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Biomedical subjects

B Hermes

Publications and source records attributed to B Hermes.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of psychological aspects during systemic provocation tests in patients with pseudoallergic drug reactions.

BACKGROUND: Basic mechanisms of pseudoallergic drug reactions as well as a possible role of the psyche are currently unknown. OBJECTIVE: Examination of psychological status and reactions during diagnostic provocation tests in patients with previous pseudoallergic reactions to drugs. SUBJECTS AND METHODS: Ten inpatients, admitted for provocation tests, were studied in a double-blind, placebo-controlled setting, with inventories of anxiety and depression being measured at baseline and psychological reactions and symptoms being recorded daily by patients and the attending physician. RESULTS: Patients reported more than twice as many symptoms as the physician, independent of the type of exposure. While the basic psychological profile of the patients was normal, anxiety trait and state values were high during testing, with a significant increase depending on whether the patients thought they had received a drug or a placebo. Similarly, frequency of symptoms was dependent on the patients' perception of the type of exposure. CONCLUSION: These findings demonstrate a high level of anxiety during systemic provocation tests in patients with previous pseudoallergic drug reactions, raising serious questions as to the diagnostic validity of the routine application of this testing.

Ampicillin↗
PubMed2004

Crossreacting IgG antibodies against fox mite antigens in human scabies.

Scabies continues to be an important parasitic disease of mammals. There remain, however, major gaps in the understanding of the human host immune response, and a simple diagnostic test is lacking. In contrast to human mites, red fox mites (Sarcoptes scabiei var. vulpis) can be collected easily and have been used, due to crossreactivity, for enzyme-linked immunosorbent assay (ELISA) studies in dogs and pigs. We wanted to investigate the possibility that crossreactivity might also exist for the human mite, and determined titers against fox mite antigens by ELISA in 41 patients with scabies. Specific IgG was significantly higher in patients with scabies than in healthy controls (P=0.01). The sensitivity was, however, only 48%, although it increased slightly during treatment (P=0.86). A positive correlation was also noted between disease duration and severity of infestation (r=0.5), with specific IgG titers increasing in parallel with severity of symptoms (P=0.01). Patients with symptomatic scabies for more than 4 weeks had furthermore significantly higher IgG titers than patients with a shorter duration of disease (P=0.007). In conclusion, these findings demonstrate IgG antibodies in human scabies that crossreact with fox mite antigens, thus encouraging the search for improved ELISAs with more specific mite antigens to produce a more sensitive detection system for scabies in humans.

Aged↗
PubMed2003

Decreased cutaneous expression of stem cell factor and of the p75NGF receptor in urticaria.

BACKGROUND: Mast cells, the main effector cells in urticaria, have been reported to be increased in number in lesional and nonlesional skin of urticaria patients, but the underlying mechanisms have so far not been studied. Serum NGF has however, been reported to be increased in urticaria. OBJECTIVES: We have therefore explored the potential involvement of known mast cell growth modulating factors in urticaria. METHODS: Tissue sections from patients with different types of urticaria and healthy controls were studied for the immunohistochemical expression of known mast cell growth factors (stem cell factor, SCF; nerve growth factor, NGF), of the inhibitory granulocyte-macrophage colony-stimulating factor (GM-CSF), and of the corresponding receptors, using the alkaline phosphatase-antialkaline phosphatase technique. RESULTS: Compared to skin of normal controls, staining for SCF, but not for NGF and GM-CSF, was significantly decreased in epidermis, endothelium and perivascular cells in lesional and nonlesional skin of all urticarias. On separate analysis of urticaria subtypes, decreased expression reached significance only in delayed pressure urticaria. Expression of the p75NGF receptor (p75NGFR) was also significantly decreased on endothelium and on perivascular cells of lesional and nonlesional skin in all urticarias. On evaluation of serial sections, p75NGFR expression was also decreased on c-Kit positive dermal mast cells. In contrast, expression of the NGF receptor tyrosine kinase and of the SCF and GM-CSF receptors was unchanged. CONCLUSIONS: These findings show that SCF and p75NGFR are selectively and systemically down-regulated in the skin of urticaria patients and may represent a negative feedback to increased mast cell reactivity and proliferation.

Endothelium↗
PubMed2003

Evidence for altered mast cell proliferation and apoptosis in cutaneous mastocytosis.

BACKGROUND: Mastocytosis presents as a focal or generalized increase of mast cells, particularly in the skin, but also in other organs. Activating mutations of KIT (formerly c-kit), the receptor of the mast cell growth factor stem cell factor (SCF), appear to play a key role in the pathogenesis of sporadic adult onset mastocytosis. However, these mutations are not present in childhood-onset and familial mastocytosis and also fail to explain the heterogeneity of adult-onset disease. Other factors such as prolonged survival of mast cells may therefore participate in causing and modulating the pathological increase of mast cells in mastocytosis. OBJECTIVES: To examine the expression of proliferation and apoptosis markers in the mast cells of cutaneous mastocytosis lesions in order to gain further insight into the pathogenesis of mastocytosis. METHODS: Lesional cutaneous biopsies from eight infants with solitary mastocytomas, five children with multiple mastocytomas, 11 children with generalized urticaria pigmentosa, 12 adults with urticaria pigmentosa, and skin from seven normal controls were used in this study. Serial sections were stained with toluidine blue to quantify mast cell numbers and with antibodies against the proliferation marker Ki67 protein, the tumour suppressor protein p53, and the inhibitor of cyclins and cyclin-dependent kinases p21WAF1/CIP1, using the alkaline phosphatase antialkaline phosphatase technique. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method was used to assess apoptosis. RESULTS: Cutaneous mast cell counts were significantly increased in all patient sections, particularly in childhood lesions, and similarly, a small but significant increase of proliferation was found in the lesional mast cells of all patients. Enhanced mast cell numbers and proliferation was associated with a significant decrease of TUNEL staining, particularly in mastocytomas. p53 expression was highly variable, with an overall significant increase in all patient skin mast cells, whereas p21 expression was barely observed at all. CONCLUSIONS: These findings further support the concept that an imbalance of mast cell proliferation and apoptosis is prevalent in mastocytosis lesions that may account in part for the increased focal mast cell accumulation in this condition.

Adolescent↗
PubMed2002

[CD8-positive, CD30-negative cutaneous T-cell lymphoma simulating pyoderma gangrenosum].

Ulcerated primary cutaneous lymphomas are not rare, but the clinical manifestation as a pyoderma gangrenosum look-alike is extraordinary. CD8-positive lymphomas are rare, unclassifiable tumours with variable prognosis. We report on a 49-year-old patient with a large ulcerated primary cutaneous lymphoma on the left chest wall presenting as pyoderma gangrenosum. With immunohistochemical staining, most lymphocytes were shown to be CD8-positive. The CD30 antigen was not expressed. After radiotherapy with complete skin irradiation, the lymphoma regressed completely. The patient has been free of relapse for 28 months so far.

CD8 Antigens↗
PubMed2002

Laser-induced weal and flare reactions: clinical aspects and pharmacological modulation.

BACKGROUND: Among the adverse effects of cutaneous laser therapy, weal and flare reactions immediately after treatment have received little attention, and the pathomechanisms are unclear. OBJECTIVES: To study clinical features and possible mechanisms of laser-induced weal and flare reactions in order to identify means of possible therapeutic intervention. METHODS: Normal skin from the inner arm of 20 volunteers was treated with an argon laser, and the size of weal and flare reactions was measured over a 60-min period. Skin biopsies were taken from four volunteers before and up to 24 h after laser treatment and examined histologically and immunohistologically. Possible underlying mechanisms were also explored using various topical or systemic pharmacological agents. RESULTS: Wealing was noted in 19 of 20, and flare reactions in all volunteers, with peak values at 15 min. Skin biopsies showed central coagulation of the tissue, cleft formation between epidermis and dermis, normal numbers of morphologically intact mast cells on toluidine blue staining close to the lesion, and only minor upregulation of endothelial and leucocyte adhesion molecules. In agreement with these findings, pretreatment with acetylsalicylic acid, the H1-blocker loratadine and triamcinolone cream was ineffective or resulted in a non-significant reduction of weal and flare reactions. In contrast, local anaesthetics as well as neuropeptide depletion of skin with capsaicin abolished the reactions almost completely. CONCLUSIONS: Transient weal and flare reactions in response to laser treatment occur in almost all persons and are based primarily on a neurogenic rather than a histamine- or mast cell-dependent mechanism.

Adult↗
PubMed2001

Adhesion molecules and cellular infiltrate: histology of urticaria.

Urticarial reactions are characterized by dermal capillary dilatation and edema, associated with a variably intense mixed inflammatory infiltrate consisting of neutrophils, eosinophils, T-helper lymphocytes, and activated macrophages. Mast cell numbers are moderately increased by a factor of 2.4, in contrast to mastocytosis where numbers are much higher (5-48-fold increase). In urticarial vasculitis there is in addition endothelial damage, leukocytoclasia, and fibrin and complement deposition. The emigration of leukocytes is regulated by vasoactive and chemotactic mediators released firom mast cells, inducing a sequential upregulation of endothelial adhesion molecules (P-selectin, E-selectin, ICAM-1, and VCAM-1), of beta2-integrins on leukocytes, and of cytokines on endothelial, epithelial, and infiltrating cells. In nonlesional skin, there is also an increase of mast cells and an upregulation of endothelial adhesion molecules, probably due to molecules in the circulation of which P-selectin and TNFalpha have so far been demonstrated. Whereas these data provide a molecular basis for the understanding of variations in mast cell-dependent pathology, they underline the fact that they are not diagnostic for different types of urticaria, except for urticarial vasculitis and mastocytosis.

Adult↗
PubMed2001

Expression of mast cell growth modulating and chemotactic factors and their receptors in human cutaneous scars.

In order to explore possible mechanisms involved in the previously documented turnover of mast cell subpopulations in human cutaneous scars, we have examined selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF, NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were significantly increased in the epidermis and throughout the dermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF-p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF expression was in contrast scarce and weak, with no differences between normal skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II, and both NGF-receptors, but not GM-CSFR, were significantly increased as well. TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were identified on 70% and 73%, respectively, of avidin-positive normal mast cells on double immunofluorescence microscopy. As described before for the SCF receptor KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin-positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orchestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of their receptors.

Cell Division↗
PubMed2001

Acute herpes zoster neuralgia: retrospective analysis of clinical aspects and therapeutic responsiveness.

BACKGROUND: Although the efficacy of modern antiviral agents for the treatment of herpes zoster is unquestioned, their ability to affect the associated pain remains controversial. OBJECTIVE: We have therefore evaluated the inpatient hospital records of 550 patients with herpes zoster with regard to pain-related clinical aspects and therapeutic responsiveness. METHODS: Intensity of pain was quantified by calculating a daily pain equivalence index (PEI) on the basis of different classes of pain medication and the number of tablets used in each category. RESULTS: The mean age of patients was 66.7 years, cranial segments were predominantly involved (55%), 64% of patients suffered from associated diseases and 77% experienced herpes-related pain. The PEI was 0.90 in the entire patient population, with significantly higher values in women and in patients with 3 or more associated diseases. It was lower in sacral and cranial nerve involvement, and it decreased rapidly in patients prior to discharge from hospital. Although there were significant differences in hospital stay between patients who received aciclovir and those who did not (mean 20.3 vs. 23.8 days), and for high- versus low-dose oral or intravenous administration, no significant differences were noted between the two groups for initial PEI values and during the course of observation, irrespective of the route of administration or the dose of aciclovir and the individual patient's PEI value. The groups were otherwise closely similar with regard to basic demographic and clinical data. 23.3% predominantly aged female patients with more associated diseases than the total patient population had a persistently elevated PEI and stayed in hospital beyond 21 days (mean 35.1 days), representing patients who went on to postherpetic neuralgia. CONCLUSION: These data further delineate clinical aspects of acute herpes zoster neuralgia, underline the unsolved therapeutic problems associated with this condition despite otherwise effective antiviral treatment, and characterise a subgroup of patients at risk to develop postherpetic neuralgia.

Acute Disease↗
PubMed2000

The human hair follicle immune system: cellular composition and immune privilege.

The immunology of the hair follicle, its relationship with the 'skin immune system' and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and gammadelta T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA-A, -B, -C) and beta2-microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.

Adolescent↗
PubMed2000

Altered expression of mast cell chymase and tryptase and of c-Kit in human cutaneous scar tissue.

In order to explore a possible involvement of mast cells during human wound healing, we studied sections from scars (4-369-d-old) (N = 20) and normal skin (N = 10) for mast-cell-specific tryptase and chymase by enzyme histochemistry, for the stem cell factor receptor c-Kit and the melanosomal marker TA99 by immunohistochemistry, and for simultaneous c-Kit expression and avidin fluorescence by double staining. Enzyme activities and mRNA expression were also studied in tissue extracts. Chymase-reactive mast cell numbers as well as chymase activity and mRNA expression were reduced in all scars, whereas overall numbers of tryptase-reactive cells did not differ from normal skin, although tryptase activity and mRNA expression were increased in scar extracts. In contrast, numbers of c-Kit positive cells were significantly increased in old scars, and in the mid and lower dermis of all scars. A marked reduction of c-Kit reactivity was noted, however, in avidin-positive dermal mast cells and in epidermal basal cells, despite unchanged numbers of melanosome-positive cells, with an associated overall decrease of c-Kit mRNA in scar extracts. These data thus show that numbers of resident mast cells are very low in human cutaneous scars, suggesting massive mediator release from these cells into fresh wounds. Downregulation of stem cell factor receptors may also prevent these cells from increasing in number even in old scars. Instead, scar tissue is populated by a mast cell subpopulation that is chymase-, avidin-, tryptase +, c-Kit +, reflecting most probably an increased immigration and/or proliferation of immature mast cells and their precursors.

Chymases↗
PubMed1999

Day- and night-time contents of monoamines and their metabolites in the medial preoptic area of the rat hypothalamus.

The present study was conducted to investigate whether monoamines and their metabolites in the medial preoptic area (mPOA) of the rat hypothalamus exhibit differences in their contents between day and night. We therefore sampled the mPOA from adult animals of either sex at the middle of the light or dark period, respectively, and analyzed the tissue by means of high performance liquid chromatography with electrochemical detection. We found that, in female animals at mid-night, dopamine and 3,4-dihydroxyphenyl acetic acid (DOPAC) was reduced to 43 and 30%, respectively, of daytime levels, while the norepinephrine content was doubled. No significant differences were observed in male animals. We also conducted immunohistochemistry of the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), in sections from perfusion-fixed male rats and showed that TH is present in neuronal perikarya and processes in the anteroventral periventricular region of the mPOA, while DBH was only seen in fibers and terminals. Our results of sex-specific and day time-dependent variations in dopamine and norepinephrine concentrations indicate that the two monoamines are candidate neurotransmitters that may transmit diurnal information to the mPOA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Upregulation of TNF-alpha and IL-3 expression in lesional and uninvolved skin in different types of urticaria.

BACKGROUND: Although mast cells are known to secrete a broad spectrum of proinflammatory and immunomodulatory cytokines, the role of these molecules in mast cell-dependent cutaneous inflammation is not clear. OBJECTIVE: We decided to study biopsy specimens from lesional and nonlesional skin of patients with acute, chronic recurrent, delayed pressure, and cold urticaria; from fleeting wheals of prick test reactions to allergens; and from normal skin of nonallergic subjects. METHODS: Cryostat sections were stained by immunohistochemistry with antibodies against IL-3, IL-8, TNF-alpha, and mast cell-specific tryptase. In serial sections with tryptase and each cytokine, reactivity of mast cells was studied as well. RESULTS: Compared with normal skin and prick test reactions, immunoreactivity for TNF-alpha and IL-3 was significantly increased on endothelial and perivascular cells of the upper dermis in all urticaria lesions. In nonlesional skin comparable upregulation was noted on endothelial cells and for TNF-alpha on perivascular cells of patients with delayed pressure urticaria. In addition, TNF-alpha was expressed throughout the epidermis in lesional and nonlesional skin of patients with all types of urticaria, but not in normal control subjects. Sequential biopsy specimens from patients with cold urticaria showed upregulation of TNF-alpha and IL-3 on endothelial cells 30 minutes after elicitation of lesions with an ice cube. In contrast to these findings, epidermal immunoreactivity, as well as endothelial and perivascular cell expression of IL-8, were only slightly altered in urticaria compared with normal skin. In sequentially stained sections, few tryptase-positive mast cells reacted to TNF-alpha, few reacted to IL-3 in pressure urticaria only, and practically none stained for IL-8. CONCLUSION: These findings suggest that the cytokines studied here are involved in the pathology of urticaria, possibly by inducing subthreshold inflammation in endothelial cells of uninvolved skin.

Cytokines↗
PubMed1999

Mast cells and their mediators in cutaneous wound healing--active participants or innocent bystanders?

Mast cells are traditionally viewed as effector cells of immediate type hypersensitivity reactions. There is, however, a growing body of evidence that the cells might play an important role in the maintenance of tissue homeostasis and repair. We here present our own data and those from the literature elucidating the possible role of mast cells during wound healing. Studies on the fate of mast cells in scars of varying ages suggest that these cells degranulate during wounding, with a marked decrease of chymase-positive cells, although the total number of cells does not decrease, based on SCF-receptor staining. Mast cells contain a plethora of preformed mediators like heparin, histamine, tryptase, chymase, VEGF and TNF-alpha which, on release during the initial stages of wound healing, affect bleeding and subsequent coagulation and acute inflammation. Various additional vasoactive and chemotactic, rapidly generated mediators (C3a, C5a, LTB4, LTC4, PAF) will contribute to these processes, whereas mast cell-derived proinflammatory and growth promoting peptide mediators (VEGF, FGF-2, PDGF, TGF-beta, NGF, IL-4, IL-8) contribute to neoangiogenesis, fibrinogenesis or re-epithelization during the repair process. The increasing number of tryptase-positive mast cells in older scars suggest that these cells continue to be exposed to specific chemotactic, growth- and differentiation-promoting factors throughout the process of tissue remodelling. All these data indicate that mast cells contribute in a major way to wound healing. their role as potential initiators of or as contributors to this process, compared to other cell types, will however have to be further elucidated.

Humans↗
PubMed1999

Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars.

In order to shed further light on the potential role of mast cells during tissue turnover, we have investigated the number of mast cells containing only tryptase and those storing both tryptase and chymase by enzyme histochemistry in normal versus healing skin. Furthermore, we have studied the in vitro effect of these enzymes on the mitogenesis of subconfluent quiescent fibroblast and HaCaT keratinocyte cultures, using flowcytometric DNA analysis. Chymase-containing mast cell numbers were markedly decreased in scars (P<0.001), whereas the overall number of tryptase-containing mast cells was not decreased, although these cells were smaller and stained more faintly in scars. Chymase (5 to 300 mU/ml) induced a marked, dose-dependent in vitro mitogenic response in 3T3 fibroblasts, whereas the effects of tryptase, at up to 60 nM, were only moderate, compared to the known fibroblast mitogens EGF, TGF-alpha, alpha-thrombin and trypsin at optimal concentrations. Coincubation of either protease with EGF or alpha-thrombin had additive effects. In contrast to fibroblasts, keratinocytes showed only minor mitogenic responses to tryptase and chymase, also in comparison to other known mitogenic stimuli, and responses to EGF and alpha-thrombin were inhibited on costimulation of cells with the proteases. These findings document for the first time a potential role of mast cell chymase in connective tissue repair, with tryptase being less active on fibroblasts, and with inhibitory effects of both mast cell proteases on keratinocytes.

3T3 Cells↗
PubMed1998

[Scar forming alopecia. Comments on classification, differential diagnosis and pathobiology].

Numerous different diseases lead to scarring alopecia with irreversible follicular destruction as a common ending. Current classifications are based on clinical, histopathological or prognostic parameters, as well as on pathogenetic criteria which allow only a rough assessment because the precise mechanisms leading to scarring alopecia are still unknown. Inadequacies of the established classifications are obvious when regarding special forms of scarring alopecia like lichen planopilaris or pseudopelade Brocq. In order to develop more satisfying classifications, recent insights into biology and pathology of the hair follicle and follicular cycling have to be considered. The most important structures for the survival of the hair follicle are the epithelial stem cells which reside in the follicular bulge and the fibroblasts of the dermal papilla including the molecular communication between these two cell populations. Research in the field of scarring alopecia should aim at defining the pathological processes on any of the above mentioned levels which will lead to an irreversible damage of the hair follicle thus allowing the development of new therapeutic agents.

Alopecia↗