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1.
Tokai J Exp Clin Med ; 43(4): 168-172, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30488405

RESUMO

OBJECTIVE: We aimed to assess whether patients who underwent early palatoplasty have normal speech. METHODS: 19 patients with unilateral cleft lip and palate were enrolled in this study. At 6 months of age, we performed simultaneous lip, maxilla, and palate repair using presurgical orthodontics. Speech development was assessed by evaluating velopharyngeal function (VPF) and development of articulation for 10 years. RESULTS: No articulation disorders were observed after 4 years of age. Although palatalized articulation was evidently temporary in 3 cases before 4 years of age, all patients recovered without any speech training. Normal VPF rates were as follows: at 4 and 7 years of age 78.9% (n = 15), 10 years of age 73.7% (n = 4). 10 patients temporarily presented with mild VPI after 5 years of age although they had a normal VPF until 4 years of age. CONCLUSION: Early palatoplasty after narrowing the cleft palate using presurgical orthodontics is beneficial for development of articulation. The rate of normal VPF did not decrease over the years.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Ortodontia/métodos , Procedimentos Cirúrgicos Ortognáticos/métodos , Procedimentos de Cirurgia Plástica/métodos , Cuidados Pré-Operatórios/métodos , Fala/fisiologia , Fatores Etários , Transtornos da Articulação/prevenção & controle , Criança , Pré-Escolar , Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Feminino , Humanos , Lactente , Lábio/cirurgia , Masculino , Maxila/cirurgia , Palato/cirurgia , Insuficiência Velofaríngea/prevenção & controle
2.
Clin Exp Rheumatol ; 36(6): 1003-1007, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29846157

RESUMO

OBJECTIVES: The present study was carried out to elucidate the roles of serum autoantibodies in the development of blood-brain barrier (BBB) damages in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Paired serum and CSF samples were obtained from 101 SLE patients when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral neuropathy [focal NPSLE]). IgG anti-NR2 subunit of NMDA receptor (anti-NR2), anti-Sm, anti-ribosomal P and IgG anti-cardiolipin in sera and albumin in CSF and sera were measured by ELISA. Blood-brain barrier (BBB) function was evaluated by Q albumin (CSF/serum albumin quotient x 1,000). RESULTS: Q albumin was significantly higher in acute confusional state (ACS) than in non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE. Anti-Sm, but not anti-NR2, anti-P or anticardiolipin, was significantly elevated in ACS compared with the other 2 groups of NPSLE, although serum anti-NR2 was significantly higher in ACS than that in focal NPSLE. Multiple regression analysis confirmed the significant contribution of anti-Sm (p=0.0040), but not anti-NR2 (p=0.5023), anti-P (p=0.2651), or anti-cardiolipin (p=0.6769) in the elevation of Q albumin. CONCLUSIONS: The data demonstrate that serum anti-Sm antibodies play a most important role in the disruption of BBB in NPSLE.


Assuntos
Anticorpos Antinucleares/sangue , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Proteínas Centrais de snRNP/imunologia , Adulto , Anticorpos Antinucleares/líquido cefalorraquidiano , Anticorpos Antinucleares/imunologia , Biomarcadores/sangue , Barreira Hematoencefálica/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
3.
Arthritis Rheumatol ; 70(2): 277-286, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29073350

RESUMO

OBJECTIVE: IgG anti-DWEYS antibodies cross-reactive with DNA and the N-methyl-d-aspartate receptor subunits GluN2A and GluN2B are known to be associated with neuropsychiatric systemic lupus erythematosus (NPSLE). IgG anti-DWEYS have not been investigated in demyelinating NPSLE or in another demyelinating disorder, neuromyelitis optica spectrum disorder (NMOSD), which is a disease also found mainly in young women and associated with aquaporin 4 (AQP-4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. This study was undertaken to investigate the frequency of all of these brain-reactive antibodies in patients with NPSLE, those with demyelinating NPSLE, and those with NMOSD. METHODS: Serum samples from patients with NPSLE (n = 108), patients with SLE without neuropsychiatric manifestations (n = 38), patients with NMOSD (n = 33), and healthy controls (n = 106) were assessed for the frequency of IgG anti-brain antibodies as well as IgG antibodies to AQP-4, MOG, GluN2A/GluN2B, and double-stranded DNA (dsDNA). RESULTS: Sera were positive for IgG anti-AQP-4 antibodies in 27 (82%) of 33 patients with NMOSD and 3 (27%) of 11 patients with demyelinating NPSLE, whereas all sera from patients with non-demyelinating NPSLE, patients with SLE, and healthy controls were negative for IgG anti-AQP-4. IgG anti-MOG were detected at high titers in 3 (50%) of 6 patients with NMOSD who were negative for IgG anti-AQP-4, and at low titers in 2 (18%) of 11 patients with demyelinating NPSLE and 1 (1%) of 97 patients with non-demyelinating NPSLE. IgG antibodies to dsDNA were present in 11 (33%) of 33 patients with NMOSD. Only 4 (12%) of 33 patients with NMOSD were positive for IgG anti-DWEYS, compared to 11 (29%) of 38 patients with SLE and 59 (55%) of 108 patients with NPSLE. IgG anti-DWEYS antibodies were present in 56 (58%) of 97 patients with non-demyelinating NPSLE and 3 (27%) of 11 patients with demyelinating NPSLE. Serum IgG brain-reactive antibodies were present at a similar frequency in patients with non-demyelinating NPSLE (72 [75%] of 96), those with demyelinating NPSLE (9 [82%] of 11), and those with SLE (32 [84%] of 38), but were less frequent in patients with NMOSD (20 [61%] of 33). CONCLUSION: Patients with demyelinating NPSLE should be tested for IgG antibodies to AQP-4, MOG, and DWEYS. IgG anti-AQP-4 can be considered diagnostic for NMOSD, whereas none of these antibodies appear to be diagnostic for demyelinating NPSLE. Moreover, IgG anti-dsDNA are present in patients with NMOSD but are not cross-reactive with IgG anti-DWEYS, indicating that the antigenic stimulus and mechanisms of tissue damage are potentially different between demyelinating NPSLE and NMOSD.


Assuntos
Autoanticorpos/sangue , Encéfalo/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Neuromielite Óptica/imunologia , Animais , Aquaporina 4/imunologia , DNA/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/imunologia , Receptores de N-Metil-D-Aspartato/imunologia
4.
Mod Rheumatol ; 27(2): 292-297, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27319578

RESUMO

OBJECTIVE: To explore the role of C5a in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and lupus nephritis (LN). METHODS: Sera were obtained from 29 patients with NPSLE, 25 with LN, 26 without NPSLE or LN [SLE alone], and 21 healthy donors. Cerebrospinal fluid (CSF) was obtained from 29 NPSLE patients. C5a and C5 were measured by ELISA. Blood-brain barrier (BBB) function was evaluated by Q albumin ([CSF albumin/serum albumin] × 103). RESULTS: Serum C5a, but not C5, was significantly increased in SLE compared with healthy control. Serum C5a, but not C5, was significantly higher in NPSLE and in LN than in SLE alone. Serum C4, but not C3, was lower in LN than in NPSLE. Q albumin was significantly higher in diffuse NPSLE than in focal NPSLE, whereas there were no significant differences in CSF or serum C5a between both groups. Notably, CSF C5 and C5a were significantly correlated with Q albumin, whereas serum C5a, but not C5, appeared to be inversely correlated with Q albumin. CONCLUSION: These results disclosed that serum C5a was elevated not only in NPSLE but also in LN through different mechanisms. Moreover, it is suggested that C5a might be consumed during BBB damages.


Assuntos
Complemento C5a/imunologia , Nefrite Lúpica/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Adulto , Barreira Hematoencefálica/metabolismo , Feminino , Humanos , Nefrite Lúpica/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Masculino , Pessoa de Meia-Idade
5.
Mod Rheumatol ; 26(3): 377-83, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26429674

RESUMO

OBJECTIVE: To determine epitope reactivity of autoantibodies to N-methyl-D-aspartate (NMDA) receptor NR1 subunit and their association with neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Paired serum and CSF specimens were obtained from 41 patients with NPSLE (22 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 19 with neurologic syndromes or polyneuropathy [focal NPSLE]), 21 patients with various rheumatic diseases other than SLE (non-SLERD). Sera were also obtained from 27 SLE patients without neuropsychiatric manifestations (non-CNS SLE). Antibodies to murine NR1 (mNR1) or to 4 different preparations of synthetic 25-amino-acid (AA) peptides of human NR1 were measured by enzyme-linked immune sorbent assay (ELISA). RESULTS: Serum anti-mNR1 levels were significantly higher in NPSLE than in non-SLERD. Sera from NPSLE patients bound efficiently to the AA residues 19-44 from the N-terminus of NR1 (NR1-A) or 56-81 (NR1-C). Accordingly, serum anti-NR1-A and anti-NR1-C were also elevated in NPSLE compared with non-SLERD. Of note, anti-NR1-A as well as anti-NR1-C levels in CSF, but not in sera, were significantly elevated in diffuse NPSLE compared with focal NPSLE or with non-SLERD. CONCLUSION: These results suggest that autoantibodies to NMDA receptor NR1, especially to the AA residues 19-44 and 56-81 from the N-terminus play a pivotal role in the pathogenesis of diffuse NPSLE.


Assuntos
Autoanticorpos/sangue , Autoimunidade , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Biomarcadores/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Masculino , Receptores de N-Metil-D-Aspartato/sangue
6.
Mod Rheumatol ; 26(6): 958-962, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25119257

RESUMO

A 42-year-old woman was admitted due to systemic lupus erythematosus complicated with glomerulonephritis and pulmonary hypertension. During the treatment for these complications, she presented motor paresis and sensory loss caused by transverse myelitis. In spite of methyl prednisolone pulse therapy, she further developed acute confusional state due to disseminated encephalitis and fell into respiratory arrest. On laboratory examination, elevation of anti-NR2 antibodies in serum as well as in cerebrospinal fluid was noted. Although she recovered from the disseminated encephalitis after extensive treatment with high doses of corticosteroid and intravenous cyclophosphamide, she suddenly died of pulmonary hypertension. Autopsy findings confirmed the presence of liquefaction necrosis in the entire circumference of the whole spinal cord along with intimal hyperplasia and obliteration of the small arteries, accompanied by mononuclear cell infiltration and disruption of internal elastic lamina. It is therefore most likely that our patient developed longitudinal transverse myelitis through spinal cord vasculitis, which extended to brainstem and brain parenchyma, leading to the development of disseminated encephalitis.


Assuntos
Encefalite/patologia , Lúpus Eritematoso Sistêmico/patologia , Mielite Transversa/patologia , Vasculite/patologia , Adulto , Encéfalo/patologia , Encefalite/complicações , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Mielite Transversa/complicações , Vasculite/complicações
7.
Arthritis Res Ther ; 16(5): 450, 2014 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-25273532

RESUMO

INTRODUCTION: Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. Previous studies revealed the strong association between serum anti-Sm and organic brain syndrome, consisting mainly of acute confusional state (ACS) of diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). However, the precise mechanism by which anti-Sm causes diffuse NPSLE remains unclear. Of note, recent studies demonstrated that anti-U1 RNP antibodies (anti-RNP) in cerebrospinal fluid (CSF) are associated with NPSLE. The present study was designed to explore the association of anti-Sm antibodies in CSF with NPSLE. METHODS: Paired serum and CSF specimens were obtained from 72 patients with NPSLE (49 with diffuse NPSLE, 23 with neurological syndromes or peripheral neuropathy (focal NPSLE) and from 22 control patients with non-SLE neurological diseases. Sera were also obtained from 41 patients with active SLE without neuropsychiatric manifestations (non-NPSLE). Anti-Sm and anti-RNP were measured by enzyme-linked immunosorbent assay (ELISA). Blood-brain barrier (BBB) function and intrathecal anti-Sm production were evaluated by Q albumin and CSF anti-Sm index, respectively. Binding of anti-Sm to neuroblastoma cell lines SK-N-MC and Neuro2a was examined by flow cytometry and by cell ELISA. RESULTS: Anti-Sm and anti-RNP in CSF and sera were elevated in NPSLE compared with non-SLE control. CSF anti-Sm, but not CSF anti-RNP, was significantly elevated in ACS compared with non-ACS diffuse NPSLE or with focal NPSLE. By contrast, there were no significant differences in serum anti-Sm or anti-RNP among subsets of NPSLE and non-NPSLE. Whereas there were no significant differences in CSF anti-Sm index, Q albumin was elevated in ACS compared with non-ACS or with focal NPSLE. Notably, CSF anti-Sm was correlated with Q albumin (r = 0.2373, P = 0.0447) or with serum anti-Sm (r = 0.7185, P <0.0001) in 72 patients with NPSLE. Finally, monoclonal anti-Sm and purified human anti-Sm bound to the surface of SK-N-MC and Neuro2a. CONCLUSIONS: These results demonstrate that the elevation of CSF anti-Sm through transudation from systemic circulation due to damaged BBB plays a critical role in the pathogenesis of ACS. More importantly, the data indicate that anti-Sm is yet another autoantibody with presumed neural toxicity, but might not be the last.


Assuntos
Autoanticorpos/imunologia , Confusão/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Proteínas Centrais de snRNP/imunologia , Doença Aguda , Adulto , Animais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Confusão/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Ligação Proteica/imunologia
8.
Nucleic Acids Res ; 37(8): e64, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19336414

RESUMO

In vitro antibody-display technologies are powerful approaches for isolating monoclonal antibodies from recombinant antibody libraries. However, these display techniques require several rounds of affinity selection which is time-consuming. Here, we combined mRNA display with a microfluidic system for in vitro selection and evolution of antibodies and achieved ultrahigh enrichment efficiency of 10(6)- to 10(8)-fold per round. After only one or two rounds of selection, antibodies with high affinity and specificity were obtained from naive and randomized single-chain Fv libraries of approximately 10(12) molecules. Furthermore, we confirmed that not only protein-protein (antigen-antibody) interactions, but also protein-DNA and protein-drug interactions were selected with ultrahigh efficiencies. This method will facilitate high-throughput preparation of antibodies and identification of protein interactions in proteomic and therapeutic fields.


Assuntos
Evolução Molecular Direcionada , Região Variável de Imunoglobulina/genética , Técnicas Analíticas Microfluídicas/métodos , RNA Mensageiro/biossíntese , Animais , Linhagem Celular , Biblioteca Gênica , Humanos , Região Variável de Imunoglobulina/biossíntese , Região Variável de Imunoglobulina/imunologia , Camundongos , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/imunologia , Transcrição Gênica , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia
9.
Tokai J Exp Clin Med ; 33(1): 21-7, 2008 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-21318960

RESUMO

In the treatment of a protruded premaxilla associated with complete bilateral cleft lip and palate, some patients require surgical setback of the premaxilla with osteotomy as functional and aesthetic treatment. No satisfactory surgical approaches have been established for the setback because it is usually difficult to fix the premaxilla after osteotomy in the mixed dentition period. This paper reports the new method for fixing the premaxilla with osteotomy in a child with a severely protruded premaxilla in the mixed dentition period. To fix the segment, we fabricated a device consisting of a palatal bite plate and an anterior tray before surgery. The space between the tray and the premaxilla was filled with soft resin during surgery so that the reposition of the premaxilla could be adjusted. This approach produced a favorable result. Our device has several advantages. It allows the adjustment of repositioning of the premaxilla during surgery. It can change the range of the adjustment according to the intended position of the premaxilla. It allows secure fixation of the segment. It is removable for tooth brushing and observation of bone union. Our device can be applied to many children similar to our patient reported in this paper.


Assuntos
Placas Ósseas , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Dentição Mista , Maxila/cirurgia , Osteotomia/métodos , Transplante Ósseo/métodos , Criança , Humanos , Masculino , Maxila/anormalidades , Ortodontia Corretiva , Resinas Sintéticas , Retalhos Cirúrgicos , Técnicas de Sutura , Resultado do Tratamento
10.
Tokai J Exp Clin Med ; 29(3): 111-22, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15595469

RESUMO

Palatal growth and articulation in two different palatal closure techniques, Osada's two-stage procedure and the conventional one-stage procedure, were evaluated in 12 patients. Osada's procedure (hard palate closure using a vomer flap with complete closure of the raw surface by a full thickness skin graft) is a two-stage operation that consists of early soft palate closure at the time of lip closure (3 to 6 months of age). The palatal sizes and the depth of the palatal arch were significantly greater in the two-stage group than in the one-stage group at 1 year of age and, 3 to 5 years of age. There were no differences between the two groups at the velopharyngeal closure evaluation after hard palate closure and at final speech evaluation. Osada's two-stage palatoplasty has many advantages and we believe that this is one of the most recommendable procedures at present.


Assuntos
Transtornos da Articulação/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Palato/crescimento & desenvolvimento , Palato/cirurgia , Fala , Transtornos da Articulação/etiologia , Transtornos da Articulação/fisiopatologia , Pré-Escolar , Fissura Palatina/complicações , Fissura Palatina/cirurgia , Técnica de Fundição Odontológica , Humanos , Lactente , Palato/patologia , Transplante de Pele , Testes de Articulação da Fala , Retalhos Cirúrgicos , Resultado do Tratamento , Insuficiência Velofaríngea/complicações , Insuficiência Velofaríngea/cirurgia
11.
Appl Environ Microbiol ; 70(10): 6247-56, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15466572

RESUMO

The complete SfiI and I-CeuI physical maps of four Bacillus subtilis (natto) strains, which were previously isolated as natto (fermented soybean) starters, were constructed to elucidate the genome structure. Not only the similarity in genome size and organization but also the microheterogeneity of the gene context was revealed. No large-scale genome rearrangements among the four strains were indicated by mapping of the genes, including 10 rRNA operons (rrn) and relevant genes required for natto production, to the loci corresponding to those of the B. subtilis strain Marburg 168. However, restriction fragment length polymorphism and the presence or absence of strain-specific DNA sequences, such as the prophages SP beta, skin element, and PBSX, as well as the insertion element IS4Bsu1, could be used to identify one of these strains as a Marburg type and the other three strains as natto types. The genome structure and gene heterogeneity were also consistent with the type of indigenous plasmids harbored by the strains.


Assuntos
Bacillus subtilis/genética , Genoma Bacteriano , Fagos Bacilares/genética , Bacillus subtilis/isolamento & purificação , Bacillus subtilis/virologia , Sequência de Bases , Mapeamento Cromossômico , DNA Bacteriano/genética , Desoxirribonucleases de Sítio Específico do Tipo II , Microbiologia de Alimentos , Plasmídeos/genética , Polimorfismo de Fragmento de Restrição , Alimentos de Soja/microbiologia , Especificidade da Espécie
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