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PubMed1989

Kinetics of cell spreading on protein precoated substrata: a study of interfacial aspects.

In this paper, interfacial aspects of spreading and adhesion of human skin fibroblasts on solid substrata after protein precoating have been studied. Three solid substrata were used with different surface free energy (gamma s): Tissue Culture Polystyrene (TCPS) with gamma s = 70 erg.cm-2, Polyvinylfluoride (PVF) with gamma s = 56 erg.cm-2 and Fluoroethylenepropylene (FEP) copolymer with gamma s = 18 erg.cm-2. The substrata were precoated with fetal calf serum, bovine fibronectin or bovine serum albumin. Cell spreading was evaluated by means of light microscopy and scanning electron microscopy (SEM). Adhesion sites were studied by transmission electron microscopy (TEM). In general, spreading was lowest on FEP and highest on TCPS. Although protein precoating markedly increased cell spreading, the relative order in which the cells spread on the protein precoated substrata remained identical to that on the bare substrata. Analysis of the kinetics of spreading demonstrated that spreading was fastest on the high-energy substratum and slowest on the low-energy substratum. In the presence of all three types of protein precoating, the average distance between a cell and a substratum after spreading was smaller (20-50 nm) than without a coating (greater than 100 nm).

Albumins↗
PubMed1993

Study of fibroblast spreading: pH dependence, involvement of the Na+/H(+)-antiporter and PKC.

The pH dependence of spreading of normal mouse embryo fibroblasts was investigated. It was shown that, in contrast to DNA synthesis, cell spreading did not depend on intracellular pH in the same pH range. Serum growth factors had no influence on intracellular pH in the suspended cells. Spreading of the fibroblasts on poly-L-lysine-coated coverslips in a serum-free medium did not alter intracellular pH. Cytoplasm alkalynization accompanying the fibroblasts spreading in a medium with serum is suggested to be due to the effect of serum growth factors on the spread cells. The inhibitor of the Na+ H(+)-antiporter, MIBA, and the inhibitor of PKC, staurosporin, as well as the PMA-induced cell depletion of PKC prevented pH increase, but had no effect on the spreading itself. It is concluded that the pH increase observed during fibroblasts spreading in a serum-containing medium is not required for the spreading itself being due to the activation of both the Na+/H(+)-antiporter and PKC.

Alkaloids↗
PubMed2006

Spreading on and penetration into thin, permeable print media: application to ink-jet printing.

This paper examines spreading and penetration of surfactant-laden drops on thin-permeable media with reference to ink-jet printing. A detailed review of the interaction of both pure liquids and surfactant containing solutions with porous substrates is given for individual spreading and penetration and for the combined processes. A new model based on energy arguments is derived and compared to current hydrodynamic equations used to describe simultaneous spreading and penetration. Three studies of how surfactant solutions interact with thin commercial ink-jet photographic quality papers are presented. Here, two relevant systems are examined: Tergitol 15-S-5 and 1,2-octanediol. The first study examines the spreading and penetration profiles for surfactant solutions over a range of concentrations spanning their critical micelle concentration. As expected, these profiles depend on the concentration of surfactant and the chemistry of the medium with which it interacts. In many cases, partial vertical penetration of the region directly beneath the drop dominates at low interaction times and will be significant in ink-jet applications. The second study consists of a parametric investigation of the energy-based model derived herein. It shows that the model can capture all of the behaviors observed in the first study. In the final study, the ability of the energy-based model to fully predict the spreading behavior of Tergitol 15-S-5 solutions is tested. It is found that the model produces good quantitative agreement at the highest concentrations and, as such, will be useful in screening spreading dynamics concentrated systems like ink-jet inks. Agreement at low to intermediate concentrations is often limited by finite induction periods prior to significant spreading and penetration. Possible corrections that could improve the agreement for weakly concentrated solutions are discussed, and directions for future studies of simultaneous spreading and penetration are proposed.

Journal Article↗
PubMed2005

Spreading speeds as slowest wave speeds for cooperative systems.

It is well known that in many scalar models for the spread of a fitter phenotype or species into the territory of a less fit one, the asymptotic spreading speed can be characterized as the lowest speed of a suitable family of traveling waves of the model. Despite a general belief that multi-species (vector) models have the same property, we are unaware of any proof to support this belief. The present work establishes this result for a class of multi-species model of a kind studied by Lui [Biological growth and spread modeled by systems of recursions. I: Mathematical theory, Math. Biosci. 93 (1989) 269] and generalized by the authors [Weinberger et al., Analysis of the linear conjecture for spread in cooperative models, J. Math. Biol. 45 (2002) 183; Lewis et al., Spreading speeds and the linear conjecture for two-species competition models, J. Math. Biol. 45 (2002) 219]. Lui showed the existence of a single spreading speed c(*) for all species. For the systems in the two aforementioned studies by the authors, which include related continuous-time models such as reaction-diffusion systems, as well as some standard competition models, it sometimes happens that different species spread at different rates, so that there are a slowest speed c(*) and a fastest speed c(f)(*). It is shown here that, for a large class of such multi-species systems, the slowest spreading speed c(*) is always characterized as the slowest speed of a class of traveling wave solutions.

Alleles↗
PubMedDate not supplied

A description of the spread of injectate after psoas compartment block using magnetic resonance imaging.

BACKGROUND AND OBJECTIVES: Magnetic resonance imaging (MRI) provides for excellent visualization of spread of solution after peripheral nerve block. The aim of this observational study was to utilize MRI to describe the distribution of injectate (gadopentetate dimeglumine) administered for continuous psoas compartment block (PCB) performed by use of two approaches (Capdevila and modified Winnie) and to describe the spread of injectate to the lumbar plexus. METHODS: Four volunteers were enrolled in a prospective crossover study. Each volunteer underwent PCB with catheter placement performed by use of Capdevila's approach followed 1 week later by PCB, with catheter placement performed by use of a modified Winnie approach. MRI of injectate distribution was performed after each PCB. RESULTS: The catheter was unable to be inserted in 1 volunteer undergoing Winnie's approach; therefore, 7 sets of MR images were analyzed. In 6 of 7 cases (4 Capdevila and 2 Winnie) spread was primarily within the psoas muscle. Contrast surrounded the L2-3 lumbar branch of the femoral nerve at L4 and cleaved the fascial plane within the psoas muscle and spread cephalad to reach the lumbar nerve roots. In 1 case (Winnie approach) contrast spread between the psoas and quadratus lumborum muscles. Contrast surrounded the femoral and obturator nerves where they lie outside the psoas muscle at L5. CONCLUSION: The most common pattern of injectate spread seen on MRI with both approaches to PCB was spread within the body of the psoas muscle around the lumbar branches (L2-4), with cephalad spread to the lumbar nerve roots. One catheter resulted in injectate between the psoas and quadratus lumborum muscles.

Adult↗
PubMed2005

Evaluation of prognostic significance in extracapsular spread of lymph node metastasis in patients with gastric cancer.

BACKGROUND: Extracapsular spread of lymph node metastasis has been shown as a negative prognostic factor in cancers of several other organs. This study was performed to clarify the prognostic significance of extracapsular spread in patients receiving curative resection for gastric cancer. METHODS: Extracapsular spread was defined as infiltration of cancer cells beyond the capsule of the metastatic lymph node. Four hundred and two patients who underwent curative gastrectomy were evaluated. Eight potential prognostic factors, including the International Union Against Cancer (Union International Contra la Cancrum; [UICC]) N stage and nodal status classified by the presence of lymph node metastasis or extracapsular spread, were examined. RESULTS: Three survival curves grouped by nodal status differed significantly, and prognosis of patients with extracapsular spread was significantly worse than for the other groups. Both UICC N stage ( P < .001) and nodal status ( P < .001) were significant prognostic factors by multivariate analysis. UICC N stages were subcategorized by nodal status, and survival was shown to be significantly worse in patients with extracapsular spread in the UICC N1 group ( P = .04). CONCLUSIONS: Extracapsular spread was a significant negative prognostic indicator on multivariate analysis, and may be useful in combination with UICC N stage. Extracapsular spread was regarded as an important indicator to refine the nodal staging system in gastric cancer.

Adult↗
PubMed2006

Metabolic regulation of neutrophil spreading, membrane tubulovesicular extensions (cytonemes) formation and intracellular pH upon adhesion to fibronectin.

Circulating leukocytes have a round cell shape and roll along vessel walls. However, metabolic disorders can lead them to adhere to the endothelium and spread (flatten). We studied the metabolic regulation of adhesion, spreading and intracellular pH (pHi) of neutrophils (polymorphonuclear leukocytes) upon adhesion to fibronectin-coated substrata. Resting neutrophils adhered and spread on fibronectin. An increase in pHi accompanied neutrophil spreading. Inhibition of oxidative phosphorylation or inhibition of P- and F-type ATPases affected neither neutrophil spreading nor pHi. Inhibition of glucose metabolism or V-ATPase impaired neutrophil spreading, blocked the increase in the pHi and induced extrusion of membrane tubulovesicular extensions (cytonemes), anchoring cells to substrata. Omission of extracellular Na(+) and inhibition of chloride channels caused a similar effect. We propose that these tubulovesicular extensions represent protrusions of exocytotic trafficking, supplying the plasma membrane of neutrophils with ion exchange mechanisms and additional membrane for spreading. Glucose metabolism and V-type ATPase could affect fusion of exocytotic trafficking with the plasma membrane, thus controlling neutrophil adhesive state and pHi. Cl(-) efflux through chloride channels and Na(+) influx seem to be involved in the regulation of the V-ATPase by carrying out charge compensation for the proton-pumping activity and through V-ATPase in regulation of neutrophil spreading and pHi.

Amiloride↗
PubMed2003

Interfacial effects in the spreading kinetics of liquid droplets on solid substrates.

Several theories deal with the spreading kinetics of liquids on solid substrate, most of which relate the rate of spreading to the surface tension and the viscosity of the liquid. Measurements of the spreading of a number of liquids exhibiting a wide range of surface tension and viscosity on dry soda-lime glass have been carried out to validate the proposed models. The measurements used a small droplet of constant volume to minimize gravitational effects. The contact radius was acquired as a function of time by an image analysis system. It was noted that power law theories describe the spreading rate for silicone oil on glass. However, significant departures were noted in the case of other liquids. Mechanistic considerations of our data suggest that equal volume droplets of similar surface tension and of diverse viscosity spread to the same area but at different rates. On the other hand, the spreading rate of glycerine, which exhibits incomplete spreading on glass, and that of silicone oil, with comparable viscosity behave similarly. These observations seemingly support the view that surface tension acts to retain the spherical shape of the droplet, whereas the difference between the solid-liquid and solid-vapor interfacial energies acts to enlarge the contact area. In the meantime, viscous dissipation acts to retard the spreading rate, past a constant rate regime.

Journal Article↗
PubMed1999

Leukocyte spreading behavior on vascular biomaterial surfaces: consequences of chemoattractant stimulation.

Chemoattractant-induced phenomena of polarity and migration of polymorphonuclear leukocytes (PMN) are believed to play a key physiological role in controlling bacterial infections on implantable vascular biomaterials. Our study targeted the spreading behavior of human PMN adherent to expanded polytetrafluoroethylene (ePTFE), pretreated with various plasma proteins, in response to the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (fMLP). To this end, a novel imaging configuration was developed to allow in situ reconstructive analysis of PMN 3-D morphology on opaque ePTFE surfaces, using optical sectioning confocal microscopy. Following fMLP stimulation, PMN morphological polarity was enhanced on all substrates studied except fibrinogen treated ePTFE. 3-D PMN morphometry revealed that in the absence of fMLP, overall cell spreading was minimized on albumin-treated ePTFE and maximized on fibrinogen and immunoglobulin-G-treated ePTFE. Following fMLP stimulation, overall PMN spreading increased markedly on untreated and albumin-coated ePTFE, while it stayed invariant on IgG and plasma treated ePTFE, and decreased on fibrinogen-treated ePTFE. Spatial analysis of PMN spreading following fMLP stimulation revealed enhanced PMN attachment on untreated and albumin treated ePTFE and diminished attachment on fibrinogen and plasma treated ePTFE. Thus, chemoattractant stimulation altered a wide range of PMN spreading attributes on ePTFE, including morphological polarity, substrate attachment, and 3-D membrane spreading, in a substrate dependent manner. These chemoattractant-induced spreading responses may also have important consequences for PMN phagocytosis. We report that fMLP stimulation led to enhanced unopsonized particulate phagocytosis on untreated and albumin treated ePTFE, but caused no discernible change in phagocytosis on other protein substrates. Thus, chemoattractant modulation of PMN spreading on ePTFE is highly substrate-regulated, and manifests in concerted effects on PMN phagocytosis.

Blood Vessel Prosthesis↗
PubMed1996

Epitope spreading occurs in active but not passive EAE induced by myelin basic protein.

Using experimental allergic encephalomyelitis, EAE, as a model for the study of autoimmune demyelinating disease in the CNS, previous studies have indicated that spread may occur with respect to the specificity of T cell responses during disease. This phenomenon, known as epitope spreading, is central to therapeutic strategies in multiple sclerosis (MS). However, in EAE, the clinical course, neuropathology and immunopathogenesis vary depending upon host factors and the method of disease induction. Since passive EAE in SJL/J mice resembles MS clinically and neuropathologically, this model was chosen to study the immune phenomenon of epitope spreading. T cells specific for whole 18.5 kDa MBP were used to initiate disease since MBP or one of its naturally occurring cleavage fragments may initiate a more physiological immune response than one generated to an artificially designed synthetic peptide. While a progressive increase in T cell responsiveness specific for the immunodominant MBP 87-106 region was observed during disease, there was no evidence of either intermolecular epitope spreading to the immunodominant region of proteolipid protein (PLP) 139-151 or of intramolecular epitope spreading to the exon 2 encoded region of MBP, which is spliced out of 18.5 kDa MBP. In addition there was no shift in immunodominance toward the subdominant MBP 16-35 region during disease. In contrast during active EAE induced by MBP, epitope spreading to the immunodominant epitope of PLP, 139-151, was observed. These data demonstrate that immune responses generated during passive versus active EAE may differ, and suggest that significant epitope spreading does not occur in chronic relapsing demyelinating disease initiated with T cells specific for whole MBP in the absence of exogenous antigen, complete Freund's adjuvant and pertussis. Implications of these findings with regard to epitope spreading in MS are discussed.

Adoptive Transfer↗
PubMed1996

Extracapsular spread in the clinically negative neck (N0): implications and outcome.

Cervical metastasis is the most important prognostic factor in head and neck cancer patients. The prognostic significance of extracapsular spread of tumor in metastatic lymph nodes has also been documented. The presence of extracapsular spread further reduces the survival by 50% in those patients with cervical metastatic disease. Most patients with clinically negative necks (stage N0) have a good prognosis. However, some of these patients will have neck disease and distant metastasis and will eventually die. Because the presence of extracapsular spread is a predictor of poor outcome, we hypothesized that extracapsular spread may be a factor in the subset of patients with clinically negative necks who have poor outcomes. One hundred nine patients with clinically negative necks who had undergone neck dissection were identified. Occult metastasis was observed in 34% of patients. In this group, extracapsular spread was present in 18 (49%) patients. Overall, 103 patients were evaluable, of whom 70 (68%) remain free of disease 2 or more years after treatment. A subgroup of 68 patients had histologically negative nodes, of whom 56 (82%) are free of disease. Of patients with extracapsular spread, only 5 (31%) of 16 are free of disease. This is in contrast to patients with metastasis confined to the lymph node, of whom 9 (47%) of 19 are free of disease. Statistical analysis of these data shows that for this sample size this difference is significant. The addition of radiation therapy did not improve outcome in these patients. Extracapsular spread predicts a worse outcome in patients with subclinical cervical metastasis. Alternative modes of adjuvant therapy are suggested because of the poor results of postoperative radiation therapy in patients with extracapsular spread.

Carcinoma, Squamous Cell↗
PubMed1998

Transneuronal spread of Semliki Forest virus in the developing mouse olfactory system is determined by neuronal maturity.

Many neurotropic virus infections have been shown to be virulent in neonatal and suckling mice but avirulent in weaned mice. The neurotropic alphavirus Semliki Forest virus is a well-studied example of this and importantly the age-related change in neurovirulence of this virus has been shown to be independent of specific immune responses. During the first two postnatal weeks many major physiological changes including axonogenesis, synaptogenesis and myelination occur within the rodent CNS. To investigate whether these changes affect virus replication, spread and virulence we have studied the course of infection in the mouse olfactory system. The olfactory system is well-characterized with regard to its development and neuroanatomy and represents an important route of entry of many neurotropic viruses. Following Semliki Forest virus infection, mice younger than 14 days-of-age died from a fulminant panencephalitis, whilst those 15 days and older survived and cleared the infection. Microscopic examination of brains from mice inoculated intranasally either bilaterally or unilaterally and stained by in situ hybridization to detect viral RNA revealed spread of infection along neurites in a circuit-specific manner. Spread in the main olfactory bulb and to primary, secondary and tertiary olfactory connections was observed. In neonatal mice virus rapidly spread throughout the olfactory system and the temporal progress of the infection correlated with the known connectivity patterns of this system. Both anterograde and retrograde axonal spread were observed. During the first three postnatal weeks the rate and extent of virus spread decreased with increasing age. Spread of infection between specific structures was closely related to neuronal maturation. As olfactory system connections matured transmission of virus was curtailed. In mice inoculated at six weeks or six months-of-age infection was minimal in and rarely observed beyond the continually renewed olfactory nerve layer. The ability of this virus to replicate and, or spread in the CNS is clearly linked to neuronal maturation.

Alphavirus Infections↗
PubMed2002

Directional spread of an alpha-herpesvirus in the nervous system.

Pseudorabies virus (PRV), an alpha-herpesvirus, is capable of spreading between synaptically connected neurons in diverse hosts. In this report, two lines of experimentation are summarized that provide insight into the mechanism of virus spread in neurons. First, techniques were developed to measure the transport dynamics of capsids in infected neurons. Individual viral capsids labeled with green fluorescent protein (GFP) were visualized and tracked as they moved in axons away from infected neuronal cell bodies in culture during egress. Second, the effects of three viral membrane proteins (gE, gI and Us9) on the localization of envelope, tegument, and capsid proteins in infected, cultured sympathetic neurons were determined. These three proteins are necessary for spread of infection from pre-synaptic neurons to post-synaptic neurons in vivo (anterograde spread). Us9 mutants apparently are defective in anterograde spread in neural circuits because essential viral membrane proteins such as gB are not transported to axon terminals to facilitate spread to the connected neuron. By contrast, gE and gI mutants manifest their phenotype because these proteins most likely function at the axon terminal of the infected neuron to promote spread. These two sets of experiments are consistent with a model for herpesvirus spread in neurons first suggested by Cunningham and colleagues where capsids and envelope proteins, but not whole virions, are transported separately into the axon.

Animals↗
PubMedDate not supplied

The effects of arm position on central spread of local anesthetics and on quality of the block with axillary brachial plexus block.

BACKGROUND AND OBJECTIVES: Spread of local anesthetic solution in axillary brachial plexus block is thought to be influenced by the position of the arm and the use of compression maneuvers. We investigated how these two factors affected central local anesthetic spread and block quality. METHODS: Radiographic spread of local anesthetic was studied in 80 adult patients. They received mepivacaine mixed with contrast agent through an indwelling catheter with the arm abducted to either 0 or 90 degrees , and with or without local digital compression. Central and peripheral spread of the contrast agent was evaluated with anteroposterior radiographs of the axilla. Block quality was studied in a separate series of 70 adult patients. They received mepivacaine with the arm abducted 0 degrees or 90 degrees . The degree of sensory and motor block was assessed 20 minutes after the injection. RESULTS: Arm position at 0 degrees abduction promoted central spread of the contrast agent. Although digital compression suppressed peripheral spread effectively, it did not improve the central spread of the solution. Sensory block was comparable in all terminal nerves of the arm in both arm positions, whereas motor block of the radial nerve was promoted with no abduction. CONCLUSIONS: The central spread of local anesthetics is facilitated by injection without abduction of the arm but not by the use of compression at the injection site. This, however, did not alter the quality of the block.

Adult↗
PubMed2003

An ultraslow-spreading class of ocean ridge.

New investigations of the Southwest Indian and Arctic ridges reveal an ultraslow-spreading class of ocean ridge that is characterized by intermittent volcanism and a lack of transform faults. We find that the mantle beneath such ridges is emplaced continuously to the seafloor over large regions. The differences between ultraslow- and slow-spreading ridges are as great as those between slow- and fast-spreading ridges. The ultraslow-spreading ridges usually form at full spreading rates less than about 12 mm yr(-1), though their characteristics are commonly found at rates up to approximately 20 mm yr(-1). The ultraslow-spreading ridges consist of linked magmatic and amagmatic accretionary ridge segments. The amagmatic segments are a previously unrecognized class of accretionary plate boundary structure and can assume any orientation, with angles relative to the spreading direction ranging from orthogonal to acute. These amagmatic segments sometimes coexist with magmatic ridge segments for millions of years to form stable plate boundaries, or may displace or be displaced by transforms and magmatic ridge segments as spreading rate, mantle thermal structure and ridge geometry change.

Journal Article↗
PubMed2003

Plant sterol-enriched spread enhances the cholesterol-lowering potential of a fat-reduced diet.

OBJECTIVE: To determine the effect of a plant sterol-enriched spread on plasma cholesterol concentrations when replacing butter or a standard polyunsaturated spread in a diet containing 30% of energy fat. DESIGN: Parallel butter phase followed by double-blind, randomized, cross-over polyunsaturated spread phases. SETTING: General community. SUBJECTS: Volunteer sample of 50 free-living men and women with mean age (s.d.) 46.7 y (10.5), moderately elevated plasma total cholesterol 5.95 mmol/l (0.78), and body mass index 26.0 (3.9) kg/m(2). INTERVENTION: Participants ate a moderately low-fat diet (30% of energy) for the 11-week intervention. During the first 3 weeks the diet included 20 g per day of butter. Participants were then randomized to replace the butter with 25 g of polyunsaturated spread with or without 2 g of plant sterols for 4 weeks, crossing over in the last 4 weeks to the alternate spread. MAIN OUTCOME MEASURES: Plasma cholesterol and fatty acids. RESULTS: Replacing butter with a standard polyunsaturated fat spread reduced mean plasma total cholesterol concentrations by 4.6% (from 6.09 (0.82) to 5.81 (0.77) mmol/l, P<0.01) and low-density lipoprotein cholesterol by 5.5% (from 3.98 (0.76) to 3.76 (0.74) mmol/l, P<0.05). Replacing butter with a polyunsaturated spread containing plant sterols reduced plasma total cholesterol by 8.9% (from 6.09 (0.82) to 5.55 (0.76) mmol/l, P<0.01) and low density lipoprotein cholesterol by 12.3% (from 3.98 (0.76) to 3.49 (0.72) mmol/l, P<0.01). Plasma high density lipoprotein cholesterol concentration was the same on the three diets. CONCLUSION: In people with moderately raised plasma cholesterol concentrations consuming reduced-fat diets the reduction in plasma total and low-density lipoprotein cholesterol concentrations achieved by replacing butter with a polyunsaturated spread is enhanced by addition of plant sterols.

Body Mass Index↗
PubMed2004

Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms.

The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucinous epithelium, mucinous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass.

Appendiceal Neoplasms↗
PubMed2004

AlphaPIX associates with calpain 4, the small subunit of calpain, and has a dual role in integrin-mediated cell spreading.

Binding of integrins to the extracellular matrix results in actin cytoskeletal rearrangements, e.g. during cell spreading, by regulating the activity of Rho GTP-ases. We have shown previously that alphaPIX (Cool-2 or ARHGEF6), a Rac1/Cdc42-specific guanine nucleotide exchange factor (GEF), binds to beta-parvin/affixin and colocalizes with integrin-linked kinase in actively spreading cells, suggesting that alphaPIX is involved in integrin-induced signaling leading to activation of Rac1/Cdc42. Here we report calpain 4, the small subunit of the proteases mu-calpain and m-calpain, as a novel binding partner of alphaPIX. This association was identified by the CytoTrap system and confirmed by coimmunoprecipitation and glutathione S-transferase pull-down assays. The alphaPIX triple domain SH3-DH-PH was found to be required for calpain 4 binding. During integrin-dependent spreading of CHO-K1 cells, alphaPIX colocalized with mu- and m-calpain, integrin-linked kinase, and beta1 integrin in early integrin-containing clusters. Overexpression of alphaPIX wild type but not the GEF-deficient mutant (L386R/L387S) resulted in enhanced formation of characteristic cellular protrusions during cell spreading, suggesting that alphaPIX GEF activity is necessary for this specific actin cytoskeletal reorganization. The calpain inhibitors calpeptin and calpain inhibitor IV significantly inhibited integrin-dependent cell spreading. However, concomitant overexpression of alphaPIX wild type or the L386R/L387S mutant restored cell spreading. Together, these data suggest that alphaPIX is a component of early integrin clusters and plays a dual role in integrin-dependent cell spreading. Whereas alphaPIX GEF activity contributes to enhanced formation of cellular protrusions, the GEF-independent association with calpain 4 leads to induction of a yet unknown signaling cascade resulting in cell spreading.

Amino Acid Substitution↗