Comparison of Single and Dual Monitoring during Carotid Endarterectomy

We compared the rate of selective shunt and pattern of monitoring change between single and dual monitoring in patients undergoing carotid endarterectomy (CEA). A total of 121 patients underwent 128 consecutive CEA procedures. Excluding five procedures using internal shunts in a premeditated manner, we classified patients according to the monitoring: Group A (n = 72), patients with single somatosensory evoked potential (SSEP) monitoring; and Group B (n = 51), patients with dual SSEP and motor evoked potential (MEP). Among the 123 CEAs, an internal shunt was inserted in 12 procedures (9.8%) due to significant changes in monitoring (Group A 5.6%, Group B 15.7%, p = 0.07). The rate of shunt use was significantly higher in patients with the absence of contralateral proximal anterior cerebral artery (A1) on magnetic resonance angiography (MRA) than in patients with other types of MRA (p <0.001). Significant monitor changes were seen in 16 (12.5%) in both groups. In four of nine patients in Group B, SSEP and MEP changes were synchronized, and in the remaining five patients, a time lag was evident between SSEP and MEP changes. In conclusion, the rate of internal shunt use tended to be more frequent in patients with dual monitoring than in patients with single SSEP monitoring, but the difference was not significant. Contralateral A1 absence may predict the need for a shunt and care should be taken to monitor changes throughout the entire CEA procedure. Use of dual monitoring can capture ischemic changes due to the complementary relationship, and may reduce the rate of false-negative monitor changes during CEA.     

Allogeneic hepatocyte transplantation: Contribution of Fas-Fas ligand interaction to allogeneic hepatocyte rejection

Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted hepatocytes, induction of donor-specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas-Fas ligand system plays a critical role in the CD28-independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti-CD80/86 monoclonal antibodies and anti-FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.     

INDUCTION OF SIALYL LEWISX ON THE SURFACE OF CULTURED RAT VASCULAR ENDOTHELIAL CELLS AND CARDIAC MYOCYTES BY HYPOXIA/REOXYGENATION IN VITRO

Neutrophils adhere to and roll on vascular endothelial cells (VECs) through interaction of selectins and their carbohydrate ligands in the early stages of inflammation; this adhesion is then later strengthened through interaction of integrins on neutrophils with intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. Recent, as yet unpublished studies showed that myocardial ischaemia/reperfusion caused rapid expression of sialyl Lewis^X (SLe^X), one of the carbohydrate ligands of selectins, on VECs and cardiac myocytes and that an anti-SLe^X monoclonal antibody (MAb) significantly reduced myocardial reperfusion injury in vivo . In the present study, to investigate whether or not ischaemia/reperfusion itself can induce the expression of SLe^X on VECs and cardiac myocytes, the expression of SLe^X on cultured rat VECs and cardiac myocytes was examined by treatment with hypoxia/reoxygenation in vitro , because ischaemia/reperfusion stimuli may partly be due to hypoxia/reoxygenation. The expression of SLe^X was induced rapidly and temporarily on the surface of cultured rat cardiac myocytes and VECs by hypoxia/reoxygenation in vitro . This strongly suggests that the expression of SLe^X on the surface of myocardial cells is induced initially and directly by ischaemia/reperfusion, which results in the rolling attachment of neutrophils in the early stages of myocardial reperfusion injury.     

A case of anomalous origin of the right coronary artery from the left sinus of Valsalva exhibiting the Wolff-Parkinson-White syndrome

A 56-year-old male with the Wolff-Parkinson-White syndrome wassuspected of having suffered a myocardial infarction followingattacks of chest pain. Serial measurements of serum creatinephosphokinase and the electrocardiographic findings after ajmalineloading virtually excluded the possibility of myocardial infarction.Paroxysmal tachycardia was not noted on 24 Holler electrocardiographicmonitoring. Both the left and right coronary arteries were foundby selective coronary angiography to originate from the leftsinus of Valsalva, but neither of the arteries showed organicstenoses. However, myocardial²⁰¹ Tl scintigraphy after exerciseindicated poor uptake in the high anterolateral wall, and atthe apex and septum near the anterior wall, which suggestedthe absence ofischaemia in the area supplied by the right coronaryartery. We speculate that a left coronary artery steal phenomenonwas the cause of the ischaemia after exercise in this patient.     

REDUCTION OF RAT MYOCARDIAL ISCHAEMIA/REPERFUSION INJURY BY A SYNTHETIC SELECTIN OLIGOPEPTIDE

Neutrophils infiltrate into myocardial tissue subjected to ischaemia followed by reperfusion and play a major role in myocardial reperfusion injury. The infiltration of neutrophils begins within 2 h after reperfusion, indicating the engagement of rapidly inducible adhesion molecules, such as P-selectin, on vascular endothelial cells of myocardial tissue. To investigate the essential role of P-selectin in myocardial reperfusion injury, this study examined the expression of P-selectin in rat hearts subjected to 30 min of ischaemia followed by reperfusion. The induction of P-selectin was also evaluated on the surface of cultured rat vascular endothelial cells subjected to 60 min of hypoxia, followed by reoxygenation in vitro . Finally, the effects of in vitro administration of a synthetic selectin oligopeptide on myocardial necrosis were analysed. Reperfusion of ischaemic myocardial tissue resulted in enhanced expression of P-selectin on the luminal surface of vascular endothelium and surface expression of P-selectin was induced on cultured vascular endothelial cells by hypoxia/reoxygenation in vitro . The in vitro administration of a synthetic selectin oligopeptide significantly reduced the area of myocardial infarction produced by 30 min of ischaemia, followed by 48 h of reperfusion. These data offer therapeutic possibilities for acute myocardial infarction.     

EXPRESSION OF VASCULAR CELL ADHESION MOLECULE-1 IN MURINE HEARTS WITH ACUTE MYOCARDITIS CAUSED BY COXSACKIEVIRUS B3

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of the myocardial cell damage involved in viral myocarditis. Using a murine model of acute myocarditis caused by Coxsackievirus B3 (CVB3), perforin-expressing killer cells have been shown to infiltrate the heart, and intercellular adhesion molecular-1 (ICAM-1) together with major histocompatibility complex (MHC) antigen was induced on myocardial cells in acute viral myocarditis. To clarify the immunological mechanisms in more detail, the expression of vascular cell adhesion molecular-1 (VCAM-1) has been examined in the heart of acute myocarditis and on cultured cardiac myocytes treated with interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The effects of in vivo antibody treatment to VCAM-1 on myocardial damage involved in acute myocarditis were also analysed. CVB3-induced myocarditis resulted in enhanced expression of VCAM-1 on myocardial cells. VCAM-1 expression was also induced on cultured cardiac myocytes by treatment with IFN-γ and TNF-α. The in vivo antibody treatment to VCAM-1 decreased the myocardial damage to some extent, but the effects were not statistically significant. These data suggest that the expression of VCAM-1 on myocardial cells may play at least a partial role in the myocardial damage involved in acute viral myocarditis.     

Swainsonine, an Inhibitor of Glycoprotein Processing, Enhances Cytotoxicity of Large Granular Lymphocytes

In the present study we investigated the effects of inhibitors of glycoprotein processing on cytotoxicity of human large granular lymphocytes (LGL). The incubation of LGL for 36 h with 0.5 microgram/ml swainsonine (SW), which is an inhibitor of mannosidase II, resulted in the augmentation of cytotoxicity of LGL against an NK-resistant colon carcinoma cell line (Colo-320DM) without increase of binding frequency of LGL to target cells or of cell proliferation. The enhanced cytotoxicity was associated with increased binding of concanavalin A to SW-treated LGL. The augmentation of cytotoxicity was also seen by 1-deoxymannojirimycin (1-DMN), an inhibitor of mannosidase I, but much higher amounts of this agent were needed to get the same level of augmentation as that with SW. Other inhibitors of glycoprotein processing such as castanospermine and 1-deoxynojirimycin (1-DN) did not show any augmentative effects on LGL cytotoxicity. The enhancement of cytotoxicity by SW was abolished by the addition of rabbit anti-human interleukin (IL-2) antibody to the culture. This result suggests that IL-2 is involved in the augmentation of cytotoxicity of LGL by SW. The presence of SW in the culture of LGL together with IL-2 also enhanced LAK generation compared to that with IL-2 alone. Thus, our results suggest that SW should be recognized as an efficient immunopotentiator and that modulation of carbohydrate moieties elicited by SW may shed further light on the mechanism of LGL activation.     

Serum levels of soluble Fas/APO-1 (CD95) and its molecular structure in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases

There are two major forms of the Fas molecule, membranous Fas and soluble Fas (sFas). To clarify the clinical significance of sFas in autoimmune diseases, we designed a sandwich ELISA to determine serum concentrations of sFas and its molecular structure, and we then analysed the correlation between levels of sFas and laboratory findings in patients with SLE and other autoimmune diseases. The levels of serum sFas were significantly higher in SLE patients than in subjects with other autoimmune diseases and in healthy donors, and the frequency of a positive serum sFas was much greater in SLE patients with high SLE disease activity index scores than in those with low scores. In addition, sFas-positive SLE patients showed a significant difference in various laboratory parameters from sFas-negative SLE patients. Serial measurements of serum sFas levels in SLE patients with active disease revealed that the elevated level of sFas dramatically decreased with improvement in clinical and laboratory findings, following corticosteroid therapy. We propose that the serum level of sFas can serve as an appropriate marker for evaluating SLE disease activity. Serum sFas is heterogeneous with respect to molecular structure, thus several mechanisms are involved in the generation of sFas.