Biomedical subjects

M L Phillips

Publications and source records attributed to M L Phillips.

At least 55 records · Page 3Linked to original sources

PubMed1997

A specific neural substrate for perceiving facial expressions of disgust.

Recognition of facial expressions is critical to our appreciation of the social and physical environment, with separate emotions having distinct facial expressions. Perception of fearful facial expressions has been extensively studied, appearing to depend upon the amygdala. Disgust-literally 'bad taste'-is another important emotion, with a distinct evolutionary history, and is conveyed by a characteristic facial expression. We have used functional magnetic resonance imaging (fMRI) to examine the neural substrate for perceiving disgust expressions. Normal volunteers were presented with faces showing mild or strong disgust or fear. Cerebral activation in response to these stimuli was contrasted with that for neutral faces. Results for fear generally confirmed previous positron emission tomography findings of amygdala involvement. Both strong and mild expressions of disgust activated anterior insular cortex but not the amygdala; strong disgust also activated structures linked to a limbic cortico-striatal-thalamic circuit. The anterior insula is known to be involved in responses to offensive tastes. The neural response to facial expressions of disgust in others is thus closely related to appraisal of distasteful stimuli.

Adult↗

PubMed1997

Corpus callosum size and inter-hemispheric function in schizophrenia.

We studied the relationship between corpus callosum area and both inter-hemispheric facilitation and interference in schizophrenics and controls. Mid-sagittal sections through the corpus callosum were measured using structural magnetic resonance imaging on 42 patients and 43 normal controls, along with symptom profiles. In a sub-sample, a modified version of the Stroop Test was also performed (27 patients and 29 controls) to assess inter-hemispheric facilitation and interference of colour naming. In the larger sample (total subjects, n = 85), there were no significant differences between patients and controls in CC area but a trend towards smaller values in patients in all but the posterior segment. In the sub-sample, bilateral facilitation was greater, and interference, less in schizophrenics compared with controls. There was a positive correlation between facilitation and posterior CC area, parallelled by a negative correlation between interference and posterior CC area, in both patients and controls, which only reached statistical significance when both groups were combined. These findings suggest that the link, between CC size and neuropsychological processes involving inter-hemispheric transfer of information, is common to both schizophrenics and normal controls. There were significant negative correlations between anterior CC area and psychomotor poverty (avolition, anhedonia and affective flattening), and a suggestion that the negative correlation between age and CC size in controls was not present in patients.

Adult↗

PubMed1997

A cognitive neuropsychological approach to the study of delusions in late-onset schizophrenia.

OBJECTIVE: Hypotheses to explain delusion formation include distorted perceptual processing of meaningful stimuli (e.g. faces), abnormal reasoning, or a combination of both. The study investigated these hypotheses using standardized neuropsychological tests. DESIGN: A three-patient case-study, compared with a small group (n = 8) of age-matched normal control subjects. SETTING: Hospital in- and outpatients. Age-matched normal controls were from local residential homes. PATIENTS: Three subjects with late-onset schizophrenia, two currently deluded and one in remission. Both deluded subjects had persecutory beliefs. One had a delusion of misidentification. INTERVENTIONS: All subjects were administered standardized neuropsychological tests of facial processing and tests of verbal reasoning. MAIN OUTCOME MEASURES: The test scores of the three patients were compared with published normal values and the age-matched control data. RESULTS: The tests demonstrated impaired matching of unfamiliar faces in deluded subjects, particularly in the subject with delusional misidentification. Increasing the emotional content of logical reasoning problems had a significant effect on the deluded subjects' reasoning but not that of the normal controls. CONCLUSION: The findings suggest impaired visual processing plus abnormal reasoning in deluded subjects. However, these impairments are relatively subtle given the severity of psychiatric disorder in the patients studied.

Age of Onset↗

PubMed1997

Viewing strategies for simple and chimeric faces: an investigation of perceptual bias in normals and schizophrenic patients using visual scan paths.

Left hemi-face (LHF) perceptual bias of chimeric faces in normal right-handers is well-documented. We investigated mechanisms underlying this by measuring visual scan paths in right-handed normal controls (n = 9) and schizophrenics (n = 8) for simple, full-face photographs and schematic, happy-sad chimeric faces over 5 s. Normals viewed the left side/ LHF first, more so than the right of all stimuli. Schizophrenics viewed the LHF first more than the right of stimuli for which there was a LHF choice of predominant affect. Neither group demonstrated an overall LHF perceptual bias for the chimeric stimuli. Readjustment of the initial LHF bias in controls was probably a result of increased attention to stimulus detail with scanning, whereas the schizophrenics demonstrated difficulty in redirection of the initial focus of attention. The study highlights the role of visual scan paths as a marker of normal and abnormal attentional processes.

Adult↗

PubMed1997

Visual scan paths are abnormal in deluded schizophrenics.

One explanation for delusion formation is that they result from distorted appreciation of complex stimuli. The study investigated delusions in schizophrenia using a physiological marker of visual attention and information processing, the visual scan path-a map tracing the direction and duration of gaze when an individual views a stimulus. The aim was to demonstrate the presence of a specific deficit in processing meaningful stimuli (e.g. human faces) in deluded schizophrenics (DS) by relating this to abnormal viewing strategies. Visual scan paths were measured in acutely-deluded (n = 7) and non-deluded (n = 7) schizophrenics matched for medication, illness duration and negative symptoms, plus 10 age-matched normal controls. DS employed abnormal strategies for viewing single faces and face pairs in a recognition task, staring at fewer points and fixating non-feature areas to a significantly greater extent than both control groups (P < 0.05). The results indicate that DS direct their attention to less salient visual information when viewing faces. Future paradigms employing more complex stimuli and testing DS when less-deluded will allow further clarification of the relationship between viewing strategies and delusions.

Adult↗

PubMed1997

Probing the structure of C1 with an anti-C1s monoclonal antibody: the possible existence of two forms of C1 in solution.

Anti-human C1s monoclonal antibody H1532, a mouse gamma-1-immunoglobulin elicited by a C1r2C1s2 immunogen, appeared to bind to the beta-domain of C1s by electron microscopy. In agreement with this observation, Western blotting demonstrated good binding to unreduced C1s, but no binding to the alpha or gamma-B domains. When added to solutions of the C1r2C1s2 tetramer, HI532 converted the 8.7 S tetramer into an 18 S complex, which was seen by electron microscopy to be a dimer of parallel C1s x C1r x C1r x C1s molecules cross-linked by two bivalent monoclonal antibodies. If increasing amounts of HI532 were added to C1r2C1s2 followed by addition of equivalent C1q, there was a progressive loss of hemolytic activity, which became zero when two equivalents of antibody HI532 were added. When two equivalents of HI532 were added to serum or C1 reconstituted overnight from purified subcomponents, there was an immediate loss of approximately 50% of the hemolytic activity; thereafter, activity decayed slowly and even after 24 hr, 10-30% of the activity remained. The rapid loss of only 50% of the activity would be readily explained by the existence of two conformations of C1, one of which was rapidly disassembled by antibody, and the other was resistant to disassembly. These two conformations may correspond to two previously proposed structures for the C1 complex.

Animals↗

PubMed1997

Anti-rejection prophylaxis by blocking selectin dependent cell adhesion after rat allogeneic and xenogeneic lung transplantation.

OBJECTIVE: Adhesion molecules regulate the infiltration of leukocytes into the graft during rejection after lung transplantation. The first step of the adhesion cascade is mediated by selectins. Sialyl-LewisX is a ligand of P-selectin. The purpose of the study was to evaluate SLX, a synthetic oligosaccharide analog of Sialyl-LewisX, for anti-rejection prophylaxis after allogeneic and xenogeneic left lateral, orthotopic rat lung transplantation. METHODS: In groups A and B, allogeneic lung transplantation was performed using fully incompatible rat strains (donors: Dark-Agouti (RT1a); recipients: Lewis (RT11)). In group A (n = 10), recipients recieved 200 microg/d SLX i.v. on day 0-4. Group B rats (n = 10) served as untreated controls. The animals were sacrificed on days 5 and 10, respectively. In groups C and D, xenogenic lung transplantation was performed using Gold Syrian hamsters as donors and Lewis rats as recipients. In group C (n = 10), recipients received 200 microg/d SLX i.v. on day 0-4. Group D rats (n = 10) served as untreated controls. The animals were sacrificed on days 2 and 5, respectively. Rejection was graded by histology from 0 (no rejection) to 5 (necrosis). By immunhistology, alveolar, interstitial CD11a, CD18 and VLA-4 positive leukocytes were counted. RESULTS: Histologically, there were a lower grade of rejection (A: 2.7 +/- 0.6; B: 4.0 +/- 0.0; P < 0.05) and fewer CD11a positive leukocytes (A: 66 +/- 27; B: 186 +/- 73; P < 0.05) on day 5 in the SLX-treated allograft group compared to the untreated group. In xenotransplantation, SLX also reduced the grade of rejection (C: 3.3 +/- 0.5; D: 4.7 +/- 0.5; P < 0.05) and the number of CD11a positive leukocytes (C: 145 +/- 22; D: 176 +/- 20; P < 0.05) on day 2. CONCLUSIONS: It is concluded, that the administration of SLX significantly reduces allograft rejection. After discontinuation treatment with SLX unmodified rejection appeared. SLX also modifies xenograft rejection, but to a lesser extent, and xenograft necrosis appeared during treatment in this model.

Animals↗

PubMed1997

Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury.

Proper engagement of leukocyte and endothelial cell selectins with their counterreceptors is an initial step in neutrophil trafficking to sites of inflammation. Certain fucosylated carbohydrate determinants such as sialyl Lewis-x are proposed to act as these counterreceptors. We studied the effects of a synthetic sialyl Lewis-x analog, CY-1503, on the course of hemodynamic derangements and acute lung injury during experimental gram-negative sepsis. Anesthetized ventilated swine were made septic with an infusion of live Pseudomonas aeruginosa. A treatment group received an initial bolus of CY-1503 (60 mg/kg) before sepsis, followed by continuous infusion of CY-1503 (15 mg.kg-1.h-1). Treatment with CY-1503 did not prevent the development of pulmonary hypertension, systemic hypotension, decline in cardiac output, or severe neutropenia. However, CY-1503 significantly attenuated lung injury, demonstrated by decreased bronchoalveolar lavage protein content and neutrophil influx, lowered lung myeloperoxidase activity, and improved arterial oxygenation. Neutrophils from septic and CY-1503 animals showed significant activation, reflected by upregulated CD18 expression and priming for oxidant burst compared with control animals. This study suggests blockade of selectin interactions as a potential therapeutic intervention in sepsis-induced lung injury.

Animals↗

PubMed1997

Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation.

BACKGROUND: During rejection and reperfusion injury, infiltration of leukocytes into the lung allograft is regulated by adhesion molecules, especially selectins. Sialyl-Lewis X (SLX), an oligosaccharide, is a membrane ligand molecule of P-selectin adhesion receptors. In this study, we investigated the effect of intravenous administration of a synthetic oligosaccharide analog of SLX on rejection and reperfusion injury after rat lung transplantation. METHODS: Left lateral, orthotopic, allogeneic lung transplantation was performed between fully incompatible rat strains (Dark Agouti-->Lewis) after an average total ischemic time of 45 minutes. Group A (n = 6) served as control; no immunosuppression was used. In group B (n = 6), rats received 200 micrograms/kg/day SLX intravenously on days 0 to 4. The animals were killed on days 5 and 10, respectively. In groups C and D, syngeneic lung transplantation was performed (Lewis-->Lewis), with an ischemic time of 7 hours. Group C (n = 6) served as untreated controls. Group D rats (n = 6) received a single dose of 20 mg/kg SLX at the end of the ischemic time. The animals were killed on days 2 and 5, respectively. RESULTS: In group B rats, treated for rejection, a lower grade of rejection (2.7 +/- 0.6 vs 4.0 +/- 0.0, p < 0.05) and fewer infiltrating CD11a-positive leukocytes (6.6 +/- 2.7 vs 18.6 +/- 7.3, p < 0.05) were found histologically compared with group A. In group D rats, treated for reperfusion injury, a significant reduction of reperfusion injury was detected on chest radiograms and by histologic study. CONCLUSIONS: A synthetic oligosaccharide analog of SLX reduces allograft rejection and reperfusion injury by abrogation of P-selectin-dependent leukocyte-endothelial interaction. According to these findings, treatment with oligosaccharides to reduce reperfusion injury and rejection seems to be a promising strategy for clinical lung transplantation.

Animals↗

PubMed1997

A single copy of apolipoprotein B-48 is present on the human chylomicron remnant.

Individuals homozygous for the e2 allele encoding apolipoprotein E exhibit a remnant removal defect and accumulate substantial levels of intestinally derived particles containing apolipoprotein B-48 (apoB-48). Such lipoproteins were isolated from the plasma of E2/E2 individuals, and further purified by affinity chromatography using a polyclonal antibody specific for selective binding and removal of apoB-100-containing lipoproteins. The unbound lipoproteins, termed chylomicron remnants, were particles with average hydrated diameters of 31.2 nm as determined by dynamic light scattering. They contained apoB-48 and ApoE as their only protein components. The number of apoB-48 molecules on each lipoprotein was assessed by counting the number of antibody molecules bound to the surface of the chylomicron remnants, using either a monoclonal antibody specific for a single epitope on apoB-48 or a mixture of two such monoclonal antibodies specific for widely separated epitopes. The results of this analysis seem unambiguous: no more than one apoB-48 resides on the chylomicron remnant. Because apoB appears to be unable to transfer among lipoprotein particles, it may be inferred that nascent chylomicrons also contain a single copy of apoB-48.

Antibodies, Monoclonal↗

PubMed1997

Secretion from cell culture of HDL and VLDL bearing apoB-33 with a large internal deletion.

Rat hepatoma McA-RH7777 cells synthesize and secrete two populations of apoB-containing lipoproteins: a larger, VLDL-sized population floating in the Sf 40-150 range and a smaller, LDL and HDL-sized population. Three permanently transfected cell lines of McA-RH7777 cells secreted (in addition to the endogenous lipoproteins) lipoproteins containing 1) a carboxyl-terminally truncated human apoB-53 (2377 amino acids in length); 2) a carboxyl-terminally truncated human apoB-31 (1420 amino acids in length); or 3) an internally deleted human apoB protein, apoB-18/95, containing a total of 1490 amino acid residues, equivalent in length to an apoB33. The apoB-18/95 protein contained amino acid residues 1-782 joined to 708 residues near the C-terminus of apoB (residues 36364343). All three of the apoB peptides, apoB53, apoB-31, and apoB-18/95, were present on smaller LDL-HDL-class lipoproteins, with buoyant densities in the HDL density range. The sizes of the HDL class lipoproteins agreed with prior observations that lipoprotein core circumference is directly proportional to apoB size. As HDL containing apoB-18/95 conformed to this rule, contiguous apoB amino acid sequence is not required for the rule to be obeyed. In addition, apoB-18/95, but not apoB-31, was also present on the VLDL-sized lipoproteins even in the absence of serum or oleate supplementation. As the latter two constructs encode equally sized apoB peptides, their particular amino acid sequences rather than just overall length must determine whether they can assemble into a VLDL particle.

Animals↗

PubMed1996

Human hepatic lipase subunit structure determination.

Chinese hamster ovary cells were stably transfected with a human hepatic lipase (HL) cDNA. The recombinant enzyme was purified from culture medium in milligram quantities and shown to have a molecular weight, specific activity, and heparin affinity equivalent to HL present in human post-heparin plasma. The techniques of intensity light scattering, sedimentation equilibrium, and radiation inactivation were employed to assess the subunit structure of HL. For intensity light scattering, purified enzyme was subjected to size exclusion chromatography coupled to three detectors in series: an ultraviolet absorbance monitor, a differential refractometer, and a light scattering photometer. The polypeptide molecular weight (without carbohydrate contributions) was calculated using the measurements from the three detectors combined with the extinction coefficient of human HL. A single protein peak containing HL activity was identified and calculated to have a molecular mass of 107,000 in excellent agreement with the expected value for a dimer of HL (106.8 kDa). In addition, sedimentation equilibrium studies revealed that HL had a molecular mass (with carbohydrate contributions) of 121 kDa. Finally, to determine the smallest structural unit required for lipolytic activity, HL was subjected to radiation inactivation. Purified HL was exposed to various doses of high energy electrons at -135 degrees C; lipase activity decreased as a single exponential function of the radiation dose to less than 0.01% remaining activity. The target size of functional HL was calculated to be 109 kDa, whereas the size of the structural unit was determined to be 63 kDa. These data indicate that two HL monomer subunits are required for lipolytic activity, consistent with an HL homodimer. A model for active dimeric hepatic lipase is presented with implications for physiological function.

Animals↗

PubMed1996

P-selectin and TNF inhibition reduce venous thrombosis inflammation.

Venous thrombosis induces a detrimental inflammatory response in the vein wall. The cytokine tumor necrosis factor-alpha (TNF) and the adhesion molecules, selectins, have been found to be important in mediating inflammatory cell stimulation and leukocyte-endothelial cell adhesion, respectively. This study assesses the role of TNF and P-selectin in the inflammatory events associated with venous thrombosis. Rats were passively immunized with neutralizing anti-TNF serum alone, anti-TNF plus anti-P-selectin antibody, anti-P-selectin antibody alone, control serum, or control anti-P-selectin antibody. Antibodies or control sera were given prior to occlusion and at Days 2 and 4 postocclusion. Rats were sacrificed at Days 1-6 and Day 13 after occlusion for inferior vena caval (IVC) wall histopathology and TNF analysis. Differences in the extent of inflammatory cell infiltrate into the vein wall were found on Days 2, 6, and 13. TNF levels were elevated in the vein wall of the three groups not given anti-TNF antibody. The levels of TNF at Day 6 positively correlated with both total inflammatory cell (r = 0.53, P < 0.05) and neutrophil presence (r = 0.72, P < 0.01). The lowest IVC wall neutrophil and total inflammatory cell count at Days 2 and 6 and the lowest neutrophil count at Day 13 were found in the anti-TNF plus anti-P-selectin antibody group. Monocyte influx was also inhibited at Day 13 in this group. These results suggest a role for combined neutralization of TNF and P-selectin in the attenuation of inflammation induced by venous thrombosis.

Animals↗

PubMed1996

"Mirror, mirror on the wall, who...?": towards a model of visual self-recognition.

Self-recognition and self-awareness are processes fundamental to human development. This report describes the case of an 80-year-old woman who demonstrated the ''mirror sign'', an inability to recognise the reflection of oneself in a mirror. An attempt has been made to provide a cognitive neuropsychological explanation for this profound impairment in visual self-recognition, incorporating current cognitive theories of delusion formation and, specifically, delusions involving distorted appreciation of the self or others. We speculate that the impairment in visual self-recognition arises from deficits in visual and personal semantic memory related to bilateral hippocampal lesions, and that the greater extent of impairment in visual self-recognition compared with that for other familiar persons is possible evidence for a specific self-recognition process, represented as a separate ''self-identity node'' in the current face-processing model of Bruce and Young (1986).

Journal Article↗

PubMed1996

Stroop interference and facilitation in the cerebral hemispheres in schizophrenia.

A divided visual field presentation of the Stroop colour-word test was used to study interhemispheric (transcallosal) function in schizophrenic and normal subjects. The modified test used a colour strip paired with either an incongruent, neutral or congruent colour word. Interference and facilitation were defined as the difference between the mean reaction times for incongruent stimuli and neutral stimuli and that between neutral stimuli and congruent stimuli, respectively. The stimuli were presented tachistoscopically with the two components either separated across the midline centrally, up or down from the midpoint (bilateral presentation), or presented to a single visual half-field (unilateral presentation). The inclusion of the 'up' and 'down' bilateral conditions controlled for the reaction time advantage for central compared with unilateral stimulus presentations noted in an earlier study (David, 1993a). The difference in reaction time to an incongruent compared with a congruent colour-word pairing, the Combined Stroop Effect (CSE), was not affected significantly by stimulus presentation position (bilateral vs. unilateral) in either the control or schizophrenic group, unlike in the earlier study of David. For controls, interference was significantly greater than facilitation for both bilaterally- and unilaterally-presented stimuli. Schizophrenics had a significantly smaller interference effect for bilaterally-presented stimuli, indicating reduced interhemispheric interference in this group. For the control group, there was no significant difference between right and left CSEs, interference being significantly greater than facilitation on both visual half-field presentations. For schizophrenics, the CSE for left-presented stimuli was significantly greater than that for right-presented stimuli. In addition, left-field facilitation was significantly greater than right-field. Reduced Stroop facilitation with right-field presentations in schizophrenic subjects may reflect increased vulnerability of colour-naming by word-reading in the left hemisphere-evidence for the non-unitary nature of attentional processes and disintegration of these in schizophrenia.

Adult↗

PubMed1996

E-selectin in focal cerebral ischemia and reperfusion in the rat.

The selectin family of glycoproteins facilitates the early phase of polymorphonuclear leukocyte adhesion to the endothelial cell and, thus, may promote ischemic cell damage. To evaluate E-selectin in the pathogenesis of focal cerebral ischemia and reperfusion injury, we cloned rat E-selectin cDNA and measured the temporal profiles E-selectin mRNA (Northern blot) and protein (immunohistochemistry) during (1 h of ischemia) and after (up to 1 week) transient (2 h) middle cerebral artery (MCA) occlusion in the male Wistar rat. We also tested the effect on these rats of administration of CY-1503, an analog of sialyl Lewis(x) (SLe(x)), on ischemia cell damage. mRNA for E-selectin was first detected in the ischemic hemisphere at 2 h of reperfusion and persisted to 46 h of reperfusion. E-selectin (protein) was localized to microvessels within the ischemic lesion at 0 h of reperfusion and persisted to 70 h of reperfusion. Treatment of the ischemic animals with CY-1503 (50 mg/kg) (n = 8) significantly reduced infarct volume by 42% (p < 0.05) and significantly reduced myeloperoxidase immunoreactive cells in the ischemic lesion by 60% (p < 0.05). These findings provide the first direct evidence for the involvement of E-selectin in transient MCA occlusion in rats and suggest that the E-selectin may facilitate neutrophil adhesion and subsequent cerebral ischemic cell damage.

Amino Acid Sequence↗

PubMed1996

Role of sialyl Lewis(x) in total hepatic ischemia and reperfusion.

BACKGROUND: Neutrophil adhesion and migration is associated with hepatic ischemia and reperfusion. The role of a Sialyl Lewis(x) (SLe)(x) oligosaccharide, a ligand for selections, was studied in hepatic ischemia and reperfusion injury. STUDY DESIGN: Total hepatic ischemia was produced in rats for 90 minutes using an extracorporeal portosystemic shunt. To assess the role of SLe(x) in hepatic ischemia and reperfusion injury, 25 mg/kg of an SLe(x) analog, CY-1503, was given five minutes before reperfusion or at reperfusion. Biochemical tests of hepatic injury, myeloperoxidase activity in hepatic tissue, and histologic studies, including neutrophil infiltration determined by the naphthol esterase technique, were analyzed six hours after reperfusion. RESULTS: Significantly improved protection in biochemical hepatic injury tests (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) was noted between the ischemic and the SLe(x) treated groups. Myeloperoxidase activity and polymorphonuclear cell infiltration in hepatic tissue were decreased in the SLe(x) groups. Histologic protection from hepatic damage was observed in the treated groups. CONCLUSIONS: The SLe(x) oligosaccharide analog, CY-1503, had an important protective role in hepatic ischemia and reperfusion injury. Modulation of SLe(x) in the neutrophil decreased the adhesion of polymorphonuclear cells and their subsequent migration after hepatic ischemia and reperfusion.

Animals↗

PubMed1995

Sialyl Lewis(x) oligosaccharide reduces ischemia-reperfusion injury in the rabbit ear.

Ischemia-reperfusion injury in the rabbit ear is neutrophil (PMN)-mediated, and is significantly reduced by anti-adhesion agents directed against beta 2 integrins, P-selectin, or L-selectin. We further examined selectin-mediated adherence in this setting following the administration of soluble sialyl Lewis(x) (SLe(x)), the principal carbohydrate ligand for P-, L-, and E-selectin, at various times following reperfusion. Under constant ambient temperature conditions, the rabbit ear vascular supply was isolated and occluded with an atraumatic vascular clamp for 6 h, then allowed to reperfuse. Animals receiving i.v. SLe(x) (25 mg/kg bolus + 50 mg/kg infusion over 10 h) 1) at the time of reperfusion, 2) 1 h after reperfusion, 3) 4 h after reperfusion, or 4) 12 h after reperfusion were compared with control animals receiving either saline or sialyl lactosamine, an oligosaccharide structurally similar to SLe(x) but not involved in selectin recognition. Tissue injury was assessed by serial measurement of ear edema and by visual determination of ear necrosis over 7 days. Tissue edema and necrosis were significantly reduced in animals treated with SLe(x) immediately upon reperfusion or after a 1-h delay, but not in animals for whom SLe(x) administration was delayed by 4 or 12 h. Furthermore, SLe(x) administration alone had no effect on circulating leukocyte or PMN counts, or PMN expression of CD18 or L-selectin. We conclude that interruption of selectin-mediated adherence with soluble SLe(x) oligosaccharide attenuates reperfusion in the rabbit ear. The observation that SLe(x) is efficacious only if administered in the first hour after reperfusion suggests that the more immediately available P- and L-selectin participate in this PMN adhesion/injury process, whereas E-selectin, with its delayed endothelial expression, does not.

Amino Sugars↗