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1.
BJS Open ; 4(5): 804-810, 2020 10.
Article in English | MEDLINE | ID: mdl-32700415

ABSTRACT

BACKGROUND: The role of antithrombotic chemoprophylaxis in prevention of venous thromboembolism (VTE) in laparoscopic surgery for gastric and colorectal malignancies is unknown. This study compared the addition of enoxaparin following intermittent pneumatic compression (IPC) with IPC alone in patients undergoing laparoscopic surgery for gastrointestinal malignancy. METHODS: In this multicentre RCT, eligible patients were older than 40 years and had a WHO performance status of 0 or 1. Exclusion criteria were prescription of antiplatelet or anticoagulant drugs and history of VTE. Patients were allocated to IPC or to ICP with enoxaparin in a 1 : 1 ratio. Stratification factors included sex, location of cancer, age 61 years and over, and institution. Enoxaparin was administered on days 1-7 after surgery. Primary outcome was VTE, evaluated by multidetector CT on day 7. RESULTS: Of 448 patients randomized, 208 in the IPC group and 182 in the IPC with enoxaparin group were evaluated. VTE occurred in ten patients (4·8 per cent) in the IPC group and six (3·3 per cent) in the IPC with enoxaparin group (P = 0·453). Proximal deep vein thrombosis and/or pulmonary embolism occurred in seven patients (3·4 per cent) in the IPC group and one patient (0·5 per cent) in the IPC with enoxaparin group (P = 0·050). All VTE events were asymptomatic and non-fatal. Bleeding occurred in 11 of 202 patients in the IPC with enoxaparin group, and one patient needed a transfusion. All bleeding events were managed by discontinuation of the drug. CONCLUSION: IPC with enoxaparin after laparoscopic surgery for gastric and colorectal malignancies did not reduce the rate of VTE. Registration number: UMIN000011667 ( https://www.umin.ac.jp/).


ANTECEDENTES: El papel de la quimioprofilaxis para la prevención del tromboembolismo venoso (venous thromboembolism, VTE) en la cirugía laparoscópica de los tumores malignos gástricos y colorrectales se desconoce. El objetivo de este estudio fue comparar la quimioprofilaxis antitrombótica (enoxaparina) y la compresión neumática intermitente (intermittent pneumatic compression, IPC) en pacientes sometidos a cirugía laparoscópica de tumores malignos abdominales. MÉTODOS: Se efectuó un ensayo aleatorizado, controlado y multicéntrico de pacientes sometidos a cirugía laparoscópica de tumores gástricos y colorrectales en Japón. Los criterios de inclusión eran pacientes mayores de 40 años de edad y con un estado funcional de WHO de 0-1. Los criterios de exclusión fueron la prescripción al paciente de fármacos antiagregantes o anticoagulantes y la historia de VTE. Los pacientes fueron asignados a IPC y ICP con la adición de enoxaparina en una relación 1:1. Los factores de estratificación incluyeron el sexo, la localización del cáncer, la edad mayor o menor de 61 años, y la institución. La enoxaparina fue administrada en los días postoperatorios (postoperative day, POD) 1-7. El resultado primario fue la VTE evaluada mediante tomografía computarizada multidetector en el POD7. Los cálculos de la potencia determinaron que se requerían 184 pacientes en cada grupo. RESULTADOS: De los 448 pacientes aleatorizados, se evaluaron finalmente 208 pacientes en el grupo IPC y 182 pacientes en el grupo IPC más enoxaparina. La VTE ocurrió en 10 de 208 pacientes en el grupo IPC (4,8%) y 6 de 182 pacientes en el grupo IPC más enoxaparina (3,3%) (P = 0,45). La trombosis venosa profunda proximal (proximal deep vein thrombosis, DVT) y/o el embolismo pulmonar (pulmonary embolism, PE) ocurrieron en 7 de 208 pacientes en el grupo IPC (3,4%) y 1 de 182 pacientes en el grupo IPC más enoxaparina (0,55%) (riesgo relativo 0,163, i.c. del 95% 0,020-1,314, P = 0,0503). Todos los eventos de VTE fueron asintomáticos y no mortales. Se produjo una hemorragia en 11 de 202 pacientes en el grupo IPC con enoxaparina (5,4%, i.c. del 95% 3,1%-9,5%, P < 0,001), y un paciente precisó transfusión. Todos los eventos hemorrágicos pudieron ser tratados con la interrupción del fármaco. CONCLUSIÓN: La IPC con la adición de enoxaparina tras cirugía laparoscópica de los tumores malignos gástricos y colorrectales no disminuye la VTE.


Subject(s)
Enoxaparin/therapeutic use , Intermittent Pneumatic Compression Devices , Laparoscopy/adverse effects , Postoperative Complications/prevention & control , Venous Thromboembolism/prevention & control , Aged , Anticoagulants/therapeutic use , Colorectal Neoplasms/surgery , Female , Hemorrhage/epidemiology , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Pulmonary Embolism/prevention & control , Stomach Neoplasms/surgery , Venous Thromboembolism/epidemiology
2.
BJS Open ; 4(3): 486-498, 2020 06.
Article in English | MEDLINE | ID: mdl-32207580

ABSTRACT

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) was introduced in Japan to improve the quality of laparoscopic surgery. This cohort study investigated the short- and long-term postoperative outcomes of colorectal cancer laparoscopic procedures performed by or with qualified surgeons compared with outcomes for unqualified surgeons. METHODS: All laparoscopic colorectal resections performed from 2010 to 2013 in 11 Japanese hospitals were reviewed retrospectively. The procedures were categorized as performed by surgeons with or without the ESSQS qualification and patients' clinical, pathological and surgical features were used to match subgroups using propensity scoring. Outcome measures included postoperative and long-term results. RESULTS: Overall, 1428 procedures were analysed; 586 procedures were performed with ESSQS-qualified surgeons and 842 were done by ESSQS-unqualified surgeons. Upon matching, two cohorts of 426 patients were selected for comparison of short-term results. A prevalence of rectal resection (50·3 versus 40·5 per cent; P < 0·001) and shorter duration of surgery (230 versus 238 min; P = 0·045) was reported for the ESSQS group. Intraoperative and postoperative complication and reoperation rates were significantly lower in the ESSQS group than in the non-ESSQS group (1·2 versus 3·6 per cent, P = 0·014; 4·6 versus 7·5 per cent, P = 0·025; 1·9 versus 3·9 per cent, P = 0·023, respectively). These findings were confirmed after propensity score matching. Cox regression analysis found that non-attendance of ESSQS-qualified surgeons (hazard ratio 12·30, 95 per cent c.i. 1·28 to 119·10; P = 0·038) was independently associated with local recurrence in patients with stage II disease. CONCLUSION: Laparoscopic colorectal procedures performed with ESSQS-qualified surgeons showed improved postoperative results. Further studies are needed to investigate the impact of the qualification on long-term oncological outcomes.


ANTECEDENTES: El Sistema de Certificación de Habilidades Quirúrgicas Endoscópicas (Endoscopic Surgical Skill Qualification System, ESSQS) fue introducido en Japón para mejorar la calidad de la cirugía laparoscópica. En este estudio de cohortes se investigaron los resultados postoperatorios a corto y a largo plazo de las intervenciones laparoscópicas de cáncer colorrectal realizadas por o con la asistencia de cirujanos con certificación en comparación con cirujanos no certificados. MÉTODOS: Todas las resecciones colorrectales laparoscópicas realizadas entre 2010 y 2013 en 11 hospitales japoneses fueron revisadas retrospectivamente. Los procedimientos se clasificaron en función de si habían sido realizados por cirujanos con o sin certificación del ESSQS, y las características clínicas, patológicas y quirúrgicas de los pacientes se utilizaron para emparejar los subgrupos mediante puntuaciones de propensión. Las variables de resultado incluyeron los resultados postoperatorios y a largo plazo RESULTADOS: En total se analizaron 1.428 procedimientos, incluyendo 586 y 842 procedimientos realizados con y sin cirujanos certificados por ESSQS, respectivamente. Tras el emparejamiento, se seleccionaron dos cohortes de 426 pacientes para la comparación de resultados a corto plazo. Se observó una mayor prevalencia de resecciones rectales (50,3% versus 40,1%, P = 0,0001) y un tiempo quirúrgico más corto (230 versus 238 min, P = 0,04) en el grupo ESSQS. Las tasas de complicaciones intra- y postoperatorias y de reoperaciones fueron significativamente más bajas en el grupo ESSQS que en el grupo no ESSQS (1,2%, 4,6% y 1,9% versus 3,6%, 7,5% y 3,9%, P = 0,01; 0,03, y 0,02, respectivamente). Estos hallazgos se confirmaron tras el análisis de emparejamiento por puntaje de propensión. El análisis de regresión de Cox mostró que la no participación de cirujanos certificados con ESSQS (razón de oportunidades, odds ratio, OR 12,3; i.c. del 95%, 1,28-119,1; P = 0,03) se asoció independientemente con la recidiva local en los casos en estadio II. CONCLUSIÓN: Los procedimientos colorrectales laparoscópicos realizados por cirujanos certificados por ESSQS presentaron mejores resultados postoperatorios. Son necesarios más estudios para determinar el impacto de la certificación en los resultados oncológicos a largo plazo.


Subject(s)
Clinical Competence , Colorectal Neoplasms/surgery , Digestive System Surgical Procedures/standards , Laparoscopy/standards , Aged , Conversion to Open Surgery , Digestive System Surgical Procedures/adverse effects , Female , Humans , Japan , Laparoscopy/adverse effects , Laparoscopy/methods , Male , Operative Time , Postoperative Complications , Propensity Score , Retrospective Studies
3.
Psychol Med ; 48(7): 1148-1156, 2018 05.
Article in English | MEDLINE | ID: mdl-28893330

ABSTRACT

BACKGROUND: Cognitive-behavioral therapy (CBT) is thought to be useful for chronic pain, with the pathology of the latter being closely associated with cognitive-emotional components. However, there are few resting-state functional magnetic resonance imaging (R-fMRI) studies. We used the independent component analysis method to examine neural changes after CBT and to assess whether brain regions predict treatment response. METHODS: We performed R-fMRI on a group of 29 chronic pain (somatoform pain disorder) patients and 30 age-matched healthy controls (T1). Patients were enrolled in a weekly 12-session group CBT (T2). We assessed selected regions of interest that exhibited differences in intrinsic connectivity network (ICN) connectivity strength between the patients and controls at T1, and compared T1 and T2. We also examined the correlations between treatment effects and rs-fMRI data. RESULTS: Abnormal ICN connectivity of the orbitofrontal cortex (OFC) and inferior parietal lobule within the dorsal attention network (DAN) and of the paracentral lobule within the sensorimotor network in patients with chronic pain normalized after CBT. Higher ICN connectivity strength in the OFC indicated greater improvements in pain intensity. Furthermore, ICN connectivity strength in the dorsal posterior cingulate cortex (PCC) within the DAN at T1 was negatively correlated with CBT-related clinical improvements. CONCLUSIONS: We conclude that the OFC is crucial for CBT-related improvement of pain intensity, and that the dorsal PCC activation at pretreatment also plays an important role in improvement of clinical symptoms via CBT.


Subject(s)
Chronic Pain/therapy , Cognitive Behavioral Therapy , Gyrus Cinguli/physiopathology , Magnetic Resonance Imaging , Prefrontal Cortex/physiopathology , Adult , Brain Mapping , Case-Control Studies , Chronic Pain/physiopathology , Female , Humans , Japan , Male , Middle Aged , Neural Pathways/physiopathology , Psychotherapy, Group , Rest , Spatial Regression
4.
Leukemia ; 26(5): 883-92, 2012 May.
Article in English | MEDLINE | ID: mdl-22005789

ABSTRACT

We and others have previously demonstrated that p210 Bcr-Abl tyrosine kinase inhibits stromal cell-derived factor-1α/CXCR4 chemokine receptor signaling, contributing to the deficient adhesion of chronic myeloid leukemia (CML) cells to bone marrow stroma. Conversely, exposure of CML cells to a tyrosine kinase inhibitor (TKI) enhances migration of CML cells towards stromal cell layers and promotes non-pharmacological resistance to imatinib. Src-related kinase Lyn is known to interact with CXCL12/CXCR4 signaling and is directly activated by p210 Bcr-Abl. In this study, we demonstrate that TKI treatment promoted CXCR4 redistribution into the lipid raft fraction, in which it co-localized with active phosphorylated form of Lyn (LynTyr396) in CML cells. Lyn inhibition or cholesterol depletion abrogated imatinib-induced migration, and dual Src/Abl kinase inhibitor dasatinib induced fewer CML cells to migrate to the stroma. These findings demonstrate the novel mechanism of microenvironment-mediated resistance through lipid raft modulation, which involves compartmental changes of the multivalent CXCR4 and Lyn complex. We propose that pharmacological targeting of lipid rafts may eliminate bone marrow-resident CML cells through interference with microenvironment-mediated resistance.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Membrane Microdomains/metabolism , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Receptors, CXCR4/metabolism , Stromal Cells/metabolism , src-Family Kinases/metabolism , Animals , Benzamides , Blotting, Western , Chemokine CXCL12/metabolism , Drug Resistance, Neoplasm , Flow Cytometry , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Mice , Microscopy, Confocal , Microscopy, Fluorescence , Phosphorylation , Protein Binding , Signal Transduction
5.
Neuroscience ; 167(2): 372-83, 2010 May 05.
Article in English | MEDLINE | ID: mdl-20109533

ABSTRACT

Memantine is classified as an NMDA receptor antagonist. We recently reported that memantine promoted the proliferation of neural progenitor cells and the production of mature granule neurons in the adult hippocampus. However, the molecular mechanism responsible for the memantine-induced promotion of cellular proliferation remains unknown. In this study we searched for a factor that mediates memantine-induced cellular proliferation, and found that pigment epithelium-derived factor (PEDF), a broad-acting neurotrophic factor, is up-regulated in the dentate gyrus of adult mice after the injection of memantine. PEDF mRNA expression increased significantly by 3.5-fold at 1 day after the injection of memantine. In addition, the expression level of PEDF protein also increased by 1.8-fold at 2 days after the injection of memantine. Immunohistochemical study using anti-PEDF antibody showed that the majority of the PEDF-expressing cells were protoplasmic and perivascular astrocytes. Using a neurosphere assay, we confirmed that PEDF enhanced cellular proliferation under the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) but was not involved in the multilineage potency of hippocampal progenitor cells. Over expression of PEDF by adeno-associated virus, however, did not stimulate cellular proliferation, suggesting PEDF per se does not promote cellular proliferation in vivo. These findings suggest that the memantine induced PEDF up-regulation is involved in increased proliferation of hippocampal progenitor cells.


Subject(s)
Eye Proteins/biosynthesis , Hippocampus/drug effects , Memantine/pharmacology , Nerve Growth Factors/biosynthesis , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Serpins/biosynthesis , Stem Cells/drug effects , Adenoviridae/genetics , Animals , Astrocytes/cytology , Astrocytes/drug effects , Astrocytes/metabolism , Brain-Derived Neurotrophic Factor/biosynthesis , Cell Proliferation , Eye Proteins/genetics , Fibroblast Growth Factor 2/biosynthesis , Hippocampus/cytology , Hippocampus/metabolism , Male , Mice , Mice, Inbred C57BL , Nerve Growth Factors/genetics , Serpins/genetics , Stem Cells/cytology , Stem Cells/metabolism , Up-Regulation
7.
Clin Exp Rheumatol ; 26(5): 918-21, 2008.
Article in English | MEDLINE | ID: mdl-19032829

ABSTRACT

OBJECTIVE: Our goal was to evaluate the associations of antibodies (Abs) to glucose-6-phosphate isomerase (GPI) with Abs to cyclic citrullinated peptide (CCP) and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis (RA). METHODS: One hundred and eight patients with early RA (85 female, 23 male) who visited our clinic within 1 year of symptom onset were examined for anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotype. Anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotypes were also determined in 63 controls and 265 healthy controls, respectively. RESULTS: Of the 108 patients with early RA and the 63 controls, 20 (18.5%) and 3 (4.8%) were anti-GPI Ab-positive, respectively. Of the 20 patients with anti-GPI Abs, 17 (85%) were positive for anti-CCP Abs. HLA-DRB1*0405 and shared epitope (SE) carrier frequencies were significantly increased not only in anti-GPI Ab-positive patients (p=0.00057, odds ratio [OR] 4.6, 95% CI 1.8-11.8; p=0.0011, OR 5.0, 95% CI 1.7-14.0), but also in anti-GPI Ab-negative patients (p=0.0017, OR 2.2, 95% CI 1.3-3.7; p=0.00011, OR 2.6, 95% CI 1.6-4.3), when compared with controls. In addition, the carrier frequency of HLA-DRB1*1201 was significantly increased in anti-GPI Ab-positive patients compared with controls (p=0.0056, OR 4.3, 95% CI 1.4-13.2). CONCLUSIONS: The majority of anti-GPI Ab-positive RA patients constitute a subset of HLA-DRB1* SE-associated, anti-CCP Ab-positive RA patients.


Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease/genetics , Glucose-6-Phosphate Isomerase/immunology , HLA-DR Antigens/genetics , Peptides, Cyclic/immunology , Adult , Arthritis, Rheumatoid/immunology , Autoantibodies , Case-Control Studies , Female , Genotype , HLA-DRB1 Chains , Humans , Japan , Male , Middle Aged , Odds Ratio
10.
Clin Exp Rheumatol ; 25(2): 219-24, 2007.
Article in English | MEDLINE | ID: mdl-17543145

ABSTRACT

OBJECTIVE: To evaluate the role of HLA-DRB1 genotypes and antibodies to cyclic citrullinated peptides (anti-CCP antibodies) in the development and radiographic progression of Japanese patients with rheumatoid arthritis (RA). METHODS: One hundred and ten patients with early RA (88 female, 22 male) who visited our clinic within 1 year of symptom onset were examined for anti-CCP antibody levels and HLA-DRB1 genotypes. HLA-DRB1 genotypes were also determined in 265 healthy controls. Radiographic progression over a 2-year interval was evaluated using the Larsen's method in 66 patients. RESULTS: Among the 110 patients with early RA, 82 patients (74.5%) were anti-CCP positive. Carrier frequency of HLA-DRB1*0405 was significantly increased in RA patients with anti-CCP antibodies compared with controls and RA patients without anti-CCP antibodies (odds ratio [OR] 3.4, 95% confidence interval [95% CI] 2.0-5.7 and OR 3.3, 95% CI 1.3-8.6, respectively). Carriership of one or two SE alleles was significantly associated with production of anti-CCP antibodies (OR 2.7, 95% CI 1.1-6.7 and OR 9.3, 95% CI 1.1-78.2, respectively). On the other hand, allele frequency of HLA-DRB1*0901 was significantly increased in RA patients without anti-CCP antibodies compared with controls and RA patients with anti-CCP antibodies (OR 2.2, 95% CI 1.1-4.1 and OR 3.0, 95% CI 1.4-6.4, respectively). CONCLUSION: In Japanese patients with RA, HLA-DRB1 SE alleles are associated with production of anti-CCP antibodies and HLA-DRB1 alleles appear to be differently associated with early RA depending on anti-CCP positivity as in Caucasian patients with RA.


Subject(s)
Alleles , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , HLA-DR Antigens/genetics , Peptides, Cyclic/immunology , Adult , Arthritis, Rheumatoid/ethnology , Asian People/ethnology , Asian People/genetics , Case-Control Studies , Disease Progression , Epitopes/genetics , Female , Foot/diagnostic imaging , Genotype , HLA-DRB1 Chains , Hand/diagnostic imaging , Heterozygote , Humans , Japan , Male , Middle Aged , Peptides, Cyclic/genetics , Radiography
12.
Spinal Cord ; 44(8): 518-21, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16331310

ABSTRACT

STUDY DESIGN: Case report. OBJECTIVE: To describe the mechanism of injury in this case and its clinical features. Magnetic resonance (MR) images of hemorrhage in spinal cord injury due to stab wound are discussed. METHODS: We describe the case of a 21-year-old woman who was stabbed in the right side of her neck and developed left-sided Brown-Séquard syndrome plus loss of bilateral proprioceptive sensation. Neither plain radiographs nor computed tomography of the cervical spine demonstrated any foreign bodies or fractures of the cervical spine. T2-weighted cervical MR images confirm spinal cord hemiresection at C5-C6. RESULTS: MR imaging was performed serially at 4 days, 4 weeks, and 8 weeks after trauma. The signal pattern of the spinal cord at the site of injury varied iso, iso, and low on T1-weighted consecutive images. Meanwhile, high signal intensity on T2-weighted images was consistent during the 8 weeks after incidence of trauma. A T2-weighted sagittal image showed a tiny spot of low intensity in the high signal band at the site of penetration, demonstrating hemosiderin formation in the spinal cord. The patient was treated conservatively and, recovered from Frankel grade C to grade D. CONCLUSION: Spinal cord injuries (SCI) following stab wounds are rare. MR imaging is definitely useful for recording and monitoring the pathology of SCI.


Subject(s)
Brown-Sequard Syndrome/diagnosis , Cervical Vertebrae/injuries , Spinal Cord Injuries/diagnosis , Wounds, Stab/diagnosis , Adult , Female , Humans , Magnetic Resonance Imaging
14.
Ann Rheum Dis ; 64(6): 947-50, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15897313

ABSTRACT

BACKGROUND: The major histocompatibility complex (MHC) class II transactivator (CIITA) is a master switch of antigen presentation and activates expression of the MHC II gene. Insufficient up regulation of MHC class II molecules is reported to be one of the major immunological mechanisms in systemic lupus erythematosus (SLE). OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE. METHODS: Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs. RESULTS: Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A-->A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE. CONCLUSIONS: A newly identified polymorphism in an intronic region at nt 485 (A-->A/G) may have an important role in the pathogenesis of SLE.


Subject(s)
Lupus Erythematosus, Systemic/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Trans-Activators/genetics , Adolescent , Adult , Base Sequence , DNA, Complementary/genetics , Gene Frequency , Genes, MHC Class II , Genetic Predisposition to Disease , Humans , Linkage Disequilibrium , Polymerase Chain Reaction/methods , Promoter Regions, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods
15.
Genes Immun ; 3(7): 394-9, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12424620

ABSTRACT

Recently, we reported that serum concentration of IL-18 is strikingly high in patients with adult-onset Still's disease (AOSD). The aim of the present study was to screen for genetic polymorphisms in the human IL-18 (hIL-18) gene and to determine the association of polymorphisms with susceptibility to AOSD. We investigated the 6.7 kb region upstream of exon 2 of hIL-18 gene, in which a promoter activity had been reported. Sixteen AOSD patients, 144 rheumatoid arthritis (RA) patients and 92 healthy control individuals were studied. We found seven single nucleotide polymorphisms and a single 9 bp insertion which were frequently present in the AOSD patients. Three haplotypes including a unique combination of these polymorphisms were also determined. Of them, haplotype S01 contained all eight of these polymorphisms. The frequency of individuals carrying a diplotype configuration, ie a combination of two haplotypes, of S01/S01 was significantly higher in the AOSD patients than in the healthy controls (P=0.00059, Fischer's exact probability test, odds ratio [OR]=7.81, 95% confidence interval [95% CI]=2.48-24.65) and the RA patients (P=0.015, Fischer's exact probability test, OR=4.0, 95% CI=1.39-11.54). We therefore conclude that possession of the diplotype configuration of S01/S01 is a major genetic risk factor for susceptibility to AOSD.


Subject(s)
Interleukin-18/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Still's Disease, Adult-Onset/genetics , Female , Genetic Predisposition to Disease , Haplotypes , Humans , Introns , Male
16.
J Biochem ; 130(6): 873-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11726289

ABSTRACT

T(1), a mutant yeast lacking three regulatory proteins of F(1)F(o)ATPase, namely ATPase inhibitor, 9K protein and 15K protein, grew on non-fermentable carbon source at the same rate as normal cells but was less viable when incubated in water. During the incubation, the cellular ATP content decreased rapidly in the T(1) cells but not in normal cells, and respiration-deficient cells appeared among the T(1) cells. The same mutation was also induced in D26 cells lacking only the ATPase inhibitor. Overexpression of the ATPase inhibitor in YC63 cells, which were derived from the D26 strain harboring an expression vector containing the gene of the ATPase inhibitor, prevented the decrease of cellular ATP level and the mutation. Isolated T(1) mitochondria exhibited ATP hydrolysis for maintenance of membrane potential when antimycin A was added to the mitochondrial suspension, while normal and YC63 mitochondria continued to show low hydrolytic activity and low membrane potential. Thus, it is likely that deletion of the ATPase inhibitor induces ATPase activity of F(1)F(o)ATPase to create a dispensable membrane potential under the non-nutritional conditions and that this depletes mitochondrial and cellular ATP. The depletion of mitochondrial ATP in turn leads to occurrence of aberrant DNA in mitochondria.


Subject(s)
Adenosine Triphosphate/metabolism , Gene Deletion , Mitochondria/metabolism , Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Adenosine Triphosphate/genetics , Cell Division/genetics , Cell Respiration/genetics , DNA, Mitochondrial/physiology , Hydrolysis , Membrane Potentials/physiology , Mitochondria/genetics , Mitochondria/physiology , Mutation , Proteins/genetics , Proton-Translocating ATPases/antagonists & inhibitors , Saccharomyces cerevisiae/cytology , ATPase Inhibitory Protein
17.
J Biochem ; 130(5): 687-93, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11686932

ABSTRACT

Mitochondrial ATP synthase (F(1)F(o)-ATPase) is regulated by an intrinsic ATPase inhibitor protein. In the present study, we investigated the structure-function relationship of the yeast ATPase inhibitor by amino acid replacement. A total of 22 mutants were isolated and characterized. Five mutants (F17S, R20G, R22G, E25A, and F28S) were entirely inactive, indicating that the residues, Phe17, Arg20, Arg22, Glu25, and Phe28, are essential for the ATPase inhibitory activity of the protein. The activity of 7 mutants (A23G, R30G, R32G, Q36G, L37G, L40S, and L44G) decreased, indicating that the residues, Ala23, Arg30, Arg32, Gln36, Leu37, Leu40, and Leu44, are also involved in the activity. Three mutants, V29G, K34Q, and K41Q, retained normal activity at pH 6.5, but were less active at pH 7.2, indicating that the residues, Val29, Lys34, and Lys41, are required for the protein's action at higher pH. The effects of 6 mutants (D26A, E35V, H39N, H39R, K46Q, and K49Q) were slight or undetectable, and the residues Asp26, Glu35, His39, Lys46, and Lys49 thus appear to be dispensable. The mutant E21A retained normal ATPase inhibitory activity but lacked pH-sensitivity. Competition experiments suggested that the 5 inactivated mutants (F17S, R20G, R22G, E25A, and F28S) could still bind to the inhibitory site on F(1)F(o)-ATPase. These results show that the region from the position 17 to 28 of the yeast inhibitor is the most important for its activity and is required for the inhibition of F(1), rather than binding to the enzyme.


Subject(s)
Enzyme Inhibitors/metabolism , Proteins/metabolism , Saccharomyces cerevisiae/chemistry , Amino Acid Motifs , Amino Acid Sequence , Amino Acid Substitution , Animals , Binding, Competitive , Cattle , Enzyme Inhibitors/chemistry , Histidine/genetics , Humans , Lysine/genetics , Mice , Mitochondrial Proton-Translocating ATPases/antagonists & inhibitors , Molecular Sequence Data , Mutagenesis , Phenylalanine/genetics , Phenylalanine/metabolism , Proteins/chemistry , Proteins/genetics , Rats , Sequence Homology, Amino Acid , Structure-Activity Relationship , ATPase Inhibitory Protein
18.
Acta Med Okayama ; 55(5): 261-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11688948

ABSTRACT

A prospective study was performed to determine the accuracy of magnetic resonance imaging (MRI) compared with operative findings in the evaluation of patients associated with rotator cuff tears. Fifty-four of 60 shoulders (58 patients) examined by MRI were confirmed as full-thickness tears and 6 as partial-thickness tears at the time of surgery. The oblique coronal, oblique sagittal, and axial planes of T2-weighted images with the 0.5 tesla MRI system were obtained preoperatively and compared with operative findings. MRI correctly identified 46 of 54 full-thickness rotator cuff tears and 5 of 6 partial-thickness tears. A comparison of MRI and operative findings in full-thickness cuff tears showed a sensitivity of 85%, a specificity of 83%, and a positive prospective value (PPV) of 99%. A comparison of partial-thickness tears showed a sensitivity of 83%, a specificity of 85%, and PPV of 39%. Linear regression analysis showed an excellent correlation between the MRI assessment and measurement at the time of surgery (r = 0.90, P < 0.01). MRI was useful in evaluating large and medium-sized rotator cuff tears, but less useful in distinguishing small full-thickness tears from partial-thickness tears.


Subject(s)
Magnetic Resonance Imaging , Rotator Cuff Injuries , Rotator Cuff/pathology , Wounds and Injuries/diagnosis , Adult , Aged , Aged, 80 and over , Arthrography , Female , Humans , Male , Middle Aged , Prospective Studies , Rotator Cuff/surgery , Sensitivity and Specificity , Wounds and Injuries/pathology , Wounds and Injuries/surgery
19.
Hand Surg ; 6(1): 109-11, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11677673

ABSTRACT

We present a case report of a 15-year-old kendo (Japanese fencing) player who suffered a stress fracture of the ulnar styloid process. Exercise of the kendo requires the athlete to flex his non-dominant wrist repeatedly in an ulnar direction, and causes the disorder. Excision of the osteochondral fragment relieved the symptoms. This lesion is likely to occur with other sports or activities which demand similar motion of the wrists.


Subject(s)
Athletic Injuries/surgery , Fractures, Stress/surgery , Ulna Fractures/surgery , Wrist Injuries/surgery , Adolescent , Athletic Injuries/diagnosis , Fracture Fixation, Internal/methods , Fracture Healing/physiology , Fractures, Stress/diagnostic imaging , Humans , Japan , Male , Radiography , Range of Motion, Articular , Treatment Outcome , Ulna Fractures/diagnostic imaging , Wrist Injuries/diagnostic imaging
20.
J Immunol ; 167(8): 4504-10, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11591777

ABSTRACT

Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of host defense against pathogens and it requires MBL-associated serine protease (MASP) for activation of the complement lectin pathway. To elucidate the origin and evolution of MBL, MBL-like lectin was isolated from the plasma of a urochordate, the solitary ascidian Halocynthia roretzi, using affinity chromatography on a yeast mannan-Sepharose. SDS-PAGE of the eluted proteins revealed a major band of approximately 36 kDa (p36). p36 cDNA was cloned from an ascidian hepatopancreas cDNA library. Sequence analysis revealed that the carboxy-terminal half of the ascidian lectin contains a carbohydrate recognition domain (CRD) that is homologous to C-type lectin, but it lacks a collagen-like domain that is present in mammalian MBLs. Purified p36 binds specifically to glucose but not to mannose or N-acetylglucosamine, and it was designated glucose-binding lectin (GBL). The two ascidian MASPs associated with GBL activate ascidian C3, which had been reported to act as an opsonin. The removal of GBL-MASPs complex from ascidian plasma using Ab against GBL inhibits C3-dependent phagocytosis. These observations strongly suggest that GBL acts as a recognition molecule and that the primitive complement system, consisting of the lectin-proteases complex and C3, played a major role in innate immunity before the evolution of an adaptive immune system in vertebrates.


Subject(s)
Carrier Proteins/metabolism , Complement Activation , Complement C3/metabolism , Lectins/metabolism , Urochordata/immunology , Amino Acid Sequence , Animals , Carrier Proteins/blood , Collectins , Digestive System , Evolution, Molecular , Gene Library , Lectins/blood , Lectins/isolation & purification , Mannose-Binding Protein-Associated Serine Proteases , Molecular Sequence Data , Protein Binding , Sequence Homology, Amino Acid , Serine Endopeptidases/metabolism
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