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Biomedical subjects

U Mrowietz

Publications and source records attributed to U Mrowietz.

At least 19 recordsLinked to original sources
PubMed1992

Cyclosporine in psoriasis: a multicenter dose-finding study in severe plaque psoriasis. The German Multicenter Study.

Interim results of a randomized, controlled, dose-finding study conducted in 24 dermatology centers on 217 patients with severe chronic plaque psoriasis (entry psoriasis area and severity index of at least 15) are presented. Patients were first treated with cyclosporine either 1.25 or 2.5 mg/kg/day (Sandimmune); in case of inadequate response the dosage was increased to a maximum of 5 mg/kg/day. Cyclosporine was given for 12 to 36 weeks. Treatment was classified as "successful" if the psoriasis area and severity index was reduced to 25% or less of the baseline value or below 8. At the end of the treatment period 18% of patients had improved their psoriasis area and severity index "successfully" with the initial dose of 1.25 mg/kg/day. "Successful" improvement with the initial dose of 2.5 mg/kg/day was achieved in 56% of the cases. In the 1.25 mg group, 44 patients had to increase their dose to 2.5 mg/kg/day and 31 patients to 5 mg/kg/day. In 29 patients whose dosages were started at 2.5 mg/kg/day the dosage was subsequently increased to 5 mg/kg/day. Although 1.25 mg/kg/day proved to be effective in some cases, 2.5 mg/kg/day of cyclosporine is the optimal starting dose. Adverse events were observed in 10% of the patients taking 1.25 mg/kg/day, in 20% taking 2.5 mg/kg/day, and in 32% taking 5 mg/kg/day. The most common were gastrointestinal complaints, followed by the common cold and other viral infections. An increase of serum creatinine level above 130 mumols/L occurred in five patients who could continue therapy after reducing the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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

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↗
PubMed1991

Neutrophil-activating peptide 1/interleukin 8 mRNA expression and protein secretion by human monocytes: effect of cyclosporin A.

Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, a chronic hyperproliferative and inflammatory skin disorder, PMN and T cells are found as prominent cells in the inflammatory infiltrate of the lesions; however, monocytes were shown to be the first cells invading a newly formed plaque. NAP-1/IL-8 was found to be present in high amounts in the skin and in scale material of psoriatic patients. Psoriasis responds well to systemic treatment with cyclosporin A (CsA), an immunosuppressive peptide. Therefore, we addressed the question of whether the clinical improvement of psoriatic patients during CsA therapy may be due to an inhibition of NAP-1/IL-8 production and secretion from monocytes. Purified human monocytes were stimulated by lipopolysaccharide in the presence or absence of various concentrations of CsA. Production of NAP-1/IL-8 was determined as expression of specific mRNA by fluorescent in situ hybridization. Secreted peptide was measured by bioassay (PMN chemotaxis) and enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies. The results show that CsA neither inhibited mRNA expression for NAP-1/IL-8 nor secretion of the peptide. These findings support the hypothesis that the pharmacological effect of CsA may be restricted to the inhibition of T-cell activation and proliferation.

Cyclosporins↗
PubMed1991

Selective inactivation of human neutrophil elastase by synthetic tannin.

Tannins of natural or synthetic origin are well-known adjuvants in topical anti-inflammatory therapy of skin diseases. In this study, the influence of synthetic tannin on neutrophil accumulation, enzyme release, and on the proinflammatory activity of neutrophil-derived enzymes was investigated. The results show that synthetic tannin (Tamol) specifically inhibits the neutrophil serine protease human leukocyte elastase (HLE) in an irreversible manner with a half-maximal inhibitory concentration (IC50) of 0.3 microgram/ml. Exogenous protein partially abolished the tannin-dependent HLE inhibition (IC50 of Tamol at 1% protein-concentration:1.0 microgram/ml). Synthetic tannin did not influence the activities of other neutrophil enzymes like Cathepsin G, beta-glucuronidase, and myeloperoxidase. The specificity of Tamol for HLE was further substantiated by the lack of inhibition of other serine proteases. Additionally, Tamol had no effect on f-met-leu-phe-induced neutrophil chemotaxis and did not alter enzyme degranulation of neutrophils in response to f-met-leu-phe and opsonized zymosan. We conclude from our results that the anti-inflammatory properties of synthetic tannin may at least in part be due to inactivation of the proinflammatory protease HLE.

Cell Degranulation↗
PubMed1989

Recombinant human tumour necrosis factor beta (lymphotoxin) lacks chemotactic activity for human peripheral blood neutrophils, monocytes, and T cells.

Human recombinant tumour necrosis factor beta (rhuTNF beta)/lymphotoxin was tested for human neutrophil granulocyte (PMN), monocytes (MO), and T-cell chemotactic activity by means of a modified Boyden chamber system. Over a wide range of concentrations (10(-7)-10(-14)M)rhuTNF beta showed no chemotactic activity for PMN, MO, or T cells. In contrast, strong chemotactic migration was elicited in PMN and MO with the tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and in T cells when complement split product C5a and leukotriene B4 (LTB4) were used as chemotaxins. The results of this study indicate that rhuTNF beta/lymphotoxin is not a chemotaxin for human PMN, MO, or T lymphocytes in vitro.

Chemotactic Factors↗
PubMed1989

Identification of two endogenous neutrophil-activating peptides in psoriatic skin and inflammatory cells: C5ades arg and NAP.

Migration of polymorphonuclear leukocytes (PMN) into the upper layers of involved epidermis represents a characteristic feature of psoriasis. By analysis of psoriatic scale material we were able to identify two potent proinflammatory peptides, which are present in the upper epidermis from psoriatic lesions. Both factors (C5ades arg and NAP) show strong chemotactic activity for human neutrophils in vitro as well as in vivo. Whereas C5ades arg is a known mediator activated by either alternative or classical activation of the complement cascade, NAP represents a newly detected peptide with a molecular weight of 8,000 daltons which is produced by a variety of cells participating in the psoriatic tissue reaction.

Cell Movement↗
PubMed1988

Recombinant human tumor necrosis factor alpha lacks chemotactic activity for human peripheral blood neutrophils and monocytes.

Preparations of recombinant human tumor necrosis factor alpha (rhuTNF alpha) free of aminoterminal methionine were tested for human neutrophil granulocyte (PMN) and monocyte (MO) chemotactic activity using the Boyden chamber system. Over a wide range of concentrations (10(-7)-10(-15) M) rhuTNF alpha of two different sources failed to elicit chemotactic responses in PMN or MO, whereas strong PMN and MO chemotactic activity could be detected using the tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, rhuTNF alpha containing 62% aminoterminal methionine failed to induce PMN and MO chemotaxis. It is concluded that rhuTNF alpha may not be a chemotaxin for human PMN and MO in vitro.

Chemotaxis, Leukocyte↗
PubMed1988

Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity.

A novel neutrophil-activating peptide is detected in supernatants from mitogen-stimulated human T lymphocyte preparations. This chemotaxin was purified to apparent homogeneity by sequential Gel G-75 permeation chromatography, wide pore reversed phase (RP-8) HPLC, size exclusion HPLC, and reversed phase (RP-18) HPLC. Additional characterization of this lymphocyte-derived neutrophil-activating peptide (LYNAP) resulted in a single peak upon reversed phase HPLC and size exclusion HPLC. SDS-PAGE under nonreducing conditions revealed a single line at 10 kDa. LYNAP stimulated neutrophil chemotaxis (ED50 of 3 +/- 3 ng/ml), chemokinesis (ED50 of 2 +/- 2 ng/ml), and caused degranulation of cytochalasin B pretreated human neutrophils (ED50 of 20 ng/ml). In purified human monocytes, chemotactic responses to LYNAP at doses up to 100 ng/ml were absent, indicating nonidentity with a lymphocyte-derived monocyte chemotactic factor previously described by other workers. LYNAP shows biochemical and biologic similarities to a recently detected monocyte-derived neutrophil-activating peptide (MONAP). Moreover, desensitization experiments revealed cross-deactivation between LYNAP and MONAP, not, however, between these two chemotactic peptides and other well characterized polymorphonuclear leukocyte chemotaxins, e.g., C5a, FMLP, leukotriene B4, or platelet-activating factor. This finding points toward structure identity or homology of both chemotaxins, MONAP and LYNAP.

Chemical Phenomena↗
PubMed1988

Identification of different charged species of a human monocyte derived neutrophil activating peptide (MONAP).

Lipopolysaccharide-stimulated human monocytes secrete a 10 kD peptide (MONAP) of high neutrophil, not however monocyte or eosinophil stimulating activity. By reversed phase HPLC MONAP could be distinguished from Interleukin 1. Analytic isoelecto-focusing of pure MONAP (single line upon sodiumdodecylsulfate polyacrylamide gel electrophoresis, single peak after RP-18-HPLC), obtained by size exclusion HPLC followed by two different reversed phase HPLC steps revealed charge heterogeneity giving major components with isoelectric points at 4.7, 4.9, 6.4 and 6.9, all of which exhibited chemotactic activity.

Chromatography, High Pressure Liquid↗
PubMed1988

Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP).

Phytohemagglutinin or Concanavalin A-stimulated human T-lymphocytes produce a factor (LYNAP) with potent chemotactic and enzyme degranulating activity in peripheral human neutrophils. Sequence analysis of LYNAP established an apparently novel 72 residue polypeptide structure. Examination of protein data bases showed that LYNAP had about 30% sequence homology with recently characterised connective tissue activating proteins produced by platelets. Furthermore, it was subsequently found that the amino acid sequence is largely the same as that predicted from a cDNA clone derived from mRNA elevated in peripheral human leukocytes stimulated by mitogens.

Amino Acid Sequence↗
PubMed1988

Atopic dermatitis: influence of bacterial infections on human monocyte and neutrophil granulocyte functional activities.

In 15 patients with atopic dermatitis (AD) and without concomitant viral or bacterial infections, chemotaxis, superoxide-anion (O2-) generation, and beta-glucuronidase release of purified monocytes (MO) and neutrophils (PMN) were determined. Defined receptor-dependent stimulators (i.e., N-formyl-methionyl-leucyl-phenylalanine, C5a, and leukotriene B4, as well as native and opsonized zymosan particles) were used for phagocyte stimulation. PMN functional activities in response to the stimuli tested were found to be normal in patients with AD and without infections. MO from these patients revealed a slight enhancement of O2- production after stimulation with opsonized zymosan and a small increase of N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis. Other MO functions tested were within the normal range. However, investigations of MO and PMN functions during the course of concomitant bacterial infections of three patients with AD demonstrated striking alterations of cellular responsiveness. These changes ranged from enhanced to decreased phagocyte functions, depending on the activity of the infectious disorder. Chemotaxis of PMN and MO was depressed around the third day after onset of the infectious disease. In the beginning of infection, there was a decreased O2- generation and beta-glucuronidase release in PMNs. In MOs, both parameters were enhanced. The results of these investigations provide evidence that functional abnormalities of phagocytes observed in patients with AD are sequelae of concomitant skin infections and not signs of an intrinsic defect present in MOs and PMNs.

Adolescent↗
PubMed1988

Modulation of human monocyte functions during acute bacterial infection.

The in vitro functions of highly purified blood monocytes were studied in 11 patients suffering from acute bacterial infections (e.g. erysipelas, appendicitis, abscesses). Chemotaxis, superoxide-anion generation, and beta-glucuronidase release of the patients' monocytes in response to the receptor-dependent stimuli formyl-methionyl-leucyl-phenylalanine (FMLP), complement split product C5a, leukotriene B4 (LTB4), and opsonized zymosan particles were measured. All the patients were examined in a follow-up study during the course of illness. A group of 33 healthy volunteers served as control. The patients revealed a transient decrease in monocyte chemotactic migration in response to all stimuli between days 3 and 5 after onset of clinical symptoms. Superoxide-anion generation from patients' monocytes was found to be enhanced 3 days after impaired chemotaxis. Stimulated release of lysosomal beta-glucuronidase showed a decrease in the first days of the disease. However, spontaneous beta-glucuronidase release was enhanced between days 3 and 7 in the patients' monocytes. Serial measurements of monocyte responsiveness. These results indicate a distinct modulation of monocyte functions during the course of an acute bacterial infection. Changes in monocyte maturity and/or activation under inflammatory conditions may be responsible for these alterations in monocyte function.

Acute Disease↗