Biomedical subjects

K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 55 records · Page 3Linked to original sources

PubMed2001

Biochemical response to interferon therapy correlates with interferon sensitivity-determining region in hepatitis C virus genotype 1b infection.

Biochemical responders maintain normal alanine aminotransferase levels after interferon (IFN) therapy despite persistent presence of hepatitis C virus (HCV) RNA in their sera. There have been few reports on predictive factors for biochemical response. A region associated with sensitivity to IFN was identified in the nonstructural protein 5 A of genotype 1b [aa 2209-2248; IFN sensitivity-determining region (ISDR)]. The substitutions in ISDR correlate with sustained response to IFN. In this report, we assessed the association of ISDR with biochemical response. The sequences of ISDR were determined in 62 patients with HCV genotype 1b treated by IFN in two randomized controlled trials. 30 patients had wild ISDR (identical to HCV-J), 20 intermediate ISDR (1-3 amino acid substitutions compared with HCV-J), and 12 mutant ISDR (four or more amino acid substitutions). All 12 patients with mutant ISDR had a sustained response, while only one of those with wild or intermediate ISDR had a sustained response (P < 0.0001). In the 49 patients other than sustained responders, the patients with intermediate ISDR obtained biochemical response significantly more frequently (52.6%, 10/19) than those with wild-type ISDR (20.0%, 6/30) (P < 0.05). Multivariate analysis indicated the number of substitutions in ISDR as the most important predictor for biochemical response (discriminant coefficient=1.08, P < 0.05) and sustained response (discriminant coefficient=6.13, P < 0.0001). In phylogenetic analysis, clustering of sustained responders and biochemical responders was observed. These results demonstrate that the substitutions in ISDR are the most important predictor for biochemical response to IFN in patients infected with genotype 1b as well as for sustained response.

Adult↗

PubMed2001

Probenazole induces systemic acquired resistance in Arabidopsis with a novel type of action.

Probenazole (PBZ; 3-allyloxy-1,2-benzisothiazole-1,1-dioxide), which is the active ingredient in Oryzemate, has been used widely in Asia to protect rice plants against the rice blast fungus Magnaporthe grisea. To study PBZ's mode of action, we analyzed its ability, as well as that of its active metabolite 1, 2-benzisothiazol-3 (2H)-one 1,1-dioxide (BIT) to induce defense gene expression and resistance in Arabidopsis mutants that are defective in various defense signaling pathways. Wild-type Arabidopsis treated with PBZ or BIT exhibited increased expression of several pathogenesis-related genes, increased levels of total salicylic acid (SA), and enhanced resistance to the bacterial pathogen Pseudomonas syringae pv. tomato DC 3000 and the oomycete pathogen Peronospora parasitica Emco5. The role of several defense signaling hormones, such as SA, ethylene and jasmonic acid (JA), in activating resistance following PBZ or BIT treatment was analyzed using NahG transgenic plants and etr1-1 and coi1-1 mutant plants, respectively. In addition, the involvement of NPR1, a key component in the SA signaling pathway leading to defense responses, was assessed. PBZ or BIT treatment did not induce disease resistance or PR-1 expression in NahG transgenic or npr1 mutant plants, but it did activate these phenomena in etr1-1 and coi 1-1 mutant plants. Thus SA and NPR1 appear to be required for PBZ- and BIT-mediated activation of defense responses, while ethylene and JA are not. Furthermore, our data suggest that PBZ and BIT comprise a novel class of defense activators that stimulate the SA/NPR1-mediated defense signaling pathway upstream of SA.

Arabidopsis↗

PubMed2001

Environmentally sensitive, SA-dependent defense responses in the cpr22 mutant of Arabidopsis.

To investigate the signaling pathways through which defense responses are activated following pathogen infection, we have isolated and characterized the cpr22 mutant. This plant carries a semidominant, conditional lethal mutation that confers constitutive expression of the pathogenesis-related (PR) genes PR-1, PR-2, PR-5 and the defensin gene PDF1.2. cpr22 plants also display spontaneous lesion formation, elevated levels of salicylic acid (SA) and heightened resistance to Peronospora parasitica Emco5. The cpr22 locus was mapped to chromosome 2, approximately 2 cM telomeric to the AthB102 marker. By analyzing the progeny of crosses between cpr22 plants and either NahG transgenic plants or npr1 mutants, all of the cpr22-associated phenotypes except PDF1.2 expression were found to be SA dependent. However, the SA signal transducer NPR1 was required only for constitutive PR-1 expression. A cross between cpr22 and ndr1-1 mutants revealed that enhanced resistance to P. parasitica is mediated by an NDR1-dependent pathway, while the other cpr22-induced defenses are not. Crosses between either coi1-1 or etr1-1 mutants further demonstrated that constitutive PDF1.2 expression is mediated by a JA- and ethylene-dependent pathway. Based on these results, the cpr22 mutation appears to induce its associated phenotypes by activating NPR1-dependent and NPR1-independent branches of the SA pathway, as well as an ethylene/JA signaling pathway. Interestingly, the SA-dependent phenotypes, but not the SA-independent phenotypes, are suppressed when cpr22 mutants are grown under high humidity.

Arabidopsis↗

PubMed2001

Pharmacology of a unique adenosine binding site in rat brain using a selective ligand.

1. In order to further characterize the adenosine binding sites that we previously purified and termed P3 purinergic receptor-like protein (P3LP), a reliable binding assay method was developed using [3H]-5'-N-ethylcarboxamidoadenosine (NECA) as a radioligand and the newly developed high-affinity selective ligand 9-(6,7-dideoxy-beta-D-allo-hept-5-ynofuranosyl) adenine (HAK2701) as a selective displacer. 2. Using this assay method, it was found that rat brain membranes possess high- and low-affinity [3H]-NECA binding sites. The high-affinity binding site showed KD and Bmax values of 19.7+/-2.5 nmol/L and 0.192+/-0.05 pmol/mg protein, respectively, and the KD value for the low-affinity binding site was 4260+/-330 nmol/L. The KD value for the high-affinity site agreed well with that of the [3H]-NECA binding site determined with the partially purified P3LP preparation described previously. 3. The distribution of P3LP in rat tissues was determined using the [3H]-NECA binding method described above. The highest level of P3LP was in the cerebellum followed by the olfactory bulb and the spinal cord. 4. The order of the affinity for various purinergic or related compounds to P3LP in rat brain preparations was also determined by the [3H]-NECA binding method to be HAK2701 > NECA = adenosine 5'-O-(2-thiodiphosphate) > cAMP = beta,gamma-methyleneadenosine 5'-triphosphate > diadenosine tetraphosphate > alpha,beta-methyleneadenosine 5'-triphosphate > 5'-deoxy-5'-methylthioadenosine > N6-cyclopentyladenosine. 5. These studies reveal that the [3H]-NECA binding assay in combination with HAK2701 is successful in the characterization of P3LP, especially the membrane-bound form.

Adenosine↗

PubMed2001

Effect of exercise training on serum leptin levels in type 2 diabetic patients.

To evaluate the effect of exercise training on serum leptin levels 50 sedentary subjects with type 2 diabetes were enrolled in either 6 weeks of aerobic exercise training with diet therapy (n = 23) or diet therapy alone (n = 27). The training program consisted of walking and cycle ergometer exercise for 1 hour at least 5 times per week, with the intensity of exercise maintained at 50% of maximum oxygen uptake. Serum leptin levels decreased significantly in the exercise training (TR) group (7.2 +/- 3.6 to 4.6 +/- 2.5 ng/mL, P <.05), but not in the sedentary (SED) group (6.9 +/- 3.4 to 5.6 +/- 2.9 ng/mL). Leptin levels standardized for percentage body fat (dividing serum leptin level by percentage body fat) after treatment were lower in the TR subjects compared with the SED subjects. Body weight and percentage body fat decreased in all patients; however, no significant changes were observed in either group. Fasting concentrations of plasma insulin and cortisol and the urinary excretion of 17-hydroxycorticosteroid (17-OHCS) did not differ between the groups either before or after treatment. Fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) improved significantly in both groups, although no significant differences were observed between the groups either before or after treatment. Ventilatory threshold increased significantly in the exercise training subjects. This study demonstrates that exercise training in type 2 diabetic subjects reduces serum leptin levels independent of changes in body fat mass, insulin, or glucocorticoids.

17-Hydroxycorticosteroids↗

PubMed2001

Chromosome 9 and 17 aberrations and p53 gene deletion detected by fluorescence in situ hybridization in renal-cell carcinoma.

BACKGROUND AND PURPOSE: Nuclear grade and tumor stage have been reported as important prognostic factors for renal-cell carcinoma (RCC), but tumors of similar stage and grade can still exhibit wide variations in biologic behavior and clinical outcome. Fluorescence in situ hybridization (FISH) has recently been applied to RCC. This study was designed to investigate whether aberrations of some chromosomes or genes detected by FISH are related to the progression of RCC. MATERIALS AND METHODS: We examined 52 patients with RCC, including 31 patients without metastasis (control group) and 21 patients with either concurrent or subsequent metastasis (metastatic group). Paraffin-embedded specimens of the primary tumors were analyzed by FISH for aberrations of chromosomes 9 and 17, as well as for p53 gene alterations. RESULTS: The incidence of aberrations of chromosome 9 was higher in the metastatic group than in the control group. The p53 gene deletion rate was significantly higher in the metastatic group than in the control group. When the metastatic group was separated into concurrent and subsequent metastasis subgroups, chromosome 17 aberrations as well as p53 gene deletion were significantly more common in the subsequent metastasis group than in the control group. CONCLUSIONS: Numerical aberrations of chromosome 17 as well as p53 gene deletion detected by FISH may be markers of chromosomal instability in RCC and are probably associated with an increased propensity to metastasize.

Adult↗

PubMed2001

HMG box A in HMG2 protein functions as a mediator of DNA structural alteration together with box B.

Nonhistone protein HMG2, like HMG1, binds with B-DNA in a sequence-nonspecific manner and causes structural alterations in DNA such as bending, kinking and unwinding. Here, we studied the functions of HMG2 domains in the DNA structural alteration and modulation by using various HMG2 peptides, and we demonstrated several new findings. The HMG box itself as a DNA-binding motif may have the basic function of inducing curvature, resulting in the apparent DNA bending in the DNA cyclization assay, but not of abruptly kinking DNA. The DNA-binding activity of HMG box B, which is enhanced by the presence of box A, together with the flanking regions of box B, causes DNA bending accompanying the kinking of the DNA main chain. The DNA unwinding accompanied by DNA kinking diminishes cruciform structures in supercoiled DNA. Analysis using mutant peptides for box A confirmed that box A in HMG2 functions as a mediator of DNA structural alteration together with box B. The present studies on the functional properties of the respective regions of HMG2 may help to elucidate the protein function.

Amino Acid Motifs↗

PubMed2001

Gonadotropin-releasing hormone in third ventricular cerebrospinal fluid of the heifer during the estrous cycle.

The release profile of GnRH in cerebrospinal fluid (CSF) and its correlation with LH in peripheral blood of ovary-intact heifers during the estrous cycle were investigated. A silicon catheter was placed into the third ventricle of six heifers using ultrasonography. During the mid-luteal phase, the heifers were injected with prostaglandin F(2alpha) to induce luteolysis. Surges of CSF GnRH (66.7 h after prostaglandin F(2alpha) administration) and peripheral LH (66.3 h) occurred simultaneously and were coincident with the onset of estrus (67.0 h). Duration of elevated GnRH concentration considerably overlapped with the estrous phase in each of the heifers. Mean pulse frequencies of both GnRH and LH were significantly higher during the proestrous and early luteal phases than during the mid-luteal phase, while mean concentration and pulse amplitude of both GnRH and LH were not different between these three phases. Of all the GnRH pulses identified, more than 80% were accompanied by an LH pulse during the proestrous and early luteal phases. However, the proportion of GnRH pulses that were coincident with an LH pulse during the mid-luteal phase decreased to 60%. The results clearly demonstrate that a dynamic (pulse) and longer-term (surge) changes of GnRH release into CSF are physiologically expressed during the estrous cycle in heifers, and the pattern of pulsatile GnRH secretion in heifers depends upon their estrous cycle.

Animals↗

PubMed2001

Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis.

BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Sodium sensitivity of blood pressure appearing before hypertension and related to histological damage in immunoglobulin a nephropathy.

Patients with renal parenchymal disease exhibit sodium-sensitive hypertension. We examined patients with immunoglobulin A (IgA) nephropathy to determine whether this sensitivity appears before hypertension begins and whether this sensitivity is related to histological damage. Thirty-eight patients with IgA nephropathy followed a diet with an ordinary sodium level for 1 week and a sodium-restricted diet for 1 week, in random order, and were divided into 3 groups by their systemic blood pressure on the diet with an ordinary sodium level (optimal, <120/<80 mm Hg, n=15; normal to high-normal, 120 to 139/80 to 89 mm Hg, n=18; hypertensive, >/=140/>/=90 mm Hg, n=5). The sodium sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linkage of 2 datum points obtained during the different diets. The scores for glomerulosclerosis and tubulointerstitial damage were evaluated semiquantitatively. The sensitivity index, glomerulosclerosis score, and score for tubulointerstitial damage were higher in patients with normal to high-normal blood pressure or hypertension than in patients with optimal pressure. The sensitivity index was significantly correlated with glomerulosclerosis (P=0.001) and tubulointerstitial damage (P=0.002). In patients with normal to high-normal pressure, sodium restriction lowered blood pressure to the optimal range and decreased proteinuria. In patients with IgA nephropathy, sodium sensitivity of blood pressure related to renal histological damage appears before hypertension.

Adult↗

PubMed2001

Absence of endothelium in invertebrate blood vessels: significance of endothelium and sympathetic nerve/medial smooth muscle in the vertebrate vascular system.

In the course of evolution, two remarkable changes seem to have occurred in vertebrate circulation: the appearance and development of the "endothelium or endothelial tubular system" and "sympathetic nerve/medial smooth muscle system". In the present article, some relevant literature is reviewed and discussed. Absence of endothelium in the vascular wall of most invertebrates had been known and was confirmed by recent electron microscopic studies. The medial smooth muscle is rather proper to vertebrate vessels. It seems to have appeared after emergence of and in association with the endothelial tubular system. Phylogenetically, the parasympathetic nervous system is thought to be older than the sympathetic system. The former is distributed to viscera and the latter developed in close relation with the vascular system. It is assumed that during evolution, a circulatory system composed of the heart and endothelial tubular system first formed in vertebrates, medial smooth muscle then appeared for regulation of the system, and innervation of the muscle tissue took place. This sequence of development assumed for phylogenesis is actually realized in the ontogenetic processes. We thus propose a hypothesis that the "sympathetic nerve/medial smooth muscle system" may be regarded as a new neuroeffector mechanism that developed for systemic regulation of the endothelium-lined closed vascular system in vertebrates. A few implications of the hypothesis are presented.

Animals↗

PubMed2001

Characterization of PBZ1, a probenazole-inducible gene, in suspension-cultured rice cells.

Probenazole (PBZ) induces non-race specific resistance in rice plants against rice blast fungus and PBZ1 was identified as a PBZ-inducible gene from rice. The induction of PBZ1 expression in suspension-cultured rice cells was investigated. Northern blot analysis indicated that PBZ1 was induced by PBZ in a dose-dependent manner. Enzyme-linked immunosorbent assay (ELISA) showed a dose and time-dependent accumulation of PBZ1 protein. Both mRNA and protein analysis showed that PBZ1 was not induced by salicylic acid or an active metabolite, 1,2-benzisothiazole-1,1-dioxide.

Cell Line↗

PubMed2001

Endothelin-1 in smooth muscle cells and mast cells of mouse uterus after parturition.

To elucidate the physiological importance of endothelin-1 (ET-1) in mouse uterus, we investigated quantitative changes in ET-1 mRNA levels in the uterus during the estrous cycle, pregnancy and post-parturient period by use of the real-time PCR technique and we examined the cellular distribution of the ET-1 peptide by use of immunohistochemical techniques. Low and constant mRNA levels were observed in the uterus from cyclic or pregnant mice. However, a significant increase in mRNA levels was found immediately after parturition (day 0 postpartum) which then decreased gradually to a basal level at day 14 postpartum. Discernible immunopositivity was found in myometrial cells as well as in endometrial epithelial cells in the post-parturient uterus. Myometrial cells showed the strongest staining at day 0 postpartum, and some large cells in the myometrial layers, intensely positive for ET-1, were characterized as mast cells. These findings suggest the possibility that in mouse uterus ET-1 may play a role in recovery from the uterine changes caused by pregnancy and parturition.

Animals↗

PubMed2001

A patient with chronic hepatitis C who obtained sustained response by retreatment of interferon after decrease of viral load and mutation in interferon sensitivity determining region.

A 44-year-old man with chronic hepatitis C received three courses of interferon (IFN) therapy. HCV genotype was 1b, viral load was 1,200 kcopies/ml and interferon sensitivity determining region (ISDR) was the intermediate type before the 1st IFN therapy. The 1st and 2nd IFN therapies resulted in failure to yield a sustained response. Seven years after from the 1st therapy, viral load had decreased to 15 kcopies/ml and ISDR had changed to mutant type. The 3rd IFN therapy yielded sustained response. Thus, we should consider retreatment with IFN when a decrease of the viral load and change of ISDR to mutant type are observed.

Adult↗

PubMed2001

Acute respiratory failure caused by vinorelbine tartrate in a patient with non-small cell lung cancer.

We describe a case of vinorelbine tartrate (VNR) associated acute respiratory failure. A 65-year-old man with non-small cell lung cancer developed acute respiratory failure 50 minutes after his first infusion with VNR in combination with mitomycin-C. The patient was treated with furosemide, dopamine and high-dose methylprednisolone, and recovered with no discernible sequelae. Although clinical trials have shown that respiratory symptoms associated with VNR treatment have only rarely been observed and the putative mechanism remains to be elucidated, patients receiving VNR should be monitored carefully, particularly in the first few hours after intravenous administration.

Acute Disease↗

PubMed2001

C282Y and H63D mutations in the HFE gene have no effect on iron overload disorders in Japan.

OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human leukocyte antigen A locus was previously identified and designated as HFE. This study was performed to evaluate the clinical significance of two mutations, C282Y and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis, 94 patients with chronic hepatitis C, 54 patients with miscellaneous liver diseases, and 151 healthy volunteers. The HFE gene region of DNA samples extracted from peripheral leukocytes was amplified by polymerase chain reaction. Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for H63D. Direct sequence analysis was then performed when products suggested the presence of a mutation. RESULTS: All the subjects studied were free from C282Y. None of the patients with hemochromatosis had H63D. One patient with chronic hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two patients with alcoholic liver disease were heterozygous for H63D. The prevalence of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C, 2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in healthy volunteers. These differences were not significant. CONCLUSION: Our results suggested that neither C282Y nor H63D in HFE affect Japanese patients with hemochromatosis or chronic hepatitis C.

Adult↗

PubMed2001

Sodium sensitivity related to albuminuria appearing before hypertension in type 2 diabetic patients.

OBJECTIVE: To find whether sodium sensitivity of blood pressure appears before hypertension and whether the sensitivity is related to diabetic nephropathy, we examined type 2 diabetic patients with normal levels of serum creatinine. RESEARCH DESIGN AND METHODS: A total of 32 patients were divided into three age-matched groups: 11 patients had normoalbuminuria, 12 had microalbuminuria, and 9 had macroalbuminuria. Patients stayed on a diet with ordinary sodium levels for 1 week and a sodium-restricted diet for 1 week, in random order. Urinary excretion of sodium and albumin and systemic blood pressure were measured daily. A pressure-natriuresis curve was drawn by linkage of the two datum points obtained in the steady state during the different diets. We calculated the sodium sensitivity index as the reciprocal of the slope of this curve. RESULTS: The median sodium sensitivity index and the mean blood pressure were higher in micro- and macroalbuminuric patients than in normoalbuminuric patients. Eighteen patients were without hypertension (<140/90 mmHg); of these, 10 had blood pressure readings <130/85 mmHg with ordinary sodium levels. Urinary albumin was correlated with the index but not with blood pressure. For these 10 patients, the index in those with albuminuria was higher than in those with normoalbuminuria. In such patients with albuminuria, sodium restriction decreased albuminuria and blood pressure. CONCLUSIONS: In type 2 diabetic patients with albuminuria but normal levels of serum creatinine, sodium sensitivity of blood pressure appears before hypertension and is related to albuminuria; sodium restriction is one treatment for diabetic nephropath, even without hypertension.

Adult↗

PubMed2001

Body iron stores and iron restoration rate in Japanese patients with chronic hepatitis C as measured during therapeutic iron removal revealed neither increased body iron stores nor effects of C282Y and H63D mutations on iron indices.

Information on the level of iron stores in chronic hepatitis C is clinically important because its reduction is technically simple and therapeutically effective. This study was performed to measure the levels of iron stores from the total amounts of hemoglobin removed during iron reduction therapy. The C282Y and H63D mutations of HFE gene were analyzed in 94 patients. All of the patients were negative for C282Y mutation. One patient was homozygous, and 4 patients were heterozygous for H63D mutation. The body iron stores and iron restoration rate were measured in 59 patients in serial courses of iron reduction therapy. Mean values of body iron stores in the two groups with and without H63D mutation were 890 and 606 mg, while those of iron restoration rate were 1.85 and 1.52 mg/day, respectively. None of the indices of iron metabolism were different from the reference values measured similarly in healthy subjects, suggesting that the iron deposition in chronic hepatitis C is limited to the liver, probably due to changes in the iron distribution in tissues.

Female↗