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  • 1
    Electronic Resource
    Electronic Resource
    Dermal fibroblasts are one of the therapeutic targets for topical application of 1α,25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-β induction (2000)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Transforming growth factor (TGF) -β has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-β are biologically latent complexes, activation is essential for TGF-β-mediated cellular responses in vitro and in vivo. Objectives Here we report the response of the TGF-β regulation system to 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. Results 1,25(OH)2D3 caused a dose-dependent induction of latent and active TGF-β1 proteins in both cell cultures. The increases were significant over 72 h, but not within 48 h after stimulation. The time course of TGF-β1 mRNA expression showed a biphasic response consisting of early (≈1 h) and late phases (≈ 96 h) of induction. Concomitant increases of TGF-β2 and -β3, other mammalian isoforms , were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Co-incubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-β1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-β1 protein production. The late induction of TGF-β1 mRNA was partially blocked by adding isoform-specific antibodies to TGF-β1, -β2 and -β3, indicating TGF-β autoregulation. Despite these marked responses, there were no significant differences in the TGF-β expression between normal and psoriatic fibroblasts. Conclusions These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-β regulation in local dermal fibroblasts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2000.03880.x
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    In vivo evaluation of antithrombogenicity and surface analysis of ion-implanted silicone rubber
    Amsterdam : Elsevier
    International Journal of Radiation Applications & Instrumentation. Part C, 39 (1992), S. 553-560 
    Details
    ISSN: 1359-0197
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/1359-0197(92)90112-S
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    In vivo evaluation of antithrombogenicity for ion implanted silicone rubber using indium-111-tropolone platelets
    Amsterdam : Elsevier
    Nuclear Inst. and Methods in Physics Research, B 59-60 (1991), S. 698-704 
    Details
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0168-583X(91)95306-X
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  • 4
    Electronic Resource
    Electronic Resource
    Clinical and biological studies of 26 cases of xeroderma pigmentosum in Northeast District of Japan (1984)
    Springer
    Archives of dermatological research 277 (1984), S. 1-7 
    Details
    ISSN: 1432-069X
    Keywords: Xeroderma pigmentosum ; Unscheduled DNA synthesis ; Ultraviolet light sensitivity ; Sister chromatid exchanges
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-six patients with xeroderma pigmentosum (XP), who live in the Northeast (Tohoku) District of Japan, were examined for the clinical characteristics of UV-induced DNA synthesis (unscheduled DNA synthesis, UDS) and UV sensitivity of skin fibroblasts or lymphoblastoid cells, or both. A history of consanguineous marriage within two generations was found in 19 of 26 cases (73%). Two pairs of siblings showed similar manifestations and almost the same levels of UDS and of UV sensitivity. Squamous cell carcinoma, basal cell carcinoma, or both were observed on the exposed skin in 14 patients, but no malignant melanoma was found. Cancer had developed in approximately 71% (10/14) of the cancer-bearing patients by the age of 20, and 8 of them belonged to the UDS-deficient group. Neurological manifestations were associated with nine patients, including 3 with typical de Sanctis-Cacchione syndrome (DSC), and most of the cells derived from these patients had a UDS level less than 10% of that of the normal cells. A clear correlation between the levels of UDS and UV sensitivity, on the one hand, and the severity of clinical manifestations on the other could not be detected, but it seems that the UDS-deficient group is generally much more sensitive to UV in terms of cell killing and the induction of sister chromatid exchange (SCE) than the UDS-proficient group. After a photosensitivity test, one patient with mild skin manifestations showed distinct skin tanning without preceding erythema.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00406472
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  • 5
    Electronic Resource
    Electronic Resource
    Spontaneously reduced midgut malrotation: CT diagnosis (2000)
    Springer
    Abdominal imaging 25 (2000), S. 132-133 
    Details
    ISSN: 1432-0509
    Keywords: Key words: Reduced—Midgut malrotation—CT reducible.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Midgut malrotation is a relatively rare congenital malformation that arises from an error of rotation and fixation of the midgut. We report a case of spontaneously reduced duodenal malrotation diagnosed by computed tomography and roentgenography after the ingestion of barium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002619910031
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  • 6
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    Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-01
    Description: Antibodies (immunoglobulins) bind specific molecules ( i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody–antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody–antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.
    Print ISSN: 0021-924X
    Electronic ISSN: 1756-2651
    Topics: Biology , Chemistry and Pharmacology
    Published by Oxford University Press on behalf of The Japanese Biochemical Society (JBS).
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  • 7
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    T-Cell Immunoglobulin and Mucin Domain 3 Acts as a Negative Regulator of Atherosclerosis [Basic Science] (2013)
    American Heart Association (AHA)
    Details
    Publication Date: 2013-10-17
    Description: Objective— Atherosclerosis is a chronic autoimmune-like disease in which lipids and fibrous elements accumulate in the arterial blood vessels. T cells are present within atherosclerotic plaques, and their activation is partially dependent on costimulatory signals, which can either provide positive or negative signals that promote T-cell activation or limit T-cell responses, respectively. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a coinhibitory type 1 transmembrane protein that affects the function of several immune cells involved in atherosclerosis, such as monocytes, macrophages, effector T cells, and regulatory T cells. In the present study, we determined the role of Tim-3 in the development of atherosclerosis. Approach and Results— Western-type diet–fed low-density lipoprotein receptor–deficient (LDLr –/– ) mice were treated with an anti–Tim-3 antibody for 3 and 8 weeks. Anti–Tim-3 administration increased fatty streak formation with 66% and increased atherosclerotic plaque formation after 8 weeks with 35% in the aortic root and with 50% in the aortic arch. Furthermore, blockade of Tim-3 signaling increased percentages of circulating monocytes with 33% and lesional macrophages with 20%. In addition, anti–Tim-3 administration increased CD4 + T cells with 17%, enhanced their activation status, and reduced percentages of regulatory T cells with 18% and regulatory B cells with 37%. Conclusions— It is known that Tim-3 acts as a negative regulator of both innate and adaptive immune responses, and in the present study, we show that anti–Tim-3 treatment augments lesion development, accompanied by an increase in the number of monocytes/macrophages and CD4 + T cells and by decreased regulatory T cells and regulatory B cells.
    Keywords: Pathophysiology, Mechanism of atherosclerosis/growth factors
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 8
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    Interruption of Dendritic Cell-Mediated TIM-4 Signaling Induces Regulatory T Cells and Promotes Skin Allograft Survival [TRANSPLANTATION] (2013)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2013-10-05
    Description: Dendritic cells (DCs) are the central architects of the immune response, inducing inflammatory or tolerogenic immunity, dependent on their activation status. As such, DCs are highly attractive therapeutic targets and may hold the potential to control detrimental immune responses. TIM-4, expressed on APCs, has complex functions in vivo, acting both as a costimulatory molecule and a phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell activation remains unclear. In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4 + T cells, both in vitro and in vivo. iTreg induction occurs through suppression of IL-4/STAT6/Gata3–induced Th2 differentiation. In addition, blockade of TIM-4 on previously activated DCs still leads to increased iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to control and, upon adoptive transfer, significantly prolong skin allograft survival in vivo. In RAG –/– recipients of skin allografts adoptively transferred with CD4 + T cells, we show that TIM-4 blockade in vivo is associated with a 3-fold prolongation in allograft survival. Furthermore, in this mouse model of skin transplantation, increased induction of allospecific iTregs and a reduction in T effector responses were observed, with decreased Th1 and Th2 responses. This enhanced allograft survival and protolerogenic skewing of the alloresponse is critically dependent on conversion of naive CD4 + to Tregs in vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a novel strategy that holds the capacity to induce regulatory immunity in vivo.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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  • 9
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    Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice [CUTTING EDGE] (2017)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2017-11-21
    Description: Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti–TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti–TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti–TIM-3–treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti–TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-β1 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti–TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti–TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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  • 10
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    Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development (2012)
    Oxford University Press
    Details
    Publication Date: 2012-05-18
    Description: Receptor activator of nuclear factor kappa-B ligand (RANKL) expression was examined during the development of mouse fetal peripheral lymphoid organs. A shift in the expression pattern was detected during the transition from lymphoid tissue inducer (LTi) cells to lymphoid tissue organizer (LTo) cells in the lymph node (LN) anlagen but not in the Peyer’s patch anlagen. In order to understand the functional impact of these changes in the fetal expression of RANKL, the RANKL function was blocked by a blocking antibody. Excess anti-RANKL antibody was administered to pregnant mice between 13.5 and 16.5 dpc and was found to completely block LN anlagen development, suggesting that RANKL function during this period is critical for LN development. In addition, small amounts of anti-RANKL antibodies were injected directly into the amniotic space at 13.5 dpc, resulting in perturbed B-cell follicle formation and high endothelial venule differentiation after birth. These results suggest that RANKL expression on LTi cells during the early phase of LN development is critical for the development LN microarchitecture.
    Print ISSN: 0953-8178
    Electronic ISSN: 1460-2377
    Topics: Medicine
    Published by Oxford University Press
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