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Biomedical subjects

J Phelps

Publications and source records attributed to J Phelps.

16 recordsLinked to original sources

Spinal cord injury and sexuality in married or partnered men: activities, function, needs, and predictors of sexual adjustment.

The sexual behaviors, functioning, needs, and sexual satisfaction levels of men with spinal cord injuries (SCI) were studied. A sample of 50 men with SCI (median age = 50; median age at injury = 25.0), either married or in a committed relationship, responded to an anonymous survey of a large southern California regional spinal injury rehabilitation center. Multiple regression analyses indicated that perceived partner satisfaction, relationship quality, and sexual desire were significant predictors of sexual satisfaction and behavior. Erectile function, level of genital sensation, and orgasmic capacity all varied widely in the sample, as well. However, none of these variables were significantly related to sexual satisfaction. A varied sexual repertoire was independently related to sexual satisfaction and behavior, but did not offer additional predictive power. Results suggest that for married or partnered men with SCI, relationship factors including partner satisfaction and relationship quality are significantly and positively related to sexual satisfaction. Married or partnered men with SCI who report low relationship satisfaction, have difficulty satisfying their partner, and/or report low sexual desire may benefit from assessments and interventions that address these issues.

Adaptation, Psychological↗

Viscoelastic response of fibroblasts to tension transmitted through adherens junctions.

Cytoplasmic deformation was monitored by observing the displacements of 200-nm green fluorescent beads microinjected into the cytoplasm of Swiss 3T3 fibroblasts. We noted a novel protrusion of nonruffling cell margins that was accompanied by axial flow of beads and cytoplasmic vesicles as far as 50 microm behind the protruding plasma membrane. Fluorescent analog cytochemistry and immunofluorescence localization of F-actin, alpha-actinin, N-cadherin, and beta-catenin showed that the protruding margins of deforming cells were mechanically coupled to neighboring cells by adherens junctions. Observations suggested that protrusion resulted from passive linear deformation in response to tensile stress exerted by centripetal contraction of the neighboring cell. The time dependence of cytoplasmic strain calculated from the displacements of beads and vesicles was fit quantitatively by a Kelvin-Voight model for a viscoelastic solid with a mean limiting strain of 0.58 and a mean strain rate of 4.3 x 10(-3) s(-1). In rare instances, the deforming cell and its neighbor spontaneously became uncoupled, and recoil of the protruding margin was observed. The time dependence of strain during recoil also fit a Kelvin-Voight model with similar parameters, suggesting that the kinetics of deformation primarily reflect the mechanical properties of the deformed cell rather than the contractile properties of its neighbor. The existence of mechanical coupling between adjacent fibroblasts through adherens junctions and the viscoelastic responses of cells to tension transmitted directly from cell to cell are factors that must be taken into account to fully understand the role of fibroblasts in such biological processes as wound closure and extracellular matrix remodeling during tissue development.

3T3 Cells↗

The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps.

Colorectal cancers continue as the second most common cause of death from cancer in the United States. Only a few prospective, randomized clinical trials have been performed to evaluate the potential preventive effects of dietary fiber or calcium in patients with an increased risk for the development or recurrence of colorectal cancer. We designed and conducted a double-blinded, placebo-controlled randomized trial involving supplementation of fiber and calcium intake and measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal biopsies obtained from patients with resected colorectal adenomas to examine the potential mechanisms by which dietary interventions might reduce colorectal cancer risk. We performed a randomized, double-blinded, Phase II study, using a factorial design to measure the effects of supplemental dietary wheat bran fiber (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium) supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h in vitro outgrowth cultures. Measurements were made at baseline randomization (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus 250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100 randomized participants who had a history of colon adenoma resection. Neither the wheat bran fiber nor the calcium carbonate supplements significantly reduced [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily supplementation in the 93 evaluable participants. We conclude that 9 months of high-dose wheat bran fiber and calcium carbonate supplementation in study participants with a history of recently resected colorectal adenomas does not have a significant effect on cellular proliferation rates in rectal mucosal biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there is great need for the evaluation of these two different nutrient interventions in the setting of Phase III studies wherein adenomatous polyp recurrence, rather than a rectal mucosal biomarker, serves as the primary end point.

Adenomatous Polyps↗

Differential sensitivity of mouse mononuclear phagocytes to CSF-1 and LPS: the potential in vivo relevance of enhanced IL-6 gene expression.

In this report, we compared the responsiveness of subpopulations of mononuclear phagocytes (MNP) to the actions of the monocyte-macrophage colony-stimulating factor (CSF-1) and lipopolysaccharide (LPS), as measured by the expression of the IL-6 (Il6) gene. It was seen that neither monocytes nor elicited peritoneal macrophages (PMphi) responded directly to CSF-1 compared with resident PMphi that were induced to express high levels of Il6 mRNA and release IL-6 protein. Resident PMphi released basal (constitutive) amounts of IL-6, while constitutive release by monocytes and elicited PMphi was barely detectable. Monocytes and elicited PMphi expressed similar levels of sensitivity to LPS, as measured by IL-6 release, and were less reactive than resident PMphi. When CSF-1 and LPS were added simultaneously to resident PMphi, a dose-dependent synergistic release of IL-6 was seen. Elicited PMphi also responded synergistically but required higher levels of CSF-1 and LPS, while monocytes failed to respond synergistically under any conditions. A similar synergistic effect was also seen in vivo when mice were injected with CSF-1 and LPS. Under these conditions, only resident peritoneal cells were shown to release IL-6 ex vivo while blood leukocytes and spleen cells released minimal amounts. These findings indicate that the stage of differentiation/maturation of MNP may be important for the ability of CSF-1 to render the cells sensitive to secondary stimulation, such as by LPS, and determines to what extent MNP subpopulations contribute to inflammatory responses in vivo.

Animals↗

Randomized, double-blinded, placebo-controlled study of effect of wheat bran fiber and calcium on fecal bile acids in patients with resected adenomatous colon polyps.

BACKGROUND: Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions between genetic susceptibility and environmental and dietary factors. Among the dietary components found to reduce colon cancer risk are high intakes of dietary fiber and calcium. PURPOSE: We designed and conducted a randomized, double-blinded, placebo-controlled trial involving supplementation of the customary dietary intake with fiber and calcium and measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer risk. METHODS: In a randomized, double-blinded, phase II study, we used a factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and excretion rates. Measurements were made at base-line randomization (i.e., after a 3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient subsample of the 95 fully assessable study participants who had a history of colon adenoma resection. Concentrations of fecal bile acids, total, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas-liquid chromatography. All P values resulted from two-sided tests. RESULTS: All geometric mean fecal bile acid concentrations and excretion rates were lower at 9 months than at 0 months or 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high-dose fiber effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentrations and excretion rates. For example at 9 months versus 0 months, high-dose fiber supplementation caused a reduction in fecal concentrations of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the geometric mean total bile acid (35% reduction; P = .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations. CONCLUSIONS: High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excretion rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neoplasia and cancer is by reduction of the concentrations of fecal bile acids. IMPLICATION: Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and have now been initiated at multiple institutions.

Adenomatous Polyposis Coli↗

Development of sensitive immunoassays to detect amylin and amylin-like peptides in unextracted plasma.

Amylin is a 37-amino-acid polypeptide synthesized in and secreted from pancreatic beta cells along with insulin. Its biological actions include the slowing and reduction of postmeal increases in plasma glucose concentrations. Studies of the basic amylin biology in humans have been hampered by the lack of a rapid, sensitive assay capable of measuring physiological concentrations of amylin in small volumes of plasma. We report here two sandwich-type immunoassays that use pairs of monoclonal antibodies, the fluorescent substrate 4-methylumbelliferyl phosphate, and the enzyme alkaline phosphatase. The minimum detectable concentration of amylin in 50 microL of plasma was 0.5 to 2 pmol/L, and the dynamic range was 2 to 100 pmol/L. The assays had average intraassay CVs of <10%, average interassay CVs of <15%, and good linearity on dilution and recovery of added amylin. The two assays use the same detection antibody, which binds to the carboxyl terminus of the molecule, but different capture antibodies. One of the assays measures only human amylin; the other also detects amylin-like peptides. Examples of measurements in human plasma are provided in subjects with impaired glucose tolerance and in nondiabetic controls.

Alkaline Phosphatase↗

Cloning and high level expression of a chimeric antibody with specificity for human carcinoembryonic antigen.

A mouse/human chimeric antibody has been constructed by using variable light and variable heavy regions from a murine hybridoma specific for human carcinoembryonic antigen (CEA) (CEM231.6.7). These V regions were combined with kappa and gamma-1 constant region genes cloned from human lymphocytes. The chimeric constructs were sequentially electroporated into murine non-Ig-producing myeloma (P3.653) and hybridoma (SP2/0) cell. Significant differences were seen in expression levels between the two cell types. High levels of expression (24 to 32 micrograms/ml/10(6) cells) were seen with several of the anti-CEA SP2/0 transfectomas but not with the P3.653 cells. The SP2/0 transfectoma lines were adapted to serum-free, chemically defined media and grown in large scale fermentation cultures where they continued to secrete high levels of antibody. The chimeric antibodies remain reactive against human CEA with affinity constants comparable to that of the parental hybridoma antibody. High level expression will make practical the production of chimeric antibodies for in vivo therapeutic and diagnostic purposes.

Amino Acid Sequence↗

Relationship of exercise, oral contraceptive use, and body fat to concentrations of plasma lipids and lipoprotein cholesterol in young women.

To investigate the relationship of exercise and oral contraceptive use to plasma lipids and lipoproteins, a cross-sectional study was designed to compare lipid levels in 96 exercising and non-exercising women who used or did not use oral contraceptives. Exercisers had significantly lower plasma triglyceride concentrations and low-density/high-density lipoprotein ratios than non-exercisers after adjustment for differences in pill type distribution between groups. Women using progestin-dominant pills had significantly lower plasma triglyceride and high-density lipoprotein concentrations and significantly higher low-density/high-density lipoprotein ratios compared with women using estrogen/progestin-balanced pills. As body fat was significantly associated with both pill type and physical activity, it is unclear how much of these lipoprotein differences were due to body fat, exercise, or pill use. Regular physical activity together with reduced body fat partially compensated for plasma lipoprotein differences associated with oral contraceptive use.

Adipose Tissue↗

Functional mutants of yeast alcohol dehydrogenase affecting kinetics, cellular redox balance, and electrophoretic mobility.

Repeated selection of petite (respiratorily incompetent) Saccharomyces cerevisiae on medium containing allyl alcohol, both on plates and in the turbidostat, results in mutants with a remarkably similar response. Most of the mutations affect the constitutive alcohol dehydrogenase, resulting in enzymes with a cathodal shift in electrophoretic mobility, and none shows a significant anodal shift. The genetics, kinetics, and physiological effect of three of the mutants have been investigated in detail, and while all confer resistance to allyl alcohol through a shift in the NAD/NADH ratio, they do so in slightly different ways. The potential of this system for exploring the range of short-term adaptations open to this organism is discussed.

Alcohol Oxidoreductases↗

Further evidence for selective differences between isoalleles in Drosophila.

A number of separate strains of Drosophila pseudoobscura were inbred for 38 generations of brother-sister mating with forced heterozygosity for two alleles of either the octanol dehydrogenase or esterase-5 locus. Crosses were set up within each of these inbred lines such that simple mendelian ratios were expected, and eggs from these crosses were placed on media with additions simple chemicals likely to interact with alleles of the two loci--octanol and ethanol for the ODH locus and tributyrin and triacetin for the E-5 locus. Similar crosses were set up involving parental flies with normally heterozygous genetic background as a control.--Significant deviations from mendelian expectation were observed in inbred E-5 flies grown on tributyrin, inbred ODH males grown on octanol, and inbred ODH females grown on ethanol. There was also a strong effect of octanol medium on males of one of the inbred E-5 lines, and a weak effect of tributyrin medium on ODH inbred females.--The probability that these results reflect interactions between these loci and the environment is assessed in the light of differences between the present results and those obtained at earlier stages of inbreeding.

Alcohol Oxidoreductases↗