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Biomedical subjects

G McCabe

Publications and source records attributed to G McCabe.

13 recordsLinked to original sources

Using functional data analysis to summarise and interpret lactate curves.

John Tukey used the term exploratory data analysis (EDA) to describe a philosophy for analyzing data where graphical and numerical summaries are used to uncover interesting structures. The applied statistician today has a much more sophisticated set of methods to use when applying the EDA philosophy. One such collection of methods is functional data analysis (FDA), which was used to explore the structure of lactate curves. A principal components analysis and plots of the second derivatives provide new intuitive endurance markers which correlates highly with other numerical summaries of lactate curves that have been suggested in the literature.

Humans↗

Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix.

INTRODUCTION: The source of cells that participate in wound repair directly affects outcome. The extracellular matrix (ECM) and other acellular biomaterials have been used as therapeutic scaffolds for cell attachment and proliferation and as templates for tissue repair. The ECM consists of structural and functional proteins that influence cell attachment, gene expression patterns, and the differentiation of cells. OBJECTIVE: The objective of this study was to determine if the composition of acellular matrix scaffolds affects the recruitment of bone marrow-derived cellular elements that populate the scaffolds in vivo. METHODS: Scaffolds composed of porcine tissue ECM, purified Type I collagen, poly(L)lactic coglycolic acid (PLGA), or a mixture of porcine ECM and PLGA were implanted into subcutaneous pouches on the dorsum of mice. The origin of cells that populated the matrices was determined by first performing bone marrow transplantation to convert the marrow of glucose phosphate isomerase 1b (Gpi-1(b)) mice to cells expressing glucose phosphate isomerase 1a (Gpi-1(a)). RESULTS: A significant increase in Gpi-1(a) expressing cells was present in sites implanted with the porcine ECM compared to sites implanted with either Type I collagen or PLGA. Use of recipient mice transplanted with marrow cells that expressed beta-galactosidase confirmed that the majority of cells that populated and remodeled the naturally occurring porcine ECM were marrow derived. Addition of porcine ECM to the PLGA scaffold caused a significant increase in the number of marrow-derived cells that became part of the remodeled implant site. CONCLUSION: The composition of bioscaffolds affects the cellular recruitment pattern during tissue repair. ECM scaffolds facilitate the recruitment of marrow-derived cells into sites of remodeling.

Animals↗

Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18-31 years of age.

Women who exercise during their second and third decades may increase their peak bone mass and lower their eventual risk for postmenopausal fracture. However, the effects of exercise in younger women can be modulated by the use of oral contraceptives, which may prevent the normal accretion of bone mass that would otherwise occur. We hypothesized that exercise intervention in young adult women would significantly increase both bone mass and the bending rigidity of the femoral neck. We further hypothesized that exercise intervention in the presence of oral contraceptive use would have a negative effect on bone mass and bending rigidity. Women 18-31 years of age (n = 123) were classified by oral contraceptive use (OC, NOC) and age (18-23, 24-31 years), and then randomized into exercise or nonexercise groups. The exercise protocol consisted of three sessions/week of aerobic and nonaerobic exercises, and continued for 2 years. Each 6 months, the femoral neck of each subject was scanned using a Lunar dual-energy X-ray absorptiometry (DEXA) scanner, and bone mineral content, density and geometric information were used to calculate estimated stresses and bending rigidity at the hip. Percent changes from baseline were analyzed using two-way analysis of variance (ANOVA) at 6, 12, 18, and 24 months. Women who neither exercised nor took oral contraceptives (NE/NOC) had the greatest percentage increases in cross-sectional area (4.98 +/- 2.29%), cross-sectional moment of inertia (9.45 +/- 2.37%), total bone mineral density (2.07 +/- 2.09%), fracture index (8.03 +/- 2.03%), and safety factor (20.03 +/- 5.79%) over the 24 month exercise program. Women who exercised and did not take oral contraceptives (E/NOC) declined on most variables related to femoral strength and bone mass, whereas those women who took oral contraceptives were usually intermediate between NE/NOC and E/NOC, whether they exercised or not. These data show that either exercise or OC use is associated with a suppression of the normal increase in bone mass and mechanical strength in the femoral neck in women 18-31 years old, but the combination of exercise and OC use appears to have a less suppressive effect.

Absorptiometry, Photon↗

Chondrocyte-derived apoptotic bodies and calcification of articular cartilage.

Chondrocytes exposed to nitric oxide (NO) or antibody to Fas undergo cell death by apoptosis. This study examines structural and functional properties of chondrocyte-derived apoptotic bodies. In NO treated cartilage, the dense pericellular matrix that normally surrounds the cells is degraded and apoptotic bodies accumulate within and in the vicinity of the chondrocyte lacunae. Functional analysis shows that apoptotic bodies isolated from NO-treated chondrocytes or cartilage produce pyrophosphate. The levels of pyrophosphate produced by apoptotic bodies are increased by pretreatment of the chondrocytes with transforming growth factor beta and decreased by interleukin 1. Apoptotic bodies contain alkaline phosphatase and NTP pyrophosphohydrolase activities and can precipitate calcium. These results suggest that chondrocyte-derived apoptotic bodies express functional properties that may contribute to the pathologic cartilage calcification observed in aging and osteoarthritis.

Adult↗

Making the most of MEDLINE.

The MEDLINE database is firmly established as an essential tool in medical research and practice, and all doctors should develop MEDLINE search skills. This article reviews key elements of the database, looking particularly at areas of common error, and the options available when fine-tuning a search. A better understanding of MEDLINE should lead to more effective use of this invaluable resource.

CD-ROM↗

Differential effects of aging on human chondrocyte responses to transforming growth factor beta: increased pyrophosphate production and decreased cell proliferation.

OBJECTIVE: To address the influence of age on inorganic pyrophosphate (PPi) accumulation in human articular chondrocytes. METHODS: Articular cartilage was obtained from men and women in 2 different age groups: ages 15-55 and 56-91. The effects of transforming growth factor beta1 (TGFbeta1) on PPi levels in the media and cell lysates of chondrocytes were investigated. In addition, the effects of TGFbeta on PPi accumulation were compared with chondrocyte proliferation. RESULTS: TGFbeta1 increased PPi levels to a greater extent in chondrocytes from subjects in the older age group compared with those obtained from younger subjects. Treatment of chondrocytes with TGFbeta1 led to a similar increase in total intracellular protein in both age groups. Although TGFbeta increased nucleoside triphosphate pyrophosphohydrolase activity and decreased alkaline phosphatase activity, these effects did not differ between the 2 age groups. Analysis of the same cell preparations showed an age-related decrease in TGFbeta-induced chondrocyte proliferation, whereas these same cells showed an increased response with respect to PPi elaboration. CONCLUSION: These results show that aging differentially affected TGFbeta-induced PPi accumulation versus proliferation in human articular chondrocytes. These differences in TGFbeta response are likely to contribute to the development of age-associated cartilage diseases such as osteoarthritis.

Adolescent↗

Earth-Based Observations of the Galileo Probe Entry Site

Earth-based observations of Jupiter indicate that the Galileo probe probably entered Jupiter's atmosphere just inside a region that has less cloud cover and drier conditions than more than 99 percent of the rest of the planet. The visual appearance of the clouds at the site was generally dark at longer wavelengths. The tropospheric and stratospheric temperature fields have a strong longitudinal wave structure that is expected to manifest itself in the vertical temperature profile.

Journal Article↗

Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes.

Articular cartilage chondrocytes have the unique ability to elaborate large amounts of extracellular pyrophosphate (PPi), and transforming growth factor beta (TGF beta) appears singular among cartilage regulatory factors in stimulating PPi production. TGF beta caused a time and dose-dependent increase in intracellular and extracellular PPi in human articular chondrocyte cultures. TGF beta and interleukin 1 beta (IL-1 beta) antagonistically regulate certain chondrocyte functions. IL-1 beta profoundly inhibited basal and TGF beta-induced PPi elaboration. To address mechanisms involved with the regulation of PPi synthesis by IL-1 beta and TGF beta, we analyzed the activity of the PPi-generating enzyme NTP pyrophosphohydrolase (NTPPPH) and the PPi-hydrolyzing enzyme alkaline phosphatase. Human chondrocyte NTPPPH activity was largely attributable to plasma cell membrane glycoprotein 1, PC-1. Furthermore, TGF beta induced comparable increases in the activity of extracellular PPi, intracellular PPi, and cellular NTPPPH and in the levels of PC-1 protein and mRNA in chondrocytes as well as a decrease in alkaline phosphatase. All of these TGF beta-induced responses were completely blocked by IL-1 beta. Thus, IL-1 beta may be an important regulator of mineralization in chondrocytes by inhibiting TGF beta-induced PPi production and PC-1 expression.

Adult↗

Relation of rearing environment to adaptive behavior of Egyptian toddlers.

2 questions were explored: (1) Do observed relations found in Western cultures between specific psychosocial environmental factors and toddlers adaptive behavior resemble the pattern of relations found in a non-Western setting? (2) Does the specificity of relations between environment and performance found in Western cultures also operate in a non-Western culture? Subjects were 153 Egyptian toddlers, 18-30 months of age, and their caregivers. Twice a month between 18 and 30 months toddlers were observed in naturalistic interactions with their caregivers, and measures of caregiver behavior and toddler functioning were coded. Replicating previous results from Western cultures, canonical analysis indicated that caregiver vocal stimulation was positively related to indices of toddler behavioral competence, while nonverbal response to vocalization and physical contact stimulation were negatively related. The salience of sib caregivers was also noted. Particularly for the age period between 24 and 29 months, results indicated specificity of environmental action such that measures of caregiver vocal stimulation were uniquely related to measures of toddler vocalization, while caregiver response to distress was uniquely related to toddler emotionality. The present pattern of results suggests at least some degree of cross-cultural generalizability of environment-development relations and of the specificity model of environmental action.

Adaptation, Psychological↗

Expression of c-fos and AP-1 activity in senescent human fibroblasts is not sufficient for DNA synthesis.

Human fibroblasts have a limited replicative life span when maintained in culture after which they become unresponsive to treatment with mitogens, a phenomenon most commonly called senescence. Experiments indicating that serum does not induce expression of the c-fos proto-oncogene in senescent fibroblasts raised the issue of a potential central role for c-fos in the phenotype of sustained growth arrest. This was directly tested by microinjection of oncogenic c-Ha-ras protein into senescent fibroblasts. While ras injection was found to induce marked nuclear c-fos expression and functional AP-1 transcription activity, this did not lead to DNA synthesis. These results suggest that the senescence phenotype cannot be solely attributed to the absence of c-fos expression and that the proliferative block in these cells is either independent of AP-1 transcriptional activity, downstream of it, or involves multiple molecular mechanisms.

Cell Division↗

Spatial topological constraints in a bimanual task.

Previous research has shown that the concurrent performance of two manual tasks results in a tight temporal coupling of the limbs. The intent of the present experiment was to investigate whether a similar coupling exists in the spatial domain. Subjects produced continuous drawing of circles and lines, one task at a time or bimanually, for a 20 s trial. In bimanual conditions in which subjects produced the circle task with one hand and the line task with the other, there was a clear tendency for the movement path of the circle task to become more line-like and the movement path of the line task to become more circle-like, i.e., a spatial magnet effect. A bimanual circle task and a bimanual line task did not exhibit changes in the movement path when compared to single-hand controls. In all bimanual conditions, the hands were tightly temporally locked. The evidence of temporal coupling and concomitant accommodation in the movement path for the conditions in which the hands were producing different shapes suggests that spatial constraints play a role in the governance of bimanual coordinated actions.

Adult↗

Effects of respirators on performance of physical, psychomotor and cognitive tasks.

Possible work decrements caused by respirator usage were examined. A battery of physical, psychomotor and cognitive tasks was used to investigate the effects of respirator wear on 12 subjects. A repeated measures experimental design was used to study the effects of three types of respirators: a disposable dust mask; an air purifying half-mask; and a full-face airline mask. Performance while wearing a mask was compared to the control condition without a respirator. The results from the physical work task of riding a bicycle ergometer indicated approximately a 10% increase in oxygen consumption when subjects wore half and full-face masks in comparison to when they performed the tasks without a mask. The results indicate that wearing the respirators did not have a significant effect on the performance of cognitive tasks but did affect significantly the performance of psychomotor tasks such as steadiness of work performance and movements requiring accurate control for positioning of objects.

Adult↗

Serum potassium testing in diuretic-treated outpatients. A multivariate approach.

We evaluated risk factors for abnormal serum potassium (K+) concentrations in 5817 outpatients on chronic diuretic therapy. Hypokalemia (K+ less than 3.5 meq/L) occurred in 18.8 percent at the last clinic measurement. Hyperkalemia (K+ greater than 5.5) was rare (0.5%) and was even less common in those also taking KCl or a K+ sparing drug (0.2%). Hypokalemic patients were younger, healthier, more often hypertensive, more commonly taking a thiazide diuretic, and more likely to have been hypokalemic in the past. Hyperkalemic patients were older, more often suffering from heart or renal failure, and more commonly taking furosemide. Logistic regression analysis yielded eight variables that contributed significantly to the prediction of hypokalemia: mean and most recent serum K+, thiazide use, the use and duration of use of potassium-sparing diuretics, age, and most recent serum sodium and bicarbonate determinations. The regression equation allowed us to identify a group of patients (63% of the total) at low risk for hypokalemia (K+ less than 3.5 in 9.4%; K+ less than 3.0 in 0.5%) and another group (37% of the total) at high risk for hypokalemia (K+ less than 3.5 in 35%; K+ less than 3.0 in 5%). Information about the risk of hypokalemia can be used to decide when to measure serum potassium concentration in individual diuretic-treated outpatients.

Benzothiadiazines↗