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Biomedical subjects

K Shizume

Publications and source records attributed to K Shizume.

At least 91 records · Page 5Linked to original sources
PubMed1990

Radioimmunoassay for insulin-like growth factor II (IGF-II).

Insulin-like growth factor II (IGF-II) levels in human plasma were measured in physiological and pathological conditions by radioimmunoassay (RIA) with biosynthetic IGF-II. This RIA was specific for IGF-II and cross-reactivity with IGF-I was 1%. The sensitivity was 15 pg/tube with 50% displacement at 50 pg/tube. The intra- and inter-assay coefficients of variation for IGF-II were 6.3 and 9.3%, respectively. The plasma IGF-II levels in normal adults, patients with hypopituitarism and patients with active acromegaly were 589.6 +/- 15.8, 800.9 +/- 45.6 and 330.3 +/- 24.3 ng/ml, respectively. After human growth hormone (hGH) treatment in hypopituitarism, IGF-II slightly increased, but not significantly. After adenomectomy in patients with acromegaly, IGF-II significantly decreased. These data indicate that IGF-II concentrations in plasma were partially GH dependent. This GH dependency was less than that of IGF-I. IGF-II was low in patients with anorexia nervosa and with liver cirrhosis and high in patients with renal failure. In two cases with extrapancreatic tumor-associated hypoglycemia, plasma IGF-II was increased to 1123.8 and 843.5 ng/ml, and returned to normal after tumor resection. These data showed that IGF-II was partly dependent on GH and nutritional conditions and that IGF-II was the most likely cause of some cases of hypoglycemia with extrapancreatic tumor. This specific and sensitive RIA of IGF-II would be useful in evaluating its physiological and pathological role in plasma and tissue.

Acromegaly↗
PubMed1990

Recurrent pneumothoraces and mediastinal emphysema in systemic lupus erythematosus.

Neither pneumothorax or mediastinal emphysema are well recognized pulmonary manifestations of systemic lupus erythematosus (SLE). We describe a 41-year-old woman with severe lupus pneumonitis complicated by recurrent pneumothoraces and mediastinal emphysema. Other features of SLE were minimal. She died of progressive respiratory failure. Autopsy revealed innumerable blebs in both lungs responsible for the pneumothoraces and mediastinal emphysema. Both pneumothoraces and mediastinal emphysema occurred during a course of corticosteroid therapy. The course of her illness was unaffected by treatments that included high dose corticosteroids, immunosuppressives and plasmapheresis. Better medical treatment for these lupus complications should be sought in addition to surgery.

Adrenal Cortex Hormones↗
PubMed1989

Growth hormone and insulin-like growth factor I stimulate Leydig cell steroidogenesis.

Leydig cells from 40 days old rats were incubated with or without human growth hormone (hGH) or insulin-like growth factor I (IGF-I) in the presence or absence of human chorionic gonadotropin (hCG), and testosterone and cyclic AMP (cAMP) levels in the medium were measured. Neither hGH nor IGF-I increased testosterone production in the absence of hCG in concentrations up to 1000 and 100 ng/ml, respectively. However, both peptides increased hCG-induced testosterone production in a dose-dependent manner. The maximal stimulatory concentrations of hGH and IGF-I were 100 and 50 ng/ml, respectively. Human GH did not further enhance the IGF-I-stimulated steroidogenesis. The hGH-augmented steroidogenesis was inhibited by anti-hGH IgG and anti-IGF-I IgG. hGH also enhanced hCG-stimulated cAMP production time dependently, suggesting that the stimulatory effect of hGH on steroidogenesis was due to an increased cAMP production. These data suggest that the effect of hGH might be mediated by locally produced IGF-I, which may act as a modulator on gonadal development in the presence of gonadotropin.

Animals↗
PubMed1989

Human growth hormone stimulates liver regeneration in rats.

To study the effect of human growth hormone (hGH) on liver regeneration in rats, 200 micrograms hGH was administered to partial hepatectomized rats twice a day for three days. The bw of hGH-treated rats was higher than that in untreated rats. After three day administration, the liver weight was 3.18 +/- 0.13 g, significant higher than that of untreated rats (2.68 +/- 0.17 g). Human GH also stimulated the mitosis in the liver. Serum insulin-like growth factor I (IGF-I) and albumin levels were significantly increased and urea nitrogen levels were significantly decreased in hGH-treated rats compared with those in untreated rats. When 120 micrograms/day IGF-I was continuously administered to partial hepatectomized rats for three days, the bw and the liver weight were not higher than those of controls. These data indicate that hGH directly stimulates liver regeneration and recover liver dysfunction in rats.

Animals↗
PubMed1989

Effects of ingestion of glucose on GH and TSH secretion: evidence for stimulation of somatostatin release from the hypothalamus by acute hyperglycemia in normal man and its impairment in acromegalic patients.

Ingestion of glucose is known to induce suppression of GH secretion in normal subjects and this phenomenon is often absent in acromegalic patients. To clarify the mechanism of GH suppression in acute hyperglycemia in normal subjects and disturbed GH response in acromegalic patients, the effects of acute hyperglycemia on plasma GH and TSH levels were examined in normal subjects and acromegalic patients. Plasma GH levels were significantly lowered 45-60 min after ingestion of 75 g glucose and elevated at 210 and 240 min in nine normal subjects. Plasma TSH levels were also significantly lowered between 45 and 120 min after ingestion; levels then gradually rose. Subcutaneous administration of 50 micrograms SMS 201-995, a long acting somatostatin analog, lowered plasma TSH levels in both normal subjects and acromegalic patients, and there was no significant difference in the degree of decrease in plasma TSH levels between the normal subjects and patients. These results, taken together with several reports that somatostatin suppresses TSH secretion as well as GH secretion, suggest that acute hyperglycemia stimulates somatostatin release from the hypothalamus, thus causing inhibition of GH and TSH secretion. However, in ten acromegalic patients, only two showed suppression of plasma GH levels to below 50% of basal level and the degree of suppression of TSH secretion was significantly less than in normal subjects in the glucose tolerance test. It is, therefore, suggested that somatostatin release in response to acute hyperglycemia is impaired in most acromegalic patients and that this abnormality may be one of causes for the absence of the normal GH response to acute hyperglycemia in this disorder.

Acromegaly↗
PubMed1989

Hypothalamic growth hormone-releasing factor (GRF) participates in the negative feedback regulation of growth hormone secretion.

Effects of growth hormone (GH) excess on immunoreactive hypothalamic GH-releasing factor (GRF) and somatostatin (SRIF) were studied in rats. Hypothalamic GRF content significantly reduced after 7-day daily treatment with 160 micrograms of rat GH or after inoculation of GH-secreting rat pituitary tumors, MtT-F4 for 9 or 13 days and GH3 for 3 months. Basal and 59 mM K+-evoked release of GRF from incubated hypothalami diminished, more than the content, by 43-51% in MtT-F4 tumor- or by 67-83% in GH3 tumor-bearing rats. In contrast, there was a small but significant increase in content or release of SRIF in rats harboring the GH3 or MtT-F4 tumor, respectively. These results indicate the existence of a negative feedback loop via hypothalamic GRF as well as SRIF in control of GH secretion.

Animals↗
PubMed1989

Effect of interleukin-1 (IL-1) on thyroid hormone metabolism in mice: stimulation by IL-1 of iodothyronine 5'-deiodinating activity (type I) in the liver.

To elucidate the mechanism by which the low T3 and low T4 syndrome occurs in patients with infection, recombinant human interleukin-1 (IL-1) was administered to mice, and their thyroid hormone metabolism was studied. Continuous sc infusion of IL-1 alpha or IL-1 beta at a dose of 0.015-1 microgram/day for 3 days decreased food intake and serum T4, T3, and rT3 concentrations in a dose-dependent manner. In pair-fed control (PFC) mice, serum T4 and T3 also decreased, but rT3 was reciprocally increased. The T3/T4 ratio was greater in IL-1-treated mice than in PFC mice. Although food intake was decreased by 65% in IL-1-treated mice (1 microgram/day) compared with that in fed control mice, type I iodothyronine 5'-deiodinating activity in liver was significantly increased compared with that in fed control mice. Furthermore, the T3 and T4 responses to TSH were greatly diminished in IL-1-treated mice. These findings suggest that IL-1 directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T4 and T3, and that an increase in type I iodothyronine 5'-deiodinating activity in livers of IL-1-treated mice may account for the greater T3/T4 ratio and lower serum rT3 concentration than those in PFC mice. Since tumor necrosis factor-alpha has a similar effect, we speculate that both cytokines may be synergistically involved in the altered thyroid hormone metabolism in mice (decreased serum T4, T3, and rT3 concentrations) and hypercatabolism in a febrile state.

Animals↗
PubMed1989

Porcine luteinizing hormone isoform(s): relationship between their molecular structures, and renotropic versus gonadotropic activities.

We recently demonstrated the renotropic activity in ovine LH isoform(s). In this study we purified porcine (p) LH isoforms and analyzed their structures and bioactivities. Purified pLH preparation (G-100 fraction 3) was dissociated into alpha- and beta-subunits, followed by isolation with reverse phase HPLC. Six components were isolated and analyzed for their amino acid compositions and amino-terminal amino acid sequences. alpha-Subunits were found to have heterogeneous N-terminal sequences, which started at Phe-1, Gly-4, Phe-6, or Thr-7. This N-terminal heterogeneity and the presence of the initial 6 amino acids has not been reported previously to the best of our knowledge. Moreover, the first 10 residues, Phe-Pro-Asp-Gly-Glu-Phe-Thr-Met-Gln-Gly, were identical with those of the ovine LH alpha subunit. At least 3 different beta-subunits were identified as heterogeneous in their carboxyl-terminal amino acids. The pLH preparation (G-100-fraction 3) was then chromatographed by an isoelectrofocusing (IEF) column. Four IEF fractions were obtained. Their amino acid structures appeared to be identical, as judged by the identical elution profiles on reverse phase HPLC, but their carbohydrate compositions were slightly different, especially in N-acetylgalactosamine in alpha-subunits. Thus, fractionation on IEF depended on the heterogeneity in carbohydrate structures. Each IEF fraction had different potencies in terms of its gonadotropic activity (in vitro) and renotropic activity (in vivo and in vitro). The discrepancy was observed not only between gonadotropic activity and renotropic activity, but also between in vivo and in vitro renotropic activity. This study identified the structural heterogeneity of pLH isoforms and demonstrated their biological heterogeneity. We concluded that the carbohydrate structure of the pLH isoform is important for expressing its biological heterogeneity (gonadotropic and renotropic activity.

Amino Acid Sequence↗
PubMed1989

Effects of protein kinase-C-related adrenocorticotropin secretagogues and interleukin-1 on proopiomelanocortin gene expression in rat anterior pituitary cells.

To examine the effects of the cAMP-independent protein kinase-C system and interleukin-1 (IL-1) on secretion of ACTH and POMC gene expression in cultured rat anterior pituitary (AP) cells, AP cells were incubated with CRF, 8-bromo-cAMP, arginine vasopressin, angiotensin II, norepinephrine, and phorbol 12-myristate 13-acetate. After 15 h of incubation, CRF and 8-bromo-cAMP increased both ACTH release and the POMC mRNA level. Arginine vasopressin, angiotensin II, norepinephrine, or phorbol 12-myristate 13-acetate stimulated ACTH release but failed to increase basal or CRF-stimulated POMC mRNA levels. Human recombinant IL-1 alpha and -beta increased neither ACTH release nor POMC mRNA levels after 3 h of incubation. After 15 h of incubation, 100 pM to 10 nM IL-1 alpha and -beta increased ACTH release. However, POMC mRNA levels were significantly elevated only by 10 pM IL-1 beta. These results suggest that the CRF-cAMP system plays a major role in both ACTH release and expression of the POMC gene in AP cells, but the cAMP-independent protein kinase-C system contributes only to ACTH release; that acute stimulation of ACTH release from AP with IL-1 administration is not due to direct action of IL-1 at the pituitary level; that chronic exposure of AP cells to IL-1 alpha or -beta can stimulate ACTH release; and that the direct effects of IL-1 alpha and -beta on POMC gene expression, if any, seem to be minimal.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Parathyroid hormone-related protein and interleukin-1 alpha synergistically stimulate bone resorption in vitro and increase the serum calcium concentration in mice in vivo.

To elucidate the mechanism of humoral hypercalcemia elicited by human esophageal carcinoma cells (EC-GI), which constitutively produced interleukin-1 alpha (IL-1 alpha) and PTH-like factor, the effects of IL-1 alpha and PTH-related protein (PTH-rP) on bone resorption in vitro and on serum calcium concentrations in vivo were investigated. Nude mice transplanted with EC-GI cells invariably developed hypercalcemia, although their urinary cAMP excretion remained within the normal range. IL-1 alpha or PTH-rP-(1-34) stimulated 45Ca release from prelabeled fetal mouse forearm bones in a concentration-dependent manner, and when combined, IL-1 alpha and PTH-rP-(1-34) synergistically stimulated bone resorption in vitro. Injection of PTH-rP-(1-34) into mice three times a day for 2 days increased the serum calcium concentration in a dose-dependent manner. Continuous infusion of IL-1 alpha occasionally increased the serum calcium concentration. Simultaneous administration of IL-1 alpha at rates of 1-2.7 micrograms/day and PTH-rP-(1-34) at doses of 15-30 micrograms/day synergistically increased the serum calcium concentration in vivo. These findings suggest that PTH-rP and IL-1 alpha produced by the tumor cells were synergistically responsible for the humoral hypercalcemia observed in both the original patient and the tumor-bearing nude mice, and that at least two bone-resorbing factors [PTH-rP and another nonadenylate cyclase-stimulating bone-resorbing factor(s)] are active in patients with malignancy-associated hypercalcemia, in whom nephrogenous cAMP excretion is neither increased nor decreased.

Animals↗
PubMed1989

Adrenergic modulation of adrenocorticotropin responses to insulin-induced hypoglycemia and corticotropin-releasing hormone.

To study possible adrenergic modulation of pituitary-adrenal responses to insulin-induced hypoglycemia and CRH we examined the effect of nonselective alpha-blockade (phentolamine) and nonselective beta-blockade (propranolol) on plasma ACTH, cortisol, and vasopressin (AVP) responses to hypoglycemia and CRH in five normal men. Infusion of propranolol or phentolamine did not alter basal plasma ACTH or cortisol levels. The propranolol infusion enhanced the stimulatory effect of hypoglycemia on ACTH, cortisol, and AVP secretion and also enhanced the stimulatory effect of CRH on ACTH and cortisol secretion. Infusion of phentolamine inhibited hypoglycemia-induced ACTH and AVP secretion, but had no effect on the stimulatory effect of CRH on ACTH and cortisol secretion. The increments of plasma ACTH and cortisol induced by an almost maximal dose of CRH (1 microgram/kg) were smaller than those induced by hypoglycemia. The propranolol-induced enhancement of the ACTH response to hypoglycemia was almost the same as the ACTH response to CRH alone. From these results we conclude that propranolol may act at the pituitary level to enhance CRH action, rather than AVP action, and that the ACTH response to hypoglycemia may be mediated by hypothalamic alpha-adrenergic activation.

Adrenocorticotropic Hormone↗
PubMed1989

Responses to corticotropin-releasing hormone and its bound and free forms in pregnant and nonpregnant women.

Plasma CRH levels are considerably higher in women during the third trimester of pregnancy than in non-pregnant women. Most of plasma CRH in pregnant women is bound to CRH-binding protein (CRH-BP). To gain further insight into CRH physiology during pregnancy, we measured the responses of plasma ACTH and cortisol and the changes in bound and free forms of CRH in plasma after human CRH administration (2 micrograms/kg) in five pregnant (39-40 weeks of pregnancy) and five nonpregnant women. The mean basal plasma ACTH and cortisol levels in the pregnant women were higher than those in the nonpregnant women. However, the maximum increments in plasma ACTH and cortisol levels and the integrated ACTH and cortisol responses, after subtraction of the basal levels after CRH administration, were similar in the two groups. The plasma CRH half-time in the pregnant group was similar to that in the nonpregnant group. The mean basal plasma CRH level in the nonpregnant women was 1.5 +/- 0.2 (+/- SE) pmol/L, and that in the pregnant women was 360 +/- 35 pmol/L. On gel filtration chromatography, almost all of the CRH in the plasma was protein bound (320 +/- 30 pmol/L) in the pregnant women; no CRH peaks were detected in nonpregnant women because of the low plasma CRH levels. After CRH administration, the level of the bound form of plasma CRH was highest at 5 min, and then declined to a plateau at 15 min and 30 min in the pregnant women. In the nonpregnant women, protein-bound CRH also was highest at 5 min, but it progressively declined thereafter. The disappearance rate of the bound CRH in plasma from the nonpregnant women was similar to that of the second compartment of the plasma decay curves of the free CRH from both groups. We conclude that the plasma ACTH and cortisol responses to exogenous CRH are similar in pregnant and nonpregnant women, the effect of CRH-BP on the disappearance of plasma CRH is minimal, and plasma CRH-BP in pregnant women has the capacity to bind additional CRH.

Adrenocorticotropic Hormone↗
PubMed1989

The influence of gonadal function and the effect of gonadal suppression treatment on final height in growth hormone (GH)-treated GH-deficient children.

One hundred and sixty-one children with idiopathic GH deficiency who received GH treatment were followed until they reached their final height. Final height was found to be influenced by gonadal function. In 108 patients who had spontaneous puberty (91 boys and 17 girls; group A), the mean final height was 151.8 +/- 6.6 (+/- SD) cm in boys and 141.7 +/- 7.4 cm in girls. In 29 patients with combined GH and gonadotropin deficiency (23 boys and 6 girls; group C), whose pubertal development was induced artificially at age 19.5 +/- 2.1 yr in the boys and 18.6 +/- 1.8 yr in the girls, the mean final height was 163.7 +/- 3.9 cm in boys and 151.0 +/- 5.1 cm in girls. The differences in final height between groups A and C were significant in both boys and girls. The shorter final height in group A was caused by the shorter pubertal duration and smaller pubertal height gain than those in normal children. In 24 patients (17 boys and 7 girls; group B) who developed early signs of puberty, gonadal suppression therapy with cyproterone acetate and/or medroxyprogesterone acetate was given. The mean SD score of the final height in these 24 patients was -2.1 +/- 0.6, significantly higher than that in group A. This beneficial effect of gonadal suppression treatment on final height was caused by increases in the duration of puberty and the pubertal height gain.

Adolescent↗
PubMed1989

The somatostatin analog octreotide inhibits the secretion of growth hormone (GH)-releasing hormone, thyrotropin, and GH in man.

The effects of the somatostatin analog octreotide on plasma GH, TSH, and immunoreactive GH-releasing hormone (IR-GHRH) were studied in 10 normal men. After morning sc administration of 50 or 100 micrograms octreotide or placebo, plasma GH, TSH and GHRH were measured frequently for 6 h. Plasma GH or IR-GHRH concentrations did not change after placebo injection, but plasma TSH levels gradually decreased, in conformity with a circadian rhythm during the morning. The mean plasma GH levels after sc injection of 50 or 100 micrograms octreotide declined, and no spontaneous GH pulses occurred for 5 h. Plasma TSH decreased rapidly after both doses of octreotide and was significantly lower than the level after placebo treatment from 90-315 min (P less than 0.05) and 60-360 min (P less than 0.05 or P less than 0.01), respectively. Plasma IR-GHRH levels also were significantly lower from 30-360 min (P less than 0.05) in the group given 100 micrograms octreotide compared with the value in the placebo group. We conclude that octreotide inhibits not only GH and TSH secretion from the pituitary, but also GHRH release from the hypothalamus and/or peripheral tissues. These findings suggest that somatostatin controls GH secretion not only by suppressing pituitary secretion of GH but also by suppressing GHRH release from the hypothalamus.

Adult↗
PubMed1989

Treatment of 80 patients with Turner's syndrome with recombinant human growth hormone (YM-17798) for one year: the results of a multicentric study in Japan. Committee for the Treatment of Turner's Syndrome.

A total of 80 patients with Turner's syndrome were treated with methionine-free recombinant hGH (r-hGH) for one year. Thirty-nine patients were treated with r-hGH at weekly dosage of 0.5 IU/kg and forty-one were treated with 1.0 IU/kg/w by daily sc injection. Both treatment groups showed a statistically significant growth increase during the treatment from 3.7 +/- 1.0 to 6.0 +/- 1.1 and 7.2 +/- 1.3 (mean +/- SD) cm/year, respectively. Fifty-nine percent of the patients treated with 0.5 IU/kg/w and 87.8% of the patients treated with 1.0 IU/kg/w showed a growth rate more than 2 cm greater than the pretreatment values. Plasma somatomedin C levels were elevated and no remarkable advances in bone age were observed during the treatment in both treatment groups. An antibody against to hGH was observed in 6.8% of the patients. Otherwise, there were no significant changes in physical or laboratory examinations. No glucose intolerance was observed. These results indicate that hGH treatment is useful in accelerating growth velocity in patients with Turner's syndrome.

Adolescent↗
PubMed1989

Treatment of 94 patients with Turner's syndrome with recombinant human growth hormone (SM-9500) for two years--the results of a multicentric study in Japan. Committee for the Treatment of Turner's Syndrome.

A total of 94 patients with Turner's syndrome were treated with methionine-free recombinant hGH for one to two years. Forty-seven patients were treated with r-hGH at a weekly dosage of 0.5 IU/kg and another 47 were treated with 1.0 IU/kg/w by daily sc injection. Both treatment groups showed statistically significant growth increase during the treatment from 3.7 +/- 1.0 to 5.2 +/- 1.3 and from 3.5 +/- 0.9 to 6.3 +/- 1.4 (Mean +/- SD) cm/year, respectively, during the first year of treatment. During the 2nd year of treatment, the growth rate declined to 4.1 +/- 1.1 cm/year under 0.5 IU/kg/w treatment and to 4.6 +/- 1.1 cm/year under 1.0 IU/kg/w treatment. Nevertheless, the growth rates in the treatment groups remained significantly greater than in the untreated controls. Plasma somatomedin C increased and no remarkable increase in bone age was observed during the treatment in either treatment group. Antibody to hGH was observed in 14.8% of the patients at the end of the first year of treatment, however the incidence was decreased to 4.7% by the end of the second year of treatment. Otherwise, there were no significant changes detected in physical or laboratory tests. No glucose intolerance necessitating treatment was observed. These results indicate that hGH treatment is useful in accelerating growth in patients with Turner's syndrome.

Adolescent↗
PubMed1989

Measurement of plasma free and total growth hormone concentrations in patients with growth hormone antibodies developed in response to therapy.

Recombinant human growth hormone is more antigenic than pituitary preparations. Since GH antibodies interfere with radioimmunoassay of GH, we measured plasma free and total GH in patients with pituitary dwarfism with GH antibodies during treatment with a recombinant methionyl GH preparation. Plasma free GH was measured in the supernatant after polyethylene glycol precipitation. Total GH was measured after extracting plasma with acid-ethanol. In normal subjects, both free and total GH levels were similar to those measured in plasma by a direct conventional RIA. Peak free GH levels after administration of 4 IU methionyl GH to 3 normal subjects were 38.0, 30.7 and 13.2 micrograms/1, values similar to those measured in most of the patients with GH antibodies. All values were undetectable in one patient with a very high antibody titre. Total GH levels were similar to free GH levels in normal subjects. In patients with GH antibodies, total GH levels were high compared with their free levels, but similar to those assayed by conventional RIA. The patient with the highest antibody titre had total GH levels which were the lowest of those observed in the patients with GH antibodies in spite of having the highest GH levels measured by conventional RIA. The antibody in this particular case may have a high capacity and a high affinity. A relatively poor growth rate in this patient may be associated with the finding of undetectable free GH levels. Measurement of plasma free and total GH may be of value in examining GH dynamics and their relation to the clinical effectiveness of GH treatment in patients with GH antibodies.

Adolescent↗