Congenital total absence of the pericardium: case report of a 72-year-old man and review of the literature.
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Aged↗
Biomedical subjects
M E Kelly
Publications and source records attributed to M E Kelly.
Patch-clamp recording from identified rat ciliary ganglion neurons in primary culture.
Adult rat parasympathetic ciliary ganglion (CG) neurons were retrogradely labelled by intraocular injection of the carbocyanine fluorescent dye 1,1-dioleyl-3,3,3',3'-tetramethylindocarbocyanine methanesulfonate (DiI). Whole-cell and nystatin perforated patch recording techniques were then used to examine the electrophysiological properties of labelled CG neurons growing in primary culture. The resting membrane potential of CG neurons in dissociated cell culture was -50 +/- 8 mV, and isolated neurons fired overshooting action potentials in response to depolarizing current injection. Voltage-clamp recordings of membrane currents revealed a transient tetrodotoxin-sensitive Na+ inward current and both sustained and transient outward K+ currents. Sustained outward K+ current was reduced (55-77%) by 5 mM tetraethylammonium and to a lesser extent (42-46%) by superfusion with nominally Ca2+ free external solution. Transient outward current was blocked by 100 microns 4-aminopyridine and exhibited steady-state inactivation at potentials depolarized to -50 mV. These data demonstrate that identified adult mammalian CG neurons can be successfully maintained in culture. Cultured CG neurons retain electrical excitability, with voltage-sensitive Na+ and K+ currents giving rise to action potentials.
Action Potentials↗
Aged Stone maze-impaired rats exhibit reduced striatal muscarinic receptor densities.
Muscarinic receptor densities, measured by saturation radioligand binding using the muscarinic antagonist [3H]QNB, were compared in the striatum, frontal cortex and hippocampus between two populations of young (3 month) and aged (12-20 month) Hooded Lister rats which had previously been tested in a complex maze task. Aged rats were impaired in their performance of a Stone (14-unit T-maze) task and were less spontaneously active than young rats. Muscarinic receptor numbers were significantly decreased in the striatum of aged rats, whilst numbers in the hippocampus and frontal cortex and receptor affinities in all three areas were unaltered. These results indicate that the age-associated depletion of striatal muscarinic receptors may contribute to deficits in cognitive processing and/or motor behaviour which underlie impairments in the performance of complex spatial tasks.
Aging↗
Functional consequences of posttranslational isomerization of Ser46 in a calcium channel toxin.
The venom of the funnel-web spider Agelenopsis aperta contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, omega-Aga-IVB (IVB) and omega-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in A. aperta venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.
Agatoxins↗
Ondansetron fails to attenuate a scopolamine-induced deficit in a Stone maze task.
The 5-HT3 receptor antagonist ondansetron has previously been reported to improve cognition in the mouse, rat and marmoset in a variety of behavioural paradigms. The present study used the Stone maze to test the effect of ondansetron on the deficit caused by scopolamine in the performance of a highly complex spatial memory task in the rat. Ondansetron administered over a large dose range (1.0 ng kg-1-1.0 micrograms kg-1, i.p., b.d.) for a period of 10-15 days failed to attenuate the scopolamine deficit. Indeed at one dose level ondansetron (100 ng kg-1, i.p., b.d.) administered in combination with scopolamine (0.5 mg kg-1, i.p.) significantly potentiated the deficit, compared with the performance of rats receiving scopolamine alone.
Animals↗
Actions of 5-hydroxytryptophan to inhibit and disinhibit mouse behaviour in the light/dark test.
The involvement of 5-HT receptors in behavioural responding to an aversive situation was investigated in the mouse light/dark test. The administration of 5-hydroxytryptophan (5-HTP) (12.5-50 mg/kg i.p.) increased brain 5-HT turnover and inhibited mouse behaviour in the light/dark test box. The 5-HT2C/5-HT2A receptor antagonists methysergide (1.0 and 5.0 mg/kg i.p.) and ritanserin (0.1-1.0 mg/kg i.p.) antagonised (methysergide) or reversed (ritanserin) the effects of 5-HTP to an increased exploration of the light compartment; a low dose of the 5-HT3 receptor antagonist ondansetron (0.01 mg/kg i.p.) had a similar effect. The disinhibitory effect of the 5-HTP/ritanserin interaction was antagonised by the 5-HT3/5-HT4 receptor antagonists SDZ205-557 (0.001-0.1 mg/kg) and a high dose of tropisetron (1.0 mg/kg i.p.) but not by ondansetron (1.0 mg/kg i.p.). At these doses tropisetron and ondansetron had no effect in their own right. Thus the dominant effect of 5-HTP in the mouse is to inhibit behaviour, a response mediated via 5-HT2C/5-HT2A and 5-HT3 receptors. A 5-HT4 receptor may effect an opposing disinhibitory potential as revealed by ritanserin.
4-Aminobenzoic Acid↗
Outwardly rectifying chloride current in rabbit osteoclasts is activated by hyposmotic stimulation.
1. We characterized chloride currents in freshly isolated rabbit osteoclasts using whole-cell and single channel patch-clamp recording configurations. Depolarization activated an outwardly rectifying current in 40-50% of cells, distinct from the inwardly rectifying K+ current we have previously reported in osteoclasts. 2. The outwardly rectifying current persisted under conditions where all K+ currents were blocked. Furthermore, the outward current was reversibly inhibited by Cl- transport blockers 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS); 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS); 4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS); and niflumic acid. The blocked current had a reversal potential close to the predicted chloride equilibrium potential and was dependent on the chloride concentration gradient. 3. In those osteoclasts in which outwardly rectifying current was not initially apparent, exposure to hyposmotic extracellular solution resulted in its reversible activation. The induced current was due to Cl-, based on its reversal close to the chloride equilibrium potential and sensitivity to blockade by Cl- channel inhibitors. The hyposmotically induced current could be activated in Ca(2+)-free solutions containing 0.2 mM EGTA. 4. When studied in the current-clamp configuration, hyposmotic stimulation caused depolarization from -76 +/- 5 to -5 +/- 6 mV (mean +/- S.D., n = 7). 5. Unitary Cl- currents were recorded in the cell-attached patch configuration at positive potentials. Single channels had a slope conductance of 19 +/- 3 pS (n = 5). Reduction of the external [Cl-] shifted the current-voltage relationship in the positive direction, supporting the conclusion that these were Cl- currents. Like the whole-cell currents, single channel Cl- currents were activated by exposure of cells to hyposmotic bathing solution. 6. We conclude that rabbit osteoclasts express an outwardly rectifying Cl- current that can be activated by osmotic stress. Cl- channels may play a role in cell volume regulation and may also provide conductive pathways for dissipating the potential difference that arises from electrogenic proton transport during bone resorption.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Hippocampal kindling protects several structures from the neuronal damage resulting from kainic acid-induced status epilepticus.
In an attempt to study the effects of piriform cortex damage on kindled seizure propagation, we administered kainic acid (12 mg/kg; i.p.) to rats previously kindled from the dorsal hippocampus. Unexpectedly, the ensuing status epilepticus (SE) in the kindled rats did not result in the piriform cortex damage normally observed in naive rats. As a result of this surprising finding, a more comprehensive investigation was undertaken to compare dorsal hippocampal kindled and control rats on their electrographic and behavioral SE development and subsequent brain damage. The SE induction profile and the pattern of brain damage observed in our control rats was similar to previous reports [Neuroscience, 14 (1985) 375-403; Brain Res., 218 (1981) 299-318]. By contrast, although fewer kindled rats than controls responded to the initial dose of kainic acid with electrographic and behavioral seizures, those many kindled rats that did respond, showed a pattern of SE induction that was different from controls. Kindled rats manifested fewer 'wet dog shakes', more generalized convulsions and a faster development of severe limbic status (SLS) than controls. In addition, without pharmacological intervention, the SLS continued longer in kindled rats than in controls. Histological examination revealed brain damage in kindled rats that was markedly different from controls. Unlike controls, kindled rats had no damage in the piriform cortex or substantia nigra reticulata and minimal hippocampal damage, yet showed midline thalamic and anterior olfactory nuclei damage similar to controls. These differences were observed from 1 to 28 days after kindling. Although the mechanism(s) of this kindling-based neuroprotection is not known, its discovery should add importantly to our understanding of epilepsy-induced alterations of subsequent neuronal function.
Animals↗
Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity.
Apolipoprotein E (apoE), but not apoAI or apoCIII, suppresses mitogen-activated T lymphocyte proliferation, independent of the type of activation signal. Both CD4 and CD8 T cells are inhibited. ApoE inhibits T cell proliferation, in part, by reducing the production of bioactive interleukin 2 (IL2). IL2 activity is reduced by approximately 50-65% in cultures of mitogen-stimulated T cells when apoE is present. ApoE does not significantly alter levels of IL2 mRNA or the mass of secreted IL2 protein, quantitated by enzyme immunoassay. Reduced IL2 activity was not a consequence of induction of IL2 inhibitors in response to apoE or effects of apoE on the bioassay. These results suggest that apoE antagonizes post-translational events in mitogen-activated T lymphocytes that are required for the secretion of a bioactive IL2 protein.
Apolipoproteins E↗
Potassium currents in cultured rabbit retinal pigment epithelial cells.
Membrane potential and ionic currents were studied in cultured rabbit retinal pigment epithelial (RPE) cells using whole-cell patch clamp and perforated-patch recording techniques. RPE cells exhibited both outward and inward voltage-dependent currents and had a mean membrane capacitance of 26 +/- 12 pF (SD, n = 92). The resting membrane potential averaged -31 +/- 15 mV (n = 37), but it was as high as -60 mV in some cells. When K+ was the principal cation in the recording electrode, depolarization-activated outward currents were apparent in 91% of cells studied. Tail current analysis revealed that the outward currents were primarily K+ selective. The most frequently observed outward K+ current was a voltage- and time-dependent outward current (IK) which resembled the delayed rectifier K+ current described in other cells. IK was blocked by tetraethylammonium ions (TEA) and barium (Ba2+) and reduced by 4-aminopyridine (4-AP). In a few cells (3-4%), depolarization to -50 mV or more negative potentials evoked an outwardly rectifying K+ current (IKt) which showed more rapid inactivation at depolarized potentials. Inwardly rectifying K+ current (IKI) was also present in 41% of cells. IKI was blocked by extracellular Ba2+ or Cs+ and exhibited time-dependent decay, due to Na+ blockade, at negative potentials. We conclude that cultured rabbit RPE cells exhibit at least three voltage-dependent K+ currents. The K+ conductances reported here may provide conductive pathways important in maintaining ion and fluid homeostasis in the subretinal space.
Animals↗
Complications of plombage in a Cuban exile.
Collapse of the affected lung, or plombage, was a common operative treatment for tuberculosis in the United States in the 1930s and 40s. Due to the lack of antitubercular drugs, this practice continued in Cuba into the 1950s. After 41 years the plombage material in an exile patient was found to be infected. This resulted in the bronchopleural fistula which required a pectoralis muscle flap to close. Physicians should be aware that many Cuban exiles have been treated for tuberculosis via plombage and are at risk for similar complications.
Bronchial Fistula↗
A justification for high resolution hematocrit measurement.
The purpose of this study was to determine the feasibility of using a 6" digital caliper and a 20x viewing microscope to measure hematocrit (HCT) from microhematocrit tubes. The reliability and validity of the digital caliper technique (DC) was simultaneously compared with that of the conventional "turntable" style microhematocrit method (MC) and the Coulter Counter hematocrit (CC) for a comprehensive comparison of the three methods. The reliability of the three methods was assessed by computing the standard error of the measurement (SEm) on triplicate readings of human blood samples. The SEm for MC, CC, and DC methods were 0.3555, 0.3004, and 0.1491, respectively. Validity was assessed by comparing the average of the triplicate HCT readings for each method with HCT determined by densitometry. Average HCT values (+/- SE) for the MC, CC, DC, and densitometry methods were 42.3 +/- 3.2, 42.4 +/- 3.4, 43.1 +/- 3.4, 43.7 +/- 3.3, respectively. Only the DC HCT values were not different from the densitometry HCT (P > 0.05). The MC and CC values were significantly lower (P < 0.01). It is concluded that accurate, highly precise measurements of HCT are obtainable using the digital caliper. The significance for this is the increased ability to perform extremely accurate measurement of changes in plasma volume. With this information, research labs can reliably measure smaller changes in plasma than was previously possible with commercial procedures.
Adolescent↗
Kindling in the perirhinal cortex.
In vitro experiments have indicated that the perirhinal cortex is highly excitable and its relationship to the basolateral amygdala and piriform cortex is altered by previous amygdala or dorsal hippocampal kindling. As a result, we felt it was important to assess the excitability of the perirhinal cortex in vivo by comparing its kindling profile to that of the basal amygdala, piriform cortex or dorsal hippocampus. We observed that the after-discharge (AD) threshold of the perirhinal cortex was higher than the other 3 structures but the AD duration was not different. Subsequently, the perirhinal cortex kindled more rapidly than the other 3 structures, and with extremely short latencies to onset of forelimb clonus. With the view that synchronized discharge in the perirhinal-piriform area provides the critical trigger for limbic kindled convulsions, the relationship of kindling rate and convulsion latencies and durations between the 4 structures was discussed.
Amygdala↗
The effect of the 5-HT3 receptor antagonist, RS-42358-197, in animal models of anxiety.
The S-isomer of the novel 5-HT3 receptor antagonist RS-42358 ((S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1-H- benzo[de]isoquinolin-1-one, RS-42358-197) disinhibited behaviour in the mouse suppressed by the aversive situation of the light/dark test box. RS-42358-197 was effective at sub-ng/kg dose levels and the efficacy was maintained over a 100 million-fold dose range. In contrast, the R-isomer was ineffective at all doses studied. The S-isomer also disinhibited a suppressed behaviour in social interaction and elevated X-maze tests in the rat and reduced anxiety-related behaviours in a marmoset human threat test. RS-42358-197 prevented the exacerbation of the suppression of behaviour in the mouse light/dark test following withdrawal from treatment with alcohol, nicotine, cocaine and diazepam. Thus, the S-isomer of RS-42358 has a consistent non-sedating anxiolytic profile in rodent and primate models. It is exceptionally potent and a maintained efficacy at high doses distinguishes its actions from many other 5-HT3 receptor antagonists.
Animals↗
Are differences in dorsal hippocampal kindling related to amygdala-piriform area excitability?
It has been suggested that several structures associated with the amygdala-piriform (A-P) area are important, if not critical, for convulsive generalization of limbic seizures. In experiment 1, when examining the development of convulsive seizures kindled from the dorsal hippocampus (cornus ammonis; DH), a broad range of kindling rates was observed. Independent of electrode location within the hippocampus, kindling rates were correlated positively with both local and, more dramatically, distant excitability (measured by the duration of the primary and secondary hippocampal afterdischarges, respectively) at all stages of epileptogenesis. Because kindling rates were bimodally distributed, we bisected the distribution into 'faster' and 'slower' kindling rats. Here we examined the magnitude of both electrophysiological and behavioral differences between 'faster' and 'slower' rats and their changes over time. The 'faster' rats had longer primary and secondary afterdischarge (AD) durations than 'slower' rats throughout all stages of kindling. With the appearance of generalized convulsions, the 'faster' rats showed longer latencies to clonus onset, with longer clonus and AD durations than 'slower' rats. Also, the generalized convulsions of 'faster' rats appeared during a much enlarged secondary AD period, while 'slower' rats convulsed during primary AD. In both groups, convulsions were invariably associated with increased discharge in A-P associated structures. We interpreted the differences between 'faster' and 'slower' DH rats to reflect genetic differences in excitability in both local and A-P associated structures. If the DH kindling profile of the 'faster' rats differed from 'slower' rats largely because of naturally greater excitability in A-P associated structures, then experimentally increased excitability in those structures (via amygdala kindling) in a random sample of rats should duplicate much of the 'faster' DH kindling profile. In experiment 2, this outcome was observed. In conclusion, we suggest that either natural or induced differences in the excitability of A-P associated structures affect both the genesis and the profile of convulsive generalization of limbic kindled seizures.
Amygdala↗
The effects of 5-HT3 receptor antagonists in models of dependency and withdrawal.
Pharmacological manipulations to enhance 5-HT synthesis and release have been reported to reduce alcohol intake. However, recent evidence indicates that 5-HT3 receptor antagonists may also exert a similar effect in a number of species. This report reviews the existing data which implicates a central role for 5-HT3 receptors in the control of psychoactive substance abuse.
Alcohol Drinking↗
Ionic conductances in mammalian osteoclasts.
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Animals↗
Effect of charybdotoxin and leiurotoxin I on potassium currents in bullfrog sympathetic ganglion and hippocampal neurons.
The effects of charybdotoxin and leiurotoxin I were examined on several classes of K+ currents in bullfrog sympathetic ganglion and hippocampal CA1 pyramidal neurons. Highly purified preparations of charybdotoxin selectively blocked a large voltage- and Ca(2+)-dependent K+ current (IC) responsible for action potential repolarization (IC50 = 6 nM) while leiurotoxin I selectively blocked a small Ca(2+)-dependent K+ conductance (IAHP) responsible for the slow afterhyperpolarization following an action potential (IC50 = 7.5 nM) in bullfrog sympathetic ganglion neurons. Neither of the toxins had significant effects on other K+ currents (M-current [IM], A-current [IA] and the delayed rectifier [IK]) present in these cells. Leiurotoxin I at a concentration of 20 nM had no detectable effect on currents in hippocampal CA1 pyramidal neurons. This lack of effect on IAHP in central neurons suggests that the channels underlying slow AHPs in those neurons are pharmacologically distinct from analogous channels in peripheral neurons.
Animals↗