Search PubMed⌕ Search

Biomedical subjects

T L McCarthy

Publications and source records attributed to T L McCarthy.

81 records · Page 5Linked to original sources
PubMed1988

Parathyroid hormone modulates transforming growth factor beta activity and binding in osteoblast-enriched cell cultures from fetal rat parietal bone.

Transforming growth factor beta (TGF-beta) is produced by bone cells, is abundant in bone matrix, and regulates bone cell biochemical processes. In osteoblast-enriched fetal rat parietal bone cell cultures, low TGF-beta doses increase DNA synthesis, whereas higher levels are less mitogenic, stimulate collagen production, and decrease alkaline phosphatase activity. Parathyroid hormone by itself has minimal effects on these processes, but it opposes the effects of TGF-beta and alters TGF-beta binding to its receptors in osteoblast-enriched cultures. Some functions ascribed to parathyroid hormone in bone may therefore result from alterations in TGF-beta activity, suggesting that the local effects of TGF-beta in bone are under systemic hormonal control.

Animals↗
PubMed1988

Skeletal tissue and transforming growth factor beta.

Normal skeletal growth results from a balance between the processes of bone matrix synthesis and resorption. These activities are regulated by both systemic and local factors. Bone turnover is dynamic, and skeletal growth must be maintained throughout life. Although many growth promoters are associated with bone matrix, it is enriched particularly with transforming growth factor beta (TGF-beta) activity. Experimental evidence indicates that TGF-beta regulates replication and differentiation of mesenchymal precursor cells, chondrocytes, osteoblasts, and osteoclasts. Recent studies further suggest that TGF-beta activity in skeletal tissue may be controlled at multiple levels by other local and systemic agents. Consequently, the intricate mechanisms by which TGF-beta regulates bone formation are likely to be fundamental to understanding the processes of skeletal growth during development, maintenance of bone mass in adult life, and healing subsequent to bone fracture.

Alkaline Phosphatase↗
PubMed1988

Tumor necrosis factor-alpha inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures.

Tumor necrosis factor-alpha (TNF alpha), a product of activated monocytes, induces tissue wasting in certain solid tumors in vivo and in in vitro model systems. Recent studies indicate that TNF alpha also regulates cell replication and expression of differentiated function in a variety of nonneoplastic cell systems. Since monocyte products could accumulate in bone with trauma, inflammation, or other disease states, bone cell activity might be altered by the presence of these pathophysiological molecules. Using cells obtained by sequential enzyme release from fetal rat parietal bone, we find that TNF alpha has acute stimulatory and inhibitory effects on bone cell macromolecular synthesis. Within 24 h of exposure, recombinant human TNF alpha at 0.3-100 nM progressively increases the rate of DNA synthesis in osteoblast-enriched cell cultures up to 3- to 4-fold, and 3-100 nM TNF alpha reduces collagen production and alkaline phosphatase activity by 20-30%. These decreases are not altered by 1 mM hydroxyurea, which blocks the mitogenic effect of TNF alpha by 85-90%. In addition, hydroxyproline levels in the culture medium do not increase relative to the control value after TNF alpha treatment, suggesting that decreased collagen production results from less synthesis rather than increased collagen degradation. Hybridization studies with cDNA encoding the alpha 1-chain of rat type I collagen show that TNF alpha increases type I collagen mRNA to an extent similar to its effect on cell replication. Therefore, TNF alpha appears to inhibit collagen synthesis and alkaline phosphatase activity in osteoblast-enriched cell cultures by mechanisms that are not related to its effects on cell replication.

Alkaline Phosphatase↗
PubMed1987

Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone.

Transforming growth factor beta (TGF beta) stimulates cell replication in fetal rat calvariae, and studies with isolated bone cells suggest that the primary mitogenically responsive cell is of the osteoblast lineage. The effect of TGF beta on bone cell replication is biphasic and depends on both the TGF beta concentration and cell density in monolayer culture. After 23 h of treatment, DNA synthesis in confluent cells is progressively enhanced by 0.15-15 ng/ml TGF beta; but in subconfluent cells, 15 ng/ml is less than maximal; and in sparse cell cultures, it is inhibitory. At all cell densities, however, 15 ng/ml TGF beta stimulates collagen synthesis, an effect which is more pronounced when DNA synthesis rates are declining. Furthermore, 1 mM hydroxyurea, which blocks the mitogenic effect of TGF beta by 85%, only minimally influences the increase in collagen synthesis. Cytoplasmic slot blot analysis reveals alterations in the amount of type I collagen mRNA in TGF beta-treated cells, suggesting that control is exerted, at least in part, at the transcriptional level. Since TGF beta is found in culture medium conditioned by bone explants and in bone tissue extracts, these results support that TGF beta is an important and multifunctional autocrine regulator of bone formation.

Animals↗
PubMed1987

Mitogenesis in fetal rat bone cells simultaneously exposed to type beta transforming growth factor and other growth regulators.

Type beta transforming growth factor (TGF-beta) is found in large amounts in bone tissue, and is a potent mitogen for osteoblast-enriched cell cultures obtained from fetal rat parietal bone. Because other local and systemic factors may be presented to bone cells simultaneously with TGF-beta, it is important to understand the effects of this complex growth regulator in such circumstances. Unlike the effects observed in many tissue systems, TGF-beta does not invariably inhibit the mitogenic response of bone cells to other growth promoters. In contrast, other factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and type alpha tumor necrosis factor (TNF-alpha) limit the response of osteoblastic bone cells to TGF-beta. TGF-beta is a much weaker mitogen for fibroblastic cells obtained from fetal rat bone, whereas fetal bovine serum, EGF, bFGF, and TNF-alpha are more potent stimulators. In addition, TGF-beta does not significantly impair the response of the fibroblastic bone cells to the other tested agents. These findings reinforce a role of TGF-beta as an anabolic bone growth regulator, and suggest that its function may be modified by other local or systemic agents that can also affect bone cells.

Animals↗
PubMed1984

Relationship of serum thiocyanate concentrations to smoking characteristics.

Thiocyanate (SCN) concentrations were determined in serum samples from 130 young healthy persons (60 smokers) and related to their smoking and physiologic characteristics. Serum thiocyanate correlated strongly and approximately equally with the number of cigarettes/d X kg of ideal body weight (IBW) (r = 0.748), total nicotine intake in mg/d X kg IBW (r = 0.735), and total tar intake in mg/d X kg IBW (r = 0.731). Multiple linear regression analysis that included these factors as well as sex, marijuana use, menthol, and degree of inhalation only increased the multiple r to 0.803. A more sensitive statistical method (NYBAID) was also used to determine the most significant influences of these variables on serum SCN. The association with depth of inhalation (i.e., smoking versus nonsmoking) was dominant among the relationships considered. The highest SCN levels were exhibited in heavy nicotine users (8.58 +/- 3.00 mg/l), while average users had slightly lower concentrations (6.49 +/- 2.37 mg/l) (p less than 0.03). In nontobacco smokers, those who smoked marijuana several times weekly had higher SCN levels (4.66 +/- 2.16 mg/l) than noncannabis users (2.38 +/- 1.38 mg/l) (p less than 0.03). These studies confirm the utility of serum SCN as an index of smoking rate and demonstrate the role of secondary variables in accounting for the chemical in serum.

Adult↗
PubMed1983

Characterization of translational-control ribonucleic acid isolated from embryonic chick muscle.

Myosin heavy chain (MHC) mRNP particles have been purified from 13-day chick embryonic skeletal muscle by a combination of sucrose density gradient centrifugation and metrizamide buoyant density centrifugation. Associated with the mRNPs are at least three distinct low molecular weight RNA molecules including translational-control RNA (tcRNA). This particular RNA contains 102 nucleotides and is uridine and guanine rich, and its nucleotide sequence has been determined. tcRNA102 is capable of inhibiting the translation of the mRNAs with which it is associated upon preincubation in stoichiometric amounts. Under these conditions, endogenous reticulocyte mRNA is not inhibited. Under appropriate salt and temperature conditions, tcRNA102 is capable of reassociating with myosin heavy chain (MHC) mRNA, thus altering the sedimentation characteristics of the mRNA. This suggests that the mRNA-tcRNA102 interactions alter the secondary structure of the mRNA. In addition, tcRNA102 does not associate with ribosomal RNA or globin mRNA, suggesting that some degree of specificity is involved with the RNA-RNA interactions.

Animals↗
PubMed1982

Effect of chronic oral contraceptive steroids on theophylline disposition.

The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (greater than 6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.1 +/- 5.6 vs. 53.1 +/- 14.5 ml/h/kg). The t1/2 was also significantly prolonged in the OC group (9.79 +/- 1.43 vs. 7.34 +/- 1.75 h) while the volume of distribution was similar between the 2 groups. The serum ethinylestradiol (EE) concentrations after oral OC administration were measured simultaneously. The apparent clearance of EE was about 30% lower in the OC users. A significant positive correlation was found between the apparent clearance of EE and the plasma clearance of theophylline. The effects of OC are predominantly due to chronic use with decreased elimination of both theophylline and EE.

Adult↗