Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 109 records · Page 6Linked to original sources

PubMed2000

Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation.

Telomere length of peripheral blood mononuclear cells (PBMCs) from 23 autologous HSCT patients ranging from 4 to 61 years old, and 46 allogeneic HSCT recipients from 6 to 52 years old were studied to confirm whether excessive shortening of telomeres is associated with HSCT. After autologous HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. The comparison between transplanted PBMCs and PBMCs after autologous HSCT showed shortening by up to 1.9 kb (mean +/- s.d.: 0.64 +/- 0.50 kb). There was a difference between autologous HSCT patients and normal volunteers in the slopes of regression lines. After allogeneic HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. Telomeres of recipients were up to 2.1 kb (0.60 +/- 0.468 kb) shorter than those of donors. The slope of regression lines for allogeneic HSCT patients and normal volunteers were parallel. Although all patients were transplanted with more than 2.0 x 10(8) cells/kg, telomere length did not correlate with the number of transplanted cells. There was no significant correlation between telomere length and recovery of hematological parameters. However, three patients with an average telomere length of 6.8 kb after HSCT took a longer period to reach the normal hematological state. Taken together, these data suggest that most HSCTs are performed within the biological safety range of telomeres, while the patients who have telomeres shorter than 7.0 kb after HSCT should be observed carefully for long-term hematopoiesis and the occurrence of hematopoietic disorders.

Adolescent↗

PubMed2000

Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation.

Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has been reported that TNF-alpha and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure after organ transplantation and systemic lupus erythematosus. We examined whether TNF-alpha and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from pre- and post-transplant blood cells. Donor-derived TNF2 allele (A) was more frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs 2/56) (P = 0.04). The donors of the patients with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10.G than those without (13/26 vs 5/28) (P = 0.02), and the patients with cGVHD had more CA repeats in donor-derived IL-10.G than those without (mean = 25.2 vs 23.4) (P = 0.01). Donor-derived TNF-308 and IL-10.G alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us distinguish those patients at high risk for GVHD.

Acute Disease↗

PubMed2000

Monitoring the melt-extrusion transesterification of ethylene-vinylacetate copolymer by self-modeling curve resolution analysis of on-line near-infrared spectra.

The transesterification of molten ethylene-vinylacetate (EVA) copolymers by octanol with sodium methoxide as catalyst in an extruder has been monitored by on-line near infrared (NIR) spectroscopy. A total of 60 NIR spectra were acquired for 37 min with the last spectrum recorded 31 min after the addition of octanol and catalyst was stopped. The experimental spectra show strong baseline fluctuations which are corrected for by multiplicative scatter correction (MSC). The chemometric methods of the orthogonal projection approach (OPA) and multivariate curve resolution (MCR) were used to resolve the spectra and to derive concentration profiles of the species. The detailed analysis reveals the absence of completely pure variables which leads to small errors in the calculation of pure spectra. The initial estimation of a concentration that is necessary as an input parameter for MCR also presents a non-trivial task. We obtained results that were not ideal but applicable for practical concentration control. They enable a fast monitoring of the process in real-time and resolve the spectra of the EVA copolymer and the ethylene-vinyl alcohol (EVAL) copolymer to be very close to the reference spectra. The chemometric methods used and the decomposed spectra are discussed in detail.

Journal Article↗

PubMed2000

Quantitative trait loci (QTL) analysis in a Meishan x Göttingen cross population.

In order to locate the genetic regions in the swine genome that are responsible for economically important traits, a resource population has been constructed by mating two female Meishan pigs with a male Göttingen miniature pig. In subsequent generations, 265 F2 offspring were produced from two F1 males and 19 F1 females. The F2 offspring were scored for eight traits including growth rate, teat number, vertebra number and backfat thickness, and genotyped for 318 genetic markers spanning the swine genome. Least-square analysis revealed quantitative trait loci (QTL) effects for vertebra number on chromosomes 1 and 2; for teat number on chromosomes 1 and 7; for birth weight on chromosome 1; for average daily gain between 4 and 13 weeks of age on chromosomes 9 and 10; for backfat thickness on chromosome 7; and for backskin thickness on chromosome 3.

Animals↗

PubMed2000

Relationship between EEG dimensional complexity and neuropsychological findings in Alzheimer's disease.

The aim of the present study was to examine the region-specific correlations between electroencephalography (EEG) dimensional complexity (DC), a measure of non-linear dynamics, and neuropsychological performance in 25 right-handed patients with Alzheimer's disease (AD). Electroencephalography recording sites were according to the international 10-20 system. Neuropsychological tests included Wechelor Adult Intelligence Scale-Revised (WAIS-R) (Full-scale Intelligence Quotient (FIQ), Verbal Intelligence Quotient (VIQ), Performance Intelligent Quotient (PIQ)); Mini-Mental State Examination; Raven's Coloured Progressive Matrices (RCPM); Rey Auditory-Verbal Learning Test (RAVLT); seven word pairs-revised Miyake Paired-Associate Word Learning Test; Benton Visual Retention Test; and Rey Complex Figure Test. A partial correlational analysis was carried out, controlling for age and sex (P< 0.005). The FIQ, VIQ and RCPM scores were found to be significantly correlated with DC at the F3, C3 and T3 electrodes. Significant correlations were also found between RAVLT scores and DC at the C3, P3 and T5 electrodes. The study on AD indicated region-specific correlations between DC and neuropsychological performance: one between the DC value in the left frontal, central and mid-temporal areas and intellectual function; and another between the DC value in the left central, parietal and post-temporal areas and verbal memory. Dimensional complexity would therefore seem to be a useful indicator for the assessment of neuropsychological deficits in AD.

Aged↗

PubMed2000

Results of surgical treatment of lung cancer involving the diaphragm.

OBJECTIVES: Lung cancers with diaphragmatic invasion are categorized as T3 lesions, but the surgical results have not been well known. We retrospectively surveyed patients with resected primary lung cancers involving the diaphragm. METHODS: A total of 16,771 patients underwent surgical resection for lung carcinoma between 1986 and 1995 at 31 institutions of the Lung Cancer Surgical Study Group in Japan. By investigating the database, we identified 63 patients (0. 38%) who underwent resection of T3 lung cancer invading the diaphragm. These patients constituted the study population, and their clinical and pathologic records were retrospectively analyzed. RESULTS: Tumor invasion to the diaphragm was diagnosed before operation only in 17 patients (27.0%). Complete resections of the primary lung tumors with the invaded diaphragm were performed in 55 patients (87.3%), of whom 26 had T3 N0 M0 diseases and 29 had T3 Nl-2 M0 diseases. The operative mortality was 1.6% in all patients. The 5-year survival of patients with complete resection was 22.6%, but there was no 4-year survivor in patients with incomplete resection (P =.024). The survivals of patients with completely resected T3 N0 M0 and T3 N1-2 M0 tumors were 28.3% and 18.1%, respectively (P =.013). In those patients, the depth of diaphragmatic involvement significantly affected the prognosis. The 5-year survival of the patients with shallow invasion (parietal pleura or subpleural tissue involvement) was 33.0%, whereas that of the patients with deep invasion (muscle or peritoneal infiltration) was 14.3% (P =.036). CONCLUSIONS: In selected patients with lung carcinoma and diaphragmatic invasion, combined resection of the lung and diaphragm offers the prospect of cure with acceptable mortality. However, primary lung tumors with diaphragmatic invasion, especially invasion of the muscle layer or deeper tissue, are not considered to be T3 lesions, because these cancers are generally technically resectable but oncologically almost incurable.

Aged↗

PubMed2000

The role of thymidine phosphorylase in the pathogenesis of allergic rhinitis.

The activity and distribution of thymidine phosphorylase (TP) in the nasal mucosa of patients with nasal allergy was examined and compared with those in healthy subjects. TP activity was analyzed by spectrophotometry and expression was examined by immunoblotting and immunohistochemical staining using a monoclonal antibody specific to TP. The expression level of TP detected by immunoblotting showed a correlation with the activity detected by spectrophotometry. In nasal mucosa obtained from patients with nasal allergy, the level of TP was significantly higher than that from normal subjects. Eosinophils, basal cells in mucosal epithelium and fibroblasts in nasal mucosa obtained from patients with nasal allergy were stained with anti-TP monoclonal antibody. Strong staining of eosinophils present in nasal discharge was observed. The present results indicate that an increased number of TP-expressing cells, especially eosinophils in nasal mucosa, might be associated with the pathogenesis of nasal allergy.

Adolescent↗

PubMed2000

Generation of dendritic cells from adherent cells of cord blood by culture with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha.

Although dendritic cells (DC) can be cultured from cord blood (CB) CD34+ progenitor cells, the generation of DC from CB monocytes has not been reported. In this paper, we explored the generation of DC from CB monocytes to establish the simplest way to obtain a substantial number of DC from CB. We isolated monocytes from CB mononuclear cells (CB-MNC) by the plastic adherence method. These adherent cells (monocyte-rich cells) were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) or in serum-free X-VIVO 15 medium (SFM) for 7 days, both of which contained 100 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml interleukin-4 (IL-4) with or without 10 ng/ml tumor necrosis factor-alpha (TNF-alpha) (added at day 5). In the presence of GM-CSF and IL-4, CB-adherent cells became nonadherent, acquired DC morphology, and showed increased expression of CD1a, CD80, CD86, and HLA-DR; they lost membrane CD14 and some cells with the expression of CD83 and CMRF-44 were generated. With the addition of TNF-alpha to these cultures and culturing for further 2 days, the proportion of CD83+ cells was elevated in both the FBS and SFM culture systems, compared with the culture without TNF-alpha. In the culture with TNF-alpha, cells expressing CD1a, CD80, CD86, HLA-DR, and HLA-DQ were markedly increased. TNF-alpha-treated cells were demonstrated to be stronger stimulators for proliferation of both allogeneic CB lymphocytes and PB lymphocytes than were cells not treated with TNF-alpha. The yield of CD83+ DC at day 7 of cultures was 4.9 +/- 1.1 x 10(5) or 3.0 +/- 0.5 x 10(5) per 1.2 x 10(7) CB-MNC plated initially when cultured in FBS or SFM, respectively. These results have shown that a substantial number of mature DC could be generated from CB-adherent cells even by serum-free culture. We then compared these CB-adherent cell-derived DC (CB-DC) with peripheral blood (PB)-adherent cell-derived DC (PB-DC) in cell-surface phenotype and function. We found day 7 CB-DC have lower expression of CD80, CD1a, CD83, and CMRF-44 than day 7 PB-DC, but CB-DC have a similar capacity to stimulate the proliferation of both allo-CB lymphocytes and PB lymphocytes, compared with PB-DC. CB-DC cultured with GM-CSF and IL-4 have almost identical capacity of phagocytosis to take up fluorescein isothiocyanate (FITC)-dextran and Lucifer yellow (LY), compared with PB-DC. In summary, our findings suggest CB adherent cells, when cultured with GM-CSF, IL-4, and TNF-alpha, are a potent source of functional DC. Thus, CB-DC as well as PB-DC may become valuable tools for immunotherapy.

Cell Adhesion↗

PubMed2000

Two-terpyridine.Cu(II) complexes-containing antisense systems for rapid and highly site-specific RNA cleavage.

In an approach toward artificial ribonucleases, novel RNA cleaving systems were constructed that contained two terpyridine.Cu(II) residues. The first antisense system used tandem Cu(II) complex--2'-O-methyloligonucleotide 5'- and 3'-conjugates to cleave an RNA substrate. The second system, which will be described in a future paper, contained two contiguous Cu(II) complex residues at an internal site of a 2'-O-methyloligonucleotide. We found that the first system rapidly cleaved RNA with high site-specificity. Based on these results, we expect the second system to also show efficient RNA cleavage.

Base Sequence↗

PubMed2000

Genetic characterization of rbt mutants that enhance basal transcription from core promoters in Saccharomyces cerevisiae.

While this Saccharomyces cerevisiae SIN4 gene product is a component of a mediator complex associated with RNA polymerase II, various studies suggest the involvement of Sin4 in the alteration of higher-order chromatin structure. Our previous analysis of a sin4 mutant suggested that the mechanisms of transcriptional repression by Sin4 (mediator) and the Tup1-Ssn6 complex (general repressor) are different. To elucidate the way in which these two repression systems are interrelated, we isolated mutants that exhibit enhanced transcription of a reporter gene harboring the upstream activation sequence (UAS), but still are subject to Tup1-Ssn6-mediated repression. Besides sin4, rgr1, tup1, and ssn6 mutants, we also obtained new mutants that enhance basal transcription even from a core promoter without UAS. Such mutants, designated rbt for regulator of basal transcription, can be classified into at least six complementation groups, i.e., four single (rbt1 to rbt4) and two apparently double (rbt5 rbt6 and rbt7 rbt8) mutations. The phenotype of rbt mutants is dependent on the TATA box and not specific to the integration site or kind of core promoter. No significant difference in micrococcal nuclease (MNase) accessibility to the core promoter of test genes was observed between rbt mutants and the wild-type strain, indicating that the higher-order chromatin structure of the core promoter region is not significantly altered in these mutants. The rbt1 to rbt4 mutations are suppressed by the Dgal11 mutation as in the case of the sin4 mutation, but give rise to a different profile from the sin4 mutation with regard to the activity of some of the promoters. From these observations, we suggest that RBT gene product(s) could be novel mediators that act with or in close association with Sin4 but have a function distinct from that of Sin4. Moreover, the fact that rbt mutations nullify Tup1-Ssn6 general repressor-mediated repression is consistent with the idea that the mechanisms of Rbt (mediator)- and Tup1-Ssn6 (general repressor)-mediated repression are interconnected but substantially different.

Acid Phosphatase↗

PubMed2000

Bone bonding ability of a new biodegradable composite for internal fixation of bone fractures.

Hydroxyapatite particles and poly(L-lactide) composites for internal fixation of bone fractures have been developed based on the hypothesis that incorporation of hydroxyapatite particles in a poly(L-lactide) matrix might enhance bone bonding. This study evaluated the bone bonding ability of these biodegradable composites. Two types of hydroxyapatite and poly(L-lactide) composite were used in this study: calcined hydroxyapatite/poly(L-lactide) and uncalcined hydroxyapatite/poly(L-lactide). Rectangular plates (2 x 10 x 15 mm) of each composite or poly(L-lactide) were implanted into the metaphysis of the tibiae of 33 male rabbits, and the failure load was measured by conducting a detaching test 8, 16, and 25 weeks after implantation. The failure loads of calcined hydroxyapatite/poly(L-lactide), uncalcined hydroxyapatite/poly(L-lactide), and poly(L-lactide), respectively, were 13.60, 13.95, and 0.46 N at 8 weeks; 29.84, 24.09, and 2.86 N at 16 weeks; and 25.50, 29.67, and 2.43 N at 25 weeks. Histologic observation revealed that the composites formed direct contact with the bone. The results in this study indicate that the composites improved the strength of the interface between bone and plate. This improved interfacial strength lead to a substantial decrease in the frequency of implant loosening in the treatment of fractured bones by internal fixation.

Absorbable Implants↗

PubMed2000

Comprehensive analysis of the renin-angiotensin gene polymorphisms with relation to hypertension in the Japanese.

BACKGROUND: Components of the renin-angiotensin (R-A) system have been repeatedly investigated as candidate genes for essential hypertension. In particular, suggestive or significant association has been detected in some studies for the angiotensinogen M235T, angiotensin I-converting enzyme I/D, angiotensin II type 1 receptor A1166C, and aldosterone synthase C-344T polymorphisms, although the results remain inconclusive. OBJECTIVE AND METHODS: To evaluate the importance of these candidate genes for hypertension, we undertook an extensive association study in the Japanese. This case-control study was conducted in a total of 1476 individuals using the four R-A gene polymorphisms. In the assessment of genotyping data, 843 hypertensive subjects were divided into three case subgroups according to severity of hypertension, while 633 normotensive subjects divided into two control subgroups by the age of enrollment. Each subgroup was further divided by sex. Subsequently, the presence of synergy (or gene-gene interaction) was evaluated among four R-A gene polymorphisms. RESULTS: No significant association was observed between the individual R-A gene polymorphisms and hypertension status in our case-control study. The results were almost unchanged when severity of hypertension, sex-specificity, and synergy were taken into account CONCLUSIONS: Despite a relatively large number of subjects, we did not find significant evidence for disease association in the Japanese population. Given confounding factors in the case-control strategy, the lack of association does not exclude the relevance of the R-A genes to hypertension. Further investigation needs to be performed in large-scale populations, where the use of not only hypertension status, but also 'intermediate' phenotypes would be useful.

Angiotensin II↗

PubMed2000

UCN-01 (7-hydroxystaurosporine) enhances 5-fluorouracil cytotoxicity through down-regulation of thymidylate synthetase messenger RNA.

UCN-01 (7-hydroxystaurosporine) is a newly developed cell cycle inhibitor known to have several modes of action, including inhibition of cyclin-dependent kinase, induction of p21 and suppression of pRb phosphorylation. In order to test a combination therapy of UCN-01 and 5-fluorouracil (5-FU), growth inhibition of CRL 1420 (MIA PaCa-2; undifferentiated pancreatic carcinoma) by four different treatments was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The treatments used were UCN-01 alone, 5-FU alone, 5-FU followed by UCN-01 (5-FU/UCN-01) and UCN-01 followed by 5-FU (UCN-01/5-FU). We also assessed changes in thymidylate synthetase (TS) mRNA levels, TS activity, and 5-FU incorporation by RNA (F-RNA) for each treatment. Although treatment with UCN-01 alone, 5-FU alone, and 5-FU/UCN-01 inhibited CRL 1420 growth in a concentration-dependent manner, treatment with UCN-01/5-FU inhibited the growth of CRL 1420 synergistically at less than 1 microg/ml drug concentration. The down-regulation of TS mRNA by UCN-01 resulted in stable total TS and decreased free TS, and UCN-01/ 5-FU resulted in enhanced thymidylate synthetase inhibition rate (TSIR) compared to UCN-01 alone and 5-FU/UCN-01. This increased TSIR due to UCN-01 pretreatment was accompanied by elevated F-RNA concentrations in the UCN-01/5-FU treatment. The suppression of TS mRNA and TS activity by UCN-01 may lead to higher sensitivity of tumor cells to 5-FU and may explain the synergistic antitumor effect of UCN-01/5-FU. In conclusion, low concentrations of UCN-01 (from 0.01 to 1 microg/ml) may be clinically useful, affording low cytotoxicity of UCN-01, while enhancing the antitumor effect of 5-FU.

Alkaloids↗

PubMed2000

Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic cancer is one of the diseases with the poorest prognosis, but the associated genetic alterations are not yet well understood. The genetic alterations reported to date in pancreatic cancer include frequent mutations of the KRAS, TP53, p16, and SMAD4 genes. Mutation of the TP53 gene was reported to be associated with a poor prognosis. In this study, we analyzed the association of loss of heterozygosity (LOH) with clinicopathological features to attempt to devise effective methods in the future for clinically applying our results to diagnosis and treatment. METHODS: A total of 55 tumors from patients with primary pancreatic ductal carcinomas (34 men and 21 women, mean average age 63.9 yr) in which all the relevant clinical and pathological data were available were analyzed. A total of 46 cases were surgically resected, and nine cases were not. Tumor cells as well as corresponding normal cells were collected by microdissection under a microscope, and DNAs were purified. Allelotype analysis was performed by the PCR-based method, and the results were statistically analyzed. RESULTS: LOH of > or =30% were observed on chromosome arms 17p (47%, 17/36), 9p (45%, 14/31), 18q (43%, 15/35), 12q (34%, 10/29), and 6q (30%, 10/33). LOH of 12q, 17p, and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and 18q were significantly associated with a poor prognosis. Concordant losses of 6q with 17p and of 12q with 18q were also found. CONCLUSIONS: Because LOH of 12q, 17p, and 18q are significantly associated with a poor prognosis, mutation of the putative tumor suppressor genes on these chromosome arms may play significant roles in the disease progression. Concordant losses of 6q with 17p and of 12q with 18q suggest that protein products of putative tumor suppressor genes on 6q and 12q may function in association with TP53 and SMAD4, respectively.

Alleles↗

PubMed2000

Reversal of P-glycoprotein and multidrug-resistance protein-mediated drug resistance in KB cells by 5-O-benzoylated taxinine K.

A newly synthesized taxoid originally from the Japanese yew Taxus cuspidata, 5-O-benzoylated taxinine K (BTK) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein (MRP)-mediated multidrug resistance. BTK reversed the resistance to paclitaxel, doxorubicin (ADM), and vincristine (VCR) of KB-8-5 and KB-C2 cells that overexpress P-gp by directly interacting with P-gp. BTK also moderately reversed the resistance to ADM of KB/MRP cells that overexpress MRP. However, BTK neither inhibited the transporting activity of MRP nor reduced intracellular glutathione levels in KB/MRP cells. BTK shifted the distribution of ADM in KB/MRP cells from punctate cytoplasmic compartments to the nucleoplasm and cytoplasm by inhibiting acidification of cytoplasmic organelles. These two functions of BTK make it able to reverse both P-gp- and MRP-mediated MDR. BTK in combination with ADM should be useful for treating patients with tumors that overexpress both P-gp and MRP.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2000

Pathogenesis of non-familial colorectal carcinomas with high microsatellite instability.

AIMS: Microsatellite instability (MSI) was first observed in hereditary non-polyposis colorectal carcinoma (HNPCC) and was subsequently seen in non-familial colorectal carcinoma. The relation between MSI and cancer associated genes in non-familial colorectal carcinomas has yet to be evaluated. To clarify this matter, changes in cancer associated genes were examined in non-familial colorectal carcinomas. METHODS: Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ras genes were analysed in 24 MSI high (alterations in four to seven of seven loci), nine MSI low (alterations in one to three of seven loci), and 31 MSI negative non-familial carcinomas. The hMSH2 and hMLH1 genes were also analysed in 24 MSI high carcinomas. RESULTS: Both the frequencies and types of alterations in the APC and p53 genes in MSI high carcinomas were the same as those in MSI low and MSI negative carcinomas; however, they were different from those seen in HNPCC. The frequency of Ki-ras mutation was significantly lower in the MSI high cases (two of 24; 8%) than in the others (15 of 38; 39%). Somatic mutation of hMSH2 or hMLH1 was detected in six of 24 (25%) of the MSI high cases. CONCLUSIONS: These results suggest that APC and p53 alterations occur irrespective of microsatellite instability status in non-familial colorectal carcinomas, and that Ki-ras mutation is not involved in MSI high non-familial colorectal carcinoma. The pathogenesis of these carcinomas may differ from both the usual adenoma-carcinoma sequence and HNPCC carcinogenesis.

Base Sequence↗

PubMed2000

Myocardial viability detected by dobutamine echocardiography in patients with chronic coronary artery disease, and long-term outcome after coronary angioplasty.

Viable but dysfunctional myocardium detected by dobutamine echocardiography (DE) predicts early improvement in regional left ventricular (LV) function after percutaneous transluminal coronary angioplasty (PTCA). Whether DE can predict the long-term (>2 years) outcome after PTCA is still unclear. Thus, 50 patients (age 60.4+/-9.5 years) with chronic coronary artery disease and regional LV dysfunction who underwent DE 1 week before PTCA to assess myocardial viability were followed for 4.0+/-0.8 years. Regional LV function and LV ejection fraction (LVEF) were evaluated by 2-dimensional echocardiography in patients who remained event-free (cardiac death or myocardial infarction or unstable angina pectoris) after PTCA. At late follow-up (>2 years after PTCA), 29 patients showed regional LV function improvement, 15 showed no improvement, 3 showed worsening and 3 patients had cardiac events (1 nonfatal myocardial infarction and 2 unstable angina pectoris). LVEF improved (0.53+/-0.09 to 0.60+/-0.09, p<0.001) in patients with improved regional LV function, but deteriorated (0.38+/-0.03 to 0.30+/-0.03) in the 3 patients with worsened regional LV function. Of the 29 patients with improvement, 27 (93%) had viable myocardium, whereas only 3 (20%) of the 15 with no improvement had viable myocardium and all 6 of those with poor outcomes (3 with cardiac events and 3 with worsening) had viable myocardium (chi2 = 28.9, p<0.001). Patients with viable myocardium and a poor outcome had a lower mean LVEF before PTCA, and at 1 week and 3 months after PTCA (p = 0.004, <0.001, and =0.001, respectively), and a higher restenosis rate (p = 0.007) than patients with viable myocardium and without a poor outcome. It is concluded that viable myocardium detected by DE may predict long-term improvement in regional and global LV function after PTCA. However, patients with viable myocardium and persistent low LVEF are at risk for cardiac events or worsening of LV function.

Aged↗

PubMed2000

Polymorphisms of tumor necrosis factor-alpha and interleukin-10 genes in Japanese patients with idiopathic dilated cardiomyopathy.

Various cytokines play important roles in the pathogenesis of congestive heart failure. TNF-alpha is one of the pro-inflammatory cytokines, and IL-10 has anti-inflammatory actions. The -308 (G / A) polymorphism of the TNF-alpha gene (TNFA1 and A2) and the single base -1082 (G / A) polymorphism of the IL-10 gene (IL-10 1*G and 1*A) have been identified as causing alterations to the in vivo production of TNF-alpha and IL-10, respectively. We examined TNF-alpha and IL-10 gene polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism technique in 48 Japanese patients with idiopathic dilated cardiomyopathy. The frequency of these polymorphisms was compared with 50 healthy Japanese. The clinical courses, such as disease onset, left ventricular function, progression during the follow up period and hospitalization from congestive heart failure, were also analyzed. Serum TNF-alpha levels were measured using an enzyme-linked immunosorbent assay (ELISA) technique in the patients with idiopathic dilated cardiomyopathy to reveal the correlation with genotypes. Patients with ischemic cardiomyopathy or other secondary cardiomyopathies were excluded from this study. The allele frequency of TNFA2 in idiopathic dilated cardiomyopathy was significantly higher than that of the healthy group (13.5% and 3.0%, respectively, p = 0.0084). There was no difference in the allele frequency of the IL-10 gene between the two groups. Polymorphism of the TNFA2 gene was not associated with the clinical course. Serum TNF-alpha levels were elevated in the patient group compared with the healthy group. There were no differences in serum TNF-alpha levels between the patients with TNFA1 and those with TNFA2. In conclusion, the TNFA2 allele may be linked to the pathogenesis of idiopathic dilated cardiomyopathy in Japanese patients.

Adult↗