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1.
Acta Orthop Belg ; 89(3): 469-475, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37935231

RESUMO

Intravenous acetaminophen is an integral component of multimodal postoperative pain management. This prospective study aims to assess the efficacy of the repeated administration of intravenous acetaminophen and the impact on postoperative patient satisfaction with postoperative pain management after total knee arthroplasty (TKA). We enrolled 98 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals (AAP group) or not to receive intravenous acetaminophen (control group). All patients underwent single-shot femoral nerve block after general anesthesia, as well as intraoperative periarticular infiltration of analgesia prior to implantation. The primary outcome was the postoperative numerical rating scale (NRS) pain score at rest. The NRS score was measured just before the administration of study drugs, immediately after arrival in the ward (time 0), and at 6, 12, 18, 24, and 48 h (time 1 to time 5, respectively) postoperatively. We also evaluated the mean doses of rescue opioid use for 24 h postoperatively. At time 5, the AAP group had significantly improved mean NRS score than controls (3.0 vs. 4.0; P < 0.01). Rescue opioid use was significantly lower in the AAP group for 24 hours compared to controls (0.3 µg vs. 0.9 µg; P < 0.01). Repeated intravenous acetaminophen administration after TKA may provide better analgesia and reduce opioid use.


Assuntos
Acetaminofen , Artroplastia do Joelho , Humanos , Acetaminofen/uso terapêutico , Manejo da Dor , Artroplastia do Joelho/efeitos adversos , Analgésicos Opioides/uso terapêutico , Estudos Prospectivos , Dor Pós-Operatória/tratamento farmacológico
2.
Phys Chem Chem Phys ; 22(46): 27191-27205, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33226053

RESUMO

Domain-based local pair natural orbital (DLPNO) coupled cluster single and double (CCSD) with triple perturbation (T) correction methods were performed to elucidate the relative stabilities of ten different intermediate structures of the CaMn4Ox cluster in the S0 state of the oxygen evolving complex (OEC) of photosystem II (PSII). Full geometry optimizations of all the S0 intermediates were performed by the UB3LYP-D3/Def2-TZVP methods, providing the assumed geometrical structures and starting natural orbitals (UNO) for DLPNO-CCSD(T)/Def2TZVP calculations. The effective exchange integrals (J) for the spin Hamiltonian models for the ten intermediates were obtained by the UB3LYP/Def2-TZVP calculations followed by the general spin projections. DLPNO-CCSD(T) calculations followed by the CBS extrapolation procedure elucidated that the (II, III, IV, IV) and (III, III, III, IV) valence states in the CaMn4O5 cluster of the OEC of the PS II were nearly degenerated in energy in the S0 state, indicating an important role of dynamical electron correlation effects for the valence and spin fluctuations in strongly correlated electron systems (SCESs) consisting of 3d transition metals.


Assuntos
Cálcio/química , Manganês/química , Oxigênio/química , Complexo de Proteína do Fotossistema II/química , Proteínas de Bactérias/química , Teoria da Densidade Funcional , Modelos Químicos , Domínios Proteicos , Prótons , Termodinâmica , Thermosynechococcus/enzimologia
3.
Am J Transplant ; 17(9): 2338-2349, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28251796

RESUMO

Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin-KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D-ligand in allografts and demonstrated the significance of this using grafts expressing Rae-1, a murine NKG2D-ligand, which induced severe bronchiolitis obliterans in WT and Rag-1 KO recipients. This effect was ameliorated by injection of anti-NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.


Assuntos
Bronquiolite Obliterante/etiologia , Modelos Animais de Doenças , Rejeição de Enxerto/etiologia , Células Matadoras Naturais/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Traqueia/transplante , Transplante Heterotópico/efeitos adversos , Animais , Bronquiolite Obliterante/metabolismo , Bronquiolite Obliterante/patologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Proteínas de Homeodomínio/fisiologia , Imunidade Celular , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos SCID
4.
Br J Dermatol ; 177(1): 141-151, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27716903

RESUMO

BACKGROUND: IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes. OBJECTIVES: To develop reliable enzyme-linked immunosorbent assays (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features. METHODS: We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amounts of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of the IgE ELISAs were statistically compared with various ELISAs and various clinical parameters, including our own severity scores and BP phenotypes. RESULTS: IgG adsorption generally showed no changes in sensitivity and specificity for IgE ELISAs, although slight cross-reactivity of anti-IgE secondary antibody to IgG and interference of excess amounts of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti-BP180 antibodies correlated with disease activity but IgG and IgE anti-BP230 autoantibodies did not. IgE anti-BP230 autoantibodies correlated with nodular phenotype but not erythematous phenotype. CONCLUSIONS: The results of this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti-BP180 autoantibodies seemed to be pathogenic, while an association between IgE autoantibodies and inflammatory BP phenotype was not indicated.


Assuntos
Autoanticorpos/metabolismo , Autoantígenos/imunologia , Distonina/imunologia , Imunoglobulina E/imunologia , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Índice de Gravidade de Doença , Colágeno Tipo XVII
5.
J Fish Biol ; 90(4): 1533-1547, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28097653

RESUMO

The embryonic development of the Japanese eel Anguilla japonica and pike eel Muraenesox cinereus was morphologically investigated with laboratory-reared specimens to clarify the characteristics of somitogenesis. In A. japonica, somites were first observed at 18 h post fertilization (hpf) when epiboly reached 90%. Somitogenesis progressed at a rate of 1·6 h-1 at mean ± s.d. 22·6 ± 0·7° C and completed at 107 hpf (3 days post hatching; dph) when total number of somites (ST) reached 114, which corresponds to the species' number of vertebrae (112-119). In M. cinereus, somites were first observed at 14 hpf when epiboly completed. Somitogenesis progressed at a rate of 1·9 h-1 at mean ± s.d. 24·4 ± 0·2° C and completed at 90 hpf (2 dph) with 149 ± 4 ST, which corresponds to the species' number of vertebrae (142-158). Both species hatched before somitogenesis was completed, at 37 hpf with 47 ST and 42 hpf with 82 ± 4 ST, respectively. The formation of other organs such as the heart, mouth and pectoral fin bud occurred during somitogenesis. Comparison with the development of zebrafish Danio rerio indicates a prolongation of somitogenesis in A. japonica and M. cinereus. Their somitogenesis rates, however, correspond well with that of D. rerio estimated at the same temperature and their developmental stages at hatching are almost equivalent to other fishes having similar yolk sizes. Therefore, the prolongation of somitogenesis in A. japonica and M. cinereus may be accounted for solely by the increased numbers of somites to be formed, not by a slow somitogenesis rate or an acceleration in organogenesis.


Assuntos
Anguilla/embriologia , Anguilla/genética , Desenvolvimento Embrionário/fisiologia , Organogênese/fisiologia , Animais , Especificidade da Espécie
7.
Br J Dermatol ; 172(1): 120-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25154546

RESUMO

BACKGROUND: Systematic study of pemphigoid gestationis (PG) has not been performed owing to its rarity. OBJECTIVES: To perform clinical and immunological analyses of 25 patients with PG. METHODS: In addition to clinical and histopathological assessments, we performed immunofluorescence (IF), immunoblotting (IB) and enzyme-linked immunosorbent assays (ELISAs). RESULTS: PG developed preferentially during the second or third trimester of pregnancy, with a mean age at onset of 30·5 years. Histopathology showed subepidermal blisters less frequently. Direct IF showed C3 deposition in the basement membrane zone (BMZ) in all patients, with rare reactivity with keratinocyte cell surfaces. Ninety-two per cent of patients showed circulating IgG anti-BMZ autoantibodies during indirect IF of either normal or 1 mol L(-1) NaCl-split skin. Complement IF revealed linear C3 reactivity with the BMZ of normal skin in 68% of patients, and all patients had C3 reactivity on the epidermal side of 1 mol L(-1) NaCl-split skin. IB and ELISA of the NC16a domain of BP180 recombinant protein was positive in 96% and 92% of patients, respectively, while only four patients had a positive ELISA for BP230. In IB tests, 28% of patients reacted with the C-terminal domain of BP180 and 20% reacted with leucocyte adhesion deficiency-1 protein. Multigravidae developed PG during a significantly (P < 0·01) earlier stage (21·1 weeks) of pregnancy than primigravidae (31·3 weeks). CONCLUSIONS: IB and ELISA of the NC16a domain of BP180 were shown to be sensitive and diagnostic methods in PG. Patients with PG rarely reacted with BP230, suggesting a different pathogenesis between PG and bullous pemphigoid. Multigravidae developed PG skin lesions significantly earlier in pregnancy than primigravidae.


Assuntos
Penfigoide Gestacional/imunologia , Adulto , Idade de Início , Fármacos Dermatológicos/uso terapêutico , Feminino , Número de Gestações , Humanos , Penfigoide Gestacional/tratamento farmacológico , Gravidez , Cuidado Pré-Natal , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Br J Dermatol ; 173(6): 1447-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26358412

RESUMO

BACKGROUND: Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported. OBJECTIVES: To analyse the clinical and immunological findings in a large cohort of patients with PNP. METHODS: This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assays (ELISAs) were analysed. RESULTS: The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty-two (60%) of 53 patients had antibodies to alpha-2-macroglobulin-like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans. CONCLUSIONS: We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.


Assuntos
Síndromes Paraneoplásicas/imunologia , Pênfigo/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/metabolismo , Criança , Desmocolinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/diagnóstico , Pênfigo/complicações , Pênfigo/diagnóstico , Prognóstico , Estudos Retrospectivos , Adulto Jovem , alfa-Macroglobulinas/imunologia
9.
Br J Dermatol ; 173(1): 59-68, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25640111

RESUMO

BACKGROUND: Despite the established pathogenic role of anti-desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed. OBJECTIVES: The aim of this study was to develop reliable assays to detect anti-Dsc autoantibodies. METHODS: We expressed soluble recombinant proteins (RPs) of human Dsc1-3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme-linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs. RESULTS: Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16.5%, 36.7% and 59.5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc-positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre-absorption with Dsg RPs. CONCLUSIONS: The results of these novel ELISAs indicated that IgG anti-Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.


Assuntos
Autoanticorpos/sangue , Desmocolinas/imunologia , Pênfigo/imunologia , DNA Complementar/análise , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulina G/sangue , Imunoprecipitação/métodos , Curva ROC , Proteínas Recombinantes , Transfecção
10.
Phys Rev Lett ; 110(15): 157205, 2013 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-25167306

RESUMO

We have succeeded in synthesizing single crystals of a new organic radical 3-Cl-4-F-V [3-(3-chloro-4-fluorophenyl)-1,5-diphenylverdazyl]. Through the ab initio molecular orbital calculation and the analysis of the magnetic properties, this compound was confirmed to be the first experimental realization of an S=1/2 spin-ladder system with ferromagnetic leg interactions. The field-temperature phase diagram indicated that the ground state is situated very close to the quantum critical point. Furthermore, we found an unexpected field-induced successive phase transition, which possibly originates from the interplay of low dimensionality and frustration.

11.
Clin Exp Dermatol ; 38(7): 730-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24073654

RESUMO

BACKGROUND: The long-term prognosis of Henoch-Schönlein purpura (HSP) is determined by the severity of renal involvement, known as HSP nephritis, which varies considerably from patient to patient. There is now increasing evidence that dysregulated cytokine production plays a crucial role in human autoimmune and inflammatory processes. AIM: To explore the possible contributions of serum antistreptolysin O, C-reactive protein, IgA, interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α, anticardiolipin antibody (aCL) and antiphosphatidylserine-prothrombin complex antibody (anti-PSPT) in the pathogenesis of HSP, and to evaluate correlations between those biological parameters and the clinical features. METHODS: Records were reviewed of 58 patients with HSP who presented initially with palpable purpura between 2003 and 2009. Serum IL-6 levels were determined by chemiluminescent enzyme immunoassay, IL-8 levels by ELISA and TNF-α levels by quantitative sandwich enzyme immunoassay. Serum aCL and anti-PSPT levels were measured according to our previously published procedures. RESULTS: There was a significant correlation between the serum IL-6 and IgA anti-PSPT levels, and also between the serum IL-8 and IgA anti-PSPT levels. Serum IL-8 and IgA aCL levels were both significantly higher in patients with renal involvement than in those without. Serum IL-6 and IgM anti-PSPT levels were also significantly higher in patients with gastrointestinal symptoms than in those without. CONCLUSIONS: We suggest that serum IL-6 and IL-8 associated with antiphospholipid antibodies play a pivotal role in the induction of HSP. Based on our results, IL-8 and IgA aCL levels could be useful as markers to monitor the development of HSP nephritis, and IL-6 and IgM anti-PSPT levels could be used as markers to monitor the development of gastrointestinal involvement.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Vasculite por IgA/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antiestreptolisina/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Vasculite por IgA/imunologia , Imunoglobulina A/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa , Adulto Jovem
12.
Clin Exp Dermatol ; 38(4): 370-3, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23517469

RESUMO

A 79-year-old Japanese woman presented with severe recalcitrant erosions on her oral mucosa, resembling paraneoplastic pemphigus. Using indirect immunofluorescence, we detected IgA antibodies against the cell surface, and both IgG and IgA antibodies against the basement membrane zone. Immunoblotting showed that the IgG antibodies reacted weakly with bullous pemphigoid 230 and periplakin, whereas the IgA antibodies did not react with any antigen. IgA antibodies to both desmoglein (Dsg)1 and Dsg3 were detected by ELISA. IgA antibodies to desmocollin (Dsc)3 were also detected by using cDNAs for human Dsc1-3 transfected into COS-7 cells. Despite treatment with oral prednisolone, high-dose intravenous immunoglobulin and double-filtration plasmapheresis, the skin lesions remained active, and the patient died from bronchiolitis obliterans-like respiratory failure. Despite extensive investigations and postmortem examination, no underlying neoplasms were found. The complex immunopathological findings probably played an important role in the development of the patient's unusual clinical features.


Assuntos
Membrana Basal/imunologia , Caderinas de Desmossomos/imunologia , Imunoglobulina A/imunologia , Neoplasias Bucais/imunologia , Síndromes Paraneoplásicas/imunologia , Penfigoide Bolhoso/imunologia , Idoso , Desmocolinas/imunologia , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Evolução Fatal , Feminino , Humanos , Imunoglobulina G/imunologia
13.
Nat Genet ; 16(4): 391-6, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9241280

RESUMO

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.


Assuntos
Desenvolvimento Ósseo/fisiologia , Transtornos do Crescimento , Receptores de Calcitriol/fisiologia , Útero/anormalidades , Alopecia/etiologia , Alopecia/genética , Animais , Peso Corporal , Desenvolvimento Ósseo/genética , Calbindinas , Linhagem Celular , Durapatita/farmacologia , Feminino , Deleção de Genes , Expressão Gênica , Transtornos do Crescimento/genética , Humanos , Masculino , Camundongos , Osteopontina , Receptores de Calcitriol/genética , Raquitismo , Proteína G de Ligação ao Cálcio S100/genética , Sialoglicoproteínas/genética , Desmame
14.
Eur J Paediatr Dent ; 14(4): 263-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24313575

RESUMO

AIM: Few studies have examined psychological stress and personal anxiety in children exhibiting cooperative behaviour during dental treatment. We assessed psychological stress and personal anxiety during dental treatment in cooperative children, and investigated the influence of various factors. MATERIALS AND METHODS: We measured pre- and post-treatment salivary alpha amylase (sAA) levels of 28 children aged 8-13 years and their parents. Children completed the State-Trait Anxiety Inventory for Children (STAIC); their parents completed the STAI. The IA group included children whose sAA levels increased >10%, whereas the DA group included children whose sAA levels decreased >10%. We used regression models to calculate the power of variables to predict children's psychological stress. RESULTS: The mean anxiety trait score in the IA group was significantly higher than in the DA group (t-test, P = 0.021). For children with higher STAIC-Trait scores, the OR for increasing sAA was 1.16 (95% CI [1.02-1.31]). Parental or treatment factors did not significantly contribute to incremental sAA levels in children. CONCLUSION: Well-behaved children with high anxiety traits may experience high stress levels during dental treatment; however, parental and dental treatment factors may not affect psychological stress in these children.


Assuntos
Comportamento Cooperativo , Ansiedade ao Tratamento Odontológico/psicologia , Assistência Odontológica para Crianças/psicologia , Estresse Psicológico , Criança , Comportamento Infantil , Relações Dentista-Paciente , Feminino , Humanos , Modelos Logísticos , Masculino , Projetos Piloto , Saliva/enzimologia , alfa-Amilases/análise
15.
ESMO Open ; 8(6): 102071, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38016249

RESUMO

BACKGROUND: Nivolumab therapy is a standard-of-care treatment for heavily pretreated patients with advanced gastric cancer (AGC). Previous studies have reported improvement in the objective response rate to chemotherapy after nivolumab therapy for other types of cancer. This study evaluated the efficacy and safety of chemotherapy after nivolumab therapy in AGC. PATIENTS AND METHODS: We conducted a prospective, multicenter, observational study in pretreated patients with nivolumab-refractory or -intolerant AGC. Patients received irinotecan, oxaliplatin-containing regimens, or trifluridine/tipiracil. The primary endpoint was overall survival. RESULTS: A total of 199 patients were included (median age: 69 years; male: 70%; female: 30%). Median overall survival and progression-free survival were 7.5 months [95% confidence interval (CI): 6.7-9.7 months] and 2.9 months (95% CI: 2.2-3.5 months), respectively. Objective response and disease control rates were 16.8% (95% CI: 11.6% to 23.6%) and 18.9% (95% CI: 38.9% to 54.6%), respectively. A prognostic index using alkaline phosphatase and the Glasgow Prognostic Score was generated to classify patients into three risk groups (good, moderate, and poor). The hazard ratios of the moderate and poor groups to the good group were 1.88 (95% CI: 1.22-2.92) and 3.29 (95% CI: 1.92-5.63), respectively. At the initiation of chemotherapy, 42 patients had experienced immune-related adverse events due to prior nivolumab therapy. The most common grade 3-4 adverse events were neutropenia (7.5%), anemia (8.0%), and anorexia (7.5%). CONCLUSIONS: The administration of cytotoxic chemotherapy after nivolumab therapy may give rise to a synergistic antitumor effect in AGC. Further investigation is warranted to confirm these findings.


Assuntos
Nivolumabe , Neoplasias Gástricas , Humanos , Masculino , Feminino , Idoso , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Estudos Prospectivos , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Prognóstico
16.
Br J Dermatol ; 166(6): 1206-12, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22309950

RESUMO

BACKGROUND: Henoch-Schönlein purpura (HSP) is characterized by IgA-containing immune complexes within leucocytoclastic vasculitis. Lysosomal-associated membrane protein-2 (LAMP-2) was first identified as part of a systematic search for antineutrophil cytoplasmic antibody (ANCA) antigens expressed on neutrophils and endothelial cells. OBJECTIVES: To investigate the presence of ANCA in patients with adult HSP and microscopic polyangiitis (MPA), and to measure serum LAMP-2 antibody levels in these patients. METHODS: Twenty-four adult patients with HSP, eight with MPA and 24 normal healthy controls were examined. ANCA detection was performed using indirect immunofluorescence (IIF), a direct enzyme-linked immunosorbent assay (ELISA) and a capture ELISA specific for myeloperoxidase (MPO) and proteinase 3 (PR3). We measured other ANCA-associated antibodies including anti-LAMP-2 antibody in serum using ELISA. Immunohistochemical (IHC) staining was used for anti-LAMP-2 antibody expression in patient skin biopsies. To determine the cut-off value of the serum anti-LAMP-2 antibody, a receiver operating characteristic (ROC) curve was constructed using statistical analysis software (JMP 8·0·2; SAS Institute Inc., Cary, NC, U.S.A.). RESULTS: The sera of all patients with HSP were negative for MPO-ANCA and PR3-ANCA by direct ELISA and by capture ELISA. However, ANCA was present in 17 (71%) of the 24 patients with HSP based on IIF. In contrast, we found MPO-ANCA in all eight patients with MPA using both ELISA methods. We found serum anti-LAMP-2 antibody levels in HSP significantly higher than in MPA and in healthy individuals (P = 0·002 and P = 0·00167, respectively). The area under the curve of serum anti-LAMP-2 antibody between HSP and MPA was 0·8698 by ROC analysis. The optimal cut-off point was 0·267 U mL(-1) (sensitivity 1·000, specificity 0·583). We found a significant positive correlation between serum anti-LAMP-2 antibody levels and serum IgA levels in HSP (r(s) = 0·731, P = 0·00226). Anti-LAMP-2 antibody overexpression in IHC staining was present in 20 (83%) of the patients with HSP. The overexpression was observed within the neutrophils and endothelial cells of leucocytoclastic vasculitis. There was a significant positive correlation between IHC staining score and positive serum anti-LAMP-2 antibody. The 24 patients with HSP and the eight patients with MPA were negative for antiazurocidin antibodies, antibactericidal permeability increasing protein antibodies, anticathepsin G antibodies, antielastase antibodies, antilactoferrin antibodies and antilysozyme antibodies. CONCLUSIONS: We suggest that anti-LAMP-2 antibody could play some role in the pathogenesis of adult HSP, and have excluded a role for MPO-ANCA and PR3-ANCA. We propose that measuring serum anti-LAMP-2 antibody could be a feasible method of differential diagnosis between HSP and MPA.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Vasculite por IgA/imunologia , Proteína 2 de Membrana Associada ao Lisossomo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Heredity (Edinb) ; 107(3): 215-30, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21343944

RESUMO

The evolution of subterranean animals following multiple colonisation events from the surface has been well documented, but few studies have investigated the potential for species diversification within cavernicolous habitats. Isolated calcrete (carbonate) aquifers in central Western Australia have been shown to contain diverse assemblages of aquatic subterranean invertebrate species (stygofauna) and to offer a unique model system for exploring the mechanisms of speciation in subterranean ecosystems. In this paper, we investigated the hypothesis that microallopatric speciation processes (fragmentation and isolation by distance (IBD)) occur within calcretes using a comparative phylogeographic study of three stygobiontic diving beetle species, one amphipod species and a lineage of isopods. Specimens were sequenced for the mitochondrial cytochrome c oxidase 1 gene from three main sites: Quandong Well, Shady Well (SW) and Mt. Windarra (MW), spanning a 15 km region of the Laverton Downs Calcrete. Phylogenetic and haplotype network analyses revealed that each species possessed a single divergent clade of haplotypes that were present only at the southern MW site, despite the existence of other haplotypes at MW that were shared with SW. IBD between MW and SW was evident, but the common phylogeographic pattern most likely resulted from fragmentation, possibly by a salt lake adjacent to MW. These findings suggest that microallopatric speciation within calcretes may be a significant diversifying force, although the proportion of stygofauna species that may have resulted from in situ speciation in this system remains to be determined.


Assuntos
Anfípodes/genética , Besouros/genética , Ecossistema , Especiação Genética , Isópodes/genética , Animais , Austrália , Sequência de Bases , DNA Mitocondrial/análise , DNA Mitocondrial/genética , Evolução Molecular , Variação Genética , Água Subterrânea , Haplótipos , Filogenia , Filogeografia , Análise de Sequência de DNA
18.
Eur J Med Res ; 16(7): 328-30, 2011 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-21813374

RESUMO

We aimed to evaluate the subcutaneous tissue reaction to a newly developed adhesive silicone denture relining material, SG, (Neo Dental Chemical Products Co., Ltd. Tokyo, Japan). We embedded the experimental material SG and another existing control material, Roeko Seal (RS), in the dorsal area of 22 male ddY mice. One week and 12 weeks after the embedding, the tissues surrounding the embedded materials were removed and a histopathological examination was performed. The results demonstrate that the basic histopathological aspects are the formation of granulation tissue and the change of the tissue to fibrous capsule over time. The results suggests that the newly-developed SG is safe as compared with the control RS, whose composition is similar.


Assuntos
Materiais Biocompatíveis , Reembasadores de Dentadura , Reembasamento de Dentadura , Tecido de Granulação/patologia , Silicones , Adesivos , Animais , Masculino , Camundongos
19.
Eur J Med Res ; 16(12): 526-30, 2011 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-22112358

RESUMO

We aimed to evaluate the subcutaneous tissue reaction to a newly-developed MgO Sealer for root canals. We injected the experimental material and three existing control materials into the dorsal area of 43 male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding sites was removed and histopathological examination was performed. The results demonstrate that the basic histopathological reaction is the formation of fibrous capsules consisting of granulation tissue around the experimental and control embedded materials. Based on our results, we believe that the newly-developed MgO Sealer is as safe as the existing control materials and can be considered for dental use as a root canal sealer.


Assuntos
Materiais Restauradores do Canal Radicular/farmacologia , Animais , Tecido de Granulação/efeitos dos fármacos , Tecido de Granulação/patologia , Óxido de Magnésio/farmacologia , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos , Materiais Restauradores do Canal Radicular/efeitos adversos , Tela Subcutânea/efeitos dos fármacos
20.
Caries Res ; 45(6): 561-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22067411

RESUMO

OBJECTIVES: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on caries risk and experimental dental caries. METHODS: Experimental dental caries was induced in rat maxillary molars which were inoculated orally with Streptococcus mutans MT8148 and maintained on a cariogenic diet (diet 2000) and high sucrose water during the experimental period. CS-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (day 0) and for 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. Maxillary molars were harvested on day 31. RESULTS: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rate, concentration of S. mutans in the stimulated saliva and caries activity score did not significantly differ between 0 and 30 days after the start of CS exposure. Histological examination of the caries-affected area on maxillary molars 30 days after CS exposure showed expansion compared to control rats. In the electron probe microanalysis, no differences were observed between the mineral components of the CS-exposed teeth and the control teeth. CONCLUSION: These results suggest that CS exposure expands the caries-affected area in the maxillary molars of the rat.


Assuntos
Cárie Dentária/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Cotinina/análise , DNA Bacteriano/análise , Testes de Atividade de Cárie Dentária , Dieta Cariogênica , Progressão da Doença , Corantes Fluorescentes , Masculino , Maxila , Dente Molar/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Rodaminas , Saliva/química , Saliva/metabolismo , Saliva/microbiologia , Taxa Secretória , Streptococcus mutans , Redução de Peso
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