Two SSCP alleles detected in the 5'-flanking region of bovine IGF1 gene.
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Alleles↗
Biomedical subjects
M E Davis
Publications and source records attributed to M E Davis.
Construction of a mouse whole-genome radiation hybrid panel and application to MMU11.
Whole-genome radiation hybrids have been used to construct human genome maps that integrate different types of markers. To investigate this methodology in mammalian species other than humans, a panel of 164 mouse x hamster whole-genome radiation hybrids was constructed. This set of hybrids was used to produce a high-resolution map of a region on MMU11 that included microsatellite markers and cDNA sequences. The mouse homologue of the human SRY-related gene SOX9 was mapped to an interval of approximately 1.1 cM flanked by the microsatellite markers D11Mit11 and D11Mit291. This interval includes the region containing the mouse Tail-short mutation, a possible homologue of the human syndrome campomelic dysplasia, which is caused by mutations in SOX9. Our results suggest that whole-genome radiation hybrid technology will be a useful adjunct to mapping the genomes of nonhuman mammalian species.
Animals↗
Dichloroacetic acid treatment increases hepatic CYP2E1 in male and female rats.
Previously, we showed that the pretreatment of dichloroacetic acid (DCA) increased CHCl3-induced hepatotoxicity in vivo and CHCl3 metabolism in vitro in both male and female rats. The effects of DCA on hepatic cytochrome P450-dependent monooxygenases were studied in this experiment. Male and female Sprague-Dawley rats were treated with DCA (each 2.45 mmol/kg) three times (9 AM, 4 PM, and 9 AM) and hepatic microsomes were prepared 3 hr after the last treatment (the same procedure as previous studies). After DCA treatment, the total content of cytochrome P450 (0.67 nmol/mg protein vs 0.79) and the activity of NADPH-dependent cytochrome P450 reductase (227 nmol/mg protein/min vs 332) were significantly increased in female rats, but they were unchanged in males (0.99 vs 0.98 for P450; 315 vs 311 for reductase). Induction of CYP2E1 was observed in both sexes, evidenced as increased activities of aniline and p-nitrophenol hydroxylases and increased CYP2E1 protein amount determined by immunoblot assay. In contrast, the CYP2B-related activity (dealkylation of pentoxyresorufin) and immunoreactive protein did not increase after DCA treatment in either males or females. The activity of ethoxyresorufin dealkylase was decreased in DCA-treated males compared to their controls (310 pmol/mg protein/min vs 229, p < 0.05), but it was not significantly affected in females. These data demonstrate that DCA treatment of both male and female rats altered the population of hepatic cytochrome P450. The results support the hypothesis that DCA increases CHCl3 metabolism, and therefore hepatotoxicity, by inducing CYP2E1.
Animals↗
Chemical stability of artesunate injection and proposal for its administration by intravenous infusion.
Artesunate, the only artemisinin analogue that can be given intravenously, produces rapid parasite and fever clearance in falciparum malaria. A significant therapeutic problem is a high, late recrudescence rate, probably due to short half-lives of both artesunate and its active metabolite dihydroartemisinin relative to conventional dosing intervals. One method of extending the duration of action of artesunate could be to administer the drug by infusion rather than bolus injection, provided that it is chemically stable at ambient temperature. Artesunate was found to be stable in 0.9% w/v sodium chloride at 9 degrees C, 23 degrees C and 36.5 degrees C for 130, 10.6 and 1.6 h, respectively. Interpolating from an Arrhenius plot, artesunate should be stable for approximately 4 h at 30 degrees C, a temperature representative of ambient conditions in tropical countries. Exposure to light did not affect the degradation rate. Single compartment pharmacokinetic modelling was used to evaluate potential differences in artesunate and dihydroartemisinin plasma concentrations following administration of artesunate by intravenous bolus or infusion. A bolus injection of artesunate at a dose of 4 mg kg-1 gives a peak concentration of 5.3 mg L-1, falling to 0.005 mg L-1 at 5 h. The same dose infused over 4 h results in a peak concentration of 0.92 mg L-1, falling to 0.005 mg L-1 at 8 h. Simultaneous modelling of dihydroartemisinin showed that while its peak plasma concentration was reduced by 27% and the peak delayed by 2.5 h following artesunate administration by infusion, substantially higher concentrations were maintained compared with those predicted after bolus artesunate. These data indicate that artesunate can be administered as a high-dose intravenous infusion, thus avoiding high plasma concentrations. This strategy also has the potential to prolong the duration of antimalarial effect and reduce toxicity, and consequently improve clinical outcome in seriously ill patients.
Antimalarials↗
A metric for assessing acuity in positioning joints and limbs.
In this paper, we present a method for assessing the exactness of sensing and setting the positions of joints and limbs, using a measure we call target resolution. Target resolution, derived from information theory but ultimately based on variance, estimates the fewest number of discrete, equally spaced targets required within a range to provide the maximum possible information transfer from any target set. We argue that target resolution provides better insight into the exactness of position sense than does the usual measure of accuracy based on mean or constant error. Studies have shown that measures of mean error in setting or indicating positions of joints or limbs exhibit lability; they drift and show considerable sensitivity to factors such as previous positions of the limb and learning. We derive the equation for calculating target resolution and give example resolutions for several joints we have tested. Target resolution often gives a quite different impression of proprioceptive exactness than do measures of accuracy based on mean error.
Extremities↗
Multifield magic-angle spinning and double-rotation nuclear magnetic resonance studies of a hydrated aluminophosphate molecular sieve: AlPO4-H2.
AlPO4-H2 is a microporous hydrated aluminophosphate, structurally related to VPI-5, whose framework has highly elliptical 10-ring channels (2.9 x 7.6 A) parallel to the c crystallographic axis. To resolve a previously reported discrepancy between nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) data a highly crystalline AlPO4-H2 has been further characterized with 27Al and 31P magic-angle spinning (MAS) NMR at 11.7 T and 27Al double-rotation (DOR) NMR at 4.7 T. These present NMR data definitively show that the true space group symmetry of the AlPO4-H2 framework structure is triclinic rather than the higher orthorhombic symmetry proposed earlier from XRD studies.
Aluminum Compounds↗
Divergent selection for blood serum insulin-like growth factor I concentration in beef cattle: I. Nongenetic effects.
Data were obtained from an ongoing experiment involving divergent selection for blood serum IGF-I concentration in purebred Angus cattle. The experiment includes approximately 100 spring-calving (50 high and 50 low line) and 100 fall-calving (50 high and 50 low line) cows. The selection criterion is the mean of IGF-I concentrations measured on each animal at d 28, 42, and 56 of the postweaning performance test. Mean IGF-I values were available for a total of 526 bull and heifer calves. Pooled across years and breeding seasons, high line progeny averaged 21 +/- 6, 17 +/- 6, and 23 +/- 5 ng/mL more IGF-I (P < .01) than low line progeny at d 28, 42, and 56 of the postweaning test. Season effects on IGF-I approached statistical significance only at d 42 and 56 of the postweaning period. Pooled across years and selection lines, spring minus fall differences were 9 +/- 10 (P = .52), -17 +/- 10 (P = .10), -22 +/- 9 (P = .07), and -9 +/- 6 (P = .45) ng/mL for IGF-I concentrations at d 28, 42, and 56 of the postweaning test and for mean IGF-I, respectively. Sex effects on serum IGF-I concentration were highly significant, with greater IGF-I expression in bulls, but were confounded with diet and location. Age of dam effects were not significant. Regressions of IGF-I concentration on on-test age of calf ranged from .46 +/- .13 to 1.08 +/- .20 ng.mL-1.d-1 and were highly significant for all measures of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
A flow sheet for follow-up after chemotherapy extravasation.
PURPOSE/OBJECTIVES: To introduce and describe the development and implementation of a flow sheet used to document patient follow-up after chemotherapy extravasation. DATA SOURCES: Published articles, institutional standards of nursing practice, and the Oncology Nursing Society Cancer Chemotherapy Guidelines. DATA SYNTHESIS: Extravasation is a potentially serious and severe complication of vesicant chemotherapy administration. A tool was designed to streamline documentation of patient symptoms, nursing interventions, patient education, and follow-up care after a suspected or actual extravasation. CONCLUSIONS: The flow sheet improves nursing documentation after a suspected or actual vesicant chemotherapy extravasation and provides a consistent, concise method for monitoring extravasations over time. IMPLICATIONS FOR NURSING PRACTICE: The flow sheet standardizes nursing assessment, intervention, patient education, and follow-up care after a suspected or actual chemotherapy extravasation. Use of the flow sheet saves time and improves consistency of nursing documentation.
Antineoplastic Agents↗
Combined conformational search and finite-difference Poisson-Boltzmann approach for flexible docking. Application to an operator mutation in the lambda repressor-operator complex.
The N-terminal domain of the phage lambda repressor binds as a dimer to its palindromic DNA operator sequence. In addition to a helix-turn-helix DNA recognition motif, the first six amino acids of the phage lambda repressor form a flexible peptide segment which wraps around DNA. Site-directed mutagenesis studies have shown that amino acid replacements or partial removal of the arm structure, or changes in the DNA sequence contacting the N-terminal arm, can lower the repressor-operator binding affinity by several orders of magnitude. The finite-difference Poisson-Boltzmann approach in combination with a conformational search procedure was used to study energetic contributions of the lambda arm to repressor-operator recognition based on the high resolution X-ray structure. It allows for the local relaxation of the structure upon changing the DNA sequence in the lambda arm binding region. A simplified potential energy function including torsional, truncated Lennard-Jones and approximate electrostatic terms is used in the initial step to screen out energetically unfavorable structures. The electrostatic energy of selected conformations is subsequently calculated more accurately using the finite-difference Poisson-Boltzmann approach. The method was applied to study the effect of a C-->T mutation at position 6 of the consensus half-site of the operator. This base-pair contacts Lys4 which is part of the arm segment. Keeping only the Lys4 side-chain mobile and with the wild-type DNA operator sequence, several conformations close to the X-ray structure were identified as those with lowest energy. In the case of the DNA mutation, lowest energy conformations differed significantly from those selected for the wild-type sequence. These initial calculations indicate that the approach might be a useful tool to estimate conformational and energetic effects upon mutagenesis of protein-DNA complexes.
Base Sequence↗
Relationship of air temperature, relative humidity, precipitation, photoperiod, wind speed and solar radiation with serum insulin-like growth factor I (IGF-I) concentration in Angus beef cattle.
Eight paternal half-sib Angus calves born in late April and early May, 1988 were used to investigate the potential relationship of serum IGF-I concentration with photoperiod and various weather variables including minimum, maximum and average air temperatures, relative humidity, precipitation, wind speed and solar radiation. To determine IGF-I concentration, blood samples were obtained at birth and then weekly until the calves reached 1 mo of age and bi-weekly thereafter. Blood sampling continued until the calves reached puberty as determined by progesterone and testosterone assays. Photoperiod and each weather variable were averaged over the 3 d prior to and including the day of blood sampling (4-d average). Data were divided into two periods: (1) birth through the end of the postweaning period and (2) postweaning period only. Serum IGF-I concentrations were analyzed using a model which included the fixed effects of sex and sample number, the random effect of calf nested within sex and the fixed interaction of sex x sample number, in addition to covariates for weight, photoperiod and weather variables. From birth through the end of the postweaning test, none of the weather variables or photoperiod had significant effects on serum IGF-I concentrations when each was fitted separately. For the postweaning period only, cubic regression coefficients for minimum and average temperatures were .0962 +/- .0325 ng/ml/degrees C3 and .0976 +/- .0272 ng/ml/degrees C3, respectively (P < .01). The quadratic regression coefficient for relative humidity during the postweaning period was -.2991 +/- .1142 ng/ml/%2 (P < .05). The quartic regression coefficient for wind speed during the postweaning period was -36.435 +/- 13.00 ng/ml/(km/hr)4 (P < .01). Maximum temperature, precipitation, solar radiation and photoperiod did not have significant effects on postweaning serum IGF-I concentrations. Based on these data, we conclude that temperature, humidity and wind speed were contributing factors to variation in serum IGF-I concentrations in postweaned beef calves.
Aging↗
Simulation of enzyme-substrate encounter with gated active sites.
We describe a brownian dynamics simulation method that allows investigation of the effects of receptor flexibility on ligand binding rates. The method is applied to the encounter of substrate, glyceraldehyde 3-phosphate, with triose phosphate isomerase, a diffusion-controlled enzyme with flexible peptide loops at its active sites. The simulations show that while the electrostatic field surrounding the enzyme steers the substrate into its active sites, the flexible loops appear to have little influence on the substrate binding rate. The dynamics of the loops may therefore have been optimized during evolution to minimize their interference with the substrate's access to the active sites. The calculated and experimental rate constants are in good agreement.
Animals↗
Chronic fatigue syndrome and a disorder resembling Sjögren's syndrome: preliminary report.
Chronic fatigue syndrome (CFS), as currently described in the working criteria proposed by the Centers for Disease Control and Prevention (Atlanta), may be associated with multiple, distinct, and possibly unique clinical and/or etiopathogenic subsets. Sjögren's syndrome (SS) is a disease of unknown etiology that is characterized by dryness of the mucous membranes and a variety of autoimmune phenomena and conditions. Subjective manifestations of SS such as neurocognitive dysfunction and fatigue have been stressed by some observers. We have detected a large number of patients with unrecognized SS-like illness in a clinical specializing in CFS and believe the relationship to be more than casual. From January 1991 through April 1992, 172 patients were evaluated for CFS; the SS cohort consisted of 27 females (mean age, 41.9 years). Sixteen of these patients had previously been found to have CFS by a physician, and 11 were self-referred. All patients complained of severe, dominating, chronic fatigue. Complaints of myalgia were prominent; 20 of 27 patients met the criteria for fibromyalgia. Neurocognitive complaints and/or a history of neuropsychiatric disease was frequent. Results of Schirmer's test were abnormal for 16 of 27, and results of minor salivary-gland biopsy were abnormal for 20 of 25. Antibodies to nuclear antigen were present in 16 of 27, but anti-Ro was present in only 1 of 21. In the SS group, 13 of 27 patients met eight or more CDC minor criteria for CFS, and 18 of 27 met six or more of the criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A microbiological study of recurrent dentinal caries.
A cross-sectional microbiological study of recurrent (secondary) dentinal caries was conducted. Freshly extracted human teeth containing amalgam restorations judged to be clinically intact were scrubbed with chlorhexidine soap and soaked in povidone-iodine solution. The teeth were then split to remove the fillings and examined for dentinal caries. Of 54 teeth examined, 22 (40%) were free of dentinal caries in the restored site. The remainder were assigned to arbitrary groups of questionable (15), initial (8) and active caries (9), based on the amount of dentinal decay observed. Comparison of pre-extraction bite-wing radiographs with the in situ findings revealed the sensitivity for secondary caries detection to be only about 50%. In contrast, the specificity for absence of caries was 73%. There was considerable variation in the numbers and types of micro-organisms found in dentine samples from lesions of comparable severity. Facultatively, anaerobic streptococci were the most numerous and most prevalent micro-organisms in the affected dentine, but no single species was significantly associated with recurrent caries. Mutans streptococci were found in 40% of sites with any degree of caries and in only 3 of the 9 sites with the most caries. Homofermentative lactobacilli were present in 18 of the 54 dentine samples, including 4 from caries-free sites. While the prevalence and numbers of lactobacilli increased with the degree of caries, they occurred in less than half of the affected dentine samples. Actinomyces occurred in 15 of 32 affected sites but only in 2 of the 9 most active sites. Their numbers never exceeded 3 x 10(3) CFU/mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Actinomyces↗
Use of real-time ultrasound to identify multiple fetuses in beef cattle.
To examine the feasibility of producing multiple births in beef cattle by means of superovulation, realtime ultrasound was used to identify cows carrying multiple fetuses. Three replicates of the superovulation experiment were conducted with groups of 52, 25 and 89 purebred Angus cows, respectively. Both uterine horns of cows from Replicate 1 were examined via the rectum using ultrasound at averages of 43 (range = 30 to 68 days), 51 (range = 38 to 76 days) and 126 (range = 113 to 151 days) days after AI. Cows in Replicate 2 were examined in the same fashion at averages of 55 and 97 days post insemination. In Replicate 3 the number of fetuses was estimated on a single date (average number of days post insemination = 49 days). Across the 3 replicates, the number of fetuses was most accurately assessed at an average of between 49 and 55 days post insemination. In most instances for which comparability between ultrasound estimations and calving results was low, the lack of correspondence was likely due to embryo mortality in cows identified as carrying multiple fetuses. For all 3 replicates combined, only 1 cow diagnosed with a single fetus produced multiple calves at birth when the diagnoses were conducted at 49 to 55 days post insemination. Real-time ultrasound can be used to accurately identify open cows and to differentiate between cows carrying single or multiple fetuses.
Journal Article↗
Gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme.
The enzyme triose phosphate isomerase has flexible peptide loops at its active sites. The loops close over these sites upon substrate binding, suggesting that the dynamics of the loops could be of mechanistic and kinetic importance. To investigate these issues, the loop motions in the dimeric enzyme were simulated by Brownian dynamics. The two loops, one on each monomer, were represented by linear chains of appropriately parameterized spheres, each sphere corresponding to an amino acid residue. The loops moved in the electrostatic field of the rest of the enzyme, which was held rigid in its crystallographically observed conformation. In the absence of substrate, the loops exhibited gating of the active site with a period of about 1 ns and occupied "closed" conformations for about half of the time. As the period of gating is much shorter than the enzyme-substrate relaxation time, the motion of the loops does not reduce the rate constant for the approach of substrate from its simple diffusion-controlled value. This suggests that the flexible loops may have evolved to create the appropriate environment for catalysis while, at the same time, minimizing the kinetic penalty for gating the active site.
Amino Acid Sequence↗
Divergent selection for postweaning feed conversion in Angus beef cattle: III. Linear body measurements of progeny.
Postweaning performance data were obtained on 401 group-fed, purebred Angus calves from 24 selected sires (12 high- and 12 low-feed-conversion sires) from 1983 through 1986 at the Northwestern Branch of the Ohio Agricultural Research and Development Center. Body measurements of progeny were taken from 1983 through 1986 for hip height and backfat, whereas others, except chest measurements (depth and width) that were available only in 1985, were taken from 183 progeny born in 1985 and 1986. The objective of this portion of the study was to determine whether differences in linear body measurements exist between progeny of high- and low-feed-conversion sires. Differences between progeny of high- and low-feed-conversion sires tended to exist (P < .10) for heart girth (176.3 +/- 1.2 vs 173.2 +/- 1.2 cm) and were significant for backfat thickness (.94 +/- .01 vs .87 +/- .02 cm). No significant differences were observed for hip height (115.3 +/- .5 vs 115.5 +/- .5 cm), chest depth (58.8 +/- .6 vs 57.4 +/- .6 cm), chest width (44.4 +/- .5 vs 44.0 +/- .5 cm), head width (21.2 +/- .2 vs 21.1 +/- .2 cm), head length (42.4 +/- .3 vs 41.6 +/- .3 cm), muzzle circumference (41.0 +/- .4 vs 41.6 +/- .3 cm), length between hooks and pins (46.7 +/- .5 vs 46.2 +/- .5 cm), length between shoulder and hooks (94.9 +/- 1.0 vs 93.1 +/- 1.0 cm), or volume (361,199 +/- 4,885 vs 352,718 +/- 5,026 cm3).
Animals↗
Address of Mary E. P. Davis. Third annual convention of the Superintendents' Society, 1896, Philadelphia, Pennsylvania.
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Boston↗
Sex differences in monochloroacetate pretreatment effects on chloroform toxicity in rats.
Previous studies have shown that dichloroacetate and trichloroacetate increase the toxicity of CHCl3. The present experiments were designed to determine if monochloroacetate (MCA) similarly affects CHCl3 toxicity. There were occasional differences, but overall kidney function indices (urine volume, osmolality and electrolyte concentration, glucosuria, retention of urea nitrogen in plasma) were not affected differently at either 24 or 48 hr after CHCl3 in saline and MCA pretreated Sprague-Dawley rats of either sex. Males pretreated with MCA had 45-fold greater plasma alanine aminotransferase (ALT) compared to the saline pretreated group similarly dosed with CHCl3. ALT was increased threefold in female rats, a modest change that suggests hepatic damage, and BUN was nonsignificantly increased. Therefore hepatic and renal functions were assessed in females. MCA pretreatment did not alter the effects of CHCl3 on hepatic excretory function or glomerular or tubular function. Bile production and glomerular filtration were both decreased in the MCA group treated with peanut oil, suggesting that MCA impairs both liver and kidney function in female rats. MCA pretreatment increases CHCl3 hepatoxicity markedly in male rats and only slightly in female rats. This difference is likely due to the different effects, in males and females, of MCA on the cytochrome P450 isoforms that activate CHCl3. The effects of MCA on renal function in females would decrease CHCl3 delivery to kidney cells, suggesting that MCA may alter the distribution of CHCl3.
Acetates↗