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2.
Clin Exp Dermatol ; 36(8): 903-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21883401

RESUMO

BACKGROUND: Cytotoxic T lymphocytes (CTLs) have been recognized as an important effector cell in Behçet disease (BD). Granulysin is a cytolytic granule protein expressed by CTLs and natural killer cells. AIM: To evaluate the involvement of granulysin-producing T cells in the pathogenesis of BD. METHODS: Using immunohistochemistry, lymphocyte subsets expressing granulysin were investigated in mucocutaneous lesions of BD. Serum granulysin levels were assayed by ELISA. RESULTS: Granulysin-positive cells were seen in specimens from oral ulcers, genital ulcers and acne-like eruptions, but not erythema nodosum-like lesions. Both CD4+ and CD8+ T cells expressed granulysin. Serum granulysin levels did not correlate with disease activity in BD. CONCLUSION: Immune reactions mediated by granulysin-positive CTLs may play an important role in the pathogenesis of acne-like eruptions, oral ulcers and genital ulcers in BD.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Síndrome de Behçet/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Diferenciação de Linfócitos T/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
J Eur Acad Dermatol Venereol ; 21(7): 897-901, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17658997

RESUMO

BACKGROUND: Extramammary Paget's disease is an intra-epidermal carcinoma that occurs preferentially in genital areas. Patients with genital Paget's disease (GPD) sometimes develop severe post-surgical infections because of this anatomical disadvantage. OBJECTIVE: To study perioperative micro-organisms and surgical site infection (SSI) in GPD. METHODS: We examined micro-organisms isolated from preoperative lesions, necrotic sites and infected wounds in 60 adult patients with GPD who underwent surgery at our hospital between November 1990 and December 2005. Based on the obtained microbiological data, we assessed the incidence, risk factors and treatment of SSI. RESULTS: The colonized organisms found in preoperative GPD were Enterobacteriaceae (27.6%), methicillin-sensitive Staphylococcus aureus (MSSA) (22.4%) and coagulase-negative staphylococci (CNS) (15.5%), among others. In the postoperative necrotic sites, the frequency of MSSA isolation was reduced to 9.4%, while Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA) both increased in frequency from 3.4% and 0% upon preoperative examination to 18.8% and 9.4%, respectively. The incidence of SSI was 15%. In 7 of 9 SSIs, MRSA and/or P. aeruginosa were isolated. CONCLUSION: We have successfully identified a number of perioperative micro-organisms in GPD. The present observations may be extremely useful in choosing appropriate antimicrobial agents for use in the surgical treatment of GPD.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Masculinos/cirurgia , Doença de Paget Extramamária/cirurgia , Infecção da Ferida Cirúrgica/microbiologia , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do Tratamento
4.
Abdom Imaging ; 32(3): 348-50, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16897276

RESUMO

We report a unique case of acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum, which could be detected by abdominal ultrasonography. We believe this case to be the first case of reported literatures in English.


Assuntos
Colecistite Aguda/etiologia , Vesícula Biliar/anormalidades , Adulto , Bromoexina , Colecistite Aguda/diagnóstico por imagem , Colecistografia , Feminino , Humanos , Omento , Anormalidade Torcional , Ultrassonografia
5.
Gut ; 54(12): 1759-67, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16284287

RESUMO

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. AIM: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. METHODS: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 microg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. RESULTS: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, alpha-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. CONCLUSIONS: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.


Assuntos
Quimiocina CCL2/antagonistas & inibidores , Terapia Genética/métodos , Pancreatite Crônica/prevenção & controle , Actinas/metabolismo , Animais , Western Blotting/métodos , Quimiocina CCL2/sangue , Quimiocina CCL2/genética , Quimiocinas/biossíntese , Citocinas/biossíntese , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Hidroxiprolina/metabolismo , Injeções Intramusculares , Masculino , Compostos Orgânicos de Estanho , Pâncreas/patologia , Pancreatite Crônica/induzido quimicamente , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transdução de Sinais
7.
Br J Dermatol ; 153(5): 981-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16225610

RESUMO

BACKGROUND: Herpetic vesicles caused by herpes simplex virus and varicella zoster virus, and hydroa vacciniforme (HV) are characterized by umbilicated vesicule formation. OBJECTIVES: To understand the histogenesis of umbilicated vesicles in herpetic vesicles and HV, we demonstrated the presence of the virus-associated molecules in the lesions, and the pathogenic role of cytotoxic T-lymphocyte (CTL) immune responses. METHODS: Phenotyping of infiltrating cells was carried out in biopsy specimens from herpes simplex, varicella, herpes zoster and HV, and compared with nonviral contact dermatitis. Viral antigens and Epstein-Barr virus-encoded small nuclear RNA (EBER) were detected by immunostaining and by in situ hybridization, respectively. Infiltrating CTLs expressing granzyme B and granulysin were determined by double immunostaining using confocal laser scanning microscopy. RESULTS: In all herpetic vesicles, the corresponding viral antigens were observed in the cytopathic keratinocytes, and infiltration of lymphoid cells was present in the upper dermis and around the vessels. In all HV lesions studied, EBER+ T cells made up 5-10% of the dermal infiltrates and the dermal infiltrates contained almost no CD56 cells. CTLs expressing granzyme B and granulysin were present in both herpetic and HV lesions, in which they made up 10-30% of the total dermal infiltrates, whereas they comprised less than 5% of the infiltrates of biopsy specimens from nonviral contact dermatitis. Confocal laser microscopic examination demonstrated that both CD4+ and CD8+ T cells expressed granzyme B and granulysin. CONCLUSIONS: CD4+ and/or CD8+ CTLs reactive to the virus-infected cells might be responsible for the histogenesis of herpetic and HV lesions characterized by umbilicated vesicles.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Dermatopatias Vesiculobolhosas/imunologia , Dermatopatias Virais/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Antígenos Virais/análise , Biópsia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citotoxicidade Imunológica , Granzimas , Herpes Simples/imunologia , Herpes Simples/patologia , Herpes Zoster/imunologia , Herpes Zoster/patologia , Humanos , Hidroa Vaciniforme/imunologia , Hidroa Vaciniforme/patologia , Imunofenotipagem , Hibridização In Situ/métodos , Microscopia Confocal , Proteínas de Ligação a RNA/análise , Proteínas Ribossômicas/análise , Serina Endopeptidases/metabolismo , Dermatopatias Vesiculobolhosas/patologia , Dermatopatias Virais/patologia
8.
Br J Dermatol ; 150(5): 904-9, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15149502

RESUMO

BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, alpha-defensin, a human neutrophil peptide, and beta-defensin (human beta-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.


Assuntos
Infecções Bacterianas/imunologia , Foliculite/imunologia , Receptores Imunológicos/biossíntese , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Antígenos de Diferenciação de Linfócitos T , Infecções Bacterianas/patologia , Complexo CD3/análise , Linfócitos T CD8-Positivos/imunologia , Feminino , Foliculite/microbiologia , Foliculite/patologia , Humanos , Imunofenotipagem , Antígenos Comuns de Leucócito/análise , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Receptores Imunológicos/imunologia , Pele/imunologia
9.
Br J Dermatol ; 148(3): 526-32, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12653745

RESUMO

BACKGROUND: Glycocalyx collapses during dehydration to produce electron-dense accretions. Confocal laser scanning microscopy (CLSM) may be used to visualize fully hydrated microbial biofilms. OBJECTIVES: Using CLSM, to analyse glycocalyx production by Staphylococcus aureus cells in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus. A second objective was to compare numbers of S. aureus cells in tissue sections prepared by different methods for routine light microscopy. METHODS: S. aureus cells in skin lesions of impetigo, atopic dermatitis and pemphigus were stained with safranin, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested in skin lesions of impetigo, atopic dermatitis and pemphigus were covered with glycocalyx and formed microcolonies. The numbers of S. aureus cells in a routine light microscopy section were significantly lower than those in a frozen section that had not been dehydrated with ethanol. CONCLUSIONS: S. aureus cells generally produce glycocalyx in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus, which accounts for the difficulty of removing S. aureus cells from these skin lesions. The glycocalyx may collapse during dehydration and most of the S. aureus cells may be carried away during preparation of routine light microscope sections.


Assuntos
Biofilmes/crescimento & desenvolvimento , Dermatite Atópica/microbiologia , Glicocálix/metabolismo , Impetigo/microbiologia , Microscopia Confocal/métodos , Pênfigo/microbiologia , Staphylococcus aureus/fisiologia , Ácido Acético/farmacologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Feminino , Fibrina , Ácido Fusídico/farmacologia , Humanos , Ácido Clorídrico/farmacologia , Masculino , Pessoa de Meia-Idade , Staphylococcus aureus/efeitos dos fármacos
11.
Heart ; 89(1): 66-70, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12482795

RESUMO

OBJECTIVE: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia. PATIENTS AND METHODS: Questionnaire responses and ECGs of 29 patients with CPVT were evaluated. Mean (SD) age of onset was 10.3 (6.1) years. RESULTS: The initial CPVT manifestations were syncope (79%), cardiac arrest (7%), and a family history (14%). ECGs showed sinus bradycardia and a normal QTc. Mean heart rate during CPVT was 192 (30) beats/min. Most cases were non-sustained (72%), but 21% were sustained and 7% were associated with ventricular fibrillation. The morphology of CPVT was polymorphic (62%), polymorphic and bidirectional (21%), bidirectional (10%), or polymorphic with ventricular fibrillation (7%). There was 100% inducement of CPVT by exercise, 75% by catecholamine infusion, and none by programmed stimulation. No late potential was recorded. Onset was in the right ventricular outflow tract in more than half the cases. During a follow up of 6.8 (4.9) years, sudden death occurred in 24% of the patients, 7% of whom had anoxic brain damage. Autosomal dominant inheritance was seen in 8% of the patients' families. beta Blockers completely controlled CPVT in only 31% of cases. Calcium antagonists partially suppressed CPVT in autosomal dominant cases. CONCLUSIONS: CPVT may arise in certain distinct areas but the prognosis is poor. The onset of CPVT may be an indication for an implanted cardioverter-defibrillator.


Assuntos
Catecolaminas/genética , Morte Súbita Cardíaca/prevenção & controle , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Antiarrítmicos/uso terapêutico , Ablação por Cateter/métodos , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia , Feminino , Frequência Cardíaca , Humanos , Masculino , Polimorfismo Genético , Taxa de Sobrevida , Taquicardia Ventricular/mortalidade , Resultado do Tratamento , Verapamil/uso terapêutico
12.
Br J Dermatol ; 147(5): 879-85, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12410696

RESUMO

BACKGROUND: Bacteria that adhere to damaged tissues encase themselves in a hydrated matrix of polysaccharides, forming a slimy layer known as a biofilm. This is the first report of detection of glycocalyx production by Staphylococcus aureus using confocal laser scanning microscopy (CLSM) on damaged skin tissues. OBJECTIVES: To analyse glycocalyx production by S. aureus cells on damaged skin tissues and the influence of polymorphonuclear leucocytes (PMNs) and various antimicrobial agents on its production using CLSM in cyclophosphamide (Cy)-treated (neutropenic) or non-Cy-treated (normal) mice. METHODS: S. aureus cells were inoculated on damaged skin tissues in neutropenic or normal mice with or without topical application of antimicrobial agents. S. aureus cells were stained with safranine, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. RESULTS: All S. aureus cells tested on damaged skin tissues formed microcolonies encircled by glycocalyx. The colony counts of S. aureus cells on croton oil dermatitis in normal mice treated with 2% fusidic acid ointment were about 100 times lower than those in neutropenic mice (control). CONCLUSIONS: As S. aureus cells can generally produce a biofilm on damaged skin tissues, antimicrobial agents may not eradicate S. aureus cells without the help of PMNs. S. aureus glycocalyx may play a crucial role in colonization and adherence to damaged skin tissues.


Assuntos
Biofilmes/crescimento & desenvolvimento , Glicocálix/microbiologia , Pele/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Animais , Anti-Infecciosos Locais/uso terapêutico , Contagem de Colônia Microbiana , Dermatite de Contato/complicações , Feminino , Ácido Fusídico/uso terapêutico , Glicocálix/efeitos dos fármacos , Glicocálix/patologia , Camundongos , Microscopia Confocal , Neutropenia/complicações , Infecções Oportunistas/complicações , Infecções Oportunistas/prevenção & controle , Povidona-Iodo/uso terapêutico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/prevenção & controle
13.
Ultramicroscopy ; 91(1-4): 215-20, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12211471

RESUMO

Scanning surface potential microscopy was applied to detect the photo-voltaic response of Langmuir-Blodgett (LB) monolayer assemblies containing an amphiphilic A-S-D triad molecule (ASD) with two different concentrations. The triad acts as a charge separation unit in the same way as the photosynthetic reaction center. In addition, the photo-induced multistep electron transfer systems can be organized in the LB monolayers: first electrons and holes are separated across the monolayer through the ASD triads upon photo-excitation and then the resultant electrons and holes are further separated by lateral diffusion among the concentrated A and the D moieties, respectively. The change in surface potential was clearly observed on an LB assembly with the high ASD concentration in a mixed ASD monolayer with omega-tricosenoic acid (T) (the molar ratio of ASD:T = 1:5), while the photo-response could not be observed on an LB monolayer with the low ASD concentration (the molar ratio of ASD:T = 1:30). It was interesting to note that the average surface concentration of ASD in the latter diluted monolayer was decreased only to 6 of that of the former concentrated monolayer. If the photo-response depended linearly on the ASD concentration, the surface potential would be readily detected in the latter monolayer. The nonlinearity can be attributed to the effect of succeeding lateral diffusion of the separated charges among the ASD triads. To clarify the effect of the lateral diffusion, the other type of LB assemblies, i.e., A/A-S-D double layers, was fabricated by alternate deposition of an additional acceptor (A) layer and the ASD layer. In the A/A-S-D assemblies, significant photo-induced surface potential change was observed with an A layer of a high A concentration (A:T = 1:2) even when the ASD concentration was low in the ASD layer (ASD:T = 1:30). This result supported an idea that the additional A layer enhanced lateral electron diffusion and resulted in electron accumulation in A layer and hole accumulation in the diluted ASD layer in the A/A-S-D system.

14.
J Clin Invest ; 108(11): 1589-96, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11733554

RESUMO

Organ-specific autoimmune diseases have been postulated to be the result of T cell response against organ-specific self-peptides bound to MHC molecules. Contrary to this paradigm, we report here that transgenic mice lacking MHC class I expression and expressing an MHC class II I-A(b) molecule that presents only a single peptide (E alpha 52-68) spontaneously develops peripheral nervous system-specific autoimmune disease with many of the histopathological features found in experimental allergic neuritis. Reciprocal bone marrow chimeras produced using susceptible and resistant lines revealed that bone marrow-derived cells determined disease susceptibility. While the expression of the I-A(b)-E alpha 52-68 complex in the periphery was readily detectable in both lines, its expression on thymic dendritic cells responsible for tolerance induction was markedly lower in the susceptible line than in the resistant line. Consistent with this, CD4(+) T cells that can be activated by the I-A(b)-E alpha 52-68 complex were found in the susceptible line, but not in the resistant line. Such CD4(+) T cells conferred the disease to the resistant line by adoptive transfer, and administration of Ab specific for the I-A(b)-E alpha 52-68 complex inhibited disease manifestation in the susceptible line. These results indicate that disease development involves systemic T cell reactivity to I-A(b)-E alpha 52-68 complex, probably caused by incomplete negative thymocyte selection.


Assuntos
Antígenos de Superfície/imunologia , Doenças Autoimunes/etiologia , Linfócitos T CD4-Positivos/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Fragmentos de Peptídeos , Doenças do Sistema Nervoso Periférico/etiologia , Receptores de Antígenos de Linfócitos T , Animais , Camundongos , Camundongos Transgênicos , Especificidade de Órgãos
15.
J Antimicrob Chemother ; 48(4): 487-91, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11581226

RESUMO

We examined the antibacterial action of several tannins on plasma coagulation by Staphylococcus aureus and the effect of conventional chemotherapy combined with tannic acid below the MIC. Coagulation was inhibited in plasma containing tannic acid (100 mg/L), gallic acid (5000 mg/L), ellagic acid (5000 mg/L), (-)-epicatechin (1500 mg/L), (-)-epicatechin gallate (500 mg/L) or (-)-epigallocatechin gallate (200 mg/L) after incubation for 24 h. All tannins inhibited coagulation at a concentration below the MIC. The MICs of oxacillin and cefdinir for S. aureus were reduced to < or = 0.06 mg/L in Mueller-Hinton agar plates with tannic acid (100 mg/L) at a concentration below the MIC. The antistaphylococcal activity of tannic acid was reduced in plates with 10% rabbit blood, but not in those with 10% rabbit plasma. Membranous structures formed in a culture medium containing equal proportions of plasma and tryptic soy broth after incubation for 24 h. The colony counts of S. aureus in membranous structures in the medium containing oxacillin (40 mg/L) and tannic acid (100 mg/L) were c. 10-fold lower than those in medium containing oxacillin (40 mg/L) alone (P < 0.01). Tannic acid merits further investigation as a possible adjuvant agent against S. aureus skin infections treated with beta-lactam antibiotics.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Taninos/farmacologia , Antibacterianos/farmacologia , Cefdinir , Cefalosporinas/farmacologia , Contagem de Colônia Microbiana , Meios de Cultura , Quimioterapia Combinada , Humanos , Taninos Hidrolisáveis/farmacologia , Testes de Sensibilidade Microbiana , Oxacilina/farmacologia , Infecções Estafilocócicas/microbiologia , Taninos/classificação
16.
Nature ; 412(6849): 826-31, 2001 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-11518968

RESUMO

Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics, both of which are regulated by Rho family GTPases. Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement. The CDM family proteins, Caenorhabditis elegans CED-5, human DOCK180 and Drosophila melanogaster Myoblast City (MBC), are implicated to mediate membrane extension by functioning upstream of Rac. Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells, physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is indispensable for lymphocyte chemotaxis. DOCK2-deficient mice (DOCK2-/-) exhibited migration defects of T and B lymphocytes, but not of monocytes, in response to chemokines, resulting in several abnormalities including T lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. In DOCK2-/- lymphocytes, chemokine-induced Rac activation and actin polymerization were almost totally abolished. Thus, in lymphocyte migration DOCK2 functions as a central regulator that mediates cytoskeletal reorganization through Rac activation.


Assuntos
Linfócitos B/fisiologia , Proteínas de Transporte/fisiologia , Quimiotaxia de Leucócito , Fatores de Troca do Nucleotídeo Guanina , Células-Tronco Hematopoéticas/fisiologia , Linfócitos T/fisiologia , Proteínas rac1 de Ligação ao GTP , Animais , Linhagem Celular , Quimiocina CXCL12 , Quimiocinas CXC/fisiologia , Citocinas/fisiologia , Citoesqueleto/fisiologia , Feminino , Proteínas Ativadoras de GTPase , Memória Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Baço/citologia , Células-Tronco , Proteínas rac de Ligação ao GTP/fisiologia
17.
Proc Natl Acad Sci U S A ; 97(25): 13760-5, 2000 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-11087837

RESUMO

T cell differentiation in the thymus is driven by positive selection through the interaction of alphabeta T cell receptors (TCRs) with self-peptides bound to self-major histocompatibility complex molecules, yet the influence of the peptide sequence on this process remains unknown. To address this issue, we have compared CD4(+) T cell differentiation between two sets of mouse lines in which MHC class II I-A(b) molecules are occupied with either Ealpha chain-derived peptide ((p)Ealpha) or its variant, (p)60K, with one amino acid substitution from leucine to lysine at P5 residue of TCR contacts. Here, we show that despite the comparable expression of I-A(b)-peptide complex in the thymus, this substitution from leucine to lysine affects efficiency of positive selection, resulting in extremely small numbers of CD4(+) T cells to be selected to mature on I-A(b)-(p)60K complex. Furthermore, we show that, although I-A(b)-(p)Ealpha complex selects diverse T cells, T cell repertoire shaped by I-A(b)-(p)60K complex is markedly constrained. Our findings thus suggest that positive selection is both specific and degenerate, depending on the amino acid residues at TCR contacts of the selecting self-peptides.


Assuntos
Oligopeptídeos/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Regiões Determinantes de Complementaridade , Primers do DNA , Ligantes , Tecido Linfoide/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Dados de Sequência Molecular , Oligopeptídeos/química , Linfócitos T/metabolismo
18.
Nihon Koshu Eisei Zasshi ; 47(6): 476-85, 2000 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-10921300

RESUMO

Although interest in mental health promotion has recently been increasing, the most appropriate approaches remain to be determined. Therefore we conducted Stress Management Classes (SMCs) at Higashi Osaka City Naka Health Center in an attempt to help residents to improve their mental health. The purpose of this study was to evaluate the efficacy of SMCs, held four times over 2 months, with an educational program including the concept of stress and instruction in autogenic training as a relaxation technique. Subjects who attended a Health Promotion Class (HPC) at Osaka Prefectural Kaizuka Health Center were used as controls for the study. The aim of the HPC was to prevent chronic physical diseases such as hypertension, diabetes, and hyperlipidemia, with the program consisting mainly of exercise once a week for 3 months. The results were as follows: 1) People who attended SMCs were more likely to have mental health problems than those who attended the HPC. As a result, mentally ill patients could be diagnosed and receive psychiatric treatment at an early stage in the SMC group. 2) Both SMC and HPC attenders reported improvement of their mental health status with the use of POMS (Profile of Mood States). 3) Both SMC and HPC attenders exhibited significant decrease of blood pressure. Although attenders of both classes improved their mental health status, it is important to be able to attract individuals who are in a poor mental condition in case of mental health promotion. In this trial, we found that the term "stress management" was very useful because people who suffered stress were likely to be interested in it. After the Community Health Law was established in 1994, the flow of community health activities has been shifting from the prefectural government to the municipality. However, promoting mental health and welfare is still mainly the role of the prefectural government. In this sense, health centers are appropriate institutions to hold classes as in this trial.


Assuntos
Treinamento Autógeno/educação , Serviços de Saúde Comunitária , Terapia de Relaxamento/educação , Estresse Psicológico/terapia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prática de Saúde Pública
19.
Eur J Dermatol ; 9(7): 577-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10523742

RESUMO

Trichosporon asahii fungemia was associated with multiple, purpuric, papular lesions on the abdomen and extremities in a 53-year-old man with acute myeloblastic leukemia. Histologically, budding yeasts were demonstrated in the dermis. The yeast-form fungus was identified as T. asahii.


Assuntos
Dermatomicoses/microbiologia , Leucemia Mieloide Aguda/complicações , Infecções Oportunistas/microbiologia , Trichosporon/isolamento & purificação , DNA Fúngico/análise , DNA Fúngico/genética , Dermatomicoses/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Pele/microbiologia , Pele/patologia , Trichosporon/genética
20.
Clin Diagn Lab Immunol ; 6(3): 336-40, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10225832

RESUMO

Defensins are widely distributed and broad-spectrum antimicrobial peptides with activities against bacteria, fungi, and enveloped viruses. Defensins have been isolated from granules of neutrophils from humans, rabbits, rats, and guinea pigs. They have also been found in lung macrophages as well as in Paneth cells of the human, rabbit, and mouse small intestine. The human beta-defensin-2 was recently isolated from human skin. In this study, we detected the expression of mRNA for the defensin cryptdin in BALB/c mouse skin by means of reverse transcriptase PCR amplification. Expression was also detected in dispase-separated epidermis and cultured keratinocytes, but expression was not detected in fibroblasts. The expression of cryptdin mRNA was found to begin on embryonic day 17.5. As determined with specific primers, the cDNA sequence cloned from the skin was found to be identical to that previously reported for cryptdin-5. cDNA derived from cultured keratinocytes demonstrated the sequences of the cryptdin-6 and cryptdin-1 isoforms. In situ hybridization analysis showed that the mRNA of cryptdin was expressed in the suprabasal keratinocytes of the skin in embryonic and neonatal days and then shifted to the hair bulbs in the skin of adult mice.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Precursores de Proteínas/análise , Precursores de Proteínas/genética , Pele/embriologia , Pele/metabolismo , Animais , Sequência de Bases , DNA Complementar , Epiderme/embriologia , Epiderme/metabolismo , Hibridização In Situ , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Análise de Sequência de DNA
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