Mycobacterium interjectum Lung Infection.

A 62-year-old male presented with productive cough, weight loss, and night sweats. CXR revealed a right upper lobe cavitary lesion. Evaluation was negative for Mycobacterium tuberculosis, and sputum revealed Mycobacterium avium intracellulare (MAI). Since his clinical course was atypical for MAI, further investigations were pursued which identified Mycobacterium interjectum in lung specimens, a very rarely described etiology of pulmonary disease. Appropriate therapy with rifampin, intravenous amikacin, trimethoprim/sulfamethoxazole (TMP/SMX), and ethambutol resulted in clinical and radiographic improvement. This is the third case described over a period of 20 years of destructive lung disease in an immunocompetent adult due to M. interjectum.

Analysis of behavior-related excitatory inputs to a central pacemaker nucleus in a weakly electric fish.

Gymnotid electric fish explore their environment and communicate with conspecifics by means of rhythmic electric organ discharges. The neural command for each electric organ discharge arises from activity of a medullary pacemaker nucleus composed of two neuronal types: pacemaker and relay cells. During different behaviors as in courtship, exploration and agonistic interactions, these species display specific electric organ discharge frequency and/or waveform modulations. The neural bases of these modulations have been explained in terms of segregation of inputs to pacemaker or relay cells, as well as differential activation of the glutamate receptors of these cells. One of the most conspicuous electric organ discharge frequency modulations in Gymnotus carapo results from the activation of Mauthner cells, a pair of reticulospinal neurons that are involved in the organization of sensory-evoked escape responses in teleost fish. The activation of Mauthner cells in these animals produces a prolonged increase in electric organ discharge rate, whose neural mechanisms involves the activation of both N-methyl-D-aspartate (NMDA) and metabotropic glutamatergic receptors of pacemaker cells. Here we provide evidence which indicates that pacemaker cells are the only cellular target of the synaptic inputs responsible for the Mauthner cell initiated electric organ discharge modulation at the medullary pacemaker nucleus. Additionally, although pacemaker cells express both NMDA and non-NMDA ionotropic receptors, we found that non-NMDA receptors are not involved in this synaptic action which suggests that NMDA and non-NMDA receptor subtypes are not co-localized at the subsynaptic membrane. NMDA receptor activation of pacemaker cells seems to be an efficient neural strategy to produce long-lasting enhancements of the fish sampling capability during Mauthner cell-initiated motor behaviors.

[Central modulation of a sensory system by a motor command. One intention with two results]. / Modulación central de un sistema sensorial por un comando motor. Una intención con dos resultados.

INTRODUCTION AND DEVELOPMENT: Neuronal mechanisms that underlie diverse sensory motor integration processes (SMI) are essential for the motor control and determine the general organization of the nervous system. Spinal cord, sensory relay nucleus of brainstem and thalamus as well as higher motor control structures are some of the levels, of increasing complexity, at which several processes of SMI occurs during the execution of a motor act. The mechanisms that underlie SMI strategies operating at higher hierarchical levels of motor control are poorly understood. Escape response in teleosts fish is an advantageous experimental model for the analysis of the neural basis of behavior and of the mechanisms and functional consequences of diverse strategies of ISM. We describe several levels of ISM that operate in the neural system that organize this response in most teleosts and we deal with a detailed description of a novel strategy that occurs in Gymnotus carapo, a South American weakly electric fish. In this species, the activation of the Mauthner cell, a command neuron for the initial phase of escape, produces a powerful modulation of the sensory system responsible for active electrorreception, its main sensory modality. CONCLUSION: The neural basis of behavior, even those relatively simple, exhibit several strategies of complex SMI that determine its performance and whose cellular mechanisms begin to be unraveled.

Modulación central de un sistema sensorial por un comando motor. Una intención con dos resultados / Central modulation of a sensory system by a motor command. One intention with two results

Introducción y desarrollo. Los mecanismos neuronales que subyacen a los procesos de integración sensoriomotora (ISM) son esenciales para el control motor y pautan la organización general del sistema nervioso. La médula espinal, los núcleos de relevo sensorial en el tronco encefálico y tálamo, así como los centros superiores de control motor, son algunos niveles, de complejidad creciente, en los que se verifican procesos de ISM durante la ejecución de un acto motor. Los mecanismos que subyacen a las estrategias más complejas de ISM, en general, se conocen poco. La respuesta de escape en peces teleósteos constituye un modelo experimental de elección para el análisis de las bases neuronales de la conducta, y particularmente de los mecanismos y consecuencias funcionales de diversas estrategias de ISM. Se describen los niveles de ISM que operan en este sistema en la mayoría de los teleósteos y se refiere en detalle una estrategia novedosa que ocurre en Gymnotus carapo, pez eléctrico sudamericano de descarga débil. En esta especie, la activación de la célula de Mauthner, responsable de la fase inicial del comportamiento de escape, produce una poderosa modulación del sistema sensorial que organiza la electrorrecepción activa, su principal modalidad sensorial. Conclusión. Las claves de organización del sistema nervioso para la elaboración de comportamientos efectores, aún aquellos relativamente sencillos, incluyen estrategias complejas de ISM que determinan de su desempeño y cuyos mecanismos comienzan a develarse (AU)

Introduction and development. Neuronal mechanisms that underlie diverse sensory-motor integration processes (SMI) are essential for the motor control and determine the general organization of the nervous system. Spinal cord, sensory relay nucleus of brainstem and thalamus as well as higher motor control structures are some of the levels, of increasing complexity, at which several processes of SMI occurs during the execution of a motor act. The mechanisms that underlie SMI strategies operating at higher hierarchical levels of motor control are poorly understood. Escape response in teleosts fish is an advantageous experimental model for the analysis of the neural basis of behavior and of the mechanisms and functional consequences of diverse strategies of ISM. We describe several levels of ISM that operate in the neural system that organize this response in most teleosts and we deal with a detailed description of a novel strategy that occurs in Gymnotus carapo, a South American weakly electric fish. In this species, the activation of the Mauthner cell, a command neuron for the initial phase of escape, produces a powerful modulation of the sensory system responsible for active electrorreception, its main sensory modality. Conclusion. The neural basis of behavior, even those relatively simple, exhibit several strategies of complex SMI that determine its performance and whose cellular mechanisms begin to be unraveled (AU)

PD-L2 is a second ligand for PD-1 and inhibits T cell activation.

Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines. Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

Voltage-clamp analysis of the potentiation of the slow Ca2+-activated K+ current in hippocampal pyramidal neurons.

Exploring the principles that govern activity-dependent changes in excitability is an essential step to understand the function of the nervous system, because they act as a general postsynaptic control mechanism that modulates the flow of synaptic signals. We show an activity-dependent potentiation of the slow Ca2+-activated K+ current (sl(AHP)) which induces sustained decreases in the excitability in CA1 pyramidal neurons. We analyzed the sl(AHP) using the slice technique and voltage-clamp recordings with sharp or patch-electrodes. Using sharp electrodes-repeated activation with depolarizing pulses evoked a prolonged (8-min) potentiation of the amplitude (171%) and duration (208%) of the sl(AHP). Using patch electrodes, early after entering the whole-cell configuration (<20 min), responses were as those reported above. However, although the sl(AHP) remained unchanged, its potentiation was markedly reduced in later recordings, suggesting that the underlying mechanisms were rapidly eliminated by intracellular dialysis. Inhibition of L-type Ca2+ current by nifedipine (20 microM) markedly reduced the sl(AHP) (79%) and its potentiation (55%). Ryanodine (20 microM) that blocks the release of intracellular Ca2+ also reduced sl(AHP) (29%) and its potentiation (25%). The potentiation of the sl(AHP) induced a marked and prolonged (>50%; approximately equals 8 min) decrease in excitability. The results suggest that sl(AHP) is potentiated as a result of an increased intracellular Ca2+ concentration ([Ca2+]i) following activation of voltage-gated L-type Ca2+ channels, aided by the subsequent release of Ca2+ from intracellular stores. Another possibility is that repeated activation increases the Ca2+-binding capacity of the channels mediating the sl(AHP). This potentiation of the sl(AHP) could be relevant in hippocampal physiology, because the changes in excitability it causes may regulate the induction threshold of the long-term potentiation of synaptic efficacy. Moreover, the potentiation would act as a protective mechanism by reducing excitability and preventing the accumulation of intracellular Ca2+ to toxic levels when intense synaptic activation occurs.

Mauthner cell-initiated electromotor behavior is mediated via NMDA and metabotropic glutamatergic receptors on medullary pacemaker neurons in a gymnotid fish.

Weakly electric fish generate meaningful electromotor behaviors by specific modulations of the discharge of their medullary pacemaker nucleus from which the rhythmic command for each electric organ discharge (EOD) arises. Certain electromotor behaviors seem to involve the activation of specific neurotransmitter receptors on particular target cells within the nucleus, i.e., on pacemaker or on relay cells. This paper deals with the neural basis of the electromotor behavior elicited by activation of Mauthner cells in Gymnotus carapo. This behavior consists of an abrupt and prolonged increase in the rate of the EOD. The effects of specific glutamate agonists and antagonists on basal EOD frequency and on EOD accelerations induced by Mauthner cell activation were assessed. Injections of both ionotropic (AMPA, kainate, and NMDA) and metabotropic (trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid) glutamate agonists induced increases in EOD rate that were maximal when performed close to the soma of pacemaker cells. In contrast, injections in the proximity of relay cells were ineffective. Therefore, pacemaker neurons are probably endowed with diverse glutamate receptor subtypes, whereas relay cells are probably not. The Mauthner cell-evoked electromotor behavior was suppressed by injections of AP-5 and (+/-)-amino-4-carboxy-methyl-phenylacetic acid, NMDA receptor and metabotropic glutamate receptor antagonists, respectively. Thus, this electromotor behavior relies on the activation of the NMDA and metabotropic glutamate receptor subtypes of pacemaker cells. Our study gives evidence for the synergistic effects of NMDA and metabotropic receptor activation and shows how a simple circuit can produce specific electromotor outputs.

The activity-dependent potentiation of the slow Ca2+-activated K+ current regulates synaptic efficacy in rat CA1 pyramidal neurons.

Activity-dependent modifications of neuronal excitability are of key functional importance because they accomplish general postsynaptic control of the flow of synaptic signals. We tested the modifications of synaptic efficacy evoked in rat CA1 hippocampal pyramidal neurons during the short-term activity-dependent reduction in excitability termed "response depression". The in vitro slice technique and recordings with sharp electrodes in the current- and voltage-clamp modes were used. Depression was induced by repeatedly stimulating the Schaffer collateral and stratum oriens. Repeated synaptic stimuli also depressed subsequent responses evoked by transmembrane current pulse injection and vice versa. Depression was characterised by a marked decrease in synaptic efficacy that outlasted stimuli for several minutes and was generalized to all pyramidal cells. The action potential frequency adaptation, the slow after-hyperpolarization and the underlying slow Ca2+-dependent K+ current (IAHP) were potentiated during depression. The potentiated IAHP caused depression by acting as a cumulative negative feedback that reduced synaptic efficacy by increasing the membrane conductance and hyperpolarizing the neurone. This depression may act as a homeostatic negative feedback mechanism to limit the rise in intracellular Ca2+ concentration and stabilize the membrane potential following intense synaptic activation.

[Maternal and neonatal Pasteurella multocida infection]. / Infection maternelle et néonatale à pasteurella multocida.

BACKGROUND: Materno-fetal infection due to Pasteurella multocida is rare; it may be severe in the neonate. CASE REPORT: A 27-year old woman was admitted at 37 weeks' gestation with a history of abdominal cramps. Twenty-four hours after delivery, the mother was febrile (40 degrees C) and was given intravenous cefotaxime (2 days), followed by cefpodoxime (15 days). The newborn was febrile and hypotonic 24 hours after birth; he received an infusion of hydroxyethylamidon and was given cefotaxime (3 days), netilmicin (6 days) and amoxicillin (10 days). Pasteurella multocida was isolated from placenta, blood and gastric fluid in the baby and in blood cultures and vaginal swab in the mother. It was established that the mother was bitten by her dog during the pregnancy and wounded a few days before delivery. CONCLUSION: This neonate was infected during the delivery and the source of mother's contamination was easy to determinate: pet animals were kept by the family and there was an history of wounds during her pregnancy.

The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat.

The nature of the synaptic drive from the locomotor spinal network onto the motoneurons was studied in the newborn rat. For this purpose, an in vitro isolated spinal cord preparation of newborn rat was used. The recording chamber was partitioned with Vaseline walls to separate the L1/L2 lumbar segments, in which the spinal locomotor network is located, from the motoneurons in the lower lumbar segments. Locomoter-like activity was induced by bath-applying a mixture of serotonin and NMDA to segments L1/L2. In this way, the synaptic activity could be modified at the lower lumbar level without affecting the motor pattern. The drive elicited onto the motoneurons during sequences of locomoter-like activity, which was monitored by performing intracellular recordings, consisting of an inhibitory component followed by an excitatory component. The inhibitory synaptic volley was reversed at a membrane potential of --60 mV with K acetate electrodes, whereas it was shifted toward positive values with KCl electrodes. The glycinergic blocker strychnine, bath-applied to segments L3/L5, blocked the inhibitory drive without affecting the rhythmic activity, whereas it disrupted the locomoter-like activity when bath-applied to segments L1/L2. The inhibitory part of the drive was more sensitive than the excitatory part to changes in the membrane potential. The excitatory phase was mixed and consisted of an NMDA and a non-NMDA component, which were sensitive to 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. It was concluded that the locomotor network located in segments L1/L2 sends a biphasic projection to the various groups of motoneurons located along the lumbar spinal cord.

Right hemispheric function in normals, affective disorder and schizophrenia.

The happy-sad chimeric faces test has been established as a useful test of right hemispheric function. It is known to elicit a left hemifacial bias (LHF bias) in right handed subjects. 41 normals and 19 manic, depressive and schizophrenic patients each were tested. All subjects were strictly right handed. Normals and depressives showed significant LHF bias. Monies and schizophrenics did not show significant LHF Bias. This suggests right hemispheric dysfunction in both mania and schizophrenia.

Activity-dependent response depression in rat hippocampal CA1 pyramidal neurons in vitro.

1. A gradual and prolonged decrease of the response, termed here "depression," evoked by repeated activation with transmembrane current stimuli was analyzed in rat CA1 hippocampal pyramidal cells under single-electrode current clamp by the use of the in vitro slice technique. 2. Depression was induced by 2-s duration 0.3- to 0.7-nA current pulses presented as a sequence of 12 stimuli at 3- to 60-s intervals. Sinusoidal currents (0.5-1.0 nA) at 5-Hz or 200-ms pulses repeated at 0.3-0.5/s, which may be more natural stimulations, also induced depression. 3. Depression outlasted stimulation up to 170 s in all cells tested. The initial high rate spike burst changed little (< 20%), whereas the lower rate adapted response decreased markedly (> 40%). Thus neurons increased their rate of adaptation. The afterhyperpolarizations following pulse-evoked responses increased in duration and amplitude with depression. There were input resistance (Rin) reductions at depolarized membrane potentials and during pulses. However, Rin reductions were considerably smaller or altogether absent late during interpulse intervals. Sub-threshold current stimuli were ineffective, indicating that spike activity was necessary to elicit depression. 4. Depression was 1) insensitive to the toxin omega-Agatoxin-IVA (omega-Aga-IVA; 0.5 microM), which blocked synaptic transmission, revealing a key involvement of intrinsic properties and little if any synaptic participation; 2) insensitive to 4-aminopyrydine (2.00-4.00 mM), which greatly enhanced excitatory and inhibitory synaptic efficacy, again suggesting little synaptic involvement and a principal postsynaptic participation, and no participation of the K(+)-mediated currents IA and ID; 3) abolished by carbamalcholine (5.0-20.0 microM)- an effect blocked by atropine (1.0-10.0 microM)- and reduced by Ca(2+)-free solutions, and by intracellular injection of the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), suggesting that Ca(2+)-dependent K(+)-mediated currents are key factors, with a less important participation of the K(+)-mediated IM current. 5. We conclude that depression was due to activity-dependent modifications in intrinsic properties, with little if any synaptic participation. Depression may be functionally significant because it was induced by potentially natural stimulations. A model is proposed that accounts for the main traits of depression. In the model, depression was induced by a gradual decline of the speed at which Ca2+ was buffered intracellularly; an increase in the IK(Ca)S activation rate constant also simulated depression.

Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat.

An in vitro preparation of newborn rat isolated brainstem/spinal cord was used in order to locate the spinal network responsible in mammals for producing patterned locomotor activity. The spinal cord was partitioned by building Vaseline walls at various lumbar levels. When a mixture of serotonin and N-methyl-D,L-aspartate was bath applied to the upper lumbar cord (L1/L2 segments), rhythmic locomotor-like activity was induced and recorded in all the lumbar segments (from L1 to L5). Conversely, when the mixture of transmitters was bath applied to the lower lumbar cord, only tonic activity was induced in the lower lumbar segments. Intracellular recordings performed on motoneurons revealed that during elicited L1/L2 locomotor-like activity, they received a rhythmic synaptic drive that was often below the threshold for spiking, because the excitability of the neurons was too low. When the L1/L2 segments were isolated, their burst production capacities remained. The network located at the L1/L2 level was found to be responsible not only for generating the rhythm but also for organizing its alternating pattern. We demonstrated that the rhythmic synaptic drive that the motoneurons receive during locomotor-like activity comes directly from the L1/L2 network and that there is no relay at the segmental level. We conclude from our study that the network that organizes locomotion in the newborn rat is not segmentally distributed but is restricted to a specific part of the cord. This finding has important consequences, since it means that it is now feasible to study the activity of the rhythmic spinal network independently from that of the motoneurons.

Brain abscess presenting with catatonia.

A fifty year old man presented to a psychiatric unit with catatonia. He was later found to have a brain abscess in the left frontal region. Brain abscess has not been previously reported to be associated with catatonia.

Wilson's disease and catatonia.

A 12-year-old Indian boy presented to a psychiatric unit with catatonia. He was subsequently diagnosed to have Wilson's disease. Symptoms improved on treatment with penicillamine, zinc sulphate, and benzodiazepines.

Tardive dyskinesia and type II schizophrenia.

Cognitive impairment, negative and positive symptoms, primitive release reflexes, and age/temporal disorientation were assessed in 20 male patients meeting the DSM-III-R criteria for chronic schizophrenia and Schooler & Kane's criteria for TD. The control group comprised 20 age-matched male chronic schizophrenic patients without TD. Significant associations were found between TD, cognitive impairment, some negative symptoms, and formal thought disorder. These associations were independent of other illness and treatment variables. The severity of TD correlated significantly with that of cognitive impairment.

The stability of symptoms and syndromes in chronic schizophrenic patients.

36 chronic schizophrenic patients meeting D.S.M. III - R criteria were assessed by a single rater using the Positive and Negative Syndrome Scale (PANSS). Ratings were repeated 9 months later by the same rater. Negative symptoms and syndromes were much more stable over time than positive symptoms and syndromes. Only hallucinations had stability comparable to the negative symptoms. Positive and negative subtypes of schizophrenia based on the composite score were very stable. Relatively few symptoms from the general psychopathology subscale were stable over time. The implications of these findings are discussed.

Electrophysiological characteristics of the Mauthner cell of the weakly electric fish Gymnotus carapo.

The Mauthner cell (M-cell) of the 'weakly electric fish' Gymnotus carapo was investigated with electrophysiological techniques. The antidromic action potential, the recurrent inhibitory input and the posterior VIIIth nerve excitatory input in this cell exhibited characteristics similar to those described in the goldfish. In addition, we found an excitatory input evoked by spinal stimulation at intensities subthreshold for M-cell axons.