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Edge-spreading lithography: use of patterned photoresist structures to direct the spreading of alkanethiols on gold.

Edge-spreading lithography (ESL) has been extended to fabricate gold structures with different geometries and feature sizes on silicon substrates. In the present variant of ESL, we used photoresist structures patterned on a thin film of gold to transport alkanethiol molecules from an elastomeric stamp to the gold surface where they formed a self-assembled monolayer (SAM) along the edge of each resist feature. The emerging SAM could expand laterally on the gold via reactive spreading, during which the footprints of the resist structures were enlarged in the same fashion. Upon removal of the photoresist, selective etching of gold revealed those regions that were protected by the SAM, yielding accurate outlines of the resist features on the substrate. The width of resultant gold structures was determined by the distance over which the monolayer expanded during spreading, and could be conveniently controlled well below 200 nm by varying the contact time and/or the concentration of alkanethiol in the ink.

Journal Article↗

Dynamic modulation of cytoskeletal proteins linking integrins to signaling complexes in spreading cells. Role of skelemin in initial integrin-induced spreading.

Recently we showed that signaling across beta3-integrin leads to activation of calpain and formation of integrin clusters that are involved in Rac activation. The subsequent activation of Rac and Rho leads to the formation of focal complexes and focal adhesions, respectively. The goal of the present study was to determine whether different proteins link the integrin to the cytoskeleton in the different complexes. We show that talin is present in focal adhesions but not in the calpain-induced clusters. alpha-Actinin colocalized with integrin at various sites, including the calpain-induced clusters. Skelemin, a protein shown recently to interact with beta1- and beta3-integrin in vitro, colocalized with integrin in calpain-induced clusters but was absent from focal adhesions. Cells transiently expressing skelemin C2 motifs, which contain the integrin binding site, failed to form integrin clusters or to spread on a substrate for beta1- and beta3-integrins. These results 1) suggest a dynamic reorganization of integrin complexes during cell spreading, 2) show that different cytoskeletal proteins link integrins in different complexes, and 3) demonstrate that skelemin is responsible for linking integrin to the calpain-induced clusters, and 4) show that the integrin-skelemin interaction is essential for transmission of signals leading to the initial steps of cell spreading.

Actinin↗

"See and Treat": spreading like wildfire? A qualitative study into factors affecting its introduction and spread.

OBJECTIVES: The aim of this paper was to explore key factors that influenced the spread of "See and Treat" in a range of accident and emergency (A&E) departments. METHODS: The study adopted a qualitative approach, and semi-structured interviews were undertaken with 21 key individuals working across 10 A&E departments operating See and Treat. Participants included clinicians, managers, and chief executives. RESULTS: Many factors influenced the spread of See and Treat. The initiative was well supported and monitored by external agencies, patients benefited and no staff groups lost out, waiting times were reduced, and Department of Health targets were achieved. However, this study indicates there were also a range of factors that limited the spread of See and Treat, including lack of additional resources and suitably experienced staff, impact upon quality of care, and no prior evaluation of its benefits. An interesting additional factor that may be both facilitating and limiting is the complexity of the A&E culture, in particular staff perspectives about working with minor injuries. CONCLUSIONS: See and Treat was promoted as a solution to waiting times problems in A&E, without evidence from any national evaluation. However, many staff members referred to its usefulness as a tool to reduce waiting times and enhance the patient journey, although resource, quality, and staffing issues may mean such an initiative may be difficult to sustain in its present form.

Appointments and Schedules↗

Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K+ in hippocampus of anesthetized rats.

The potential shifts (delta Vo) associated with spreading depression (SD) were analysed with the help of multiple extracellular recording and ion-selective microelectrodes in the CA1 region of the dorsal hippocampus of anesthetized rats. Recurrent waves of SD were induced by perfusing high K+ solution through microdialysis probes. SD-related delta Vo had a composite wave shape, consisting of an early, rapidly shifting part (phase I) followed by a slower shift to a second negative maximum (phase II). delta Vo shifts in stratum radiatum usually started earlier, always lasted longer and had larger amplitude than those recorded in stratum pyramidale. The delta Vo responses in stratum radiatum had an inverted saddle shape created by a transient relatively positive "hump" interposed between phases I and II. During this "hump", the potentials in the two layers transiently approached one another. During continuous high K+ dialysis, successive delta Vo waves episodes evolved according to a consistent pattern: while phase I remained unchanged, phase II increased in amplitude and duration with each episode. Eventually, a depressed state developed which lasted for many minutes, termed here prolonged unstable spreading depression. During phase I, delta Vo and extracellular K ([K+]o) changes were correlated. During phase II, [K+]o decreased even as delta Vo continued to increase. During SD, [Ca2+]o decreased to < 0.01 mM. During phases I and II, both [Ca2+]o and [Na+]o remained low. The recoveries of [Ca2+]o and [Na+]o had an initial fast and a later much slower phase and took several minutes longer than the recoveries of [K+]o and delta Vo. Depth profiles of delta Vo and delta [K+]o revealed strikingly steep gradients early and late during a wave; but voltage and ion gradients were not precisely correlated either in time or in space. We conclude that delta Vo of phases I and II are generated by different processes. Membrane ion currents cannot fully explain the delta Vo responses. The possible contributions by ion diffusion and by active ion transport are discussed. The extremely low level to which [Ca2+]o sinks during SD, and its two-phase recovery, indicate intracellular sequestration or binding of substantial amounts of Ca2+ ions. The residual deficit of [Ca2+]o following recovery of SP shifts may account for the persistent depression of synaptic transmission after repolarization of neurons.

Anesthesia↗

Plasmatocyte spreading peptide does not induce Microplitis demolitor polydnavirus-infected plasmatocytes to spread on foreign surfaces.

Capsule formation by the moth Pseudopulsia includens requires that plasmatocytes change from being nonadhesive cells in circulation to strongly adhesive cells capable of attaching to the foreign target and one another. This change in adhesive state is induced by Plasmatocyte Spreading Peptide (PSP1); a 23 amino acid peptide isolated from P. includens plasma. Plasmatocytes from hosts parasitized by Microplitis demolitor remain in a nonadhesive state after infection by Microplitis demolitor polydnavirus (MdPDV). This alteration in plasmatocyte function prevents P. includens from encapsulating the developing parasitoid. In the current study, we examined whether MdPDV infection eliminates PSP1-responsive plasmatocytes from circulation or disrupts the ability of PSP1 to induce adhesion and spreading of plasmatocytes to foreign surfaces. In vivo experiments revealed that infection of P. includens by MdPDV induced an increase in the total number of hemocytes in circulation but reduced the proportion of hemocytes in circulation that were plasmatocytes. However, plasmatocytes normally capable of responding to PSP1 were not eliminated from circulation. Both in vivo and in vitro experiments indicated that plasmatocytes inoculated with MdPDV lost the capacity to respond to PSP1 4-6 h post-infection. Infection of P. includens with MdPDV reduced expression levels of prepro-PSP1 mRNA in hemocytes but did not appear to alter expression levels in fat body.

Animals↗

Does inhibition spread in a manner analogous to spreading activation?

Two experiments explored limited capacity inhibitory selective attention processes in working memory. Experiment 1 used a modified Sternberg-type 'short-term memory scanning' task, where both irrelevant and relevant memory-set words were included to see if an inhibitory fan effect operated on lexical associates of the should-be-ignored (irrelevant) words. Experiment 2 used a 'negative priming' task, where a target letter to be named was flanked by one, two, or three distractor letters to see if an inhibitory fan effect operated on the should-be-ignored letters. Results from both experiments supported the existence of a limited capacity spreading inhibition counterpart to spreading activation. The findings were discussed in terms of a model recently proposed by Neumann and DeSchepper (1991; 1992) in which two selective attention subprocesses (one excitatory and one inhibitory) in the brain each maximise opposed functions within their respective resource limitations in working memory.

Analysis of Variance↗

[Relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF) in CT image system.].

In the CT image system, we revealed the relationship between line spread function (LSF), or slice sensitivity profile (SSP), and point spread function (PSF). In the system, the following equation has been reported; I(x,y) = O(x,y) ** PSF(x,y), in which I(x,y) and O(x,y) are CT image and object function, respectively, and ** is 2-dimensional convolution. In the same way, the following 3-dimensional expression applies; I'(x,y,z) = O'(x,y,z) *** PSF'(x,y,z), in which z-axis is the direction perpendicular to the x/y-scan plane. We defined that the CT image system was separable, when the above two equations could be transformed into following equations; I(x,y) = [O(x,y) * LSF(x)(x) ] * LSF(y)(y) and I' (x,y,z) = [ O'(x,y,z) * SSP(z) ] ** PSF(x,y), respectively, in which LSF(x)(x) and LSF(y)(y) are LSFs in x- and y-direction, respectively. Previous reports for the LSF and SSP are considered to assume the separable-system. Under the condition of separable-system, we derived following equations; PSF(x,y)=LSF(x)(x) LSF(y)(y) and PSF' (x,y,z) = PSF(x,y) SSP(z). They were validated by the computer-simulations. When the study based on 1-dimensional functions of LSF and SSP are expanded to that based on 2- or 3-dimensional functions of PSF, derived equations must be required.

Computer Simulation↗

Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats.

Vascular changes accompanying spreading depression (SD) remain controversial. We examined dynamic alterations of local cerebral blood volume (CBV) during SD by observing light transmission at an isosbestic point of hemoglobin (550 nm) in seven rats and five cats under alpha-chloralose/urethane anesthesia. The two species were used for comparison between the lissencephalic and gyrencephalic brains. We found that a concentrated K(+) solution microinjected into the sensorimotor cortex provoked CBV changes that appeared as a repetitive propagation of concentric wave-rings of ischemia followed by hyperemia expanding peripherally from the injection site at speeds of 1.9-3.2 mm/min. The dynamic CBV changes continued repeatedly every 1-5 min for more than 30 min in three rats, ceased within 30 min in three rats and remained at the site of K(+) injection in one rat. Similar repeated CBV changes occurred in two out of five cats.

Animals↗

Mechanisms of spreading depression and hypoxic spreading depression-like depolarization.

Spreading depression (SD) and the related hypoxic SD-like depolarization (HSD) are characterized by rapid and nearly complete depolarization of a sizable population of brain cells with massive redistribution of ions between intracellular and extracellular compartments, that evolves as a regenerative, "all-or-none" type process, and propagates slowly as a wave in brain tissue. This article reviews the characteristics of SD and HSD and the main hypotheses that have been proposed to explain them. Both SD and HSD are composites of concurrent processes. Antagonists of N-methyl-D-aspartate (NMDA) channels or voltage-gated Na(+) or certain types of Ca(2+) channels can postpone or mitigate SD or HSD, but it takes a combination of drugs blocking all known major inward currents to effectively prevent HSD. Recent computer simulation confirmed that SD can be produced by positive feedback achieved by increase of extracellular K(+) concentration that activates persistent inward currents which then activate K(+) channels and release more K(+). Any slowly inactivating voltage and/or K(+)-dependent inward current could generate SD-like depolarization, but ordinarily, it is brought about by the cooperative action of the persistent Na(+) current I(Na,P) plus NMDA receptor-controlled current. SD is ignited when the sum of persistent inward currents exceeds persistent outward currents so that total membrane current turns inward. The degree of depolarization is not determined by the number of channels available, but by the feedback that governs the SD process. Short bouts of SD and HSD are well tolerated, but prolonged depolarization results in lasting loss of neuron function. Irreversible damage can, however, be avoided if Ca(2+) influx into neurons is prevented.

Calcium Channels↗

Perineural spread of cutaneous basal and squamous cell carcinomas. The clinical appearance of spread into the trigeminal and facial nerves.

Five patients were studied in whom a trigeminal or facial neuropathy resulted from perineural spread of basal or squamous cell carcinomas arising in the skin of the face. The cause of the neuropathy was not immediately apparent because there was no evidence of local skin recurrence in any of the patients after the onset of their neurologic symptoms. Pain was a prominent feature in those patients with trigeminal involvement. Radiologic investigations were helpful in only one patient. The diagnosis should be suspected when symptoms and signs are confined initially to superficial branches of the trigeminal or facial nerves and later extend to more central branches in the order in which they arise. Confirmation can be made by microscopic examination of the nerves involved.

Aged↗

[Intraepithelial spread of the squamous cell carcinoma of the uterine cervix into the endometrium. A contribution to the question of a surface spread of the cervical carcinoma].

Four cases have been reported in which a squamous cell carcinoma of the uterine cervix was spreading on the surface of nearly the whole endometrial cavity by expansive intra-epithelial growth. In one of these cases, in the portio, there was only a beginning invasion into the stroma, whereas in the other three cases the wall of the cervix was variably infiltrated. In two cases a change to infiltrating growth into the corpus uteri could be observed.

Aged↗

Pulmonary surfactant proteins SP-B and SP-C in spread monolayers at the air-water interface: III. Proteins SP-B plus SP-C with phospholipids in spread monolayers.

Spread binary monolayers of surfactant-associated proteins SP-B and SP-C were formed at the air-water interface. Surface pressure measurements showed no interactions between the hydrophobic proteins. The effects of a mixture of SP-B plus SP-C (2:1, w/w) on the properties of monolayers of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and DPPC:DPPG (7:3, mol:mol) were studied. During compression of ternary and quaternary films, containing less than 0.4 mol% or 5 weight% total protein, the proteins were not squeezed out and appeared to remain associated with the film until collapse at surface pressures of about 65-70 mN.m-1. At initial concentrations of total protein of about 0.9 mol% or 10 weight%, exclusion of protein-lipid complexes was observed at 40-50 mN.m-1. Larger amounts of phospholipid were removed by proteins from (SP-B:SP-C)/DPPG films than from (SP-B:SP-C)/DPPC ones. Separate squeeze-out of SP-B (or SP-B plus DPPC) at about 40 mN.m-1, followed by exclusion of SP-C (or SP-C plus DPPC) at about 50 mN.m-1, was observed in (SP-B:SP-C)/DPPC films. This led to a conclusion that there was independent behavior of SP-B and SP-C in (SP-B:SP-C)/DPPC monolayers. The quaternary (SP-B:SP-C)/(DPPC:DPPG) films showed qualitatively similar process of squeeze-out of the proteins. In the ternary mixtures of SP-B plus SP-C with DPPG separate exclusion of SP-B was not detected; rather, the data was consistent with exclusion of a (SP-B:SP-C)/DPPG complex at about 50 mN.m-1. The results imply possible interactions between SP-B and SP-C and the acidic phospholipid.

1,2-Dipalmitoylphosphatidylcholine↗

Rapid epidemic spread of HIV type 1 subtype A1 among intravenous drug users in Latvia and slower spread of subtype B among other risk groups.

To investigate the rapid HIV epidemic in Latvia, 97 newly detected individuals were sampled in 2000-2001. To establish the molecular epidemiology we sequenced the env V3 and gag p17 regions of the HIV genome and compared them with reference sequences using phylogenetic analyses. As expected, the vast majority (n = 88; 91%) were intravenous drug users (IDUs) from the Riga region. Also, the majority of the investigated individuals (n = 93; 96%) were found to carry a subtype A1 virus that may have entered the Latvian IDU population several times. In addition, one IDU was infected with CRF03_AB and three other individuals, who had been infected through sexual contacts, carried subtype B virus. Thus, subtype A1 dominates the Latvian epidemic and is strongly associated with the IDU risk group. Although some spread of subtype A1 has occurred in the heterosexual group, subtype B dominates among homosexually and heterosexually infected individuals.

Disease Outbreaks↗

[Evaluation of the accuracy of line spread function (LSF) and point spread function (PSF) measured in the computed tomography.].

We propose a method to estimate the accuracy of the line spread function (LSF) in computed tomography (CT). When we assume an object for scanning has a shape and CT-value in the x-y scan-plane that are constant in the z-direction perpendicular to the scan-plane, blurring in the image of the object is predicted with calculation by the LSF measured in the scanner. When using the precise LSF, the calculated image must agree well with the scanned image of the phantom corresponding to the object. Then, verification of LSF is performed by comparing the calculated image with the scanned image. We measured the LSF in our scanner, and scanned a cylindrical phantom with constant diameter and CT-value in which the direction of cylinder was parallel to the z-direction, as mentioned above. Images calculated by using the LSF corresponded well to scanned images, indicating the validity of the LSF. We obtained another LSF by an inappropriate manner, and calculated images using it. Those images showed an apparent difference with scanned images, indicating the inaccuracy of the LSF. Our technique is effective to evaluate the accuracy of LSF, PSF, and also modulation transfer function (MTF) derived from the LSF or PSF.

Phantoms, Imaging↗

Histologic characteristics and tumor spread of recurrent glottic carcinoma: analysis on whole-organ sections and comparison with tumor spread of primary glottic carcinomas.

BACKGROUND: The assessment of the precise tumor extent of recurrent glottic carcinomas is a challenge. METHODS: The histologic characteristics of 29 recurrent glottic carcinomas after radiation failures, initially classified as T1 and T2, were analyzed on whole-organ slices. The growth patterns of 21 recurrent prT3 and prT4 and 52 primary pT3 and pT4 carcinomas were compared. RESULTS: Fifteen of 29 (52%) recurrent carcinomas were under-staged by imaging studies and endoscopy. Most recurrent carcinomas presented with multicentric tumor foci, whereas most primary carcinomas with a concentric tumor growth pattern (p < .05). Undifferentiated dissociated tumor cells were observed more often in the vicinity of recurrent tumor foci than of the primary tumor mass (p < .05). CONCLUSION: Recurrent glottic carcinomas are often under-staged and present with multiple tumor foci dispersed in different regions of the larynx. If voice-preserving salvage surgery is considered as a treatment option, these facts should be kept in mind.

Carcinoma↗