Testing for hearing loss after meningitis.
Explore the source record for details and available documents.
Acoustic Impedance Tests↗
Biomedical subjects
M Richardson
Publications and source records attributed to M Richardson.
Pretreatment of rabbits with either hirudin, ancrod, or warfarin significantly reduces the immediate uptake of fibrinogen and platelets by the deendothelialized aorta wall after balloon-catheter injury in vivo.
Fibrinogen and platelets rapidly saturate the exposed subendothelium of a freshly deendothelialized aorta in vivo. As thrombin generated within the site of injury is largely responsible for fibrin(ogen) deposition, we questioned whether various anticoagulant treatments would inhibit uptake of both fibrinogen and platelets in vivo. Rabbits were anticoagulated by pretreatment with either Warfarin, Ancrod, or recombinant hirudin. Each anesthetized, anticoagulated (or saline-injected control) rabbit was injected i.v. with rabbit 51Cr-platelets and 125I-fibrinogen before a balloon-catheter deendothelializing (or sham) injury of the thoracic aorta. At 10 minutes after injury, the rabbit was exsanguinated and the aorta excised. Platelet adsorption by the deendothelialized aorta surface was substantially reduced in anticoagulated rabbits (controls, 2.2x10(5)/mm2; Warfarin-treated, 1.2x10(5)/mm2; Ancrod-treated, 5.3x10(4)/mm2; r-hirudin-treated [5 mg/kg], 5.3x10(4)/mm2), and a significant reduction of fibrinogen associated with the platelet layer (from 5.3 to 1 to 2 pmol/cm2) and within the underlying intima-media layer (from 16.9 to 5 to 6 pmol/cm2) was observed in the r-hirudin-and Warfarin-treated rabbits. The pattern of aorta-deposited 51Cr-platelets and 125I-fibrin in the anticoagulated rabbits corresponded well with an assessment by transmission electron microscopy of aortic tissue samples. We conclude that approximately 70% of fibrinogen uptake is thrombin dependent and that approximately 80% of platelet adsorption depends on codeposited fibrin(ogen) during the 10-minute interval after balloon injury. Pretreatment with an agent that interferes with either thrombin or fibrin production will inhibit the immediate interaction of fibrinogen and platelets with the freshly exposed subendothelium.
Ancrod↗
Morphologic and biochemical features affecting the antithrombotic properties of the inferior vena cava of rabbit pups and adult rabbits.
The incidence of venous thromboembolic disease is reduced in children compared with adults. Thromboprotective mechanisms, some of which have already been identified in plasma, must be present in children. Blood vessel walls have important antithrombotic properties that maintain blood fluidity. This is in part due to proteoglycan (PG)-related glycosaminoglycan (GAG) molecules within vessel walls. PGs are macromolecules with covalently attached GAG chains, either chondroitin, dermatan, heparan, or keratan sulfate. The influence of age on the concentration and anticoagulant activities of PGs and GAGs, within vein walls before puberty has not been previously investigated. We hypothesized that developmental differences in vein walls may contribute to the reduced risk of thrombosis in children. We used a rabbit model to examine morphologic and biochemical features of inferior venae cavae (IVCs). We assessed IVC wall morphology, PG distribution, GAG mass, and GAG antithrombin activity. Morphologically, there were only minor differences between pups and adult rabbits' IVCs. However, there was a significant increase in GAGs by mass in IVCs from pups compared with adult rabbits (p = 0.012). In addition the total antithrombin activity (p = 0.04), and especially that of heparan sulfate (p = 0.01) was significantly increased in pups compared with adult rabbits. These results demonstrate important differences in the antithrombotic properties of IVC walls in pups and adult rabbits. In summary, developmental differences in vein wall PG content and activity exist which may contribute to the reduced risk of venous thromboembolism in children. Further characterization of these differences is required.
Age Factors↗
Development of insulin resistance in the JCR:LA-cp rat: role of triacylglycerols and effects of MEDICA 16.
The JCR:LA-cp rat develops an extreme obese/insulin-resistant syndrome such that by 12 weeks of age, there is no longer any insulin-mediated glucose turnover. At 4 weeks of age, obese and lean rats have essentially identical basal and insulin-mediated glucose uptake in skeletal muscle. By 8 weeks of age, however, the obese rats no longer exhibit such intake. Plasma insulin concentrations in the normal fed state show only small increases up to 4 weeks, with a rapid rise to a marked hyperinsulinemia thereafter, with an age at half-development of 5.5 weeks. Plasma triacylglycerol concentrations in fed obese rats are elevated at 3 weeks and rise rapidly thereafter. The triacylglycerol content of skeletal muscle is significantly elevated in the obese rats at 4 weeks of age. Histological examination of Oil Red O-stained muscle tissue and transmission electron microscopy shows the presence of intracellular lipid droplets. Treatment with the potent triacylglycerol-lowering agent MEDICA 16 (beta,beta'-tetramethylhexadecanedioic acid) from 6 weeks of age reduces plasma lipids markedly, but it reduces body weight and insulin resistance only modestly. In contrast, treatment with MEDICA 16 from the time of weaning at 3 weeks of age results in the normalization of food intake and body weight to over 8 weeks of age. The development of hyperinsulinemia is also delayed until 8.5 weeks of age, and insulin levels remain strongly reduced. Plasma triacylglycerol concentrations remain at the same level as in lean rats, and neither an elevated muscle triacylglycerol content nor intracellular lipid droplets are found at 4 weeks of age. The results indicate that insulin resistance develops in the young animals and is not directly due to a genetically determined defect in insulin metabolism. The mechanism of induction instead appears to be related to an exaggerated triacylglycerol metabolism.
Animals↗
Significance of an echogenic intracardiac focus in fetuses at high and low risk for aneuploidy.
Our objective was to evaluate the significance of an echogenic intracardiac focus in a mixed population of fetuses at high and low risk for aneuploidy. Over a 1 year period, we prospectively identified all fetuses with an echogenic intracardiac focus seen during prenatal sonography. A detailed structural evaluation was performed on each fetus as permitted by gestational age. The location and number of foci were tabulated prospectively, as were associated abnormalities. Follow-up was obtained by review of the medical record. Of the 290 fetuses who had an echogenic intracardiac focus, 14 of them were aneuploid (4.8%). Of the 290 mothers, 125 women were aged 35 years or older and 165 women were younger than 35 years old. Among the 125 fetuses born to women 35 years or older, eight were aneuploid fetuses (6.4%), while among the 165 fetuses of younger mothers, six were aneuploid fetuses (3.6%) (rate ratio = 1.8; 95% confidence interval [extremes] = 0.6, 4.9). Only one of the 14 aneuploid fetuses had an echogenic intracardiac focus as the only sonographic finding, and this occurred in a woman aged 41 years. The majority of the echogenic intracardiac foci (87.6%) were located in the left ventricle, while 4.8% of the foci were right-sided and 7.6% were bilateral. Among the 14 aneuploid fetuses, 14% had bilateral echogenic intracardiac foci and 7% had right-sided foci. Among the euploid fetuses, 7.3% had bilateral echogenic intracardiac foci and 4.7% had right-sided foci. In conclusion, we have shown that the presence of an echogenic intracardiac focus does raise the risk that the fetus has a chromosomal abnormality, most commonly Down syndrome, although all but one aneuploid fetus in our study had other sonographic findings.
Adult↗
Morphological and biochemical features affecting the antithrombotic properties of the aorta in adult rabbits and rabbit pups.
We hypothesised that there are important physiologic differences in arterial wall structure and function with respect to antithrombotic activity in the very young (pre-puberty) compared to adults. Electron microscopy, gel electrophoresis, and activity assays were used to examine differences in aorta structure and function comparing prepubertal rabbits (pups) to adult rabbits. Differences in endothelial function, extracellular matrix structure, proteoglycan (PG) distribution and glycosaminoglycan (GAG) content and function were shown. In both intima and media, total PG, chondroitin sulfate (CS) PG and heparan sulfate (HS) PG content were significantly increased in pups compared to adult rabbits. These findings corresponded to increased concentrations by mass analyses of CS GAG and DS GAG in aortas from pups. There was also a significant increase in antithrombin activity in pups due to HS GAG. In conclusion, differences in both structure and antithrombin activity of aortas from pups compared to adult rabbits suggest that young arteries may have greater antithrombotic potential that is, at least in part, related to increased HS GAG.
Aging↗
Functional diversity and interactions between the repeat domains of rat intestinal lactase.
Lactase-phlorizin hydrolase (LPH), a major digestive enzyme in the small intestine of newborns, is synthesized as a high-molecular-mass precursor comprising four tandemly repeated domains. Proteolytic cleavage of the precursor liberates the pro segment (LPHalpha) corresponding to domains I and II and devoid of known enzymic function. The mature enzyme (LPHbeta) comprises domains III and IV and is anchored in the brush border membrane via a C-terminal hydrophobic segment. To analyse the roles of the different domains of LPHalpha and LPHbeta, and the interactions between them, we have engineered a series of modified derivatives of the rat LPH precursor. These were expressed in cultured cells under the control of a cytomegalovirus promoter. The results show that recombinant LPHbeta harbouring both domains III and IV produces lactase activity. Neither domain III nor IV is alone sufficient to generate active enzyme, although the corresponding proteins are transport-competent. Tandem duplication of domains III or IV did not restore lactase activity, demonstrating the separate roles of both domains within LPHbeta. Further, the development of lactase activity did not require LPHalpha; however, LPHalpha potentiated the production of active LPHbeta but the individual LPHalpha subdomains I and II were unable to do so. Lactase activity and targeting required the C-terminal transmembrane anchor of LPH; this requirement was terminal transmembrane anchor or LPH; this requirement was not satisfied by the signal/anchor region of another digestive enzyme: sucrase-isomaltase. On the basis of this study we suggest that multiple levels of intramolecular interactions occur within the LPH precursor to produce the mature enzyme, and that the repeat domains of the precursor have distinct and specific functions in protein processing, substrate recognition and catalysis. We propose a functional model of LPHbeta in which substrate is channelled from an entry point located within domain II to the active site located in domain IV.
Animals↗
Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases.
The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate and desensitize agonist-occupied GPCRs. GRK2-mediated receptor phosphorylation is preceded by the agonist-dependent membrane association of this enzyme. Previous in vitro studies with purified proteins have suggested that this translocation may be mediated by the recruitment of GRK2 to the plasma membrane by its interaction with the free betagamma subunits of heterotrimeric G proteins (G betagamma). Here we demonstrate that this mechanism operates in intact cells and that specificity is imparted by the selective interaction of discrete pools of G betagamma with receptors and GRKs. Treatment of Cos-7 cells transiently overexpressing GRK2 with a beta-receptor agonist promotes a 3-fold increase in plasma membrane-associated GRK2. This translocation of GRK2 is inhibited by the carboxyl terminus of GRK2, a known G betagamma sequestrant. Furthermore, in cells overexpressing both GRK2 and G beta1 gamma2, activation of lysophosphatidic acid receptors leads to the rapid and transient formation of a GRK/G betagamma complex. That G betagamma specificity exists at the level of the GPCR and the GRK is indicated by the observation that a GRK2/G betagamma complex is formed after agonist occupancy of the lysophosphatidic acid and beta-adrenergic but not thrombin receptors. In contrast to GRK2, GRK3 forms a G betagamma complex after stimulation of all three GPCRs. This G betagamma binding specificity of the GRKs is also reflected at the level of the purified proteins. Thus the GRK2 carboxyl terminus binds G beta1 and G beta2 but not G beta3, while the GRK3 fusion protein binds all three G beta isoforms. This study provides a direct demonstration of a role for G betagamma in mediating the agonist-stimulated translocation of GRK2 and GRK3 in an intact cellular system and demonstrates isoform specificity in the interaction of these components.
Animals↗
Molecular cloning and functional reconstitution of a urate transporter/channel.
Maintenance of urate homeostasis requires urate efflux from urate-producing cells with subsequent renal and gastrointestinal excretion. The molecular basis for urate transport, however, has not been identified. A novel full-length cDNA encoding a 322-amino acid protein, designated UAT (urate transporter), has been cloned from a rat renal cDNA library by antibody screening. UAT mRNA transcripts that approximate 1.55 kilobases are present, but differentially expressed in various rat tissues. Recombinant UAT protein that was expressed from the cloned cDNA in Escherichia coli and purified via immobilized metal affinity chromatography has been functionally reconstituted as a highly selective urate transporter/channel in planar lipid bilayers. The IgG fraction of the polyclonal antibody that was used to select the UAT clone from the cDNA library, but not nonimmune IgG, blocked urate channel activity. Based on the wide tissue distribution of the mRNA for UAT we propose that UAT provides the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion.
Amino Acid Sequence↗
Comparative catabolism of prothrombin and antithrombin in normal and alloxan-diabetic rabbits.
Previous studies have shown that alloxan-induced diabetes in rabbits effects a slower release of plasma proteins from the liver, a slower synthesis of 35S-glycosaminoglycan in the extracellular matrix of the arterial wall, and a concurrent reduction in the fractional catabolic rates of several plasma proteins. In the present study, the catabolism of two hemostatic proteins, prothrombin and antithrombin, are compared in alloxan-induced diabetic rabbits (of 6 months' duration) and age-matched control rabbits. Differentially radiolabeled prothrombin and antithrombin were injected intravenously, and arterial blood was sampled over a 7-day period to measure the clearance from plasma. A three-compartment model was used to determine the fractional catabolic rate and compartmental distribution of the two proteins. As observed for other plasma proteins, the whole-body fractional catabolic rates (jt) for prothrombin and antithrombin were significantly less in diabetic rabbits (prothrombin, 0.33 d-1; antithrombin, 0.27 d-1) than in control rabbits (prothrombin, 0.37 d-1; antithrombin, 0.30 d-1; P < .001 and P < .005, respectively). In absolute terms, the catabolism of antithrombin and prothrombin in diabetic rabbits was 5.1 and 6.2 mg.kg-1.d-1, respectively, equivalent to a molar ratio for antithrombin to prothrombin of 0.94. For the control rabbits, catabolism accounted for 6.3 mg.kg-1.d-1 of antithrombin and 7.3 mg.kg-1.d-1 of prothrombin, equivalent to a molar ratio of 1.01. The fractional distribution of these proteins was not significantly different within the intravascular and extravascular spaces in diabetic and control rabbits. The decreased catabolic rates observed for prothrombin and antithrombin in diabetic rabbits conform with results obtained previously for other plasma proteins, and probably reflect a generally decreased rate of plasma protein production by diabetic rabbit liver compared with control liver.
Alloxan↗
Hazardous materials exposure information service: development, analysis, and medical implications.
The Hazardous Materials Exposure Information Service (HMEIS) was established at the Washington Poison Center (WPC) to rapidly provide information to medical professionals who treat victims of hazardous-materials exposure. Incident description and exposure information is collected from on-site hazardous-materials teams and immediately analyzed by WPC medical toxicologists. Diagnostic and treatment recommendations are provided to prehospital personnel and receiving physicians. Over the first 22 months of operation, 50 calls were received that met HMEIS criteria. Of the 466 individuals exposed, 256 (55%) were transported to a medical facility for treatment. When the WPC was contacted before the decision to transport a patient to a medical facility, 28 of 185 exposure victims (15%) were transported, compared with a transport rate of 81% of exposure victims (66% change; 95% confidence interval [CI], 60% to 72%) in all other concurrent incidents and a historical transport rate of 63% (25% change; 95% CI, 14% to 36%) before the establishment of the HMEIS. These findings, although preliminary and subject to potential confounding, suggest that the HMEIS reduces health care costs through more efficient use of medical resources.
Costs and Cost Analysis↗
Addressing barriers: disabled rights and the implications for nursing of the social construct of disability.
Drawing upon the writings of disabled people, this paper explores some of the issues which nurses working with disabled people are trying to address, in particular the barriers model of disability. Traditionally disability has been regarded as a personal tragedy afflicting the individual, hence the response to disability has been via the charity, health and welfare systems. Disabled people over the past two decades have substantially challenged this view of disability and the responses it prompts, arguing that disability is created by social barriers and barriers in the built environment. This requires a different response. Nurses working with disabled people, such as learning disability nurses, have struggled to develop more appropriate responses to disability, for example by developing working alliances with people with learning difficulties in order to both promote health and address disabling barriers. The issues these nurses face and some of the lessons disabled people have taught them are relevant to the nursing profession's wider struggle to shed its medical and dependency image.
Attitude of Health Personnel↗
X-ray microscopy and imaging of Escherichia coli, LPS and DNA.
Ultrastructural examination by transmission and scanning electron microscopy involves a series of specialized preparation steps which may introduce artefacts in the micrographs. X-ray microscopy can take instant images of specimens but is mostly restricted to a few synchrotron X-ray sources. We have utilized a bench-top nanosecond laser-plasma to produce a single-shot source of nanosecond X-rays tuned for maximum contrast with carbon-rich material. To examine the ultrastructure by absorption profiles, we utilized a laser-produced plasma generated by a single-shot laser (1.06 microns wavelength, 5 x 10(12) W cm-2 intensity) focused on to a silicon target as an X-ray source for high-resolution X-ray microscopy. This approach eliminates the specimen preparation steps. Whole hydrated cells of Escherichia coli and purified preparations of lipopolysaccharide (LPS) and chromosomal DNA (cDNA) were streaked onto poly(methyl methacrylate) (PMMA)-coated grids (resist). This resist was exposed to X-rays under vacuum at a distance of 2.5 cm from the target disc. The silicon plasma produced by a 10-ns burst of laser energy (at 20J) radiates strong emission lines in the region of 300 eV. The X-rays penetrate the sample and their absorption profile is transferred on to the resist where PMMA acts as a negative to generate an image. By atomic force microscopy imaging of this photoresist we have visualized layers around cells of E.coli, darker areas inside the cell probably corresponding to cDNA, and preliminary images of LPS and DNA molecules. This technique has resolution at the 100 A level, produces images similar to the space-filling models of macromolecules and may be of great value in the study of the ultrastructure of hydrated live biological specimens.
DNA, Bacterial↗
An evaluation of nebulized prostacyclin in patients with primary and secondary pulmonary hypertension.
AIMS: To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. METHODS AND RESULTS: Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81.min-1 of oxygen and administered in doses increasing from 15 to 50 ng.kg-1.min-1 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 ng.kg-1.min-1 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56 +/- 5 to 45 +/- 4 mmHg (P = 0.0001). The pulmonary vascular resistance decreased by 38% from 964 +/- 169 to 595 +/- 116 dyne.s-1.cm-5 (P = 0.0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. CONCLUSION: Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertensions.
Administration, Inhalation↗
Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis.
Mycobacterium tuberculosis strains resistant to two or more of the first line antituberculosis drugs (MDR) are a serious threat to successful tuberculosis control programmes. For this retrospective study, 85 follow-up drug resistant isolates from 23 patients residing in a community with a high incidence of tuberculosis were collected and the level of in-vitro resistance to antibiotics determined quantitatively. PCR-SSCP and sequencing techniques were used to screen for gene mutations associated with resistance in 31 follow-up samples from a smaller group of eight patients. DNA fingerprint analysis was done on sequential isolates to confirm identity. Although treatment had a profound effect on changes in drug resistance patterns, the MIC for a particular agent remained constant in follow-up isolates. DNA fingerprinting and mutational analysis (14 different loci) showed that the genome of MDR strains of M. tuberculosis is relatively stable during the course of therapy. The rpoB gene was the most frequently mutated structural gene involved in drug resistance and a novel C to T mutation upstream of open reading frame (ORF)1 of the inhA operon was detected. No evidence was found of the presence of strain W (New York) in this group of MDR strains. The results stress the importance of confirming individuality of strains for the accurate calculation of frequencies of particular mutations associated with drug resistance, particularly in a high incidence area. Approximately one-half (47.8%) of the patients had isolates resistant to concentrations just above the critical concentration for isoniazid (MICs of 0.2-5 mg/L). Therefore, these patients and their contacts who develop primary drug-resistant tuberculosis may respond to higher dosages of treatment which could have a considerable impact on the cost and the ease of management of resistant tuberculosis.
Antitubercular Agents↗
Increased expression of vascular cell adhesion molecule-1 by the aortic endothelium of rabbits with Pasteurella multocida pneumonia.
Vascular cell adhesion molecule-1 (VCAM-1) is expressed by endothelial cells in a variety of inflammatory conditions in experimental animals and humans. It is increased in rabbit endothelium after the intravenous administration of endotoxin, after cholesterol feeding, in regeneration after injury, and in alloxan-induced diabetes mellitus. The effect of a respiratory tract infection with Pasteurella multocida, a common laboratory pathogen in rabbits, on VCAM-1 expression by aortic endothelial cells and on the endothelial ultrastructure was examined in specific-pathogen-free (SPF) New Zealand White rabbits infected by the instillation of a suspension of live organisms into the nose and in conventionally raised rabbits with naturally acquired P. multocida infection. Age-matched SPF rabbits maintained in a disease-free environment were controls. Rabbits were euthanized 50 days after infection, the aorta was excised, and the endothelial cells expressing VCAM-1 were identified by immunohistochemistry. Perfusion-fixed aortas from infected and SPF rabbits were prepared for examination by electron microscopy. All infected animals had pneumonitis and leukocytosis. In SPF rabbits the total leukocyte count was highest at postinfection day 25. There was a significant (P < 0.05) increase in the number of VCAM-1-positive aortic endothelial cells in infected SPF rabbits (34 +/- 4/10(4) endothelial cells; n = 5) and rabbits with naturally acquired infection (57 +/- 14/10(4) endothelial cells; n = 5) compared with control animals (12 +/- 3 per 10(4) endothelial cells; n = 4). The endothelium of infected rabbits had morphologic alterations consistent with injury. Thus infection at remote sites can activate arterial endothelium and induce the expression of VCAM-1.
Animals↗
Respiratory infection in lipid-fed rabbits enhances sudanophilia and the expression of VCAM-1.
The pathogenesis of atherosclerosis has been related to infection of the arterial wall, but it is not clear whether this occurs before or after the development of lipid-containing lesions. Respiratory bacterial infection increases the expression of vascular cell adhesion molecule-1 (VCAM-1). We therefore examined whether a similar infection would enhance atherosclerosis in New Zealand White rabbits fed chow supplemented by 15% (w/w) egg yolk for 50 days. Rabbits with naturally acquired respiratory infection by Pasteurella multocida, pathogen-free (SPF) animals infected by P. multocida in the laboratory, and age-matched SPF rabbits maintained in a disease-free environment were used. Endothelial cells expressing VCAM-1 in the aorta between intercostal arteries 3 and 5 were identified using anti-VCAM-1 (Rb1/9) and an alkaline-phosphatase-linked secondary antibody and quantified in Häutchen preparations. The remainder of the aorta was stained with Sudan IV to show lipid deposition. The expression of VCAM-1 (mean +/- SEM per 10,000 cells) was 22 +/- 8 (n = 5) in the lipid-fed SPF rabbits, significantly different from that in the lipid-fed rabbits with naturally occurring infection (190 +/- 51 (n = 5)) or from rabbits infected in the laboratory (106 +/- 25 (n = 5)). The extent of Sudanophilia was significantly greater in the naturally infected rabbits (8.3 +/- 1.2%) or infected SPF rabbits (10.3 +/- 1.8%) than in the SPF rabbits (2.7 +/- 0.8%; P < 0.05). Antibiotic treatment in naturally infected rabbits reduced the number of cells expressing VCAM-1 and the extent of the Sudanophilia to baseline levels. Thus, Sudanophilia is enhanced by bacterial infection in rabbits fed egg yolk and is associated with a significant increase in VCAM-1.
Animals↗
The platelet cytoskeleton stabilizes the interaction between alphaIIbbeta3 and its ligand and induces selective movements of ligand-occupied integrin.
Previously, we showed that a subpopulation of the major platelet integrin, alphaIIbbeta3, co-sediments from detergent lysates with talin and other membrane skeleton proteins. Once alphaIIbbeta3 has bound adhesive ligand in a platelet aggregate, the detergent-insoluble alphaIIbbeta3 redistributes (along with the detergent-insoluble membrane skeleton proteins and a variety of signaling molecules) to a fraction that contains cytoplasmic actin filaments. Concomitantly, certain signaling molecules are activated. The present study shows that, in intact platelets, alphaIIbbeta3 forms clusters when occupied by ligand and is selectively moved into the open canalicular system; alphaIIbbeta3 that has not bound ligand remains diffusely distributed at the periphery of the cell. When cytoplasmic actin filaments are depolymerized by cytochalasins, the ability of alphaIIbbeta3 to bind ligand is decreased, and the movement of ligand-occupied alphaIIbbeta3 is prevented. Together with the previous findings, these results suggest that (i) membrane skeleton-associated alphaIIbbeta3 is selectively induced to bind ligand in activated platelets, (ii) ligand-induced transmembrane signaling causes an altered association of membrane skeleton-associated alphaIIbbeta3 with the cytoplasmic component of the cytoskeleton, (iii) ligand-induced cytoskeletal reorganizations stabilize the interaction between ligand and integrin, and (iv) ligand-occupancy triggers cytoskeletal reorganizations that result in selective movements of occupied ligand.
Actins↗