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Plasmatocyte sensitivity to plasmatocyte spreading peptide (PSP) fluctuates with the larval molting cycle.

Plasmatocyte spreading peptide (PSP) is a cytokine from the moth Pseudoplusia includens that activates a class of hemocytes called plasmatocytes to bind and spread on foreign surfaces. Previous structure-function studies on PSP used plasmatocytes collected from P. includens larvae that were in the late stages of the last (fifth) instar. Here, we report that plasmatocyte sensitivity to PSP varied significantly during the fourth and fifth instar. PSP weakly activated plasmatocytes early in the instar when hemolymph juvenile hormone (JH) titers were relatively high and ecdysteroid titers were low, but strongly activated plasmatocytes late in the instar after JH titers declined and ecdysteroid titers rose. In contrast, plasmatocytes did not vary in their response to plasma, which contains other factors besides PSP that affect plasmatocyte function. In vitro assays indicated that 20-hydroxyecdysone (20E) dose-dependently synergized PSP activity, whereas the JH analog methoprene antagonized PSP activity. Methoprene had no effect on adhesion and spreading of granular cells, but plasmatocytes from larvae topically treated with methoprene exhibited a reduction in sensitivity to PSP. Collectively, these results indicate that plasmatocyte sensitivity to PSP fluctuates in relation to the molting cycle, and that PSP activity is affected by juvenoids and ecdysone.

Animals↗

Characteristics of HIV-1 env V3 loop sequences for subtype A1 variant spread in Eastern Europe.

OBJECTIVES: The aim of our investigation was to study the HIV-1 env V3 loop sequences of the subtype A variant of the virus actively circulating in the territory of Eastern Europe (A1-EE). DESIGN: It appears that the characteristics of HIV-1 V3 loop sequences of the thoroughly studied subtype B strains determine the viruses tropism and phenotype. We were interested to find out to what extent these trends are preserved with the subtype A isolates spread in Eastern Europe. METHODS: About 474 HIV-1 strains were isolated by cocultivation with phytohemagglutinin stimulated and interleukin-2 activated PBMC. Isolates were subtyped after distinct regions gag, pol and env were amplified by nested polymerase chain reaction. V3 sequences were studied in detail and compared with the isolates that appeared as SI or NSI in test-cultures MT-2. RESULTS: The subtype A HIV-1 strains spread in Eastern Europe appeared to have V3 loop sequences with a high level of conservatism. The consensus sequences of the SI and NSI isolates proved identical, and correspond to the phenotype markers of subtype B NSI strains. Nevertheless, the subtype A SI isolates induced active syncytium-formation processes in the MT-2 test culture. CONCLUSION: The data obtained evidenced to the following: the HIV-1 subtype A variant spread in Eastern Europe, is capable of using for interaction with receptor structures of sensitive cells the tools and mechanisms, which are significantly different from those described for subtype B.

Amino Acid Motifs↗

Seizure spread through the life cycle: optical imaging in combined brain slices from immature, adult, and senile rats in vitro.

The semiology of epileptic seizures changes during the lifetime. Hence, it can be assumed that age-related changes in brain plasticity influence the patterns of seizure onset, spread and propagation velocity. We employed the 4-aminopyridine model of epilepsy to study seizure-like events in vitro. Combined entorhinal cortex-hippocampus brain slices from juvenile (10-13 days), adult (2-3 months), and senile (24-27 months) rats were examined using electrophysiological recordings and imaging of intrinsic optical signals. In the juvenile group, seizure onset was multifocal in all slice regions including the hippocampus. Onset in adult animals was confined to the entorhinal cortex and to neocortical regions. In slices from senile animals, there was a preponderance of seizure onsets in the neocortex. Spread patterns were highly variable in the juvenile group and became gradually more monomorph with increasing age. Propagation velocities were highest in the adult group, with maximum values of 1.51 +/- 0.68 mm/s. In the juvenile group, they amounted to 0.97 +/- 0.39 mm/s, and to 1.18 +/- 0.42 mm/s in senile slices. The results of this study indicate that age-related changes in brain plasticity profoundly affect spread patterns, which may contribute to the clinically observed changes in seizure semiology during early childhood, adulthood and senescence.

Aging↗

MR imaging of perineural tumor spread.

Perineural tumor spread (PNS) is a common and potentially devastating complication of head and neck cancer. Because perineural tumor spread may be asymptomatic, the radi-ologist plays a critical role in the evaluation of the head and neck cancer patient. Although PNS may be seen on CT, MR imaging is far more sensitive and is the imaging modality of choice in the evaluation of perineural tumor spread.

Journal Article↗

Network analysis of Danish cattle industry trade patterns as an evaluation of risk potential for disease spread.

Trade patterns of animal movements in a specific industry are complex and difficult to study because there are many stakeholders, premises that are heterogeneously spread over the country, and a highly dynamic flow of animals exists among them. The Danish cattle industry was defined as a network of animal movements and graph theory was used to analyse the movements of cattle within this network. A premise was defined as a farm, an abattoir or a market. These premises constituted the network nodes in the graph and the animal movements between them were the links. In this framework, each premise had a sub-network of other premises to which it was linked by these animal movements. If no movement of animals were registered for a specific farm, then the sub-network for that premise consisted of only that premise. Otherwise, the sub-network linked the premise of interest to all premises from which and to which animals were moved, as long as there was a path linking animal movements to that specific premise. This approach allowed visualization and analyses of four levels of organization that existed in Denmark animal registers: (1) the animal that was moved, (2) the movements of all animals between two premises, (3) the specific premise network, and (4) the overall industry network. When contagious animals are moved from one premise to another, then to a third and so forth, these movements create a path for potential transfer of pathogens. The paths within which pathogens are present identify the transmission risks. A network of animal movements should provide information about pathogen transmission and disease spread. The network of the Danish cattle industry network was a directed scale-free graph (the direction of a movement was known), with an in-degree power of 2 an out-degree power of 1.46, consisted of 29,999 nodes, and 130,265 movements during a 6-month period. The in clustering coefficient was calculated to be 0.52 for the inward direction (movement to), while it was 0.02 for the outward direction (movement from). In Denmark, the cattle movements between premises demonstrated a large degree of heterogeneity. This heterogeneity in movements between farms should be used to evaluate the risk potential of disease transmission for each premise and must be considered when modelling disease spread between premises. The objective of this research was to describe the network of animal movements and not just the animal movements per se.

Animals↗

Space-time interaction as an indicator of local spread during the 2001 FMD outbreak in the UK.

During the 2001 FMD outbreak in the UK, decisions on the level of implementation of control measures were supported by predictive models. Models were mainly used as macro-level tools to predict the behaviour of the disease in the whole country rather than at the local level. Here we explore the use of the magnitude and characteristics of the space-time interaction as an indicator of local spread and, indirectly, of the effectiveness of control measures aimed at reducing short-range transmission during the course of a major livestock disease epidemic. The spatiotemporal evolution patterns are described in the four main clusters that were observed during the outbreak by means of the hazard rate and space-time K-function (K(s,t)). For each local outbreak, the relative measure D(0)(s,t), derived from K(s,t), which represents the excess risk attributable to the space-time interaction was calculated for consecutive 20-day temporal windows to represent the dynamics of the space-time interaction. The dynamics of the spatiotemporal interaction were very different among the four local clusters, suggesting that the intensity of local spread, and therefore the effectiveness of control measures, markedly differed between local outbreaks. The large heterogeneity observed in the relative impact of being close in time and space to an infected premises suggests that the decision making in relation to control of the outbreak would have benefited from indicators of local spread which could be used to complement global predictive modelling results. Despite its limitations, our results suggest that the real-time analysis of the space-time interaction can be a valuable decision support tool during the course of a livestock disease epidemic.

Animals↗

Epidural spread after continuous cervical paravertebral block: a case report.

BACKGROUND AND OBJECTIVE: This report illustrates epidural spread after continuous cervical paravertebral block (CCPVB). By fluoroscopy, it also explains the mechanism of the complication. CASE REPORT: A healthy 22-year-old male developed bilateral upper-extremity motor weakness immediately after placement of a continuous cervical paravertebral block for postoperative pain control after shoulder stabilization surgery. The tip of the stimulating catheter was demonstrated in the C7 neuroforamen. Contrast injected through the catheter demonstrated epidural spread. The contralateral block resolved after 4 hours and the patient suffered no respiratory embarrassment or other untoward sequelae. CONCLUSION: Continuous cervical paravertebral block is a relatively new, but generally well-accepted, modality for postoperative pain control after major surgery to the upper limb. Epidural spread is recognized as a complication. In this particular case, medial placement of the catheter was possibly caused by unintentional medial direction of the bevel of the Tuohy needle. Meticulous attention to the direction of the needle bevel and early recognition and management of adverse events are mandatory. The same principles may apply for continuous thoracic, lumbar, and sacral paravertebral blocks.

Adult↗

Spread of odontogenic infection originating in the maxillary teeth: computerized tomographic assessment.

OBJECTIVE: The aim of this study was to investigate the pathways of infection originating in the maxillary teeth through the interpretation of computerized tomographic (CT) appearances. STUDY DESIGN: CT images of 78 patients were analyzed with reference to lateral asymmetry of shape and density of fascial spaces and tissues. RESULTS: Changes in the alveolar cortical plates were observed more frequently in the labial/buccal side than in the palatal side. The facial expression muscles were involved in 23 (19.4%) patients. Infection caused by anterior teeth often spread into the levator labii superioris and levator anguli oris muscles. Deep spread into the fascial space was found in 9 (11.5%) patients. Masticator space changes were predominantly seen in the patients with infection caused by molars. Maxillary sinus changes were found in 57 (71.3%) patients with infection originating in the canines, premolars and molars. CONCLUSION: Infection spread characteristics are related to the causal teeth, and the pathways were clearly demonstrated on CT images.

Adolescent↗

VP22 enhances antibody responses from DNA vaccines but not by intercellular spread.

In some species DNA vaccines elicit potent humoral and cellular immune responses. However, their performance in humans and non-human primates is less impressive. There are suggestions in the literature that an increase in the intercellular distribution of protein expressed from a DNA vaccine may enhance immunogenicity. We incorporated the Herpes Simplex Virus type 1 (HSV) VP22 gene, which encodes a protein that has been described as promoting intercellular spread, into a DNA vector in which it was fused to enhanced green fluorescent protein (EGFP). Following transfection of the plasmid DNA into mammalian cells, distribution of the fusion protein VP22-EGFP was not increased compared to EGFP alone. Furthermore, we found no evidence to suggest that VP22 was capable of mediating intercellular spread. However, when these constructs were used as DNA vaccines to immunise mice, antibody levels specific to EGFP were significantly enhanced when EGFP was fused to VP22. These data suggest that amplification of the immune response may occur via mechanisms other than VP22-mediated intercellular spread of antigen.

Adjuvants, Immunologic↗

A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread.

Heparan sulfate (HS) 3-O-sulfotransferase isoform-2 (3-OST-2), which belongs to a family of enzymes capable of generating herpes simplex virus type-1 (HSV-1) entry and spread receptors, is predominantly expressed in human brain. Despite its unique expression pattern, the ability of 3-OST-2 to mediate HSV-1 entry and cell-to-cell fusion is not known. Our results demonstrate that expression of 3-OST-2 can render Chinese hamster ovary K1 (CHO-K1) cells susceptible to entry of wild-type and mutant strains of HSV-1. Evidence for generation of gD receptors by 3-OST-2 were suggested by gD-mediated interference assay and the ability of 3-OST-2-expressing CHO-K1 cells to preferentially bind HSV-1 gD, which could be reversed by prior treatment of cells with HS lyases (heparinases II/III). In addition, 3-OST-2-expressing CHO-K1 cells acquired the ability to fuse with cells-expressing HSV-1 glycoproteins, a phenomenon that mimics a way of viral spread in vivo. Demonstrating specificity, the cell fusion was inhibited by soluble 3-O-sulfated forms of HS, but not unmodified HS. Taken together, our results raise the possibility of a role of 3-OST-2 in the spread of HSV-1 infection in the brain.

Animals↗

Galectin-8 binds specific beta1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells.

Integrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), a beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha1beta1, alpha3beta1 and alpha5beta1 but not alpha2beta1 and alpha4beta1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha5beta1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha1 and alpha5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders.

Androstadienes↗

The spreading of surfactant solutions on thin liquid films.

The spreading of a surfactant solution on a water film at first glance seems a trivial problem. However, in the last 30 years or so this has been shown to be anything like the case. There have been numerous studies which show that Marongoni driven fingering of the spreading surfactant front exists. In this paper this work has been reviewed and an attempt has been made to rationalise the results. The paper concludes with some recent observations of ours concerning the spreading of sodium dodecyl sulfate over relatively thick water films, 200 microm or less.

Journal Article↗

Gelatin-resorcinol-formaldehyde-glutaraldehyde glue-spread stapler prevents air leakage from the lung.

BACKGROUND: To reinforce the staple line of the emphysematous lung and thereby prevent air leakage during thoracoscopic operations, we have developed a procedure of lung excision that uses a gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue-spread stapler. METHODS: Formaldehyde-glutaraldehyde (FG) jelly is prepared by mixing FG fluid with 2.5% sodium carboxymethyl cellulose. The FG jelly is placed in the stapler groove and staple holes, and a gelatin-resorcinol (GR) mixture is applied. The GRFG glue-spread stapler was applied to emphysematous lung cutting during thoracoscopic operations in 10 cases. RESULTS: An adhesion-strength test showed no difference in glue adhesion between FG fluid and FG jelly. An experiment using swine lung showed that with this newly developed stapler, no resistance in firing occurred, and GRFG glue covered every staple hole. Clinical application in 10 cases with emphysematous lung demonstrated no air leakage from the staple line, even long after the operation. CONCLUSIONS: Emphysematous lung excision using the GRFG glue-spread stapler during thoracoscopic operations is useful in preventing air leakage from the staple line and is a simple, safe, and low-cost procedure.

Drug Combinations↗

One hundred video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading.

BACKGROUND: This study was performed to evaluate and determine the validity and benefits of video-assisted thoracic surgical simultaneously stapled pulmonary lobectomy without rib spreading. METHODS: Between September 1992 and August 1995, 100 consecutive video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading were performed. RESULTS: Forty-five male and 55 female patients had 24 right upper, 8 right middle, 29 right lower, 24 left upper, 15 left lower lobectomies for 66 adenocarcinomas, 20 squamous cell carcinomas, 4 large cell carcinomas, 8 benign lesions, and 2 metastatic lesions. Seventy-six patients had negative nodes. Nine patients had positive nodes. Every bronchoscopy was visually and cytologically negative. Forty-nine cervical mediastinoscopies were negative. Operating time for the series averaged 90.3 minutes. Hospitalization averaged 3.5 days for the entire group, but was 2.6 days for the last 20 patients. Lesions ranged from 1.5 to 8 cm, averaging 3.4 cm. There was no surgical mortality, no hemorrhage, no transfusion, and no urgent conversion to an open procedure. No bronchial fistula, vascular fistula, or bronchovascular fistula has occurred. Complications included 6 air leaks, 2 cerebrovascular accidents, 1 infected chest tube site, 2 cases of pneumonitis, and 1 subcutaneous emphysema. CONCLUSIONS: Video-assisted thoracic surgical simultaneously stapled lobectomy without rib spreading is a safe operation that can be combined with lymph node sampling. At this early stage, therapeutic outcomes (survival) for resected neoplasms appear similar to results obtained from traditional open techniques.

Adenocarcinoma↗

Expression of constitutive and inducible HSP70 and HSP47 is enhanced in cells persistently spread on OPN1 or collagen.

Cells persistently spread on OPN or collagen survive heat shock better than cells transiently spread on fibronectin or tissue culture plates. Thus, a central question is whether constitutively or inducible stress proteins are enhanced in cells grown on adhesive proteins that maintain a persistent spread cell shape. Levels of Hsp 72,73, and colligin/Hsp47 were determined by Western blot analyses. The inducible Hsp 72 was prominently expressed following heat shock in cells grown on OPN or collagen, but not in cells plated on fibronectin coated substratum or on tissue culture plates. Colligin/Hsp 47 and Hsp 73 manifested a similar pattern of expression indicating that these adhesive attachment proteins accommodate cell function through organization of cell architecture.

Cell Adhesion↗

Cortical spreading depression recorded from the human brain using a multiparametric monitoring system.

The number of parameters (i.e., EEG or ICP-intracranial pressure) routinely monitored under clinical situations is limited. The brain function analyzer described in this paper enables simultaneous, continuous on-line monitoring of cerebral blood flow (CBF) and volume (CBV), intramitochondrial NADH redox state, extracellular K+ concentrations, DC potential, electrocorticography and ICP from the cerebral cortex. Brain function of 14 patients with severe head injury (GCS < or = 8), who were hospitalized in the neurosurgical or general intensive care unit was monitored using this analyzer. Leao cortical spreading depression (SD) has been reported in many experimental animals but not in the human cerebral cortex. In one of the patients monitored, spreading depression was observed. This is the first time that spontaneous repetitive cortical SD cycles have been recorded from the cerebral cortex of a patient suffering from severe head injury. Typical SD cycles appeared 4-5 h after the beginning of monitoring this patient. During the first 3-4 cycles the responses of this patient were very similar to the responses to SD recorded in normoxic experimental animals. Electrocorticography was depressed whereas extracellular K+ levels increased. The metabolic response to spreading depression was characterized by oxidation of intramitochondrial NADH concomitant to a large increase in CBF. During brain death, an ischemic depolarization, characterized by decrease in CBF and an irreversible increase in extracellular K+, was recorded.

Brain↗

Neuronal adhesion molecule telencephalin induces rapid cell spreading of microglia.

Telencephalin (TLCN) is a neuronal surface glycoprotein whose expression is restricted to the telencephalon, the most rostral segment of the brain. TLCN binds to lymphocyte function-associated antigen-1 (LFA-1) integrin. In the central nervous system, LFA-1 is selectively and constitutively expressed by microglia, suggesting that TLCN/LFA-1 binding may mediate cell-cell interactions between telencephalic neurons and microglia. In the present study, we investigated the effects of recombinant TLCN protein on the morphology of microglia. TLCN induced an intensive spreading of lamellipodia, causing a rapid change in microglial morphology. In contrast, TLCN induced no significant change in morphology of neuroblastoma and fibroblasts. Furthermore, the TLCN-induced spreading of microglia was accompanied by a clustering of LFA-1 on cell surface membrane. These results provide evidence that TLCN binding to the surface of microglia transduces signals into microglia that mediate or accelerate cell spreading and LFA-1 redistribution, implying that neuronal TLCN may control the state and/or function of microglia in both physiological and pathological conditions.

Animals↗

High-affinity urokinase-derived cyclic peptides inhibiting urokinase/urokinase receptor-interaction: effects on tumor growth and spread.

Urokinase-type plasminogen activator (uPA) binds with high affinity to its specific cell surface receptor (uPAR) (CD87) via a well-defined sequence within the N-terminal region of uPA (uPA(19-31)). Since this uPA/uPAR-interaction plays a significant role in tumor cell invasion and metastasis, it has become an attractive therapeutic target. Two small peptidic cyclic competitive antagonists of uPA/uPAR-interaction have been developed, based on the uPAR binding site in uPA: WX-360 (cyclo(21,29)[D-Cys21]-uPA(21-30)[S21C;H29C]) and its norleucine (Nle) derivative WX-360-Nle (cyclo(21,29)[D-Cys21]-uPA(21-30)[S21C;K23Nle;H29C]). These peptides display an only five to 10-fold lower affinity to uPAR as compared to the naturally occurring uPAR-ligand uPA. In this study, WX-360 and WX-360-Nle were tested in nude mice for their potency to inhibit tumor growth and intraperitoneal spread of lacZ-tagged human ovarian cancer cells. Intraperitoneal administration of either cyclic peptide (20 mg peptide/kg; 1x daily for 37 days) into the tumor-bearing nude mice resulted in a significant reduction of tumor weight and spread within the peritoneum as compared to the untreated control group. This is the first report demonstrating effective reduction of tumor growth and spread of human ovarian cancer cells in vivo by small synthetic uPA-derived cyclic peptides competitively interfering with uPA/uPAR-interaction. Thus, both WX-360 and WX-360-Nle are promising novel compounds to reduce dissemination of human ovarian carcinoma.

Animals↗