Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allotransplantation (TPL) of the abdominal aortic segments of BN donors was performed in 32 Lewis recipients with or without cyclosporin A (CyA) immunosuppression, and the vascular changes were compared to those of 10 syngeneic grafts (Lewis-->Lewis) and to the autologous rat aortae. The vessels were examined 2, 3, 4 and 5 months post TPL by light microscopy, the thickness of intima and media was measured morphometrically and the cell infiltration of adventitia and intima was assessed semiquantitatively. Thirty-six aortae were examined by three-step enzyme immunohistochemistry (proof of selected differentiation, proliferation, cytoskeletal and connective tissue matrix antigens). The adventitia displayed an intense focal and scattered mononuclear cell infiltration; it was more discrete and focal in the intima. This cellularity persisted in the allografts but disappeared from the intima and was reduced in the adventitia of the isografts after four and five months. Disseminated ED1+ activated macrophages were the most prominent population of infiltrates whereas modest numbers of adventitial ED2+ tissue macrophages remained constant throughout the intervals examined. CD4+ cells (focal and scattered) outnumbered (roughly twice) the scattered CD8+ lymphocytes; both these types were rare in the intima. Leukocyte invasion of the media was lacking (except for scarce isolated CD8+ cells in some allografts). In syngeneic grafts the smooth muscle cells (SMC) of media remained intact and the intimal thickening was slight to absent (about 5 microns) four and five months post TPL. On the other hand, the allograft media underwent severe destructive changes (karyolysis, depletion of alpha-SMC actin, focal calcification and general thinning without rupture or aneurysm). The prominent allograft intimal thickening (70-80 microns) was due to the proliferation of longitudinally oriented myointimal cells (alpha-SMC actin, FD2, PCNA and Ki67+) and an increase in matrix substance (strong metachromasia and positivity of chondroitin-sulfate proteoglycan). The deposition of lipids remained discrete, without atheromatous plaques and mural thrombosis. All changes were comparable in CyA-treated and untreated animals. Thus the main lesions of the allografts were (i) persistent mononuclear infiltration chiefly in adventitia, (ii) destruction of medial SMC, and (iii) intimal thickening by proliferation of myointimal cells. At the postTPL intervals examined the proliferation and intimal migration of medial SMC were not apparent and a morphological correlate of significant anti-medial-SMC cytotoxic attack was lacking.
 ...
PMID:Morphology and immunohistochemistry of rat aortic grafts. 1066 91

It is well-established that cartilage grows by a combination of matrix secretion, cell hypertrophy and cell proliferation. The extent to which this growth is by appositional, as opposed to interstitial mechanisms, however, remains unclear. Using the knee joints of the marsupial Monodelphis domestica to study cartilage growth, we have combined an immunohistochemical study of the TGF-beta family of cartilage growth and differentiation factors between 30 days postpartum to 8 months, together with a stereological analysis of cartilage morphology during growth. Furthermore, to gain an insight into the generation of the characteristic zones within cartilage, we have examined the effects of intra-articular administration of bromodeoxyuridine, an agent that is incorporated into DNA during cell division and blocks further cell cycling. During early growth, TGF-beta2 and -beta3 were widely expressed but TGF-beta1 was less so. After the formation of the secondary centre of ossification, all isoforms became more restricted to the upper half of the tissue depth and their distribution was similar to that previously described for IGFs, and PCNA-positive cells. Stereological analysis of tissue sections from the femoral condylar cartilage at 3 and 6 months showed that there was a 17% increase in total cartilage volume but a 31% decrease in cell density on a unit volume basis. Finally, cell-cycle perturbation with BrDU, which was injected into the knee joints of 3-month-old animals and analysed 1 and 4 months post-injection, revealed that the chondrocytes occupying the transitional zone were depleted 1 month post-injection, resulting in thinning of the articular cartilage. This effect was reversed 4 months post-injection. Immunohistochemical analysis revealed that BrDU-treatment altered the expression patterns of all TGF-beta isoforms, with a marked reduction in labelling of TGF-beta1 and -beta3 isoforms in the upper half of the cartilage depth. Overall, the data lends further support to the notion of articular cartilage growing by apposition from the articular surface rather than by interstitial mechanisms.
 ...
PMID:The development of articular cartilage: evidence for an appositional growth mechanism. 1145 64

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.
 ...
PMID:Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization. 1656 44

Androgenetic alopecia (AGA), a hereditary disorder that involves the progressive thinning of hair in a defined pattern, is driven by androgens. The hair follicle dermal papilla (DP) expresses androgen receptors (AR) and plays an important role in the control of normal hair growth. In AGA, it has been proposed that the inhibitory actions of androgens are mediated via the DP although the molecular nature of these interactions is poorly understood. To investigate mechanisms of AGA, we cultured DP cells (DPC) from balding and non-balding scalp and confirmed previous reports that balding DPC grow slower in vitro than non-balding DPC. Loss of proliferative capacity of balding DPC was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, as well as decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA.
 ...
PMID:Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression. 1798 30

Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1-14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures.
 ...
PMID:Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage. 2167 37