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S K Lo

Publications and source records attributed to S K Lo.

At least 145 records · Page 8Linked to original sources
PubMed1988

Occurrence of rotaviruses in Guangzhou and Hong Kong.

Electropherotypes of human rotavirus (HRV) isolated from Hong Kong and Guangzhou were compared to study the transmission of HRV between the cities. Forty-one electropherotypes were identified from 418 hospitalized patients with HRV infection at the Queen Mary Hospital, and 22 were detected from 66 outpatients in community clinics at a separate area in Hong Kong. Nineteen electropherotypes were detected in 370 hospitalized cases of HRV infection from seven hospitals in Guangzhou. Results showed that HRV electropherotypes appeared to circulate freely within each area, yet the HRV population between the two cities remained different. Six electropherotypes were common to both cities. Three of these were predominant types found in Guangzhou and later detected in Hong Kong. One of these was found to cause an outbreak in Hong Kong. Of the remaining three electropherotypes, two were detected in both cities simultaneously, whereas one was first detected in Hong Kong.

Child, Preschool↗
PubMed1988

Role of platelets in maintenance of pulmonary vascular permeability to protein.

We examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Qlym). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (Pla). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. Platelet count decreased from 460,000 +/- 77,000 to 16,000 +/- 4,000 platelets/microliters, without significant changes in the leukocyte count and hematocrit. Studies were made in three groups: 1) control sheep having a normal platelet count; 2) thrombocytopenic sheep; and 3) PRP-infused thrombocytopenic sheep. Elevation in Pla in control sheep increased pulmonary transvascular protein clearance (CL) to 12.1 +/- 2.1 ml/h, whereas the same Pla elevation in thrombocytopenia increased CL to 24.1 +/- 4.0 ml/h, indicating an increase in pulmonary vascular permeability to protein in thrombocytopenic animals. Infusion of PRP restored normal permeability, since it prevented the increase in CL. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelial permeability of 125I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 X 10(7) or 5 X 10(7) platelets were added onto endothelial monolayers. However, addition of 5 X 10(6) platelets or 5 X 10(7) red blood cells did not reduce endothelial monolayer albumin permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Fibrin is a determinant of neutrophil sequestration in the lung.

We investigated the role of fibrin in the sequestration of neutrophils in lungs challenged with microembolism. Lungs of chronically prepared awake sheep were imaged after infusion of 111In-neutrophils and 131I-fibrinogen. Thrombin (80 units/kg) was administered to induce fibrin sequestration in the lung. One group received tranexamic acid (4 mg/kg i.v.) to inhibit fibrinolysis, and the control group received a saline infusion. Thrombin infusion increased both 131I-fibrinogen and 111In-neutrophils in the lung, but the increases were greater and more prolonged in the fibrinolysis-inhibited group. We examined the adherence of isolated neutrophils to fibrin matrix to investigate how neutrophil-fibrin interactions could mediate neutrophil sequestration. Unstimulated neutrophils showed a 37.5 +/- 3.1% adherence to fibrin in contrast to a 3.9 +/- 0.4% neutrophil adherence to endothelium and a 6.5 +/- 0.5% adherence to agarose. Neutrophil adherence to fibrin increased to 81.7 +/- 6.2% with activation by phorbol myristate acetate (10(-8) M) and was inhibited by a monoclonal antibody directed against the beta-chain of the CD18 leukocyte adhesion glycoprotein. The findings indicate that retention of pulmonary fibrin microthrombi is associated with increased lung uptake of neutrophils. Fibrin serves as a substrate for neutrophil adherence, and this adherence is mediated by expression of the CD18 glycoprotein complex on neutrophils. Fibrin sequestration in the lung may contribute to lung vascular injury by inducing pulmonary neutrophil uptake.

Animals↗
PubMed1988

Thrombin-induced generation of neutrophil activating factors in blood.

The authors examined the in vitro effects of serum generated by the action of alpha-thrombin on citrated whole blood or plasma. Serum samples were assessed for their ability to induce neutrophil aggregation, neutrophil adherence to cultured endothelial cell monolayer, and superoxide anion generation. The results indicated that both blood- and plasma-derived sera induced similar increases in neutrophil aggregation. Both sera also induced neutrophil adherence to cultured bovine pulmonary artery endothelial monolayer. The adherence increased in a time-dependent manner, producing little change after 5 minutes, and reached maximal response at 60 minutes. Full potency of the neutrophil adherence was evident with serum samples obtained after clotting time of 20 minutes but not at 5 minutes clotting time. The adherence-inducing activity of serum was gradually lost after storage at -20 C and was abolished by 100 C treatment for 2 minutes. In contrast, heating serum to 56 C for 30 minutes did not alter the adherence-inducing activity. Both ether and aqueous fractions obtained after ether extraction of serum possessed adherence-promoting activities, indicating that multiple factors (both lipid and water soluble) were involved. Pretreatment of the endothelium with serum resulted in increased endothelial adhesiveness, but the serum pretreatment failed to induce adhesiveness to subendothelial matrix, indicating that endothelial cells play an active role in acquiring the adhesive property. Serum obtained from thrombin-generated whole blood also resulted in a modest degree of neutrophil superoxide anion generation, but this did not occur with plasma-derived serum. The results indicate that serum factors obtained by clotting blood with thrombin induce neutrophil aggregation and neutrophil adherence to the endothelium as well as superoxide production. These factors appear to be generated in the plasma phase, because the responses were similar in blood- and plasma-derived serum.

Animals↗
PubMed1987

A comprehensive search for segregation distortion in HLA.

Segregation distortion, the non-Mendelian segregation of gametes, has been well documented among diverse groups of organisms. These cases are characterized by extreme segregation ratios found only in males. Previous reports have suggested the existence of segregation distortion operating in the HLA system of humans, a tightly linked complex of genes which regulates the immune system. In mice, some alleles of the T/t complex, which is linked to H-2 (the HLA homologue of mice), cause extreme segregation distortion in wild mice populations. Here we report on the examination of a large body of pedigree data on non-diseased families, scored for the alleles of five HLA region loci. We searched for segregation distortion on the basis of five different models of inheritance: allelic, haplotypic, genotypic, diffuse occurrence in families, and autosomal effects on the sex ratio. There was no clear evidence for segregation distortion. In particular, the possibility of extreme levels of segregation distortion was firmly rejected in the populations examined, thus reducing the likelihood of common distortion-causing HLA associated haplotypes in our species.

Alleles↗
PubMed1987

CVF-induced decomplementation: effect on lung transvascular protein flux after thrombin.

We examined the effects of cobra venom factor (CVF) on the changes in pulmonary hemodynamics and transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in unanesthetized sheep prepared with lung lymph fistulas. The animals received tranexamic acid (100 mg) to suppress fibrinolysis and were then challenged with an intravenous infusion of alpha-thrombin (80 U/kg). Control-thrombin challenged sheep were compared with the CVF-treated sheep challenged with the same thrombin dosage. CVF treatment (187 U X kg-1 X day-1 for 4 days) decreased the total hemolytic complement activity by 45% of control. Thrombin infusion in control sheep increased the mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and lymph protein clearance (pulmonary lymph flow X lymph-to-plasma protein concentration ratio, Clym). Thrombin infusion in CVF-treated sheep produced smaller increments in Ppa, PVR, and Clym. Pulmonary lymph obtained from control-thrombin and CVF-thrombin sheep induced migration of granulocytes obtained from normal unchallenged sheep. The granulocytes obtained from CVF-treated sheep responded relatively less to the migratory and O-2-generating stimuli (i.e., zymosan-treated serum, pulmonary lymph from sheep after thrombin challenge, and plasma from sheep after CVF treatment) compared with normal granulocytes. The attenuation of the thrombin-induced increases in Ppa, PVR, and lung transvascular fluid and protein exchange by CVF treatment may be the result of impaired function of granulocytes.

Animals↗
PubMed1986

Thrombin-induced alterations in endothelial permeability.

Figure 15 summarizes the current understanding of mechanisms of endothelial permeability alterations induced with thrombin. If thrombin generation exceeds the antiprotease activity, thrombin results in clotting of fibrinogen and intravascular fibrin accumulation. Pulmonary neutrophil sequestration also occurs after fibrin deposition, and this is related to the degree and duration of fibrin sequestration. Neutrophil activation appears to be an essential requirement for the mediation of the pulmonary vascular injury. Thrombin-induced intravascular coagulation results in the generation of lipid mediators (LTB4 and HETEs), which may be involved in increasing endothelial permeability. The release of thrombin in higher concentrations during lysis of fibrin (sequence; see text) FIGURE 15. Hypothesis showing mechanisms of thrombin-induced increase in endothelial permeability to proteins. Thrombin may have direct effects on endothelial permeability, or thrombin induced fibrinogen clotting, activation of neutrophils, and the release of lipid metabolites that subsequently lead to an increase in endothelial permeability. clots may induce a direct formation of interendothelial "gaps." Therefore, the vascular injury induced by neutrophil activation and the formation of endothelial "gaps" induced directly by thrombin can both increase the endothelial permeability to proteins. Thrombin is an important mediator of increased endothelial permeability to macromolecules, and may participate in the inflammatory response. In this regard, thrombin may be similar to other mediators (such as histamine and serotonin) that have been previously documented to increase macromolecule transport across the endothelium. The implications of free thrombin in increasing endothelial permeability may be greater because thrombin not only has a direct effect on endothelial permeability, but also induces clotting of fibrinogen and the subsequent generation of mediators that activate neutrophils and that in turn can induce endothelial injury.

Actin Cytoskeleton↗
PubMed1986

Effect of prostacyclin on pulmonary vascular response to thrombin in awake sheep.

We determined the effects of infusion of prostacyclin (PGI2) and 6-alpha-carba-PGI2 (6-cPGI2), a stable PGI2 analogue, on pulmonary transvascular fluid and protein fluxes after intravascular coagulation induced by thrombin. Studies were made in control awake sheep prepared with lung lymph fistulas (n = 6) and in similarly prepared awake sheep pretreated with either 6-cPGI2 (n = 5) or PGI2 (n = 5). Both prostacyclin compounds (500 ng X kg-1 X min-1) were infused intravenously. All groups were challenged with 80 U/kg thrombin. Pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), pulmonary lymph flow (Qlym), lymph protein clearance (Qlym X lymph/plasma protein concentration ratio), and neutrophil and platelet counts were determined. In vitro tests assessed sheep neutrophil chemotaxis and chemiluminescence and platelet aggregation. In both 6-cPGI2 and PGI2 groups, the increases in Qlym after thrombin were less than those in the control group. The increase in lymph protein clearance in the 6-cPGI2 group was the same as that in control, whereas the increase in clearance in the PGI2 group was reduced. PVR and Ppa increased to a greater extent in the 6-cPGI2 group than in the control group, whereas the increases in PVR and Ppa were inhibited in the PGI2 group. Neutrophil and platelet counts decreased after thrombin in PGI2 and 6-cPGI2 groups, as they did in the control group. Neither 6-cPGI2 altered neutrophil chemotaxis induced by thrombin and chemiluminescence induced by opsonized zymosan. Both prostacyclin compounds inhibited platelet aggregation induced by ADP or thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Platelet-activating factor increases lung vascular permeability to protein.

We studied the effects of platelet-activating factor (PAF) on pulmonary hemodynamics and microvascular permeability in unanesthetized sheep prepared with lung-lymph fistulas. Since cyclooxygenase metabolites have been implicated in mediating these responses, we also examined the role of the cyclooxygenase pathway. PAF infusion (4 micrograms X kg-1 X h-1 for 3 h) produced a rapid, transient rise in pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), plasma thromboxane B2 concentration (TxB2), and pulmonary lymph flow (Qlym). The lymph-to-plasma protein concentration ratio (L/P) did not change from base line. Pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate, prevented the generation of TxB2 and the hemodynamic changes but did not prevent the increase in Qlym. The estimated protein reflection coefficient decreased from a control value of 0.66 +/- 0.04 to 0.43 +/- 0.06 after PAF infusion. We also studied the effects of PAF on endothelial permeability in vitro by measuring the flux of 125I-albumin across cultured bovine pulmonary artery endothelial cells (EC) grown to confluency on a gelatinized micropore filter and mounted within a modified Boyden chemotaxis chamber. PAF (10(-8) to 10(-4) M) had no direct effect on EC albumin permeability, suggesting that the increase in permeability in sheep was not the direct lytic effect of PAF. In conclusion, PAF produces pulmonary vasoconstriction mediated by cyclooxygenase metabolites. PAF also increases pulmonary vascular permeability to protein that is independent of cyclooxygenase products and is not the result of a direct effect of PAF on the endothelium.

Animals↗
PubMed1985

Thrombin-induced alterations in lung fluid balance in awake sheep.

We examined the effect of fibrinolysis depression on thrombin-induced pulmonary microembolism in awake sheep prepared with chronic lung lymph fistulas. Fibrinolysis was depressed by an intravenous infusion (100 mg) of tranexamic acid [trans-4-(Aminomethyl)cyclohexanecarboxylic acid]. Pulmonary microembolism was induced by an intravenous infusion of alpha-thrombin (80 NIH U/kg) in normal (n = 7) and in tranexamic acid-treated (n = 6) sheep. Thrombin immediately increased pulmonary lymph flow (Qlym) in both groups. The increased Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio in the control group and with a small decrease in the tranexamic acid-treated group. The increases in Qlym and pulmonary transvascular protein clearance (Qlym X L/P ratio) in the tranexamic acid-treated group were greater and sustained at four- to fivefold above base line for 10 h after the thrombin and remained elevated at twofold above base line even at 24 h. In contrast, Qlym and protein clearance were transiently increased in the control group. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) increased after thrombin in tranexamic acid-treated group; the increases in Ppa and PVR in the control group were transient. Protein reflection coefficient as determined by the filtration independent method decreased after thrombin in tranexamic acid-treated sheep (n = 5), indicating an increased vascular permeability to proteins. We conclude that prolongation of microthrombi retention in the pulmonary circulation results in an increased vascular permeability to proteins. Both increased vascular permeability and vascular hydrostatic pressure are important determinants of the increases in Qlym and transvascular protein clearance after thrombin-induced pulmonary microembolism.

Amino Acids↗
PubMed1984

Comparison of alpha- and gamma-thrombin on lung fluid balance in anesthetized sheep.

We examined the effects of varying dosages of thrombin on lung fluid balance in halothane-anesthetized sheep prepared with lung lymph fistulas. A 15-min iv infusion of sublethal doses of alpha-thrombin (2.5 clotting units/micrograms), the native enzyme, at 0.6 or 1.1 nmol active enzyme/kg body wt increased the mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) two- to threefold. Neither parameter increased in a dose-dependent manner. Platelet counts decreased 50% with both dosages. Leukocyte counts decreased 35 and 75% from base line in the low- and high-dosage groups, respectively, and reached comparable levels of 50% below base line at 60-min postinfusion in both groups. Plasma fibrinogen concentrations decreased in a dose-dependent manner preceding dose-dependent increases in pulmonary lymph flow (Qlym) and lymph protein clearance (Clym). Fibrin deposition in pulmonary vessels was greater at 30 than at 180 min postinfusion. In contrast, a 15-min iv infusion of gamma-thrombin (0.002 clotting units/micrograms), which lacks the fibrinogen recognition site, at 1.2 nmol active enzyme/kg produced no significant increases in PVR, Ppa, Qlym, or Clym. The fibrinogen concentration did not change significantly, whereas platelet and leukocyte counts decreased 25% within 15 min. Fibrin microthrombi were less prominent in pulmonary vessels. Fibrin deposition associated with intravascular coagulation may be an important factor mediating thrombin-induced increases in pulmonary transvascular fluid and protein exchange.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: the differences and implications in pathogenesis.

Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA- CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.

Antigens, CD↗