Effects of chronic treatment with haloperidol and methamphetamine on hippocampal kindled seizures in the cat

We assessed the effects of chronic treatment with haloperidol (0.5-2 mg/kg/day, p.o., 17 days) and methamphetamine (1-2 mg/kg/day, p.o., 17 days; 4 mg/kg/day, p.o. 9 days) on hippocampal kindled seizures using a kindling procedure with low-frequency (about 3 Hz) electrical stimulation in cats. The number of stimulating pulses required to trigger epileptic afterdischarge (pulse-number threshold, PNT) was considered an indicator of seizure threshold. Haloperidol, 0.5 and 1.0 mg/kg, reduced the duration of epileptic afterdischarge (afterdischarge duration, ADD) without affecting PNT, and 2.0 mg/kg strongly reduced PNT and ADD. Methamphetamine, 2.0 mg/kg, reduced PNT and ADD, and 4.0 mg/kg preferentially reduced PNT. The effects of the two drugs on hippocampal kindled seizures were found to be partially opposite to those on amygdala kindled seizures, suggesting the different response of these limbic structures to dopamine receptor manipulation.     

Surgical treatment of infected intralobar pulmonary sequestration: a collective review of patients older than 50 years reported in the literature.

We report on the rare and surgical treatment of a senile patient of infected intralobar pulmonary sequestration. A 56-year-old male who had complained of headache, vomiting, cough, sputum production, and high fever was admitted to our hospital. Chest computed tomography (CT) showed an infected intralobar pulmonary sequestration as an 8x6 cm cystic mass with multiple air-fluid cavities in the left lower basal segment and severe pneumonia in the left upper and lower lobes around the mass. A 3-D CT showed an aberrant artery entering the consolidation from the descending aorta. A standard lower lobectomy was performed with a ligation of the aberrant artery with a diameter of 1 cm supplying the posterior segment of the left lower lobe. A histological examination of the lung revealed acute and chronic broncho-bronchiolitis with cystic dilatation consistent with intralobar pulmonary sequestration. We discuss the characters of senile patients compared with juvenile patients, with reference to a collective review of patients older than 50 reported in the literature.     

Schizotypal disorder and schizophrenia: a profile analysis of neuropsychological functioning in Japanese patients.

This study compares neuropsychological functioning in a Japanese schizophrenia spectrum disorder group and a group of healthy Japanese volunteers. Participants were 37 patients diagnosed with schizophrenia, 28 schizotypal patients, and 99 psychiatrically-normal volunteers. A wide range of cognitive measures were examined. All participants completed a Japanese version of a neuropsychological battery assessing executive function, working memory, processing speed, language, verbal memory, and spatial organization. Comparisons of neuropsychological function demonstrated similarities and differences between patients diagnosed with schizotypal disorder and those diagnosed with schizophrenia. Impairments in verbal memory, language, and processing speed were common to both patient groups and may represent a vulnerability to schizophrenia. Impairments in aspects of working memory, spatial organization and executive function were preferentially observed in schizophrenia and may be features of the overt manifestation of psychosis. Possible differences in the contributions of prefrontal and temporo-limbic structures provide direction for further studies.     

Activation of the cardiac ATP-sensitive K+ channel by ER-001533, a newly synthesized vasorelaxant.

Effects of ER-001533 (ER), a newly synthesized vasorelaxant, on the membrane currents were examined in single ventricular cells of guinea pigs. The patch-clamp technique was used in the "whole-cell" and "inside-out" patch configurations. In the whole-cell clamp condition, ER induced a time-independent K(+)-dominant current, which was inhibited by glibenclamide (1-3 microM), suggesting that ER activated the cardiac ATP-sensitive K+ channel (KATP). To elucidate the mechanism of ER-mediated KATP channel activation, the drug was applied to the inside-out patches before and after channel "run-down." Since nucleotide diphosphates could induce the channel openings after complete run-down, effects of the drug on the nucleotide diphosphate-induced channel openings were also examined. Before run-down, ER activated the KATP channel only in the presence of ATP. ER shifted the relation between [ATP]i and the channel activity to the right in a concentration-dependent fashion without a significant alteration of the slope. After channel run-down, ER did not affect the channel openings either in the absence or in the presence of UDP. However, ER could relieve the ATP-gamma-S inhibition of the UDP-induced channel openings. Thus, we conclude that ER antagonizes the inhibitory effect of ATP on the KATP channel in a competitive manner, thereby enhancing the channel openings.     

Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes

Summary Effects of verapamil on the acetylcholine (ACh)-induced K⁺ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5-triphosphate (GTP) or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K⁺ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1–100 M) depressed the ACh-induced K⁺ current in a concentration-dependent fashion. In GTP-S-loaded cells, the K⁺ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-S. Verapamil (0.1–100 M) also depressed the intracellular GTP-S-induced K⁺ current. However, the magnitude of verapamil-depression of the K⁺ current in GTP-S-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 M of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K⁺ channel itself and thereby depress the ACh-induced K⁺ current in isolated atrial myocytes.Supported by grants from the Ministry of Education, Science and Culture of Japan and the Research Program on Ca Signal Control Send offprint requests to Y. Kurachi at the above address     

Afferent fiber connections from lower brain stem to hypothalamus studied by the horseradish peroxidase method with special reference to noradrenaline innervation

Summary Attempts were made to determine the afferent projections to the anterior hypothalamus including the preoptic area from the lower brain stem by means of the horseradish peroxidase method combined with monoamine oxidase staining to identify noradrenaline (NA) neurons. In addition to this technique, a histofluorescence analysis was performed. NA fibers in the medial part of the anterior hypothalamus were mainly supplied by A1 and A2 NA neuron groups, while the lateral part and periventricular zone received NA terminals from both pontine and medulla oblongata NA neuron groups. Furthermore, the present study indicated that there were direct projections to the anterior hypothalamus from non-noradrenergic neurons in the lower brain stem: nuclei raphe dorsalis, centralis superior, cells in the mesencephalic and pontine central gray matter, nuclei parabrachialis lateralis and medialis, cells around fasciculus longitudinalis medialis.Abbreviations CA Commissura anterior - CO Chiasma opticum - DP Decussatio pyramidum - DPCS Decussatio pedunculorum cerebellarium superiorum - F Columna fornicis - FLM Fasciculus longitudinalis medialis - FMT Fasciculus mamillothalamicus - GCM Griseum centrale mesencephali - GCP Griseum centrale pontis - LL Lemniscus lateralis - LM Lemniscus medialis - PCM Pedunculus cerebellaris medius - PCS Pedunculus cerebellaris superior - TO Tractus opticus - TS Tractus solitarius - TVme Tractus mesencephalicus nervi trigemini - V Ventriculus tertius - VTS Tractus spinalis nervi trigemini - am nucleus ambiguus - B Barrington nucleus - com nucleus commissuralis - cp nucleus caudatus putamen - cs nucleus centralis superior - ct nucleus corporis trapezoidei - cu nucleus cuneatus - dX nucleus dorsalis nervi vagi - Gd nucleus tegmentalis dorsalis (von Gudden) - gr nucleus gracilis - Gv nucleus tegmentalis ventralis (von Gudden) - ha nucleus hypothalamicus anterior - hl nucleus hypothalamicus lateralis - hpe nucleus periventricularis (hypothalami) - hvm nucleus ventromedialis hypothalami - lc nucleus locus coeruleus - oi nucleus olivaris inferior - p nucleus pontis - pa nucleus paraventricularis - pbl nucleus parabrachialis lateralis - pbm nucleus parabrachialis medialis - ph nucleus praepositus hypoglossi - pol nucleus preopticus lateralis - pom nucleus preopticus medialis - pop nucleus preopticus periventricularis - rd nucleus raphe dorsalis - re nucleus reuniens - rl nucleus reticularis lateralis - rm nucleus raphe magnus - ro nucleus raphe obscrus - sc nucleus suprachiasmaticus - so nucleus supraopticus - st nucleus interstitialis striae terminalis - td nucleus tractus diagonalis (Broca) - ts nucleus tractus solitarii - Vme nucleus mesencephalicus nervi trigemini - Vmo nucleus motorius nervi trigemini - Vts nucleus tractus spinalis nervi trigemini - XII nucleus nervi hypoglossi     

The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells

 The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (K_ATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a K _i value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATP_i) equipotently in the presence and in the absence of intracellular Mg²⁺ (Mg²⁺ _i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATP_i only in the presence of Mg²⁺ _i. Uridine 5’-diphosphate (UDP) antagonized the ATP_i-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATP_i-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac K_ATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the K_ATP channel. Received: 24 October 1997 / Received after revision and accepted: 4 December 1997     

Priming effect of RANTES on eosinophil oxidative metabolism

Background RANTES has been shown to possess chemotactic activity for eosinophils, which have also been considered to play a role in allergic inflammation through reactive oxygen species. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils.
Methods Purified eosinophils by CD16-negative selection or an eosinophilic cell line (EoL-1) were incubated with or without RANTES (2.5 x 10⁻⁶). To the mixture of eosinophils and luminol, calcium ionophore (A23187) or opsonized zymosan (OZ) was added, and radical oxygen products were determined by luminol-dependent chemiluminescence for 600 s.
Results Eosinophil-mediated radical oxygen products of untreated eosinophils produced with A23187 gave a peak value of 14.09 + 2.40 (mean±SE, n = 12) relative light units (RLU) and an integrated value of 3232.20 + 513.09 RLU. However, with treatment with RANTES, a peak value of 18.66 + 2.40 RLU and an integrated value of 5301.05 ±561.02 RLU were obtained. Eosinophil oxidative metabolism-induced A23187 or OZ was apparently augmented by the preincubation with RANTES. In addition, the radical oxygen products of EoL-1 showed similar results.
Conclusions Thus, we concluded that RANTES may play an important role the pathogenesis of allergic inflammation through its involvement in eosinophil activation, as evidenced by oxygen products, as well as in selective eosinophil infiltration as selective eosinophil chemoattractant.     

Short-term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP-binding proteins

The short-term desensitization of the acetylcholine (ACh)-induced K⁺ channel current was examined in single atrial cells of guinea-pig heart. The tight-seal whole cell voltage clamp technique was used. The solution in the pipettes contained GTP or guanosine-5-O-(3-thiotriphosphate) (GTP-S, a non-hydrolyzable GTP analogue). In GTP-loaded cells, ACh evoked a specific K⁺ channel current via GTP-binding proteins (G) in a dose-dependent manner. The K⁺ current showed agonist-dependent desensitization similar to those reported in other cardiac tissues (Nilius 1983; Carmeliet and Mubagwa 1986). The cellular response to ACh was also desensitized by activation of P1-purinergic receptors with adenosine (Ado). In GTP-S-loaded cells, the K⁺ current was gradually induced even in the absence of agonists, probably due to direct activation of G proteins by GTP-S. In the early phase of the spontaneous current increase, ACh evoked a large current transiently. As the GTP-S-induced activation of the current progressed, the magnitude of the ACh-evoked current transient became smaller and finally negligible. Similar results were obtained when Ado was used as an agonist instead of ACh to induce the K⁺ current. Therefore, it is indicated that the agonistreceptor interaction may not be essential for the desensitization of ACh-induced K⁺ current in atrial myocytes.     

Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: a MRI study

BACKGROUND: Schneider's first-rank symptoms involve an alienated feature of the sense of one's own mental or physical activity. To clarify the brain morphological basis for the production of these symptoms, volumes of the frontal and medial temporal regions and their clinical correlates were examined in patients with schizophrenia. METHOD: Twenty-two patients with schizophrenia and 44 age- and gender-matched healthy control subjects were included. All patients were in their psychotic episodes with definite Schneiderian symptoms, rated by using the Scale for Assessment of Positive Symptoms. Volumetric measurements of high-resolution magnetic resonance imaging were performed in the prefrontal area, cingulate gyrus, and precentral gyrus, and the medial temporal structures such as the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: Patients had significantly decreased volumes in the cingulate gray matter and the amygdala compared to controls. In the patient group, Schneiderian symptom severity showed significant inverse correlations with volumes of the right posterior cingulate gray matter and of the left anterior parahippocampal gyrus. CONCLUSIONS: Schneiderian symptoms may be associated with morphological abnormalities in the limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus, which possibly serve the self-monitoring function and the coherent storage and reactivation of information.