 h after a 50 micrograms sc injection of SMS in 8 patients. Multiple injections of 300-600 micrograms/day SMS (25-50 micrograms X 12) suppressed GH throughout the day. Plasma IGF-I was completely normalized in 4 patients, and, in all but one of the others, decreased markedly. Urinary GH decreased within the first week of treatment in all patients and normalization was obtained in 3 patients. Shrinkage of the pituitary tumor, as determined by CT or MRI, was observed in 7 of 9 patients. Other clinical improvements, such as diminution or complete disappearance of swelling of soft tissues, excessive perspiration, and headache, were observed in 7 of 8 patients. Changes in serum TSH, IRI and FBG were seen in 3-4 patients, but without any apparent clinical problems. In conclusion, SMS is a useful clinical tool for treatment of acromegaly, and a multiple sc injection method seems to be preferable.

Acromegaly↗

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

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↗

PubMed1987

Demonstration of insulin-like growth factor I in human urine.

Immunoreactive and receptor-reactive insulin-like growth factor I (IGF-I) was demonstrated in human urine. Thirty percent of the IGF-I immunoreactivity in urine was free, and the remainder was a high mol wt form (approximately 43K). Urinary IGF-I was quantitated by RIA after extraction with octadecylsilyl silica cartridges (Sep-Pak C18 cartridge), a method that measures only free IGF-I. The mean urinary immunoreactive IGF-I levels in normal adults (n = 8) and patients with acromegaly (n = 10) or hypopituitarism (n = 9) were 72 +/- 7 (+/- SEM), 225 +/- 34, and 19 +/- 4 pg/mg creatinine, respectively; these mean values were significantly different from one another. The results indicate that IGF-I is present in human urine and that the quantity in urine is altered in patients with GH excess and deficiency.

Acromegaly↗

PubMed1987

Characterization of insulin-like growth factor I receptors on Madin-Darby canine kidney (MDCK) cell line.

Specific insulin-like growth factor I (IGF-I) receptors on the Madin-Darby canine kidney (MDCK) cell line were identified and characterized. [125I]IGF-I specifically bound to the cells, but [125I]insulin bindings to the cells was minimal. Unlabeled IGF-I displaced both the IGF-I and insulin bindings with potencies that were 100 and 10 times as great as insulin. By an affinity labeling technique, IGF type I receptors were present in the MDCK cells. IGF-I stimulated DNA synthesis and cell proliferation at physiological concentrations. On the other hand, insulin had a little effect on DNA synthesis. These data suggest that IGF type I receptors as demonstrated in MDCK cells are involved in DNA synthesis and cell proliferation.

Animals↗

PubMed1987

Decrease in IGF-I binding sites on human promyelocytic leukemia cell line (HL-60) with differentiation.

Specific insulin-like growth factor I (IGF-I) receptors on human promyelocytic leukemia cell line (HL-60) were identified and characterized. [125I]IGF-I specifically bound to the cells, and [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose dependent manner. [125I]IGF-I binding to the cells were displaced by multiplication stimulating activity (MSA) and porcine insulin, with potencies that were 10 and 100 times less than that of IGF-I, respectively. By an affinity labeling technique, IGF type I receptors were found to be present on the HL-60 cells. After the cells were differentiated to the macrophage-like cells by 12-o-tetra-decanoyl-phorbol-13-acetate (TPA) and 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), [125I]IGF-I binding to the cells decreased significantly. By Scatchard analysis, it was found to be due to a decrease in the number of IGF-I receptors. Thus, the differentiation of HL-60 cells to the macrophage-like cells was accompanied by a decrease in IGF-I receptors.

Affinity Labels↗

PubMed1987

Effects of IGF-I on proliferation and steroidogenesis of cultured adrenal zona glomerulosa cells.

In a primary culture of bovine adrenal zona glomerulosa cells, insulin-like growth factor I (IGF-I)/somatomedin C stimulated DNA synthesis, as measured by [3H] thymidine uptake, at concentrations of 10(-9) and 10(-7) M. IGF-I also prevented ACTH-induced suppression of [3H] thymidine uptake. IGF-I in no way affected aldosterone secretion during short-term exposure to cultured cells, however. Our findings suggest that IGF-I plays an important role in the proliferation of adrenal zona glomerulosa cells.

Adrenal Cortex↗

PubMed1987

A case report of growth attenuation during methionyl human growth hormone treatment.

A 10-year-old child with idiopathic growth hormone deficiency was treated with recombinant methionyl human growth hormone (m-hGH, Somatonorm) at a dose of 14 IU/week. Height increased from 122.3 to 126.5 cm during the first 9 months of treatment (5.6 cm/y), but only from 126.5 to 126.6 cm during the next 3 month of treatment (0.4 cm/y). Anti-hGH antibody was detected at 2 months of treatment, reached its maximum at the end of 9 months with a titer of 10(6) and a binding capacity of 2.0 mg/L. After switching from m-hGH to pituitary extracted hGH (p-hGH) treatment, his height increased again from 126.6 to 132.2 cm during the next 12 months of p-hGH treatment (5.6 cm/y). The cause of growth attenuation during m-hGH treatment was concluded to be the high titer of anti-hGH antibody. This is the first case in Japan and one of only three cases in which growth attenuation occurred during m-hGH treatment.

Antibodies↗

PubMed1987

Characterization of insulin-like growth factor I receptors on human erythroleukemia cell line (K-562 cells).

Specific insulin-like growth factor I (IGF-I) receptors on a human erythroleukemia cell line (K-562 cells) were identified and characterized. [125I]-IGF-I specifically bound to K-562 cells and the binding was displaced by unlabeled IGF-I in a dose dependent manner, and half maximal inhibition of the binding was observed at 7 ng/ml IGF-I. [125I]IGF-I binding to the cells was displaced by multiplication stimulating activity (MSA) and by porcine insulin, with potencies that were 10, and 100 times less than that of IGF-I, respectively. By an affinity labeling technique, IGF type I receptors were found to be present in the K-562 cells. When the cells were differentiated by hemin (40 microM), specific binding of [125I]IGF-I to the cells was decreased to 56.8 +/- 5.0% of that for undifferentiated cells. Furthermore, at physiological concentration of IGF-I stimulated thymidine incorporation into DNA and increased the number of cells. These data demonstrate that K-562 cells have specific receptors for IGF-I which may be functionally important for these cells, and that the IGF-I binding sites decrease with cell differentiation. This system might be useful in studying the interaction of IGF-I receptors.

Cell Differentiation↗

PubMed1986

Insulin-like growth factor I stimulates growth in normal growing rats.

The scarcity of purified somatomedin/insulin-like growth factor (SM/IGF) has prevented investigation of the mechanisms of SM/IGF action. Recently insulin-like growth factor I (IGF-I) has been synthesized by recombinant DNA technology. The availability of large quantities of the biosynthetic IGF-I made it possible to study its effects by administering 120 micrograms/day via s.c. implanted minipump to rats for 7 days. After this 7 day administration of IGF-I, the body weight increased to 197.6 +/- 3.5% of initial values; the value was significantly greater than that of the control (179.4 +/- 3.7% of initial values, P less than 0.01). The body length and tibial epiphyseal width in IGF-I-treated rats were also significantly increased over those of control rats. The weights of kidneys, liver, testes and pituitary in IGF-I-treated rats were greater than those in control rats as well. These results provide a first demonstration that IGF-I stimulates growth in normal rats in vivo, and suggest that IGF-I might be useful in the treatment of growth retardation.

Animals↗

PubMed1986

Growth hormone treatment in Turner's syndrome.

A total of 21 patients with Turner's syndrome were treated with pituitary hGH and/or somatrem for 1-2 years. Plasma non-esterified fatty acid increased significantly from 0.52 +/- 0.06 to 1.30 +/- 0.09 mEq/litre at 4 hours after injection of hGH, 4 IU (mean +/- SEM, p less than 0.001). Basal plasma IGF-1 levels were within the normal range; however, they increased significantly at 24 hours after the first three daily injections of hGH, 4 IU (basal, 0.92 +/- 0.14 units/ml; 24 hours, 1.39 +/- 0.16 units/ml; 48 hours, 1.68 +/- 0.19 units/ml; 72 hours, 1.91 +/- 0.22 units/ml; p less than 0.001). For long-term treatment, patients were given hGH, 4-16 IU for 1-2 years. Their height velocity increased to 5.5 +/- 1.2 cm/year and 5.1 +/- 0.6 cm/year in the first and second year of the treatment, respectively. These values were greater than the pretreatment value of 3.6 +/- 0.8 cm/year (p less than 0.001). Antibody against hGH was observed in 60% of the patients at the end of 12 months of somatrem treatment. 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

Characteristics of human erythrocyte insulin-like growth factor I receptors.

The scarcity of purified materials has prevented studies of the mechanism of insulin-like growth factor I (IGF-I) action. Recently, an IGF-I analog, Thr59-IGF-I, was synthesized by recombinant DNA technology. We found that this analog had binding characteristics similar to those of natural IGF-I in the radioreceptor assay system. We used this analog to characterize human erythrocyte IGF-I receptors as follows. Erythrocytes from 33 normal subjects specifically bound 6.9 +/- 0.7% (mean +/- SD)/2.8 X 10(9) cells/ml. Scatchard analysis of the binding data showed that the total number of receptors per erythrocyte was 13, and the affinity constant was 1.26 X 10(9) M-1, similar to that of other human IGF-I receptors previously reported. We also examined IGF-I receptors in patients with insulin receptor abnormalities. Although the specific values of IGF-I binding to erythrocytes were decreased or increased in parallel with those of insulin, the degrees of decrease or increase were much smaller. This suggests that the expression of insulin receptors and that of IGF-I receptors are discordant.

Adolescent↗

PubMed1986

Studies on the response of growth hormone (GH) secretion to GH-releasing hormone, thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin in acromegaly.

The plasma GH response to GH-releasing hormone (GHRH), TRH, or GnRH administration was examined in 25 acromegalic patients. Plasma GH levels increased in 21 patients after GHRH, in 19 after TRH, and in 4 after GnRH. The four GHRH nonresponders had had acromegaly longer than had the GHRH responders. No specific combination of GH responsiveness to these 3 releasing hormones was found among the patients. Infusion of 1 mg GHRH for 150 min gradually increased plasma GH levels, with some fluctuations, from the beginning to the end of infusion in normal subjects and in 7 patients who were GHRH responders, but a bolus injection of 100 micrograms GHRH at the end of the infusion did not further elevate plasma GH levels. These results suggest that desensitization to GHRH occurred in the normal subjects and acromegalic patients. However, in 5 acromegalic patients who responded to both GHRH and TRH, a bolus injection of 500 micrograms TRH given at the end of the 150-min infusion of 1 mg GHRH evoked a further plasma GH rise. In 5 normal subjects and 2 patients who were responders to GHRH but not TRH, a bolus injection of 500 micrograms TRH did not cause plasma GH elevation at the end of 150-min infusion of 1 mg GHRH. These results imply that TRH and GnRH stimulate GH secretion from the adenoma cells in vivo through receptors different from those for GHRH. In vitro studies using cultured pituitary adenoma cells from 2 patients revealed that the responses of GH secretion to GHRH were similar to those in vivo. These data, therefore, suggest that the responsiveness of GH secretion to stimuli is determined by the specificity of the receptors on adenoma cells. The action of somatostatin-28 was more potent than that of somatostatin-14 in the suppression of GH secretion from adenoma cells.

Acromegaly↗

PubMed1986

Treatment of pituitary dwarfism with methionyl human growth hormone in Japan.

Sixty-two patients with pituitary dwarfism were treated with three different preparations of methionyl hGH (m-hGH) for 3 to 14 months. They were given 0.5 IU/kg/week intramuscularly. The growth rate during treatment with the three different preparations was the same for each and increased from 3.5 +/- 0.9 to 8.2 +/- 1.7 cm/year. A high incidence of hGH antibody formation was observed following the treatment, but the titer of antibody was decreased according to the purity of m-hGH preparations. At the end of 12 month treatment with a highly purified preparation (Somatonorm III), 76.2% of the patients had hGH antibody. However, the presence of antibodies did not affect the growth rate except in one patient. No clinical or laboratory side-effects were observed following the treatment with m-hGH. Thus, m-hGH was considered to be useful for the treatment of GH deficient children.

Adolescent↗

PubMed1986

Oro-maxillofacial development in patients with GH deficiency and in normal short children.

Detailed oro-maxillofacial studies using dental cast, pantomogram and cephalogram were performed in 43 patients with GH deficiency aged 7-17 years and compared statistically to the results from 62 short children with normal GH secretion. The dental age was retarded as compared to the chronological age in patients with GH deficiency by a mean of 2.0 +/- 1.3 years. This value did not differ statistically from that observed in normal short children (1.7 +/- 0.8 years). However the bone age was significantly retarded in patients with GH deficiency (3.2 +/- 1.7 yrs vs 1.5 +/- 1.1 yrs, p less than 0.001). There was no difference between tooth size or cephalogram analysis results in the children in the two groups. The coronal arch length, basal arch width and basal arch length were shorter in patients with GH deficiency. These data indicate underdevelopment of the maxilla in patients with GH deficiency.

Adolescent↗

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↗