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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 109 records · Page 6Linked to original sources
PubMed1996

Trunk muscle parameters determined from MRI for lean to obese males.

Transverse magnetic resonance images at the L(4)-L(5) level of 26 males ranging in body mass index from 19.7 to 39.5 were digitized using a computer video monitor with mouse-mediated digitization software. The digitized musculature included the right and left psoas, rectus, abdominis, quadratus lumborum, oblique, and paraspinal muscle groups. From the digitized profiles, cross-sectional areas, and anteroposterior and mediolateral moments from the vertebral centroid were subsequently calculated. Multiple regression formulae were derived to predict the muscle parameters from the most strongly related anthropometrics. Cross-sectional area and moment arms for lean and obese groups were also compared. Significant regression formulae were derived for the cross-sectional area of the rectus abdominis and obliques, for mediolateral moment arms of the paraspinals, psoas, and obliques, and for anteroposterior moments of all four muscles. Comparison of muscle parameters for lean and obese subjects revealed minimal differences, though normalization of muscle cross-sectional areas by trunk area produced values which were statistically smaller for all muscles of the obese relative to lean subjects. RELEVANCE:--Identifying variations in trunk muscular geometry across specific population groups will assist in further refining the existing morphometric data base used to estimate the forces experienced about the lower back. By identifying these variations, it may be possible to observe factors which may predispose a specific population to low back pain.

Journal Article↗
PubMed1996

Magnetic resonance imaging to study lesions of atherosclerosis in the hyperlipidemic rabbit aorta.

We have developed a high resolution magnetic resonance (MR) imaging technique to serially assess lesions of atherosclerosis in a rabbit model. A volume phased array coil was designed and used to image the abdominal aortas of six atherosclerotic rabbits and two age-, sex-, and weight-matched controls. Lesions of atherosclerosis were induced by a combination of repeat balloon injury and a hyperlipidemic diet. All animals were imaged on at least two occasions 9-16 months after initiation of atherosclerosis. In addition, animals were imaged immediately after sacrifice. Anatomic dissection and histology were performed to verify the MR findings. The volume phased array coil improves the image signal-to-noise ratio over existing extremity coils and resulted in higher resolution images of the abdominal aorta. Proton density-weighted images acquired with 2D/3D fast spin-echo are the most useful sequence to outline the vessel wall and to differentiate wall from lumen and background. Progressive wall thickening and lumen stenosis were observed in the serial images of the diseased rabbits. Wall thickness and lumen area derived noninvasively from the in vivo MR images correlate with postmortem MR images and sections of aorta examined by dissection microscopy and histology. Spin-echo and fast spin-echo imaging with a phased array body coil can be used to accurately assess plaque dimensions, and potentially can be used to image intraplaque features and to monitor lesion progression or regression. It should also be possible to adapt these techniques to assess human disease, especially for peripheral vascular problems.

Animals↗
PubMed1996

Costimulatory signalling potential of murine MHC class II-positive T-clone cells.

Activated human and rat T cells as well as mouse T-cell clones have been reported to synthesize and express major histocompatibility complex (MHC) class II molecules. However, the capacity of class II+ antigen (Ag) presenting T cells to induce proliferation of Ag-specific cloned T cells has been controversial. We analysed whether the failure of some T-cell clones to proliferate in response to Ag presented by class II+ T cells is because of a lack of costimulatory cytokine production by the antigen-presenting cells (APC). As a model system the mouse class II+ cloned BI/O4.1 T cells were used as APC in order to activate the T cell clone KIII5. This T-helper 1 (Th1) type, GAT (synthetic copolymer of L-glutamic acid, L-alanine and L-tyrosine)-specific clone is characterized by an efficient downregulation of interleukin-2 receptor (IL-2R) with time following antigenic stimulation. KIII5 cells respond to GAT-presenting splenic antigen-presenting cells (APC) by IL-2 production, IL-2R upregulation and proliferation. When BI/O4.1 T cells were used as APC, KIII5 cells produced IL-2, but did not proliferate. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a lack of IL-12 production by BI/O4.1 cells. Addition of IL-12 to a coculture of Ag-presenting BI/O4.1 cells and KIII5 cells fully reconstituted a proliferative response. IL-12 in synergy with IL-2 upregulated IL-2R alpha chain expression and enhanced proliferation of KIII5 cells. Our data suggest, that class II+ T cells are not functional in inducing Ag-mediated expansion of resting Th1 cells owing to their failure to produce IL-12, but rather that they play a role in amplification loops during an ongoing immune response.

Animals↗
PubMed1996

Mycobacterium genavense infections in pet animals.

Mycobacterium genavense, a recently reported cause of a wasting illness in patients with AIDS, was isolated from a cervical lymph mode from a dog with severe hind limb weakness and from trachael tissue from a parrot with acute onset respiratory distress. Physicians caring for immunocompromised patients should consider birds and dogs potential sources of M. genavense infection and submit appropriate specimens for culture.

AIDS-Related Opportunistic Infections↗
PubMed1996

Structural analysis of human immunodeficiency virus type 1 Gag protein interactions, using cysteine-specific reagents.

We have examined structural interactions of Gag proteins in human immunodeficiency virus type 1 (HIV-1) particles by utilizing cysteine mutagenesis and cysteine-specific modifying reagents. In immature protease-minus but otherwise wild-type (wt) particles, precursor Pr55Gag proteins did not form intermolecular cystines naturally but could be cross-linked at cysteines, and cross-linking appeared to occur across nucleocapsid (NC) domains. Capsid (CA) proteins in wt mature viruses possess cysteines near their carboxy termini at gag codons 330 and 350, but these residues are not involved in natural covalent intermolecular bonds, nor can they be intermolecularly cross-linked by using the membrane-permeable cross-linker bis-maleimido hexane. The cysteine at gag codon 350 (C-350) is highly reactive to thiol-specific modifying reagents, while the one at codon 330 (C-330) appears considerably less reactive, even in the presence of ionic detergent. These results suggest that the HIV-1 CA C terminus forms an unusually stable conformation. Mutagenesis of C-350 to a serine residue in the mutant C350S (C-350 changed to serine) virtually eliminated particle assembly, attesting to the importance of this region. We also examined a C330S mutant, as well as mutants in which cysteines were created midway through the capsid domain or in the C-terminal section of the major homology region. All such mutants appeared wt on the basis of biochemical assays but showed greatly reduced infectivities, indicative of a postassembly, postprocessing replicative block. Interestingly, capsid proteins of mature major homology region mutant particles could be cysteine cross-linked, implying either that these mutations permit cross-linking of the native C-terminal CA cysteines or that major homology regions on neighbor capsid proteins are in close proximity in mature virions.

Animals↗
PubMed1996

Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men.

The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n = 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT (P < 0.05). The reductions in body weight (approximately 10%) and SAT (approximately 25%) and VAT volume (approximately 35%) were not different between groups (P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT (P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (approximately 27%) was greater (P < 0.05) than that observed for the gluteal-femoral region (approximately 20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment (P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone (P < 0.05). Peak O2 uptake (liters) was significantly improved (approximately 14%) in the DA group as was muscular strength (approximately 20%) in the DR group (P < 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.

Adipose Tissue↗
PubMed1996

Separate associations between visceral and subcutaneous adipose tissue distribution, insulin and glucose levels in obese women.

OBJECTIVE: The primary purpose of this study was to determine the separate associations between visceral (VAT) and subcutaneous adipose tissue (SAT) distribution, skeletal muscle (SM), and plasma insulin and glucose levels, and. A second objective was to determine whether anthropometric methods could be used to identify those women who are at increased metabolic risk. RESEARCH DESIGN AND METHODS: Whole-body SAT, SM, and VAT volume were measured (in liters), using a multislice magnetic resonance imaging (MRI) protocol in 40 premenopausal obese women. Plasma insulin and glucose levels were measured after an overnight fast and in response to a 75-g oral glucose tolerance test (OGTT). RESULTS: With the exception of fasting glucose, VAT was positively correlated with all insulin and glucose variables (P < 0.01). This observation remained true whether VAT was derived from multiple MR images (i.e., VAT volume [in liters]) or from a single MR image (i.e., VAT area [in squared centimeters]). Furthermore, the segmentation of intraperitoneal adipose tissue (portally drained adipose tissue) from VAT did not improve the observed relationships. VAT remained a significant (P < 0.05) correlate of insulin and glucose area after adjusting for either SAT or abdominal SAT (ASAT). SAT, ASAT, and SM volume were not related to any metabolic variable. Waist circumference (WC) was the single strongest anthropometric correlate for fasting insulin and insulin area (P < 0.05). Because it has been reported that disturbances in insulin-glucose homeostasis are more likely associated with a WC value > 1 m, in subjects matched for total adiposity, we compared the glucose and insulin area values for those with a WC above (n = 17) and below (n = 15) this value. The group with a WC > 1 m had significantly higher values for both insulin and glucose areas (P < 0.05). CONCLUSIONS: The primary observation is that VAT is associated with plasma insulin and glucose variables independent of whole-body SAT, ASAT, and SM in obese women. In addition, the findings provide support for the utility of WC as an anthropometric tool that may be used to identify a subgroup of obese patients at increased metabolic risk.

Adipose Tissue↗
PubMed1996

Sensitivity associated with the identification of visceral adipose tissue levels using waist circumference in men and women: effects of weight loss.

OBJECTIVE: The first objective was to determine the associated sensitivity (true positives) and specificity (false positives) associated with the use of waist circumference (WC) to predict specific visceral adipose tissue (VAT) levels. Because WC is a strong correlate of VAT, and, a WC of 100 cm and a VAT area of 130 cm2 (L4-L5) have been suggested as thresholds for increased disturbances in insulin-glucose homeostasis and lipid metabolism, we assessed the sensitivity and specificity when using a WC of 100 cm to identify a VAT of 130 cm2 or greater. A second objective was to evaluate the effects of diet and exercise induced weight loss on VAT and WC to establish the utility of using WC to follow reductions in VAT. RESEARCH DESIGN AND METHODS: The sensitivity between WC and VAT was assessed using 50 male (BMI: 30.9 +/- 4.7, age: 41.0 +/- 11.2 y) and 49 female (BMI: 33.3 +/- 5.0, age: 36.9 +/- 7.4 y) subjects. The effects of weight loss on WC and VAT were evaluated in a subgroup of 20 male and 38 female subjects. VAT was measured by magnetic resonance imaging. RESULTS: The sensitivity associated with the prediction of a VAT of 130 cm2 or greater using a WC of 100 cm was high (83%), however, so too was the incidence of false positives (38%). Significant (p < 0.01) correlations were obtained between concurrent reductions in VAT and WC for both the male (r = 0.69) and female (r = 0.47) groups. For the two groups combined, regression analysis indicated that a 1 cm reduction in WC was associated with a 4% reduction in VAT mass (p < 0.01). CONCLUSIONS: The misclassification of individuals with VAT accumulation above 130 cm2 suggest that WC alone lacks the sensitivity required to identify specific VAT values. The diet and exercise induced reductions in visceral adiposity are positively related to corresponding reductions in WC for both genders is a positive result, and demonstrates the potential utility of using WC to follow changes in the AT depot that conveys the greatest health risk.

Adipose Tissue↗
PubMed1996

Magnetic resonance imaging provides new insights into the characterization of adipose and lean tissue distribution.

Magnetic resonance imaging (MRI) represents a major advance in the study of human body composition and nutritional status. Measurement of whole body and regional adipose tissue (AT) distribution, quantification of lean tissue (LT) and its principal constituent skeletal muscle, and the assessment of visceral AT are among the advantages made possible by MRI. Indeed, the ability to quantify visceral AT has provided the researcher with significant insight into the complex relationships between body composition and health risk. Because there are no known health risks associated with MRI, this methodology is well suited for studying the effects of various nutritional perturbations on both AT and LT, in particular visceral AT and skeletal muscle. An overview of the historical development and current status of MRI within the context of body composition research is provided. Validation studies are reviewed, and new insights into the nature of AT and LT distribution in both sexes and the effects of weight loss on these same parameters are presented. Finally, directions for future MRI research are suggested.

Adipose Tissue↗
PubMed1995

Platelet-derived growth factor. Distinct signal transduction pathways associated with migration versus proliferation.

Figure 2 summarizes our current interpretation of data concerning signals from the activated PDGF receptor involved in directed migration and proliferation of human arterial SMC. Binding of PDGF (PDGF-BB or PDGF-AA) causes PDGF-receptor dimerization, tyrosine autophosphorylation, and subsequent binding of several molecules containing SH2 domains to the activated receptor. Binding and activation of PLC gamma by the PDGF receptor leads to PIP2 hydrolysis, resulting in generation of diacylglycerol (DAG) and IP3. Subsequently, intracellular levels of calcium are elevated as a result of IP3-mediated calcium release from intracellular compartments. The decreased levels of PIP2 and increased levels of calcium both favor actin-filament disassembly by inducing capping of actin-filament barbed ends and actin-monomer sequestration. A localized, and transient, actin-filament disassembly enables the cell to extend filopodia towards PDGF, thereby enabling chemotaxis to take place. At a later time and/or in a different compartment, actin-filament assembly is promoted by PDGF by a mechanism that is not completely understood, but that may involve small GTP-binding proteins, such as Rho, and formation of DAG. Migration on collagen requires functional alpha 2 beta 1 integrins, which may either constitute a permissive state required for a cell to migrate, or which may be actively involved in intracellular signals leading to migration. PDGF-induced DNA synthesis and proliferation involves activation of Ras, MAP kinase kinase, and MAP kinase. Cross-talk between PKA signaling and tyrosine-kinase receptor signaling results in PKA inhibition of the MAP kinase cascade, probably at the level of Raf. Activation of PI 3-kinase, or a PI 3-kinase-like enzyme, is also likely to contribute to the mitogenic effects of PDGF in these cells (Bornfeldt, unpublished observation). What determines if a SMC will migrate and/or proliferate in response to PDGF? Results are starting to emerge that show regulation of expression of molecules involved in intracellular signaling with different phenotypic states of SMC. For example, expression of PLC gamma is very low in intact vascular wall (where SMC show a "contractile phenotype"), and induced when SMC are converted to a "synthetic phenotype" in culture. Proliferation and expression of MAP kinase, but not calcium signaling, appear to be regulated by the extracellular matrix, and the profile of integrin expression is different in SMC in culture compared to SMC in the vascular wall. Thus, the relation between expression of signaling molecules involved in migration and signaling molecules involved in proliferation, as well as cross-talk between different signal-transduction pathways, may determine the net effect of PDGF.

Animals↗
PubMed1995

TNF-alpha stimulation of fibroblast proliferation. Dependence on platelet-derived growth factor (PDGF) secretion and alteration of PDGF receptor expression.

TNF-alpha stimulates DNA synthesis and proliferation of cultured human fibroblasts. Maximal DNA synthesis in response to TNF-alpha occurs approximately 28 h after addition of TNF-alpha to quiescent fibroblasts, a delay of about 12 to 14 h as compared with DNA synthesis elicited by platelet-derived growth factor (PDGF). TNF-alpha induces PDGF A chain gene expression with a maximum at 4 h. DNA synthesis is abrogated in response to TNF-alpha by a goat anti-PDGF IgG but not by nonimmune goat IgG, suggesting induction of an autocrine PDGF-AA loop by TNF-alpha. The response to PDGF-AA requires the presence of PDGF receptor alpha-receptors. TNF-alpha does not significantly affect PDGF alpha-receptor mRNA or protein expression, nor does it alter the proliferative response to externally added PDGF-AA. In contrast, TNF-alpha reduces the levels of PDGF beta-receptor mRNA, protein expression, and cell proliferation in response to PDGF-BB. Thus, DNA synthesis in response to TNF-alpha depends upon autocrinely induced PDGF-AA. At the same time, TNF-alpha may alter the response to PDGF-BB from exogenous sources.

Blotting, Northern↗
PubMed1995

Coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial, Phase II (TIMI II).

OBJECTIVES: We examined the results of coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction trial, Phase II (TIMI II) with particular emphasis on patient characteristics, the impact of antecedent percutaneous transluminal coronary angioplasty and morbidity and mortality in certain subgroups. BACKGROUND: Coronary bypass surgery is frequently used after thrombolytic therapy, but there is relatively little information with regard to early and late outcomes. METHODS: We analyzed 3,339 patients enrolled in the TIMI II trial. Bypass surgery was performed in 390 patients (11.7%): 54 (14%) within 24 h after entry into the trial or within 24 h of coronary angioplasty and 336 (86%) between 24 h and 42 days after entry. RESULTS: Perioperative mortality rates were, respectively, 16.7% and 3.9% (p < 0.001); perioperative myocardial infarction rates were 5.6% and 6.2%, respectively; and major hemorrhagic events occurred in 74% and 50.9%, respectively (p = 0.002). On multivariate analysis, the only independent predictor of perioperative mortality was bypass surgery within 24 h after entry or after coronary angioplasty. Among patients undergoing bypass surgery within 24 h of entry or after coronary angioplasty, the prevalence of multivessel disease (59.1% vs. 77.8%) and use of the internal thoracic artery (18.5% vs. 62.5%) were lower than in the remaining surgical patients. Among the 322 perioperative survivors, the 1-year mortality rate after discharge was only 2.2% and 1.9%, respectively, in the two groups. Only one patient had a documented recurrent myocardial infarction during the first year. CONCLUSIONS: The increased mortality rate with bypass surgery after thrombolytic therapy, particularly in patients undergoing operation within 24 h of coronary angioplasty or during the involving phase of infarction, must be balanced against the excellent 1-year prognosis and perioperative survivors, who are in general a group at higher risk of death or recurrent infarction. These data provide a basis for comparison for future studies.

Angioplasty, Balloon, Coronary↗
PubMed1995

Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo.

A major problem in the study of lesions of atherosclerosis is the difficulty of imaging noninvasively the lesions and following their progression in vivo. To address this problem, we have developed advanced magnetic resonance techniques to noninvasively and serially image advanced lesions of atherosclerosis in the rabbit abdominal aorta. Both lumen and wall were imaged with high resolution. Progression of disease, resulting in increase in lesion mass, decrease in arterial lumen, or stenosis, and intralesion complications, can be detected. Images acquired in vivo correlate with the fine structure of the lesions of atherosclerosis, including the fibrous cap, necrotic core, and lesion fissures, as verified by gross examination, dissection microscopy, and histology. The ability to noninvasively identify the features of atherosclerotic plaques, has significant implications for determining risks and benefits associated with different therapeutic approaches.

Animals↗