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  • 1
    Publication Date: 1993-12-24
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 52 (1993), S. 110-119 
    ISSN: 1432-0827
    Keywords: Chondrocyte ; Growth plate ; Bromodeoxyuridine ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Postnatal bone growth occurs by the process of endochondral ossification in cartilaginous growth plates at the ends of long bones. The rate and extent of long bone growth is determined by a combination of chondrocytic proliferation, matrix production, and increase in chondrocytic height in the direction of growth during cellular enlargement. In this study, single pulse and/or repeated pulse labeling with the thymidine analog bromodeoxyuridine (BrdU) was used to study the role of cellular proliferation in controlling long bone growth. Variables studied included progression of the label over time following a pulse, and patterns and progression of the label over time following repeated pulse labeling for 24 and 48 hours. Examination was made of the proliferative characteristics of chondrocytes, the spatial pattern of cellular proliferation, and cell cycle kinetics. With respect to the spatial pattern of proliferative chondrocytes, results suggest that chondrocytes within a column are more synchronized with each other than are chondrocytes in different columns. This is consistent with the concept that each column represents a clonal expansion of a stem cell, which may proceed independently from adjacent columns. Despite this apparent heterogeneity, all chondrocytes in the proliferative zone complete at least one cell cycle in 24–28 hours. This estimate of the cell cycle time is significantly shorter than previous estimates of cell cycle times in similar growth plates. Our results also suggest that chondrocytes entering the cell cycle in the proximal part of the growth plate spend an average of 4 days in the proliferative cell zone, representing approximately four cellular divisions. After leaving the cell cycle, an additional 48 hours is required for the label to reach the terminal chondrocyte, which represents the time required to complete hypertrophy. These data are important when considering hypotheses concerning both the role of controls on proliferation in the determination of overall rate of long bone growth, as well as the interplay between proliferation and hypertrophy in regulating the overall amount of growth achieved by a given growth plate.
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  • 3
    ISSN: 1432-0827
    Keywords: Chondrodysplasia ; Stereology ; Chondrocyte ; Hypertrophy ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Ocular-chondrodysplasia in Labrador Retriever dogs is characterized by short-limbed dwarfism and ocular abnormalities. The purposes of the present study were to develop morphological criteria to define the matrix and/or chondrocytic abnormalities associated with this chondrodysplasia, and to test the hypothesis that ineffective matrix-directed cellular swelling was associated with the decreased longitudinal bone growth in these animals. The proximal and distal radial growth plates were collected from four affected animals of the same litter. Stereological techniques were used to analyze both cellular shapes and cellular volume changes in the hypertrophic zone. The pathological changes seen in these growth plates varied between animals and included disorganization of cellular columns with abnormal extent of calcification. Chondrocytes of all zones contained two types of abnormal cellular inclusions classified as light and dark, based on the intensity of eosinophilic staining. Both types of inclusions contained material that resembled the surrounding extracellular matrix, varying only in the apparent hydration of the contents. It could be demonstrated that light inclusions were located in the peripheral cytoplasm and connected to the extracellular matrix through narrow channels. By contrast, dark inclusions were membrane bound and perinuclear. Chondrocytes with multiple, large inclusions appeared to be undergoing degenerative changes. Although the final volume achieved by hypertrophic chondrocytes was consistent with that of normal growth plates, there was a high level of variability of chondrocytic shape and evidence of premature cellular condensation in the maturation zone. The severity of the dwarfism correlated both with the extent of chondrocytic changes and the severity of the ocular lesions. Although the pathogenesis of the disease remains to be precisely defined, the decreased longitudinal bone growth could be attributed to premature chondrocytic death prior to cellular hypertrophy.
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