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Biomedical subjects

A L Davis

Publications and source records attributed to A L Davis.

At least 19 recordsLinked to original sources

Effects of cattle treatment with a cypermethrin/cymiazol spray on survival and reproduction of the dung beetle species Euoniticellus intermedius (Coleoptera: Scarabaeidae).

In a bioassay to determine non-target ecotoxicological effects of a pyrethroid spray (Ektoban) on dung beetles, dung from both cypermethrin/cymiazol-treated and control cattle was collected one, two, three, five, seven, 14, 21 and 28 days after treatment and fed to a treatment and control group (respectively) of beetles of the species Euoniticellus intermedius (Reiche). This was done to assess whether a spray formulation of cypermethrin may affect dung beetles differently than previously tested pour-on formulations. Following three beetle generations for two weeks each, the experiment retrieved no significant differences in adult or larval survival, egg production, fecundity and fertility between the control and treatment group. These results demonstrated that the used spray formulation of cypermethrin is likely to be far less detrimental to dung beetles than previously tested pour-ons.

Animals↗

Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer.

BACKGROUND: Activation of gastrin-releasing peptide receptor (GRPR) in human airways has been associated with a proliferative response of bronchial cells to gastrin-releasing peptide and with long-term tobacco use. The GRPR gene is located on the X chromosome and escapes X-chromosome inactivation, which occurs in females. Increasing evidence demonstrates that women are more susceptible than men to tobacco carcinogenesis. We hypothesized that the susceptibility of women to the effects of tobacco may be associated with airway expression of GRPR. METHODS: We analyzed GRPR messenger RNA (mRNA) expression in lung tissues and cultured airway cells from 78 individuals (40 males and 38 females) and in lung fibroblasts exposed to nicotine in vitro. Nicotinic acetylcholine receptors in airway cells were assayed by use of radioactively labeled nicotine and nicotine antagonists. A polymorphism in exon 2 of the GRPR gene was used to detect allele-specific GRPR mRNA expression in some individuals. Statistical tests were two-sided. RESULTS: GRPR mRNA expression was detected in airway cells and tissues of more female than male nonsmokers (55% versus 0%) and short-term smokers (1-25 pack-years [pack-years = number of packs of cigarettes smoked per day multiplied by the number of years of smoking]) (75% versus 20%) (P =.018 for nonsmoking and short-term smoking females versus nonsmoking and short-term smoking males). Female smokers exhibited expression of GRPR mRNA at a lower mean pack-year exposure than male smokers (37.4 pack-years versus 56.3 pack-years; P =.037). Lung fibroblasts and bronchial epithelial cells exhibited high-affinity, saturable nicotinic acetylcholine-binding sites. Expression of GRPR mRNA in lung fibroblasts was elevated following exposure to nicotine. CONCLUSIONS: Our results suggest that the GRPR gene is expressed more frequently in women than in men in the absence of smoking and that expression of this gene is activated earlier in women in response to tobacco exposure. The presence of two expressed copies of the GRPR gene in females may be a factor in the increased susceptibility of women to tobacco-induced lung cancer.

Adult↗

Two novel flavanones from Greigia sphacelata.

As part of our continuing phytochemical investigations of plants from arid environments in Chile, the aerial parts of Greigia sphacelata were examined. Two novel flavanones, 5,7,3'-trihydroxy-6, 4',5'-trimethoxyflavanone (1) and 5,3'-dihydroxy-6,7,4', 5'-tetramethoxyflavanone (2), as well as eight known compounds-1, 3-O-di-trans-p-coumaroylglycerol (3), 1-O-trans-p-coumaroylglycerol (4), a mixture of 1-(omega-feruloyldocosanoyl)glycerol (5) and 1-(omega-feruloyltetracosanoyl)glycerol (6), trans-ferulic acid 22-hydroxydocosanoic acid ester (7), arborinone (8), arborinol (9), and isoarborinol (10)-were isolated.

Flavanones↗

Measurement of refractive error in Native American preschoolers: validity and reproducibility of autorefraction.

PURPOSE: To examine (1) reproducibility of cycloplegic retinoscopy (C-RNS), cycloplegic autorefraction (C-Autoref), and noncycloplegic autorefraction (NC-Autoref), and (2) validity of C-Autoref and NC-Autoref compared with C-RNS in preschoolers with astigmatism. METHODS: Subjects were 36 Native American preschoolers. Three measurements of right eye refractive error were obtained with each of three methods: C-RNS (by three different retinoscopists), C-Autoref, and NC-Autoref (Nikon Retinomax K+). Vector methods (vector dioptric distance, VDD) were used in the analyses. RESULTS: Mean reproducibility was 0.41 D (SD = 0.18) for C-RNS, 0.25 D (SD = 0.17) for C-Autoref, and 0.37 D (SD = 0.21) for NC-Autoref. Mean agreement between C-Autoref and C-RNS ranged from 0.51 to 0.61 VDD (SD = 0.24 to 0.35), and ranged from 1.66 to 1.74 VDD (SD = 1.11 to 1.25) for agreement between NC-Autoref and C-RNS. Mean bias was -0.07 +0.21 x 149 and -1.33 +0.34 x 178 for C-Autoref and NC-Autoref, respectively. CONCLUSIONS: C-Autoref provided reliable and valid measurements of refractive error in young children. NC-Autoref measurements were reliable within subjects, but there was large variability in validity among subjects.

Arizona↗

Documentation of care outcomes in an academic nursing clinic: an assessment.

PURPOSE: To assess documentation of client data collected at an academic nursing clinic using the Wilson and Cleary Health Related Quality of Life (HRQOL) conceptual model as a framework. DATA SOURCES: A chart audit of 100 randomly selected active client records was conducted. CONCLUSIONS: Although several significant HRQOL variables were documented, data regarding general health perception and quality of life were not present. The HRQOL conceptual model provided an appropriate structure for evaluating the documentation. Further effort must be made to include key HRQOL dimensions in the clinic's documentation system. IMPLICATIONS FOR PRACTICE: Documenting the quality of care provided in nursing clinics is essential in order for other professionals and the public to recognize nursing professionals as accountable and credible. This project formed the basis for a computerized outcomes-based client record system.

Academic Medical Centers↗

Investigations by HPLC-electrospray mass spectrometry and NMR spectroscopy into the isomerisation of salinomycin.

HPLC-MS studies have indicated that certain polyether ionophore veterinary drugs are prone to degradation when stored as water-methanol solutions at ambient temperature. Salinomycin and narasin were particularly susceptible, disappearing completely within weeks to produce more polar species, which were identified as isomers of the original compounds. Lasalocid appeared to be stable under such conditions. Structural elucidation of the principal ultimate salinomycin isomerisation product was achieved by 2D NMR spectroscopy. This indicated that the isomerisation process consists of the opening of the spiro rings in the salinomycin structure with the concomitant formation of a furan moiety. The MS data indicated that the isomers retain the ability to complex alkali metal ions and may therefore retain their pharmacological activity. These discoveries may have implications both for the development of legislation covering acceptable levels of polyether ionophore residues in foodstuffs and also for analytical protocols designed to detect them.

Anti-Bacterial Agents↗

Backbone and side chain dynamics of lac repressor headpiece (1-56) and its complex with DNA.

The dynamics of the backbone and (some of) the side chains of lac headpiece (1-56; lac HP56) have been studied for the free protein and for its complex with lac half-operator DNA by 15N T1 and T1p relaxation measurements combined with [1H-15N] NOE experiments. For the structurally well-defined part of the free lac HP56 (i.e., residues 3-49) a rigid backbone was found for residues in the three alpha-helices and for the turn of the helix-turn-helix motif. The loop between helices II and III of lac headpiece, which was characterized by slight disorder in the structure calculations, shows increased mobility. The detected side chains are very mobile. These data are in full agreement with the rms deviations in the structural data of free lac HP56. When lac HP56 is complexed with DNA, several changes in mobility take place. The most remarkable change was found for the loop region between helices II and III: residue His-29 within this loop interacts with Thy-3 of the operator DNA. As a result this mobile loop adapts itself to the DNA and becomes more rigid. Moreover, most DNA-contacting side chains show a significant decrease in flexibility, although these side chains do not become as rigid as the backbone. These results suggest that the mobility of the regions within lac HP56 important for complexation, i.e., the loop and the DNA-contacting side chains, is essential for a good fit onto the counterparts of the target DNA.

Bacterial Proteins↗

Outcome of MDR-TB patients, 1983-1993. Prolonged survival with appropriate therapy.

We analyzed the clinical and laboratory findings and outcome of 173 patients hospitalized at our institution from 1983 to 1994 with multidrug-resistant tuberculosis (MDR-TB) and evaluated outcome. The 173 patients (mean age 40 +/- 1 yr) were predominantly male (92%), African American or Hispanic (80%), and mostly undomiciled. Over half (52%) were known to be HIV-infected. HIV-positive MDR-TB patients had significantly more pulmonary and constitutional symptoms, more extrapulmonary disease, and fewer cavitary lesions on chest radiographs. Fifty-five percent of the patients in the cohort have died; mortality was significantly greater for HIV-positive than HIV-negative (72% versus 20%, p < 0.01). The median duration of survival of MDR-TB patients was 22 +/- 1 mo. Overall, extrapulmonary involvement was a risk factor for shorter survival, while a cavitary lesion on initial chest film and institution of appropriate treatment were positive predictors of survival. In HIV+ patients, only appropriate therapy was associated with prolonged survival (median of 14.1 mo). Interestingly, there was a trend toward better outcome in the first half of the decade reviewed. We conclude that although mortality from MDR-TB is high in both HIV-positive and HIV-negative patients, institution of appropriate therapy is the factor most strongly associated with a favorable outcome. Development of new diagnostic and therapeutic strategies for MDR-TB are urgently needed.

Acquired Immunodeficiency Syndrome↗

1H- and 13C-NMR characterization of the digalactosylmannopentaose liberated from legume seed galactomannan by beta-mannanase action.

Incubation of Locust bean gum with an Aspergillus niger beta-D-mannanase released a wide variety of galactomannan oligomers. A single heptasaccharide, digalactosylmannopentaose, was obtained from fractionation of the mixture by size exclusion chromatography. The purity and chemical composition of the sample was demonstrated using mass spectrometry, high performance anion-exchange chromatography and monosaccharide composition analysis. The primary structure of this heptasaccharide was unambiguously identified using 2D 1H and 13C homonuclear and heteronuclear NMR. A complete assignment of the 1H and 13C signals of this oligomer was achieved, producing an NMR dataset that will be of importance in the primary structure elucidation of larger and more complex galactomannan oligomers.

Aspergillus niger↗

Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations.

The solution structure of the glucocorticoid receptor (GR) DNA-binding domain (DBD), consisting of 93 residues, has been refined from two and three-dimensional NMR data using an ensemble iterative relaxation matrix approach followed by direct NOE refinement with DINOSAUR. A set of 47 structures of the rat GR fragment Cys440-Arg510 was generated with distance geometry and further refined with a combination of restrained energy minimization and restrained molecular dynamics in a parallel refinement protocol. Distance constraints were obtained from an extensive set of NOE build-up curves in H2O and 2H2O via relaxation matrix calculations (1186 distance constraints from NOE intensities, 10 phi and 22 chi 1 dihedral angle constraints from J- coupling data were used for the calculations). The root-mean-square deviation values of the 11 best structures on the well-determined part of the protein (Cys440 to Ser448, His451 to Glu469 and Pro493 to Glu508) are 0.60 A and 1.20 A from the average for backbone and all heavy atoms, respectively. The final structures have R-factors around 0.40 and good stereochemical qualities. The first zinc-coordinating domain of the GR DBD is very similar to the crystal structure with a root-mean-square difference of 1.4 A. The second zinc-coordinating domain is still disordered in solution. No secondary structure element is found in this domain in the free state. As suggested by crystallographic studies on the estrogen receptor DBD-DNA and GR DBD-DNA complexes, part of this region will form a distorted helix and the D-box will undergo a conformational change upon cooperative binding to DNA.

Amino Acid Sequence↗

Effect of airway pressure on inferior vena cava pressure as a measure of central venous pressure in children.

We evaluated the effect of elevated airway pressure on the validity of intravascular pressure obtained in the distal inferior vena cava (IVC) as a measure of central venous pressure (CVP) in a group of children receiving mechanical ventilation. The IVC pressure correlated well with CVP in the patients without abdominal distention, but the disparity was wider in those with abdominal distention. Elevated mean airway pressure or positive end-expiratory pressure had no effect on the relationship of IVC to CVP.

Adolescent↗

Ability to culture resectable non-small cell lung carcinomas is correlated with recurrence.

Present clinicopathologic staging of non-small cell lung cancer is limited in its ability to provide more than a general prognostic estimate in patients with lung cancer who have resectable disease. This study was performed to identify whether the ability to adapt tumor tissue from resectable (stage I to IIIa) non-small cell lung cancer was associated with a poorer prognosis and an increased risk for early tumor recurrence. We attempted to culture a tumor specimen obtained from 90 patients with resectable non-small cell lung cancer. We used a culture medium conditioned by exposure to the lung cancer cell line A549-1, a known producer of autocrine lung cancer growth factors, and provided tumor colony scaffolding using a feeder layer of inactivated fibroblasts, and found these measures improved tumor culture yields. Twenty-two cell lines were obtained, a success rate of 24.4%. Tumor recurrences were more common (79%) among the culture-positive patients than among the culture-negative patients (37.5%; p < 0.002). For all patients, survival at 19 months in the culture-positive patients was 50.0%, compared with 83.6% in the culture-negative patients (p < 0.005). The median survival for the culture-positive patients was 15 months, versus 21.7 months for the culture-negative patients (p < 0.004). The establishment of a culture was a predictor of shortened survival for patients with stage I disease. In patients with stage I disease, survival at 19 months was 54.5% for the culture-positive patients, versus 89% for the culture-negative patients (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Non-Small-Cell Lung↗

Expression of mRNA for three bombesin receptor subtypes in human bronchial epithelial cells.

Gastrin-releasing peptide (GRP), the mammalian form of the amphibian peptide bombesin, may act as a growth-regulatory peptide in the lung. Cultured human bronchial epithelial (HBE) cells have previously been found to proliferate in response to GRP or bombesin. Three receptors have been identified for bombesin and its analogs, namely gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR), and bombesin receptor subtype 3 (BRS-3). The human genes for these receptors have been cloned and sequenced. We used the polymerase chain reaction to detect transcripts for these three receptor subtypes in HBE cells cultured from bronchial mucosal biopsies. Primers specific for each receptor subtype were used to amplify DNA fragments from reverse-transcribed mRNA isolated from these cultures. An amplified fragment was detected for GRPR in seven of nine cases, for NMBR in six of 10 cases, and the BRS-3 in three of nine cases. We have also amplified message for NMBR in five of five fresh bronchial biopsies, but message for GRPR could not be detected. In preliminary evaluation of two biopsies, there was also no evidence of BRS-3 expression. Additionally, we have detected transcripts for GRPR and NMBR in four of seven and seven of seven cases, respectively, of cultured non-small cell lung carcinomas (NSCLC). BRS-3 expression was seen in one of seven carcinomas in culture. Identity of the amplified fragments was confirmed by restriction enzyme digestion and Southern blotting. Furthermore, GRP induced expression of the early-response gene, c-jun, in an HBE cell culture and an NSCLC cell line. GRP also promoted colony formation in the NSCLC cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Carotid blood-flow velocity changes detected by Doppler ultrasound in determination of brain death in children. A preliminary report.

To investigate the value of Doppler ultrasonography of the carotid arteries as a diagnostic test for the determination of brain death in children, we enrolled 17 patients in a blinded fashion in the pediatric intensive care unit of Memorial Miller Children's Hospital of Long Beach between the period of December 1990 and October 1992. After institutional review board approval and parental consent, children who sustained severe brain injury underwent Doppler ultrasonography study of their carotid arteries. Seven of 17 patients were diagnosed as having brain death by clinical criteria (complete loss of cerebral and brainstem functions) and electroencephalogram (EEG). Five of seven (71%) patients with the diagnosis of brain death had bilateral reverse flow (characteristic of increased cerebrovascular resistance and absent cerebral circulation) on their Doppler ultrasonography, yielding a specificity of 100% and sensitivity of 71.4% (P = 0.01). All surviving patients (five) and the five who did not fulfill the brain-death criteria at the time of Doppler ultrasonography and were later taken off life supportive measures had normal Doppler findings. These data indicate that Doppler ultrasonography of the carotid arteries is a very specific test and can be used as an adjunctive modality for determination of brain death in children.

Blood Flow Velocity↗

Three-dimensional structure of the lipoyl domain from Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex.

The structure of the lipoyl domain from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been determined by means of nuclear magnetic resonance spectroscopy. A total of 452 nuclear Overhauser effect distance constraints and 76 dihedral angle restraints were employed as the input for the structure calculations, which were performed using a hybrid distance geometry-simulated annealing strategy and the programs DISGEO and X-PLOR. The overall structure of the lipoyl domain (residues 1 to 79 of the dihydrolipoamide acetyltransferase polypeptide chain) is that of a flattened eight-stranded beta-barrel folded around a core of well-defined hydrophobic residues. The lipoylation site, lysine 42, is located in the middle of a beta-turn, and the N and C-terminal residues of the domain are close together in adjacent beta-strands at the opposite end of the molecule. The polypeptide backbone exhibits a 2-fold axis of quasi-symmetry, with the C alpha atoms of residues 15 to 39 and 52 to 76 being almost superimposable on those of residues 52 to 76 and 15 to 39, respectively (root-mean-square deviation = 1.48 A). The amino acid residues at key positions in the structure are conserved among all the reported primary structures of lipoyl domains, suggesting that the domains all fold in a similar way.

Amino Acid Sequence↗

Application of a simplified method to determine bioavailability of an oral dose of phenytoin.

The bioavailability of capsules of phenytoin was determined by two methods: a method involving the numerical integration of the Michaelis-Menten equation and an alternative method involving fitting the time course of plasma concentrations, following the administration of the reference intravenous dosage, to an empirical quadratic function of time. The latter procedure requires much simpler computations. The two methods yielded very similar estimates of the rate and extent of absorption of phenytoin. Total absorption was 0.90 +/- 0.05 and 0.89 +/- 0.05 (mean +/- SE, n = 6) using the methods of numerical integration and quadratic curve fitting, respectively. Both methods indicated that the rate of absorption of phenytoin was inconsistent and slow. Half the total absorption of phenytoin occurred over 2.5 +/- 0.3 hr but the remainder was absorbed very slowly over a period of about 30 hr. Empirical functions may be more generally useful in the determinations of the bioavailability of drugs, particularly if some aspects of the disposition are saturable.

Administration, Oral↗

Pharmacokinetics of exogenous epinephrine in critically ill children.

OBJECTIVES: This study was designed to determine the steady-state plasma concentrations and clearance rates of epinephrine in critically ill children, to examine if epinephrine pharmacokinetics conform to a linear model, and to compare epinephrine clearance rates with clearance rates of dopamine and dobutamine. DESIGN: This study was prospective, without intervention or control groups. SETTING: The pediatric ICUs of two tertiary care teaching hospitals. PATIENTS: All patients who were hemodynamically stable while requiring continuous epinephrine infusions were eligible for the study. INTERVENTIONS: Blood samples were taken at steady state and analyzed for epinephrine concentrations, as well as dopamine and dobutamine concentrations, if present, by high-pressure liquid chromatography with electrochemical detection. RESULTS: Plasma epinephrine concentrations during steady-state infusions of 0.03 to 0.2 micrograms/kg/min ranged from 670 to 9430 pg/mL (3660 to 51,490 pmol/L), with a mean of 4360 +/- 3090 pg/mL (23,810 +/- 16,870 pmol/L) and were linearly related to dose. Epinephrine clearance rates ranged from 15.6 to 79.2 mL/kg/min (mean 29.3 +/- 16.1) and were not dependent on steady-state plasma concentrations. Epinephrine clearance rate was in the same range as the clearance rates of dopamine (34.1 +/- 16.6) and dobutamine (35.9 +/- 27.8) and was linearly related to them (p < .005). CONCLUSIONS: Epinephrine infusions produce pharmacologic plasma concentrations of epinephrine in critically ill children. The plasma concentration of epinephrine correlates with the infusion rate, suggesting linear pharmacokinetics. Epinephrine clearance rates in critically ill children appear to be lower than the reported clearance rates in healthy adults. The clearance rates of two other inotropic catecholamines, dopamine and dobutamine, are significantly correlated with the clearance rate of epinephrine.

Adolescent↗