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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 235 records · Page 13Linked to original sources
PubMed1989

Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA.

Both interleukin-1 (IL-1) and platelet-derived growth factor (PDGF) induce proliferation of cultured fibroblasts and smooth muscle cells. These polypeptide mediators are released by activated macrophages and other cell types in response to injury and are thought to have a role in tissue remodeling and a number of pathologic processes. Analysis of the kinetics of [3H]thymidine incorporation by cultured fibroblasts demonstrated that the response to IL-1 is delayed approximately 8 hours relative to their response to PDGF. IL-1 transiently stimulated expression of the PDGF A-chain gene, with maximum induction after approximately 2 hours. Subsequent synthesis and release of PDGF activity into the medium was detected as early as 4 hours after IL-1 stimulation, and downregulation of the binding site for the PDGF-AA isoform of PDGF followed PDGF-AA secretion. Antibodies to PDGF completely block the mitogenic response to IL-1. Therefore, the mitogenic activity of IL-1 for fibroblasts and smooth muscle cells appears to be indirect and mediated by induction of the PDGF A-chain gene.

Cells, Cultured↗
PubMed1989

Selective expression of mRNA encoding platelet-derived growth factor B chain following transfection of foreign genes into cell lines derived from baby hamster kidney.

The genes for platelet-derived growth factor (PDGF) A and PDGF B chains are expressed in a variety of biological situations. Active PDGF consists of two distinct but homologous polypeptide chains, PDGF A and PDGF B, which are found as heterodimers or homodimers. We report a novel situation in which there is selective expression of mRNA encoding PDGF B in cell lines derived from baby hamster kidney (BHK) following transfection with various gene/cDNA constructs and following growth selection with methotrexate. The process of transfection itself, and not expression of the proteins encoded by the transfected genes/cDNAs (hormones, enzymes, and structural proteins), induces expression of PDGF B. No PDGF B mRNA is detectable in control cell lines. Low levels of mRNA encoding PDGF A are constitutively present and are not changed by transfection and or growth selection. PDGF-like activity is present in the medium whenever PDGF B mRNA is detected. The composition of the secreted PDGF dimer cannot be established from our data, but quantitative analysis of mRNA suggests that the PDGF is a B-B dimer. However, the data show that transcription of the PDGF A and PDGF B genes in BHK cells is regulated independently, similar to that reported for some human tumor cells. Furthermore, the selective expression of PDGF B in response to the introduction of foreign genes and to growth selection may be an important aspect of the reaction of these cells to nonoptimal growth conditions, allowing survival and growth of the cells that express PDGF B.

Animals↗
PubMed1989

Unexpected sex-ratios in families of language/learning-impaired children.

There is a well-documented propensity of males affected with developmental language/learning impairment. Results from this study demonstrate, unexpectedly, that this sex-ratio difference of males to females with developmental language/learning disorders was found to occur significantly only in families with a language/learning-impaired mother. In addition, a remarkably aberrant offspring sex-ratio was found in families of language/learning-impaired children who had an affected mother, but not father. Mothers who were developmentally language/learning-impaired had three times as many sons as daughters, and five times as many language/learning-impaired sons as daughters. Genetic and hormonal influences that might affect both sex-ratio and neuroanatomical development and disorders are discussed.

Child, Preschool↗
PubMed1989

Familial aggregation in specific language impairment.

Self-report data from the families of children participating in the San Diego Longitudinal Study of specific developmental language impairment were used to assess familial aggregation in the disorder. Families of impaired children reported higher rates of affected first-degree relatives than did families of matched controls. Significantly higher incidence of maternal and paternal childhood language and/or learning disabilities, as well as sibling disability rates, were reported. The extent to which familial aggregation reflects genetic or environmental influences in specific language disorders remains to be determined.

Adult↗
PubMed1989

Cross-institutional stability of behavioral criteria desirable for success in radiology residency.

Certain dimensions of job performance are critical to radiology residents, and several of these dimensions are noncognitive in nature (eg, interpersonal skills, conscientiousness, recognition of limits). Our initial study examined these factors in only one residency program, so the general nature of these dimensions must be documented. The current study was a cross institutional analysis involving 31 faculty radiologists at three separate academic institutions (82% of total faculty) who participated in a critical incident interview to obtain data on important resident behaviors and attitudes. The resultant 172 incidents were sorted by two physicians into the six categories (knowledge, technical skills, attitudes toward self and [both recognitions of limits and confidence in abilities], conscientiousness, curiosity, and interpersonal skills); inter-rater reliability was 92%, kappa = .89. A Chi square analysis revealed similar distributions of incidents across categories (x2 12 = 17.22) among the three institutions, supporting the general reliability of these dimensions across the institutions studied. Further, the distributions of these incidents demonstrated that the noncognitive dimensions again were given considerable importance by faculty radiologists. For example, more than 40% of the critical incidents pertained to the conscientiousness dimension. These findings documented the generalization of these behavioral dimensions across several sites and support their importance in selection and evaluation of residents.

Attitude of Health Personnel↗
PubMed1989

Sensitivity of bioelectrical impedance to detect changes in human body composition.

The purpose of this study was to compare the estimates of lean body mass (LBM) and percent body fat (%BF), as predicted by bioelectrical impedance (BIA) and sum of skinfolds (SF), with those derived by hydrostatic weighing (HW) obtained before and after a 10-wk diet and exercise regimen. The experimental (E) group consisted of 17 healthy male subjects; 20 healthy males served as the control (C) group. Post hoc Scheffé contrasts computed on E group data indicated that, for both LBM and %BF, the Lukaski and Segal BIA equations, as well as the Durnin SF equation, derived mean values that were not significantly different (0.05 significance level) from HW in both pre- and postregimen conditions. For LBM, the same equations derived the following significant (P less than 0.01) correlation coefficients for both pre- and postregimen data: Lukaski, 0.87 and 0.85; Segal, 0.89 and 0.87; and Durnin, 0.90 and 0.88. For %BF, the correlation coefficients were slightly lower but remained statistically significant (P less than 0.01). The findings of this study suggest that the BIA method, by use of either the Lukaski or Segal prediction equations, is a valid means of predicting changes in human body composition as measured by the Siri transformation of body density.

Adipose Tissue↗
PubMed1989

Clearance of calcium across in situ perfused placentas of intrauterine growth-retarded rat fetuses.

Maternofetal clearance of 45Ca and 51Cr-EDTA (diffusional marker) were simultaneously measured across in situ perfused placentas of intrauterine growth-retarded (IUGR) and control rat fetuses on d 20 of gestation. IUGR was induced by uterine artery and vein ligation on d 17 of gestation. Control fetuses and their placentas were taken from sham-operated dams. We hypothesized that calcium transfer would be impaired across placentas of IUGR fetuses. The mean body wt of IUGR fetuses was 42% lower, and the mean nose-anus length was 16% lower than those of control fetuses. The mean total calcium content of IUGR fetuses was significantly lower than that of control fetuses, but not when it was normalized to body wt. The mean maternal whole blood ionized calcium concentration was not significantly different in the two groups. The materno-fetal clearance of 45Ca across IUGR placentas was significantly lower than that across control placentas (IUGR = 35.2 +/- 1.9 micro L/min/g placenta, mean +/- SEM; control = 93.1 +/- 12 microliters/min/g placenta, p less than 0.002). In contrast, the maternofetal clearance of 51Cr-EDTA, the reference diffusional marker, was not significantly different across IUGR and control placentas. We conclude that maternofetal transfer of calcium is reduced across placentas of IUGR rat fetuses.

Animals↗
PubMed1989

Determination of the production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 in the pregnant sheep and its chronically catheterized fetus by primed infusion technique.

Because little is known regarding the determinants of plasma 1,25-dihydroxyvitamin D3(1,25(OH)2D3), or its fate in the fetus, we used a primed infusion technique, using physiologic amounts of high specific activity 3H-1,25(OH)2D3 to study the in vivo production rate (PR) and metabolic clearance rate (MCR) of 1,25(OH)2D3 in chronically catheterized maternal and fetal sheep during the last month of gestation (term = 145 d). The fetal MCR of 1,25(OH)2D3 was calculated at steady state, achieved within 2 h, and was found to be 2.53 +/- 0.19 mL/min (mean +/- SEM) compared to the maternal value of 15.9 +/- 0.94 mL/min. When expressed on a body wt basis, the fetal MCR of 1.22 +/- 0.09 mL/min/kg was more than 4-fold higher than the corresponding maternal value of 0.27 +/- 0.02 mL/min/kg. Measurement of endogenous plasma 1,25(OH)2D3 by RIA revealed mean fetal values of 89 +/- 10 pg/mL compared to the maternal value of 65 +/- 9 pg/mL. Fetal daily PR of 0.33 +/- 0.024 micrograms/d was 22% of the maternal PR of 1.49 +/- 0.11 micrograms/d. However, calculation of PR on a body wt basis revealed a fetal value of 0.159 +/- 0.012 micrograms/d/kg that was more than 6-fold higher than the maternal value of 0.025 +/- 0.002 micrograms/d/kg. Thus, fetal plasma concentrations of 1,25(OH)2D3 are sustained in the face of a high clearance rate of the hormone. The high MCR may be related to the high in vivo circulating concentrations of 1,25(OH)2D3, fetal to maternal placental transfer or target tissue uptake. In view of the high turnover of 1,25(OH)2D3, we suggest that this hormone has a biologic importance that warrants further investigation.

Animals↗
PubMed1988

Two classes of PDGF receptor recognize different isoforms of PDGF.

Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation.

Binding, Competitive↗
PubMed1988

Stimulation of receptor-dependent and receptor-independent pathways of low-density lipoprotein degradation in arterial smooth muscle cells by platelet-derived growth factor.

Platelet-derived growth factor (PDGF), a powerful mitogen released by platelets, promoted the degradation of low-density lipoprotein (LDL) by cultured primate arterial smooth muscle cells and human skin fibroblasts by stimulating both receptor-mediated and LDL-receptor-independent uptake of LDL. Stimulation of LDL-receptor-independent LDL uptake and degradation by PDGF was demonstrated in three ways. First, the small amount of LDL that was degraded by LDL-receptor-negative skin fibroblasts was stimulated by PDGF. Second, PDGF led to increased degradation of LDL that had been reductively methylated to prevent its binding to LDL receptors. Third, 125I-labeled LDL degradation was stimulated by PDGF in the presence of high concentrations of unlabeled LDL, i.e., conditions under which the contribution of the LDL receptor to cellular uptake and degradation is reduced. These observations suggest that mitogens, as typified by PDGF, can facilitate the cellular delivery of LDL cholesterol by both LDL-receptor-mediated and non-LDL-receptor-mediated mechanisms to provide exogenous cholesterol for use during cell replication.

Animals↗
PubMed1988

Induction of transforming growth factor-alpha in activated human alveolar macrophages.

The early monocyte infiltration observed in normal wound repair and in a number of pathologic processes precedes the epithelial and connective tissue proliferative responses, suggesting that the monocyte/macrophage may be an important source of growth factors for these tissues. In culture, activated macrophages secrete growth factors active on fibroblasts, smooth muscle, endothelium, and epithelium. This report demonstrates that activated human alveolar macrophages express the gene for transforming growth factor-alpha (TGF-alpha) in an inducible manner and secrete a factor into the culture medium that is functionally and immunologically identical to TGF-alpha. Two different molecular species of TGF-alpha activity (approximately 8,500-12,000 and 28,500 daltons) are identified in macrophage-conditioned medium. These observations establish the macrophage as a diploid human cell capable of synthesizing and secreting TGF-alpha. The activated macrophage therefore represents a cellular source of a mitogenic factor that is potentially important in epithelial proliferation and repair.

Animals↗
PubMed1988

Hormonal effects of vitamin D3 on epidermal melanocytes.

The role of cholecalciferol, 25(OH) D3, and 1,25(OH)2 D3, as modulators of melanocyte function and proliferation has been examined. Topical application of 100 micrograms cholecalciferol to the pinnal epidermis of DBA/2J mice for 5 or 10 days increased the number of L-dihydroxyphenylalanine-positive (DOPA-positive) melanocytes and had a synergistic effect with a low dose of ultraviolet B light (UVB). Application of 1 microgram 1,25(OH)2 D3 had a transient effect on epidermal melanocytes. Addition of cholecalciferol to pure cultures of human melanocytes did not alter their tyrosinase activity (therefore, melanin synthesis) or growth rate even after 72 hours of treatment. However, treatment of similar cultures with 1,25(OH)2 D3 at a concentration equal to or greater than 10(-8) M suppressed tyrosinase activity but did not affect proliferation. The effect of 25(OH) D3 was similar to, but lower in magnitude than, that of 1,25(OH)2 D3. We attempted to demonstrate the presence of specific receptors for 1,25(OH)2 D3 in normal human melanocytes using the monoclonal antibody (Mo Ab) 9A7 gamma raised against the receptor for 1,25(OH)2 D3. Melanocytes were exposed to 9A7 gamma and to a secondary biotinylated Ab and analyzed by the fluorescence activated cell sorter (FACS). An increase in the specific fluorescent signal was constantly observed. By using the immunoblotting technique, we observed a major immunoreactive species that migrated in the 53-kD region in normal melanocytes. The size of this major immunoreactive species was smaller in melanoma cells than in normal melanocytes. This correlates with the finding that the former cells were unresponsive to cholecalciferol, 25(OH) D3, or 1,25(OH)2 D3 treatment. These results predict a direct role for 1,25(OH)2 D3 as an effector of normal melanocyte function.

Animals↗