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  1. Article: Molecular biology and immunology for clinicians DNA polymerase and the polymerase chain reaction.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 3, Issue 3, Page(s) 135–139

    Abstract: By using enzymes that underlie the molecular mechanisms of normal cell function, scientists have advanced the molecular biology of research and diagnostic testing. Normal cells divide and in so doing must accurately replicate their DNA; one of the ... ...

    Abstract By using enzymes that underlie the molecular mechanisms of normal cell function, scientists have advanced the molecular biology of research and diagnostic testing. Normal cells divide and in so doing must accurately replicate their DNA; one of the enzymes crucial in making exact copies of DNA is DNA polymerase, which is at the heart of the polymerase chain reaction. This technique allows one to make billions or trillions of copies from a single molecule of DNA in a few hours, levels of DNA easily detectable by techniques described earlier in this series. The polymerase chain reaction can be used for clinical testing, e.g., identification of DNA derived from a micro-organism. Also, one can clone DNA in large quantities and then determine the specific nucleotide sequences. This then allows one to study the DNA of certain proteins in individuals with a specific disease process and how these DNA sequences differ from those in unaffected people. With this new technology, we can identify the following: variant collagens that underlie familial osteoarthritis; the presence of the DNA of micro-organisms, such as Ureaplasma and Chlamydia, at the site of inflammatory joint diseases, establishing the infectious nature of the synovitis; different human leukocyte antigen (HLA)-B27 alleles that predispose patients to the development of the seronegative spondylarthropathies; and characteristics of different HLA class II molecules that may yield insights into antigen presentation and its role in the pathogenesis of rheumatoid arthritis.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199706000-00003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Indomethacin rectal suppository in the treatment of acute gouty arthritis.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 4, Issue 1, Page(s) 45–46

    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199802000-00013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Article: Molecular biology and immunology for clinicians, 7: the humoral immune response (continued).

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 4, Issue 1, Page(s) 22–27

    Abstract: The humoral immune response elicits the production of immunoglobulins of different structures and biologic functions. These differences are intrinsic to the various classes (isotypes), subclasses, and allotypes of the antibodies made. The binding of ... ...

    Abstract The humoral immune response elicits the production of immunoglobulins of different structures and biologic functions. These differences are intrinsic to the various classes (isotypes), subclasses, and allotypes of the antibodies made. The binding of antibodies to their respective specific antigens occurs because of physicochemical interactions between tertiary structures of the antibody and the target epitope. Understanding the nature of these interactions allows one to better understand binding affinity and the ability of an antibody made as part of a specific response to one antigen to bind to other, even unrelated, antigens. This ability of an antibody made during the immune response to an infection to bind to different antigens provides the plasticity needed to provide protection from different related or unrelated pathogens.Thus, antibodies made during the response to one adenovirus may be of assistance in the response to infection with a second adenovirus. Cross-reactivity between molecules in and on disparate organisms, e.g., different Gram-negative bacilli, is common; heat-shock proteins and flagellins are very similar and broadly cross-reactive. Antibodies made to one bacterium can be the basis of immune protection from another.The affinity of an antibody for its specific antigen is enhanced during the secondary immune response, because the interaction of the antigen with surface immunoglobulin on memory cells selects the production of antibodies with a "better fit" for the target antigen.In a previous article in this series, on the humoral immune response, we reviewed much of the basic terminology of immunology (epitopes, paratopes, etc.), and described many of the characteristics of antigens and immunoglobulins. In this article we proceed with a description of the various immunoglobulin classes (also known as isotypes) and some of their functional characteristics.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199802000-00005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Molecular biology and immunology for clinicians, 12: T-cell co-stimulatory molecules.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 6, Issue 4, Page(s) 225–227

    Abstract: T-cells are activated by their interaction with antigen-presenting cells. Antigen-presenting cells process and then express peptide fragments of the target protein in a complex with self-proteins known as major histocompatibility complex (MHC) proteins ... ...

    Abstract T-cells are activated by their interaction with antigen-presenting cells. Antigen-presenting cells process and then express peptide fragments of the target protein in a complex with self-proteins known as major histocompatibility complex (MHC) proteins on the antigen-presenting cells' surface. However, the interaction of T-cell with antigen on the antigen-presenting cell is not sufficient to elicit T-cell activation. The T-cell must receive a second signal from the antigen-presenting cell. These "co-stimulatory signals" are mediated by other proteins on the antigen-presenting cell surface that interact with T-cell surface proteins other than the antigen receptor, the protein complex receiving the peptide fragment's specific antigen signal. Some of these co-stimulatory proteins are constitutively expressed, some are up-regulated during an immune response; some interactions stimulate activation, some suppress it. Thus, these receptor-ligand protein pairs represent new sites for blockade of immune responses in immunologically-mediated diseases, like rheumatoid arthritis, lupus, and transplant graft rejection.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1536-7355 ; 1076-1608
    ISSN (online) 1536-7355
    ISSN 1076-1608
    DOI 10.1097/00124743-200008000-00012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Molecular biology and immunology for clinicians, 10 cytokines-1.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 5, Issue 6, Page(s) 360–362

    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199912000-00012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Molecular biology and immunology for clinicians, 9 pathogenesis of autoimmunity-molecular mimicry.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 5, Issue 5, Page(s) 293–296

    Abstract: The immune system generally does an excellent job of differentiating between self and non-self. In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no ... ...

    Abstract The immune system generally does an excellent job of differentiating between self and non-self. In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no longer leaves self alone; this is auto-immunity-the defense system attacks self. In studying these exceptions, some aspects of the magnificent complexity of the immune system and of the molecular biology of life become apparent.Given that evolutionary processes build on prior experience and mechanisms, it is not surprising that human cells have much in common with yeast, and bacteria molecules found in lower organisms resemble, sometimes quite closely, homologous molecules in human cells. Microbes contain molecules resembling those used by mammalian cells, perhaps because some pathogens use or subvert mammalian systems. These similarities may be sufficient to interfere with the immune system's ability to discern between self and non-self. Thus, the immune response to certain components of pathogens may recognize the host, a phenomenon called molecular mimicry. This mechanism may be involved in the pathogenesis of rheumatologic and other immune-mediated diseases.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199910000-00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  7. Article: Molecular biology and immunology for clinicians.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 2, Issue 4, Page(s) 209–214

    Abstract: Electrophoresis is a technique that allows the separation of charged molecules within a mixture into individual components. This represents a very powerful tool in research but has come into its own as a component of serologic testing. Western (immuno-) ... ...

    Abstract Electrophoresis is a technique that allows the separation of charged molecules within a mixture into individual components. This represents a very powerful tool in research but has come into its own as a component of serologic testing. Western (immuno-) blot analysis takes advantage of the protein separation accomplished by a particular type of electrophoresis, called sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), to identify antibodies to individual components of cells, be they mammalian or microbial. The specificity of this kind of testing allows more rigorous testing to be done. Western blot analysis has become a "gold standard" in certain clinical circumstances and is used to corroborate equivocal or positive ELISA results in a number of diseases, Lyme disease and HIV infection being but two examples.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199608000-00009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Molecular biology and immunology for clinicians.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 3, Issue 1, Page(s) 28–34

    Abstract: After tissue injury, homeostatic mechanisms attempt to repair the damage. Local changes in the vasculature allow inflammatory cells to exit to deal with pathogens and take part in healing. Cytokines produced locally can cause systemic changes: fever, ... ...

    Abstract After tissue injury, homeostatic mechanisms attempt to repair the damage. Local changes in the vasculature allow inflammatory cells to exit to deal with pathogens and take part in healing. Cytokines produced locally can cause systemic changes: fever, leukocytosis, transfer of amino acids from muscles to the liver, and increased glucocorticoid levels. A complicated blend of cytokines, including interleukins 1 and 6 and tumor necrosis factor, modulate patterns of hepatic protein synthesis. Changes in the production of metabolism-related enzymes occur, serving to provide fuel for the body and increase protein glycosylation. Also, there is an increase in synthesis of certain proteins exported from the liver, including components of the coagulation, complement, kinin, and fibrinolytic systems, all involved in the inflammatory response. Different inflammatory conditions elicit different responses; the types of proteins and the pattern of glycosylation may vary. Serum levels of heavy metals, including iron, copper, and zinc, change during inflammation because of altered levels of relevant transport or storage proteins.It is not clear what purpose is served by some of these changes. Many of the proteins are immunomodulatory, but some "functions" may be merely in vitro artifacts. What is clear, however, is that measurement of the protein known as C-reactive protein and of the erythrocyte sedimentation rate may provide markers of inflammation and measures of the response of certain inflammatory diseases to therapy.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199702000-00006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Molecular biology and immunology for clinicians.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 2, Issue 3, Page(s) 141–146

    Abstract: Enzyme-linked immunosorbent assay (ELISA) represents a quick, reproducible, and easy assay that allows a single technician to measure antibodies to a defined target in a large number of samples. Obviously, its limitations must be included in the ... ...

    Abstract Enzyme-linked immunosorbent assay (ELISA) represents a quick, reproducible, and easy assay that allows a single technician to measure antibodies to a defined target in a large number of samples. Obviously, its limitations must be included in the interpretation of results. Specifically, false negativity and false positivity are common problems, and the mechanisms underlying these phenomena must be understood before ELISA results can be incorporated into the clinical decision-making process. In many diseases, e.g., Lyme disease and human immunodeficiency virus (HIV) infection, Western blot analysis is necessary to corroborate the ELISA reactivity, to differentiate between true positive and false positive results, and occasionally to determine whether equivocal ELISA results are of any significance. ELISA has revolutionized the practice of medicine related to certain diseases, and its applications will doubtless expand. However, ELISA and all serologic techniques measure only the immune response to an infection, not the presence of the infectious agent itself, which can be detected by culture, immunohistochemical staining, and polymerase chain reaction (the subject of an upcoming article in this series).
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199606000-00006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  10. Article: Molecular biology and immunology for clinicians, 8 pathogenesis of autoimmunity-apoptosis.

    Sigal, L H

    Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases

    2008  Volume 5, Issue 4, Page(s) 239–242

    Abstract: Apoptosis, or programmed cell death, is another example of a physiological principle of non-immune systems adopted by the immune response. Cell death by necrosis produces inflammation and disruption of surrounding tissue. Cell elimination by apoptosis is ...

    Abstract Apoptosis, or programmed cell death, is another example of a physiological principle of non-immune systems adopted by the immune response. Cell death by necrosis produces inflammation and disruption of surrounding tissue. Cell elimination by apoptosis is neat and allows the adjacent tissue to function; thus, apoptosis probably first emerged over 1.5 billion years ago as a means of remodeling the organism during embryogenesis.Nonetheless, apoptosis has the potential to produce inflammatory mediators. Perhaps of more concern is that abnormalities of apoptosis can lead to disruption in normal T and B cell function; in two mouse models, the result of defective apoptosis is auto-immunity. As well, the remnants of the dead cell, which essentially committed suicide, contain many nuclear components; there is reason to believe that some people may not manage this particulate waste matter, called apoptotic bodies, and that the immune response to some of these components may lead to auto-immunity. Apoptosis has also been proposed as contributing to neuronal destruction in Parkinson's disease, Alzheimer's disease, and glaucoma and to the late death of neurons near areas of ischemic cell death from stroke. Thus, not only from the rheumatologist's perspective, understanding and manipulating apoptosis may be one of the major foci of medical research of the future.
    Language English
    Publishing date 2008-08-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1283266-2
    ISSN 1076-1608
    ISSN 1076-1608
    DOI 10.1097/00124743-199908000-00014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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