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B Czarnetzki

Publications and source records attributed to B Czarnetzki.

14 recordsLinked to original sources
PubMed1996

Differential expression of CRABP II, psoriasin and cytokeratin 1 mRNA in human skin diseases.

In order to confirm and further explore the significance of the overexpression of the CRABP II (cellular retinoic acid binding protein type II) and psoriasin genes in psoriatic versus normal skin, we examined the mRNA expression levels of these two genes by in situ hybridization in skin samples from psoriatic plaques and in one case from the border between a psoriatic plaque and uninvolved skin. Both genes were markedly upregulated in lesional skin, with a shift from low to high expression in the transitional zone of the plaque. Expression of the cytokeratin 1 (K1) gene was, in contrast, high in normal skin and decreased in the transition from uninvolved skin to psoriatic plaque, Examination of mRNA levels of CRABP II and psoriasin in other hyperproliferative and inflammatory skin diseases showed high expression of psoriasin, and in some cases also of CRABP II, in atopic dermatitis, mycosis fungoides, Darier's disease and inflammatory lichen sclerosus et atrophicus. In atrophic lesions of lichen sclerosus et atrophicus that lacked an inflammatory infiltrate, these changes were only weakly expressed. These findings demonstrate that altered epidermal gene expression of K1, psoriasin and CRABP II is not disease-specific and may reflect instead an altered state of epidermal differentiation and/or may be linked to the inflammation and cellular infiltration common to all the conditions studied.

Biopsy↗
PubMed1994

Inhibition of IgE- and non-IgE-mediated histamine release from human basophil leukocytes in vitro by a histamine H1-antagonist, desethoxycarbonyl-loratadine.

Loratadine, a new nonsedating histamine H1-antagonist, has been shown to inhibit immunologic release of inflammatory mediators in addition to its H1-receptor blocking properties. After oral administration, the agent is metabolized primarily to desethoxycarbonyl-loratadine (DCL). The basic piperidine, DCL, is readily soluble in water, whereas the nonbasic urethane, loratadine, is insufficiently soluble in water for some in vitro investigations. Therefore we used the metabolite, DCL, to study its influence on in vitro leukocyte histamine release (LHR) in 24 allergic and 22 nonallergic subjects. IgE-mediated and calcium ionophore A23187-induced LHR were inhibited by DCL in a dose-dependent fashion (values of drug concentration to induce 30% inhibition after stimulation with inhalant antigen, anti-IgE, concanavalin A, and calcium ionophore A23187 were 6, 8, 5, and 11 mumol/L, respectively). Higher concentrations of DCL caused mediator release in all subjects (n = 45, 30 mumol/L DC: 11% +/- 2% LHR, 100 mumol/L DCL: 35% +/- 1% LHR), abolishing any inhibitory effect of the drug. Rapid onset of inhibition by 10 mumol/L DCL was found in kinetic studies (n = 10). The inhibition of anti-IgE-induced histamine secretion was synergistically increased by simultaneous preincubation of DCL with the potent histamine H2-agonist, FRA-19. Additional data indicate that the inhibition of LHR by DCL might involve biochemical events that occur after cellular Ca++ influx because LHR induced by N-formyl-methionyl-leucyl-phenylalanine or the phorbol ester, 12-O-tetradecanoyl phorbol-12-acetate, was not significantly affected by DCL.

Basophils↗
PubMed1993

Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: diagnostic and histogenetic relevance of MS-1 high molecular weight protein expression.

Twenty-nine cases of Langerhans cell histiocytosis (LCH), non-Langerhans cell histiocytoses (N-LCH), non-infectious granulomas, and fibroblast-related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N-LCH syndromes. MS-1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N-LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS-1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N-LCH cells. MS-1-positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS-1-positive N-LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS-1-positive cell types was indicated by the fact that N-LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast-related lesions; in cellular dermatofibromas, CD34 and MS-1 expression partially overlapped. The other antigens tested showed non-specific or overlapping patterns of expression. In conclusion, assessment of MS-1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N-LCH from related skin disorders, and it may indicate a common differentiative pathway for most N-LCH disease entities.

Antibodies, Monoclonal↗
PubMed1990

Comparison of eicosanoid generation by highly purified human Langerhans cells and keratinocytes.

The present study was conducted to investigate the eicosanoid metabolism of highly enriched human Langerhans cells and keratinocytes. Arachidonic acid (100 microM) was added to the cells which were then stimulated with 1 microM calcium ionophore A 23187 for 10 and 30 min. The supernatants were examined for cyclooxygenase and lipoxygenase products using different chromatographic systems and radioimmunoassays. Compounds were identified by comparison with authentic standards. The major cyclooxygenase product of both cell types was prostaglandin D2, with minor amounts of prostaglandin E2. The main products of the lipoxygenase pathway were 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE, and their corresponding hydroperoxy derivatives, with small amounts of leukotrienes B4 and C4. The major differences in the metabolism of the two cell types were related to faster kinetics of generation of the mediators and a more complete conversion of arachidonic acid by the LC. Because eicosanoids have been implicated to be potent mediators of inflammation and immunomodulators, the present data underline the potential contributory role of epidermal cells to eicosanoid-associated pathologic processes.

Arachidonic Acid↗
PubMed1988

Combination of cisplatin, vindesine, and dacarbazine in advanced malignant melanoma. A Phase II Study of the EORTC Malignant Melanoma Cooperative Group.

A Phase II study combining cisplatin, vindesine, and dacarbazine was performed on patients with disseminated malignant melanoma by the European Organization for Research and Treatment of Cancer (EORTC) Malignant Melanoma Cooperative Group (MMCG). The treatment consisted of intravenous administrations of dacarbazine 450 mg/m2, vindesine 3 mg/m2, and cisplatin 50 mg/m2 on day 1 and 8 of each course. Courses were repeated every 4 weeks. Treatment was discontinued in case of progression after two courses, otherwise continued until progression or for a minimum of six courses. One hundred five patients entered the trial with 92 patients being evaluable. The response rate calculated after clearance by the Extramural Review Committee shows four complete and 18 partial responses, i.e., 24%, with a median remission duration of 23 weeks. Toxicity and subjective tolerance to this regimen were moderate, requiring 140 modifications of 642 administrations (22%). Main toxicities were nausea and vomiting (95%), leucopenia (70%), alopecia (56%), peripheral neuropathy (32%), and nephrotoxicity (17%). The discussion emphasizes some particular points of interest in the management of advanced malignant melanoma.

Actuarial Analysis↗
PubMed1983

In vitro studies to prove the effect of sera of eosinophilia in colony formation.

Serum samples from four patients with reactive eosinophilia and two patients with eosinophilic leukaemia were compared with normal sera with respect to formation of eosinophil colonies after addition of the sera to mononuclear cells from peripheral blood of healthy subjects. Supernatants from ConA stimulated guinea-pig spleen cells and human lymphocytes were tested in a similar way. Grown colonies were placed on glass slides and after staining with luxol fast blue the percentage of eosinophils was counted. The serum samples of the patients with reactive eosinophilia produced the greatest number of eosinophil colonies while supernatants of spleen and lymphocytes produced the greatest number of eosinophilic granulocytes. Our findings suggest the existence of a factor stimulating eosinophil colonies in the tested serum fractions. Beyond that an indication is given for a substance in the supernatants of spleen and lymphocyte suspensions which stimulates more intensively the maturing into eosinophilic granulocytes than the formation of colonies.

Colony-Stimulating Factors↗
PubMed1983

Increased monocyte chemotaxis towards leukotriene B4 and platelet activating factor in patients with inflammatory dermatoses.

In vitro monocyte chemotaxis towards leukotriene B4(LTB4) and platelet activating factor (PAF) was studied with cells from 51 patients with various inflammatory dermatoses and 12 normal volunteers. Monocytes from normal subjects responded poorly to LTB4 (10(-8)-10(-12) M) and PAF (10(-6)-10(-10) M), and cells from patients with urticaria pigmentosa and vericella were even less responsive, while monocytes from patients with severe psoriasis and atopic eczema exhibited markedly enhanced chemotaxis. These changes persisted during high dose therapy with oral steroids, but returned to normal with healing of the skin lesions. Pre-incubation of monocytes with histamine, LTB4, PAF, lymphokines or sera from patients and normal controls did not result in enhanced chemotaxis of the cells. The chemotactic activity of monocytes did not correlate with that of neutrophils in the same patients (r = 0.08). Altered monocyte chemotaxis in patients with inflammatory dermatoses is therefore a reversible process that is related to the severity of the cutaneous inflammation but is not limited to a specific disease.

Adolescent↗
PubMed1982

A rapid method for functional determination of C1 esterase inhibitor in plasma.

A functional determination of C1 esterase inhibitor (C1 INH) can be easily performed with an amidolytic assay by monitoring the inactivation of plasma kallikrein. In patients with urticaria as well as in healthy donors kallikrein inactivation, determined as the ratio of kallikrein activity at t60/t15, was found to be 0.47 +/- 0.06; in patients with hereditary angioneurotic edema (HANE). However, it amounted to 0.80 +/- 0.06. There was a good correlation between the inactivation rate of kallikrein and the protein levels of C1 INH (r = -0.93, p less than 0.001). In patients with HANE, levels of plasma kallikrein were slightly decreased (mean = 0.37 +/- 0.11 U/ml, normal mean = 0.47 +/- 0.09 U/ml), but still sufficient for monitoring kallikrein inactivation. In the case of one patient with functionally inactive C1 INH protein, the inactivation of kallikrein was impaired as in the conventional form of the disease.

Angioedema↗
PubMed1982

Cisplatin and vindesine combination chemotherapy in advanced malignant melanoma: an EORTC phase II study.

Sixty-one evaluable patients with measurable advanced malignant melanoma received 4-week courses of a combination of cisplatin 100 mg/m2 as a 24-hr i.v. infusion on day 1 and vindesine 3 mg/m2 as an i.v. bolus on days 1, 8, 15 for two courses and every other week thereafter. Two patients achieved complete response for 46 and 81+ weeks respectively, eleven patients achieved partial response for a median of 17 weeks (range 8-26) and three patients had no change for 24 weeks or more. The overall response rate of 21% did not seem to be affected by prior chemotherapy or site of indicator lesions, soft tissue vs visceral. Myelosuppression, consisting essentially of leucopenia, required dose schedule modifications in 41% of the first two courses and 12% of the remaining courses, but never produced major complications. Non-hematologic toxic effects were prominent, especially nausea and vomiting, which were universal. Alopecia was seen in 71% of the patients, neuromuscular manifestations in 39%, diarrhea in 30%, renal impairment in 25%, mucositis in 12%, ototoxicity in 7% and phlebitis in 3%. These results do not suggest striking additive or synergistic antitumor activity of cisplatin and vindesine in advanced malignant melanoma, at least with the method of drug administration selected for this trial.

Adult↗
PubMedDate not supplied

A case of chronic meningococcemia with unusual features.

A patient with chronic meningococcemia with the unusual features of subungual splinter hemorrhages, a pericardial friction rub, and a culture positive skin lesion is presented. Group specific and homologous antibody responses were absent and the nitroblue tetrazolium test for infection was negative. The clinical features and the difficulty in explaining the mechanism of the relatively benign course that characterizes this disease are discussed.

Adult↗