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Biomedical subjects

D E Williams

Publications and source records attributed to D E Williams.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1997

Flt3 ligand synergizes with granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor to mobilize hematopoietic progenitor cells into the peripheral blood of mice.

Peripheral blood progenitor cells (PBPC) are increasingly being used in the clinic as a replacement for bone marrow (BM) in the transplantation setting. We investigated the capacity of several different growth factors, including human flt3 ligand (FL), alone and in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or granulocyte colony-stimulating factor (G-CSF ), to mobilize colony forming cells (CFU) into the peripheral blood (PB) of mice. Mice were injected subcutaneously (SC) with growth factors daily for up to 10 days. Comparing the single agents, we found that FL alone was superior to GM-CSF or G-CSF in mobilizing CFU into the PB. FL synergized with both GM-CSF or G-CSF to mobilize more CFU, and in a shorter period of time, than did any single agent. Administration of FL plus G-CSF for 6 days resulted in a 1,423-fold and 2,717-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM) and colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) in PB, respectively, when compared with control mice. We also followed the kinetics of CFU numerical changes in the BM of mice treated with growth factors. While GM-CSF and G-CSF alone had little effect on BM CFU over time, FL alone increased CFU-GM and CFU-GEMM threefold and fivefold, respectively. Addition of GM-CSF or G-CSF to FL did not increase CFU in BM over levels seen with FL alone. However, after the initial increase in BM CFU after FL plus G-CSF treatment for 3 days, BM CFU returned to control levels after 5 days treatment, and CFU-GM were significantly reduced (65%) after 7 days treatment, when compared with control mice. Finally, we found that transplantation of FL or FL plus G-CSF-mobilized PB cells protected lethally irradiated mice and resulted in long-term multilineage hematopoietic reconstitution.

Animals↗
PubMed1997

Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model.

Indole-3-carbinol (I3C), a natural component from cruciferous vegetables, has been demonstrated to be a modulator of carcinogenesis in various animal models. Along with the promising perspectives of I3C as a possible chemopreventive agent for human breast cancer, some concerns have been raised regarding the tumor-promotional potency of this compound in other target organs. In this study we examined the hepatic tumor-modulatory properties of I3C fed to C57BL/6J mice, initiated with diethylnitrosamine (DEN). Infant male mice were initiated with 0, 2 or 5 mg/kg DEN (i.p. injection) at 15 days of age. Mice were weaned 9 days later and immediately put on AIN76A semipurified diet (with no antioxidants) containing 0 or 0.15% (1500 ppm) I3C. In addition, at the age of 2 months, one group of mice initiated with 2 mg/kg DEN was injected i.p. with a single dose (20 mg/kg) of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), to serve as a positive control group for promotion. Mice were sampled for hepatic tumors at the age of 6 or 8 months. Each sampled group contained 11-12 mice except the HCB group (nine animals). After 8 months, there was a statistically significant (P < 0.0005) inhibition of hepatocarcinogenesis observed for I3C-fed animals initiated with the high dose of DEN. A single injection of HCB at 2 months of age significantly (P = 0.0003) enhanced hepatocarcinogenesis in mice initiated with 2 mg/kg DEN. There was no statistically significant difference between groups sampled at 6 months of age. Our observations indicate that long term administration of I3C in the diet inhibits DEN-initiated hepatocarcinogenesis in the infant mouse model.

Administration, Oral↗
PubMed1997

Psoralen-induced growth inhibition in Wistar rats.

The linear furanocoumarins (or psoralens) are naturally occurring plant biosynthetic metabolites that have been used since ancient times in skin photochemotherapy. However, medicinal use of the psoralens has been linked with increased incidence of skin cancer in humans. To understand some of the mechanism of this toxicity, we tested increasing concentrations of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) for toxicity against Wistar rats. As dietary concentrations of each compound increased, weight gain in both male and female rats decreased. Feeding on diet containing these chemicals also decreased rat birth rate, but did not significantly affect individual litter weight or date of birth. Xanthotoxin appeared to be more toxic than bergapten.

5-Methoxypsoralen↗
PubMed1997

Pulmonary flavin-containing monooxygenase (FMO) in rhesus macaque: expression of FMO2 protein, mRNA and analysis of the cDNA.

Pulmonary microsomes from Rhesus macaque express a flavin-containing monooxygenase (FMO) resembling the FMO2 ortholog from rabbit with respect to immunochemical cross-reactivity and expression in lung, but not liver. A full-length cDNA was cloned following screening of a Rhesus macaque lung cDNA library. The nucleotide sequence contained an open reading frame encoding 535 amino acids with 85 and 84% identity to FMO2 from rabbit and guinea pig, respectively, and an identical location of the putative FAD- and NADP-binding sites. Northern blots of monkey lung mRNA revealed multiple size FMO2 transcripts. These mRNA transcripts are expressed in lung, but not in liver or kidney.

Amino Acid Sequence↗
PubMed1997

Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7.

The putative effects of interleukin (IL)-7, operating in the context of extracellular matrix (ECM), on the adhesion of human T cells were examined. Recombinant human, IL-7 was found to bind ECM or fibronectin (FN) with IC50 values of 10-100 nM. Nanogram amounts of both soluble and, especially, FN- or ECM-bound IL-7, which differentially affected the morphologies of FN-adherent T cells, induced the adhesion of resting CD4+ and CD8+ T cells in dose-dependent and beta 1 integrin-dependent manners. Under static and flow conditions, soluble IL-7 also induced the binding of unstimulated T cells to vascular cell adhesion molecule-1, suggesting that this cytokine can also modulate integrin binding to endothelial cell ligands. The effects of affinity modulation by IL-7 of FN-specific beta 1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN-bound IL-7 or by an integrin-specific affinity-modulating monoclonal antibody, but not by soluble IL-7 or phorbol 12-myristate 13-acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capable of modulating its adhesive interactions with specific immune cells by associating with and presenting a cytokine in a bio-active state.

Cell Adhesion↗
PubMed1997

In vitro metabolism of 7,12-dimethylbenz[a]anthracene by rainbow trout liver microsomes and trout P450 isoforms.

Liver microsomes from juvenile trout metabolized DMBA to unknown highly polar metabolites (X) and to DMBA-t-5,6-diol, DMBA-t-8,9-diol, 7-OHM-12-MBA, 7M-12-OHMBA, 2-OH-DMBA, 4-OH-DMBA, and trace amounts of DMBA-t-3,4-diol. Treatment of trout with beta-naphthoflavone (BNF) and isosafrole (ISF) increased the formation of these products except for the hydroxymethyl derivatives of DMBA. The production of DMBA-t-3,4-diol, 2-OH-DMBA, and 4-OH-DMBA was much greater in BNF-induced liver microsomes than that in ISF-induced liver microsomes. In contrast, the yield of DMBA-t-8,9-diol and 7-OHM-12-MBA was greater in ISF-induced microsomes than that in BNF-induced microsomes. Trout CYP1A1 (P450 LM4b) purified from BNF-treated trout catalyzed the formation of the same metabolites generated by BNF-induced microsomes in the presence of added human microsomal EH. The constitutive forms of P450 isolated from untreated trout such as P450s LMC3, LMC4, and LMC5, CYP2M1 (P450 LMC1), and CYP2K1 (P450 LMC2) did not produce any of the DMBA metabolites (except for DMBA-t-8,9-diol by CYP2K1) generated by the trout microsomes. Generation of DMBA-DNA and DMBA-protein adducts in vitro was enhanced by treatment of trout with BNF and by ISF to a lesser extent. Formation of adducts and DMBA diols by BNF-induced liver microsomes and by trout CYP1A1 was completely blocked by the CYP1A inhibitor ellipticine (100 microM). These results suggest that the BNF-inducible trout P450 (CYP1A), not the constitutive P450s, is the major catalyst for the biotransformation of DMBA to metabolites that bind to macromolecules.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Long-term maintenance of a behavioral alternative to surgery for severe vomiting and weight loss.

A 34-year-old woman with severe mental retardation suffered from gastroesophageal reflux, projectile vomiting, weight loss, and a prepyloric ulcer. Despite the implementation of non-intrusive behavior treatment procedures involving simple correction and differential reinforcement (Treatment A), fundoplication surgery with implantation of a gastrostomy feeding tube had been recommended. A descriptive functional analysis suggested that the woman's vomiting was maintained by escape. Revised treatment was implemented throughout her waking hours. Treatment B consisted of the addition of escape extinction and antecedent control procedures. Treatment C added to these procedures food choice and additional differential reinforcement procedures. Results showed the respective mean frequency of vomiting and mean weight were: Treatment A--1.4 episodes/day and 118 lbs; Treatment B--1.1 episodes/day and 105 lbs; Treatment C--0.2 incidents/day and 133 lbs. The woman's progress has been maintained for nearly 2 years.

Adult↗
PubMed1997

Rumination syndrome.

Rumination is a syndrome characterized by repetitive regurgitation of small amounts of food from the stomach. The food is then partially or completely rechewed, reswallowed, or expelled. This syndrome is relatively common in infants and mentally challenged persons, but it also occurs in adults with normal intelligence. The rumination syndrome is an underappreciated condition in adults who frequently receive a misdiagnosis of vomiting due to gastroparesis or gastroesophageal reflux. Difficulties in establishing the correct diagnosis may be caused by a lack of awareness of the condition among physicians. This syndrome must be considered in the differential diagnosis of a patient with regurgitation, vomiting (especially postprandial), and weight loss. Reassurance, explanations, and behavioral therapy are currently the mainstays of treatment in adults with normal intelligence who have the rumination syndrome. Appropriately controlled trials are needed to establish the best therapy.

Adolescent↗
PubMed1997

14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal injection provides in vivo evidence for covalent binding of microcystin-LR in salmon livers.

The tissue distribution and clearance of radiolabeled microcystin-LR administered to Atlantic salmon via i.p. injection has been re-examined using uniformly 14C-labeled toxin. Significant differences were found to exist between these results and those obtained when fish received an i.p. injection of tritium-labeled dihydromicrocystin-LR. In addition, MeOH liver extracts were assayed by both phosphatase assay and 14C counts and the results compared with the total levels of incorporation determined by digestion and subsequent 14C counting of the same live tissues. An attempt to investigate the metabolism and to document the putative products was also undertaken. It was found that microcystin-LR was extensively metabolized to compounds that are more polar than the parent compound.

Animals↗
PubMed1997

Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues.

Over a period of 3 days saltwater mussels, Mytilus edulis, were fed a cyanobacteria, Microcystis aeruginosa, that contained a high concentration of microcystins. The mussels were killed on a periodic basis over the course of 2 months. Mussels were also collected at two sites were high levels of microcystins in tissues had been noted. A strategy based on the chemically unique nature of the C20 beta-amino acid, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda), portion of the microcystins was used in conjunction with a protein phosphatase (PPase) assay to analyse for both covalently bound microcystins and free microcystins in the mussel tissues. The mussel PPase assay results were compared with the Lemieux oxidation gas chromatography-mass spectrometry (GCMS) analysis. Less than 0.1% of the total microcystin burden in the mussel tissue was found to be extractable with MeOH. Thus, direct evidence was provided for the existence of covalently bound microcystins in mussel tissues in vivo. The mussels rapidly cleared the covalently bound microcystins when transferred to untreated seawater. Within 4 days the total microcystin burden dropped from a high of 336.9 (+/- 45.8) micrograms/g wet tissue to 11.3 (+/- 2.6) micrograms/g. After 4 days postexposure until completion of the experiment the total levels remained below the detection limits of the GCMS method. The levels of free microcystins, extracted with MeOH and detected by the PPase assay, fell from 204 ng/g wet tissue to a residual 14 ng/g over a 53 day postexposure period. Presumably the bound microcystin present in the mussel tissue exists as a covalent complex with the PP-1 and PP-2A enzymes. We conclude that in any shellfish monitoring program it is the total tissue microcystin burden that needs to be considered.

Animals↗
PubMed1997

Evidence for a covalently bound form of microcystin-LR in salmon liver and Dungeness crab larvae.

The chemically unique nature of the C20 beta-amino acid (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda) portion of the microcystins has been exploited to develop a strategy to analyze for the total microcystin-LR (1; see Figure 1) burden in salmon liver and crab larvae tissues. Lemieux oxidation of microcystin-LR (1) gives 2-methyl-3-methoxy-4-phenylbutanoic acid (2), a unique marker for the presence of microcystins. The butanoic acid 2 can be isolated and detected by GC/MS from the livers of Atlantic salmon that received an ip injection of microcystin-LR (1) and from tissues of wild-caught crab larvae. The Lemieux oxidation-GC/MS results are compared with those from MeOH extraction-PPase analysis. Only approximately 24% of the total microcystin-LR (1) burden in salmon liver tissue is found to be extractable with MeOH. Similarly, the Lemieux oxidation-GC/MS method detected 10,000-fold greater microcystin concentrations in Cypress Island Dungeness crab larvae than did the MeOH extraction-PPase method. The disparity in microcystin concentrations measured by the two methods is taken as direct evidence for the existence of covalently bound microcystins in vivo.

Animals↗
PubMed1997

Patterns of eye movements during parallel and serial visual search tasks.

Eye movements were monitored while subjects performed parallel and serial search tasks. In Experiment 1a, subjects searched for an "O" among "X"s (parallel condition) and for a "T" among "L"s (serial condition). In the parallel condition in Experiment 1b, "[symbol: see text]" was the target, and "O"s were distractors; in the serial condition these stimuli switched roles. Displays contained 1, 12, or 24 stimuli, with both target-present and target-absent trials. RT and eye-movement measures (number of fixations, saccadic error, and latency to move) indicated that search efficiency was greatest in the parallel conditions, followed by the serial condition of experiment 1a and, finally, by the serial condition of Experiment 1b. This suggests that eye movements are correlated with the attentional processes underlying visual search.

Attention↗