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Biomedical subjects

L Wheeler

Publications and source records attributed to L Wheeler.

At least 37 records · Page 2Linked to original sources
PubMed1988

The role of arachidonic acid metabolism in IL-3-induced proliferation.

The role of arachidonic acid metabolites as second messengers in the IL-3-induced activation of DA-1 cells was examined. By using inhibitors of either the cyclooxygenase (CO) or lipoxygenase (LPO) pathways, we determined that neither prostaglandins nor leukotrienes were involved in signal transduction, since aspirin, indomethacin, meclofenamic acid, and nordihydroguaiaretic acid (NDGA) failed to inhibit the proliferation response of DA-1 cells to IL-3. Furthermore, two combination CO/LPO inhibitors, benoxaprofen and BW755c, failed to inhibit DA-1 proliferation. A new CO/LPO compound examined, SK&F 86002, did inhibit proliferation (IC50 = 30 microM +/- 14, N = 11), leading us to conclude this drug has other actions besides CO/LPO inhibition. Finally, direct measurement of 3H-arachidonic acid uptake by DA-1 cells failed to show a difference in the amount of 3H-arachidonic acid incorporated in the presence of limiting or saturating amounts of IL-3. We conclude from these data that arachidonic acid metabolites are not involved in transmembrane signalling by IL-3 in DA-1 cells.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

Inhibition of phosphoinositide-specific phospholipase C by manoalide.

Manoalide is a novel sesterterpenoid which has previously been shown to be a potent inhibitor of venom phospholipases A2. To determine whether manoalide inhibited other phospholipases, the sensitivity of phosphoinsitide-specific phospholipase C (PI-PLC) to inactivation by manoalide was examined using crude cytosolic PI-PLC and a PI-PLC purified to homogeneity from guinea pig uterus cytosol (PI-PLC I). Manoalide inhibited both cytosolic and purified PI-PLC I in a concentration-dependent fashion, exhibiting an IC50 of 3-6 microM. Inactivation of PI-PLC I was calcium- and pH-dependent, with greater inactivation occurring at alkaline pH. Manoalide inhibited hydrolysis of all three phosphoinositides by purified PI-PLC I. The substrate kinetics of PI-PLC I suggest that manoalide does not inhibit purified PI-PLC I by simple competitive or noncompetitive inhibition. Enzyme activity was not recovered after dialysis of manoalide-treated PI-PLC I, indicating that inactivation of PI-PLC I was irreversible. To determine whether manoalide inhibited PI-PLC in cells, the effects of manoalide on norepinephrine (NE)-stimulated phosphoinositide hydrolysis and calcium mobilization were investigated in a smooth muscle-like cell line, DDT1MF-2. Manoalide inhibited NE-induced inositol 1,4,5-trisphosphate and inositol 1-phosphate formation in a concentration-dependent manner. The IC50 for inhibition of inositol 1-phosphate formation was 1.5 microM. Manoalide also inhibited NE-induced calcium transients in DDT1MF-2 cells, exhibiting an IC50 of 2 microM. These data suggest that inhibition of PI-PLC may account, in part, for the anti-inflammatory actions of manoalide.

Animals↗
PubMed1986

Extracellular calcium alters the effects of retinoic acid on DNA synthesis in cultured murine keratinocytes.

The rate of proliferation of epidermal keratinocytes was manipulated by growing the cells in medium containing high or low concentrations of calcium. Keratinocytes cultured in high extracellular Ca++ (1.4 mM and 2.8 mM) proliferated twice as fast as those grown in low Ca++ medium (0.09 mM) as measured by incorporation of [3H]thymidine into DNA. Exposure of high calcium keratinocytes to all-trans retinoic acid for 4 days caused a dose-related inhibition of DNA synthesis with an IC50 of about 10 microM. In contrast, incubating low calcium keratinocytes with all-trans retinoic acid caused a dose-related stimulation of DNA synthesis with maximum increase of 278% over control at 10 microM. This increase was accompanied by increases in culture confluency with maximum increase of 109% in cell number over control at 10 microM. These results are of importance since they suggest Ca++ may influence the effect of retinoids on keratinocytes.

Animals↗
PubMed1986

Back school and chiropractic practice.

The back school as a method for teaching back pain prevention and self-care is discussed. Methods of developing and utilizing back schools are examined, and a review of research investigating the use of back school is presented. Future trends in back school are discussed. It is concluded that back schools can play an important part in the chiropractic office.

Back Pain↗
PubMed1985

On specificity in the impact of social participation on physical and psychological health.

Although it has been suggested that social participation is likely to be beneficial for health and well-being, there is little research demonstrating specifically which aspects of socializing may be responsible. This study distinguishes specific components of social interaction and health and examines differential relationships among them. Three distinct categories of social participation variables were posited: quality, quantity, and social traits. If was hypothesized that health problems would be more frequent among persons with poor quality interaction. The only exception to this prediction was that illnesses that are socially communicated were expected to be more prevalent among persons with a greater quantity of social participation, regardless of quality. Results confirmed these predictions for females. For males, the pattern of results was more complex, in that masculinity and femininity influenced the manner in which symptoms were expressed. These results supported the notion that social relations have a specific impact on health, and that if research is to provide useful information for intervention, we must learn more about which specific aspects of social participation are beneficial as well as how this occurs.

Adaptation, Psychological↗
PubMed1983

Loneliness, social interaction, and sex roles.

Forty-three male and 53 female college seniors maintained the Rochester Interaction Record for 2 weeks, providing information about every social interaction of 10 minutes or more. Subjects then completed the revised UCLA (University of California, Los Angeles) Loneliness Scale and the Personal Attributes Questionnaire, measuring sex-role orientation. For both sexes, loneliness was negatively related to the amount of time spent with females and to the meaningfulness of interaction with males and females. However, meaningfulness with males was more important than meaningfulness with females. Femininity was negatively related to loneliness for both sexes and partially mediated the above relationships. There were sex differences, however, in the extent to which variables overlapped in predicting loneliness. For example, a large group of nonlonely males was characterized both by having meaningful relationships with males and by spending time with females, whereas a second group of nonlonely males was characterized simply by having meaningful relationships with males. The largest group of nonlonely females was characterized simply by having meaningful relationships with males, but another sizable group was characterized simply by spending time with females. Females doing both accounted for very little of the variance.

Adult↗
PubMed1981

A comparison of aflatoxin B1-induced cytotoxicity, mutagenicity and prophage induction in Salmonella typhimurium mutagen tester strains TA1535, TA1538, TA98 and TA100.

Treatment of Ames mutagen tester strains with aflatoxin B1 (AFB1) and S9 mix results not only in the production of a potent mutagen, but induces a pathway that leads to the induction of prophages present in all Ames tester strains. Characterization of the prophage induction and mutagenic response following AFB1 treatment showed that plasmid pKM101 dramatically enhances mutagenesis, but suppressed prophage induction. Spontaneous release of phage by TA98 and TA100 was also lower than in TA1535 and TA1538. In addition to mutagenesis and prophage induction, survival of all 4 tester strains was quantitated after AFB1 treatment. The data show that the frameshift tester strains (TA1538 and TA98) are more sensitive to the bactericidal action of AFB1 than the base-pair tester strains (TA1535 and TA100), survival being significantly affected above 100 ng. One of several hypotheses examined was the difference in the number and types of prophages present in base-pair tester strains that are not detectable in the frame-shift tester strains. These data suggest that prophage induction can detect DNA damage that is non-mutagenic; and that it is important to characterize the lysogenic nature of the Ames strains since it may influence the observed histidine revertant rate and the survival of the tester strain.

Aflatoxins↗
PubMed1980

Excretion and disposition of [14C]carbaryl in pregnant, non-pregnant and foetal tissues of the rat after acute administration.

1. Non-pregnant or pregnant Sprague-Dawley rats on the 18th and 19th days of gestation were injected i.p. with a tracter dose (2.8 microCi/kg) of either [ring-14C]carbaryl or [carbonyl-14C]carbaryl. Distribution of total 14C was examined in foetal, maternal and non-pregnant rat tissues. Pregnancy alters the disposition and excretion of carbaryl. 2. Carbaryl crossed the placenta and was rapidly distributed in all foetal tissues. Highest concentrations were seen in foetal kidney. At 8 h after injection, foetal brain, heart and lung all contained more 14C, on a weight basis, than their maternal organ counterparts. Elimination from the whole foetus was biphasic, and after 8 h approx. 3% of the dose was still present in the whole foetus. 3. Significantly more 14CO2 was exhaled by the pregnant rat during 8 h than by non-pregnant. Urinary excretion of 14C after dosage with [ring-14C]carbaryl was significantly less in pregnant than in non-pregnant rats. 4. Kinetically, the tissue distribution of 14C from carbaryl or metabolites was biphasic in pregnant and non-pregnant animals. [14C]carbaryl concn. declined rapidly for 1 to 2 h. After 2 h the 14C levels from animals dosed with [ring-14C]carbaryl declined more slowly. 5. The pattern of 14C distribution was more complicated after injection of [carbonyl-14C]carbaryl. The 14C activity increased in the animal tissues after 2 h, in contrast to animals dosed with [ring-14C]carbaryl. Non-pregnant animals treated with [carbonyl-14C]carbaryl did not show a similar pattern of distribution. Carbamylated tissue proteins may, after time, release some bound carbonyl-14C label, causing the increase in 14C activity seen between 2 and 8 h. However, this does not necessarily imply uptake of the intact carbamate.

Animals↗
PubMed1975

Heterochromatic chromosomes and satellite DNAs of Drosophila nasutoides.

Drosophila nasutoides is distinguished from other Drosophila species in that the metaphase karyotype shows a pair of very large V-shaped chromosomes. With Giemsa, a distinctive C-banding pattern is revealed along the arms of this large chromosome, indicating a largely heterochromatic nature. Furthermore, the banding patterns of the arms are symmetrical, indicating that it is an iso-chromosome. A comparison between the metaphase karyotype and polytene chromosomes suggests that the large V chromosome appears as the dot chromosome in polytene squash. One autosome has twice the arm length of typical Drosophila polytene chromosomes and arose either by centric fusion and a pericentric inversion, or by translocation connecting distal ends with a subsequent loss of one centromere. This chromosome appears to have a short arm which ectopically pairs with the proximal region of the long arm, representing a duplication of about ten bands. When the nuclear DNA is examined by neutral CsCl gradient, four satellites are observed. As much as sixty percent of the total DNA appears as satellites in the lysate of larval brains. No satellite was detectable in the lysate of salivary glands. These observations led us to suggest that the heterochromatic nature of the large V chromosome is due to the presence of all four satellites in this chromosome and that this large chromosome appears as the dot because of the under-reduplication of the satellites during polytenization.

Animals↗
PubMed1975

Age-adjusted analysis of insulin responses during normal and abnormal glucose tolerance tests in children and adolescents.

This report analyzes age-specific glucose (PG) and immunoassayable insulin (IRI) responses during oral glucose tolerance testing (OGTT) and examines test results in children and adolescents with OGTT abnormality using the age-appropriate control data. Controls' (n = 93) and patients' (n = 63) results were compared on the basis of statural age (SA) at the time of testing. Control tests (n = 101) showed significant positive correlation of fasting and four-hour postingestion PG with SA (p less than 0.001), but mean area under the PG curves did not vary between the SA groups (I--18.69 months, II--70-131 months, III--132+ months). The absence of differences of other sampling times permits uniform diagnostic criteria for this age group. IRI was positively correlated with SA at all testing times, and mean levels differed significantly between each SA group at every sampling time; the mean areas under the IRI curve also differed significantly between SA groups as did the mean ratios of IRI area to PG area (group I--0.2639 +/- 0.0175 S.E.M., group II--0.3864 +/- 0.0235, group III--0.6262 +/-0.0491). Patient tests (n = 110) were separated into normal (N), borderline (B), and chemical-diabetic (C) for each SA group. IRI means were above control data for each test type in each SA group at all sampling times; one fourth of these differences were significant. IRI responses also increased within each SA group from N to B to C tests. Mean IRI areas and IRI area to PG are mean ratios were higher than in controls, and this difference was greatest with the most abnormal (C) test type in each SA group. A subgroup of three patients who had low IRI responses from the outset and developed overt diabetes in one to three years was excluded from the analysis. In contrast to apparent relative insulin inefficiency with normal maturation and with chemical diabetes, they had exceptional responsiveness to their low IRI levels. Variable involvement of alpha as well as beta cells in the pathophysiology of diabetes is suggested as one explanation for these paradoxic observations. Changing receptor affinity might also be implicated.

Adolescent↗