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1.
Pathol Res Pract ; : 153653, 2021 Oct 09.
Article in English | MEDLINE | ID: mdl-34763954

ABSTRACT

Systemic lupus erythematosus (SLE) is a classic autoimmune connective tissue disease, which leads to multiple organ system injury. Tumor necrosis factor-induced protein 3 (TNFAIP3), generally called A20, has been documented to go together with the development of SLE. However, the role and mechanism of A20 in the progression of SLE are still unrevealed. In our study, A20 was downregulated in B cells from SLE patients and B cell responsiveness was significantly elevated in SLE patients. Overexpression of A20 restrained the proliferation and induced the apoptosis of B cells. Additionally, trimethylation of histone H3 Lysine 4 (H3K4me3) was decreased in the A20 promoter of SLE B cells. Lysine demethylase 5 A (Kdm5a) was significantly increased in B cells from SLE patients and negatively correlated with A20 expression. Further, Kdm5a knockdown increased the H3K4me3 level and A20 expression. More importantly, Kdm5a promoted the proliferation and inhibited the apoptosis of B cells in SLE via downregulation of A20. In general, Kdm5a promoted the proliferation and inhibited the apoptosis of B cells in SLE via downregulation of A20 by decreasing H3K4me3 enrichment level in the A20 promoter, suggesting a novel mechanism underlying SLE progression, and providing a promising therapeutic target for SLE. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article and its additional files.

2.
Rev Sci Instrum ; 90(3): 035106, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30927768

ABSTRACT

Continuous cell monitoring is very important for the maintenance and control of cell multiplication and differentiation. This paper presents a compact microplate reader that is able to continuously measure a 24-well microplate (6 × 4 wells) using the optical absorption measurement method. The 24-channel plate reader consisted of a spatial filter, light emitting diode light source, and color sensors and was similarly sized with the cell culture microwell plates. A spatial filter was previously fabricated by our group using silicone optical technology (SOT). This SOT-based spatial filter has an excellent noise reduction effect. Light reflection at the optical path interface can be absorbed and only forward light can be transmitted; accordingly, a larger S/N ratio than that of conventional optical systems is expected. The fabricated 24-channel plate reader permits real-time cell monitoring during cultivation on the clean bench and in cell culture conditions by incorporating the SOT spatial filter. Using the device, it was possible to continuously evaluate the concentration and pH of reagents in the 24 wells in real time. Moreover, cell activity and protein production were detectable using the device. These results suggest that the newly fabricated device is a promising tool for the evaluation of cell behaviors for cell management.

3.
Lupus ; 27(7): 1202-1206, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29523055

ABSTRACT

It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Interleukin-17/antagonists & inhibitors , Lupus Nephritis/complications , Psoriasis/drug therapy , Antibodies, Monoclonal, Humanized , Female , Humans , Interleukin-17/blood , Middle Aged
4.
Lupus ; 27(5): 802-811, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29308726

ABSTRACT

Objective We examined the efficacy and safety of rituximab in patients with refractory systemic lupus erythematosus (SLE). Methods The study enrolled 63 SLE patients who were treated with rituximab between 2002 and 2015. The participants underwent a battery of tests before treatment and at one year. Treatment ranged from two to four times at 500 or 1000 mg. Results Baseline characteristics were males:females = 6:57, age 33.9 years, and disease duration 87.2 months. The primary endpoint: The rate of major clinical response (MCR) was 60% while the partial clinical response (PCR) was 25%. Thirty of 36 (83%) patients with lupus nephritis (WHO II: 2, III: 5, IV: 22, V: 4, IV+V: 2, not assessed: 1) and 22 of 24 patients (92%) with neuropsychiatric SLE, who could be followed at one year, showed changes from BILAG A or B score to C or D score at one year. Multivariate analysis identified high anti-dsDNA antibody and shorter disease duration as significant determinants of MCR at one year. Repeat examination was conducted at five years. Primary failure was recorded in 8.8% and secondary failure in 32.4% (time to relapse: 24.4 months). Rituximab was well tolerated although 65 adverse events, mostly infections, were recorded within one year. Conclusion Rituximab is potentially efficacious for the treatment of patients with refractory SLE.


Subject(s)
Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/drug therapy , Lupus Vasculitis, Central Nervous System/drug therapy , Rituximab/therapeutic use , Adolescent , Adult , Aged , Chi-Square Distribution , Female , Humans , Immunosuppressive Agents/adverse effects , Japan , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/diagnosis , Lupus Nephritis/immunology , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/immunology , Male , Middle Aged , Multivariate Analysis , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Rituximab/adverse effects , Time Factors , Treatment Outcome , Young Adult
5.
Transplant Proc ; 48(7): 2423-2428, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27742314

ABSTRACT

BACKGROUND: Because tissue transplantation (TTx) has not been familiar to the general public or even to medical staffs in Japan, awareness of TTx is very important to increase tissue donation. Our primary aim was to describe the current status of awareness of TTx in medical staffs and in the general public around Osaka. METHODS: Between July 2014 and February 2015, 1015 general public citizens, 203 medical staff members working in emergency hospitals, and 168 cardiothoracic surgeons were invited to complete a letter or web-based survey through the use of a self-designed questionnaire. RESULTS: In the general public citizens, only 25.1% knew about TTx, whereas 54.7% knew about organ transplantation (OTx); 25.4% agreed to donate their organs or tissues and 17.3% disagreed to donate their organs or tissues. In medical staff members working in emergency hospitals, 58.7% knew about TTx; 82.3% agreed to support organ or tissue procurement and 10.8% disagreed to do so. Among cardiothoracic surgeons, 78.7% knew about TTx; 33.2% had used valve or vascular homografts and 57.4% wanted to use them if possible. CONCLUSIONS: According to these surveys, public awareness of TTx has been less than that of OTx, but willingness to donate tissue was not different from that of donating organs. Awareness of TTx in medical staffs in emergency hospitals was higher but still not satisfactory. To increase tissue donation in Japan, the East and West Japan Tissue Transplant Network, in collaboration with cardiothoracic surgeons, should make more effort to carry out dissemination and awareness regarding TTx to the general public and to medical staffs.


Subject(s)
Medical Staff/psychology , Public Opinion , Tissue and Organ Procurement , Adolescent , Adult , Aged , Awareness , Cardiologists/psychology , Female , Humans , Japan , Male , Medical Staff, Hospital/education , Medical Staff, Hospital/psychology , Middle Aged , Practice Patterns, Physicians' , Surveys and Questionnaires , Tissue Donors/psychology , Young Adult
6.
Lupus ; 25(8): 850-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27252261

ABSTRACT

B cells play a pivotal role in the pathogenesis of autoimmune diseases. In patients with systemic lupus erythematosus (SLE), the percentages of plasmablasts and IgD(-)CD27(-) double-negative memory B cells in peripheral blood are significantly increased, while IgD(+)CD27(+) IgM memory B cells are significantly decreased compared to healthy donors. The phenotypic change is significantly associated with disease activity and concentration of autoantibodies. Treatment of B-cell depletion using rituximab results in the reconstitution of peripheral B cells in SLE patients with subsequent improvement in disease activity. Numerous studies have described abnormalities in B-cell receptor (BCR)-mediated signaling in B cells of SLE patients. Since differences in BCR signaling are considered to dictate the survival or death of naïve and memory B cells, aberrant BCR signal can lead to abnormality of B-cell subsets in SLE patients. Although Syk and Btk function as key molecules in BCR signaling, their pathological role in SLE remains unclear. We found that Syk and Btk do not only transduce activation signal through BCR, but also mediate crosstalk between BCR and Toll-like receptor (TLR) as well as BCR and JAK-STAT pathways in human B cells in vitro. In addition, pronounced Syk and Btk phosphorylation was observed in B cells of patients with active SLE compared to those of healthy individuals. The results suggest the involvement of Syk and Btk activation in abnormalities of BCR-mediated signaling and B-cell phenotypes during the pathological process of SLE and that Syk, Btk and JAK are potential therapeutic targets in SLE.


Subject(s)
Autoantibodies/blood , B-Lymphocyte Subsets/immunology , Lupus Erythematosus, Systemic/immunology , Protein-Tyrosine Kinases/metabolism , Signal Transduction , Syk Kinase/metabolism , Agammaglobulinaemia Tyrosine Kinase , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Phosphorylation , Toll-Like Receptors/metabolism
7.
Rev Sci Instrum ; 86(8): 083901, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26329205

ABSTRACT

Ultrafast magnetization reversal of a ferrimagnetic metallic alloy GdFeCo was investigated by time-resolved resonant magneto-optical Kerr effect measurements using a seeded free electron laser. The GdFeCo alloy was pumped by a linearly polarized optical laser pulse, and the following temporal evolution of the magnetization of Fe in GdFeCo was element-selectively traced by a probe free electron laser pulse with a photon energy tuned to the Fe M-edge. The results have been measured using rotating analyzer ellipsometry method and confirmed magnetization switching caused by ultrafast heating.

8.
Lupus ; 24(7): 695-704, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25432781

ABSTRACT

OBJECTIVE: Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown. METHODS: Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients. RESULTS: Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-naïve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression. CONCLUSION: Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.


Subject(s)
B-Lymphocytes/metabolism , Intracellular Signaling Peptides and Proteins/biosynthesis , Intracellular Signaling Peptides and Proteins/metabolism , Lupus Erythematosus, Systemic/metabolism , Neoplasm Proteins/biosynthesis , Protein-Tyrosine Kinases/metabolism , Adolescent , Adult , Antigens, CD19/metabolism , B-Lymphocytes/enzymology , B-Lymphocytes/immunology , Case-Control Studies , Female , Flow Cytometry , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/immunology , Lupus Erythematosus, Systemic/enzymology , Lupus Erythematosus, Systemic/immunology , Lymphocyte Activation , Male , Middle Aged , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Phosphorylation/drug effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/immunology , Pyrimidines/pharmacology , Syk Kinase , Tumor Necrosis Factor Receptor Superfamily, Member 7/biosynthesis , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology , Young Adult
9.
Eur J Surg Oncol ; 40(9): 1095-100, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25037733

ABSTRACT

AIMS: The aim of this study was to clarify the clinical features and outcomes of diaphyseal osteosarcoma. METHODS: Patients with newly-diagnosed high-grade osteosarcoma occurring in the long bone were eligible for this retrospective study. Clinicopathological information was collected from our database and compared with 36 diaphyseal, 405 proximal and 519 distal metaphyseal, and 14 whole bone osteosarcoma patients. Additionally, case-control study matching by age, gender, site, and metastatic status at diagnosis with 1:3 ratio of 36 diaphyseal to 108 metaphyseal osteosarcomas patients was also conducted. RESULTS: Five-year overall survival and metastasis-free survival of the three groups including diaphyseal, metaphyseal, and whole bone osteosarcoma patients showed significant difference (P = .029 and P = .013, respectively), although there is no difference for the survivals between proximal and distal metaphyseal osteosarcoma patients. Case-control study showed that patients with diaphyseal osteosarcomas had a significantly larger tumour (mean 13.5 cm vs 10 cm, P = .026), and demonstrated higher pathologic fracture rate (28% vs 12%, P = .033), superior 5-year metastasis-free survival (74% vs 40%, P = .0068), and slightly better 5-year overall survival (68% vs 46%, P = .074). Prognostic factor analysis showed that a pathologic fracture significantly decreased the survival of the patients with diaphyseal osteosarcoma. CONCLUSIONS: The current study showed that diaphyseal osteosarcoma has distinct clinical features from metaphyseal osteosarcoma having an increased risk of pathologic fractures but with favorable survival outcome.


Subject(s)
Bone Neoplasms/pathology , Diaphyses/pathology , Osteosarcoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Amputation, Surgical , Antineoplastic Agents , Bone Neoplasms/complications , Bone Neoplasms/therapy , Case-Control Studies , Child , Child, Preschool , Disease-Free Survival , Female , Femoral Neoplasms/complications , Femoral Neoplasms/pathology , Femoral Neoplasms/therapy , Fibula/pathology , Fractures, Spontaneous/etiology , Humans , Humerus/pathology , Male , Middle Aged , Osteosarcoma/complications , Osteosarcoma/therapy , Prognosis , Radiotherapy , Radius/pathology , Retrospective Studies , Tibia/pathology , Treatment Outcome , Ulna/pathology , Young Adult
10.
Transplant Proc ; 46(4): 1104-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24815139

ABSTRACT

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is a high risk factor in liver transplantation and it influences graft survival. One of the major events during I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to have antioxidant properties and protective effects against organ dysfunction induced by I/R injury. The aim of this study is to investigate effects of hydrogen on porcine liver reperfusion injury. MATERIALS AND METHODS: Six outbred pigs weighing 20 kg were used for the experiment. Under general anesthesia, the venous bypass between the left femoral vein and the splenic vein to the left jugular vein was made using a centrifugal pump. Then, we used a total vascular exclusion clamp (all in- and out-flow to the liver was clamped) for 60 minutes. Hydrogen (5 ppm) saturated with lactate Ringer's solution was prepared. This solution was infused through the portal vein just before reperfusion (hydrogen group). RESULTS: Aspartate aminotransferase levels in the control versus hydrogen group in 30, 60, and 120 minutes after reperfusion were 1560.3, 1925.3, and 2342.5 versus 175.3, 200.7, and 661.00 IU/L, respectively. Lactate dehydrogenase (LDH) levels in the control versus hydrogen groups in 30, 60, and 120 minutes after reperfusion were 23,235.0, 3496.7, and 4793.5 versus 663.3, 802.0, and 983.7 IU/L, respectively. The hydrogen gas level in liver tissue increased to 954.6 ppm immediately after reperfusion; however, it disappeared within 30 minutes. CONCLUSION: The solution containing hydrogen gas was safe and had remarkably protective effects on the porcine during liver I/R and may be applied in the clinical setting.


Subject(s)
Antioxidants/pharmacology , Hydrogen/administration & dosage , Liver Diseases/prevention & control , Liver/drug effects , Reperfusion Injury/prevention & control , Animals , Aspartate Aminotransferases/metabolism , Biomarkers/metabolism , Disease Models, Animal , Female , Gases , Infusions, Intravenous , Isotonic Solutions/administration & dosage , L-Lactate Dehydrogenase/metabolism , Liver/blood supply , Liver/enzymology , Liver/surgery , Liver Diseases/metabolism , Portal Vein , Reperfusion Injury/metabolism , Ringer's Lactate , Sus scrofa , Time Factors
11.
Transplant Proc ; 46(4): 1095-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24815137

ABSTRACT

BACKGROUND: Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. RESULTS: The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. CONCLUSION: RMP is expected to facilitate the recovery of the DCD liver grafts.


Subject(s)
Heart Arrest , Liver Transplantation/methods , Liver/surgery , Organ Preservation/methods , Perfusion/methods , Reperfusion Injury/prevention & control , Rewarming/methods , Tissue and Organ Harvesting/methods , Adenosine/pharmacology , Alanine Transaminase/metabolism , Allopurinol/pharmacology , Animals , Aspartate Aminotransferases/metabolism , Biomarkers/metabolism , Cold Ischemia , Disease Models, Animal , Female , Glutathione/pharmacology , Graft Survival , Hepatectomy , Insulin/pharmacology , L-Lactate Dehydrogenase/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Transplantation/adverse effects , Necrosis , Organ Preservation/adverse effects , Organ Preservation Solutions/pharmacology , Perfusion/adverse effects , Raffinose/pharmacology , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Rewarming/adverse effects , Sus scrofa , Time Factors , Tissue and Organ Harvesting/adverse effects , Warm Ischemia
12.
Br J Cancer ; 110(9): 2232-45, 2014 Apr 29.
Article in English | MEDLINE | ID: mdl-24743707

ABSTRACT

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm arising from mesothelial lining of pleura. CD26 molecules preferentially expressed on epithelioid type of MPM. This study investigates the molecular mechanisms of CD26 regulating MPM cells in vitro and in vivo. METHODS: Biochemical and cell biological approaches were used for identifying a novel molecular target of MPM. Its contribution to tumour expansion has been also assessed using animal models. The clinical samples of MPM were also assessed for its expression. RESULTS: We identify that cytostatic effects in MPM are mediated by somatostatin (SST) receptor 4 (SSTR4), being inhibited by the interaction of CD26 molecules. We also indicates that SSTR4-mediated cytostatic effects are regulated by SHP-2 PTP, and that this inhibitory effect by SST agonist is enhanced via lipid raft clustering of associated molecules following crosslinking of anti-CD26 antibody. Finally, using an in vivo xenograft model, we demonstrate that the anti-tumour effect of anti-CD26 mAb is enhanced when combined with SSTR4 agonist treatment, and that SSTR4 is highly coexpressed with CD26 on epithelioid or biphasic types of MPM tissues obtained from patients' surgical specimens. CONCLUSIONS: Combination therapy with humanised anti-CD26 mAb and SSTR4 agonist may therefore potentiate anti-tumour effect on MPM.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Cytostatic Agents/therapeutic use , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Receptors, Somatostatin/agonists , Animals , Cell Line, Tumor , Gene Deletion , Humans , Mesothelioma, Malignant , Mice , Receptors, Somatostatin/genetics , Xenograft Model Antitumor Assays
13.
Transl Psychiatry ; 4: e371, 2014 Mar 11.
Article in English | MEDLINE | ID: mdl-24618690

ABSTRACT

Exposure to maternal stress (MS) and mutations in GAD1, which encodes the γ-aminobutyric acid (GABA) synthesizing enzyme glutamate decarboxylase (GAD) 67, are both risk factors for psychiatric disorders. However, the relationship between these risk factors remains unclear. Interestingly, the critical period of MS for psychiatric disorders in offspring corresponds to the period of GABAergic neuron neurogenesis and migration in the fetal brain, that is, in the late stage of gestation. Indeed, decrement of parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has often been observed in schizophrenia patients. In the present study, we used GAD67-green fluorescent protein (GFP) knock-in mice (that is, mice in which the Gad1 gene is heterozygously deleted; GAD67(+/GFP)) that underwent prenatal stress from embryonic day 15.0 to 17.5 and monitored PV-positive GABAergic neurons to address the interaction between Gad1 disruption and stress. Administration of 5-bromo-2-deoxyuridine revealed that neurogenesis of GFP-positive GABAergic neurons, but not cortical plate cells, was significantly diminished in fetal brains during MS. Differential expression of glucocorticoid receptors by different progenitor cell types may underlie this differential outcome. Postnatally, the density of PV-positive, but not PV-negative, GABAergic neurons was significantly decreased in the mPFC, HIP and somatosensory cortex but not in the motor cortex of GAD67(+/GFP) mice. By contrast, these findings were not observed in wild-type (GAD67(+/+)) offspring. These results suggest that prenatal stress, in addition to heterozygous deletion of Gad1, could specifically disturb the proliferation of neurons destined to be PV-positive GABAergic interneurons.


Subject(s)
Cerebral Cortex/pathology , GABAergic Neurons/pathology , Gene-Environment Interaction , Glutamate Decarboxylase/genetics , Stress, Psychological/complications , Animals , Cerebral Cortex/embryology , Cerebral Cortex/growth & development , Female , Interneurons/pathology , Mice , Mice, Transgenic , Neurogenesis/physiology , Parvalbumins/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Receptors, Glucocorticoid/metabolism , Risk Factors
14.
Epidemiol Infect ; 142(4): 812-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23866831

ABSTRACT

SUMMARY Streptococcus agalactiae (group B streptococcus; GBS) isolates (n = 150) from infants with invasive infections between 2006 and 2011 were analysed for capsular serotype, multilocus sequence type, and antibiotic susceptibility. In cases with late-onset disease (n = 115), primary meningitis was predominant (62.6%), but represented only 39.1% in cases with early-onset disease (n = 23). The most common serotype was III (58.7%), followed by Ia (21.3%) and Ib (12.7%). Sequence types (STs) of serotype III strains included ST17 (50.0%), ST19 (26.1%), ST335 (18.2%), ST27 (4.5%), and ST1 (1.1%). Predominant STs of serotypes Ia and Ib were ST23 (81.3%) and ST10 (84.2%), respectively. No penicillin-resistant strains were detected, but 22·0% of strains had mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance. A new ST335, possessing an mef(A/E) gene belonging to clonal complex 19 gradually increased in frequency. Improved prevention of invasive GBS infections in infants requires timely identification, and ultimately vaccine development.


Subject(s)
Bacterial Capsules/genetics , Macrolides/pharmacology , Streptococcal Infections/microbiology , Streptococcus agalactiae/classification , Streptococcus agalactiae/drug effects , Anti-Bacterial Agents/pharmacology , Cohort Studies , Drug Resistance, Bacterial , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases , Japan , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Serotyping , Streptococcus agalactiae/genetics , Streptococcus agalactiae/isolation & purification
16.
Eur J Endocrinol ; 167(2): 277-85, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22660025

ABSTRACT

OBJECTIVE: We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN: Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. RESULTS: Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. CONCLUSIONS: In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.


Subject(s)
Cardiovascular Diseases/epidemiology , Hyperparathyroidism, Primary/surgery , Parathyroidectomy/statistics & numerical data , Aged , Asymptomatic Diseases/epidemiology , Blood Pressure/physiology , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Carotid Intima-Media Thickness , Cohort Studies , Echocardiography , Female , Humans , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/physiopathology , Male , Middle Aged , Parathyroidectomy/rehabilitation , Risk Factors , Severity of Illness Index
17.
Phys Rev E Stat Nonlin Soft Matter Phys ; 85(1 Pt 2): 015304, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22400618

ABSTRACT

An experimental demonstration of reaction-driven viscous fingering developing when a more viscous solution of a reactant A displaces a less viscous miscible solution of another reactant B is presented. In the absence of reaction, such a displacement of one fluid by another less mobile one is classically stable. However, a simple A+B→C reaction can destabilize this interface if the product C is either more or less viscous than both reactant solutions. Using the pH dependence of the viscosity of some polymer solutions, we provide experimental evidence of both scenarios. We demonstrate quantitatively that reactive viscous fingering results from the buildup in time of nonmonotonic viscosity profiles with patterns behind or ahead of the reaction zone, depending on whether the product is more or less viscous than the reactants. The experimental findings are backed up by numerical simulations.

18.
J Clin Pharm Ther ; 37(1): 112-6, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21385196

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Montelukast, a cysteinyl leukotriene receptor 1 antagonist, is safe and efficacious in patients with asthma. The mechanisms underlying the significant interpatient variability in response to montelukast are not clear but are believed to be, in part, because of genetic variability. METHODS: To examine the associations between polymorphisms in candidate genes in the leukotriene pathway and outcomes in patients with asthma on montelukast for 4-8 weeks, we evaluated the changes in peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1·0) ) and patients' subjective symptom before and after montelukast treatment. DNA was collected from 252 Japanese participants. RESULTS AND DISCUSSION: Two single-nucleotide polymorphisms (SNPs) in the ALOX5 (rs2115819) and LTA4H (rs2660845) genes were successfully typed. There was no difference between members of the general population (n = 200) and patients (n = 52) in each genotype frequency. Significant associations were found between SNP genotypes in the LTA4H gene and changes in PEF and FEV(1·0) . The PEF and FEV(1·0) responses to montelukast in the A/A genotypes (n = 4) for the LTA4H SNP were significantly higher than those in the G allele carriers (A/G+G/G) (n = 17). WHAT IS NEW AND CONCLUSION: Despite the small sample size, our results suggest that genetic variation in leukotriene pathway candidate genes contributes to variability in clinical responses to montelukast in Japanese patients with asthma.


Subject(s)
Acetates/pharmacology , Anti-Asthmatic Agents/pharmacology , Arachidonate 5-Lipoxygenase/genetics , Asthma/drug therapy , Epoxide Hydrolases/genetics , Quinolines/pharmacology , Acetates/therapeutic use , Adult , Aged , Alleles , Anti-Asthmatic Agents/therapeutic use , Asian People/genetics , Asthma/genetics , Cyclopropanes , Female , Forced Expiratory Volume/drug effects , Genotype , Humans , Japan , Leukotriene Antagonists/pharmacology , Leukotriene Antagonists/therapeutic use , Leukotrienes/genetics , Male , Middle Aged , Peak Expiratory Flow Rate/drug effects , Polymorphism, Single Nucleotide , Quinolines/therapeutic use , Sequence Analysis, DNA , Sulfides , Treatment Outcome
19.
Arch Dis Child ; 96(10): 936-41, 2011 Oct.
Article in English | MEDLINE | ID: mdl-20554765

ABSTRACT

BACKGROUND: Acute encephalopathy/encephalitis is one of the most important causatives of mortality and neurological deficit during childhood. The aim of this retrospective observational study was to investigate clinical variables and therapeutic options associated with the outcome of children with acute encephalopathy/encephalitis. METHODS: Relationships between the clinical information at admission and the neurological outcome evaluated using Pediatric Cerebral Performance Category Scale (PCPC) at 12 months after admission were assessed in 43 patients who were treated at 10 Japanese paediatric intensive care units. RESULTS: Sixteen patients were cared for at normothermia, whereas mild hypothermia was applied to 27 children. In univariate analysis, ages ≤ 18 months, marked elevation in serum lactate dehydrogenase (LD) and aspartate transaminase, diagnosis of either acute necrotising encephalopathy or haemorrhagic shock and encephalopathy syndrome and longer hypothermic periods were associated with increased risks of death or severe neurological deficit, whereas hypothermia showed pivotal effects: the outcome of children cooled after 12 h of diagnosis was statistically invariant with normothermic children, but was significantly worse compared with children cooled ≤ 12 h. In multivariate analysis, younger ages and elevated serum LD were associated with adverse outcomes, whereas early initiation of cooling was related to favourable outcomes. For normothermic children, PCPC scores were dependent on the computed tomographic findings suggestive of cerebral oedema, serum LD levels and Glasgow Coma Scale at admission. For hypothermic children, PCPC scores depended on longer delays in cooling initiation. CONCLUSION: Without therapeutic hypothermia, the outcome of children was determined by variables suggestive of the severity of encephalopathy/encephalitis at admission. Hypothermia may have pivotal impacts on the outcome of children according to the timing of cooling initiation following acute encephalopathy/encephalitis.


Subject(s)
Encephalitis/therapy , Hypothermia, Induced/methods , Intellectual Disability/therapy , Spasms, Infantile/therapy , Acute Disease , Adolescent , Age Factors , Biomarkers/blood , Child , Child, Preschool , Encephalitis/diagnosis , Female , Humans , Hypothermia, Induced/adverse effects , Infant , Intellectual Disability/diagnosis , L-Lactate Dehydrogenase/blood , Lennox Gastaut Syndrome , Male , Prognosis , Retrospective Studies , Spasms, Infantile/diagnosis , Time Factors , Treatment Outcome
20.
Cytogenet Genome Res ; 125(4): 306-20, 2009.
Article in English | MEDLINE | ID: mdl-19864894

ABSTRACT

A new class of rye-specific repetitive DNA elements designated Superior has been identified. The rye genome library was constructed by cleavage with EcoO109I, the recognition sites of which consisted of 5'-PuGGNCCPy-3' multi-sequences and were present with high frequency in the rye repetitive families. A novel 495-bp segment enriched in the rye genome was successfully identified. Southern blot hybridization and fluorescence in situ hybridization using the repetitive element showed a dispersed array through all 7 chromosomes of rye. The repetitive DNA element did not share identity with known class I or class II transposable elements or known repetitive elements. Only several DNA segments in BACs and ESTs of barley showed partial similarity to the repetitive DNA element in all DNA databases of living species. The new class of dispersed repetitive elements was designated Superior. The entire structure of Superior was determined by using a rye genomic library of lambda FIXII screened by the 495-bp probe. The Superior family consisted of 1,292-bp, 1,324-bp, and 1,432-bp elements in which the 5' regions had been destroyed, indicating the presence of considerable structural diversity. Superior might be a useful tool for studying genomic organization and differentiation.


Subject(s)
DNA, Plant/genetics , Genome, Plant/genetics , Repetitive Sequences, Nucleic Acid/genetics , Secale/genetics , Base Sequence , Chromosomes, Plant , DNA Probes/chemistry , DNA, Plant/isolation & purification , Databases, Genetic , Genomic Library , Haploidy , In Situ Hybridization, Fluorescence , Molecular Sequence Data , Nucleic Acid Conformation , Plant Leaves/chemistry , RNA, Plant/chemistry , Sequence Analysis, DNA
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