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1.
World Neurosurg ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32599180

RESUMO

BACKGROUND: The endoscopic approach, chiefly via the maxillary sinus, has growing applications for the lateral skull base, and can be classified into the use of "endonasal" or "sublabial" entry. While the "endonasal" transmaxillary approach has been well-accepted, it has a limitation with respect to the lateral exposure. A possible solution is the use of the "sublabial" transmaxillary approach via the canine fossa, which assures lateral accessibility. In clinical practice, we have taken advantage of the concomitant use of the endonasal and sublabial transmaxillary approach for selected patients harboring lateral skull base lesions. In addition to binostril pathways, canine fossa trephination was constructed to facilitate this combined approach, termed the endoscopic triportal transmaxillary approach (ETTA). METHODS: The efficacy of the ETTA was evaluated within a case series. A single-institution retrospective analysis was performed in patients with lateral middle skull base tumors treated via ETTA. RESULTS: In clinical practice, four patients were eligible for the study, including one receiving a combined endoscopic and transcranial approach. No major complications occurred in patients included in this series. The ETTA facilitated the dynamic manipulation of instruments, which led to rapid hemostasis and the satisfactory surgical resection of tumors. Furthermore, it reduced intraoperative postural stress experienced by the surgeons who performed the procedures. CONCLUSIONS: The concomitant use of the trans-canine fossa approach effectively ameliorated significant technical challenges that tend to occur when using a purely endonasal approach. The ETTA can be an attractive option for treating lateral and middle skull base lesions.

2.
J Allergy Clin Immunol ; 145(3): 843-854.e4, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035658

RESUMO

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis. Clinical markers for ECRS disease activity and treatment strategies have not been sufficiently established. Although semaphorins are originally identified as neuronal guidance factors, it is becoming clear that they play key roles in immune regulation and inflammatory diseases. OBJECTIVE: We sought to investigate the pathological functions and therapeutic potential of semaphorin 4D (SEMA4D) in ECRS. METHODS: Serum soluble SEMA4D levels in patients with paranasal sinus diseases were measured by ELISA. The expression of SEMA4D in blood cells and nasal polyp tissues was assessed by flow cytometry and immunohistochemistry, respectively. Generation of soluble SEMA4D was evaluated in matrix metalloproteinase-treated eosinophils. Endothelial cells were stimulated with recombinant SEMA4D, followed by eosinophil transendothelial migration assays. Allergic chronic rhinosinusitis was induced in mice using Aspergillus protease with ovalbumin. The efficacy of treatment with anti-SEMA4D antibody was evaluated histologically and by nasal lavage fluid analysis. RESULTS: Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Tissue-infiltrated eosinophils in nasal polyps from patients with ECRS stained strongly with anti-SEMA4D antibody. Cell surface expression of SEMA4D on eosinophils from patients with ECRS was reduced, which was due to matrix metalloproteinase-9-mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model. CONCLUSIONS: Eosinophil-derived SEMA4D aggravates ECRS. Levels of serum SEMA4D reflect disease severity, and anti-SEMA4D antibody has therapeutic potential as a treatment for ECRS.

4.
Int Immunol ; 31(1): 33-40, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30239772

RESUMO

Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by intractable nasal polyp formation. Eosinophil-derived neurotoxin (EDN) is an eosinophil granule protein that is closely related to allergic inflammation, but the pathological implications of EDN in ECRS remain unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and assessed its potential as a disease activity marker. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases, and were positively correlated with clinical disease activity. Production of EDN from isolated human eosinophils was induced by stimulation with IL-5 in vitro. Human nasal epithelial cells were stimulated with EDN, and the resultant changes in gene expression were detected by RNA sequencing. Pathway analysis revealed that the major canonical pathway affected by EDN stimulation was 'regulation of the epithelial-mesenchymal transition pathway'; the only gene in this pathway to be up-regulated was matrix metalloproteinase 9 (MMP-9). Consistent with this, immunostaining analysis revealed intense staining of both EDN and MMP-9 in nasal polyps from patients with ECRS. In conclusion, our data demonstrate that serum EDN level is a useful marker for the evaluation of ECRS severity. Furthermore, EDN induces production of MMP-9 from the nasal epithelium, which may be involved in the pathogenesis of ECRS.


Assuntos
Remodelação das Vias Aéreas , Neurotoxina Derivada de Eosinófilo/metabolismo , Eosinófilos/imunologia , Eosinófilos/metabolismo , Rinite/etiologia , Rinite/metabolismo , Sinusite/etiologia , Sinusite/metabolismo , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Degranulação Celular/imunologia , Doença Crônica , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Contagem de Leucócitos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Rinite/diagnóstico , Índice de Gravidade de Doença , Sinusite/diagnóstico
5.
J Allergy Clin Immunol ; 143(3): 1163-1175.e15, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30053529

RESUMO

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown. OBJECTIVE: We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs. METHODS: IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin. RESULTS: About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A TH2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA1. The Iε-Cα1 circle transcript was detected in NPs. CONCLUSIONS: In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA1-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.


Assuntos
Linfócitos B/imunologia , Bactérias/imunologia , Imunidade nas Mucosas , Imunoglobulina E/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Células Cultivadas , Doença Crônica , Eosinofilia/imunologia , Eosinofilia/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/microbiologia , Pólipos Nasais/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Adulto Jovem
7.
Nihon Jibiinkoka Gakkai Kaiho ; 117(2): 103-10, 2014 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-24720157

RESUMO

Surgical site infection (SSI) is a common complication in head and neck surgeries. The aim of this study was to assess the rate of, and risk factors for SSI following surgical procedures of the head and neck. The study population comprised 206 patients who underwent surgery of head and neck region in NTT West Osaka Hospital between 2009 and 2011. The incidence rate and risk factors were estimated by the chi-square test and a logistic regression analysis. SSI occurred in 22 cases (10.8%) of 203 patients. A broad range of putative risk factors was recorded in each patient and statistically analyzed to elucidate SSI related factors. Univariate analysis indicated that low BMI, diabetes mellitus, anemia, hypoalbuminemia, surgical wound classification, duration of operation, blood loss, left implants and preoperative radiotherapy were risk factors associated with SSI. Multivariate statistics revealed four independent risk factors: surgical wound classification (odds ratio (OR) 5.88, p = 0.02), hypoalbuminemia (OR 11.48, p < 0.01), duration of operation (OR 18.66, p < 0.01) and left implants (OR 20.24, p < 0.01). Thus, to achieve a reduction in SSI, we need to take care of not only the factors related with surgical technique such as the duration of the operation or left implants, but the preoperative nutrition status.


Assuntos
Cabeça/cirurgia , Pescoço/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Influenza Other Respir Viruses ; 6(6): 396-403, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22226319

RESUMO

OBJECTIVES: To determine the induction and changes in anti-influenza virus secretory IgA (s-IgA) levels in nasal washes and serum IgG levels in patients with influenza. METHODS: The study recruited 16 patients with influenza aged 35.6 ± 9.6 years in 2007/2008 and 2008/2009 seasons. Nasal washes and serum were obtained throughout the first year. Anti-viral s-IgA levels and neutralization activities in nasal washes, and serum anti-viral IgG levels and hemagglutination inhibition (HI) titers were measured. RESULTS: Anti-viral(H1N1) s-IgA to total IgA ratio and neutralizing antibody titer were low in nasal washes of all patients, whereas serum levels of anti-viral IgG and HI titers varied widely at day 1.4 ± 1.0 postinfection. Both nasal s-IgA and serum IgG levels later increased significantly, reaching peak levels at day 9.6 ± 3.3 postinfection. The induced nasal s-IgA then returned toward the initial levels within 300 days, although the levels at day 143 ± 70 were 3.03-fold of the initial. Individual serum IgG levels also returned toward the initial levels within 300 days, although the mean levels remained high probably because of re-infection in a subgroup of patients. Although influenza A (H3N2) was a minor epidemic subtype in both flu seasons, a significant rise in nasal anti-viral (H3N2) s-IgA levels and a slightly increase in serum IgG levels were noted. CONCLUSION: Low levels of nasal anti-viral s-IgA and neutralizing antibody were noted compared with a wide range of serum anti-viral IgG and HI titers at the onset of infection. Elevated s-IgA and IgG returned toward the initial levels within 300 days of infection with minor exceptions.


Assuntos
Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Imunoglobulina A Secretora/análise , Imunoglobulina G/sangue , Influenza Humana/imunologia , Orthomyxoviridae/imunologia , Adulto , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Testes de Neutralização , Estudos Retrospectivos , Soro/imunologia , Adulto Jovem
9.
Auris Nasus Larynx ; 36(3): 300-4, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19013037

RESUMO

OBJECTIVE: Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. METHODS: This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. RESULTS: In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. CONCLUSION: These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.


Assuntos
Imunoglobulina A/imunologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Administração por Inalação , Adulto , Feminino , Humanos , Indicadores e Reagentes , Masculino , Pessoa de Meia-Idade , Lavagem Nasal , Quinolinas , Sucção , Adulto Jovem
10.
Biol Chem ; 388(8): 853-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17655505

RESUMO

Polyserase-1/TMPRSS9 and its alternative transcripts, serase-1B and serase-2B, are novel type II transmembrane serine proteases that may regulate physiological and pathological phenomena on the cell surface. To understand the mechanisms of gene expression and regulation of these transcripts, we cloned and characterized the 5' promoter region of the mouse polyserase-1 (mpolyserase-1) gene. Using 5'-rapid amplification of cDNA ends, we located the transcription initiation site 272 nucleotides upstream of the translation initiation site. Luciferase reporter gene analysis revealed that the region from +186 to +272 bp in the 5'-untranslated region (UTR), containing the GATA motif (AGATAA), glucocorticoid responsible element (TGTTCT), and E-box sequence (CAGGTG), is required for maximal promoter activity. Mutations introduced into the E-box sequence but not elsewhere in the promoter region caused a selective decrease in transcriptional activity. Furthermore, a DNA probe (+229 to +255 bp) containing the E-box sequence formed a single nuclear protein complex in a sequence-specific manner. These data suggest that the expression of mpolyserase-1 and its transcript variants is positively regulated by the E-box in its 5'-UTR, which might be responsible for the binding of basic helix-loop-helix transcription factors involved in the development of various organelles.


Assuntos
Regiões Promotoras Genéticas/genética , Serina Endopeptidases/genética , Região 5'-Flanqueadora/genética , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Elementos E-Box/genética , Ensaio de Desvio de Mobilidade Eletroforética , Regulação Enzimológica da Expressão Gênica , Genes Reporter , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sítio de Iniciação de Transcrição
11.
Int Arch Allergy Immunol ; 143(1): 75-82, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17199093

RESUMO

BACKGROUND: Lactobacillus casei strain Shirota (LcS) has been found to exert antiallergic effects in animal experiments, but there is little information about its clinical effects in human patients with allergy. METHODS: We performed a randomized double-blind, placebo-controlled study to investigate the effects of LcS in patients with allergic rhinitis triggered by Japanese cedar pollen (JCP). Participants were asked to drink fermented milk containing LcS (LcS group) or placebo (control group) for 8 weeks. Clinical symptoms and immunological parameters were compared between the two groups. RESULTS: Symptom-medication scores (SMS) worsened in accordance with the increase in the amount of scattered JCP. In terms of the nasal and ocular SMS, there was no significant difference between the LcS group and the placebo group during the ingestion period. In the subgroup of patients with moderate-to-severe nasal symptom scores before starting the ingestion of test samples, supplementation with LcS tended to reduce nasal SMS. CONCLUSION: These results indicate that fermented milk containing LcS does not prevent allergic symptoms in patients sensitive to JCP, but may delay the occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom scores.


Assuntos
Cedrus/imunologia , Pólen/imunologia , Probióticos/uso terapêutico , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/efeitos adversos , Células Th1/imunologia , Células Th2/imunologia
12.
Biochem J ; 400(3): 551-61, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16872279

RESUMO

Polyserase-1 (polyserine protease-1)/TMPRSS9 (transmembrane serine protease 9) is a type II transmembrane serine protease (TTSP) that possesses unique three tandem serine protease domains. However, the physiological function of each protease domain remains poorly understood. We discovered a new splice variant of polyserase-1, termed Serase-1B, which contains 34 extra amino acids consisting a SEA module (a domain found in sea urchin sperm protein, enterokinase and agrin) adjacent to the transmembrane domain and the first protease domain with a mucin-like box at the C-terminus. The tissue distribution of this enzyme by RT (reverse transcription)-PCR analysis revealed high expression in the liver, small intestine, pancreas, testis and peripheral blood CD14+ and CD8+ cells. To investigate the role of Serase-1B, a full-length form recombinant protein was produced. Interestingly, recombinant Serase-1B was partly secreted as a soluble inactive precursor and it was also activated by trypsin. This activated enzyme selectively cleaved synthetic peptides for trypsin and activated protein C, and it was inhibited by several natural serine protease inhibitors, such as aprotinin, alpha2-antiplasmin and plasminogen activator inhibitor 1. In addition, Serase-1B efficiently converted pro-uPA (urokinase-type plasminogen activator) into active uPA and this activation was strongly inhibited by these natural inhibitors. Furthermore, this activation was also negatively regulated by glycosaminoglycans. Our results indicate that Serase-1B is a novel member of TTSPs that might be involved in uPA/plasmin-mediated proteolysis and possibly implicated in biological events such as fibrinolysis and tumour progression.


Assuntos
Processamento Alternativo , Glicosaminoglicanos/metabolismo , Serina Endopeptidases/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Regulação para Baixo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Especificidade de Órgãos , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Serina Endopeptidases/química , Serina Endopeptidases/genética , Especificidade por Substrato , Ativador de Plasminogênio Tipo Uroquinase/genética
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