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Biomedical subjects

D L Davis

Publications and source records attributed to D L Davis.

At least 55 records · Page 3Linked to original sources
PubMed1998

Exposures from indoor spraying of chlorpyrifos pose greater health risks to children than currently estimated.

Recent findings of indoor exposure studies of chlorpyrifos indicate that young children are at higher risks to the semivolatile pesticide than had been previously estimated [Gurunathan et al., Environ Health Perspect 106:9-16 (1998)]. The study showed that after a single broadcast use of the pesticide by certified applicators in apartment rooms, chlorpyrifos continued to accumulate on children's toys and hard surfaces 2 weeks after spraying. Based on the findings of this and other research studies, the estimated chlorpyrifos exposure levels from indoor spraying for children are approximately 21-119 times above the current recommended reference dose of 3 microg/kg/day from all sources. A joint agreement reached between the U.S. Environmental Protection Agency and the registrants of chlorpyrifos-based products will phase out a number of indoor uses of the pesticide, including broadcast spraying and direct uses on pets. While crack and crevice treatment of insects (such as cockroaches and termites) by chlorpyrifos will still continue, it appears prudent to explore other insect control options, including the use of baits, traps, and insect sterilants and growth regulators. To ensure global protection, adequate dissemination of appropriate safety and regulatory information to developing regions of the world is critical, where importation and local production of chlorpyrifos-based products for indoor uses may be significant.

Air Pollution, Indoor↗
PubMed1998

Rethinking breast cancer risk and the environment: the case for the precautionary principle.

The World Health Organization recently reported that breast cancer has become the most common cancer in women throughout the world. Known risk factors account for less than half of all cases of breast cancer, and inherited germ line mutations occur in at most only 10% of all cases. Cumulative exposure to estradiol and other hormones links many of the established risk factors for breast cancer. This paper reviews epidemiologic and toxicologic evidence on breast cancer risks and presents a comprehensive construct of risk factors intended to focus on the identification of those factors that can be controlled or modified. We attempt to provide a framework for interpreting the etiologic interplay of endogenous metabolic changes and environmental changes in the etiology of breast cancer. The construct we develop distinguishes between those risk factors that are directly causal, such as ionizing radiation and inherited germ cell defects, those vulnerability factors that extend the time period during which the breast undergoes development, and those contributing factors that increase total hormonal stimulation of the breast. Some hormonally active compounds, such as those in soy and broccoli and other phytoestrogen-containing foods, can be protective against breast cancer, while others, such as some environmental contaminants, appear to increase the risk of the disease by increasing levels of harmful hormones. Efforts to explain patterns of breast cancer should distinguish between these different risk factors. Identification of vulnerability and contributing risk factors can foster the development of public policy to reduce the burden of this prevalent cancer. Prudent precautionary principles suggest that reducing exposure to avoidable or modifiable risk factors should receive high priority from the public and private sectors.

Breast Neoplasms↗
PubMed1998

Uterine and ovarian responses to puberty induction and pregnancy in prepubertal gilts.

We evaluated the effect of age on response to puberty induction in gilts. Sequential treatment with a commercial gonadotropin mixture (400 IU PMSG, 200 IU hCG) followed 96 h later with hCG (500 IU) was used to induce follicular growth and ovulation, respectively. In the first experiment, gilts (84, 104, 124, 144, and 164 d old) were used. Peripheral blood was collected on d 0 (before treatment) and on d 2, 3, 4, 8, and 16 after treatment. On d 16, all gilts were hysterectomized, uterine flushings were collected, and uterine weight (UTWT) and length (UTLG) were measured. For treated gilts, UTWT, UTLG, number of corpora lutea (CL), peripheral progesterone (P4) on d 16, and estradiol (E2) on d 4 increased (P < .05) linearly with age. Uterine luminal PGE (P < .05) and PGF (P = .07), expressed per UTWT, responded quadratically with age; gilts treated at 124 d of age or older showed decreased amounts. Overall, the number of CL correlated positively (P < .01) with UTWT and P4 on d 8 and 16. Peripheral P4 on d 4, 8, and 16 (P < .10) and E2 on d 0 and 4 (P < .01) were correlated positively with uterine weight on d 16. Gilts induced to ovulate at 104 and 144 d of age had heavier and longer uteri (P < .01), more P4 on d 8 and 16 (P < .05), and more E2 on d 2 (P < .1) and 4 (P < .05) than controls at the same age. The second experiment evaluated pregnancy success for gilts induced to ovulate at 116 vs 151 d of age. The effects of induction of two consecutive estrous cycles also were evaluated. Two of seven (28.6%) and four of nine (44.4%) gilts first treated when 116 and 151 d old but none of seven gilts treated at 96 and 116 d of age were pregnant 60 d after insemination. Results indicate that induction of a prior cycle did not improve pregnancy rates. However, some gilts in this population maintained pregnancies to 60 d when induced to ovulate and inseminated at 120 d of age.

Aging↗
PubMed1997

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

Breast Neoplasms↗
PubMed1997

Blood and nerves revisited: menopause and the privatization of the body in a Newfoundland postindustrial fishery.

Ethnographic data from a longitudinal, interpretive study of women's changing social and cultural constructions of menopause in a postindustrial, Newfoundland fishing village indicate that three major changes have taken place in the way women conceptualize female, reproductive life-cycle events and processes. First, folk idioms of nerves and blood that once linked soma, psyche, place, and tradition are now trivialized and have been superseded by biomedical models of menopause. Second, physicians, television, magazines, and school teachers have replaced the community's middle-aged women and the mutual communication of shared experience as major sources of information and advice on reproduction and aging. Third, women's bodies have become privatized, and bodily metaphors that once linked women in complex individual and collective assessments of shared, highly valued traditions and mutual judgment of moral character have lost their dominance in village life.

Aging↗
PubMed1997

Uterine response to progesterone in prepubertal gilts.

During early pregnancy, progesterone stimulates the secretion of proteins and other molecules that support the developing conceptus. Some gilts are able to support conceptus development as early as 110 days of age. The objective of this study was to evaluate the onset of responsiveness of the prepubertal uterus to progesterone. Thirty gilts were assigned to receive 2.2 mg progesterone kg-1 body mass per day or corn oil daily for 14 days starting at 6, 46, 76, 106, and 136 days of age. Hysterectomies were performed the day after the last treatment of progesterone, and the uterine horns were weighed and flushed with sterile saline (0.85% NaCl). Recovered flushings were analysed for total luminal protein, retinol binding protein, uteroferrin, prostaglandin E and prostaglandin F. An interaction between age and progesterone occurred for uterine wet mass (P < 0.001). Progesterone did not affect the uterine mass of gilts that underwent hysterectomy at 20 days of age, but did increase the uterine mass (P < 0.05) in other age groups. Progesterone increased (P < 0.01) the amount of total luminal protein in all but the youngest gilts. An increase in the amounts of retinol binding protein and uteroferrin (P < 0.001) by progesterone was first observed in 90-day-old gilts. Prostaglandins exhibited a different age-related pattern. The amount of prostaglandin E was increased (P < 0.001) by progesterone treatment in gilts aged 90-150 days, with a greater (P < 0.05) response at 120 days than at 90 days old. The response at 150 days old decreased (P < 0.05) to that observed at day 90. The response of prostaglandin F to progesterone followed a similar age-related pattern. Therefore, uterine responsiveness to progesterone develops between 20 and 90 days after birth, and uterine mass responds earlier than the secretory responses measured in our study.

Acid Phosphatase↗
PubMed1996

Steroid 5 alpha-reductase 2 deficiency: virilization in early infancy may be due to partial function of mutant enzyme.

Male pseudohermaphroditism due to steroid 5 alpha-reductase deficiency is the consequence of mutations in the gene encoding the type 2 isoenzyme. Most (60%) affected subjects have homozygous mutations, and the remainder are compound heterozygotes or presumed compound heterozygotes. We report an Italian subject with phenotypic and endocrine features of 5 alpha-reductase 2 deficiency who is homozygous for a substitution mutation (H231R). Although close consanguinity is not present, genealogical data demonstrated that the parents are distantly related, and both parents and the maternal grandmother are heterozygous carriers of the mutation. The fact that this particular mutation results in the formation of an enzyme with considerable residual activity may explain in part the significant degree of virilization that took place in this subject in early infancy. This same mutation (H231R) is present in heterozygous form in two other families, an African-American family and an American family of northern European descent.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Random sequence phosphorothioate oligonucleotides evoke dramatic phenotypic alterations in cardiac myocyte cultures.

Cardiac myocytes displayed modest and uncoordinated contractile activity regardless of whether they are cultured in the presence or absence of unmodified random sequence oligonucleotides (oligos), as expected. Much to our surprise, however, when cardiac myocytes were cultured in the presence of random sequence phosphorothioate (PS) oligos, they reorganized into cablelike aggregates and displayed surging and coordinated contractile activity. Consistent with these observations, photobleaching experiments revealed that gap junction conductivity between affected cardiac myocytes was enhanced fourfold relative to control cultures. Furthermore, whereas atrial natriuretic factor (ANF) gene expression was induced in control cultures relative to intact hearts, this aberrant expression was selectively repressed in response to PS oligos. As PS oligos appear to mitigate deleterious effects that result from the proteolytic dispersal or culturing of cardiac myocytes or both, we suggest that these may useful cell culture reagents. It is interesting to contemplate whether cardiac myocytes might also be responsive to PS oligos within intact hearts, as this issue has potential clinical significance.

Animals↗
PubMed1996

Porcine endometrial glandular epithelial cells in vitro: transcriptional activities of the pregnancy-associated genes encoding antileukoproteinase and uteroferrin.

The aim of this investigation was to establish a homologous culture system for study of the transcriptional mechanisms underlying endometrial expression of the pregnancy-associated genes encoding antileukoproteinase (ALP), an elastase/cathepsin G protease inhibitor, and uteroferrin (Uf), a transplacental iron transport protein. Glandular epithelial (GE), Luminal epithelial (LE), and stromal (ST) cells were isolated from pig endometrium at Day 12 of pregnancy by differential enzymatic digestion and sieve filtration. The three cell populations differed with respect to their morphology in culture and with respect to their expression of ALP and Uf. Expression of the ALP gene was much higher in GE than in LE cells and was undetectable in ST cells. Similarly, GE had the highest expression of the Uf gene, and expression in ST was lower but distinct. Western blot analysis of conditioned media (72 h) from GE, LE, and ST, using antiporcine Uf antiserum, detected significant levels of secreted Uf only in GE. The steroid hormone responsiveness of GE cells was monitored by changes in steady-state levels of ALP mRNA after 24-h exposure to estradiol 17 beta (E2; 10 nM) and/or progesterone (P; 10 nM). Glandular epithelial cells treated with E2, P, and E2 + P had increased (p < 0.05) ALP mRNA levels relative to those in control cultures. Glandular epithelial cells were transiently transfected with reporter constructs containing the 5'-flanking genomic regions of each gene. For ALP, the 1266-nucleotide (nt) region of the ALP 5'-flanking genomic DNA, and progressive 5' deletions within this region, were coupled to a luciferase reporter gene (LUCE). The most proximal 119-bp fragment (-119ALP LUCE), which contains the TATAA box (-21 to -26 nt) and a GC-rich sequence (-66 to -74 nt), was sufficient to confer transcriptional activity to the reporter vector. Progressively longer 5'-genomic fragments had promoter activities higher than or similar to those of the 119-nt fragment. Estrogen had no effect on the transcriptional activities of any of the ALP constructs. Uteroferrin 5'-flanking and promoter DNA constructs containing the chloramphenicol acetyl transferase (CAT) reporter gene also exhibited transcriptional activity in GE cells. The presence of multiple interacting cis-regulatory sequences within this region was demonstrated by increased promoter activity, relative to that of the smallest construct (-182 UFCAT-E; basal activity), with the inclusion of sequences between -182 and -484 nf, and drastic reduction to basal activity with the inclusion of sequences between -484 and -831 nt. In summary, primary cultures of GE from early-pregnant porcine endometrium express ALP and Uf, are steroid hormone-responsive, and support the transcriptional activity of endometrial-associated gene promoter and regulatory sequences. The use of primary GE cells thus provides a convenient in vitro system for further study of the endocrine, paracrine, and autocrine factors regulating endometrial gene expression during pregnancy.

Acid Phosphatase↗
PubMed1996

Correlation of hematologic markers of inflammation and lung function: a comparison of asymptomatic smokers and nonsmokers.

Increased inflammation of the peripheral airways has been implicated as a cause of pulmonary function impairment. However, little information is available on the correlation between subclinical decrements of pulmonary function and inflammation in asymptomatic individuals. A relationship between markers of inflammation and lung function may be useful in predicting the early onset of lung function impairment. The purpose of this study was to investigate the correlation of hematologic markers of inflammation and spirometry in asymptomatic smokers and nonsmokers. The specific objectives of this study were twofold. The first objective was to quantify and compare the spirometric measures of lung function in smokers and nonsmokers having similar demographic and lifestyle characteristics. The second objective was to define the correlation between these spirometric measurements and hematologic markers of inflammation (white blood cells, monocytes, basophils, PGE1, IgG, and IgE). Systemic blood samples and spirometric measurements were obtained from 61 age-matched (33 +/- 9 years) healthy, asymptomatic smokers and nonsmokers, with similar self reported lifestyles (i.e., food, alcohol, vitamin consumption and exercise). Both male and female smokers self reported a higher coffee consumption (P < 0.05) compared to nonsmokers. Male smokers self-reported a trend toward current blue-collar versus white-collar occupation when compared with the nonsmokers. Body weight (77.6 +/- 16.6 kg) did not differ between the smokers and nonsmokers. The male nonsmokers were taller than the male smokers (P < 0.05). All subjects were asymptomatic and had clinically normal spirometry. Compared to male nonsmokers, the male smokers had lower FEF25-75% and FEF75-45% values (P < 0.05). No additional spirometric measurements, including FEV1/FVC, FEV1 and FVC were significantly different. The female smokers did not differ from the female nonsmokers (P < 0.05) in any of the spirometric endpoints measured. Thirteen statistically significant (P < 0.05) correlations involving inflammatory (white blood cells, monocytes, basophils, and PGE1) or immunologic endpoints (IgE) and spirometric measurements were observed in female smokers, female nonsmokers and male nonsmokers. No statistically significant correlations involving immunologic or inflammatory endpoints were observed in the male smokers. A better mechanistic understanding of the observed relationship between elevated hematologic inflammatory endpoints and reduced lung function may provide valuable insight into the clinical significance of these correlations.

Adult↗
PubMed1996

Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

The chicken vitellogenin II gene is flanked by a GATA factor-dependent estrogen response unit.

The chicken vitellogenin II (VTGII) gene is flanked by an imperfect estrogen response element (ERE) at -350 and a perfect ERE at -620. In the present study we show that this imperfect ERE lies within an estrogen response unit (ERU) that requires a GATA factor and the estrogen receptor to function as an estrogen-dependent enhancer. We infer that GATA-6 contributes to the estrogen-dependent and liver-specific regulation of the endogenous VTGII gene since this is the predominant GATA factor expressed in adult liver. Our analysis of the VTGII ERU revealed four salient points. First, this ERU is comprised of an ERE and a bank of functionally redundant GATA-binding sites. Second, the GATA-6 transactivation domain is necessary (and sufficient, when tethered near the ERE) to render this ERU functional. Third, ERU enhancer activity is dependent on GATA 6, regardless of whether the resident ERE is imperfect or perfect. Fourth, in contrast to a report that the estrogen receptor antagonizes the activity of another GATA factor (GATA-1), we show that these two factors can function in a synergistic manner within the context of the VTGII ERU.

Animals↗
PubMed1996

Measuring habituation in infants: an approach using regression analysis.

The effectiveness of different habituation criteria was examined by means of computer simulations. A criterion based on fitting a second-order polynomial regression function to the looking time data was described. This criterion produced more accurate estimation of looking times as well as higher experimental power for detecting novelty effects, compared to the traditional windowed running average criterion or to a criterion based on linear regression. The polynomial regression approach probably has this advantage because it utilizes all of the available looking time data, rather than just the data in the current windowed average, and because it is sensitive to nonlinear trends in looking time. This new habituation criterion is easy to implement on a laboratory computer, and it should increase session lengths by no more than one trial or so, compared to windowed average criteria. With regard to test-retest reliability, all of the habituation criteria that were evaluated appear to have low reliability on average, with high sample-to-sample variability. These undesirable reliability characteristics are attributable to the high variability of infants' attentional behavior.

Attention↗
PubMed1995

Contribution of listeners' approaching motion to auditory distance perception.

Of the several sources of acoustic information for distance perception, those arising from motion of the listener or sound source have received little attention. This motion-related information (recently called acoustic tau) is described, and experiments evaluating its utilization are presented. Accuracy and consistency at walking to the locations of briefly presented sounds were better when people listened while walking than while standing still. Manipulations of the sound to simulate shorter or longer target distances produced appropriate undershooting but not overshooting. The results indicate that people use motion-related acoustic information about distance to guide their locomotor actions, although they do not take full advantage of this information.

Adult↗
PubMed1995

Effects of pesticides on the ratio of 16 alpha/2-hydroxyestrone: a biologic marker of breast cancer risk.

Xenobiotic estrogens are external compounds with estrogenic activity that may thereby affect the risk of breast cancer. This paper describes a mechanism by which xeno-estrogens may affect the development of breast cancer. Estradiol metabolism proceeds by hydroxylation at one of two mutually exclusive sites at C-2 and C-16 alpha. The catechol pathway yields the weakly estrogenic 2-hydroxyestrone (2-OHE1), which inhibits breast cell proliferation. In contrast, the alternative pathway yields the genotoxic 16 alpha-hydroxyestrone (16 alpha-OHE1), which enhances breast cell growth, increases unscheduled DNA synthesis, and oncogene and virus expression, and increases anchorage-independent growth. Using a radiometric assay that measures the relative formation of 16 alpha-OHE1 versus 2-OHE1 from specifically tritiated estradiol in (ER+) MCF-7 cells, we compared the ratio of 16 alpha-OHE1/2-OHE1 observed after treatment with the known rodent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) with the ratios after treatment with DDT, atrazine, gamma-benzene hexachloride, kepone, coplanar PCBs, endosulfans I and II, linoleic and eicosapentenoic acids, and indole-3-carbinol (I3C). These pesticides significantly increase the ratio of 16 alpha-OHE1/2-OHE1 metabolites to values comparable to or greater than those observed after DMBA. In contrast, the antitumor agent I3C increased 2-OHE1 formation and yielded ratios that are 1/3 of those found in unexposed control cells and 1/10th of those found in DMBA-treated cells. Thus the ratio of 16 alpha-OHE1/2-OHE1 may provide a marker for the risk of breast cancer. Assays of this ratio, which can be measured in spot urines, may prove useful for a variety of in vitro and in vivo studies bearing on breast cancer risk.

Biomarkers↗