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Biomedical subjects

P E de Wit

Publications and source records attributed to P E de Wit.

8 recordsLinked to original sources
PubMed1999

Severe, non X-linked congenital microcephaly with absence of the pyramidal tracts in two siblings.

In two siblings (a female and a male neonate), severe microcephaly, bilateral absence of the pyramids, severe hypoplasia of the cerebral peduncles, and dysplasia of the inferior olives was found together with microphthalmia, facial malformations and multiple contractures of the extremities. In both cases, the cerebral hemispheres otherwise showed a more or less normal gyral pattern with the insula incompletely covered by the opercula, and a tom but otherwise intact corpus callosum. In case 2, congenital cataract was also observed. The present cases can be characterized as a rapidly fatal, familial syndrome, probably transmitted as an autosomal recessive trait, and have several features in common with the Neu-Laxova syndrome. They differ in having a less severe form of microcephaly, a rather normal cytoarchitecture of the cerebral cortex, an apparently normal corpus callosum, no gross cerebellar abnormalities, and no other organ malformations. The present cases belong to a group of heterogeneous syndromes which have microcephaly, ocular and facial malformations, multiple contractures, and ichthyosis-like skin in common.

Brain↗
PubMed1998

An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation.

Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied. In contrast to the first hit in the generally accepted two-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event leading to (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor-suppressor gene. The risk of developing renal cell cancer may be correlated directly with the extent of somatic (kidney) mosaicism resulting from this loss.

Carcinoma, Renal Cell↗
PubMed1993

Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

Diagnosis, Differential↗
PubMed1992

In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections.

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.

Aged↗
PubMed1992

Increasing epidermal growth factor receptor expression in human melanocytic tumor progression.

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.

Blotting, Northern↗
PubMed1990

Prevalence of naevocytic naevi after chemotherapy for childhood cancer.

The frequency of naevocytic naevi (moles) in patients with childhood haematologic malignancies was studied. All patients had received multiple chemotherapy. The majority had also received cranial irradiation as part of their central nervous system leukaemia/lymphoma prophylaxis. Total body mole counts of the patients were compared with those of their healthy brothers and sisters. The median number of moles in the patient group was 20.0 (n = 79), in the healthy sibs 11.0 (n = 88). In two subgroups mole counts of male and female patients were compared with those of their closet brother or sister. There were 19 male and 19 female pairs for comparison. Median numbers of moles were significantly higher in both patient groups than in the controls (P less than 0.05). It is suggested that multiple chemotherapy (and/or cranial irradiation) may induce or activate naevocytic naevi. These findings may have important implications with regard to the aetiology of melanoma.

Adolescent↗
PubMed1989

Racial differences in mole proneness.

Mole counts were studied in relation to skin complexion in various racial groups. White children had a median total number of naevocytic naevi of 17.0, versus 2.5 in non-white children (p less than 0.001). Young white adults showed a similar mole proneness to that of coloured subjects (61.0 versus 16.0; p less than 0.001). With regard to moles greater than 2 mm diameter in the young-adult group, white subjects again exhibited a higher median count than non-white subjects (5.5 versus 1.0; p less than 0.001). There was an inverse gradient of mole counts in young adults from subjects of white complexion through those of mixed ancestry, Oriental ancestry, to those of Negroid descent. This study indicates that there is a strong racial background predisposing to the development of naevocytic naevi.

Adolescent↗