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PubMed2003

Evaluation of time-dependent spread of tissue damage in experimental spinal cord injury by killed-end evoked potential: effect of high-dose methylprednisolone.

OBJECT: Histopathological studies on spinal cord injury (SCI) have demonstrated time-dependent spread of tissue damage during the initial several hours postinjury. When the long tract within the spinal cord is stimulated, a large monophasic positivity occurs at the injury site. This type of potential, termed the killed-end evoked potential (KEEP), indicates that a nerve impulse approaches but does not pass beyond the injury site. The authors tested the hypothesis that the damage spread can be evaluated as a progressive shift of the KEEP on a real-time basis. The effect of high-dose methylprednisolone sodium succinate (MPSS) on the spread of tissue damage was also examined by this methodology. METHODS: The KEEP was recorded using an electrode array placed on the spinal cord at the T-10 level in cats. This electrode array consisted of multiple 0.2-mm-diameter electrodes, each separated by 0.5 mm. Spinal cord injury was induced using a vascular clip (65 g pinching pressure for 30 seconds). The midline posterior surface of the spinal cord was stimulated bipolarly at the C-7 level by applying a single pulse at supramaximal intensity. During the initial period of 6 hours postinjury, the localization of the largest KEEP shifted progressively up to 2.5 mm rostral from the injury site. The amplitude of the KEEP recorded at the injury site decreased to 55 to 70% and became slightly shortened in latency as the localization of the largest KEEP shifted rostrally. These findings imply that the injury site KEEP represents the volume-conducted potential of the largest KEEP at the site of the conduction block. It moved away from the injury site in association with the damage spread, and this was confirmed histopathologically. A decrease in amplitude of KEEP at the injury site appeared to be the most sensitive measure of the damage spread, because the amplitude of the volume-conducted KEEP is inversely proportional to the square of the distance between the recording site and site of conduction block. Administered immediately after SCI, MPSS clearly inhibited these events, especially within 30 minutes postinjury. CONCLUSIONS: The KEEP enables sequential evaluation to be made of the time-dependent spread of tissue damage in SCI in the same animal. It is, therefore, useful for detecting the effect of therapeutic interventions and for determining the therapeutic time window. The efficiency of MPSS to inhibit the spread of damaged tissue appeared to be maximized when it was administered within the initial 30-minute period postinjury.

Animals↗
PubMed1990

The relation between color spreading and illusory contours.

In the present study, we examine the relation between neon color spreading (Redies & Spillmann, 1981) and illusory contours. In Experiment 1, the effects of misalignment between the line elements on the illusory contours in the Ehrenstein figure and in the Redies-Spillmann figure were examined. The remarkable overlap of the two curves for the likelihood of perceiving illusory contours in the Ehrenstein figure and in the Redies-Spillmann figure suggests that the illusory contours surrounding brightness enhancement (Ehrenstein, 1941) and those surrounding neon color spreading are caused by the same mechanism. We further examined both the effects of the interposed grids seen either in front of or behind the figures (Experiment 2) and the effects of misalignment (Experiment 3) on the illusory contours and range of color spreading, and found a high correlation between the appearance/disappearance of illusory contours and global/local color spreading. In Experiment 4, we added new lines to induce illusory contours to the line elements inducing local color spreading. We found that global color spreading was seen to cover the area surrounded by the illusory contours. On the basis of these findings, we suggest that there is an interaction between illusory contours and local color spreading.

Adult↗
PubMed2003

Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis.

The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.

Adoptive Transfer↗
PubMed2006

B cells are crucial for determinant spreading of T cell autoimmunity among beta cell antigens in diabetes-prone nonobese diabetic mice.

The determinant spreading of T cell autoimmunity plays an important role in the pathogenesis of type 1 diabetes and in the protective mechanism of Ag-based immunotherapy in NOD mice. However, little is known about the role of APCs, particularly B cells, in the spreading of T cell autoimmunity. We studied determinant spreading in NOD/scid or Igmu(-/-) NOD mice reconstituted with NOD T and/or B cells and found that mice with mature B cells (TB NOD/scid and BMB Igmu(-/-) NOD), but not mice that lacked mature B cells (T NOD/scid and BM Igmu(-/-) NOD), spontaneously developed Th1 autoimmunity, which spread sequentially among different beta cell Ags. Immunization of T NOD/scid and BM Igmu(-/-) NOD mice with a beta cell Ag could prime Ag-specific Th1 or Th2 responses, but those T cell responses did not spread to other beta cell Ags. In contrast, immunization of TB NOD/scid and BMB Igmu(-/-) NOD mice with a beta cell Ag in IFA induced Th2 responses, which spread to other beta cell Ags. Furthermore, we found that while macrophages and dendritic cells could evoke memory and effector T cell responses in vitro, B cells significantly enhanced the detection of spontaneously primed and induced Th1 responses to beta cell Ags. Our data suggest that B cells, but not other APCs, mediate the spreading of T cell responses during the type 1 diabetes process and following Ag-based immunotherapy. Conceivably, the modulation of the capacity of B cells to present Ag may provide new interventions for enhancing Ag-based immunotherapy and controlling autoimmune diseases.

Animals↗
PubMed1999

[CT findings of localized lymphatic spread of lung cancer: correlation with pathologic findings].

PURPOSE: The appearance of localized lymphatic spread of lung cancer as evaluated by computed tomography (CT) was correlated with the pathologic specimens in 178 patients. Clinical significance was also studied, with emphasis on nodal staging (N factor). MATERIALS AND METHODS: Eighteen of 178 patients histopathologically demonstrated severe lymphatic spread of lung cancer along the bronchovascular bundles. CT findings of localized lymphatic spread of lung cancer and nodal staging of 18 patients were retrospectively reviewed and compared with 160 patients with no severe localized lymphatic spread of lung cancer. RESULTS: All 18 patients with severe lymphatic spread showed linear opacities extending from the tumor to the pulmonary hilum or peripheral pleura depending on the location of lung cancer. Ten of the 18 patients also showed regional thickening of bronchovascular bundles. The nodal staging of these 18 patients was more aggressive than that of other patients without severe lymphatic spread. CONCLUSION: If linear opacities and regional thickening of bronchovascular bundles extending from the tumor to pulmonary hilum or peripheral pleura are demonstrated on CT, severe lymphatic spread of lung cancer can be strongly suspected, and lung cancer staging should be done carefully.

Adult↗
PubMed2001

Simulating the spread of membrane potential changes in arteriolar networks.

OBJECTIVE: Our aim was to simulate the spread of membrane potential changes in microvascular trees and then make the simulation programs accessible to other researchers. We have applied our simulations to demonstrate the implications of electrical coupling between arteriolar smooth muscle and endothelium. METHODS: A two-layered, cable-like model of an arteriole was used, and the assumptions involved in the approach explicitly stated. Several common experimental situations that involve the passive spread of membrane potential changes in microvascular trees were simulated. The calculations were performed using NEURON, a well-established computer simulation program that we have modified for use with vascular trees. RESULTS: Simulated results show that membrane potential changes would probably not spread as far in the endothelium as they would in the smooth muscle of arterioles. Where feed arteries are connected to larger distributing arteries, passive spread alone may not explain the physiologically observed spread of diameter changes. CONCLUSIONS: Simulated results suggest that the morphology of an arteriole, in which the muscle layer is much thicker than the endothelium, favors electrical conduction along smooth muscle rather than the endothelium. However, it seems that passive electrical spread is insufficient to explain the apparent spread of membrane potential changes in experimental situations. Active responses involving voltage-dependent conductances may be involved, and these can also be included in our simulation.

Animals↗
PubMed2001

In vitro model of infectious crystalline keratopathy: tissue architecture determines pattern of microbial spread.

PURPOSE: To develop an in vitro model of infectious crystalline keratopathy using human corneal buttons and to test the hypothesis that the compactness of the corneal stroma determines the pattern of microbial spread. METHODS: Twenty human corneal buttons obtained after penetrating keratoplasty for keratoconus (KC) and eight human corneal buttons obtained from eye bank (EB) donor eyes were maintained in organ culture. Fourteen buttons (10 KC and 4 EB donors) were maintained in a turgid state (swollen, edematous) and 14 in a nonturgid state (compact, normal state of deturgescence) by the omission or addition of 5% dextran to the culture medium. Eight KC and four EB nonturgid buttons and eight KC and four EB turgid buttons were inoculated with Streptococcus viridans (Lancefield group G, gram-positive) organisms. Two KC nonturgid and two KC turgid buttons were inoculated with Klebsiella oxytoca (gram-negative) organisms. Bacterial migration and spread in the tissue were observed by light and electron microscopy. RESULTS: Of the nonturgid buttons, six KC buttons and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated an arborizing, crystallike pattern of bacterial spread. In the turgid buttons, five KC and all four EB buttons inoculated with S. viridans and both KC buttons inoculated with K. oxytoca demonstrated globular, amorphous colonies. This was in complete contrast to the needlelike branching appearance seen in nonturgid corneal buttons. Electron microscopy confirmed an interlamellar spread of the bacterial colonies. CONCLUSIONS: This is the first in vitro model of bacterial keratitis. It demonstrates that the pattern of spread of bacteria within corneal tissue is largely determined by the compactness of the corneal stroma. Altering tissue architecture changed the pattern of bacterial migration and spread. This model has considerable potential in further understanding host-microbe interactions and microbial spread that occurs during infection.

Adult↗
PubMed1992

Cytochalasin D and E: effects on fibrinogen receptor movement and cytoskeletal reorganization in fully spread, surface-activated platelets: a correlative light and electron microscopic investigation.

This study investigates the involvement of actin microfilaments in fibrinogen receptor redistribution and cytoskeletal reorganization that takes place in fully spread, surface-activated platelets. Colloidal gold-labeled fibrinogen (Fgn-Au label) in conjunction with video-enhanced differential interference contrast light microscopy (VDIC) was used to identify fibrinogen binding sites, glycoprotein IIb/IIIb (GPIIb/IIIa), on fully spread platelets. Platelets were treated with cytochalasins D and E (5 x 10(-5) mol/L to 5 x 10(-8) mol/L) for 10 minutes, before or after incubation with Fgn-Au label. Results observed with VDIC were subsequently confirmed by high-voltage transmission and low voltage-high resolution scanning electron microscopic examination of the specimens. Preincubation of activated platelets with cytochalasin D or E (5 x 10(-5) and 5 x 10(-6) mol/L) inhibited fibrinogen receptor redistribution and abolished cytoskeletal reorganization in fully spread platelets. After surface-activated platelets were incubated with Fgn-Au label, treatment with the above concentrations of cytochalasin D or E disrupted cytoskeletal reorganization and caused random movement of previously redistributed receptor-ligand complexes. Incubation of platelets with cytochalasin E 5 x 10(-6) mol/L prevented platelet activation and spreading. Thus, actin filaments appear necessary for platelet spreading from the discoid to the fully spread stage. The ligand-triggered, cytoskeletally directed movement of fibrinogen receptors in fully spread platelets appears to be dependent on the presence of intact, polymerized actin. This movement is distinct from the cytochalasin-insensitive accumulation of GPIIb/IIIa-ligand in the channels of the open canalicular system.

Actins↗
PubMedDate not supplied

Anatomic spread of india ink in the human intercostal space with radiographic correlation.

In a study designed to determine the spread of anesthetic solutions in the intercostal space, the spread of india ink was studied in fresh cadavers. They were turned prone and had epidural catheters placed at ribs 4, 6, 8 and 10, 7-8 cm lateral to the midline, by two different techniques. Group 1 had epidural catheters directed laterally into the subcostal groove. Group 2 had catheters directed medially into the intercostal space. A window was dissected in the anterior chest wall to visualize the location of the catheters and the spread of india ink. Catheters in Group 1 were observed to be lateral to the medial border of the intercostalis intimus muscle and injection of india ink resulted in spread entirely within a single intercostal space. Catheters in Group 2 were observed to be 2-3 cm medial to the border of the intercostalis intimus muscle and injection of ink resulted in concentric spread over 3-5 intercostal spaces. Posteroanterior and lateral radiographs taken with contrast material in live patients confirmed these patterns of spread. The catheters in Groups 1 and 2 were within the same tissue plane. The results indicate that the pattern of spread obtained by injection of fluid in the intercostal space is dependent upon the site of injection in relation to the angle of the rib.

Cadaver↗
PubMed1990

[The effect of volume and dosage of isobaric bupivacaine on the sensory spread of spinal anesthesia].

There is some controversy about the relationship of volume, concentration and total dose of bupivacaine in the sensory spread of spinal anesthesia. In this study the effects of volume and dose were investigated. MATERIAL AND METHODS. In this study 120 patients undergoing lower extremity, inguinal or transurethral surgery were randomly divided into six groups. Bupivacaine 15 mg with the addition of epinephrine 1:200,000 was administered in 2 ml (0.75%), 3 ml (0.5%), 6 ml (0.25%) and 9 ml (0.166%) solutions. In addition 3 ml isobaric bupivacaine in doses of 7.5 mg (0.25%), 15 mg (0.5%) and 22.5 mg (0.75%). The spinal puncture was performed via the midline approach at the L3-4 interspace, with the patient in the sitting position. The injection speed was 0.5 ml per second. Immediately after the injection the patients were placed in the supine position. The spread of sensory blockade was assessed by means of the pin-prick method in the midline. Motor blockade was assessed on the Bromage scale 0-3. RESULTS. There were no statistically significant differences in motor blockade or cardiovascular changes. The maximum cephalad spread of analgesia (30 min) between the 15 mg groups with different volumes and concentration was: group I (9 ml): T7.7, group II (6 ml): T7.8, group III (3 ml): T8.5 and group IV (2 ml): T10.1. The differences between group IV 2 ml and the groups receiving 3, 6 and 9 ml were statistically significant (P less than 0.05). There were no statistically significant differences in maximum cephalad spread between the 7.5 mg (3 ml), 15 mg (3 ml) and the 22.5 mg (3 ml) groups. The regression after 180 min was significantly shorter in the 7.5 mg group than in the 15 mg and 22.5 mg groups (P less than 0.05). DISCUSSION. Earlier published results indicate that the dose of isobaric bupivacaine is more important in spinal anesthesia than the concentration or the volume of the solution. The comparison between 3 ml:6 ml and 3 ml:9 ml bupivacaine showed no statistically significant differences in cephalad spread. A volume-dependent increase in segmental spread was between the 2 ml (0.75%) and 3 ml (0.5%) bupivacaine. The same statistically significant differences were between the 2 ml and 6 ml groups and the 2 ml and 9 ml groups. No statistically significant difference in cephalad spread resulted from increasing the dose of bupivacaine from 7.5 mg to 22.5 mg. Earlier studies on the effects of changes in volume, concentration and dose of bupivacaine showed similar "jumps of blockade" between 2 ml and 3 ml injected volume. Assembling the results the relation between volume and total dose does not suggest a no linear dependence. The anatomic configuration of the spinal cord at the conus medullaris may affect the distribution of the solution.

Adult↗
PubMed1990

Distal intramural spread of carcinoma of the rectum correlated with lymph nodal involvement.

One hundred and nineteen operative specimens of carcinoma of the rectum were prospectively studied to evaluate distant microscopic intramural spread with respect to gross tumoral margins and to determine if the degree of spread was related to involvement of the lymph nodes. Eighty-eight of the 119 specimens (74 per cent) did not have intramural extension distal to the gross distal margin of the tumor. Twenty-five (21 per cent) had intramural extension of less than 5 millimeters from the gross distal limit of the tumor. In these instances, tumoral spread was contiguous. In six (5 per cent), tumoral spread was found at more than 5 millimeters from the gross distal margin of the lesion. In all six specimens, the tumoral extension was separated from the gross lesion by undiseased tissue, the foci being located between 5 and 15 millimeters from the distal margin of the lesion. Lymph nodal involvement was found in 19 of 88 lesions without distal intramural spread, in 14 of 25 tumors with intramural spread of less than 5 millimeters and in five of six with intramural extension of 5 millimeters or more, respectively. The difference was statistically significant. With respect to the same three categories of distal extension, more than one lymph node was involved in 11 of 88 lesions, six of 25 and five of six, respectively. This difference was also statistically significant. In the six instances with distal intramural extension, results of immunohistochemical staining demonstrated the presence of tumoral embolism in both the blood and lymphatic vessels. In carcinoma of the rectum, lymph nodal involvement and its multiplicity are directly related to the extent of intramural spread.

Adenocarcinoma↗
PubMed1990

[A clinico-pathological study of the intraepithelial spreading of esophageal carcinomas].

One hundred and twenty-nine esophageal epidermoid carcinomas have been found to have 60 intraepithelial-spreading lesions. According to the histological of these intraepithelial-spreading lesions, 60 of these lesions could be divided to two types: a whole type and a basal type. Thirty-three lesions (55%) were found to be a whole type and twenty-three lesions (38%) a basal type, and the remaining four lesions (7%) a mixed type. Sixty-seven percent of the whole type lesions were accompanied by well differentiated epidermoid carcinomas, and 33% with poorly or moderately differentiated epidermoid carcinomas. On the other hand, 17% of the basal type lesions were accompanied by well differentiated epidermoid carcinomas, and 83% with a poorly or moderately differentiated epidermoid carcinomas. The average length of spreading of the whole type was 14.5 mm, and the average length of spreading of the basal type, 19.6 mm. It was found that the intraepithelial spreading of the poorly differentiated epidermoid carcinomas (average: 23.6 mm) was longer than the well differentiated epidermoid carcinomas (average: 15.8 mm). A histological examination of step sections revealed that 34% of the intra-spreading lesions had erosions. Further half of the lesions over 10 mm in length also had erosions. Basal type carcinomas had a greater frequency of erosion than did the whole type carcinomas. Papillary growth pattern was a special histological feature of the whole type, and a pagetoid spreading was distinctive in the basal type. The macroscopical appearance of the mucosal surface of the whole type was granular or nodular, whereas for the basal type it was redness or no change.

Carcinoma, Papillary↗
PubMed1990

[Extra-abdominal spread of pelvic neoplasms. CT evaluation and radiotherapeutic implications].

Meyers and other authors have described the extra-abdominal spread of inflammatory abdominal diseases. Conversely, little attention has been paid to the extra-abdominal spread of pelvic neoplasms. The authors have detected, by means of CT, 17 cases of extra-abdominal neoplastic spread in a series of 203 patients with pelvic neoplasms. Neoplastic spread involved the inguinal region in 1 case, the buttock in 6 cases, and the ischiorectal fossa and/or perineum in 12 cases, with more than one region involved in some patients. In such cases CT showed the extension of tumoral tissue beyond the muscular walls of the pelvis. Recurrent pelvic carcinomas are the most common neoplasms spreading outside the pelvis. Surgical obliteration of the pelvic fasciae can explain such a behavior. Differential diagnosis is to be made with inflammatory pelvic diseases with extrapelvic spread. When a pelvic tumor spreads outside the pelvis it can be seen as a primitive gluteal or inguinal or perineal mass. CT demonstration of such an insidious event is mandatory for both a correct diagnosis and radiation treatment planning.

Adult↗
PubMed1987

Effect of adhesion factors fibronectin, laminin, and type IV collagen on spreading and growth of transformed and control rat liver epithelial cells.

To examine the specific effects of individual basement membrane components on the behavior of transformed cells of epithelial origin, ethionine-transformed cells and control cells at low and high passage levels were seeded on glass that had been coated with fibronectin, laminin, or type IV collagen. The cells used were sublines of the liver-derived TRL 1215 epithelial cell line, a line in which transformation has been shown to be accompanied by increased cell-substrate adhesion and cell spreading. Cell spreading on the different basement membrane components was determined by morphometry, and growth (proliferation) was measured by protein and DNA analyses. Laminin increased spreading and growth in transformed and control sublines. Laminin also induced changes in cell shape that were indicative of increased cell motility. For the control cells, fibronectin and also type IV collagen were less effective than laminin in stimulating cell spreading and growth. However, for the ethionine-transformed cells, fibronectin was as effective as laminin in stimulating cell spreading. With the exception of the spreading response to fibronectin, the ethionine-transformed cells were less sensitive to the defined substrata than were the control sublines. Moreover, only the ethionine-transformed cells were able to proliferate in serum-free medium. Thus, greater autonomy is characteristic of transformation for these epithelial cells and is exemplified by the reduced influence of and dependence on exogenous factors, both substrate-bound and soluble, for spreading and growth.

Animals↗
PubMed1982

The role of microtubules in cell shape and pigment distribution in spreading erythrophores.

In order to investigate the role of microtubules in determining overall shape of the cell and distribution of pigment granules, a correlative whole cell electron microscopic and immunofluorescence light microscopic study was done of microtubule distribution during spreading of cultured erythrophores from scales of the squirrel fish, Holocentrus. After dissociation from the scale and immediately after attachment, erythrophores are round with long thin processes containing bundles of microtubules with associated pigment granules. In time these processes attach, and elongate, and cytoplasmic ground substance fills areas between microtubule bundles, preceding the appearance of microtubules in these areas of the cell. By 8 h cells are fully spread (star-shaped), prominent microtubule bundles have disappeared, and microtubules (along with pigment granules) are more evenly dispersed throughout the cell. After 24 h cells have increased in size, in number of microtubules, and in the length of preexisting tubules. The sequence of events in normal spreading is altered if cytochalasin D, cycloheximide, or nocodazole is included in the culture medium. Cytochalasin D, a microfilament-disrupting drug, prevents attachment and spreading, but allows elongation to occur. Cycloheximide, a protein synthesis inhibitor, allows for attachment and elongation, but no spreading. Nocodazole, a microtubule-disrupting drug, allows for attachment and spreading, but an irregular cell outline is the result. Even though spreading can occur without them, it is concluded that a normal number and distribution of microtubules are required for the development of normal cell shape and pigment distribution.

Animals↗
PubMed1981

Effects of temperature and duration of storage on granulocyte adhesion, spreading, and ultrastructure.

The effects of storage duration and temperature on granulocyte adhesion, spreading, and ultrastructure were examined. Normal adherence and spreading of granulocytes detected by either phase contrast or scanning electron microscopy was maintained for up to 48 hours when granulocytes were stored at 20 to 24 degrees C. By contrast, storage of granulocytes for 24 hours at 1 to 6 degrees C. led to a substantial decrease in granulocyte adherence and spreading. When granulocytes were stored for 24 hours at 1 to 6 degrees C. and then shifted to 20 to 24 degrees C. for a second 24 hours, granulocytes failed to regain the normal adherence and spreading. The cytoskeleton has been implicated in cell morphology, movement, chemotaxis, and spreading of cells. Transmission electron microscopy of thin sections of whole cells or cytoskeleton preparations revealed a well-organized system of microtubules and microfilaments in granulocytes stored for up to 48 hours at 20 to 24 degrees C. In granulocytes stored at 0 to 6 degrees C. that have the decreased adhesion and spreading, there is a paucity of microtubules, and the microfilaments have a disorganized criss-crossed appearance when compared with normal cells. It appears that storage of granulocytes at reduced temperatures is associated with decreased adhesion and spreading, and a concomitant alteration in the cytoskeleton may be responsible for this.

Blood Preservation↗
PubMed1995

Spreading and focal contact formation of human melanoma cells in response to the stimulation of both melanoma-associated proteoglycan (NG2) and alpha 4 beta 1 integrin.

In this study, we evaluated the potential role for a specific melanoma-associated chondroitin sulfate proteoglycan core protein, termed NG2, to collaborate with alpha 4 beta 1 integrin in focal contact formation in human melanoma cells. Although melanoma cells adhered to substrata coated with either the alpha 4 beta 1 integrin binding fibronectin synthetic peptide CS1-OVA or anti-NG2 mAbs, no spreading or focal contact formation was observed on either substratum. However, melanoma cells spread and formed focal contacts on "chimeric substrata" coated with CS1-OVA and the anti-NG2 mAb, 9.2.27, indicating that engaging both adhesion receptors changes the adhesion phenotype of melanoma cells by reorganizing the cytoskeleton. The collaboration between the two receptors is specific to fibronectin, since cells adherent on substrata coated with low concentrations of either laminin and 9.2.27 or type IV collagen and 9.2.27 failed to spread, while cells adherent on low concentrations of fibronectin and 9.2.27 exhibited a fully spread morphology. Two selective tyrosine kinase inhibitors, genistein and herbimycin A, totally inhibited cell spreading on the substrata coated with CS1-OVA and 9.2.27, indicating that tyrosine kinase(s) is important for cell spreading and focal contact formation. When cells were cultured on substrata coated with CS1-OVA and 9.2.27, two proteins (M(r) 130,000 and 120,000) were tyrosine phosphorylated in a genistein- and herbimycin A-sensitive fashion. These proteins were not immunologically related to pp125FAK or alpha 4 beta 1 integrin. Importantly, when melanoma cells were cultured on substrata coated with CS1 and then stimulated with 9.2.27-conjugated microsphere beads, formation of focal contacts and stress fibers was also observed, indicating that NG2 can collaborate with alpha 4 beta 1 integrin when each receptor is engaged on distinct and separate substrata. These results demonstrate that NG2 acts as a coreceptor for spreading and focal contact formation in association with alpha 4 beta 1 integrin in melanoma cells and suggest a model in which the NG2 core protein communicates to alpha 4 beta 1 integrin by an inside-out signaling mechanism.

Antibodies, Monoclonal↗
PubMedDate not supplied

Comparison of direct spreading and local recurrence of neoplasms.

Neoplastic progression proceeds most commonly with metastatic spreading but also with direct spreading and some minor forms of neoplastic distribution. The difference between metastatic spreading and direct tumor spreading is shown by the fact that metastatic cells are motile and separate from the primary tumor, whereas in direct spreading the progressing cells are less motile and connected with the primary tumor. This latter type of spreading is especially common in kidney cancers. In the case of local recurrence where portions of the primary tumor have been spared from destruction, regrowth of these portions may occur after different intervals. It is a precondition that the neoplastic metabolism has gained power again. Local recurrence is an offspring of growth from the primary tumor or from a not fully removed metastasis and should be considered as a growth comparable to direct spreading. It may switch during further progression to metastatic progression.

Female↗