The Journal of pathology
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The Journal of pathology · Aug 2002
Induction of PDX-1-positive cells in the main duct during regeneration after acute necrotizing pancreatitis in rats.
Pancreatic regeneration involves two pathways; proliferation and differentiation of pancreatic progenitor cells, which probably exist in pancreatic ductal epithelium, and replication of pre-existing differentiated acinar, islet, and ductal epithelial cells. During pancreatic development, differentiated cells arise from the ductal progenitor cells expressing the pancreatic/duodenal homeobox-1 (PDX-1) homeodomain transcription factor. The aims of this study were to characterize cell proliferation and differentiation during regeneration after acute necrotizing pancreatitis and to evaluate the role of PDX-1-positive stem cells. ⋯ Proliferation started in the main and large ducts at 24 h; marked mitotic activity was evident in small ductal epithelial cells and tubular complexes on day 3, and in acinar cells on day 7. At 24 h after induction of pancreatitis, epithelial cells of the main duct with PDX-1-positive nuclei were greatly increased, simultaneously with the peak LI of BrdU. These results suggest that regeneration after necrotizing pancreatitis involves proliferation and differentiation of pancreatic progenitor cells, and that ductal epithelial cells with PDX-1-positive nuclei may contribute to the differentiation of pancreatic stem cells in the main duct.
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The Journal of pathology · Jun 2002
Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events.
Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil-dependent hyperalgesia in the rat. ⋯ It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF-induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil-depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration.
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The Journal of pathology · May 2002
Frequent genomic imbalances in chromosomes 17, 19, and 22q in peripheral nerve sheath tumours detected by comparative genomic hybridization analysis.
Comparative genomic hybridization (CGH) was used to detect changes in relative chromosome copy number in 50 cases of peripheral nerve sheath tumour (PNSTs), including nine malignant peripheral nerve sheath tumours (MPNSTs), 27 neurofibromas (with three plexiform neurofibromas) and 14 schwannomas. Chromosome imbalances were frequently detected in benign as well as malignant PNSTs. In both NF1-associated and sporadic MPNSTs, the number of gains was higher than the number of losses, suggesting proto-oncogene activation during MPNST progression. ⋯ Since this 17p11.2-p13 region is known to contain the tumour suppressor gene TP53, patients with NF1 may be at high risk of malignant neoplasms including MPNSTs. Gains were more frequently detected in plexiform neurofibromas (2/3 cases) than other benign tumours, suggesting proto-oncogene activation in tumourigenesis of plexiform neurofibroma. The significance of the losses of chromosome 19 in these cases is not clear at present, but in NF1-associated neurofibromas, the presence of some as yet unknown tumour suppressor genes on chromosome 19 cannot be ruled out.
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The Journal of pathology · Jun 2001
Keratinocyte-derived growth factors play a role in the formation of hypertrophic scars.
In predisposed individuals, wound healing can lead to hypertrophic scar or keloid formation, characterized by an overabundant extracellular matrix. It has recently been shown that hypertrophic scars are accompanied by abnormal keratinocyte differentiation and proliferation, and significantly increased acanthosis, compared with normal scars. This study addressed the question of whether the development of normal and hypertrophic scars is regulated by differences in the growth factor profiles of both the epidermis and the dermis. ⋯ IL-1beta, TNF-alpha, TGF-beta and bFGF showed no differences. It is hypothesized that impaired production of keratinocyte-derived growth factors, such as IL-1alpha, leads to a decrease in the catabolism of the dermal matrix, whereas augmented epidermal PDGF production leads to increased formation of the dermal matrix in hypertrophic scars. These observations support the possibility that the epidermis is involved in preventing the formation of hypertrophic scars.
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The Journal of pathology · Jun 2001
Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in several diseases. This study was undertaken to investigate the mRNA synthesis of MMP2, MMP9, membrane-type 1 (MT1)-MMP, and matrix metalloproteinase inhibitors TIMP1 and TIMP2 by in situ hybridization in a set of heart mitral and aortic valves operatively removed due to degenerative or inflammatory valvular diseases. The material consisted of 21 valves, eight with endocarditis and 13 with a degenerative valvular disease. ⋯ TIMP2 mRNA was found in three cases of endocarditis. The signals for MMP2, MMP9, TIMP1, and TIMP2 mRNA were localized in endothelial cells and in fibroblast-like cells expressing alpha-smooth muscle actin, thus showing myofibroblast-type differentiation. The results show that matrix metalloproteinases MMP2 and MMP9, and matrix metalloproteinase inhibitors TIMP1 and TIMP2 mRNAs are synthesized in diseased valves and suggest that they may contribute to matrix remodelling in valvular disease.