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Biomedical subjects

B M Henz

Publications and source records attributed to B M Henz.

144 records · Page 8Linked to original sources
PubMed1996

Dermal and bronchial hyperreactivity in urticarial dermographism and urticaria factitia.

For investigation of a possible relationship between cutaneous and bronchial hyperreactivity, 74 subjects were grouped according to the presence (n = 33) or absence (n = 41) of urticarial dermographism after application of a standardized shearing pressure with a dermographometer (12.7 x 10(5) Pa). the two groups did not differ in age, sex, smoking habits, presence of urticaria and atopy, or serum IgE levels. Erythema of the dermographic test sites was always significantly greater (P < 0.001) in the group with urticarial dermographism at 2, 4, and 8 min, and cutaneous reactivity with titrated prick tests was significantly increased in this group with low concentrations of histamine, 0.01% and substance P (0.25 mM) (P < 0.05). After bronchial provocation with acetylcholine, 51 of the 74 subjects, 25 with and 26 without urticarial dermographism, exhibited bronchial hyperreactivity. However, significantly more subjects with urticarial dermographism had an increase in airway resistance and a decrease in specific airway conductance (P < 0.05). In the subgroup (n = 9) of subjects with symptomatic urticarial dermographism (urticaria factitia), these differences were even more significant (P < 0.001). These subjects also had larger skin test reactions and significantly higher IgE levels (P < 0.01). Thus, the present data show an association, which may be based on common mechanisms of allergic inflammation, between cutaneous and bronchial hyperreactivity.

Adult↗
PubMed1996

Absence of MHC class II antigen on mast cells at sites of inflammation in human skin.

Since the presence of major histocompatibility complex (MHC) antigens has recently been reported on murine and human mast cells under various conditions, we have investigated their expression on mast cells in different types of cutaneous inflammation. Cryostat sections from lesional biopsies of patients with psoriasis, atopic eczema, chronic urticaria, lichen planus, bullous pemphigoid and urticaria pigmentosa were immunohistochemically stained with monoclonal antibodies against MHC class I and class II antigens using a double staining APAAP/toluidine blue methodology. While strongly positive staining with the antibody directed against MHC class I antigens was found on nearly all mast cells in normal skin and in inflammatory dermatoses, reactivity for HLA-DR and HLA-DQ antigens on mast cells could not be detected, except for less than 2% of cells with doubtful staining. Human mast cells therefore probably play no significant rôle as antigen-presenting cells in the conditions studied.

Antibodies, Monoclonal↗
PubMed1996

Modulation of in vitro cytokine release from human leukemic mast cells (HMC-1) by glucocorticoids.

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (10(-5) M-10(-9) M), on the IL-1 beta, IL-3, IL-8, and tumor necrosis factor alpha secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 x 10(-7) M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.

Administration, Topical↗
PubMed1996

Prognostic value of tuberculin and BCG immunoreactivity in stage I high-risk malignant melanoma (EORTC protocol 18781).

BACKGROUND: Since the immune system is considered to be a major determinant in the outcome of malignant melanoma, vaccination with BCG (bacillus Calmette-Guérin) or more recently with interleukins is used in this condition, although the effects of this immunotherapy are unclear. OBJECTIVE: The present study was to elucidate clinical aspects and the prognostic relevance of the cellular and humoral immune responses of melanoma patients treated with two different BCG vaccines. METHODS: A subgroup of patients from a multicenter adjuvant trial with BCG in stage I (pT3-4N0M0) high-risk melanoma was prospectively subjected to detailed analysis regarding tuberculin (PPD, purified protein derivate) skin test reactivity, local, regional and systemic reactions to BCG vaccination, PPD antibody response and disease-free survival. Patients were randomized into three arms and received either no adjuvant treatment (22 patients), BCG RIV (40 patients) or BCG Pasteur (44 patients). All patients were followed for up to 10 years (median follow-up 6 years). RESULTS: Patients treated with BCG Pasteur mounted a stronger antibody response, experienced stronger regional and systemic reactions to vaccination and converted more frequently to positive PPD skin tests, compared to controls and to patients vaccinated with BCG RIV. All BCG-treated patients who developed an antibody response had a longer disease-free interval (p = 0.05), with slightly higher significance for BCG Pasteur-treated patients (p = 0.02). CONCLUSIONS: Cellular as well as humoral immune responses to PPD and BCG thus identify stage I malignant melanoma patients with an overall better prognosis.

Adolescent↗
PubMed1996

Double-blind crossover study of high-dose cetirizine in cholinergic urticaria.

BACKGROUND: Cholinergic urticaria does not respond well to treatment with conventional antihistamines and is difficult to study because of its highly variable clinical expression which depends on the presence of eliciting factors. OBJECTIVE: We have therefore designed a double-blind, crossover, placebo-controlled trial, with a 3-week treatment period using either 20 mg/day of cetirizine or placebo. METHODS AND RESULTS: Presence of eliciting factors and symptoms were scored daily on a diary card by the patient, with a scale from 0 to 3 for erythema, wheals and pruritus. Statistical analysis was done on 11 evaluable patients during the last 2 weeks of each treatment period (to allow for 1 week of washout) and only for days when eliciting factors were present. Compared to placebo, cetirizine caused a statistically significant reduction of wheals (p = 0.015), erythema (p = 0.033), pruritus (p = 0.006) and all symptoms (p = 0.013). No adverse events were observed. CONCLUSION: These data show a high efficacy of cetirizine at twice its normally recommended dose which may be related to the specific antiallergic effects of this newer-generation antihistamine.

Adolescent↗
PubMed1996

Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage.

BACKGROUND: Adhesion is crucial in the metastatic process of malignant tumours. Recently, the expression of certain selectins on intratumoral vessels has been shown to be associated with the clinical outcome of melanoma patients. OBJECTIVES AND METHODS: For the first time, this study examines the serum concentrations of circulating soluble vascular cellular adhesion molecule 1 (CD 106), endothelial leucocyte adhesion molecule (CD62E), sP-selectin (CD62P) and sCD44v5 in comparison to soluble intercellular adhesion molecule 1 (sICAM-1, CD54) in a series of 34 melanoma patients at different clinical stages and 11 normal donors using ELISA: RESULTS: sICAM-1 and sP-selectin levels were statistically elevated in all subgroups of melanoma patients compared to controls (p < 0.01). Circulating ICAM-1 as well as sP-selectin might be valuable additional serological tumour markers which correspond to tumour load and correlate with progression of malignant melanoma. CONCLUSION: Measurement of sICAM-1 and sP-selectin serum levels might therefore provide a sensitive tool for monitoring the clinical course of melanoma.

Adult↗
PubMed1996

Acute urticaria: clinical aspects and therapeutic responsiveness.

Although acute urticaria is common, its eliciting factors, clinical course and therapeutic responsiveness have not been intensively investigated. We have therefore prospectively studied all patients with acute urticaria attending the department of dermatology (n = 72) and a rural dermatology office (n = 37) during the course of 1 year. After a standardized history and physical examination, patients were randomized into treatment with either loratadine (10 mg/day for 3 days) or prednisolene (50 mg/day for 3 days). All patients were followed up until complete remission. Most patients suffered from moderate (42%) to severe (40%) disease. Possible eliciting factors were identified in less than 50% of the cases. Associated upper respiratory tract infections were found most commonly (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and suspected food intolerance (0.9%). The course of the disease was self-limited in all cases, the longest episode lasting for 3 weeks. Both treatment regimens were effective in controlling whealing, but in corticosteroid-treated patients, symptoms ceased earlier, with complete remission occurring within 3 days of treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p < 0.001). Acute urticaria is thus frequently idiopathic and only rarely associated with IgE-mediated events. It is, however, largely self-limited, with prompt response to symptomatic treatment.

Acute Disease↗
PubMed1995

Membrane transport proteins associated with drug resistance expressed in human melanoma.

Melanoma cells often display a multidrug-resistant phenotype, but the mechanisms involved are largely unknown. We have studied here the recently identified transport-associated proteins, MRP and LRP, and the well-known drug resistance marker P-glycoprotein using a panel of 16 human melanoma cell lines and 71 benign and malignant melanocytic tissue samples. By flow cytometry and immunohistochemistry, expression of P-glycoprotein was not detectable on the protein level in the 10 cell lines analyzed, although by reverse transcriptase polymerase chain reaction, MDR-1 gene expression was demonstrated in 2 of 10 cell lines. In addition, immunohistology revealed P-glycoprotein expression in only 1 of 71 melanocytic lesions. In contrast, MRP was detected in a subset of melanoma cell lines by reverse transcriptase polymerase chain reaction and immunohistology (4 of 10). LRP expression was observed in 8 of 10 melanoma cell lines by immunochemistry and in 10 of 10 by reverse transcriptase polymerase chain reaction. Furthermore, MRP was detected immunohistologically in almost 50% of primary and metastatic melanoma specimens, although no significant differences were found between metastases taken before or after chemotherapy. Expression of LRP was detected in a subset of nevi with nevus cells exhibiting up to 25% positive LRP reactivity. In 13 of 21 primary melanomas and 23 of 37 metastases, more than 25% of tumor cells were stained by the LRP-56 monoclonal antibody. Particularly in the group of metastases with more than 50% of LRP-positive cells, 7 of 11 of the metastases had been previously exposed to chemotherapeutic drugs. Although the expression of membrane transport proteins may explain only the chemoresistance toward lipophilic, natural compounds and not resistance against alkylating agents, the lack of P-glycoprotein expression after chemotherapeutic treatment and the significant expression of MRP and LRP in melanoma cells provide first insights into the drug-resistant phenotype in melanoma. Additional studies analyzing the role of MRP and LRP in chemoresistance of melanoma are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Expression and functional role of co-stimulatory molecules in CD40+IL-4-stimulated B cells from atopic and non-atopic donors.

As immunological dysregulation is a possible key defect in atopic diseases, we have studied the expression and function of costimulatory molecules in atopic dermatitis (AD) patients compared with normal controls. Using flow cytometry, we showed that CD80 and CD86 are expressed at increased levels on human peripheral B cells in both groups after stimulation with anti-CD40 and interleukin 4 (IL-4), but to a significantly higher extent in the AD group. Furthermore, baseline expression of CD80 and CD86 on peripheral B cells was low in normal donors and increased in AD donors. To study the functional role of the costimulatory molecules in CD40+IL-4-stimulated peripheral mononuclear cells from normal and atopic donors, proliferation and IgE production were analysed in the presence of antibodies against the receptors of the costimulatory molecules. In the presence of either anti-CD28 or anti-CTLA-4, cell proliferation and IgE synthesis were significantly enhanced in the atopic group in anti-CD40+IL-4-stimulated peripheral mononuclear cells. These findings suggest that interaction of CD80 and CD86 with their receptors CD28 and CTLA-4 selectively promotes cell activation, including proliferation and IgE production in CD40+IL-4-stimulated peripheral blood mononuclear cells from atopic donors. It remains to be elucidated whether these changes are primary, based on the genetic background of atopics, or whether they are induced secondarily in the context of atopic pathology.

Abatacept↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions.

Since adverse effects due to angiotensin-converting enzyme (ACE) inhibitors frequently occur in cutaneous locations, this review summarizes the spectrum of expected and unexpected adverse effects of these drugs, possible associated mechanisms, and their basic functions for dermatologists. ACE inhibitors block the activity of the metalloproteinase ACE by binding to its active site, thus displacing angiotensin I and preventing its conversion to vasopressive angiotensin II. Furthermore, ACE degrades bradykinin, substance P, enkephalins and some of the reproductive peptide hormones. The overall incidence of adverse effects to ACE inhibitors is estimated at 28%, approximately half of which occurs in the skin. General reactions are first-dose hypotension, hyperkalaemia and renal failure. Cutaneous reactions comprise life-threatening angioedema, pruritus, bullous eruptions, urticaria, other generalized rashes, photosensitivity and hair loss. ACE inhibitors thus mimic a broad variety of skin diseases, why these drugs should be thought of when sudden, unexplainable skin eruptions are observed.

Acantholysis↗
PubMedDate not supplied

Effects of retinoids on in vitro and in vivo IgE production.

BACKGROUND: Retinoids modulate the growth and number of different cell types, including B cells. We could previously show that retinoic acid (RA) strongly inhibits CD40 + IL-4-mediated IgE production in vitro. The aim of the present study was to extend these findings regarding the potential use of retinoids for the treatment of allergic diseases. METHODS: In vitro IgE production was studied in anti-CD40 + IL-4-stimulated peripheral blood mononuclear cells (PBMC) from allergic donors in the presence of 10(-15)-10(-5) M all-trans and 13-cis RA and in ovalbumin (OVA)-sensitized BALB/c mice treated with RA (20 mg/kg) before and during sensitization. IgE and IgG1 levels were determined in the sera of the mice at day 21 after 2 injections (days 1 and 8) of aluminum hydroxide-absorbed OVA. RESULTS: All-trans and 13-cis RA inhibited in vitro IgE production from PBMC in a dose-dependent manner, but were more efficient in atopic dermatitis patients with low total serum IgE levels (< 400 kU/ml), maximal inhibition for all-trans RA at 10(-7) M (87%) and for 13-cis RA at 10(-5) M (96%) compared to patients with high serum IgE levels (>2,000 kU/ml), maximal inhibition for both all-trans and 13-cis RA at 10(-5) M (53 and 39%, respectively). In contrast, the in vivo data from OVA-sensitized mice revealed comparable total IgE and IgG1 levels in control versus all-trans RA or CD336-treated groups, specific IgE was even higher in the CD336-treated group (n = 10, 2,814 ng/ml), and was comparable in mice treated with OVA alone or with additional all-trans RA (n = 10, 1,447 and 1,354 ng/ml, respectively). CONCLUSIONS: These results indicate that the efficacy of retinoids to inhibit IgE production in vitro depends on the frequency of switched cells in the peripheral blood and that in an in vivo model using OVA-sensitized mice, retinoids fail to inhibit IgE production.

Allergens↗
PubMedDate not supplied

Dithranol in an emulsifying oil base (bio-wash-oil) for the treatment of psoriasis of the scalp.

On the scalp, dithranol has been studied in only a few trials. The dithranol molecule that contains both hydrophilic and lipophilic centers can be incorporated into detergents and allows easy removal from hair. This property has led to the incorporation of dithranol in an emulsifying oil base (bio-wash-oil). The formulation has been used routinely for more than two decades in East Germany. We reexamined the efficacy and safety of dithranol in bio-wash-oil and compared it to dithranol embedded in crystalline monoglycerides (Micanol) in patients with psoriasis of the scalp. In a prospective, parallel group study, 64 patients attending a day-care clinic were randomly allocated to 3 treatment groups: (1) dithranol in bio-wash-oil; (2) Micanol cream, and (3) Micanol cream in bio-wash-oil. Treatment was carried out for 3 weeks and results assessed using a modified Psoriasis Area and Severity Index score. Dithranol in bio-wash-oil resulted in a reduction in the score of 34% on day 7 and 57% on day 14. This was significantly better than in groups 2 and 3, as were the overall response and patients' assessment at the end of treatment (p < 0.05). Dithranol in a bio-wash-oil is an effective, well-tolerated and low-priced treatment in psoriasis of the scalp.

Administration, Topical↗
PubMedDate not supplied

GM-CSF downregulates expression of tryptase, Fc epsilon RI and histamine in HMC-1 mast cells.

Fibroblast-derived growth factors like SCF are able to upregulate the expression of mast cell characteristics in human multilineage hematopoietic progenitor cells. Other factors, like GM-CSF, have been reported to inhibit this process, probably by the competitive recruitment of cells not belonging to the mast cell lineage. In this study, we investigated the influence of GM-CSF on immature mast cells of the HMC-1 cell line which already show low-level expression of mast cell tryptase, histamine and Fc epsilonRI alpha. Culture of HMC-1 cells with mast-cell-conditioning medium, containing fibroblast supernatants, upregulated tryptase activity, histamine contents and expression of Fc epsilonRI alpha. However, addition of GM-CSF (10 ng/ml) markedly downregulated these mast cell markers, without affecting proliferation and viability of cells. Thus, GM-CSF may provide an inhibitory signal during mast cell differentiation and probably even downregulates mast cell characteristics in more differentiated cells.

Cells, Cultured↗
PubMedDate not supplied

Preclinical diagnosis of pseudoxanthoma elasticum - methodological restrictions and ethical problems.

Pseudoxanthoma elasticum (PXE) is an inherited connective tissue disease. Only recently, mutations in the MRP6 gene on chromosome 16p13.1 have been identified in PXE families. Up to now, predictive testing has not been available. Since ultrastructural connective tissue alterations in overtly normal skin of predilection sites have supported preclinical diagnosis in children of affected individuals, we have screened the daughters of a PXE patient for these alterations. The patient's biopsy from lesional skin revealed elastin and collagen fibril abnormalities, but biopsies from the clinically inconspicuous daughters showed only ultrastructural alterations of collagen fibrils. These findings are inconclusive regarding the diagnosis of PXE in the daughters. Predictive or preclinical diagnosis of incurable, late-onset disorders creates complex social, ethical, and legal problems which call for special management strategies.

Adult↗