RESUMO
Diminished tissue injury and shortened clinical recovery are benefits of using an endoscopic approach for patients needing operative procedure. In the course of developing an experimental model requiring procurement of topographically precise lung biopsy specimens, we sought to apply thoracoscopy as a research alternative to thoracotomy. In addition, we investigated the influence of thoracoscopy on postprocedure recovery practices using rabbits divided into four treatment groups. Rabbit groups 1 and 2 underwent thoracoscopy and lung biopsy while maintained by one-lung anesthesia. Additionally, group 2 had ketoprofen and bupivacaine HCl analgesics injected for treatment during postprocedure recovery. These two groups were compared to control rabbits in groups 3 and 4, which underwent inhalant anesthesia without thoracoscopy. Control group 3 also received the injection analgesic combination. During recovery, rabbit behavior was systematically assessed for evidence of pain. No behavior considered indicative of pain needing intervention was observed regardless of treatment group. Limited changes in plasma corticosterone, catecholamines, and prostaglandin E2 levels measured during recovery were difficult to associate with any treatment. Unexpectedly, significantly different mean corticosterone and catecholamines levels were detected in rabbits given the injection analgesic combination in the absence of thoracoscopic procedure, as compared to other treatment groups. The results highlight the importance of awareness that analgesic drug administration has the potential to alter homeostasis and affect interpretation of some study findings by its own guise. Correlation of the mean pain study results with plasma biochemical data supports preferential use of thoracoscopy as a refinement for limiting postprocedural pain in research models.
Assuntos
Pulmão/cirurgia , Dor Pós-Operatória/prevenção & controle , Toracoscopia , Anestesia por Inalação/métodos , Bem-Estar do Animal , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Comportamento Animal , Biópsia/métodos , Gasometria , Broncoscopia , Corticosterona/sangue , Dinoprostona/sangue , Modelos Animais de Doenças , Feminino , Pulmão/patologia , Masculino , Norepinefrina/sangue , Coelhos , Organismos Livres de Patógenos EspecíficosRESUMO
BACKGROUND: Intravenous naloxone frequently ameliorates the pruritus of cholestasis, but its low oral bioavailability precludes its use as a long-term therapy. Nalmefene is an orally bioavailable opiate antagonist. OBJECTIVE: We assessed the efficacy of oral nalmefene in ameliorating the pruritus of cholestasis. METHODS: In a prospective controlled study conducted in a tertiary referral hospital, 11 patients with generalized pruritus complicating chronic liver disease were randomized to receive either nalmefene or placebo in a double-blinded fashion for 2-month periods. Scratching activity was measured continuously for 24-hour periods at baseline and at the end of each treatment period. RESULTS: Data on 8 patients who received at least 1 course of nalmefene were available for comparison with corresponding control data, which consisted of observations obtained during a course of placebo and/or at baseline. Nalmefene therapy was associated with a 75% reduction in the geometric mean hourly scratching activity (P <.01) and a decrease in the mean of a visual analogue score of the perception of pruritus in all 8 patients (mean decrease 77%, P <.01). CONCLUSION: Oral administration of nalmefene can ameliorate pruritus complicating chronic liver disease.
Assuntos
Antipruriginosos/administração & dosagem , Colestase/complicações , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/administração & dosagem , Prurido/tratamento farmacológico , Administração Oral , Adulto , Antipruriginosos/efeitos adversos , Método Duplo-Cego , Humanos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Medição da Dor , Prurido/etiologia , Comprimidos , Fatores de TempoRESUMO
The tumorigenicity of adenovirus (Ad) 12-transformed mouse cells was evaluated by analyzing the relationship of tumor cell dose to tumor incidence and tumor latency. The tumor producing dose 50% endpoint values used to define these relationships remained stable during 52 weeks of serial passage in tissue culture and were not determined by low frequency events within the cell population. The data from these analyses suggest that the phenotype of Ad12-transformed mouse cells is influenced by two set of traits--those traits that determine the threshold number of cells required for tumor formation and those that extend the cell dose-dependent tumor latency period. Both traits are established independently of cell immortalization, and both can be influenced by the immunological status of tumor-challenged animals. These observations were verified by using mouse cells transformed by Ad5 and SV40. The biological and molecular processes that contribute to these traits remain to be determined. The approach developed by this analysis provides a reliable, quantitative means of evaluating endogenous traits that determine transformed cell tumorigenicity. This method can also be used to test the effects of tumor cell manipulations or changes in host response that could alter expression or detection of these neoplastic cell traits.
Assuntos
Adenoviridae/fisiologia , Transformação Celular Neoplásica , Transformação Celular Viral/fisiologia , Neoplasias Experimentais/virologia , Vírus 40 dos Símios/fisiologia , Animais , Linhagem Celular Transformada , Transplante de Células , Cricetinae , Estudos de Avaliação como Assunto , Camundongos , Camundongos Endogâmicos BALB C , FenótipoRESUMO
BACKGROUND: We previously studied the occurrence of muscle tone reduction (MTR), sawtooth waves (STW), and REM in sleep, and found a stereotypical sequence of these events in normal subjects. Patients with the postpolio syndrome may have involvement of the reticular formation in the brainstem, an area known to mediate initiation of REM sleep. We hypothesized that such brainstem pathology might affect the stereotyped sequence of events initiating REM sleep. METHODS: We measured the latencies to the onsets of the first MTR, the first STW, and the first REM in 13 patients with postpolio syndrome, 7 of whom had bulbar involvement. All latencies were calculated from the last body movement before the onset of REM sleep. RESULTS: Using analysis of variance, we found highly significant differences among the overall mean latencies of the three types of onset (MTR, STW, REM) and also between the mean latencies of the two subgroups of patients (bulbar, nonbulbar). Although the latencies for the entire group were longer than those of the normal volunteers, the differences were not significant. However, when the bulbar and nonbulbar groups were compared, analysis of variance showed significantly longer latencies for the bulbar group than for the nonbulbar group (p < 0.0001). The values for the nonbulbar patients closely resembled those for the normal controls. Although the latencies differed, the slopes of the regressions of REM on STW, STW on MTR, and REM on MTR resembled each other closely (p = 0.924). CONCLUSION: Prolongation of these latencies may be due to prolonged recruitment time for neurons in the pontine tegmentum, following damage from polio. This may be a sensitive marker of a brainstem lesion, and may also represent a type of sleep pathology not previously explored.
Assuntos
Síndrome Pós-Poliomielite/fisiopatologia , Sono REM/fisiologia , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Polissonografia , Tempo de Reação/fisiologiaRESUMO
The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued. Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis.
Assuntos
Colestase/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/uso terapêutico , Prurido/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Criança , Humanos , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/farmacocinética , Naltrexona/uso terapêuticoRESUMO
The DBA/2 and C57BL/6 mouse strains, as well as the BXD RI lines derived from these strains, were used to map the genes controlling experimentally induced systemic lupus erythematosus (SLE). SLE was induced using two immunologic approaches: (1) immunization with the human monoclonal anti-DNA antibody expressing the 16/6Id, to which the DBA/2 strain is susceptible (responder) and the C57BL/6 strain is resistant (nonresponder); and (2) induction of autoimmune GVHD in B6D2F1 hosts by inoculation of parental DBA/2 (induces SLE) or C57BL/6 (does not induce SLE) T cells. By both approaches the BXD RI lines could be divided into distinct DBA/2-like and C57BL/6-like categories. Concordance of SLE induced by both methods was observed for susceptibility and resistance in 13/15 BXD lines (P < 0.005). The results suggest that at least two non-H-2 genes control susceptibility and resistance to experimentally induced SLE, one mapping to chromosome 7 and the other mapping to chromosome 14.
Assuntos
Lúpus Eritematoso Sistêmico/genética , Animais , Anticorpos Antinucleares/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Complexo Antígeno-Anticorpo/metabolismo , Autoimunidade , Mapeamento Cromossômico , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunização , Rim/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Linfócitos T Citotóxicos/imunologiaRESUMO
We examined the effects of a human milk diet on rats with chemical colitis induced with a 4% acetic acid enema. Colonic myeloperoxidase activity was used as a surrogate marker for neutrophil infiltration. Control rats fed rat chow had little colonic myeloperoxidase activity; geometric mean, 0.27 U/g of tissue. Rats with colitis fed rat chow had significantly increased colonic myeloperoxidase activity (geometric mean, 6.76 U/g, p < 0.01 versus no colitis), as did rats with colitis fed infant formula or Pedialyte (geometric mean, 6.92 and 8.13 U/g, respectively, both p < 0.01 versus no colitis). Animals with colitis fed human milk had significantly lower colonic myeloperoxidase activity (geometric mean, 2.34 U/g) than did animals with colitis fed either chow or infant formula (p < 0.001). Similar effects were seen in rats with colitis fed infant formula supplemented with recombinant human IL-1 receptor antagonist (geometric mean, 1.95 U/g). These data show that orally administered human milk has an antiinflammatory effect on chemically induced colitis in rats, which may be mediated in part by IL-1 receptor antagonist contained in human milk.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/terapia , Nutrição Enteral , Leite Humano , Ácido Acético , Doença Aguda , Animais , Colite/induzido quimicamente , Colite/patologia , Feminino , Humanos , Leucócitos/patologia , Masculino , Peroxidase/isolamento & purificação , Projetos Piloto , Ratos , Ratos Sprague-DawleyRESUMO
To enhance and steer immune responses to synthetic peptide vaccines toward selected functional types and to understand the cooperative action of cytokines in fine-tuning the immune response, we attempted to influence the in vivo cytokine environment by delivering cytokines directly to the microenvironment in which the immune response is initiated. Here we study the effects of IL-2, IL-4, IL-7, IL-1beta, IL-12, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF) incorporated with peptide in adjuvant on a variety of responses elicited: CTL, T cell proliferation, cytokine production and message, and Ab isotype. We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs. Novel synergies were also detected. GM-CSF synergized with IL-12 for CTL induction in BALB/c mice concomitant with suppression of Th2 cytokines IL-4 and IL-10. TNF-alpha also synergized with IL-12, but by a different mechanism, inducing IFN-gamma production in BALB/c mice and thus shifting the response to a Th1 phenotype. The results presented here suggest that in addition to IL-2, optimum induction of CD8+ CTL in vivo requires a combination of cytokines, including GM-CSF (probably acting to enhance Ag presentation and CD4+ cell help) and IL-12 (steering the Th response toward Th1 cytokines).
Assuntos
Vacinas contra a AIDS/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade , Ativação Linfocitária/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Sequência de Aminoácidos , Animais , Citocinas/administração & dosagem , Sinergismo Farmacológico , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/imunologia , Humanos , Interleucina-12/administração & dosagem , Interleucina-12/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Peptídeos/administração & dosagem , Peptídeos/imunologia , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/imunologiaRESUMO
'Sawtoothed' waves occur during rapid eye movement (REM) sleep, but their source as well as their function is not known. We studied the onset of sawtooth waves (STW) in relation to the onset of muscle tone reduction (MTR) and to REM during 20 polysomnographic recordings in 11 normal volunteers. Seventy-seven (85%) of a total of 91 REM sleep cycles were used for further analysis, because within a 1000 s interval they showed a relatively stereotyped sequence of events: a generalized body movement, followed by MTR, then the appearance of STW, and ending with the first REM. The first STW often occurred during the electrographic stage II period prior to the beginning of the REM, by which time muscle tone was either already at or close to the tone level of the REM sleep period in all subjects. The overall mean onset time of MTR was 267 s (range 89-660 s), STW was 378 s (range 169-779), and REM was 448 s (range 265-849); their differences were highly significant (F = 27.1, df 2,20, P < 0.001). Our data suggest that a predictable sequence of muscle tone reduction, then STW, and then REM, precedes the generally accepted onset of the REM sleep period, and may have implications for the redesignation of physiologic REM sleep onset.
Assuntos
Eletroencefalografia/estatística & dados numéricos , Movimentos Oculares/fisiologia , Tono Muscular/fisiologia , Sono REM/fisiologia , Adulto , Mapeamento Encefálico , Eletromiografia , Feminino , Humanos , Masculino , Periodicidade , PolissonografiaRESUMO
The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys. To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background. Multiple H-2-linked loci were found to contribute, each with a different mechanism. One locus mapped to the I-A region based on the strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice. Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent. Two loci mapped to the right of I-A (FE, H-2S, or H-2D) based on a correlation with the number of H-2k loci to the right of I-A in mice that were I-Ak. One effect was Ab independent and may correspond to a possible negative effect of the I-Ek locus. T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection. Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms. These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population.
Assuntos
Antígenos H-2/genética , Antígenos H-2/imunologia , Vacinas Antimaláricas/imunologia , Plasmodium falciparum/imunologia , Precursores de Proteínas/imunologia , Proteínas de Protozoários/imunologia , Animais , Antígenos de Superfície/imunologia , Sequência de Bases , Western Blotting , Ensaio de Imunoadsorção Enzimática , Genes MHC Classe I , Glutationa Transferase , Imunidade/genética , Imunização Passiva , Proteína 1 de Superfície de Merozoito , Camundongos , Dados de Sequência Molecular , Especificidade da EspécieRESUMO
We studied phagocyte reduced nicotinamide adenine dinucleotide phosphate function to evaluate production of reactive oxygen species in both X-linked and autosomal forms of chronic granulomatous disease. We found a consistent and significant difference between the activated granulocyte response of the X-linked (gp91-phagocyte oxidase) form of chronic granulomatous disease (n = 18) and that of the most common autosomal recessive (p47-phagocyte oxidase) form of the disease (n = 17). The data indicate that mutations in the p47-phagocyte oxidase component of the reduced nicotinamide adenine dinucleotide phosphate oxidase component do not completely prevent oxidation despite severe defects in superoxide generation.
Assuntos
Doença Granulomatosa Crônica/enzimologia , Doença Granulomatosa Crônica/genética , Complexos Multienzimáticos/metabolismo , NADH NADPH Oxirredutases/metabolismo , Citometria de Fluxo , Genótipo , HumanosRESUMO
In this study, we report that differences between T-cell receptor (TCR) V beta gene family usage in CD4+ and CD8+ T cells are significantly greater in a subgroup of patients with common variable immunodeficiency (CVI) and high levels of activated CD8+ T cells (CD8hi CVI) than in controls (P < 0.001). In CD8hi CVI patients, such differences were also significantly greater for V beta 12 than for other V beta families. As the causes of the differential usage of V beta gene families by CD4+ and CD8+ T cells are under investigation, it was interesting that the combined differences between V beta gene family usage in the CD4+ and CD8+ T-cell subpopulations as a whole were significantly lower than the combined differences between individual V beta gene family usage in either CD4+ or CD8+ T-cell subpopulations (P < 0.001 in both control and CD8hi CVI patients). Further, the pattern of V beta gene family usage in CD4+ T cells was remarkably similar to that in CD8+ T cells in both groups. These data strongly suggest that differences in V beta gene family usage arising from coselection by major histocompatibility complex (MHC) class I versus MHC class II restriction elements do not fundamentally distort 'basic' V beta gene family usage patterns. They also support the concept that differences in CD4+ and CD8+ T-cell V beta gene family usage, which were increased in CD8hi CVI, can arise from high-affinity interactions between disease-associated antigens or superantigens and T cells in the post-thymic T-cell compartment.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunodeficiência de Variável Comum/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Sequência de Bases , Imunodeficiência de Variável Comum/genética , Regulação da Expressão Gênica/imunologia , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Timo/imunologiaRESUMO
We developed a method to study the DNA synthetic cycles of Entamoeba histolytica and Entamoeba invadens by flow cytometry (FCM) based on a preparative procedure to reduce both high levels of natural fluorescence and non-specific adsorption of fluorochromes. We modeled G1, S, and G2 phases as a series of overlapping Gaussian curves. Both E. histolytica and E. invadens displayed G1, S, and G2 proportions that are consistent with eukaryotic cell populations in exponential or stationary growth phase. Exponential phase E. histolytica populations contained a hypodiploid subset with a mass of about 20% less than the diploid value which we estimate by FCM to be 24 x 10(-14) g DNA/cell. Exponential phase E. invadens populations contained a hypodiploid subset with a mass of about 6% less than the diploid value which we estimate by FCM to be 30 x 10(-14) g DNA/cell.
Assuntos
DNA de Protozoário/biossíntese , Entamoeba histolytica/metabolismo , Entamoeba/metabolismo , Citometria de Fluxo/métodos , Modelos Biológicos , Animais , Simulação por Computador , Entamoeba/citologia , Entamoeba histolytica/citologia , Corantes Fluorescentes , Interfase , Coloração e Rotulagem , Fixação de TecidosRESUMO
OBJECTIVE: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. DESIGN: Double-blind, placebo-controlled, crossover trial with four periods. SETTING: Clinical research referral center. PATIENTS: 29 pruritic patients with liver diseases of various causes. INTERVENTION: Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. MEASUREMENTS: During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. RESULTS: One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. CONCLUSIONS: Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.
Assuntos
Colestase/complicações , Naloxona/uso terapêutico , Prurido/tratamento farmacológico , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Atividade Motora , Naloxona/administração & dosagem , Naloxona/efeitos adversos , Prurido/etiologia , Resultado do TratamentoRESUMO
Rabbits can be infected with human immunodeficiency virus (HIV-1), but no disease signs similar to acquired immunodeficiency syndrome (AIDS) have been reported to date. In our attempt to develop types of HIV-1 more virulent for rabbits, an immunodeficiency characterized by CD4+ lymphocytopenia and opportunistic infection was induced by transfusion from HIV-1-infected rabbits. The original donor was infected for 27 months; initial passage resulted in infection of two rabbits. Transfusions from these two infected rabbits. Transfusions from these two infected rabbits caused immunodeficiency in 12 recipients. One rabbit died at 3 months and a second at 8 months postransfusion with lymphocyte depletion in lymphoid organs; one of these and another of the CD4+ lymphocytopenic rabbits had opportunistic infections. Lentivirus-like particles were detected in thymus and spleen from an affected rabbit. Despite appearance of AIDS-like disease signs, antibodies to HIV-1 probes were detected in rabbits receiving passaged blood. However, RNA transcripts hybridizing with HIV-1 probes were detected in organs of some rabbits, implicating the initial HIV infection in the disease. Transfusion from uninfected donors produced no signs of immunodeficiency, which suggests the involvement of an HIV-related agent. The present data do not allow definitive characterization of the agent(s) involved in the immunodeficiency. Possibilities include activation of a rabbit retrovirus or, alternatively, development of a mutated HIV-1 strain.
Assuntos
Sangue/virologia , Linfócitos T CD4-Positivos/patologia , Infecções por HIV/transmissão , HIV-1/patogenicidade , Síndromes de Imunodeficiência/virologia , Animais , Transfusão de Sangue , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , HIV-1/imunologia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Linfonodos/virologia , Microscopia Eletrônica , RNA Viral/análise , Coelhos , Baço/ultraestrutura , Baço/virologia , Timo/ultraestrutura , Timo/virologiaRESUMO
The age-specific seroprevalence of antibody to hepatitis A virus (HAV) and antibody to hepatitis E virus (HEV) were studied in persons in Pune, India, where both viruses are endemic. The data showed that HAV infected the majority of persons by age 3 years and virtually 100% by late childhood. In contrast, infection with HEV was rare in children and did not reach peak prevalence (33%-40%) until early adulthood. The reason for the differences in infection rates between HAV and HEV is not known. Age-specific antibody patterns in serum samples obtained 10 years apart show that neither HAV nor HEV has diminished in medical importance in this Indian community.
Assuntos
Hepatite A/epidemiologia , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite A/imunologia , Anticorpos Anti-Hepatite A , Hepatite E/imunologia , Hepatovirus/imunologia , Humanos , Índia/epidemiologia , Masculino , Prevalência , Fatores de TempoRESUMO
In a controlled, randomized trial, the authors investigated the effects of reconstituted human high-density lipoprotein (R-HDL) on survival, endotoxemia, cytokine production and pathophysiologic and metabolic events in an animal model of gram-negative septic shock. At 0.5, 8 and 16 hr after implantation of a clot infected with Escherichia coli, canines received intravenous R-HDL (n = 13), control lipid (n = 7) or human serum albumin (HSA, n = 7) divided into three doses (0.3, 0.1 and 0.1 g/kg, respectively) at an hourly rate of 0.1 g/kg. All animals were treated with antibiotics and fluids. Animals treated with R-HDL had lower levels of circulating endotoxin and tumor necrosis factor and a smaller decrease in white blood cell counts than did animals treated with lipids and HSA (all P < .05). The survival times of lipid- and HSA-treated animals were similar (P = .3) and were significantly greater than those of R-HDL-treated animals (P = .02). During the first 6 hr after clot implantation, R-HDL-treated animals had significantly greater abnormalities in liver function test findings compared with lipid- and HSA-treated animals (all P < .05). For the first 24 hr, R-HDL-treated animals had significant increases in HDL levels; however, there were no significant relationships between these levels and the constituents of HDL (apolipoprotein AI and phosphatidylcholine) or liver function abnormalities and survival times (all r < .2, P > .3). In normal animals, administration of R-HDL (in similar doses) caused transient elevation of liver enzymes; in animals given sterile clot i.p., R-HDL caused seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Lipoproteínas LDL/uso terapêutico , Choque Séptico/tratamento farmacológico , Animais , Apolipoproteínas/sangue , Modelos Animais de Doenças , Cães , Endotoxinas/sangue , Fígado/fisiopatologia , Choque Séptico/sangue , Choque Séptico/fisiopatologia , Fator de Necrose Tumoral alfa/análiseRESUMO
: In this study the TCR-Vß repertoire expressed in T cells of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) was examined using a reverse transcription-PCR (RT-PCR) technique for TCR-Vß mRNA. Using a qualitative RT-PCR method, LPMC of patients with IBD and control individuals were shown to contain mRNA for each of 20 TCR-Vß families, indicating that IBD is not associated with a major deletion or expansion of any TCR-Vß family. Subsequently, using a quantitative method for four frequently expressed TCR-Vß families, it was shown that the pattern of TCR-Vß expression was different in PBMC and LPMC of both IBD patients and control individuals. In addition, it was shown that the LPMC/PBMC ratio of mean mRNA values for TCR-Vß2, but not for TCR-Vß6, 7, and 14 was lower in IBD patients than control individuals. These results show that the TCR-Vß repertoire in PBMC and LPMC is different both in IBD patients and control individuals. In addition, they show that the TCR-Vß repertoire is altered in IBD, possibly due to an immune response to disease specific antigens, superantigens or neoantigens.
RESUMO
The mucosa of the gastrointestinal tract is presumably an important reservoir for human immunodeficiency virus type 1 (HIV-1), but the level of virus-expressing cells within the mucosa of infected patients is not known. To study this issue, we identified HIV-1 mRNA-expressing (positive) mononuclear cells by in situ hybridization in specimens of esophageal mucosa from eight patients with acquired immune deficiency syndrome (AIDS) and esophageal infections. Such cells were not found in four patients with AIDS and no esophageal disease. Immunocytochemical staining revealed that the mononuclear cells expressing HIV-1 mRNA were lamina propria macrophages. The prevalence of positive cells was measured by triplicate determinations in each of three experiments using an inverse sampling technique. No significant differences in prevalence were found among patients or among experiments. The overall prevalence of HIV-1 mRNA-expressing cells in the esophageal lamina propria was 0.059 +/- 0.01%. This prevalence of cells expressing HIV-1 mRNA in the mucosa of patients with mucosal infections may reflect the local abundance of stimuli such as bacterial endotoxin and certain cytokines capable of inducing viral transcription.
Assuntos
Esôfago/microbiologia , HIV-1/genética , RNA Mensageiro/análise , RNA Viral/análise , Síndrome da Imunodeficiência Adquirida/microbiologia , Esôfago/citologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Mucosa/citologia , Mucosa/microbiologiaRESUMO
Invasion of erythrocytes by malaria parasites involves multiple receptor-ligand interactions. To elucidate these pathways, we made use of four parasite clones with differing specificities for invasion, erythrocytes that are mutant for either glycophorin A or B, and enzyme modification of the erythrocyte surface with neuraminidase and trypsin. Neuraminidase alone abolishes invasion of two parasite clones (Dd2, FCR3/A2); these invade after trypsin treatment alone. A third clone (7G8) is unable to invade trypsin-treated erythrocytes. The fourth clone (HB3) can invade after either neuraminidase or trypsin treatment. The receptor for invasion of trypsin-treated erythrocytes was explored in two ways: treatment of trypsin-treated normal cells with neuraminidase, and trypsin treatment of glycophorin B-deficient cells. Both treatments eliminated invasion by all clones, indicating that the trypsin-independent pathway uses sialic acid and glycophorin B. To identify parasite proteins involved in the different pathways, erythrocyte binding assays were performed with soluble parasite proteins from each clone. Based on binding assays using erythrocytes that lack glycophorin A, the parasite protein known as EBA-175 appears to bind predominantly to glycophorin A. In contrast, the glycophorin B pathway does not appear to involve EBA-175, as binding of EBA-175 was similarly reduced to trypsin-treated normal and trypsin-treated glycophorin B-deficient erythrocytes. Thus, the glycophorin B-dependent, sialic acid-dependent invasion of trypsin-treated normal erythrocytes uses a different parasite ligand, indicating two or more sialic-dependent pathways for invasion. Clone 7G8, which cannot invade trypsin-treated erythrocytes, may be missing the ligand for invasion via glycophorin B.(ABSTRACT TRUNCATED AT 250 WORDS)