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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 8 (1999), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: First, a method of microinjection of antibodies in primary human keratinocytes in culture was established. Second, in acute UV irradiation, the physiological role of heat shock protein (HSP) 72 in keratinocytes was studied with this method. Primary human keratinocytes in culture were injected with “controls” as fluorescent dyes, phosphate buffered saline (PBS), an irrelevant secondary antibody and an antibody against a protein with known protective function in UV erythema, HSP 72. UV irradiation was applied and survival, colony forming and immunohistochemistry for injected and non-injected keratinocytes were evaluated in a time course. Puncturing the plasma membrane with injections of “controls” as FITC, PBS and the IgG anti-mouse antibody did not result in reflux of injected material or any alteration in morphology or colony-forming ability for 24 h. Keratinocytes injected with an mAb to HSP 72 without UV irradiation survived microinjection for up to 12 days, while surprisingly, more than double of injected and irradiated ones died after 12 h compared to not injected and irradiated ones. Moreover, microinjection of the antibody to HSP 72 in the nucleus resulted in a loss of the immunohistochemical labeling for HSP 72 in these cells after 12 h. Microinjection of the “controls” did not harm the survival, forming of colonies and expression of HSP 72 in keratinocytes for 24 h. In contrast, microinjection of an mAb against HSP 72 led to an increase in cell death after UV irradiation, confirming that HSP 72 is important for UV protection. Microinjection of antibodies in human keratinocytes in culture might allow the study of the physiological role of some proteins.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 133 (1995), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the present study, we investigated the expression of the tumour suppressor protein p53 in 1 primary and 43 metastatic malignant melanomas by immunohistochernistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome.In primary melanomas, the polyclonal anti-p5 3 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohis-tochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immuno-reactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P〈0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P〈0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (〈1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant.The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells. The observation of similar staining frequencies in thin, thick and metastatic lesions indicates that p53 over-expression is an early event in the pathogenesis of malignant melanoma. However, the immunohistochemical detection of p53 in primary melanomas is not related to prognosis.
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P 〈 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P 〈 0.01) and the 400-mg groups (P 〈 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose dependent, and appeared to be similar to those seen with cyclosporin. Changes in liver function tests showed a clearcut dose-dependent increase of some liver enzymes, principally alanine aminotransferase (ALAT). SDZ IMM 125 is effective in clearing psoriasis. However, long-term studies comparing the efficacy and safety of SDZ IMM 125 and cyclosporin must be performed, to determine whether SDZ IMM 125 has a better risk-benefit ratio than cyclosporin.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 220 (1964), S. 38-59 
    ISSN: 1432-069X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Entsprechend der eingangs festgehaltenen Klassifikation wurden 33 schweizerische Patienten mit hereditärer Epidermolysis klinisch und gerinnungsphysiologisch untersucht. Die Großzahl davon war auch einer histologischen Studie zugänglich. Histologisch konnte die Blasenbildung bei der Epidermolysis b. h. simplex (Köbner) eindeutig intraepithelial charakterisiert werden. Bei der E. b. h. hystrophica polydysplastica (Hallopeau-Siemens) wird die Blasenbildung an oder in der Grenzmembran, also eindeutig subepidermal gefunden. Je nach Schweregrad des klinischen Bildes findet sich eine Veränderung an Elastica und fibrillärem Bindegewebe des Papillarkörpers, ohne daß festgelegt werden könnte, ob es sich dabei um ein primäres oder sekundäres Geschehen handle. Die E. b. h. dystrophica hyperplastica (Cockayne-Touraine) nimmt histologisch wahrscheinlich eine Zwischenstellung ein. Gerinnungsphysiologisch fanden sich bei allen drei Epidermolysis-Typen keine konstanten Abweichungen von der Norm. Nach Vergleich mit der zugänglichen Literatur muß der Ansicht widersprochen werden, daß der hereditären Epidermolysis eine Gerinnungsstörung eigen ist. Therapieversuche mit Heparinkörpern und Chloroquine wurden angestellt. Einzig mit Chloroquine bei Kindern der Köbenerschen Epidermolysisform konnte symptomatisch eine Blasenhemmung erreicht werden.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 259 (1977), S. 293-298 
    ISSN: 1432-069X
    Keywords: 8-Methoxypsoralen ; UVA-irradiation ; Psoriasis ; Lymphocyte stimulation ; E-rosettes ; EAC-rosettes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die unspezifische Stimulierung der Blutlymphocyten von 37 Psoriatikern durch HgCl2 in der Leukocytenkultur wurde vor und während der PUVA-Therapie gemessen (Maßzahl: Incorporation von3H-Thymidin, Kulturdauer 120 h, Konzentration 10 µg/ml). Oral verabreichtes 8-MOP in therapeutischer Dosis vermindert in der ersten Therapiewoche die Lymphocyten-Stimulierung ebenso wie 8-MOP plus UVA-Bestrahlung. Nach einer Woche jedoch wird die Lymphocyten-Stimulierbarkeit durch UVA Bestrahlung signifikant erhöht. Über Lymphoprep isolierte Lymphocyten wurden in vitro PUVA-Bedingungen ausgesetzt (Hank's solution 8-MOP 1 µg/ml, Bestrahlung mit 350 nm und Energien zwischen 93-372 mJ/ml). Bestimmt wurden die Gesamtzellzahl, der Prozentsatz der E-Rosetten (als Maßzahl für T-Lymphocyten) und der EAC-Rosetten (als Maßzahl für B-Lymphocyten). PUVA-Bedingungen senken energieabhängig die Zellzahl, während der prozentuale Anteil der T- und B-Lymphocyten konstant bleibt. UVA allein hat diesen Effekt nur bei sehr hohen Energien, 8-MOP allein hat gar keine Wirkung.
    Notes: Summary Peripheral lymphocytes of 37 psoriatic patients are tested before and under PUVA treatment using as parameter the non specific stimulation effect of HgCl2 (10 µg/ml) in culture, measuring the3H-thymidine incorporation after the last 16 h of a 5-days culture. Oral 8-MOP in therapeutic doses is decreasing the lymphocyte stimulation as well as 8-MOP together with UVA irradiation during the first week of treatment. After 1 week, the stimulation is, on the contrary, significantly enhanced after irradiation. Lymphocytes isolated by centrifugation over Lymphoprep are submitted to PUVA conditions in petri dishes (Hank's solution 8-MOP 1 µg/ml, irradiation with 350 nm, 93-372 mJ/cm2). The total cell number, the E-rosette formation (as marker for T-Lymphocytes) and the EAC-rosette formation (as marker for B-Lymphocytes) are determined. PUVA conditions have an energy dependent decreasing effect on the cell number, while the T- and B-cell proportions remain constant. UVA irradiation alone has such an effect only with high energies. 8-MOP without UVA has no significant influence on the cell number.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 259 (1977), S. 21-28 
    ISSN: 1432-069X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1966–1969 wurden 100 evolutive Hämangiome einer prospektiven randomisierten Studie zugeführt, wobei die eine Hälfte einer Weichstrahlbehandlung unterzogen wurde, die andere Hälfte einer Pseudobestrahlung. Die Nachkontrolle nach 6 Jahren zeigt bei einer Rücklaufquote von 54%, daß beide Serien eine gleich große Abheilungsquote haben und daß das Muster der Residuen der nicht vollständig abgeheilten Hämangiome bei beiden Gruppen gleich ist. Die biologische Gesetzmäßigkeit der Rückbildung frühkindlicher Hämangiome scheint also unabhängig von der durchgeführten Röntgenbestrahlung zu sein. Es fällt auf, daß die Röntgenbestrahlung von Hämangiomen bei Kindern vom dunkelhäutigen Typ eine bessere Abheilungschance erbringt, als eine solche beim hellhäutigen Typ.
    Notes: Summary In the years 1966–1969 100 haemangiomata which had developed in early childhood were prospectively investigated in a randomised study. Half of them were treated by soft X-ray radiation, the other half underwent mock-radiation as a control. 54% of the orginal group could be examined after 6 years. The results showed that the ratio of cure was similar in the both groups. The skin pattern of the incomplety cured haemangiomata was also comparable. The biological rule of regression of haemangiomata in early childhood seems not to be influenced by X-ray treatment. It is stiking that X-ray treatment in darkskinned children leads to a better therapy-result than in fair-skinned ones.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 241 (1971), S. 284-291 
    ISSN: 1432-069X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die ultraviolette Strahlung bewirkt in Epidermiszellen DNS-Schäden, die durch den Mechanismus des Excisions-Repair wieder ausgebessert werden. Dieser Vorgang kann am besten autoradiographisch anhand der leicht markierten Zellen bewertet werden. Ein weiterer UV-Effekt besteht in einer Verzögerung des Zellcyclus, was anhand der Zahl markierter S-Phasen abgeschätzt werden kann. Die vorliegenden Versuche wurden an haarlosen Albinomäusen durchgeführt; die Bestrahlung erfolgte mittels einer Xenonlampe unter Vorschaltung von Interferenzfiltern oder eines Prismen-Monochromators. Reparationsaktivität wurde dargestellt nach Bestrahlung mit UV C und B, wobei eine besondere Betonung bei 280–290 nm lag. Die relativ tiefen Werte bei 250 und 260 nm sind nur erklärlich, wenn man bei diesen Wellenlängen schon eine deutliche Dimerspaltung als reversiblen Vorgang annimmt. Das wird gestützt durch die Tatsache, daß bei 260 nm praktisch keine Verzögerung des Zellcyclus zu beobachten ist, was im Bereich 270–310 nm durchaus der Fall ist. Es scheint, daß das Spektrum der UV-induzierten und reparablen DNS-Schäden in vivo weit breiter ist als es die Absorption in vitro vermuten läßt.
    Notes: Summary Ultraviolet radiation is known to produce DNA damage in epidermal cells that can be removed by the mechanism of excision repair, measured by the number of lightly marked cells in autoradiography. Another effect consists in a delay of the mitotic cycle measured by a reduction of heavy labelled S-phases in the basal cell layer. Irradiation was carried out in hairless albino mice by a Xenon arc lamp with interference filters and with a prism monochromator. Repairing activity was demonstrated in UV C and B with a high peak from 280–290 nm. The relatively low values at 250 and 260 nm are explained by the simultaneously occuring dimer breakage with these wavelengths. This is confirmed by the fact that after 260 nm irradiation we did not find a depression of S-phases in the basal cell layer, while in the range from 270–310 nm there is a clear decrease in the number of replicating cells. There is evidence that the spectrum of UV induced repairable DNA alterations in vivo is broader than the absorption of DNA in vitro.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 240 (1971), S. 123-137 
    ISSN: 1432-069X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Biochemische und elektronenoptische Untersuchungen wurden an einem 20 jährigen Patienten mit einem kompletten oculocutanen Albinismus durchgeführt. Durch eine 4 wöchige UV-Stimulation kombiniert mit α-Methyl-Dopa undl-Dopa konnte eine deutliche Zunahme normal strukturierter Melanocyten dargestellt werden, während jegliche Anzeichen einer Pigmentinduktion fehlen. Vor und nach Stimulierung sind die Prämelanosomen und andere Zellorganellen der Melanocyten normal strukturiert. Eine eindrückliche Zunahme der Golgi-Zonen, des ribosomenbesetzten endoplasmatischen Reticulums, der Mitochondrien und Prämelanosomen konnte durch die Stimulierung im gleichen Ausmaß erreicht werden, wie dies bei normaler Haut der Fall ist. Der Schutz der Albinohaut durch die Lichtschwiele ist im Vergleich zum Schutzeffekt von Lichtschwiele mit Pigmentierung bei normaler Haut sehr schwach. Die Struktur der Melanocyten und deren Organellen sind beim oculocutanen Albinismus normal und können auch normal stimuliert werden. Der Defekt liegt auf der Stufe der Tyrosinase oder deren Verwendung. Elektronenoptische Untersuchungen erlauben den oculocutanen Albinismus vom partiellen Albinismus abzugrenzen (Piebaldismus und Chediak-Higashi-Syndrom).
    Notes: Summary Biochemical and electron microscopical studies were done in a 20 year old male patient with complete albinism. The number of normally structured melanocytes was elevated by a four week stimulation by UV irradiation combined with α-methyl-Dopa and l-Dopa, but there was no sign of induction of pigmentation. Before and after stimulation the melanocytes contain normally structured premelanosomes and other organelles. There is an impressive increase in Golgi areas, of rough surfaced endoplasmic reticulum, mitochondria and premelanosomes in the melanocytes after stimulation. The protection of albino skin by the “Lichtschwiele” is weak in comparison to its combined effect together with pigmentation in normal caucasian skin. In oculocutaneous albinism the melanocytes are structurally normal and can be stimulated in the normal way. There must be a defect of tyrosinase or its transfer to the premelanosomes, perhaps by an inhibitor. By electron microscopy the oculocutaneous albinism can easily be distinguished from partial albinism in piebaldism and in the Chediak-Higashi-syndrome.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 244 (1972), S. 40-44 
    ISSN: 1432-069X
    Keywords: Replication ; Reparation of epidermal DNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 260 (1977), S. 63-70 
    ISSN: 1432-069X
    Keywords: UV-C ; UV-A ; 8-MOP ; LTT ; Mitogens ; E-rosettes ; EAC-rosettes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An UV-C bestrahlten Leukocyten und Lymphocyten werden im LTT mit den Mitogenen Con A, PHA und PWM nach 3 Tagen Kultivierung die3H-Thymidineinbauraten in die überlebenden Zellen gemessen. T- und B-Zellen werden anhand der Bildung von E- und EAC-Rosetten bestimmt. Bei Leukocyten ist mit 450 mJ/cm2, bei isolierten Lymphocyten schon mit 5–10 mJ/cm2 eine deutliche Hemmung der Zellaktivität festzustellen. Es ergeben sich keine statistisch signifikanten Unterschiede in der Wirkung der verschiedenen Mitogene. Bei bestrahlten Lymphocyten nimmt die Zahl der T-Zellen proportional zur Bestrahlungsintensität ab, die Zahl der B-Zellen bleibt weitgehend konstant. UV-A-Bestrahlung von Lymphocyten mit 8-MOP bewirkt im LTT, gleichmäßig für alle Mitogene, eine dosisabhängige Hemmung des Thymidineinbaus.
    Notes: Summary The transformation of UV-C irradiated leucocytes and lymphocytes by the mitogens Con A, PHA and PWM is measured by the3H-Tdr. incorporation after 72 h incubation. Furthermore T-and B-cells are determined by the method of rosette formation. A clear inhibition of the cell activity is seen after irradiation of leucocytes with 450 mJ/cm2 and of a lymphocyte suspension with 5–10 mJ/cm2. There are no significant differences between the effects of the various mitogens. The number of T-cells decreases proportionality to the various intensity, the number of B-cells remain constant. Irradiation with UV-A + 8-MOP cause, equaly for all mitogens, a dosis dependent inhibition of thymidine incorporation.
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