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  • 1
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 70 (1997), S. 2318-2320 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Arrays of cantilevers with integrated self-sharpening tips and self-exciting piezoelectric sensors have been fabricated using monocrystalline silicon micromachining. During the fabrication process, tips are first formed with a wet etching technique allowing a good homogeneity of tip shape over a whole wafer and then protected with a local thick silicon dioxide layer. Single cantilevers have been used to achieve atomic force microscopy images of grids with periods of 0.25, 1, and 5 μm and with height differences of 100, 15, and 180 nm, respectively. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1–5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Crohn's disease ; Cytokines ; Ki-67 ; Cell proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract T-cell activation and local cytokine production probably contribute to the pathogenesis of Crohn's disease. This study investigates the proliferative status of intestinal mononuclear cells (MNC) and cytokine messenger RNA (mRNA) production in gut tissue sections from patients with Crohn's disease and noninflamed controls. mRNA in situ hybridization was performed using 33P-labelled riboprobes for human interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, tumour necrosis factor-α and interferon-γ. The expression of the proliferation-associated antigen Ki-67 was analysed by immunohistochemical single and double staining. Compared with controls, where proliferation of MNC and cytokine expression was restricted to mucosal lymphoid follicles, inflamed gut tissue contained increased numbers of cells expressing cytokine mRNA, most prominently IL-1β and IL-6, but also interferon-γ and tumour necrosis factor-α. Proliferating T-cells were increased in number, and small amounts of IL-2-expressing cells were detected. IL-4 was expressed by a few cells exclusively in follicular germinal centres. IL-5 was negative. Proinflammatory cytokines are strongly expressed in situ in Crohn's disease and largely predominate over lymphokine mRNA. Our results provide in situ evidence of a local lymphocyte response in Crohn's disease with characteristics of a delayed-type hypersensitivity reaction.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    International journal of colorectal disease 14 (1999), S. 41-46 
    ISSN: 1432-1262
    Keywords: Key words Inflammatory bowel disease ; Permeability ; Transepithelial transport ; Immunoelectron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown etiology. Oral absorption studies have shown an increased intestinal permeability for various sugar molecules in patients with IBD and their healthy relatives as a possible pathogenetic factor. However, the various transport pathways through the mucosal barrier have not yet been examined. This study therefore investigated whether antigens pass the epithelial barrier by a transcellular or a paracellular pathway. Mucosa of freshly resected specimens from CD (n = 10) or UC (n = 10) patients was investigated by immunoelectron microscopy and compared with healthy mucosa. Epithelial transport was studied with the antigens ovalbumin and horseradish peroxidase after defined incubation. Labeling density of subunit c of ATP synthetase was determined in mitochondria of enterocytes of all specimens. In all specimens epithelial transport of OVA and HRP was principally transcellular through enterocytes with normal ultrastructure, although some tight junctions in CD and UC were dilated. Antigens were transported within vesicles to the basolateral membrane 2.5 min after incubation. The level of enterocytes with electron-lucent cytoplasm containing a high amount of antigens was higher in CD and UC than in healthy mucosa, depending on the grade of inflammation. ATP synthetase was significantly decreased in electron-lucent cytoplasm of CD and UC to normal ultrastructure of healthy mucosa. Our study shows that ovalbumin and horseradish peroxidase taken up by the apical membrane reach the paracellular space by vesicular transport in healthy and IBD enterocytes within a few minutes. Transcellular pathway is affected in both CD and UC, which is indicated by a high level of antigens within the cytosol. We speculate that increased intestinal permeability in IBD results substantially from enhanced transcellular transport.
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  • 6
    ISSN: 1432-1262
    Keywords: Key words MAC-1 (CD11b/CD18) ; ICAM-1(CD54) ; Inflammatory bowel disease ; Intravital microscopy ; Microcirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (αM-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P〈0.05) in rolling (from 5.41±2.87 to 32.41±15.03 100 µm–1 s–1) and sticking (from 0.16±0.18 to 9.11±5.3 100 µm–1 s–1) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P〈0.05) reduction in rolling (from 32.41±15.03 to 6.6±2.7 100 µm–1 s–1) and sticking (from 9.11±5.3 to 0.07±0.09 100 µm–1 s–1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29±0.76 points (P〈0.05) and anti-CD11b to a reduction from 4.29±0.76 to 1.29±1.11 points (P〈0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 68 (1997), S. 477-487 
    ISSN: 1433-0385
    Keywords: Key words: Celladhesion molecules ; Organ transplantation ; Tumor metastasis ; Inflammation ; Review article. ; Schlüsselwörter: Zelladhäsionsmoleküle ; Organtransplantation ; Entzündung ; Tumormetastasierung ; Übersichtsartikel.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die Adhäsion zirkulierender Zellen an Endothelzellen wird durch Zelladhäsionsmoleküle vermittelt und läuft kaskadenförmig ab. Die ersten Schritte dieser Zelladhäsionskaskade (rolling, tethering) werden vornehmlich durch Selektine (P-, E- und L-Selektin) reguliert, während an der stabilen Zelladhäsion und der anschließenden Migration hauptsächlich Integrine (LFA-1 u. a.) und Mitglieder der Immunglobulinsupergenfamilie (ICAM-1 u. a.) beteiligt sind. Die Leukocytenendothelinteraktion läuft unter physiologischen und pathophysiologischen Bedingungen sowie in verschiedenen Organen sehr ähnlich ab; möglicherweise wird die Zellwanderung in individuelle Gewebe/Organe (z. B. beim homing) durch zusätzliche organspezifische, topische Adhäsionsmoleküle (wie MAdCAM) ergänzt. Die mögliche klinisch-chirurgische Bedeutung von Zelladhäsionsmolekülen kommt insbesondere in der Transplantationsmedizin (Ischämie/Reperfusion und Rejektion), bei Entzündungen (z. B. chronisch entzündliche Darmerkrankungen) und in der Tumormetastasierung zum Tragen. Die Ergebnisse tierexperimenteller Untersuchungen zur Antiadhäsionstherapie zeigen, daß durch Blockade der Leukocytenendothelinteraktion die Entstehung von Entzündungsinfiltraten und die Abstoßungsreaktion verhindert werden können – Erfahrungen im Humansystem liegen bisher nur vereinzelt vor. Voraussetzung für die klinische Umsetzung ist u. a. ein besseres Verständnis der Regulation von Zelladhäsionsmolekülen (Cytokine, chemotaktische Substanzen etc.) und der Spezifität dieser Prozesse. Schon heute legen die experimentellen Daten nahe, daß durch Interaktion mit dem Zelladhäsionssystem durch frühe Beeinflussung eines grundlegenden pathophysiologischen Prinzips ein innovatives Therapiekonzept etabliert werden kann.
    Notes: Summary. This article reviews the molecular basis of cell adhesion and its possible implications in surgery. Adhesion of circulating cells to endothelial cells is mediated by a variety of celladhesion molecules. The first steps in the celladhesion cascade (rolling, tethering) are regulated by selectins (P, E, L selectin). Stable adhesion and transmural migration predominantly involve integrins (LFA-1, etc.) and members of the immunoglobulin supergene family (ICAM-1, etc.). The mechanisms of leucocyte-endothelial interaction are markedly similar in various organs under both physiological and pathophysiological conditions. However, it is likely that cell trafficing to specific tissues/organs (e.g., homing) is regulated by additional organ-specific, topical adhesion molecules (e. g., MAdCAM-1). In surgery, cell adhesion molecules are involved in organ-transplantation pathology (ischemia/reperfusion injury, rejection), inflammation (e.g., chronic inflammatory bowel diseases), tumor metastasis. Animal experiments with anti-adhesive substances show that blocking the leukocyte-endothelial interaction reduces the cellular inflammatory infiltrate and organ rejection. The transfer of experimental data into clinical practice requires further understanding of the regulators of cell adhesion (cytokines, chemoattractant substances, etc.) and the specificity of the process. Current experimental data suggest that early intervention in cell-adhesion mechanisms may offer innovative therapeutic strategies.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 375 (1990), S. 95-101 
    ISSN: 1435-2451
    Keywords: Thyroid ; Follicular adenoma ; Follicular carcinoma ; Stereology ; Flow cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Gut differenzierte follikuläre Neoplasien (FN) der Schilddrüse wurden unter der Frage analysiert, ob eine Differentialdiagnose ausschlielßlich anhand zytometrischer Kriterien möglich ist. Es wurden stereologische und flowzytometrische Tumorzellcharakteristika von 15 follikulären Karzinomen (FK) and 15 follikulären Adenomen (FA) untersucht mit den morphometrischen Primdrädaten Fldche, Umfang, Schnittsehnenldnge, numerische Dichte der Tumorzellkerne and der neue stereologische Schätzwert Vv. FK and FA unterschieden sich in keinem der untersuchten Tumorzellkernparameter. Diploide und aneuploide Tumoren kamen in beiden Gruppen gleichhdufig vor. Im Vergleich von diploiden mit aneuploiden FN zeigen aneuploide eine signifikante Vergrölßerung von Fläche, Umfang and Volumen der Tumorzellkerne. Unsere Ergebnisse schlielßen eine Differentialdiagnose der FN allein auf der Basis eines Aspirates aus. Die mangelnde zytologische Differenzierbarkeit zwischen beiden Typen der FN and der Nachweis malignomtypischer Stigmata bei den FA geben zu der Vermutung Anlaß, daß einige FA prdinvasive Karzinome sent könn-ten, die zum Zeitpunkt der Diagnose noch kein infiltratives Wachstum zeigen.
    Notes: Summary Fifteen resected follicular adenomas and 15 well-differentiated follicular carcinomas of the thyroid gland were analysed to determine whether a differential diagnosis of both “follicular neoplasms” can be performed by cytological criteria exclusively. 150–200 tumor cell nuclei (TCN) were studied per case for their TCN profile area, perimeter, density and for stereological estimates including the new parameter Vv, volume-weighted mean particle volume. Flow-cytometric analyses included measurement of the DNA index, the percentage of cells in S-phase and in G2/M phase. Follicular adenomas and follicular carcinomas did not show any significant differences in stereological estimates related to TCN size. Both groups included similar proportions of diploid and aneuploid neoplasms. Aneuploid follicular neoplasms showed a significantly greater area, perimeter and volume of TCN as compared to diploid tumors, regardless of their histological diagnosis. From our results a differential diagnosis of follicular neoplasms cannot be performed on the basis of cytological aspirates exclusively. Infiltration of capsula or vessels remain the only safe indicators of malignancy in the absence of metastases. The lack of cytological differences provides evidence that some follicular adenomas are preinvasive carcinomas, not yet showing infiltrative growth at the time of resection.
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  • 9
    ISSN: 1435-2451
    Keywords: Morbus Crohn ; Diagnostik ; Mononukleäre Zellen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In Crohn's disease (CD) the intestinal lesion is supposed to be the cause of the observed systemic immunologic changes. Based on this assumption, peripheral blood mononuclear cells (PBMC) are of specific interest as a possible indicator of intestinal activity of the disease. From 151 surgical patients CD3+, CD4+, CD8+, B cells, macrophages, leucocytes and the relative number of lymphocytes were analysed preoperatively and 10 days, 3 and 6 months postoperatively. The cell data were correlated with the main clinical data of disease. There was a highly significant preoperative increase of leucocytes, macrophages, CD8+, and B cells in the CD group, and a marked decrease of CD3+, CD4+ cells, and the relative lymphocyte count in the same group. Six months postoperatively, highly elevated macrophages, and leucocytes, and a depressed number of CD4+ cells were the only changes. The preoperative cell data did not correlate with the duration of illness, CDAI, localisation, and extent of the intestinal lesion nor did they correlate with any modality of preoperative drug treatment. Thus, the determination of PBMC characteristics in CD is only of limited value for routine diagnostic purposes. However, the persistence of some pathological values long after operation might be caused by residual microscopic lesions and thus reflect the intestinal process.
    Notes: Zusammenfassung Systemische immunologische Veränderungen bei Morbus Crohn sind wahrscheinlich durch die intestinale Entzündung verursacht. So könnte es sein, daß Veränderungen unter den mononuklären Zellen des peripheren Venenblutes ein diagnostisch relevanter Indikator der intestinalen Krankheitsaktivität sind. Zur Überprüfung dieser Hypothese wurden von 151 chirurgischen Crohn-Patienten CD3+, CD4+, CD8+, B Zellen, Makrophagen, Leukozyten und die relative Lymphozytenzahl im Vergleich zu einem Kontrollkollektiv präoperativ analysiert. Bei einem Teil der Patienten wurde die Analyse 10 Tage, 3 Monate und 6 Monate postoperativ wiederholt. Die präoperativen Blutzelldaten wurden mit Anamnesedauer, Ausdehnung und Lokalisation der Erkrankung, Medikation und dem CDAI nach Best korreliert. Gesamtleukozytenzahl, Makrophagen, CD8+ und B Zellen waren bei Crohn-Patienten präoperativ signifikant erhöht. Hingegen zeigten CD3+, CD4+ Zellen und die relative Lymphozytenzahl eine signifikante Erniedrigung. Sechs Monate postoperativ persistierten eine erhöhte Makrophagen- und Leukozytenzahl sowie eine Erniedrigung der CD4+ Zellen als einzige pathologische Veränderungen. Die präoperativen Blutzelldaten korrelierten mit keinem der untersuchten klinischen Eckdaten der Crohn-Erkrankung. Die Analyse von mononukleä-ren Zellen des peripheren Venenblutes ist somit für klinisch-diagnostische Fragestellungen von untergeordneter Bedeutung. Der postoperative Fortbestand einiger Veränderungen dieser Zellpopulationen ist dennoch ein wichtiger Hinweis auf die enge Verbindung zwischen peripherem Venenblut und intestinaler Läsion.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 71 (2000), S. 30-40 
    ISSN: 1433-0385
    Keywords: Key words: Crohn's disease – Ulcerative colitis – Mucosal immunology – Cytokines. ; Schlüsselwörter: Morbus Crohn – Colitis ulcerosa – mucosale Immunologie – Cytokine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die chronisch entzündlichen Darmerkrankungen (CED: Morbus Crohn, Colitis ulcerosa) sind durch schubartig verlaufende destruierende Entzündungsreaktionen der Darmschleimhaut gekennzeichnet. In den letzten Jahren konnte gezeigt werden, daß bei diesen Erkrankungen eine pathologische Aktivierung des intestinalen Immunsystems durch mucosale Antigene auftritt. In der chronischen Phase der Erkankungen sowie bei der Entwicklung postoperativer Rezidive sind Änderungen in der Zellmigration sowie der Cytokinproduktion intestinaler Zellen wahrscheinlich von entscheidender Bedeutung. Basierend auf diesen neuen pathogenetischen Erkenntnissen werden zur Zeit innovative klinische Behandlungsstrategien getestet, die rekombinante antiinflammatorische Cytokine (IFN-α, IL-10, IL-11) und Inhibitoren von Adhäsionsmolekülen (ICAM), proinflammatorischen Cytokinen (TNF, IL-12) und deren Rezeptoren (TNF, IL-6R) umfassen.
    Notes: Summary. Inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) are chronic inflammatory and frequently relapsing diseases of the gut that ultimately lead to destruction of the intestinal tissue. Recent evidence suggests that a pathologic activation of the mucosal immune system in response to antigens is a key factor in the pathogenesis of IBD. Furthermore, changes in cell migration and cytokine production appear to contribute to the perpetuation of IBD and the postoperative recurrence of Crohn's disease. Based on recent advances in our understanding of the pathogenesis of IBD, several new therapeutic strategies are currently being tested in clinical practice, including recombinant anti-inflammatory cytokines (IFN-α, IL-10, IL-11) and inhibitors of cell adhesion molecules (ICAM), proinflammatory cytokines (TNF, IL-12) and their receptors (TNF, IL-6R).
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