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Biomedical subjects

M E Morris

Publications and source records attributed to M E Morris.

At least 91 records · Page 5Linked to original sources
PubMed1991

Depolarizing effects of anoxia on pyramidal cells of rat neocortex.

The response of rat neocortical pyramidal neurons (layers II III) in vitro to brief periods of anoxia is a reversible depolarization of 3.8 +/- 1.01 mV (mean +/- S.E.M.; n = 114), which is accompanied by a moderate decrease in input resistance and significant depression of evoked synaptic activity. This effect is mimicked by ouabain, and is partially attenuated by the excitatory amino acid (EAA) antagonist, kynurenic acid. The estimated reversal potential (Vrev) for the anoxic depolarization (AD) is between -35 and -40 mV; in the presence of TTX a Vrev of -65 mV is obtained. Although a partial failure of Na(+)-K(+) pump activity and release of EAAs may contribute the generation of the AD, other processes are likely to be involved.

Animals↗
PubMed1991

Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase 1.

The Saccharomyces cerevisiae LYS2 gene, which encodes alpha-aminoadipate reductase, an essential enzyme in the yeast lysine biosynthetic pathway, has been sequenced. A large open reading frame (ORF) has been identified which can specify a 1392-amino acid protein with a deduced Mr of 155,344. A DNA database search using the translated LYS2 ORF as a probe has revealed significant aa sequence homology to the Bacillus brevis enzyme tyrocidine synthetase 1.

Aldehyde Oxidoreductases↗
PubMed1991

Changes in extracellular K+ evoked by GABA, THIP and baclofen in the guinea-pig hippocampal slice.

Changes in [K+]0 evoked by the inhibitory amino acid transmitter, GABA (gamma-aminobutyric acid) and its agonists were recorded with ion-selective microelectrodes in the CA1 stratum pyramidale of guinea-pig hippocampal slices. Bath applications of GABA (0.1-10 mM) produced dose-dependent increases in [K+]0 (EC50 = 4 mM, Rmax = 1.6 mM), with a peak and decline during exposure, followed by undershoot during recovery. In contrast the selective GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol) (0.01-1 mM) showed approximately ten-fold greater potency and evoked only increases in [K+]0 (EC50 = 0.5 mM, Rmax = 2 mM). Reduction of temperature from 34 degrees to 22 degrees C caused a more than two-fold augmentation of the K+0 accumulation evoked by GABA, but no change in that due to THIP. The GABAA antagonist, BMI (bicuculline methiodide) (100 microM) completely blocked responses to THIP and partially antagonized those to GABA. Responses to GABA were synergistically enhanced by pentobarbital (100 microM). Only small, delayed and inconsistent changes could be evoked by relatively high concentrations of the GABAB agonist, DL-baclofen (0.01-1 mM). The K+ changes evoked by GABA appear to be mediated by the activation of GABAA receptors with low affinity and to be related to their depolarizing action. Although the response includes an electrogenic component which suggests the involvement of Na-dependent transmitter uptake/transport, the increase in K+0 probably reflects an outward counter/co-transport of K+ with Cl/HCO3 anion shifts and/or activation of a voltage-dependent K+ conductance.

Animals↗
PubMed1991

Sulfate homeostasis. IV. Probenecid-induced alterations of inorganic sulfate in rats.

Homeostasis of inorganic sulfate is maintained by the capacity-limited renal reabsorption of sulfate in the proximal tubule. The purpose of the present investigation was to determine if probenecid, the classical inhibitor of renal organic anion secretion, may affect sulfate renal clearance. Two groups of rats were administered in a randomized crossover design, an i.v. bolus dose (20.6 or 92.4 mg/kg) and 4-hr infusion (0.28 or 0.59 mg/min/kg) of probenecid or vehicle, and blood and urine samples were collected. At a steady-state serum concentration of 0.45 mM, probenecid had no significant effect on the serum concentrations or renal clearance of inorganic sulfate, whereas at a serum concentration of 1.4 mM, probenecid treatment caused a significant decrease in serum sulfate concentrations (0.57 +/- 0.11 vs 0.96 +/- 0.19 mM in controls, mean +/- SD, n = 6, P less than 0.001) due to an increase in the renal clearance of sulfate (3.88 +/- 1.18 vs 2.13 +/- 0.84 ml/min/kg in controls, P less than 0.01). The fraction of the filtered sulfate that was reabsorbed was significantly decreased (0.38 +/- 0.23, vs 0.74 +/- 0.09 in controls, P less than 0.01). Therefore, probenecid treatment results in the inhibition of the renal reabsorption of inorganic sulfate in rats in vivo.

Animals↗
PubMed1991

Evaluation of "true" creatinine clearance in rats reveals extensive renal secretion.

The renal clearance of endogenous creatinine is widely used to assess glomerular filtration rate (GFR) and renal function in animal investigations. The objective of the present investigation was to evaluate the extent of renal secretion of endogenous creatinine in rats and the effect of probenecid, the classical inhibitor of organic anion transport, on creatinine clearance. Ten female Lewis rats received 3H-inulin (5-muCi i.v. bolus followed by 5 muCi/hr) throughout a 6-hr period. Three hours after initiation of the inulin infusion, probenecid was administered (92.4-mg/kg i.v. bolus followed by 0.59 mg/min/kg). Steady-state serum concentrations of about 500 micrograms/ml probenecid were achieved. Renal clearance was assessed between 1 and 3 hr (control) and between 4 and 6 hr (probenecid treatment). A preliminary study in seven rats demonstrated no time-dependent change in inulin or creatinine clearance between these two study intervals. Creatinine clearances were determined by an alkaline picrate assay which incorporated Fuller's earth (Lloyd reagent) to remove interfering noncreatinine chromogens from serum samples and these values were compared with those using a nonspecific picrate assay. "True" clearance ratios of creatinine to inulin (Clcr/CLin) were greater than unity (2.33 +/- 0.83, mean +/- SD) and were significantly decreased after probenecid treatment (1.26 +/- 0.28, P less than 0.01). Probenecid had no effect on GFR, as assessed by inulin clearance. Using the nonspecific picrate assay, CLcr/CLin was 1.12 +/- 0.41, which was not significantly different from unity and which decreased to 0.53 +/- 0.12 after probenecid treatment. Therefore, creatinine undergoes extensive renal secretion in female Lewis rats.

Animals↗
PubMed1991

Sulfate homeostasis. III. Effect of chronic naproxen or sulindac treatment on inorganic sulfate disposition in arthritic patients with renal impairment.

The purpose of the present investigation was to examine the influence of chronic naproxen (500 mg twice daily) or sulindac (200 mg twice daily) therapy on the disposition of inorganic sulfate in arthritic subjects with impaired renal function. Subjects were studied during a control period (after a 7-day NSAID washout) and after 14 days of treatment with either naproxen or sulindac. During the control period subjects in this investigation exhibited higher serum sulfate concentrations and lower sulfate renal clearance values than reported for younger subjects with normal renal function. Treatment with either sulindac or naproxen significantly decreased creatinine clearance. Sulindac therapy also increased the serum sulfate concentration and decreased the clearance of sulfate; a similar trend was observed after naproxen therapy but the average change was smaller and not statistically significant. There were significant correlations between the creatinine and the sulfate clearances or serum concentrations. The glomerular filtration rate of inorganic sulfate was not altered by drug treatment and there was no impairment of reabsorption. The serum concentrations and renal clearance of other electrolytes (sodium, potassium, magnesium, calcium, phosphorus) were largely unaffected. Therefore, chronic treatment with naproxen or sulindac decreases the renal clearance of endogenous sulfate in humans: this appears to be a consequence of the decrement in renal function observed in subjects with preexisting mild renal impairment.

Aged↗
PubMed1991

Allelic and ectopic interactions in recombination-defective yeast strains.

Ectopic recombination in the yeast Saccharomyces cerevisiae has been investigated by examining the effects of mutations known to alter allelic recombination frequencies. A haploid yeast strain disomic for chromosome III was constructed in which allelic recombination can be monitored using leu2 heteroalleles on chromosome III and ectopic recombination can be monitored using ura3 heteroalleles on chromosomes V and II. This strain contains the spo13-1 mutation which permits haploid strains to successfully complete meiosis and which rescues many recombination-defective mutants from the associated meiotic lethality. Mutations in the genes RAD50, SPO11 and HOP1 were introduced individually into this disomic strain using transformation procedures. Mitotic and meiotic comparisons of each mutant strain with the wild-type parental strain has shown that the mutation in question has comparable effects on ectopic and allelic recombination. Similar results have been obtained using diploid strains constructed by mating MATa and MAT alpha haploid derivatives of each of the disomic strains. These data demonstrate that ectopic and allelic recombination are affected by the same gene products and suggest that the two types of recombination are mechanistically similar. In addition, the comparison of disomic and diploid strains indicates that the presence of a chromosome pairing partner during meiosis does not affect the frequency of ectopic recombination events involving nonhomologous chromosomes.

Alleles↗
PubMed1991

Temperature dependence of extracellular ionic changes evoked by anoxia in hippocampal slices.

1. Extracellular [K] and [Ca] were measured with ion-selective microelectrodes in CA1 pyramidal cell layer of rat hippocampal slices in an interface chamber. 2. Near room temperature (21-22 degrees C), brief periods of anoxia (3- to 4-min substitution of 95% N2-5% CO2 for 95% O2-5% CO2) produced very small changes in [K]o [-0.022 +/- 0.10 (SE) mM] or [Ca]o (-0.030 +/- 0.0029 mM) and were associated with only minor depression of population spikes (-22.5 +/- 11%). 3. Stratum radiatum (SR) stimulation (0.2-5 Hz) could evoke substantial increases in [K]o (by 0.2-2 mM); although variable, they were consistent in any one slice. The same stimulation regularly caused only small depressions of [Ca]o (by less than 0.1 mM, typically). 4. Also at 21-22 degrees neither stimulation nor anoxia generated more than minimal reductions in extracellular space [by 2.3 +/- 0.94%, as measured by the tetramethylammonium (TMA) method], and spreading depression (SD) occurred in only 1 out of 20 slices. 5. At 33-34 degrees C, anoxia (also for 3-4 min) consistently produced more substantial increases in [K]o (0.83 +/- 0.18 mM); but the apparent changes in [Ca]o at 33 degrees C (0.058 +/- 0.12 mM) could not with certainty be distinguished from thermoelectric artifacts. There was a severe depression of population spikes (-76 +/- 10%). 6. Although electrical stimulation evoked greater reductions in [Ca]o, increases in [K]o were 50% smaller. 7. During anoxia at 33-34 degrees C, the extracellular space was significantly reduced, by 6.1 +/- 0.9%. Moreover, in 37% of the slices, either stimulation or anoxia triggered massive increases in [K]o (greater than 10 mM) and large reductions in [Ca]o (less than 1 mM), associated with SD-like swings in focal potential. 8. It is concluded that the extracellular ionic changes evoked by brief anoxia do not contribute in a major way to the depression of synaptic transmission.

Action Potentials↗
PubMed1990

High-performance liquid chromatographic analysis of p-nitrophenol and its conjugates in biological samples.

p-Nitrophenol (pNP) and its conjugated metabolites, generated in a perfused rat liver preparation, are readily separated and quantitated in serum perfusate and bile samples using a reverse-phase high-performance liquid chromatographic method. Serum perfusate samples can be analyzed following protein precipitation with acetonitrile: following protein precipitation with 1.5 M perchloric acid (1 part to 2 parts serum) there was degradation of pNP sulfate to pNP when samples were stored at room temperature. pNP can also be analyzed in blood perfusate samples following extraction with a number of organic solvents including ethyl acetate or isobutanol-methylene chloride (4:1, v/v). Rat liver perfusions at a constant input concentration of 40 microM demonstrated a high hepatic extraction ratio of pNP (mean of 0.90) due to the formation of the sulfate and glucuronide conjugates; no pNP glucoside was detected in perfusate or bile samples.

Animals↗
PubMed1990

Effects of ketamine on GABA-evoked excitability of peripheral nerve.

The effects of the dissociative anaesthetic, ketamine on GABA-evoked changes in the excitability of myelinated fibers of dorsal and ventral roots of isolated bullfrog sciatic nerves were examined. Ketamine alone (0.01-1000 microM) evoked small increases (less than 5%) in dorsal root fiber excitability, as reflected in the half-maximal A-fiber compound action potential when concentrations were greater than 10 microM; with greater than or equal to 0.1 microM even larger increases (greater than or equal to 10%) were elicited in the ventral root fibers. As well, the increases evoked by greater than or equal to 10 microM ketamine were followed by graded decreases. 0.1 and 10 microM ketamine, concentrations which by themselves had small or no effect, produced a dose-dependent depression of the large increases in excitability which are induced by activation of GABA receptors. In the presence of ketamine GABA concentration-response curves of the dorsal root fibers showed depression of the maximal response, while those of the ventral root fibers were shifted to the right. This apparent antagonism of GABA responses by ketamine may arise from blockade of receptor-mediated effects (e.g. K+/Cl- currents and/or secondary depolarization from K+ accumulation), but could also be caused by a selective potentiation of hyperpolarizing receptors.

Action Potentials↗
PubMed1990

Sulfate homeostasis. II. Influence of chronic aspirin administration on inorganic sulfate in humans.

The purpose of the present investigation was to determine the effect of chronic aspirin administration on the serum concentration and renal clearance of inorganic sulfate in healthy volunteers. In a randomized crossover study, eight male subjects received either no treatment or 975 mg of enteric-coated aspirin three times daily for 8 days. Blood and urine samples were collected on the eighth day over a 7-hr period. Midpoint salicylic acid concentrations in serum varied between 55 and 182 micrograms/ml (mean concentration of 109 micrograms/ml). Serum inorganic sulfate concentrations demonstrated a small but significant decrease on the eighth day of aspirin administration but there was no apparent change in the renal clearance of sulfate. There were significant correlations between the renal clearances, urinary excretion rates, and serum concentrations of creatinine and sulfate, reflecting the dependence of sulfate homeostasis on renal function. The serum concentration and renal clearance of creatinine, sodium, potassium, calcium, magnesium, and phosphorus were unaffected by aspirin treatment.

Adult↗
PubMed1990

Surgical exposure and orthodontic alignment of an unerupted primary maxillary second molar impacted by an odontoma and a dentigerous cyst: a case report.

This report describes the surgical and orthodontic management of a 3-year old girl with an unerupted primary maxillary second molar impacted by an odontoma and a dentigerous cyst. Following surgical removal of the odontoma and dentigerous cyst, further surgical intervention and orthodontic traction were required to bring the primary maxillary second molar into correct occlusion with resultant proper functioning and good periodontal health.

Child, Preschool↗
PubMed1989

Calibration of ion-selective microelectrodes: flow-system and analysis program for the IBM PC.

A menu-driven program--written in C and Assembly language--has been developed for use with an IBM PC or compatible computer for calibration of ion-selective microelectrodes. Available features include (i) user-logical commands, (ii) rapid, accurate construction and display of calibration curves (fitted by least squares non-linear regression), (iii) analysis of data (stored either on- or off-line), with correction for drift and conversion from voltage or length to ion concentration or activity, (iv) calculation of selectivity coefficients, (v) optional storage and use of activity coefficients, and (vi) output of data, calculations and graphics to printer and plotter. A simple chamber and valve-activated flow-system for rapid change of solutions with either manual selection or computer control is also described.

Microelectrodes↗
PubMed1989

N-acetylator variability in Down's syndrome: characterization with caffeine.

Little is known regarding the biotransformation of drugs in Down's syndrome. In particular, there are no published studies that examine metabolic pathways such as N-acetylation, which can exhibit genetically-determined variability. The objective of the present investigation was to compare the acetylator phenotypes of white subjects with Down's syndrome with age-matched control subjects, with use of caffeine as the pharmacologic probe. After the ingestion of caffeine-containing beverages, spot urine collections were obtained at 2 and 4 hours in 22 subjects with Down's syndrome and in 22 control subjects (age range of 4 to 49 years). The urinary excretion ratios of 5-acetylamino-6-amino-3-methyluracil (AAMU) to 1-methylxanthine (1X) determined in these 2-hour and 4-hour samples were highly correlated (r = 0.82; p less than 0.001). In addition, more extensive urinary excretion studies performed for an 8-hour period in three subjects with Down's syndrome demonstrated that the coefficient of variability for the ratio of AAMU/1X ranged from 10.1% to 14.2%, which is similar to the reproducibility previously reported for control subjects. A trimodal distribution of acetylator phenotypes was observed, with no differences in average or frequency distribution of ratio values between the subjects with Down's syndrome and the control subjects. This study demonstrates that polymorphic N-acetylator status, as assessed by caffeine metabolism, is similar in subjects with Down's syndrome and in control subjects.

Acetylation↗
PubMed1989

Effects of GABA, THIP, and potassium on excitability of myelinated axons of isolated amphibian spinal roots.

The effects of direct applications of GABA (gamma-aminobutyric acid) and the GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the excitability of myelinated axons of individual dorsal and ventral spinal roots (lumbar VI and (or) VII) of the isolated bullfrog peripheral nerve are reported. Increases evoked by the GABA agonists (0.01-10 mM) in the amplitude of half-maximal A-fiber compound action potentials indicate the presence of depolarizing responses with apparently greater localization to the dorsal roots, and a sensitivity to GABA twofold greater than that for THIP. The changes evoked by GABA and THIP, as well as potassium have components that closely resemble those of sensory and motor fibers in the more distal, desheathed nerve bundle but are smaller and delayed, differences attributable to a closely attached root sheath that acts as a diffusion barrier. These results confirm the likely existence of GABAA receptors on both dorsal and ventral spinal roots.

Anesthetics↗
PubMed1989

Ionic mechanisms of action of GABA on dorsal and ventral root myelinated fibers: effects of K+ channel blockers.

Excitability changes evoked by the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) in myelinated axons of dorsal and ventral roots of the isolated bullfrog sciatic nerve were compared in the absence and presence of K+ channel blockers. Half-maximal A-fiber responses to a 0.5-Hz stimulation of the whole nerve were recorded from individual roots. Direct applications of Ringer with raised K+ levels to the site of stimulation caused increases in excitability of both dorsal and ventral root fibers, which resembled those evoked in the ventral root by the GABA agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]ol). The increases in dorsal root fiber responses produced by GABA were depressed by tetraethylammonium (TEA) (3 mM), 4-aminopyridine (4-AP) (50 microM), Cs (2 mM), and Ba (1 mM). Ventral root fibers were less consistently affected. The early component of GABA-evoked excitability increases was depressed by 4-AP, Cs, and Ba, but greatly augmented by TEA. THIP-evoked changes in the excitability of the dorsal and ventral root fibers were, respectively, depressed and enhanced by TEA. The augmenting effect of TEA on the early component of GABA agonist effects on the ventral root fibers is attributed to their high resting K+ conductance and the presence of a slowly inactivating, fast K+ current (If1). The depressant effects of K+ channel blockade on depolarizing components of agonist-evoked changes in dorsal and ventral root responses indicate interference with release and (or) sensitivity to K+ and a possible contribution from a mechanism involving voltage-dependent delayed rectifier K+ currents.

4-Aminopyridine↗