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Biomedical subjects

Y Ikeda

Publications and source records attributed to Y Ikeda.

At least 37 records · Page 2Linked to original sources

Effects of the Cdx-2 polymorphism of the vitamin D receptor gene and lifestyle factors on bone mineral density in a representative sample of Japanese women: the Japanese Population-based Osteoporosis (JPOS) Study.

Using a large-scale representative sample of the Japanese female population, we examined the effects of a single nucleotide polymorphism within a binding site of Cdx-2 in the promoter region of the vitamin D receptor gene on bone mineral density (BMD), and the interactions between this polymorphism and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15-79 years) in each of three chosen municipalities as a part of the Japanese Population-based Osteoporosis Study. BMD at the lumbar spine, hip, and distal forearm was measured using dual-energy X-ray absorptiometry at baseline and again in a follow-up study conducted 3 years later. Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The G-to-A polymorphism within the Cdx-2 binding site was determined by a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. The baseline BMD in the ultradistal forearm in premenopausal women with the GG genotype was significantly lower than in those with other genotypes. There was no association between the Cdx-2 genotype and the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites but only in subjects with the GG genotype. In conclusion, the Cdx-2 polymorphism alone did not have a substantial effect on BMD in Japanese women. However, this polymorphism might have some effect in women with low calcium intake.

Absorptiometry, Photon↗

Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism.

OBJECTIVES: To examine the prevalence, clinical associations and pathogenic roles of autoantibodies to CD40 ligand (CD40L) in patients with systemic lupus erythematosus (SLE). METHODS: Plasma anti-CD40L antibodies from 125 patients with SLE, 24 with primary antiphospholipid syndrome (APS) and 90 with idiopathic thrombocytopenic purpura (ITP) and from 62 healthy individuals were measured with an enzyme-linked immunosorbent assay (ELISA). HeLa cells transfected with human CD40L cDNA (HeLa/CD40L) were used to confirm the presence of anti-CD40L autoantibodies. The effect of anti-CD40L antibodies on the CD40L-CD40 interaction was evaluated by observing CD40L-induced IkappaB activation in CD40-expressing fibroblasts. RESULTS: Anti-CD40L autoantibody was detected in seven (6%) SLE, three (13%) primary APS and 11 (12%) ITP patients, but in no healthy controls. Antibody binding in an ELISA was competitively inhibited by membrane components of HeLa/CD40L. Anti-CD40L antibody-positive IgG specifically bound the surface of living HeLa/CD40L, as shown by flow cytometry. The frequency of thrombocytopenia was significantly higher in SLE patients with the anti-CD40L antibody than in those without (100 vs 14%; P<0.00001), whereas there was no association between the anti-CD40L antibody and thrombosis. Binding of the anti-CD40L antibodies in patients' plasma to CD40L was competitively inhibited by a series of mouse anti-CD40L monoclonal antibodies. Anti-CD40L antibody-positive IgG failed to inhibit CD40L-induced IkappaB activation. CONCLUSIONS: Anti-CD40L autoantibody is associated with thrombocytopenia but not thromboembolism. Our findings are potentially useful in understanding the complex roles of CD40L in the pathophysiology of thrombosis and haemostasis as well as the thromboembolic complications that occur during treatment with anti-CD40L humanized antibody.

Adult↗

Risk factors of cerebrospinal fluid rhinorrhea following transsphenoidal surgery.

OBJECTIVE: Cerebrospinal fluid (CSF) rhinorrhea is a potentially life-threatening complication following transsphenoidal surgery (TSS). METHODS: To elucidate the risk factors that may affect the incidence of postoperative CSF rhinorrhea, we retrospectively reviewed 200 consecutive cases of TSS performed by a single surgeon for 168 adenomas and 32 other sellar and parasellar lesions. RESULTS: Intra-operative CSF leakage was encountered in 38 cases (19.0%). Its incidence did not correlate to tumor size. Among 4 microadenoma cases with CSF leak, 3 were ACTH adenomas. In contrast, postoperative CSF rhinorrhea was observed in 5 cases (2.5%), all following TSS for adenomas. It was frequently noted in cases with prior TSS (3/40, 7.5%, p = 0.0235) and prior radiotherapy (2/7, 28.6%, p < 0.0001). Two cases who required surgical intervention had received TSS and radiotherapy previously. CONCLUSION: The risk of postoperative CSF rhinorrhea is significantly increased in cases with prior TSS or radiotherapy or both. In addition, these cases tended to show delayed CSF leaks and require sellar reconstruction for its treatment. When a CSF leak was encountered during TSS in these high-risk cases, thorough sellar reconstruction and long-term follow-up is necessary.

Adenoma↗

Effective follow-up for recurrence or a second primary cancer in patients with early gastric cancer.

BACKGROUND: Patients with early gastric cancer have an excellent prognosis with low rates of recurrence, but may have an increased risk of developing a second primary cancer. Because the number of early gastric cancers has increased, clarification of both recurrences and second primary cancers is important for the development of effective postoperative follow-up programmes. METHODS: Data on 1070 patients with early gastric cancer were analysed retrospectively with respect to the clinicopathological features of both recurrence and second primary cancers after surgical treatment. RESULTS: Multivariate analysis showed that lymph node metastasis and older age were independent risk factors for recurrence of early gastric cancer. The incidence of second primary cancers was 5.0 per cent; lung and colorectal cancers were detected most frequently, followed by cancers in the oesophagus, breast and remnant stomach. CONCLUSION: Clinicopathological features of patients with early gastric cancer can be used to identify those most at risk of developing either recurrence or a second primary cancer.

Age Factors↗

Relationship between distance of schools from the nearest municipal waste incineration plant and child health in Japan.

In Japan, the main source of dioxins is incinerators. This study examined the relationship between the distance of schools from municipal waste incineration plants and the prevalence of allergic disorders and general symptoms in Japanese children. Study subjects were 450,807 elementary school children aged 6-12 years who attended 996 public elementary schools in Osaka Prefecture in Japan. Parents of school children completed a questionnaire that included items about illnesses and symptoms in the study child. Distance of each of the public elementary schools from all of the 37 municipal waste incineration plants in Osaka Prefecture was measured using geographical information systems packages. Adjustment was made for grade, socioeconomic status and access to health care per municipality. Decreases in the distance of schools from the nearest municipal waste incineration plant were independently associated with an increased prevalence of wheeze, headache, stomach ache, and fatigue (adjusted odds ratios [95% confidence intervals] for shortest vs. longest distance categories =1.08 [1.01-1.15], 1.05 [1.00-1.11], 1.06 [1.01-1.11], and 1.12 [1.08-1.17], respectively). A positive association with fatigue was pronounced in schools within 4 km of the second nearest municipal waste incineration plant. There was no evident relationship between the distance of schools from such a plant and the prevalence of atopic dermatitis or allergic rhinitis. The findings suggest that proximity of schools to municipal waste incineration plants may be associated with an increased prevalence of wheeze, headache, stomach ache, and fatigue in Japanese children.

Age Factors↗

Various costimulatory pathways are essential for induction of regulatory cells by intratracheal delivery of alloantigen.

BACKGROUND: We previously reported that intratracheal delivery of alloantigen induced regulatory cells in a mouse heart transplantation model. We investigated the roles of costimulatory pathways in the induction of regulatory cells by intratracheal delivery of alloantigen. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of splenocytes (1 x 10(7)) from C57BL/10 (H-2b) mice and administration of monoclonal antibodies (mAb) specific for programmed death (PD)-1 and its ligands, programmed death-ligand (PD-L)1 and PD-L2, CD70, CD134 ligand (CD134L), CD153, CD137L, or receptor activator of nuclear factor-kappaB (NF-kappaB) (RANK). Seven days later, naive CBA mice underwent adoptive transfer of splenocytes (5 x 10(7)) from the pretreated CBA mice and transplantation of C57BL/10 heart. RESULTS: Adoptive transfer of splenocytes from CBA mice that had been pretreated with intratracheal delivery of C57BL/10 splenocytes significantly prolonged the survival of C57BL/10 allograft (median survival time [MST], 68 days) as compared with adoptive transfer from untreated CBA mice (MST, 12 days). Concomitant administration of control immunoglobulin (Ig)G, anti-PD-L2 mAb, or anti-CD137L along with intratracheal delivery did not significantly affect the prolongation (MST, 72, 68, and 65 days, respectively). In contrast, anti-PD-1, anti-PD-L1, anti-CD70, anti-CD134L, anti-CD153, or anti-RANK mAb abrogated the prolongation induced by adoptive transfer from the pretreated mice with intratracheal delivery (MST, 18, 17, 16, 14, 10, and 18 days, respectively). CONCLUSION: The PD-1/PD-L1, CD27/CD70, CD134/CD134L, CD30/CD153, and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE)/RANK interactions are independently required for generation of regulatory cells by intratracheal delivery of alloantigen.

Adoptive Transfer↗

Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

Animals↗

In vivo assessment of the cutaneous bioavailability of topically applied maxacalcitol.

Maxacalcitol (22-oxacalcitriol), a vitamin D3 analogue, is widely used for the treatment of psoriasis. The effects of topical dermatologic drugs have been assessed by their pharmacodynamic activities, and concentrations in the skin correlate with these activities. In this study, we assessed the cutaneous bioavailability of topically applied maxacalcitol ointment in vivo by tape stripping. Six drug application sites were randomly assigned on the left volar forearm of six healthy men. Fifty milligrams of maxacalcitol ointment (25 microg/g) was applied to each site. After 0 (15 s), 0.5, 1, 2, 4, or 6 h, the ointment was gently removed, and tape stripping was performed. Maxacalcitol was extracted from the tape strips and quantified by liquid chromatographic tandem mass spectrometry. Average concentrations of maxacalcitol in the stratum corneum (SC) were 2.61, 4.37, 6.23, 9.37, and 9.46 microg/g at 0.5, 1, 2, 4, and 6 h, respectively, after drug application. The steady state was attained approx. 4 h after drug application. The cutaneous bioavailability of topical maxacalcitol ointment can be assessed by the tape-stripping method. This approach will probably be useful in the assessment of the bioequivalence of topical dermatologic products and as a parameter for pharmacokinetic/pharmacodynamic studies.

Adhesives↗

[Strategy for thrombosed type A acute aortic dissection].

The surgical treatment for thrombosed type A aortic dissection is controversial. We treated 15 cases (28.8%) with thrombosed type A acute aortic dissection among 52 cases of all type A acute aortic dissection during past 7 years and 8 months. Nine cases was treated conservatively and 6 cases received emergent operation due to cardiac tamponade, shock, and ulcer-like projection (ULP) in the ascending aorta (> 50 mm). In the group of conservative therapy, 2 cases in which the ascending aorta was enlarged (54, 60 mm), was converted to operation in the acute phase because of further enlargement of ascending aorta and increase of cardiac effusion. The other patients (aortic diameter: 40-46 mm) who received conservative therapy were well controlled by medical therapy in the early and late phase except 1 who died suddenly in the follow-up. There was no mortality and late death in the operated patients. From these results, we conclude that thrombosed type A aortic dissection in which the diameter of ascending aortic aorta is larger than 50 mm, have cardiac tamponade and ULP in the ascending aorta might needs operation.

Aged↗

[Left coronary ostial stenosis caused by syphilitic aortitis].

We report 2 cases of cardiovascular disease related to end-stage syphilitic infection, which is now relatively rare. A 49-year-old man (case 1), and a 45-year-old man (case 2) were admitted to our hospital for angina pectoris. Cardiac catheterization showed severe aortic regurgitation and left coronary ostial stenosis. Active syphilis was detected in both cases by routine blood examination on admission. Oral ampicillin was started immediately to treat the syphilis; however, during the course of treatment, acute heart failure developed in both patients. We performed emergency aortic valve replacement and coronary artery bypass grafting. Intraoperatively, the orifice of the left coronary artery was almost occluded, and retrograde perfusion of cardioplegia was needed to induce cardiac arrest. Both patients recovered uneventfully. When treating patients with antibiotics for syphilitic disease, it is important to prepare for the possibility of urgent surgery.

Coronary Stenosis↗

[Ruptured infected descending aortic aneurysm successfully treated by omentopexy and a rifampicin-soaked vascular prosthesis; report of a case].

A 73-year-old man was admitted for investigation of back pain, blood-stained sputum, and a high fever. Computed tomography (CT) showed a pseudoaneurysm in the descending aorta and intravenous antibiotic therapy was begun immediately after blood had been taken for culture. However, his temperature continued to spike daily, up to 38 degrees C, and his CRP was also elevated. The blood cultures were negative. The aneurysm ruptured and we replaced the descending aorta with a rifampicin (RFP)-soaked vascular prosthesis, and wrapped it with greater omentum. Postoperative antibiotic therapy with vancomycin hydrochloride, RFP, and amikacin sulfate was continued for 8 weeks. The patient recovered uneventfully. Thus, an infected aneurysm was effectively treated with a RFP-soaked vascular prosthesis and omentopexy.

Aged↗

[Fungal endocarditis found at onset of lower limb acute aortic occlusion; report of a case].

Fungal endocarditis caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment. We reported a case of fungal endocarditis due to Candida lusitaniae found at onset of lower limb acute aortic occlusion cured by emergency operation. This case suggests that Candida endocariditis can be managed medically with antifungal drug therapy in life time.

Acute Disease↗

Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection.

T cells mediating chronic rejection (CR) of human kidney allografts were characterized by comparing them with those mediating acute rejection (AR). Two lines of analysis were performed using biopsy specimens (23 CR and 8 AR). First, the extent of infiltration of CD4+ and CD8+ T cells into allografts was assessed from mRNA expression of CD4 and CD8. The group of CR specimens was not significantly different from the group of AR specimens in terms of the extent of CD4+ and CD8+ T cell infiltration, underlining the importance of the immunological contribution to the progress of CR. Second, Th1/Th2 polarization in infiltrating T cells was investigated by measuring mRNA expression of interferon gamma (IFN-gamma; a Th1 cytokine) and interleukin 4 (IL-4; a Th2 cytokine). IFN-gamma expression was detected in most CR specimens, and was not significantly different between the group of CR specimens and the group of AR specimens. On the other hand, IL-4 expression was detected in only two CR specimens and one AR specimen; from its pathological features, the AR in this last case was concomitant with CR. These results suggest that most cases of CR and of AR are mediated by Th1 mechanisms, although some cases of CR show features of both Th1 and Th2.

Acute Disease↗

Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 19 patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received two cycles of chemotherapy. Cycles were repeated every 4 weeks. The starting doses (dose level 1) were docetaxel 60 mg m(-2), cisplatin 70 mg m(-2), and 5-day continuous infusion of 5-FU 600 mg m(-2) day(-1). Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose to the primary tumour site and neck lymph nodes was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was docetaxel 60 mg m(-2), cisplatin 60 mg m(-2) and 5-FU 600 mg m(-2) day(-1). The main toxicities were mucositis (grade 3 and 4, 79%), leukocytopenia (grade 3 and 4, 53%), neutropenia (grade 3 and 4, 42%), anaemia (grade 3, 16%), liver dysfunction (grade 3, 11%) and renal dysfunction (grade 2, 11%). The overall response rate was 100%, including 84% complete responses (CRs). This concurrent chemoradiotherapy with TPF was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients.

Aged↗