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Biomedical subjects

M Wolter

Publications and source records attributed to M Wolter.

At least 55 records · Page 3Linked to original sources
PubMed1999

Photoallergic skin reaction to ribavirin.

A 65-yr-old woman with chronic hepatitis C was treated with three million units interferon-alpha t.i.w. and 1000 mg ribavirin daily. At wk 16 of combination therapy the patient developed an itchy eczematous erythema, partly of urticarial character, which was almost confined to ultraviolet (UV)-exposed sites. Histopathological examination of the skin lesions was consistent with a photoallergic reaction. The minimal erythematous dose for UVA and UVB was assessed on healthy skin. After 24 h, a distinct erythema at the UVB irradiated site was found, whereas no reaction was seen with UVA provocation up to a dose of 10 J/cm2. Correspondingly, determination of the absorption spectrum of ribavirin revealed maximum absorption within UVB at 282.5 nm. Ribavirin was stopped, and the cutaneous lesions and pruritus completely disappeared without subsequent hyperpigmentation. This case indicates that ribavirin is a potential photosensitizer for UVB, which may become increasingly relevant in patients with chronic hepatitis C undergoing combination therapy for 6-12 months with interferon-alpha and ribavirin.

Aged↗
PubMed1999

Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity.

Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.

Adult↗
PubMed1999

Submammary granular parakeratosis: an acquired punctate hyperkeratosis of exogenic origin.

Granular parakeratosis is a histologic phenomenon that produces a characteristic clinical picture with multiple brownish and hyperkeratotic papules. In all 6 published cases of localized axillary parakeratosis, excessive use of different topical preparations (cream-type products, deodorants that include roll-on and stick types, antiperspirants, shampoos, bath soaps) was reported by the authors. The exact pathogenic causal relationships have not yet been resolved. In the case reported below, we demonstrate for the first time that the macro- and micromorphological entities can also occur in the submammary region.

Adult↗
PubMed1999

Mid-dermal elastolysis associated with Hashimoto's thyroiditis.

We report the case of a 38-year-old Caucasian female presenting asymptomatic plaques of fine wrinkling and perifollicular papular protrusions especially on the trunk. Histological examination evidenced loss of elastic fibers in the mid-dermis due to elastophagocytosis, with giant cells and granuloma formation. Moreover, elevated titers of thyroid autoantibodies were detected and thyroid ultrasound revealed echo-poor tissue. These findings met the diagnoses of mid-dermal elastolysis and Hashimoto's thyroiditis. This association has not been reported before. We present a comprehensive overview of the literature and discuss the pathogenetic aspects of mid-dermal elastolysis and the significance of the association with Hashimoto's thyroiditis.

Adult↗
PubMed1998

Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.

About one-third of sporadic basal cell carcinomas (BCCs) of the skin and 10-15% of primitive neuroectodermal tumors (PNETs) of the central nervous system show mutations in the PTCH tumor suppressor gene. The PTCH gene product (Ptch) functions as a transmembrane receptor for the Sonic hedgehog protein (Shh) and interacts with another transmembrane protein called Smoh. To further elucidate the significance of alterations in the Shh signaling pathway, we investigated 31 sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, and GL11. In addition, we fine-mapped the SMOH gene locus by fluorescence in situ hybridization to chromosomal band 7q32. Mutational analysis identified four BCCs with somatic missense mutations in SMOH affecting codon 535 (TGG==>TTG: Trp==>Leu) in three tumors and codon 199 (CGG==>TGG: Arg==>Trp) in one tumor. A missense mutation at codon 533 (AGC==>AAC: Ser==>Asn) was found in one PNET. PTCH mutations were detected in eight BCCs and one PNET. Two BCCs demonstrated mutations in both SMOH and PTCH. The majority of tumors showed an increased expression of SMOH, PTCH, and GL11 transcripts as compared with that of normal skin and nonneoplastic brain tissue, respectively. In contrast, only one BCC and one PNET expressed SHH mRNA at levels detectable by reverse transcription-PCR, and no SHH gene mutations were found. In summary, our results indicate that both PTCH and SMOH represent important targets for genetic alterations in sporadic BCCs and PNETs.

Adolescent↗
PubMed1998

Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q.

The PTEN (MMAC1) gene, which has been identified as a tumor suppressor gene at 10q23.3, is mutated in multiple malignant tumors, including glioblastomas [J. Li et al., Science (Washington DC), 275: 1943-1947, 1997; P. A. Steck et al., Nat. Genet., 15: 356-362, 1997]. Among tumors of the central nervous system, loss of 10q is not restricted to glioblastomas but is also common in atypical and anaplastic meningiomas. Therefore, we have investigated 36 glioblastomas and 34 meningiomas (2 benign, 17 atypical, and 15 anaplastic meningiomas) for loss on 10q, as well as deletion, mutation, and expression of PTEN. Analysis of eight microsatellites from 10q revealed loss of heterozygosity (LOH) in 25 of 36 glioblastomas (69%). Twenty-three of these tumors demonstrated LOH at all informative loci. Two glioblastomas showed LOH restricted to markers located distally to PTEN, with breakpoints mapping telomeric to D10S541 and D10S185. One glioblastoma demonstrated evidence of homozygous deletion of PTEN by differential PCR analysis. PTEN mutations were detected in 9 of 36 glioblastomas (25%). Seven of these tumors showed LOH at all informative loci from 10q, indicating complete loss of wild-type PTEN. Although loss of 10q was detected by comparative genomic hybridization and/or LOH analysis in 14 of the 34 meningiomas investigated (41%), none of these tumors showed evidence of PTEN mutations or homozygous gene deletions. Our findings corroborate that PTEN is inactivated in a subset of glioblastomas. However, the lack of detectable PTEN alterations in a considerable fraction of glioblastomas and all meningiomas with 10q loss strongly supports the hypothesis that at least one additional tumor suppressor gene is located on 10q.

Adolescent↗
PubMed1998

L-tryptophan-related eosinophilia-myalgia syndrome possibly associated with a chronic B-lymphocytic leukemia.

A female patient presenting with B-CLL and coincident eosinophilia-myalgia syndrome (EMS) after ingestion of L-tryptophan is described. The manifestations of EMS disappeared completely during treatment with cyclophosphamide/prednisone. and there was an intermittent clinical remission of CLL with absence of the monoclonal B-cell population. A few years later, the B-CLL relapsed, but without sign and symptoms of EMS. Whereas other eosinophilic syndromes such as eosinophilic fasciitis, panniculitis, or cellulitis Wells have been found to occur in relation to malignant underlying diseases, only a single patient with malignant fibrous histiocytoma following EMS has been described. There are no reports about an increased occurrence of B-CLL or other non-Hodgkin's lymphomas combined with or following EMS or related to L-tryptophan itself. The variant types of eosinophilic syndromes occurring due to malignant disorders, the differentiation from EMS, and the possible association between B-CLL and L-tryptophan-related EMS are discussed.

Adult↗
PubMed1998

[Coincidence of balloon cell melanoma with balloon cells in a dermal nevus].

We report a coincidence of balloon cell melanoma and balloon cell transformation in a dermal nevus of a 56 years old female patient. The foamy cells in both tumors with different dignity expressed S-100 and Vimentin. HMB45 was expressed in all balloon cells of the melanoma. Detection of HMB45 in some of the nevus-associated balloon cells was considered as an expression of cellular activation.

Antigens, Neoplasm↗
PubMed1998

Dermatomyositis presenting as plaque-like mucinosis.

We describe two women, aged 65 and 37 years, who presented with mucinous plaques as the initial skin signs of dermatomyositis. Other cutaneous manifestations were lacking, but typical myositis appeared later in the course of the disease.

Adult↗
PubMed1998

DNA content and cell proliferation in giant congenital melanocytic naevi (GCMN). An analysis by image cytometry.

GCMN may be precursors of melanoma, and it has been suggested that the presence of atypical foci could increase the risk of malignant transformation. In order to better define atypical GCMN, we analyzed DNA content and proliferative activity in 21 samples of GCMN, with (n=13) or without (n=8) cytologic atypia. Six benign acquired naevi (AN) and 6 malignant melanoma (MM) were used as controls. DNA content was determined with the CAS 200 image analyzer, and DNA histograms were classified according to the Auer classification. The proliferative indices (PI) were measured after Ki 67 immunostaining using the CAS 200 system. All AN and GCMN without atypia showed class I histograms (normal DNA content) and low PI (mean 1.9 and 2.1). Atypical GCMN showed in 10 cases an abnormal DNA content (class III or IV histograms) with low PI (mean 2.7), and in 3 cases a normal DNA content (class I histograms) with higher PI (mean 16.2). All MM displayed abnormal DNA content and high PI (mean 32.6). In conclusion, abnormal DNA content seems to correlate with cytologic atypia in GCMN. Atypical GCMN exhibit an overall pattern of DNA content and cell proliferation intermediate between non-atypical naevi and MM.

Cell Division↗
PubMed1998

Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL.

Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A, CDKN2A, MDM2, MYC, RB1, REL, and TP53. The gene found to be altered most frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%) hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL without homozygous CDKN2A loss revealed methylation of the CpG island within exon 1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA expression was performed for 11 tumors and showed either no or weak signals. Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either completely negative or showed expression restricted to single tumor cells. None of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1 revealed no amplification, rearrangement or overexpression. The retinoblastoma protein was strongly expressed in all tumors. Only one PCNSL showed a mutation of the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG:Arg to Trp). No evidence of BCL2 gene rearrangement was found in 11 tumors investigated. The bcl-2 protein, however, was strongly expressed in most tumors. None of the 20 PCNSL demonstrated gene amplification of MDM2, MYC or REL. In summary, inactivation of CDKN2A by either homozygous deletion or DNA methylation represents an important molecular mechanism in PCNSL. Mutation of the TP53 gene and alterations of the other genes investigated appear to be of minor significance in these tumors.

Aged↗
PubMed1998

Focusing on resistance development in a case based teleconsultation system for antibiotics therapy advice.

In this paper, we describe an approach to support physicians when they select a calculated antibiotic therapy for intensive care patients who have developed an infection as an additional complication. As advice is needed quickly and the pathogen is not yet known, we use an expected pathogen spectrum based on medical background knowledge and known resistances, which both will be adapted to the results of the laboratory. Case-Based Reasoning retrieval methods provide the advice for similar previous patients. Their solutions are adapted to be applicable to the new medical situation of the current patient. Furthermore, we present the recent resistance developments of the antibiotics to the physician.

Anti-Bacterial Agents↗
PubMed1997

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.

Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII, and 13.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was loss on 22q (58%). In MII, aberrations most commonly identified were losses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9q (33%), and 17q (33%). In MIII, most of these alterations were found at similar frequencies. However, an increase in losses on 6q (53%), 10 (68%), and 14q (63%) was observed. In addition, 32% of MIII demonstrated loss on 9p. Homozygous deletions in the CDKN2A gene at 9p21 were found in 4 of 16 MIII (25%). Highly amplified DNA sequences were mapped to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor revealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q were found to be amplified in 1 MII and 8 MIII, involving 17q23 in all cases. Despite the high frequency of chromosomal aberrations in the MII and MIII investigated, none of these tumors showed mutations in exons 5-8 of the TP53 gene. On the basis of the most common aberrations identified in the various malignancy grades, a model for the genomic alterations associated with meningioma progression is proposed.

Adult↗
PubMed1997

Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.

The human homologue of the Drosophila segment polarity gene patched (PTCH) has recently been identified as the tumor suppressor gene responsible for the nevoid basal cell carcinoma (BCC) syndrome (H. Hahn et al., Cell, 85: 841-851, 1996; R. L. Johnson et al., Science (Washington DC), 272: 1668-1671, 1996). In addition to multiple BCCs, patients with nevoid BCC syndrome have a predisposition for the development of primitive neuroectodermal tumors (PNETs) of the central nervous system. We have analyzed 9 sporadic BCCs and 37 PNETs for mutation and expression of the PTCH gene. PTCH mutations were found in 3 BCCs (33.3%) and in 5 PNETs (14%), including 1 of 5 cerebral PNETs, 2 of 15 medulloblastomas, and 2 of 17 desmoplastic medulloblastomas. The sequence changes in six of these tumors (four PNETs, two BCCs) were mutations predicted to result in truncated proteins. Missense mutations were detected in one PNET and one BCC each. In addition, novel sequence polymorphisms were found in exon 2, intron 5, intron 10, and intron 14 of PTCH. Reverse transcription-PCR analysis revealed increased PTCH expression levels compared to nonneoplastic brain tissue and normal skin in the majority of PNETs and BCCs investigated. Our data suggest that genetic alterations of PTCH are not only of significance in hereditary and sporadic BCCs but are also involved in the molecular pathogenesis of a subset of sporadic central nervous system PNETs.

Adolescent↗
PubMed1997

The barley Mlo gene: a novel control element of plant pathogen resistance.

Mutation-induced recessive alleles (mlo) of the barley Mlo locus confer a leaf lesion phenotype and broad spectrum resistance to the fungal pathogen, Erysiphe graminis f. sp. hordei. The gene has been isolated using a positional cloning approach. Analysis of 11 mutagen-induced mlo alleles revealed mutations leading in each case to alterations of the deduced Mlo wild-type amino acid sequence. Susceptible intragenic recombinants, isolated from mlo heteroallelic crosses, show restored Mlo wild-type sequences. The deduced 60 kDa protein is predicted to be membrane-anchored by at least six membrane-spanning helices. The findings are compatible with a dual negative control function of the Mlo protein in leaf cell death and in the onset of pathogen defense; absence of Mlo primes the responsiveness for the onset of multiple defense functions.

Amino Acid Sequence↗