DEVELOPMENTAL NEUROBIOLOGY, Issue 12 2007
Annette K. McCabe
Abstract Spontaneous, synchronized electrical activity (SSA) plays important roles in nervous system development, but it is not clear what causes it to start and stop at the appropriate times. In previous work, we showed that when SSA in neonatal mouse cortex is blocked by TTX in cultured slices during its normal time of occurrence (E17,P3), it fails to stop at P3 as it does in control cultured slices, but instead persists through at least P10. This indicates that SSA is self-extinguishing. Here we use whole-cell recordings and [Ca2+]i imaging to compare control and TTX-treated slices to isolate the factors that normally extinguish SSA on schedule. In TTX-treated slices, SSA bursts average 4 s in duration, and have two components. The first, lasting about 1 s, is mediated by AMPA receptors; the second, which extends the burst to 4 s and is responsible for most of the action potential generation during the burst, is mediated by NMDA receptors. In later stage (P5,P9) control slices, after SSA has declined to about 4% of its peak frequency, bursts lack this long NMDA component. Blocking this NMDA component in P5,P9 TTX-treated slices reduces SSA frequency, but not to the low values found in control slices, implying that additional factors help extinguish SSA. GABAA inhibitors restore SSA in control slices, indicating that the emergence of GABAA -mediated inhibition is another major factor that helps terminate SSA. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source]

Nonoperative treatment of four esophageal perforations with hemostatic clips

DISEASES OF THE ESOPHAGUS, Issue 5 2007
A. Fischer
SUMMARY., Spontaneous or iatrogenic esophageal perforations are despite advances of modern surgery and intensive care medicine still potentially life-threatening events with a considerable mortality rate. Recently, encouraging results on the sealing of esophageal perforations by placement of endoluminal prostheses were reported. However, if the perforation is very proximal (close to the larynx) or very distal (involving the cardia), the situation is to our experience unsuitable for stent therapy. In these special cases non-operative treatment is still possible by application of hemostatic metal clips. We present four cases unsuitable for stent therapy where the perforation was sealed by endoscopic clip application. All patients had an uneventful recovery. Non-operative treatment of esophageal perforations with hemostatic metal clips is feasible and safe in cases not treatable with self-expanding metal stents. [source]

Characterization of the Tetanus Toxin Model of Refractory Focal Neocortical Epilepsy in the Rat

EPILEPSIA, Issue 2 2005
Karen E. Nilsen
Summary:,Purpose: To characterize in detail a model of focal neocortical epilepsy. Methods: Chronic focal epilepsy was induced by injecting 25,50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. Results: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80% of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. Conclusions: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches. [source]

Cyclosporine Induces Epileptiform Activity in an In Vitro Seizure Model

EPILEPSIA, Issue 3 2000
Michael Wong
Summary: Purpose: Cyclosporine (CSA) toxicity represents a common cause of seizures in transplant patients, but the specific mechanisms by which CSA induces seizures are unknown. Although CSA may promote seizure activity by various metabolic, toxic, vascular, or structural mechanisms, CSA also has been hypothesized to modulate neuronal excitability directly. The objective of this study was to determine if CSA exerts direct epileptogenic actions on neurons in an in vitro seizure model. Methods: Combined hippocampal-entorhinal cortex slices from juvenile rats were exposed directly to artificial cerebro-spinal fluid (ACSF) containing either (a) 1.0 mM magnesium sulfate (control), (b) 1.0 mM sodium sulfate (low-magnesium), or (c) 1.0 mM magnesium sulfate + CSA (1,000,10,000 ng/ml). Spontaneous and evoked extracellular field potentials were recorded simultaneously from the dentate gyrus (DG) and CA3 hippocampal regions. Evoked synaptic responses were elicited by stimulation of the entorhinal cortex/perforant pathway. Results: CSA elicited spontaneous or stimulation-induced epileptiform activity in the DG or CA3 region of ,40% of slices, consisting of brief repetitive "interictal" discharges or prolonged stereotypical "ictal" discharges. Mean latency to epileptiform activity was ,100 min after onset of CSA application. The interictal discharges were inhibited by the non-NMDA antagonist, NBQX. Similar epileptiform activity was observed in low-magnesium ACSF without CSA. In control ACSF alone, epileptiform activity was not seen, except for rare spontaneous potentials in the DG. Conclusions: Direct effects of CSA on neuronal excitability and synaptic transmission may contribute to seizures seen in clinical CSA neurotoxicity. [source]

Epidemiology of sharka disease in France

EPPO BULLETIN, Issue 2 2006
G. Labonne
Plum pox virus was first detected in France in the 1960s. Both PPV-D and PPV-M strains are present but epidemics related to the PPV-M strain detected in the late 1980s are the most problematic. The two PPV strains have unequal distributions in peach and apricot orchards and different prevalences. More than 20 different aphid species have been identified as vectors of PPV but most of them do not colonize Prunus species. Thus, aphids involved in the spread of PPV in orchards are essentially visiting aphids. The main sources of inoculum for the vectors are leaves and fruits of infected stone-fruit trees. Spontaneous, wild and ornamental Prunus species such as Prunus dulcis, P. spinosa or P. pissardii are susceptible to PPV isolates found in France but their role as a reservoir in sharka epidemics is probably negligible. The disease spreads rapidly in orchards but the rate of progression may vary according to the identity of the PPV strain and the Prunus species. Analysis of spatial patterns of disease has shown that secondary spread by aphids frequently occurs over short distances in the orchards (aggregated patterns) but also that dissemination at longer distances (of several hundred metres) is a common event. [source]

I think I like you: Spontaneous and deliberate evaluations of potential romantic partners in an online dating context

EUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 6 2010
Rajees Sritharan
The present research examined processes of impression formation within an online dating context. Across two studies, female participants formed impressions of a potential partner based on an online dating profile containing information about the target's facial attractiveness and self-described ambition. Afterwards, deliberate evaluations of the target were assessed with a self-report measure and spontaneous evaluations were measured with an affective priming task. The results showed that deliberate evaluations varied as a function of both self-described ambition and facial attractiveness. In contrast, spontaneous evaluations varied only as a function of facial attractiveness. Experiment 2 further showed that these effects were independent of the order in which the two types of information had been encoded. The results are discussed in terms of associative and propositional processes, and the conditions under which these processes can lead to conflicting evaluations of the same potential romantic partner. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Gastric Stasis Occurs in Spontaneous, Visually Induced, and Interictal Migraine

HEADACHE, Issue 10 2007
Sheena Aurora MD
Objective., To evaluate and compare gastric motility and emptying during spontaneous migraine to previous observations from induced migraine. Blackground., We have previously demonstrated a delay in gastric emptying both during the interictal period and during an induced migraine. A limitation noted in these studies was whether there are differences gastrointestinally during a visually induced migraine compared to spontaneous migraines. To address this, 9 additional studies have been performed to ascertain if there is a similar delay during spontaneous migraine Methods., Gastric scintigraphy using a standard meal was performed in 3 subjects during 3 periods: spontaneous migraine, induced migraine, and interictal period. Results., On average, the time to half emptying was delayed during spontaneous migraine (124 minutes), during induced migraine (182 minutes), and during the interictal period migraine (243 minutes) compared to normative values established at our center (112 minutes). On average, similar gastric slowing was seen in all 3 groups when the percentage of nuclear material remaining in the stomach at 2 hours was measured. Conclusions., This study provides additional evidence of gastric stasis in migraineurs interictally during induced and spontaneous migraine. [source]

Dyskeratosis congenita with isolated neutropenia and granulocyte colony-stimulating factor treatment

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2002
Kutluhan Yilmaz
A 3-year-old Turkish boy with a history of chronic cough, recurrent bronchopneumonia, and a borderline sweat chloride test (40 mEq/L) was referred for further evaluation to our department. He was born at term (2100 g) to a marriage with no consanguinity. His mother and father were 40 and 46 years old, respectively. Physical examination (Fig. 1) revealed hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation on the entire body, predominantly on the face, neck, arms, shoulders, and legs, which had been noticed initially at the age of 18 months. Dystrophic toenails, sparse and thin hair, and phimosis were also observed. Laboratory tests disclosed an isolated neutropenia (white blood cell count, 1800/mm3). Bone marrow (BM) aspiration showed a decreased myelopoiesis without myelodysplastic changes, but normal erythropoiesis, megakaryopoiesis, and normal stroma. Lymphocyte subgroups containing CD4, CD5, CD6, CD8, CD19, CD23, and CD25, and immunoglobulin G (IgG), IgM, IgA, and IgE, were in the normal range; hemoglobin F (HbF), 2.8%. Spontaneous and clastogen-induced chromosome breaks were not increased. A skin biopsy showed increased pigmentation at the basal layer, dyskeratotic epidermal cells, and marked IgM deposition and cytoid bodies and mild IgA and IgG deposits at the dermo-epidermal junction. Lactate response to glucose challenge, amino acid chromatography, and urine organic acid analysis were normal. Figure 1. Hypopigmented, atrophic, and hyperkeratotic skin lesions surrounded by reticulate hyperpigmentation involving predominantly the face, neck, arms, shoulders, and legs, dystrophic toenails, and sparse and thin hair A diagnosis of dyskeratosis congenita (DC) was made with typical skin lesions, dystrophic toenails, thin and sparse hair, and neutropenia with decreased myelopoiesis in BM. Treatment with granulocyte colony-stimulating factor (G-CSF) was considered for the neutropenia. As the increase in neutrophil count at a dose of 5 µg/kg was not adequate, 10 µg/kg G-CSF was tried (Fig. 2). With 10 µg/kg once to three times a week, a 1.8,4.8-fold increase in the absolute neutrophil count (ANC) was achieved with no side-effects. Treatment was more frequent during infection (days 22,28). Figure 2. Response of absolute neutrophil count (ANC) to granulocyte colony-stimulating factor (G-CSF) administration (5 µg/kg on days 1 and 3; 10 µg/kg on days 5, 10, 16, 23, 26, 28, 34, 40, 48, 54) [source]

A physics-based model of DC and microwave characteristics of GaN/AlGaN HEMTs

INTERNATIONAL JOURNAL OF RF AND MICROWAVE COMPUTER-AIDED ENGINEERING, Issue 3 2007
Jonathan C. Sippel
Abstract A physics-based model of AlGaN/GaN High Electron Mobility Transistor (HEMT) is developed for the analysis of DC and microwave characteristics. Large- and small-signal parameters are calculated for a given device dimensions and operating conditions. Spontaneous and piezoelectric polarizations at the heterointerface and finite effective width of the 2DEG gas have been incorporated in the analysis. The model predicts a maximum drain current of 523 mA/mm and transconductance of 138 mS/mm for a 1 ,m × 75 ,m device, which are in agreement with the experimental data. © 2007 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2007. [source]

Prostaglandin E2 -Mediated Anabolic Effect of a Novel Inhibitor of Phosphodiesterase 4, XT-611, in the In Vitro Bone Marrow Culture,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003
Ken-Ichi Miyamoto
Abstract The mechanism of osteoblast formation by a novel PDE4 inhibitor, XT-611, was studied in the in vitro bone marrow culture system. The compound potentiated the osteoblast differentiation through accumulation of cyclic AMP after autocrine stimulation of EP4 receptor by PGE2 in pro-osteoblastic cells. Introduction: We previously reported that inhibitors of phosphodiesterase (PDE)4 isoenzyme increase osteoblast formation in an in vitro bone marrow culture system and inhibit bone loss in animal osteoporosis models. Here we investigated the mechanism of the effect of a novel PDE4 inhibitor, 3,4-dipropyl-4,5,7,8-tetrahydro-3H -imidazo[1,2- i]-purin-5-one (XT-611), on osteoblast formation in the in vitro bone marrow culture system. Materials and Methods: Rodent bone marrow cells were cultured in the presence of 0.2 mM ascorbic acid phosphate ester, 1 mM ,-glycerophosphate, and 10 nM dexamethasone for 10 days. Drug treatments were done for 24 h on day 3 of culture. Results: PDE4 inhibitors, including XT-611, but not PDE3 and PDE5 inhibitors, increased mineralized nodule formation in rat and mouse bone marrow cell cultures. During culture of the bone marrow cells, prostaglandin E2 (PGE2) production increased with a peak on day 4, but the increase was completely inhibited by indomethacin, an unselective cyclo-oxygenase (COX) inhibitor. Spontaneous and XT-611-induced mineralized-nodule formation was also inhibited by indomethacin and COX-2 inhibitors, in a similar potential. Alkaline phosphatase-positive nodule formation in the absence or presence of XT-611 was inhibited by an antagonist of EP4 receptor, AH23848B, and synergistically potentiated by 11-deoxy-PGE1, but it was not influenced by other EP antagonists and agonists examined. The expression of PDE4 and EP4 mRNAs was observed in bone marrow cells. The effect of XT-611 was also confirmed to involve an increase of cyclic AMP and the cyclic AMP-dependent protein kinase pathway. Conclusion: These results suggest that PGE2 stimulates differentiation of osteoblast progenitor cells through the EP4 receptor in an autocrine manner, and the PDE4 inhibitor potentiates the differentiation by inhibiting hydrolysis of cyclic AMP in the cells. [source]

Dor Operation for a Young Male with Left Ventricular Aneurysm due to Spontaneous Left Anterior Descending Coronary Artery Dissection

JOURNAL OF CARDIAC SURGERY, Issue 1 2004
Masato Nakajima M.D.
We describe a young male who had a myocardial infarction with left ventricular aneurysm due to spontaneous left anterior descending coronary artery dissection. He was successfully treated with Dor's left ventriculoplasty without coronary artery revascularization. The Dor procedure was a simple and effective treatment. To our knowledge, this is the first report in which the Dor procedure was used to treat spontaneous coronary artery dissection with left ventricular aneurysm. (J Card Surg 2004;19:54-56) [source]

Clinical Characteristics of Patients With Spontaneous or Inducible Ventricular Fibrillation Without Apparent Heart Disease Presenting with J Wave and ST Segment Elevation in Inferior Leads

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2000
MASAHTKO TAKAGI M.D., Ph.D.
Ventricular Fibrillation with J Wave in Inferior Leads. Introduction: The clinical characteristics of three patients with spontaneous or inducible ventricular fibrillation (VF) without apparent heart disease, who presented with J wave and ST segment elevation in inferior leads, are described. Methods and Results: All patients were male and experienced syncope. Their symptoms occurred at night or early in the morning. Holter ECG revealed infrequent premature ventricular complexes. Injection with disopyramide 2 mg/kg augmented ST segment elevation. Conclusion: These characteristics were very similar to those of patients with Brugada syndrome. These three patients with these specific features might have a variant of Brugada syndrome. [source]

Spontaneous and catalyzed isomerizations of the acetamide radical cation

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2001
Philippe Mourgues
No abstract is available for this article. [source]

Degenerative and regenerative processes involved in midgut pseudotumor formation in the stick insect (Carausius morosus)

JOURNAL OF MORPHOLOGY, Issue 12 2009
Paul Hoffmann
Abstract Spontaneous and experimentally induced pseudotumor formation in Carausius morosus impairs the midgut tissue homeostasis. Spontaneous pseudotumor formation begins by the break down of a single or a small group of columnar cells (CCs) and is followed by the degeneration of neighboring CCs. There are not only marked similarities but also decisive differences between normal dying CCs in healthy specimens and the degeneration of CCs leading to pseudotumors: in both cases, the apical cell parts with the nucleus are extruded into the midgut lumen, but only during of pseudotumor formation an "amorphous substance" originates from the basal parts of the CCs. Hemocytes are attracted to this substance and form a nodule-like aggregation, which is responsible for the phenotype of pseudotumors. Pseudotumor infestation has also an impact on the midgut nidi, which consist of an intestinal stem cell and several CC progenitor cells. In healthy specimens only one progenitor cell per nidus differentiates at a time, but, several to all progenitor cells differentiate simultaneously in pseudotumor-infested specimens. Extirpation of the ingluvial ganglion in healthy specimens results in an immediate onset of pseudotumor formation and a dramatic acceleration of pseudotumor growth. Importantly, the ultrastructural characteristics of spontaneous and experimentally induced pseudotumors are identical. This supports the idea that the stomatogastric nervous system plays an integral role in the maintenance of midgut tissue homeostasis. J. Morphol., 2009. © 2009 Wiley-Liss, Inc. [source]

Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2000
Carty
Background: Platelets play an important role in inflammation and are activated in inflammatory bowel disease. Micro-vascular thrombosis in the gut wall leading to intestinal micro-infarction may be a pathogenic feature of Crohn's disease. 5-Aminosalicylic acid is an effective treatment for patients with inflammatory bowel disease. Aims: To assess the effects of 5-aminosalicylic acid on platelet activation, when taken orally and in vitro by patients with inflammatory bowel disease. Methods: Spontaneous and thrombin-induced platelet activation were studied using fluorescent antibodies to the activated platelet surface glycoprotein P-selectin and flow cytometry. Results: Baseline platelet activation in inflammatory bowel disease was significantly greater than that in controls (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex-vivo platelet activation was 50% lower in patients with inflammatory bowel disease taking 5-aminosalicylic acid orally than in those not on such treatment (P < 0.05). In vitro, 5-aminosalicylic acid significantly reduced both spontaneous (P < 0.03 for ,1 ,M 5-aminosalicylic acid) and thrombin-induced platelet activation (P < 0.02 for , 1 ,M 5-aminosalicylic acid). Conclusions: 5-Aminosalicylic acid given either orally or in vitro inhibits platelet activation. If this effect reflects an in vivo action in the gut, it could contribute to the beneficial actions of 5-aminosalicylic acid in inflammatory bowel disease. [source]

Acquisition of iron from human transferrin by Porphyromonas gingivalis: a role for Arg- and Lys-gingipain activities

MOLECULAR ORAL MICROBIOLOGY, Issue 2 2001
V. Brochu
Porphyromonas gingivalis, a key causative agent of adult periodontitis, is known to produce a variety of virulence factors including proteases. The aim of this study was to evaluate the participation of Arg- and Lys-gingipain activities of P. gingivalis in the acquisition of iron from human transferrin and its subsequent utilization in growth. Iron-saturated transferrin was found to support the long-term growth of P. gingivalis. Our results indicated that P. gingivalis does not produce siderophore and does not possess ferric reductase and transferrin-binding activities. Incubating transferrin with P. gingivalis resulted in degradation of the protein, a step that may be critical for the acquisition of iron from transferrin. Spontaneous and site-directed mutants of P. gingivalis deficient in one or several proteases were used to demonstrate the key role of specific enzymes in degradation of transferrin and subsequent utilization for growth. The lack of both Arg- and Lys-gingipain activities (mutants M1 and KDP128) was associated with an absence of degradation of transferrin and the incapacity of bacteria to grow in the presence of transferrin as the sole source of iron. It was also found that the Lys-gingipain activity is more critical than the Arg-gingipain activity since the mutant KDP112 (deficient in Arg-gingipain A and B) could grow whereas the mutant KDP129 (deficient in Lys-gingipain) could not. The fact that growth of mutant KDP112 was associated with a lower final optical density and a generation time much longer compared with the parent strain suggests that the Arg-gingipain activity also participates in the acquisition of iron from transferrin. Selected inhibitors of cysteine proteases (TLCK, leupeptin and cathepsin B inhibitor II) were tested for their capacity to reduce or inhibit the growth of P. gingivalis under different iron conditions. All three inhibitors were found to completely inhibit growth of strain ATCC 33277 in a medium supplemented with transferrin as the source of iron. The inhibitors had no effects when the bacteria were grown in a medium containing hemin instead of transferrin. The ability of P. gingivalis to cleave transferrin may be an important mechanism for the acquisition of iron from this protein during periodontitis. [source]

Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability

MUSCLE AND NERVE, Issue 6 2006
Paul Maddison MD
Abstract Acquired autoimmune neuromyotonia is regarded as part of the spectrum of peripheral nerve hyperexcitability disorders. We aimed to use clinical neurophysiological measurements to study the extent, distribution, and characteristics of spontaneous motor unit potentials in 11 patients with acquired neuromyotonia. Investigations revealed that most spontaneous discharges recorded were motor unit, or partial motor unit potentials of normal size. Bursts of motor unit potentials arose more commonly from distal portions of the peripheral nerve and had abnormal absolute and relative refractory periods. Spontaneous discharges in some patients occurred in semirhythmic bursts in certain muscles. No patient had neurophysiological abnormalities detectable in first-order neurons of the central nervous system when using transcranial magnetic stimulation to estimate the threshold for corticomotor excitation and determine central motor conduction time. Only patients with coexistent myasthenia gravis had neurophysiologically detectable defects in neuromuscular transmission. The pathogenic region of abnormality in peripheral nerve hyperexcitability disorders therefore seems to lie within the terminal branches of peripheral motor nerves. Muscle Nerve, 2006 [source]

Spontaneous and stimulated emission in InAs LEDs with cavity formed by gold anode and semiconductor/Air interface

PHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 2 2005
B. Matveev
Abstract The paper presents results on spectral and power measurements in InAsSbP/InAs double heterostructure flip-chip LEDs with cavity formed by bottom anode mirror and air/semiconductor interface in the temperature range of 77,573 K. Data on near and far field patterns in the 3 µm range together with the threshold characteristincs of the L-I curves are discussed with respect to resonant cavity effects at 77,573 K and stimulated emission at 77 K in the direction perpendicular to the p-n junction. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Heterogeneous Susceptibility to Spontaneous and Induced Apoptosis Characterizes Two Related Transplantable Melanomas with Different Biological Properties

PIGMENT CELL & MELANOMA RESEARCH, Issue 3 2002
Krystyna Koz, owska
A family of phenotypically and biologically different transplantable hamster melanomas was derived from a single tumor more than 40 yr ago. In this work, we were seeking the differences between the abilities of the cells from two biologically heterogeneous (melanotic and amelanotic) members of this family to undergo spontaneous or camptothecin-induced apoptosis. We studied these differences by looking at three important features of the apoptotic process, i.e. binding of annexin V, DNA fragmentation and caspase-3 activity. Of these, annexin binding and DNA fragmentation were more pronounced in the parental, melanotic line while the activity of caspase-3 was stronger in the amelanotic tumor cells. We concluded that a spontaneous alteration of the original, melanotic melanoma line into an amelanotic one, associated with more aggressive tumor progression, was accompanied by significant decrease in ability to undergo spontaneous and camptothecin-induced apoptosis, and that apoptosis of these two cell types may not depend on the activity of caspase-3. [source]

Cholinergic switch associated with morphological differentiation in neuroblastoma,

THE JOURNAL OF PATHOLOGY, Issue 4 2009
Franck Bourdeaut
Abstract The morphology of malignant cells distinguishes between undifferentiated, poorly differentiated and differentiating neuroblastomas and constitutes a strong prognostic factor. Spontaneous or treatment-induced maturation characterizes a subset of neuroblastomas. It constitutes the basis of retinoic acid treatment to improve survival in aggressive neuroblastomas. However, the molecular events that drive differentiation are poorly understood. In the present study we have investigated the relationships between gene expression profiles and differentiation criteria in stroma-poor neuroblastomas. This study included three undifferentiated (UN), 20 poorly differentiated (PDN) and 11 differentiating (DN) neuroblastomas. These groups could be clearly separated using unsupervised clustering methods, which further enabled a major classification impact of genes involved in neural development, differentiation and function to be identified. UNs are characterized by high ASCL1, high PHOX2B, low GATA2, low TH and low DBH expressions. Most PDNs harbour a clear adrenergic phenotype, even in the presence of missense PHOX2B mutations. Finally, all DN tumours demonstrate cholinergic features. Depending upon their association with adrenergic characteristics, this enables dual ,cholinergic/adrenergic' and ,fully cholinergic' neuroblastomas to be defined. This suggests that the cholinergic switch, a final specification process that occurs physiologically in a minority of sympathetic neurons, is a critical step of differentiation in some neuroblastic tumours. This switch is associated with a down regulation of DBH that is apparently not strictly dependent upon PHOX2B. Conversely, GATA2 and TFAP2B may play critical roles in maintaining adrenergic features in poorly differentiated tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Real-time measurement of serotonin release and motility in guinea pig ileum

THE JOURNAL OF PHYSIOLOGY, Issue 2 2006
Paul P. Bertrand
Enterochromaffin (EC) cells are sensors that detect chemical or mechanical stimuli and respond with release of serotonin (5-HT). 5-HT activates local motor reflexes, but whether local motor reflexes also evoke 5-HT release is unknown. The aim of the present study was to establish the relationship between the release of 5-HT and the enteric neural circuits controlling the movements of the intestine. Recordings were made from full-thickness preparations of guinea pig ileum using electrochemical techniques with carbon fibre electrodes to measure local concentrations of 5-HT. The tension in the circular muscle (CM) and longitudinal muscle (LM) was recorded with force transducers. The release of 5-HT from the EC cells was detected selectively and the timing of the events quantified. Pressure-evoked peristalsis caused detectable 5-HT release only when the recording site was invaded by a ring of CM contraction. Spontaneous and stretch-evoked reflex contraction of the CM and LM occurred simultaneously with 5-HT release. Paralysis of the smooth muscle significantly reduced the stretch-evoked release. Muscarinic agonists evoked reflexes that were associated with increases in tension in CM and LM simultaneous with 5-HT release. Tetrodotoxin abolished the coordination between the CM contraction and 5-HT release but not the direct activation of the CM and EC cells by the agonists. In conclusion, the correlation between local motor reflexes and 5-HT release observed in the present study is caused primarily by the contraction of the smooth muscle and subsequent deformation of the mucosa. The EC cell is, thus, a site of convergence for mechanical forces that contribute to the release of 5-HT during motor reflexes. [source]

Activation of AMP-activated protein kinase by adiponectin rescues salivary gland epithelial cells from spontaneous and interferon-,,induced apoptosis

ARTHRITIS & RHEUMATISM, Issue 2 2010
Stergios Katsiougiannis
Objective Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltrates associated with destruction of salivary gland epithelial cells (SGECs) induced mainly by apoptosis. Adiponectin is an immunoregulatory hormone. We have previously shown that SGECs from patients with primary SS as well as from controls differentially express adiponectin. SGECs derived from patients with primary SS constitutively produce and secrete adiponectin in higher quantities. The aim of this study was to investigate the effect of adiponectin on the proliferation and apoptosis of SGECs. Methods Cultured, non-neoplastic SGECs were treated with recombinant human adiponectin, and the rate of cell proliferation was assessed. Spontaneous and interferon-, (IFN,),induced apoptosis was evaluated with a specific single-stranded DNA enzyme-linked immunosorbent assay. The AMP-activated protein kinase (AMPK) inhibitor Compound C was used to test the involvement of AMPK in adiponectin effects. Western blotting was applied to detect the phosphorylation levels of AMPK after adiponectin treatment. Results Adiponectin treatment resulted in a dose-dependent suppression of proliferation of SGECs from patients with primary SS and control donors. Adiponectin protected cells from spontaneous as well as from IFN,-induced apoptosis. Furthermore, the antiapoptotic effects of adiponectin were dependent upon AMPK phosphorylation at Thr172, since pretreatment of SGECs with Compound C abolished the adiponectin protective effect. Conclusion Adiponectin exerted antiproliferative effects on SGECs without inducing apoptosis and protected SGECs from spontaneous as well as from IFN,-induced apoptosis through an AMPK-dependent pathway. Our observations suggest that adiponectin may protect SGECs in this specific inflammatory milieu, providing a potential pathway through which AMPK may regulate cell survival under energy stress conditions such as autoimmune inflammation. [source]

The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats

BIOFACTORS, Issue 1-4 2003
Ludmila Korkina
Abstract Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment. [source]

Activity of corneal nociceptive nerve fibers during allergic challenge of the ocular surface

ACTA OPHTHALMOLOGICA, Issue 2009
J GALLAR
Purpose The aim of this work was to study in vitro the spontaneous and stimulus-evoked electrical activity of corneal nociceptive nerve fibers during acute allergic inflammation of the ocular surface induced in the guinea-pig. Methods Animals received i.p. 10% ovalbumin (OVA). 14 days later, a 10µl drop of OVA was applied topically to each eye. Blinking and scratching movements directed to the eye were measured during 10 min, and ocular symptoms (edema and hyperemia) and tear rate were measured. Animals were killed afterwards and both eyes were immediately excised and mounted in a superfused (32°C) recording chamber. Electrical activity of corneal sensory receptors was recorded from nerve filaments dissected from the ciliary nerves. Mechanical (calibrated von Frey hairs), thermal (bath solution temperature down to 20°C or up to 52°C), and chemical stimulation (30s-pulses of 98%CO2) were performed. Spontaneous (SA) and stimulus-evoked activity were analyzed. Results After the allergic challenge, eye-scratching behavior was present in 4 out of 15 animals and blinking movements increased from 1±0.05 to 26±5. Tearing also increased compared to control (33±3 vs. 5±1 mm). Compared to naive eyes, proportion of nociceptors with SA (17% vs. 5%) and spontaneous discharge rate (0.13±0.07 vs. 0.01±0.01 imp/s) were increased. Mechanical threshold of mechano-nociceptive units decreased significantly (0.37±0.05 vs. 0.89±0.13 mN). Chemosensitivity of polymodal nociceptors was slightly increased (1.87±0.42 vs. 1.34±0.23 imp/s). Conclusion Changes in corneal sensory nerve activity observed acutely after allergic challenge of the eye surface may constitute the basis of itching and discomfort sensations, and hypersensitivity observed in allergic patients. [source]

Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction

ACTA PHYSIOLOGICA, Issue 1 2010
H. Post
Abstract Aim:, The induction of mild hypothermia (MH; 33 °C) has become the guideline therapy to attenuate hypoxic brain injury after out-of-hospital cardiopulmonary resuscitation. While MH exerts a positive inotropic effect in vitro, MH reduces cardiac output in vivo and is thus discussed critically when severe cardiac dysfunction is present in patients. We thus assessed the effect of MH on the function of the normal heart in an in vivo model closely mimicking the clinical setting. Methods:, Ten anaesthetized, female human-sized pigs were acutely catheterized for measurement of pressure,volume loops (conductance catheter), cardiac output (Swan-Ganz catheter) and for vena cava inferior occlusion. Controlled MH (from 37 to 33 °C) was induced by a vena cava inferior cooling catheter. Results:, With MH, heart rate (HR) and whole body oxygen consumption decreased, while lactate levels remained normal. Cardiac output, left ventricular (LV) volumes, peak systolic and end-diastolic pressure and dP/dtmax did not change significantly. Changes in dP/dtmin and the time constant of isovolumetric relaxation demonstrated impaired active relaxation. In addition, MH prolonged the systolic and shortened the diastolic time interval. Pressure,volume analysis revealed increased end-systolic and end-diastolic stiffness, indicating positive inotropy and reduced end-diastolic distensibility. Positive inotropy was preserved during pacing, while LV end-diastolic pressure increased and diastolic filling was substantially impaired due to delayed LV relaxation. Conclusion:, MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart. [source]

THE IMPULSE OF PHILANTHROPY

CULTURAL ANTHROPOLOGY, Issue 4 2009
ERICA BORNSTEIN
ABSTRACT In practices of philanthropy and charity, the impulse to give to immediate others in distress is often tempered by its regulation. Although much of what is written on charity and philanthropy focuses on the effects of the gift, I suggest more attention be paid to the impulse of philanthropy. To coerce the impulse to give into rational accountability is to obliterate its freedom; to render giving into pure impulse is to reinforce social inequality. The only solution is to allow both to exist, and to create structures to encourage them. This essay examines the power of the spontaneous and fleeting impulse to give and its regulation through an analysis of contemporary practices of philanthropy and their relation to sacred conceptions of d,n (donation) in New Delhi. When scriptural ideas of disinterested giving intersect with contemporary notions of social responsibility, new philanthropic practices are formed. On the basis of ethnographic research with philanthropists who built temples, started NGOs, and managed social welfare programs, as well as families who gave d,n daily out of their homes, this essay documents how both NGO and government efforts to regulate one of the most meritorious forms of d,n, gupt d,n (or, anonymous d,n) expresses critical issues in philanthropy between the urge to give in response to immediate suffering and the social obligation to find a worthy recipient for the gift. [source]

Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus,

CYTOMETRY, Issue 4 2009
Susana Mellor-Pita
Abstract Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNF,), interferon gamma (IFN,), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNF, levels were increased in patients (P , 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P , 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNF,+ (P= 0.02), CD4+IFN,+ (P = 0.04) and CD8+ IFN,+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society [source]

Symmetry-breaking in mammalian cell cohort migration during tissue pattern formation: Role of random-walk persistence

CYTOSKELETON, Issue 4 2005
S. Huang
Abstract Coordinated, cohort cell migration plays an important role in the morphogenesis of tissue patterns in metazoa. However, individual cells intrinsically move in a random walk-like fashion when studied in vitro. Hence, in the absence of an external orchestrating influence or template, the emergence of cohort cell migration must involve a symmetry-breaking event. To study this process, we used a novel experimental system in which multiple capillary endothelial cells exhibit spontaneous and robust cohort migration in the absence of chemical gradients when cultured on micrometer-scale extracellular matrix islands fabricated using microcontact printing. A computational model suggested that directional persistence of random-walk and dynamic mechanical coupling of adjacent cells are the critical control parameters for this symmetry-breaking behavior that is induced in spatially-constrained cell ensembles. The model predicted our finding that fibroblasts, which exhibit a much shorter motility persistence time than endothelial cells, failed to undergo symmetry breaking or produce cohort migration on the matrix islands. These findings suggest that cells have intrinsic motility characteristics that are tuned to match their role in tissue patterning. Our results underscore the importance of studying cell motility in the context of cell populations, and the need to address emergent features in multicellular organisms that arise not only from cell-cell and cell-matrix interactions, but also from properties that are intrinsic to individual cells. Cell Motil. Cytoskeleton 61:201,213, 2005. © 2005 Wiley-Liss, Inc. [source]

Previous experience of spontaneous or elective abortion and risk for posttraumatic stress and depression during subsequent pregnancy

DEPRESSION AND ANXIETY, Issue 8 2010
Lydia Hamama
Abstract Background: Few studies have considered whether elective and/or spontaneous abortion (EAB/SAB) may be risk factors for mental health sequelae in subsequent pregnancy. This paper examines the impact of EAB/SAB on mental health during subsequent pregnancy in a sample of women involved in a larger prospective study of posttraumatic stress disorder (PTSD) across the childbearing year (n=1,581). Methods: Women expecting their first baby completed standardized telephone assessments including demographics, trauma history, PTSD, depression, and pregnancy wantedness, and religiosity. Results: Fourteen percent (n=221) experienced a prior elective abortion (EAB), 13.1% (n=206) experienced a prior spontaneous abortion (SAB), and 1.4% (n=22) experienced both. Of those women who experienced either an EAB or SAB, 13.9% (n=220) appraised the EAB or SAB experience as having been "a hard time" (i.e., potentially traumatic) and 32.6% (n=132) rated it as their index trauma (i.e., their worst or second worst lifetime exposure). Among the subset of 405 women with prior EAB or SAB, the rate of PTSD during the subsequent pregnancy was 12.6% (n,51), the rate of depression was 16.8% (n=68), and 5.4% (n,22) met criteria for both disorders. Conclusions: History of sexual trauma predicted appraising the experience of EAB or SAB as "a hard time." Wanting to be pregnant sooner was predictive of appraising the experience of EAB or SAB as the worst or second worst (index) trauma. EAB or SAB was appraised as less traumatic than sexual or medical trauma exposures and conveyed relatively lower risk for PTSD. The patterns of predictors for depression were similar. Depression and Anxiety, 2010.© 2010 Wiley-Liss, Inc. [source]

Environmental complexity and central nervous system development and function

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004
Mark H. Lewis
Abstract Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical,basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus. MRDD Research Reviews 2004;10:91,95. © 2004 Wiley-Liss, Inc. [source]