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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 19 recordsLinked to original sources
PubMed1992

Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils.

Thrombin stimulation of human platelets results in the release of a preformed proteinaceous human eosinophil (Eo)-chemotactic activity. By the use of different high-performance liquid chromatography techniques, two Eo-chemotactic polypeptides (EoCPs), tentatively termed EoCP-1 and EoCP-2, were purified to homogeneity. Upon SDS-PAGE analysis, these chemotaxins showed molecular masses near 8 kD. NH2-terminal amino acid sequence analysis revealed identical sequences for both EoCP-1 and EoCP-2, which are also identical to that of RANTES, a cytokine that structurally belongs to the interleukin 8 superfamily of leukocyte selective attractants, and that is known to be a "memory-type" T lymphocyte-selective attractant. In the major Eo chemotaxin, EoCP-1, the residues 4 and 5, which in EoCP-2 were found to be serine residues, could not be identified. Electrospray mass spectrometry (ESP-MS) of EoCPs revealed for EoCP-2 a molecular mass of 7,862.8 +/- 1.1 daltons, which is 15.8 mass units higher than the calculated value of RANTES, indicating that EoCP-2 is identical to the full-length cytokine, and oxygenation, probably at methionine residue number 64, has taken place. Upon ESP-MS, EoCP-1 showed an average molecular mass of 8,355 +/- 10 daltons, suggesting O-glycosylation at these serine residues. Both natural forms of RANTES showed strong Eo-chemotactic activity (ED50 = 2 nM) with optimal chemotactic migration at concentrations near 10 nM, however, there were no significant migratory responses with human neutrophils. Chemotactic activity of RANTES for human Eos could be confirmed using recombinant material, which has been found to be as active as the natural forms. Since RANTES gene expression has been detected in activated T lymphocytes, and recombinant RANTES was shown to be a "memory" T lymphocyte-selective attractant, it is now tempting to speculate about an important role of RANTES in clinical situations such as allergene-induced late-phase skin reactions in atopic subjects or asthma, where in affected tissues both memory T cells and Eos are characteristic.

Amino Acid Sequence↗
PubMed1992

Mesna side effects which imitate vasculitis.

Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated with "low dose" CYC and prednisone for vasculitis developed severe side effects to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane lesions, and abdominal complaints with profuse diarrhea were noted approximately 3 weeks after the initiation of therapy for CYC-induced leukopenia and a conservatively reduced prednisone dosage. Positive reexposure tests confirmed the association to Mesna use, and hypersensitivity skin tests demonstrated a delayed hypersensitivity reaction.

Adult↗
PubMed1992

Inhibition of human monocyte functions by anthralin.

Anthralin is a well-established and widely used compound for topical treatment of psoriasis. In recent years attention has been focused on the anti-inflammatory properties of anthralin, with particular reference to psoriasis. In this study the effect of anthralin on human monocyte chemotaxis, superoxide-anion generation, and enzyme degranulation, were investigated. For comparison, the effect of the clinically inactive anthralin derivative danthrone and the solvent (acetone) were also studied. The results show that anthralin potently inhibits stimulated human monocyte superoxide-anion generation and enzyme degranulation, with a half-maximal inhibitory concentration (IC50) of as low as 0.02 micrograms/ml. Chemotactic migration of monocytes, however, was only affected when very high doses of anthralin (10 micrograms/ml) were used for pretreatment of the cells. Danthrone, up to a concentration of 10 micrograms/ml, or acetone alone (0.1%, v/v), did not inhibit the monocyte functions tested. Our results indicate that anthralin at pharmacological concentrations is a potent and selective inhibitor of human monocyte pro-inflammatory activities, by inhibiting respiratory burst activity (e.g. superoxide-anion generation) and enzyme degranulation, without affecting chemotactic migration.

Acetone↗
PubMed1992

Infiltrating neutrophils differ from circulating neutrophils when stimulated with C5a, NAP-1/IL-8, LTB4 and FMLP.

In this study we report on functional characteristics of pustule as well as blood polymorphonuclear neutrophils (PMN) in a patient suffering from relapsing bullous staphyloderma. Large numbers of viable PMN from newly formed pustules as well as from the peripheral blood were investigated. During the course of disease chemotactic migration, enzyme degranulation, superoxide-anion generation and leukotriene B4 production were determined simultaneously. The results revealed C5a- and NAP-1/IL-8-specific dysfunction of pustule PMN as compared with blood PMN. In contrast, FMLP-elicited functional activities of pustule PMN were only slightly affected. Our findings provide evidence that in inflamed tissue invading PMN are regulated by in situ generated mediators. C5a produced by staph, aureus-induced activation of the alternative pathway of the complement cascade represents a predominant regulatory factor in situ. Furthermore, the results substantiate previous observations concerning different modulation of C5a and f-met-peptide receptors on human PMN.

Chemotaxis, Leukocyte↗
PubMed1992

Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils within the airspaces of the lungs. In order to determine if neutrophil activating protein (NAP)-1/interleukin-8 (NAP-1/IL-8) could be an important cause of neutrophil influx and activation in ARDS, we examined fluid, which was either directly aspirated or lavaged with saline from the lungs of patients with ARDS. NAP-1/IL-8 was present in significantly higher concentrations in the fluids of patients with ARDS compared with control subjects. There was a significant correlation between the percentage of neutrophils in the lavage fluids and the NAP-1/IL-8 concentration (r2 = 0.74). Furthermore, the NAP-1/IL-8 concentration of the pulmonary edema fluid was equivalent to the optimal concentration required to induce neutrophil chemotaxis in vitro. Although not all of the chemotactic activity of the edema fluid was removed by an anti-NAP-1/IL-8 affinity column, the data established that NAP-1/IL-8 is an important neutrophil chemotaxin in the airspaces of patients with ARDS. In addition, those patients with very high concentrations of NAP-1/IL-8 in their bronchoalveolar lavage fluids had a higher mortality rate than those patients with lower concentrations of NAP-1/IL-8. The correlation between NAP-1/IL-8 concentration and mortality is not paralleled by total protein concentration and mortality.

Adolescent↗
PubMed1992

Candida albicans grown in glucose-free media contains serum-independent chemotactic activity.

Infection of skin with Candida albicans is usually followed by infiltration of neutrophil granulocytes (PMN). So far, chemotaxins for PMN have been isolated from C. albicans cultures grown in the presence of glucose. However, since glucose is not present in skin in vivo, a contribution of such factors to Candida-triggered cutaneous inflammation would appear unlikely. In order to clarify this question, chemotactic activity was measured in extracts from three different strains of C. albicans which were grown in five different peptone media free of carbohydrates and serum. In addition, four culture systems were supplemented with lipids normally present in human stratum corneum, including a triglyceride, cholesterol, and sphingomyelin. In all sugar-free grown cultures, serum-independent chemotactic activity was detected by use of the Boyden chamber technique. Since, as shown here in vitro, production of neutrophil chemotaxins by C. albicans is independent of glucose-feeding, a possible role of Candida-chemotaxins in the pathophysiology of cutaneous candidosis can no longer be excluded.

Candida albicans↗
PubMed1992

Relapsing bullous staphyloderma.

Relapsing eruptions of bullae rapidly turning into pustules were seen in a 69-year-old woman of good general health. At different times during several months of observation, strains of S. aureus were grown from various lesions, including one (phage group III) producing enterotoxin C. Systemic involvement except for high BSR was absent and repeated blood cultures were negative. Histopathological findings resembled impetigo. Antibiotic treatment was effective. As this disease does not fit into any of the well-known pustular infectious dermatoses, we suggest calling it relapsing bullous staphyloderma.

Aged↗
PubMed1979

Therapy of psoriasis with retinoid plus PUVA: clinical and histologic data.

In a group of 40 patients suffering from wide-spread psoriasis oral administration of a retinoid (Ro 10-9359) was followed by PUVA therapy. The clearance rate was increased by 30% as compared to PUVA alone. Except for cheilitis no side effects were seen. Histological analysis in 20 patients before, during and after therapy revealed an intensification of psoriatic tissue changes after retinoid treatment. Loss of corneal layers, massive exoserosis, and neutrophil migration were prominent features. Mitotic counts were not increased by the pretreatment. The increased susceptibility of diseased skin to PUVA as produced by this drug appears to be based on several factors related to the tissue changes revealed by histology.

Humans↗
PubMed1979

Thrombin and fibrin-induced growth of fibroblasts: role in wound repair and thrombus organization.

Skin fibroblast cultures were treated with various components of the blood clotting system (thrombin, fibrinogen and fibrin) during the logarithmic growth phase. Fibrin as well as thrombin showed dose-dependent growth promoting activities as revealed by cell counting and 3H-thymidine uptake. No effect was seen with fibrinogen. After entrapping in polymerizing fibrin enriched by complete culture medium the cells elongated, multiplied and formed net-like interconnecting cell strands throughout the clots. Nutritional deprivation appeared as a limiting factor for eventual growth cessation. The results demonstrate active growth of fibroblasts in fibrin clots such as present in healing wounds and thrombi. The production of thrombin by the coagulation cascade does not only result in the conversion of fibrinogen to fibrin but has also a long-lasting hormone-like effect on fibroblast proliferation which is of essential importance in wound healing, thrombus organization and progression of chronic atherosclerotic lesions.

Animals↗
PubMed1979

Dose-effects of 8-methoxypsoralen and long wave UV-light in 3T3 cells: evaluation of phototoxic index.

3T3 cells were cultured until confluency and treated with various doses of 8-methoxypsoralen followed by long wave UV light irradiation. The inhibition of 3H-thymidine incorporation was dose-dependent for both, psoralen and light. A phototoxic index (PTI) was established demonstrating that a constant correlation between psoralen and UVA light exists for the photoinactivation in living cells.

Animals↗
PubMed1979

Growth characteristics of skin fibroblasts and 3T3 cells entrapped by polymerizing fibrin.

Skin fibroblasts as well as 3T3 cells were cultured after entrapping freshly prepared cells in medium containing polymerizing fibrin. In contrast to cells grown on plastic substratum, fibrin-clot-cultured cells became highly elongated forming strands of cells. The strands interconnected by lateral cellular protrusions so that horizontal networks of cells were present throughout the clots. Cell growth as well as stretching were dependent upon the concentrations of fibrin. Highest growth rates were obtained with low fibrin concentrations (0.3 mg fibrinogen per ml). As shown by deprivation experiments nutritional limitations appear to be responsible for differences in growth rates observed in fibrin clots of higher density. In this system the fibrin meshwork serves as substratum for adhesion, elongation and multiplication of fibroblasts. The method makes it possible to study single cells in culture and the effects of persistent microenvironmental influences.

Animals↗
PubMed1979

Photoinactivation of skin fibroblasts by fractionated treatment with 8-methoxypsoralen and UVA.

Guinea pig skin fibroblasts treated with low doses of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet light (UVA) showed a dose-dependent inhibition of 3H-Thymidine incorporation as determined by liquid scintillation counting. The minimum incubation time necessary to obtain constant inhibition rates was 60 min. By washing the drug was removed from the reactive sites within 30 min. Repeated light exposure at a constant concentration of 8-MOP caused a cumulative inhibition of DNA synthesis. Irradiation of 8-MOP-plus-UVA treated cells, from which the drug was removed, produced a small increase in photoinhibition. Split dose treatment at various time intervals (ranging from 1--48 hr) revealed inhibitory rates, which correspond to the total amount of UVA applied. No recovery effects were seen in cultures treated by single or multiple applications of 8-MOP-plus-UVA.

Animals↗
PubMed1979

Leiomyomatosis cutis et uteri.

A 32 year old female patient showed multiple plaque-like leiomyomata cutis and an uterus myomatosous of early onset. In the skin large areas of plaque-like confluent erythematous nodules consisting of smooth muscle tissue are formed. The patient suffered from frequent attacks of severe pain elicited by temperature changes or trauma. Treatment with nitroglycerine and nifedipine together with phenoxybenzamine completely suppressed the symptoms.

Adult↗