RGS14 limits seizure-induced mitochondrial oxidative stress and pathology in hippocampus.

RGS14 is a complex multifunctional scaffolding protein that is highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, RGS14 suppresses glutamate-induced calcium influx and related G protein and ERK signaling in dendritic spines to restrain postsynaptic signaling and plasticity. Previous findings show that, unlike PCs of hippocampal areas CA1 and CA3, CA2 PCs are resistant to a number of neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While RGS14 is protective against peripheral injury, similar roles for RGS14 during pathological injury in hippocampus remain unexplored. Recent studies showed that area CA2 modulates hippocampal excitability, generates epileptiform activity and promotes hippocampal pathology in animal models and patients with TLE. Because RGS14 suppresses CA2 excitability and signaling, we hypothesized that RGS14 would moderate seizure behavior and early hippocampal pathology following seizure activity, possibly affording protection to CA2 PCs. Using kainic acid (KA) to induce status epilepticus (KA-SE) in mice, we show that the loss of RGS14 (RGS14 KO) accelerated onset of limbic motor seizures and mortality compared to wild type (WT) mice, and that KA-SE upregulated RGS14 protein expression in CA2 and CA1 PCs of WT. Our proteomics data show that the loss of RGS14 impacted the expression of a number of proteins at baseline and after KA-SE, many of which associated unexpectedly with mitochondrial function and oxidative stress. RGS14 was shown to localize to the mitochondria in CA2 PCs of mice and reduce mitochondrial respiration in vitro. As a readout of oxidative stress, we found that RGS14 KO dramatically increased 3- nitrotyrosine levels in CA2 PCs, which was greatly exacerbated following KA-SE and correlated with a lack of superoxide dismutase 2 (SOD2) induction. Assessing for hallmarks of seizure pathology in RGS14 KO, we unexpectedly found no differences in neuronal injury in CA2 PCs. However, we observed a striking and surprising lack of microgliosis in CA1 and CA2 of RGS14 KO compared to WT. Together, our data demonstrate a newly appreciated role for RGS14 in limiting intense seizure activity and pathology in hippocampus. Our findings are consistent with a model where RGS14 limits seizure onset and mortality and, after seizure, is upregulated to support mitochondrial function, prevent oxidative stress in CA2 PCs, and promote microglial activation in hippocampus.

Diseases of captive yellow seahorse Hippocampus kuda Bleeker, pot-bellied seahorse Hippocampus abdominalis Lesson and weedy seadragon Phyllopteryx taeniolatus (Lacépède).

Seahorses, pipefish and seadragons are fish of the Family Syngnathidae. From 1998 to 2010, 172 syngnathid cases from the Toronto Zoo were submitted for post-mortem diagnostics and retrospectively examined. Among the submitted species were yellow seahorses Hippocampus kuda Bleeker (n=133), pot-bellied seahorses Hippocampus abdominalis Lesson (n=35) and weedy seadragons Phyllopteryx taeniolatus (Lacépède; n=4). The three most common causes of morbidity and mortality in this population were bacterial dermatitis, bilaterally symmetrical myopathy and mycobacteriosis, accounting for 24%, 17% and 15% of cases, respectively. Inflammatory processes were the most common diagnoses, present in 117 cases. Seven neoplasms were diagnosed, environmental aetiologies were identified in 46 cases, and two congenital defects were identified.

Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-Treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis.

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei. In contrast to GPi terminals, the ultrastructure of putative GABAergic nonpallidal terminals was not affected. Our results also revealed striking morphological differences in terminal volume, number/area of synapses, and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that morphologically distinct pallidothalamic terminals from single pallidal neurons may underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.

Remarks on various applications of microwave energy.

Microwave energy is an alternative energy source that is receiving a considerable amount of attention from researchers for a wide spectrum of applications. The fundamentally different method of transferring energy from the source to the sample is the main benefit of utilizing microwave energy; by directly delivering energy to microwave-absorbing materials, conventional issues such as long heating periods, thermal gradients, and energy lost to the system environment can be minimized or avoided. Furthermore, the penetrating capacity of microwave allows volumetric heating of samples. These attributes of microwave energy make utilizing it very attractive for industrial applications as an alternative to conventional processing methods. The reality is otherwise however, and limited literature is found in any given area of work. Despite the lack of focus, in most published cases, the utilization of microwave energy has produced improved results compared to conventional methods with reduced heating times or reaction temperatures. This review provides a general overview of reported applications of microwave energy in the open literature. It also attempts to summarize the results obtained for various common uses and highlights some applications that have not gathered as much attention as anticipated.

The alpha1-fetoprotein locus is activated by a nuclear receptor of the Drosophila FTZ-F1 family.

The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.

Evaluation of Microwave-Assisted Process technology for HAPSITE's headspace analysis of volatile organic compounds (VOCs).

The use of microwave energy as a heating source for the field-based headspace sampling and the subsequent determination of various volatile organic compounds (VOCs) using a field-portable HAPSITE gas chromatograph-mass spectrometer has been evaluated. A significant advantage in time reduction has been observed when using microwave energy when compared to conventional resistive-based heating. Such time savings are critical in field operations involving equipment such as the HAPSITE where non-routine sampling is commonly performed and very quick turnaround time is usually needed. Further, the technology also showed significant improvements in terms of sensitivity, thus suggesting its applicability to a broader range of compounds and detection levels than current technologies.

Incidence of fecal excretion of Mycobacterium avium subsp. paratuberculosis in dairy cows before and after the enrolment in the Québec voluntary program.

Paratuberculosis is a chronic and contagious enteric disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This disease of worldwide distribution is responsible for significant economic losses and the bacteria itself has been linked to human Crohn's disease. Paratuberculosis control programs focus on reducing MAP transmission by implementing better management practices that target infection routes. In Québec, a Voluntary Paratuberculosis Prevention and Control Program (QVPPCP) was launched in 2007. The objectives of this prospective cohort study were threefold. The first was to describe the changes in the incidence of fecal excretion of MAP in cows born before and after farm enrolment in the QVPPCP. The second was to estimate the impact of the risk of within-herd transmission of MAP (measured by the risk assessment score (RAS)) on the incidence of fecal excretion of MAP. And the third was to evaluate the impact of calf rearing practices on the incidence of fecal excretion of MAP. Eighteen MAP-positive herds were visited annually from 2011 to 2015. At each visit, individual fecal samples from all adult cows were collected. MAP was cultured using liquid media and an automated system. A risk assessment questionnaire was completed upon enrolment in the QVPPCP and at each visit. The RAS of the farm was attributed to each cow according to its birthdate. Cox proportional hazards models were used to estimate the hazard ratios (HR) for the exposure variables. Herd clustering was taken into account using robust standard errors. A total of 2158 cows were included (cohort born before n=919; cohort born after n=1239). The incidence and hazard of fecal excretion were significantly lower for the cohort-after than the cohort-before (incidence rate ratio=0.38; 95% CI: 0.18-0.78 and HR=0.48; 95% CI: 0.23-0.98). The HR of fecal excretion for cows exposed to a high RAS was 2.20 times (95% CI: 1.21-3.99) that of cows exposed to a low RAS. Poor calving cow hygiene (HR=3.41; 95% CI: 1.40-8.31) and contact between pre-weaned heifers and adult cows or their feces were significantly associated with an increased hazard of fecal excretion of MAP (HR=2.66; 95% CI: 1.08-6.56). Our results suggest that enrolment in the QVPPCP reduces the risk of MAP fecal excretion. They support the hypothesis that contact between calves and adult cows or their feces increases MAP transmission. The incidence results also suggest that MAP prevalence could be reduced to low levels regardless of initial MAP prevalence.

Cryopreserved mitral homograft in the tricuspid position for infective endocarditis: a valve that can be repaired in the long-term (13 years).

Herein is reported the long-term repair of a cryopreserved mitral homograft in the tricuspid position. A 34-year-old HIV-infected patient underwent tricuspid valve replacement in 1991 with a cryopreserved mitral homograft because of infective endocarditis. Chronic tricuspid regurgitation secondary to repeated endocarditis led to reoperation 13 years later. Mitral valve repair was performed with a rigid ring as there was annular dilatation; the valve tissue was intact. One year later, transthoracic echocardiography showed no tricuspid regurgitation. The cryopreserved mitral homograft is a potentially repairable valve in the long-term.

Subcellular and subsynaptic localization of presynaptic and postsynaptic kainate receptor subunits in the monkey striatum.

The localization and functions of kainate receptors (KARs) in the CNS are still poorly known. In the striatum, GluR6/7 and KA2 immunoreactivity is expressed presynaptically in a subpopulation of glutamatergic terminals and postsynaptically in dendrites and spines. The goal of this study was to further characterize the subcellular and subsynaptic localization of kainate receptor subunits in the monkey striatum. Immunoperoxidase data reveal that the relative abundance of GluR6/7- and KA2-immunoreactive terminals is homogeneous throughout the striatum irrespective of the differential degree of striatal degeneration in Huntington's disease. Pre-embedding and post-embedding immunogold data indicate that >70% of the presynaptic or postsynaptic GluR6/7 and KA2 labeling is expressed intracellularly. In material stained with the post-embedding immunogold method, approximately one-third of plasma membrane-bound gold particles labeling in axon terminals and spines is associated with asymmetric synapses, thereby representing synaptic kainate receptor subunits. On the other hand, >60% of the plasma-membrane bound labeling is extrasynaptic. Both GluR6/7 and KA2 labeling in glutamatergic terminals often occurs in clusters of gold particles along the membrane of large vesicular organelles located at various distances from the presynaptic grid. Anterograde labeling from the primary motor cortex or the centromedian thalamic nucleus indicate that both corticostriatal and thalamostriatal terminals express presynaptic GluR6/7 and KA2 immunoreactivity in the postcommissural putamen. In conclusion, these data demonstrate that kainate receptors in the striatum display a pattern of subcellular distribution different from other ionotropic glutamate receptor subtypes, but consistent with their metabotropic-like functions recently shown in the hippocampus.

Synaptic and extrasynaptic GABA-A and GABA-B receptors in the globus pallidus: an electron microscopic immunogold analysis in monkeys.

GABA-A and GABA-B receptors mediate differential effects in the CNS. To better understand the role of these receptors in regulating pallidal functions, we compared their subcellular and subsynaptic localization in the external and internal segments of the globus pallidus (GPe and GPi) in monkeys, using pre- and post-embedding immunocytochemistry with antibodies against GABA-A (alpha1, beta2/3 subunits) and GABA-BR1 receptor subtype. Our results demonstrate that GABA-A and GABA-B receptors display a differential pattern of subcellular and subsynaptic localization in both segments of the globus pallidus. The majority of GABA-BR1 immunolabeling is intracellular, whereas immunoreactivity for GABA-A receptor subunits is mostly bound to the plasma membrane. A significant proportion of both GABA-BR1 and GABA-A receptor immunolabeling is extrasynaptic, but GABA-A receptor subunits also aggregate in the main body of putative GABAergic symmetric synapses established by striatal- and pallidal-like terminals. GABA-BR1 immunoreactivity is expressed presynaptically in putative glutamatergic terminals, while GABA-A alpha1 and beta2/3 receptor subunits are exclusively post-synaptic and often coexist at individual symmetric synapses in both GPe and GPi. In conclusion, our findings corroborate the concept that ionotropic and metabotropic GABA receptors are located to subserve different effects in pallidal neurons. Although the aggregation of GABA-A receptors at symmetric synapses is consistent with their role in fast inhibitory synaptic transmission, the extrasynaptic distribution of both GABA-A and GABA-B receptors provides a substrate for complex modulatory functions that rely predominantly on the spillover of GABA.

Influence of human immunodeficiency virus 1 infection and degree of immunosuppression in the clinical characteristics and outcome of infective endocarditis in intravenous drug users.

BACKGROUND: Immunosuppression caused by human immunodeficiency virus 1 (HIV) infection appears to modify the clinical characteristics and to increase the severity of several bacterial infections. The impact of HIV infection and the degree of immunosuppression on the clinical characteristics and outcome of infective endocarditis (IE) in intravenous (IV) drug users has not been well characterized. METHODS: Prospective cohort study among 292 consecutive IV drug users with IE diagnosed in 2 academic institutional hospitals in Barcelona, Spain, from January 1, 1984, to October 31, 1995. Serostatus of HIV infection was documented in 283 patients. We measured demographics, clinical and biological data, cause, echocardiographic findings, HIV serostatus and classification, CD4 cell count, complications, and mortality. RESULTS: Among the 283 episodes of IE, 216 (76.3%) were in HIV-infected patients and 67 (23.7%) in non-HIV-infected patients. Rate of IE per 1000 admissions ranged from 0.17 to 0.82 per year, peaking in 1989. Characteristics of IE independently associated with HIV infection were right-side involvement (odds ratio [OR], 7.6; 95% confidence interval [CI], 3.5-16.7), a micro-organism different from viridans streptococci (OR, 2.5; 95% CI, 1.1-5.9), duration of drug abuse longer than 5 years (OR, 5.0; 95% CI, 2.4-10.3), and white blood cell count of no more than 10 X 10(9)/L (OR, 2.2; 95% CI, 1.1-4.2). There were no significant differences in mortality due to IE according to HIV serostatus. Among the 216 patients with HIV infection, the variables independently associated with worse outcome were CD4 cell count lower than 0.200 x 10(9)/L and left-sided or mixed IE. CONCLUSIONS: Although there is a difference in clinical presentation in IE in IV drug users, outcome was similar according to their HIV status. However, among HIV-infected patients, severe immunosuppression and mixed or left-side valvular involvement were strong risk factors for mortality.

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

G-Protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension.

A functional genetic variant consisting of a C825T substitution in the GNB3 gene, encoding for the G-protein beta(3) subunit, has been associated with enhanced G-protein activation and cell growth. The aim of the study was to investigate the association of this polymorphism with left ventricular hypertrophy (LVH) in a sample of patients with essential hypertension. Left ventricular mass was assessed by 2-mode echocardiography in 86 patients with essential hypertension, and GNB3 C825T genotype was determined by polymerase chain reaction and restriction digestion. Thirty-seven (0.43) patients were homozygous for the C allele (CC), 40 (0.47) were heterozygous (CT), and 9 (0.10) were homozygous for the T allele (TT). The genotype distribution among the patients was in Hardy-Weinberg equilibrium. Values of left ventricular end-diastolic diameter (52.0+/-0.7 versus 48.9+/-0.9 mm, P=0.007), posterior wall thickness (11.3+/-0.2 versus 10.6+/-0.2 mm, P=0.042), and left ventricular mass index (152.7+/-4.4 versus 135.2+/-6.4 g/m(2), P=0. 023) were significantly higher in patients with CT and TT genotypes considered together (CT+TT) than in CC patients. The distribution of the genotypes was significantly different when comparing patients with LVH: 20 (0.33) CC and 40 (0.67) CT+TT patients had this complication, and 17 (0.65) CC and 9 (0.35) CT+TT patients did not (P<0.01). The frequency of the T allele was significantly different among patients with (0.40) and without (0.20) LVH (P<0.01). A logistic regression analysis showed that the association between the T allele and LVH was independent of age, mean blood pressure, body mass index, and alcohol consumption. The relative risk of LVH in patients bearing the T allele (CT+TT group) compared with CC hypertensive patients was 3.03 (95% CI 1.14 to 8.05). The findings suggest an association between LVH and the 825T allele in hypertensive patients.

Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse.

Seventeen intravenous abusers of methadone underwent clinical, roentgenologic and physiologic assessment. Two complained of dyspnea on exertion and two had cor pulmonale. Of 15 patients whose fundi were examined, nine had talc particles in their retinal vessels. The chest roentgenograms of seven showed a diffuse pin-point micronodular pattern and two of the seven also manifested volume loss, one with coalescence of opacities simulating progressive massive fibrosis. Twelve patients had some degree of pulmonary dysfunction, 10 with lowered steady state diffusing capacity and 11 with decreased flow rates (FEV1 and MMF). There was no hyperinflation, but two showed an increase in residual volume. Corticosteroid therapy was attempted on two and was ineffective. Necropsy on the one patient who died revealed severe pulmonary fibrosis and talc granulomas in lungs, liver, kidneys and lymph nodes.

Differential innervation of parvalbumin-immunoreactive interneurons of the basolateral amygdaloid complex by cortical and intrinsic inputs.

In the basolateral (BL) amygdaloid complex, the excitability of projection cells is regulated by intrinsic inhibitory interneurons using gamma-aminobutyric acid (GABA) as a transmitter. A subset of these cells are labeled in a Golgi-like manner by Parvalbumin (PV) immunohistochemistry. Recently, we have shown that the overwhelming majority of axon terminals contacting these PV-immunoreactive neurons form asymmetric synapses. The present study was undertaken to identify the source(s) of these inputs. Since previous work had revealed that thalamic axons form very few synapses on BL interneurons (< 1%), we focused on cortical and intra-amygdaloid inputs. Iontophoretic injections of the anterograde tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine were performed in various cortical fields in cats (perirhinal, entorhinal, pre/infralimbic cortices) and monkeys (orbitofrontal region) or in the BL amygdaloid nucleus in cats. These injections resulted in a large number of anterogradely labeled terminals forming asymmetric synapses in the BL complex. Following cortical injections, numerous anterogradely labeled terminals were found in the vicinity of PV-immunoreactive interneurons in the BL amygdala. However, only approximately 1% of these terminals formed synaptic contacts with PV-immunoreactive profiles. In contrast, as many as 11% of the terminals contributed by the intranuclear axon collaterals of BL projection cells established synapses with PV-immunoreactive elements. Since the axon terminals of PV-immunoreactive interneurons are enriched in GABA and they exclusively form symmetric synapses, these results suggest that PV-immunoreactive interneurons are predominantly involved in feedback inhibition in the BL amygdaloid complex.

Cat intraamygdaloid inhibitory network: ultrastructural organization of parvalbumin-immunoreactive elements.

Projection neurons of the basolateral (BL) amygdaloid complex are regulated by an intrinsic inhibitory network. To improve our understanding of this inhibitory circuit, we studied the synaptology of parvalbumin-immunopositive (PV+) elements as this calcium-binding protein is localized in a subpopulation of gamma-aminobutyric acid (GABA)-ergic interneurons. Two populations of PV+ cells were identified on the basis of soma shape (ovoid, type A vs. polygonal, type B). In the lateral and BL nuclei, the majority of boutons in contact with PV+ cells formed asymmetric synapses (types 1-3; 94%), whereas a minority (type 4, 6%) established symmetric synaptic contacts and resembled GABAergic terminals. In both nuclei, type B PV+ perikarya were more densely innervated than were type A neurons. However, the pattern of synaptic innervation of type B PV+ neurons differed in the two nuclei: in the lateral nucleus, they were almost exclusively innervated by a population of small, presumed excitatory terminals (type 1), whereas the four categories of terminals contributed more equally to their innervation in the BL nucleus. PV+ boutons belonged to a single category of terminals that was enriched with GABA and formed symmetric synapses mostly with the proximal part of PV neurons. The proportion of axosomatic synapses was significantly higher in the lateral nucleus than in the BL nucleus (33% vs. 18%). The reverse was true for the contacts with proximal dendrites (33% in the lateral nucleus vs. 46% in the BL nucleus). The remaining terminals formed synapses with distal dendrites (23-28%) and spines (8-12%). These results indicate that PV+ interneurons receive massive excitatory inputs and that PV+ terminals are strategically located to exert a powerful inhibitory control of amygdala neurons.

Superior vena caval obstruction. Is it a medical emergency?

With the question in mind is superior vena caval obstruction a medical emergency, we reviewed 107 cases of superior vena caval obstruction in adult patients. We sought details of the time duration between the onset of symptoms and the treatment, and examined the complication and survival of patients with this disorder. Fifteen percent of the cases developed from benign causes. In 41 percent there was a previously recognized disease as the etiology. Benign disorders required longer to make the diagnosis. No serious complication resulted from the superior vena caval obstruction itself nor investigative procedures leading to the diagnosis despite, in some cases, a prolonged period between the onset of symptoms and the initiation of therapy. Prognosis and response to treatment were dependent on the underlying cause of the superior vena caval obstruction. Although several cases of tracheal obstruction were included in this series, we did not address the question of whether tracheal obstruction is or is not a medical emergency. No support was found for the notion that superior vena caval obstruction in itself represents a radiotherapeutic emergency.

Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat: Phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level.

The amygdaloid complex plays an essential role in auditory fear conditioning of the Pavlovian type. The available evidence suggests that the lateral nucleus is the input station of the amygdala for auditory conditioned stimuli, whereas the central medial nucleus is the output for conditioned fear responses. However, the intrinsic pathway transmitting auditory information about the conditioned stimulus from the lateral to the central medial nuclei is unknown as there are no direct projections between these nuclei. The present study was undertaken to determine if the main intra-amygdaloid targets of the lateral nucleus, namely the basomedial and basolateral nuclei, project to the central medial nucleus. To this end, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin were performed in these nuclei. To rule out the possibility that the anterograde labeling reflected passing fibers merging with the major fiber bundles that course in and around the central medial nucleus, labeled terminals and varicosities were observed in the electron microscope. It was determined that the basolateral and basomedial nuclei have partially overlapping intraamygdaloid targets. They both project to the central medial nucleus, nucleus of the lateral olfactory tract and peri-amygdaloid cortex, but have limited projections to each other. Small Phaseolus vulgaris-leucoagglutinin injections in both nuclei gave rise to prominent intranuclear projections but only the basomedial nucleus was found to project to the lateral and anterior cortical nuclei. At the electron microscopic level, all labeled axon terminals and varicosities formed asymmetric synapses (n = 245) with dendritic spines (83%) or with dendritic shafts (17%). This is the first unambiguous demonstration that the basolateral and basomedial nuclei project to the central medial nucleus. Since these nuclei constitute the main intra-amygdaloid targets of the lateral nucleus, they represent likely candidates for the transmission of auditory conditioned stimuli to the central medial nucleus in auditory fear conditioning.

Differential subcellular and subsynaptic distribution of GABA(A) and GABA(B) receptors in the monkey subthalamic nucleus.

The activation of GABA receptor subtype A (GABA(A)) and GABA receptor subtype B (GABA(B)) receptors mediates differential effects on GABAergic and non-GABAergic transmission in the basal ganglia. To further characterize the anatomical substrate that underlies these functions, we used immunogold labeling to compare the subcellular and subsynaptic localization of GABA(A) and GABA(B) receptors in the subthalamic nucleus (STN). Our findings demonstrate major differences and some similarities in the distribution of GABA(A) and GABA(B) receptors in the monkey STN. The immunoreactivity for GABA(A) receptor alpha1 subunits is mostly bound to the plasma membrane, whereas GABA(B) R1 subunit alpha1 immunoreactivity is largely expressed intracellularly. Plasma membrane-bound GABA(A) alpha1 subunit aggregate in the main body of putative GABAergic synapses, while GABA(B) R1 receptors are found at the edges of putative glutamatergic or GABAergic synapses. A large pool of plasma membrane-bound GABA(A) and GABA(B) receptors is extrasynaptic. In conclusion, these findings demonstrate a significant degree of heterogeneity between the distributions of the two major GABA receptor subtypes in the monkey STN. Their pattern of synaptic localization puts forward interesting questions regarding their mechanisms of activation and functions at GABAergic and non-GABAergic synapses.

Myocardial infarction with normal coronary arteries: a prospective clinical-angiographic study.

The association of myocardial infarction with normal coronary arteries was analyzed prospectively. A series of 259 consecutive men aged 60 years or less underwent selective coronary angiography 30 days after a definite infarct. Coronary arterial lesions were documented in 251 patients, normal coronary arteries in the remaining 8. The latter patients had a significantly lower (p less than 0.001) mean age than the former; no patient older than 50 years had patent coronary arteries, whereas 5 of the 11 patients under age 35 had normal arteries. The prevalence of risk factors was similar in both groups of patients. Although there were no group differences in infarct size or location, patients with normal coronary arteries had a higher ejection fraction (p less than 0.01) and a lower left ventricular end-diastolic pressure (p less than 0.05). A previous history of angina or infarction and the occurrence of new coronary events were confined to patients with coronary arterial lesions. The clinical course of patients presenting with normal angiograms was uneventful. Transient coronary occlusion, the most likely mechanism of infarction in this group of patients, could not be ascribed to either spasm or platelet hyperactivity.