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Biomedical subjects

M E Davis

Publications and source records attributed to M E Davis.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Poisson-Boltzmann analysis of the lambda repressor-operator interaction.

A theoretical study of the ion atmosphere contribution to the binding free energy of the lambda repressor-operator complex is presented. The finite-difference form of the Poisson-Boltzmann equation was solved to calculate the electrostatic interaction energy of the amino-terminal domain of the lambda repressor with a 9 or 45 base pair oligonucleotide. Calculations were performed at various distances between repressor and operator as well as at different salt concentrations to determine ion atmosphere contributions to the total electrostatic interaction. Details in the distribution of charges on DNA and protein atoms had a strong influence on the calculated total interaction energies. In contrast, the calculated salt contributions are relatively insensitive to changes in the details of the charge distribution. The results indicate that the ion atmosphere contribution favors association at all protein-DNA distances studied. The theoretical number of ions released upon repressor-operator binding appears to be in reasonable agreement with experimental data.

Bacteriophage lambda↗
PubMed1992

Dichloroacetic acid and trichloroacetic acid increase chloroform toxicity.

Dichloro- and trichloroacetic acids (DCA and TCA) and chloroform are formed during chlorination disinfection of drinking water. The effects of DCA and TCA treatment on CHCl3 toxicity were assessed in these studies. Male and female rats were gavaged with DCA or TCA (0.92 and 2.45 mmol/kg administered 3 times over 24 h). Three hours after the last dose CHCl3 was injected ip (0.75 mg/kg). Male rats experienced some weight loss (15%) and slight increases of ALT and BUN, but there were no effects of either DCA or TCA on any of these responses. In females, CHCl3 increased plasma ALT and this response was greater (up to threefold) in the DCA group, compared to saline controls. Similarly, BUN was increased by CHCl3 and this was more severe (up to threefold) in both the DCA and TCA pretreated groups. These results show that CHCl3 toxicity is increased by DCA and TCA, and this effect is gender-specific, occurring only in females. DCA increases both liver and kidney toxicity, whereas TCA affects only kidney toxicity.

Alanine Transaminase↗
PubMed1991

The haemodynamic effects of bronchoscopy. Comparison of propofol and thiopentone with and without alfentanil pretreatment.

The haemodynamic response to bronchoscopy under general anaesthesia was investigated. Forty patients were allocated at random to receive either thiopentone or propofol; half the patients in each group received in addition 18 micrograms/kg of alfentanil one minute before induction of anaesthesia. The heart rate, noninvasive blood pressure and Holter ECG was monitored in all patients. Significant increases in heart rate (p less than 0.05), systolic and diastolic arterial pressures (p less than 0.01) occurred in the thiopentone only group, following bronchoscopy. Systolic and diastolic arterial pressure decreased in patients receiving thiopentone plus alfentanil, following induction of anaesthesia and laryngoscopy (p less than 0.05). No significant haemodynamic changes were seen in either of the groups which received propofol. ST segment changes on subsequent Holter analysis were seen in four patients, but there were no significant differences between the groups. Anaesthesia with propofol alone provides adequate haemodynamic stability for bronchoscopy and the addition is superfluous.

Aged↗
PubMed1991

Satellite cell activation in the stretch-enlarged anterior latissimus dorsi muscle of the adult quail.

Satellite cell activity was examined in the stretch-enlarge anterior latissimus dorsi muscle (ALD) of the adult quail. Thirty-seven birds had a weight equal to 10% of their body mass attached to one wing while the contralateral wing served as an intra-animal control. At various time intervals after application of the wing weight (from 1 to 30 days), the birds were injected with tritiated thymidine and killed 1 h later. Stretched muscle length was greater by day 1 and mass by day 3 when compared with the contralateral muscle. Satellite cells actively synthesizing DNA were quantitated in fiber segments of the control and stretched ALD. A minimum of 1,500 muscle nuclei (satellite cell nuclei and myonuclei) were counted in each muscle. Labeling in stretched muscle was expressed by the percent labeled nuclei per total nuclei counted. Satellite cell labeling was initiated by day 1, peaked between days 3 and 7, and was not statistically different from control values at day 30. These results demonstrate that satellite cells are induced to enter the cell cycle in the stretch-enlarged ALD muscle from the adult quail, and the peak of proliferative activity is within the first week of stretch.

Animals↗
PubMed1991

Somatic cell mapping and restriction fragment length polymorphism analysis of bovine insulin-like growth factor I.

The DNA isolated from cow-hamster hybrid somatic cells segregating bovine chromosomes was analyzed by Southern blotting and hybridization with a heterologous [32P]-labeled porcine cDNA probe encoding insulin-like growth factor I (IGF-I). Thirteen of 25 cow-hamster hybrid cell lines exhibited the bovine-specific IGF-I fragment. Analysis for the retention or loss of bovine IGF-I with markers previously screened against the same panel of hybrid cells revealed a 100% concordance with lactate dehydrogenase B of bovine syntenic group U3 located on bovine chromosome 5. Restriction fragment length analyses of genomic DNA from animals representing five breeds (Angus, Polled Hereford, Simmental, Gelbvieh, and Belgian Blue) and from seven half-sib Angus calves indicated that polymorphisms for the genomic composition of the bovine IGF-I gene may exist in cattle populations.

Animals↗
PubMed1991

Divergent selection for postweaning feed conversion in Angus beef cattle: I. Mean comparisons.

Each year from 1979 through 1983, 35 Angus bull calves were selected from a herd at the Eastern Ohio Resource Development Center to be individually fed in a 140-d postweaning performance test. From these 35 individually fed bulls, the three highest and three lowest for feed conversion (feed:gain) were selected and randomly mated to approximately 20 cows each. A different set of high vs low feed conversion sires was used each year. Four replicates (403 progeny) from high vs low sires were evaluated by sire groups for subsequent postweaning and carcass performance. Progeny were slaughtered when estimated by ultrasonic measurement to have 8.9 mm or more of subcutaneous fat at the conclusion of a 140-d postweaning performance test. Progeny with less than 8.9 mm of subcutaneous fat were fed for additional 28-d periods until they reached the required minimum. No differences were found between high and low feed conversion progeny for 140-d feed intake (P less than .30) although high feed conversion progeny gained .09 kg/d more weight (P less than .01) during the 140-d postweaning test. Differences tended to exist between high and low feed conversion progeny for unadjusted (P less than .15) and maintenance-adjusted (P less than .15) feed:gain ratios. Progeny of the high feed conversion group had greater subcutaneous fat (P less than .05) at the end of the 140-d postweaning test and when slaughtered (P less than .05), indicating a genetic difference for composition of BW gain between high- and low-sired progeny. However, no significant differences existed for any other carcass traits evaluated. Bulls had more desirable unadjusted (P less than .001) and maintenance-adjusted (P less than .001) feed:gain ratios than heifers with increased 140-d ADG (P less than .001) and pen feed intakes (P less than .001).

Animals↗
PubMed1991

Divergent selection for postweaning feed conversion in Angus beef cattle: II. Genetic and phenotypic correlations and realized heritability estimate.

A single generation divergent selection study, replicated four times (1983, 1984, 1985, and 1986), was conducted to assess genetic differences between progeny of high and low feed conversion sires in Angus beef cattle and to determine correlated response for weight gain (ADG140), feed intake (AVFD140), and BW (OFFTSTWT) in a time- (140-d) and fat-constant (8.9 mm) period. Realized heritability estimates for unadjusted (feed/gain; FEFF140; .26) and adjusted feed conversion (adjusted as recommended by the BIF, 1986; ADJFDEFF; .46) were obtained. The difference in heritability estimates reflects variation accounted for by adjustment for BW differences, and thus maintenance requirements, of individual progeny. Phenotypic and "pseudo" realized genetic correlations of FEFF140 with ADG140, AVFD 140, and OFFTSTWT were -.33 and -.66, .49 and -.26, and .15 and -.41, respectively. Phenotypic and "pseudo" realized genetic correlations of ADJFDEFF with ADG140, AVFD140, OFFTSTWT, and FEFF140 were -.54 and -.59, .30 and -.23, .27 and -.36, and .97 and .49, respectively. Subcutaneous fat (as estimated by ultrasonic measurement; BF140) had phenotypic and "pseudo" realized genetic correlations with FEFF140 of -.33 and .66, respectively, and with ADJFDEFF of -.44 and -.58, respectively.

Animals↗
PubMed1990

Effects of the inotrope DPI 201-106 on cardiac performance following cardiac surgery.

The haemodynamic, cardiac metabolic and electrocardiographic effects of the intravenous inotropic agent DPI 201-106, in 20 and 40 milligram doses, were studied in patients after coronary arterial bypass grafting. The patients were randomly allocated to receive placebo or DPI 201-106. Those receiving the active drug received either the 20 or the 40 milligram dosages of DPI 201-106. Both the placebo and the active drug were infused over 20 minute periods. Two baseline readings confirmed haemodynamic stability, and readings were taken immediately following the infusions and then at 20 minutes and at 40 minutes afterwards. Comparison of all the haemodynamic and metabolic data did not reveal any significant intra or inter group differences. Comparison of the electrocardiographic data revealed some differences. Patients receiving DPI 201-106 showed prolongation of the QTc interval immediately following the infusions. Changes in ST segments and T waves were observed. Independent analysis of the affected electrocardiographs reported that the changes were suggestive of, but not pathognomonic of, myocardial ischaemia. The metabolic data showed that the electrocardiographic changes were not associated with any evidence of anaerobic metabolism. The indication for DPI 201-106 as a positive inotropic agent in patients following coronary revascularization surgery was not established.

Adult↗
PubMed1990

Subacute toxicity of trichloroacetic acid in male and female rats.

Trichloroacetic acid, TCA, is a water chlorination by-product similar to dichloroacetic acid, DCA. Because DCA has been shown to have effects on intermediary metabolism, TCA was tested to determine if it possesses similar capabilities. The effects were more pronounced in females. High doses of TCA (2.45 mumol/kg three times) decreased plasma glucose and lactate concentrations and liver lactate concentration. DCA had similar, less pronounced effects. In males DCA and TCA each decreased plasma lactate concentrations. Rats were exposed to TCA in drinking water for 14 days. The highest concentration (2.38 g/l) caused decreases of water and food consumption and loss of body weight. At 7 days females had decreased urine volume accompanied by a modest increase of urine osmolality, resulting in a significant decrease of excretion of solute. Concentrations of glucose in plasma and lactate in tissues were not significantly affected by this subchronic TCA exposure. These results indicate that TCA may have effects on intermediary metabolism similar to those of DCA.

Animals↗
PubMed1990

Diacylglycerol-induced stimulation of neurotransmitter release from rat brain striatal synaptosomes.

These studies were undertaken to test the hypothesis that alterations in phosphatidylinositol metabolism can modulate neurotransmitter release in the central nervous system. The effects of 1,2-diacylglycerols (DAGs) on dopamine release in the rat central nervous system were determined by measuring dopamine release from rat striatal synaptosomes in response to two DAGs (sn-1,2-dioctanoylglycerol and 1-oleoyl-2-acetylglycerol) that can activate protein kinase C and one DAG (deoxydioctanoylglycerol) that does not activate this kinase. Dioctanoylglycerol and 1-oleoyl-2-acetylglycerol, at a concentration of 50 micrograms/ml, stimulated the release of labeled dopamine from striatal synaptosomes by 35-50 and 17%, respectively. Dioctanoylglycerol-induced release was also demonstrated for endogenous dopamine. In contrast, deoxydioctanoylglycerol (50 micrograms/ml) did not stimulate dopamine release. Dioctanoylglycerol-induced dopamine release was independent of external calcium concentration, indicating a utilization of internal calcium stores. Dioctanoylglycerol (50 micrograms/ml) also produced a 38% increase in labeled serotonin release from striatal synaptosomes. The addition of dioctanoylglycerol to the striatal supernatant fraction increased protein kinase C activity. These results are consistent with the concept that an increase in phosphatidylinositol metabolism can stimulate neurotransmitter release in the central nervous system via an increase in DAG concentration. The data suggest an involvement of protein kinase C in the DAG-induced release, but other sites for DAG action are also possible.

Animals↗
PubMed1990

Muscle fiber formation and fiber hypertrophy during the onset of stretch-overload.

The contributions of fiber hypertrophy and new fiber formation to the onset of stretch-induced muscle enlargement were evaluated in the anterior latissimus dorsi (ALD) of adult Japanese quails, because it was not known whether the mechanisms which initiate new fiber formation were dependent on first achieving significant fiber hypertrophy. A weight corresponding to 10% of the bird's body mass was attached to one wing, and eight birds were killed after each day during the first week of stretch. Muscle mass was significantly increased after 48 h of stretch; however, the elevation in nonmuscle tissue accounted for this increase. Muscle mass corrected for non-muscle tissue was significantly greater than the intra-animal control by the fourth day of stretch. Mean fiber cross-sectional area did not change during days 0-6, but cross-sectional area was 30.0 +/- 17.2% greater than the intra-animal control areas at day 7. Fiber number determined after nitric acid digestion of connective tissue was 27.1 +/- 5.8% greater than the intra-animal control at days 5-7 of stretch, but the number of fibers in the control muscles at days 5 and 6 were lower than at day 0. Thus new fiber formation was not preceded by significant fiber hypertrophy. These results fail to support a mechanism for new fiber formation which involves fiber splitting from hypertrophied myofibers during the first week of stretch.

Animals↗
PubMed1989

Alterations in the renal function of male and female rats exposed to maleic acid, dichloromaleic acid, and both compounds.

Maleic acid (MA), a known nephrotoxicant in experimental animals, and its chlorinated derivative dichloromaleic acid (DCMA) are present in urban drinking water supplies as by-products of the chlorination process. This study was designed to characterize the effects of simultaneous exposure of subtoxic doses of DCMA and MA on renal function in both sexes of the Sprague-Dawley rat. Urine was collected at 24-h intervals from rats housed individually in stainless steel metabolism cages. Subcutaneous administration of MA at a dose of 150 mg/kg had no effect on several parameters of renal function in either sex at 24 h and only modest effects at 48 h. Renal slice studies showed that treatment of both male and female rats with DCMA (300 mg/kg) reduced p-aminohippurate (PAH) accumulation at 24 h with no effect on the uptake of tetraethylammonium ion (TEA). The combination of MA + DCMA caused a depression of TEA accumulation by slices from the female. Also, changes in urinary glucose excretion and blood urea nitrogen, although additive in the male following coexposure, appeared synergistic or potentiated in the female. These results suggest an enhanced susceptibility of the female rate to the nephrotoxic action of combined exposure to MA and DCMA.

Animals↗
PubMed1989

Temperature and concentration behavior of anomalous microwave resonances in DNA.

We have calculated the expected absorption of microwave radiation in the gigaHertz frequency range by fixed-length DNA polymer molecules dissolved in saline solution. While the effects of counterions and solvent dynamics have been accounted for in detail, the features of the absorption are completely dominated by the interaction between the charged polymer and the so-called first hydration layer, that is, the nearest layer of solvent water molecules not actually bonded to the polymer. The relevant parameters of the interaction are the strength of the water-to-polymer coupling and the average persistence time of the individual water-to-polymer bonds. These are presumably hydrogen bonds to the oxygen atoms of the backbone phosphate structure. Using a given parameterization we can obtain the structured absorption corresponding to compressional wave phonon excitations on the polymer, "organ pipe" modes, such as have been claimed to be seen by Edwards, Davis, Swicord, and Saffer. While further studies have not confirmed these resonances, at some frequency and hydration these modes must become visible because of the high relaxation time measured by Lindsay, the existence of the resonances in relatively dry fibers and films of DNA, and the existence of underdamped modes in the ir spectrum of DNA in solution. We have examined the effects of varying salt concentration and the system temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA↗
PubMed1989

Mechanism of allyl formate-induced hepatotoxicity in rainbow trout.

Hepatotoxicity of allyl formate (AF) was studied in trout, to characterize the response of the teleost liver to a mammalian periportal hepatotoxicant. A dose-dependent decrease in liver nonprotein sulfhydryl (NPSH) concentration was observed at 3, 6, and 24 hr following 9.5, 28, and 95 mg/kg) AF with maximal depression seen at 6 hr (51, 40, and 29% control, respectively). Further evidence for glutathione (GSH) protection against AF toxicity was seen when diethylmaleate, a GSH depleting agent (0.6 ml/kg ip), administered 30 min prior to AF (9.5 and 28 mg/kg), increased AF hepatotoxicity (10-fold shift in the dose-response effect on SGPT). Also, N-acetyl-L-cysteine (150 mg/kg ip), a GSH precursor, protected liver against AF toxicity when injected 5 min prior to and 1, 5, and 9 hr after AF (28 and 95 mg/kg). Pyrazole (375 mg/kg ip), an alcohol dehydrogenase inhibitor, given 4 hr before AF (95 mg/kg), attenuated the histopathological effect of AF. These results indicate that AF, once bioactivated by alcohol dehydrogenase, causes significant toxicity in trout liver. GSH protects against AF-induced effects since greater than 50% decreases in liver GSH are required before toxicity is expressed.

Acetylcysteine↗
PubMed1989

Effect in the rat of the interaction of dichloromaleic acid and carbon tetrachloride on renal and hepatic function.

Water purification generates a variety of chlorinated contaminants, one of which is dichloromaleic acid (DCMA). Exposure to this compound is likely to occur in combination with other drinking water pollutants, some of which are hepatotoxic. This study was designed to examine the interactive effects of carbon tetrachloride (CCl4), a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA (200-400 mg/kg, ip) caused modest dose-dependent increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and plasma urea nitrogen, as well as a marked depletion of nonprotein sulfhydryls (NPSH) in the liver, but not the kidney, by 24 hr. Pretreatment with inducers (phenobarbital or 3-methylcholanthrene) or an inhibitor (SKF 525A) of cytochrome P-450 activity failed to alter the response observed with DCMA alone. Alterations in 24-hr urine volume, osmolality, and water consumption also were observed. DCMA-mediated changes in plasma urea nitrogen and NPSH were reduced in magnitude with coadministration of CCl4 (1 ml/kg, ip), while anticipated CCl4-induced increases in ALT and AST were reduced with coexposure to DCMA. Renal slice experiments indicated that DCMA-treated rats were less able to accumulate the organic anion p-aminohippurate (PAH), whereas DCMA had no effect on accumulation of the organic cation tetraethylammonium (TEA). The combination of CCl4 and DCMA produced only additive effects on organic ion accumulation. These results suggest hepatic interaction possibly related to the metabolism of CCl4 and DCMA, resulting in renal and hepatic toxicity diminished from that observed with exposure to either agent alone.

Animals↗