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Biomedical subjects

S Fukuhara

Publications and source records attributed to S Fukuhara.

At least 19 recordsLinked to original sources
PubMed2006

Symptoms of depression, prescription of benzodiazepines, and the risk of death in hemodialysis patients in Japan.

Many hemodialysis patients in Japan have symptoms of depression, but whether those patients are treated appropriately is unknown. As part of the Dialysis Outcomes and Practice Patterns Study, data on symptoms of depression, physician-diagnosed depression, prescribed medications, and death were collected prospectively in cohorts in Japan (n=1603) and 11 other countries (n=5872). Symptoms of depression were as prevalent in Japan as elsewhere, but in Japan a much smaller percentage of patients had physician-diagnosed depression: only 2% in Japan vs 17% elsewhere. Antidepressants were much less commonly prescribed in Japan: only 1% in Japan vs 17% elsewhere for patients with many and frequent symptoms of depression, and 16% in Japan vs 34% elsewhere for patients with physician-diagnosed depression. In Japan, symptoms of depression were associated with prescription of benzodiazepines (without antidepressants), and patients with physician-diagnosed depression were twice as likely to be given benzodiazepines: 32% in Japan vs 16% elsewhere. Benzodiazepine monotherapy was associated with death (relative risk 1.56, 95% confidence interval (CI), 1.25-1.94), even after adjustments for 13 likely confounders (relative risk 1.27, 95% CI, 1.01-1.59). Hemodialysis patients in Japan with symptoms of depression are given not antidepressants but benzodiazepines, a practice associated with higher mortality.

Anti-Anxiety Agents↗
PubMed2006

Intracerebral haemorrhage associated with hourly concentration of ambient particulate matter: case-crossover analysis.

AIMS: To examine the association of hourly time lagged concentration of ambient particulate matter and death due to stroke. METHODS: Mortality data for five years (January 1990 to December 1994) were obtained from the Ministry of Health, Labour, and Welfare of Japan. Data were used only if the deceased was 65 years old or older at the time of death, if death was attributed to intracerebral haemorrhage or ischaemic stroke, and if the deceased lived in one of 13 major urban areas. Hourly mean concentrations of PM7, NO2, and photochemical oxidants were measured at monitoring stations in the 13 areas. Time stratified case-crossover analysis was used to examine the data for evidence of triggering stroke mortality. RESULTS: The 1-hour mean concentration of PM7 measured about 2 hours before death was associated with the risk of death due to intracerebral haemorrhage from April to September (odds ratio = 2.40, 95% CI 1.48 to 3.89, for exposure to PM7 of more than 200 microg/m3 (threshold)). The higher risk was independent of the 24-hour mean concentration of PM7. PM7 was not associated with death due to ischaemic stroke. CONCLUSIONS: Transiently high concentrations of PM7 are associated with death due to intracerebral haemorrhage. Air quality standards or guidelines for particulate matter should be based not only on 24-hour mean concentrations, but also on hourly data.

Aged↗
PubMed2006

Genetic analysis of HLA, NA and HPA typing in type 2 diabetes and ASO.

We examined the genetic status of human leucocyte antigens (HLA), human platelet alloantigens (HPA) and neutrophil-specific antigens (NA) in patients with type 2 diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our knowledge, the present study is the first report showing the relationship among three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing was performed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-specific primer method. The incidence of HLA-DRB1*1501 was found to be significant in type 2 diabetes and non-diabetic, particularly ASO-positive patients, compared to control subjects. There were no differences in NA1/NA2 between the control and diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO-positive diabetes and non-diabetic ASO patients was significantly higher than controls. The a/b genotype of HPA-5a/5b was significantly lower in type 2 diabetes and non-diabetic ASO-positive patients than in controls. These findings suggest that genetic studies of HLA, NA and HPA could be useful to understand the pathogenesis of type 2 diabetes and ASO.

Adult↗
PubMed2006

Cost-effectiveness of Liple (LipoPGE1) for arteriosclerosis obliterans patients in Japan: an economic evaluation using the EQ-5D instrument.

AIM: This study was conducted to evaluate the health-related quality of life (HRQOL) and cost-effectiveness of LipoPGE(1) when added to the conventional treatment of arteriosclerosis obliterans (ASO) patients. The research design consisted of a before and after-treatment study without comparison groups. We collected data from May 1999 through July 2001 at 473 institutions located throughout Japan. The subjects were ASO patients who experienced pain at rest or had ulcers of the extremities. METHODS: The observation period was a 2-month period that commenced with the start of administration of LipoPGE1. The HRQOL score (utility value) was obtained from the EQ-5D instrument, and the incremental cost-effectiveness ratio was calculated on the basis of quality-adjusted life years (QALYs). RESULTS: The mean utility value for the 2 months after the start of the administration of LipoPGE(1) was 0.672, and it was a significantly higher (P<0.0001) than the 0.616 before administration of LipoPGE(1). The incremental cost-effectiveness ratio was 18,807 US dollar/QALY assuming that drug efficacy persisted for 1 year after the end of LipoPGE1 therapy, and 75,227 dollar/QALY assuming a duration of just 3 months. CONCLUSIONS: We concluded that when LipoPGE1 is added to the conventional treatment of ASO patients, the HRQOL of the patient improves, and it is highly cost-effective.

Adolescent↗
PubMed2005

Household income is strongly associated with health-related quality of life among Japanese men but not women.

OBJECTIVES: As socio-economic status (SES) strongly reflects individual economic status, evaluating the association between SES and health could provide information that is important for planning integrated economic and public health policies. We examined the association between annual household income as a measure of SES and the eight scale scores of the Medical Outcomes Study Short Form-36 Health Survey (SF-36) as a quantifier of health-related quality of life (HRQOL) in Japan. STUDY DESIGN: Cross-sectional survey. METHODS: Data were from the SF-36 national survey in Japan. A total of 4500 people aged 16 years or older were selected from the entire population of Japan using stratified-random sampling, and 3395 responded to the survey. RESULTS: Men with lower levels of annual household income had lower scores in all SF-36 domains. However, only 'general health perceptions' and 'social functioning' showed statistically significant trends among the women surveyed. In the subgroup of women working full-time, there were no domains that showed significant trends. CONCLUSIONS: A strong association exists between annual household income and SF-36 scores among men, but there is only a limited association among women. The employment and economic policies that affect annual household income potentially influence HRQOL.

Adult↗
PubMed2005

IL-4-producing CD8(+) T cells may be an immunological hallmark of chronic GVHD.

Chronic graft-versus-host disease (cGVHD) occurs in approximately 60-80% of those who survive over 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the pathophysiology of cGVHD is poorly understood. To gain more insight into the immunological mechanism of cGVHD, we examine cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allo-HSCT. The percentage of IFN-gamma-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with or without cGVHD than in normal control subjects (P<0.001). On the other hand, the percentage of IL-4-producing CD8(+) T cells among CD8(+) T cells was significantly higher in patients with cGVHD (mean 3.3%; range 1.3-8.2%) than in patients without cGVHD (mean 1.2%; range 0.8-1.7%) and normal control subjects (mean 1.1%; range 0.1-1.6%) (both P<0.001). By contrast, the percentage of IL-4-producing CD4(+) T cells was not different among patients with and without cGVHD and normal controls. These findings suggest that IL-4-producing CD8(+) T cells may be an immunological marker of cGVHD.

Adolescent↗
PubMed2005

Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS). The object of this study was to evaluate the impact of chemotherapy before allo-SCT. We analyzed the data of 283 patients who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidence of grade II-IV acute GVHD was 33%. Overall survival (OS) at 5 and 10 years was 48.8 and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81). The proportion of patients with a poor karyotype was equivalent between the two groups (P=0.44). Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.

Adolescent↗
PubMed2005

Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma.

BACKGROUND: The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. METHODS: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by radicalBSA of a segmental bronchus (T/ radicalBSA), was examined. RESULTS: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/ radicalBSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/ radicalBSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume. CONCLUSION: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Asthma↗
PubMed2005

Association of leukocyte activation, but not the common cold, with restenosis after percutaneous coronary intervention in patients with angina pectoris.

We investigated the relationship between the common cold and restenosis after percutaneous coronary intervention (PCI) in Japanese patients with angina pectoris, because suffering from a common cold during the follow-up period after PCI may be involved in the development of restenosis. In addition, we measured the soluble (s) L-selectin level early after PCI in patients with and without restenosis. The study group included 104 effort angina pectoris patients. We examined whether or not they had had a common cold in the 6 months following angioplasty. Finally, 88 patients, whose common cold status was known, were selected as the study subjects. Twelve patients caught a common cold after PCI. All of these patients were given antibiotics and/or anti-inflammatory agents and recovered within 2 weeks. None had clinically detectable influenza infection. Thirty-three patients suffered from restenosis and 55 did not. There was no significant difference in the restenosis frequency between effort angina pectoris patients with and without a common cold. The sL-selectin level was significantly increased in patients with restenosis early after PCI, whereas in patients without restenosis, sL-selectin remained unchanged. These findings suggest that restenosis development after PCI in patients with effort angina pectoris may involve leukocyte activation early after PCI, while suffering from a common cold during the follow-up period after PCI has no effect.

Aged↗
PubMed2004

Blood dendritic cells are decreased in acute graft-versus-host disease.

The recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop acute graft-versus-host disease (aGVHD), which is closely related to morbidity and mortality. However, the essential part of the immune responses elicited in aGVHD remains largely unknown. We attempt to determine if peripheral blood dendritic cells (PBDCs) are altered in aGVHD, and find that the number of PBDCs (both myeloid and lymphoid DCs) is significantly decreased. Immunohistochemical staining of the biopsied skin from patients with aGVHD demonstrates that a number of fascin(+) cells with dendritic projections infiltrate the dermis of the skin. Based on these findings, we hypothesize that the PBDCs are recruited to the affected tissues and may thus play important roles in immune responses elicited in aGVHD.

Acute Disease↗
PubMed2004

Intra-arterial steroid-injection therapy for steroid-refractory acute graft-versus-host disease with the evaluation of angiography.

We treated three patients with steroid-refractory acute graft-versus-host disease (aGVHD) with intra-arterial steroid-injection therapy (IAST). Two patients with gut aGVHD received IAST into both superior and inferior mesenteric arteries, while one patient with liver aGVHD received IAST into the proper hepatic artery. The volume of stools and the bilirubin level improved soon after IAST. Angiography of the superior and inferior mesenteric arteries was performed in the two patients with steroid-refractory gut aGVHD, and identical abnormal findings were obtained. IAST might be an earlier option for steroid-refractory aGVHD.

Acute Disease↗
PubMed2004

Involvement of dendritic cells in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. METHODS: The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. RESULTS: The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-gamma (IFN-gamma) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. CONCLUSIONS: These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.

Adult↗
PubMed2004

The effect of Liple on physical and emotional quality of life in the treatment of arteriosclerosis obliterans.

AIM: The purpose of this study was to determine the effect of treatment with prostaglandin E1, Liple, on both the physical and emotional health-related quality of life (QOL) of patients with arteriosclerosis obliterans (ASO). METHODS: Treatment with Liple was evaluated using the before and after treatment results obtained using the SF-36, a QOL questionnaire, and an assessment of symptoms by a physician. The study was designed as a non-randomized before and after treatment study without comparison groups, and the study was conducted from May 1999 to July 2001 at 473 facilities located within Japan targeting patients with ASO. No intervention other than the administration of Liple was performed, and no restrictions were placed on the dose amount or administration interval for Liple. RESULTS: The results suggest that there was a significant improvement in patients' symptoms after treatment with Liple. CONCLUSIONS: Both physical and emotional QOL also improved after administration of Liple compared to baseline, based on the results of the SF-36 and assessment of symptoms by a physician.

Adolescent↗
PubMed2002

Detection of monocyte-derived microparticles in patients with Type II diabetes mellitus.

AIMS/HYPOTHESIS: The role of plasma monocyte-derived microparticles (MDMPs) and platelet-activation markers (platelet-derived microparticle [PDMP], platelet-bound CD62P [plt-CD62P], and platelet-bound CD63 [plt-CD63]) in diabetic vascular complications is not clear. We measured and compared plasma concentrations of MDMPs and the platelet-activation markers to investigate their possible contribution to diabetic vascular complications. METHODS: Activated platelets and microparticles (PDMP and MDMP) were analysed by flow cytometry. Concentrations of serum sE-selectin were measured with enzyme-linked immunosorbent assay. RESULTS: The concentration of MDMPs in diabetic patients was higher than in normal subjects. We found no differences in the binding of anti-GPIIb/IIIa and anti-GPIb monoclonal antibodies between groups. There were differences, however, in the concentrations of PDMPs, plt-CD62P, and plt-CD63 between Type II (non-insulin-dependent) diabetes mellitus patients and control subjects (PDMPs: 585 +/- 25 vs 263 +/- 9, p < 0.01; plt-CD62P: 28.1 % +/- 1.4 % vs 9.4 % +/- 0.6 %, p < 0.001; plt-CD63: 28.1 % +/- 1.4 % vs 8.6 % +/- 0.5 %, p < 0.001). Amounts of MDMPs correlated positively with these platelet activation markers, and the relation between PDMP and MDMP was the most significant. The concentration of MDMP in patients who had diabetes complicated with nephropathy, retinopathy, or neuropathy was higher than in those without diabetes-related complications. The increase in MDMP was particularly significant in patients with nephropathy. Concentrations of sE-selectin were higher in Type II diabetes patients than in control subjects, and correlated with MDMP, PDMP, plt-CD62P, and plt-CD63 levels in nephropathy patients. CONCLUSION/INTERPRETATION: In Type II diabetes patients, we detected increased activation of monocytes, which could have been stimulated by activated platelets and PDMPs. Because the activation of monocytes is associated with vascular endothelial damage, high concentrations of MDMPs could indicate vascular complications in diabetes patients, especially those who have diabetes-related nephropathy.

Antigens, CD↗
PubMed2002

Effects of efonidipine on platelet and monocyte activation markers in hypertensive patients with and without type 2 diabetes mellitus.

We compared the levels of microparticles, platelet activation markers, soluble cell adhesion molecules, and soluble selectins between hypertensive patients with and without type 2 diabetes and control subjects. Binding of anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib monoclonal antibodies to platelets did not differ significantly between the hypertensive patients and controls, but platelet expression of activation markers (CD62P, CD63, PAC-1, and annexin V) was higher in the hypertensive patients. Platelet-derived microparticle (PDMP) and monocyte-derived microparticle (MDMP) levels were significantly higher in the hypertensive patients than in the controls. Soluble ICAM-1, VCAM-1, P-selectin, and E-selectin levels were also higher in the hypertensive patients, and they were significantly higher in the hypertensive patients with diabetes. After treatment with efonidipine, the levels of PDMPs, CD62P-, CD63-, PAC-1-, and annexin V-positive platelets, sICAM-1, sVCAM-1, sP-selectin, and sE-selectin all decreased significantly. The MDMP levels decreased, and the decrease was significant in the hypertensive patients with diabetes. These findings suggest that administration of efonidipine to hypertension patients with diabetes may prevent the development of cardiovascular complications caused by cell adhesion molecules or activated platelets and monocytes.

Aged↗
PubMed2001

A novel mouse beta-defensin, mBD-6, predominantly expressed in skeletal muscle.

Defensins comprise a family of cationic antimicrobial peptides that is characterized by the conserved 6 cysteine residues. They are expressed in the epithelial cells of various organs and are identified as key elements in the host defense system at the mucosal surface. We isolated a novel mouse beta-defensin gene from the bacterial artificial chromosome DNA containing the mouse beta-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse beta-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse beta-defensin-3 and 59% identity with mouse beta-defensin-4. We demonstrated the expression of mBD-6 in skeletal muscle in addition to the esophagus, tongue, and trachea. In animal models of endotoxemia, mBD-6 expression was also induced in the lung. mBD-6 showed potent antimicrobial activity against Escherichia coli and would play an important role in host defense in the esophagus, airways, and skeletal muscle. mBD-6 is the first reported beta-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.

Amino Acid Sequence↗