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Biomedical subjects

J A Jackson

Publications and source records attributed to J A Jackson.

At least 145 records · Page 8Linked to original sources

Measurements of left-to-right intracardiac shunting in adults: oximetric versus indicator dilution techniques.

Of the various techniques that are available to assess the presence and magnitude of intracardiac shunting, oximetry and indicator dilution are used most frequently. This study was performed to compare these methods in adult patients with pure left-to-right intracardiac shunting. In 27 patients [12 men, 15 women, aged 32 +/- 12 (mean +/- SD) years], shunt magnitude was assessed in close temporal proximity by both techniques. The oximetric percentage left-to-right shunt averaged 55 +/- 16%, whereas the indocyanine green dye percentage shunt was significantly less (36 +/- 14%, p less than 0.001). The oximetric percentage shunt exceeded the indocyanine green dye percentage shunt in 26 and did so by greater than 20% in 23 patients. Thus, there is a substantial difference in shunt magnitude between the oximetric and the indicator dilution techniques. In infants, indicator dilution yields results that are larger than those obtained with the oximetric method. Conversely, in adults, the indicator dilution technique gives results that are consistently smaller than those obtained with oximetry. As a result, the decision regarding therapy of an intracardiac shunt should be made with this in mind.

Adolescent↗

Improvements in the clinical utility of calculated T2 images of the human brain.

Magnetic Resonance Imaging (MRI) affords a considerable improvement in image contrast over other methods by virtue of the intrinsic NMR parameters spin density, T1, and T2. However, the clinical utility of routine quantification of these parameters is currently unknown. Calculated T2 images might afford additional disease specific information provided the calculation algorithm generates accurate T2 values. In this study, calculated T2 images of a MnCl2 phantom (spanning a T2 range of interest of 45.7 ms to 346.6 ms at 6 MHz) were generated utilizing a variety of calculation algorithms based upon a data set of 32 sequential spin-echo (SE) images. In general, when utilizing only the earliest sequential SE after the 90 degree pulse for the T2 calculation, the greater the number of SE used in the calculation algorithm, regardless of how they were averaged, the more accurate and less noisy was the calculated image. When only limited numbers of SE were used in the calculation algorithm, accuracy and noise varied with the choice of TE suggesting that there may be optimal timings for TE for a particular T2 range of interest. Forty-two calculated T2 head images of normal subjects, based upon data sets of 16 sequential SE, were evaluated for the T2 values of normal brain. These were compared to T2 images calculated via 7 different algorithms based upon 16 SE data sets from two patients with CNS pathology. An optimal algorithm was identified in which 16 SE Carr-Purcell-Meiboom-Gill (CPMG) were averaged into two images for the T2 calculation. With this algorithm, calculated images could be generated efficiently which were accurate and relatively noise free. The availability of such images maximized whatever disease specificity, and thus clinical utility, T2 information affords.

Brain↗

Meiotic recombination between duplicated genetic elements in Saccharomyces cerevisiae.

We have studied the meiotic recombination behavior of strains carrying two types of duplications of an 18.6-kilobase HIS4 Bam HI fragment. The first type is a direct duplication of the HIS4 Bam HI fragment in which the repeated sequences are separated by Escherichia coli plasmid sequences. The second type, a tandem duplication, has no sequences intervening between the repeated yeast DNA. The HIS4 genes in each region were marked genetically so that recombination events between the duplicated segments could be identified. Meiotic progeny of the strains carrying the duplication were analyzed genetically and biochemically to determine the types of recombination events that had occurred. Analysis of the direct vs. tandem duplication suggests that the E. coli plasmid sequences are recombinogenic in yeast when homozygous. In both types of duplications recombination between the duplicated HIS4 regions occurs at high frequency and involves predominantly interchromosomal reciprocal exchanges (equal and unequal crossovers). The striking observation is that intrachromosomal reciprocal recombination is very rare in comparison with interchromosomal reciprocal recombination. However, intrachromosomal gene conversion occurs at about the same frequency as interchromosomal gene conversion. Reciprocal recombination events between regions on the same chromatid are the most infrequent exchanges. These data suggest that intrachromosomal reciprocal exchanges are suppressed.

Chromosomes↗

The development of placental androstenedione and testosterone production and their utilization by the ovary for aromatization to estrogen during rat pregnancy.

During rat pregnancy the placenta may provide androgens as a source of precursor for estradiol (E2) formation by the ovary. However, the relative importance of testosterone (T) and delta 4-androstenedione (delta 4 A) for ovarian E2 production is unknown. The present study therefore determined the ability of the rat placenta to convert [3H] pregnenolone (P5) substrate to [3H] delta 4 A and [3H] T, and to [3H] progesterone (P4) in vitro on Days 12, 14, 16 and 18 of gestation. The placental formation of delta 4 A and T was correlated with the uterine vein and peripheral sera concentrations of both androgens, and with their ability to be aromatized to E2 in vitro by the ovary. Placental androgen formation from P5 increased and formation of P4 decreased with advancing gestation, with the formation of delta 4 A being approximately 2- to 4-fold greater (P less than 0.01) than the formation of T on Days 12 to 16 of gestation. The conversion of P5 to delta 4 A increased (P less than 0.001) from 18 +/- 0.9 (mean percent conversion +/- SEM) on Day 12 to 53 +/- 3 and 57 +/- 4 on Days 14 and 16, respectively, then decreased (P less than 0.05) to 42 +/- 2 on Day 18. The uterine vein and peripheral sera concentrations of delta 4 A were 2- and 3-fold greater (P less than 0.05-0.001) than T, respectively, on Days 12 to 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

"Peripheral-type" binding sites for benzodiazepines in brain: relationship to the convulsant actions of Ro 5-4864.

Previous studies have shown that Ro 5-4864 is a potent convulsant and increases the firing rate of substantia nigra zona reticulata neurons. The pharmacologic profile of compounds that antagonize these actions suggested that the effects of Ro 5-4864 were not mediated by "brain-type" benzodiazepine receptors. We examined a number of compounds that are structurally related to Ro 5-4864 for their capacities to displace [3H]Ro 5-4864 from "peripheral-type" binding sites and their potencies as convulsants (or as antagonists of Ro 5-4864-induced convulsions). It was observed that compounds such as KW 3600 (the N-desmethyl analog of Ro 5-4864), which have very low affinities for "peripheral-type" sites, are convulsants with a potency nearly equal to that of Ro 5-4864. In contrast, compounds such as Ro 5-6900 and PK 11195, which bind with very high affinities to "peripheral-type" binding sites, are neither convulsants nor do they antagonize the convulsant actions of Ro 5-4864. Within a series of compounds that are structurally related to Ro 5-4864 there is a good correlation (r = 0.93; p less than 0.01) between their potencies as convulsants and their capacities to displace [35S]t-butylbicyclophosphorothionate from sites that may be associated with the chloride ionophore. Thus, it appears that occupation of "peripheral-type" binding sites by high-affinity ligands may not be directly involved in the convulsant actions of Ro 5-4864 and related compounds.

Animals↗

Characterization of barbiturate-stimulated chloride efflux from rat brain synaptoneurosomes.

Membrane chloride (Cl-) permeability was studied in a novel subcellular brain preparation, the synaptoneurosome. Using a radioactive tracer exchange technique, Cl- transport was determined by measuring 36Cl- efflux from rat cerebral cortical synaptoneurosomes. Barbiturates increased 36Cl- efflux in a dose-dependent manner with the following relative order of potency: 5-(1,3-dimethylbutyl)-5-ethyl barbituric acid ((-)-DMBB) greater than pentobarbital greater than secobarbital greater than (+)-DMBB greater than hexobarbital greater than amobarbital greater than mephobarbital. Phenobarbital and barbital were virtually inactive. A good correlation was observed between the potencies of these barbiturates in stimulating 36Cl- efflux and their anesthetic potencies in mice (r = 0.90, p less than 0.01) and their abilities to enhance [3H] diazepam binding to brain membranes (r = 0.77, p less than 0.05). The effect of pentobarbital in enhancing 36Cl- efflux was reversed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline. Picrotoxin and bicuculline both decreased 36Cl- efflux in the absence of pentobarbital, suggesting the presence of endogenous GABA. Incubation of synaptoneurosomes with 4,4'-di-isothiocyano- or dinitro-2,2'-disulfonic acid stilbene, inhibitors of anion transport, also decreased both basal and pentobarbital-induced 36Cl- efflux. Pentobarbital (500 microM) was most effective in inducing 36Cl- efflux in the cerebellum, hippocampus, and cortex (23.7, 23.6, and 22.5%, respectively), and was less effective in stimulating 36Cl- efflux in the striatum (15.1%) and pons-medulla (6.2%). The relative efficacy of pentobarbital in enhancing 36Cl- efflux among these various brain regions was highly correlated (r = 0.96, p 0.01) with the relative densities of [35S]-t-butylbicyclophosphorothionate-binding sites, a measure of GABA-gated Cl- channel density.(ABSTRACT TRUNCATED AT 250 WORDS)

Amobarbital↗

Mechanism of nitroglycerin-induced coronary dilatation: lack of relation to intracoronary thromboxane concentrations.

Intracoronary nitroglycerin (NTG) increases coronary blood flow and NTG inhibits thromboxane (Tx) A2 production and release. However, whether an alteration in TxA2 is the mechanism by which NTG increases coronary blood flow is not known. Coronary sinus (CS) blood flow (BF) (by thermodilution) and the concentration of TxB2 (the stable metabolite of TxA2) in CS blood were measured in 23 patients (16 men and 7 women, aged 26 to 65 years) with coronary artery disease before, during and after injection of normal saline solution (n = 5, control subjects) or NTG, 100 micrograms (n = 18), into the left coronary artery. In the 5 control subjects, saline solution caused no change in CSBF or the concentration of TxB2 in CS blood. Ten of the 18 patients to whom NTG was given had received no cyclooxygenase inhibitors for 10 days. In these patients, NTG caused a marked increase in CSBF (from 112 +/- 64 to 152 +/- 70 ml/min, p less than 0.01) but no consistent change in the concentration of TxB2 in CS blood (141 +/- 132 to 160 +/- 155 pg/ml, difference not significant [NS]). The remaining 8 patients to whom NTG was given received aspirin before the study. In these patients, NTG caused a marked increase in CSBF (from 111 +/- 39 to 180 +/- 63 ml/min, p less than 0.01), even though the concentration of TxB2 in CS blood (8 +/- 10 to 6 +/- 6 pg/ml, NS) was lower (p less than 0.05) than that in control subjects and patients not receiving aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nuclear magnetic resonance diagnosis of an anaplastic astrocytoma.

A patient presented with an 8-month history of a progressive left homonymous visual field deficit, left hemiparesis, and a left thalamocortical sensory deficit that was not detectable by repeated conventional neurodiagnostic evaluations. Proton nuclear magnetic resonance (NMR) imaging revealed a right parietal lesion characterized by a prolonged T2 (spin-spin relaxation time). At surgery, the mass proved to be an anaplastic astrocytoma. NMR appears to be more sensitive than x-ray computerized tomography scanning in some patients with malignant gliomas and offers the clinician an additional probe with which to evaluate these patients.

Astrocytoma↗

Toxic factors in tall fescue.

Tall fescue ( Festuca arundinacea Schreb .), a well adapted perennial grass grown in the transition zone of the U.S., frequently produces toxic symptoms and(or) reduced animal performance. Specific syndromes associated with tall fescue include fescue foot, summer syndrome and fat necrosis. Summer syndrome is related to high environmental temperatures rather than an increase of toxic compound(s) during the summer months. Recent studies have related the summer syndrome to the presence of an endophytic fungus. The fungus has been identified as Epichlo ë typhina or Acremonium coenophialum Morgan-Jones and Gams by different research groups. Only one fungus is probably involved and it is only the identification that is questioned. The toxic compound(s) involved in fescue toxicity syndromes has not been identified, however, several alkaloids have been associated with depressed animal performance. Other evidence indicates that compounds other than alkaloids may be involved. The depressed prolactin levels associated with fescue toxicosis may provide a technique to aid in the identification of the toxic compound. The development of an enzyme-linked immunosorbant assay for the detection of the fungus should prove an effective tool to identify and thus select fungus free tall fescue seed.

Animal Feed↗

Summer fescue toxicity in dairy steers fed tall fescue seed.

Seeds of the tall fescue ( Festuca arundinacea Schreb .) cultivars Kentucky 31 and an experimental ryegrass X tall fescue hybrid derivative strain (G1-307), and orchard grass (OG) seed were fed in a carrier diet to calves in controlled environmental rooms (31 to 32 C). Both tall fescue varieties produced symptoms of summer toxicosis in dairy steers. Total feed intake (P less than .01) and water intake (P less than .01) of calves were reduced by the tall fescue seed diets when compared with orchard grass. Steers fed G1-307 and Kentucky 31 tall fescue lost (NS) 17.5 and 7.8 kg of body weight, respectively, while those consuming orchard grass gained (P less than .01) 6.2 kg during the experiment. Rectal temperatures were lower (P less than .05) in the calves fed OG (39.4 C) when compared with those fed G1-307 (40.6 C) and Kentucky 31 (40.8 C) tall fescue seed, respectively. In a second trial Kentucky 31 seed was fed in a carrier diet to Holstein steers at graded levels of 0, 350, 700 and 1,050 g seed/d. Consumption of 700 and 1,050 g seed/d adversely affected performance of steers. Total feed intake was lower and water intake was reduced (P less than .05), with rectal temperatures being elevated (P less than .01) in these two groups when compared with 0- or 350-g treatments. No significant differences were detected in body weight changes in this trial. Respiration rates were not significantly affected in either trial. Results of these trials with the young bovine indicate that a toxic substance(s) is present in tall fescue seed.

Alkaloids↗

Loline alkaloids in tall fescue hay and seed and their relationship to summer fescue toxicosis in cattle.

In three trials, young Holstein steers housed in restraint type crates in a controlled environment room were fed tall fescue hay or seed diets to determine the ability of the diets to produce signs of summer syndrome. Trial 1 examined the effects of dehydration and extended storage of G1-307 fescue compared to alfalfa on dairy steers. Calves fed G1-307 fescue had lower daily feed intake, higher rectal temperatures and respiration rates, and lost 13.4 kg more body weight during the experimental period as compared to those fed alfalfa hay. In trial 2, benomyl (a systemic fungicide) was used to eliminate the fungus Epichloe typhina from treated G1-307 fescue plants. Steers fed the treated G1-307 fescue progeny had higher daily intakes, lower rectal temperature, lower respiration rates, and lost less body weight over the trial period as compared with those fed untreated G1-307 fescue. Kenhy tall fescue seeds with and without analyzable N-acetyl and N-formyl loline alkaloids and a control diet were fed in trial 3. Steers fed the seed with the loline alkaloids had reduced intake, higher rectal temperatures, and lost 10.9 kg more body weight over the trial period than steers fed seed that did not contain loline alkaloids.

Animal Feed↗

New instrumentation in urinalysis.

Automated instrumentation and electronic data processing now assist in performing and standardizing urinalyses. These innovations include specific gravity instruments and reagent "strip readers," and one system designed to automate the physical, chemical, and microscopic urinalysis. In this article, the author reviews the features of some examples of these new instruments.

Autoanalysis↗

Evaluation of free radical effects and catecholamine alterations in adriamycin cardiotoxicity.

With the goal of evaluating the potential roles of free radicals and catecholamines in the pathogenesis of acute and chronic Adriamycin (ADR) cardiotoxicity, evidence was sought for myocardial free radical toxicity and alterations in myocardial catecholamine levels after acute and chronic administration of ADR to rabbits. In acute studies, male New Zealand white rabbits received intravenous ADR, 1.1 or 5 mg/kg per day for 1 or 3 days or 10 mg/kg for 1 day and were sacrificed 3-72 hours later. Because the glutathione-glutathione peroxidase system is a major pathway for free radical detoxification, glutathione levels and glutathione peroxidase activity were measured. In the acute studies, ADR-treated rabbits exhibited significantly increased levels (up to 50%) of total and reduced glutathione, unchanged levels of oxidized glutathione, and a slight decrease in the percentage of oxidized glutathione. Major effects of dose and sacrifice interval were not observed. However, in animals receiving three injections of 5 mg/kg or one injection of 10 mg/kg ADR, myocytes exhibited fine vacuolization, due to lipid accumulation and dilatation of the sarcoplasmic reticulum, without evidence of coagulation necrosis. In the chronic study, rabbits received 1.1 mg/kg ADR twice weekly for up to 10 weeks. Levels of total and reduced glutathione were increased significantly by 23-36% after 9-12 and 16-20 injections without change in the percentage of oxidized glutathione. The mean percentage of myocytes with vacuolar-myofibrillar degeneration, the characteristic lesion of chronic ADR cardiotoxicity, was 0 after 5-7 injections, 3.3 after 9-12 injection, and 17.2 after 16-20 injections. Glutathione peroxidase activity was not reduced significantly in any group of acute or chronic ADR-treated animals. Tests for lipid peroxidation (malondialdehyde and ethane production) were negative in acute studies. Myocardial catecholamine levels were unchanged in acute and chronic ADR animals. Thus, the cardiac glutathione-glutathione peroxidase system is activated with ADR treatment at the onset of cellular damage, and cellular damage progresses without further alteration of this system, loss of glutathione peroxidase activity, or reduction in myocardial catecholamines in rabbit models of ADR cardiotoxicity. These findings suggest that free radical generation in the heart may contribute to ADR cardiotoxicity, but that other factors probably play a more important role in the pathogenesis of the myocardial damage.

Animals↗

Adult onset idiopathic familial brain calcifications.

We treated a family with idiopathic calcifications of symmetric areas of the brain, including the basal ganglia, dentate, and cerebral white matter. Dementia, progressive dysarthria, incontinence, propulsive-ataxic gait, fixed facies, and cogwheel rigidity without dysmorphic features develop in affected persons. Calcium, phosphorus, and parathyroid hormone levels were normal in the two siblings tested. The literature is reviewed and five other families with a similar syndrome are identified. These six families seem to be clinically distinct from the larger group of idiopathic cerebral calcifications usually referred to as Fahr's disease.

Adult↗

Progressive supranuclear palsy: clinical features and response to treatment in 16 patients.

Among 415 patients with parkinsonism, 16 (3.9%) had findings of progressive supranuclear palsy (PSP). This report reviews the clinical features and response to drug therapy in those 16 patients. Anticholinergic drugs failed to benefit any of the 5 patients treated, while presynaptic dopaminergic drugs (Sinemet or amantadine) were beneficial in only 5 of 22 patient trials. Alternatively, dopamine agonists (bromocriptine and pergolide) caused improvement in 9 of 14 patient trials despite the fact that all but 1 of these patients had previously failed to respond to presynaptic dopaminergic drugs. Dopamine agonists such as bromocriptine and pergolide may be useful in some patients with PSP.

Aged↗

Purge and trap flame photometric gas chromatography technique for the speciation of trace organotin and organosulfur compounds in a human urine standard reference material (SRM).

Ultratrace levels of organotin species and an organosulfur compound were detected in a National Bureau of Standards (NBS) human urine Standard Reference Material, SRM 2670, and a previously certified urine SRM 2672, using a purge and trap system coupled to a gas chromatograph equipped with a flame photometric detector. samples of the SRM were treated with sodium borohydride to form volatile tin hydrides. Species detected included dimethyltin (1.04 ng/ml), butyltin (0.03 ng/ml), and dimethyl-disulfide (2.73 ng/ml) in the new stock of freeze dried human urine SRM 2670 being prepared for issue by NBS and methyltin (1.0 ng/ml), butyltin (1.5 ng/ml), and inorganic tin (28.1 ng/ml) in the old stock of SRM 2672. This analytical technique should have useful applications in studies that are needed to develop a toxicological data base and monitoring programs for human organotin exposure.

Chromatography, Gas↗

Development of fluorescent-antibody reagents for demonstration of Pseudallescheria boydii in tissues.

We prepared fluorescent-antibody reagents to detect and identify Pseudallescheria boydii in tissue. Antisera to broken mycelium and condidia (particulate antigens) and to culture filtrates (soluble antigens) of P. boydii were produced in rabbits. Antisera and globulin fractions of the antisera were labeled with fluorescein isothiocyanate and evaluated for their ability to stain P. boydii in tissues. The conjugates were first tested with cultures of 25 P. boydii isolates and 26 heterologous fungi that are morphologically similar to P. boydii in tissues. Labeled antibody to the soluble antigens reacted only weakly with cultures of P. boydii. Labeled antibody to particulate antigens brightly stained all P. boydii isolates and cross-reacted with Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, Aspergillus terreus, Fusarium oxysporum, Fusarium solani, and a Scopulariopsis sp. The cross-reacting antibodies were removed by adsorption with A. fumigatus and F. oxysporum. The adsorbed conjugates stained P. boydii in Formalin-fixed tissues from experimentally infected mice and in Formalin-fixed tissues from humans and animals with natural infections. They did not stain the heterologous fungi in tissues.

Antibodies, Fungal↗