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Biomedical subjects

H Morii

Publications and source records attributed to H Morii.

At least 181 records · Page 10Linked to original sources

Reduction of intermediate density lipoprotein by pravastatin in hemo- and peritoneal dialysis patients.

Elevated plasma intermediate density lipoprotein (IDL) is one of the features of uremic dyslipidemia which is potentially atherogenic. We examined the effects of pravastatin, an HMG-CoA reductase inhibitor, on IDL levels as well as other lipoprotein parameters in 19 uremic patients treated with hemodialysis (HD, n = 11) or continuous ambulatory peritoneal dialysis (CAPD, n = 8). The patients were administered 5 mg/day pravastatin for the initial 4 weeks and 10 mg/day for the subsequent 12 weeks. In the analysis of the total subjects, IDL-cholesterol was reduced by 31% as well as low density lipoprotein (LDL)-cholesterol. Cholesterol in very low density lipoprotein (VLDL) also decreased whereas that in high density lipoprotein (HDL) did not. Significant decrease of serum triglycerides was due mainly to reduced IDL- and LDL-triglycerides. Apolipoprotein (apo) A-I did not change, whereas apo A-II, B, C-II, C-III, E, and B/A-I ratio were significantly lowered. Pravastatin did not affect measured activity of lecithin: cholesterol acyltransferase, post-heparin plasma lipoprotein lipase or hepatic triglyceride lipase. HD and CAPD patients responded almost equally to the treatment. IDL elevation was present independent of serum total cholesterol, and it was lowered by pravastatin even in non-hypercholesterolemic subjects. There was no critical adverse effect besides transient and asymptomatic increase of serum creatine kinase level. We conclude that pravastatin can be a safe and effective approach to the management of dyslipidemia in uremic patients who have an elevated level of IDL.

Apolipoproteins↗

Interleukin-1 beta stimulates phospholipase A2 activity in rat C6 glioma cells.

Phospholipase A2 activities could be detected in both cytosolic and membrane fractions prepared from rat C6 glioma cells. The activities in both fractions were significantly increased by human recombinant interleukin-1 beta in a dose-dependent manner. Such a stimulation required a long-time exposure over 72 h and was partially inhibited by cycloheximide, a potent protein synthesis inhibitor. These results suggested that interleukin-1 beta may stimulate phospholipase A2 activity through its gene activation.

Animals↗

[Polyglandular autoimmune syndrome].

Among numerous etiologies for hypoparathyroidism, one of the inheritable forms of hypoparathyroidism, called polyglandular autoimmune syndrome, appears as a complex of hypofunction of several endocrine glands, candidiasis, pernicious anemia and vitiligo. Idiopathic hypoparathyroidism in the PGA syndrome typically presents by 20 years of age. Among the three major components of the PGAI syndrome, candidiasis is usually the first manifestation. Hypoparathyroidism almost invariably precedes the onset of Addison's disease. One should keep in mind that Addison's disease can mask the presence of hypoparathyroidism and that glucocorticoid replacement therapy alone can cause hypocalcemic crisis.

Addison Disease↗

Interleukin-1 beta induces cytosolic phospholipase A2 gene in rats C6 glioma cell line.

Treatment of the rat C6 glioma cell line with interleukin-1 beta (IL-1 beta) resulted in an accumulation of cytosolic phospholipase A2 (cPLA2) in mRNA level. The increase of cPLA2 in mRNA level was observed at 6 hours after treatment of IL-1 beta and reached to the maximal level at 12 hours. The accumulation also remained sustained for up to 72 hours. Dose response curve of IL-1 beta showed that as little as 40 units/ml concentration induced the accumulation of mRNA and 100 units/ml concentration showed the maximal effect. In contrast, cyclooxygenase 2 gene was not affected with treatment of IL-1 beta.

Animals↗

22-Oxa-1,25(OH)2vitamin D3, a synthetic analogue of vitamin D3, has no promoting activity in a rat liver medium-term bioassay.

Modifying effects of 22-oxa-1,25(OH)2vitamin D3(OCT), a synthetic analogue of vitamin D3, were evaluated in a liver medium-term bioassay using glutathione S-transferase placental form (GST-P)-positive foci and 5-bromo-2'-deoxyuridine (BrdU) labeling to give an index of DNA synthesis. F344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body wt.) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, 500 p.p.m. phenobarbital sodium and/or basal diet were fed to the rats for 6 weeks, at the same time as OCT and/or propylene glycol as the vehicle injected intraperitoneally 5 times a week. OCT demonstrated no promoting activity for rat hepatocarcinogenesis, and, in fact, showed a tendency to decrease the area per unit area of (GST-P)-positive foci in the livers of rats fed 500 p.p.m. phenobarbital sodium. However, intergroup differences in areas and numbers per unit area as well as in BrdU labeling indices were not statistically significant.

Animals↗

Asymmetrical topology of diether- and tetraether-type polar lipids in membranes of Methanobacterium thermoautotrophicum cells.

We investigated the distribution of diether polar lipids between the inner and outer leaflets of the membrane of Methanobacterium thermoautotrophicum comparing the orientation of tetraether polar lipids, which constitute a monolayer in the same membrane. Three kinds of reactions were employed for intact cells or protoplasts and unsealed membrane fragments prepared from the organism: glycosidase digestion for glycolipids, NaIO4 oxidation for glycolipids and inositol lipids, and trinitrophenylation for aminophospholipids. The results indicated that (a) most gentiobiose residues of both diether and tetraether polar lipids were exposed on the outside of the cells; (b) serine and inositol residues of both diether and tetraether polar lipids were mainly oriented to the cytoplasmic surface of the membrane; and (c) approximately 80% of archaetidylethanolamine (diether type) was distributed in the outer leaflet of the membrane bilayer, while only 25% of the ethanolamine residue of gentiobiosyl caldarchaetidylethanolamine (tetraether type) was oriented to the outer surface of the membrane. These results, except for ethanolamine lipids, are consistent with the hypothesis that the tetraether polar lipids are synthesized from the corresponding diether polar lipid precursors that have been already substituted by polar groups in the membrane by head-to-head condensation without rearrangement of lipids.

Carbohydrate Conformation↗

The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa.

In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene. In this paper, the effects of polyamines and their analogues on the sedimentation properties of vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding activity of the receptor, were studied. In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D receptor dose-dependently. These findings show that polyamines can activate vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well. Sucrose density gradient analysis using various kinds of polyamine analogues having various numbers of cations showed that the number of cation of polyamines is important for the efficiency to change the sedimentation coefficient of vitamin D receptor, and that the distance between two cationic charges does not play an important role.

Animals↗

Presence of gene expression of vitamin D receptor and 24-hydroxylase in OK cells.

We investigated the gene expression of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptors (VDR) and 25-hydroxy-vitamin D3-24-hydroxylase (24-hydroxylase) in opossum kidney (OK) cells. Reverse transcription-polymerase chain reaction demonstrated the presence of VDR gene expression in OK cells. Northern hybridization, using rat VDR cDNA, also demonstrated a 4.4 kbp VDR mRNA expression which was affected by serum but not by 1,25(OH)2D3 and/or parathyroid hormone stimulation. Stimulation with 1,25(OH)2D3 induced 24-hydroxylase mRNA expression which peaked at 6 h. This study clearly demonstrates for the first time the presence of VDR and 24-hydroxylase gene expression in OK cells, suggesting that OK cells are a useful model for investigating the genetic action mechanisms of 1,25(OH)2D3.

Animals↗

Alpha-helical assembly of biologically active peptides and designed helix bundle protein.

The formation of alpha-helical assembly by complexing biologically active peptides with de novo designed protein is described. The de novo designed protein described here is a cystine-linked 4-helix bundle protein constructed with 80 amino acid residues and forms a hydrophobic core region surrounded by 4 helices in an aqueous solution. The biologically active peptides, such as melittin and human growth hormone releasing factor, contain the sequences that are able to form amphiphilic helices. These peptides alone do not form the alpha-helix structure in a diluted solution with low ion strength. But on mixing with the designed helix bundle protein, the peptides are strongly bound to the protein with the induction of alpha-helical structure in the biologically active peptides. The content of induced alpha-helix is in accord with that estimated from the amphiphilic sequence. The results mean that a novel architecture composed of alpha-helices is formed. Fluorescent and temperature-scanning measurement revealed that the alpha-helical assembly is constructed with hydrophobic interaction. Also, it is shown by means of fluorescence depolarization that the assembly has a compact globular form corresponding to 1:1 complex.

Amino Acid Sequence↗

Protein kinase C is involved in 24-hydroxylase gene expression induced by 1,25(OH)2D3 in rat intestinal epithelial cells.

Effects of protein kinase C (PKC) inhibitor and activator on 1,25(OH)2D3-induced gene expression were examined in rat intestinal epithelial cells, IEC-6 cells. A potent PKC inhibitor, H-7 (20 microM), completely abated 1,25(OH)2D3-induced 24-hydroxylase gene expression at 3 and 6 h. The effect of H-7 was dose dependent with IC50 around 5 microM. Other protein kinase inhibitors, HA-1004 and H-89 (20 microM), had no effects. Furthermore, the activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) potentiated the effect of 1,25(OH)2D3 by 1 h. TPA appeared to exert its effect at a transcriptional step, since mRNA stability was not affected by TPA treatment. At 3 h after the treatment of the cells with H-7 and TPA, vitamin D receptor (VDR) contents estimated by 3H-1,25(OH)2D3 binding capacity were 72.4 and 63.2% of vehicle-treated cells without significant changes of binding affinities, suggesting that the effect of H-7 and TPA was not the result of changes in VDR content or its binding affinity. In conclusion, PKC is involved in 1,25(OH)2D3-induced 24-hydroxylase gene expression in IEC-6 cells between 1,25(OH)2D3-VDR binding and VDR-induced gene transactivation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Total body and regional bone mineral content in hemodialysis patients.

Bone mineral content (BMC) in the total body and lumbar spine was evaluated in 126 hemodialysis patients (60 males, 66 females) by dual photon absorptiometry with the Norland DBD 2600. Measurements of: 1) total body BMC divided by lean body mass (BMCTB/LBM), 2) bone mineral density (BMD) of total body, 3) BMD of four regional sections (head, trunk, pelvis, and legs), and 4) BMD of lumbar spine, generally showed a significant decrease in the hemodialysis patients compared to the reference population. However, arm BMD did not show a significant difference between patients and control populations. The z-score of BMCTB/LBM declined significantly throughout the duration of hemodialysis, although that of the lumbar spine BMD did not. It should be noted that the degree of decrease in BMC was more prominent in the total body measurement than in the lumbar spine measurement. There was preferential osteopenia of the total body in the hemodialysis patients. Although the lumbar spine BMD showed a lower value than the control population, the lumbar spine is not the recommended region to monitor the BMD change in hemodialysis patients.

Absorptiometry, Photon↗

Antroduodenal motility and transpyloric fluid movement in patients with diabetes studied using duplex sonography.

BACKGROUND/AIMS: To elucidate the relationship between diabetic autonomic neuropathy and gastrointestinal motility, antroduodenal motility was studied in patients with diabetes using duplex sonography. METHODS: Antroduodenal motility, transpyloric fluid movement, and velocity curves of fluid flow were studied using duplex sonography in 32 patients with diabetes and 10 healthy subjects after their ingestion of a meat soup. RESULTS: The frequency of antroduodenal coordination was significantly reduced in patients with diabetes with both early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency and duration of end-cycle reflux episodes were also significantly reduced in patients with early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency of end-cycle reflux episodes was closely correlated with the frequency of antroduodenal coordination in both healthy subjects (r = 0.859; P = 0.002) and patients with diabetes (r = 0.929; P = 0.0001). There was a significant correlation between fasting plasma glucose concentrations and the frequency of antroduodenal coordination in patients with diabetes (r = -0.361; P = 0.039). CONCLUSIONS: These findings suggest that reduced frequency and duration of end-cycle reflux episodes may be an early indicator of diabetic gastroparesis that may be related mainly to autonomic neuropathy but also in part to acute hyperglycemia.

Adult↗

Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure.

We studied the homologous regulation of the vitamin D receptor (VDR) in the duodenum of rats with chronic renal failure. Mean basal nuclear 3H-labeled 1 alpha,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) binding capacity was 48 and 43 fmol/mg protein for sham-operated and uremic rats with similar dissociation constants (Kd), respectively. These results coincided with those of immunoblot analysis, which found that VDR protein level of uremic rats was 87.6% that of sham-operated rats. In uremic rats, 1,25(OH)2D3, 2.0 micrograms/kg, failed to upregulate VDR protein levels until 24 h, in contrast to the significant increases produced in sham-operated rats at both 12 (1.55-fold) and 24 h (1.75-fold). Baseline level of VDR mRNA in uremic rats, determined by Northern blot analysis, was comparable to that in sham-operated rats. Treatment with 1,25(OH)2D3 slightly decreased VDR mRNA at 6-24 h in the sham-operated rats, in contrast to the increase seen at 6 h in uremic rats. These results suggest that the homologous upregulation of VDR was attenuated in rats with chronic renal failure because of an impairment at a translational and/or posttranslational step.

Analysis of Variance↗

Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine.

24-Hydroxylase has been considered a major enzyme regulating metabolism of circulating 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. To understand the metabolism of 1,25(OH)2D3 in chronic renal failure, we examined 1,25(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) gene expression in the intestine of uremic rats. Northern blot and dot blot analyses showed that the induction of duodenal 24-hydroxylase gene expression was 2.0- to 3.8-fold greater in uremic rats than in sham-operated rats (P < 0.05, Student's t-test) at 6 h after 1,25(OH)2D3 administration. Gene induction of calbindin D9k by 1,25(OH)2D3 was not augmented in uremic group. In situ hybridization analysis revealed that the induction of 24-hydroxylase mRNA by 1,25(OH)2D3 was observed exclusively in the columnar epithelium of the crypt and the lower part of the villi, suggesting that the stage of epithelial cell differentiation is a major determinant of 1,25(OH)2D3-induced 24-hydroxylase gene expression. In uremia, 1,25(OH)2D3-induced 24-hydroxylase gene expression was accelerated selectively, possibly because of poorly differentiated epithelial cells.

Animals↗

[A case of temporary severe disequilibrium hypercalcemia].

The patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. Laboratory data on admission revealed severe hypercalcemia of 14.9 mg/dl and renal dysfunction with serum creatinine of 2.9 mg/dl. As reflected by increased urinary excretions of pyridinoline and deoxypyridinoline and suppressed serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D, increased bone resorption seemed to be a main factor for the development of hypercalcemia. The development of hypercalcemia seemed to be acute because of (i) her severe symptoms caused by hypercalcemia and (ii) impaired renal function which improved after normalization of serum calcium. Following combination therapy of saline infusion and furosemide, there was a gradual decrease and later normalization of serum calcium together with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level has remained within the normal range. Measurement of serum factors which have hypercalcemia effects such as PTH, parathyroid hormone-related peptide and cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, hypercalcemia in this patient was regarded as a kind of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and has not recurred despite no treatment, her hypercalcemia developed due to imbalance in calcium regulation but not due to any organic disease.

Acute Disease↗

Levels of hepatocyte growth factor in synovial fluid and serum of patients with rheumatoid arthritis and release of hepatocyte growth factor by rheumatoid synovial fluid cells.

OBJECTIVE: To determine the levels of hepatocyte growth factor (HGF) in synovial fluids (SF) and sera from patients with rheumatoid arthritis (RA); to examine how these correlate with several disease variables in patients with RA and with levels of interleukin-6 (IL-6) in SF of these patients; and to examine whether HGF is released from adherent synovial cells (ASC) and synovial fluid cells (SF cells). METHODS: An enzyme linked immunosorbent assay was used to measure levels of HGF and IL-6. SF samples were obtained from 22 patients with RA, 12 with osteoarthritis (OA), and one with septic arthritis. Serum samples were collected from 40 patients with RA. HGF levels in culture supernatants from ASC and SF cells were measured. RESULTS: The mean values of HGF in SF were 1.21 ng/ml for patients with RA, 0.19 ng/ml for those with OA and 0.18 ng/ml for the one with septic arthritis. HGF levels in SF of patients with RA were significantly higher than of those with OA (p < 0.01). The levels for patients with RA correlated with the serum C-reactive protein concentrations (r = 0.626, p < 0.01) and IL-6 levels in SF (r = 0.476, p < 0.05). The mean value of HGF in sera from patients with RA was 0.28 ng/ml. HGF levels in SF were higher than those in sera drawn simultaneously from the same patients with RA. In vitro, release of HGF from rheumatoid ASC was not detected. However, SF cells from patients with RA released HGF spontaneously. CONCLUSION: Our observations suggest that HGF in SF of patients with RA is produced by SF cells and is related to disease activity of RA, and thus that HGF may play a role in RA.

Adult↗