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

The aim of this study was to determine any differences in the collagen molecular and fibrillar packing, or the arrangement of the proteoglycans along the fibril axis, in the stroma of keratoconus and control corneas. High and low-angle x-ray diffraction patterns from the fibrillar and molecular packing of collagen in keratoconus and control corneas were obtained using a synchrotron radiation source. The results indicate no difference in interfibrillar spacing between keratoconus and control corneas at normal physiological hydration, or over a range of hydrations (H = 1-11). This unambiguously demonstrates that the thinning of the stroma that occurs in keratoconus is not a result of closer packing of the collagen fibrils in the stroma. Intermolecular spacings were shown to be significantly (P less than 0.001) lower in keratoconus corneas at normal physiological hydration and over a range of hydrations (H = 1-11). Meridional patterns from the axial distribution of electron density along the collagen fibrils were obtained from untreated control and keratoconus corneas and from the corneas after their proteoglycans were stained with cupromeronic blue. Analysis of the integrated intensities of the first nine orders of these reflections show there is a difference in the staining behavior of collagen-associated proteoglycans in control and keratoconus corneas. Determination of the electron density vectors along the collagen fibrils of cupromeronic blue-stained corneas by the use of Patterson functions indicates that the keratoconus corneal stroma has a specific, ordered proteoglycan that is present in lower numbers along the collagen fibrils, and that it stains less with cupromeronic blue or is in a more disordered arrangement than in the controls.
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PMID:Synchrotron x-ray diffraction studies of keratoconus corneal stroma. 155 73

Although the complete pathogenesis of cartilage damage in canine hip dysplasia has not been completely worked out, it appears that joint laxity with resultant excessive stresses upon articular cartilage is the initiating factor. Grossly, this damage is characterized by cartilage thinning with potential exposure of subchondral bone, osteophyte formation, and pannus formation. Microscopically, there is a marked variation in chondrocyte cellularity, with focal regions of hypocellularity and chondrocyte clusters and synovial lining cell hyperplasia and hypertrophy as well as a decrease in proteoglycan content. This latter change has been substantiated biomechanically. Ultrastructural studies indicate that there is extensive alteration of collagen organization within the cartilage.
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PMID:The pathology of canine hip dysplasia. 160 71

The oscillatory and steady shear rheological properties of concentrated solutions of proteoglycan subunit (PGS) and aggregate (PGA) from bovine articular cartilage have been studied using a Rheometrics fluids spectrometer. At comparable concentrations in the physiological range tan delta increases from 0.5 to 1.0 for PGA as the oscillation frequency (omega) increases from 10(-1) to 10(2) rads/s, compared to a decrease from 40 to 5 for PGS. Thus PGA solutions exhibit predominantly elastic response whereas those of PGS exhibit primarily viscous behavior. PGA solutions show pronounced shear-thinning behavior at all shear rates (gamma) in the range 10(-2) less than gamma (s-1) less than 10(2), whereas PGS solutions exhibit predominantly Newtonian flow. For PGA, the small-strain complex viscosity eta* (omega) is substantially smaller than the steady-flow viscosity eta(gamma) at comparable values of omega and gamma. These observations indicate that the presence of proteoglycan aggregates leads to formation of a transient or weak-gel network. Since aggregation leads to a large increase in molecular hydrodynamic volume and hence in the relaxation times for macromolecular rotation, it appears that role of aggregate formation is to shift the linear viscoelastic response from the terminal viscous flow into the plateau elastomeric regime of relaxational behavior. Normal or pathological changes that produce a decrease in aggregation will result in a loss of elastomeric behavior of the proteoglycan matrix.
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PMID:Viscoelastic and rheological properties of concentrated solutions of proteoglycan subunit and proteoglycan aggregate. 238 8

Keratoconus is a bilateral disorder of corneal shape which may be sporadic or genetically determined. Early corneal thinning suggests that a functional loss of structural elements is a primary event in the disease. Tensile strength of the cornea is reduced and is expressed by signs of rupture and scarring in Bowman's layer, scarring in the substantia propria, and rupture of Descemet's membrane. The overall stretching of the cornea results in an increase in curvature while an increased area of the corneal surfaces probably determines the onset and form of Fleischer's ring and the occurrence of endothelial polymegathism. Biochemical studies have shown an increase in collagenolysis and of reduceable collagen cross-links, but there is inconsistent evidence of altered solubility or of hydroxyproline or proteoglycan content. Of recent interest is the characterization of proteoglycan bridges along and between corneal collagen fibrils in keratoconus and the apparent loss of keratan sulphate demonstrated by electron-histochemical and x-ray diffraction techniques. The manner in which this could interfere with corneal strength is discussed.
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PMID:Keratoconus. 304 80

The purpose of this paper was to describe the remodeling of adult coxofemoral articular cartilage (AC) in response to altered weight bearing. Twelve adult male Sprague-Dawley rats underwent unilateral hindpaw transection at the distal tibiofibular junction (AmpCont group); another group of eight rats served as normal controls (Norm group). Subpopulations of both groups were injected with 35SO4 24 hr before harvest. All femora were harvested after 8 weeks. Safranin O stained longitudinal sections were used to determine AC thickness, cellularity, and proteoglycan (PG) staining. Regional grain counting was performed on autoradiographs. Analysis of the data revealed that the AC of Norm hips in the region near the fovea capitis femoris was significantly thicker, had a lower cell density, a greater PG density, and a lower 35SO4 incorporation rate per chondrocyte than the AC of the Norm lateral edge region. The intact limbs of the AmpCont animals demonstrated a relative thinning of the AC near the fovea capitis femoris, compared with the edge region, and reduced 35SO4 incorporation rate in the lateral edge region, compared with normal values. The operated limb of the AmpCont animals displayed a relative increase of PG density in the edge region compared with the foveal region and a reduced 35SO4 incorporation rate in the lateral edge region, compared with normal values. We concluded that rat coxofemoral AC responds bilaterally to unilateral hindpaw amputation through appropriate morphologic remodeling.
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PMID:Unilateral hindpaw amputation causes bilateral articular cartilage remodeling of the rat hip joint. 341 81

Monomer and aggregated proteoglycans were prepared from pig laryngeal cartilage. Vascoelastic flow properties, comprising linear complex dynamic shear modulus, nonlinear steady-state shear-rate dependent viscosity, and primary normal stress difference, were measured in proteoglycan solutions containing varying proportions of aggregate (0-80%) and at different concentrations (10-50 mg/ml). Results were analyzed using the simple Oldroyd four-parameter nonlinear rate-type rheological equation. All solution properties were strongly dependent on proteoglycan concentration and on the proportion of aggregates present. Aggregation was found to have a great effect on the zero shear-rate viscosity at 50 mg/ml, which increased fivefold from 0-100% aggregate. The results showed that network formation in proteoglycan solutions increased with concentration from 10-50 mg/ml and also increased with aggregation. All proteoglycan solutions showed shear thinning, which was most marked with aggregated proteoglycan at high concentration (50 mg/ml), where the viscosity decreased tenfold from the zero shear-rate limit to the infinite shear-rate limit. The intermolecular interactions in the network were therefore increasingly disrupted by increasing shear rate, but repeated measurements showed that these were reversible changes and that testing did not induce disaggregation or degradation of proteoglycan. These rheological properties show that aggregation is likely to immobilize proteoglycan at high concentration within cartilage and to contribute to the material properties of the porous solid matrix of articular cartilage that are important for its load-bearing function.
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PMID:Viscoelastic properties of proteoglycan solutions with varying proportions present as aggregates. 381 10

After a dose of 800 micrograms of hydroxyurea (HU) was administered to day-4 chick embryos in ovo, the limb deformity including micromelia was observed. We examined the teratogenic mechanism of the action for HU by using histochemical and biochemical techniques. The present study provides histological evidence for the cell death and the depression of cell proliferation just after the treatment with HU and the retardation in periosteal ossification during the process of repair and/or recovery from cell death. On the other hand, the incorporation of [3H]glucosamine and [35S]sulfate into glycosaminoglycan was inhibited at day-7 and day-9, when the embryos are in the process of repair and/or recovery. The cartilage specific proteoglycan, an index of chondrogenesis, appeared at day-7, but the ratio of cartilagenous proteoglycan/noncartilagenous proteoglycan in the treated limbs was depressed. These results suggest that the slight retardation in chondrogenesis and/or the incomplete function of chondrocyte were induced by the treatment with HU in chick embryos. It is considered from above observation that the retardation in chondrogenesis and osteogenesis caused during the repair and/or recovery process of cell death brought about the limb deformity; shortening, thinning and bending of hind limbs.
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PMID:Limb deformity induced in chick embryo by hydroxyurea. 666 44

Mechanical load is an important regulator of chondrocyte metabolic activity. Changes in amplitude or frequency of the load can have a significant effect on the production of matrix macromolecules and of agents leading to cartilage breakdown. The composition of cartilage reflects the net response of the chondrocytes to the prevailing loading pattern, with cartilage proteoglycan content highest in heavily loaded regions and removal of load leading to cartilage thinning and proteoglycan loss. The mechanism of mechanotransduction is poorly understood; the chondrocytes appear to react to cartilage deformation and to the changes in hydrostatic pressure, extracellular ionic composition and streaming potentials induced by the load.
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PMID:The chondrocyte: a cell under pressure. 792 48

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.
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PMID:Morphology and immunohistochemistry of rat aortic grafts. 1066 91

Decorin (dcn) and biglycan (bgn), two members of the family of small leucine-rich proteoglycans (SLRPs), are the predominant proteoglycans expressed in skin and bone, respectively. Targeted disruption of the dcn gene results in skin laxity and fragility, whereas disruption of the bgn gene results in reduced skeletal growth and bone mass leading to generalized osteopenia, particularly in older animals. Here, we report that bgn deficiency leads to structural abnormality in collagen fibrils in bone, dermis, and tendon, and to a "subclinical" cutaneous phenotype with thinning of the dermis but without overt skin fragility. A comparative ultrastructural study of different tissues from bgn- and dcn-deficient mice revealed that bgn and dcn deficiency have similar effects on collagen fibril structure in the dermis but not in bone. Ultrastructural and phenotypic analysis of newly generated bgn/dcn double-knockout (KO) mice revealed that the effects of dcn and bgn deficiency are additive in the dermis and synergistic in bone. Severe skin fragility and marked osteopenia characterize the phenotype of double-KO animals in which progeroid changes are observed also in the skin. Ultrastructural analysis of bone collagen fibrils in bone of double-KO mice reveals a complete loss of the basic fibril geometry with the emergence of marked "serrated fibril" morphology. The phenotype of the double-KO animal mimics directly the rare progeroid variant of human Ehlers-Danlos syndrome (EDS), in which skin fragility, progeroid changes in the skin (reduced hypodermis), and osteopenia concur as a result of impaired glycosaminoglycan (GAG) linking to bgn and dcn core proteins. Our data show that changes in collagen fibril morphology reminiscent of those occurring in the varied spectrum of human EDS are induced by both bgn deficiency and den deficiency in mice. The effects of an individual SLRP deficiency are tissue specific, and the expression of a gross phenotype depends on multiple variables including level of expression of individual SLRPs in different tissues and synergisms between different SLRPs (and likely other macromolecules) in determining matrix structure and functional properties.
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PMID:Phenotypic effects of biglycan deficiency are linked to collagen fibril abnormalities, are synergized by decorin deficiency, and mimic Ehlers-Danlos-like changes in bone and other connective tissues. 1210 52


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