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Biomedical subjects

R G Young

Publications and source records attributed to R G Young.

16 recordsLinked to original sources

A chemically defined medium supports in vitro proliferation and maintains the osteochondral potential of rat marrow-derived mesenchymal stem cells.

Among the stromal elements in mammalian and avian bone marrow there exists a pluripotent subset of cells which we refer to as mesenchymal stem cells (MSCs). These cells can be isolated and will proliferate in culture. When such subcultured cells are introduced into porous tricalcium phosphate-hydroxyapatite ceramic cubes and implanted subcutaneously into syngeneic or immunocompromised hosts, the passaged MSCs are observed to differentiate into bone and cartilage. Heretofore, those assays have been conducted with MSCs which had been maintained in vitro in serum-containing medium. A serum-free medium (RDM-F), which consists of insulin, 5 micrograms/ml, linoleic acid-bovine serum albumin, 0.1%, platelet-derived growth factor-BB, 10 ng/ml, and basic fibroblast growth factor, 1 ng/ml in a base medium of 60% Dulbecco's modified Eagle's medium with low glucose and 40% MCDB-201, has been developed for rat marrow-derived MSCs. Proliferation rates of MSCs maintained in RDM-F equal those of cells maintained in serum-containing medium through Day 4 following subculturing and continue at up to 80% of the rate of the latter through Day 8 of subculture. When tested in the in vivo ceramic cube assay, MSCs cultured in RDM-F retain their osteochondral potential and differentiate into bone and cartilage in a manner indistinguishable from those cultivated in serum-containing medium. Utilization of this serum-free medium will facilitate analysis of the effects of other growth factors and cytokines on the proliferation and differentiation of MSCs, without the complexity of exogenous serum.

Animals

Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage.

UNLABELLED: Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits. Adherent cells from bone marrow, or cells from the periosteum that had been liberated from connective tissue by collagenase digestion, were grown in culture, dispersed in a type-I collagen gel, and transplanted into a large (three-by-six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either the defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed similar patterns of differentiation into articular cartilage and subchondral bone. Specimens of reparative tissue were analyzed with use of a semiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cells from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor cells had uniformly differentiated into chondrocytes throughout the defects. This repair cartilage was subsequently replaced with bone in a proximal-to-distal direction, until, at twenty-four weeks after transplantation, the subchondral bone was completely repaired, without loss of overlying articular cartilage. The mechanical testing data were a useful index of the quality of the long-term repair. Twenty-four weeks after transplantation, the reparative tissue of both the bone-marrow and the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage. CLINICAL RELEVANCE: The current modalities for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor cells that will form cartilage and bone offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their capacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage and the reformation of subchondral bone. The repair tissues appear to undergo the same developmental transitions that originally led to the formation of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Osteogenesis in marrow-derived mesenchymal cell porous ceramic composites transplanted subcutaneously: effect of fibronectin and laminin on cell retention and rate of osteogenic expression.

Cultured-expanded rat marrow-derived mesenchymal cells differentiate into osteoblasts when combined with a porous calcium phosphate delivery vehicle and subsequently implanted in vivo. In this study, the effects of ceramic pretreatment with the cell-binding proteins fibronectin and laminin on the osteogenic expression of marrow-derived mesenchymal cells were assessed by scanning electron microscopy, [3H]-thymidine-labeled cell quantitation, and histological evaluation of bone formation. Scanning electron microscopic observations showed that marrow-derived mesenchymal cells rapidly spread and attach to both fibronectin- or laminin-adsorbed ceramic surfaces but retain a rounded morphology on untreated ceramic surfaces. Quantitation of [3H]-thymidine labeled cells demonstrated that laminin and fibronectin preadsorbed ceramics retain approximately double the number of marrow-derived mesenchymal cells than do untreated ceramics harvested 1 wk postimplantation. Histological observations indicate that the amount of time required to first detect osteogenesis was shortened significantly by pretreatment of the ceramic with either fibronectin or laminin. Fibronectin- and laminin-coated ceramic composite samples were observed to contain bone within 2 wk postimplantation, while in untreated ceramic the earliest observation of bone was at 4 wk postimplantation. A comparison was made of the initial cell-loading, in vivo cell retention characteristics, and rate of osteogenesis initiation of marrow-derived mesenchymal cells on two types of ceramic with different pore structure and chemical composition, with and without preadsorption with fibronectin or laminin. "Biphasic" ceramics contain randomly distributed pores 200-400 microns in diameter, and "coral-based" ceramics have continuous pores of approximately 200 microns in diameter. Laminin or fibronectin preadsorption significantly increases the number of cells retained in all ceramic test groups by day 7 postimplantation. In addition, by day 7 postimplantation, the biphasic ceramics retain a significantly greater number of cells for all test groups than do coral-based ceramics. The biphasic ceramics consistently have more specimens positive for bone with the identical cell-loading conditions used throughout this study. These results indicate that the retention of cells within the ceramic is an important factor for optimization of marrow mesenchymal cell initiated bone formation. The retention of cells within ceramics is augmented by the adsorption of the cell-binding proteins laminin and fibronectin, but this effect varies depending on ceramic pore structure and/or chemical composition.

Animals

The effects of Rumalon, a glycosaminoglycan peptide complex, in a partial meniscectomy model of osteoarthritis in rabbits.

The effects of Rumalon, a glycosaminoglycan peptide complex (GP-C), were evaluated in a partial meniscectomy model of osteoarthritis (OA). When rabbits were treated with Rumalon, 0.25 ml/kg 3 times/week for 12 weeks after partial meniscectomy, the proportion of animals that developed cartilage ulceration was lower than that in untreated meniscectomized rabbits (p less than 0.05). At 6 weeks sacrifice, the same dose of Rumalon was associated with a trend toward reduction in the number of animals with ulcerations. Rumalon administered at a dose of 0.5 ml/kg for 12 weeks reduced the number of animals with ulcers, although not at the p less than 0.05 level of significance. Semiquantitative histologic evaluations revealed no differences between control and treatment groups either in the thickness of articular cartilage, density of cells present, safranin-O stain or ratio of DNA/protein. Increased proteoglycan synthesis characteristic of OA was modulated toward normal in association with Rumalon therapy. Diminished OA changes in response to Rumalon are consistent with an ameliorative response to this agent in the partial meniscectomy model in the rabbit.

Animals

Age and oxygen toxicity related fluorescence in the honey bee thorax.

The blue fluorescent material in thoraxes of honey bees of known adult age from eclosion to 28 days was measured. The amount was greater in older insects and exposure to ozone (ppm) augmented the rate of accumulation. The nearly constant daylight flying by the bees and the ozone effect suggest radical peroxidative origin of the fluorescence. The material was partially purified by chromatography. It is a relatively non-polar lipid.

Aging

Computer analysis of processor status.

The authors describe the use of a desk-top computer to analyze processor status. Quality control data (sensitometry, densitometry, thermometry, etc.) are collected conventionally. Analysis of the data is subsequently performed using specially designed software. This computer analysis results in a small savings in time and in greatly improved management and presentation of quality control data.

Diagnosis, Computer-Assisted

Early CT findings of global central nervous system hypoperfusion.

The early computed tomographic (CT) findings of acute global central nervous system hypoperfusion were studied in 10 patients. The findings could be characterized as: (1) diffuse mass effect with effacement of the cerebral sulci and of the brainstem cisterns (nine patients); (2) global decrease in the cortical gray-matter density from edema, causing loss of the normal gray-white matter differentiation (six patients); (3) low-density lesions of the basal ganglia bilaterally (five patients); and (4) decreased gray-matter density in watershed distributions bilaterally (two patients). Subsequent contrast-enhanced scans in three of the 10 patients demonstrated selective enhancement of the cerebral cortex or the basal ganglia or both. The CT findings seen in this study predicted a poor outcome; nine of the 10 patients died from the insult. The abnormal CT findings can be ascribed to increased vulnerability of the cerebral cortex and basal ganglia to hypotensive episodes. This vulnerability is due to the large metabolic demand of these regions and their characteristic local cerebral blood flow.

Adult

Fluorescent age pigment in insect lysosomes.

Fluorescent pigment accumulates in the lysosomal fraction of spodoptera sixth instars. It was purified by silicic acid chromatography. The fluorescent fraction was characterized by conjugated unsaturation, reactivity with thiobarbituric acid, and lability in alkali; all reminiscent of age pigment. The phosphorus content of the purified fraction was negligible and nitrogen was not detected. It is suggested that the material is degraded, perhaps polymerized lipid fragments.

Aging

Economic impact of quality control in diagnostic radiology.

With ever-increasing costs confronting health care facilities, much attention is being focused on various cost-containment projects. Although it is generally assumed that a radiology department quality control program will increase costs, institutional savings may also result. A comprehensive quality control program involving continuing education, simplification of technic, processor control, standardization of cassettes, and preventive maintenance resulted in substantial savings for a medical school radiology department.

Allied Health Personnel

Interactions of standard antibody with Australia antigens in Au Ag-Ab radioimmunoassay.

Human antisera against Australia (Au) antigen have been characterized by liquid-phase radioimmunoassay (RIA) for their precipitation of (125)I-labeled Au antigen. The end-point dilutions of sera (anti-Au) which precipitated 50% of (125)I-Au antigen by RIA correlated well with complement fixation titers but had a much wider range, indicating a greater precision and perhaps a better sensitivity of assay. Anti-Au serum diluted to precipitate 50% of (125)I-labeled Au antigen was used as standard antibody in RIA tests to detect either inhibition or enhancement of the reaction by preincubated mixtures of Au antigen and antibody specimens. Without free Au antigen or antibody in the resultant mixtures there was no inhibition or enhancement; the mixtures presumably contained immunoreactively equivalent proportions of Au antigen and antibody. RIA data for diagnostic specimens indicated an end-point sensitivity which was proportional to the dilution of the standard anti-Au sera used in the test. High concentrations of the standard antibody permitted detectable inhibition of (125)I-Au antigen precipitation at lower antigen specimen concentrations. Similarly, low concentrations of the standard antibody permitted detectable enhancement of (125)I-Au antigen precipitation at lower antibody specimen concentrations. Omitting the standard antibody altogether resulted in a more sensitive RIA for Au antibody in test sera.

Antibodies, Viral