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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 289 records · Page 16Linked to original sources
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

[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

[A mechanism for the anti-inflammatory effect of nedocromil; inhibition of both adhesion molecule expression on eosinophils and endothelial cells, and eosinophil chemotactic activities].

The accumulation of eosinophils in the airway is one of the characteristics seen in patients with bronchial asthma. One of the newly developed anti-asthma drugs (controller), nedocromil sodium (nedocromil) is known to suppress the influx of eosinophils into allergic lesions. However, little is known about this mechanism. Therefore, in this report we investigated the effects of nedocromil on Mac-1 expression on PAF-stimulated eosinophils, and adhesion molecule expression on endothelial cells stimulated by either IL-1 beta or IL-4. We also investigated the eosinophil chemotaxis. A significant suppression of the Mac-1 expression on PAF-induced eosinophils was observed at both concentrations of 10(-5) and 10(-7) M of nedocromil. The expression of adhesion molecules, particularly ICAM-1 and E-selectin, on IL-1 beta-stimulated human umbilical vascular endothelial cells (HUVEC) was significantly suppressed at these concentrations, whereas the VCAM-1 expression was not changed. No significant suppression of VCAM-1 expression on IL-4-stimulated HUVEC was observed, although there was a tendency of suppression at these concentrations. On the other hand, the expression of the E-selectin molecule was significantly suppressed by nedocromil even under resting (non-stimulated) condition. PAF-induced eosinophil chemotactic activities were also suppressed at these concentrations in a dose-dependent manner. These results suggested that nedocromil suppressed the influx of eosinophils to inflammatory lesions by inhibiting not only the expression of the Mac-1 on eosinophils and of E-selectin and ICAM-1 molecules on HUVEC, but also the eosinophil chemotactic activities.

Anti-Asthmatic Agents↗
PubMed1998

Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats.

BMAL1 is a putative transcription factor which is involved in circadian rhythm generation in Drosophila. Northern blot analysis was performed to investigate the expression of rat BMAL1 mRNA in the suprachiasmatic nucleus (SCN) and peripheral tissues. In the SCN, circadian expression of BMAL1 mRNA which reaches its peak level at the time of dark-light transition was observed, and the expression pattern was antiphase to those of two period (per) homologues, rPer1 and rPer2. However, no circadian oscillation for rat Clock mRNA was detected. The circadian expression of BMAL1 mRNA was also observed in peripheral tissues such as brain (excluding the SCN), eye, heart, kidney, and lung. The amplitudes of BMAL1 and rPer2 mRNA expression levels were correlated between the different tissues, suggesting that the circadian expression of BMAL1 mRNA plays an important role in generating the circadian expression of per homologue genes in mammals.

ARNTL Transcription Factors↗
PubMed1998

Physicochemical factors for cytotoxic activity in platinum dinuclear complexes with pyrimidine and imide ligands.

The relationship between cytotoxic activity of platinum dinuclear complexes toward cancer cells and their intrinsic properties (electrophilicity and hydrophobicity) have been examined. It is shown that the reactivity with chloride anion is a good index of the electrophilicity of the platinum complexes. By assuming a cell kill pharmacodynamic model, the relation between IC50 value and the electrophilicity is obtained. It is concluded that inside cells the reactivity of the platinum complexes having imide ligands is higher than that of CDDP. The other important factor which affects the cytotoxic activity is hydrophobicity. The log k' values (k': capacity factor) are found useful to estimate the hydrophobicity of platinum complexes. The accumulation of platinum into cells is dominated by the hydrophobicity and the charge of platinum complexes. Highly hydrophobic complexes are thought to be adsorbed in cell membranes, resulting in low cytotoxic activity since they cannot reach DNA. A schematic model of the interaction between platinum complexes and serum proteins reveals that more hydrophobic complexes tend to bind to serum proteins more stably. At least three possible paths of the cellular platinum accumulation are suggested: direct accumulation of the platinum complexes, incorporation in the form of CDDP produced from the complexes, and incorporation through protein-platinum complexes, although the contribution of the third one may be small.

Animals↗
PubMed1998

Human megasatellite DNA RS447: copy-number polymorphisms and interspecies conservation.

We previously isolated a novel 4.7-kb RS447 sequence, which tandemly repeated approximately 50-70 copies and resided on human chromosome 4p15 (M. Kogi et al., 1997, Genomics 42: 278-283). Another tandem array (or arrays) of several RS447 copies was hereby identified on the distal part of chromosome 8p. To analyze copy-number polymorphisms of the RS447 repeats, genomic DNA samples of eight nonkindred Japanese were subjected to pulsed-field gel electrophoresis. The copy numbers of the RS447 tandem arrays on 4p15 varied drastically from allele to allele and ranged from approximately 34 to 94 copies. All eight Japanese subjects were apparently heterozygous for the RS447 copy number, and 12 copy-number-different alleles have been at least clearly distinguished. The RS447 tandem repeats were thus found to be hypervariable and highly polymorphic in a human population. The RS447 sequences, however, do not appear to be either "selfish" or "junk" DNA. The unit size and sequence of RS447 were found to be very similar between members in the human genome. The unit size of 4746 bp comprises a putative open reading frame of 1590 bp. The RS447 sequence was well conserved in all the tested mammalian species. The head-to-tail tandem repetitive structure in the RS447 homologs was also confirmed in those species. The RS447 sequence is, therefore, considered to consist of a new class of tandemly repeated satellite DNA elements in the mammalian genome, which may thus be called "megasatellite DNA."

Animals↗
PubMed1998

Humoral signals mediate the circadian expression of rat period homologue (rPer2) mRNA in peripheral tissues.

Northern blot analysis revealed the circadian expression of rat period homologue (rPer2) mRNA in peripheral mononuclear leukocytes that have no neuronal connections. The mRNA expression in the suprachiasmatic nucleus (SCN), peripheral mononuclear leukocytes, and other peripheral tissues exhibited prominent, synchronous circadian oscillation with peaks at early night. As we have previously shown the peripheral circadian expression of rPer2 mRNA is abolished in SCN-lesioned rats [Sakamoto, K., Nagase, T. Fukui, H., Horikawa, K., Okada, T., Tanaka, H., Sato, K., Miyake, Y., Ohara, O., Kako, K. and Ishida, N., J. Biol. Chem., 273 (1998) 27039-27042], our findings suggest that some humoral signals, driven by the SCN, mediate the circadian expression of mammalian per homologues in peripheral tissues.

Animals↗
PubMed1998

A novel three-dimensional crystal of bacteriorhodopsin obtained by successive fusion of the vesicular assemblies.

When the two-dimensional crystal of bacteriorhodopsin (bR), purple membrane, is incubated at high temperature (32 degreesC) with a small amount of the neutral detergent octylthioglucoside in the presence of the precipitant ammonium sulfate, a large fraction of the membrane fragments is converted into spherical vesicles with a diameter of 50 nm, which are able to assemble into optically isotropic hexagonal crystals when the precipitant concentration is increased. The vesicularization of purple membrane takes place under such a condition that the miscibility of the detergent to the aqueous phase becomes very low, and we suggest that it is initiated by insertion of the detergent molecules into the membrane. At low temperature, the transformation into the vesicular structure is inhibited and no large crystal is produced directly from membrane/detergent/precipitant mixtures. When a suspension of the spherical vesicles produced at the high temperature is cooled and concentrated below 15 degreesC, however, a birefringent hexagonal crystal is produced that diffracts X-rays beyond 2.5 A resolution. This new crystal belongs to the space group P622 with unit cell dimensions of a=b=104.7 A and c=114.1 A, and it is shown to be made up of stacked planar membranes, in each of which the bR trimers are arranged on a honeycomb lattice and the space among the proteins is filled with the detergent molecules and native lipids. These stacked membranes are suggested to be produced by successive fusion of the spherical vesicles. This implies that the crystallization is achieved without any step for complete solubilization of the protein. The present result offers a unique crystallization method that may be applicable to such membrane proteins that are liable to denature in the presence of an excess amount of detergent.

Bacteriorhodopsins↗
PubMed1998

Multitissue circadian expression of rat period homolog (rPer2) mRNA is governed by the mammalian circadian clock, the suprachiasmatic nucleus in the brain.

The period (per) gene, controlling circadian rhythms in Drosophila, is expressed throughout the body in a circadian manner. A homolog of Drosophila per was isolated from rat and designated as rPer2. The rPER2 protein showed 39 and 95% amino acid identity with mPER1 and mPER2 (mouse homologs of per) proteins, respectively. A robust circadian fluctuation of rPer2 mRNA expression was discovered not only in the suprachiasmatic nucleus (SCN) of the hypothalamus but also in other tissues including eye, brain, heart, lung, spleen, liver, and kidney. Furthermore, the peripheral circadian expression of rPer2 mRNA was abolished in SCN-lesioned rats that showed behavioral arrhythmicity. These findings suggest that the multitissue circadian expression of rPer2 mRNA was governed by the mammalian brain clock SCN and also suggest that the rPer2 gene was involved in the circadian rhythm of locomotor behavior in mammals.

Amino Acid Sequence↗
PubMed1998

Requirement of GM2 ganglioside activator for phospholipase D activation.

Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known GM2 ganglioside activator whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2 to GM3 ganglioside that is catalyzed by beta-hexosaminidase A. Inversely, GM2 ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792-815] stimulates ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown.

Amino Acid Sequence↗
PubMed1998

Lysosomal glycogen storage disease with normal acid maltase with early fatal outcome.

In a male infant who had cardiomyopathy, generalized muscle weakness and increased serum creatine kinase levels, his muscle biopsy revealed myopathic changes with tiny intracytoplasmic vacuoles containing PAS-positive material and high acid phosphatase activity, but had normal acid maltase activity biochemically. These findings were consistent with those seen in lysosomal glycogen storage disease with normal acid maltase (Danon disease). Sarcolemmal indentations commonly seen in this disease were missing, but a complement membrane attack complex, C5b-9 was positive along the surface membrane of the muscle fibers as seen in X-linked vacuolar myopathy. The patient was on a respirator and died at 27 months of age from pneumonia and hypertrophic cardiomyopathy. Lysosomal glycogen storage disease with normal acid maltase may be manifested at birth with marked skeletal and cardiac involvement leading to death in early infancy.

Biomarkers↗
PubMed1998

A functional MRI analysis of comprehension processes of Japanese sentences.

We tried to identify the mechanisms directly related to syntactic processing in an fMRI experiment using strictly controlled sets of verbal stimuli. In two conditions, center-embedding and left-branching conditions, the same sets of words were used to construct stimulus sentences, while only the word order reflecting their syntactic structure was different. The subject's task was to understand the relationship among three characters mentioned in the sentences. A difference of activation in Broca's area (BA44 and 45) between the two conditions was found. This result suggests that these areas are involved in syntax-related processing. Furthermore, it was suggested that the posterior part of the frontal lobe (BA6/9) and the inferior parietal area (BA39/40) are involved in the understanding of the relationship among the three characters mentioned in each sentence.

Frontal Lobe↗
PubMed1998

Engineering of hypoallergenic mutants of the Brassica pollen allergen, Bra r 1, for immunotherapy.

The Brassica pollen allergen Bra r 1 belongs to a new family of Ca2+-binding proteins, characterized by the presence of two potential EF-hand calcium-binding domains. Disruption of these EF-hand motifs by amino acid substitutions demonstrated that both domains of Bra r 1 constitute functional Ca2+-binding sites. Calcium-binding deficient mutants displayed significantly reduced IgE-binding activity. Injection of these mutated Bra r 1 variants into a murine model system showed that mouse IgG raised against the mutants recognized native Bra r 1 in Brassica pollen extracts suggesting the potential use of the engineered allergens for effective immunotherapy.

Allergens↗
PubMed1998

Synthesis and pharmacological activity of triazolo[1,5-a]triazine derivatives inhibiting eosinophilia.

In continuation of our previous work on eosinophilia inhibitors, we synthesized an additional series of inhibitors, which consisted of 5-amino-1-[(methylamino)thiocarbonyl]-1H-1,2,4-triazole derivatives and a newly developed series of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives. We evaluated their inhibitory activity on the airway eosinophilia model, which was induced by the intravenous (iv) injection of Sephadex particles. In the 1,2,4-triazole series with various substituents at the 3 position of the triazole ring such as 2-furyl, pyridyl, and phenoxy, none of derivatives had comparable activity to the previously reported compound GCC-AP0341, 5-amino-3-(4-chlorophenyl)-1-[(methylamino)thiocarbonyl]-1H-1,2, 4-triazole. In the triazolo[1,5-a]triazine series, 2-(4-chlorophenyl)-6-methyl-1,2,4-triazolo[1,5-a]-1,3, 5-triazine-7(6H)-thione (3h) was highly potent, and when given orally it had an ID50 value of 0.3 mg/kg, which is comparable to that of GCC-AP0341. The fact that the structure-activity relationship of these two series was quite similar suggests that a common substructure, such as the 1,2,4-triazole ring with a substituted phenyl ring at the 3 position and a thiocarbonyl moiety at the 1 position, could contribute to the activity. Our selected compound 3h was less active than GCC-AP0341 in the antigen-induced hyper-responsiveness model in guinea pigs; however, we plan to carry out further studies on eosinophil functions, especially on their activation, using our two compounds, 3h and GCC-AP0341.

Animals↗
PubMed1998

FADD gene therapy for malignant gliomas in vitro and in vivo.

Fas/APO-1 (CD95), a cell surface cytokine receptor, triggers apoptotic cell death by specific agonist antibody, suggesting that Fas/APO-1 may be a promising target for treatment of tumors. In this study, we show that treatment with anti-Fas antibody effectively induced apoptosis in malignant glioma cell lines with high expression of Fas/APO-1 (n = 3). Malignant glioma cells with low or undetectable expression of Fas/APO-1 (n = 6), however, were resistant to Fas/APO-1-dependent cytotoxicity. The purpose of this study, therefore, was to determine whether resistant tumors could be made susceptible to apoptosis. FADD/MORT1 constitutes a novel protein that associates specifically with the cytoplasmic death domain of Fas/APO-1 and induces apoptosis. We investigated whether overexpression of FADD would induce apoptosis in malignant glioma cells without activating Fas/APO-1. Results indicated that about 85% of malignant glioma cells, regardless of Fas/APO-1 expression levels, underwent apoptosis after transient transfection with FADD expression vector. To further improve gene transfer of FADD into malignant glioma cells, we constructed a retroviral vector containing the FADD gene. The retroviral transfer of FADD gene significantly enhanced the transduction efficiency and effectively inhibited both in vitro and in vivo survival of malignant glioma cells through induction of apoptosis. These findings suggest that the FADD gene is a novel and useful tool for the treatment of malignant gliomas.

Adaptor Proteins, Signal Transducing↗