Biomedical subjects

Tomomi Kimura

Publications and source records attributed to Tomomi Kimura.

13 recordsLinked to original sources

PubMed2006

Association of transforming growth factor-beta 1 functional polymorphisms with natural clearance of hepatitis C virus.

Transforming growth factor (TGF)-beta 1 suppresses the proliferation and cytotoxicity of natural killer (NK) cells, which play critical roles in resolving hepatitis C virus (HCV) infection, especially during the acute phase. We examined 230 anti-HCV antibody-positive subjects for HCV RNA and the -509T/C genotype in the TGF-beta 1 gene promoter. The -509CC genotype and the -509C allele were significantly associated with higher HCV clearance rates (P=.01) and with lower transcriptional activity. The genetic effect remained significant even after adjustment for a history of transfusion. Low TGF- beta 1 producers might have less suppression of NK cells and be more likely to resolve HCV infection.

Adult↗

PubMed2006

Effect of concurrent elemental diet on infliximab treatment for Crohn's disease.

BACKGROUND: Infliximab and elemental diet (ED) have been shown to be effective in the management of Crohn's disease. However, few experiences have been reported regarding their combination therapy. The aim of the present study was to investigate the efficacy and safety of infliximab in Japanese patients, the first such study in Asia, as well as the effect of concomitant ED. METHODS: One hundred and ten consecutive patients receiving infliximab were followed up to week 16 after the last infusion, and clinical response and primary outcome were collected. A response was defined as a reduction in Harvey-Bradshaw Index for inflammatory disease and closure of fistula in fistulizing disease. RESULTS: Out of 75 inflammatory and 35 fistulizing disease patients, 68 (90.7%) and 25 (71.4%) responded at week 4, and 38 (50.7%) and 14 (40.0%) continued to respond until week 16, respectively. Interestingly, inflammatory disease patients with concurrent ED had a significantly higher response rate at week 16 (68.4%) than those without ED (32.4%, P = 0.0026). The effects of ED were independent of the usage of azathioprine and smoking habit. CONCLUSIONS: Infliximab was clinically useful in the treatment of Crohn's disease in Japanese patients as well as in those in Western countries. The efficacy of concurrent ED was suggestive and should be confirmed in a randomized controlled study.

Adult↗

PubMed2005

A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity.

Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p<0.0001). These findings suggest that the A(-816)C polymorphism affects the transcriptional activity, and that this may account for the responsiveness to imidapril.

Adult↗

PubMed2004

Metabolic syndrome and robustness tradeoffs.

The metabolic syndrome is a highly complex breakdown of normal physiology characterized by obesity, insulin resistance, hyperlipidemia, and hypertension. Type 2 diabetes is a major manifestation of this syndrome, although increased risk for cardiovascular disease (CVD) often precedes the onset of frank clinical diabetes. Prevention and cure for this disease constellation is of major importance to world health. Because the metabolic syndrome affects multiple interacting organ systems (i.e., it is a systemic disease), a systems-level analysis of disease evolution is essential for both complete elucidation of its pathophysiology and improved approaches to therapy. The goal of this review is to provide a perspective on systems-level approaches to metabolic syndrome, with particular emphasis on type 2 diabetes. We consider that metabolic syndromes take over inherent dynamics of our body that ensure robustness against unstable food supply and pathogenic infections, and lead to chronic inflammation that ultimately results in CVD. This exemplifies how trade-offs between robustness against common perturbations (unstable food and infections) and fragility against unusual perturbations (high-energy content foods and low-energy utilization lifestyle) is exploited to form chronic diseases. Possible therapeutic approaches that target fragility of emergent robustness of the disease state have been discussed. A detailed molecular interaction map for adipocyte, hepatocyte, skeletal muscle cell, and pancreatic beta-cell cross-talk in the metabolic syndrome can be viewed at http://www.systems-biology.org/001/003.html.

Diabetes Mellitus, Type 2↗

PubMed2004

Criteria for predicting the recurrence and metastasis of stage I and II gastric cancer without lymph node metastasis.

This study examined whether detection of occult neoplastic cells (ONCs) in lymph nodes or the high-risk criteria for recurrence/metastasis of colorectal cancer were useful for predicting the recurrence of primary gastric cancer. The subjects were 122 patients with node-negative stage I or stage II primary gastric cancer. Prediction of recurrence using ONCs showed a sensitivity of 25.0% (2/8), specificity of 97.1% (100/103), and accuracy of 61.1% in stage I patients, while the respective values were 75.0% (3/4), 100.0% (7/7), and 87.5% in stage II patients. Prediction of recurrence in patients who fulfilled 2 or more of the high-risk criteria showed a sensitivity of 37.5% (3/8), specificity of 94.2% (97/103), and accuracy of 65.9% for stage I patients, while the respective values were 100.0% (4/4), 85.7% (6/7), and 92.9% for stage II patients. These results suggest that the prediction of recurrence based on the high-risk criteria shows a high sensitivity, specificity, and accuracy in patients of stage II gastric cancer without lymph node metastasis.

Humans↗

PubMed2004

Accuracy of criteria for predicting recurrence and metastasis in stage II and III gastric cancer patients with lymph node metastasis.

This study assessed the prediction of gastric cancer recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes, and by using criteria that were developed to identify patients with a high risk of recurrence/metastasis. The subjects were 60 patients of stage II or III gastric cancer with lymph node metastasis. Prediction of recurrence based on the detection of ONCs showed a sensitivity of 33.3% (2/6), specificity of 70.0% (7/10), and accuracy of 51.7% in stage II patients, while the sensitivity was 73.5% (25/34), specificity was 100.0% (10/10), and accuracy was 86.8% in stage III patients. Prediction of recurrence based on the presence of at least 2 high-risk criteria had a sensitivity of 33.3% (2/6), specificity of 100.0% (10/10), and accuracy of 66.7% in stage II patients, while the sensitivity was 82.4% (28/34), specificity was 80.0% (8/10), and accuracy was 81.2% in stage III patients. These results suggest that prediction of recurrence/metastasis soon after surgery using ONCs plus the high-risk criteria can increase the specificity in stage II cancer, and can achieve a sensitivity of 80% or more with a high specificity and accuracy in stage III cancer.

Humans↗

PubMed2004

Predicting the recurrence/metastasis of stage II and III breast cancer with lymph node metastasis.

This study compared prediction of the recurrence of breast cancer by detection of occult neoplastic cells (ONCs) in lymph nodes or by using the criteria for a high risk of recurrence and metastasis of gastric/large bowel cancer. The subjects were 45 patients with stage II and III node-positive breast cancer. Prediction of recurrence by detection of ONCs showed a sensitivity of 78.6% (11/14), a false-negative rate of 21.4% (3/14), a specificity of 96.4% (30/31), a false-positive rate of 3.2% (1/31), and an accuracy of 87.7% in patients with stage II and III node-positive cancer. Prediction of recurrence based on positivity for at least 2 of the high-risk criteria showed a sensitivity of 92.9% (13/14), a false-negative rate of 7.1% (1/14), a specificity of 87.1% (27/31), a false-positive rate of 12.9% (4/31), and an accuracy of 90.0% in patients with stage II and III node-positive cancer. These results suggest that ONCs plus the high-risk criteria are useful for predicting recurrence/metastasis of stage II and III node-positive breast cancer during the early postoperative period with a high sensitivity and accuracy.

Breast Neoplasms↗

PubMed2004

Predicting the recurrence/metastasis of stage I and II breast cancer without lymph node metastasis.

Prediction of the recurrence of primary breast cancer was attempted by detection of occult neoplastic cells (ONCs) in lymph nodes or by using the high-risk criteria for recurrence/metastasis of gastric and colorectal cancer. The subjects were 70 patients with stage I or II node-negative primary breast cancer. Prediction of recurrence using ONCs had a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5) in the recurrence group, while the specificity was 96.9% (63/65) and the false-positive rate was 3.1% (2/65) in the non-recurrence group. The accuracy of ONCs was 78.5%. Prediction of recurrence based on positivity for at least 2 of the high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5) in the recurrence group, while the specificity was 95.4% (62/65) and the false-positive rate was 4.6% (3/65) in the non-recurrence group. The accuracy of the high-risk criteria was 77.7%. These results suggest that ONCs show the same accuracy as the high-risk criteria for predicting recurrence/metastasis of stage I and II node-negative breast cancer with a high specificity.

Breast Neoplasms↗

PubMed2004

Predicting recurrence and metastasis of stage II/Dukes' B colorectal cancer without lymph node metastasis.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or by using high-risk criteria for recurrence/metastasis in patients with Dukes' B colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 59.1% (13/22), a false-positive rate of 7.8% (8/102), a specificity of 92.2% (94/102), and a negative predictive value (NPV) of 91.3% (94/103). Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 90.9% (20/22), a false-positive rate of 49.0% (50/102), a specificity of 51.0% (52/102), and an NPV of 96.3% (52/54). Among the 21 patients in whom ONCs were detected, prediction of recurrence based on the presence of all 3 high-risk criteria including ONCs had a sensitivity of 84.6% (11/13) and a positive predictive value (PPV) of 78.6% (11/14). These results suggest that colorectal cancer is unlikely to recur in patients without ONCs, while recurrence is likely in patients who fulfill 2 or more of the high-risk criteria. Accordingly, a combination of these parameters may be useful for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

Colorectal Neoplasms↗

PubMed2004

Predicting recurrence and metastasis of stage III/Dukes' C colorectal cancer with lymph node metastasis.

This study was designed to compare the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using specific criteria to identify patients at high risk of recurrence/metastasis among 105 patients with Dukes' C colorectal cancer. Prediction of recurrence based on the detection of ONCs had a sensitivity of 50.0% (22/44), specificity of 80.3% (49/61), and an accuracy of 65.2%. Prediction of recurrence based on positivity for at least 2 of the 3 high-risk criteria had a sensitivity of 54.5% (24/44), specificity of 83.6% (51/61), and an accuracy of 69.1%. Among the 34 patients with ONCs, prediction of recurrence based on positivity for all 3 high-risk criteria had a sensitivity of 27.3% (6/22), specificity of 91.7% (11/12), an accuracy of 59.5%, and a positive predictive value (PPV) of 85.7% (6/7). These results suggest that the predictive value of ONCs and the high-risk criteria was similar, and that recurrence is likely to occur in patients who fulfill < or =2 of the high-risk criteria. Accordingly, combined use of these parameters may be more effective for the early prediction of recurrence/metastasis to assist in the choice of postoperative systemic chemotherapy.

Colorectal Neoplasms↗

PubMed2004

Predicting recurrence and metastasis of Dukes' A primary colorectal cancer with or without proper muscle invasion.

This study compared the prediction of recurrence based on detection of occult neoplastic cells (ONCs) in lymph nodes or using 3 criteria to identify high-risk patients among 72 patients who had Dukes' A colorectal cancer with or without proper muscle invasion. Predicting recurrence based on the detection of ONCs had a sensitivity of 40.0% (2/5) and a false-negative rate of 60.0% (3/5), while there was a specificity of 97.0% (65/67) and false-positive rate of 3.0% (2/67), resulting in an accuracy of 68.5%, PPV of 50.0% (2/4), and NPV of 95.6% (65/68). Predicting recurrence based on the presence of at least 2 of the 3 high-risk criteria showed a sensitivity of 60.0% (3/5) and a false-negative rate of 40.0% (2/5), while it had a specificity of 74.6% (50/67) and a false-positive rate of 25.4% (17/67), resulting in an accuracy of 67.3%, PPV of 15.0% (3/20), and NPV of 96.2% (50/52). These results suggest that a prediction based on ONCs was similar to use of the high-risk criteria, with both methods having a high specificity for recurrence/metastasis of Dukes' A colorectal cancer.

Colorectal Neoplasms↗

PubMed2003

NOS3 genotype-dependent correlation between blood pressure and physical activity.

Endothelium-dependent vasorelaxation plays an important role in reduction of blood pressure and is mediated through release of nitric oxide (NO), which is generated by constitutively expressed endothelial nitric oxide synthase (NOS3). Exercise also augments NO release and has been recommended for primary prevention and improvement of hypertension, but individual responses are highly variable. We therefore postulated that genetic polymorphisms of NOS3 might interact with physical activity level to differentially influence blood pressure level. We genotyped 832 healthy Japanese (mean age of 54.4+/-8.6 years, 372 men and 460 women) for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474). In the present study, we found a significant interaction between the genotype and physical activity level on systolic blood pressure. These results might allow a better understanding of the mechanism to improve hypertension by exercise and to thereby reduce the risk of cardiovascular disease.

Adult↗

PubMed2002

[DNA chip and SNP].

Single nucleotide polymorphism (SNP) is high-density genetic marker that could be utilized to dissect genetic traits that influence susceptibility to common diseases and responsiveness to drugs. Requirement for massive SNP analysis has enhanced development of various SNP genotyping technologies. DNA chip is one of such methods, which detects SNPs in parallel on an array of surface bound oligonucleotides. Recent application of DNA chip for high-throughput SNP analysis as well as clinical diagnosis will be presented.

Genetic Markers↗