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H Morii

Publications and source records attributed to H Morii.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Effects of the aldose reductase inhibitor on diabetic polyneuropathy--the efficacy of F wave measurement].

The effects of the aldose reductase inhibitor epalrestat (150 mg/day) on electrophysiological function were examined in 22 NIDDM patients with diabetic polyneuropathy for 6 months. Although no significant differences were observed in sensory (the sural nerve) or motor (the posterior tibial nerve) conduction velocities and amplitude, only F wave conduction velocities were significantly improved at 3 and 6 months after the treatment. There were no significant changes in CV-RR, vibration threshold and laboratory data. No serious side effects were observed during the therapeutic trial. This study suggests F wave is appropriate for the assessment of diabetic neuropathy and for therapeutic trials.

Aldehyde Reductase↗
PubMed1997

Special folding pathway to tetramer only through the micelle state of the corticotropin-releasing factor.

The ovine corticotropin-releasing factor (CRF), a peptide hormone of 41 residues stimulating the secretion of adrenocorticotropic hormone, was thermodynamically investigated. By means of size exclusion chromatography and/or ultrafiltration, the CRF solution could be separated into random coil monomers and highly alpha-helical tetramers, which seem to have amphipathic helix bundle structure. Circular dichroism measurements along with diluting or concentrating the CRF solution revealed that there exists the micelle state above the concentration of 0.1 mM, which would be the critical micelle concentration (cmc). The micelle state was also proved by binding ability for 8-anilino-1-naphthalenesulfonate and endothermic change by dilution across the cmc. The tetramer showed the cooperative thermal transition at about 55 degrees C in the buffer solution (pH 7.5), so that it would have native-protein-like folding. On the other hand, the micelle undergoes gradual change to dissociated state by heating, regardless of the similar alpha-helicity to the tetramer. Above the cmc the equilibrium between the tetramer and the micelle takes place as well as that between the monomer and the micelle. Whereas, the direct conversion between the tetramer and the monomer scarcely occurred below the cmc. The titration experiment with 2,2,2-trifluoroethanol (TFE) revealed that the cmc decreases with increasing the concentration of TFE. This tendency is the same as that of general surfactants. Most of experimental results can be well explained by this three-phase model involving the monomer, the tetramer, and the micelle. The lack of the equilibrium between the monomer and the tetramer indicates that the folding pathway of the tetramer is the transformation only through the micelle state and not from the monomer. This pathway resembles the collapse model among the phenomenological models for thermodynamic protein folding. By the mathematical consideration for the dissociation of micelle, we have demonstrated that the expected content of undegradable k-mer is 2/(k + 1), which agreed well with the observed tetramer content of CRF (40%).

Anilino Naphthalenesulfonates↗
PubMed1997

A postsynaptic excitatory amino acid transporter with chloride conductance functionally regulated by neuronal activity in cerebellar Purkinje cells.

Excitatory amino acid (EAA) neurotransmitters induce postsynaptic depolarization by activating receptor-mediated cation conductances, a process known to underlie changes in synaptic efficacy. Using a patch-clamp method, we demonstrate here an EAA-dependent postsynaptic anion conductance mediated by EAA transporters present on cerebellar Purkinje cell bodies and dendrites in culture. This transporter-mediated current was modulated by neuronal activity: it exhibited facilitation for >20 min after transient depolarization accompanied by Ca2+ influx. Evidence is presented suggesting that the transporter facilitation is mediated by arachidonate release after Ca2+-dependent activation of phospholipase A2, which exists in Purkinje cells. This postsynaptic reuptake system may represent a novel modulatory mechanism of synaptic transmission as well as prevent neuronal excitotoxicity.

Animals↗
PubMed1997

Inhibition by 1alpha,25-dihydroxyvitamin D3 of activin A-induced differentiation of murine erythroleukemic F5-5 cells.

1alpha,25-Dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and other vitamin D3 (VD3) analogs enhanced the inhibitory effect of Activin A on murine erythroleukemia (MEL) cell proliferation and differentiation in a dose-dependent manner. 1alpha,25-(OH)2D3 inhibited differentiation more potently than proliferation by one order of magnitude. The VD3 analog study demonstrated either effect of VD3 on MEL cells via vitamin D receptor (VDR), as evidenced from the close relationship with the reported affinities for VDR. The effects of 1alpha,25-(OH)2D3 were preceded by the suppression of ornithine decarboxylase (ODC) activity, a rate-limiting enzyme in polyamine metabolism. Difluoromethylornithine (DFMO), an inhibitor of ODC, inhibited MEL cell proliferation, which was reversed by the simultaneous addition of putrescine, a product of ODC, but did not affect differentiation. 1alpha,25-(OH)2D3 inhibited cell differentiation during the phenotype-expression stage as reflected by the inhibition of beta-globin gene expression, while it inhibited proliferation in the commitment stage. Furthermore, it seems unlikely that the different effects of VD3 on proliferation and differentiation may be a result of upregulation of VDR or nongenomic action. In summary, it was suggested that 1alpha,25-(OH)2D3 inhibited Activin A-induced MEL cell proliferation and differentiation by distinct mechanisms and inhibited the proliferation by inhibiting ODC activity. We demonstrated the presence of 1alpha,25-(OH)2D3 action on leukemic cells at physiological concentration, which was distinct from the pharmacological effect of VD3 reported thus far.

Acetyltransferases↗
PubMed1997

Hydrolysis of AMPPNP by the motor domain of ncd, a kinesin-related protein.

AMPPNP was found to be hydrolyzed by the motor domain of ncd (the product of a Drosophila gene, non-claret disjunctional), a kinesin-related protein. This hydrolysis could be monitored by 31P NMR spectroscopy and by an assay of phosphate, one of the products of the hydrolysis. The rate was approximately 0.00004 s(-1), 1% of the ATP turnover rate. The AMPPNP turnover was not stimulated by microtubules. Kinesin motor domain also turned over AMPPNP but at a somewhat lower rate. Although the turnover was slow, the present finding may present an important caveat, since AMPPNP has been widely used for investigations of kinesin and kinesin-related proteins as a non-hydrolyzable ATP analogue.

Adenosine Triphosphate↗
PubMed1997

Protein kinase C delta inhibits the proliferation of vascular smooth muscle cells by suppressing G1 cyclin expression.

To elucidate the physiological role of protein kinase C (PKC) delta, a ubiquitously expressed isoform in vascular smooth muscle cells (VSMC), PKC delta was stably overexpressed in A7r5 cells, rat clonal VSMC. The [3H]thymidine incorporation in A7r5 overexpressed with PKC delta (DVs) was suppressed to 37.1 +/- 16.3% (mean +/- S.D.) of the level in control or A7r5 transfected with vector alone (EVs). The reduction of [3H]thymidine incorporation was strongly correlated with overexpressed PKC levels. Moreover, transient transfection of a dominant negative mutant of PKC delta restored the reduced proliferation in DVs. Flow cytometry analysis demonstrated that DVs were arrested in the G0/G1 phase of the cell cycle. Expression of cyclins D1 and E and retinoblastoma protein phosphorylation were reduced, while the protein levels of p27 were elevated in DVs as compared with EVs. There were no significant differences in the expression of c-fos, c-jun, c-myc, cyclin D2, D3, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and p21 among the clones. We conclude that PKC delta inhibits the proliferation of VSMC by arresting cells in G1 via mainly inhibiting the expression of cyclin D1 and cyclin E.

Animals↗
PubMed1997

Osteopontin gene expression and protein synthesis in cultured rat mesangial cells.

It is controversial whether osteopontin (OP) is expressed in glomeruli and involved in glomerular diseases. We examined whether the OP expression is present at gene and protein levels in cultured rat mesangial cells (MCs). Northern blotting revealed a 1.7 kb OP-mRNA expression in MCs. Fetal calf serum (FCS) and TNF-alpha increased OP gene expression in serum-starved MCs by 2.7- and 1.8-fold over 24- and 12-hour periods, respectively. PDGF, IL-1beta, and TGF-beta had little effect on OP gene expression. Western blotting detected the OP protein expression (69 kDa). FCS and TNF-alpha increased OP protein expression in serum-starved MCs over 48- and 24-hour periods, respectively. The present study clearly demonstrated the expression of OP gene and protein in cultured rat MCs. Increased OP production under serum or TNF-alpha stimulation suggests that intraglomerular OP may contribute to the development of glomerular diseases.

Animals↗
PubMed1997

Identification of kinesin neck region as a stable alpha-helical coiled coil and its thermodynamic characterization.

The kinesin heavy chain consists of an N-terminal globular domain, referred to as the motor domain, a rod-like middle region, and a C-terminal domain. In this study, the human kinesin neck region, the region adjacent to the motor domain which promotes dimerization, has been investigated. First, we predicted coiled-coil regions including the neck region by our newly devised statistical method. The sequence (335-372) was predominated by a unique heptad amphipathy. A comparison of the bacterially expressed human kinesin heavy chain fragments, K349 (1-349), a monomeric motor domain, and K379 (1-379), a dimer, by circular dichroism (CD) spectroscopy showed that K379 had more alpha-helical content. Chemically synthesized peptides, (332-349), (350-379), and (332-369), gave CD spectra with an alpha-helix-rich pattern, but the spectra varied depending on the peptide concentration. Analysis of the molar ellipticity at 222 nm indicated that those peptides were in monomer-dimer equilibria, and the dissociation isotherms established dissociation constants of 9.6 mM. 60 microM, and 62 nM for the above peptides, respectively. Sedimentation equilibrium measurements verified that the peptide (332-369) existed as a dimeric form. These results strongly suggest that the sequence from 332 to 369 of the neck region forms an alpha-helical coiled coil. The differential peptide of K349 and K379, (350-379), did not show sufficient ability to make K379 dimeric. It is likely that the region (350-379) forms a stable alpha-helical coiled coil only together with the (332-349) region. Fluorescence energy transfer studies of [Cys363]-(332-369) labeled with a fluorescence donor and an acceptor revealed that the peptide formed a parallel coiled coil. This coiled coil was thermodynamically stable against urea and thermal denaturation, and peptide exchange of the coiled coil was undetectable, or extremely slow, at neutral pH. The dissociation free energy was estimated to be 57.7 kJ mol-1 at a peptide concentration of 22 microM. These results indicate that the neck region of kinesin forms a stable coiled coil which may be important for the motility of dimeric kinesin.

Amino Acid Sequence↗
PubMed1997

Renal function and insulin resistance as determinants of plasma leptin levels in patients with NIDDM.

Plasma leptin level is known to correlate with the degree of obesity. To determine the influences of renal function and insulin resistance on plasma leptin concentrations, we measured plasma leptin concentrations and performed the euglycaemic hyperinsulinaemic clamp studies in 57 patients with non-insulin-dependent diabetes mellitus with a wide range of renal function. In simple regression analyses, plasma leptin concentration showed significant positive correlations with percentage of body fat measured by dual energy X-ray absorptiometry, body mass index, waist to hip ratio and fasting plasma insulin. Leptin level was higher in females than males. Multiple regression analyses indicated that percent body fat, waist to hip ratio, plasma insulin, gender and renal function (1/creatinine), but not insulin sensitivity, were significant and independent determinants of plasma leptin level. These results suggest that plasma leptin level is regulated or affected by multiple factors including renal function. Insulin resistance appeared to increase leptin levels indirectly by raising plasma insulin.

Absorptiometry, Photon↗
PubMed1997

Atherogenic lipoprotein changes in the absence of hyperlipidemia in patients with chronic renal failure treated by hemodialysis.

We compared plasma lipid and lipoprotein parameters between 210 chronic renal failure patients treated by hemodialysis and 223 age- and sex-matched healthy control subjects to examine whether atherogenic lipoprotein changes were present in hemodialysis patients in the absence of hyperlipidemia. The hemodialysis group showed higher levels of plasma triglycerides, very low density lipoprotein (VLDL) cholesterol, and intermediate density lipoprotein (IDL) cholesterol and a lower level of high density lipoprotein (HDL) cholesterol. Low density lipoprotein (LDL) cholesterol of the hemodialysis group was not elevated but their LDL was significantly more triglyceride-enriched than that of controls. Subjects were then divided into five categories according to their plasma triglyceride levels at an interval of 50 mg/dl, and comparison was made between the two groups in the same range of plasma triglycerides. Hemodialysis patients again showed higher levels of VLDL- and IDL-cholesterol, and lower levels of HDL-cholesterol than the control group even in the plasma triglycerides-matched comparisons. Similarly, higher VLDL- and IDL-cholesterol levels in hemodialysis patients were significant in plasma total cholesterol-matched subgroup comparisons. Multiple regression analysis indicated that the relationship between plasma lipid concentrations and individual lipoprotein levels were substantially altered in uremic state. The 95th percentile level of IDL-cholesterol in the nonuremic controls was 15 mg/dl, and 45% of hemodialysis patients exceeded this level. Decreased HDL-cholesterol levels < or = 35 mg/dl were seen in 6% of the control and 38% of the hemodialysis group. Elevated IDL-cholesterol and decreased HDL-cholesterol were persistently found in hemodialysis patients with normal lipid levels. It is concluded that hemodialysis patients exhibited more atherogenic lipoprotein profile than nonuremic subjects with comparable levels of plasma triglycerides and total cholesterol. Especially, increased IDL- and decreased HDL-cholesterol levels in hemodialysis patients persisted even at very low levels of plasma lipids. Since elevated IDL and decreased HDL-cholesterol are implicated in the progression of atherosclerosis, these findings are of clinical importance in the diagnosis of lipoprotein disorder in chronic renal failure.

Arteriosclerosis↗
PubMed1997

Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis.

The present study determined the levels in synovial fluid (SF) of vitamin D metabolites (1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D) and 25-hydroxyvitamin D (25-OH-D)), and of the cytokines. We evaluated SF from 21 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA). The levels of vitamin D metabolites in SF, as determined by two different extraction methods, were significantly correlated (p < 0.05, n=7). The levels of 3 vitamin D metabolites were significantly higher in the RA SF than in OA SF (p < 0.05). The ratio of 1,25(OH)2D/25-OH-D in RA SF, which is presumed to reflect the activity of 25-OH-D-1-hydroxylase (1-OH-ase), was positively correlated with the levels of interleukin-1alpha (IL-1alpha), IL-1beta, and IL-2 in such SF, and was significantly higher than that in sera from RA patients. This suggests an important role for these cytokines in the activation of 1-OH-ase in RA synovium. The ratio of 24,25(OH)2D/25-OH-D, which is presumed to reflect 25-OH-D-24-hydroxylase (24-OH-ase) activity, was significantly correlated with 1,25(OH)2D levels only in RA SF, but not in sera from RA patients, suggesting a local regulation of vitamin D metabolism that 1,25-(OH)2D induces 24-OH-ase as in other target cells. Our observations suggested that 1,25(OH)2D and 24,25(OH)2D are produced locally from 25-OH-D in RA synovium, and that the syntheses of 1,25(OH)2D and 24,25(OH)2D may be affected by IL-1/IL-2 and 1,25(OH)2D in RA SF, respectively.

Arthritis, Rheumatoid↗
PubMed1997

Insulin resistance in non-obese, non-insulin-dependent diabetic patients with diabetic nephropathy.

To investigate the association between insulin resistance and diabetic nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10 with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c) among the four groups. No significant difference in M/I values was seen between stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x 100, respectively). M/I values in the stage I and stage II groups were strongly correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively). M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I group, although not significantly so. M/I values in the stage IV group (3.16 +/- 0.37) were significantly lower than in the stage I group (P = .025). In multiple regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine clearance (Ccr) were included as independent variables, BMI and Ccr were demonstrated to be significant and independent contributors to insulin sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272, respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional study demonstrated in non-obese NIDDM patients with nephropathy that microalbuminuria did not affect peripheral insulin resistance, but uremia did, as in nondiabetic patients, and that the peripheral insulin resistance was significantly contributed to by the degree of obesity and uremia.

Adult↗