Isolation of differentially expressed genes in epidermal Langerhans cells.
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Animals↗
Biomedical subjects
R Ross
Publications and source records attributed to R Ross.
Complex evolution of tandem-repetitive DNA in the Chironomus thummi species group.
The subspecies Chironomus thummi thummi and C. t. piger display dramatic differences in the copy number and chromosomal localization of a tandemly repeated DNA family (Cla elements). In order to analyze the evolutionary dynamics of this repeat family, we studied the organization of Cla elements in the related outgroup species C. luridus. We find three different patterns of Cla element organization in C. luridus, showing that Cla elements may be either strictly tandem-repetitive or be an integral part of two higher-order tandem repeats (i.e., Hinf[lur] elements, Sal[lur] elements). All three types of Cla-related repeats are localized in the centromeres of C. luridus chromosomes. This suggests that the dispersed chromosomal localization of Cla elements in C. t. thummi may be the result of an amplification and transposition during evolution of this subspecies.
Animals↗
Cellular and molecular studies of atherogenesis.
The lesions of atherosclerosis represent a protective, inflammatory-fibroproliferative response against the different agents which can cause the disease. With a chronic insult, the response may become excessive and thus constitute part of the disease process. The excessive response may be reversed, given sufficient opportunity for modification of the injurious factors. Approaches to modifying specific cellular interactions, growth-regulatory molecules or intracellular signaling molecules may afford opportunities for lesion prevention or regression. For further reading see [1,2].
Arteriosclerosis↗
A dominant-negative mutation of the growth hormone receptor causes familial short stature.
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Binding Sites↗
Diminished contact hypersensitivity response in IL-4 deficient mice at a late phase of the elicitation reaction.
Contact hypersensitivity (CHS) is thought to depend on the activation of T cells of Th1 and/or Tc1 type. The role of Th2/Tc2 cells in the contact allergic reaction is not clear. The aim of this study was to analyse the functional contribution of Th2/Tc2 cells in CHS using the interleukin-4 (IL-4) deficient mouse model. Interleukin-4 deficient (IL4T) and control (wt) mice were sensitized by epicutaneous application of 2,4-dinitrofluorobenzene. The ear swelling response measured 24 h after challenge was similar in IL4T and control mice. However, from 48 h onwards, ear swelling values were significantly reduced in IL4T mice. The stimulatory capacity of freshly isolated as well as 3-day cultured epidermal cells, prepared from IL4T and wt mice, for allogeneic T cells in a primary and secondary response, was comparable. The reduced number of T cell receptor (TCR) gamma delta+ cells observed in epidermal sheets prepared from IL4T mice was not responsible for the decreased ear swelling response in IL4T mice, because the use of TCR delta deficient mice lacking TCR gamma delta+ cells revealed a down-regulatory role of this cell population in the CHS response. The data indicate that the effector stage of the CHS response can be subdivided into two phases. The first phase proceeds efficiently in IL-4 deficient mice indicating the dependence on Th1/Tc1 cells, while the second phase does not develop in mice lacking IL-4, suggesting the possibility that Th2/Tc2 cells intensify the reaction.
Animals↗
Growth hormone therapy in patients with cirrhosis: a pilot study of efficacy and safety.
BACKGROUND & AIMS: The protein catabolic state of cirrhosis is associated with severe growth hormone (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding protein (IGFBP)-3. The aim of this study was to conduct a randomized, double-blind, placebo-controlled pilot study of GH therapy in 20 cirrhotic patients to assess the reversibility of GH resistance and subsequent impact on protein economy and safety. METHODS: Patients were treated with GH (0.25 IU/kg body wt) or placebo for 7 days. Serum levels of GH, IGF-I, IGFBP-3, and insulin were measured by radioimmunoassay and 24-hour urinary nitrogen by the Kjeldahl technique. RESULTS: IGF-I levels increased only in the GH-treated group (mean, 69.2 +/- SE 7.0 to 170.6 +/- 48.8 ng/mL; P < 0.05) together with IGFBP-3 (1.65 +/- 0.3 to 2.94 +/- 0.6 mg/L; P < 0.005). Cumulative nitrogen balance similarly improved only in the GH group (2.87-24.16 g; P < 0.05). No significant side effects of GH were observed. CONCLUSIONS: GH therapy can overcome the GH resistance of cirrhosis. The resulting improvement in nitrogen economy and possible influences on clinical outcomes will need to be confirmed in controlled studies of longer duration.
Aged↗
Whole-body protein turnover in the healthy elderly.
We tested the hypothesis that aging affects whole-body protein turnover via altered fat-free mass (FFM). Whole-body protein kinetics were estimated by the 60-h oral [15N]glycine method. Results from 16 healthy, elderly subjects (8 men and 8 women with a mean age of 72.6 y) were compared for age and sex effects with those of 15 lean young subjects (8 men and 7 women with a mean age of 28.4 y) during isoenergetic formula diets. Per kilogram body weight, nitrogen flux was lower only as an effect of age (P = 0.006) whereas age and female sex significantly lowered synthesis and breakdown (P < or = 0.04). However, per kilogram FFM, no significant age or sex effects on rates of protein kinetics remained. Age and female sex contributed significantly to decreased muscle protein catabolism (based on 3-methylhistidine excretion), both in absolute terms and as a percentage of whole-body protein breakdown in the elderly compared with the young: 20.2% compared with 30.9% in women and 27.9% compared with 39.8% in men. No significant age or sex effects on rates of nonmuscle lean tissue protein breakdown were observed with or without correction for body composition. We conclude that the lower rates of flux, synthesis, and breakdown per kilogram body weight in elderly compared with young persons are due to changes in body composition with aging because rates are not different per kilogram FFM. However, there is a reduced contribution by muscle to whole-body protein catabolism in older persons. This has potential implications for the nutrition of both normal and sick elderly persons.
Adult↗
Risk adjustment of nursing home quality indicators.
The purpose of this study was to develop a method for risk adjusting nursing home quality indicators (QI's). The QI's measure incidence and prevalence of resident-level care processes and outcomes which are indicative of care quality. Risk adjustment was carried out by stratifying residents into risk groups (high and low), calculating QI rates within groups, and then drawing comparisons across facilities. The method was examined through analysis of data from over 800 nursing homes in four states. Results showed that facilities differed substantially in QI rates even after risk had been taken into account. Also, results suggested differences in care quality which may not have been apparent without controlling for risk.
Activities of Daily Living↗
Expression of a disintegrin-like protein in cultured human vascular cells and in vivo.
Metalloproteinase-like, disintegrin-like, and cysteine-rich proteins (MDCs) are potential novel regulators of cell-cell and cell-matrix interactions, as well as of matrix degradation. We have asked whether MDCs are expressed in cultured diploid vascular cells, and have identified MDC 15 in human aortic smooth muscle (SMC) and umbilical vein endothelium (HUVEC). MDC 15 mRNA is expressed at higher levels in HUVECs than in SMCs. In cultured SMCs, MDC 15 mRNA levels are not regulated by PDGF or IGF-I or by adherence to different extracellular matrices. Nor is regulation of MDC 15 mRNA levels observed in HUVEC monolayers at different cell densities, after multi-scratch wounding, or after treatment with TNF-alpha, LPS, or thrombin. However, differences in proteolytic processing of MDC 15 are observed in different HUVEC strains. In contrast to cultured arterial cells, MDC 15 protein is not expressed in vivo in normal vessels, but is up-regulated in lesions of atherosclerosis. These findings suggest that MDC 15 may be a potential regulator of vascular cell function and may be involved in the development of lesions of atherosclerosis.
ADAM Proteins↗
Human body composition: advances in models and methods.
The field of human body composition research is reaching a mature stage in its development: The three interconnected areas that define body composition research--models and their rules, methodology, and biological effects--are well-defined and are actively investigated by scientists in diverse disciplines from many different nations; and methods are available for measuring all major atomic, molecular, cellular, and tissue-system level body composition components in research, clinical, and epidemiological settings. This review summarizes main body composition research concepts, examines new component-measurement methodologies, and identifies potential areas of future research.
Adipose Tissue↗
PCR-amplified cDNA probes for verification of differentially expressed genes.
Differential display has proven to be a powerful technique for the detection and isolation of differentially expressed genes. By generating reproducible cDNA expression patterns, it is possible to compare gene expression by two or more cell types, developmental stages or tissues and to isolate as yet unknown differentially expressed genes. A sensitive method is necessary to verify the differential expression of the isolated cDNAs. Here we describe the use of adaptor-ligated. PCR-amplified total cDNA of the two cell types compared as a probe for Southern hybridizations with the isolated cDNAs.
Animals↗
Effects of diet- and exercise-induced weight loss on visceral adipose tissue in men and women.
The effects of diet- and exercise-induced weight loss on visceral adipose tissue (VAT) distribution in both men and women have been reviewed. In general, current knowledge is based on studies that have assessed the influence of diet alone on VAT in obese women. For every kilogram of diet-induced weight loss, the corresponding reduction in VAT expressed in absolute terms is approximately 3 to 4 cm2, and in relative terms is approximately 2 to 3%. Thus, a diet-induced weight loss of approximately 12 kg corresponds to a 30 to 35% reduction in VAT. Two studies that consider the effects of exercise per se on VAT report conflicting results. There appears to be a resistance to VAT reduction in obese women, whereas exercise-induced weight loss is associated with significant reductions in VAT in men. It was also reported that in obese men, reductions in VAT induced by the combination of diet and exercise are not different from those observed in response to diet alone. It is unclear whether the results of these studies reflect a biological truth or are confounded by methodological problems associated with the control of energy intake and expenditure in free-living patients. Evidence suggests that changes in waist circumference and sagittal diameter are well correlated with corresponding changes in VAT. A 1 cm reduction in waist circumference corresponds to a 5 cm2 (4%) reduction in VAT area at the L3 level. Data on the separate effects of diet- and exercise-induced weight loss on VAT from well controlled studies are required to advance current knowledge with respect to the effects of diet and exercise on the adipose tissue depot that conveys the greatest health risk.
Adipose Tissue↗
On some peculiar pigmented cells found in two mosquitoes fed on malarial blood. 1897.
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Animals↗
A memorandum on the present position of malaria prevention in India by Ronald Ross, CB., DPH., FRCS., MD., D.Sc., LLD., FRS., Major, Indian Medical Services, retired professor of tropical medicine, University of Liverpool.
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Humans↗
Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors.
Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen, and levels of the cdk2 inhibitors p27Kip1 and p21Cip1/Waf1 are increased compared with SMCs on monomer collagen. p27Kip1 associates with the cyclin E-cdk2-p21Cip1/Waf1 complex in SMCs on polymerized collagen. Monovalent blocking antibodies to alpha2 integrins, integrins that mediate adhesion to both forms of collagen, mimic these effects on monomer collagen. Furthermore, polymerized collagen rapidly suppresses p70 S6 kinase, a possible regulator of p27Kip1. Thus, fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation.
Antibodies↗
Application of proton NMR spectroscopy to measurement of whole-body RNA degradation rates: effects of surgical stress in human patients.
The urinary catabolites, N2,N2-dimethylguanosine (DMG), pseudouridine (PSU) and 7-methylguanine (m7-Gua) are formed from post-transcriptional methylation of RNA bases and are not reincorporated into RNA upon its degradation. Their quantitative urinary excretion may be used to determine rates of whole body degradation of individual RNA species since DMG occurs exclusively in tRNA, PSU occurs in rRNA and tRNA and m7-Gua occurs in all RNA species. Conventional HPLC analysis has several drawbacks since pre-analytical steps may involve selective losses and, under certain conditions, other urinary analytes may co-elute. In the present paper, we report analysis of these compounds by high-field 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. Urinary concentrations of these metabolites were found to be in agreement with previously published HPLC and ELISA determinations. However, NMR analysis required minimal sample preparation (other than lyophilisation and reconstitution) and was capable of the simultaneous determination of other relevant analytes such as creatinine. This technique was therefore applied to urine samples from patients who had undergone surgical stress and insulin-like growth factor-1 (IGF-I) therapy. Surgical stress increased the excretion of DMG and m7-Gua. Degradation rates for tRNA and mRNA were also higher in surgically stressed subjects when compared with controls but degradation rates of rRNA decreased by approx. 30%. However, injection of IGF-I (40 micrograms/kg s.c.) had no significant effect on the excretion of these nucleosides. These data indicated that IGF-I therapy has no marked effects on RNA turnover following trauma. We suggest that this technique can be applied to study of RNA metabolism in any surgical or medical condition. Furthermore, since only 0.6 ml of urine is required, studies in neonates seem to be feasible.
Adult↗
Platelet-derived growth factor stimulates protein kinase A through a mitogen-activated protein kinase-dependent pathway in human arterial smooth muscle cells.
The abilities of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I) to regulate cAMP metabolism and mitogen-activated protein kinase (MAP kinase) activity were compared in human arterial smooth muscle cells (hSMC). PDGF-BB stimulated cAMP accumulation up to 150-fold in a concentration-dependent manner (EC50 approximately 0.7 nM). The peak of cAMP formation and cAMP-dependent protein kinase (PKA) activity occurred approximately 5 min after the addition of PDGF and rapidly declined thereafter. Incubating cells with PDGF and 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor) enhanced the accumulation of cAMP and PKA activity by an additional 2.5-3-fold, whereas IBMX alone was essentially without effect. The PDGF-stimulated increase in cAMP was prevented by addition of the cyclooxygenase inhibitor indomethacin, consistent with release of prostaglandins stimulating cAMP. PDGF, but not IGF-I, stimulated MAPK activity, cytosolic phospholipase A2 (cPLA2) phosphorylation, and cAMP synthesis which indicated a key role for MAP kinase in the activation of cPLA2. Further, PDGF stimulated the rapid release of arachidonic acid and synthesis of prostaglandin E2 (PGE2) which could be inhibited by a cPLA2 inhibitor (AACOCF3). Calcium mobilization was required for PDGF-induced arachidonic acid release and PGE2 synthesis but not for MAPK activation, whereas PKC was required for PGE2-mediated activation of PKA. In summary, these results demonstrated that PDGF increases cAMP formation and PKA activity through a MAP kinase-mediated activation of cPLA2, arachidonic acid release, and PGE2 synthesis in human arterial smooth muscle cells.
1-Methyl-3-isobutylxanthine↗
Multiple growth factors are associated with lesions of atherosclerosis: specificity or redundancy?
Within the last five years, a number of specific growth factors have been localized in developing lesions of atherosclerosis. This localization of growth factors that is not observed in normal vessels, together with the pleotrophic activities of growth factors, have suggested a role for growth factors in atherosclerotic lesion progression. However, based on in vitro studies, many of the growth factors identified in lesions have overlapping target cells and are derived from the same cellular sources. What is the relative role of the specific growth factors identified? How is the their activity altered by the local conditions in the vessel wall? How do different risk factors for atherosclerosis alter the balance between growth factors and their natural regulators? Evidence for the involvement of specific growth factors in the progression of lesions of atherosclerosis is discussed, as well as the multiple levels at which the activities of these growth factors may be regulated by the vessel wall.
Arteriosclerosis↗