Biomedical subjects

N Hizuka

Publications and source records attributed to N Hizuka.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1985

Characterization of insulin-like growth factor I receptor on human erythrocytes.

[125I]Insulin-like growth factor I (IGF-I) specifically bound to erythrocytes; the binding was saturable, and time and temperature dependent. Steady state binding was reached at 16 h at 4 C, and specific binding averaged 14.3 +/- 0.7% (+/- SEM) at a concentration of 3.6 X 10(9) cells/ml in seven normal subjects. [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose-dependent manner. Scatchard analysis indicated a linear plot, and Ka and number of binding sites/cell were 1.43 +/- 0.07 X 10(9) M-1 and 20.7 +/- 2.2, respectively. Compared to IGF-I, the relative potencies of multiplication-stimulating activity and insulin for displacing [125I]IGF-I binding were 20% and 1%, respectively. [125I]IGF-I binding to erythrocytes from patients with acromegaly was lower than binding to cells from pituitary dwarfs. An inverse correlation between plasma IGF-I level and the number of IGF-I-binding sites per cell was found (r = -0.75; P less than 0.005). These results demonstrate that [125I]IGF-I binding to erythrocytes can be used for clinical measurement of the IGF-I receptor.

Acromegaly↗

PubMed1985

Plasma growth hormone and somatomedin-C responses to continuous growth hormone-releasing factor infusion in normal adult men.

The pituitary growth hormone (GH) responses during a 20-hour iv infusion of saline or human GH-releasing factor (hGRF-44) at 40 micrograms/h, followed by an iv bolus injection of hGRF at 2 micrograms/kg body weight, were studied in four normal adult men. During saline infusion only one or two pulses of plasma GH were observed. However, during hGRF infusion up to eight or ten pulses of GH were measured with an amplitude not different from that obtained during saline infusion. The mean +/- SEM integrated amount of GH secreted was 107 +/- 38.2 ng/ml.h in response to hGRF infusion, which was greater than the value of 25.4 +/- 3.5 ng/ml.h obtained during saline infusion. Plasma somatomedin-C also increased after hGRF infusion, but not after saline. After saline or hGRF infusion most of the subjects still responded to an iv bolus injection of the peptide (2 micrograms/kg). These results indicate that hGRF infusion augments GH secretion by increasing the number, but not the amplitude of GH pulses and that the infusion does not cause the pituitary somatotrophs to lose their capacity and ability to respond to hGRF subsequently.

Adult↗

PubMed1985

Effects of hGRF treatment of a patient with hGRF deficiency.

A 12-year old girl was admitted to our hospital for evaluation of her short stature. Her height was below -3.5 SD of the mean height for her age. She was diagnosed as having craniopharyngioma and treated surgically. Thereafter she was treated with thyroxine and hydrocortisone. One and a half years later, she revisited our hospital for treatment of short stature. Her plasma GH did not respond to insulin-induced hypoglycemia but increased after hGRF-44 administration, indicating hGRF deficiency. hGRF was therefore administered at a dosage of 100 micrograms twice a day subcutaneously for three months. Her height increased 1.6 cm during treatment, which corresponded to a height increase of 6.4 cm/year. These findings indicate that hGRF treatment stimulates height increase in patients with GRF deficiency. For complete evaluation of hGRF therapy, further studies will be required.

Child↗

PubMed1985

Plasma GH and somatomedin C responses to single and repeated administrations of human growth hormone releasing factor (hGRF).

Plasma growth hormone (GH) and somatomedin C responses to single and repeated administrations of synthetic human growth hormone releasing factor (hGRF-44) were studied in 29 patients with GH deficiency. hGRF-44 administered by single iv bolus (10 micrograms/kg), repeated iv boluses (50 or 100 micrograms, once a day), repeated iv infusions (2.5 micrograms/min for 90 min, once a day), and/or repeated im injections (100 micrograms, twice a day) for three to six consecutive days. Ten of 16 patients had plasma GH responses to a single iv bolus injection, i.e., their plasma GH increased above 5 ng/ml or twice the basal level. However none of them showed a plasma somatomedin C increase. To repeated iv bolus injections and repeated iv infusions of hGRF-44, 7 of 17 patients showed plasma GH responses, however in none of 7 patients did somatomedin C increase. Plasma somatomedin C did not increase after repeated im administrations of hGRF-44 for 5 days. Plasma somatomedin C increase was observed in two patients, from 0.32 to 0.54 U/ml and from 0.16 to 0.46 U/ml, in response to repeated iv boluses and repeated iv infusions, respectively. These results suggest that hGRF-44 stimulates plasma GH secretion in some patients with GH deficiency, however the increases are not enough to stimulate somatomedin generation.

Adolescent↗

PubMed1985

Oro-maxillofacial development in patients with Turner's syndrome.

Detailed oro-maxillofacial studies using dental casts, pantomograms and cephalograms were performed in 28 patients with Turner's syndrome and compared statistically to the results from 23 normal short children. Small tooth crown size, short tooth roots and advanced dental age were characteristic of patients with Turner's syndrome. However, the incidence of peg shaped teeth, malocclusion, high arched palate and congenital anodontia were not characteristic of patients with Turner's syndrome. The coronal arch width (C.A.W.) and basal arch width (B.A.W.) were greater and the coronal arch length (C.A.L.) and basal arch length (B.A.L.) were less in patient's with Turner's syndrome. These data indicate underdevelopment of the maxilla in the forward direction forming the wide-, flat-shaped facial characteristic of patients with Turner's syndrome.

Adolescent↗

PubMed1985

Plasma growth hormone (GH) responses to single and repetitive subcutaneous administration of GH releasing factor (hpGRF-44) in normal and GH deficient children.

Synthetic human pancreatic GRF (hpGRF-44) was administered sc to 8 normal children with short stature and 11 patients with GH deficiency. After a dose of 100-200 micrograms hpGRF-44, mean plasma GH levels reached a peak at 15 min of 27.2 +/- 6.4 (+/- SE) ng/ml in normal children. However the responses were variable and peak plasma GH varied from 10.1 to 56.5 ng/ml. Eight of 11 patients with idiopathic GH deficiency did not respond to sc administration of 100-300 micrograms hpGRF-44. However, a plasma GH increase of more than 5 ng/ml occurred in 2 patients and to twice the basal level in 1 patient. Their GH values were 14.3, 5.2 and 3.4 ng/ml, respectively. After repetitive administration of hpGRF-44 (200 micrograms, twice a day) sc for 5 consecutive days, 2 of 8 patients restored their responsiveness, but the remaining patients did not show GH rise in response to both sc and iv bolus administration of hpGRF-44. Repetitive hpGRF-44 administrations for 5 days had no effect on somatomedin-C production.

Adolescent↗

PubMed1985

Plasma growth hormone (GH) and somatomedin C response to continuous growth hormone-releasing factor (GRF) infusion in patients with GH deficiency.

Pituitary growth hormone (GH) responses during a 10-h iv infusion of saline or human GH-releasing factor (hGRF-44) at 500 ng/kg/h, followed by an iv bolus injection of hGRF-44 at 2 micrograms/kg body weight, were studied in 10 patients with GH deficiency. During saline infusion in 4 patients, small plasma GH increase were observed in 2 patients. However, during hGRF infusion in 6 patients, up to 4 or 13 pulses of GH secretion were observed. The mean integrated GH pulse area during hGRF infusion was 22.5 +/- 5.2 (SE) ng/ml X h, which was greater than that obtained during saline infusion. Plasma somatomedin C levels did not increase after hGRF infusion. After saline or hGRF infusion all patients responded to an iv bolus injection of the peptide. These results indicate that hGRF infusion augments GH secretion by increasing the number and amplitude of GH pulses and that the infusion does not cause pituitary somatotrophs to lose their capacity to respond to hGRF subsequently.

Adolescent↗

PubMed1984

Failure of bromocriptine to alter the qualitative characteristics of human growth hormone in acromegaly.

The role of bromocriptine as a therapeutic agent for acromegaly is uncertain. In the present study we have attempted to determine whether bromocriptine therapy causes qualitative changes in plasma human growth hormone (hGH) in acromegaly. When eight paired samples obtained before and during bromocriptine therapy were filtered over Sephadex G-100 there was no difference in the elution profiles. When the "little" hGH peak from each of the eight paired samples was pooled, lyophilized, and assayed in both radioreceptor assay (RRA) and radioimmunoassay (RIA), the RRA/RIA before treatment was not different than during treatment. When bromocriptine in pharmacologically significant concentrations was incubated with cultured human lymphocytes in vitro, there was no alteration in hGH binding properties. These results demonstrate directly that bromocriptine does not change the form or receptor-reactive properties of plasma hGH and, further, that the drug does not alter at least one form of human growth-hormone receptor.

Acromegaly↗

PubMed1984

Plasma growth hormone response to growth hormone-releasing factor in acromegalic patients.

Synthetic growth hormone-releasing factor (hpGRF-44) (100 micrograms) was administered intravenously to ten acromegalic patients. The time when the peak of plasma GH occurred as well as the magnitude of the response were highly variable among these ten patients. From the GH response patterns the ten acromegalic patients were tentatively classified into three groups: (1) those highly GRF-dependent whose GH level increased to four times basal, (2) those moderately GRF-dependent whose GH level rose to less than two times basal and (3) those GRF-resistant whose GH level did not change. These data suggest that there may be differences in the GRF-receptor system in pituitary adenomas causing acromegaly.

Acromegaly↗

PubMed1984

Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism.

Synthetic human pancreatic GRF (hpGRF-44) was administered as an iv bolus to 28 normal children with short stature and 27 patients with GH deficiency. After a dose of 1 or 2 micrograms hpGRF-44/kg BW, mean plasma GH levels peaked at 15 and 30 min, respectively, with corresponding values of 30.1 +/- 4.7 and 33.2 +/- 3.7 ( +/- SE) ng/ml in normal but short children. The overall plasma GH response was greater than that of other GH stimulation tests such as insulin-induced hypoglycemia, glucagon-propranolol or L-dopa administration. Plasma LH, FSH, TSH, PRL, and cortisol levels were not altered by hpGRF-44 injection. Sixteen of 27 patients with GH deficiency did not respond to a 2 micrograms/kg BW hpGRF-44. However, plasma GH increases to greater than 5 ng/ml occurred in the remaining 11 patients. Their GH levels reached peaks between 15 and 90 min, with values ranging between 5.8 and 17.8 ng/ml. Two of these responding patients were infused iv with hpGRF-44 at 2.5 micrograms/min for 90 min after receiving an iv bolus injection of 2 micrograms/kg BW. Their plasma GH levels increased and remained near peak values throughout the infusion period. However, no increase in plasma GH levels occurred after a second bolus injection of hpGRF-44 given at the end of the infusion. These results suggest that hpGRF-44 is useful for the diagnosis of GH deficiency in individuals with short stature and that some patients with GH deficiency, diagnosed on the basis of established tests, have GH responses to hpGRF-44.

Adolescent↗

PubMed1984

Stimulation of glycosaminoglycan synthesis by somatomedin and insulin in rat chondrocytes via somatomedin receptors.

Using cultured normal rat chondrocytes we have investigated 1) the effects of somatomedin and insulin on glycosaminoglycan (GAG) synthesis and 2) somatomedin and insulin binding sites. We confirmed that somatomedin and insulin stimulate GAG synthesis in normal rat chondrocytes. The maximal responses of somatomedin and insulin in GAG synthesis were the same, but the stimulation of GAG synthesis by maximally effective concentrations of insulin plus somatomedin was not cumulative. Cultured rat chondrocytes had binding sites for somatomedin and insulin, and the binding was displaced by both somatomedin and insulin. Somatomedin is much more effective than even large amounts of unlabelled insulin in displacing both somatomedin and insulin binding. Anti-insulin receptor IgG, which inhibits insulin binding to human placental membrane, did not affect GAG synthesis stimulated by insulin nor did it inhibit insulin binding to chondrocytes. Somatomedin used for GAG synthesis and displacement was the partially purified somatomedin A with a biological activity of 80 U/mg. Therefore the possibility that substances other than somatomedin A, which was contaminated in this preparation, affected this result could not be excluded completely. However, these results suggest that somatomedin and insulin act on normal rat chondrocytes through a somatomedin receptor.

Animals↗

PubMed1984

Plasma GH response to hpGRF-44 in normal children of short stature and patients with GH deficiency.

Synthetic human pancreatic GRF (hpGRF-44) was administered as an iv bolus to 139 normal children of short stature and 63 patients with GH deficiency. After a dose of 1 and 2 micrograms hpGRF-44/kg BW, mean plasma GH levels peaked at 15 and 30 min, respectively, with corresponding values of 32.2 +/- 3.6 and 31.8 +/- 2.4 (+/- SE) ng/ml in normal but short children. There were no differences according to sex or age in plasma GH response to hpGRF-44 between the ages of 4 and 18 years. A similar plasma GH response was observed when 2 micrograms hpGRF-44/kg BW was administered two hours after lunch. The overall plasma GH response was greater than that of insulin-induced hypoglycemia and was similar to that obtained in the glucagon-propranolol test. Thirty-five of 63 patients with GH deficiency did not respond to a 2 micrograms hpGRF-44/kg BW. However, plasma GH increases to greater than 5 ng/ml occurred in the remaining 28 patients. Their mean GH level reached a peak at 90 min with a value of 8.8 +/- 0.8 ng/ml. These results suggest that hpGRF-44 is useful for evaluating pituitary GH reserve in children of short stature and that some patients with GH deficiency, diagnosed on the basis of established tests, have GH responses to hpGRF-44.

Adolescent↗

PubMed1984

Plasma growth hormone secretion during constant growth hormone-releasing factor infusion.

Synthetic human pancreatic growth hormone-releasing factor (hpGRF-44) was infused intravenously at a constant rate of 2.5 micrograms/min for 180 minutes in 3 normal boys of short stature. Plasma GH levels reached a peak at 60-120 min with a mean value (+/- SEM) of 69.1 +/- 14.3 ng/ml, and then, declined gradually in spite of continuous hpGRF-44 infusion up to 180 minutes. Similarly, constant infusion of hpGRF-44 at a rate of 2.5 micrograms/min in 5 normal but short boys for 90 minutes, together with an iv bolus injection of hpGRF-44 (2 micrograms/kg) administered at 0 and 90 minutes, elicited a prompt rise in plasma GH 15-30 minutes after the first bolus but no significant elevation of GH was observed after the second bolus. In contrast, when two iv bolus injections of hpGRF-44 (2 micrograms/kg) were given in 4 normal boys with short stature at 0 and 90 minutes, respectively, significant elevation of plasma GH was found after each bolus. These results suggest that under constant infusion of GRF the pituitary experiences a down-regulation after the initial peak of GH response, possibly due to desensitization to GRF.

Adolescent↗

PubMed1984

Plasma growth hormone responses to repetitive administrations of growth hormone releasing factor in patients with pituitary dwarfism.

Plasma growth hormone (GH) responses to the repetitive administrations of synthetic human pancreatic growth hormone releasing factor (hpGRF-44) were studied in 15 patients with GH deficiency (11 diagnosed as idiopathic and 4 diagnosed as secondary to hypothalamo-pituitary tumor). hpGRF-44 was administered by single iv bolus (2 micrograms/kg), repetitive im (100 micrograms, twice a day), and/or repetitive iv infusion (2.5 micrograms/min for 90 min, once a day) for three to six consecutive days. Three of the eleven idiopathic GH deficient patients had plasma GH responses to both single iv bolus injection and repetitive administrations by im, or iv infusion of hpGRF. In four of the remaining eight, who had not had peak plasma GH levels above 5 ng/ml to a single iv bolus of the peptide, repetitive administrations of hpGRF-44 by im injection and/or iv infusion induced GH responses to the peptide. In the four patients with secondary GH deficiency, three had plasma GH response to hpGRF administration but one patient, who had indications of pituitary disorder, did not show any plasma GH response to either single iv injection or repetitive administrations of hpGRF-44. These data show that repetitive administrations of hpGRF-44 can induce plasma GH responses in some GH deficient patients who do not respond to a single iv bolus of the peptide.

Adolescent↗

PubMed1984

Quantitative differences between immunological and receptor binding activities of hGH in pituitary adenomas from patients with acromegaly.

Human growth hormone (hGH) in the pituitary extracts from patients with acromegaly and normal subjects was measured by radioimmunoassay (RIA) and radioreceptor assay (RRA) using pregnant rabbit liver membrane, and the RRA to RIA ratios of hGH were calculated. The RRA to RIA ratio of hGH for acromegaly was higher than that for normal (0.90 +/- 0.03 vs 0.75 +/- 0.03, p less than 0.01). When the pituitary extracts were gel filtered on Sephadex G-100 column there were three immunoreactive hGH peaks ("pre-big", "big", and "little" hGH); there were no significant differences in gel filtration patterns of hGH between acromegaly and normal. The "little" hGH component (major component) had a higher RRA to RIA ratio than "pre-big" hGH and "big" hGH in both acromegaly and normal. "Little" hGH extracted from acromegaly had a higher RRA to RIA ratio than that from normal (1.14 +/- 0.09 vs 0.93 +/- 0.04, p less than 0.05). These data support the hypothesis that hGH synthesized in acromegaly may be different from normal.

Acromegaly↗

PubMed1983

Treatment of idiopathic pituitary dwarfism with methionyl human growth hormone.

Ten patients with idiopathic pituitary dwarfism were treated with methionyl human growth hormone (met-hGH) produced by recombinant DNA technology. They were given 0.5 IU/kg/week of met-hGH for three months. There were no significant changes in physical, blood, urine examinations. Their height increased between 1.5 and 2.7 cm during the 3 months of treatment, which was calculated to be equivalent 6.0 and 10.8 cm per year with a mean increase of 8.7 cm. Anti-hGH antibody was observed in all patients between one and two months of treatment with a titer between 10(1)X and 10(4)X. In spite of the formation of antibodies, the growth rate did not decrease in 7 of the 10 cases.

Adolescent↗

PubMed1983

Effects of somatomedin and other factors on glycosaminoglycan synthesis in cultured rat chondrocytes.

We have investigated the effects of hormones and serum on glycosaminoglycan (GAG) synthesis, using cultured rat chondrocytes isolated from growing cartilage. Somatomedin A stimulated GAG synthesis at a physiological concentration, however in the case of insulin the dose required to stimulate GAG synthesis was 500 times as great as the physiological concentration. Parathyroid hormone also increased GAG synthesis. In contrast, hydrocortisone inhibited GAG synthesis at a pharmacological dosage. None of the following had any effect on GAG synthesis: epidermal growth factor, fibroblast growth factor, triiodothyronine, growth hormone, sex steroid or vitamin D3. Human serum up to a concentration of 1% stimulated GAG synthesis. Serum from patients with acromegaly stimulated GAG synthesis more than that from those with hypopituitarism.

Animals↗