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Biomedical subjects

D Verhoeven

Publications and source records attributed to D Verhoeven.

16 recordsLinked to original sources
PubMed2006

Gene expression profiling of gut mucosa and mesenteric lymph nodes in simian immunodeficiency virus-infected macaques with divergent disease course.

BACKGROUND: Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. METHODS: We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. RESULTS: Chronically SIV-infected macaques with disease progression had high viral loads and CD4(+) T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4(+) T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. CONCLUSIONS: Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques.

Animals↗
PubMed1995

Vegetable and animal products as determinants of colon cancer risk in Dutch men and women.

To examine the relationship between colon cancer and food groups from vegetable or animal sources and their possible interactions with gender, we analyzed data from a Dutch case-control study. Dietary patterns were assessed for 232 colon cancer cases and 259 population controls. In multivariate analyses, the consumption of vegetables was associated significantly with reduced colon-cancer risk (odds ratio [OR] for highest cf lowest quartile of consumption = 0.4, 95 percent confidence interval [CI] = 0.2-0.7, P-trend = 0.0004). Consumption of fresh red meat was associated positively with risk in women (OR = 2.4, 95% CI = 1.0-5.7, P-trend = 0.04), especially for those with a high consumption of red meat relative to the consumption of vegetables and fruits (OR = 3.1). For men, no association with consumption of fresh red meat was found (OR = 0.9). No clear associations were found for other products of vegetable or animal origin. The results of this Dutch case-control study support the preventive potential of a high-vegetable diet in colon cancer risk. This study suggest this may be important for women consuming a diet high in red meat.

Aged↗
PubMed1995

Microvessel quantification in primary colorectal carcinoma: an immunohistochemical study.

The vascularisation of human primary colorectal carcinomas was studied immunohistochemically using the endothelial cell markers CD31 and factor VIII-related antigen. Tumour sections were systematically scanned at a magnification of x 100 to find areas of intense neovascularisation. Microvessel counts within these vascular 'hotspots' were performed at magnification x 250. Regions in which tumour cords were surrounded by a collagen IV-positive basement membrane were compared with those in which this was absent and with normal mucosa. CD31 appeared to be a more sensitive marker for endothelial cells than factor VIII-related antigen (mean 185 +/- 59 and 120 +/- 38 microvessels mm-2). Within individual tumour sections microvessel counts in vascular hotspots with highest vessel density correlated significantly with microvessel counts in vascular hotspots with second highest vessel density (P < 0.01). Microvessel counts in tumour areas where collagen IV-positive basement membrane were absent exceeded those in areas where it was present (factor of 1.7) and those in normal mucosa (factor of 1.6). The differences in vessel density between individual tumours and the low variability in vessel density within individual tumours using this quantification technique allow us to investigate the prognostic value of vessel density in areas of intense neovascularisation in human primary colorectal carcinomas.

Adult↗
PubMed1995

Microvessel density, endothelial cell proliferation and tumour cell proliferation in human colorectal adenocarcinomas.

BACKGROUND: Thymidine incorporation studies performed in animal tumour models, revealed major differences in endothelial cell proliferation when tumour tissue was compared with normal tissue. The fraction of proliferating endothelial cells is reported to be increased by a factor of 30 to 40 in tumour tissue. PATIENTS AND METHODS: To make it possible to analyze the endothelial cell proliferation in human tumours, an immunohistochemical double staining technique comprising CD31, an endothelial cell marker, and Ki-67, a proliferation marker, was developed. Endothelial cell proliferation was analysed in 21 primary human colorectal adenocarcinomas and in the adjacent mucosa. RESULTS: Proliferating endothelial cells were found throughout the entire carcinoma. The mean overall endothelial cell labeling index (ECLI) was 9.9% (range, 5.4-18.0), and the labeling index of endothelial cells in areas of intense neovascularisation was even higher. Mean ECLI in the vascular hot spots was 21.0% (range, 6.8-35.0), and the mean tumour cell labeling index (TCLI) in the maximally Ki-67 immunostained areas was 78.3% (range 47.0-89.7). In 14 of 21 carcinomas, these areas were predominantly found at the luminal margin of the tumour, as were the vascular hot spots. A significant positive correlation was found between tumour vascularity, measured in the vascular hot spots, and tumour cell proliferation, measured in the maximally Ki-67 immunostained areas (p < 0.05). To analyse this relation in more detail, microvessel density (MVD), TCLI and ECLI were determined per x400 microscopic field by scanning in sequence from the luminal tumour margin to the invasive tumour base. In all tumours, the pattern of the MVD per x400 field, from the luminal margin to the tumour base, was similar to that of the TCLI and ECLI. CONCLUSIONS: These findings confirm that the fraction of cycling endothelial cells is higher in human colorectal carcinoma than in the adjacent mucosa which suggests that endothelial cells are proliferating in most of the individual capillaries in tumour tissue. Regional differences in MVD correlate with differences in tumour cell proliferation in these tumours.

Adenocarcinoma↗
PubMed1993

Ultrastructural demonstration of type IV collagen deposits in periductal elastosis in breast cancer.

In a previous study we demonstrated at light microscopical level the presence of variable amounts of type IV collagen in the areas of periductal and interstitial elastosis in breast cancer. The present work was directed towards a further study by immunoelectron microscopy of the distribution of type IV collagen in the areas of periductal elastosis. The semithin sections showed a distinct immunoreactivity of all basement membranes for type IV collagen but no staining of the interstitial stroma. Corresponding ultrathin sections demonstrated a broad basement membrane with immunoreactivity for type IV collagen at its outer side. Many punctiform deposits of type IV collagen were observed in the areas of periductal elastosis but not around normal ducts or vessels. Recently the role of type IV collagen as a structural component on anchoring plaques between the basement membrane and the underlying stroma in the dermis has been emphasized. The results of this study demonstrate the presence of type IV collagen deposits below a thickened basement membrane in breast cancer.

Breast Neoplasms↗
PubMed1993

Proliferation, basement membrane changes, metastasis and vascularization patterns in human breast cancer.

Tumour cell proliferation shows a heterogeneous intratumour distribution. By comparison with the infiltrating component of breast cancers, the intraductal component has a significantly lower proliferation index. The cells at the periphery of infiltrating tumour strands have a higher proliferation activity than the cells in the core. A variable turn-over of basement membrane material is reported in infiltrating cancers. Increased amounts of type IV collagen are demonstrated in areas of periductal elastosis and of interstitial elastosis in breast cancer. Important parallels are found between metastatic tumour cells and the macrophages acting in the process of inflammation. We found evidence that displacements of tumour cells and macrophages are similar. Studies of vascularization in transplanted tumours cannot be extrapolated to man. A striking heterogeneity in the organization of vessels and in the expression of some markers is observed in human breast cancer.

Basement Membrane↗
PubMed1990

Comparison of cell growth in different parts of breast cancers.

This study was performed to answer the question: which parts of breast cancers are active in terms of proliferation as measured by the Ki-67 antibody and in terms of cell division as measured by the mitotic index. Forty-six breast samples were studied, including 34 breast cancers and 12 benign conditions. The intraductal component of infiltrating breast cancers showed a significantly lower proliferation index than the infiltrating component. The cells at the periphery of infiltrating tumour strands showed a higher proliferation activity than the cells in the core. These findings suggest that infiltration advances through preferential active growth of the cells at the invasion front.

Antigens, Surface↗
PubMed1990

The presence of a type IV collagen skeleton associated with periductal elastosis in breast cancer.

Using serial sections of frozen and AFA-fixed tissues from 34 breast cancers, we studied the presence of basement membrane material in the areas of elastosis. Various amounts of type IV collagen but not of laminin were demonstrated in areas of periductal elastosis. In some tumors, type IV collagen accumulated beneath the basement membrane. Periductal elastosis in areas of extensive fibrosis showed focal type IV collagen immunoreactivity, indicating remnants of ducts. Interstitial elastosis corresponded with weak type IV collagen reactivity. Each tumor showed type IV collagen immunostaining of the elastotic areas, with various degrees of intensity. Negative crossreactivity of the type IV collagen antibody with elastin was verified in skin biopsies with solar elastosis. Pre-incubation of the antibody with large amounts of elastin demonstrated an identical immunoreactivity. The specificity of the antibody was confirmed by ELISA and by Western blot analysis. To explain the periductal elastosis, we propose the following hypothesis. Excessive production of basement membrane material by the epithelial cells of the ducts leads to formation of a type IV collagen skeleton. This skeleton can act as the matrix for a secondary deposition of elastic material.

Basement Membrane↗
PubMed1988

Desmin-positive stellate cells associated with angiogenesis in a tumour and non-tumour system.

The angiogenesis induced after implantation of fragments of the Walker 256 carcinoma was compared with the angiogenesis following implantation of different amounts of Indian ink. Morphologically and chronologically the tumour system showed no difference from the Indian ink system, provided sufficient amounts of ink were implanted. Both systems were characterized by significant macrophage infiltration. The vascular development, which was clearly concentrated in a dense rim around the tumour, remained present when the tumour enlarged, suggesting an acquisition of vasculature by the tumour through vessel incorporation and not vessel ingrowth. Initially, scattered desmin-positive cells, in contact or encircled by collagen IV, were found in the developing angiogenic rim. Later many desmin-positive cells were found around vessels and could be identified by electron microscopy as pericytes. They exhibited close local contacts with endothelial cells. After incorporation of the peritumour vascular rim into the tumour the number of pericytes decreased and their shape became flattened and elongated.

Animals↗