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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 145 records · Page 8Linked to original sources

Visceral adiposity, androgens, and plasma lipids in obese men.

The primary purpose of this study was to investigate the relationships between adipose tissue (AT) distribution, particularly visceral adipose tissue (VAT), circulating androgens, and plasma lipids in a group of 17 obese (body mass index [kg/m2], 31.8 +/- 3.8) android (waist to hip ratio [WHR], 1.01 +/- 0.05) men. AT distribution was measured by magnetic resonance imaging (MRI) using a multislice model in which 41 equidistant images were acquired from head to foot. Although the subjects were homogenous with respect to total adiposity, a sevenfold variation in VAT was observed. VAT and the visceral to subcutaneous ratio (VSR) were significantly correlated with triglyceride (TG) levels and the ratio of apolipoprotein (apo) B to low-density lipoprotein cholesterol ([LDL-C] P < .05). Neither proximal-thigh AT area nor lower-body subcutaneous adipose tissue (SAT) volume was significantly related to any lipid variable. However, the ratio of visceral AT area to thigh AT area (VTH) was positively correlated with TG (P < .05), and the ratio of VAT volume to lower-body SAT volume (VLBS) was positively correlated with TG, total cholesterol (TC), LDL-C (P < .05), and apo B (P = .057). Total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) were not significantly related to any of the plasma lipid variables; however, the percentage of FT (%FT) was positively correlated with high-density lipoprotein cholesterol ([HDL-C]P < .01) and HDL-C/LDL-C (P < .05). TT, FT, %FT, and SHBG were not related to MRI-measured VAT. Age waa not related to either VAT or androgen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Olfactory ensheathing glia and platelet-derived growth factor B-chain reactivity in the transplanted rat olfactory bulb.

Using a monoclonal antibody against the B-chain of platelet-derived growth factor as a marker, we have examined the behavior of olfactory ensheathing glia in the normal and transplanted rat olfactory bulb. In the normal postnatal olfactory bulb, these glia are found to ensheath the bundles of incoming primary olfactory nerve fibers as well as those in the olfactory nerve layer. Olfactory marker protein antibody was used to identify the olfactory nerve proper. Within the transplant, the same glia: (1) ensheath bundles of both primary olfactory and non-primary olfactory axons, (2) ensheath axonal bundles deep within the donor tissue, and (3) eventually permit radiation of individual axons from bundles to surrounding neuropil. We believe that ensheathing glia (being rich in growth-related factors and extracellular matrix molecules) may be useful in providing trophic support and guidance for the reconstruction of developmentally or traumatically damaged neuronal pathways not directly related to the olfactory system. The evidence presented here indicates that ensheathing glia are capable of existing in deep brain areas and ensheathing other than primary olfactory axons. The special molecular characteristics of these glia along with the morphological findings presented here provide a foundation for further studies of these unique glia and their potential utility in the restoration of damaged neural pathways.

Animals↗

Electric and magnetic fields at three pulp and paper mills.

Extremely low frequency (60 Hz) electric and magnetic field levels were measured at three Canadian pulp and paper mills, using area point-in-time measurements. Most electric field levels were below the limit of detection of 1 V/m (92 of 132 measurements); the highest measured field was 47 V/m. Measured magnetic field strengths ranged from less than the limit of detection (0.125 mG, 2 of 132 measurements) to 706 mG, with a median of 1.6 mG. Magnetic field levels were higher in mills that consume more electric power, but worker exposures could not be predicted according to plant power consumption. Overall, electric and magnetic field levels in the three pulp and paper mills were similar to those experienced by the general population. However, maximum magnetic field intensities in some areas were as high as those experienced by electrical workers.

British Columbia↗

Sex differences in lean and adipose tissue distribution by magnetic resonance imaging: anthropometric relationships.

This study compared total and regional adipose tissue (AT) and lean tissue (LT) distribution measured by magnetic resonance imaging (MRI) in obese, android women (n = 40) and mean (n = 17). Women had significantly (P < 0.01) greater subcutaneous AT (39.6 +/- 11.6 vs 30.7 +/- 7.5 L) but significantly (P < 0.01) less visceral AT (2.5 +/- 1.1 vs 4.8 +/- 2.1 L) and LT (42.8 +/- 4.7 vs 58.2 +/- 6.2 L) compared with men. Segmentation of the visceral AT volume demonstrated that women had significantly (P < 0.01) less intraperitoneal (1.98 +/- 0.84 vs 3.74 +/- 1.61 L) and extraperitoneal AT (0.51 +/- 0.23 vs 1.04 +/- 0.47 L). When the legs, hip and pelvic region, and abdomen and torso regions were compared, women had significantly greater absolute quantities of subcutaneous AT and significantly less LT in all regions (P < 0.01); however, in all regions the relative distribution of both was similar. Anthropometric prediction of MRI-measured total AT gave SEs of 7.7% for women and 7.5% for men, for visceral AT 30% for women and 19% for men. Anthropometric prediction of LT gave SEs of 6.5% for women and 3.6% for men.

Adipose Tissue↗

Mobilization of visceral and subcutaneous adipose tissue in response to energy restriction and exercise.

The effects of energy restriction (diet) in combination with either aerobic (DA) or resistance exercise (DR) on adipose tissue (AT) distribution were evaluated in 24 obese women (DA, n = 10; DR, n = 14). AT distribution was measured by magnetic resonance imaging (MRI). Comparison between groups demonstrated that the relative losses observed for body weight, subcutaneous AT (SAT), and visceral AT (VAT) volume were not significantly different (P > 0.05). A significant reduction in the volume ratio of VAT to SAT was observed for both groups (P < 0.01). Comparison of arm, abdomen and torso, and lower-body regions revealed that the regional mobilization of SAT was not significantly different between groups (P > 0.05) and that for both groups there was a preferential mobilization of SAT from the abdominal region (P < 0.05). Within the VAT depot, significant reductions were observed for both intraperitoneal and extraperitoneal AT (P < 0.01). These findings suggest that the combination of moderate energy restriction and either resistance or aerobic exercise induces significant reductions in VAT and SAT, with a preferential loss of VAT, and are thus effective means of reducing total and upper-body obesity in obese women.

Abdomen↗

Families of chronically mentally ill patients: their structure, coping resources, and tolerance for deviant behavior.

The attitudes of families toward caring for a mentally ill member in the home are explored through in-depth interviews with 105 families of chronically ill psychiatric patients from a public and a private hospital. Family readiness, defined as having the ability and the willingness to supervise the patient, was measured by the St. Paul Scale of Family Functioning and the Tolerance of Deviant Behavior Scale. Findings revealed a significant relationship between the respondent's belief in his or her ability to manage the behavior of the patient and willingness to accept the patient into the home as measured by tolerance for deviant behavior. No significant relationships were found between family resources, level of functioning, income, or community connectedness. Implications for practice and study limitations are discussed.

Adaptation, Psychological↗

DMS-IV meets philosophy.

The authors discuss some of the conceptual issues that must be considered in using and understanding psychiatric classification. DMS-IV is a practical and common sense nosology of psychiatric disorders that is intended to improve communication in clinical practice and in research studies. DSM-IV has no philosophic pretensions but does raise many philosophical questions. This paper describes the development of DSM-IV and the way in which it addresses a number of philosophic issues: nominalism vs. realism, epistemology in science, the mind/body dichotomy, the definition of mental disorders, and dimensional vs. categorical classification.

Humans↗

Secondary prevention of childhood firesetting.

OBJECTIVE: The Juvenile Fire Awareness and Intervention Program was established to develop and evaluate an intervention to be offered by fire fighters for children who set fires. METHOD: One hundred thirty-eight children, aged 5 to 16 years, with a history of firesetting participated in a randomized, controlled trial. The intervention involved education about fire safety and a behavior modification program designed to extinguish the desire to set fires through satiation. The frequency and severity of firesetting were recorded for 12 months after the intervention to measure outcome. RESULTS: There was a significant decrease in the frequency and severity of firesetting across all groups, with no additional improvement resulting from participation in the fire fighters' intervention. CONCLUSIONS: There is no evidence to suggest that the multicomponent program offered by trained fire fighters is effective in reducing firesetting. The marked reduction in firesetting across all groups suggests that fire safety education by the fire fighters is the most appropriate approach to this serious community problem.

Adolescent↗

ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high-fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western-type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.

Animals↗

Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation.

Directed migration or chemotaxis of arterial smooth muscle cells (SMC) contributes to intimal SMC accumulation, a key event in the development of atherosclerotic lesions and in restenosis after angioplasty. The present study compares and contrasts insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF-BB) as chemoattractants and mitogens for human arterial SMC. Compared with PDGF-BB, IGF-I is a weaker SMC mitogen. Thus, PDGF-BB, but not IGF-I, evokes a strong and rapid activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. However, IGF-I is a potent stimulator of directed migration of human arterial SMC, as measured in a Boyden chamber assay. The half-maximal concentration for migration is similar to the Kd for IGF-I receptor interaction. An IGF-I receptor-blocking antibody blocks the effects of IGF-I, IGF-II, and insulin, indicating that the effects are indeed mediated through the IGF-I receptor. The maximal effect of IGF-I on directed migration ranges between 50% and 100% of the effect of PDGF-BB, the strongest known chemoattractant for SMC. The ability of IGF-I and PDGF-BB to induce chemotaxis coincides with their ability to stimulate phosphatidylinositol turnover, diacylglycerol formation, and intracellular Ca2+ flux and suggests that these signaling pathways, but not activation of the MAP kinase cascade, are required for chemotaxis of human arterial SMC.

Amino Acid Sequence↗

Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation?

Lipoprotein oxidation is believed to play an important role in atherogenesis. To investigate whether inhibition of oxidation of low density lipoprotein (LDL) would alter atherogenesis in the nonhuman primate, we administered probucol, a potent antioxidant, to Macaca nemestrina fed a high-fat, high-cholesterol diet. Probucol was administered to half of the 16 monkeys 14 wk after starting the hypercholesterolemic diet, and was given daily until they were sacrificed after 11 mos. To evaluate the antioxidant effect of probucol, the resistance of isolated plasma LDL to in vitro oxidation was evaluated. Probucol significantly increased the resistance of LDL to oxidative modification, as shown by an increase in the lag time required for conjugated diene formation. Lesions in the probucol-treated animals appeared less mature, and increased accumulation of lipid was observed in smooth muscle cells. Comparison of all control and probucol-treated monkeys demonstrated that intimal lesion areas in the thoracic aortas of the probucol-treated monkeys were reduced by 43% (P < 0.0001), but no significant difference in lesion area was found in the abdominal aortas or in the iliac arteries. However, the lag phase of conjugated diene formation was not prolonged in 2 of the 8 probucol-treated animals. A plot of intimal lesion size versus lag phase of all 16 animals showed a trend that lesion size was inversely related to oxidation resistance for all anatomic sites. The strong inverse relationship between intimal lesion size and resistance of LDL to oxidation supports a role for lipoprotein oxidation in the development and progression of lesions of atherosclerosis. The possibility that some of the effect is due to other biological properties of probucol cannot be ruled out.

Animals↗

Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3.

The human placenta synthesizes 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and expresses the vitamin D receptor (VDR), but the roles of 1,25-(OH)2D3 and the VDR in placental physiology are poorly understood. In this study, we have demonstrated that 1,25-(OH)2D3 stimulates the synthesis and release of human placental lactogen (hPL), one of the major secretory products of syncytiotrophoblast cells. Enzymatically dispersed trophoblast cells from term placentas exposed continuously to 1,25-(OH)2D3 (0.1, 6, and 37 microM) for 5 days released significantly more hPL than control cells after the third day of exposure. On days 4 and 5, the amounts of hPL released by cells exposed to 1,25-(OH)2D3 were 2.54- and 4.14-fold that of control cells (P < 0.001 in each instance). The stimulation by 1,25-(OH)2D3 was dose dependent and was accompanied by stimulation of hPL messenger RNA levels. Transient transfection studies of BeWo choriocarcinoma cells transfected with hPL promoter constructs coupled to the chloramphenicol acetyltransferase reporter gene indicated that the stimulation of hPL expression is due at least in part to stimulation of hPL gene expression. Deletion analysis studies of the hPL promoter indicated that a region between -500 to -1200 basepairs is necessary for 1,25-(OH)2D3 responsiveness. Analysis of this region shows a consensus vitamin D response element (VDRE) DNA-binding site of a direct repeat motif separated by three bases. Ligation of this placental VDRE site into a heterologous chloramphenicol acetyltransferase vector caused 1,25-(OH)2D3 responsiveness. Moreover, mobility shift assays demonstrated binding of VDR to placental VDRE. These results indicate that 1,25-(OH)2D3 stimulates the synthesis and release of hPL by a mechanism involving hPL gene transcription and support a role for vitamin D and the VDR in placental function.

Base Sequence↗

Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene.

We have recently reported an A to G transition at nucleotide position 3243 in the mitochondrial DNA (mtDNA) tRNA(Leu(UUR)) gene in a large family with non-insulin-dependent diabetes mellitus (NIDDM). Characteristic was its maternal transmission and an associated sensorineural hearing loss. In a screening of a Dutch and French NIDDM population for the presence of the tRNA(Leu(UUR)) mutation we identified two new pedigrees in which NIDDM is present in combination with deafness. The mode of inheritance agrees with a maternal one. This result shows that patients with a phenotype of NIDDM and deafness can be identified within groups of NIDDM patients based on the tRNA(Leu(UUR)) mutation. The same mutation has also been linked to the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). How the same mutation can give rise to different clinical phenotypes is not clear. We obtained the complete mtDNA sequence from our initial pedigree and identified a number of additional mutations that could confer the phenotype of the tRNA(Leu(UUR)) mutation to diabetes. We examined the presence of these additional, potentially pathogenic mutations in the mtDNA from the two new pedigrees and from a previously described British pedigree. The absence of these mutations in all three pedigrees shows that the tRNA(Leu(UUR)) mutation alone associates with the phenotype of NIDDM and deafness. We conclude that maternally inherited diabetes and deafness is a distinct subtype of diabetes that is associated with a single mitochondrial tRNA(Leu(UUR)) mutation. We propose the abbreviation MIDD for this particular subtype.

Base Sequence↗

Cultural factors associated with health-risk behavior among the Cheyenne River Sioux.

A field study was conducted to identify cultural factors--values, beliefs, and related characteristics--associated with health-risk behavior among adult members of the Cheyenne River Sioux Tribe. The Cultural Values Survey (CVS), an instrument for measuring cultural values and related characteristics, was developed and pilot tested in the study population. This instrument, along with the Health Risk Appraisal (HRA) (an instrument developed by the Centers for Disease Control to quantify major health-related behaviors), was administered to a random sample of 429 adults in the study community. Significant differences between females and males for both cultural characteristics and health-risk behaviors were found. Females had significantly higher HRA-calculated Health Index values than males, reflecting overall healthier behaviors. Females who scored higher on cultural factors consistent with more traditional Lakota Indian lifestyles (e.g., degree of Indian blood, Lakota language spoken in the home, traditional Lakota beliefs) had higher HRA Health Index values than females scoring lower in these characteristics. Males who scored higher in factors related to self-determination (e.g., hard work, personal control, industriousness, individual action) had higher Health Index values than those who scored lower in these areas. Further testing of the CVS instrument, as well as further research from both epidemiologic and social science perspectives is essential to elucidate the nature of the relationship between cultural factors and health-related behavior.

Adolescent↗

Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes.

Vascular smooth muscle cells (SMCs) in the media of normal arteries express alpha 1 beta 1 integrin with no detectable alpha 2 beta 1 as determined by immunocytochemistry. In contrast, immunoprecipitation of integrins expressed by human SMCs cultured from medial explants shows strong expression of alpha 2 beta 1 and no expression of alpha 1 beta 1. The apparent reciprocal expression of these two collagen and laminin receptors was confirmed by flow cytometric analysis of fluorescent labeled cells. Freshly isolated SMCs had detectable alpha 1, alpha 3, alpha 5, and alpha v subunits with low levels of detectable beta 3 and no detectable alpha 2. Cultured SMCs expressed alpha 2, alpha 3, alpha 5 and alpha v subunits with little or no alpha 1 or beta 3. Neither alpha 4 nor alpha 6 were detectable in freshly isolated or cultured cells. Expression of alpha 2 beta 1 receptors by cultured SMCs appears to be required for the migration of these cells on type I collagen. Migration of cultured SMCs across a type I collagen-coated membrane toward two different chemotactic stimuli, platelet-derived growth factor-BB (1 nmol/L) and insulin-like growth factor-(1 nmol/L), was Mg2+ dependent and inhibited by preincubation of cells with an affinity-purified polyclonal anti-alpha 2 beta 1 antibody or by monoclonal antibodies directed against the individual alpha 2 or beta 1 subunits. Attachment to type 1 collagen membranes was not affected by antibodies under conditions where migration was significantly impeded. The combined data show that SMC expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors for collagen and laminin is dynamic and reciprocal and may be important with respect to SMC migration on type I collagen. These findings are potentially important in understanding the pathophysiology of vascular diseases, for example, atherosclerosis and restenosis following balloon angioplasty, where SMC migration is a contributing factor.

Antibodies, Monoclonal↗

Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells.

Stimulation of aortic smooth muscle cells with platelet-derived growth factor BB homodimer (PDGF-BB) leads to the rapid activation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MAPKK). Compounds that increase cAMP and activate protein kinase A (PKA)--prostaglandin E2, isoproterenol, cholera toxin, and forskolin--were found to inhibit the PDGF-BB-induced activation of MAPKK and MAPK. Forskolin, but not the inactive analogue 1,9-dideoxyforskolin, inhibited PDGF-BB-stimulated MAPKK and MAPK activation in a dose-dependent manner. PKA antagonism of MAPK signaling was observed at all doses of PDGF-BB or PDGF-AA. PKA did not inhibit MAPKK and MAPK activity in vitro, and MAPKK and MAPK from extracts of forskolin-treated cells could be activated normally with purified Raf-1 and MAPKK, respectively, suggesting that PKA blocked signaling upstream of MAPKK. Neither PDGF-BB-stimulated tyrosine autophosphorylation of the PDGF receptor beta subunit nor inositol monophosphate accumulation was affected by increased PKA activity, suggesting that PKA inhibits events downstream of the PDGF receptor. This study provides an example of cross talk between two important signaling systems activated by physiological stimuli in smooth muscle cells--namely, the PKA pathway and the growth factor-activated MAPK cascade.

1-Methyl-3-isobutylxanthine↗