Objective Until today, the true pathophysiology of hemorrhoidal disease (HD) has not yet been unr... more Objective Until today, the true pathophysiology of hemorrhoidal disease (HD) has not yet been unraveled. More and more evidence guides us towards the hypothesis that reduced connective tissue stability is associated with a higher incidence of hemorrhoids. The present study aimed to compare the quantity and quality of collagen, and vessel morphometrics, in patients with symptomatic HD compared with normal controls. Methods Twenty-two samples of grade III and grade IV HD tissue from patients undergoing a hemorrhoidectomy between January 2004 and June 2015 were included in the study group. Samples of 15 individuals without symptomatic HD who donated their body to science and died a natural death served as controls. The quantity and quality of anal collagen, and anal vessel morphometrics were objectified. The quality of collagen was subdivided in young (immature) and old (mature) collagen. Results Patients with HD had an increased percentage of total anal collagen (62.1 ± 13.8 versus 18...
Journal of Molecular and Cellular Cardiology, Sep 1, 1997
Fibronectin is a known chemoattractant for several cell types which play a role in the wound heal... more Fibronectin is a known chemoattractant for several cell types which play a role in the wound healing process, like fibroblasts, endothelial cells and macrophages. In addition, fibronectin generates a scaffold to which other extracellular matrix components can attach. The possible involvement of fibronectin in the wound healing process after myocardial infarction (MI) was investigated by studying the expression of fibronectin isoforms after induction of a MI in the rat. Deposition of plasma (pFN) and cellular fibronectin (cFN) protein was determined immunohistochemically, using monoclonal antibodies specific for cFN and polyclonal anti-human total FN (tFN antibodies). Expression of the mRNAs of total cFN and the embryonic isoforms EIIIA and EIIIB was investigated, using in situ hybridization (ISH). The ratio between EIIIA containing fibronectin (EIIIA+-FN) mRNA and total cFN mRNA was determined using a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). cFN protein was present from day 4 until day 35 after infarction and was located around the area of infarction, in the epi- and endomyocardium and in the wall of larger vessels. pFN was found in the infarcted cardiomyocytes 1 day after the induction of the MI. From day 4 on pFN protein deposition was found in the border zone of the infarction and in the wall of larger vessels. pFN immunoreactivity remained present at high levels around the area of infarction and in the vessel wall throughout the entire period of investigation (90 days). From day 35 after the infarction pFN protein was detected in cardiomyocytes of the right ventricle and septum. cFN mRNA, determined by in situ hybridization, was present in the border zone of the infarcted area as early as 1 day after MI, and its expression peaked at 4 days after MI. Four days after MI the mRNA's coding for both the embryonic isoforms EIIIA and EIIIB could also be detected in the same area. Because expression of the EIIIA isoform was more abundant than the EIIIB isoform we only determined the percentage of the EIIIIA containing isoform from total FN. EIIIA+ mRNA was elevated 1 day after MI. We conclude that various fibronectin isoforms including the embryonic isoforms accumulate in the heart after MI. This suggests that these isoforms may play a role in the wound healing process in the left ventricle of the infarcted heart.
Basement membrane (BM) deposition at the inter-face of tumor cells and stroma was studied in 27 b... more Basement membrane (BM) deposition at the inter-face of tumor cells and stroma was studied in 27 bronchogenic squamous cell carcinomas. Specimens from peripheral and central parts of each tumor were collected. These were frozen, formalin fixed and paraffin embedded or fixed in Karnovsky's fixative, and processed for electron microscopy. With the use of antibodies to type IV collagen and laminin, the BM was visualized by light microscopy with an indirect immunoperoxidase technique. Light microscopic findings were compared to ultrastructural observations. The peripheral parts of the tumors showed continuous BM in a recognizable preexisting alveolar pattern without evidence of invasive growth into the alveolar septa. In contrast, central parts showed highly variable BM deposition ranging from continuous to almost completely absent. Alveolar patterns were not observed in the tumor centers. The stromal compartment of the tumor centers contained many spindle cells with irregular pericellular BM-like material that could be identified ultrastructurally as myofibroblasts. Electron microscopy and immunohistochemistry yielded virtually identical results. It is concluded that invasive growth in bronchogenic squamous cell carcinomas occurs in central parts of the tumor when the tumor periphery shows expansive growth without invasion of alveolar septa. The situation is different in invasive squamous cell carcinomas originating from other organs because of anatomical differences between the lung and solid organs.
Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molec... more Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study was designed to study the role of MMP-2, MMP-8, and MMP-9 in human infarct rupture. Heart samples were obtained from patients who died from infarct rupture and control MI patients. The MMP activity was determined by zymography and quantitative immunocapture activity assay. TIMP-1 levels were measured and immunohistochemistry for MMP-2 and MMP-9 was performed. The amounts of both total and active MMP-8 and MMP-9 were significantly higher in ruptured infarct tissue than in control MI tissue, but no differences in MMP-2 activity were observed. Furthermore, the number of inflammatory cells was significantly higher in the ruptured infarcts than in control infarcts. These data suggest that increased MMP-8 and MMP-9 activity in the infarct area, caused by a more prominent infiltration of inflammatory cells, contribute to infarct rupture in humans.
Objective Until today, the true pathophysiology of hemorrhoidal disease (HD) has not yet been unr... more Objective Until today, the true pathophysiology of hemorrhoidal disease (HD) has not yet been unraveled. More and more evidence guides us towards the hypothesis that reduced connective tissue stability is associated with a higher incidence of hemorrhoids. The present study aimed to compare the quantity and quality of collagen, and vessel morphometrics, in patients with symptomatic HD compared with normal controls. Methods Twenty-two samples of grade III and grade IV HD tissue from patients undergoing a hemorrhoidectomy between January 2004 and June 2015 were included in the study group. Samples of 15 individuals without symptomatic HD who donated their body to science and died a natural death served as controls. The quantity and quality of anal collagen, and anal vessel morphometrics were objectified. The quality of collagen was subdivided in young (immature) and old (mature) collagen. Results Patients with HD had an increased percentage of total anal collagen (62.1 ± 13.8 versus 18...
Journal of Molecular and Cellular Cardiology, Sep 1, 1997
Fibronectin is a known chemoattractant for several cell types which play a role in the wound heal... more Fibronectin is a known chemoattractant for several cell types which play a role in the wound healing process, like fibroblasts, endothelial cells and macrophages. In addition, fibronectin generates a scaffold to which other extracellular matrix components can attach. The possible involvement of fibronectin in the wound healing process after myocardial infarction (MI) was investigated by studying the expression of fibronectin isoforms after induction of a MI in the rat. Deposition of plasma (pFN) and cellular fibronectin (cFN) protein was determined immunohistochemically, using monoclonal antibodies specific for cFN and polyclonal anti-human total FN (tFN antibodies). Expression of the mRNAs of total cFN and the embryonic isoforms EIIIA and EIIIB was investigated, using in situ hybridization (ISH). The ratio between EIIIA containing fibronectin (EIIIA+-FN) mRNA and total cFN mRNA was determined using a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). cFN protein was present from day 4 until day 35 after infarction and was located around the area of infarction, in the epi- and endomyocardium and in the wall of larger vessels. pFN was found in the infarcted cardiomyocytes 1 day after the induction of the MI. From day 4 on pFN protein deposition was found in the border zone of the infarction and in the wall of larger vessels. pFN immunoreactivity remained present at high levels around the area of infarction and in the vessel wall throughout the entire period of investigation (90 days). From day 35 after the infarction pFN protein was detected in cardiomyocytes of the right ventricle and septum. cFN mRNA, determined by in situ hybridization, was present in the border zone of the infarcted area as early as 1 day after MI, and its expression peaked at 4 days after MI. Four days after MI the mRNA's coding for both the embryonic isoforms EIIIA and EIIIB could also be detected in the same area. Because expression of the EIIIA isoform was more abundant than the EIIIB isoform we only determined the percentage of the EIIIIA containing isoform from total FN. EIIIA+ mRNA was elevated 1 day after MI. We conclude that various fibronectin isoforms including the embryonic isoforms accumulate in the heart after MI. This suggests that these isoforms may play a role in the wound healing process in the left ventricle of the infarcted heart.
Basement membrane (BM) deposition at the inter-face of tumor cells and stroma was studied in 27 b... more Basement membrane (BM) deposition at the inter-face of tumor cells and stroma was studied in 27 bronchogenic squamous cell carcinomas. Specimens from peripheral and central parts of each tumor were collected. These were frozen, formalin fixed and paraffin embedded or fixed in Karnovsky's fixative, and processed for electron microscopy. With the use of antibodies to type IV collagen and laminin, the BM was visualized by light microscopy with an indirect immunoperoxidase technique. Light microscopic findings were compared to ultrastructural observations. The peripheral parts of the tumors showed continuous BM in a recognizable preexisting alveolar pattern without evidence of invasive growth into the alveolar septa. In contrast, central parts showed highly variable BM deposition ranging from continuous to almost completely absent. Alveolar patterns were not observed in the tumor centers. The stromal compartment of the tumor centers contained many spindle cells with irregular pericellular BM-like material that could be identified ultrastructurally as myofibroblasts. Electron microscopy and immunohistochemistry yielded virtually identical results. It is concluded that invasive growth in bronchogenic squamous cell carcinomas occurs in central parts of the tumor when the tumor periphery shows expansive growth without invasion of alveolar septa. The situation is different in invasive squamous cell carcinomas originating from other organs because of anatomical differences between the lung and solid organs.
Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molec... more Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study was designed to study the role of MMP-2, MMP-8, and MMP-9 in human infarct rupture. Heart samples were obtained from patients who died from infarct rupture and control MI patients. The MMP activity was determined by zymography and quantitative immunocapture activity assay. TIMP-1 levels were measured and immunohistochemistry for MMP-2 and MMP-9 was performed. The amounts of both total and active MMP-8 and MMP-9 were significantly higher in ruptured infarct tissue than in control MI tissue, but no differences in MMP-2 activity were observed. Furthermore, the number of inflammatory cells was significantly higher in the ruptured infarcts than in control infarcts. These data suggest that increased MMP-8 and MMP-9 activity in the infarct area, caused by a more prominent infiltration of inflammatory cells, contribute to infarct rupture in humans.
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Papers by Jack Cleutjens