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Biomedical subjects

D E Williams

Publications and source records attributed to D E Williams.

At least 19 recordsLinked to original sources
PubMed1999

Flavin-containing monooxygenase isoform 2: developmental expression in fetal and neonatal rabbit lung.

Mammalian flavin-containing monooxygenase functions in the oxygenation of numerous xenobiotics containing a soft nucleophile, usually a nitrogen or sulfur. A total of five distinct flavin monooxygenase (FMO) isoforms are expressed in mammals. Individual isoforms are expressed in a sex-, age-, and tissue-specific fashion. In this study, we document the early developmental appearance of the major isoform in rabbit lung, FMO2. FMO2 catalytic activity as well as protein and mRNA are not only present in fetal and neonatal lung but, in some instances, approach levels found in the adult. The expression pattern of FMO2 is similar to that of the two major constitutive cytochromes P450 found in rabbit lung, 2B4 and 4B1. The early developmental appearance of these monooxygenases indicate an important role in the protection of the fetus and neonate against toxic insult from foreign chemicals.

Animals↗
PubMed1999

A novel group of ovarian toxicants: the psoralens.

The psoralens are naturally occurring metabolites found in many crop plants; synthetic forms of 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxin) are widely used in skin photochemotherapy. Our previous research documented that dietary bergapten and xanthotoxin reduced birthrates in female rats when males and females were exposed to these chemicals. The present study was designed to determine the cause of this reduced birthrate and whether this resulted from direct impact on the females. The study demonstrates that bergapten and xanthotoxin administered, either alone or in combination to female rats (mated to undosed males), significantly reduced the number of implantation sites, pups, and corpora lutea in dosed females compared with control animals. Additionally, full uterine weight and empty uterine weight were significantly reduced. These compounds also significantly reduced circulating estrogen levels in a dose-dependent manner. Interestingly, the psoralens significantly induced mRNAs of liver enzymes typically induced by polycyclic aromatic hydrocarbons, CYP1A1 and UGT1A6; the higher the dose, the greater the induction. UGT 2B1 mRNA, typically induced by phenobarbital-like compounds, was not significantly affected. Thus, enhanced oxidative metabolism and conjugation of estrogens in psoralen-treated animals may provide a partial explanation for the effects observed. These findings are also consistent with psoralen-induced reduction in ovarian follicular function and ovulation.

Animals↗
PubMed1999

Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease: the Lung Health Study.

PURPOSE: To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms. SUBJECTS AND METHODS: A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second (FEV1) of 55% to 90% of predicted and FEV1/forced vital capacity (FVC) <0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values. RESULTS: Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P <0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in FEV1 during the study (P <0.001). Ipratropium bromide had no long-term effects on respiratory symptoms. CONCLUSIONS: In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up.

Adult↗
PubMed1999

Frequent salad vegetable consumption is associated with a reduction in the risk of diabetes mellitus.

This cross-sectional study was undertaken to investigate the association between the reported frequency of consumption of vegetables and fruits, the choice of staple carbohydrate, and glucose intolerance. One thousand one hundred twenty-two subjects aged 40-64 years in a population-based study underwent an oral glucose tolerance test, and their food consumption was assessed using a food-frequency questionnaire. The crude prevalence of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) was 4.5%, and that of impaired glucose tolerance (IGT) 16.8%. The age-standardized prevalence rates were 2.3 and 11.2%, respectively. Frequent consumption of vegetables throughout the year was inversely associated with the risk of having NIDDM (odds ratio [OR] = 0.16; 95% confidence interval [CI] = 0.04-0.69). This association was maintained after adjustment for age, gender, and family history. Vegetable consumption during the summer months had a much weaker inverse association with the risk of having NIDDM that failed to reach statistical significance. A nonsignificant inverse association between frequent consumption of fruits and NIDDM was observed. Frequent self-reported pasta and rice consumption was associated with a reduction in the risk of having IGT and NIDDM. (OR = 0.62, 95% CI = 0.44-0.87, and OR = 0.51, 95% CI = 0.27-0.99, respectively) but this relationship was not independent of age. Whether these associations reflect specific effects of particular nutrients or are a reflection of the patterning of lifestyle factors remains to be determined.

Adult↗
PubMed1999

Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumor study.

Indole-3-carbinol (I3C), a metabolite of glucobrassicin found in cruciferous vegetables, is documented as acting as a modulator of carcinogenesis and, depending on timing and dose of administration, it may promote hepatocarcinogenesis in some animal models. In this study we demonstrate that, when given post-initiation, dietary I3C promotes aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rainbow trout model at levels as low as 500 p.p.m. Trout embryos (approximately 9000) were initiated with 0, 25, 50, 100, 175 or 250 p.p.b. AFB1 by a 30 min immersion. Experimental diets containing 0, 250, 500, 750, 1000 or 1250 p.p.m. I3C were administered starting at 3 months and fish were sampled for liver tumors at 11-13 months. Promotion at the level of tumor incidence was statistically significant for all dietary levels, except 250 p.p.m. Relative potency for promotion markedly increased at dietary levels >750 p.p.m. We propose that more than one mechanism could be involved in promotion and that both estrogenic and Ah receptor-mediated pathways could be active. The estrogenicity of I3C, measured as its ability to induce vitellogenin (an estrogen biomarker in oviparous vertebrates) was evident at the lowest dietary level (250 p.p.m.), whereas CYPIA (a P450 isozyme induced through the Ah receptor pathway) was not induced until dietary levels of 1000 p.p.m. Therefore, at lower dietary levels, promotion by I3C in this model could be explained by estrogenic activities of I3C acid derivatives, as it is known that estrogens promote hepatocarcinogenesis in trout. Much stronger promotion was observed at high dietary I3C levels (1000 and 1250 p.p.m.), at which levels both CYP1A and vitellogenin were induced.

Aflatoxin B1↗
PubMed1999

A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia.

Here we report the characterization of an SV40 large-T antigen-immortalized stromal cell line, WPMY-1, derived from the same prostate as our previously described epithelial cell lines. The WPMY-1 cells were determined to be myofibroblasts on the basis of co-expression of smooth muscle alpha-actin and vimentin. They also show positive staining for androgen receptor, large-T antigen, and positive but heterogeneous staining for p53 and pRb. Their growth is stimulated by the synthetic androgen mibolerone to 145% of control (100%). Platelet-derived growth factor BB, epidermal growth factor and basic fibroblast growth factor, at 10 ng/ml, stimulated growth to 138, 143 and 146% of control, respectively. Transforming growth factor-beta, at 10 ng/ml, inhibited serum-induced growth to 65% of control in the presence of 1% serum, and bFGF-induced growth to 30% of control. A serum-free medium was developed for optimal growth of WPMY-1 cells. They show anchorage-independent growth in soft agar. Studies on paracrine interactions show that myofibroblast-conditioned medium causes a marked inhibition of growth in WPE1-10 cells, while conditioned medium from WPE1-10 prostatic epithelial cells caused only a small increase in the growth of WPMY-1 cells. WPMY-1 cells secrete very low levels of MMP-9 but high levels of MMP-2, markedly higher than the epithelial cells. These epithelial and myofibroblast cell lines, derived from the same prostate, provide novel and useful models for studies on paracrine stromal-epithelial interactions in carcinogenesis, tumor progression, prevention and treatment of prostate cancer and benign prostatic hyperplasia.

Actins↗
PubMed1999

Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function.

BACKGROUND: The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood. AIMS: To compare gastric motor and sensory functions in Helicobacter pylori positive or negative patients with non-ulcer dyspepsia. PATIENTS: Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls. METHODS: The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI). RESULTS: Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated to H pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent among H pylori positive patients (4/5 H pylori positive versus 4/12 H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI. CONCLUSION: Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

Adult↗
PubMed1999

Examination of psoralens-induced photodermatitis in Wistar rats under scanning electron microscopy.

The psoralens are photoactivated plant biosynthetic compounds which are found in several plant families, including common fruits and vegetables. Synthetic forms of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) are extensively used in skin chemotherapy in combination with long-wave ultraviolet radiation (PUVA). Side effects of PUVA therapy are not, however, desirable, and this therapy has been linked with increased incidence of skin cancer in humans. The psoralens are known to be carcinogenic, mutagenic and teratogenic, and to cause photodermatitis. The main objective of this study was to document the effect of PUVA on the epidermis of rats. Female Wistar rats were administered dietary bergapten and/or xanthotoxin (0-200 mg/kg body) and exposed to UVA radiation (45 min./day) for four weeks. At the end of the four-week period the rats were sacrificed; skin samples were taken from the ears and the top part of the tail and fixed for examination by Scanning Electron Microscopy. The animals subjected to PUVA had significantly smaller scales on the tail epidermis (mean scale size for the control 926 mu vs. 725 to 805 mu for the psoralen treatment groups. The rats that received dietary psoralens also had significantly less hair on the ears compared with the control animals (mean number of hairs per millimeter over the ear edge for the control 54.9 vs. 2.00 to 10.7 for the treatment groups). The two compounds were synergistic in their ability to reduce scale size on the tail epidermis.

5-Methoxypsoralen↗
PubMed1998

Xenobiotics and xenoestrogens in fish: modulation of cytochrome P450 and carcinogenesis.

As is the case with mammals, an ever-increasing number of cytochromes P450 (CYPs) are being characterized from fish. The focus of work on fish CYPs has been primarily on environmental induction of CYP1A by pollutants such as the polycyclic aromatic hydrocarbons, polychlorinated biphenyls, dioxins and dibenzofurans. This response has been the basis for a sensitive biomonitoring tool of ecosystem health for a number of years. Studies have documented a correlation between CYP1A induction, pollutant levels and tumor incidence, especially in bottom-dwelling species. The rainbow trout has been utilized as a tumor model to document the role of CYP1A modulation in the inhibition or promotion of cancer. Fish are also very responsive to the class of chemicals known as xenoestrogens. Recent evidence is presented documenting the modulation of CYPs by xenoestrogens and their potential role as modulators of the tumor response. In this paper, we summarize the current knowledge concerning the occurrence of CYPs in fish and focus on the role of CYP1A induction in environmental monitoring of various genotoxic carcinogens and in the modulation of cancer in the trout model. Finally, the important class of aquatic pollutants known as xenoestrogens have now been shown to modulate CYP levels perhaps leading to alterations in tumor response or other adverse effects.

Animals↗
PubMed1998

Dual skin testing with Mycobacterium avium sensitin and purified protein derivative to discriminate pulmonary disease due to M. avium complex from pulmonary disease due to Mycobacterium tuberculosis.

Skin testing with Mycobacterium avium sensitin (MAS) RS 10/2 and purified protein derivative (PPD) was conducted on patients with pulmonary disease due to M. avium complex (MAC) or Mycobacterium tuberculosis (MTB) and no known immunodeficiency. Reactions > or = 5 mm to either MAS or PPD were present in 37 (84%) of 44 MAC patients and 28 (97%) of 29 MTB patients. MAC patients had a mean MAS reaction of 13.8 (+/-8.3) mm and a mean PPD reaction of 3.5 (+/-8.6) mm (P < .001). MTB patients had a mean MAS reaction of 17.9 (+/-9.4) mm and a mean PPD reaction of 22.9 (+/-11.4) mm (P < .001). MAS-dominant skin tests (MAS reaction > or = 5 mm larger than PPD reaction) were present in 32 (73%) of 44 MAC patients and 1 (3%) of 29 MTB patients. MAS-dominant skin tests had a specificity of 97% for discriminating MAC disease from MTB disease.

Adult↗
PubMed1998

Modulation of aflatoxin-B1 hepatocarcinogenesis in trout by dehydroepiandrosterone: initiation/post-initiation and latency effects.

Previously, we demonstrated that dehydroepiandrosterone (DHEA) enhances aflatoxin B1 (AFB1) hepatocarcinogenesis in trout when administered following AFB1 exposure. This paper examines the effect of DHEA on tumor latency and the comparative potency for DHEA to modulate AFB1 carcinogenesis when administered prior to and concurrent with AFB1 compared with a post-initiation exposure. Trout were initiated by a 30 min water bath exposure to 10 p.p.b. AFB1. At 3 months post-initiation, animals were started on either control diet or a diet containing 444 p.p.m. dehydroepiandrosterone (DHEA). Fifty trout per treatment were sampled prior to the start of experimental diets, and then at monthly intervals for the next 7 months and examined for the presence of tumors. Tumors were not detected in initiated controls until 7 months after initiation. In initiated trout fed DHEA, the first tumor was detected 5 months after initiation (after just 2 months of dietary DHEA). At 6 months post-initiation, 20% of the AFB1-initiated trout fed DHEA had tumors, while no tumors were visible in either AFB1-initiated controls or noninitiated trout fed DHEA. A second experiment was designed to determine if the enhancing effect of DHEA on AFB1 carcinogenesis is dependent on the time of DHEA administration relative to the time of AFB1 exposure, and if DHEA could be chemopreventive if administered prior to and concurrent with AFB1. Trout were fed one of two levels of DHEA (888 or 1776 p.p.m.) either prior to and during a 4-week initiation period of dietary AFB1 administration, or for 8 weeks following initiation with AFB1. At 9 months after initiation the livers were examined for tumors. Neither exposure protocol provided protection towards AFB1 hepatocarcinogenesis. The strongest enhancement occurred when DHEA was fed during the post-initiation period. Levels of p53 and p34cdc2 were decreased by DHEA treatment, indicating that DHEA may act through alterations in cell-cycle control.

Aflatoxin B1↗
PubMed1998

Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome.

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls (P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls (P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension (P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.

Adolescent↗
PubMed1998

Utilizing increased response effort to reduce chronic hand mouthing.

The effects of increased response effort on levels of hand mouthing, leisure engagement, and adaptive elbow flexion were investigated with 2 individuals who had been diagnosed with profound disabilities. Arm restraints designed to alter the amount of physical effort necessary to engage in hand mouthing were used. Results indicated that the treatment strategy reduced levels of hand mouthing but produced only small to moderate reductions in levels of leisure engagement and adaptive elbow flexion. At follow-up, the effects of increased response effort on hand mouthing and leisure engagement were maintained for both participants; however, the restraints were associated with substantial reductions in adaptive elbow flexion for 1 participant.

Adaptation, Psychological↗
PubMed1998

Temporal distributions of problem behavior based on scatter plot analysis.

The scatter plot is a commonly used assessment tool for identifying temporal patterns in the occurrence of behavior problems. However, the extent to which such patterns are frequently observed is unknown because little research has evaluated the general utility of the scatter plot. We conducted a large-scale analysis of within- and across-day occurrences of problem behavior by conducting continuous observations of 20 individuals living in four residential facilities. Data were recorded during 30-min intervals throughout participants' waking hours for 30 days by direct care staff and were converted into scatter plot formats. Five sets of data were excluded from further analysis due to poor interobserver agreement (below 80%). Visual analysis of the remaining 15 scatter plots indicated that none showed any reliable temporal pattern of responding. However, when the data were transformed into aggregate "control charts" based on statistical process control procedures, 12 of the 15 sets of data revealed one or more 30-min intervals during which problem behavior was more likely to occur. Results are discussed in terms of the practicality of applying statistical analyses to scatter plot data and of collecting data for the length of time needed to show statistical significance. It was concluded that detailed functional or descriptive analyses, which would reveal cause-effect or correlational relationships between behavior and specific environmental events, may be both more precise and more efficient forms of assessment.

Adolescent↗
PubMed1998

Extraction, quantification, and biological availability of fumonisin B1 incorporated into the Oregon test diet and fed to rainbow trout.

The purpose of this study was (i) to determine whether pure fumonisin B1 could be incorporated into, recovered, and detected by high-pressure liquid chromatographic analysis from the semipurified Oregon test diet (OTD) used in rainbow trout feeding studies, and (ii) to determine if the incorporated fumonisin B1 was biologically available using the change in free sphingoid bases in liver, kidney, and serum as a mechanism-based biomarker. The results indicate that fumonisin is not easily quantified in the OTD. Recoveries ranged from 12 to 81% of the calculated concentrations based on the fumonisin B1 added to the OTD. However, the fumonisin B1 in the OTD was readily absorbed and biologically active as evidenced by marked increases in free sphinganine in liver, kidney, and serum. The magnitude of the increase in free sphinganine at 100 ppm in the OTD was comparable to that known to be associated with liver toxicity in rats, pigs, and ponies.

Animals↗