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Biomedical subjects

K Tajima

Publications and source records attributed to K Tajima.

At least 19 recordsLinked to original sources

Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection.

BACKGROUND: Some, but not all studies have provided evidence that the CagA status of Helicobacter pylori strains is a predictive factor for the outcome of eradication therapy. AIM: To clarify the association between CagA status and eradication outcome. METHODS: We included studies reporting the numbers of successful and failed cases in H. pylori-eradication therapy according to the CagA status. Fourteen studies (1529 patients) were included of 325 articles identified in the search. The pooled risk ratio for H. pylori-eradication failure in CagA-negative relative to CagA-positive strains and the pooled risk difference in eradication success between the two groups were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: The summary risk ratio for eradication failure in CagA-negative relative to CagA-positive was 2.0 (95% CI: 1.6-2.4, P < 0.001), corresponding with the summary risk difference for eradication success between the groups of 11% (95% CI: 3-19%, P = 0.011). Meta-regression analysis demonstrated that usage of polymerase chain reaction examination for CagA status and a high proportion of non-ulcer dyspepsia patients were factors for heterogeneity among studies. CONCLUSIONS: Our meta-analysis confirmed the importance of the presence of CagA as a predictor for successful eradication of H. pylori.

Antigens, Bacterial↗

Influence of smoking and CYP2C19 genotypes on H. pylori eradication success.

CYP2C19 polymorphisms and smoking influence the efficacy of H. pylori eradication therapy, but interaction between the two have hitherto not been examined. A total of 142 H. pylori-positive patients who received triple drug therapy with lansoprazole, amoxicillin and clarithromycin were categorized into three groups with regard to diplotypes of CYP2C19: homozygous extensive metabolizer (homEM), heterozygous EM (hetEM), and poor metabolizer (PM). The overall success rate was 61.3%. Smoking was an independent risk factor of eradication failure (OR 2.81, 95% CI 1.14-6.91), whereas CYP2C19 polymorphisms were less influential. Among non-smokers, the homEM and hetEM groups showed worse eradication rates (58.5 and 67.3%) relative to PM (76.2%) as expected; however, an opposite trend was observed among smokers (homEM 50.0%, hetEM 46.7%, PM 20.0%), indicating possible interactions with CYP2C19 polymorphisms. Smoking has a greater influence on H. pylori eradication than the CYP2C19 genotype. Interaction between smoking and CYP2C19 should be examined in the future.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Downregulation of inhibitor of apoptosis proteins in apoptotic human chondrocytes treated with tumor necrosis factor-alpha and actinomycin D.

OBJECTIVE: Apoptosis of chondrocytes plays a pivotal role in cartilage degeneration. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and has been assumed to cause the degradation of human cartilage. To investigate the mechanisms of TNF-alpha-mediated apoptosis of human chondrocytes from a point of view of the balance between the caspase-cascade and the expression of inhibitor of apoptosis proteins (IAPs), although both of them are induced with TNF-signals. METHODS: The expression of TNF-receptors (TNF-Rs) in normal human articular chondrocyte (NHAC-kn) was examined with immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-alpha and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the frequency of apoptotic cells visualized with nuclear staining using Hoechst 33342. The activation of caspases and the expression of IAPs were examined with Western blot analyses. RESULTS: NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn was treated with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml) for 24 h, the frequency of apoptotic cells increased to more than 25%. TNF-alpha alone, however, induced the apoptosis insufficiently (up to 8.3%), even when used at the concentration of 100 ng/ml for 48 h. In apoptotic human chondrocytes induced with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml), the caspase-3, -8, and -9 were activated and the protein expression of XIAP and c-IAP1 decreased. CONCLUSIONS: In apoptotic human chondrocytes induced with TNF-alpha and actD, the balance between caspase activation and IAPs' expression lay with the executioner caspase (caspase-3) and led to decreased expression of XIAP and c-IAP1.

Apoptosis↗

Soybean products and reduction of breast cancer risk: a case-control study in Japan.

Components of the Japanese diet, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Since soybean products are widely consumed in Japan, a case-control study taking account of the menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167 breast cancer cases were included and 854 women confirmed as free of cancer were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. There were reductions in risk of breast cancer associated with high intake of soybean products among premenopausal women. Compared with women in the lowest tertile, the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI, 0.25-0.95). A significant decrease in premenopausal breast cancer risk was also observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89 for highest vs lowest tertile; P for trend=0.02). The present study found a statistically inverse association between tofu or isoflavone intake and risk of breast cancer in Japanese premenopausal women, while no statistically significant association was evident with the risk among postmenopausal women.

Adult↗

Juxtacortical chondroma of the hand: treatment by resection of the tumour and the adjacent bone cortex.

A recurrence of a juxtacortical chondroma of the finger after marginal excision prompted us to review the treatment of this condition. Although the recommended treatment is simple curettage or marginal excision, the reported recurrence rate is significantly higher for lesions in the hand than those in other locations and recurrences only occurred in patients who had local treatments which did not include excision of the adjacent bone cortex. We report five patients with juxtacortical chondroma of the fingers. The first patient underwent marginal excision without resection of the underlying bone cortex. The other four patients underwent intralesional, marginal or wide excisions of tumour with resection of the bone cortex underlying the lesion. Recurrence was only seen in the patient who did not undergo resection of the bone cortex. Resection of the underlying bone cortex after excision of this tumour may be advisable for the treatment of this tumour in the hand to reduce the rate of recurrence.

Adolescent↗

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↗

Comparison between reduced intensity and conventional myeloablative allogeneic stem-cell transplantation in patients with hematologic malignancies aged between 50 and 59 years.

To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25-2.97; P=0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; P<0.001), risk of underlying diseases (1.85, 1.21-2.83; P=0.004), acute GVHD (2.57, 1.72-3.84; P<0.001), and CML (0.38, 0.21-0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.

Female↗

Relationship between temporary inhibition and structure of disulfide-linkage analogs of marinostatin, a natural ester-linked protein protease inhibitor.

A 12-residue marinostatin [MST(1-12): (1)FATMRYPSDSDE(12)] which contains two ester linkages of Thr(3)-Asp(9) and Ser(8)-Asp(11) strongly inhibits subtilisin. In order to study the relationship between the inhibitory activity, structure, and stability of MST, MST analogs were prepared by changing ester linkages to a disulfide linkages. The analogs without the disulfide linkage between 3 and 9 positions lost their inhibitory activity. The K(i) value of 1SS(C(3)-C(9)) ((1)FACMRYPSCSDE(12)), which has a single disulfide linkage of Cys(3)-Cys(9) was comparable with those of MST(1-12) and MST-2SS ((1)FACMRYPCCSCE(12)), a doubly linked analog of Cys(3)-Cys(9) and Cys(8)-Cys(11). However, 1SS(C(3)-C(9)) and MST-2SS showed temporary inhibition, but not MST(1-12): These analogs were inactivated after incubation with subtilisin for 30 min, and were specifically hydrolyzed at the reactive site. (1)H NMR study showed that 1SS(C(3)-C(9)) has two conformations, which contain a cis- (70%) or trans- (30%) Pro residue, while MST-2SS as well as MST(1-12) takes a single conformation containing only a cis-Pro residue. Hydrogen-deuterium exchange rate of the Arg(5) (P1') NH proton of the MST analogs was about 100 times faster than that of MST(1-12). These results indicate that the linkage between the positions 8 and 11 plays a role for fixing the cis-conformation of the Pro(7) residue, and that the linkage between 3 and 9 is indispensable for the inhibition, but not enough for stable protease-inhibitor complex.

ATP-Binding Cassette Transporters↗

Short communication: Amino acids antagonistic to the amino acids inhibitory for growth rate of mixed ruminal bacteria.

Antagonism of some amino acids (AA) to the inhibitory effects of other AA (Ile, Phe, and Thr) on the growth rate of mixed ruminal bacteria was investigated. In vitro growth rate of the mixed ruminal bacteria was inhibited when the 3 inhibitory AA (1 mM each) were each added to individual control treatments in which an ammonium salt was included as a sole N source. The inhibitory effect caused by Ile was relieved by addition of Leu or Val (equimolar to Ile), and no significant inhibition was shown when both Leu and Val were added together with Ile. The growth inhibition caused by Phe was also alleviated by supplementing with Trp, and was completely negated by adding Tyr. The inhibitory effect of Thr, on the other hand, was not affected by addition of Lys or Met (which are synthesized using a common pathway with Thr), but was mitigated by supplementation with Glu, Ser, Val, Ala, or Gln. Among the antagonistic AA, Leu, Val, Trp, Tyr, and Glu were indispensable for the maximum growth rate of the ruminal bacteria under the experimental condition of supplementation of amino-N, the removal of which from a mixture of 20 protein AA caused the growth rate to decline. Removals of Ile along with Leu or Val or both, of Phe along with Trp or Tyr, and of Thr along with Glu recovered the promotion of bacterial growth rate. It was concluded that inhibitions of the bacterial growth rate caused by Ile, Phe, or Thr could be antagonized by some other AA (Leu, Val, Tyr, Trp, or Glu), and the role of these latter AA as relievers of the inhibitory effects could explain why they are indispensable for maximum growth rate of ruminal bacteria.

Amino Acids↗

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↗

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↗

Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses.

Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identification of peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CD8+ T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8+ T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM173-181 (RYQLDPKFI) secreted interferon-gamma in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lytic to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402.

Biomarkers, Tumor↗

Binding of Cu(II) or Zn(II) in a de novo designed triple-stranded alpha-helical coiled-coil toward a prototype for a metalloenzyme.

We previously reported the IZ-3adH peptide, which formed a triple-stranded coiled-coil after binding Ni(II), Cu(II), or Zn(II). In this paper, we report the peptide, IZ-3aH, having a new metal binding specificity. The IZ-3aH peptide was found to bind Cu(II) and Zn(II) and form a triple-stranded coiled-coil. However, it did not bind Ni(II). Metal ion titrations monitored by circular dichroism revealed that the dissociation constants, K(d) were 9 microm for Zn(II) and 10 microm for Cu(II). The bound Cu(II) ion has a planar tetragonal geometry, where the coordination positions are three nitrogens of the His residues and one H(2)O.

Circular Dichroism↗

Analysis of signal transduction stimulated by gonadotropins in granulosa cells.

Gonadotropins exert their effect on ovarian follicular cells through the activation of the hormone sensitive adenylate cyclase and consequent elevation of intracellular cyclic AMP (cAMP). Desensitization to the hormone in cultured primary granulosa cells can occur within a short period and internalization of the hormone-receptor complex has been observed both in vivo and in vitro. It was recently documented that the gonadotropins as well as cAMP activate MAP kinase (MAPK) in granulosa cells. Moreover we discovered that specific inhibitors of extracellular signal-regulated kinase phosphorylation, 1 and 2, augment steroidogenesis in granulosa cells up-regulating steroidogenic acute regulatory (StAR) protein expression, and that this modulation is blocked by specific inhibitors of protein kinase A. It is therefore suggested that gonadotropins may activate both stimulatory and inhibitory pathways which regulate steroidogenesis. Moreover the ratio between the activity of these two pathways may determine the rate of steroidogenesis, and rapid activation of MAPK may account as part of the mechanism of desensitization to the hormonal action. Steroidogenic factor-1 and DAX-1 may be involved in the regulation of the MAPK-dependent attenuation of steroidogenesis, since they exhibit sites that could be potentially phosphorylated by the MAPK cascade.

Animals↗

Smoking and polymorphisms of fucosyltransferase gene Le affect success of H. pylori eradication with lansoprazole, amoxicillin, and clarithromycin.

Identification of factors influencing success of Helicobacter pylori (HP) eradication is important for clinical practice. We have prospectively conducted an HP eradication study in the Aichi Cancer Center with a total of 142 patients available for analysis. The overall success rate was 61.3% (95% confidence interval 52.7-69.3%). Smoking during the medication for eradication significantly decreased the success rate (42.9%), whereas smoking cessation during the treatment was associated with a similar rate as for non-smokers (66.7%). We also examined links between an eradication outcome and polymorphisms of Le, Se, IL1A, IL1B, IL1RN and MPO genes, but with one exception none showed any association. The non-functional le allele of Le polymorphisms, leading to decreased expression of Le(b) antigen to which HP attaches with adhesin, showed a beneficial effect for success. Although further clarification is necessary, our study indicated that smoking cessation and Le gene polymorphisms may affect the success rate of HP eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A case of inflammatory demyelinating polyradiculoneuropathy associated with T-cell lymphoma.

Malignant lymphoma may present prominent peripheral nervous system disorders with variable etiologies. We describe a patient who presented with chronic relapsing polyradiculoneuropathy accompanied by right facial nerve palsy. Gadolinium enhancement of the right facial nerve and cervical spinal roots was noted on magnetic resonance imaging (MRI). Sural nerve biopsy specimens showed mononuclear cell infiltration around the vessels in the epineurium. Histopathological and immunohistochemical investigations of sural nerve specimens revealed perivascular infiltration of lymphocytes with T-cell dominancy. No apparent direct invasion of lymphoma cells was seen. The results of nerve conduction studies, sural nerve biopsy and cerebrospinal fluid examination were suggestive of immune-mediated inflammatory demyelinating neuropathy. The chronic and relapsing fashion and unique radiological findings in our patient expand on the previously reported features of peripheral neuropathy associated with peripheral T-cell lymphoma.

Biopsy↗

Seven-hour fluorescence in situ hybridization technique for enumeration of Enterobacteriaceae in food and environmental water sample.

AIMS: A fluorescent in situ hybridization (FISH) technique using an Enterobacteriaceae-specific probe (probe D) to target 16S rRNA was improved in order to enumerate, within a single working day, Enterobacteriaceae present in food and environmental water samples. METHODS AND RESULTS: In order to minimize the time required for the FISH procedure, each step of FISH with probe D was re-evaluated using cultured Escherichia coli. Five minutes of ethanol treatment for cell fixation and hybridization were sufficient to visualize cultured E. coli, and FISH could be performed within 1 h. Because of the difficulties in detecting low levels of bacterial cells by FISH without cultivation, a FISH technique for detecting microcolonies on membrane filters was investigated to improve the bacterial detection limit. FISH with probe D following 6 h of cultivation to grow microcolonies on a 13 mm diameter membrane filter was performed, and whole Enterobacteriaceae microcolonies on the filter were then detected and enumerated by manual epifluorescence microscopic scanning at magnification of x100 in ca 5 min. The total time for FISH with probe D following cultivation (FISHFC) was reduced to within 7 h. FISHFC can be applied to enumerate cultivable Enterobacteriaceae in food (above 100 cells g-1) and environmental water samples (above 1 cell ml-1). CONCLUSIONS: Cultivable Enterobacteriaceae in food and water samples were enumerated accurately within 7 h using the FISHFC method. SIGNIFICANCE AND IMPACT OF THE STUDY: A FISHFC method capable of evaluating Enterobacteriaceae contamination in food and environmental water within a single working day was developed.

Colony Count, Microbial↗