Biomedical subjects

K E Arnold

Publications and source records attributed to K E Arnold.

8 recordsLinked to original sources

PubMed2006

Yolk androgens and embryo sex: maternal effects or confounding factors?

Maternal effects occur when offspring phenotype is affected by environmental factors experienced by the mother and, in egg-laying species, are often mediated via egg resources. There is currently great interest among behavioural ecologists in maternally allocated yolk androgens, especially their relationship with offspring sex and development. Such studies need embryonic tissue for sexing, however, requiring eggs to be incubated (usually for 3 days). Therefore, there are concerns about whether the androgen concentrations assayed reflect those allocated by the mother. In addition, studies showing sex biases in maternal allocation of androgens could be confounded if male and female embryos uptake or metabolise androgens at different rates. We ran a series of experiments using zebra finch (Taeniopygia guttata) eggs to address these potential confounding factors. First we showed, using eggs naturally incubated for up to 5 days, that eggs containing embryos had lower yolk androgen concentrations than eggs that had failed to form embryos. We then tested various hypotheses for this difference using controlled incubation treatments. Our results suggested that (a) embryo development causes the yolk to become progressively more diluted with albumin; and (b) between 3 and 5 days of incubation embryos start uptaking or metabolising androgens. Crucially, we found no decline in yolk androgen concentration at 3 days incubation, and no evidence for sex-specific rates of uptake or metabolism of androgens. This strongly suggests that yolk androgen levels up to 3 days incubation do reflect those allocated by the mother, and that studies of sex biased maternal allocation of yolk androgens are not confounded by sex differences in embryo development.

Animals↗

PubMed1999

Estrogen receptor beta activates the human retinoic acid receptor alpha-1 promoter in response to tamoxifen and other estrogen receptor antagonists, but not in response to estrogen.

Human estrogen receptor-alpha (hERalpha) or -beta (hERbeta) transfected into Hep G2 or COS1 cells each responded to estrogen to increase transcription from an estrogen-responsive element (ERE)-driven reporter vector with similar fold induction through a classical mechanism involving direct receptor binding to DNA. ER antagonists inhibited this estrogen induction through both hERalpha and hERbeta, although raloxifene was more potent through ERalpha than ERbeta, and tamoxifen was more potent via ERbeta than ERalpha. We have shown previously that estrogen stimulated the human retinoic acid receptor-alpha-1 (hRARalpha-1) promoter through nonclassical EREs by a mechanism that was ERalpha dependent, but that did not involve direct receptor binding to DNA. We show here that in contrast to hERalpha, hERbeta did not induce reporter activity driven by the hRARalpha-1 promoter in the presence of estrogen. While hERbeta did not confer estrogen responsiveness on this promoter, it did elicit transcriptional activation in the presence of 4-hydroxytamoxifen (4-OH-Tam). Additionally, this 4-OH-Tam agonist activity via ERbeta was completely blocked by estrogen. Like ERalpha, transcriptional activation of this promoter by ERbeta was not mediated by direct receptor binding to DNA. While hERalpha was shown to act through two estrogen-responsive sequences within the promoter, hERbeta acted only at the 3'-region, through two Sp1 sites, in response to 4-OH-Tam. Other ER antagonists including raloxifene, ICI-164,384 and ICI-182,780 also acted as agonists through ERbeta via the hRARalpha-1 promoter. Through the use of mutant and chimeric receptors, it was shown that the 4-OH-Tam activity via ERbeta from the hRARalpha-1 promoter in Hep G2 cells required the amino-terminal region of ERbeta, a region that was not necessary for estrogen-induced ERbeta activity from an ERE in Hep G2 cells. Additionally, the progesterone receptor (PR) antagonist RU486 acted as a weak (IC50 >1 microM) antagonist via hERalpha and as a fairly potent (IC50 approximately 200 nM) antagonist via hERbeta from an ERE-driven reporter in cells that do not express PR. Although RU486 bound only weakly to ERalpha or ERbeta in vitro, it did bind to ERbeta in whole-cell binding assays, and therefore, it is likely metabolized to an ERbeta-interacting compound in the cell. Interestingly, RU486 acted as an agonist through ERbeta to stimulate the hRARalpha-1 promoter in Hep G2 cells. These findings may have ramifications in breast cancer treatment regimens utilizing tamoxifen or other ER antagonists and may explain some of the known estrogenic or antiestrogenic biological actions of RU486.

Animals↗

PubMed1996

Risk factors for carriage of drug-resistant Streptococcus pneumoniae among children in Memphis, Tennessee.

OBJECTIVES: To determine risk factors for carriage of drug-resistant Streptococcus pneumoniae to understand better the factors promoting spread of these isolates. STUDY DESIGN: We obtained medical and demographic information and nasopharyngeal swab specimens from 216 children less than 6 years old with upper respiratory tract infections, seeking medical care at five Memphis, Tenn, study sites. We evaluated risk factors for carriage of penicillin-nonsusceptible S. pneumoniae (NSSP) among 100 children with S. pneumoniae isolates. Patterns of antimicrobial prescription were recorded for enrolled children. RESULTS: Independent risk factors for carriage of NSSP included an increased number of antimicrobial treatment courses during the previous 3 months and white race. Day care attendance approached statistical significance (p = 0.07). Most children with upper respiratory tract infection received a prescription for antimicrobial drugs. These prescriptions were more common for white children than for black children. CONCLUSIONS: Increased use of antimicrobial drugs enhances the risk of carriage of NSSP. This may contribute to the higher risk among white children of NSSP infection; however, after control for antimicrobial use, white children were still at an increased risk of infection with NSSP, possibly through greater exposure to resistant strains.

Anti-Bacterial Agents↗

PubMed1996

Vancomycin-resistant Aureobacterium species cellulitis and bacteremia in a patient with acute myelogenous leukemia.

A 39-year-old male with acute myelogenous leukemia and concomitant porphyria cutanea tarda was admitted to the hospital for consolidation chemotherapy of his leukemia. During his hospitalization, he developed cellulitis of the left hand and persistent bacteremia with a yellow-pigmented, nonfermenting coryneform bacterium that was identified as Aureobacterium sp. The portal of entry for the Aureobacterium infection was probably through the skin lesions due to porphyria cutanea tarda. The infection developed while the patient was receiving vancomycin prophylaxis, and the vancomycin MIC for the isolate was 32 micrograms/ml.

Adult↗

PubMed1996

Performance of a simple aiming task in hypergravity: I. overall accuracy.

BACKGROUND: Visuo-motor performance is known to be affected by exposure to hyper-gravity (hyper-G), but the underlying mechanisms remain to be determined; the present study investigated the role of target mislocalization. METHOD: Subjects pointed before, during and after exposure to hyper-G at targets without seeing their hand. Target positions were displayed: a) throughout each pointing response; b) before response onset; or c) in normal gravity prior to a set of movements. RESULTS AND CONCLUSIONS: For all display conditions, subjects pointed higher in hyper-G than in normal gravity from the first movement on. We attribute the discrepancy between this finding and previous results (8, 12) to different movement strategies. The effects of hyper-G on pointing performance were small, but sustained when targets were displayed before or throughout each movement, but they were large and transient when targets were memorized in normal-G. We conclude that too-high pointing in hyper-G cannot be simply explained by the "elevator illusion," and propose a tentative interpretation based on known perceptual deficits.

Adult↗

PubMed1996

Performance of a simple aiming task in hypergravity: II. detailed response characteristics.

BACKGROUND: Literature proposes three hypotheses for impaired movement execution in hyper-G. The present study attempted to discriminate between these hypotheses by comparing kinematic characteristics and final accuracy of pointing movements in different gravity levels. METHOD: Subjects pointed without seeing their hand at targets presented before, during and after exposure to hyper-G. RESULTS: After factoring out movement amplitude, peak vertical velocity and the skewness of velocity profiles tended to increase, while movement duration tended to decrease with increasing G-level. Further, final response position was slightly less modulated by target position in hyper-G than in normal-G. CONCLUSION: Although not all findings reached statistical significance, the observed pattern of results corroborates the hypothesis (2) that the motor system re-interprets hyper-G as increased arm weight.

Adult↗

PubMed1993

Portal vein thrombosis in a child with homozygous sickle-cell disease.

A 13-year-old boy with homozygous sickle-cell (SS) disease died suddenly at home following a short history of abdominal pain. Autopsy revealed venous thrombosis of the hepatic, portal, superior mesenteric and splenic veins. Venous thrombosis is rare in SS disease and thrombosis of mesenteric vessels is most frequently seen in chronic myeloproliferative disorders. Its occurrence in SS disease raises the possibility of a common pathogenesis and adds another pathology to the causes of the abdominal painful crisis.

Abdominal Pain↗

PubMed1992

Accuracy of aimed arm movements in changed gravity.

We studied the accuracy of aimed arm movements in normal gravity, and during the hypergravity (hyper-G) and microgravity (micro-G) episodes of KC-135 parabolic flights. Subjects pointed at mirror-viewed targets without sight of their arm, and final pointing position was measured by a digitizing pad. Compared with the normal gravity (normal-G) baseline, subjects pointed consistently higher in hyper-G, and still higher in micro-G. Results were not different if subjects viewed targets only during normal-G and pointed at their memorized position under changed gravity (changed-G); this suggests that the "elevator illusion" played a minor role in our study. The observed impairments were attributed to degraded proprioceptive feedback and/or inappropriate motor programs in changed-G. Pointing accuracy improved movement-to-movement but not parabola-to-parabola, indicating that prolonged exposure is needed for sustained adaptation.

Aerospace Medicine↗