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Interleukin-6 inhibits neurotransmitter release and the spread of excitation in the rat cerebral cortex.

Cytokines are extracellular mediators that have been reported to affect neurotransmitter release and synaptic plasticity phenomena when applied in vitro. Most of these effects occur rapidly after the application of the cytokines and are presumably mediated through the activation of protein phosphorylation processes. While many cytokines have an inflammatory action, interleukin-6 (IL-6) has been found to have a neuroprotective effect against ischaemia lesions and glutamate excitotoxicity, and to increase neuronal survival in a variety of experimental conditions. In this paper, the functional effects of IL-6 on the spread of excitation visualized by dark-field/infrared videomicroscopy in rat cortical slices and on glutamate release from cortical synaptosomes were analysed and correlated with the activation of the STAT3, mitogen-activated protein kinase ERK (MAPK/ERK) and stress-activated protein kinase/cJun NH2-terminal kinase (SAPK/JNK) pathways. We have found that IL-6 depresses the spread of excitation and evoked glutamate release in the cerebral cortex, and that these effects are accompanied by a stimulation of STAT3 tyrosine phosphorylation, an inhibition of MAPK/ERK activity, a decreased phosphorylation of the presynaptic MAPK/ERK substrate synapsin I and no detectable effects on SAPK/JNK. The effects of IL-6 were effectively counteracted by treatment of the cortical slices with the tyrosine kinase inhibitor lavendustin A. The inhibitory effects of IL-6 on glutamate release and on the spread of excitation in the rat cerebral cortex indicate that the protective effect of IL-6 on neuronal survival could be mediated by a downregulation of neuronal activity, release of excitatory neurotransmitters and MAPK/ERK activity.

Animals↗

Spreading oligemia in the migraine aura--most likely an artifact due to scattered radiation.

The view that "spreading oligemia" reflects spreading depression in the human brain during the migraine aura is based on a defective analysis of CBF data where the most important methodological source of error (scattered radiation) has been ignored. When scattered radiation is taken into account it appears that CBF in the low flow area during the migraine aura is reduced to the ischemic level. There is no reason to believe that "spreading" of the low flow area occurs. Most likely the blood flow decreases in an area of fixed size. All available CBF evidence in fact lends support to "the vascular theory" of migraine pathogenesis.

Animals↗

Thrombin causes cell spreading and redistribution of beta-amyloid immunoreactivity in cultured hippocampal neurons.

Culture of rat embryonic hippocampal neurons in serum-free B27/Neurobasal for 4 days enabled tests of the effect of added thrombin on differentiated cell morphology and processing of the amyloid precursor protein (APP). By fluorescence microscopy of neurons labeled with dil and by scanning electron microscopy, an increase in spreading of the neuron soma was clearly seen in cells treated with 1 microg/ml (27 nM) of thrombin for 24 h. This treatment also caused a dose-dependent increase in immunoreactive area/cell, detected with antibody 4G8 binding to the beta-amyloid region of APP. Thrombin treatment also produced a dose-dependent increase in immunoreactive brightness detected with the Alz-50 antibody. Thrombin did not affect viability or cause neurite retraction. The thrombin effect on 4G8 immunoreactivity required 24 h for full effect and could be blocked by the thrombin inhibitor antithrombin III or hirudin. A thrombin receptor appeared to be activated because a full immunoreactive response was observed by treatment of neurons with the thrombin receptor-activating peptide SFL-LRNPNNKYEPF. When cytoplasmic extracts were analyzed by western immunoblots or by pulse-chase radiolabeling, no thrombin-dependent changes in processing of 127- and 120-kDa bands were seen. Material migrating in the region of synthetic betaA4 was not found. Together, these results suggest that thrombin acts on neurons through a thrombin receptor to stimulate cell spreading and redistribution of APP without amyloidogenic changes. The adhesion responsible for this spreading could be important in altering synaptic connections in the brain.

Amyloid beta-Peptides↗

A risk scale for predicting extensive subclinical spread of nonmelanoma skin cancer.

BACKGROUND: The clinical appearance of nonmelanoma skin cancer may represent only a portion of microscopic tumor invasion. OBJECTIVE: To develop a scale based on high-risk characteristics for predicting the probability of extensive subclinical spread of nonmelanoma skin cancer. METHODS: Retrospective analysis of 1095 Mohs micrographic surgical cases (MMS) yielded high-risk factors for extensive tumor spread, defined as requirement of greater-than-or-equal3 MMS layers. Predictive characteristics included: any BCC on the nose, morpheaform BCC on the cheek, neck tumors and recurrent BCC in men, location on the eyelid, temple, or ear helix, and size>10 mm. Multivariate logistic regression was applied to develop a risk index. RESULTS: Tumor characteristics were assigned point values calculated from the respective odds of extension and categorized into six risk classes with probabilities of extensive subclinical spread ranging from 10% to 56%. CONCLUSION: A risk scale simplifies and enhances prediction of extensive tumors. The associated probabilities can help to guide patient preparation and appropriate therapy.

Adult↗

Cell spreading on laminin substrate involves Con A-binding proteins.

Concanavalin A (Con A), a tetravalent lectin, was shown to impair 8 chick embryo fibroblast (8 d CEF) spreading on a laminin (LM) substrate but not on a fibronectin substrate (FN), suggesting that cell surface Con A binding proteins could be involved in 8 d CEF spreading on a LM substrate. The interaction of Con A-binding proteins with Con A is dependent upon the carbohydrate moieties of the isolated glycoproteins; since they interact strongly with Con A-Sepharose and are eluted with 0.3 Mol/l alpha-methylmannopyranoside, the isolated Con A binding-proteins inhibit 8 d CEF adhesion to a Con A substrate to the same extent as alpha-methylmannopyranoside. Furthermore, the isolated Con A binding proteins specifically inhibit in a dose-dependent manner 8 d CEF spreading on LM but not on FN.

Animals↗

CD138-positive and Kaposi's sarcoma-associated herpesvirus (KSHV)-negative B-cell lymphoma with serosal spreading of the body cavity and lymphadenopathy: an autopsy case.

CD138-positive and Kaposi's sarcoma-associated herpes virus (KSHV)-negative B cell lymphoma with serosal spreading of the body cavity and lymphadenopathy is presented. Our lymphoma cells showed pleomorphic morphology and a clonal immunoglobulin gene rearrangement. Immunophenotypically, they lacked B- and T-cell-associated antigens but expressed strong membranous CD138 antigen along the serosa. Although our case was not conventional primary effusion lymphoma (PEL) because of the absence of KSHV and the presence of lymphadenopathy, its unique phenotype and serosal spreading were consistent with those of PEL. Our case suggests that, irrespective of KSHV infection, some pleomorphic B cell lymphomas with membranous CD138 expression show a peculiar serosal spreading.

Ascites↗

Clonal spread of methicillin-resistant Staphylococcus aureus in a large geographic area of the United States.

Methicillin resistance in Staphylococcus aureus has rapidly increased over the last two decades. This increase is paralleled by the emergence of unique multi-resistant MRSA clones. In Brazil, Argentina, Uruguay, Portugal and Czech Republic a specific MRSA clone is widely spread, the so-called Brazilian epidemic clone. Another epidemic clone, the Iberian clone, is disseminated in Spain, Portugal, Belgium, Scotland, Italy, Germany and New York. Thus, a large number of hospital-acquired infections have been caused by specific MRSA clones. Using different molecular techniques for MRSA typing, we verified that two unique epidemic clones are spread over large geographic area in the US. In addition, we showed that a previously described MRSA clone type, the New York clone (I::A:A), is widely spread beyond the New York frontiers.

Cloning, Molecular↗

Intrafamilial spread of Helicobacter pylori: a prospective study using urea breath test.

PURPOSE: The mode of Helicobacter pylori spread is not well defined. Urea breath test (UBT) is an accurate and noninvasive method for H pylori detection. This study evaluates the role of intrafamilial spread of H pylori using UBT. METHODS: The family members of 16 Hpylori-positive and 16 negative (control) children confirmed by histology and rapid urease test were investigated with UBT. A 58% change was considered positive. RESULTS: A total of 139 persons (72 in the positive group; 67 in the control group) were studied. Fifty-eight (81%, 58 of 72) and 13 (19%, 13 of 67) were found to be positive in the H pylori-positive and control groups, respectively (P < .01). Among children from 19 positive mothers, the positive rate was 60% (25 of 42), whereas among children of negative mothers, the positive rate was 16% (4 of 25; P < .01). The positive rate among children of positive fathers was 66% (23 of 35), whereas that among children of negative fathers was 30% (7 of 23; P < .01). When both parents were H pylori-positive, the children's positive rate was 83% (19 of 23); when both parents were negative, the children's positive rate was 0% (0 of 9; P < .01). CONCLUSIONS: There is strong evidence of intrafamilial spread of H pylori. The positivity of parents with H pylori has an important bearing on their children's H pylori status.

Adolescent↗

[Extracapsular spread of cervical lymph node metastases: Diagnostic value of magnetic resonance imaging].

OBJECTIVE: Assessment of the value of magnetic resonance tomography in the determination of extracapsular neoplastic spread and soft tissue infiltration of cervical lymph nodes. MATERIALS AND METHODS: The results of magnetic resonance tomographies of 110 patients with squamous cell carcinoma in the head-neck region were prospectively compared with the findings of the histologic examination after neck dissection. RESULTS: Magnetic resonance tomography reaches a specificity of 72.2 % in the detection of extracapsular neoplastic spread. The sensitivity of the method is 74.4 %. Mainly small (less than 1 cm; n = 11) extracapsular growth was not detected and was diagnosed false-negative in the MRI examinations. CONCLUSION: The specificity (72.2 %) and sensitivity (74.4 %) of MRI examinations to detect extracapsular spread of lymph nodes is only partially satisfying.

Adult↗

[Possible effects of climatic changes on the spread of malaria tropica--results of a strategical simulation].

The Earth's surface is presently undergoing a period of global warming-up, which increases the likelihood of a spread of malaria tropica. A reliable prognosis would be important for efficient prevention by initiating appropriate counter-measures well in time. The following paper presents simulations of the effects of climatic changes on the spread of malaria. We do not specifically aim at obtaining concrete data for a particular region; rather, we are concerned with gaining an insight into the complex interrelations between global environment changes and the spread of malaria.

Animals↗

P53 labeling index in cholangioscopic biopsies is useful for determining spread of bile duct carcinomas.

BACKGROUND: Preoperative biopsy specimens obtained by means of percutaneous transhepatic cholangioscopy are useful for planning curative resection of bile duct carcinoma in an effort to improve survival. However, tissue diagnosis is sometimes difficult. This study evaluated the usefulness of p53 immunostaining of cholangioscopic specimens for determination of tumor spread. METHODS: A total of 107 biopsy specimens from 28 patients with bile duct carcinoma was selected. Before surgery, these specimens were diagnosed histopathologically (hematoxylin and eosin staining) as positive or negative for carcinoma. After definitive surgery, specimens were immunostained with anti-p53 antibody. RESULTS: Eighteen of 28 cases (64%) were positive for p53. Among these, 86% obtained from the main carcinomatous lesion or an area of superficial spread of the carcinoma exhibited a p53 labeling index (LI) over 25% as opposed to a p53 LI under 25% for all specimens obtained from noncarcinomatous lesions. Twelve specimens from 8 cases were classified before surgery as indeterminate (hematoxylin and eosin staining). The criterion of p53 LI over 25% was applicable in 11 of the 12 specimens. CONCLUSION: The p53 immunostaining of biopsy specimens obtained by means of percutaneous transhepatic cholangioscopy is helpful in determining tumor spread in bile duct carcinoma.

Adenocarcinoma↗

Preventing the spread of hepatitis B and C viruses: where are germicides relevant?

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most prevalent bloodborne pathogens. Infections caused by these organisms can become chronic and may lead to liver cirrhosis and carcinoma. Limited chemotherapy is now available, but only HBV can be prevented through vaccination. Both viruses are enveloped and relatively sensitive to many physical and chemical agents; their ability to survive in the environment may not be as high as often believed. As a result, their spread occurs mainly through direct parenteral or percutaneous exposure to tainted body fluids and tissues. Careful screening of and avoiding contact with such materials remain the most effective means of protection. Nevertheless, the indirect spread of these viruses, although much less common, can occur when objects that are freshly contaminated with tainted blood enter the body or contact damaged skin. Germicidal chemicals are important in the prevention of HBV and HCV spread through shared injection devices, sharps used in personal services (such as tattooing and body piercing), and heat-sensitive medical/dental devices (such as flexible endoscopes) and in the cleanup of blood spills. Microbicides in vaginal gels may also interrupt their transmission. General-purpose environmental disinfection is unlikely to play a significant role in the prevention of the transmission of these viruses. Testing of low-level disinfectants and label claims for such products against HBV and HCV should be discouraged. Both viruses remain difficult to work with in the laboratory, but closely related animal viruses (such as the duck HBV) and the bovine viral diarrhea virus show considerable promise as surrogates for HBV and HCV, respectively. Although progress in the culturing of HBV and HCV is still underway, critical issues on virus survival and inactivation should be addressed with the use of these surrogates.

Animals↗

Neon colour spreading with and without its figural prerequisites.

Neon colour spreading has been shown to disappear if certain figural conditions are not met. Evidence is presented which suggests that these conditions are only incidentally related to the neon spreading effect; in particular, that they can be violated as long as the structure remains compatible with the interpretation of a transparent surface. It is proposed that neon spreading and classical colour assimilation share the same basic mechanism, and that the peculiar perceptual attributes of the former derive from the perceptual scissioning of ordinary assimilation colour. This process is identical to that occurring with nonillusory colours in phenomenal transparency.

Attention↗

A functional role for illusory colour spreading in the control of focused visual attention.

In cases of modal completion, illusory colour spreading fills in the surface of a subjectively completed shape. In amodal completion, shapes are likewise completed, but now behind a partial occluder, so that filling in of illusory colour to the completed region no longer arises. We consider the possible functional effects that illusory colour spreading may exert on later stages of vision, and argue that comparisons of modal with amodal completion may be particularly revealing in this regard. It is hypothesised that cueing the inducers of a modally completed object should attract attention to the entire object, including the completed region, owing to the colour spreading there. By contrast, changes to the inducers of a comparable amodally completed object should only attract attention to the inducing regions themselves. This prediction is supported by findings in two experiments with stereoscopic displays, with control conditions ruling out nonattentional accounts, or explanations in terms of stereo disparity alone rather than the presence versus absence of illusory colour. We argue that illusory colours get filled in at quite early stages during modal completion, precisely so that later stages of vision, such as focused attention, can then be driven by the completed regions in the same way as for uniform regions that are physically present in the image.

Color Perception↗

Tobacco mosaic virus infection spreads cell to cell as intact replication complexes.

Plant viruses encode movement proteins (MPs) that facilitate cell-cell transport of infection through plasmodesmata. Intracellular and intercellular spread of virus replication complexes (VRCs) of tobacco mosaic virus was followed in intact leaf tissue from 12 to 36 h post infection (hpi) by using confocal microscopy. From 12 hpi, VRCs in primary infected cells were associated with cortical endoplasmic reticulum, and at 14 hpi, exhibited high intracellular mobility ( approximately 160 nm/sec); mobility was slowed between 14 and 16 hpi ( approximately 40 nm/sec), and by 18 hpi, VRCs were stationary, adjacent to plasmodesmata. VRCs traversed the plasmodesmata between 18 and 20 hpi. The process of formation and movement of VRCs was repeated in adjacent cells in 3-4 h vs. 20 h from primary infected cells. The rapid intracellular movement of the VRCs and the spread to adjacent cells was blocked by inhibitors of filamentous actin and myosin, but not by inhibitors of microtubules. We propose a model whereby cell-cell spread of tobamovirus infection is accomplished by subviral replication complexes that initiate TMV replication immediately after entry to adjacent cells.

Actins↗

Cytoskeletal rearrangements and cell extensions induced by the US3 kinase of an alphaherpesvirus are associated with enhanced spread.

The US3 protein is a viral kinase that is conserved among the Alphaherpesvirinae. Here, we show that US3 of the swine alphaherpesvirus pseudorabies virus causes dramatic alterations in the cytoskeleton, resulting in the formation of long actin- and microtubule-containing cell projections in infected and transfected cells. Analysis with a GFP-labeled virus showed that multiple virus particles move inside the projections toward the tip. GFP-labeled virus could also be found in the cytoplasm of neighboring cells that were in contact with the projections. In addition, projection formation could be inhibited by using the actin-stabilizing drug jasplakinolide and could be induced by using the Rho kinase inhibitor Y27632. Analyzing the effect of these drugs on intercellular virus spread indicated that the observed US3-induced alterations in the host cytoskeleton are associated with enhanced intercellular virus spread, thereby suggesting a previously undescribed aspect of alphaherpesvirus spread.

Amides↗

Human cytomegalovirus cell-to-cell spread in the absence of an essential assembly protein.

The human cytomegalovirus UL99-coded pp28 is a myristoylated phosphoprotein located in the virion tegument domain, which resides between the capsid and envelope. A previous study has demonstrated that BADsubUL99, a pp28-deficient mutant virus, fails to assemble enveloped virus particles. Capsids, coated with tegument proteins, accumulate in the cytoplasm of mutant virus-infected cells. This phenotype indicates that pp28 is required for the acquisition of an envelope; it presumably acts by directing tegument-associated capsids to bud through an intracellular membrane derived from the cell's secretory apparatus that has been modified to contain viral transmembrane glycoproteins. Here we demonstrate that BADsubUL99 can spread from cell to cell, even though highly sensitive assays fail to detect infectious virus progeny in cultures of infected fibroblasts. We propose that, in the absence of pp28, tegument-coated capsids might nevertheless bud through cellular membranes, including the plasma membrane. If this suggestion is correct, the enveloped particle could potentially infect an adjacent cell to mediate the cell-to-cell spread that is observed. This mode of spread might also occur after infection with wild-type virus, and it could facilitate immune evasion, assuming that the resulting particles do not have a normal complement of virus-coded envelope glycoproteins.

Antiviral Agents↗

Cholesterol modification restricts the spread of Shh gradient in the limb bud.

Sonic hedgehog (Shh) produced in the zone of polarizing activity is the major determinant of anteroposterior development of the amniote limb. The mature and active Shh protein is cholesterol-modified at its C terminus, and the hydrophobic nature of the modification requires the function of Dispatched (mDispA), a seven-pass transmembrane protein, for Shh release from its source. The current model suggests that the cholesterol moiety promotes the spread of Shh gradient in the limb bud. However, this model is inconsistent with findings in Drosophila and not in line with current thoughts on the role of the cholesterol moiety in Shh multimerization. Therefore, it remains unclear how the cholesterol moiety affects the postrelease extracellular behavior of Shh that relates to the shape of its activity gradient in responsive tissues. Here, we report functional analyses in mice showing that Shh lacking cholesterol modification (ShhN) has an increased propensity to spread long-distance, eliciting ectopic Shh pathway activation consistent with target gene expressions and modulating the level of Gli3 processing in the anterior limb mesoderm. These molecular alterations are reflected in the mispatterning of digits in ShhN mutants. Additionally, we provide direct evidence for the long-distance movement of ShhN across the anteroposterior axis of the limb bud. Our findings suggest that the cholesterol moiety regulates the range and shape of the Shh morphogen gradient by restricting rather than promoting the postrelease spread of Shh across the limb bud during early development.

Animals↗