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Biomedical subjects

S Kanzaki

Publications and source records attributed to S Kanzaki.

At least 37 records · Page 2Linked to original sources
PubMed1997

Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25-dihydroxyvitamin D levels in children with growth hormone deficiency.

The influence of growth hormone (GH) on calcium-phosphorus metabolism and modulation of vitamin D metabolism has been demonstrated, but the mechanism remains unclear. We investigated the effect of a 6-month course of GH therapy on vitamin D and mineral metabolism in twelve GH-deficient children. Before GH therapy, levels of vitamin D metabolites and other biochemistry data were within normal ranges. All patients responded to GH therapy with increased growth velocity. 1,25-Dihydroxyvitamin D levels increased after 1 month of treatment and remained at these higher levels, with a significant increase found at 3 months (P < 0.05), whereas 24,25-dihydroxyvitamin D levels were decreased at 1 and 3 months, the latter being a significant decrease (P < 0.05), and then returned to the baseline levels at 6 months. 25-Hydroxyvitamin D levels did not change significantly. A significant increase in serum insulin-like growth factor-I (IGF-I) levels occurred during the 6 months of treatment (1 month, P < 0.01; 3 and 6 months, P < 0.001). Serum parathyroid hormone (PTH) levels decreased significantly at 3 and 6 months (3 months, P < 0.01; 6 months, P < 0.05). Serum calcium and phosphorus levels did not change significantly. Significant increases were found in the urinary calcium/urinary creatinine ratio (3 and 6 months, P < 0.05) and the percent tubular reabsorption of phosphorus levels (1 and 3 months, P < 0.05). The results of this study confirmed the actions of GH on renal tubules with increases in calcium excretion and phosphorus reabsorption, and indicate that the action of GH on modulating vitamin D metabolism may be IGF-I mediated, not PTH mediated.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme.

To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific alkaline phosphatase isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B-ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) and IGFBP-5 (r = 0.795; P < 0.0001), and the elevation of B-ALP was also significantly positively correlated with the increases in IGF-I, IGF-II, IGFBP-3, and IGFBP-5 (r = 0.544, P < 0.0001; r = 0.268, P = 0.0399; r = 0.414, P = 0.0010; and r = 0.500, P < 0.0001, respectively). Our data are consistent with the anabolic effect on bone growth of GH treatment being mediated by IGF-II, IGFBP-3, and IGFBP-5 as well as by IGF-I. This is the first evidence that GH treatment increases IGF-II in GH-deficient children. This finding was probably the result of application of a valid assay that measures IGF-II without interference of IGFBPs.

Adolescent↗
PubMed1995

Evidence that human bone cells in culture secrete insulin-like growth factor (IGF)-II and IGF binding protein-3 but not acid-labile subunit both under basal and regulated conditions.

Insulin-like growth factors (IGFs) are found in human circulation predominantly as part of a growth hormone (GH)-dependent complex of 125-150 kD, which is composed of three subunits: IGF-I or IGF-II, an acid stable IGF binding protein (IGFBP)-3, and an acid labile subunit (ALS). Although recent studies demonstrate that a number of cell types in culture secrete IGFs and IGFBP-3, very little is known with regard to the origin of circulating ALS. To test the hypothesis that human bone cells (HBCs), which produce abundant amounts of IGF-II and IGFBP-3, also produce ALS, we measured the IGF-I, IGF-II, IGFBP-3, and ALS levels using specific radioimmunoassays (RIAs) in the conditioned medium (CM) of untransformed normal HBCs and SaOS-2 osteosarcoma cells treated with various effectors (IGF-II, osteogenic protein-1 [OP-1, bone morphogenetic protein-7] and human GH) for 48 h. No detectable levels (< 3 ng/ml) of ALS were found in the CM of various HBC types under basal conditions. In contrast, CM collected from liver explants in culture contained significant amount of ALS prepared and assayed under identical conditions. The IGF-I level was also undetectable in the CM of various HBC types. In the IGF-II (3, 30 ng/ml)-treated HBC CM, the IGFBP-3 level was increased in a dose-dependent manner but neither IGF-I nor ALS could be detected. In the SaOS-2 cell culture, OP-1 (1, 100 ng/ml) increased both IGF-II and IGFBP-3 secretion but neither ALS nor IGF-I secretion. Treatment of HBCs with GH (1, 10, 100 ng/ml) had no significant effect on the secretion of either IGF-I, IGF-II, IGFBP-3, or ALS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Serum levels of carboxyterminal propeptide of type I procollagen and pyridinoline crosslinked telopeptide of type I collagen in normal children and children with growth hormone (GH) deficiency during GH therapy.

In this study, we investigated age-related changes in serum levels of both the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline crosslinked telopeptide of type I collagen (ICTP) to elucidate bone formation and resorption, respectively, in 200 normal Japanese children (141 males and 59 females, age range 0-16 years). Furthermore, to clarify the effect of GH on bone turnover, we measured serum PICP and ICTP in 26 growth hormone (GH)-deficient children (20 males and 6 females, age range 4-15 years) who showed significant bone growth during recombinant human GH therapy. In the normal children, the curves for age-related changes in both serum PICP and ICTP levels almost paralleled that of the standard height velocity curve in both sexes. The serum levels of both peptides were higher than those in adults, and the peak increases corresponded with the timing of the adolescent growth spurt. Furthermore, the serum levels of PICP and ICTP were significantly correlated with the height velocity. In the GH-deficient patients, the serum ICTP levels before GH therapy were lower than those in age- and sex-matched controls. Both PICP and ICTP levels in serum increased significantly at the beginning of GH therapy. Furthermore, the percent increase in PICP after 1 month of GH treatment was positively correlated with the percent increase in height velocity during 1 year of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Hypothyroidism and hypoparathyroidism in an 11 year old boy with hemochromatosis secondary to aplastic anemia.

This is the first reported case, to our knowledge, of hypoparathyroidism and hypothyroidism due to secondary hemochromatosis with onset during childhood. The patient was a boy with refractory aplastic anemia in whom primary hypothyroidism and hypoparathyroidism became apparent at the age of 10 and 11 years old, respectively. He had received a total of 100 L of transfused blood by the age of 10 years. The patient showed poor annual height gain due to primary hypothyroidism, together with hypocalcemia, cataract and intracranial calcification due to hypoparathyroidism. The early appearance of both thyroid and parathyroid dysfunction in this patient may have been due to the delay of initiation of iron-chelating agents and liver dysfunction due to hepatitis type C.

Anemia, Aplastic↗
PubMed1995

Activation of eosinophils in the pathophysiology of ulcerative colitis.

We studied the role of eosinophils as effector cells in the pathophysiology of ulcerative colitis. In the active stage of this disease, the colonic mucosa exhibited infiltration of numerous eosinophils positive to the EG2 antibody, which reacts specifically with the secretory form of eosinophil cationic protein. Electron microscopic studies demonstrated that the eosinophils had specific granules in various stages of degranulation. Hence, it is strongly suggested that the eosinophils infiltrating the inflamed mucosa are activated and may induce tissue damage during the degranulation and release of this cationic protein. Changes in the levels of serum eosinophil cationic protein in 14 patients who remained for in long-term remission were studied. Four of these patients showed persistently high concentrations of eosinophil cationic protein (equal to or greater than 30 micrograms/l) and persistently high percentage (mean, 30.2%) of hypodense eosinophils (specific gravity < 1.082) in the peripheral blood. Such findings were associated with mild active disease at colonoscopy. These features suggest that the activation of eosinophils is one of the factors that contribute to the chronic inflammation in ulcerative colitis.

Biopsy↗
PubMed1994

[Serum levels of intact molecular osteocalcin in children with growth hormone (GH) deficiency during GH therapy: an early predictor of GH therapy].

Recently we developed a sandwich enzyme immunoassay (EIA) specific for intact molecular osteocalcin (I-OC), produced only by osteoblast cell and partially released into blood circulation, to establish a specific biochemical marker of bone formation. In order to confirm whether serum I-OC levels constitute a specific marker for bone formation and to assess the relationship between serum I-OC levels and growth response to growth hormone (GH) therapy, we measured the serum I-OC in serial serum samples using this EIA from 61 children with GH deficiency who showed significant bone growth during GH therapy. The serum I-OC levels in children with GH deficiency before GH therapy were slightly lower than those in normal children (Kanzaki S. et al., J. Clin Endocrinol Metab. 1992;75:1104-9), and had a wide distribution overlapped with the normal range. These levels were apparently increased during GH treatment; that is, in contrast to the levels of 22.9 +/- 1.5 ng/ml (mean +/- SE) before GH treatment, the levels after 1 and 2 months of GH treatment were 29.1 +/- 1.6 ng/ml and 32.5 +/- 1.8 ng/ml, respectively. However, they decreased slightly at 3 months and then they gradually rose to 37.5 +/- 2.8 ng/ml after 12 months, I-OC ratios, represented by the I-OC level at each month of GH therapy in relation to pretreatment level, correlated well with the growth response (growth velocity, growth velocity SD score and delta growth velocity SD score) after 12 months of GH treatment. Correlation coefficients of the growth velocity versus I-OC ratio at 1 and 6 months of GH treatment were 0.677 (p < 0.001, N = 58) and 0.752 (p < 0.001, N = 55), respectively. However, both IGF-I and ALP ratios represented in the same way as the I-OC ratio, correlated poorly as compared with the I-OC ratio. These results demonstrate that the change of serum I-OC levels indicates a direct and sensitive reflection of bone formation, because serum I-OC levels significantly increased with the growth response to GH therapy. The measurement of serum I-OC levels after 1 month of GH treatment may be a useful tool in predicting improved growth velocity during long-term GH therapy.

Body Height↗
PubMed1994

Evidence that human bone cells in culture produce insulin-like growth factor-binding protein-4 and -5 proteases.

Previous studies have shown that the actions of insulin-like growth factor-II (IGF-II) in bone are determined by both its concentration and the concentrations of the IGF-binding proteins (IGFBPs). As IGFBP concentrations may be regulated not only at the level of production, but also at the level of degradation, IGFBP proteases may be an important component of the IGF-II regulatory system. In this study, we have identified IGFBP-4 and IGFBP-5 protease activity in the conditioned medium (CM) of the human osteosarcoma U2 cell line (U2OS) and untransformed normal human bone cell (HBC) derived from skull. Proteolysis of the 29-kilodalton (kDa) [125I]IGFBP-5 produced an 18- to 20-kDa fragment of IGFBP-5, and 25 kDa [125I]IGFBP-4 yielded two lower mol wt fragments in the presence of IGF-II. CM from IGF-II-treated U2OS and normal HBC cultures exhibited decreased IGFBP-5 proteolytic activity compared to control cultures. In contrast, CM from IGF-II-treated HBC cultures had increased proteolytic activity against IGFBP-4. To determine the mechanisms by which IGF-II modulates IGFBP-4 and -5 proteolytic activity, CM from control U2OS cell culture was incubated with [125I]IGFBP-4 or -5 in the presence of various concentrations of IGF-II and IGF analogs under cell-free conditions. It was found that exogenous IGF-II stimulated IGFBP-4 proteolysis, but IGF analogs that had no or extremely low affinity to IGFBP-4 failed to induce IGFBP-4 proteolysis. On the contrary, exogenous IGF-II had no effect on IGFBP-5 proteolysis in cell-free U2OS CM. Both IGFBP-4 and IGFBP-5 proteolytic activities were inhibited by aprotinin, zinc chloride, and EDTA and eluted as a single major peak between mol wt markers of 160 and 67 kDa upon gel filtration. Based on the findings that HBCs in culture produce a protease(s) capable of cleaving both IGFBP-4 and IGFBP-5 and that IGF-II can promote or inhibit proteolytic degradation of IGFBP-4 and IGFBP-5, respectively, it is proposed that IGFBP protease(s) may be an important modulator of IGF activity in bone.

Bone and Bones↗
PubMed1993

Secretion of osteocalcin and its propeptide from human osteoblastic cells: dissociation of the secretory patterns of osteocalcin and its propeptide.

Specific immunoassay systems for intact human osteocalcin (I-OC) and its 26-residue propeptide have been newly developed to assess their usefulness as biochemical markers of bone metabolism. Using human cultured osteoblastic periosteal cells, we monitored 24 h secretion of these molecules from the osteoblastic cells and also examined the deposition of Ca, P, and I-OC on the extracellular matrix. At day 5, both I-OC and its propeptide were secreted by osteoblastic cells in a concentration-dependent manner by treatment with 1,25-(OH)2D3. This propeptide was not detected in the serum of adult subjects but was detected in the serum of normal children, which confirmed this in vitro result of propeptide secretion. The secretion of I-OC into medium transiently decreased at day 11, when the rapid accumulation of I-OC, Ca, and P, namely mineralization, was observed on the extracellular matrix of osteoblastic cells, although secretion of the propeptide constantly increased throughout the culture period. Therefore, the ratio of the amount of propeptide to I-OC in the supernatant markedly increased when mineralization started. These data demonstrate the superior specificity of propeptide as a marker of osteoblastic function in vitro compared with I-OC and that monitoring the changes in propeptide to I-OC ratios in the culture supernatant may be useful for predicting the timing of mineralization on the extracellular matrix of osteoblastic cells.

Adolescent↗
PubMed1993

Malignant osteopetrosis treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma.

A male infant with malignant osteopetrosis was treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Therapy with 1 alpha-hydroxyvitamin D3 increased the serum calcium level despite the markedly elevated serum level of 1 alpha, 25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression.

Dose-Response Relationship, Drug↗
PubMed1992

Growth hormone deficiency and empty sella syndrome in a boy with dup(X) (q13.3----q21.2).

A 2 8/12-year-old boy with severe growth failure and mental retardation was found to have a maternally derived tandem duplication of the long arm of X chromosome, dup(X) (q13.3----q21.2). Karyotypic interpretation was further confirmed in this patient by a double gene dose for red blood cell phosphoglycerate kinase. DNA replication study showed that the duplicated X chromosome was always late replicating in peripheral blood lymphocytes as well as in skin fibroblasts from the mother. Endocrine studies in the patient demonstrated growth hormone deficiency. Magnetic resonance imaging of the head then disclosed the empty sella syndrome. This appears to be the first report of a dup(Xq) patient associated with a growth hormone deficiency and the empty sella syndrome. We emphasize that duplication of the proximal Xq in males represents another microduplication syndrome (Thode-Leonard syndrome).

Child, Preschool↗
PubMed1992

Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) in insulin-dependent diabetic patients.

Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) concentrations were determined in 36 insulin-dependent diabetic children aged 4-18 years with a duration of diabetes ranging from 1 month to 14 years. Abnormal urinary GP-DAP concentrations were found in 19 of the 36 patients. Twelve of 27 patients without microalbuminuria also had increased urinary concentrations of GP-DAP. There was a significant correlation between urinary GP-DAP and plasma fructosamine (r = 0.52, p < 0.001). Our data suggest that urinary GP-DAP may be used as a marker for diabetic nephropathy. However, there is also a possibility that increased urinary GP-DAP concentrations are functionally related to poor metabolic control. Longitudinal studies are needed to establish the clinical usefulness of urinary GP-DAP.

Adolescent↗
PubMed1992

1,25-Dihydroxyvitamin D3 stimulates the secretion of insulin-like growth factor binding protein 3 (IGFBP-3) by cultured human osteosarcoma cells.

Several types of specific insulin-like growth factor binding proteins have been reported. These binding proteins are produced by peripheral tissue-derived cells and they modulate the functions of insulin-like growth factors. In this study, we investigated both the secretion of insulin-like growth factor binding protein 3 (IGFBP-3) from a human osteosarcoma cell line MG63, and the effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the production of this binding protein. The beta subunit of IGFBP-3 was detected in perinuclear cytoplasm of MG63 cells by immunocytochemical study. Immunoblotting and SDS-PAGE analysis revealed that both 150KD MW entire molecules and 40-60KD MW beta subunit molecules of IGFBP-3 were present in cell-conditioned media. 1,25-(OH)2D3 stimulated the production of the IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 in conditioned media began to rise at 12 hours after the addition of 10(-8) M of 1,25-(OH)2D3 and reached peak level at 48 hours. Dose-dependent effects of 1,25-(OH)2D3 were demonstrated. The its maximum effect was observed at 10(-10) M. The concentration of IGFBP-3 in cytosol also increased at a 10(-10) M concentration of 1,25-(OH)2D3. We conclude from these results that human osteosarcoma cells MG63 produce the IGFBP-3 molecule and that 1,25-(OH)2D3 stimulates the production of this protein. These data suggests that the synergistic effects of 1,25-(OH)2D3 on the action of IGF-I on osteoblastic cells, which we reported previously, may be modulated by locally produced IGFBP-3.

Calcitriol↗
PubMed1992

Serum propeptide and intact molecular osteocalcin in normal children and children with growth hormone (GH) deficiency: a potential marker of bone growth and response to GH therapy.

To establish a sensitive marker for bone formation we have developed a sandwich enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide. Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr, and in 23 GH-deficient children treated with GH. The serum levels of the propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE) micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to 27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a 2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC levels after 1 month of GH therapy correlated with the growth response after 12 months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P < 0.01 for intact OC). These results show that since both propeptide and intact OC in serum were increased when the growth rate was elevated, these peptides are sensitive markers of bone formation. Serum levels of these peptides, particularly propeptide, after 1 month of GH therapy might be a helpful predictor of the growth response to long term GH therapy.

Adolescent↗
PubMed1992

[Congenital lobar emphysema successfully treated by right upper lobectomy at five hours after delivery: a case report].

Lobar emphysema is a rare disease and one of the causes of respiratory disturbance in the newborn and infancy. A case report is presented and compared with related data in the literature in Japan. Maternal echographic findings indicated the cystic lung disease of the fetus. The cystic space was punctured and aspirated three times. The baby was delivered by caesarean section after having taken sufficient precaution to prevent respiratory failure. Since the baby developed dyspnea gradually, at five hours following the delivery, right upper lobectomy was performed and the major symptoms were eliminated. The pathological diagnosis was congenital lobar emphysema and the etiology was concluded to be bronchiectasis.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1990

Age-related changes in urinary growth hormone level and its clinical application.

In order to establish the normal range of urinary growth hormone (GH) level for age and sex, which is important in the clinical application of urinary GH to diagnosis, we measured GH in the first morning urine specimens of 270 normal subjects aged 3 to 20 years. Urinary GH levels in patients with documented GH deficiency were compared with those of the normal controls. In normal subjects, urinary GH levels showed a statistically significant change with age. They were relatively high in infancy and mid-puberty, reaching a peak at 11 to 12 years in girls and at 13 to 14 years in boys. Urinary GH levels in patients with complete GH deficiency were apparently lower (less than -2.0 SD) than those of the normal children, while the levels in patients with partial GH deficiency overlapped with the normal range. When assessing GH secretion by using urinary GH measurement, consideration of age and sex is required, since the level changes significantly with these factors.

Adolescent↗