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Biomedical subjects

H Hidaka

Publications and source records attributed to H Hidaka.

At least 73 records · Page 4Linked to original sources
PubMed1999

Unilateral examination of olfactory threshold using the Jet Stream Olfactometer.

OBJECTIVE: The Jet Stream Olfactometer, a modification by the T&T olfactometer, has been recently developed and is now commercially available. This Jet Stream Olfactometer can routinely measure the unilateral sense of smell. Clinical usefulness of the Jet Stream Olfactometer was evaluated. METHODS: Twenty-three patients with sinus-related symptoms were examined. Unilateral olfactory acuity was examined using the Jet Stream Olfactometer and compared it with the anatomy of the olfactory cleft by computed tomographic (CT) scans. RESULTS: In 13 of the 23 patients examined the right olfactory threshold was similar to that of the left. Of these 13, in seven patients there was transport damage of the odorants and in the other six there was sensorineural damage. Ten patients showed an apparent difference between the right and left smell thresholds. Anosmia in seven of these ten patients was due to a conductive olfactory disturbance resulting from rhinosinusitis, whereas sensorineural damage was recognized in the other three patients. The difference in the detection threshold between the right and left nasal cavities was well correlated to that of the opacity between the right and left olfactory clefts. CONCLUSION: Jet Stream Olfactometer provides a convenient and reliable means for assessing the ability of unilateral smell.

Adult↗
PubMed1999

Roles of intracellular Ca2+ receptors in the pancreatic beta-cell in insulin secretion.

Ca2+ is the central second messenger in the regulation of insulin release from the pancreatic beta-cell; and intracellular Ca2+ -binding proteins, classified into two groups, the EF hand proteins and the Ca2+/phospholipid binding proteins, are considered to mediate Ca2+ signaling. A number of Ca binding proteins have been suggested to participate in the secretory machinery in the beta-cell. Calmodulin, the ubiquitous EF hand protein, is the predominant intracellular Ca2+ receptor that modulates insulin release via the multiplicity of its binding to target proteins including protein kinases. Other Ca binding proteins such as calcyclin and the Ca2+/phospholipid binding proteins may also be suggested to be involved. Ca2+ influx from the extracellular space appears to be responsible for exocytosis of insulin via Ca2+ -dependent protein/protein interactions. On the other hand, intracellular Ca2+ mobilization resulting in secretory granule movement may be controlled by Ca2+/calmodulin-dependent protein phosphorylation. Thus, Ca2+ exerts versatile effects on the secretory cascade via binding to specific binding proteins in the pancreactic beta-cells.

Animals↗
PubMed1999

Low-density lipoprotein apheresis retards the progression of hyperlipidemic overt diabetic nephropathy.

BACKGROUND: Hyperlipidemia has recently received attention as being involved in the progression of diabetic nephropathy (DN). Low-density lipoprotein apheresis (LDL-A) can remove a large amount of plasma lipid directly from the patients in a short time. METHODS: Fifteen type 2 diabetic patients with overt nephropathy received LDL-A in two different manners: short-term intensive therapy (SIT) for nine patients and long-term intermittent therapy (LIT) for six patients. RESULTS: The changes in the monthly decline rates of reciprocal serum creatinine (1/Cr) were -0.035 +/- 0.020 in the three-month period before SIT, 0.047 +/- 0.041 during and until two weeks after SIT, and -0.035 +/- 0.015 after a period of two weeks from the therapy. The mean duration of LIT in six patients was 8.2 +/- 7.4 months, and the mean monthly decline rates of 1/Cr significantly decreased during the period of LIT as compared with the six-month period before the treatment. CONCLUSION: LDL-A can retard the progression of overt DN, especially when it is performed repeatedly for a long period at two-week intervals.

Aged↗
PubMed1999

Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis.

BACKGROUND: Inflammatory bowel disease (IBD)--and Crohn's disease (CD) and ulcerative colitis (UC) in particular--could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. METHODS: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (P(IBD) and P(CD)) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for P(IBD) and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. RESULTS: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. CONCLUSIONS: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.

Adult↗
PubMed1999

Isolation of cDNAs encoding cellular drug-binding proteins using a novel expression cloning procedure: drug-western.

A rapid and convenient new method for isolating the genes encoding cellular drug-binding proteins is described. This method, drug-western, is based on the use of the drug conjugated with a marker molecule as a probe for the screening of a cDNA library. Unlike the other methods, this method allows us to identify the genes for trace amounts of cellular drug-binding proteins without purification. We have used this approach to isolate human cDNA clones encoding binding proteins of HMN-154 ((E)-4-[2-[2-(p-methoxy-benzene-sulfonamide) phenyl]ethenyl] pyridine), a novel benzenesulfonamide anticancer compound (Katoh and Hidaka 1997). The proteins encoded by two of the isolated clones are identical to NF-YB, B subunit of nuclear transcription factor NF-Y, and thymosin beta-10, respectively. Recombinants of both proteins bind specifically to HMN-154 in vitro. Comparison of amino acid sequences between these proteins shows the sequence similarity in a short amino acid stretch [K(X)AKXXK]. Deletion or mutation of this region causes the significant loss of binding of both proteins to HMN-154. Furthermore, HMN-154 inhibits DNA binding of NF-Y to the human major histocompatibility complex class II human leukocyte antigen DRA Y-box sequence in a dose-dependent manner. Interestingly, other binding proteins identified by this method also possess the same or a similar motif. These results clearly demonstrate that NF-YB and thymosin beta-10 are specific cellular binding proteins of HMN-154 and that this shared region is necessary for the binding to HMN-154. Hence, this new method is thought to be useful for the identification of drug-binding proteins.

Amino Acid Sequence↗
PubMed1999

Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats.

To examine the effects of chronic hyperinsulinemia on vascular tissues, we examined the production of superoxide anion (O(-2)) in the aortic tissues of control and exogenously hyperinsulinemic rats performed by the implantation of an insulin pellet for 4 wk. O(-2) production by aortic segments from hyperinsulinemic rats was 2. 4-fold (lucigenin chemiluminescence method) and 1.7-fold (cytochrome c method) of that of control rats without any differences in O(-2) degrading activities in aortic tissues, respectively (P < 0.025). The increment was completely abolished in the presence of either 100 micromol/l apocynin (an inhibitor of NADPH oxidase) or 10 micromol/l diphenyleneiodonium (an inhibitor of flavin-containing enzyme) and was exclusively endothelium dependent. Consistently, NAD(P)H oxidase activities in endothelial homogenate in hyperinsulinemic rats were dose dependently stimulated above the values of control rats, although these activities in nonendothelial homogenate were not significantly stimulated by insulin. Furthermore, an insulin effect was also demonstrated 1 h after exposing aortic tissues to insulin. These results indicate that O(-2) production specifically increases in endothelium of aortic tissues in chronic hyperinsulinemic rats through the activation of NAD(P)H oxidase.

Animals↗
PubMed1999

The 3'-untranslated region polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in the type 2 diabetic Japanese population.

A newly identified 3'-untranslated region (UTR) polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PPP1R3) was associated with insulin resistance and type 2 diabetes in Pima Indians (Xia J, Scherers W, Cohen PTW, Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M: A common variant in PP1R3 associated with insulin resistance and type 2 diabetes. Diabetes 47:1519-1524, 1998). Thus, we investigated the frequency of polymorphism of the adenine- and thymine-rich element (ARE-1 and its variant ARE-2) in 426 Japanese type 2 diabetic and 380 nondiabetic subjects using a polymerase chain reaction (PCR)-restriction enzyme fragment length polymorphism (RFLP) method. The allele frequency of the ARE-2 variant in diabetic subjects was higher than that in nondiabetic subjects (0.34 vs. 0.29; P < 0.05), even though its frequency in Japanese subjects was lower (P < 0.001) than the reported value in Pima Indians (0.56). An aspartate polymorphism at codon 905 was 100% coupled to the ARE-2 allele, and its allele frequency was higher also in diabetic subjects. Although a serine substitution at codon 883 was partially linked with the ARE-2 allele, there was no difference between diabetic and nondiabetic subjects. These results indicate that the frequency of polymorphism of the PPP1R3 gene (ARE-2 and Asp905) is different between two ethnic groups and is increased in Japanese people with type 2 diabetes, suggesting that these variants may be a possible marker for searching for diabetogenic genes.

3' Untranslated Regions↗
PubMed1999

Alpha1-adrenergic stimulation induced hypertrophy in protein kinase C down-regulated cultured cardiac myocytes.

To examine whether protein kinase C (PKC) activation is essential for the induction of cardiac myocyte hypertrophy caused by alpha1-adrenergic stimulation, we investigated the hypertrophic effect of phenylephrine in PKC down-regulated and non-treated cultured cardiac myocytes obtained from neonatal Sprague-Dawley rat ventricles. The treatment with 10 nmol/L 12-tetra decanoylphorbol-13-acetate (TPA) for more than 2 hours decreased PKC activity by approximately 80% without marked hypertrophy. Phenylephrine increased [14C] phenylalanine (Phe) incorporation in both TPA non-treated and treated cells, 1.54- and 1.71-fold as large as control, respectively. The cell surface area also enlarged in both groups, 1.67- and 1.74-fold, respectively. Thus, phenylephrine induced the similar grade hypertrophy in cultured cardiac myocytes even when PKC was down-regulated. These results suggest that conventional PKC activation may not be essential for mediating myocyte hypertrophy by alpha1-adrenergic stimulation.

Adrenergic alpha-Agonists↗
PubMed1999

Apolipoprotein E in cerebrospinal fluid: relation to phenotype and plasma apolipoprotein E concentrations.

BACKGROUND: Apolipoprotein (apo) E may be related to the development of Alzheimer disease, but data on apoE in cerebrospinal fluid (CSF) are limited. The aim of the present study was to measure apoE in CSF and relate its concentrations to apoE phenotype and CSF lipids. METHODS: We adapted an assay for CSF apoE sensitivity using an ELISA. It allowed us to measure CSF apoE with sufficient reproducibility and precision. RESULTS: The within- and between-run CVs were <7%, and the detection limit was 0.025 mg/L. No cross-reaction was found for other apolipoproteins. No significant differences related to sex or apoE phenotype were observed in the CSF apoE concentration. The mean CSF apoE concentration was significantly higher in the 0-5 year group (n = 6; 18.47 +/- 1.14 mg/L, mean +/- SD) than in the >5 year group (n = 34; 8.82 +/- 3.31 mg/L). The mean concentrations of total cholesterol (TC) and phospholipid (PL) in CSF were 2.68 +/- 2.16 and 6.50 +/- 2.84 mg/L (n = 52), respectively. Although no significant differences in TC or PL in the CSF were found with respect to sex or age, the concentrations in subjects with the apoE phenotype E4/E3 were significantly lower than in those with E3/E3 and E3/E2. The concentrations of apoE, TC, and PL in CSF did not correlate with those in plasma. The time-related fluctuations in CSF apoE were independent of those in total protein and IgG. CSF apoE was significantly correlated with TC and PL concentrations in the CSF, but not with the number of cells in the CSF. CONCLUSIONS: These findings support the idea that apoE and lipids are unable to cross the blood-brain barrier and that their concentrations in CSF may reflect production in central nervous tissue.

Adolescent↗
PubMed1999

The identification of specific high density lipoprotein3 binding sites on human blood monocytes using fluorescence-labeled ligand.

We previously reported the identity and purification of two HDL3-binding proteins in rat liver plasma membranes. As these proteins are candidate high density lipoprotein (HDL) receptors and probably multifunctional, including a role in HDL metabolism, we have considerable interest in identifying corresponding proteins that are present in human tissue. This report describes the identification of HDL3-binding sites on human monocytes with the use of fluorescence microscopy and flow cytometry assay. After the incubation of mononuclear cells from human blood with fluorescein isothiocyanate (FITC)-labeled human HDL3, fluorescence micrographs showed dense signals of fluorescent grains on monocytes, but not lymphocytes. A significant increase in FITC intensity on monocytes, but not lymphocytes, was observed by flow cytometry analysis, and the interaction between FITC-HDL3 and human monocytes was concentration-dependent. Although very low density (VLDL) and low density lipoprotein (LDL) were ineffective competitors and HDL2 only partially competed for binding, a 50-fold concentration of HDL3 did compete effectively for binding of FITC-HDL3 to human monocytes. Trypsin treatment reduced the FITC intensity of monocytes, showing that a portion of cell-associated FITC-HDL3 remained bound to the cell surface. Two major HDL-binding proteins were identified in CHAPS-solubilized human mononuclear cells by ligand blotting, using HDL3 as the ligand. Both showed similar binding parameters, specificity, and molecular weight identical to HB1 and HB2 from rat liver plasma membrane. We conclude that corresponding candidate HDL receptors or a similar receptor complex also exist on human blood monocytes.

Binding Sites↗
PubMed1999

[Evaluation of fat nutrition in the energy intake on low protein diets for patients with chronic renal failure].

Low protein diet has been proven to retard the progression of chronic renal failure. In this diet, the energy intake depends mainly on fats and carbohydrates instead of protein, and precautions should be taken against increasing risks of both lipid nephrotoxicity and atherosclerosis. In order to assess the adequacy of fat nutrition in a low protein diet for patients with chronic renal failure, we evaluated the total amounts of dietary fat intake, dietary individual fatty acid intake and serum individual fatty acid concentrations in 16 patients, whose mean creatinine clearance was 21.3 +/- 12.1 ml/m, serum creatinine 3.8 +/- 2.2 mg/dl and serum urea nitrogen 41.5 +/- 18.6 mg/dl. The percentage ratio of fat intake to total energy intake was 26.7 +/- 5.2%. The ratio of intake of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids was 1:2:1.8, and n-6/n-3 was 8.5 +/- 9.3. These were significant correlations between dietary intake and the serum concentrations in both EPA and the ratio of EPA/AA. Consequently, it might be considered that polyunsaturated fatty acids intake should be lowered and patients with chronic renal failure on a low protein diet should be advised about the proper selection of foods containing animal protein and plant-derived oil. It may be beneficial to recommend the intake of more EPA and lowering the ratio of n-6/n-3 intake might be useful in improving the fat nutrition to adequate levels in these patients.

Aged↗
PubMed1999

Characterization of apolipoprotein E-containing lipoproteins in cerebrospinal fluid: effect of phenotype on the distribution of apolipoprotein E.

BACKGROUND: Apolipoprotein (apo) E, one of the main apolipoproteins in the central nervous system, may play an important role in lipid metabolism; however, the details of its function are poorly understood. In this study, we characterized apoE-containing lipoproteins in cerebrospinal fluid (CSF) and examined the effect of apoE phenotype on the distribution of apoE among the lipoprotein fractions. METHODS: CSF lipoproteins were fractionated by gel filtration and ultracentrifugation, and then characterized by electrophoresis, immunoblot, electron microscopy, and analysis of apoE, total cholesterol, and phospholipid concentrations. RESULTS: The ratio of sialylated to nonsialylated apoE was higher in CSF than in serum. However, the fundamental forms containing apoE homodimers or heterodimers [such as apo(E-AII) and apo(AII-E2-AII) complexes] were similar in CSF and serum. apoE-containing lipoproteins were fractionated at densities of <1.006, 1.063-1.125, and 1.125-1.21 kg/L. Neither apoE nor apoAI was detected in the fraction with a density range of 1.006-1.063 kg/L. The diameters of the lipoprotein particles with densities of <1.006, 1.063-1.125, and 1.125-1.21 kg/L were 16.7 +/- 3.1, 14.0 +/- 3.2, and 11.6 +/- 2.8 nm (mean +/- SD, n = 200), respectively. All of these lipoproteins exhibited a spherical structure. The distribution profile of apoE-containing lipoproteins was affected by the apoE phenotype. A relatively large amount of apoE-containing lipoproteins was isolated from the fraction with a density >1.125 kg/L obtained from CSF associated with apoE2 or apoE3. This tendency was more obvious in CSF associated with apoE2 than in CSF without apoE2. apoE-containing lipoproteins were predominantly observed in the fraction with a density of <1.006 kg/L obtained from CSF associated with apoE4. CONCLUSIONS: The lipoproteins in CSF have a unique composition that is different from that of the lipoproteins in plasma. However, the differences in diameter between the CSF fractions were not as large as for the serum fractions. Our data suggest that the apoE phenotype may affect the distribution profile of apoE-containing lipoproteins in the CSF. This would mean that the metabolism of apoE-containing lipoproteins depends on the apoE isoform present.

Apolipoproteins E↗
PubMed1999

[Relationship of renal lesions with urinary protein excretion in patients with overt diabetic nephropathy].

We investigated the relationship of renal lesions with the degrees of proteinuria in 57 type 2 diabetic patients with overt proteinuria (urinary protein excretion rate (UP) >> 0.5 g/day). Creatinine clearance (Ccr) ranged from 25.4 to 131.0 ml/min/1.73 m2. Kidney specimens were obtained and the diagnosis of diabetic nephropathy was made in all patients. The degree of each of the following histologic changes were evaluated: diffuse or nodular lesion, the type of nodular change, mesangiolysis, arteriolar hyalinosis and interstitial damage. We divided the patients into the following 4 groups according to Ccr and UP: group A with Ccr >> 60 and UP >> 3 g/day (n = 10), group B with Ccr >> 60 and UP < 3 g/day (n = 10), group C with Ccr < 60 and UP >> 3 g/day (n = 23) and group D with Ccr < 60 and UP < 3 g/day (n = 14), and compared the histologic parameters among the 4 groups. Diffuse index in group A was greater than those in group B (p = 0.05), while those in groups C and D were not different. Nodular index, percentage of patients with nodular lesion did not differ among the 4 groups, however the percentage of glomeruli with complicated nodules (nodular lesion with mesangiolysis and/or microaneurysm) in group C was greater than those in group D (p < 0.05). Hyalinosis index did not differ between group A and B, nor between group C and D, respectively. Interstitial index in group A and B did not differ, however that in group C was greater than in group D (p < 0.05). In addition, the rate of Ccr decrease between renal biopsy and after 12 months was significantly greater in group A and C than in group B and D, respectively (both p < 0.01). These results suggest that 1) mesangial expansion was associated with the degree of proteinuria in patients with slight impaired renal function, 2) tubulointerstitial involvement was associated with the degree of proteinuria in patients with advanced impaired renal function, and 3) these structural changes might be associated with decrease in renal function in diabetic nephropathy.

Aged↗
PubMed1999

Symmetric covalent linkage of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) results in novel derivatives with increased inhibitory activities against calcium/calmodulin complex.

A useful calmodulin (CaM) antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), was invented by Hidaka et al. in 1978 (J. Pharmacol. Exp. Ther. 207, 8-15). Here, we have designed new CaM antagonists on the basis of the three-dimensional structure of Ca2+/CaM complexed with W-7. Eleven new compounds all share a similar architecture, in which two W-7 molecules are linked between their aminohexyl termini by a linker with different functionalities. A wide range of inhibitory activities against Ca2+/CaM-dependent protein kinase I (CaM kinase I) has been observed with these self-crosslinked W-7 analogs, (W-7)2. In vitro competitive CaM kinase I assays using CaM kinase I and nuclear magnetic resonance studies indicated that one (W-7)2 molecule binds to one CaM molecule as expected, with the two chloronaphthalene rings of (W-7)2 being anchored separately to the N- and C-terminal hydrophobic pockets of Ca2+/CaM. The most potent compound, N,N'-bis[6-(5-chloro-1-naphthalenesulfonyl)-amino-1-hexyl]-p-xylen e-diamine ((W-7)2 - 10), inhibits CaM kinase I activity at an IC50 value of 0.23 microM; about 75 times more effectively than W-7. The length and basicity of the linker sequence in (W-7)2 significantly contribute to inhibitory activity. The present study opens an avenue for developing powerful CaM antagonists that could be used at low doses in vivo.

Animals↗
PubMed1998

A new system to detect native microaggregates of platelets in vivo, with a novel platelet aggregometer employing laser light scattering.

Circulating platelets are susceptible to various stimuli in vessels, and a certain portion of platelets may thereby form native microaggregates (NMAs), which can be visualized by a bother scanning electron microscopy (SEM). We developed an easy method to evaluate the existence and extent of NMAs and the subsequent spontaneous platelet aggregation (SPA) induced by not any agonist but stirring force with a novel platelet aggregometer (PA-200; Kowa, Tsukuba, Japan) employing a particle-counting method based on laser light scattering. In this system, platelet-rich plasma obtained by a delicate centrifugation was infused in a cuvette to replace the content and to avoid stirring shear. An insertion attachment was designed in a coaxial shape to maintain a constant sample volume. Our data indicated that NMAs, tentatively defined as a "small" division by their light scattering (25-400 of the intensity threshold), could be detected by not only a complicated SEM but also by our simple system with the PA-200 in a few minutes. No correlation was found in the comparison of the existence of NMAs and the SPA generation, in aliquot platelets, respectively. These results suggested that NMAs and SPA might be mutually different cluster and have meanings as representations of platelet status.

Blood Platelets↗