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J A Moore

Publications and source records attributed to J A Moore.

At least 91 records · Page 5Linked to original sources
PubMed1992

Synthesis and anticonvulsant activity of enaminones.

A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

Amines↗
PubMed1992

Nuclear DNA content and nucleation patterns in rat cardiac myocytes from different models of cardiac hypertrophy.

Nuclear DNA content and number of nuclei were examined in cardiac myocytes isolated from controls and rats with volume and pressure overload hypertrophy to determine if haemodynamic overload alters these nuclear parameters. The experimental groups were comprised of normotensive (WKY) and Spontaneously Hypertensive rats (SHR). Additionally, Sprague-Dawley rats with aortic constriction (AC), pulmonary stenosis (PS), myocardial infarction (MI), and 5 month arteriovenous fistulas (F) were studied along with appropriate shams for each of these groups. Nuclear DNA content was measured from DAPI-stained nuclei using an image analysis microdensitometry system. Myocyte volume was measured with a Coulter Channelyzer system. Approximately 83% of the left ventricular myocytes from the SHR and WKY groups contained a diploid DNA content with the remainder being tetraploid. The remaining experimental and sham groups, all female Sprague-Dawley rats (SD), were approximately 93% diploid. The nucleation patterns differed slightly between rat strains with the SHR/WKY expressing approximately 85% binucleation, 14% mononucleation and 5% tri- or tetranucleation. All SD groups, control and hypertrophied, showed approximately 89% binucleation, and 10% mononucleation with the remainder being tri- or tetranucleated. In summary: (1) cardiac myocytes from SHR/WKY strains are predominantly diploid but to a lesser degree than myocytes from SD; (2) nuclear number follows the same pattern with SHR/WKY showing a smaller percentage of binucleated myocytes than SD myocytes; (3) neither the duration, severity, or type of overload caused a significant change in the extent of polyploidy in overloaded hearts from SD rats; and (4) the extent of polyploidy in cardiac myocytes from both the right and left ventricles of SHR and WKY animals does not differ statistically.

Animals↗
PubMed1992

Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy.

BACKGROUND: Chronic ischemic heart disease may lead to ventricular dilation and congestive heart failure (ischemic cardiomyopathy [ICM]). The changes in cardiac myocyte shape associated with this dilation, however, are not known. METHODS AND RESULTS: Left ventricular myocyte dimensions were assessed in cells isolated from explanted human hearts obtained from patients with ICM (n = 6) who were undergoing heart transplantation. Cells were also examined from three nonfailing donor hearts with normal coronary arteries (NCA). Compared with cells from patients with NCA, myocyte length was 40% longer in hearts from patients with ICM (197 +/- 8 versus 141 +/- 9 microns, p less than 0.01), cell width was not significantly different, and cell length/width ratio was 49% greater (11.2 +/- 0.9 versus 7.5 +/- 0.6, p less than 0.01). Sarcomere length was the same in myocytes from both groups. The extent of myocyte lengthening is comparable to the increase in end-diastolic diameter commonly reported in patients with ICM. CONCLUSIONS: These data suggest that increased myocyte length (an intracellular event), instead of myocyte slippage (an extracellular event), is largely responsible for the chamber dilation in ICM. Furthermore, maladaptive remodeling of myocyte shape (e.g., increased myocyte length/width ratio) may contribute to the elevated wall stress (e.g., increased chamber radius/wall thickness) in ICM.

Animals↗
PubMed1992

Influence of model and marker on digesta kinetic estimates for sheep.

Several models and markers are available for digesta kinetic studies. In this study, kinetic estimates derived from chromium-mordanted hay or pellets were compared to estimates derived from rare earth markers (Yb, Dy, or Er) applied individually to samples. Twelve yearling rams (52 kg) were given ad libitum access to either hay or a commercial pelleted diet in a crossover experiment. Digesta kinetic estimates were obtained both by nonlinear analysis with two age-independent rates (G1G1) or with gamma time dependency in the fast compartment (G2G1 to G4G1) and by linear regression of natural log transformed fecal marker concentrations (LN method of estimate). Model did not influence total tract (P > .21) or ruminal mean retention times (P > .87). Partitioning of total retention time was similar (P > .21) for the LN, G3G1, and G4G1 models, but the G1G1 and G2G1 models did not adequately fit these data. Nonlinear models overestimated, and LN underestimated, fecal DM output by 9% (SEM = 4.7) for the hay diet. All the nonlinear models provided fecal DM output estimates that were within 5% of actual fecal DM output, but the LN model underestimated it by 18% (SEM = 3.3) for the pelleted diet. Ruminal outflow rate was slower (P < .01) and both ruminal and total mean retention time estimates were longer (P < .01) for Cr than for the rare earths. Despite the marker chosen, relative diet effects were similar. The three rare earth markers gave identical results for digesta kinetic estimates, indicating that they are useful for simultaneous study of more than one ingredient or particle, but direct comparison of rare earth and Cr-mordant passage rates is not advisable.

Animal Feed↗
PubMed1991

Results of prenatal alcohol exposure on the dimensions and binucleation of cardiac myocytes in neonatal and weanling rats.

Sprague-Dawley rats were exposed to ethyl alcohol in utero. The effect of chronic prenatal exposure was examined by giving mature females alcohol in isocaloric liquid diets which served as the sole source of liquid and caloric intake before mating and throughout gestation. Controls consisted of females maintained on laboratory chow or an isocaloric liquid diet minus alcohol before and during gestation. The offspring were sacrificed at 21 days of age (weanlings) and the hearts dissociated enzymatically to give purified cardiac myocytes. The effects of daily acute prenatal alcohol exposure were studied by gastric intubation of alcohol to chow-fed females for the duration of pregnancy. The doses used approximated 4 and 5 shots of 80 proof liquor per day by a person weighing 150 lb. These offspring were sacrificed at 2, 6, and 21 days postnatal and cardiac myocytes prepared as above. Heart weights were determined and cardiac myocytes were analyzed for cell length, volume, cross-sectional area, and percent binucleation. Additionally, nuclear DNA content was measured in all of the 21 day offspring. Statistical analysis of the data showed no significant differences between hearts exposed to prenatal alcohol and nonexposed controls with either regimen with the exception of percent binucleation which was significantly but only slightly higher in the 6-day-old hearts. These findings are discussed in relation to anatomical heart defects found in patients with full fetal alcohol syndrome.

Aging↗
PubMed1991

Regional increase in isolated myocyte volume in chronic myocardial infarction in cats.

Healing of myocardial infarction is associated with hypertrophy of a region surrounding the scar. In order to characterize the pattern of regional hypertrophy after healing of small myocardial infarctions, we used a Coulter Channelyzer to measure directly regional cell volume and light microscopy to measure cell length of isolated myocytes. Acute left ventricular myocardial infarctions were surgically created in adult cat hearts. After healing for 10.4 +/- 5.0 months, cells were dissociated by collagenase perfusion. Myocardial cells were isolated from three regions of the infarcted ventricle and the same three anatomical regions of unoperated control hearts: (1) remote from the infarct, (2) non-scarred tissues adjacent to the infarct, and (3) from the infarct. The volume of cells from control hearts was correlated significantly with individual body weight resulting in large inter-animal variations, but small intra-animal variations. Inter-animal comparisons were made by normalizing adjacent and infarct regions to percent change from its remote region. Myocyte volumes from hearts with healed infarcts were increased by 31% in the infarct region and by 20% in the adjacent region, relative to the corresponding regions from control hearts (P less than 0.05). Cell lengths were not different from control in any region. Calculated cross-sectional areas followed the same pattern as was observed for cell volumes. We conclude that there is a region of hypertrophy surrounding a small, transmural healed myocardial infarction that is characterized by increased myocyte cross sectional area with no change in cell length. This pattern is typical of the concentric hypertrophy observed with pressure overload rather than eccentric hypertrophy observed with volume overload.

Analysis of Variance↗
PubMed1991

Nuclear size and DNA content in rat cardiac myocytes during growth, maturation and aging.

Changes in nuclear volume and DNA content were examined in cardiac myocytes isolated from 21-day-old (weanling, W), 3-month-old (adult, A), and 2-year-old (old, O) rats to document normal parameters for nuclear growth and DNA content. Nuclear volume was calculated from direct measurements of isolated myocyte nuclear profiles and DNA content was measured from DAPI-stained nuclei using an image analysis microdensitometry system. Myocyte volume was measured with a Coulter Channelyzer system. Nuclear volume increased 79% from W to A as a result of an increase in nuclear length. Nuclear width was unchanged. Nuclear volume was not changed from A to O. Approximately 98% of the left ventricular myocytes from all three rat groups contained a diploid DNA content with the remainder of nuclei being tetraploid. The degree of polyploidy increased slightly, but significantly, in right ventricular myocytes from O. Due to the substantially greater increase in myocyte volume relative to nuclear volume, nuclear volume percentage decreased from 3.65 +/- 0.28 to 1.64 +/- 0.13 from W to A but was unchanged from A to O. To summarize: (1) nuclear volume of rat cardiac myocytes increases significantly during normal physiological growth (W to A) but the rate of nuclear growth is less than that of cell volume; (2) the increase in nuclear size from W to A is not due to an increase in DNA content; (3) cardiac myocytes from Sprague-Dawley rats are predominantly diploid; and (4) there is little change in DNA content of cardiac myocytes from rats of this strain during growth, maturation and aging.

Aging↗
PubMed1991

Surface transport of microorganisms by water.

Several studies have reported on the quality of runoff from land that has received either an application of livestock waste or been utilized as a pasture for livestock. Unfortunately, these studies have not directed their efforts to understanding and developing the relationships among several of the important parameters that influence runoff quality. One of the reasons for this deficiency is that the list of influencing parameters is quite long. Nevertheless, it is important to identify the parameters and their probable impact on movement of organisms in water. The microbiological aspects are influenced by the fate of organisms in the environment. Radiant energy (sunlight), temperature, available nutrients, presence of toxic materials, available moisture (precipitation and humidity), and soil pH all influence the death/growth rate of the organisms in question. Site characteristics, such as slope, vegetative cover, antecedent moisture content, soil type, organic matter content, infiltration rate, and surface condition of the soil, all influence microorganism movement. Hydrologic factors, such as frequency, duration, and intensity of rainfall, are very critical in determining the characteristics of runoff events that provide the transportation to move introduced organisms from their application site. There are very few models today that can be used to calculate the microorganism population in runoff. While many of the influencing parameters have been identified, there has been little research on the surface transport of microorganisms.

Animals↗
PubMed1991

Synthesis and anticonvulsant activity of imidooxy derivatives.

Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4,4] nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of greater than 4.5.

Animals↗
PubMed1991

Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins.

The clearance and volume of distribution of five human proteins (recombinant CD4, CD4 immunoglobulin G, growth hormone, tissue-plasminogen activator, and relaxin) in humans and laboratory animals were analyzed as a function of body weight using allometric scaling techniques. These proteins cover a 16-fold range of molecular weight (6 to 98 kD), are produced by recombinant or synthetic methods, and may be cleared by different mechanisms. The analyses revealed that the clearance and volume data for each protein were satisfactorily described by an allometric equation (Y = a Wb). The allometric exponent (b) for clearance (ml/min) ranged from 0.65 to 0.84, the allometric exponent for the initial volume of distribution (ml) ranged from 0.83 to 1.05, and the allometric exponent for the volume of distribution at steady state (ml) ranged from 0.84 to 1.02. Exponent values from 0.6 to 0.8 for clearance and 0.8 to 1.0 for volumes are frequently cited for small molecules and are expected based on empirical interspecies relationships. When the preclinical data were analyzed separately, the preclinical allometric relationships were usually predictive of the human results. These findings indicate that the clearance and volume of distribution of select biomacromolecules follow well-defined, size-related physiologic relationships, and preclinical pharmacokinetic studies provide reasonable estimates of human disposition. Employing this methodology during the early phases of drug development may provide a more rational basis for dose selection in the clinical environment.

Animals↗
PubMed1991

The morphology and electrical geometry of rat jaw-elevator motoneurones.

1. The aim of this work was to quantify both the morphology and electrical geometry of the dendritic trees of jaw-elevator motoneurones. To do this we have made intracellular recordings from identified motoneurones in anaesthetized rats, determined their membrane properties and then filled them with horseradish peroxidase by ionophoretic ejection. Four neurones were subsequently fully reconstructed and the lengths and diameters of all the dendritic segments measured. 2. The mean soma diameter was 25 microns and values of mean dendritic length for individual cells ranged from 514 to 773 microns. Dendrites branched on average 9.1 times to produce 10.2 end-terminations. Dendritic segments could be represented as constant diameter cylinders between branch points. Values of dendritic surface area ranged from 1.08 to 2.52 x 10(5) microns 2 and values of dendritic to total surface area from 98 to 99%. 3. At branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was exactly 1.0. Therefore the individual branch points could be collapsed into a single cylinder. Furthermore for an individual dendrite the diameter of this cylinder remained constant with increasing electrical distance from the soma. Thus individual dendrites can be represented electrically as cylinders of constant diameter. 4. However dendrites of a given neurone terminated at different electrical distances from the soma. The equivalent-cylinder diameter of the combined dendritic tree remained constant over the proximal half and then showed a pronounced reduction over the distal half. The reduction in equivalent diameter could be ascribed to the termination of dendrites at differing electrical distances from the soma. Therefore the complete dendritic tree of these motoneurones is best represented as a cylinder over the proximal half of their electrical length but as a cone over the distal half.

Animals↗
PubMed1991

Adrenergic modulation of preoperative anxiety: a comparison of temazepam, clonidine, and timolol.

To assess the influence of adrenergic modulation on preoperative anxiety, we used a randomized, double-blind, placebo-controlled trial to compare temazepam, clonidine, and timolol as preanesthetic medications in patients undergoing minor orthopedic surgery. All the active treatments resulted in less preoperative anxiety than the placebo (control) did. Induction of anesthesia was smoother in all the treated patients compared with the control group. Recovery was slowest in the temazepam and clonidine groups, but there were no significant differences between the groups after 90 min. Cardiovascular changes were most marked in the timolol group. Pain scores were lower in the temazepam and clonidine series in the early postoperative period. Neither clonidine nor timolol offers any major advantage over temazepam for premedication in these patients.

Adult↗
PubMed1991

Influence of passage model, sampling site, and marker dosing time on passage of rare earth-labeled grain through Holstein cows.

Three duodenally cannulated, lactating Holstein cows were dosed with rare earth-labeled grain to evaluate effects of passage model, sampling site, and marker dosing time on digesta passage parameters. Cows were given ad libitum access to feed twice daily. Rare earth-labeled grain (applied by the 24-h immersion technique) was fed immediately before (Dy) or 2 h after (Yb) the morning feeding, and duodenal digesta and feces were sampled. Marker excretion curves were fit to a two-compartment, biexponential model, using curve peeling or to a series of two-compartment models, with one to six orders of gamma time-dependency in the fast compartment, using nonlinear regression. Passage estimates from the curve-peeled, biexponential model were similar to those from the best fit of the nonlinear models, which had three orders of gamma time-dependency. Ruminal passage rate of grain, averaged across models, sampling site, and dosing time, was .077/h. Estimates of time to first appearance of marker at the sampling site and mean retention times were longer (8 vs 1 h and 25 vs 17 h, respectively), but passage rates were similar, when determined from fecal compared with duodenal samples (P less than .05). Marker dosing time did not influence any of the parameters. It is concluded that both curve-peeling (linear regression) and nonlinear regression methods can be equally useful for evaluating passage kinetics of grain in dairy cows and that sampling site and time of marker dosing have little effect on passage parameter estimates.

Animal Feed↗
PubMed1991

Wheat straw or alfalfa hay in diets with 30% neutral detergent fiber for lactating Holstein cows.

Twenty-four Holstein cows near peak lactation were fed diets formulated to contain 30% NDF with forage NDF from chopped wheat straw or chopped alfalfa hay in proportions of 0:3, 1:2, 2:1, and 3:0 in an 8-wk trial to evaluate effects of fiber source on lactational performance. Concentrate was based on highly degradable carbohydrate in steam-flaked sorghum grain. Forage to concentrate ratio decreased from 49:51 to 28:72 when straw was substituted for alfalfa hay. Milk yield (38.4 kg/d) and DMI (23.1 kg/d) were not influenced by forage source. Milk fat percentage decreased and milk protein percentage increased linearly with increasing straw. Yields of 3.5% FCM and fat showed linear and quadratic responses, because they appeared to be reduced only on the 0:3 diet, and protein yield showed a quadratic response and was highest for the 1:2 diet. Digestibility of NDF averaged 43.5, 45.4, 40.7, and 31.2%, and acetate to propionate ratio was 3.0, 2.4, 2.2, and 1.9 with increasing dietary straw. Passage rates were not influenced by diet and averaged 9.3, 7.6, 6.1, and 4.7%/h for fluid, grain, alfalfa hay, and wheat straw, respectively. It is suggested that the ratio of forage NDF to ruminally degradable starch be maintained greater than or equal to 1:1 when diets based on low quality forage are fed to cows in early lactation.

Animal Feed↗
PubMed1991

Comparison of polymerase chain reaction, DNA hybridization, and histology with viral culture to detect cytomegalovirus in immunosuppressed patients.

Formalin-fixed, paraffin-embedded lung tissue from 34 autopsies and eight open-lung biopsies of bone marrow transplant recipients was analyzed for cytomegalovirus (CMV) infection. The cases were studied by the polymerase chain reaction (PCR), in situ DNA hybridization, and histologic examination. The results were compared with viral culture for CMV taken at the time of biopsy or autopsy. In the autopsy series, hybridization and histology identified CMV in 15% of the cases, whereas PCR detected CMV in 24% of the cases. In the open-lung biopsy cases, both PCR and hybridization were found to be equivalent to culture in detecting CMV. Histology was less sensitive, with the molecular biology methods detecting CMV in 50% of the lung biopsies while histologic examination identified only 25%. Specificity was high (100%) since CMV was not detected in any culture-negative case by either PCR or hybridization. However, PCR, hybridization, and histology failed to identify CMV in three known culture-positive autopsy cases. Overall, PCR and hybridization were found to be more sensitive than histology, and PCR was more sensitive than hybridization for the detection of CMV. The advantage of high sensitivity and specificity combined with more rapid diagnosis (24 to 48 h) compared with viral culture (average, 16 days in this study) makes the molecular biology methods useful adjuncts to histology for detection of CMV in formalin-fixed, paraffin-embedded tissue.

Autopsy↗
PubMed1991

Respiratory and enteric cryptosporidiosis in humans.

A 24-year-old homosexual man with acquired immunodeficiency syndrome presented with intractable diarrhea and fever. Examination of a rectal biopsy specimen and stool revealed Cryptosporidium. Approximately 4 months after admission he developed respiratory failure and died. Postmortem examination revealed cryptosporidiosis involving the entire gastrointestinal tract as well as the tracheobronchial tree. To our knowledge, this is one of the rare presented cases of tracheobronchial cryptosporidiosis documented histologically.

Acquired Immunodeficiency Syndrome↗