PubMed Health⌕ Search

Biomedical subjects

A Galecki

Publications and source records attributed to A Galecki.

8 recordsLinked to original sources
PubMed2001

Interpretation, design, and analysis of gene array expression experiments.

Experiments using arrays of cDNA targets to compare patterns of gene expression are beginning to play a prominent role in biogerontology, but drawing reliable conclusions from the resulting data sets requires careful application of statistical methods that discriminate chance events from those likely to reflect real differences among the samples under study. This essay discusses flaws in the logic of studies that base their conclusions on ratio calculations alone, reviews the multiple comparison traps inherent in high throughput systems that test a very large number of mRNAs simultaneously, and advocates a two-stage design in which significance testing applied to exploratory data is used to guide a second round of hypothesis-testing experiments conducted in a separate set of experimental samples.

Aging↗
PubMed2000

Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm.

The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2- + NO3- and L-citrulline). Twelve healthy subjects (27+/-6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45% of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150%, 335% and 585% above baseline at 15, 30 and 45% of MVC, respectively. (ANOVA, P= 0.0001). Venous plasma NO2- + NO3- levels increased from 24+/-4 micromol/L at baseline, to 29+/-5, 32+/-4 and 3+/-4 micromol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31+/-5 micromol/L at baseline to 58+/-10, 87+/-7 and 141+/-15 micromol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2- + NO3- (slope= 0.38+/-0.10, P=0.0007) and between L-citrulline, (slope= 5.1 +/-1.3, P = 0.0004). Venous plasma levels of NO2- + NO3- and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2- + NO3- and L-citrulline, in vivo markers of NO production.

Adult↗
PubMed2000

Accelerated dysfunction among the very oldest-old in nursing homes.

BACKGROUND: The population aged 65 and older is often analyzed in three categories: young-old (65-74), middle-old (75-84), and oldest-old (> or = 85). This may blind heterogeneity within the oldest category. New, large data sets allow examination of the very oldest-old (e.g., aged > or = 95) and contrasts with those who are younger. METHODS: We determined the annual change of prevalence of physical and cognitive function, and of disease problems in the old to very oldest-old, using data from existing Resident Assessment Instrument records from nursing homes in seven states during 1992-1994. We used data from 193,467 unique residents aged 80 or older, including 6,556 residents aged 100 or older. We computed the prevalence, by age, of selected conditions: physical and cognitive function, diseases, problem behavior, mood disturbance, restraint use, falls, weight loss, eating less, body mass index, chewing and swallowing problems, incontinence (bowel and bladder), catheter use, and selected diagnoses. RESULTS: Prevalence of all measures of physical and cognitive dysfunction increased most rapidly with each year of age among the very oldest-old. Most of the slope changes occurred from 95 to 100 years of age. Such changes are less pronounced or not seen in measures of disease prevalence. CONCLUSIONS: Accelerated change in prevalence of dysfunction seen in the nursing home population may suggest a change in the mechanisms of aging that occur after the mid-nineties. Examination of the very oldest-old may provide new insight into the nature of the aging process.

Activities of Daily Living↗
PubMed1999

Multiple-trait quantitative trait loci analysis using a large mouse sibship.

Quantitative trait loci influencing several phenotypes were assessed using a genetically heterogeneous mouse population. The 145 individuals were produced by a cross between (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males. The population is genetically equivalent to full siblings derived from heterozygous parents, with known linkage phase. Each individual in the population represents a unique combination of alleles from the inbred grandparents. Quantitative phenotypes for eight T cell measures were obtained at 8 and 18 mo of age. Single-marker locus, repeated measures analysis of variance identified nine marker-phenotype associations with an experimentwise significance level of P < 0.05. Six of the eight quantitative phenotypes could be associated with at least one locus having experiment-wide significance. Composite interval, repeated measures analysis of variance identified 13 chromosomal regions with comparisonwise (nominal) significance associations of P < 0.001. The heterozygous-parent cross provides a reproducible, general method for identification of loci associated with quantitative trait phenotypes or repeated phenotypic measures.

Animals↗
PubMed1997

CD4 memory T cell levels predict life span in genetically heterogeneous mice.

Aging leads to changes in the relative proportions of several functionally distinct T cell subsets, including increases in the proportions of memory cells in the CD4 and CD8 subsets and in the proportion of T cells expressing the multiple-drug resistance pump P-glycoprotein. To see whether individual differences in T cell subset levels predict life span, we measured the levels of five age-sensitive T cell subsets, at 8 and again at 18 months of age, in the peripheral blood of genetically heterogeneous mice bred as the progeny of CB6F1 females and C3D2F1 males. The strongest immunological predictor of life span in univariate regression analyses was the proportion of CD4 memory cells measured at 18 months of age (P=0.003). CD4 memory cell levels remained strongly correlated with life span (P<0.0003) in a multiple regression analysis after adjustment for sex. The proportion of CD4 cells expressing P-glycoprotein was also correlated with life span (P<0.01), but only in male mice. Weaker relationships were observed between life span and 8-month tests of CD8 memory and CD8 P-glycoprotein levels, for CD4 naive cells at 18 months, and for the change in CD4 naive cells between 8 and 18 months of age; these were, however, near the margin of statistical significance and could reflect chance relationships. The relationship between CD4 memory cell levels and life span was similarly strong regardless of the cause of death in mice whose death was attributable to lymphoma, fibrosarcoma, mammary carcinoma, and other forms of terminal pathology. Additional work is needed to discriminate between two hypotheses: 1) that high levels of CD4 memory cell themselves predispose to disease and early death, particularly from neoplasia; or 2) that accumulation of CD4 memory cells is a biomarker of some underlying process-perhaps accelerated aging-that itself leads to early mortality.

Animals↗
PubMed1994

Hypoglycemia counterregulation in elderly humans: relationship to glucose levels.

This study was designed to define the effect of human aging on hypoglycemia counterregulatory mechanisms. A hyperinsulinemic (2 mU.kg-1.min-1) glucose clamp procedure was used to control glucose and insulin levels during stepwise lowering of plasma glucose. Counterregulatory hormones, hepatic glucose production (HGP), glucose utilization, and symptoms of hypoglycemia were studied in 13 healthy young [age 24 +/- 1 (SE) yr] and 11 healthy old (age 65 +/- 1 yr) nondiabetic volunteers on two occasions: 1) at matched euglycemia and 70 and 60 mg/dl (study 1) and 2) at matched euglycemia and 60 and 50 mg/dl (study 2). The old had consistently lower epinephrine (P < 0.005), glucagon (P < 0.02), cortisol (P < 0.05), and pancreatic polypeptide (P < 0.02) responses at the 60-mg/dl glucose step in study 1. However, these differences were no longer detectable at the more severe hypoglycemic stimulus of 50 mg/dl in study 2. A consistent increase in HGP occurred in both groups only at the 50-mg/dl glucose step (study 2) and was not different between young and old. There were also no differences in symptom responses between young and old. In summary, we found that elderly individuals have a subtle impairment of the glucose counterregulatory response during moderate hypoglycemia, but this impairment is no longer detectable during more severe hypoglycemia.

Adult↗
PubMedDate not supplied

Exotic mice as models for aging research: polemic and prospectus.

Most gerontological research using rodent models employs inbred strains, or F1 hybrids derived from them, rather than populations of genetically heterogeneous individuals. This study presents the argument that reliance on genetically homogeneous rodents, though sanctioned by tradition, may not be ideal for many sorts of investigations, and that use of heterogeneous mice and rats would allow researchers to reach robust conclusions that were less likely to reflect strain-specific idiosyncrasies. Segregating stocks, bred by backcross, F2 cross, or four-way cross procedures, would be an improvement over inbred and F1 stocks, providing inexpensive, arbitrarily large, and reproducible populations of genetically diverse test subjects. These stocks would not, however, recapture allelic variations that are likely to have been lost when wild-trapped mice and rats are selected inadvertently over dozens of generations for breeding success in laboratory conditions. Development of specific pathogen free stocks from wild-trapped progenitors particularly from populations selected for relevant evolutionary history and physiological characteristics, may be of great value for analysis of aging and late-life pathophysiology.

Aging↗