ISSN:0302-3427    

DOI:10.1159/000210922

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Tissue mast cells and the closely related blood basophils are distinguished by their special mediators and their high-affinity IgE membrane receptors. These properties have made the cells be viewed traditionally as effector cells of immediate-type hypersensitivity reactions. More recently, mast cells have been shown to develop from the myeloid series of the bone marrow under the influence of interleukins 3, 4, 6, 9, 10 and 11. Mast cell and basophil lines of murine and human origin have also been shown to express and release interleukins 1, 3, 4, 5, 6, 8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulizing factor and interferon-γ. Certain cytokines are also able to induce mediator release from mast cells. Furthermore, mast cells have in the past been shown to be modestly phagocytic and to express major histocompatibility complex class II membrane markers after appropriate stimulation. These findings show that mast cells are intricately associated with immune reactions and suggest that they may not only sustain and modulate but possibly also initiate immune response

ISSN:0302-3427    

DOI:10.1159/000210983

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210923

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210924

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Circulating histamine-releasing factors have been identified in the serum and plasma of chronic-urticaria patients by in vivo skin testing and in vitro histamine release from heterologous mixed leukocytes. Quantitative mast cell studies of serum skin test biopsies and electron microscopy indicate that the serum factors release histamine by mast cell degranulation. Peripheral blood basophils and total cellular blood histamine are reduced in chronic-urticaria patients suggesting that the circulating serum factors cause sustained degranulation. Histamine-releasing activity has been identified by skin testing in ultrafiltered serum fractions 100 kDa and was present in IgG purified from some chronicurticaria sera by protein G affinity chromatography. The dose-response relationship and kinetics of histamine release in vitro were similar to those of anti-human IgE. ‘Desensitisation’ of basophils by prior incubation with anti-IgE in the absence of calcium and competitive inhibition studies with myeloma IgE serum indicated that histamine-releasing autoantibodies in chronic-urticaria sera and purified IgG have the properties of anti-IgE. Plasma exchange in 4 patients with active chronic urticaria refractory to antihistamine therapy showing in vivo and in vitro histamine-releasing activity was followed by temporary remission of disease activity in 2 of them. It is possible that chronic urticaria is an autoimmune dise

ISSN:0302-3427    

DOI:10.1159/000210984

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Human late-phase allergic skin reactions (LPSR) are characterised histologically by a mixed infiltrate of granulocytes and mononuclear cells. Quantitative immunohistology reveals a correlation between the numbers of CD4+ T-cells and the number of activated eosinophils at LPSR sites. These CD4+ T-cells are predominantly CD45RO+ and belong to the ‘memory’ T-cell subset. Immunofluorescence studies indicate that type III (immune complex) mechanisms make no significant contribution to the LPSR. On the other hand, the LPSR and classical delayed-type hypersensitivity (DHT) both have a marked CD4+ T-cell component. T-cell infiltration is a more diffuse process in DTH than in the LPSR; between 24 and 48 h, DTH sites show a further increase in T-cell numbers with the appearance of CD8+ T-cells and an influx of monocytes. Activated eosinophils are present in the early stages of both LPSR and DTH, but are more prominent in the LPSR. These different patterns of cellular infiltration and activation are probably due to differences in the cytokine secretion pattern of the infiltrating T-cells. Detailed analysis of this hypothesis will require the use of in situ hybridization techniq

ISSN:0302-3427    

DOI:10.1159/000210985

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In order to study skin tumor promotion, a cell culture model system analogous to initiated mouse epidermis was developed. Keratinocytes of the neoplastic cell line 308 display the initiated phenotype since papillomas are produced when the cells are grafted to the backs of athymic mice. Coculture of a small number of these initiated cells with confluent normal keratinocytes results in the suppression of growth of colonies of 308 cells. This inhibition, which is calcium dependent, epidermal cell specific, and requires cell contact, can be overcome by exposure to various tumor promoters. Promoters and antipromoters of diverse structure and mechanism of action are recognized in this keratinocyte coculture model.

ISSN:0302-3427    

DOI:10.1159/000210986

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Clinical and experimental evidence explaining and supporting the role of UV radiation as a causal factor for the induction and promotion of nonmelanoma and malignant melanoma skin cancer are presented. While there is excellent animal experimental data and human epidemiologic evidence supporting the causal relationship of UVR (UVB, as well as UVA radiation) for basal and squamous cell carcinomas, the data establishing a direct causal relationship between melanoma and exposure to sunlight appear to be complex. They do, however, suggest a definite promotional role of sunlight in the causation of melanoma. Using a hairless pigmented mouse strain (Skh-hr2), experiments were initiated to examine the role of UVR in the induction of melanoma. A single application of DMBA as an initiator and subsequent thrice-weekly exposures to either UVB (290–320 nm) or UVA (320–400 nm) or the combined exposures of UVA and UVB resulted in the formation of blue nevus-like lesions. Repeated UVR exposures for over 30 weeks resulted in the development of melanoma (38 %), as well as lymphoma and squamous cell carcinoma only in those mice that were pretreated with DMBA and had developed nevi. Mice receiving UVB, UVA, or the combination treatments of UVB plus UVA without DMBA pretreatment developed papillomas and squamous cell carcinoma but no melanoma. These studies indicate that some initiation event is essential to transform melanocytes to blue nevus-like lesions before UVR (UVB + UVA) can act as a promoter and accelerate the development of malignant melanoma, as well as lymphoma.

ISSN:0302-3427    

DOI:10.1159/000210987

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The toxicity of quinones – including certain chemotherapeutic agents such as doxorubicin – have been related to the enzymatic or nonenzymatic formation of the corresponding semiquinones and their subsequent reaction with molecular oxygen yielding superoxide anion radicals by spontaneous regenerating of the quinones. This semiquinone redox cycling is prevented by the NAD(P)H:quinone reductase (NQR; EC 1.6.99.2) because it mediates a 2-electron reduction which results in the formation of hydroquinones instead of semiquinones. Interestingly, inducers of this enzyme such as butylated hydroxytoluene protect against the severe ulceration of accidental infiltration of doxorubicin into the area around the intravenous infusion. Recently, it has been shown that this highly protective enzyme has a very high basal activity in the epidermis which is in the same range as in the liver. The human gene of the NQR is localized on chromosome 16 and has been cloned recently as well as the gene of the murine liver NQR. We determined NQR in the cytoplasma of murine skin, liver, and human keratinocytes using 2,6-dichlorophenol-indophenol as substrate. In order to characterize this enzyme, induction by polycyclic hydrocarbones and inhibition with several known inhibitors of dihydrodiol dehydrogenase, aldo-keto and carbonyl reductase activities were determined. There was a similar pattern of inhibition of the basal and induced activity in all tissues so far investigated. Pyrazole, progesterone and phenobarbital did not inhibit; however, rutin and indomethacin inhibited dose-dependently. The most potent inhibitor was dicoumarol. These findings suggest that the same enzymatic form is present in liver and skin, and in murine skin and human keratinocy

ISSN:0302-3427    

DOI:10.1159/000210988

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:0302-3427    

DOI:10.1159/000210989

出版商:S. Karger AG    

年代:1991

数据来源: Karger