Biomedical subjects

Osamu Yamada

Publications and source records attributed to Osamu Yamada.

At least 19 recordsLinked to original sources

PubMed2007

Gene silencing by RNA interference in the koji mold Aspergillus oryzae.

We found the orthologous genes required for RNA interference (RNAi) in the Aspergillus oryzae genome database, and constructed a set of tools for gene silencing using RNAi in A. oryzae. This system utilizes compatible restriction enzyme sites so that only a single target gene fragment is required to create the hairpin RNA cassette. For ease of handling, we also separated the construction of the hairpin RNA cassette for the target gene from its subsequent introduction into the expression vector. Using the brlA gene as a target for RNAi, we detected decreased mRNA levels and a delayed conidiation phenotype in the transformants. Furthermore, even though A. oryzae possesses three copies of the alpha-amylase gene, a single copy of an alpha-amylase RNAi construct was sufficient to downregulate the mRNA levels and decrease the enzymatic activity to 10% of control levels. Gene silencing by RNAi should provide a powerful genetic tool for post-genomic studies of the industrially important fungus A. oryzae.

Aspergillus oryzae↗

PubMed2006

Helper virus-independent trans-replication of hepatitis C virus-derived minigenome.

We have previously described a synthetic T7-driven cDNA minigenome containing the antisense sequence of luciferase gene and internal ribosome entry site of encephalomyocarditis virus flanked by 5'- and 3'-end sequences of hepatitis C virus (HCV) that contain cis-acting replication elements. Synthesis of minus-strand RNA from the artificial minigenome was determined by using Huh-7 cells harboring autonomously replicating HCV subgenome as a helper for provision of functional replication components. To further confirm and extend these studies, we investigated here whether the minigenome replication system could be reconstituted by transfection of naïve Huh-7 cells with plasmid expressing nonstructural (NS) proteins. Reporter assay and Northern blot analysis revealed that trans-expression of NS proteins from 3 to 5 resulted in high level of luciferase activity and synthesized minus-strand RNA. The analogous result was also obtained with the minigenome derived from HCV 2a, and both HCV 1b- and 2a-derived NS protein were able to support the chimeric minigenomes whose 5'- or 3'-end was replaced by the respective region of the heterologous virus. These results provide a basis for establishing the reverse genetic system that is helpful to study cis- and trans-acting factors involved in HCV RNA replication.

Cell Line, Tumor↗

PubMed2006

Hemodynamic deterioration during simulated supraventricular tachycardia in patients after the Fontan operation.

BACKGROUND: Supraventricular tachycardia (SVT) is becoming of great concern for patients long after the Fontan operation and arterial blood pressure (BP) decreases during SVT may be associated with their morbidity and mortality. METHODS: We investigated the BP during supraventricular pacing (SVP) to simulate SVT in these patients. We measured femoral venous pressure (FVP) and plasma norepinephrine (NE) during SVP at 150 and 180 per minute in 20 Fontan patients and recorded the initial BP fall, its recovery and steady-state BP. RESULTS: Wide QRS duration had a significant impact on a greater BP decline and increases in steady-state FVP and NE at 150 SVP. Changes in BP, FVP and NE were greater at 180 SVP and in adult patients. In addition to a greater impact of baseline BP and age on the initial BP drop and steady-state BP (p<0.01); older age at Fontan repair, lower ventricular ejection fraction and heart rate variability were major determinants of greater BP fluctuation during 180 SVP (p<0.05). Patients with a history of SVT (n=5) exhibited a greater initial BP drop and increase in FVP during 180 SVP (p<0.01). The type of Fontan procedure had no influence on BP dynamics during SVP. CONCLUSIONS: In Fontan patients, wide QRS duration causes a greater hemodynamic fluctuation at slower SVT. Higher baseline BP and age, impaired ventricular function, late Fontan repair and a history of SVT were major determinants of hemodynamic deterioration during faster SVT.

Adolescent↗

PubMed2006

Percutaneous transluminal coronary rotational atherectomy for localized stenosis caused by Kawasaki disease.

We report the results of percutaneous transluminal coronary rotational atherectomy (PTCRA) for localized stenosis caused by Kawasaki disease (KD) in children. Five males and a females, aged 5-15 years old (median, 9), underwent PTCRA. The interval from the onset of KD to PTCRA ranged from 5 to 12 years (median, 9). The target vessels were the left anterior descending artery (three patients), the left circumflex (two patients), and the right coronary artery (one patient). The immediate results of PTCRA were successful in all patients, and the mean stenosis degree improved from 89 +/- 10% to 27 +/- 12%. In follow-up coronary angiograms within 1 year, four vessels were restenosed, including two with complete occlusion. A 15-year-old male has had good patency for 4 years after undergoing re-PTCRA for restenosis using a larger burr size. PTCRA is feasible for severe localized stenosis with calcification caused by KD in children and the immediate results are good. However, restenosis often occurred within 1 year after PTCRA in small children and PTCRA is not always appropriate for them. When the use of a larger burr is possible, good patency can be expected and can be maintained by close follow-up and re-PTCRA.

Adolescent↗

PubMed2006

Aspergillus oryzae strains with a large deletion of the aflatoxin biosynthetic homologous gene cluster differentiated by chromosomal breakage.

Recently we divided Aspergillus oryzae RIB strains into group 1, having seven aflatoxin biosynthesis homologous genes (aflT, nor-1, aflR, norA, avnA, verB, and vbs), and group 2, having three homologues (avnA, verB, and vbs). Here, partial aflatoxin homologous gene cluster of RIB62 from group 2 was sequenced and compared with that of RIB40 from group 1. RIB62 showed a large deletion upstream of ver-1 with more than half of the aflatoxin homologous gene cluster missing including aflR, a positive transcriptional regulatory gene. Adjacent to the deletion of the aflatoxin homologous gene cluster, RIB62 has a unique sequence of about 8 kb and a telomere. Southern analysis of A. oryzae RIB strains with four kinds of probe derived from the unique sequence of RIB62 showed that all group 2 strains have identical hybridizing signals. Polymerase chain reaction with specific primer set designed to amplify the junction between ver-1 and the unique sequence of RIB62 resulted in the same size of DNA fragment only from group 2 strains. Based on these results, we developed a useful genetic tool that distinguishes A. oryzae group 2 strains from the other groups' strains and propose that it might have differentiated from the ancestral strains due to chromosomal breakage.

Aflatoxins↗

PubMed2006

Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.

In this study, we show that all-trans retinoic acid (ATRA) treatment leads to a rapid decrease in telomerase activity, which was associated with the reduction in myeloblasts and occurs before the appearance of myelocytes, in a patient with acute promyelocytic leukemia (APL). Microarray analysis by ATRA treatment for 48 hr in peripheral blood mononuclear cells (in vivo) and in cultured bone marrow mononuclear cells (in vitro) from a patient with APL revealed upregulation of CD11b, CD11c, CCAAT enhancer binding protein epsilon, Rb1, Mad, and tumor necrosis factor-related genes; and downregulation of hTERT, c-Myc, WT1, bcl-2, and eukaryotic translation elongation factor 1alpha2. The results might offer the potential to define the molecular mechanism underlying ATRA-induced granulocytic differentiation in patients with APL, and provide clues to identify novel molecular therapeutic targets.

Antigens, Differentiation↗

PubMed2006

Molecular analysis of an inactive aflatoxin biosynthesis gene cluster in Aspergillus oryzae RIB strains.

To help assess the potential for aflatoxin production by Aspergillus oryzae, the structure of an aflatoxin biosynthesis gene homolog cluster in A. oryzae RIB 40 was analyzed. Although most genes in the corresponding cluster exhibited from 97 to 99% similarity to those of Aspergillus flavus, three genes shared 93% similarity or less. A 257-bp deletion in the aflT region, a frameshift mutation in norA, and a base pair substitution in verA were found in A. oryzae RIB 40. In the aflR promoter, two substitutions were found in one of the three putative AreA binding sites and in the FacB binding site. PCR primers were designed to amplify homologs of aflT, nor-1, aflR, norA, avnA, verB, and vbs and were used to detect these genes in 210 A. oryzae strains. Based on the PCR results, the A. oryzae RIB strains were classified into three groups, although most of them fell into two of the groups. Group 1, in which amplification of all seven genes was confirmed, contained 122 RIB strains (58.1% of examined strains), including RIB 40. Seventy-seven strains (36.7%) belonged to group 2, characterized by having only vbs, verB, and avnA in half of the cluster. Although slight expression of aflR was detected by reverse transcription-PCR in some group 1 strains, including RIB 40, other genes (avnA, vbs, verB, and omtA) related to aflatoxin production were not detected. aflR was not detected in group 2 strains by Southern analysis.

Aflatoxins↗

PubMed2006

Proteomic analysis of extracellular proteins from Aspergillus oryzae grown under submerged and solid-state culture conditions.

Filamentous fungi are widely used for the production of homologous and heterologous proteins. Recently, there has been increasing interest in Aspergillus oryzae because of its ability to produce heterologous proteins in solid-state culture. To provide an overview of protein secretion by A. oryzae in solid-state culture, we carried out a comparative proteome analysis of extracellular proteins in solid-state and submerged (liquid) cultures. Extracellular proteins prepared from both cultures sequentially from 0 to 40 h were subjected to two-dimensional electrophoresis, and protein spots at 40 h were identified by peptide mass fingerprinting using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. We also attempted to identify cell wall-bound proteins of the submerged culture. We analyzed 85 spots from the solid-state culture and 110 spots from the submerged culture. We identified a total of 29 proteins, which were classified into 4 groups. Group 1 consisted of extracellular proteins specifically produced in the solid-state growth condition, such as glucoamylase B and alanyl dipeptidyl peptidase. Group 2 consisted of extracellular proteins specifically produced in the submerged condition, such as glucoamylase A (GlaA) and xylanase G2 (XynG2). Group 3 consisted of proteins produced in both conditions, such as xylanase G1. Group 4 consisted of proteins that were secreted to the medium in the solid-state growth condition but trapped in the cell wall in the submerged condition, such as alpha-amylase (TAA) and beta-glucosidase (Bgl). A Northern analysis of seven genes from the four groups suggested that the secretion of TAA and Bgl was regulated by trapping these proteins in the cell wall in submerged culture and that secretion of GlaA and XynG2 was regulated at the posttranscriptional level in the solid-state culture.

Aspergillus oryzae↗

PubMed2006

Cloning and expression of 1,2-alpha-mannosidase gene (fmanIB) from filamentous fungus Aspergillus oryzae: in vivo visualization of the FmanIBp-GFP fusion protein.

1,2-alpha-Mannosidase catalyzes the specific cleavage of 1,2-alpha-mannose residues from protein-linked N-glycan. In this study, a novel DNA sequence homologous to the authentic 1,2-alpha-mannosidase was cloned from a cDNA library prepared from solid-state cultured Aspergillus oryzae. The fmanIB cDNA consisted of 1530 nucleotides and encoded a protein of 510 amino acids in which all consensus motifs of the class I alpha-mannosidase were conserved. Expression of the full length of 1,2-alpha-mannosidase cDNA by the Aspergillus host, though it has rarely been done with other filamentous-fungal mannosidase, was successful with fmanIB and caused an increase in both intracellular and extracellular mannosidase activity. The expressed protein (FmanIBp) specifically hydrolyzed 1,2-alpha-mannobiose with maximal activity at a pH of 5.5 and a temperature of 45 degrees C. With Man(9)GlcNAc(2) as the substrate, Man(5)GlcNAc(2) finally accumulated while hydrolysis of the 1,2-alpha-mannose residue of the middle branch was rate-limiting. To examine the intracellular localization of the enzyme, a chimeric protein of FmanIBp with green fluorescent protein was constructed. It showed a dotted fluorescence pattern in the mycelia of Aspergillus, indicative of the localization in intracellular vesicles. Based on these enzymatic and microscopic results, we estimated that FmanIBp is a fungal substitute for the mammalian Golgi 1,2-alpha-mannosidase isozyme IB. This and our previous report on the presence of another ER-type mannosidase in A. oryzae (Yoshida et al., 2000) support the notion that the filamentous fungus has similar steps of N-linked glycochain trimming to those in mammalian cells.

Amino Acid Sequence↗

PubMed2005

Genome sequencing and analysis of Aspergillus oryzae.

The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.

Aspartic Acid Endopeptidases↗

PubMed2005

Neuronal expression of keratinocyte-associated transmembrane protein-4, KCT-4, in mouse brain and its up-regulation by neurite outgrowth of Neuro-2a cells.

One group of proteins that regulates neurite outgrowth and maintains neuronal networks is the immunoglobulin superfamily (IgSF). We previously identified a new member of the IgSF, keratinocyte-associated transmembrane protein-4 (KCT-4), by the signal sequence-trap method from primary cultured human keratinocytes. The KCT-4 mRNA has been found to be highly expressed in the adult human brain, although it is also distributed in various tissues. In the present study, to gain insight into the role of KCT-4 in the nervous system, we examined the expression profile and localization of KCT-4 mRNA in mouse brain. We also evaluated changes in KCT-4 mRNA expression in the differentiation of the neuroblastoma cell line Neuro-2a as the in vitro model of neurite outgrowth. KCT-4 mRNA was detected broadly in various regions of the adult mouse brain by RT-PCR. In situ hybridization revealed that it was expressed highly selectively by neurons but not by glial cells. Moreover, expression of KCT-4 mRNA was induced by neurite outgrowth of Neuro-2a. These data suggest that KCT-4 participates in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.

Animals↗

PubMed2005

Inhibition of hepatitis C virus replication by pol III-directed overexpression of RNA decoys corresponding to stem-loop structures in the NS5B coding region.

Increasing evidence has shown that the stem-loop (SL) structures in the NS5B coding region of hepatitis C virus (HCV) function as cis-replicating elements that are indispensable for viral replication. We have investigated whether small RNA molecules analogous to the SL structures could inhibit HCV replication. Reporter assays showed that both in vitro transcribed and pol III-directed transcripts corresponding to 5BSL3.1 and 5BSL3.2 efficiently inhibited HCV replicon-encoded luciferase expression. Mutagenesis studies revealed that mutation in 5BSL3.2 which debilitated its binding to NS5B also abolished the ability of 5BSL3.2 RNA to inhibit HCV replication, suggesting that SL RNA inhibits HCV by sequestering the replication complex. Further, adenoviral-mediated expression of the SL RNAs potently blocked the replication of HCV replicon in Huh-7 cells. Importantly, SL RNAs derived from HCV 2a, an evolutionarily distant genotype, were also shown to suppress the replication of HCV 1b replicon in spite of the genetic heterogeneity between the SL elements of the two viruses, implying the potential of SL RNA-based approach to inhibit a wide range of HCV isolates. These results suggest that SL RNA decoys may prove to be useful in the treatment of hepatitis C, which may be advantageous over other sequence-specific gene therapy modalities (such as antisense RNA and siRNA) in preventing the escape of genetic variants.

Adenoviridae↗

PubMed2005

Change in plasma volume during peak exercise in patients with cyanotic congenital heart disease after definitive operation.

OBJECTIVES: To evaluate changes in plasma volume (deltaPV) during exercise in patients with single ventricular physiology with cyanosis; post-Fontan patients; and in patients after right ventricular outflow tract reconstruction (RVOTR). BACKGROUND: Compensatory mechanisms which regulate body fluid volumes operate in heart failure patients to maintain blood pressure. A better understanding of this pathophysiological process, especially during exercise, should help manage and follow such patients. METHODS: Twenty-six CHD patients (14+/-4 years), including 5 cyanotic patients, 12 after the Fontan operation, 9 after RVOTR, and 13 controls (14+/-5 years), performed a treadmill exercise test. DeltaPV from rest to peak was calculated and compared with changes in cardiovascular responses, plasma total protein (TP), norepinephrine (NE), osmolality (Osm), and blood lactate concentration (La). RESULTS: DeltaPV was smaller in CHD patients than in controls (Cyanotic: -5.9%, Fontan: -10.0%, RVOTR: -11.4%, CONTROLS: -14.5%, p<0.001). In all subjects, peak heart rate, systolic blood pressure and oxygen uptake correlated inversely with deltaPV (p<0.05 to 0.005). DeltaPV correlated inversely with changes in TP, NE, and La (p<0.005 for all), but not with the change in Osm. In CHD patients, the deltaPV correlated only with the NE increase (p<0.01). CONCLUSIONS: DeltaPV is smaller in CHD patients than in controls, especially in cyanotic patients. The smaller increases in cardiovascular responses during exercise and La are associated with the small deltaPV. These mechanisms may help to maintain cardiac output and increased sympathetic nervous activity may be beneficial to ensure sufficient perfusion pressure against deltaPV during exercise.

Adolescent↗

PubMed2005

Impact of noncoronary cusp prolapse in addition to right coronary cusp prolapse in patients with a perimembranous ventricular septal defect.

BACKGROUND: Few data are available with regard to the impact of aortic cusp herniation on the evolution of aortic regurgitation (AR) in patients with a perimembranous ventricular septal defect (VSD). METHODS: One hundred and two patients with a perimembranous ventricular septal defect with right coronary cusp prolapse were divided to two groups depending on the development of aortic regurgitation. The original defect diameter, the right coronary cusp deformity index (RCCD), and the right coronary cusp imbalance index were obtained as we reported previously. RESULTS: Mild aortic regurgitation was detected in 35 patients, and moderate in three. No aortic regurgitation was observed in 64 patients. A significantly larger number of patients had noncoronary cusp prolapse and the right coronary cusp imbalance index >/=1.30 in the aortic regurgitation group than in the no regurgitation group. Relative risk and odds ratio of noncoronary cusp prolapse and the right coronary cusp imbalance index >/=1.30 for development of aortic regurgitation were 3.69 (95% CI, 0.91-15.03) and 27.90 (95.94-130.85), and 2.23 (0.83-5.98) and 4.70 (1.44-15.27), respectively. Surgical closure was performed in 29 patients. All patients with no noncoronary cusp prolapse underwent simple patch closure of the ventricular septal defect, while five patients with noncoronary cusp prolapse and aortic regurgitation underwent aortic valvuloplasty. Among these, one patient needed aortic valve replacement. CONCLUSIONS: The additional complication of noncoronary cusp prolapse is a strong risk factor for the development of aortic regurgitation in patients with a perimembranous ventricular septal defect with right coronary cusp prolapse.

Adolescent↗

PubMed2005

Post-exercise heart rate, blood pressure and oxygen uptake dynamics in pediatric patients with Fontan circulation Comparison with patients after right ventricular outflow tract reconstruction.

BACKGROUND: Post-exercise heart rate (HR) and oxygen uptake (V O(2)) recover more slowly in patients with the Fontan circulation, but little is known about the determinants of the delayed recovery. PURPOSE: To evaluate the post-exercise cardiovascular dynamics and clinical profiles in these patients. METHODS AND RESULTS: We studied 51 Fontan patients (14+/-4 years) (atriopulmonary connection, APC = 18 and total cavopulmonary connection, TCPC = 33) and compared the results with 34 patients after right ventricular outflow tract reconstruction (RVOTR) with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15+/-4 years) and with 26 controls (14+/-4 years). There were no differences in post-exercise HR or VO2 declines between the Fontan and RVOTR groups. Although the systolic blood pressure (SBP) decline was delayed in the RVOTR group (p < 0.01), its early decline in the Fontan group was rapid and equivalent to that in controls. In Fontan patients, BRS had a great impact on early HR decline (p < 0.05) and early VO2 decline was determined by peak VO2, age and cardiac index (p < 0.05-0.001). TCPC and lower BRS were the main determinants of the slower SBP decline (p < 0.05). In another study of repeated paired exercise tests before and after Fontan operation, post-exercise SBP decline became greater after the operation (p < 0.07). CONCLUSIONS: In the Fontan group, post-exercise HR and VO2 declines are markedly delayed and are determined by cardiac vagal nervous activity, exercise capacity and age, respectively. Despite identical impaired hemodynamics and exercise capacity, post-exercise SBP decline is greater in the Fontan group, especially after APC, than in the RVOTR patients.

Adult↗

PubMed2005

IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells.

Human telomerase activity is induced by Ag receptor ligation in T and B cells. However, it is unknown whether telomerase activity is increased in association with activation and proliferation of NK cells. We found that telomerase activity in a human NK cell line (NK-92), which requires IL-2 for proliferation, was increased within 24 h after stimulation with IL-2. Levels of human telomerase reverse transcriptase (hTERT) mRNA and protein correlated with telomerase activity. ERK1/2 and Akt kinase (Akt) were activated by IL-2 stimulation. LY294002, an inhibitor of PI3K, abolished expression of hTERT mRNA and protein expression and abolished hTERT activity, whereas PD98059, which inhibits MEK1/2 and thus ERK1/2, had no effect. In addition, radicicol, an inhibitor of heat shock protein 90 (Hsp90), and rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), blocked IL-2-induced hTERT activity and nuclear translocation of hTERT but not hTERT mRNA expression. hTERT was coimmunoprecipitated with Akt, Hsp90, mTOR, and p70 S6 kinase (S6K), suggesting that these molecules form a physical complex. Immunoprecipitates of Akt, Hsp90, mTOR, and S6K from IL-2-stimulated NK-92 cells contained telomerase activity. Furthermore, the findings that Hsp90 and mTOR immunoprecipitates from primary samples contained telomerase activity are consistent with the results from NK-92 cells. These results indicate that IL-2 stimulation induces hTERT activation and that the mechanism of IL-2-induced hTERT activation involves transcriptional or posttranslational regulation through the pathway including PI3K/Akt, Hsp90, mTOR, and S6K in NK cells.

Cell Line, Transformed↗

PubMed2005

Negative chronotropic response to low-dose atropine is associated with parasympathetic nerve-mediated cardiovascular response in postoperative patients with congenital heart disease.

OBJECTIVES: To investigate the negative chronotropic response (NCR) to low-dose atropine in postoperative patients with congenital heart disease (CHD). BACKGROUND: Low-dose atropine causes a NCR through the central nervous system muscarinic receptor and is attenuated in adult heart failure patients. It has never been evaluated in CHD patients. METHODS: NCR corrected for basal heart rate (HR) (minimal HR/basal HR=cNCR) was determined after low-dose atropine (3 microg/kg) administration in 124 postoperative CHD patients (97 biventricular repair and 27 Fontan patients) and 11 controls and was compared with the cardiac autonomic nervous and functional status. RESULTS: The cNCR in simple CHD (post atrial or ventricular septal defect closure), complex biventricular CHD, and Fontan patients were 0.92+/-0.04, 0.94+/-0.04 and 0.96+/-0.04, respectively, and higher than in controls (0.87+/-0.03, p<0.001). In the complex CHD patients, higher cNCR was mainly associated with the lower pharmacologically determined cardiac parasympathetic nervous tone (PST), HR variability, high atrial natriuretic peptide, and lower right ventricular ejection fraction (p<0.0001). In Fontan patients, the lower beta sensitivity of the sinus node and the PST mainly determined the higher cNCR (p<0.01) and the cNCR did not correlate with either hemodynamics or exercise capacity. CONCLUSIONS: NCR is attenuated in proportion to the impaired cardiac parasympathetic nervous system and hemodynamics in postoperative complex biventricular CHD patients. In addition to PST, beta sensitivity of the sinus node significantly influences the NCR in Fontan patients.

Adolescent↗

PubMed2005

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia.

We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count < or =150 x 10(9)/L and 22 patients with a platelet count >150 x 10(9)/L. HCV RNA, platelet-associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty-two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.

Aged↗