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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 29 (1989), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The relationship of velocity of blood flow to density and microanatomical distribution of inflammatory cells in the dermis was studied in 20 human tuberculin tests. Must positive reactions showed maximal blood flow velocities (measured as red blood cell (RBC)flux) at the centre of the reaction, but the two most intense responses showed ‘central relative slowing’(CRS) with higher RBC flux at she periphery. Two of the four clinically negative reactions showed a considerable acceleration of blood flow, but the other two showed no such acceleration. The packing density of lymphocytes/monocytes in the perivascular zone was greater in the stronger positives than in the weaker reactions. The density of cells in the intervening dermis was markedly lower than in the foci: the lesions with CRS had the highest density of cells in the diffuse infiltrate of the reticular dermis. At the centre of the reaction, blood flow velocity was generally related to density of cellular infiltrate, except in those with CRS, which had a disproportionately lower blood flow velocity. The finding that the circulatory adaptation to a delayed hypersensitivity reaction can be inadequate may explain the dermal acidosis previously observed in intense skin test reactions, and may be the underlying mechanism of necrosis in hypersensitive reactions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: cancer vaccines ; cytokines ; melanoma ; mycobacterium vaccae (SRL 172)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: This phase I–II study was designed to assess safety and clinical efficacy of SRL172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma. Induction of intracellular cytokines (IL-2 and INF-γ) in peripheral blood lymphocytes (PBLCs) from these patients was assayed and correlated to clinical outcome. Patients and methods: SRL 172 was administered intradermally to 24 patients with stage IV malignant melanoma, initially at 15-day intervals for three vaccinations and then at monthly intervals. Lymphocyte activation for cytokines in PBLCs was assayed prior to each vaccine administration using a FACS-based intracellular cytokine assay. Survival was compared to historical controls. Results: The vaccination schedule resulted in sustained intracellular IL-2 induction in PBLCs in 9 of 23 patients (39%) who received at least three doses. Cytokine induction became apparent within the first three administrations of vaccine and was maximal at 8–12 weeks. Induction of intracellular IL-2 production (group 1) was associated with improved survival (P 〈 0.036). The median survival of the nine patients demonstrating IL-2 induction was 59 (95% confidence interval (95% CI): 47–71) weeks compared to 31 (95% CI: 18–44) weeks for the non-inducers. Induction of INF-γ (group 2) was found in 10 patients and 6 patients had IL-2 and INF-γ induction (group 3). There was no survival advantage for these patient groups. Although no objective responses were documented the group as a whole had a median survival of 44 (95% CI: 31–59) weeks which is better than that of historical controls. SRL 172 was safe and well tolerated. Conclusion: SRL 172 is effective in inducing intracellular IL-2 responses in PBLCs of a significant number of patients with stage IV (AJCC) melanoma. This is correlated with improved survival. The survival analysis is sufficiently encouraging to suggest that further prospective trials are justified. The methodology we present in this study may help in developing surrogate markers that will allow rational immunotherapeutic strategies to be designed for cancer patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7381
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to investigate the possible role of Schwann cells in immune reactions, and in particular their involvement in the response to infection withMycobacterium leprae, it was determined under what conditions Schwann cells express major histocompatibility complex class II (MHC class II) antigens, since these molecules are thought to have a key role in antigen presentation during cellular immune responses. In situ andin vitro preparations from newborn and adult rat sciatic nerves were used as a model system to examine this question. Schwann cells in dissociated cell cultures did not express immunohistochemically detectable amounts of MHC class II antigens. Teased nerve preparations from the sciatic nerves of healthy adult rats showed no detectable immunolabelling of either myelin-forming or non-myelin-forming Schwann cells. When dissociated Schwann cell cultures derived from the sciatic nerves of either neonatal or adult rats were treated with 10, 50 or 100 units of gamma Interferon, MHC class II antigens were detectable on the surface of some Schwann cells 48 h after addition of the interferon. By 72 h, 32.29 ± 3.9% of Schwann cells in the cultures from neonatal rats and 53.32 ± 5.4% of Schwann cells in cultures from adult rats, identified by the presence of intracellular S-100, were clearly MHC class II-positive, especially at doses of 50 and 100 units per ml of gamma interferon. Some, but not all, of the fibroblastic cells were very weakly MHC class Il-positive. Infection of the cultures withMycobacterium leprae did not induce MHC class II antigen expression in either Schwann cells or fibroblasts. These results suggest that one of the functional roles of Schwann cells' is the presentation of foreign antigens to T lymphocytes during nerve infection, leading to activation or augmentation of the cellular immune response. With respect toMycobacterium leprae in particular, it is therefore possible that infected Schwann cells might be capable of participating in the normal immune response toMycobacterium leprae.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    World journal of microbiology and biotechnology 1 (1985), S. 1-21 
    ISSN: 1573-0972
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Description / Table of Contents: Résumé Les deux principales maladies à mycobactéries — la tuberculose et la lèpre — sont toujours des causes majeures de souffrance humaine dans de nombreuses parties du monde. La lutte contre ces maladies est entravée par l'inadéquation des méthodes diagnostiques, préventives et thérapeutiques. Spéciallement en ce qui concerne la tuberculose, l'amélioration des moyens de diagnostic est rendue nécessaire par le fait que les techniques bactériologiques existantes sont longues et peu sensibles, et que les tests immunologiques, n'étant pas spécifiques, ne permettent pas de distinguer entre une maladie en évolution et une sensibilisation ancienne. On a besoin de tests permettant de déceler soit la présence d'antigènes mycobactériens, soit l'apparition de réactions immunitaires spécifiques au cours d'une infection évolutive. La prophylaxie par le BCG n'est jamais complète et parait être pratiquement inefficace dans certaines régions. Pour expliquer cette variation géographique, produire de meilleurs vaccins, et utiliser le BCG efficacement, il convient de mieux connaître les réactions immunitaires au cours des maladies à mycobactéries. En particulier, les déterminants bactériens de la virulence et de la protection, ainsi que le mode d'action du BCG sont à approfondir. La rifampicine a considérablement transformé la thérapeutique de la tuberculose et, à un moindre degré, de la lèpre. Néanmoins, le coût des nouveaux traitements intensifs de la tuberculose limite leur application. Il est nécessaire que des médicaments bactéricides plus puissants ou des agents stimulant les défenses de l'hôte puissent raccourcir encore davantage la durée des traitements. Le progrès biotechnologique peut donc améliorer de façon significative le contrôle des maladies considérées, à la seule condition que ce but soit volontairement intégré dans les initiatives locales en matière de santé publique.
    Abstract: Resumen La dos principales enfermedades producidas por micobacterias — tuberculosis y lepra —persisten como las causas más importantes del sufrimiento humano en muchas partes del mundo. La lucha contra estas enfermedades se ha visto dificultada por lo inadecuado de los métodos para su diagnosis, prevención y terapia. Es necesaria una mejora de los métodos de diagnosis, especialmente en el caso de la tuberculosis, ya que las técnicas bacteriológicas existentes son poco sensibles y consumen mucho tiempo y los tests inmunológicos son inespecíficos y no permiten distinguir entre la enfermedad activa y la sensibilidad adquirida. Se necesitan tests capaces de detectar la presencia de antígenos microbacterianos o la existencia de reacciones de inmunización específicas de la infección activa. La profilaxis con la vacuna BCG no es nunca completa y en algunas regiones es virtualmente enefectiva. Con objeto de determinar las razones de esta variación, de producir mejores vacunas y de usar la BCG de forma más eficiente, se necesita entender con más profundidad las reacciones de inmunización en las enfermedades por micobacterias. En particular los determinantes bacterianos de la virulencia y de la protección y la forma de actuar de la BCG precisan de un estudio detallado. La terapia de la tuberculosis y en menor grado la de la lepra, han sufrido una extensa transformación desde la introducción de la rifampicina. Sin embargo, el costo de los modernos tratamientos a corto plazo de la tuberculosis limítan su aplicación. Se requieren tratamientos aún más cortos basados en el desarrollo de drogas bactericidas más potentes o de agentes que estimulen las defensas del enfermo. Los recientes avances en biotecnología podrían por tanto conducir a avances importantes en el control de estas enfermedades pero solamente si se integran en iniciativas médicas públicas consistentes.
    Notes: Summary The two principal mycobacterial diseases — tuberculosis and leprosy — remain major causes of human suffering in many parts of the world. The struggle against these diseases has been hampered by the inadequacy of methods for their diagnosis, prevention and therapy. Improvements in diagnostic methods, especially for tuberculosis, are required as existing bacteriological techniques are time consuming and insensitive, but immunological tests suffer from a lack of specificity and a failure to distinguish active disease from past sensitization. Tests are required that will either detect the presence of mycobacterial antigens or the occurrence of immune reactions specific to active infection. Prophylaxis by BCG vaccine is never complete and in some regions appears virtually ineffective. In order to determine the reason for this variation, to produce better vaccines, and to use BCG more effectively, a deeper understanding of the immune reactions in mycobacterial disease is required. In particular, the bacterial determinants of virulence and protection and the mode of action of BCG require detailed study. The therapy of tuberculosis and, to a lesser extent, leprosy has undergone an extensive transformation since the introduction of rifampicin. Nevertheless the cost of modern short course regimens for tuberculosis limit their application. Even shorter regimens, made possible by more potent bactericidal drugs or by agents that stimulate the host's defences are thus required. Recent advances in biotechnology could therefore lead to significant advances in the control of these diseases but only if they are integrated into local, self-reliant public health initiatives.
    Type of Medium: Electronic Resource
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