Treatment of axillary hyperhidrosis.
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Botulinum Toxins, Type A↗
Biomedical subjects
H Hamm
Publications and source records attributed to H Hamm.
Activation of the luteinizing hormone/choriogonadotropin hormone receptor promotes ADP ribosylation factor 6 activation in porcine ovarian follicular membranes.
Previously we demonstrated in a cell-free ovarian follicular plasma membrane model that agonist-dependent desensitization of the luteinizing hormone/choriogonadotropin receptor (LH/CG R) is GTP-dependent, mimicked by the addition of ADP-ribosylation factor (ARF) nucleotide binding site opener, which acts as a guanine nucleotide exchange factor for ARFs 1 and 6, and selectively inhibited by synthetic N-terminal ARF6 peptides. We therefore sought direct evidence that activation of the LH/CG R promotes activation of ARF1 and/or ARF6. Using a classic ARF activation assay, the cholera toxin-catalyzed ADP-ribosylation of G alpha(s), results show that LH/CG R activation stimulates an ARF protein by a brefeldin A-independent mechanism. Synthetic N-terminal inhibitory ARF6 but not ARF1 peptide blocks LH/CG R-stimulated ARF activity. LH/CG R activation also promotes the binding of a photoaffinity GTP analog to a protein that migrates on one- and two-dimensional polyacrylamide gel electrophoresis with ARF6. These results suggest that ARF6 is the predominant ARF activated by the LH/CG R. To activate ARF6, the LH/CG R does not appear to signal through the C-terminal regions of G alpha(i) or G alpha(q) or through the second or third intracellular loops or the N terminus of the cytoplasmic tail of the LH/CG R. Although exogenous recombinant ARNO promotes only a small increase in ARF6 activation in the presence of activated LH/CG R, hCG-stimulated ARF6 activation is reduced to basal levels by catalytically inactive ARF nucleotide binding-site opener. These results provide direct evidence that LH/CG R activation leads to the activation of membrane-delimited ARF6.
ADP-Ribosylation Factor 6↗
Trichorhinophalangeal syndrome type I: clinical and molecular characterization of 3 members of a family and 1 sporadic case.
BACKGROUND: Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant disorder clinically characterized by sparse and slow-growing hair, pear-shaped nose, elongated philtrum, thin upper lip, and bone deformities, in particular, cone-shaped epiphyses of the phalanges. Very recently, the responsible gene TRPS1 has been cloned on human chromosome 8q24. OBSERVATION: We describe a mother and her 2 daughters and a female patient with a sporadic case of TRPS I. In the familial case, mutation analysis showed an insertional mutation at position 2480 of the TRPS1 gene leading to a premature translational stop. Careful clinical examination showed craniofacial and radiologic features typical of TRPS I, including short stature, in all 3 affected individuals. Additionally, they presented with a receded triangular medio-occipital hairline, which has not been described in TRPS I so far. In the sporadic case, we identified a single base deletion at position 2110 of the TRPS1 gene leading to frameshift and premature translational stop at codon 766. The patient presented with the typical TRPS I phenotype but was of normal stature. CONCLUSIONS: The TRPS I is characterized by variable clinical expression of the triad of hair, craniofacial, and skeletal abnormalities. New genetic approaches, including mutation analysis, now allow identification of carriers of the TRPS1 gene mutations.
Abnormalities, Multiple↗
[Cystic papules on the breast of a 35-year-old woman].
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Adenoma, Sweat Gland↗
[Hornstein-Knickenberg and Birt-Hogg-Dube syndrome. Report of a case with spontaneous pneumothorax and aplasia of the left internal carotid artery].
A 36-year-old man presented with multiple skin-colored papules on his face, neck and back of several years duration. His father, sister and probably his grandfather suffered from similar skin lesions. The histological examination revealed fibrofolliculomas in all three cases. At the age of 33 years the patient developed a spontaneous pneumothorax, and one year later a subarachnoidal hemorrhage due to aplasia of the left carotid artery. His grandfather had died from metastatic rectal carcinoma. A diagnosis of Hornstein-Knickenberg-/Birt-Hogg-Dubé syndrome was made, which is characterized by fibrofolliculomas and colon adenomas. Our familial observation speaks in favor of autosomal dominant transmission of the Hornstein-Knickenberg-/Birt-Hogg-Dubé syndrome. Apart from the skin several other organs may be involved, including the kidneys, urogenital tract, eyes and endocrine system. By this report we wish to draw intention to the typical skin lesions which can be the marker for neoplasia and other characteristic associated findings.
Adult↗
[Erythroderma after corticosteroid withdrawal in papulosquamous dermatosis in children. Diagnosis: pityriasis rubra pilaris, classic juvenile type].
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Acitretin↗
D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade.
In spite of the recognition that striatal D(2) receptors are critical determinants in a variety of psychomotor disorders, the cellular mechanisms by which these receptors shape neuronal activity have remained a mystery. The studies presented here reveal that D(2) receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca(2+) currents through L-type Ca(2+) channels, resulting in diminished excitability. This modulation is mediated by G(beta)(gamma) activation of phospholipase C, mobilization of intracellular Ca(2+) stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D(2) receptors in striatal medium spiny neurons, this novel signaling linkage provides a foundation for understanding how this pivotal receptor shapes striatal excitability and gene expression.
Action Potentials↗
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.
Adolescent↗
Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin.
Acral melanoma (AM) is commonly distinguished from superficial spreading melanoma (SSM), the most common type of melanoma, by its clinical presentation as well as its ethnic distribution. However, justification for such a distinction is controversial because of histological overlap and lack of prognostic significance. We analyzed chromosomal aberrations of 15 AMs and 15 SSMs that were comparable for tumor thickness and patient age, using comparative genomic hybridization. All AMs had at least one (mean, 2.0) gene amplification, significantly more than the SSMs, in which only 2 of 15 (13%) had one amplification each (P < 0.0001). At least 15 different genomic regions were amplified in AM. These involved small portions of chromosomal arms, sometimes including known oncogenes implicated in melanoma. The most frequently amplified regions in AMs occurred at 11q13 (47%), 22q11-13 (40%), and 5p15 (20%). Comparison of the amplification levels of invasive and noninvasive portions of the tumors using fluorescence in situ hybridization suggested that amplifications occurred before the formation of the invasive portion. The finding of amplifications of 11q13 in three of five additional cases of AM in situ further supports the notion that amplifications arise early in the progression of AM. Very significantly, we found isolated melanocytes with amplifications in the epidermis up to 3 mm beyond the histologically recognizable extent of the melanomas in 5 of 15 invasive AMs. In conclusion, our data show that AM is a distinct type of melanoma characterized by focused gene amplifications occurring early in tumorigenesis, and that malignant cells are present beyond the histologically detectable boundary, thereby revealing one mechanism of local recurrence.
Chromosome Mapping↗
Isolated congenital nail dysplasia: a new autosomal dominant condition.
OBJECTIVE: Developmental nail abnormalities are extremely heterogeneous, with hereditary isolated conditions being a small and rare subgroup. An unusual congenital nail dysplasia observed in a large South German kindred was characterized clinically to review the question of uniqueness. DESIGN: Case series of affected family members. SETTING: University department of dermatology and houses of patients. PATIENTS: The history and clinical features in 22 affected family members (13 females and 9 males, aged 5 to 74 years) were recorded and documented by photographs. Nail biopsy samples were taken from 2 patients. INTERVENTIONS: None. RESULTS: The pedigree spanning 5 consecutive generations was best compatible with autosomal dominant inheritance with complete penetrance. Nail alterations were mostly present since birth and soon reached an individually variable degree of severity. Affected persons showed longitudinal streaks and thinning of nail plates, mostly of all fingernails and toenails, with some accentuation of the thumbnail and big toenails, poorly developed lunulae, longitudinal angular ridges of individual nail plates occasionally starting proximally from a reddish prominence, platonychia and koilonychia of individual nails often overgrowing the lateral folds, and notches and fissures of the free margins. Histological abnormalities included a prominent granular layer of the nail matrix and epithelial strands and buds extending from the nail bed. There were no associated anomalies. Other nail dystrophies were excluded by differences in clinical and histological features. CONCLUSION: The nail abnormality observed in our family represents a new autosomal dominant disorder for which we propose the term isolated congenital nail dysplasia. Arch Dermatol. 2000;136:1239-1243
Adolescent↗
Bullous pemphigoid of childhood: autoantibodies target the same epitopes within the NC16A domain of BP180 as autoantibodies in bullous pemphigoid of adulthood.
BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the elderly that rarely occurs in children. Most adult BP serum samples react with epitopes within the NC16A domain of BP180, a glycoprotein of the cutaneous basement membrane zone. OBJECTIVES: To characterize the autoimmune response in childhood BP using recombinant forms of BP180 and to determine the subclass distribution of autoantibodies and their correlation with disease activity. OBSERVATIONS: Serum samples from 2 infants with BP, aged 4 and 5 months, reacted by immunoblot analysis with 4 epitopes clustered within the N-terminal 45 amino acids of the NC16A domain. The same 4 epitopes have previously been shown to be the target in adult BP. Childhood BP antibodies to BP180 NC16A belonged to IgG1, IgG2, IgG3, and IgG4 immunoglobulin subclasses. IgE reactivity was not detected. Serum levels of antibodies targeting BP180 NC16A paralleled disease activity as detected by enzyme-linked immunosorbent assay. CONCLUSIONS: The fine specificity of autoantibodies to BP180 is the same in BP of childhood and adulthood. Childhood BP is a true variant of BP.
Adult↗
[Subepidermal bullous autoimmune dermatosis with linear deposition of IgA amd IgG].
A 29-year-old female patient with an autoimmune subepidermal blistering disease had linear deposits of both IgA and IgG at the basement membrane zone. Clinically, the patient presented with tense blisters on the face, trunk, extremities and oral mucosa. Histologically, we found a subepidermal blister formation and a predominantly neutrophilic infiltrate. Direct immunofluorescence showed linear deposits of IgA along the basement membrane zone, as well as linear deposits of IgG and C3 as typically found in bullous pemphigoid. Indirect immunofluorescence demonstrated circulating IgA and IgG autoantibodies. This case extends previous reports on a subgroup of patients with subepidermal blistering diseases characterized by the presence of both IgA and IgG anti-basement membrane antibodies. These patients reveal clinical, histological and immunopathological features of linear IgA disease and bullous pemphigoid.
Adult↗
Effective treatment of frontal hyperhidrosis with botulinum toxin A.
BACKGROUND: Focal hyperhidrosis is a common condition mostly confined to the axillae, palms and soles. In some individuals, predominantly men, increased sweating of the forehead may be the major complaint and may interfere with the person's quality of life. Botulinum toxin A has been shown to be a very effective treatment for focal hyperhidrosis of the axillae and palms. OBJECTIVES: To assess the response in 10 men suffering from frontal hyperhidrosis treated with botulinum toxin A. METHODS: Botulinum toxin A Botox was injected at multiple sites evenly distributed over the forehead (mean dose 86 mouse units). RESULTS: The mean +/- SEM amount of sweat was significantly reduced, 4 weeks after treatment, from 173.8 +/- 38.6 mg min(-1) to 53.7 +/- 17.6 mg min(-1). The effect lasted at least 5 months in nine of the 10 patients. All patients subjectively judged the treatment as very effective. Minor side-effects included painful injections and a transient weakness of forehead muscles without ptosis. CONCLUSIONS: In this study, we provide evidence that botulinum toxin A is an effective and safe treatment for frontal hyperhidrosis.
Adult↗
Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells.
The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.
Adult↗
Assignment of the gene for a new hereditary nail disorder, isolated congenital nail dysplasia, to chromosome 17p13.
Isolated congenital nail dysplasia is an autosomal dominant disorder recently observed in a large family from southern Germany. The disorder is characterized by longitudinal streaks, thinning, and impaired formation of the nail plates leading to increased vulnerability of the free nail margins. In most cases, all fingernails and toenails are similarly involved with some accentuation of the thumb and great toenails. Histologic changes include hypergranulosis of the nail matrix and epithelial outgrowths from the nail bed. Patients do not show any alterations of hair growth and dentition, no malfunction of sweat glands and sensory organs, and no skeletal abnormalities. Isolated congenital nail dysplasia manifests from the first year of life with variable expressivity. In order to localize chromosomally the gene underlying isolated congenital nail dysplasia, linkage to the known keratin gene cluster regions on chromosomes 12q12 and 17q21 was ruled out first. The analysis of 150 microsatellite markers on various chromosomes mapped the isolated congenital nail dysplasia gene to the 6 cM interval between markers at D17S926 and D17S1528 on chromosome 17p13. Markers at D17S849, D17S 1840, and D17S1529 co-segregated completely with the isolated congenital nail dysplasia locus. The maximum two-point LOD score was found for the marker at D17S 1840 (Zmax = 6.72 at Thetamax = 0.00). The identified region harbors no currently known genes involved in skin or nail abnormalities. Isolated congenital nail dysplasia probably represents a novel isolated defect of nail development. The localization of this gene is, therefore, the first step towards the identification of a new factor in nail formation.
Child↗
Mutation reports: epidermolysis bullosa simplex associated with severe mucous membrane involvement and novel mutations in the plectin gene.
We report a novel case of epidermolysis bullosa simplex with severe mucous membrane involvement and mutations in the plectin gene (PLEC1). The patient suffered from extensive blistering of the skin and oral and laryngeal mucous membranes. Electron microscopy of a lesional skin biopsy showed cleft formation within the basal cell layer of the epidermis. Antigen mapping displayed entirely negative staining for plectin, a large (>500 kDa) multifunctional adhesion protein present in hemidesmosomes of the basal keratinocytes. Mutation analysis revealed compound heterozygous, previously undisclosed nonsense mutations, Q1713X and R2351X, of paternal and maternal origin, respectively, within exon 32 of PLEC1. Based on earlier reports, plectin deficiency is associated with late onset muscular dystrophy in patients with epidermolysis bullosa. No signs of muscle weakness have been observed during the 4 y follow-up of our patient. This case illustrates the fact that molecular pathological analyses have prognostic implications in identification and evaluation of patients who appear to be at risk for development of muscular dystrophy later in life.
Biopsy↗
[Pathogenesis, diagnosis and therapy of COPD].
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Bronchodilator Agents↗
Cutaneous mosaicism of lethal mutations.
The concept of autosomal lethal genes surviving only in a mosaic state was proposed by Happle to explain the genetic basis of several syndromes characterized by (almost always) sporadic occurrence, distribution of lesions in a scattered or asymmetrical pattern, variable extent of involvement, lack of diffuse involvement of entire organs, and equal sex ratio. The mosaic may either arise from a gametic half-chromatid mutation or from an early postzygotic mutation. The purpose of this article is to review current knowledge of the genetics and cutaneous manifestations of some of the birth defects to which the lethal gene concept is thought to apply: the Schimmelpenning (Feuerstein-Mims) syndrome, Proteus syndrome, encephalocraniocutaneous lipomatosis, Sturge-Weber and Klippel-Trenaunay syndrome, cutis marmorata teleangiectatica congenita (van Lohuizen syndrome), and neurocutaneous melanosis.
Abnormalities, Multiple↗