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Biomedical subjects

L Kowalzick

Publications and source records attributed to L Kowalzick.

At least 19 recordsLinked to original sources
PubMed1995

Cytokine-mediated effects of peripheral blood mononuclear cells from patients with atopic eczema on keratinocytes (HaCaT) in a new coculture system.

Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6, IL-8 and IFN-gamma synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultured. Lymphocytes from patients with AE showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernatants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes, significantly enhanced amounts of IL-6 and IL-8, compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in IFN gamma production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-gamma in normal donors and in patients with AE. Interestingly, HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-gamma. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernatants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6, IL-8 and IFN-gamma; (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyte inhibitory soluble factors and IL-6, IL-8 as well as IFN-gamma; and (iii) secretion and/or activity of keratinocyte-derived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.

Antibodies, Monoclonal↗
PubMed1995

Elevated serum levels of soluble adhesion molecules ICAM-1 and ELAM-1 in patients with severe atopic eczema and influence of UVA1 treatment.

BACKGROUND: ICAM-1 is known to be strongly expressed on keratinocytes in lesional atopic eczema correlating with the degree of inflammation. ELAM-1 was found to be expressed on dermal vascular endothelium in lesional atopic eczematous skin. OBJECTIVE: The present study was performed to investigate whether elevated serum levels of soluble forms of these molecules are detectable in patients with severe atopic eczema and whether these parameters could be useful markers for disease activity. METHODS: Serum levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1) were measured by ELISA in 18 patients with severe atopic eczema before and after UVA1 therapy. RESULTS: Before onset of treatment, serum sICAM-1 (565 +/- 99 ng/ml) and sELAM-1 (89.7 +/- 29.9 ng/ml) levels were significantly (p < 0.001) elevated compared to 22 healthy control persons (296 +/- 46 and 48.8 +/- 22.7 ng/ml). After achievement of significant clinical improvement after 3 weeks of UVA1 therapy, there was neither a decrease in serum sICAM-1 nor in sELAM-1 levels. The posttherapeutic serum sICAM-1 and sELAM-1 values remained elevated (p < 0.001) above the normal range. CONCLUSION: Based on these data we suggest that (1) serum sICAM-1 and sELAM-1 are elevated in patients with severe atopic eczema, (2) sICAM-1 does not decrease together with reduction of ICAM-1-positive keratinocytes in atopic eczema following clinical improvement and might therefore be mainly of a different origin, i.e. leukocytes/endothelial cells, and that (3) sICAM-1 and sELAM-1 seem not to be suitable markers of actual disease activity in severe atopic eczema.

Adult↗
PubMed1995

Low dose versus medium dose UV-A1 treatment in severe atopic eczema.

Twenty-two patients with severe atopic eczema were included in a therapy study with UV-A1 (wavelengths > 340 nm) treatment. The patients were divided into two dose groups, each consisting of 11 patients. One group received 10 J/cm2 and the other 50 J/cm2 five times a week for 3 consecutive weeks. No topical or systemical steroids or antihistamines were allowed. Using the SCORAD index as a measure of disease activity before onset of therapy and after 10 and 15 treatments, we observed a significant improvement in both dose groups after 15 treatments (10 J/cm2: p < 0.05, 50 J/cm2: p < 0.005). After 10 treatments only the improvement in the 50 J/cm2 group was significant (p < 0.005); the difference between the two dose groups was significant (p < 0.05). The clinical efficacy of treatment was reflected neither by a decrease of serum IgE nor by a decrease of elevated serum levels of soluble adhesion molecules sICAM-1 and sELAM-1 in the two dose groups. In contrast, a marked but not significant decrease of serum ECP could be observed in the 50 J/cm2 group only. We conclude from these and other published data that although 10 J/cm2 UV-A1 has a limited effect on patients with severe atopic eczema, higher doses are of higher efficiency in the treatment of this condition.

Adult↗
PubMed1993

[Human papillomaviruses. Associated diseases of the breast].

In human papillomavirus-associated acanthomas of the mamilla it was possible to detect DNA of HPV types 41, 6ma and a type related to type 16. The biology of HPV infection resembles that of anogenital lesions. Some of the HPV types found are rare or are thought possibly to have oncogenic potency. Possible evidence for link between HPV and carcinomas of the breast is discussed.

Adolescent↗
PubMed1993

[Chronic mucocutaneous herpes simplex infection. Occurrence within the scope of liver-induced immunodeficiency].

Herpes simplex virus (HSV) infections causing severe disease are reported frequently in patients suffering from human immunodeficiency virus (HIV) infection. This disease pattern may also be seen in an immunocompromised disease state with other causes, however, as in the case presented in this paper. An 84-year-old woman had hepatic cirrhosis resulting from chronic hepatitis C virus infection. The woman developed ulcerative lesions in and around her mouth and in the genito-anal region, and these persisted for some months. Diagnosis of HSV infection was not obtained until after extensive laboratory investigations. Aciclovir infusion therapy started immediately afterwards led to dramatic improvement of the skin and mucous membrane changes. Complete clearing of lesions was not obtained, however, because the patient died as a result of the immunosuppression.

Acyclovir↗
PubMed1992

[Bowenoid actinic keratosis: therapy with intralesional injection of recombinant beta-interferon].

Biopsy-proven bowenoid actinic keratosis located in the pretibial region in each of two elderly women (61 and 81 years) were treated with intralesional injections with a new recombinant beta-interferon. The treatment took the form of intralesional injections three times a week over 3 consecutive weeks. The dose per single injection was 1.5 or 1.0 MU interferon, respectively. Clinical and histological examinations showed a complete response in both patients. Controls up to 18 months showed no relapse. There were no flu-like side-effects. Leukocyte counts decreased by 2700 and 500 cells per microliter during therapy.

Aged↗
PubMed1991

[Association of arteriovenous and cavernous angioma of the head and neck area].

A 20-year-old man complained of pulse-synchronous noise in the ear and recurrent bleedings in the nose and throat region. From birth he had had an extensive haemangioma, black-blue with dark-red parts. It had been diagnosed as a cavernous haemangioma, part of a Sturge-Weber syndrome. An angiogram was performed before intended dermatological treatment of the disfiguring venous angioma. It demonstrated the capillary venous angioma (slow-flow angioma) in the lateral triangle of the neck, extending up to the skull base. In addition there was an arteriovenous angioma (high flow angioma) in the region of the clivus, which was supplied bilaterally largely by the ascending pharyngeal artery. The arteriovenous angioma also had connections to the outflow area of the capillary venous angioma. These findings and absence of ocular changes excluded Sturge-Weber syndrome. Because of the risk of life-threatening bleedings, the arteriovenous malformation was superselectively embolized by multiple injections of nonresorbable polyvinyl-alcohol particles via a microcatheter. This brought about the collapse of the cutaneous angiomatous spaces. This case demonstrates that external appearance indicating a capillary venous angioma is not reliable. Before treatment of this malformation a neuroradiological diagnosis should be undertaken.

Adult↗
PubMed1991

Successful treatment of primary progressive follicular mucinosis with interferons.

Follicular mucinosis is a primary idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective standard therapy for the benign group is unknown. We describe a patient with primary benign disseminated progressive follicular mucinosis who was successfully treated with recombinant interferon alfa-2b and interferon-gamma. Interferons might act by down-regulation of activated inflammatory cells and/or by induction of enhanced elimination of extracellular mucin via increasing phagocytosis by macrophages.

Adult↗
PubMed1991

Acute febrile neutrophilic dermatosis (Sweet's syndrome) caused by minocycline.

Sweet's syndrome (acute febrile neutrophilic dermatosis) occurred in a 29-year-old woman with acne. Although Sweet's syndrome initially seemed to be triggered by an acute acne flare, minocycline could later be identified as the causal agent. Because this could be confirmed in an oral provocation test, this seems to be the first case of a true connection between Sweet's syndrome and its induction by a drug, namely minocycline.

Acne Vulgaris↗
PubMed1990

Systemic therapy of advanced metastatic malignant melanoma with a combination of fibroblast interferon-beta and recombinant interferon-gamma.

Eighteen patients with advanced metastatic malignant melanoma (stage IVUICC 1987) were entered into a prospective trial with a combination of systemic fibroblast interferon-beta and recombinant interferon-gamma. Treatment was performed over a 6-week period with 3 x 5 x 10(6) U i.v. interferon-beta and 5 X 100 micrograms s.c. interferon-gamma every week. Under this therapy 16 patients showed a progressive disease, and 2 patients had a stable disease. The median time of survival was 7.5 months. Successive immunological examinations showed no significant immunomodulating effect after the 6 weeks of interferon treatment. We conclude that the combination of interferon-beta and -gamma is insufficient in the treatment of advanced metastatic malignant melanoma when administered by this dose, route and schedule.

Adult↗
PubMed1989

[Immunomodulation by cryosurgery in malignant melanoma].

Cryosurgery is a well-known, established method for the local destruction of tumor tissue by freezing. The assumption that, in addition to a physical and blood vascular phase, an immunological phase exists, has been discussed by many authors and tested using animal models. These results can only be transferred to humans in a limited sense. During the last year, we initiated a randomized study "Cryosurgery versus Conventional Surgery", whereby the peripheral blood and the normal skin from the areas surrounding the resection were compared. We were able to demonstrate in the peripheral blood of 8 cryosurgery patients a postoperative increase in the total and helper T-cells, HLA-DR-positive cells, and the ratio helper/suppressor T-cells in comparison to preoperative values. In the 8 patients treated with conventional surgery, these parameters decreased slightly or remained the same. The differences were highly significant (p = 0.001) to significant (p = 0.01). The results from the first 16 are patients studied presented and discussed here.

Adult↗
PubMed1986

Failure of etretinate in epidermodysplasia verruciformis.

In a patient suffering from benign lesions of epidermodysplasia verruciformis due to human papillomavirus type 5 little clinical improvement could be observed after 6 months of oral etretinate. The drug was given 75 mg/day for 1 month before dosage was reduced to 50 mg/day. Control biopsy after 3 months of treatment still revealed large quantities of virions and typical cytopathic effects in light and electron microscopic examination.

Adult↗
PubMed1984

Differential substrate specificity of DNA polymerase beta and of a DNA polymerase induced by herpes simplex virus type 2 towards thymidine triphosphate analogues.

Several triphosphates of 5-substituted deoxyuridine (dU), such as 5-ethyl-, 5-n-propyl-, 5-n-hexyl- and 5-isopropyldeoxyuridine triphosphates and 5-trifluorothymidine triphosphate are substrates for HeLa cell DNA polymerase beta (2'-deoxynucleoside-5'-triphosphate:DNA-deoxynucleotidyltransferase, EC 2.7.7.7) and for a DNA polymerase isolated from HeLa cells infected with herpes simplex virus type 2 (HSV-2) strain 75. At the concentration tested (50 microM), all these analogues were incorporated more readily into DNA by the virus-coded enzyme than by DNA polymerase beta from the host cell. The DNA polymerase coded by HSV-2 showed an affinity for deoxythymidine triphosphate (dTTP) and the analogues studied higher than that of DNA polymerase beta. Analogues are preferential substrates for the viral enzyme, since they readily substitute for dTTP during synthesis in vitro. In contrast, arabinosylthymine-5'-triphosphate was readily incorporated into DNA by the host cell DNA polymerase beta, but inhibited the DNA polymerase specified by HSV-2.

DNA Polymerase I↗
PubMed1982

Differential incorporation of thymidylate analogues into DNA by DNA polymerase alpha and by DNA polymerases specified by two herpes simplex viruses.

Several triphosphates (TP) of 5-substituted deoxyuridine (dU), like 5-ethyl (Et), 5-n-propyl (n-Pr), 5-iso-propyl (iso-Pr), 5-n-hexyl (n-Hx), and 5-trifluorothymidine (F3-dT) were used as substrates for HeLa DNA polymerase alpha and for two herpes simplex virus (HSV)-coded DNA polymerases isolated from HeLa cells infected with HSV-1, strain C42 (wild-type), or its mutant resistant to phosphonoformate (PFAr). All polymerases were purified up to the DNA-cellulose column step and they showed comparable specific activities. The incorporation into DNA studied with all the alkyl analogues of dUTP is several times higher with the virus enzymes than with DNA polymerase alpha. The DNA polymerase of the mutant virus incorporates dUTP analogues to a lower extent than the wild-type polymerase. The two virus enzymes also differ in the Km and Vmax values for different substrates, indicating that the mutation to PFAr has affected the structure of the virus DNA polymerase. Surprisingly, all three enzymes use F3-dTTP as substrate for DNA synthesis to an equal but limited extent.

DNA↗