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Gerald S Lazarus - One of the best experts on this subject based on the ideXlab platform.
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determination of the primary structures of human skin chymase and cathepsin g from cutaneous mast cells of Urticaria Pigmentosa lesions
Journal of Immunology, 1994Co-Authors: Norma M Schechte, Gerald S Lazarus, Zhimei Wang, R W Lache, Stua R Lessi, Harvey RubiAbstract:This study establishes the primary structure of human skin chymase and provides further evidence for the presence of a cathepsin G-like proteinase within human mast cells. The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from Urticaria Pigmentosa (UP) lesions. UP is a disease characterized by skin lesions containing high numbers of mast cells. Proteolytic digests of human chymase purified from normal skin yielded 10 resolvable peptides that were sequenced by automated Edman degradation. The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. This partial amino acid sequence corresponded to the sequence of human heart chymase, a proteinase isolated from heart tissue with immunologic and hydrolytic properties similar to skin chymase. PCR amplification of UP-derived cDNA with primers based on the cDNA structure of heart chymase demonstrated a single amplification product of expected size which was subcloned and sequenced. The amino acid sequence (135 residues) deduced from this product was identical to that of heart chymase in the region between the primers. This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. Amplification of the same UP-cDNA with primers coding for the NH2- and COOH-terminal sequences of human neutrophil cathepsin G also produced a specific amplification product which was sequenced. The deduced amino acid sequence between the primers was identical to that reported for neutrophil cathepsin G, indicating that the protein of cutaneous mast cells previously shown to be immunologically cross-reactive with neutrophil cathepsin G has a comparable amino acid sequence. UP-cDNA demonstrating amplification products for cathepsin G did not demonstrate amplification products for human neutrophil elastase, suggesting that the cathepsin G PCR amplification product was not derived from neutrophils or monocytes possibly contaminating the lesion. These studies provide further evidence that human skin mast cells contain two different chymotrypsin-like proteinases.
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Urticaria Pigmentosa systemic evaluation and successful treatment with topical steroids
Archives of Dermatology, 1991Co-Authors: Cynthia Guzzo, Robe M Lavke, Norma M Schechte, Jackso L Roberts, Gerald S LazarusAbstract:† Nine patients with adult-onset Urticaria Pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients. (Arch Dermatol.1991;127:191-196)
U Mulle - One of the best experts on this subject based on the ideXlab platform.
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hymenoptera sting anaphylaxis and Urticaria Pigmentosa clinical findings and results of venom immunotherapy in ten patients
The Journal of Allergy and Clinical Immunology, 1997Co-Authors: Michael Fricke, A Helbling, Lawrence Schwartz, U MulleAbstract:Abstract Background: Occasional patients with Urticaria Pigmentosa and anaphylaxis after Hymenoptera stings have been described. In this situation the question arises: Is anaphylaxis IgE-mediated or induced by pharmacologic mediator release from mast cells? Methods: We investigated 10 patients with histologically confirmed Urticaria Pigmentosa and a history of anaphylaxis after honeybee or Vespula stings before and during immunotherapy with the respective venom. Results: In eight of 10 patients, an elevated serum tryptase level was found. In two of 10 patients, no venom-specific IgE could be detected by either skin tests or RAST. Five patients had no detectable venom-specific serum IgE, and in the remaining patients the level was low ( Vespula sting. Conclusion: Anaphylactic symptoms after Hymenoptera stings in patients with Urticaria Pigmentosa are most often IgE-mediated but can occasionally be observed in the absence of IgE sensitization to venom allergens. Venom immunotherapy can be safely and successfully used in patients with Urticaria Pigmentosa and sting anaphylaxis. (J Allergy Clin Immunol 1997;100:11-5.)
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mastocytosis and atopy a study of 33 patients with Urticaria Pigmentosa
Allergy, 1990Co-Authors: U Mulle, A Helbling, T Hunzike, A Pecoud, S Gilardi, E Eretta, J Fasel, W Messerli, P MaureAbstract:Thirty-three patients with histologically verified Urticaria Pigmentosa were studied for coexisting atopic disease by means of history, skin prick testing with five common inhalants and serological investigation for total IgE and specific IgE antibodies to five common inhalants. The prevalence of atopy in Urticaria Pigmentosa was similar to that observed in the normal Swiss population, both on the basis of history (7/33 = 21%) and of positive skin prick tests to common inhalants (12/33 = 36%). However, total serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a control group of 52 Swiss blood donors of comparable age and sex distribution (geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies to common inhalants were also observed less frequently in Urticaria Pigmentosa patients than in controls, although this difference was not statistically significant. Low total and specific IgE values in patients with Urticaria Pigmentosa may be explained by increased absorption of circulating IgE to abundant tissue mast cells.
Norma M Schechte - One of the best experts on this subject based on the ideXlab platform.
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determination of the primary structures of human skin chymase and cathepsin g from cutaneous mast cells of Urticaria Pigmentosa lesions
Journal of Immunology, 1994Co-Authors: Norma M Schechte, Gerald S Lazarus, Zhimei Wang, R W Lache, Stua R Lessi, Harvey RubiAbstract:This study establishes the primary structure of human skin chymase and provides further evidence for the presence of a cathepsin G-like proteinase within human mast cells. The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from Urticaria Pigmentosa (UP) lesions. UP is a disease characterized by skin lesions containing high numbers of mast cells. Proteolytic digests of human chymase purified from normal skin yielded 10 resolvable peptides that were sequenced by automated Edman degradation. The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. This partial amino acid sequence corresponded to the sequence of human heart chymase, a proteinase isolated from heart tissue with immunologic and hydrolytic properties similar to skin chymase. PCR amplification of UP-derived cDNA with primers based on the cDNA structure of heart chymase demonstrated a single amplification product of expected size which was subcloned and sequenced. The amino acid sequence (135 residues) deduced from this product was identical to that of heart chymase in the region between the primers. This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. Amplification of the same UP-cDNA with primers coding for the NH2- and COOH-terminal sequences of human neutrophil cathepsin G also produced a specific amplification product which was sequenced. The deduced amino acid sequence between the primers was identical to that reported for neutrophil cathepsin G, indicating that the protein of cutaneous mast cells previously shown to be immunologically cross-reactive with neutrophil cathepsin G has a comparable amino acid sequence. UP-cDNA demonstrating amplification products for cathepsin G did not demonstrate amplification products for human neutrophil elastase, suggesting that the cathepsin G PCR amplification product was not derived from neutrophils or monocytes possibly contaminating the lesion. These studies provide further evidence that human skin mast cells contain two different chymotrypsin-like proteinases.
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Urticaria Pigmentosa systemic evaluation and successful treatment with topical steroids
Archives of Dermatology, 1991Co-Authors: Cynthia Guzzo, Robe M Lavke, Norma M Schechte, Jackso L Roberts, Gerald S LazarusAbstract:† Nine patients with adult-onset Urticaria Pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients. (Arch Dermatol.1991;127:191-196)
Cynthia Guzzo - One of the best experts on this subject based on the ideXlab platform.
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Urticaria Pigmentosa systemic evaluation and successful treatment with topical steroids
Archives of Dermatology, 1991Co-Authors: Cynthia Guzzo, Robe M Lavke, Norma M Schechte, Jackso L Roberts, Gerald S LazarusAbstract:† Nine patients with adult-onset Urticaria Pigmentosa were studied for the incidence of extracutaneous mast cell involvement and the efficacy of potent topical corticosteroid therapy for cutaneous lesions. Seven of the nine patients had increased mast cells in the marrow biopsy specimens, and five patients had focal aggregates of mast cells. The bone scan was abnormal in one patient. Liver-spleen scans revealed a shift of colloid uptake from liver to spleen in four patients. No abnormal gastrointestinal tract roentgenograms were obtained. Urinary histamine metabolites correlated with nodular bone marrow involvement, but not with other parameters. Results of the psychoneurologic testing revealed significant deviation from the norm with a verbal memory deficit in all nine patients and abnormalities on the Minnesota Multiphasic Personality Inventory in four patients. All nine patients were treated with 0.05% betamethasone dipropionate ointment under occlusion over half of the body nightly for 6 weeks. Seven of nine patients treated responded with almost complete resolution of their lesions. Hypothalamic pituitary adrenal axis suppression was evaluated with intramuscular cosyntropin stimulation and metyrapone administration during treatment. Only two patients, both of whom used the medication improperly, developed transient abnormalities. Slow return of lesions was noted 6 months after completion of therapy. Remissions could be lengthened with single weekly applications of topical steroids. Systemic involvement is frequent in patients with cutaneous mast cell disease and it is best demonstrated by bone marrow biopsy. Mast cell lesions can be safely and effectively treated with topical steroids in motivated patients. (Arch Dermatol.1991;127:191-196)
Dea D Metcalfe - One of the best experts on this subject based on the ideXlab platform.
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telangiectasia macularis eruptiva perstans or highly vascularized Urticaria Pigmentosa
The Journal of Allergy and Clinical Immunology: In Practice, 2014Co-Authors: Kelli W Williams, Dea D Metcalfe, Calma Prussi, Melody C Carte, Hirsh D KomarowAbstract:o comment; Both, by both skin biopsy and clinical observation; Bx, skin biopsy; C sinophils, ISM, indolent systemic mastocytosis; L, lymphocytic; M, mastocytosis; M rted; SM, systemic mastocytosis; Y, yes. seen on skin biopsy specimen. This original report did not include histologic findings. Weber subsequently evaluated a second case of a patient with Urticaria Pigmentosa (UP) that closely resembled the index patient with TMEP and, based on these 2 cases, concluded that TMEP was a pigmentless variant of UP that presents primarily in adulthood. In subsequent reports, mast cell infiltration was noted histologically in both UP and TMEP; however, the gross appearance and perivascular distribution of mast cells and association with dilated vessels was said to distinguish TMEP from UP. Thus, TMEP now is usually referred to as a rare form of cutaneous mastocytosis in which the skin has flat telangiectatic macules in a generalized distribution. The relative lack of information on the consequences of a diagnosis of TMEP has led to confusion in clinical management. Based on these observations, we conducted a survey of patients who were evaluated for mastocytosis and who carried a diagnosis of TMEP to determine how the diagnosis of TMEP was being applied and if there were any consistent features to report. By using the National Institutes of Health Biomedical Translational Research Information System, we conducted a retrospective chart review of 299 subjects who were referred to the National Institute of Allergy and Infectious Diseases, with institutional review board approved mastocytosis protocols. All the subjects
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regression of Urticaria Pigmentosa in adult patients with systemic mastocytosis correlation with clinical patterns of disease
Archives of Dermatology, 2002Co-Authors: Knu Ockow, Linda M Sco, Alexandra S Worobec, Arnold S Kirshenbaum, Cem Aki, Mary M Hube, Dea D MetcalfeAbstract:Objective To determine clinical correlates of Urticaria Pigmentosa (UP) regression in adult patients with systemic mastocytosis (SM). Design Cohort study of the natural history of mastocytosis. Setting National Institutes of Health Clinical Center. Patients In a study of adult patients referred to the National Institutes of Health after 1980 and observed for a minimum of 10 years, 12 of 106 adult patients experienced clearance or fading of UP. Main Outcome Measures Data from each patient's history and results of physical examination, laboratory evaluation, and organ biopsy at presentation to the National Institutes of Health were compared with findings at the patient's most recent visit. Results In the patients in whom clearance of (n = 5) or a decrease in skin lesions (n = 7) was noted, UP had persisted from 4 to 34 years (median, 17 years). Older age was a prognostic feature for regression of UP. Despite improvement of UP, the 2 patients with SM with an associated hematologic disorder experienced a deterioration in clinical condition. In the 10 patients with indolent SM, severity and frequency of symptoms decreased as the UP regressed. However, bone marrow changes consistent with SM remained. Conclusions Urticaria Pigmentosa regresses in approximately 10% of the older patients who have SM. In patients with an associated hematologic disorder such as myelodysplasia, this regression may be accompanied by disease progression. In contrast, regression of UP in patients with indolent SM parallels a decrease in disease intensity, although bone marrow findings of indolent SM remain.