RESUMO
Psychiatric manifestations of systemic lupus erythematosus (SLE) that are commonly preceded by organic syndromes include confusional states, anxiety disorder, cognitive dysfunction, mood disorder and psychosis. A 35-year-old woman was admitted to hospital with a relapse of SLE. Laboratory data were exacerbated, with some physical symptoms, and her primary psychiatric symptom was mania. The symptoms were reduced by treatment with prednisolone, methylprednisolone and aripiprazole. Magnetic resonance imaging and single-photon emission computed tomography (SPECT) using (123)I-IMP was then performed and analyzed with three-dimensional stereotactic surface projection. This case emphasizes that SLE can commence with organic syndromes and relapse with predominantly psychiatric symptoms, and that the treatment efficacy may be confirmed using a follow-up of SPECT.
Assuntos
Transtorno Bipolar/diagnóstico , Lúpus Eritematoso Sistêmico/psicologia , Adulto , Feminino , Seguimentos , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/induzido quimicamente , Imageamento por Ressonância Magnética , Neuroimagem/métodos , Recidiva , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
AIMS: To elucidate the mechanism of marked stromal fibrosis in strictured colorectal carcinomas (SC) that cause complete ileus. METHODS AND RESULTS: Sixteen cases of SC and 29 cases of non-strictured colorectal carcinoma (NSC) were studied. These carcinomas showed similar clinicopathological features except for bowel stricture. The stricture index (SI) showing the degree of bowel stricture was 59.8 +/- 12.1% in SC versus 20.8 +/- 24.6% in NSC (P < 0.001). The fibrosis index (FI), defined to reflect the extent of stromal fibrosis, was 56.3 +/- 8.8% in SC versus 21.9 +/- 10.6% in NSC (P < 0.001). COX-2+ myofibroblasts were detected in 13 cases (81.3%) in SC versus eight cases (27.6%) in NSC (P < 0.01). The COX-2+ myofibroblast density was 276.7 +/- 181.1 cells/mm(2) in SC versus 26.6 +/- 52.7 cells/mm(2) in NSC (P < 0.001). When all cases were divided into two groups with and without COX-2+ myofibroblasts, the SI was 48.8 +/- 19.1% in those with COX-2+ myofibroblasts versus 24.8 +/- 29.3% in those with COX-2- myofibroblasts (P < 0.001). CONCLUSION: COX-2+ myofibroblasts may play an important role in extensive bowel stricture in colorectal carcinomas.
Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Fibroblastos/enzimologia , Fibrose/patologia , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Colonoscopia , Neoplasias Colorretais/cirurgia , Ciclo-Oxigenase 2 , Feminino , Fibroblastos/patologia , Fibrose/etiologia , Humanos , Íleus/diagnóstico por imagem , Íleus/etiologia , Masculino , Proteínas de Membrana , Radiografia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Situs solitus refers to the normal arrangement of body organs. Situs inversus totalis is a complete mirror image or reverse isomeric form of the thoracic and abdominal viscera. Any arrangement of organs between these two extremes is designated by heterotaxia. Several patterns of vascular and visceral abnormalities are associated with heterotaxia, and two loosely defined syndromes of splenic anomalies (asplenia and polysplenia) are most common. We present the case of a 71-year-old woman with situs inversus totalis and polysplenia syndrome who developed synchronous double cancer originating from the stomach and rectum. Abdominal manifestations were situs inversus totalis combined with multiple lobulated spleen, azygous continuation of the interrupted inferior vena cava, direct drainage of hepatic vein to left atrium, preduodenal portal vein, short pancreas, incomplete rotation of the colon, and malrotation of the intestine. Histologically, gastric cancer was diagnosed as papillary adenocarcinoma and rectal cancer, as moderately differentiated adenocarcinoma. The patient was successfully treated with total gastrectomy for gastric cancer and low-anterior resection of the rectum for rectal cancer.
Assuntos
Adenocarcinoma Papilar/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Retais/diagnóstico por imagem , Situs Inversus/diagnóstico por imagem , Baço/anormalidades , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/cirurgia , Idoso , Endoscopia Gastrointestinal , Feminino , Gastrectomia , Humanos , Metástase Linfática , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/patologia , Reto/cirurgia , Situs Inversus/patologia , Situs Inversus/cirurgia , Baço/diagnóstico por imagem , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Glucose tolerance (GT) has not been taken into consideration in investigations concerning relationships between coagulopathy and multiple organ dysfunction syndrome (MODS), and endothelial cell activation/endothelial cell injury (ECA/ECI) in septic patients, although coagulopathy is known to be influenced by blood glucose level. We investigated those relationships under strict blood glucose control and evaluation of GT with the glucose clamp method by means of the artificial pancreas in nine septic patients with glucose intolerance. The relationships between GT and blood stress related hormone levels (SRH) were also investigated. METHODS: The amount of metabolized glucose (M value), as the parameter of GT, was measured by the euglycemic hyperinsulinemic glucose clamp method, in which the blood glucose level was clamped at 80 mg/dl under a continuous insulin infusion rate of 1.12 mU/kg per min, using the artificial pancreas, STG-22. Multiple organ failure (MOF) score was calculated using the MOF criteria of Japanese Association for Critical Care Medicine. Regarding coagulopathy, the following parameters were used: disseminated intravascular coagulation (DIC) score (calculated from the DIC criteria of the Ministry of Health and Welfare of Japan) and the parameters used for calculating DIC score, protein-C, protein-S, plasminogen, antithrombin III (AT-III), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator-PAI-1 (tPA-PAI-1) complex. Thrombomodulin (TM) was measured as the indicator of ECI. RESULTS: There were no significant correlations between M value and SRH, parameters indicating coagulopathy and the MOF score. The MOF score and blood TM levels were positively correlated with DIC score, thrombin-AT-III complex and tPA-PAI-1 complex, and negatively correlated with blood platelet count. CONCLUSIONS: GT was not significantly related to SRH, coagulopathy and MODS under strict blood glucose control. Hypercoagulability was closely related to MODS and ECI. Among the parameters indicating coagulopathy, tPA-PAI-1 complex, which is considered to originate from ECA, seemed to be a sensitive parameter of MODS and ECI, and might be a predictive marker of MODS. The treatment for reducing hypercoagulability and ECA/ECI were thought to be justified as one of the therapies for acutely ill septic patients.
Assuntos
Teste de Tolerância a Glucose , Insuficiência de Múltiplos Órgãos/fisiopatologia , Pâncreas Artificial , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Ativador de Plasminogênio Tecidual/fisiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Glicemia/metabolismo , Fibrinólise , Hormônios/sangue , Humanos , Insuficiência de Múltiplos Órgãos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Sepse/sangue , Sepse/terapia , Ativador de Plasminogênio Tecidual/sangueRESUMO
More than 10 G protein-coupled receptors (GPCRs) have been reported to act as coreceptors for entry of human and simian immunodeficiency viruses (HIV and SIV). We investigated the utilization of six GPCRs as coreceptors by T-cell-line-adapted HIV-2 strains (CBL-20, CBL-21, CBL-23, GH-1, ROD, and SBL6669) and SIV strains (SIVagmTYO-1, SIVmac251, and SIVmndGB-1). NP-2/CD4 cells were transduced with CCR3, CCR5, CCR8, CXCR4, GPR1, or APJ, and examined for susceptibilities to cell-free HIV/SIV. HIV-2 strains were grouped into two types by their coreceptor usage. The first group, CBL-20 and CBL-21, used CXCR4 exclusively; the other four strains used a few or all of the six coreceptors. These strains could further infect CD4-negative NP-2/CXCR4 or NP-2/CCR5 cells in the presence (all strains) or absence (SBL6669 and ROD strains) of soluble CD4. SIVagm and SIVmnd infected NP-2/CD4/GPR1 cells. The coreceptors CCR3, CCR8, GPR1, and APJ did not mediate the CD4-independent infection. Although HIV-2ROD and SIVmnd infected both NP-2/CD4/CXCR4 and NP-2/CD4/CCR5 cells, only CXCR4 and CCR5, respectively, were used in CD4-independent infection. Binding of virions to CD4-negative cells occurred at 4 degrees C. These findings suggest that there may be a correlation between the promiscuous use of coreceptors by HIV-2/SIV strains and their ability to infect CD4-negative cells.
Assuntos
Antígenos CD4/fisiologia , HIV-2/patogenicidade , Receptores Acoplados a Proteínas G , Receptores Virais/fisiologia , Proteínas de Saccharomyces cerevisiae , Vírus da Imunodeficiência Símia/patogenicidade , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , HIV-2/genética , Humanos , Receptores CCR5/genética , Receptores CCR5/fisiologia , Receptores CXCR4/genética , Receptores CXCR4/fisiologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/fisiologia , Receptores de Quimiocinas/fisiologia , Receptores de HIV/fisiologia , Vírus da Imunodeficiência Símia/genética , Transdução GenéticaRESUMO
We theoretically study the antigenic drift of viruses within an infected host, as observed in human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) infections, assuming that a finite number of antigen-determining sites at the viral envelop gene are responsible for the specific immune response. The pattern of antigen evolution becomes more complex than that predicted from the previous one-dimensional antigen space models. If the viral growth rate is sufficiently large, the demographic stochasticity for the fate of a new antigen mutant can be neglected. The high dimensionality in the way a virus escapes the immune defense in genotype space could then causes a rapid increase in the antigenic diversity and the total viral density, until finally the whole antigen genotypes are used up. The viral population is then driven to extinction in a host by the enhanced immune response to all genotypes. In contrast, if the viral growth rate is moderate or small so that only a small fraction of new antigen mutants can survive during the initial endangered period of random extinction, the viral antigenic diversity and the total density remain bounded, thereby enabling them to persist for a prolonged period by shifting the dominant antigen types. The phylogenetic pattern of antigen divergence is well characterized by the mean number of surviving antigen mutants from an antigen genotype. The substitution rate at antigen-determining sites increases as the efficiency of host immune response increases.
Assuntos
Variação Antigênica , Modelos Genéticos , Vírus/genética , Vírus/imunologia , Animais , Antígenos Virais/genética , Anemia Infecciosa Equina/virologia , Evolução Molecular , HIV/genética , HIV/imunologia , Infecções por HIV/virologia , Humanos , Vírus da Anemia Infecciosa Equina/genética , Vírus da Anemia Infecciosa Equina/imunologia , Mutação , Filogenia , Processos EstocásticosRESUMO
To understand the relationship between oxygen tension and nitric oxide (NO) function, one animal and two human studies were designed. In the animal study, the effect of NO in inducing the relaxation of aortic specimens was significantly lower by 68% under 480 mm Hg of oxygen tension than under 28 mm Hg, indicating that oxygen tension has an important role in determining the biological effects of NO. In a clinical analysis with nonsmokers (n = 23), the alveolar-to-arterial difference for oxygen (A-aDO(2)) was reciprocally correlated with exhaled NO concentrations (r = 0.53). Because NO concentration in the lower respiratory zone depends partly on the amount of inspirable NO originating in the upper airway, a well-ventilated area, requiring much perfusion, could receive greater amounts of NO than a poorly ventilated one. Thus, the reciprocal relation of A-aDO(2) with the concentration of exhaled NO is not necessarily incompatible with the effect of hypoxic pulmonary vasoconstriction in ventilation-to-perfusion (V'A/Q') imbalance. In our third experiment, with nonsmokers (n = 21), pure oxygen inhalation during mechanical ventilation significantly decreased the concentration of exhaled NO and enhanced A-aDO(2), indicating a relationship between NO and oxygen similar to that observed in the animal experiment. These findings led us to conclude that a positive relation between exhaled NO and blood oxygenation efficiency exists in the respiratory system, and further, that oxygen might affect this relationship. Thus, the relative balance of NO and oxygen concentrations may be another factor for consideration in respiratory function.
Assuntos
Resistência das Vias Respiratórias/fisiologia , Brônquios/fisiologia , Pulmão/fisiologia , Óxido Nítrico/fisiologia , Oxigênio/sangue , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/fisiologia , Oxigenoterapia , Troca Gasosa Pulmonar/fisiologia , Ratos , Valores de ReferênciaRESUMO
BACKGROUND: Mesangial cells are an important component of the glomerulus. Dysfunction of mesangial cells is thought to be involved in the development of human immunodeficiency virus type 1 (HIV-1)-associated nephropathy (HIVAN). HIVAN is a structural renal failure frequently observed in patients with acquired immune deficiency syndrome. However, the susceptibility of mesangial cells to HIV-1 is disputable. More than ten G protein-coupled receptors, including chemokine receptors, have been shown to act as HIV-1 coreceptors that determine the susceptibilities of cells to HIV-1 strains with specific cell tropisms. METHODS: We examined the susceptibility of mesangial cells to various HIV-1, HIV type 2 (HIV-2) and simian immunodeficiency virus (SIV) strains. Expression of CD4 and HIV/SIV coreceptors was examined by Western blotting and polymerase chain reaction. RESULTS: Mesangial cells were found to be susceptible to HIV-1 variant and mutants that infect brain-derived cells, but highly resistant to T-tropic (X4), M-tropic (R5) or dual-tropic (X4R5) HIV-1 strains. In addition, mesangial cells were also susceptible to HIV-2 and SIV strains that infect the brain-derived cells. Among HIV/SIV coreceptors we tested, the expression of GPR1 mRNA was detected in mesangial cells. Expression of CD4 mRNA and protein was also detected in them. Mesangial cells and GPR1-transduced CD4-positive cells showed similar susceptibilities to the HIV-1 variant and mutants and HIV-2 and SIV strains. CONCLUSIONS: CD4 and GPR1 mRNAs were detected in mesangial cells. Mesangial cells were susceptible to HIV/SIV strains that use GPR1 as a coreceptor. Our findings suggest that an orphan G protein-coupled receptor, GPR1, is a coreceptor expressed in mesangial cells. It remains to be investigated whether the interaction of mesangial cells with specific HIV-1 strains through GPR1 plays a role in the development of HIVAN.
Assuntos
Nefropatia Associada a AIDS/virologia , Mesângio Glomerular/virologia , HIV-1/patogenicidade , HIV-2/patogenicidade , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G , Proteínas de Saccharomyces cerevisiae , Vírus da Imunodeficiência Símia/patogenicidade , Nefropatia Associada a AIDS/fisiopatologia , Apoptose , Antígenos CD4/análise , Antígenos CD4/genética , Células Cultivadas , Suscetibilidade a Doenças , Fibroblastos/química , Fibroblastos/citologia , Fibroblastos/fisiologia , Regulação Viral da Expressão Gênica , Mesângio Glomerular/citologia , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Humanos , Mutação , Fragmentos de Peptídeos/genética , RNA Mensageiro/análise , Receptores de Superfície Celular/análise , Pele/citologia , VirulênciaRESUMO
The orphan G protein-coupled receptor APJ has been shown to be a coreceptor for human and simian immunodeficiency virus (HIV and SIV) strains. We have determined that some HIV and SIV strains use APJ as a coreceptor to infect the brain-derived NP-2/CD4 cells. Because apelin is an endogenous ligand for the APJ receptor, we examined the inhibitory effects of apelin peptides on HIV infection, and found that the apelin peptides inhibit the entry of some HIV-1 and HIV-2 into the NP-2/CD4 cells expressing APJ. The inhibitory efficiency has been found to be in the order of apelin-36>apelin-17>apelin-13>apelin-12.
Assuntos
Proteínas de Transporte/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , HIV-2/efeitos dos fármacos , HIV-2/fisiologia , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G , Sequência de Aminoácidos , Apelina , Receptores de Apelina , Encéfalo , Antígenos CD4/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Quimiocinas/farmacologia , Células Gigantes/metabolismo , Células Gigantes/patologia , Células Gigantes/virologia , Glioma/metabolismo , Glioma/patologia , Glioma/virologia , Transcriptase Reversa do HIV/metabolismo , HIV-1/enzimologia , HIV-1/metabolismo , HIV-2/enzimologia , HIV-2/metabolismo , Humanos , Concentração Inibidora 50 , Peptídeos e Proteínas de Sinalização Intercelular , Ligantes , Dados de Sequência Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Vírus da Imunodeficiência Símia/enzimologia , Vírus da Imunodeficiência Símia/metabolismo , Vírus da Imunodeficiência Símia/fisiologia , Células Tumorais CultivadasRESUMO
If the transmission occurs through local contact of the individuals in a spatially structured population, the evolutionarily stable (ESS) traits of parasite might be quite different from what the classical theory with complete mixing predicts. In this paper, we theoretically study the ESS virulence and transmission rate of a parasite in a lattice-structured host population, in which the host can send progeny only to its neighboring vacant site, and the transmission occurs only in between the infected and the susceptible in the nearest-neighbor sites. Infected host is assumed to be infertile. The analysis based on the pair approximation and the Monte Carlo simulation reveal that the ESS transmission rate and virulence in a lattice-structured population are greatly reduced from those in completely mixing population. Unlike completely mixing populations, the spread of parasite can drive the host to extinction, because the local density of the susceptible next to the infected can remain high even when the global density of host becomes very low. This demographic viscosity and group selection between self-organized spatial clusters of host individuals then leads to an intermediate ESS transmission rate even if there is no tradeoff between transmission rate and virulence. The ESS transmission rate is below the region of parasite-driven extinction by a finite amount for moderately large reproductive rate of host; whereas, the evolution of transmission rate leads to the fade out of parasite for small reproductive rate, and the extinction of host for very large reproductive rate.
Assuntos
Evolução Biológica , Interações Hospedeiro-Parasita/fisiologia , Parasitos/patogenicidade , Doenças Parasitárias/transmissão , Animais , Cadeias de Markov , Modelos Biológicos , VirulênciaRESUMO
OBJECTIVE: Although the prevalence of cancer in the rectosigmoid is high compared with that in the more proximal colon, the features of cancer developing from an adenoma have yet to be elucidated. The aim of this study is to examine the clinicopathological relationship between cancer and adenoma in the rectosigmoid. METHODS: A total of 340 adenomas located in the rectosigmoid in 255 patients were retrospectively examined regarding such clinicopathological factors as location and the grade of dysplasia. RESULTS: The prevalence of adenoma was 102 in the rectum and 238 in the sigmoid colon, respectively, whereas the prevalence of adenoma with high-grade dysplasia was 39 in the rectum and 48 in the sigmoid colon, respectively. This prevalence of adenoma with high-grade dysplasia was thus significantly higher in the rectum than in the sigmoid colon (p < 0.02). CONCLUSIONS: These findings suggest the possibility of different types of cancer development between adenoma of the rectum and sigmoid colon.
Assuntos
Adenoma/patologia , Pólipos Adenomatosos/patologia , Neoplasias Retais/patologia , Neoplasias do Colo Sigmoide/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adenoma/epidemiologia , Pólipos Adenomatosos/epidemiologia , Colo Sigmoide/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias Retais/epidemiologia , Reto/patologia , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/epidemiologiaRESUMO
To identify a cell surface molecule other than CD4 involved in infection of cultured cells with human immunodeficiency virus type 1 (HIV-1), mice were immunized with the CD4-negative Raji human B-cell line in order to isolate a monoclonal antibody (mAb). We isolated mAb 33A, which inhibited the infection of CD4-positive T cells, B cells, human peripheral blood lymphocytes (PBL), and brain-derived cells with HIV-1. Formation of viral DNA was also blocked when CD4-positive Raji cells were treated with 33A after adsorption of HIV-1, but not before its adsorption. mAb 33A had little effect on syncytium formation induced by cocultivation with HIV-1-producing cells. Flow cytometry revealed that 33A reacted with HTLV-I-positive T-cell lines, Burkitt's lymphoma cell lines, phytohemagglutinin (PHA) -stimulated PBL, brain-derived fibroblast-like cells, and some adherent cell lines, but hardly at all with immature T-cell lines. Immunoblotting experiments showed that 33A recognized an antigen with an apparent molecular mass of 32 kDa, but did not recognize chemokine receptors such as CXCR4, CCR5, or CCR3. The distribution characteristic of the antigen recognized by 33A on various cells and its molecular weight suggest that mAb 33A recognizes a new cellular antigen that is necessary for HIV-1 entry.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Superfície/fisiologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/virologia , HIV-1/fisiologia , Leucócitos Mononucleares/virologia , Macrófagos/virologia , Animais , Anticorpos Monoclonais/isolamento & purificação , Antígenos de Superfície/imunologia , Linfócitos B/imunologia , Linhagem Celular , DNA Viral/biossíntese , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Células Gigantes/fisiologia , Proteína do Núcleo p24 do HIV/análise , Humanos , Imunização , Immunoblotting , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To compare the differences in intratumor DNA ploidy distribution pattern between differentiated and undifferentiated carcinoma of the stomach. STUDY DESIGN: Two hundred five cases of surgically resected gastric carcinoma were studied, comprising 125 differentiated and 80 undifferentiated carcinomas. DNA ploidy was determined by means of flow cytometry in stepwise sections of the entire tumor. The intratumor DNA ploidy distribution pattern was compared between these two histologic types. RESULTS: Differentiated carcinomas comprised 35 cases of predominantly diploid (28%) and 90 cases of predominantly aneuploid (72%) tumors, while undifferentiated carcinomas comprised 46 cases of predominantly diploid (57.5%) and 34 cases of predominantly aneuploid (42.5%) (P < .01). The frequency of cases showing predominantly aneuploidy among the differentiated carcinomas was significantly higher than among the undifferentiated carcinomas at stages IA and IIIA. The rate of cases showing heterogeneity was lower among the early-stage cases than among the advanced-stage cases in both histologic types. Among the differentiated carcinomas, there were 22 cases that had more than six DNA stemlines in each tumor, whereas among undifferentiated carcinomas, there were six such cases (P < .05). CONCLUSION: There were more cases with high malignant potential among the differentiated carcinoma cases than among the undifferentiated carcinoma cases in the present series.
Assuntos
Adenocarcinoma Papilar/genética , Adenocarcinoma/genética , Carcinoma de Células em Anel de Sinete/genética , DNA de Neoplasias/análise , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Adenocarcinoma Papilar/patologia , Aneuploidia , Carcinoma de Células em Anel de Sinete/patologia , Separação Celular , Citometria de Fluxo , Humanos , Microtomia/métodos , Estadiamento de Neoplasias , Ploidias , Neoplasias Gástricas/patologiaRESUMO
To investigate the roles of human T-cell leukemia virus type 1 (HTLV-1) envelope (Env) proteins gp46 and gp21 in the early steps of infection, the effects of the 23 synthetic peptides covering the entire Env proteins on transmission of cell-free HTLV-1 were examined by PCR and by the plaque assay using a pseudotype of vesicular stomatis virus (VSV) bearing the Env of HTLV-1 [VSV(HTLV-1)]. The synthetic peptide corresponding to amino acids 400 to 429 of the gp21 Env protein (gp21 peptide 400-429, Cys-Arg-Phe-Pro-Asn-Ile-Thr-Asn-Ser-His-Val-Pro-Ile-Leu-Gln-Glu-Arg-P ro-Pro-Leu-Glu-Asn-Arg-Val-Leu-Thr-Gly-Trp-Gly-Leu) strongly inhibited infection of cell-free HTLV-1. By using the mutant peptide, Asn407, Ser408, and Leu413, -419, -424, and -429 were confirmed to be important amino acids for neutralizing activity of the gp21 peptide 400-429. Addition of this peptide before or during adsorption of HTLV-1 at 4 degrees C did not affect its entry. However, HTLV-1 infection was inhibited about 60% when the gp21 peptide 400-429 was added even 30 min after adsorption of HTLV-1 to cells, indicating that the amino acid sequence 400 to 429 on the gp21 Env protein plays an important role at the postbinding step of HTLV-1 infection. In contrast, a monoclonal antibody reported to recognize the gp46 191-196 peptide inhibited the infection of HTLV-1 at the binding step.
Assuntos
Produtos do Gene env/farmacologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Peptídeos/farmacologia , Proteínas Oncogênicas de Retroviridae/farmacologia , Sequência de Aminoácidos , Animais , Gatos , Linhagem Celular , Produtos do Gene env/síntese química , Produtos do Gene env/química , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/química , Reação em Cadeia da Polimerase , Estrutura Terciária de Proteína , RNA Viral/metabolismo , Proteínas Oncogênicas de Retroviridae/síntese química , Proteínas Oncogênicas de Retroviridae/química , Transcrição Gênica , Proteínas do Envelope Viral/química , Ensaio de Placa Viral , Produtos do Gene env do Vírus da Imunodeficiência HumanaRESUMO
Thirty-seven metal compounds were examined for inhibitory activities against infection with human immunodeficiency virus type 1 (HIV-1). Zinc group metal compounds, namely, zinc acetate, zinc chloride, zinc nitrate, cadmium acetate and mercury chloride, showed anti-HIV-1 activities. Cadmium and mercury compounds at 1-10 microg/ml and zinc compounds at 100 microg/ml strongly inhibited HIV-1 infection, although the cadmium, mercury and zinc compounds had severe cytotoxities at 100, 100 and 1000 microg/ml, respectively. They inhibited transcription of HIV-1 RNA and HIV-1 production at concentrations at which they did not affect the growth of HIV-1-producing cells. They had little effect on syncytium formation resulting from cocultivation of uninfected with HIV-1-producing cells. Nor did they affect HIV-1 DNA synthesis following HIV-1 infection. The metal compounds may owe their anti-HIV-1 effects to inhibition of HIV-1 DNA to RNA transcription, rather than inhibition of the adsorption, penetration or reverse transcription step of HIV-1 infection.
Assuntos
HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Leucócitos Mononucleares/virologia , Linfócitos T/virologia , Replicação Viral/efeitos dos fármacos , Compostos de Zinco/farmacologia , Antivirais/farmacologia , Antivirais/toxicidade , Compostos de Cádmio/farmacologia , Compostos de Cádmio/toxicidade , Divisão Celular/efeitos dos fármacos , Linhagem Celular , DNA Viral/biossíntese , Células Gigantes/fisiologia , Humanos , Compostos de Mercúrio/farmacologia , Compostos de Mercúrio/toxicidade , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transcrição Gênica/efeitos dos fármacos , Compostos de Zinco/toxicidadeRESUMO
We examined the effect of amino acid substitutions of the GPGR (glycine-proline-glycine-arginine) tip sequence at the V3 domain of the Env protein of human immunodeficiency virus type 1 (HIV-1) on its cell tropism and coreceptor use. We changed the GPGR sequence of a T-cell line (T)- and macrophage (M)-tropic (R5-R3-X4) HIV-1 strain, GUN-1wt, to GA(alanine)GR (the resulting mutant was designated GUN-1/A), GL(leucine)GR (GUN-1/L), GP(proline)GR (GUN-1/P), GR(arginine)GR (GUN-1/R), GS(serine)GR (GUN-1/S), or GT(threonine)GR (GUN-1/T). GUN-1/A, GUN-1/S, and GUN-1/T mutants infected brain-derived cells such as a CD4-transduced glioma cell line, U87/CD4, and a brain-derived primary cell strain, BT-20/N, as well as T-cell lines in a CD4-dependent manner, although the plating of these mutants onto macrophages was inhibited. GUN-1/L, GUN-1/P, and GUN-1/R mutants showed both T- and M-tropism, but did not plate onto the brain-derived cells. A CCR3, CCR5, CCR8, or CXCR4 gene was introduced into a CD4-positive glioma cell line, NP-2/CD4, which demonstrated complete resistance to various HIV-1 strains. Not only HIV-1 strains, which were infectious to macrophages, such as GUN-1wt, GUN-1v, GUN-1/L, and GUN-1/P, but also an HIV-1 strain, GUN-1v, which was hardly infectious to macrophages, grew well in NP-2/CD4 cells expressing CCR3 or CCR5. However, the M-tropic GUN-1/R mutant could not efficiently use CCR5 nor CCR3. No point mutants, except GUN-1/L, grew well in NP-2/CD4 cells expressing CCR8. These findings indicate that the cell tropism of HIV-1 to macrophages and brain-derived cells and their use of the coreceptors were markedly, though not always concomitantly, affected by the tip sequence of the V3 domain.
Assuntos
Encéfalo/virologia , Proteína gp120 do Envelope de HIV/fisiologia , HIV-1/fisiologia , Macrófagos/virologia , Fragmentos de Peptídeos/fisiologia , Receptores de HIV/metabolismo , Linfócitos T/virologia , Encéfalo/citologia , Antígenos CD4/fisiologia , Linhagem Celular , Células Cultivadas , Antígenos HIV/metabolismo , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Humanos , Mutagênese Sítio-Dirigida , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Mutação Puntual , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Receptores de HIV/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
Six cases of carcinosarcoma of the esophagus were studied clinicopathologically, immunohistochemically and with DNA flow cytometry. Transitional areas with morphology intermediate between carcinoma and sarcoma were found microscopically in all cases. Immunohistochemically, the carcinomatous areas contained keratin-positive cell components in all cases while vimentin-positive cells were found in sarcomatous areas in 5 cases. By DNA flow analysis of microdissection, the sarcomatous components of the tumors showed an aneuploid pattern with one exception, in contrast the carcinomatous components were diploid in all cases. In these few cases, PCNA, S-phase fraction and the mitotic rate were extremely high, apparently indicating a correlation with malignant behavior. Accordingly, examination by immunohistochemistry and DNA ploidy is useful for the analysis of biological properties in the so-called carcinosarcoma of the esophagus.
Assuntos
Carcinossarcoma/patologia , Neoplasias Esofágicas/patologia , Idoso , Aneuploidia , Carcinossarcoma/química , Carcinossarcoma/genética , DNA de Neoplasias/análise , Neoplasias Esofágicas/química , Neoplasias Esofágicas/genética , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
Heat shock cognate protein 70 (HSC70) has been shown to bind to the peptide corresponding to amino acids 197 to 216 of human T-cell lymphotropic virus type I (HTLV-I) envelope protein, gp46, and an anti-HSC70 monoclonal antibody (mAb) inhibits HTLV-I-induced syncytium formation. These findings suggest that HSC70 is necessary for the entry of HTLV-I into its target cells. Here we showed that HSC70 directly binds to gp46 by co-immunoprecipitation of HSC70 and gp46 from HTLV-I-producing human T-cell lysate. However, transduction of human HSC70 cDNA into BaF3 cells, which were found to be highly resistant to HTLV-I infection, did not support the HTLV-I entry, and HSC70 expressed in NIH3T3 cells, which were found to be almost resistant to syncytium formation upon cocultivation with HTLV-I-producing cells but sensitive to infection with cell-free HTLV-I, enhanced cell fusion induced by HTLV-I-producing cells, but did not enhance the entry of cell-free HTLV-I into these cells. The mAb against HSC70 inhibited syncytium formation in NIH3T3 cells expressing HSC70, but showed little effect on infection of these cells with cell-free HTLV-I. These findings indicate that HSC70 markedly enhances syncytium formation induced by HTLV-I but does not facilitate HTLV-I entry into target cells.
Assuntos
Proteínas de Transporte/fisiologia , Fusão Celular/fisiologia , Proteínas de Choque Térmico HSP70 , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Células 3T3 , Animais , Anticorpos Monoclonais/farmacologia , Sequência de Bases , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Gatos , Linhagem Celular , Primers do DNA/genética , Produtos do Gene env/genética , Produtos do Gene env/fisiologia , Células Gigantes/patologia , Células Gigantes/fisiologia , Proteínas de Choque Térmico HSC70 , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Camundongos , Ratos , Proteínas Oncogênicas de Retroviridae/genética , Proteínas Oncogênicas de Retroviridae/fisiologia , Transdução GenéticaRESUMO
Human T cell leukemia virus type I (HTLV-I) is a retrovirus that is not lysed by human serum or complement. It has not been determined, however, whether HTLV-I directly binds to complement components or whether it retains infectivity after incubation with human serum. We investigated the effects of human serum on the infectivity of cell-free HTLV-I produced by human and animal cells. Plating of vesicular stomatitis virus (HTLV-I) pseudotypes prepared in cat or human cells and formation of HTLV-I DNA after infection of cell-free HTLV-I produced by cat or human cells were markedly inhibited by treatment with fresh human serum, but not by heat-inactivated serum. HTLV-I infection was also inhibited by treatment with C2-, C3-, C6-, or C9-deficient serum, but not by C1q-deficient serum. Inhibitory activities of normal human serum against HTLV-I were neutralized by anti-C1q serum. Furthermore, purified C1q inhibited HTLV-I infection. The direct binding of C1q to HTLV-I was confirmed by comigration of C1q with HTLV-I virion upon sucrose density gradient ultracentrifugation of HTLV-I virion treated with C1q. Binding assay using synthetic envelope peptides indicated that C1q bound to an extramembrane region of the gp21 transmembrane protein. These findings indicate that the human complement component C1q inactivates HTLV-I infectivity.
Assuntos
Antivirais/imunologia , Complemento C1q/fisiologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Imunossupressores/imunologia , Animais , Gatos , Sistema Livre de Células/imunologia , Complemento C1q/metabolismo , Via Clássica do Complemento , Proteínas do Sistema Complemento/deficiência , Citotoxicidade Imunológica , Produtos do Gene env/metabolismo , Glicoproteínas/metabolismo , Infecções por HTLV-I/sangue , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Testes de Neutralização , Ligação Proteica/imunologia , Vírus da Estomatite Vesicular Indiana/imunologia , Vírion/metabolismoRESUMO
To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.