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Biomedical subjects

D Gardner

Publications and source records attributed to D Gardner.

At least 73 records · Page 4Linked to original sources
PubMed1988

A test for modulation of synaptic efficacy by induced membrane potential variance.

A modification of Klopf's heterostatic adaptive neuron hypothesis is proposed, in which membrane potential variance, rather than depolarization, has adaptive influence on individual nerve cells. Recordings from each of two configurations of three-cell networks of Aplysia buccal ganglia test for either nonspecific or associative effects of excess membrane potential and current variance, in the form of noise injection into voltage-clamped postsynaptic neurons. No effects of noise are reported, suggesting either that the hypothesis is incorrect, or else that the frequency spectrum or duration of recording were inappropriate to produce the adaptive modulation.

Animals↗
PubMed1987

Endocardial fibroelastosis and tricuspid valve insufficiency in a calf.

A 5-month-old Holstein heifer had clinical signs of tricuspid valve insufficiency and histopathologic evidence of endocardial fibroelastosis. The calf had a 3-week history of weight loss, abdominal distention, dyspnea, and decreased appetite. Physical examination revealed signs of right-sided heart failure, and a systolic murmur (II/VI) was heard best over the right heart base. Results of cardiac catheterization and echocardiography indicated tricuspid valve insufficiency and right-sided heart failure. The calf was euthanatized after not responding to treatment with penicillin, furosemide, and removal of fluid from the thorax and abdomen. Necropsy findings included multifocal areas of thickening and opacification of the endocardium of the left and right ventricles. Excessive elastic fibers, consistent with fibroelastosis, were seen by use of special stains applied to sections of endocardium.

Animals↗
PubMed1987

Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls.

Evidence from animal and human studies suggests that procaine hydrochloride may selectively activate limbic system structures and suppress neocortical structures. We administered a series of intravenous bolus doses of procaine hydrochloride to 31 subjects (7 with affective disorders, 17 with borderline personality disorder, and 7 healthy normal volunteers). Dose-related cognitive and sensory distortions and illusions were observed; affective experiences ranged widely from euphoric to dysphoric. Topographic electroencephalogram (EEG) analysis indicated selective increases in fast activity (26-45 Hz) over the temporal lobes; the degree of increase in this activity correlated with degree of dysphoria experienced. Procaine was associated with increases in secretion of cortisol, adrenocorticotrophic hormone (ACTH), and prolactin, but not with growth hormone. These preliminary data are consistent with the possibility that procaine might serve as a clinically useful probe of psychosensory, affective, electrophysiological, and endocrine effects referable to the limbic system.

Adrenocorticotropic Hormone↗
PubMed1987

Differential early rearing affects response to overfeeding in B6D2F2 mice.

Male and female B6D2F2 mice, reared in small (Sm = 4), medium (Md = 8) and large (Lg = 12) litters, were maintained on high-fat, high-carbohydrate (EXP) or chow (CH) diets beginning at 14 weeks. EXP mice consumed more calories and gained more weight than CH mice; these effects were greatest in the Sm animals. Each sex responded similarly. Caloric efficiency was highest in the Sm EXP and male animals. Total body fat in males showed that Sm greater than Md greater than Lg and EXP greater than CH. The thermogenic capacity was measured by total oxygen consumption and body temperature response during acute cold stress, and protein content and cytochrome c oxidase activity in interscapular brown adipose tissue (1BAT). Sm mice had a smaller decrease in temperature and consumed less oxygen per gram body weight than Lg, suggestive of a contributing role of increased insulation. When oxygen consumption was expressed as a function of body weight0.75, EXP greater than CH, but there were no other significant dietary effects. Neither litter size nor diet appeared to affect protein content or cytochrome c oxidase activity in 1BAT. These results show that early rearing experience effects both behavioural and physiological variables associated with the maintenance of adult body weight in mice, but these effects do not appear to be mediated through 1BAT.

Animals↗
PubMed1987

Soft sign neurological abnormalities in borderline personality disorder and normal control subjects.

Patients with borderline personality disorder were found to have a significantly greater number of soft sign neurological abnormalities when compared with a group of normal control subjects. Sensitivity analysis revealed that the presence of two or more soft signs differentiated the two groups statistically. The authors speculate that nonfocal soft sign neurological abnormalities may reflect underlying central nervous system dysfunction, which may in turn be associated with the development of borderline personality disorders.

Adolescent↗
PubMed1986

Variations in amplitude and time course of inhibitory postsynaptic currents.

In order to examine the relative contributions of changes in amplitude and time course to synaptic plasticity, variations in peak amplitude and time constant of decay have been analyzed from inhibitory postsynaptic currents (PSC) recorded in voltage-clamped Aplysia buccal ganglia neurons. In these cells, synaptic currents with single time constant decay can be recorded with low noise under well-controlled space clamp. Over a population of 36 neurons, duration was more narrowly distributed than amplitude, but each varied. The coefficient of variation (CV) was 0.21 for decay time constant (tau) and 0.87 for peak conductance (g peak). Population variances are larger than can be accounted for by such variables as temperature and noise amplitude, suggesting that functional modifications alter each of these determinants of synaptic effectiveness over the long term. Recordings of up to several hundred PSC in each of 16 neurons show that both PSC amplitude and time course recorded in a single cell can vary independently over short time spans. Decay remained single exponential as time course changed. CV for tau averaged 0.11; CV for g peak was 0.19. Variability of tau was not an artifact of amplitude; CV was relatively uncorrelated with current amplitudes or sample size. Smoothing and adding excess noise to each individual PSC of a set produced only small changes to CV, showing that variability was not an artifact of noise. Several specific manipulations of the presynaptic neuron altered both PSC amplitude and time course. Tetanic stimulation of the presynaptic neuron produced short-term potentiation of both amplitude and time course of subsequent PSCs. Peak amplitude was increased by 80%; tau by 12%. Reducing interspike intervals from 10 to 1 s produced habituation of both amplitude and time course, with g peak decreasing by 35 to 40% and tau by 10%. Conditioning DC depolarization of the presynaptic neuron enhanced PSC amplitude with little effect on decay time constant. Although short-term plastic changes affect PSC amplitude more than duration, each is alterable. Parallel changes in both can synergistically alter synaptic charge transfer, and therefore efficacy. Similar mechanisms may produce larger long-term differences seen between neurons.

Animals↗
PubMed1986

Cloning, sequence analysis, and processing of the rat and human atrial natriuretic peptide precursors.

Complementary DNA sequences and structural genes encoding the atrial natriuretic peptide precursor (prepro-ANP) have been cloned. Analysis of DNA sequences, complementary to rat atrial prepro-ANP mRNA, has revealed that the various natriuretic peptides isolated from rat atrium reside at the carboxy terminus of a 152-amino-acid precursor protein. The human gene, comprised of three exons and two intervening sequences, encodes a protein of 151 amino acids highly homologous to the rat precursor. Although putative proteolytic processing sites can be identified throughout the prepro-ANP amino acid sequence, the natural form of the mature ANP has not been identified. Therefore, the sites and mechanisms of prepro-ANP processing to mature peptides forms are unknown. However, the successful cloning of the prepro-ANP gene and corresponding cDNAs provide the necessary molecular tools to address these fundamental questions relating to the regulation of ANP synthesis and processing in atrial and extraatrial tissues.

Amino Acid Sequence↗
PubMed1986

Acute management of the head-injured adult.

Acute nursing management of the head-injured adult is both complex and challenging. Knowledge of the underlying pathophysiology and understanding the goals of medical and nursing management allow the nurse to organize and evaluate appropriate nursing interventions.

Adolescent↗
PubMed1985

Prostacyclin synthesis in irradiated endothelial cells cultured from bovine aorta.

Confluent monolayers of bovine aortic endothelial cells were examined 2-72 h after exposure to 0.5-5.0 Gy of 60Co gamma-rays. Accumulation of prostacyclin [PGI2, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] in the culture media and PGI2 production stimulated by exogenous arachidonate were correlated with cell detachment and release of lactate dehydrogenase (LDH) activity. Platelet adherence to irradiated and control monolayers also was studied. There were simultaneous time- and dose-dependent increases in cell detachment and in the titers of 6-keto-PGF1 alpha and LDH activity in the culture medium. These changes were evident between 4 and 8 h after 5 Gy or at 24 h after 0.5 Gy. Four hours after 5 Gy, both adherent and detached endothelial cells showed a twofold increase in PGI2 production during a 15-min incubation with arachidonate (10 microM). However, by 72 h this increase was less significant. The accumulation of 6-keto-PGF1 alpha appeared to be related to cell destruction, but radiation also stimulated PGI2 synthesis independent of cell detachment. There was an increased platelet interaction with irradiated monolayers, as a result of platelet adherence to subendothelial matrix exposed after cell detachment. However, irradiation did not alter the nonadherent property of the endothelial cell surface toward platelets.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Unusual problems for the physician in managing a hospital patient who received a malicious insulin overdose.

A patient recovering normally from a biopsy and subtotal removal of a malignant brain tumor became severely hypoglycemic on the ward and died. The differential diagnosis eliminated disease as a possible cause, and medication error on the floor was also ruled out. Deliberate administration of a massive dose of insulin intravenously seemed to be the only alternative. A careful investigation supported the likelihood of a criminal act. The patient's wife came under suspicion and was subsequently arrested, charged with murder, and convicted. This sequence of events created three problems that fell outside of our normal professional training and experience as physicians. First, we were slow to suspect foul play in our search for an unusual cause. Second, the steps taken to protect the patient against further risk without denying reasonable rights to family or arousing the suspect's suspicions needed strengthening. Third, even though the occurrence of these events in a hospital allowed an unusual degree of evidence documenting the allegations to be accumulated, key parts of the evidence could not be used. The routine hospital handling of laboratory tests critical to support of the accusations was not sufficient to meet the demands of the legal system, which has its own criteria. We discuss the issues in managing these problems.

Blood Glucose↗
PubMed1984

Transcription of two classes of rat growth hormone gene-associated repetitive DNA: differences in activity and effects of tandem repeat structure.

The rat growth hormone (rGH) gene contains two classes of repetitive DNA arranged as clusters within intron B and the 3' flanking region. The major family is equivalent to the CHO type 2 DNA. The second ("truncated repeat", TR) is a truncated version of the first and occurs in certain neural-specific transcripts and genes ("identifier" elements, ID). Here we report, using the HeLa cell-free transcription assay, that RNA polymerase III (Pol III) efficiently initiates at internal promoters within a tandem array of rGH gene repetitive DNA monomers and results in a novel organization of overlapping Class III transcription units. Transcription competition studies revealed that the rat type 2 structures share Pol III transcription factors with a tRNA gene, a human Alu repeat, and a mutant VA1 gene. Also, the rGH type 2 but not the TR DNA efficiently promotes Pol III initiation, yet other TR members, which differ only in flanking DNA, are transcribed. Thus, the rGH gene is strikingly enriched with 10 repetitive DNA monomers; multimeric type 2 elements are actively transcribed; rGH-TR sequences are expressed only as part of larger transcripts promoted by type 2 DNA; and, type 2 DNA uses tRNA gene transcription factors. These studies show that flanking sequences, promoter organization and factor competition may all affect rat repetitive DNA expression.

Animals↗
PubMed1984

Voltage-dependence of synaptic time course reduces excitation at a diphasic synapse.

At a diphasic excitatory-inhibitory synapse of Aplysia, the time constant of decay of the early excitatory synaptic conductance is decreased by depolarization. As a consequence of this reduced excitation, the amplitude of the inhibitory phase is increased and its rise time shortened, and inhibitory charge transfer is greater than excitatory charge transfer at potentials more depolarized than -53 mV. Functional consequences of voltage-dependent time course can thus be identified at a central synapse.

Animals↗
PubMed1984

Choline acts as agonist and blocker for Aplysia cholinergic synapses.

Several identified neurons of the Aplysia buccal ganglia respond to choline. Iontophoretic applications of either choline or acetylcholine (ACh) to voltage-clamped inhibitory follower neurons produce similar currents. Peak amplitudes of choline responses were 10-100% of ACh responses on the same cell. Choline currents were curare blockable and reversed at -69 +/- 2 mV, within 1 mV of postsynaptic current (IPSC) reversal. Application of 1 mM choline to the bath produces more prolonged effects than an initial conductance change. Choline depressed IPSC amplitude by 42 +/- 5% and prolonged IPSC decay time constant by 25 +/- 7%. The slowing was reversible but the depression was not. Use of choline as a Na substitute may therefore involve unexpected partial agonist action; even where conductance changes are transient or inapparent, choline may alter synaptic responses. Bath choline had variable effects on cholinergic self-inhibitory synapses, blocking in six trials but not in three others. Voltage clamping cells BL and BR7, in which monosynaptic cholinergic PSPs are diphasic, reveals underlying early inward and late outward currents. Choline activates only the late outward current component. Correspondingly, bath choline blocks only the late outward component, as does eserine and ACh. This block is not seen with neostigmine, and so is unlikely to be related to cholinesterase inhibition. The early inward current component, revealed by block of the late component by choline or ACh, decays exponentially. Decay time constant is exponentially dependent on membrane potential over the range -20 to -100 mV, with 63-mV depolarization speeding decay e-fold. Eserine prolongs decay and steepens voltage dependence. The late outward component decays with voltage-independent time constant of 48 +/- 5 ms. Both the time integral of synaptic conductance and the ratio of synaptic charge transfer to peak synaptic current of the early inward component of the cell 7 response are reduced by depolarization. Voltage-dependent duration thus combines with reduced driving force in diminishing the excitatory effect of this component at depolarized levels, allowing the inhibitory component to predominate. In this diphasic synapse, voltage dependence of the time course of one component thus serves an easily identified function.

Acetylcholine↗
PubMed1983

Physostigmine prolongs the elementary event underlying decay of inhibitory postsynaptic currents in Aplysia.

Inhibitory postsynaptic currents (IPSCs) recorded at cholinergic synapses between identified neurons of the buccal ganglia of Aplysia decay exponentially. IPSC decay has been ascribed to a receptor-channel-dependent kinetic process, rather than to changes in subsynaptic acetylcholine (ACh) concentration, but is prolonged by the anticholinesterase eserine. Our data are consistent with a direct effect of 1.6 X 10(-4) M eserine on an elementary channel process. IPSC decay remains single exponential during eserine prolongation, suggesting that eserine slows the kinetic process responsible for decay, rather than substituting an additional kinetic process. In either control sea water or eserine, noise spectra computed from currents induced by pressure ejection of ACh are fitted by the sum of two Lorentzians. The slow corner frequency f1 is reduced from 6.3 to 3.5 Hz by eserine, consistent with a direct eserine action on receptor-channel kinetics, whereas apparent single-channel conductance was unchanged. Both IPSCs and ACh noise recorded in the same cells were comparably slowed by eserine. In eserine, decay time constant tau agreed with noise f1; however, tau and f1 in control sea water differed by 31%. The discrepancy may be accounted for by invoking an additional component to the recorded noise spectra, perhaps produced by synaptically active choline. In addition to the direct effect on kinetics, prolonged exposure to eserine produces a slow extra component to the IPSC decay tail.

Acetylcholine↗
PubMed1981

Self-inhibition alters firing patterns of neurons in Aplysia buccal ganglia.

The functional consequences of cholinergic self-inhibitory synaptic potentials (SISPs) upon firing patterns were examined in pairs of electrotonically coupled neurons of Aplysia buccal ganglia. In each neuron, the size of the peak SISP current decrements exponentially with increased number of previous conditioning action potentials (APs). To determine the effect of SISPs on the firing patterns of each cell, AP trains elicited by constant-current steps with the SISP intact were compared to those with the SISP blocked by curare. The SISP prolonged initial interspike intervals, providing an early supplement to accommodation, and produced a 75% increase in the sensitivity of firing frequency vs injected current plots for the first ISI. Firing rates were more regular in the presence of the SISP. However, the efficacy of the SISP, like the size of the underlying current, decrements with repetition. SISP effects were also studied in electrotonically coupled pairs of self-inhibitory neurons. Although the SISP altered the shape of the hyperpolarizing component of coupling potentials, DC coupling between the neurons was unaffected. Firing synchrony in coupled pairs stimulated with long DC pulses was assessed with cross-correlation histograms. In 60 mM Ca2+, the SISP sharpens the central peak of synchrony and deepens the flanking troughs, increasing the probability of synchronous firing within +/- 4 msec by 76%. The major determinants of synchrony were found to be common input, SISP-dependent regularity of firing, and the depolarizing phase of the coupling potential, rather than the SISP-enhanced hyperpolarizing phase.

Animals↗
PubMed1981

Indigenous nasopharyngeal, auditory canal, and middle ear bacterial flora of gerbils: animal model for otitis media.

The indigenous microbial flora of the middle ear cavity of Mongolian gerbils, Meriones unguiculatus, was isolated, characterized, and identified, showing it to be sparse and transitory. Organisms, when found in the middle ear cavity, were most likely to be Staphylococcus epidermidis-like organisms. Cerumen from the external auditory canal of these animals yielded mostly staphylococci, coryneforms, and other gram-positive rods, including some anaerobic species. The nasopharynx supported a flora consisting mainly of staphylococci, lactobacilli, and coryneforms, with a smaller incidence and numbers of many other species. No mycoplasmas were cultured or seen in scanning electron microscope studies. None of the major pathogens of human otitis media were found; therefore, Mongolian gerbils are microbiologically acceptable candidates as a model for induced otitis media, using organisms isolated from human otitic infections.

Animals↗