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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 253 records · Page 14Linked to original sources

Risk of skin tumors in psoralen- and ultraviolet A-treated patients.

From 1973 to 1981, the clinical data of 1,136 patients with psoriasis and another 1,210 with various skin tumors were accessioned with the aid of computerized data files. Skin tumors and psoriasis occurred in 48 patients. After psoralen plus 320-400 nm UV (PUVA) therapy for psoriasis was introduced in 1976, 381 patients with this disease were treated. Follow-up data revealed no change in the tumor incidence rate after this treatment began. Age-related calculations of the relative probabilities for the presence of skin cancer in patients with psoriasis after PUVA revealed a grossly normal pattern (which appeared to be unaffected by PUVA). We observed a skin tumor in 2 patients 5 years after PUVA therapy.

Adult↗

Influences of thrombin, factor XIII and fibronectin on the growth of tumor cells and leukemic cells in vitro.

Thrombin, factor XIII and fibronectin were incubated with cultures of mouse sarcoma cells, human cervix carcinoma cells (HeLa cells) and cells of an acute lymphoblastic leukemia. Thrombin induced a significant increase of 3H-thymidine uptake into cells with a 1,5- to 2-fold increase of cell count. The cells of an acute lymphoblastic leukemia showed a similar response to the influence of thrombin. Factor XIII merely induced an increase of 3H-thymidine uptake in tumor cells, the cell count remained constant. These results differ from experiments with cultures of normal fibroblasts. Decreased receptor density in tumor cells toward factor XIII and thrombin would play a role so that the mitogenic stimulus is impaired. The cells of an acute lymphoblastic leukemia showed under the influence of factor XIII a significant increase of cell count and thymidine uptake. HeLa cell growth was optimal at low fibronectin concentrations. Fibronectin concentrations of 1 mg/ml to 3 mg/ml inhibited HeLa- and mouse sarcoma cell growth.

Animals↗

Role of filter-bound IgA in inhibiting polymorphonuclear leukocyte chemotaxis.

The effects of human serum IgA on human polymorphonuclear leukocyte (PMN) function were studied. In Boyden chambers, chemotactic migration against semipurified C5a as well as the formylated tripeptide FMLP was inhibited in the presence of IgA. Under such conditions, the release of superoxide anion was not changed. In addition, chemotaxis "under agarose" using the leading front evaluation remained unaltered in the presence of IgA despite IgA-induced aggregation of PMN and reduced density of migrating cells. Chemotaxis filters incubated with radiolabelled IgA demonstrated strong binding of IgA, and further, these IgA-pretreated filters impeded PMN migration. Incubation of PMN with IgA followed by subsequent washings did not affect chemotactic migration. These data show that filter binding of IgA is responsible for the inhibition of chemotactic PMN-migration in the Boyden chambers, most probably mediated by increased cell-substrate adhesion. Experiments using casein showed displacement of IgA by casein which enables PMN to fully respond to casein.

Binding Sites, Antibody↗

Altered polymorphonuclear leukocyte responses in psoriasis: chemotaxis and degranulation.

Chemotactic activities of circulating polymorphonuclear leukocytes (PMN) were determined in twenty patients with psoriasis and twenty healthy control persons. After serial dilution of the complement split product C5a and the formylated tripeptide f-met-leu-phe (FMLP), chemotaxis profiles showed that PMN migration toward both chemotaxins was significantly increased in psoriasis. In addition, PMN from psoriatic patients responded to chemotaxins at much lower concentrations compared with controls. The liberation of (lysosomal) beta-glucuronidase was also determined in cytochalasin B-treated cells confronted with increased concentrations of the chemotaxins. Secretion of this marker enzyme started at lower concentrations in PMN derived from psoriatic patients. Our observations demonstrate migratory and secretory hyper-responsiveness of PMN from psoriatic patients. This may play a role in perpetuating the psoriatic tissue reaction.

Adult↗

Methotrexate inhibits polymorphonuclear leucocyte chemotaxis in psoriasis.

Six patients suffering from widespread psoriasis were treated with 20 mg methotrexate (MTX) intramuscularly and the chemotactic activity of peripheral polymorphonuclear leucocytes (PMN) was measured before and after treatment. The modified Boyden chamber method was used and C5a, FMLP, casein and autologous fresh serum served as chemotaxins. Following MTX the chemotactic migration of PMN was inhibited by more than 50% for 2 days and slowly recovered within the following 5 days. The inhibition was present with all of the four chemotaxins used. The results demonstrate that treatment with low dose MTX in patients with psoriasis causes a profound inhibition of PMN function. These findings support the idea that PMN play an important role in the pathogenesis of psoriasis.

Adult↗

HLA-related lymphocyte responsiveness in psoriasis.

In order to find associations among the genetic, immunological and environmental factors that might be important in the pathogenesis of psoriasis, the relationship between streptococcal antigen- or mitogen-induced lymphocyte responses in vitro and HLA phenotypes was studied in 23 patients with psoriasis. Patients showed an elevated lymphocyte response to somatic A-streptococcal antigens when compared with healthy controls. In contrast, the response to mitogens (PHA, Con A, PWM) was impaired in patients with psoriasis. The impaired mitogen-induced lymphocyte transformation was found mostly in psoriatics with HLA-B13/B17. The elevated cellular immune response to somatic A-streptococcal antigens, on the other hand, was observed mainly in psoriatics without HLA-B13/B17. The results indicate that gene products of the HLA region known to be associated with psoriasis are involved in the cellular immune response, as expected from clinical trials. These findings also provide further evidence of at least two different subtypes of psoriasis, characterized by genetically and immunologically defined markers.

Antibodies, Bacterial↗

Action spectra for 8-methoxypsoralen and 3-carbethoxypsoralen in skin fibroblasts in vitro.

8-methoxypsoralen (8-MOP) and 3-Carbethoxypsoralen (3-CPs) are known photoreagents which have been employed in the treatment of psoriasis. Using skin fibroblasts grown in vitro we have determined the action spectra of both compounds in the long ultraviolet range. Narrow-band interference filters were applied to a Xenon lamp. Reduction in methyl-3H-thymidine (3H-TdR) uptake served as a parameter for photoinhibited cells. The results show a linear increate of 8-MOP-mediated photoinhibition with increasing wavelengths; 3-CPs showed comparatively weak inhibitory rates at the lower wavelength range (349-365 nm). Possibly this is due to the formation of 3-CPs photoproducts which are unreactive with DNA. Compared to 8-MOP, the monofunctional photoreagent 3-CPs is a weak photoinhibitor.

Animals↗

[Skin manifestations in human yersiniosis (author's transl)].

Yersinia infections in 8 adults are reported. 6 patients had erythema nodosum, in 2 cases associated with maculo-papular rashes. In one patient an erythema multiforme-like rash was observed, in another one a papulo-vesicular rash. All patients were females. Yersinia infection was demonstrated serologically, in 3 cases also bacteriologically.

Adult↗

Oral 8-methoxypsoralen photochemotherapy of psoriasis. The European PUVA study: a cooperative study among 18 European centres.

In a multicentre study in eighteen European cities 3175 patients were treated with photochemotherapy (PUVA) for severe psoriasis and data obtained during a period of 39 months were analysed. A response better than marked improvement was obtained in 88.8% of patients; twenty exposures and a total cumulative UVA dose of 96 J/cm2 were required for clearing, the duration of the clearing phase being 5.3 weeks. A comparison of the results of this study with those of a similar multicentre study in the United States on 1300 patients and using a different treatment protocol, revealed that while treatment results and the number of individual treatment sessions were similar the European protocol requires only half the time and less than half the total cumulative UVA dose for clearing of psoriasis. When patients in the European study who received continuous maintenance treatment were compared with patients who received no maintenance treatment the probability that a patient would remain in remission for a period of 80 weeks was the same, irrespective of whether patients received maintenance treatment or not. This study confirms the dramatic efficacy of PUVA in clearing psoriasis and contains two important messages for the reduction of possible long-term hazards of this treatment. Firstly, the total UVA energy requirements for clearing psoriasis strongly depend on the treatment schedule and can be kept low if an individual approach aimed at rapid clearing of psoriasis is used. Secondly, maintenance therapy may not significantly prevent recurrences for prolonged periods of time and may thus not be necessary in most patients.

Administration, Oral↗

IgA-associated inhibition of polymorphonuclear leukocyte chemotaxis in neutrophilic dermatoses.

The chemotactic activity of normal human polymorphonuclear leukocytes (PMNs) confronted with heat inactivated sera from patients with psoriasis as well as various chronic proliferative diseases was determined using modified Boyden chambers. By the addition of phorbol myristate acetate (PMA) at a concentration of 1 ng/ml the chemoattractant activities of the sera were greatly potentiated. However, the chemotactic migration of normal PMNs was strongly inhibited by sera from patients with long standing and wide spread psoriasis, pyoderma gangrenosum, severe acne conglobata, Sweet syndrome, and some patients with chronic arthritis following rheumatoid fever. In acute guttate psoriasis and atopic dermatitis increased migratory activities were seen. The inhibition of chemotaxis correlated with increased serum IgA levels as determined by radial immuno diffusion. Column chromatography (Sephacryl S-300) revealed serum fractions of strong inhibitory potency at a molecular weight near 200,000 Dalton. These inhibitory fractions were seen in patients with long standing neutrophil related diseases and could not be detected in normal control sera. It appears that inhibition of PMN chemotaxis is a secondary phenomenon and may play an autoregulatory role in PMN related inflammation.

Adolescent↗

[Neutrophil granulocyte chemotaxis and psoriasis].

The presence of polymorphonuclear neutrophils (PMN) is a constant feature of Psoriatic epidermis. The reasons for this migratory activity are not clear and may be related to the presence of chemotaxigens or chemoattractants (circulating immune complexes, complement split products, or arachidonic acid metabolites) in serum and/or epidermis. On the other hand, functional abnormalities of psoriatic PMN may play a significant role as well. PMN chemotaxis, e.g., against increased chemoattractants has been found to be significantly increased in psoriasis. On the basis of these findings it may be suggested, that potent chemotaxigens or chemoattractants together with hyperactive PMN by the liberation of lysosomal enzymes cause a self-augmented increase of chemotactic factors. Recent experiments using PMN and sera from patients with psoriasis appear to support this concept. Modulating influences of immunoglobulins, specifically immunoglobulin A have recently been discovered. In chronic stationary psoriasis chemotactic activity of PMN is strongly inhibited which appears to be due to increased levels of IgA. Further, in inflammatory dermatoses with predominantly neutrophils similar IgA-related chemotaxis depression has been found. This appears to be a newly found modulation of PMN-dependent inflammatory reactions in the skin.

Chemotactic Factors↗

[Proliferating trichilemmal tumor].

The proliferating trichilemmal tumor is a rare benign neoplasm of the outer roof sheath of the terminal hair follicle. It occurs almost exclusively in elderly women as a solitary tumor of the hairy scalp. In a woman 71 years of age a proliferating trichilemmal tumor developed during two years. A large cornu cutaneum of the parietal scalp was present. The clinical and histopathologic features can be mistaken for squamous cell carcinoma.

Aged↗