[Pathogenesis, diagnosis and therapy of COPD].
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Bronchodilator Agents↗
Biomedical subjects
H Hamm
Publications and source records attributed to H Hamm.
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↗
Thrombin induces proteinase-activated receptor-1 gene expression in endothelial cells via activation of Gi-linked Ras/mitogen-activated protein kinase pathway.
We addressed the mechanisms of restoration of cell surface proteinase-activated receptor-1 (PAR-1) by investigating thrombin-activated signaling pathways involved in PAR-1 re-expression in endothelial cells. Exposure of endothelial cells transfected with PAR-1 promoter-luciferase reporter construct to either thrombin or PAR-1 activating peptide increased the steady-state PAR-1 mRNA and reporter activity, respectively. Pretreatment of reporter-transfected endothelial cells with pertussis toxin or co-expression of a minigene encoding 11-amino acid sequence of COOH-terminal Galphai prevented the thrombin-induced increase in reporter activity. Pertussis toxin treatment also prevented thrombin-induced MAPK phosphorylation, indicating a role of Galphai in activating the downstream MAPK pathway. Expression of constitutively active Galphai2 mutant or Gbeta1gamma2 subunits increased reporter activity 3-4-fold in the absence of thrombin stimulation. Co-expression of dominant negative mutants of either Ras or MEK1 with the reporter construct inhibited the thrombin-induced PAR-1 expression, whereas constitutively active forms of either Ras or MEK1 activated PAR-1 expression in the absence of thrombin stimulation. Expression of dominant negative Src kinase or inhibitors of phosphoinositide 3-kinase also prevented the MAPK activation and PAR-1 expression. We conclude that thrombin-induced activation of PAR-1 mediates PAR-1 expression by signaling through Gi1/2 coupled to Src and phosphoinositide 3-kinase, and thereby activating the downstream Ras/MAPK cascade.
Amino Acid Sequence↗
[Pilomatrix carcinoma in an unusual location. Case report and review of the literature].
A 58-year-old man developed an extensive pilomatrical carcinoma in the left axilla. Clinically, a squamous cell carcinoma was suspected. Histological examination revealed the presence of proliferating basaloid cells with many atypical mitoses and mass necrosis infiltrating into the subcutaneous tissue. The tumor was removed by micrographic surgery with a 2 cm safety margin. Histological examination of 2 regional lymph nodes as well as further diagnostic procedures ruled out metastases. We review the clinical and histopathological differences between pilomatricoma and pilomatrical carcinoma, as well as the published cases of the malignant variant.
Axilla↗
[Intertriginous acantholytic dyskeratosis: abortive form of Darier disease or a specific entity?].
A 69-year-old woman presented with widespread symmetrical papular lesions in submammary and inguinal areas. History revealed that the disease had only been present for a few years. A skin biopsy showed focal suprabasal acantholysis, dyskeratosis up to the horny layer and in part parakeratotic hyperkeratosis. The patient had no further evidence for Darier disease, Hailey-Hailey disease or pemphigus vegetans. In particular, characteristic lesions of Darier disease of hands and nails were absent. We found several reports in the literature describing similar skin lesions in intertriginous and genital areas with histological evidence of acantholytic dyskeratosis under various terms. This report discusses the difference between these cases and the differential diagnoses, in particular Darier disease. We propose to designate cases of intertriginous papulosis with histological proof of acantholytic dyskeratosis but without further evidence of Darier disease as intertriginous acantholytic dyskeratosis.
Acantholysis↗
Short duration treatment with terbinafine for tinea capitis caused by Trichophyton or Microsporum species. The Study Group.
Thirty-five patients with mycologically proven scalp infections were enrolled in a randomized, double-blind clinical trial with oral terbinafine (dose adjusted according to patient weight) for either 1 or 2 weeks. Patients were observed for 12 weeks; after 4 weeks, non-responders were offered an additional 4 weeks of treatment followed by a second observation period. The causative organisms were Microsporum canis (n = 12), Trichophyton tonsurans (n = 12) and other Trichophyton spp. (n = 11). The Trichophyton infections were treated effectively in five of nine (56%) patients treated for 1 week and 12 of 14 (86%) patients treated for 2 weeks. Three of the non-responders were treated for an additional 4 weeks, and one responded. In the Microsporum group only one of seven patients treated for 1 week and none of five treated for 2 weeks responded. However, treatment was effective in four of six (66%) patients treated for an additional 4 weeks. Mild to moderate adverse events believed to be drug related occurred in four patients in each of the two groups. Terbinafine is well tolerated, and requires 2 weeks of treatment in most patients with Trichophyton scalp infections and 4 weeks or more in Microsporum scalp infections, to achieve a successful clinical and mycological response.
Adolescent↗
Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype.
Monilethrix is an hereditary hair dystrophy recently shown to be due to mutations in the helix termination motif of two type II (basic) human hair keratin genes, hHb1 and hHb6. It has been suggested that mutation in hHb1 produces a less severe phenotype. We have studied hair keratin genes and clinical features in 18 unrelated pedigrees of monilethrix from Germany, Scotland, Northern Ireland, and Portugal, in 13 of which mutations have not previously been identified. By examining the rod domains of hHb1, hHb3 and hHb6, we have identified mutations in nine of the new pedigrees. We again found the glutamine-lysine substitution (E413K) in the helix termination motif of hHb6 in two families, and in another, the corresponding E413K substitution in the hHb1 gene. In four families a similar substitution E402K was present in a nearby residue. In addition two novel mutations within the helix initiation motif of hHb6 were found in Scottish and Portuguese cases, in whom the same highly conserved asparagine residue N114 was mutated to histidine (N114H) or aspartic acid (N114D) residues, respectively. In four other monilethrix pedigrees mutations in these domains of hHb1, hHb3, and hHb6 were not found. The mutations identified predict a variety of possible structural consequences for the keratin molecule. A comparison of clinical features and severity between cases with hHb1 and hHb6 mutations does not suggest distinct effects on phenotype, with the possible exception of nail dystrophy, commoner with hHb1 defects. Other factors are required to explain the marked variation in clinical severity within and between cases.
Amino Acid Sequence↗
A case of atypical pneumonia presenting with severe headache and disorientation. Diagnosis: Q fever (Coxiella burnetti).
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Headache↗
Roles of Gi and Gq/11 in mediating desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes.
Although desensitization of most guanine nucleotide-binding (G) protein receptors is triggered by phosphorylation of the receptor, desensitization of the LH/CG receptor (-R) in porcine follicular ovarian membranes appears to be independent of LH/CG-R phosphorylation. We therefore evaluated whether desensitization of the LH/CG-R reflected a direct inhibition of adenylyl cyclase (AC) activity by either the alpha-subunit of Gi or betagamma-subunits derived from any of the membrane G proteins activated in response to LH/CG-R activation or whether desensitization reflected a competition between Gs and a G protein that activated phospholipase C for binding sites on the LH/CG-R. The results showed that follicular membrane AC activity was not inhibited upon activation of the LH/CG-R despite evidence that the ACs in follicular membranes, when maximally activated by forskolin, could be inhibited when membrane G proteins were activated by guanyl-5'-yl imidodiphosphate, and that pertussis toxin pretreatment of membranes raised forskolin-stimulated AC activity, consistent with a tonic inhibition of follicular membrane AC activity. Similarly, agonist-stimulated desensitization of LH/CG-R-stimulated AC activity was not inhibited by pertussis toxin. Therefore, desensitization is not the result of inhibition of AC mediated by an inhibitory Gi subunit. Follicular membrane AC was also not inhibited by Gbetagamma subunits freed with activation of Gs Gq/11, or G13, based on the inabilities of exogenous Gbetagamma to promote desensitization and of a protein that sequesters Gbetagamma to inhibit desensitization. Desensitization was also not inhibited by a Gq/11 C-terminal peptide or antiserum directed toward the C-terminus of Gq/11, nor was it reversed with the addition of Gbetagamma to membranes exhibiting desensitized LH/CG-R, suggesting that desensitization is independent of coupling of the LH/CG-R to Gq/11. These results indicate that agonist-dependent desensitization of LH/CG-R-stimulated AC activity is mediated by a unique mechanism.
Adenylate Cyclase Toxin↗
Pronounced perifollicular lymphocytic infiltrates in alopecia areata are associated with poor treatment response to diphencyprone.
Some authors have reported that severe destruction of follicular structures and even scarring patterns occur in those patients with alopecia areata (AA) who fail to respond to topical immunotherapy with contact sensitizers, such as diphencyprone (DCP). Other studies, however, gave contradictory results. Therefore, we re-examined histopathological changes in scalp samples obtained from 85 patients with severe alopecia areata before initiation of DCP treatment (40 responders and 45 non-responders in terms of hair regrowth after DCP treatment). The following parameters were evaluated: i) perifollicular lymphocytic infiltration; ii) perifollicular fibrosis, and iii) miniaturized hair follicles. No difference between responders and non-responders could be observed in the degree of miniaturization of hair follicles and proliferation of perifollicular fibrous tissue. In neither group was there any evidence of scarring or severe follicular destruction. 18 non-responders but only 6 responders showed a very dense perifollicular lymphocytic infiltration. In contrast, a particularly scarce infiltrate was seen in 9 non-responders and in 19 responders. We conclude that non-responders to topical sensitizers tend to have rather pronounced inflammatory reactions with dense perifollicular lymphocytic infiltrates.
Administration, Topical↗
Point mutation in the helix termination peptide (HTP) of human type II hair keratin hHb6 causes monilethrix in five families.
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Alopecia↗
Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization.
The analysis of genetic changes in primary cutaneous melanoma has been limited by the need for fixation for diagnostic purposes. However, comparative genomic hybridization is able to analyze such specimens. We have applied comparative genomic hybridization to 32 primary melanomas to discover and map genomic regions with aberrant DNA copy numbers. The analysis was performed on native, nonamplified DNA extracted from manually dissected tumor sections. Loss of chromosome 9 was detected in 81% of the tumors, most commonly affecting the p arm. Additional common losses occurred on chromosomes 10 (63%), 6q (28%), and 8p (22%). Gains in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating areas harboring potential oncogenes were seen at 4q12, 5p14.3-pter, 7q33-qter, 8q12-13, 11q13.3-14.2, and 17q25. Correlations among the regions with copy number changes indicate that losses of chromosomes 9 and 10 occur early on in melanoma progression, whereas gains of chromosome 7 occur later. This sequence of events was further substantiated by an intratumoral comparison of copy number changes in areas with radial and vertical growth phase patterns. The overall pattern of regions affected by copy number changes is consistent with cytogenetic data from metastatic melanoma; however, the frequencies of involvement differ, providing further insight into the course of genetic events.
Age Factors↗
Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin.
OBJECTIVE: To evaluate the effect of intracutaneous injections of botulinum toxin type A on excessive focal hyperhidrosis. DESIGN: Therapeutic before-and-after trial over 4 months. SETTING: Neurological and dermatological university departments. PATIENTS: Eleven patients with excessive axillary, palmar, or plantar hyperhidrosis fulfilling the following criteria: (1) local and systemic drug therapy had failed to improve their symptoms; (2) the patients were severely disabled with respect to their occupation and social activities; and (3) a successful treatment by botulinum toxin would obviate the need for destructive surgical procedures. INTERVENTIONS: Three mouse units of botulinum toxin (Botox) per 4-cm2 skin area was injected intracutaneously in 16 axillae, 8 palms, and 2 soles. MAIN OUTCOME MEASURES: Reduction of hyperhidrosis as documented by the Minor iodine-starch test and gravimetrical assessment of local spontaneous sweat production measured over 1 minute. RESULTS: In all patients, botulinum toxin completely abolished sweating in the injected areas (P<.001) within 3 to 7 days. No relevant adverse effects occurred and no clinical recurrence of hyperhidrosis was observed within the follow-up period of up to 5 months. Occasionally, subclinical reactivation of sweat gland function was observed 4 months after treatment. CONCLUSIONS: Intracutaneous botulinum toxin seems preferable to any hitherto used conservative or surgical procedures and may become the therapy of choice in pathological focal hyperhidrosis.
Adult↗
[Annular erythema in childhood--a new eosinophilic dermatosis].
Annular erythema of infancy is a rare and little-known entity. Since its initial description by Peterson and Jarratt in 1981 only 4 further cases have been reported. We present the first case in the German literature. A 4-year-old boy developed non-itching erythematous papules on the trunk which evolved into annular and gyrate erythemas within weeks. The condition showed a relapsing course with disease-free intervals of several months duration. There were no general complaints. Laboratory investigations including detailed serological tests for infectious diseases were normal. Histopathology showed a striking eosinophilic inflammatory infiltrate predominantly in perivascular areas, without peripheral blood eosinophilia. The clinical differential diagnosis of annular erythema of infancy includes erythema annulare centrifugum, while microscopically one must exclude eosinophilic cellulitis (Wells' syndrome). The etiology is unknown and there is no effective therapy. In our case, as well as in all previously published cases, the disease resolved spontaneously. Therefore, it may be considered benign and self-limited.
Biopsy↗
[Linear and whorled nevoid hypermelanosis. Case report and review of the literature].
A 7 year old boy presented with linear and whorled nevoid hypermelanosis (LWNH). This entity, delineated in 1988, is characterized by streaked or whorled, frequently reticulate hyperpigmented lesions following the lines of Blaschko without preceding inflammation and without atrophy. The age of onset is usually within the first 2 years of life. Histologically, there is a mild basal cell hyperpigmentation with prominent melanocytes. In contrast to earlier reports, we observed some melanophages in the upper dermis. Associated abnormalities have been reported in a few patients, but were absent in our case. We present the clinical features, diagnostic criteria and differential diagnosis of this rare entity. Apparently, our patient represents the first case of LWNH in the German literature.
Basement Membrane↗
Congenital unilateral speckled lentiginous blue nevi with asymmetric spinal muscular atrophy.
We describe a 30-year-old man presenting with congenital widespread unilateral hyperpigmented areas on the right side of the face and limbs that were studded with multiple blue nevi. There was nevus of Ota-like scleral involvement of the right eye. Histologic examination showed common blue nevi, one in association with lentigo. For this unusual type of dermal melanocytosis we propose the term, congenital unilateral speckled lentiginious blue nevi. In addition, the patient had monomelic spinal muscular atrophy of his right shoulder girdle and arm.
Adult↗
Botulinum toxin for focal hyperhidrosis: technical considerations and improvements in application.
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Botulinum Toxins, Type A↗
Genitoanocrural porokeratosis following chronic exposure to benzene.
Porokeratoses are disorders of epidermal keratinization, the aetiology of which remains to be elucidated. We present the uncommon case of a 70-year-old man with genitoanocrural porokeratotic lesions successfully treated by CO2 laser vaporization. The patient's occupational history and the late onset, site and multiplicity of the lesions suggest their induction by benzene, a known carcinogen.
Aged↗