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Biomedical subjects

L Mullins

Publications and source records attributed to L Mullins.

16 recordsLinked to original sources
PubMed1999

Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization.

Nonenzymatic cytosolic fatty acid binding proteins (FABPs) are abundantly expressed in many animal tissues with high rates of fatty acid metabolism. No physiological role has been demonstrated for any FABP, although these proteins have been implicated in transport of free long-chain fatty acids (LCFAs) and protection against LCFA toxicity. We report here that mice lacking heart-type FABP (H-FABP) exhibit a severe defect of peripheral (nonhepatic, non-fat) LCFA utilization. In these mice, the heart is unable to efficiently take up plasma LCFAs, which are normally its main fuel, and switches to glucose usage. Altered plasma levels of LCFAs, glucose, lactate and beta-hydroxybutyrate are consistent with depressed peripheral LCFA utilization, intensified carbohydrate usage, and increased hepatic LCFA oxidation; these changes are most pronounced under conditions favoring LCFA oxidation. H-FABP deficiency is only incompletely compensated, however, causing acute exercise intolerance and, at old age, a localized cardiac hypertrophy. These data establish a requirement for H-FABP in cardiac intracellular lipid transport and fuel selection and a major role in metabolic homeostasis. This new animal model should be particularly useful for investigating the significance of peripheral LCFA utilization for heart function, insulin sensitivity, and blood pressure.

3-Hydroxybutyric Acid↗
PubMed1997

Decreased fat and nitrogen losses in patients with AIDS receiving medium-chain-triglyceride-enriched formula vs those receiving long-chain-triglyceride-containing formula.

OBJECTIVE: The purpose of this study was to compare two enteral formulas, differing only in fat source, for product acceptance, tolerance, and effect on fat malabsorption and nutritional status in subjects with acquired immune deficiency syndrome (AIDS). DESIGN: The double-blind, randomized 15-day trial was divided into a 3-day period in which solid food was consumed followed by a 12-day experimental period in which liquid formulas were consumed. SETTING/SUBJECTS: Twenty-three men and one woman with AIDS and fat malabsorption completed the study. The study was conducted in the General Clinical Research Center, University of Alabama Hospital, University of Alabama at Birmingham. Laboratory assays were performed in the Department of Nutrition Sciences. INTERVENTIONS: After 3 days of consuming a controlled, solid food diet containing 100 g fat per day from mixed sources to document fat malabsorption, subjects were randomly assigned to one of two groups. Each group received a liquid formula containing 35% of energy as fat for 12 days. One group received a formula containing 85% medium-chain triglycerides (MCTs) and the control group received a formula containing 100% long-chain triglycerides. MAIN OUTCOME MEASURES: Determinations included stool number, consistency, weight, and fat and nitrogen content; urine nitrogen and creatinine levels; and body weight. STATISTICAL ANALYSIS PERFORMED: Subject demographic and other baseline characteristics were compared using two-sample t tests; stool and urine assessments were compared between groups at the initial experimental period using two-sample t tests; changes from initial to final experimental periods were assessed by means of analysis of covariance; changes in pooled intake, body weight, and the number and consistency of bowel movements were also assessed using analysis of covariance. All statistical tests were two-tailed and considered significant at P < .05. RESULTS: Within-group comparisons indicated that subjects fed the MCT formula showed significantly decreased stool fat and stool nitrogen content (P = .01 and P = .03, respectively) and increased fat absorption (P = .03), whereas those fed the control formula did not. Differences in stool fat between the groups were not statistically significant. However, the difference in fat absorption from the initial to final formula period was significant (P = .04). Subjects consuming the MCT formula also tended to have a decreased number of bowel movements and abdominal symptoms, whereas subjects fed the control formula showed no improvement. All subjects maintained their body weights. APPLICATIONS: There may be advantages to using an MCT-based formula in the treatment of AIDS-associated malabsorption.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Candidate biomarkers of aging: age-sensitive indices of immune and muscle function covary in genetically heterogeneous mice.

A longitudinal experiment was designed to test the hypothesis that individual mice differ in their aging rate and to validate candidate biomarkers proposed to measure the rate of aging. Mice were bred as the genetically heterogeneous progeny of a cross between CB6F1 mothers and C3D2F1 fathers. Half of the mice were fed ad libitum (AL group), and the other half were subjected to 60% calorie restriction (CR group). Each mouse was tested at about 9 months of age using age-sensitive tests of immune status, and then again at about 12 months of age using age-sensitive tests of muscle function. The data were then analyzed using the method of partial least squares to determine the combinations of test weights that maximize the covariance of the weighted sum of immune measures with the weighted sum of muscle function measures. Both AL and CR mice exhibited a statistically significant relation between the immune status tests and the muscle function tests. Maximal covariance was obtained with a set of weighting coefficients consistent with our working hypothesis: mice with high levels of CD4 memory T cells (which increase with age) also had relatively low levels of muscle strength and endurance. Low strength was associated with low CD8 cells in the AL mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells in both diet groups. The partial least squares method generates composite indices of immune status and muscle function that can be evaluated as biomarkers of aging rate in these mice. Further work will be needed to assess whether these tests predict either longevity or the trajectory of change in other age-sensitive molecular and physiological traits.

Aging↗
PubMed1997

Coping with general and disease-related stressors by patients with multiple sclerosis: relationships to psychological distress.

This study examined the relationships between coping styles and psychological distress in a non-institutionalized sample of individuals with multiple sclerosis (MS). The MS sample completed a measure of psychological distress and identified coping strategies utilized for stressors that were disease-related and general in nature. They also self-reported their perceived efficacy of the coping strategies utilized for both stressors. Individuals with MS exhibited greater levels of depression and their indices of psychological distress than demographically matched controls but the patterns of coping strategies endorsed and the ratings of coping effectiveness were similar for the two groups. When coping with disease-related stressors, individuals with MS utilized coping strategies that were more emotion-focused and dependent but no less effective than when the same patients coped with general stressors. Within the MS group, high levels of psychological distress were positively correlated with the use of emotion-focused coping strategies, but were unrelated to the use of problem-focused strategies. Most individuals with MS individuals with MS appear to be able to modify their coping strategies to adopt to varying sorts of stressors.

Adaptation, Psychological↗
PubMed1996

Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS-M.

Normal mammalian development requires a diploid combination of both haploid parental genomes. Uniparental disomy for certain segments of specific chromosomes results in aberrant development or prenatal lethality, indicating that the parental genomes have undergone modifications during gametogenesis. These modifications result in parent-of-origin specific expression for some genes, a phenomenon called genomic imprinting. Recent work with DNA methyltransferase deficient mice showed that differential methylation is the probable basis of the imprinted character of several genes. Screening for endogenous imprinted loci using restriction landmark genomic scanning with methylation sensitive enzymes (RLGS-M) identified eight imprinted RLGS (Irigs) candidate loci. Molecular analysis of the genomic region of one of the loci (Irigs2) resulted in the discovery of the paternally imprinted U2afbp-rs gene within a previously identified imprinted region on mouse chromosome 11 (refs 5, 7). This paper describes the characterisation of a novel imprinted RLGS-M locus, Irigs3, on mouse chromosome 9 (ref. 6). Within this locus we identified the Grf1 (also called Cdc25Mm) gene, which is homologous to the RAS-specific guanine nucleotide exchange factor gene, CDC25, in Saccharomyces cerevisiae. Grf1 is located about 30 kb downstream of the methylation imprinted site, identified by RLGS-M, and shows paternal allele specific expression in mouse brain, stomach and heart. Our results indicate that imprinting may have a role in regulating mitogenic signal transduction pathways during growth and development.

Animals↗
PubMed1996

The surveillance of birth defects: the usefulness of the revised US standard birth certificate.

To assess the sensitivity and positive predictive value of birth defects reported on the 1989 revision of the US Standard Birth Certificate, a population of 76,862 Atlanta-area births during 1989 and 1990 was used as the basis for comparing 771 birth certificates that reported birth defects with 2428 live-born infant records in a birth defects registry that uses multiple sources of case ascertainment. Only 14% of birth defects in the registry records were reported on birth certificates. After the analysis was restricted to defects recognizable at birth, the sensitivity and positive predictive value of the birth certificates were 28% and 77%, respectively. Birth certificates underestimate birth defect rates and should be used cautiously for birth defect surveillance and epidemiological studies.

Birth Certificates↗
PubMed1995

Infertility in a transgenic rat due to impairment of cytoplasmic elimination and sperm release from the Sertoli cells.

In line TGR(mRen2)26 transgenic rats (TGR26) bearing a randomly inserted additional renin transgene, the males, but not the females, were found to be infertile. Tissue was obtained from TGR26 males and littermate controls after perfusion fixation, and the morphology of the testes and epididymides was examined. Testis size was normal as was gross morphology, but careful examination revealed that the release of many spermatozoa at stage IX of the spermatogenic cycle was impaired. In addition, the process of cytoplasmic elimination was abnormal, as cytoplasmic fragments of elongate spermatids were present in the epididymis. In TGR26 males, seminiferous tubule lumen size was significantly larger (p < 0.001) than in littermate controls, a difference that was most marked at stages IX-XIV--an effect that could be related to the retention of spermatozoa. In situ hybridization confirmed that expression of renin mRNA could be detected in testes of TGR26 rats but not in normal controls or in a fertile line (TGR27) of rats bearing the same transgene. Immunocytochemistry and in situ and Northern hybridization were used to elucidate the pattern of expression of genes that previous studies have implicated in the process of sperm maturation and/or release. Of the gene products examined (sulphated glycoproteins 1 and 2 [SGP-1, SGP-2], transition proteins 1 and 2 [TP-1, TP-2], urokinase, and cyclic protein 2[CP-2], none showed any major change in the pattern of expression compared with that in controls. We postulate that TGR26 transgenic male rats may be infertile because the expression of a gene (or genes) involved in the process of cytoplasmic elimination and/or sperm release has been disrupted by the presence of the transgene close to or within the gene(s). Future planned studies will involve determination of the insertion site(s) and ultrastructural analysis of the final phases of spermiogenesis.

Animals↗
PubMed1995

Infertility in a transgenic rat due to impairment of cytoplasmic elimination and sperm release from the Sertoli cells.

In line TGR(mRen2)26 transgenic rats (TGR26) bearing a randomly inserted additional renin transgene, the males, but not the females, were found to be infertile. Tissue was obtained from TGR26 males and littermate controls after perfusion fixation, and the morphology of the testes and epididymides was examined. Testis size was normal as was gross morphology, but careful examination revealed that the release of many spermatozoa at stage IX of the spermatogenic cycle was impaired. In addition, the process of cytoplasmic elimination was abnormal, as cytoplasmic fragments of elongate spermatids were present in the epididymis. In TGR26 males, seminiferous tubule lumen size was significantly larger (p < 0.001) than in littermate controls, a difference that was most marked at stages IX-XIV--an effect that could be related to the retention of spermatozoa. In situ hybridization confirmed that expression of renin mRNA could be detected in testes of TGR26 rats but not in normal controls or in a fertile line (TGR27) of rats bearing the same transgene. Immunocytochemistry and in situ and Northern hybridization were used to elucidate the pattern of expression of genes that previous studies have implicated in the process of sperm maturation and/or release. Of the gene products examined (sulphated glycoproteins 1 and 2 [SGP-1, SGP-2], transition proteins 1 and 2 [TP-1, TP-2], urokinase, and cyclic protein 2 [CP-2]), none showed any major change in the pattern of expression compared with that in controls. We postulate that TGR26 transgenic male rats may be infertile because the expression of a gene (or genes) involved in the process of cytoplasmic elimination and/or sperm release has been disrupted by the presence of the transgene close to or within the gene(s). Future planned studies will involve determination of the insertion site(s) and ultrastructural analysis of the final phases of spermiogenesis.

Animals↗
PubMed1994

An examination of demographic, socio-cultural, and health differences between congregate and home diners in a senior nutrition program.

Building upon prior research, this study investigates characteristics of participants in a senior nutrition program in Hillsborough County, Florida. The Senior Citizens Nutrition and Activities Program serves approximately 2,600 meals per day to county residents 60 years of age and over. In this study, a sample of 1,071 participants are surveyed for background characteristics, interpersonal relationships and emotional closeness, health and economic condition, emotional condition, and participation in the program. Crosstabular analyses are performed on the collected data with age, sex, and race controlled. The results indicate that the program is reaching its goals of promoting good health among the older population of Hillsborough County by providing nutritious meals and reducing social isolation, which often accompanies aging.

Aged↗
PubMed1991

Transgenic approaches to modification of cell and tissue function.

The past 18 months have seen rapid advances in the use of transgenic techniques for elucidating cellular mechanisms. The modification of gene, cellular and tissue function has been enhanced by developments in the use of antisense and ribozyme constructs, and by improvements in strategies for cell ablation and homologous recombination.

Animals↗
PubMed1989

Health care utilization of Canadian snowbirds: an example of strategic planning.

Older English-speaking Canadian seasonal migrants to Florida (N = 2046) were surveyed during the winter of 1986. They are users of two health care systems and are generally in good health. When they do need to use health care resources, however, they show a distinct preference for the Canadian system. There is a sensitivity to health concerns, especially among the older of the migrants. This sensitivity generates considerable precautionary behavior including pretravel visits to their Canadian family doctors, stocking up on drugs before the trip, and taking out health insurance for Canadians traveling abroad. The behavior is strategic in that it is both intentional and oriented to contingencies. Cost of health care may be a motivating factor because such strategic behavior is inversely related to income in this relatively affluent migrating population. The flock of Canadian snowbirds is not likely to place exorbitant demands on the U.S. health care system.

Aged↗
PubMed1989

Endogenous inhibition of red blood cell Na,K-ATPase in essential and pregnancy-induced hypertension.

Digoxin-like inhibitors of Na,K-ATPase have been implicated in the pathophysiology of essential (EH) and pregnancy-induced hypertension (PIH). A technique that enhances dissociation of digoxin from red blood cells (RBC) was used to displace endogenous digoxin-like substances from RBCs. RBC membranes were preincubated in Na and ATP (Release) or Na,K,Mg and ATP (Retention) prior to measuring ATPase activity. Groups studied were: 39 men with EH and 34 controls plus 10 women with PIH and 17 normotensive controls. All displayed similar increases in Na,K-ATPase activity (24.0 +/- 7.9%) following Release. Plasma digoxin immunoreactivity (DI) was measured in pregnant women, m = 0.25 +/- 0.07 ng/ml. No DI was detected in nonpregnant women, but RBCs from these women demonstrated the same increase in Na,K-ATPase activity after Release. The 24% increase in activity achieved by Na and ATP preincubation can be reversed by adding K and Mg to the Release suspension. However, after RBC-bound digoxin is displaced by Release preincubation, addition of K and Mg cannot promote renewed binding and pump inhibition. Thus, the observed endogenous inhibition is not due to displacement of a digoxin-like substance but probably is related to alteration of the enzyme-membrane interaction. Furthermore, even though pregnant women demonstrate DI, an inhibitory substance with digoxin-like binding could not be recognized using this technique.

Adult↗