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K Fukuo

Publications and source records attributed to K Fukuo.

At least 91 records · Page 5Linked to original sources
PubMed1987

[Radioimmunoassay of the calcitonin gene-related peptide and its measurement in the plasma of patients with medullary thyroid carcinoma and in the cerebrospinal fluid of normal subjects].

Calcitonin gene-related peptide (CGRP) is a peptide recently found by recombinant DNA and molecular biological techniques in rat medullary thyroid carcinoma cells, but its physiological role(s) is unknown. We established a radioimmunoassay for this peptide using human-CGRP (1-37) as a standard, 125I-human-CGRP (1-37) as a tracer, and anti-rat-CGRP (28-37) serum as a first antibody. Aprotinin, an inhibitor of proteolytic enzymes in the plasma, was also added to the assay system, because in its absence the tracer was degraded during incubation with plasma samples. The sensitivity of the assay was 60 pg/ml and the intra- and inter-assay coefficients of variation were 6.0% and 8.5%, respectively. The recovery was 105 +/- 17%. The plasma levels of CGRP in 17 normal subjects (mean +/- S.D. age, 45 +/- 12 years) were all below 300 pg/ml, the mean level being 132 +/- 77 pg/ml. The levels were also below 300 pg/ml in 20 of 21 patients with medullary thyroid carcinoma, but one patient who had a high level of 942 pg/ml (mean value, 142 +/- 193 pg/ml). There was no significant difference between the mean plasma levels of CGRP in normal subjects and patients with medullary thyroid carcinoma. The mean plasma levels of CGRP in 5 patients with medullary thyroid carcinoma did not increase in response to infusion of either 4.3 mg/kg of calcium in 10 minutes or 4 micrograms/kg of tetragastrin in 5 minutes, although the plasma levels of calcitonin in these patients increased markedly during these provocation tests. The levels of CGRP in the cerebrospinal fluid of 16 normal volunteers were all below the detectable limit (less than 60 pg/ml). These findings suggest that fewer patients with medullary thyroid carcinoma than reported previously have high plasma levels of CGRP, either in the basal state or in response to calcium or gastrin, and that the levels of CGRP in the cerebrospinal fluid of normal subjects are very low.

Adolescent↗
PubMed1987

Effects of nitrates and calcium channel blockers on Ca2+-ATPase in the microsomal fraction of porcine coronary artery smooth muscle cells.

The effects of the antianginal drugs nitroglycerin, nicorandil, diltiazem, verapamil and nicardipine on the activity of calcium-stimulated magnesium-dependent ATPase (Ca2+-ATPase) were investigated in the microsomal fraction from porcine coronary artery smooth muscle cells. Two discrete Ca2+-dependent ATPase components were observed: [1] a high affinity component, which was a specific Ca2+-ATPase, [with a half saturation constant for Ca2+ (Km) of 0.44 microM, and maximum velocity (Vmax) of 124.3 pmol of phosphate (Pi) released/micrograms of protein/30 min]: [2] a low affinity component in which Ca2+ could be replaced by Mg2+ without loss of its activity. Nitroglycerin and nicorandil (1 microM and 10 microM) both stimulated the activity of the Ca2+-ATPase significantly [142 +/- 12 (mean +/- standard error), and 137 +/- 10% of the control with nitroglycerin, and 152 +/- 17 and 135 +/- 20% with nicorandil] at a Ca2+ concentration of 0.3 microM. Diltiazem, verapamil and nicardipine did not cause significant stimulation. Nitroglycerin and nicorandil (1 microM), significantly decreased the Km for Ca2+ from the control value of 0.44 +/- 0.06 microM to 0.26 +/- 0.03 and 0.22 +/- 0.03 microM, respectively. Nitroglycerin and nicorandil may dilate coronary arteries by stimulating this Ca2+ extrusion pump enzyme through reduction of intracellular Ca2+ in smooth muscle cells.

Animals↗
PubMed1987

Effects of various tumor promoters on expression of cartilage phenotypes in rabbit costal chondrocytes in culture.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a skin tumor-promoting phorbol ester, and teleocidin and aplysiatoxin, which are potent tumor promoters in mouse skin but are chemically unrelated to phorbol esters, induced change of cultured rabbit costal chondrocytes from a polygonal to a fibroblastic shape and inhibited glycosaminoglycan (GAG) synthesis and metachromatic matrix formation in these cells. The potencies of teleocidin and aplysiatoxin to inhibit GAG synthesis were almost the same as that of TPA. On the other hand, Tween 60 and cantharidin, weak mouse skin tumor promoters, phenobarbital, a liver tumor promoter, and saccharin, a bladder tumor promoter, had no effect on the morphology or GAG synthesis of cultured chondrocytes. Like TPA, teleocidin and aplysiatoxin increased DNA and RNA syntheses of chondrocytes. Parathyroid hormone (PTH) and dibutyryl cyclic AMP reversed the morphological and histochemical changes caused by a 4-day treatment with teleocidin or aplysiatoxin as well as with TPA, reversal being apparent after 2 days. PTH increased intracellular cyclic AMP after 2 min in chondrocytes pretreated with teleocidin or aplysiatoxin as well as with TPA. PTH also increased ornithine decarboxylase [ODC; EC 4.1.1.17] activity in these chondrocytes after 4 h. These results show that retention of responsiveness to PTH is a typical characteristic of chondrocytes dedifferentiated by treatment with TPA-type tumor promoters such as TPA, teleocidin and aplysiatoxin. The results also suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of teleocidin- and aplysiatoxin-treated chondrocytes.

Animals↗
PubMed1987

Effect of nicorandil on the cytosolic free calcium concentration and microsomal (Ca2+ + Mg2+)-ATPase activity of vascular smooth muscle cells.

The influence of nicorandil, a potent antianginal drug, on cellular calcium in vascular smooth muscle cells (VSMC) was investigated by studying its effects on the cytosolic free calcium concentration ([Ca2+]i) and calcium-stimulated magnesium-dependent ATPase [(Ca2+ + Mg2+)-ATPase] in the cells. VSMC were prepared from rat aorta, and their [Ca2+]i level was determined by measuring the fluorescence of the free calcium indicator, fura 2. Preincubation with nicorandil for 5 min significantly decreased the rise in [Ca2+]i evoked by addition of either angiotensin II in control solution or prostaglandin F2 alpha, the latter in either the presence or absence of extracellular calcium. The effect of nicorandil on (Ca2+ + Mg2+)-ATPase activity in the microsomal fraction of porcine coronary artery smooth muscle, which is rich in plasma membranes and sarcoplasmic reticulum, was also investigated. Nicorandil at concentrations of 10(-6) and 10(-5) M increased the activity of (Ca2+ + Mg2+)-ATPase significantly at a free calcium concentration of 0.3 microM. At 10(-6) M, nicorandil significantly decreased the Kd for calcium of this enzyme without significantly changing its Vmax. These data suggest that nicorandil suppressed increase of [Ca2+]i, possibly by stimulating (Ca2+ + Mg2+)-ATPase, thereby inhibiting contraction of vascular smooth muscle.

Angiotensin II↗
PubMed1987

Chondrocytes dedifferentiated by serial monolayer culture form cartilage nodules in nude mice.

Chondrocytes isolated from rabbit costal growth cartilage grew rapidly and expressed the differentiated phenotypes of chondrocytes in primary monolayer cultures. They had a typical polygonal shape, synthesized glycosaminoglycan (GAG) actively and responded to parathyroid hormone (PTH). However, during successive passages they lost the abilities to proliferate and express differentiated phenotypes. They changed from polygonal to fibroblast-like morphology during the third to fourth passage. Their GAG synthesis rapidly decreased in the 4th passage to 10% of that during primary culture. The increase in GAG synthesis and intracellular cyclic AMP induced by PTH also became smaller and were lost in the 4th passage. From these findings, cells in the 4th passage appeared to be dedifferentiated. However, subcutaneous transplantation of cells at the 5th passage into nude mice resulted in the formation of cartilaginous nodules. Moreover, cells isolated from these nodules and cultured in vitro had a typical polygonal shape and synthesized GAG actively and PTH increased their metachromatic matrix and intracellular cyclic AMP level. These findings suggest that chondrocytes that appear to be dedifferentiated after serial passages still have the potential to differentiate.

Animals↗
PubMed1987

Immunoreactive parathyroid hormones in the circulation and cerebrospinal fluid from patients with renal failure: possible restriction of parathyroid hormone by the blood-brain barrier.

Parathyroid hormone is reported to be a possible causal factor of abnormalities of electroencephalograms of patients with renal failure. In this study, the parathyroid hormone levels were compared in the circulation and cerebrospinal fluid of seven normal subjects and 22 patients with renal failure including those who showed abnormal electroencephalograms. The circulating levels of both C-terminal and N-terminal parathyroid hormone in the subjects studied showed a positive correlation (C-terminal, r = 0.58, P less than 0.01; N-terminal, r = 0.61, P less than 0.01) with the grade of abnormality of the electroencephalogram. However, the levels of C-terminal and N-terminal parathyroid hormone in the cerebrospinal fluid of both normal subjects and patients with renal failure were below the detectable limit (C-terminal, less than 0.1 ng/ml; N-terminal, less than 2.3 pg/ml). These data suggest that in patients with renal failure, the effect of parathyroid hormone on the central nervous system is mediated in some other way than via the cerebrospinal fluid.

Adult↗
PubMed1986

Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells.

The effects of prostaglandin (PG) F2 alpha and 9,11-epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of thromboxane A2, on the cytosolic free calcium concentration ([Ca2+]i) in vascular smooth muscle cells were studied with a new fluorescent Ca2+ indicator fura 2. PGF2 alpha and STA2, which are strong vasoconstrictors, caused rapid phasic and subsequent tonic increases in [Ca2+]i. PGF2 alpha caused dose-dependent elevation of [Ca2+]i not only in control solution but also in the calcium-free solution. A first stimulation with PGF2 alpha caused dose-dependent decrease in the response of [Ca2+]i to a second stimulation with PGF2 alpha. Pretreatment with 13-Azaprostanoic acid, a receptor level antagonist of thromboxane A2 inhibited the increase of [Ca2+]i induced by STA2. These results suggest that PGF2 alpha induces calcium mobilization followed by smooth muscle contraction through its specific receptors.

Angiotensin II↗
PubMed1986

Treatment of psoriasis vulgaris by oral administration of 1 alpha-hydroxyvitamin D3--open-design study.

In an open-design study 1 alpha-hydroxyvitamin D3 was administered orally to 17 patients with psoriasis vulgaris at a dose of 1.0 micrograms/day for 6 months. More than moderate improvement was observed in 13 (76%) of the 17 patients from 2.7 +/- 0.6 months (mean +/- SD) after the start of treatment. No side effects of the treatment were observed. The mechanism of the effect of 1 alpha-hydroxyvitamin D3 requires study, but these data suggest that its oral administration is effective for treatment of psoriasis vulgaris.

Administration, Oral↗
PubMed1986

Eel calcitonin suppresses plasma human calcitonin levels in medullary carcinoma of the thyroid.

The effects of synthetic [Asu1,7]-eel calcitonin (0.5 MRC unit/kg body weight intravenously for 30 min) on circulating levels of human calcitonin, calcium and gastrin were investigated in five patients with medullary carcinoma of the thyroid. Blood samples were obtained before and 15, 30, 60, 90, 120 and 180 min after commencement of infusion of [Asu1,7]-eel calcitonin. Plasma levels of human calcitonin were measured by radioimmunoassay. Cross-reactivity with [Asu1,7]-eel calcitonin in this assay was negligible. On infusion of [Asu1,7]-eel calcitonin, the mean plasma level of human calcitonin decreased significantly to 71.0 +/- 8.7% of the basal level (mean +/- SEM, P less than 0.05) after 30 min and 68.4 +/- 25.4% of the basal level (P less than 0.05) after 60 min. The serum calcium level also decreased significantly, but lagged behind the decrease of human calcitonin, being 95.1 +/- 0.7% of the basal level (P less than 0.01) at 120 min and 94.8 +/- 0.6% of the basal level (P less than 0.02) at 180 min. The mean plasma gastrin level did not change significantly on infusion of [Asu1,7]-eel calcitonin. In pooled data for all times, the percentage change in human calcitonin was not significantly correlated with either the percentage change in calcium (r = -0.25, P greater than 0.1) or the percentage change in gastrin (r = -0.38, P greater than 0.1).

Adolescent↗
PubMed1986

Comparison of inhibition by a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) of expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture with inhibition by retinoic acid.

Both retinoids and the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibit expression of the differentiated phenotype by rabbit costal chondrocytes in culture, as judged by morphological changes and decreased sulfation of glycosaminoglycans (GAG). However, the inhibition of the differentiated phenotype of chondrocytes in TPA-treated cells is restored by parathyroid hormone (PTH), while the inhibition by retinoids is not [Takigawa et al. (1982) Mol. Cell. Biochem. 42, 145-153; Takigawa et al. (1983) Cell Differ. 13, 283-291]. In the present study, we examined the difference between TPA-treated chondrocytes and retinoic acid-treated chondrocytes to determine the mechanism of the restoration of the differentiated phenotype in de-differentiated cells treated with TPA. PTH increased the activity of ornithine decarboxylase [ODC; EC 4.1.1.17], a rate limiting enzyme of polyamine biosynthesis, and proteoglycan synthesis in chondrocytes pretreated with TPA as well as in normal chondrocytes. The maximal stimulations of ODC activity and GAG synthesis were observed 4 h and 24-36 h, respectively, after addition of PTH. The dose-response curve for ODC induction by PTH was parallel to that of PTH-stimulated proteoglycan synthesis both in TPA-treated chondrocytes and in normal chondrocytes. PTH also increased the intracellular cyclic AMP level after 2 min in TPA-treated cells as in normal cells. Addition of dibutyryl cyclic AMP (DBcAMP) induced ODC and restored proteoglycan synthesis in TPA-treated cells. The dose-response curve for induction of ODC by DBcAMP was parallel to that of DBcAMP-stimulated proteoglycan synthesis in both TPA-treated chondrocytes and normal chondrocytes. On the other hand, the increases by PTH in the intracellular cyclic AMP level, ODC activity, and proteoglycan synthesis were inhibited in chondrocytes pretreated with a combination of TPA and retinoic acid as well as in those pretreated with retinoic acid alone. TPA stimulated the syntheses of DNA and RNA in chondrocytes but did not increase the cyclic AMP level or ODC activity. PTH and DBcAMP inhibited the syntheses of DNA and RNA both in TPA-treated cells and in normal cells. These results suggest that ODC induction mediated by elevation of cyclic AMP plays an important role in re-differentiation of de-differentiated cells pretreated with these agents.

Animals↗
PubMed1986

An open study of vitamin D3 treatment in psoriasis vulgaris.

Active forms of vitamin D3, 1 alpha-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3, were administered in an open-design study to 40 patients with psoriasis vulgaris in three ways: to 17 patients 1 alpha-hydroxyvitamin D3 was given orally at a dose of 1.0 micrograms/day for 6 months, to four patients 1 alpha,25-dihydroxyvitamin D3 was given orally at a dose of 0.5 microgram/day for 6 months, and 19 patients were given 1 alpha,25-dihydroxyvitamin D3 applied topically at concentration of 0.5 microgram/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group 1 with a mean period of treatment (+/- SD) of 2.7 +/- 0.6 months, in one patient in Group 2 at 3 months after the start of treatment, and in 16 (84%) patients in Group 3 when the chemical was applied for 3.3 +/- 1.2 weeks. No side-effects were observed in any of these trials. These data suggest that psoriasis may respond to active metabolites of vitamin D3 and that abnormalities in vitamin D metabolism or in responsiveness of the skin cells to active metabolites of vitamin D may be involved in the pathogenesis of this skin disease.

Adolescent↗
PubMed1986

Age and sex influences on urine calcitonin-like immunoreactivity in normal subjects.

Calcitonin-like immunoreactivity levels were determined in urine specimens in 585 normal subjects of various ages. Urine calcitonin-like immunoreactivity (uCTi) was measured by the midportion-specific radioimmunoassay after extraction of urine by gel chromatography on a 0.8 X 20 cm column of Bio Gel P-2. In 197 males and 169 females below 20 years old, significant negative correlations between the age and uCTi were observed (male: r = -0.684, female: r = -0.690). In 75 males and 80 females above 41 years, however, no significant correlation was observed between age and uCTi. The high level of uCTi in children could be explained by high levels of circulating calcitonin, associated with rapid bone growth; however the uCTi level in the elderly may not reflect the physiological significance of calcitonin for them because of a suspected age-related decrease in renal clearance of uCTi in the elderly.

Adolescent↗
PubMed1985

An acromegalic patient with recurrent urolithiasis.

A 52-year-old man with an acromegalic appearance of prolonged duration suffered abdominal colic attacks and hematuria during the middle of the course of the disease. The patient was diagnosed as having urolithiasis caused by increased urinary calcium. The calcium metabolic disorder was not considered to be due to hyperparathyroidism because serum calcium and PTH levels were within the normal range and no abnormality was observed in a parathyroidal scintigraph. The serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels (55.0 and 73.0 pg/ml) were higher than the normal range (27.2-53.8 pg/ml). A selective adenomectomy by the transsphenoidal route (Hardy's method) was performed, resulting in an improvement in the hypercalciuria and urolithiasis, and a decrease in the levels of serum 1,25-(OH)2D (23.0 and 23.0 pg/ml). These findings suggest that GH may promote the activation of vitamin D in the kidney in acromegaly, resulting in an acceleration of calcium absorption in the intestine through the action of activated vitamin D and the induction of increased urinary calcium excretion by the urinary excretion of excessive blood calcium.

Acromegaly↗
PubMed1983

Restoration by parathyroid hormone and dibutyryl cyclic AMP of expression of the differentiated phenotype of chondrocytes inhibited by a tumor promoter, 12-0-tetradecanoylphorbol-13-acetate.

12-0-Tetradecanoylphorbol-13-acetate (TPA) inhibited expression of the differentiated phenotype of chondrocytes in rabbit costal chondrocytes in culture. TPA transformed typical polygonal chondrocytes into multilayered, fibroblastic cells and also inhibited the rate of [35S]sulfate incorporation into glycosaminoglycan (GAG), a differentiated phenotype of chondrocytes. These changes were apparent within 24 h and reached a plateau at 48 h after the addition of TPA. Phorbol didecanoate and phorbol dibenzoate also inhibited sulfation of GAG, even though the effect was weaker than that of TPA. Phorbol diacetate and 4-0-methyl TPA did not inhibit sulfation of GAG. Addition of parathyroid hormone (PTH) or dibutyryl cyclic AMP simultaneously with TPA overcame the inhibition caused by TPA. PTH and dibutyryl cyclic AMP also reversed the inhibition and stimulated expression of the differentiated phenotype of chondrocytes even in de-differentiated cells which had been pretreated for 3 days with TPA. These findings suggest that cyclic AMP plays an important role in the restoration of the differentiated phenotype of chondrocytes in TPA-treated chondrocytes, and that the TPA-treated cells retain some of the differentiated phenotype of the original cells, such as responsiveness to PTH.

Animals↗