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D C Anderson

Publications and source records attributed to D C Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1993

Role of leukocyte adhesion molecules in complement-induced lung injury.

The bolus i.v. infusion of cobra venom factor into rats results in acute lung injury that is neutrophil-dependent, oxygen radical-mediated, and requires CD18. In our studies a more precise definition regarding the role of beta-integrins and requirements for cytokines was obtained by the use of blocking antibodies. Lung injury was quantitated by changes in permeability (leakage of 125I-BSA) and hemorrhage (extravasation of 51Cr-RBC). In animals treated with anti-CD11a, the permeability and hemorrhage parameters were reduced by 30 and 29%, respectively. Treatment with anti-CD11b resulted in reductions in permeability and hemorrhage by 53 and 48%, respectively, whereas anti-intercellular adhesion molecule-1 reduced the parameters of injury by 60 and 75%, respectively. Not surprisingly, treatment with antibodies to very late Ag-4, TNF-alpha and IL-1 failed to show any protective effects, which contrasts to the requirements for these molecules in lung injury after deposition of IgG immune complexes. Protective interventions were associated with a reduction in lung content of myeloperoxidase. These studies indicate that, in the cobra venom factor model of acute lung injury in rats, engagement of Mac-1, lymphocyte function-associated Ag-1, and intercellular adhesion molecule-1 are essential, whereas, in contrast to other models of neutrophil mediated lung injury, cytokines (TNF-alpha and IL-1) and very late Ag-4 are not required for the full development of injury.

Animals↗
PubMed1993

How Twin Cities neurologists treat ischemic stroke. Policies and trends.

OBJECTIVE: To examine community practices. DESIGN: Physician practice policies were surveyed using case vignettes in which evaluation for carotid endarterectomy or use of anticoagulation therapy was at issue. Virtually the same group was surveyed in 1988 and again in 1991, after publication of carotid endarterectomy trials in symptomatic patients. SETTING: Greater Metropolitan Minneapolis-St. Paul, Minnesota. PARTICIPANTS: Community and academic neurologists in practice of general adult neurology. MEASUREMENT: Percentage of respondents who would recommend the management option in question for each vignette. RESULTS: Ninety-eight percent favored evaluation for carotid endarterectomy in appropriately symptomatic "good risk" patients in 1988 before proof of efficacy became available. Proof increased the percentage (from 67% to 92%) favoring evaluation in older, sicker, symptomatic patients but not the percentage of those favoring evaluation of bruit patients (1988: 33%; 1991: 24%). In 1991, a lower percentage recommended warfarin therapy after noncardioembolic transient ischemic attack; this was especially apparent in the vertebrobasilar case (1988: 59%; 1991: 37%). Both years, nine of 10 neurologists recommended heparin therapy for progressing stroke, while half to three-fourths used it after partial stroke or transient ischemic attack. Almost all would use anticoagulants for secondary prophylaxis after suspected cardioembolic stroke. CONCLUSION: The results reflect a treatment-oriented empirical approach in this community and document quick clinical application of scientific evidence when it became available.

Aged↗
PubMed1993

Role of bone matrix in osteoclast recruitment in cultured fetal rat calvariae.

In cultured 19 day fetal rat calvaria, osteoclasts first appear after 48 h, more rapidly than with other cultured embryonic long bone rudiments. This may be because the calvarial osteoclast precursors are more differentiated or intramembraneous bone is a more powerful stimulus for osteoclast maturation than endochondral bone. To investigate this further, 19 day calvariae were stripped of their endocranial membranes, devoiding them of osteoclast precursors, and cocultured with the membranes or with other sources of these cells, such as bone marrow, fetal liver, spleen, and blood. There was similar recruitment of mature osteoclasts onto the surface of the "stripped" calvariae from the endocranial membranes and from the hematopoietic tissues after 48 h culture. Intact 19 day fetal calvariae were cultured with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) or with 1,25-dihydroxyvitamin D3, [1,25-(OH)2D3], each thought to influence different stages of osteoclast maturation. They stimulated osteoclast recruitment, although 1,25-(OH)2D3 was effective only in the first 24 h of culture. They also increased osteoclast recruitment from fetal liver onto stripped calvariae. When intact bones were cultured with hrGM-CSF and 1,25-(OH)2D3 together, osteoclast number decreased but their area increased. Calvariae therefore appear to contain osteoclast precursors at earlier (GM-CSF-sensitive) and later [1,25-(OH)2D3-sensitive] stages. As recruitment onto stripped calvariae was similar whichever source of precursors was used, it is likely that calvarial bone matrix is an important influence on rapid osteoclast maturation in these bones in vitro.

Animals↗
PubMed1993

Paramyxoviruses and Paget's disease.

Using the technique of in situ hybridisation, we extended our initial studies of the occurrence of canine distemper and measles virus in Paget's disease. Bone samples from untreated patients and patients treated with 3-amino-hydroxypropylidene 1,1 bisphosphonate pamidronate (APD) were examined for canine distemper nucleocapsid (CDV-N), measles nucleocapsid (MV-N), respiratory syncytial virus fusion (RSV-F), and simian virus 5 haemoglutinin-neuraminidase (SV5-HN) sequences using 35S-labelled sense and antisense riboprobes. Only CDV-N mRNA was detected in osteoclasts, osteoblasts, and mononuclear cells. In untreated Paget's patients, 63.5% were found to have CDV sequences residing in bone cells, and 48.2% of those undergoing APD treatment were still found to have the viral sequences. RSV-F mRNA was only found in one patient. None of the other paramyxoviruses tested were detected. This study shows that CDV can infect a human host and may be an aetiological agent of Paget's disease of bone.

Distemper Virus, Canine↗
PubMed1993

Mechanisms involved in Helicobacter pylori-induced inflammation.

BACKGROUND: Helicobacter pylori infection is associated with mucosal inflammation. The aims of the present study were to assess whether a water extract of H. pylori promotes neutrophil (polymorphonuclear leukocyte [PMN]) adherence to endothelial cells and define the molecular basis of this adhesive interaction. METHODS: Intravital microscopy was used to study leukocyte adhesive interactions in rat mesenteric venules in situ. PMN-endothelial cell adhesive interactions were studied in vitro using human PMNs and monolayers of human umbilical vein endothelial cells (HUVEC). RESULTS: In vivo, superfusion of rat mesentery with the H. pylori extract increased leukocyte adhesion and emigration in venules. In vitro, adhesion of human PMNs to HUVEC was increased by the H. pylori extract in a concentration-dependent manner. Pretreatment of HUVEC alone with H. pylori extract had no effect on PMN adherence, whereas pretreatment of PMN alone significantly increased their adherence to HUVEC. The extract-induced adhesion was significantly diminished by monoclonal antibodies (MAb) directed against either CD11a, CD11b, or CD18 on neutrophils, and by MAbs against intercellular adhesion molecule-1 (ICAM-1), but not E- or P-selectin, on endothelial cells. CONCLUSIONS: These studies suggest that products of H. pylori elicit gastrointestinal inflammation by promoting PMN adhesion to endothelial cells via CD11a/CD18- and CD11b/CD18-dependent interactions with ICAM-1.

Animals↗
PubMed1993

Molecular determinants of aspirin-induced neutrophil adherence to endothelial cells.

BACKGROUND: Previous studies indicate that aspirin can promote neutrophil adhesion to venular endothelium in vivo. The objectives of the present study were (1) to identify the leukocyte and endothelial cell surface glycoproteins that mediate this adhesive interaction and (2) to assess the role of lipoxygenase products, prostanoids, and platelet activating factor in aspirin-induced neutrophil adhesion. METHODS: Human neutrophils (polymorphonuclear leukocytes [PMN]) were added to confluent monolayers of human umbilical vein endothelial cells (HUVEC) and coincubated with or without aspirin (30, 150, or 300 micrograms/mL). RESULTS: Aspirin increased neutrophil adherence to HUVEC in a dose-dependent manner. Pretreatment of HUVEC with aspirin had no effect on PMN adherence whereas pretreatment of PMN significantly increased adherence to HUVEC. Incubation of neutrophils with aspirin increased surface expression of CD11b and CD18 on neutrophils. The aspirin-induced increase in PMN adherence to HUVEC was significantly reduced by monoclonal antibodies against CD18, CD11b, CD11a, and intercellular adhesion molecule 1. Aspirin-induced neutrophil adhesion was diminished by treatment with either a lipoxygenase inhibitor or a leukotriene B4 (LTB4) receptor antagonist. CONCLUSIONS: These studies indicate that aspirin promotes neutrophil adherence to endothelium via CD11a/CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule 1; the adhesion response is partially mediated by leukotriene B4.

Adult↗
PubMed1993

Canine distemper virus transcripts detected in the bone cells of dogs with metaphyseal osteopathy.

Using the technique of in situ hybridisation, we have recently extended our observations that canine distemper virus (CDV) is present in the bone cells of patients with Paget's disease, and have shown that CDV is also detectable in the bone cells of dogs that are naturally infected with the virus. Since hybridisation was localised to bone cells within the metaphyses of the affected dogs, we investigated the possibility that CDV might be involved in the canine metaphyseal bone disorder, metaphyseal osteopathy. Bone samples from three cases of metaphyseal osteopathy were examined for the presence of the CDV nucleocapsid (CDV-N) gene and the measles virus nucleocapsid (MV-N) gene, using 35S-labelled sense and antisense riboprobes. As with our previous findings in Paget's disease of bone, only the antisense probe was found to hybridize to the osteoblasts and osteoclasts within the affected metaphyses. No hybridisation was seen with the CDV-N sense and MV-N probes in any of the samples tested. Bone samples were also taken from one of the cases to check for the presence of the CDV-N gene using the polymerase chain reaction (PCR). Our findings with in situ hybridisation were confirmed by PCR and subsequent Southern blotting and probing with a 32P-labelled cDNA probe. The detection of CDV RNA within the bone cells of dogs with metaphyseal osteopathy suggests that this virus may be a cause of the disease and provides further, indirect evidence that CDV might be responsible for the bony abnormalities seen in Paget's disease of bone.

Animals↗
PubMed1993

Nitroglycerin ointment in the treatment of impotence.

Topical nitroglycerin ointment has been studied in the laboratory as a possible treatment for impotence of various etiologies. However, there is limited information on the topical administration of nitroglycerin in a natural environment allowing normal sexual function. We report 3 cases of impotence that were successfully treated with topical nitroglycerin ointment.

Administration, Cutaneous↗
PubMed1993

Immune complex-stimulated neutrophil LTB4 production is dependent on beta 2 integrins.

The beta 2 integrins (LFA-1, Mac-1, and p150,95) are critical for many adhesive functions of leukocytes. Although the binding of the IgG-opsonized particles occurs normally in the absence of beta 2 integrins, phagocytosis of IgG-opsonized particles by activated neutrophils (PMN) requires these integrins. This observation suggests a role for beta 2 integrins in phagocytosis subsequent to particle binding. To investigate the mechanism of involvement of beta 2 integrins in IgG-mediated functions, we examined the role of beta 2 integrins in adhesion to immune complex (IC)-coated surfaces. Initial adhesion and spreading on IC-coated surfaces were equivalent in control and beta 2-deficient phagocytes. However, both genetically beta 2-deficient PMN and PMN treated with the anti-beta 2 mAb IB4 subsequently detached from the IC-coated surfaces. To determine whether biochemical consequences of IgG activation were also affected by beta 2 deficiency, LTB4 production in response to Fc receptor ligation was assessed. LTB4 production by beta 2-deficient PMN adherent to IC-coated surfaces was markedly decreased in comparison with control PMN. Importantly, LTB4 production by PMN stimulated with fluid phase heat-aggregated IgG also required the beta 2 integrins, showing that the defect was not a simple consequence of abnormal adhesion. In contrast, superoxide production by IC-adherent PMN was equivalent in control and beta 2-deficient PMN. The initial rises in intracytoplasmic [Ca2+]i in response to aggregated IgG also were unaffected by inhibition of beta 2 integrins. These data show that lack of beta 2 integrins does not inhibit all FcR-dependent signal transduction. Finally, LTB4 production by normal PMN adherent to ICs was inhibited by antibodies to FcRII, but not FcRIII, showing that FcRII ligation was required for this effect. Together these data identify a role for the beta 2 integrins in a signal transduction pathway leading to sustained adhesion and LTB4 production in response to IC. Since both beta 2 integrins and FcRII are required for these effects, the data further suggest cooperation between these receptors in generating PMN activation in response to IC stimulation.

Actins↗
PubMed1993

Expression of human CD18 in murine granulocytes and improved efficiency for infection of deficient human lymphoblasts.

The CD18 gene encodes the beta 2-subunit of leukocyte integrins, and mutations in this gene cause extreme host susceptibility to bacterial and fungal infection. Because expression of CD18 is restricted to bone marrow-derived cells, this disorder is considered an excellent candidate for somatic gene therapy utilizing ex vivo infection of bone marrow stem cells. We have constructed a retroviral vector expressing CD18 with the Moloney murine leukemia virus (Mo-MLV) long terminal repeat (LTR) as the promoter, and high-titer ecotropic and amphotropic producer cell lines were isolated using the GP+E-86 and GP+envAM12 safe packaging cell lines. Infection of CD18-deficient lymphoblasts resulted both in expression of immunodetectable CD18 at 35-40% of normal levels on 55-60% of cells and in functional restoration of CD18-dependent aggregation. All of 16 mice transplanted with syngeneic bone marrow infected with the CD18 retrovirus expressed human CD18 on 17-36% of granulocytes at 2 weeks after transplantation, and expression was appropriately up-regulated in response to stimulation with zymosan-activated serum. This recombinant retrovirus should prove useful for further studies of somatic gene therapy for CD18 deficiency.

3T3 Cells↗
PubMed1993

Hospital-based versus community-based clinical education: comparing performances and course evaluations by students in their second-year pediatrics rotation.

BACKGROUND: Increasing use of outpatient settings for clinical education raises the question of their effectiveness compared with that of inpatient settings. METHOD: At the University of Minnesota Medical School-Minneapolis in 1987-88, the 190 second-year students participated in a six-week tutorial rotation introducing them to clinical pediatrics: 52 (27%) were in hospital settings and 138 (73%) were in community outpatient settings. Almost all the students (178) evaluated their rotations by responding to both structured and open-ended questions, using a Likert scale for the structured questions. At the completion of the second year, all 190 students took an objective structured clinical examination (OSCE) that included five pediatrics stations. Student's t-test was used to compare (1) the mean ratings the hospital-based and community-based students gave their pediatrics rotations and (2) the mean scores earned by the two groups of students on the five pediatrics stations in the OSCE. RESULTS: There were no statistically significant differences between (1) the two groups' mean ratings of the clinical experience overall or of the quality of teaching or (2) the groups' mean scores on any of the OSCE stations. CONCLUSION: That the hospital-based and community-based students performed comparably on the OSCE and gave similar evaluations of their pediatrics rotations supports the use of community practitioners to provide students with their initial clinical training. Moreover, community-based teaching sites replicate situations in which most students will eventually practice medicine.

Ambulatory Care↗
PubMed1993

Efficacy of low dose purified FSH in ovulation induction following pituitary desensitization in polycystic ovarian syndrome.

OBJECTIVES: We evaluated the efficacy of ovulation induction using purified FSH in either low dose or conventional dosage in patients with polycystic ovarian syndrome. We assessed whether gonadotrophin measurement by radioimmunoassay or immunoradiometric assay is a better indicator of whether pituitary desensitization with a GnRH agonist (Zoladex) has occurred. DESIGN: Two different protocols were used. Pituitary desensitization was carried out with a GnRH agonist (Zoladex, ICI Pharmaceuticals UK). The patients were then randomized into one of two treatment groups. Conventional dose protocol: Patients commenced with a daily FSH (Metrodin, Serono Laboratories Ltd, UK) dose of 75 units for at least 7 days. The FSH dose was then increased, if necessary, based on ultrasound scans and plasma oestradiol (E2) levels in 75-unit increments. Low dose protocol: The same protocol was used except that the starting dose of FSH was 37.5 units daily with increments of 37.5 units. RESULTS: Low dose protocol (six patients, six cycles). There was a high incidence of multiple follicular development (10.3 +/- 5.6 (+/- SD) follicles, 5.0 +/- 3.8 follicles > 14 mm in diameter). Three cycles resulted in ovulation, one was anovulatory and two patients underwent gamete intrafallopian transfer due to multiple follicular development. Conventional dose protocol (seven patients, eight cycles). Again there was multiple follicular development (10.1 +/- 8.6 follicles, 2.0 +/- 2.3 > 14 mm). Three cycles were ovulatory, one anovulatory, three abandoned due to multiple follicular development and one underwent gamete intrafallopian transfer with the development of severe hyperstimulation necessitating steroid therapy. There was no difference between the two protocols in the number of days of FSH administration (low dose protocol 26 +/- 6.5, conventional dose protocol 23 +/- 8.1 days), the total number of units of FSH given per patient was 2844 +/- 1816 vs 2635 +/- 1726. The peak E2 level (pmol/l) during FSH treatment was 3193 +/- 662 vs 2389 +/- 3099 and the rate of increase in the FSH dose in ampoules of Metrodin per day was 0.058 +/- 0.03 vs 0.057 +/- 0.03. All patients were 'downregulated' (E2 < 70 pmol/l) prior to ovulation induction. However, gonadotrophin levels (IU/l) were 4.3 +/- 1.5 (LH) and 2.8 +/- 1.2 (FSH) by radioimmunoassay and LH was unchanged throughout FSH treatment whereas LH measured by immunoradiometric assay was < 1.0 IU/l prior to ovulation induction and remained so throughout. The mean LH radioimmunoassay to immunoradiometric assay ratio was 6.2 +/- 2.1. CONCLUSIONS: We conclude that regardless of the starting dose the use of pure FSH in patients with polycystic ovarian syndrome whose LH has been completely down regulated may be associated with multiple follicular development and a poor outcome. LH measured by radioimmunoassay is not a good indicator of whether pituitary densensitization has occurred but LH measured by immunoradiometric assay appears to be. These results strongly suggest that a basic minimum amount of LH is necessary for normal ovulatory development.

Adult↗
PubMed1993

Linkage analysis of 7 polymorphic markers at chromosome 11p11.2-11q13 in 27 multiple endocrine neoplasia type 1 families.

The multiple endocrine neoplasia type 1 (MEN1) locus has been previously localized to 11q13 by combined tumour deletion mapping and linkage studies. Family linkage analysis has defined the locus order as 11 cen-PGA-(PYGM, MEN1)-(D11S97, D11S146)-INT2-11qter, and tumour deletion mapping studies have suggested that the MEN1 locus is proximal to D11S146 but distal to PYGM. In order to establish further the location of MEN1, we have utilized the seven polymorphic DNA probes: D11S288, D11S149, PGA, PYGM, D11S97, D11S146 and INT2, in linkage studies of 339 members (116 affected) from 27 MEN1 families. Linkage between MEN1 and 6 of the 7 loci was established, and the highest peak lod scores [Z(theta)] were observed with PYGM and D11S97 at Z(theta) = 13.71, theta = 0.047 and Z(theta) = 13.76, theta = 0.076 respectively. Multilocus analysis suggested the most likely locus order as: 11 pter-(D11S288, D11S149)-11 cen-PGA-PYGM-MEN1-D11S97-D11S146-INT2-1 1qter. In addition, an examination of individual recombinants indicated a centromeric location of D11S149 in relation to D11S288. Thus, the results of our study, which favoured a location of MEN1 proximal to D11S97 and distal to PYGM, have established a panel of recombinants that will facilitate further meiotic mapping studies of the MEN1 locus.

Chromosomes, Human, Pair 11↗
PubMed1993

Arcobacter (Campylobacter) butzleri-associated diarrheal illness in a nonhuman primate population.

After DNA hybridization identified an isolate from an ill rhesus macaque (Macaca mulatta) as Arcobacter (Campylobacter) butzleri, we initiated a study to determine whether A. butzleri was associated with diarrheal disease in nonhuman primates at the Yerkes Primate Research Center. By using Campy-CVA medium incubated at 35 degrees C, 15 A. butzleri isolates were obtained from 14 macaques; 7 macaques were coinfected with Campylobacter coli and Campylobacter jejuni. A. butzleri was not isolated from normal feces, despite the fact that feces from 76 macaques were cultured at necropsy. Histologic evaluation of colonic specimens from three macaques from which A. butzleri had been isolated showed mild to moderately severe chronic, active colitis. Ribotype analysis of the 15 A. butzleri isolates revealed nine different strains; these data suggest that A. butzleri may be endemic in this primate population and that a point source of infection is unlikely. This is the first report of the presence of A. butzleri in juvenile and adult macaques with diarrhea, and it may present an opportunity to study the pathogenesis of this organism, which appears to be associated with persistent diarrhea in humans.

Animals↗
PubMed1993

Multiple viral determinants contribute to pathogenicity of the acutely lethal simian immunodeficiency virus SIVsmmPBj variant.

Simian immunodeficiency virus (SIV) induces an immunodeficiency syndrome similar to human AIDS. Although the disease course of SIV-induced immunodeficiency is generally measured in months to years, a disease syndrome that results in death in 5 to 14 days has been described in pig-tailed macaques infected with the SIVsmmPBj (PBj) strain. The purpose of this study was to derive an acutely lethal PBj molecular clone in order to study viral genes involved in pathogenesis. Six infectious molecular clones were generated; acutely fatal disease was induced by experimental inoculation of pig-tailed macaques with virus stocks derived from either of two clones, PBj6.6 or PBj14.6. Molecular chimeras were constructed by exchange of regions of the genome of PBj6.6 and a nonlethal, related clone, SIVsmH4. Only a chimera expressing the PBj genome under the control of a SIVsmH4 long terminal repeat induced death soon after inoculation. These studies suggest that multiple viral genes of PBj are critical for development of acute disease. More specifically, the env gene but not the long terminal repeat PBj was required for acute disease induction; however env must act in concert with another gene(s) of the PBj genome.

Animals↗
PubMed1993

Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury.

A number of recent studies have demonstrated that neutrophil adherence to the vascular endothelium is a critical early event in the pathogenesis of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Although a role in this process for the leukocyte adhesion molecule, CD11/CD18, has been demonstrated, the involvement of endothelial adhesion molecules has not previously been examined. Therefore, using monoclonal antibodies directed against a number of endothelial adhesion molecules (ICAM-1, P-selectin, E-selectin), we studied the role of these molecules in the production of mucosal injury after indomethacin administration and in indomethacin-induced leukocyte adherence. As previously shown in the rabbit, anti-CD18 markedly reduced (by 75%) the severity of damage induced by indomethacin in the rat. Moreover, this antibody completely prevented indomethacin-induced leukocyte adherence. Similarly, anti-ICAM-1 significantly attenuated (by 74%) the severity of indomethacin-induced gastric injury while also markedly reducing leukocyte adherence (by 83%). Anti-P-selectin and anti-E-selectin produced only small (approximately 35%), but statistically significant, reductions of mucosal injury, but only anti-P-selectin significantly affected indomethacin-induced leukocyte adherence (by approximately 50%). These results demonstrate that indomethacin-induced leukocyte adherence and mucosal injury are dependent on the expression of CD18 and ICAM-1. P-selectin also appears to play a small, but important, role in these processes, whereas the role of E-selectin remains equivocal. These studies support the hypothesis that interactions at the leukocyte-endothelium interface are critical in the pathogenesis of NSAID-induced mucosal injury, and this interface may represent a rational target for therapies aimed at preventing this form of injury.

Animals↗
PubMed1993

Inhibition of nitric oxide production. Mechanisms of vascular albumin leakage.

The mechanisms by which nitric oxide modulates microvascular albumin exchange were investigated by monitoring leukocyte-endothelial cell adhesion and fluorescein isothiocyanate-albumin leakage in rat mesenteric venules exposed to NG-nitro-L-arginine methyl ester (L-NAME). L-NAME elicited an initial rapid increase followed by a slower rate of albumin accumulation in the interstitial space. The initial phase of albumin leakage preceded the L-NAME-induced leukocyte adherence and emigration, whereas the magnitude of the albumin leakage observed in the later phase of L-NAME exposure was highly correlated with the number of adherent and emigrated leukocytes in the same segment of venule. Monoclonal antibodies (MAbs) directed against adhesion molecules CD11/CD18, ICAM-1, or P-selectin, but not a nonbinding MAb, attenuated the albumin leakage induced by L-NAME. WEB2086, a platelet activating factor antagonist, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) reduced the leukocyte adherence and emigration as well as the increased albumin leakage. Only 8-br-cGMP and the P-selectin MAb attenuated the platelet-leukocyte aggregation elicited by L-NAME. Phalloidin, which promotes endothelial junctional integrity, inhibited both the early and late phases of albumin leakage. Overall, these findings suggest that the increased albumin leakage observed in postcapillary venules after inhibition of nitric oxide production involves a mechanism that includes a role for cGMP, platelet activating factor, leukocyte-endothelial cell adhesion, and the endothelial cell cytoskeleton.

Albumins↗