PubMed Health⌕ Search

Biomedical subjects

J J van den Oord

Publications and source records attributed to J J van den Oord.

At least 19 recordsLinked to original sources

Chronic radiodermatitis following percutaneous coronary interventions: a report of two cases.

We describe two patients in whom chronic radiodermatitis with therapy-resistant ulceration of the right scapular region developed, following percutaneous coronary intervention with fluoroscopic imaging. Contrary to most reported cases in the literature, which involve numerous cardiac catheterization procedures, in both patients described here the total radiation dose was given during two successive procedures, involving difficult and prolonged coronary intervention with stent implantation. In both cases, local treatment of the ulcerative lesions was insufficient, necessitating excision of the radiodermatitis area and replacement with a skin graft, with good therapeutic result. The incidence of radiodermatitis after percutaneous coronary interventions is rising with the increasing number and complexity of these procedures. The main risk factor is a long duration of fluoroscopy using the same incidence. The skin lesions encompass a wide spectrum, ranging from erythema, telangiectasia, atrophy, hyperpigmentation and hypopigmentation to necrosis, chronic ulceration and squamous cell carcinoma. The lesions can appear from 15 days to 10 years after the procedure. To prevent radiation-induced injury, the radiation dose has to be limited and monitored. Also, careful inspection of the skin at the site of exposure is necessary and the radiographic beam has to be restricted to the smallest field size. A good clinical follow-up at regular intervals is important after long and complicated procedures.

Aged↗

Expression of neurotrophins and their receptors in pigment cell lesions of the skin.

The neurotrophins (NTs) are a group of growth factors involved in the development of the nervous system and presumed to play a role in neural crest-derived tumours. The expression of three NTs (NGF, BDNF, and NT-3) and their receptors (NTRs; i.e. low-affinity pan-NT receptor p75, Trk-B, and Trk-C) was studied in frozen sections of benign and malignant cutaneous pigment cell lesions, using immunohistochemistry. In order to understand the possible role of these growth factors and their receptors in the progression of primary cutaneous malignant melanomas (PCMMs), their distribution in the radial (RGP) and vertical (VGP) growth phases was particularly studied. While most of the common acquired naevi were unreactive, Spitz and blue naevi showed scattered immunoreactive cells, especially for the p75 NTR. Dysplastic naevi, but not common naevi, expressed NT-3 in their junctional component. PCMM and melanoma metastases often showed a diffuse pattern of immunostaining. NT-3 was significantly more frequently expressed in the RGP of PCMMs than in the junctional component of benign naevi, whereas more extensive immunoreactivity for NGF was found in the VGP of PCMMs, compared with the RGP; metastases more frequently expressed NGF, BDNF, and Trk-B than PCMMs. Interestingly, neurotropic melanoma expressed all NTs/NTRs except Trk-B. These immuunohistochemical data confirm suggestions from previous in vitro studies that autocrine loops of certain NTs and their respective receptors may be involved in melanoma progression; in addition, NT-3 may be involved in the junctional growth of dysplastic naevi. The precise role of these growth factors in melanoma, however, will await further functional studies.

Disease Progression↗

Microstaging in cutaneous melanoma.

Recent papers have addressed critical issues regarding the microstaging of cutaneous melanoma. They concern the new staging proposal by the American Joint Committee on Cancer (AJCC), the presentation of new prognostic models than seem applicable in daily practice, and new immunohistochemical findings than demonstrate prognostic information independently of the conventional major factors. These issues are commented on by the Pathology Committee of the EORTC Melanoma Group.

Biomarkers, Tumor↗

Expression of the endothelin-B receptor in pigment cell lesions of the skin. Evidence for its role as tumor progression marker in malignant melanoma.

Endothelins (ETs) exert several functions in human melanocytes, including proliferation, dendrite formation, and melanin synthesis. Among the ET receptors, the non-selective endothelin-B (ETB) receptor is the major receptor in melanocytes and malignant melanoma (MM) cells. In spite of the important role of ETs and their receptors in the growth and differentiation of melanocytes, the distribution and expression levels of ETB receptors in tissue sections of benign and malignant pigment cell lesions is still unknown. We combined immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to study ETB receptor expression in benign and malignant pigment cell lesions and in normal skin. Immunohistochemistry on paraffin-embedded tissue sections of 159 cases revealed a significant increase in intensity of ETB receptor expression from common nevi over dysplastic nevi and primary MM to metastatic MM. Quantitative PCR using realtime detection on 75 samples confirmed the immunohistochemical results. These data add the ETB receptor to the growing list of tumor progression markers in MM and suggest that ETs play a role in the progression of MM in the skin.

Biomarkers, Tumor↗

Analysis of N- and K-ras mutations in the distinctive tumor progression phases of melanoma.

Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the "intraepidermal" radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma.

Disease Progression↗

Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin.

Expression of activated leukocyte cell adhesion molecule (ALCAM)/CD166 correlates with the aggregation and metastatic capacity of human melanoma cell lines (Am J Pathol 1998, 152:805-813). Immunohistochemistry on a series of human melanocytic lesions reveals that ALCAM expression correlates with melanoma progression. Most nevi (34/38) and all thin melanomas studied (Clark levels I and II) did not express ALCAM. In contrast, immunoreactivity was detected in the invasive, vertical growth phase of 2 of the 13 Clark level III lesions tested. The fraction of positive lesions further increased in Clark level IV (13/19) and in Clark level V (4/4) lesions. ALCAM expression was exclusively detectable in the vertical growth phase of the primary tumor. In melanoma metastases, approximately half of the lesions tested (13/28) were ALCAM positive. According to the Breslow-thickness, ALCAM expression was observed in less than 10% of the lesions that were thinner than 1.5 mm and in over 70% of the lesions that were thicker than 1.5 mm. Our results strongly suggest that ALCAM plays an important role in melanocytic tumor progression and depict it as a new molecular marker for neoplastic progression of primary human melanoma.

Activated-Leukocyte Cell Adhesion Molecule↗

Minimal deviation and/or naevoid melanoma: is recognition worthwhile? A clinicopathological study of nine cases.

One to two per cent of primary cutaneous melanomas share clinical features with benign melanocytic and non-melanocytic skin lesions, and even at histology recognition of their malignant nature is problematic, mainly due to the lack of an intraepithelial component, their nodular aspect and the monotonous cell population throughout the lesion. These tumours were termed minimal deviation melanomas (MDMs) by Reed et al. and later naevoid melanomas by Schmoeckel et al. The name MDM suggests the concept of a more favourable outcome for these melanomas that do not (yet) show the typical features of fully evolved lesions able to metastasize, although naevoid melanomas seem to behave like 'common' melanomas. In a retrospective analysis of nine cases of MDM collected from our database and followed for a median duration of 112 months, we faced similar clinical and histological pitfalls and observed local recurrence following marginal resection. Wide excision, even of local recurrence, and therapeutic node dissection could nevertheless provide survival comparable at least to that predicted by mathematical models for patients who initially had optimal treatment.

Adult↗

Representational difference analysis using minute quantities of DNA.

Representational difference analysis (RDA) is a differential hybridization method which can effectively isolate unique DNA sequences from complex and highly related genomes or cDNA libraries. A major drawback of the RDA analysis is the requirement for pure driver and relatively pure tester samples, ruling out the analysis of whole tissue biopsies. To circumvent this problem, we have modified the technique for the analysis of very small quantities of DNA so that pure cell populations isolated by micromanipulation from tissue sections can be analyzed. Using this modified technique, as few as 50 diploid cells ( approximately 500 pg of DNA) can be analyzed.

DNA↗

Prognostic significance of nm23 protein expression in malignant melanoma. An immunohistochemical study.

The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not all cancers in man. To investigate the role of NM23 in the progression of human malignant melanoma, we studied the expression and distribution of the nm23 protein with a sensitive immunohistochemical technique and a well-characterized monoclonal antibody in 41 benign pigment cell lesions and 71 uniformly treated malignant melanomas with a long follow up-up. In benign naevi, the junctional nests frequently expressed nm23 protein, whereas the immunoreactivity tended to decrease when the lesions matured. All malignant melanomas expressed nm23 protein in their vertical and/or radial growth phases, and the immunoreactivity tended to increase towards the deeper parts of the lesion. No relation was found between nm23 expression and patient outcome. In addition, nm23 was found in activated lymphoid cells, and this feature was significantly associated with a brisk lymphocytic stroma response in malignant melanomas. Our data are at variance with previous mRNA studies on malignant melanoma, and indicate that routine immunohistochemical analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be used as a prognostic marker for patients suffering from malignant melanoma. In contrast, our findings suggest that the nm23 protein in pigment cell lesions is related to the proliferative or activated state of pigment cells, rather than to their metastatic potential.

Adult↗

Vascular wound healing and neointima formation induced by perivascular electric injury in mice.

Vascular interventions for atherothrombotic disease frequently induce neointima formation, which can contribute to restenosis of blood vessels. As the molecular mechanisms of this process remain largely unknown, quantitative models of arterial injury in transgenic animals may be useful to study this process at the genetic level. Here, an injury model is proposed in which surgically exposed femoral arteries in mice were injured perivascularly via a single delivery of an electric current. Transmission electron microscopy, light microscopy, and immunohistochemistry revealed that electric injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and transiently induced platelet-rich mural thrombosis. A vascular wound-healing response resulted that was characterized by degradation of the mural thrombus, transient infiltration of the vessel wall by inflammatory cells, and progressive removal of the necrotic debris. Topographic analysis revealed repopulation of the media and accumulation in the neointima of smooth muscle cells originating from the uninjured borders and progressing into the necrotic center. Within 3 weeks after injury, a neointima of 0.026 +/- 0.003 mm2 (n = 7 arteries) was formed that contained a maximum of 12 +/- 1 layers of smooth muscle alpha-actin-immunoreactive cells. Evans blue staining in five electrically injured arteries revealed a denuded distance of 2.8 +/- 0.2 mm immediately after injury, which became progressively re-endothelialized from the uninjured borders to 2.2 +/- 0.08 mm (P = 0.013 vs freshly injured by analysis of variance), 0.8 +/- 0.22 mm (P < 0.001), and 0.005 +/- 0.003 mm (P < 0.001) within 2, 7, and 14 days after injury, respectively. Analysis of 5'-bromo-2'-deoxyuridine incorporation revealed that a maximum of 35 +/- 10% endothelial cells proliferated within 2 days after injury and that in the media and neointima, a maximum of, respectively, 12 +/- 2% and 18 +/- 3% smooth muscle cells proliferated within 2 weeks after injury. Thus, electric injury of arteries provides a model of vascular wound healing with arterial neointima formation and re-endothelialization that may be useful for the genetic analysis of its molecular mechanisms in transgenic mice.

Animals↗

Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin.

By the degradative effect on basement membrane collagen type IV, matrix metalloproteinases (MMPs) or gelatinases are important in the early invasion of malignant tumors. These enzymes may be released by the tumor cells themselves or may be derived from nearby fibroblasts that have been stimulated by the extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd gelatinase B (MMP-9) and of EMMPRIN in 33 benign and 41 malignant, paraffin-embedded pigment cell lesions using immunohistochemistry and monoclonal antibodies. In benign pigment cell lesions, EMMPRIN but not gelatinase B was expressed in cellular blue nevi whereas all other benign lesions, including common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B and EMMPRIN were variably expressed in the pure and invasive radial growth phase but not in the vertical growth phase. All lentigo maligna cases and all metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63% expressed gelatinase B and 70% expressed EMMPRIN, whereas in MMs with > 1.6 mm thickness, only 10% expressed gelatinase B and only 25% expressed EMMPRIN. We conclude that early invasion of MM is associated with de novo expression of gelatinase B and EMMPRIN by neoplastic melanocytes. Expression of EMMPRIN and MMP-9 may be partly responsible for the stromal changes observed in thin MM. Their absence in the vertical growth phase and in metastatic lesions suggests that other factors are involved in tissue degradation during later stages of tumor progression in MM. The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to the indolent behavior of this type of pigment cell lesion.

Antigens, CD↗

Results of histo-pathologic examination of three enucleated eyes with a choroidal melanoma after strontium-90 irradiation.

Three patients with a choroidal melanoma, treated with HDR (High Dose Rate) Strontium-90 brachytherapy, underwent an enucleation. Radiation effect was only visible at the irradiation zone with a brisk transition to normal tissue. Tumour was replaced by necrotic and scar tissue. The underlying sclera had a markedly reduced number of fibrocytes, but no structural alteration of the collagen stroma.

Aged↗

Small, freshly arrived histiocytes in cutaneous and mucosal herpetic lesions.

We report on the predominance of a special type of small histiocyte in the inflammatory infiltrate accompanying herpetic bullae. These histiocytes, which have previously been taken to be neutrophils, are freshly arrived cells with a hitherto unknown function. Until now, they have been found only in Sweet's syndrome and erythema nodosum where they form Miesscher's radial granulomas. Similar small histiocytes were found in half of those herpetic lesions with intact bullae, and in over two-thirds of ulcerated lesions in which these cells formed a palisade in the fibrinoid material covering the floor of the ulcerated vesicles. Small histiocytes, admixed with neutrophils, were in close proximity to virally infected keratinocytes. Immunohistochemical analysis confirmed their histiocytic nature. With the exception of ecthyma contagiosum (orf), similar small histiocytes were not found in other viral infections or in nonspecific ulcers of the skin. In cases of herpetic folliculitis, small histiocytes showed massive epidermotropism towards hair follicle epithelium. We conclude that cutaneous and oral herpetic infections represent yet another disease in which small, freshly arrived histiocytes occur. They may be involved in antigen presentation, or in killing of infected keratinocytes.

Antigens, CD↗

CD40 is a prognostic marker in primary cutaneous malignant melanoma.

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.

Biomarkers, Tumor↗

Immunopathogenesis of vernal keratoconjunctivitis.

We have analyzed the in situ distribution of immune cells in the conjunctival biopsy specimens obtained from patients with active vernal keratoconjunctivitis (VKC). We used immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies. Our data point to a complex immunopathogenesis of the disease. Distinct components involved in IgE-mediated immune mechanisms, as well as humoral and cell mediated immune mechanisms were detected in the conjunctival tissues. In addition, we investigated the presence and distribution of adhesion molecules. In the normal conjunctiva, intercellular adhesion molecule-1 (ICAM-1) was expressed only on the vascular endothelium, lymphocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-3 (ICAM-3) on epithelial and stromal mononuclear cells, and very late activation antigen-4 (VLA-4) on a few stromal mononuclear cells. Endothelial leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression was not detected. In VKC a marked increase of all these antigens was observed. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelium. Furthermore, about 30% of the stromal mononuclear cells expressed ICAM-1. LFA-1 and ICAM-3 were expressed on the majority of infiltrating mononuclear cells. VLA-4 expression was noted on about 25% of the stromal mononuclear cells. ELAM-1 and VCAM-1 were induced on the vascular endothelial cells. Our results suggests that increased expression of adhesion molecules in VKC promotes the recruitment of inflammatory cells through blood vessels and the cell interaction between lymphocytes and antigen presenting cells, among lymphocytes, as well as between lymphocytes and epithelial cells.

Antigens, CD↗

Linear IgA dermatosis: a new cause of fever of unknown origin.

We describe a 60-year-old patient who presented with prolonged fever, weight loss, adenopathies and malaise. Two months later, an aphthous stomatitis and pharyngitis developed, together with ulcerations bilaterally in the groin. Two separate skin biopsies revealed the diagnosis of linear IgA dermatosis. This entity, which is well known to dermatologists but not to internists, should be added to the extensive list of disorders than can provoke the syndrome of fever of unknown origin.

Autoimmune Diseases↗