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Biomedical subjects

S K Lo

Publications and source records attributed to S K Lo.

At least 127 records · Page 7Linked to original sources
PubMed1992

Prevalence of anti-neutrophil antibody in primary sclerosing cholangitis and ulcerative colitis using an alkaline phosphatase technique.

The detection of a nuclear anti-neutrophil antibody in patients with primary sclerosing cholangitis (PSC), using an immunoperoxidase technique, was recently reported by us. Subsequently, detection of a cytoplasmic anti-neutrophil antibody was reported by others, using a two stage procedure of enzyme linked immunosorbent assay followed by an immunofluorescent method. Detection of cytoplasmic anti-neutrophil antibody in PSC, which, in contrast to that two stage procedure, uses a simple one step immuno-alkaline phosphatase method is now reported. Normal human neutrophils were cytocentrifuged, ethanol fixed, and then incubated with coded patients' sera. Rabbit anti-human immunoglobulin conjugated with alkaline phosphatase was used to detect the bound antibody. Fast red was used to visualise the reaction. Twenty three of 30 (77%) PSC patients showed positive granular cytoplasmic staining (with some perinuclear accentuation) with a network of cytoplasmic filaments. Fifteen of 45 (33%) ulcerative colitis patients and 1 of 3 chronic active hepatitis patients showed similar staining. Thirty five of 152 patients with ulcerative colitis, chronic active hepatitis, and a variety of other liver diseases showed a different pattern of cytoplasmic labelling, with no surrounding filaments. Seventy nine patients, including seven PSC patients and 33 normal subjects, were negative. In comparison, 86% of PSC patients, 57% of patients with primary biliary cirrhosis, 50% of normal subjects, and well over 60% of patients with ulcerative colitis, Crohn's disease, alcoholic liver disease, and chronic active hepatitis were positive using the one step immunofluorescent method. This method is more specific for PSC than those described in recent reports and may be of diagnostic importance.

Adult↗
PubMed1992

Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms.

(TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers-albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO). The activation of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha prestimulation was required for these responses since activation of PMN with PMA in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01) and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha-induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap, Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha prestimulation of lungs mediates PMN uptake and that this requires the expression of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN sequestered by ICAM-1-dependent mechanism contributes to the development of pulmonary vascular injury and edema.

Animals↗
PubMed1992

Young people, alcohol, and driving in two Australian states.

Road traffic accidents are the single largest cause of death in Australia among people aged 15-24. The proposition that a broadly based deterrence measure, such as random breath testing (RBT), would be sufficient to change the behavior of young drivers was tested in a comparison of young drivers in New South Wales (NSW), which has had RBT for 6 years, with young drivers in Western Australia (WA), where there was no RBT. The results demonstrated that NSW young drivers were less likely to drink and drive and more likely to believe their peers would disapprove of drink-driving than were their counterparts in WA. It was concluded that RBT had altered the drink-driving behavior and possibly the beliefs about drink-driving of young people in NSW.

Accidents, Traffic↗
PubMed1992

Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.

The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined.

Carbohydrate Metabolism↗
PubMed1991

Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study.

OBJECTIVE: To evaluate the efficacy and safety of a pH-sensitive, polymer-coated oral preparation of mesalamine in patients with mildly to moderately active ulcerative colitis. DESIGN: A multicenter, double-blind, placebo-controlled randomized trial. SETTING: Five university-based medical centers, one inflammatory bowel disease center, and three private practice sites. PATIENTS: A total of 158 patients with newly or previously diagnosed active ulcerative colitis. INTERVENTION: A pH-sensitive, polymer-coated oral preparation of mesalamine (5-aminosalicylic acid) was used at 1.6 and 2.4 g/d for 6 weeks. MEASUREMENTS: Efficacy was measured by scores for stool frequency, rectal bleeding, patient's functional assessment, sigmoidoscopic findings, and physician's global assessment. Stringent criteria for disease activity were established prospectively. RESULTS: The analysis of protocol-compliant patients showed a significant improvement at 3 weeks in patients taking 2.4 g/d of mesalamine compared with patients taking placebo (32% versus 9%; P = 0.003). At 6 weeks, both the 1.6 g/d (43%) and 2.4 g/d (49%) doses were significantly superior to placebo (23%) (P = 0.03 and P = 0.003, respectively). In addition, more patients worsened in the placebo group compared with the 2.4 g/d group (50% versus 19%; P = 0.003); however, there was no statistically significant difference in worsening between the 1.6 g/d mesalamine group and the placebo group. The oral mesalamine tablet was well tolerated, and no clinically significant changes were observed in hematologic, hepatic, or renal laboratory profiles. CONCLUSION: Colon-targeted oral mesalamine at 2.4 g/d is effective therapy for mildly to moderately active ulcerative colitis. It is well tolerated and should provide a viable therapeutic alternative to sulfasalazine.

Administration, Oral↗
PubMed1991

Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils.

Two classes of adhesion molecules have well-defined roles in the attachment of unstimulated polymorphonuclear leukocytes (PMN) to cytokine-treated endothelial cells. Endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial cells interacts with specific carbohydrate residues on the PMN, and the leukocyte integrins (CD18 antigens) on PMN interact with intracellular adhesion molecule 1 and other structures on endothelium. Here we show that these two classes of molecules can act sequentially in an "adhesion cascade". Interaction of PMN with ELAM-1-bearing endothelial cells causes PMN to express enhanced adhesive activity of the integrin CR3 (CD11b/CD18). Expression of ELAM-1 on the cytokine-treated endothelium appears both necessary and sufficient for the stimulation of CR3 activity since blockade of ELAM-1 with mAbs prevents the activation of CR3 by cytokine-treated endothelium, and immobilized recombinant ELAM-1 activates CR3. The ability to activate CR3 is shared by chemattractants, suggesting that ELAM-1 may serve as a "tethered chemattractant." This hypothesis is strengthened by the observation that recombinant soluble ELAM-1 directs movement of PMN in chemotaxis chambers. These results suggest a mechanism by which multiple adhesive molecules may function together in diapedesis. ELAM-1 serves both as an adhesin and as a trigger that recruits the participation of additional adhesion molecules. Our results also suggest that ligands for adhesion molecules may also be "receptors" capable of generating intracellular signals.

Antibodies, Monoclonal↗
PubMed1991

Age and injecting drug use in Perth, Western Australia: the Australian national AIDS and injecting drug use study.

Young injecting drug users (IDUs) in Australia are a group about whom little is known. It is suggested, however, that their drug using behaviours and life styles put them at particular risk for HIV/AIDS. Data collected in Perth from 195 respondents in the Australian National AIDS and Injecting Drug Use Study was analyzed with emphasis on the distinctions between young and older injecting drug users. It was found that, relative to those aged 23 or over, IDUs under 23 used more stimulants and LSD and fewer opiates and benzodiazepines; were more likely to inject all or most of their drugs; were less likely to have been in treatment; had more sex partners; were less likely to have changed their drug taking behaviour because of AIDS; were less likely to use alone; shared needles less frequently but shared at least some of the time; and had less knowledge of AIDS and were more pessimistic about the long term outcomes of AIDS. Such characteristics need to be taken into account if effective intervention and prevention strategies for this group are planned.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils.

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.

Antibodies, Monoclonal↗
PubMed1990

Distinct populations of rotaviruses circulating among neonates and older infants.

We obtained three stool specimens from each of 371 neonates. Two specimens were obtained between days 1 and 3 after birth, while they were in the hospital, and one specimen was obtained between days 6 and 14 after birth, after they had been discharged from the hospital. Seventy neonates excreted human rotavirus (HRV) while they were in the hospital, and the incidence rate for the cohort was 0.094 episodes per infant day. The incidence rate of community-acquired neonatal infections was markedly reduced to 0.022 episodes per infant day, with eight additional episodes of infection being detected after the infants were discharged from the hospital. Nevertheless, this was higher than the incidence of community-acquired HRV infection of 0.0037 episodes per infant day previously estimated by serology for the same cohort during the subsequent 2 years of infancy. None of the 78 episodes of neonatal HRV infection was accompanied by diarrhea. There were at least 44 distinct electropherotypes of HRV circulating among older infants in the community during the study period, and they comprised at least four different serotypes. Despite the genetic and antigenic diversity of the prevalent HRV isolates, only five electropherotypes with either serotype 2 or 4 specificity were isolated from the neonates, while serotype 1 and 3 viruses were not detected. Two of these electropherotypes, including one which was isolated from 57 of the 78 infants with episodes of infection, were isolated exclusively from the neonates. The other three electropherotypes were also isolated from the older infants; one was a major electropherotype and two were minor electropherotypes which were prevalent among the older infants. These results suggest that distinct populations of HRV cocirculate among neonates and older infants.

Age Factors↗
PubMed1990

Leukocyte repletion reverses protective effect of neutropenia in thrombin-induced increase in lung vascular permeability.

We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.

Agranulocytosis↗
PubMed1989

Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding to different ligands.

Upon stimulation with C5a, TNF, or phorbol dibutyrate (PDB), polymorphonuclear leukocytes (PMN) exhibit first an increase then a decrease in adhesion to unstimulated endothelial cells (EC). Essentially all of this adhesion is mediated by the CD18 family of leukocyte integrins on PMN. To determine the individual roles of CD11a/CD18 (LFA-1), CD11b/CD18 (CR3, Mac-1) and CD11c/CD18 (p150,95) in adhesion of PDB-stimulated PMN to unstimulated EC, mAb against the CD11 chains were used. mAb against CD11a or CD11b each blocked adhesion of PMN to EC by approximately 50%, but mAb against CD11c had no effect. Inasmuch as a combination of anti-CD11a and CD11b mAb completely blocked adhesion, it appears that CD11a/CD18 and CD11b/CD18 make approximately equal contributions to binding, and CD11c does not participate. Anti-CD11a or CD11b each blocked adhesion by about 50% throughout the transient time course of PDB-stimulated adhesion, indicating that the capacity of each of these receptors to bind EC is transiently activated by PDB. We next examined the role of ICAM-1 on EC as a ligand for CD18. Two anti-ICAM-1 mAb (LB-2 and 84H10) each inhibited PMN adhesion in a dose-dependent fashion, reaching a maximal inhibition of approximately 50%. Anti-ICAM-1 mAb blocked the CD11a/CD18-dependent portion of adhesion because concomitant use of anti-CD11a and anti-ICAM-1 did not cause additive inhibition. In contrast, anti-CD11b plus anti-ICAM-1 resulted in complete blockade of adhesion. This result suggests that CD11a/CD18 recognizes ICAM-1 on EC, but CD11b/CD18 recognizes a different ligand(s). To determine if CD11b CD18 has the ability to recognize ICAM-1, human macrophages were plated on culture surfaces coated with purified ICAM-1. Interaction of CD11a/CD18 with the surface-bound ICAM-1 resulted in selective down-modulation of CD11a/CD18 from the apical portion of the macrophages. In contrast, ICAM-1-coated surfaces did not down-modulate CD11b/CD18. The data suggest that CD11b/CD18 does not recognize ICAM-1, and that this receptor functions in adhesion of PMN to EC by recognizing novel ligand(s) on EC.

Antibodies, Monoclonal↗
PubMed1989

Transient adhesion of neutrophils to endothelium.

Fluorescently labeled polymorphonuclear leukocytes (PMN) were used to measure adhesion to human umbilical vein endothelial cells (EC) cultured in vitro. Stimulation of PMN with phorbol dibutyrate (PDB), TNF, or C5a caused an increase in adhesion followed by a return to prestimulation levels of adhesion of longer times of incubation. Maximal adhesion of PMN to EC occurred rapidly in response to C5a (5 min) and more slowly with TNF or PDB (15 min). PMN stimulated to adhere with C5a detached from EC by 15 min. PMN from CD11/CD18-deficient patients and PMN incubated with anti-CD18 mAbs failed to bind to EC despite maximal stimulation. Anti-CD11a/CD18 and anti-CD11b/CD18 each partially inhibited adhesion, and a combination of these two reagents completely blocked adhesion. The adhesion we measured was therefore completely dependent on CD11/CD18, and CD11a/CD18 and CD11b/CD18 each contributed to adhesion. Stimuli that enhanced adhesion of PMN to EC also enhanced expression of CD11b/CD18 on the cell surface, but the time course of expression correlated poorly with changes in adhesivity. To determine if changes in the expression of CD11b/CD18 are necessary for the changes in adhesivity, we used enucleate cytoplasts that did not increase expression of CD11b/CD18. Cytoplasts showed a normal rise and fall in adhesivity in response to PDB. We conclude that the transient adhesion of stimulated PMN to naive EC is regulated by changes in the nature of existing CD11/CD18 molecules on the PMN surface. Changes in expression of CD11b/CD18 may contribute to enhancement of adhesivity, but a definite role for this phenomenon has yet to be established.

Antibodies, Monoclonal↗
PubMed1989

Direct identification of serotypes of natural human rotavirus isolates by hybridization using cDNA probes derived from segment 9 of the rotavirus genome.

Under stringent hybridization conditions, cDNA of segment 9 of the rotavirus genome, which codes for the viral protein VP7, permitted differentiation of serotypes of culture-grown rotaviruses and natural isolates of human rotaviruses directly from clinical specimens. This was evident for the following reasons. (i) The cDNA of one serotype selectively hybridized with the RNA of the same serotype of culture-grown rotaviruses. (ii) Natural isolates of the virus thus identified as serotype 2 were also those which gave the short electrophoretic pattern characteristic of the genome of serotype 2, subgroup 1 viruses. Isolates having the long electrophoretic pattern characteristic of the genome of subgroup 2 viruses were identified as serotype 1, 3, or 4 by this method. (iii) For patients who had previously undergone serological analysis, the serotypes being excreted were the same serotypes against which there was the most marked serum neutralizing antibody response. Although the virus population was genetically diverse, the preponderance of the population prevalent in Guangzhou and Foshan in each of the three successive years between 1982 and 1985 comprised a single serotype. The dominant serotype changed from one year to another, but there was minimal cocirculation of different serotypes in this community. All virus isolates belonged to serotype 1,2,3, or 4, and there was no evidence to suggest that the other human rotavirus serotypes were prevalent in this community.

Antigens, Viral↗
PubMed1989

Prospective study of community-acquired rotavirus infection.

We determined titers of group A rotavirus common antibodies and neutralizing antibodies against serotypes 1 to 4 of prototype human rotavirus (HRV) in cord blood and serum specimens obtained from 38 infants at 4-month intervals from birth until 2 years of age. Nineteen of the infants developed one episode of HRV diarrhea each, and they were matched by age and birth weight with the other 19 infants, who did not develop HRV diarrhea during the follow-up period. We estimated the incidence rate of HRV infection for the two groups of infants combined to be a minimum of 1.34 episodes per infant per year, which is 22 times more common than the occurrence of overt disease caused by the virus in this community. The infection occurred constantly throughout the first 2 years of infancy, whereas all but one of the 19 episodes of overt disease occurred before 12 months of age. Seven of these overt episodes were preceded by at least one episode of subclinical infection earlier, and the other seven were probably due to primary HRV infection. The remaining five episodes occurred before 4 months of age, so that we could not ascertain whether they were due to primary infections because of the presence of maternal antibodies. We showed that levels of HRV antibodies in serum specimens obtained before clinical onset of diarrhea varied widely, and, for most infants in the diarrheal group, levels of these antibodies were similar to those in the serum specimens obtained at the same times from the corresponding age- and birth weight-matched control infants. Nevertheless, the age at which overt disease caused by HRV was most prevalent coincided with the time when the maternal antibodies had declined to low levels but the infants had not yet acquired high titers of these antibodies in their sera.

Antibodies, Viral↗
PubMed1989

Increased transvascular protein transport in lungs induced by nonthrombogenic gamma-thrombin.

Infusion of 1.2 nmol/kg body wt of alpha-thrombin (2.6 clotting U/micrograms) or 12 nmol/kg of gamma-thrombin (less than 0.005 U/microgram) into the pulmonary artery of halothane-anesthetized sheep produced two-to threefold increases in mean pulmonary arterial pressure (Ppa), mean pulmonary arterial wedge pressure (Ppw), and pulmonary vascular resistance (PVR). Pulmonary lymph flow (Qlym) also increased two- to threefold without significant changes in the lymph-to-plasma protein concentration ratio (L/P). Leukocyte counts decreased 75% in both groups and rebounded in the gamma-thrombin group but remained depressed in the alpha-thrombin group. Platelet counts decreased 30 and 85% in alpha- and gamma-thrombin groups, respectively, and remained low at 4 h postinfusion in both groups. Plasma fibrinogen concentrations decreased similarly within 15 min after thrombin infusion in both groups, and concentrations of fibrin(ogen) degradation products (FDP) increased similarly. Fibrin was present in pulmonary vessels after alpha-thrombin challenge but not after gamma-thrombin challenge. In contrast, infusion of 1.2 nmol/kg of gamma-thrombin (matching the alpha-thrombin dosage) produced no significant increases in Ppa, Ppw, PVR, Qlym or in the leukocyte and platelet counts. These data demonstrate that high concentrations of the nonthrombogenic gamma-thrombin increase lung transvascular protein transport independent of intravascular clotting in the lung.

Animals↗
PubMed1989

Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium.

Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.

Animals↗
PubMed1988

Protection against absolute-ethanol-induced gastric antral and corpus mucosal injury. A gross and histologic study.

The purpose of this study was to systematically assess 100% ethanol-induced gross and histologic injury of the antral and the corpus mucosa of the rat stomach and the effect of two protective agents, a prostaglandin analog and meciadanol (a flavenoid) on this injury. The gross antral injury was much more subtle than the corpus injury. Therefore, different scoring criteria were developed for the antrum. Surprisingly, however, the extent and severity of histologic injury was similar in both areas. Pretreatment with either meciadanol or 16,16-dimethyl prostaglandin E2 significantly protected against this injury in the antrum as well as in the corpus.

Animals↗