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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As oxidative stress has been implicated in the pathogenesis of certain viral diseases we determined antioxidant and prooxidant parameters in lungs and bronchoalveolar lavage fluid (BALF) of mice infected with a lethal dose of influenza A/PR8/34 virus. Viral infection was characterized by massive infiltration of leukocytes, mainly polymorphonuclear leukocytes, into the alveolar space. The total number of BALF cells increased up to 8-fold (day 3 post-infection) and these cells appeared activated as judged by their increased rates of superoxide anion radical (O2-.) generation upon stimulation. Maximal rates of radical generation by BALF cells during the early stages of infection were 15- or 70-fold higher than those of cells from control animals when expressed per cell or total BALF cells, respectively. At the terminal stages of infection the total capacity of BALF cells to release O2-. declined to approximately 35-fold the control values. Infection also resulted in increased in vivo formation of hydrogen peroxide (H2O2) within the lungs at a time that coincided with the maximal capacity of BALF cells to release O2-.. Whereas pulmonary activities of glutathione peroxidase and reductase remained unaltered, levels of ascorbate in the cell-free BALF decreased significantly during the early stages of the infection and then returned to normal levels and above, late in infection. The oxidation state of the dehydroascorbic acid/ascorbate couple increased concomitantly with the decrease in ascorbate concentrations early in infection and remained elevated throughout the infection. As assessed by the prevention of peroxyl radical-induced loss of phycoerythrin fluorescence, the total antioxidant capacity present in lung tissue homogenate from terminally ill animals was not diminished when compared to that prepared from lungs of control mice. We conclude that although early stages of influenza infection are associated with the presence of oxidative stress in the lung tissue and alveolar fluid lining the epithelial cells, this stress does not appear to overwhelm local antioxidant defenses. The results therefore do not support a direct causative role of oxidative tissue damage in the pathogenesis of influenza virus infection.
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PMID:Oxidative stress in lungs of mice infected with influenza A virus. 132 Oct 77

The brief description of two virus systems, influenza and infectious bursal disease, shows enigmatically how at least two requirements must be met to render a virus pathogenic: the array of the whole genome rather than the formation of a particular "pathogenicity gene" and the capacity of the host cell to provide the appropriate microenvironment for an optimal posttranslational processing of structural proteins. In the case of influenza viruses this relates particularly to the cleavability of the haemagglutinin. Efficient virus replication in cells of vital importance, however, does not necessarily result in the development of pathological conditions, as in Borna disease, where neural cells are loaded with virus, and the disease is mediated by a T cell immune response. Immunological stimuli against this virus do not induce neutralizing antibodies which could mount a protective immunity. Infection with influenza viruses is inhibited by neutralizing antibodies, but the course of the disease in an infected organism is largely influenced by virus-specific antibodies which block virus release. It is difficult, however, to evaluate the effectiveness of this type of mechanism directed against the infected cell besides antibody-dependent and cell-mediated cytolysis.
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PMID:Virus disease as a consequence of viral pathogenicity and the anti-viral immune response. 132 73

Combinations of porcine respiratory coronavirus (PRCV) and either of two swine influenza viruses (H1N1 or H3N2) were administered intranasally and by aerosol to six- to eight-week-old specific pathogen-free pigs. The clinical responses, gross respiratory lesions and growth performances of these pigs were studied and compared with those of single (PRCV, H1N1 or H3N2) and mock-infected animals. PRCV infection caused fever, growth retardation and lung lesions, but no respiratory symptoms. Infection with swine influenza viruses caused rather similar, mild symptoms of disease, with H1N1 infection being the least severe. Combined infections with influenza viruses and PRCV did not appear to enhance the pathogenicity of these viruses. Furthermore, viruses were isolated more frequently from tissues and nasal swabs taken from 'single' than 'dual' infected animals, suggesting a possible in vivo interference between replication of PRCV and swine influenza virus.
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PMID:Pathogenicity of concurrent infection of pigs with porcine respiratory coronavirus and swine influenza virus. 133 65

In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.
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PMID:Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. 134 69

Sindbis virus (SIN) is a small positive-strand enveloped RNA virus that infects a broad range of vertebrate and insect cells. A SIN vector (called dsSIN), designed for transient expression of heterologous RNAs and proteins, was engineered by inserting a second subgenomic mRNA promoter sequence into a nonessential region of the SIN genome. By using this vector, dsSIN recombinants have been constructed that express either bacterial chloramphenicol acetyltransferase, a truncated form of the influenza hemagglutinin (HA), or mini-genes encoding two distinct immunodominant cytotoxic T lymphocyte (CTL) HA epitopes. Infection of murine cell lines with these recombinants resulted in the expression of approximately 10(6)-10(7) chloramphenicol acetyltransferase polypeptides per cell and efficient sensitization of target cells for lysis by appropriate major histocompatibility complex-restricted HA-specific CTL clones in vitro. In addition, priming of an influenza-specific T-cell response was observed after immunizing mice with dsSIN recombinants expressing either a truncated form of HA or the immunodominant influenza CTL epitopes. This SIN expression system allows the generation of high-titered recombinant virus stocks in a matter of days and should facilitate mapping and mutational analysis of class I major histocompatibility complex-restricted T-cell epitopes expressed via the endogenous pathway of antigen processing and presentation.
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PMID:Infectious Sindbis virus transient expression vectors for studying antigen processing and presentation. 137 87

Standardized bacterial and viral mouse infection models have been developed. Infections with extracellular bacteria (K. pneumoniae, S. pneumoniae, S. pyogenes A) were produced by either of two routes: via the intravenous route (i.v.) resulting in septicaemia and the intranasal route (i.n.) giving infections confined to the respiratory apparatus. Infections with intracellular bacteria (L. monocytogenes, S. typhimurium) were produced only by the i.v. route. Two types of viral infection, mild and severe, were produced. Infection with influenza virus was by aerosol and herpes virus HSV-1 by the intraperitoneal route. All infection models produced under strictly controlled conditions were shown to be characterized by a remarkable reproducibility regarding both the pattern of development and death rate. The infection models lend themselves to estimation of the efficacy of a drug as well as the designing of new therapeutic strategies.
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PMID:Standardized mouse infection models as a way of evaluating the potency of anti-infectious agents. 142 54

Ageing is associated with a progressive decline of the immune systems, characterized by impaired T cells and changes in the antigenic repertory related to both the humoral and cell-mediated immune responses. The major alterations have been demonstrated in the T cells which undergo functional changes, such as a decrease in precursor frequencies of helper and cytotoxic T-cells, and accumulation of T cells which does not respond to activators. In general, T cell-dependent, cell-mediated responses decline with age. The elderly are at great risk for low consumption of proteins and of several micronutrients, such as zinc or vitamins C, E and B6 which play a critical role in the maintenance of normal immune function. As a consequence, the incidence of inflammatory and infectious disease, auto-immune disorders, cutaneous pathological changes, and skin cancers increases. Morbidity and mortality rates due to tetanus, pulmonary infections and influenza remain high in elderly populations. Depressing the rate of immunosenescence and restoring a normal immunocompetence in the elderly may involve improved nutrition through proteins, micronutrients and vitamins, and should deal with the economic and psychosocial problems of the elderly. Vaccinations against tetanus, pneumococcus and influenza proved to be efficacious and well-tolerated. Consequently, they should be applied systematically to non protected elderly individuals.
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PMID:[Immunocompetence in the elderly]. 144 20

Infection by influenza virus results in the stimulation of cytotoxic T lymphocytes specific for killing virally infected cells. Specificity is provided by clonally distributed, hypervariable T-cell receptors on cytotoxic T lymphocytes which react with peptide fragments that are derived from viral proteins expressed in the cytoplasm and 'presented' on the surface of infected cells, bound to class I histocompatibility glycoproteins. Here we describe the structure of the complex between the human class I histocompatibility glycoprotein HLA-Aw68 and the influenza virus nucleoprotein peptide Np 91-99 as determined by X-ray cryocrystallography. Residues at both ends of the peptide are substantially buried in the peptide binding-site, whereas those in the middle of the peptide, P4 to P8, are predominantly exposed and could be recognized directly by T-cell receptors. The extended conformation of the bound viral peptide is remarkably similar to that of a collection of endogenous peptides with a different sequence motif bound to another human allele, HLA-B27. The structure defines in atomic detail the antigenic surface constructed of major histocompatibility complex and viral peptide atoms that is recognized by T-cell receptors.
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PMID:Atomic structure of a human MHC molecule presenting an influenza virus peptide. 144 44

Several reports have described an inverse relationship between the frequency of infections and various malignancies. In this paper results of a hospital-based case control study on 139 melanoma patients and 271 suitable selected controls are presented, addressing the question of whether this relationship exists with respect to malignant melanoma while simultaneously controlling for the effects of other risk factors. Data on childhood diseases (group I), febrile diseases of adulthood (group II) and common febrile infections within a 5-year period prior to the diagnosis of melanoma (group III) were collected using a standardized interview. Group I diseases did not show a marked influence on the risk of malignant melanoma. Considering group II diseases, a significant protective effect was determined for chronic infectious diseases (OR = 0.32) and also for wound infections, abscesses and furunculosis (OR = 0.21). In group III, herpes simplex infections (OR = 0.45) and influenza/common cold (OR = 0.32) substantially reduced the melanoma risk. This effect was less pronounced for gastroenteritis (OR = 0.52). Analysis of the cumulative influence of infections pointed to a strong dose-response relationship between the frequency of febrile infections in adulthood and malignant melanoma. In particular, the risk reduction was striking when two or more febrile infections were compared to no febrile infections in group II (OR = 0.09) and group III (OR = 0.20). The study confirms the hypothesis that an inverse relationship exists between febrile infections and malignant melanoma, but these results have to be interpreted cautiously due to the inherent limitations of the case-control design.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Febrile infections and malignant melanoma: results of a case-control study. 145 Jun 74

The development is outlined of some synthetic vaccines against infectious diseases, in particular cholera, shigella and influenza. In the last case, use of the synthetic adjuvant MDP in combination with a haemagglutinin peptide has led to a synthetic vaccine with built-in adjuvanticity. The production of vaccines both by chemical synthesis and genetic engineering is described. The successful use of the synthetic amino acid copolymer COP-1 as an immunomodulatory vaccine to suppress the onset of allergic encephalomyelitis in experimental animals has led to clinical trials with patients suffering from exacerbating remitting multiple sclerosis. T-cell vaccination is an alternative approach to immunization against autoimmune diseases.
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PMID:Synthetic approaches to vaccines for infectious and autoimmune diseases. 147 27


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