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  1. Article: Attenuation of the Fas-L independent B16BL6 melanoma lymphocidic capacity by H-2K class I molecules.

    Kellman-Pressman, Sigal / Fishman, Daniel / Tsory, Sylvia / Segal, Shraga

    Immunology letters

    2005  Volume 100, Issue 2, Page(s) 146–152

    Abstract: ... of apoptosis in naive lymphocytes by H-2K-deficient melanoma cells does not involve the Fas ligand (Fas-L)/FAS ... of H-2K (but not H-2D or H-2L) MHC class I glycoproteins is reconstituted in these cells. The induction ... signaling module, as demonstrated by employing lymphocytes derived from Fas-L(gld)- or Fas(lpr)-deficient ...

    Abstract We have previously reported that the capacity of highly malignant B16BL6 murine melanoma cells to induce cell death in naive syngeneic lymphocytes stems from the absence of major histocompatibility complex (MHC) class I glycoproteins in these melanoma cells. Our present study provides evidence that the above-mentioned lymphocidic activities of B16BL6 cells are selectively attenuated when the expression of H-2K (but not H-2D or H-2L) MHC class I glycoproteins is reconstituted in these cells. The induction of apoptosis in naive lymphocytes by H-2K-deficient melanoma cells does not involve the Fas ligand (Fas-L)/FAS signaling module, as demonstrated by employing lymphocytes derived from Fas-L(gld)- or Fas(lpr)-deficient mice in co-culture experiments. Furthermore, these tumor cells fail to induce Fas-L-mediated fratricide in co-cultured lymphocytes and do not express Fas-L either when grown alone or co-cultured with lymphocytes. These findings explain the previously widely reported selective down-regulation of certain MHC class I-encoded glycoproteins (H-2K, bur not H-2D or H-2L) during tumor progression. Namely, the initiation of an effective immune response against H-2K-deficient cells could be abrogated at very early steps, as the result of the induction of Fas-L/Fas-independent cell death among naive lymphoid cells.
    MeSH term(s) Animals ; Apoptosis/immunology ; Coculture Techniques ; Fas Ligand Protein ; H-2 Antigens/genetics ; H-2 Antigens/immunology ; Histocompatibility Antigen H-2D ; Lymphocytes/immunology ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; RNA, Messenger/analysis ; Spleen/cytology ; Spleen/immunology ; Time Factors ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factors/genetics ; Tumor Necrosis Factors/immunology
    Chemical Substances Fas Ligand Protein ; Fasl protein, mouse ; H-2 Antigens ; H-2K(K) antigen ; Histocompatibility Antigen H-2D ; Membrane Glycoproteins ; RNA, Messenger ; Tumor Necrosis Factors
    Language English
    Publishing date 2005-09-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 445150-8
    ISSN 1879-0542 ; 0165-2478
    ISSN (online) 1879-0542
    ISSN 0165-2478
    DOI 10.1016/j.imlet.2005.03.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Short-term mucosal disruption enables colibactin-producing

    Harnack, Christine / Berger, Hilmar / Liu, Lichao / Mollenkopf, Hans-Joachim / Strowig, Till / Sigal, Michael

    Gut microbes

    2023  Volume 15, Issue 1, Page(s) 2233689

    Abstract: Colibactin, a bacterial genotoxin produced ... ...

    Abstract Colibactin, a bacterial genotoxin produced by
    MeSH term(s) Humans ; Mice ; Animals ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Colitis, Ulcerative/pathology ; Gastrointestinal Microbiome ; Polyketides/metabolism ; Intestinal Mucosa/metabolism
    Chemical Substances colibactin ; Polyketides
    Language English
    Publishing date 2023-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2575755-6
    ISSN 1949-0984 ; 1949-0984
    ISSN (online) 1949-0984
    ISSN 1949-0984
    DOI 10.1080/19490976.2023.2233689
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. 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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  4. Article ; Online: Can Renal Parameters Predict the Mortality of Hospitalized COVID-19 Patients?

    Zolotov, Eli / Sigal, Anat / Havrda, Martin / Jeřábková, Karolína / Krátká, Karolína / Uzlová, Nikola / Rychlík, Ivan

    Kidney & blood pressure research

    2022  Volume 47, Issue 5, Page(s) 309–319

    Abstract: ... by ≥50% within 7 days or by ≥26.5 μmol/L within 48 h during hospitalization). Then, we used eGFR ...

    Abstract Introduction: Our study aimed to analyze whether renal parameters can predict mortality from COVID-19 disease in hospitalized patients.
    Methods: This retrospective cohort includes all adult patients with confirmed COVID-19 disease who were consecutively admitted to the tertiary hospital during the 4-month period (September 1 to December 31, 2020). We analyzed their basic laboratory values, urinalysis, comorbidities, length of hospitalization, and survival. The RIFLE and KDIGO criteria were used for AKI and CKD grading, respectively. To display renal function evolution and the severity of renal damage, we subdivided patients further into 6 groups as follows: group 1 (normal renal function), group 2 (CKD grades 2 + 3a), group 3 (AKI-DROP defined as whose s-Cr level dropped by >33.3% during the hospitalization), group 4 (CKD 3b), group 5 (CKD 4 + 5), and group 6 (AKI-RISE defined as whose s-Cr level was elevated by ≥50% within 7 days or by ≥26.5 μmol/L within 48 h during hospitalization). Then, we used eGFR on admission independently of renal damage to check whether it can predict mortality. Only 4 groups were used: group I - normal renal function (eGFR > 1.5 mL/s), group II - mild renal involvement (eGFR 0.75-1.5), group III - moderate (eGFR 0.5-0.75), and group IV - severe (GFR <0.5).
    Results: A total of 680 patients were included in our cohort; among them, 244 patients displayed normal renal function, 207 patients fulfilled AKI, and 229 patients suffered from CKD. In total, a significantly higher mortality rate was found in the AKI and the CKD groups versus normal renal function - 37.2% and 32.3% versus 9.4%, respectively (p < 0.001). In addition, the groups 1-6 divided by severity of renal damage reported mortality of 9.4%, 21.2%, 24.1%, 48.7%, 62.8%, and 55.1%, respectively (p < 0.001). The mean hospitalization duration of alive patients with normal renal findings was 9.5 days, while it was 12.1 days in patients with any renal damage (p < 0.001). When all patients were compared according to eGFR on admission, the mortality was as follows: group I (normal) 9.8%, group II (mild) 22.1%, group III (moderate) 40.9%, and group IV (severe) 50.5%, respectively (p < 0.001). It was a significantly better mortality predictor than CRP on admission (AUC 0.7053 vs. 0.6053).
    Conclusions: Mortality in patients with abnormal renal function was 3 times higher compared to patients with normal renal function. Also, patients with renal damage had a worse and longer hospitalization course. Lastly, eGFR on admission, independently of renal damage type, was an excellent tool for predicting mortality. Further, the change in s-Cr levels during hospitalization reflected the mortality prognosis.
    MeSH term(s) Acute Kidney Injury ; Adult ; COVID-19 ; Female ; Hospital Mortality ; Humans ; Kidney/physiology ; Male ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors
    Language English
    Publishing date 2022-01-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1326018-2
    ISSN 1423-0143 ; 1420-4096
    ISSN (online) 1423-0143
    ISSN 1420-4096
    DOI 10.1159/000522100
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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.

    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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  7. 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
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  8. 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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  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
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  10. 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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