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At least 811 records · Page 45Linked to original sources
PubMed2002

Perforin-mediated CTL cytolysis counteracts direct cell-cell spread of Listeria monocytogenes.

The immune system has evolved various effector cells and functions to combat diverse infectious agents equipped with different virulence strategies. CD8 T cells play a critical role in protective immunity to Listeria monocytogenes (Lm), a bacterium that grows within the host cell cytosol and spreads directly into neighboring cells. The importance of CD8 T cells during Lm infection is currently attributed to the cytosolic niche of this organism, which allows it to evade many aspects of immune surveillance. CTL lysis of infected cells is believed to be an essential protective mechanism, presumably functioning to release intracellular bacteria, although its precise role remains to be fully defined. In this study, we examined the contribution of perforin-mediated CTL cytolysis to protective immunity against recombinant Lm capable of or defective in cell-cell spread. We found that CTL cytolysis is critical for protective immunity to Lm capable of cell-cell spread while protective immunity against spread-defective Lm is largely independent of CTL cytolysis. These results demonstrate that an important function of CTL cytolysis is to counter the microbial virulence strategy of direct cell-cell spread. We propose a model that advances the current view of the role of CTL cytolysis in immunity to intracellular pathogens.

Animals↗
PubMed2005

Induction and inhibition of the Th2 phenotype spread: implications for childhood asthma.

The interactions between genetic and environmental factors play a major role in the development of childhood asthma. We hypothesized that a pre-existing Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e., phenotype spread). To test this hypothesis, we developed a mouse model in which the requirements for the induction and inhibition of phenotype spread to a clinically relevant neo-allergen (i.e., ragweed) were investigated. Our results indicate that 1) phenotype spread to the neo-allergen can be induced only within the first 8 h after a bronchial challenge with the first Ag (OVA); 2) Th2 differentiation of naive CD4(+) T cells occurs in bronchial lymph nodes; 3) trafficking of naive CD4(+) T cells to local lymph nodes and IL-4 produced by OVA-activated Th2 cells play essential roles in the differentiation of naive CD4(+) T cells to Th2 cells; and 4) suppression of the production of chemokines involved in the homing of naive CD4(+) T and Th2 cells to bronchial lymph nodes by a TLR9 agonist inhibited phenotype spread and abrogated the consequent development of experimental asthma. These findings provide a mechanistic insight into Th2 phenotype spread and offer an animal model for testing relevant immunomodulatory interventions.

Adjuvants, Immunologic↗
PubMed2026

DNA-FISH Metaphase Spreads to Distinguish Extrachromosomal DNA from Homogeneously Staining Regions in Human Cancer Cell Lines.

UNLABELLED: Whole-genome sequencing identifies focal DNA amplifications with base-pair resolution but cannot determine whether amplified sequences reside on extrachromosomal DNA (ecDNA, also known as double minutes) or within chromosomally integrated homogeneously staining regions (HSRs). DNA fluorescence in situ hybridization (DNA-FISH) metaphase spreads remain the gold standard for distinguishing these amplification states at single-cell resolution. Here, we present a detailed protocol for DNA-FISH metaphase spreads using human cancer cell lines, encompassing cell culture, metaphase arrest, hypotonic treatment, fixation, chromosome spreading, fluorescent probe hybridization, and fluorescence imaging. The protocol incorporates intermediate quality-control steps to verify successful chromosome dispersion and optimize metaphase spread quality, making the workflow accessible to laboratories without specialized cytogenetics expertise. Results demonstrate clear visualization of ecDNA and HSR amplification states using locus-specific probes and illustrate common technical artifacts that can affect interpretation. This protocol provides a robust and reproducible approach for studying the structural organization of oncogene amplification in cancer cells. SUMMARY: We report a DNA-FISH metaphase spread protocol that visually detects locus copy number and location within the genome. This approach enables single-cell resolution of amplification states, specifically in cancer cell lines containing extrachromosomal DNA and homogeneously staining regions.

Journal Article↗
PubMed2000

Investigation of signal transduction pathways involved in melanoma cell spreading.

Integrins are a major family of heterodimeric adhesion receptors that are responsible for anchoring cells to extracellular matrix and they also can initiate intracellular signal pathways. Here parental and alpha 4-expressing human malignant melanoma cell lines were used to study the effect of protein kinase C (PKC), protein tyrosine kinases (PTKs) and intracellular Ca2+ on alpha 4 beta 1-mediated cell spreading on VCAM-1. Incubation of melanoma cells with PKC inhibitor inhibited alpha 4 beta 1-mediated melanoma cell spreading completely. Effect of intracellular Ca2+ on melanoma cell spreading was also investigated by non-phorbol ester tumor promotor, thapsigargin, which blocks the ability of the endoplasmic reticulum to replenish stocks of calcium which naturally leak out into the cytosol leading to a transient increase in concentration of intracellular calcium. The results showed that alpha 4 beta 1-mediated spreading was also required intracellular calcium involvement. However, in the presence of PTKs inhibitor melanoma cells showed long, thin dendiritic projections compared to control cells. Previously, data was obtained from immunofluorescense experiments showed that after genistein treatment, alpha 4-expressing cells exhibited considerable amounts of alpha 4 integrin and PTKs in both the focal contact points as well as over the whole cell. PTKs inhibitor did not have any effect on alpha 4-expressing cells spreading. This could be related to the amount of the PTKs present in these cells.

Calcium↗
PubMed2000

Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels.

Fibrin is found at sites of vascular injury and is one of the major matrix ligands for beta3 integrins. Blocking the beta3 integrin on smooth muscle cell is hypothesized as a potential target to prevent restenosis because it could inhibit cell attachment and migration into fibrin provisional matrix. Human aortic smooth muscle cells (HNB18E6E7) spread stably in plasma gels within 24 h. Cell spreading was dramatically blocked by simultaneous use of alpha5beta1 and alphavbeta3 integrin antibodies (P <0.0001), however, blocking of either integrin alone failed to inhibit spreading. GPenGRGDSPCA, which has been considered a specific alphavbeta3 antagonist, inhibited spreading at 500 microM, suggesting that the peptide blocked both alpha5beta1 and alphavbeta3. Similarly, invasive migration into fibrin gels was blocked by simultaneous use of both alpha5beta1 and alphavbeta3 antibodies, however, blocking of either integrin alone failed to effect cell migration. Another migration assay using transwell indicated similar results. In conclusion, both alpha5beta1 and alphavbeta3 integrins are responsible for smooth muscle cell spreading and migration into fibrin gels. These data suggest that blocking beta3 integrin alone would not affect smooth muscle cell interaction with fibrin.

Cell Adhesion↗
PubMedDate not supplied

Clinicopathologic characteristics of superficial spreading type squamous cell carcinoma of the esophagus.

Intraepithelial carcinoma concomitant with the main tumor is a conspicuous feature in squamous cell carcinoma (SCC) of the esophagus. The aim of the current study was to clarify the clinicopathologic features of superficial spreading type SCC of the esophagus. Ninety-seven patients with esophageal squamous cell carcinoma, whose main carcinoma is invading the mucosa or submucosa, were investigated in the current study. The clinicopathologic features were compared between 13 cases demonstrating a superficial spreading type carcinoma in which the spreading size of the tumor was 5 cm or more in length and 84 cases with the size less than 5 cm. Although no significant difference was observed regarding lymphatic invasion, venous invasion, intramural metastasis and lymph node metastasis, the survival rate of patients with superficial spreading type carcinoma was much better than that of patients with ordinary superficial carcinoma of the esophagus. Coexistence of superficial spreading type carcinoma may be correlated with a favorable prognosis of patients with superficial esophageal SCC.

Aged↗
PubMed2002

Perineural tumor spread along the auriculotemporal nerve.

BACKGROUND AND PURPOSE: Evaluation of images of perineural tumor spread in patients with head and neck malignancies is essential for planning treatment and determining the patient's prognosis. Although the communications between the facial and trigeminal nerves are not widely known, they may provide a route for tumor growth. The purpose of this study was to elucidate the course of the auriculotemporal nerve, as well as the clinical and imaging findings that suggest involvement of the communication between the facial nerve and the mandibular division (V(3)) of the trigeminal nerve. METHODS: Images in 15 patients with clinical or radiologic findings suggestive of perineural tumor spread along the auriculotemporal nerve were reviewed. Involvement of the main trunk of the facial nerve, auriculotemporal nerve, V(3), trigeminal cistern, and ganglion and adjacent anatomic structures were noted in each patient. RESULTS: The course of the auriculotemporal nerve was described in detail. More than 50% of patients with perineural tumor spread along the auriculotemporal nerve had clinical signs of auriculotemporal nerve dysfunction, including periauricular pain and temporomandibular joint (TMJ) dysfunction or tenderness. Images in 13 of 15 patients with such tumor spread demonstrated findings of tumor growth along V(3.). CONCLUSION: Knowledge of the course of the auriculotemporal nerve is critical in evaluating images for findings of tumor spread along this nerve. Periauricular pain, TMJ dysfunction or tenderness, and imaging signs of V(3) involvement are important indicators of potential involvement of the auriculotemporal nerve.

Adult↗
PubMed2003

Growth and survival of selected pathogens in margarine-style table spreads.

Although margarine-style table spreads can have a pH above 4.6 and a water activity greater than 0.85, there is some question if such products can support the growth of pathogenic bacteria. The objective of this study was to evaluate the growth and survival of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella typhi in 60-percent- and 70-percent-vegetable-oil, margarine-style, water-in-oil-emulsion table spreads stored at different temperatures. Samples of 25 grams of each table spread were inoculated with 1 x 10(3) cells of each bacterial mixture. The samples were stored at 5 degrees C, 7 degrees C, and 21 degrees C, and the microbial population in colony-forming units per gram (CFU/gram) was enumerated over time. In almost all storage conditions, bacterial levels were shown to decrease over time. Inactivation was observed in (listed from fastest to slowest, respectively) S. aureus, L. monocytogenes, E. coli O157:H7, and S. typhi. Growth was observed only for S. typhi in table spreads stored at 21 degrees C, but the rate of growth was extremely slow. Based on these findings, the table spreads evaluated in this study are not potentially hazardous foods, and cold temperature storage is not necessary from a food safety perspective.

Cold Temperature↗
PubMed1992

Axonal and transsynaptic (transneuronal) spread of Herpesvirus simiae (B virus) in experimentally infected mice.

In order to study the pathogenesis of B virus infection of the nervous system, newborn and young mice were inoculated by four different routes: 1. Intramuscular (i.m.) in the forelimb; 2. I.m. in the hindlimb; 3. Subcutaneous (s.c.) in the abdominal wall; 4. Intraperitoneal (i.p.). Spread of virus was followed by immunohistochemical demonstration of viral antigen in tissue sections of the peripheral and central nervous system. Three distinct patterns emerged: 1. After i.m. limb inoculations, virus progressed along the ipsilateral dorsal column, the bilateral spinothalamic and bilateral spinoreticular systems and along central autonomic pathways. 2. After s.c. inoculation, the dorsal column was spared, otherwise the spread was similar to that following i.m. inoculations. 3. After i.p. inoculation, virus spread in the spinal cord bilaterally, mainly along spinothalamic and central autonomic pathways. The peripheral motoneurons were conspicuously spared, even in the i.m. inoculation mode. In the brain stem, B virus antigen appeared bilaterally, at multiple sites. In the cerebrum, virus infected cells appeared first in the thalamus, hypothalamus and the motor cortex. The mode of spread from spinal levels was mainly orthograde along the ascending systems (dorsal columns, spinothalamic, spinoreticular tracts), but also retrograde along descending systems (pyramidal tract, central autonomic pathways). Oligosynaptic systems transmitted virus more quickly than the polysynaptic ones. In the involvement of various neuronal systems in virus spread, a certain selectivity, sparing the peripheral motoneuron and the cerebellar systems, could be assessed.

Aging↗
PubMedDate not supplied

[Molecular epidemiological analysis of the spread of human immunodeficiency virus (HIV) infection in the Novosibirsk region].

The dynamics of the spread of individual subtypes of type 1 HIV (HIV-1), circulating in the Novosibirsk region during the epidemic rise of HIV infection was under study. The epidemic of HIV-1 in Novosibirsk has a pattern similar to that in Russia as a whole. At the initial stage of epidemics multiple sources of virus determine the heterogeneity of the isolated subtypes of HIV-1. Then the parenteral route of HIV transmission, connected with the intravenous use of narcotic drugs, becomes dominant. Recently the spread of HIV-1 from the group of intravenous drug users to other groups of the population has been observed. In the circulation of HIV-1 among drug users the leading role was shown to belong to subtype A, which ensures its rapid spread and dominating role in the epidemic process. Further spread of the HIV-1 epidemic is expected to proceed in parallel to the spread of viral hepatitis, sexually transmitted diseases and drug addiction. Thus, HIV-1, subtype A, may be assumed to be dominant in the Novosibirsk region in the nearest future.

HIV Infections↗
PubMed1992

[Does an injection filter modify the cranial spread of a sensory blockade in epidural anesthesia?].

UNLABELLED: In a prospective study we compared the spread of sensory blockade in epidural anaesthesia with and without Micropore filter. MATERIALS AND METHODS: A total of 32 patients undergoing varicose vein stripping under epidural anaesthesia were randomly assigned to two groups of 16 each. Bupivacaine 0.75% and POR 8 (0.1 IU/ml) were administered by means of a constant-velocity perfusor. In group A a Micropore filter was inserted between the perfusor syringe and the epidural catheter. In group B the epidural catheter was connected to the syringe without the filter. The puncture was performed at the L3-4 interspace with the patient in a sitting position. An epidural catheter was advanced 3 cm cephalad. Using the pin-prick method, the sensory level of the blockade was tested 5, 7, 10, 15, 20 and 30 min after injection of the local anesthetic solution. Statistical evaluation was performed with the t-test for unpaired samples. RESULTS. After 10 min the spread of analgesia was 5.75 +/- 1.26 segments in group A and 8 +/- 1.89 segments in group B; after 15 min it was 7.06 +/- 1.62 segments and 9.56 +/- 1.54 segments; after 20 min, 7.87 +/- 1.62 segments and 10.62 +/- 1.45 segments; and after 30 min 8.12 +/- 1.66 segments and 11.12 +/- 1.45 segments in group A and B, respectively. At any time sensory blockade was higher in group B (without Micropore filters) than in group A. The mean difference between the two groups amounted to 2-3 segments. The differences were significant at any time (P less than 0.001). These results show that the use of a Micropore filter in epidural anaesthesia leads to a reduced spread of sensory blockade. In our own examinations we found lowering of the pressure of the local anaesthetic solution that passes through the Micropore filter compared with the pressure of the solution injected without the filter. This seems to be the reason for the reduced spread of sensory blockade. Using these filters the onset of analgesia is delayed, and a given spread of analgesia needs a larger dose of local anaesthetic and is thus accompanied by a higher toxicity.

Adult↗
PubMedDate not supplied

PINP as serum marker of metastatic spread to the bone in breast cancer patients.

BACKGROUND: Early detection before scintigraphic appearance of osseous metastatic spread might improve the outcome of breast cancer patients. The amino-terminal propeptide (PINP) of type I collagen as an indicator of bone formation is a very promising candidate among all markers of bone metabolism. We investigated the utility of total PINP in breast cancer patients at different stages of the disease. PATIENTS AND METHODS: Precision tests using controls and serum pools were done for total PINP on the Elecsys2010 analyzer (electrochemiluminescence immunoassay - ECLLA). Baseline samples of 51 breast cancer patients with metastatic disease plus 11 patients under neoadjuvant treatment were available. Altogether, 38 patients had been diagnosed with bone metastases while 24 had no evidence of metastatic spread to the bone. RESULTS: For serial precision (intra assay), we found coefficients of variation between 1.2-2%. Total imprecision according to the NCCLS protocol ranged from 1. 7-5.4% only. Retrieval in ring trials was between 94% and 103%. ROC analysis of osseous versus nonosseous metastatic disease revealed an area under the curve (AUC) of 0.72. The sensitivity for the detection of bone lesions was 50% at the preliminary normal cut-off of 95 ng/mL. The baseline levels of the patients with bone metastases were significantly higher than those of patients with visceral of soft tissue spread only (p<0.001). PINP concentrations correlated with osseous spread in terms of number and size of the bone lesions. Generally, non-osseous metastases did not produce elevated PINP levels in only 2/24 patients without bone metastases showing minimally elevated PINP concentrations (95 and 112 ng/ml). CONCLUSION: The Elecsys test for total PINP is highly reproducible. PINP concentrations can discriminate patients with bone metastases from those without osseous spread. The moderate sensitivity for the diagnosis of bone lesions may be biologically related to ineffective bone repair in a certain subset of patients. Further studies must focus on the monitoring of patients with elevated baseline levels and on those patients with low PINP levels in the case of otherwise proven bone metastases.

Adult↗
PubMed2005

[Localisation and direction of spread in oral and oropharyngeal cancer in the material of Head and Neck Oncological Surgery Department, University of Medical Sciences in Poznań].

UNLABELLED: The directions of tumor spread are determined by the anatomy of the affected organ. The vessel, nerve anatomy and presence of structures, that may potentially constitute a barrier for spread out of the tumor are of crucial importance. The aim of this paper was to presentation of the spreading directions of oral cavity and oropharyngeal squamous cell cancer based on the own experience. Material include 163 patients surgically treated between 2003-2003 in Department of ENT, Head and Neck Oncological Surgery Department in Poznań. The examination was conducted on the base of retrospective analysis of ambulatory charts and the hospital files. RESULTS: 163 (90%) patients were operated for primary oral and oropharyngeal cancer. The primary localization included in the palatine tonsil (82 patients), trunk of the tongue (48 patients) and floor of the mouth (20 patients) were predominated. The spread directions included: floor of the mouth (36) soft palate (35), base of tongue (33), hypopharynx (20) and trunk of tongue (16). The 31 crossed the midline, 27 infiltrated the tonsillopalatine angle, 9 retromolar area and 3 the mucosa of the cheek. Knowledge of anatomy facility in clinical evaluation of spreading malignancy. It helps in proper qualification to surgery or radiotherapy.

Adult↗
PubMedDate not supplied

Quantitative measurement of wound spreading in radial keratotomy.

BACKGROUND: Many studies of radial keratotomy have been performed, however quantitative laboratory evaluation of the biomechanics of this procedure is still incomplete. Furthermore, most measurements of strain in the past have utilized strip testing, thus destroying the normal physiological structure and water balance of the cornea. METHODS: We report on a membrane inflation method of wound spreading in intact human corneas using the Baribeau Micronscope. RESULTS: We measured a secant elastic modulus of 7.58 x 10(6) N/m2 between 25 and 100 mm Hg. The spreading of radial keratotomy incisions as a function of intraocular pressure showed a maximum spreading of approximately 50 mu at 25 mm Hg at a radius of 3.50 mm from the optical center. A slight increase in spreading was observed in proceeding from a single to four radial incisions. CONCLUSIONS: Quantitative measurement of wound spreading is an important parameter of radial keratotomy and can provide important information regarding opposing theories of the biomechanics of this operation.

Biomechanical Phenomena↗
PubMed1991

Cell adhesion, spreading, and motility of GM3-expressing cells based on glycolipid-glycolipid interaction.

Cell lines expressing varying levels of ganglioside GM3 at the cell surface show different degrees of adhesion and spreading on solid phase coated with such glycosphingolipids (GSLs) as Gg3 (GalNAc beta 1----4Gal beta 1----4Glc beta 1----1Cer), LacCer (Gal beta 1----4Glc beta 1----1Cer), or Gb4 (GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc beta 1----1Cer) (where Cer is ceramide), which may have structures complementary to GM3, but not on solid phase coated with various other GSLs. The degree of cell adhesion and spreading on Gg3 was correlated with the degree of cell-surface GM3 expression, as defined by reactivity with anti-GM3 monoclonal antibody (mAb) DH2. Only cells with high GM3 expression adhered on solid phase coated with LacCer or Gb4. Adhesion of GM3-expressing cells on Gg3-, LacCer-, and Gb4-coated solid phase is based on interaction of GM3 with Gg3 and, to a lesser extent, with LacCer and Gb4, as demonstrated by: (i) the interaction of the GM3 liposome with solid phase coated with Gg3, LacCer, and Gb4, respectively; (ii) the abolition of cell adhesion on each GSL-coated solid phase by treatment of cells with mAb DH2 or sialidase; and (iii) the inhibition of cell adhesion by treatment of GSL-coated solid phase with mAb specific to each GSL. Sialosyllactosyl-lysyllysine conjugate was bound to Gg3 adsorbed on a C18 silica gel column in the presence of bivalent cation, suggesting that the carbohydrate moiety of GM3 is involved in GM3-Gg3 interaction. Not only the adhesion and spreading of GM3-expressing cells, but also their cell motility was greatly enhanced on Gg3-coated solid phase, as determined by Transwell assay and phagokinetic track assay on a gold sol-coated surface. Spreading and motility of GM3-expressing cells on Gg3-coated solid phase were both inhibited by treatment of cells with mAb DH2 or sialidase. These results provide evidence that not only cell adhesion, but also spreading and motility in these cell lines are controlled by complementary GSL-GSL interaction.

Animals↗
PubMed1976

Functional characteristics of the intraspinal spread of viscerosomatic activity.

The functional characteristics of the intraspinal spread of the dual-component viscerosomatic reflex response were studied in chloralose-anaesthetized cats. In the region of the direct inputs of splanchnic afferents into the spinal cord, the initial part of the early (propriospinal) component is evoked by afflux from the extraspinal pathway in the sympathetic chain and has the shortest latent period. At segment Th8 to Th12 level this was 5.2--8.1 msec; cranially and caudally from this level it was longer. Activity spreading from the adjacent segments via intraspinal longitudinal systems also participates in the origin and course of the early component of the efferent discharge. The rate of ascending intraspinal irradiation in the thoracic region was 3.2--12 m/sec (6.6 +/- 2.4 m/sec). The rate of the descending spread of propriospinal activity in the thoracic region via intraspinal pathways was 3.6--18.3 m/sec (12.5 +/- 4.5 m/sec); in the lumbar region it was significantly lower -- 2.9--19.3 m/sec (7 +/- 4.5 m/sec). The latent period of the later component varied from 20 to 30 msec and displayed a cranio-caudal increase in length. The rate of the descending spread of the later component in the thoracic and lumbar cord did not differ significantly (20 +/- 10 m/sec and 22 +/- 13 m/sec respectively). The continuous splanchnic discharge in the lumbosacral region is correlated to the different rate of the intraspinal spread of the early and the late response and to their overlapping.

Animals↗
PubMed1990

Spread of herpes simplex virus (HSV) strains SC16, ANG, ANGpath and its glyC minus and GlyE minus mutants in DBA-2 mice.

Herpes simplex virus type 1 (HSV-1) strains SC16, ANG, its pathogenic variant ANGpath and the mutants ANG-pathgC18 glycoprotein C (glyC) negative and ANGpathI2-4 (glyE negative) were compared for their ability to spread in DBA-2 mice after peripheral inoculation. Virus infectivity assay in 9 organs at days 2, 3, 4, 5, 6, and 10 post-infection (p.i.) and morphologic examinations (immunofluorescence, PAP staining) showed the following: SC16, ANG, and ANGpath spread first (days 2-3 p.i.) by haematogenic route to spleen, liver, and adrenal gland. Since day 4 the invasion of the vegetative and peripheral nervous system took place in SC16 and ANGpath-infected mice, followed by virus spread to the spinal cord and brain stem. In ANG-infected mice the invasion of peripheral nervous system was minimal although both ANG as well as ANGpath spread along the axons. In ANG pathC18-infected mice a relatively prolonged viraemic phase (days 2-4 p.i.) represented with foci of virus antigen-containing cells in spleen, liver, and mesenterial connective tissue was accompanied with a low grade invasion of the peripheral nervous system (days 3-4 p.i.). No spread by any route of ANGpathI2-4 was observed after intraperitoneal inoculation. When comparing ANGpath and SC16, the latter seemed slightly more lethal, since ANGpath killed 67.2% of DBA-2 mice which were given 2 X 10(6) PFU/0.1 ml by i.p. route as compared to the 100% lethality of SC16-infected animals.

Animals↗
PubMed1991

Further evidence that glycoprotein IIb-IIIa mediates platelet spreading on subendothelium.

In order to explore further the mechanism by which glycoprotein GPIIb-IIIa promotes platelet vessel wall interaction, platelet adhesion to subendothelium was studied in an annular chamber in which subendothelium from rabbit aorta was exposed at a shear rate of 2,600 s-1 to blood from patients with thrombasthenia. Perfusions were conducted for each of 5 exposure times (1, 2, 3, 5 and 10 min), and the percent surface coverage of the vessel segment with platelets in the contact (C) and spread (S) stage was determined. Increased values of platelet contact (C) were obtained in thrombasthenia at all exposure times; this finding is consistent with a defect in platelet spreading, based on a previously described kinetic model of platelet attachment to subendothelium. According to this model of attachment, increased values of platelet contact (C) at a single exposure time may be indicative of either a defect in spreading (S) or initial contact (C), but multiple exposures will result in increased contact only for defects which are related to defective platelet spreading (S). The results obtained over a broad range of exposure times provide more conclusive evidence that GPIIb-IIIa mediates platelet spreading than those previously obtained at single exposure times.

Animals↗