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M Wolter

Publications and source records attributed to M Wolter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas.

We investigated 67 meningothelial tumors (20 benign meningiomas, 34 atypical meningiomas, and 13 anaplastic meningiomas) for losses of genetic information from chromosome arms 1p and 9p, as well as for deletion, mutation, and expression of the tumor suppressor genes CDKN2A (p16(INKa)/MTS1), p14(ARF), CDKN2B (p15(INK4b)/MTS2) (all located at 9p21) and CDKN2C (1p32). Comparative genomic hybridization and microsatellite analysis showed losses on 1p in 11 anaplastic meningiomas (85%), 23 atypical meningiomas (68%), and 5 benign meningiomas (25%). One atypical meningioma with loss of heterozygosity on 1p carried a somatic CDKN2C mutation (c.202C>T: R68X). Losses on 9p were found in five anaplastic meningiomas (38%), six atypical meningiomas (18%), and one benign meningioma (5%). Six anaplastic meningiomas (46%) and one atypical meningioma (3%) showed homozygous deletions of the CDKN2A, p14(ARF), and CDKN2B genes. Two anaplastic meningiomas carried somatic point mutations in CDKN2A (c.262G>T: E88X and c.262G>A: E88K) and p14(ARF) (c.305G>T: G102V and c.305G>A: G102E). One anaplastic meningioma, three atypical meningiomas, and one benign meningioma without a demonstrated homozygous deletion or mutation of CDKN2A, p14(ARF), or CDKN2B lacked detectable transcripts from at least one of these genes. Hypermethylation of CDKN2A, p14(ARF), and CDKN2B could be demonstrated in one of these cases. Taken together, our results indicate that CDKN2C is rarely altered in meningiomas. However, the majority of anaplastic meningiomas either show homozygous deletions of CDKN2A, p14(ARF), and CDKN2B, mutations in CDKN2A and p14(ARF), or lack of expression of one or more of these genes. Thus, inactivation of the G(1)/S-phase cell-cycle checkpoint is an important aberration in anaplastic meningiomas.

Adult↗
PubMed2001

Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease.

Cowden disease is an autosomal dominant syndrome characterized by facial trichilemmomas, acral keratoses, papillomatous papules, mucosal lesions, and an increased risk for breast and nonmedullary thyroid cancer. Here, we describe a novel PTEN splicing site mutation in a family with classical Cowden disease and we studied benign skin lesions typical for Cowden disease for loss of heterozygosity. We found a PTEN IVS2 + 1G > Alpha 5'-splicing acceptor mutation resulting in activation of a cryptic splice site. Activation of this cryptic splice site is predicted to result in a frameshift with a premature stop codon, thus disrupting the phosphatase core motif of PTEN. Loss of heterozygosity analysis of two trichilemmomas, one fibroma, and three acanthomas of the index patient demonstrated loss of heterozygosity at the PTEN locus in four of these lesions. In conclusion, our data demonstrate that a PTEN splicing site mutation causes activation of a cryptic splice site, which results in aberrant transcripts.

Aged↗
PubMed2001

Cutaneous mucinosis of infancy: is it a real entity or the paediatric form of lichen myxoedematosus (papular mucinosis)?

We describe a girl presenting with a childhood dermal mucinosis in which we had the unique opportunity to find all the transitional histological features of lichen myxoedematosus (papular mucinosis), from its early focal mucin deposition in the reticular dermis to its late findings of interstitial mucin deposition, dermal fibrosis and fibroblast proliferation. Her father reported having had similar lesions when he was a child, which completely disappeared during adolescence. This case, and a re-evaluation of the literature, suggests that cases of cutaneous mucinosis of infancy that are not hamartomatous conditions such as mucinous naevi are in fact the infantile presentation of lichen myxoedematosus (papular mucinosis) and, in addition to other cases in the literature, suggests a genetic and familial factor in lichen myxoedematosus (papular mucinosis).

Child↗
PubMed2001

Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases.

BACKGROUND: Sneddon's syndrome is defined as a combination of idiopathic livedo racemosa generalisata and symptoms of cerebrovascular defect. The disease usually starts with vascular symptoms in the epidermis, with neurological deficits becoming evident later. For this reason, histological examination of skin biopsies and determination of arteriolar occlusion is of particular importance for reliable categorization and early diagnosis. To date, these methods have been considered to be too insensitive. OBJECTIVES: To evaluate the sensitivity of skin biopsies in Sneddon's syndrome. METHODS: We took a total of five deep punch biopsies (4 mm) from different areas of the livedo (three from white and two from red areas) in 15 patients. Present knowledge of the pathogenic relationships and the particular anatomical features of the skin were taken into account. RESULTS: The method had a sensitivity of 27% with one biopsy, 53% with two biopsies and 80% with three biopsies taken from white areas in all cases. CONCLUSIONS: Skin biopsies using the method presented achieved a high sensitivity, suggesting that the diagnosis in clinically suspected cases could be confirmed in the majority of cases with this technique.

Adolescent↗
PubMed2001

Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model.

Psoriasis is a T-cell-mediated immune dermatosis probably triggered by bacterial superantigens. This pathomechanism has been experimentally reproduced in a SCID-hu xenogeneic transplantation model. We analyzed the effects of different bacterial superantigens on the induction of psoriasis in this model. Staphylococcal enterotoxin B and exfoliative toxin triggered the onset of psoriasis when administered repetitively intracutaneously over a period of 2 wk, whereas staphylococcal enterotoxin A representing a distinct subfamily of staphylococcal enterotoxins only mimicked certain aspects of psoriasis. The biologic effects of staphylococcal enterotoxin A were more pronounced when a mutated form, SEA(H187A), of this superantigen with reduced affinity to major histocompatibility complex class II was coinjected. Another mutated variant, SEA(F47A/D227A), exhibiting no measurable major histocompatibility complex class II affinity blocked the effects triggered by wild-type staphylococcal enterotoxin A when injected in a 10-fold higher dose. Inhibition was specific as induction of psoriasiform epidermal changes by staphylococcal enterotoxin B could not be blocked. As staphylococcal enterotoxin A, in contrast to the other superantigens tested, is capable of inducing epidermal thickening but not the typical appearance of psoriasis, we conclude that bacterial superantigens may differ with regard to their effects on human nonlesional psoriatic skin. Staphylococcal-enterotoxin-A-mediated effects were blocked by a genetically engineered superantigen highlighting the potential therapeutic use of mutated superantigens.

Animals↗
PubMed2001

Monitoring of phagocytic activity in histiocytic cytophagic panniculitis.

Histiocytic cytophagic panniculitis presents with subcutaneous panniculitis. Histologically, it is characterized by phagocytosis of blood cells in the subcutaneous tissue and bone marrow. One patient with histiocytic cytophagic panniculitis is described in whom hemophagocytosis macrophages and histiocytes was observed histologically and was confirmed in vitro measuring phagocytosis by peripheral blood monocytes by means of chemiluminescence. In vitro measurements of phagocytosis corresponded well with the clinical course. Chemiluminescence for measuring phagocytosis in vitro may be suitable for analyzing disease activity and for testing therapeutic compounds in vitro.

Adult↗
PubMed2001

Oligodendroglial tumors frequently demonstrate hypermethylation of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes.

We investigated 34 oligodendroglial tumors (7 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas) for deletion, mutation, hypermethylation, and expression of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes at 9p21. One anaplastic oligoastrocytoma carried a homozygous deletion including all 3 genes. None of the tumors demonstrated point mutations in any of the genes. Methylation-specific polymerase chain reaction (MSP) analysis and sequencing of bisulfite-modified DNA, however, revealed frequent hypermethylation of the 5'-CpG islands in CDKN2A, p14ARF, and CDKN2B. Partial or complete methylation of the majority of CpG sites analyzed from each gene was detected in 32% of the tumors at the CDKN2A gene and at a similar percentage (41%) of the tumors at the p14ARF gene and the CDKN2B gene. Most tumors with CDKN2A, p14ARF, and/or CDKN2B hypermethylation either lacked detectable transcripts from these genes or had lower mRNA levels than those determined for non-neoplastic brain tissue. There was a significant correlation between hypermethylation of these genes and the presence of allelic losses on chromosomal arms 1p and 19q. In addition, p14ARF hypermethylation was predominantly found in tumors without a demonstrated TP53 mutation. Taken together, our results indicate that hypermethylation of CDKN2A, p14ARF, and CDKN2B is an important epigenetic mechanism by which oligodendroglial tumors may escape from p53- and pRb-dependent growth control.

Adolescent↗
PubMed2001

Frequent c-myc amplification in high-grade dysplasia and adenocarcinoma in Barrett esophagus.

Barrett esophagus (BE) is a condition in which the normal squamous epithelium of the esophagus is replaced by a metaplastic columnar epithelium. BE is a premalignant lesion that represents the initial step in a metaplasia-dysplasia-carcinoma sequence. In the present study, amplification of the proto-oncogene c-myc was determined by means of differential polymerase chain reaction analysis of metaplastic specialized epithelium, low-grade dysplasia, high-grade dysplasia, and invasive adenocarcinoma obtained by microscopic dissection of 43 esophagectomy specimens. Amplification of c-myc was found in none of 29 specialized epithelial specimens, none of 23 low-grade dysplasia specimens, 6 of 24 high-grade dysplasia specimens, and 17 of 39 adenocarcinoma specimens. Our data indicate that amplification of c-myc is a late event in the metaplasia-dysplasia-carcinoma sequence in BE. Furthermore, determination of c-myc amplification may help identify high-risk patients who would benefit from intensified endoscopic surveillance or from immediate treatment.

Adenocarcinoma↗
PubMed2000

[Bilateral segmental neurofibromatosis simulating epidermal nevus].

Neurofibromatosis is a neuroectodermal systemic disease. A rare variant of this condition is bilateral segmental neurofibromatosis. A 29-year-old man presented with bilateral papillomatous plaques in the lumbar dermatomes. Clinically, the lesions were very similar to an epidermal nevus but histologic examination revealed superficial neurofibromas. Family history, ophthalmologic and neurologic investigations were unremarkable. The unusual morphologic presentation of bilateral segmental neurofibromas in this case points to the wide clinical spectrum of the disease and the significance of histologic examination in systematic nevoid lesions.

Adult↗
PubMed2000

[Diagnosis of body dysmorphic disorder. A pilot study].

The assessment of body dysmorphic disorder (BDD) is complicated by poorly defined diagnostic criteria and a lack of valid instruments. The present pilot study examines the possible benefit of specific instruments in the discrimination of other body image disorders. Thirteen patients with BDD, 13 with disfiguring defects, and 21 with no significant impairment of appearance participated in the study. The participants were recruited from dermatological outpatients on the basis of semistructured diagnostic interviews and clinical ratings of disfigurement. Furthermore, structured interviews were conducted to determine comorbidity with depressive disorders and social phobia and to obtain a clinical rating of obsessive-compulsive symptoms using the modified version of the YBOCS for body dysmorphic disorders. In addition, the Beck depression inventory, the Social Phobia Scale, and the Social Interaction Anxiety Scale were completed. Patients with BDD differed significantly from disfigured and unimpaired patients in obsessive-compulsive symptoms, in particular obsessions, and the discrepancy between personal and clinical rating of disfigurement. However, depression and social phobia scores were only higher in comparison with unimpaired patients. Comorbidity with depressive disorders was significantly increased. Our results support the utility of the specific diagnostic instruments and indicate the particular importance of obsessive-compulsive symptoms in BDD.

Adult↗
PubMed2000

Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas.

Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.

Adult↗
PubMed2000

Expression of the basal cell adhesion molecule (B-CAM) in normal and diseased human skin.

The basal cell adhesion molecule (B-CAM) is a 90-kD cell surface glycoprotein with a characteristic immunoglobulin domain structure. The pattern of B-CAM expression in cultured cells suggests that the molecule is associated with a substrate-adherent growth pattern in some lineages. We investigated the expression of B-CAM in normal and diseased human epidermis by means of immunohistochemistry employing a single batch of high-titer mouse monoclonal antibody G253. Snap-frozen biopsy material from normal skin (n = 8), psoriasis (n = 5), contact dermatitis (n = 6), basal cell carcinoma (n = 5) and fetal skin (n = 6) was studied. In normal human skin, B-CAM was found in varying degrees throughout the epidermis with a preference for suprabasal expression, hair follicles were regularly of a B-CAM-positive phenotype. There were no qualitative differences with regard to the B-CAM expression pattern in normal skin in comparison to psoriasis and contact dermatitis. In contrast, fetal skin (15th to 18th week of gestation) was characterized by B-CAM-positive cells in the basal layer of the epidermis as well as in the outer root sheath of hair follicles. Basal cell carcinomas also regularly expressed high levels of B-CAM. A strong B-CAM-positive phenotype can be found in the outer root sheath of hair follicles of adult and fetal human skin as well as in fetal basal keratinocytes.

Basal Cell Carcinoma↗
PubMed2000

Treatment of Birt-Hogg-Dubé syndrome with erbium:YAG laser.

We describe a female patient with Birt-Hogg-Dubé syndrome presenting with multiple, disfiguring papules on the cheeks, nose, and ears. In addition, there was evidence of photoaggravation and inflammatory processes in this case. The patient was treated with an erbium:YAG laser. Although the lesions could be successfully ablated up to the papillary dermis without scar formation, a relapse was observed after 6 months. Thus deeper laser ablations may possibly prevent relapses from dermal residual lesions.

Erbium↗
PubMed1999

Amplification and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplification.

We have previously reported on the amplification and overexpression of the MDM2 proto-oncogene in a subset of malignant gliomas without TP53 mutation (G. Reifenberger et al, Cancer Res., 53: 2736-2739, 1993). Here, we show that the MDM4 (MDMX) gene located on 1q32 is a further target for amplification in malignant gliomas. MDM4 codes for a Mdm2-related protein that can bind to p53 and inhibits p53-mediated transcriptional transactivation. We investigated a series of 208 gliomas (106 glioblastomas, 46 anaplastic gliomas, and 56 low-grade gliomas) and identified 5 tumors (4 glioblastomas and 1 anaplastic oligodendroglioma) with MDM4 amplification and overexpression. Several other genes from 1q32 were found to be coamplified with MDM4, such as GAC1 in five tumors, REN in four tumors, and RBBP5 in three tumors. Additional analyses revealed that the malignant gliomas with MDM4 amplification and overexpression carried neither mutations in conserved regions of the TP53 gene nor amplification of the MDM2 gene. Taken together, our data indicate that amplification and overexpression of MDM4 is a novel molecular mechanism by which a small fraction of human malignant gliomas escapes p53-dependent growth control.

Cell Division↗
PubMed1999

Expression of Bcl-2 and amplification of c-myc are frequent in basaloid squamous cell carcinomas of the esophagus.

Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare, poorly differentiated variant of typical esophageal squamous cell carcinoma (SCC) characterized by high proliferative activity and frequent spontaneous apoptoses. In the present study, we investigated the expression of the apoptosis-suppressing protein Bcl-2 in 23 BSCC of the esophagus and 23 stage-matched typical esophageal SCC by means of immunohistochemistry. In addition, amplification of the apoptosis- and proliferation-inducing gene c-myc was determined by means of differential polymerase chain reaction. Bcl-2 expression was found significantly more often in BSCC than in SCC (86.9% vs. 17.4%, P < 0.0001). Amplification of c-myc was nearly twice as common in BSCC as in SCC (47.8% vs. 26.1%, not significant). Bcl-2 protein expression together with c-myc amplification was detected in 43.5% of the BSCC but in none of the typical SCC (P < 0.0001). Taken together, our findings indicate that the molecular pathogenesis of esophageal BSCC differs from that of typical SCC and frequently involves coactivation of c-myc and Bcl-2.

Adult↗
PubMed1999

Ablative techniques in Psoriasis vulgaris resistant to conventional therapies.

BACKGROUND: Treatment of patients with psoriasis vulgaris exhibiting only solitary plaque-stage lesions might become difficult since topical treatments often fail and systemic therapies seem inappropriate. OBJECTIVE: We evaluated the feasibility of ablative techniques in this clinical setting comparing dermatome shaving to the application of an Er:YAG laser. METHODS: Six patients were treated by means of dermatome shaving; in four of these patients additional lesions were ablated utilizing an Er:YAG laser (2 J, 10 Hz, 5 mm spot size). RESULTS: Four of six patients experienced complete clearance of the lesions treated, three of the four patients receiving additional Er:YAG treatment also showed a complete clinical response. CONCLUSION: Our observations document that removal of epidermis and the papillary dermis is effective in treating recalcitrant psoriatic plaques. The Er:YAG laser represents a state-of-the-art device for performing this task. The beneficial effect on skin might be due to clearance of the putative autoantigen along with a considerable part of the potential effector cell population.

Debridement↗
PubMed1999

Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors.

Oligodendroglial tumors frequently show allelic losses on the short arm of chromosome 1. To narrow down the putative tumor suppressor gene site(s) on 1p, we have investigated 35 oligodendrogliomas and 10 mixed gliomas (oligoastrocytomas) for loss of heterozygosity (LOH) at 21 highly polymorphic loci on chromosome 1 (19 loci on 1p and 2 loci on 1q). LOH at loci on 1p was found in 30 of the 45 tumors (67%). Two distinct regions of common allelic loss were identified: a distal region between D1S76 and D1S253 at 1p36.3, and a proximal region between D1S482 and D1S2743 at 1p34-p35. We also analyzed our tumor series for genetic alterations and expression of the cyclin dependent kinase inhibitor gene CDKN2C (p18INK4c) from 1p32. We found 1 recurrent anaplastic oligodendroglioma that carried a somatic CDKN2C mutation at codon 113 (GAA ==> TAA: Glu ==> Stop). The remaining 44 tumors of our series showed neither coding sequence mutations nor homozygous deletions of CDKN2C. Investigation of 35 tumors by differential reverse transcription-PCR revealed expression of CDKN2C transcripts in all instances. Our data thus provide evidence for more than a single oligodendroglioma-associated tumor suppressor gene on 1p and implicate CDKN2C as a candidate tumor suppressor gene altered in a low fraction of oligodendroglial tumors.

Adult↗