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Biomedical subjects

H Morii

Publications and source records attributed to H Morii.

At least 19 recordsLinked to original sources
PubMed1992

[A case of esophageal carcinoma with hypercalcemia caused by PTH-rP--the effect of therapy on the bone and calcium metabolism].

The changes in the bone and in calcium metabolism during cisplatin or bisphosphonate administration is reported in a 50-year-old patient with esophageal carcinoma who had humoral hypercalcemia of malignancy (HHM). Laboratory findings on admission showed that ionized calcium was 1.65mmol/L, phosphorus was 2.4mg/dl, and PTH-rP was 151pmol/L, without any evidence of bone metastasis. After admission, cisplatin and/or bisphosphonate were administrated for hypercalcemia. These administrations ameliorated serum ionized calcium, urinary pyridinoline and hydroxyproline level within a few days. Although cisplatin administration decreased the serum osteocalcin level, bisphosphonate administration kept up the level, suggesting that bisphosphonate maintained bone formation and cisplatin decreased its formation. The discrepancy may be due to the coupling with the reduction of bone resorption and/or direct toxic effect on osteoblasts during cisplatin administration, and preservation of osteoblastic activity during bisphosphonate administration. Cisplatin and bisphosphonate may have different effects on bone formation. Serum 1,25(OH)2D level was slightly decreased or unchangeable after cisplatin administration, although the level was increased after bisphosphonate administration. Direct toxic effect on 1 alpha-hydroxylase of the kidney or increase in phosphrous level may explain the change of 1,25(OH)2D after cisplatin administration. These results suggested that cisplatin and bisphosphonate have the same effect of preventing bone resorption but different effects on bone formation and/or serum 1,25(OH)2D level.

Bone Resorption↗
PubMed1992

Adenosine(5')hexaphospho(5')adenosine stimulation of a Ca(2+)-induced Ca(2+)-release channel from skeletal muscle sarcoplasmic reticulum.

Stimulation of a Ca(2+)-induced Ca(2+)-release channel from skeletal muscle sarcoplasmic reticulum by various adenosine(5')oligophospho(5')adenosines (ApnA, n = 2-6) by a rapid quenching technique using radioactive calcium was studied. Ap4A, Ap5A and Ap6A, as well as adenosine 5'-[beta, gamma-methylene]triphosphate (AdoPP [CH2]P), a non-hydrolyzable ATP analogue, stimulated the Ca(2+)-release channel, whereas Ap2A and Ap3A had no effect. At a concentration of 0.5 mM, the order of stimulation was AdoPP[CH2]P less than Ap4A less than Ap5A much less than Ap6A. As well as having the highest affinity (0.44 mM for half-maximal stimulation), Ap6A showed an extraordinarily high Hill coefficient of 3.3 (1.9 for AdoPP[CH2]P, 2.1 for Ap5A). The stimulating effect of Ap6A was reversible, yet its dissociation proceeded very slowly. Stimulation of Ca2+ release by Ap6A was counteracted by Mg2+ and ruthenium red. A 2',3'-dialdehyde derivative of Ap6A, which is a chemical probe for amino groups, stimulated irreversibly the Ca(2+)-release channel and modified some high-molecular-mass sarcoplasmic reticulum proteins, possibly including the channel protein. Our data suggest that Ap6A stimulates the Ca2+ channel by binding to the activation site of the channel subunit and simultaneously preventing the spontaneous decay of the Ca2+ channel by keeping together two of the four channel subunits by bridging them with its two adenosine groups.

Animals↗
PubMed1992

Dibutyryl cAMP enhances the effect of 1,25-dihydroxyvitamin D3 on a human promyelocytic leukemia cell, HL-60, at both the receptor and the postreceptor steps.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) induces differentiation of a human promyelocytic leukemia cell line, HL-60, into monocytes/macrophages, and 25-hydroxyvitamin D3- and 1,25-(OH)2D3-24-hydroxylase activities in HL-60 mitochondria via a steroid-hormone receptor mechanism. Dibutyryl cyclic adenosine monophosphate (dbcAMP), a granulocyte inducer, significantly augmented the differentiation-inducing effect of 1,25-(OH)2D3 along the monocyte/macrophage pathway. Furthermore, dbcAMP significantly potentiated the effect of 1,25-(OH)2D3 on HL-60 cells to hydroxylate 1,25-(OH)2[26,27-3H]D3 to form 1,24,25-(OH)3[26,27-3H]D3. DbcAMP seemed to augment the effect of 1,25-(OH)2D3 in part through upregulation of the 1,25-(OH)2D3 receptor, because 10(-7) M dbcAMP increased 1,25-(OH)2D3 receptor levels approximately 2.3-fold, which was similar to a 1.9-fold augmentation by the same concentrations of dbcAMP of 1,25-(OH)2D3-induced cell characteristics to hydroxylate C-24 of 1,25-(OH)2[26,27-3H]D3. However, dbcAMP is also known to enhance HL-60 cell differentiation caused by other differentiation inducers. We have established another HL-60 clone which acquires resistance to 1,25-(OH)2D3 in the induction of cell differentiation by a defect at the postreceptor step, as reflected by resistance to other differentiation inducers, such as retinoic acid and dimethyl sulfoxide. Even in this resistant clone, dbcAMP significantly enhanced the differentiation-inducing effect of 1,25-(OH)2D3. Of interest, this clone showed resistance to dbcAMP in the induction of cell differentiation. Furthermore, we have demonstrated that intracellular cAMP levels were significantly lower in uremic serum-treated cells than in cells treated with normal human serum and that a significant positive correlation was found between intracellular cAMP levels and 1,25-(OH)2D3-induced cell differentiation. These data indicated that the intracellular cAMP level is one of the major determinants of 1,25-(OH)2D3-induced HL-60 cell differentiation and that dbcAMP could enhance the effects of 1,25-(OH)2D3 on HL-60 cells not only by increasing 1,25-(OH)2D3 receptor levels but also at the postreceptor step.

Bucladesine↗
PubMed1992

A new, highly sensitive assay for 1,25-dihydroxyvitamin D not requiring high-performance liquid chromatography: application of monoclonal antibody against vitamin D receptor to radioreceptor assay.

A new, highly sensitive radioreceptor assay, which does not require high-performance liquid chromatography, has been developed for the determination of 1,25-dihydroxyvitamin D3 (1,25-(OH2)D3) in serum. The assay involves rapid extraction of serum, Sep Pak silica purification, and addition of 1,25-dihydroxyvitamin D3 receptor, radiolabeled 1,25-dihydroxyvitamin D3, bovine serum albumin, and monoclonal antibody to specifically precipitate the receptor. This method is sensitive to 0.3-0.6 pg/tube, with B50 occurring at 5.8 pg/tube. This sensitivity combined with overall recovery of 1,25-dihydroxyvitamin D3 (81.5 +/- 5.2%, n = 50, mean +/- SD) allows the measurement of serum 1,25-(OH)2D3 in duplicates with only 0.5 ml of serum. Intra- and interassay coefficient of variation were 9.5 and 14.6%, respectively. Dilution analysis, analytical recovery of added 1,25-dihydroxyvitamin D3, and comparison with a standard method using HPLC have been used to validate the assay. Serum 1,25-dihydroxyvitamin D3 level was for normal adults, 36.6 +/- 10.5 pg/ml (n = 14); in primary hyperparathyroidism, 98.9 +/- 19.9 pg/ml (n = 16); in chronic renal failure, 17.8 +/- 5.1 pg/ml (n = 12). This method allows large numbers of samples to be processed at once. Further, the method is rapid and provides an accurate assay using small amounts of serum.

Administration, Oral↗
PubMed1992

A possible role of carbohydrate moieties in prostaglandin D2 and prostaglandin E2 receptor proteins from the porcine temporal cortex.

The binding activities of prostaglandins (PGs) D2 and E2 were measured after deglycosylation of P2 membranes prepared from the porcine temporal cortex in order to investigate the role of carbohydrate moieties in the receptor binding. PGD2 and PGE2 binding activities were significantly decreased by pretreatment with various exoglycosidases, such as neuraminidase for PGE2 binding, alpha-mannosidase and beta-galactosidase for PGD2 binding, and beta-N-acetylhexosaminidase for both. Further, peptide N-glycohydrolase F and endo-alpha-N-acetylgalactosaminidase, which are specific for the cleavage of N-glycan and O-glycan linkages, respectively, in glycoproteins were used. Pretreatment with either of them also reduced both PGD2 and PGE2 binding activities. The reduction was dependent on the pretreatment time and enzyme concentration. The time courses of the reduction were typically characterized by a marked increase in the nonspecific bindings. Scatchard plot analysis revealed that the reduction was caused by a decrease in the affinity rather than one in the maximal binding capacity. The specificity of the binding sites thereby shifted to be more nonspecific without affecting the order of the relative affinities among PGs for the binding sites. These results suggest that the carbohydrate moieties on PG receptor proteins of the brain are essential for the expression of their binding activities.

Amidohydrolases↗
PubMed1992

Partial protection of 1 alpha-hydroxyvitamin D3 against the development of diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice.

1 alpha-Hydroxyvitamin D3 (1 alpha-OH-D3), a precursor of active vitamin D3, 1 alpha,25-dihydroxyvitamin D3, was tested in CD-1 mice for its in vivo effect against the development of diabetes induced by administering multiple low doses of streptozotocin (STZ). Daily intraperitoneal (IP) injections of 35 mg/kg body weight of STZ administered for 5 consecutive days to mice from 7 weeks of age induced a delayed-onset hyperglycemia, insulitis, and beta-cell degranulation in 26 of 28 mice. Only 12 of 29 mice developed diabetes when treated with simultaneous daily IP injections of 1 alpha-OH-D3 for 14 consecutive days, with diabetes defined as a plasma glucose level greater than 200 mg/dL. A daily dose of 0.3 micrograms/kg 1 alpha-OH-D3 also protected against the development of hyperglycemia in five of 13 mice, whereas 0.2 micrograms/kg 1 alpha-OH-D3 was ineffective, indicating a dose-related effect. Histological study showed that, among the 1 alpha-OH-D3-treated mice, the pancreatic islets of euglycemic mice showed neither massive islet infiltration nor beta-cell degranulation, whereas those of the hyperglycemic mice showed insulitis. However, when diabetes was chemically induced with a single high dose of STZ, the simultaneous administration of 1 alpha-OH-D3 to mice failed to protect against the development of hyperglycemia; all five mice so treated developed hyperglycemia. Their pancreatic islets did not show insulitis. Therefore, it is suggested that 1 alpha-OH-D3 may protect against the development of diabetes following administration of multiple low doses of STZ, probably via an immune mechanism.

Animals↗
PubMed1992

Segmental gut transit in diabetes mellitus: effect of cisapride.

Gut transit using radiopaque markers was assessed in 5 healthy subjects and 24 diabetic patients. In the diabetics, various parameters including duration of the disease and diabetic complications, such as neuropathy, retinopathy and nephropathy, were determined, and the relationships between gut transit times and these complications were evaluated. The effect of cisapride on gut transit was studied in 10 diabetic patients. Large intestinal, descending colon, distal colon, and whole gut transit times were delayed in diabetics with autonomic neuropathy compared to controls and to diabetics without autonomic neuropathy (P less than 0.01). There was no difference in proximal colon transit times among them. An inverse correlation was observed between CVRR and the transit times for descending colon, distal colon, large intestine and whole gut. Large intestinal and whole-gut transit times were delayed in diabetics with retinopathy or with nephropathy compared to diabetics without those complications (P less than 0.01). In the diabetics, oral administration of 7.5 mg/day of cisapride for 2 weeks significantly accelerated descending colon transit (P less than 0.05) and partially accelerated distal colon, large intestinal and whole-gut transit. It is concluded that diabetics with autonomic neuropathy have delayed transits for the whole gut and that this finding is apparent to some extent in the distal colon but not in the proximal colon. Chronic oral administration of cisapride, a gastrointestinal prokinetic drug, was effective to improve these gastrointestinal motility disorders in diabetics with autonomic neuropathy.

Administration, Oral↗
PubMed1992

Impaired metabolism of high density lipoprotein in uremic patients.

We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglyceride/cholesterol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1992

Transport of 1,5-anhydro-D-glucitol into human polymorphonuclear leukocytes.

1,5-Anhydro-D-glucitol (AG) is one of the main polyols and its structure resembles glucose. It has been proposed that decreased serum AG concentrations in diabetic patients are a novel indicator of diabetic metabolic derangement. However, the pathway of AG metabolism still remains to be clarified. In this study we investigated the transport of AG into human polymorphonuclear leukocytes (PMNLs) isolated from healthy volunteers and found that 0.1 mM 3-O-methy-D-glucose (3OMG) was equilibrated with a half saturation time of 10 s, while the uptake rate of AG was much slower. The concentration dependence of AG uptake revealed that the AG transport velocity reached a plateau, with a Km of about 50 mM and Vmax of about 25 nmol/min/10(7) cells. Transport of 14C-labeled 3OMG was inhibited by unlabeled D-glucose or AG in a dose-dependent manner. The mean inhibition constant (Ki) for D-glucose and for AG were 1.06 and 4.93 mM, respectively. Cytochalasin B (20 microM) inhibited 3OMG transport by 90% but AG transport by only 50%. S/V for 14C-labeled AG transport plotted against the concentration of unlabeled 3OMG showed a non-linear and biphasic pattern. These results suggest that AG influx into PMNLs is mediated not only by the cytochalasin B-sensitive glucose transport system but also via another facilitated transport system.

3-O-Methylglucose↗
PubMed1992

Radioimmunoassay for calcitonin gene-related peptide and its measurement in sera of patients with thyroid disease.

To investigate serum levels of calcitonin gene-related peptide (CGRP), we developed a sensitive radioimmunoassay (RIA). RIA for CGRP in serum can present some problems: the serum may degradate the tracer during incubation and suppress the antigen-antibody reaction. We avoided these problems by using aprotinin and CGRP-free serum instead of a buffer for the standard curve. We detected serum CGRP in all 39 healthy subjects when CGRP-free serum was not used for the standard curve, but 34 of these subjects had serum CGRP levels below the detection limit (less than 80 pmol/l) when CGRP-free serum was used for the standard curve. We defined the normal range for serum CGRP as below 100.8 pmol/l, which was the maximum level found in the healthy subjects. We studied serum levels of this peptide in patients with thyroid diseases, because the thyroid may be one origin of circulating CGRP. Four of 10 patients with medullary thyroid carcinoma had elevated serum levels of CGRP. Seven of 24 patients with subacute thyroiditis had elevated serum levels of CGRP, but at least one year after clinical recovery, CGRP was undetectable in all. Seven of the 37 patients with hypothyroidism had elevated serum levels of CGRP. None of the patients with hyperthyroidism, adenomatous goiter, thyroid adenoma, or thyroid carcinoma had elevated serum CGRP levels. It is necessary to use a standard curve obtained by the addition of aprotinin and CGRP-free serum to the assay standards to measure serum CGRP levels. Some patients with subacute thyroiditis, hypothyroidism, or medullary thyroid carcinoma had elevated serum CGRP levels.

Adult↗
PubMed1992

Magnesium deficiency enhances secretion of parathyroid hormone in normal and 5/6-nephrectomized uremic rats.

Hypercalcemia, rather than hypocalcemia, has been observed in conjunction with severe magnesium (Mg) depletion in rat, in contrast to the development of hypocalcemia in Mg deficiency in various animal models. In the present study, a possible involvement of parathyroid hormone (PTH) in the development of hypercalcemia in rat was studied by using a newly-developed sensitive and specific radioimmunoassay system for the determination of rat PTH. In normal rat model, hypercalcemia occurred in association with a decrease of serum phosphate levels in Mg deficiency. However, serum PTH levels were not suppressed despite the occurrence of hypercalcemia, suggesting PTH as an important factor for the development of hypercalcemia. Of interest, in 5/6-nephrectomized uremic model, hypocalcemia, rather than hypercalcemia, was observed in Mg-deficient rats. Serum PTH levels seemed to be higher, but not statistically significant probably due to a small number of rats. However, infusion study clearly demonstrated that PTH secretion was significantly increased in Mg-deficient uremic rats compared with Mg-replete counterparts. The reason for an increase of serum PTH responses might be explained by Mg depletion itself in addition to a fall in serum Ca levels, because infusion study revealed that the magnitude of the stimulation of PTH secretion was increased in Mg deficiency despite the similar degrees of changes in serum Ca levels and that the set point for the suppression of PTH secretion by Ca might be altered in Mg deficiency. Taken these data together, it was strongly suggested that Mg depletion might enhance PTH secretion in rat.

Animals↗
PubMed1992

[Vitamin D3].

With the application of biochemical technique came the discovery that vitamin D is metabolized sequentially to 25-hydroxyvitamin D in liver and then to 1.25-dihydroxyvitamin D (1.25D), the hormonal form of vitamin D, in kidney. The latter process is strictly controlled with the demand of calcium and phosphorus. The produced 1.25D binds its specific receptor probably located in the nuclei. With the application of modern tools of molecular biology came the discovery that vitamin D receptor (VDR), which belongs to steroid receptor family, acquires increased affinity for DNA when it binds to 1.25D and then VDR complexes bind to DNA with its two zinc-finger projections. VDR complexes recognize vitamin D responsive element on DNA, two tandemly repeated hexanucleotide sequences separated by three base pairs. Furthermore, to interact with the VDRE, VDR complexes require nuclear accessory factor, which might be retinoid X receptor (RXR). As above, molecular biology helps us to extend our knowledge in the field of vitamin D.

Calcitriol↗
PubMed1992

A two-site immunochemiluminometric assay for intact parathyroid hormone and its clinical utility in hemodialysis patients.

Measurement of serum parathyroid hormone (PTH) concentrations is complicated by the fact that there are several fragments of the hormone in the circulating as a result of the metabolism of PTH. The best way to study the secretory activity of the parathyroid glands directly may be to measure the biologically active intact PTH molecule. Recently, it has become possible to overcome these limitations by application of the two-site immunoradiometric assay (IRMA) to the measurement of intact PTH. The two-site immunometric technique has been applied to the two-site immunochemiluminescent assay (ICMA) for the measurement of circulating intact PTH. To evaluate the utility of measurements of serum intact PTH by two-site ICMA in hemodialysis patients, two-site ICMA and IRMA were compared in 104 hemodialysis patients. We found a good correlation (r = 0.93) between values obtained by ICMA and by IRMA. Although serum intact PTH by ICMA was significantly suppressed by rising plasma ionized calcium after a session of hemodialysis in 29 patients, mid-region PTH did not show a significant change. This result suggests the intact PTH assay is more suitable for the earlier detection of secondary hyperparathyroidism than the mid-region assay and may be useful for precise assessment of clinical status and response to therapeutic intervention designed to correct the progressive bone disease in hemodialysis patients. We conclude that two-site ICMA for serum intact PTH which could be measured without radioisotopes nor scintillation counter is as useful as IRMA in hemodialysis patients.

Humans↗
PubMed1992

High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis.

We measured serum lipoprotein(a) [Lp (a)] concentrations in 50 uremic patients treated on continuous ambulatory peritoneal dialysis (CAPD) and compared them with those in 29 uremic patients on hemodialysis (HD) and those in 62 normal controls. The median values were 47.9 mg/dl in CAPD patients, 25.2 mg/dl in HD patients, and 11.7 mg/dl in controls, respectively. These differences were statistically significant when assessed by Kruskal-Wallis test (p < 0.0001). Thirty-five out of 50 patients on CAPD (70%) and 12 out of 29 patients on HD (41%) had Lp(a) concentrations above 30 mg/dl, whereas these high values were observed in only 15% of normal controls. This difference in prevalence of high Lp(a) was also significant by 2 x 3 chi-square test (p < 0.01). There was a significant positive correlation between Lp(a) and apolipoprotein B (r = 0.517, p < 0.0001). In CAPD patients, 9 with ischemic heart disease had a significantly higher median Lp(a) than those without it (67.4 vs 40.9 mg/dl, p < 0.01 by Mann-Whitney U-test). These results suggest that high levels of serum Lp(a) might contribute to an increased risk for ischemic heart disease in CAPD patients, and that there may be a relationship between Lp(a) and apolipoprotein B metabolism in CAPD patients.

Adult↗
PubMed1992

Inhibitory effect by 1,25-dihydroxyvitamin D3 on concanavalin A-stimulated proliferation of rat thymic lymphocytes.

It has been reported that vitamin D3 derivatives promote the differentiation of monocytes into macrophages, while the derivatives suppress mitogen-stimulated proliferation of human peripheral blood-mononuclear cells (PBMC). However, their effect on thymic lymphocytes which are in the course of differentiation and maturation into T cells has not been thoroughly examined. The authors studied the inhibitory effect by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on concanavalin A (Con A)-stimulated proliferation of rat thymic lymphocytes and explored its mechanism. The proliferation of rat thymic lymphocytes stimulated with Con A was suppressed by 1,25-(OH)2D3 in a dose-dependent manner between a range of 10(-10) M to 10(-8) M. Because this suppressive action of 1,25-(OH)2D3 was markedly reduced by removal of coexisting adherent cells or by treatment with indomethacin which suppresses the prostaglandin E2 (PGE2) synthesis, it seems likely that PGE2, released from macrophages with the stimulation of 1,25-(OH)2D3, is involved in the suppressive action. Further studies on the inhibitory mechanism clarified that PGE2 from the contaminated macrophages suppressed the formation and release of interleukin-2 (IL-2), whereas the expression of IL-2 receptors on thymic lymphocyte with Con A stimulation was not affected. These results suggest that vitamin D3 derivatives might possibly contribute to regulation of in vitro proliferation of thymic lymphocytes.

Animals↗