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A Gentry

Publications and source records attributed to A Gentry.

5 recordsLinked to original sources

Inhibition of chondrocyte differentiation in vitro by constitutive and inducible overexpression of the c-fos proto-oncogene.

We have investigated the role of c-Fos in chondrocyte differentiation in vitro using both constitutive and inducible overexpression approaches in ATDC5 chondrogenic cells, which undergo a well-defined sequence of differentiation from chondroprogenitors to fully differentiated hypertrophic chondrocytes. Initially, we constitutively overexpressed exogenous c-fos in ATDC5 cells. Several stable clones expressing high levels of exogenous c-fos were isolated and those also expressing the cartilage marker type II collagen showed a marked decrease in cartilage nodule formation. To investigate further whether c-Fos directly regulates cartilage differentiation independently of potential clonal variation, we generated additional clones in which exogenous c-fos expression was tightly controlled by a tetracycline-regulatable promoter. Two clones, DT7.1 and DT12.4 were capable of nodule formation in the absence of c-fos. However, upon induction of exogenous c-fos, differentiation was markedly reduced in DT7.1 cells and was virtually abolished in clone DT12.4. Pulse experiments indicated that induction of c-fos only at early stages of proliferation/differentiation inhibited nodule formation, and limiting dilution studies suggested that overexpression of c-fos decreased the frequency of chondroprogenitor cells within the clonal population. Interestingly, rates of proliferation and apoptosis were unaffected by c-fos overexpression under standard conditions, suggesting that these processes do not contribute to the observed inhibition of differentiation. Finally, gene expression analyses demonstrated that the expression of the cartilage markers type II collagen and PTH/PTHrP receptor were down-regulated in the presence of exogenous c-Fos and correlated well with the differentiation status. Moreover, induction of c-fos resulted in the concomitant increase in the expression of fra-1 and c-jun, further highlighting the importance of AP-1 transcription factors in chondrocyte differentiation. These data demonstrate that c-fos overexpression directly inhibits chondrocyte differentiation in vitro, and therefore these cell lines provide very useful tools for identifying novel c-Fos-responsive genes that regulate the differentiation and activity of chondrocytes.

Apoptosis↗

Intrinsic tone of cerebral artery segments of human infants between 23 weeks of gestation and term.

Segments of basilar and middle cerebral arteries of eight human preterm and early postnatal infants have been examined using the resistance artery myograph technique for wire-mounted segments and the pressure perfusion arteriograph. Myograph-mounted segments spontaneously developed tone of varying duration and time course. Perfused segments showed maintained tone levels of approximately 40% of maximum possible constriction when the intraluminal pressure was 60 mm Hg. This level is not different from that found in adult human pial arteries of similar lumen diameter. Indomethacin (10[-5] M) either initiated tone increase or potentiated existing tone in the isometrically mounted segments. After washout of vasoconstrictors norepinephrine (10[-6] M) and angiotensin II (10[-8] M), indomethacin caused a pronounced, long lasting increase in basal tone. Spontaneous tone was reversed by acetylcholine (10[-6] M), isoproterenol (10[-8] to 10[-5] M), histamine (10[-8] to 10[-5] M), and papaverine (10[-5] M). Low levels of tone were increased and higher levels decreased by intraluminal flow. The pressure/diameter curves of these vessels were of similar shape as those of the equivalent size in the adult. It is concluded that intrinsic tone is a prominent feature of these large cerebral arteries, and it is modified by an endogenous indomethacin-sensitive process.

Brain↗

Periodontal status of HIV-seropositive and AIDS patients.

Few reported studies have evaluated the periodontal status of individuals infected by human immunodeficiency virus (HIV). The majority of these reports have evaluated the periodontal status of individuals presenting to dental care facilities due to oral problems. These reports suggest that severe gingival inflammation and attachment loss are often associated with HIV seropositive patients. The purpose of this study was to evaluate the periodontal status of HIV seropositive patients without biasing the data towards those presenting to dentists with oral problems. Sixty-three consenting male patients presenting to the infectious disease clinic at the Medical College of Virginia Hospitals were examined to determine the status of their periodontal health. Gingival index, plaque index, pocket depths, and attachment loss were determined using standard indices. Participants were first grouped according to the modified CDC Classification System for HIV infection and then categorized according to HIV risk factors for purposes of statistical analysis. No significant differences could be found in the gingival or periodontal status of subjects who were HIV seropositive versus those with AIDS. Periodontal status was also not significantly different for individuals based upon risk group. Periodontal health of the participants was similar to the general population (HIV status unknown). This would indicate that, although HIV gingivitis and HIV periodontitis have been documented in a number of HIV-infected patients, the frequency of affected individuals is less than previous reports would suggest.

Acquired Immunodeficiency Syndrome↗