Search

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

The prognostic nutritional index (PNI), which is calculated using serum albumin level and total lymphocyte count in the peripheral blood, is regarded as an index that reflects the immunonutritional status of patients. PNI was calculated in 217 systemic lupus erythematosus (SLE) patients according to the following formula: 10 × serum albumin value (g/dL) + 0.005 × peripheral lymphocyte count (/mm 3 ). Pearson's correlation analysis was used to elucidate the correlation between continuous variables. Linear and logistic regression analyses were performed to assess the correlation between laboratory variables and SLE Disease Activity Index-2000 (SLEDAI-2 K) and to differentiate between active and inactive SLE. Ninety-three patients were classified as active SLE (SLEDAI-2 K ≥ 5) and 124 as inactive SLE. Patients with active SLE exhibited lower median PNI than those with inactive SLE (39.0 vs. 49.1, p < 0.001). Multivariable logistic regression analysis revealed PNI as an independent predictor of active SLE. Multivariable linear regression analysis revealed that PNI was significantly correlated with laboratory variables of SLEDAI-2 K, erythrocyte sedimentation rate, C-reactive protein and SLEDAI-2 K. Furthermore, in patients who switched from active to inactive SLE after treatment ( n = 55), PNI increased as disease activity improved ( p < 0.001), which suggests that PNI may be useful for estimating SLE activity.

Serum Mac-2-binding protein (M2BP) is elevated in various chronic inflammatory diseases, and evidence suggests that glycosylation of M2BP induces discrete biological effects. However, the role of serum M2BP in systemic lupus erythematosus (SLE) is still unclear. Recently, a Wisteria floribunda agglutinin-positive-M2BP (WFA + -M2BP) immunoassay has shown promise in detecting highly glycosylated M2BP. In this study, by using WFA + -M2BP immunoassay, we measured serum M2BP in 203 SLE patients and evaluated its clinical significance. Eighty patients were classified as having active SLE and 123 patients as having inactive SLE. The median serum M2BP was higher in patients with active SLE than in those with inactive SLE (2.1 vs. 0.9, p < 0.001). In multivariate linear regression analysis, serum M2BP, anti-dsDNA, C3 and erythrocyte sedimentation rate (ESR) were associated with SLEDAI-2K. Serum M2BP also strongly correlated with laboratory variables related to SLEDAI-2K, ESR and C-reactive protein. Furthermore, multivariate logistic regression analysis demonstrated that serum M2BP was useful in predicting active SLE. Finally, following immunosuppressive treatment, elevated serum M2BP significantly decreased along with improvement in disease activity. These findings suggest that serum M2BP might contribute to the inflammatory process in SLE, and measuring serum M2BP might be a useful marker to assess SLE disease activity.

We investigated renal outcome of kidney-transplantation in 19 Korean recipients with biopsy-proven lupus nephritis and compared it with 18 Korean age- and gender-matched recipients without lupus nephritis who were diagnosed with end-stage renal disease caused by renal diseases other than lupus nephritis in a single centre. We reviewed histological findings of kidneys and calculated cumulative dose of immunosuppressive agents. We assessed renal flare of systemic lupus erythematosus, recurrence of lupus nephritis and graft failure as prognosis. The mean age of recipients with lupus nephritis was 43.5 years and all patients were female. Six patients had class III, 10 had class IV and three had class V. There were no meaningful differences in demographic data, renal replacement modality, cumulative doses of immunosuppressants and prognosis between recipients with and without lupus nephritis. Eight patients experienced renal flare of systemic lupus erythematosus, but there were no cases of recurrence of lupus nephritis or graft failure in recipients with lupus nephritis. Kidney-recipients with class IV lupus nephritis exhibited a lower cumulative renal flare of systemic lupus erythematosus free survival rate than those with class III lupus nephritis. In conclusion, renal outcome of kidney-transplantation in patients with lupus nephritis is similar to that in those without lupus nephritis, and class IV was associated with renal flare of systemic lupus erythematosus.

Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbβ3., Summary: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin. Objectives To determine if GPVI-dimer, GPVI-monomer, or both bind to fibrinogen substrates, and which region common to these substrates contains the interaction site. Methods Recombinant GPVI monomeric extracellular domain (GPVI ex ) or dimeric Fc-fusion protein (GPVI-Fc 2 ) binding to immobilized fibrinogen derivatives was measured by ELISA, including competition assays involving collagenous substrates and fibrinogen derivatives. Flow adhesion was performed with normal or Glanzmann thrombasthenic (GT) platelets over immobilized fibrinogen, with or without anti-GPVI-dimer or anti-αIIbβ3. Results Under static conditions, GPVI ex did not bind to any fibrinogen substrate. GPVI-Fc 2 exhibited specific, saturable binding to both D-fragment and D-dimer, which was inhibited by mFab-F (anti-GPVI-dimer), but showed low binding to fibrinogen and fibrin under our conditions. GPVI-Fc 2 binding to D-fragment or D-dimer was abrogated by collagen type III, Horm collagen or CRP-XL (crosslinked collagen-related peptide), suggesting proximity between the D-domain and collagen binding sites on GPVI-dimer. Under low shear, adhesion of normal platelets to D-fragment, D-dimer, fibrinogen and fibrin was inhibited by mFab-F (inhibitor of GPVI-dimer) and abolished by Eptifibatide (inhibitor of αIIbβ3), suggesting that both receptors contribute to thrombus formation on these substrates, but αIIbβ3 makes a greater contribution. Notably, thrombasthenic platelets showed limited adhesion to fibrinogen substrates under flow, which was further reduced by mFab-F, supporting some independent GPVI-dimer involvement in this interaction. Conclusion Only dimeric GPVI interacts with fibrinogen D-domain, at a site proximate to its collagen binding site, to support platelet adhesion/activation/aggregate formation on immobilized fibrinogen and polymerized fibrin., (© 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

The toxicity of the antifouling biocides Irgarol 1051, Diuron, Chlorothalonil, Dichlofluanid, Sea-nine 211, Copper pyrithione, Zinc pyrithione, Ziram and Zineb were evaluated on Nitzschia pungens and Artemia larvae. Results showed that EC 50 for Irgarol 1051 was 0.586μgl -1 was the strongest effect on N. pungens following by Copper pyrithione (4.908μgl -1 ), Ziram (5.421μgl -1 ), Zinc pyrithione (5.513μgl -1 ), Diuron (6.640μgl -1 ), Zineb (232.249μgl -1 ), Sea-nine 211(267.368μgl -1 ), Chlorothalonil (360.963μgl -1 ) and Dichlofluanid (377.010μgl -1 ) in 96h. In Artemia larvae, the biocides were evaluated the LC 50 for larval survivals at 48h. Sea-nine 211 and Copper pyrithione were 0.318 and 0.319mgl -1 . Chlorothalonil, Zinc pyrithione and Ziram were 2.683, 3.147 and 4.778mgl -1 . Irgarol 1051, Diuron, Zineb and Dichlofluanid were 9.734, 30.573, 41.170 and 154.944mgl -1 . These results provide baseline data concerning the toxicity of antifouling biocides against marine environment., (Copyright © 2016. Published by Elsevier Ltd.)

Essentials Dimeric high-affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets. Spatio-temporal organization of platelet GPVI-dimers was evaluated using advanced microscopy. Upon platelet adhesion to collagenous substrates, GPVI-dimers coalesce to form clusters. Clustering of GPVI-dimers may increase avidity and facilitate platelet activation SUMMARY: Background Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen, and occurs constitutively on resting platelets. Objective To identify higher-order oligomerization (clustering) of pre-existing GPVI dimers upon interaction with collagen as a mechanism to initiate GPVI-mediated signaling. Methods GPVI was located by use of fluorophore-conjugated GPVI dimer-specific Fab (antigen-binding fragment). The tested substrates include Horm collagen I fibers, soluble collagen III, GPVI-specific collagen peptides, and fibrinogen. GPVI dimer clusters on the platelet surface interacting with these substrates were visualized with complementary imaging techniques: total internal reflection fluorescence microscopy to monitor real-time interactions, and direct stochastic optical reconstruction microscopy (dSTORM), providing relative quantification of GPVI cluster size and density. Confocal microscopy was used to locate GPVI dimer clusters, glycoprotein Ib, integrin α 2 β 1 , and phosphotyrosine. Results Upon platelet adhesion to all collagenous substrates, GPVI dimers coalesced to form clusters; notably clusters formed along the fibers of Horm collagen. dSTORM revealed that GPVI density within clusters depended on the substrate, collagen III being the most effective. Clusters on fibrinogen-adhered platelets were much smaller and more numerous; whether these are pre-existing oligomers of GPVI dimers or fibrinogen-induced is not clear. Some GPVI dimer clusters colocalized with areas of phosphotyrosine, indicative of signaling activity. Integrin α 2 β 1 was localized to collagen fibers close to GPVI dimer clusters. GPVI clustering depends on a dynamic actin cytoskeleton. Conclusions Platelet adhesion to collagen induces GPVI dimer clustering. GPVI clustering increases both avidity for collagen and the proximity of GPVI-associated signaling molecules, which may be crucial for the initiation and persistence of signaling., (© 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment and follow-up are needed, especially in the presence of complications., (© The Author(s) 2015.)

We investigated obstetric outcomes and comorbidities during pregnancy in females with preexisting lupus nephritis (LN) and identified predictors for renal flare. In cases of renal flare during pregnancy, we assessed the long-term post-delivery renal outcome. We performed a retrospective analysis of 183 systemic lupus erythematosus (SLE) pregnancies including blood chemistry, urinalysis, urinary protein, and disease activity recorded at prepregnancy, during pregnancy, and at one month, six months, and one year post-delivery. Pregnancies with preexisting LN had a greater frequency of adverse obstetric outcomes and maternal comorbidity. Renal flares occurred in 50.7% of pregnancies with preexisting LN, 89.2% of which were reactivations. Renal flare among pregnancies with SLE was predicted based on preexisting lupus nephritis (OR 17.73; 95% CI, 5.770-54.484), an active disease prior to pregnancy (OR 2.743; 95% CI, 1.074-7.004), and prepregnancy eGFR < 90 ml/min/1.73 m(2) (OR 11.151; 95% CI, 3.292-37.768). Persistent LN one year after delivery was observed in 33.3% of pregnancies. The median follow-up time after delivery was 5.9 (3.1-9.7) years and chronic kidney disease (CKD) occurred in 21.4% of pregnancies with renal flare. In patients with renal flare, failing to achieve a ≥ 50% reduction in urine protein levels within six months, longer total duration of renal flare, and acute kidney injury at renal flare was associated with CKD development. Females with preexisting LN should achieve remission before pregnancy. When patients experience renal flares during pregnancy, it is important to reduce the proteinuria level by >50% within six months and to achieve early remission for excellent long-term renal outcomes., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

Background: this study was to estimate the predicted effect-site concentration of propofol administered by a target-controlled infusion (TCI) for maintenance of anesthesia based on the bispectral (BIS) index as a measure of hypnosis in laparoscopic surgery., Method: one-hundred and sixty unpremedicated patients undergoing gynecologic laparoscopy were assigned randomly to receive one of the target effect-site concentrations of propofol 2.0, 2.5, 3.0, 3.5 and 4.0 microg/ml during TCI with propofol and sufentanil. The dose-response relationship of propofol for the maintenance of adequate anesthesia based on BIS, movement and hemodynamic response was investigated using a fixed effect-site concentration of sufentanil (0.2 ng/ml). The BIS values, hemodynamic variables, time course during emergence and intraoperative awareness were also assessed., Results: the predicted effect-site propofol concentrations for adequate anesthesia at the skin incision in 50% (EC(50) ) and 95% (EC(95) ) of patients undergoing gynecologic laparoscopy were 2.2 and 3.7 microg/ml, respectively. The predicted propofol EC(50) and EC(95) to maintain adequate anesthesia in these patients were 2.6 microg/ml (95% CI 2.3-2.7 microg/ml) and 3.6 microg/ml (95% CI 3.3-4.0 microg/ml), respectively. The BIS values, effect-site concentration of propofol, hemodynamic data and time course during emergence and post-operative adverse events were comparable in each group. There were no reports of intraoperative awareness in the post-anesthetic care unit., Conclusion: based on the anesthetic depth assessed by the clinical signs and BIS monitoring, the predicted effect-site propofol concentrations for the maintenance of anesthesia in patients undergoing gynecologic laparoscopy were similar in those administered adequate anesthesia at the skin incision during TCI., (2010 The Acta Anaesthesiologica Scandinavica Foundation.)

Background: Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican-null (Lum(-/-) ) mice. This defect is rescued by the addition of glycosylated lumican core protein to the injured corneas., Objectives: We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum(-/-) mice., Methods: We demonstrated the basic thinner skin phenotypes in Lum(-/-) mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum(-/-) and wild-type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti-CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to elucidate the transforming growth factor (TGF)-β1-induced myofibroblast phenotypic genes., Results: Skin of adult Lum(-/-) mice (3 months and older) was much thinner (40% less) than that of age-matched wild-type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum(-/-) mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF-β1, type I collagen α1 and fibronectin at the mRNA level by semiquantitative RT-PCR in the Lum(-/-) mice., Conclusions: Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Background: The platelet collagen receptor glycoprotein (GP) VI is suggested to exist as a dimer on the platelet surface, but no direct proof of the functional importance of dimer formation has been provided., Objectives: To obtain direct evidence for GPVI dimers on the platelet membrane and their functional importance, Fab antibodies were developed that bind to GPVI dimer (GPVI-Fc2) but not to GPVI monomer (GPVIex) through a phage display method., Results: Six Fabs were found: B-F, only reactive with GPVI-Fc2, and A, mainly reactive with GPVI-Fc2, with some reactivity towards GPVIex; each Fab (Fab-dHLX-MH) forms a bivalent dimer (b-Fab) by dimerizing the dHLX domains from two Fab molecules. Fab F was subcloned to a monovalent format by deleting its dHLX domain. All b-Fabs induced platelet aggregation, but the monomeric form of Fab F (m-Fab-F) specifically inhibited collagen-induced aggregation. All b-Fabs and m-Fab-F inhibited GPVI-Fc2 binding to fibrous collagen. Immunoblotting showed that b-Fab-F and m-Fab-F bound weakly to GPVI-Fc2. Adding the anti-GPVI monoclonal antibody 204-11 increased the B(max) of m-Fab-F binding to GPVI-Fc2, suggesting that 204-11 binds to GPVI-Fc2 molecules not already in the appropriate conformation to recognize the Fab, converting them to a conformation reactive to the Fab., Conclusions: GPVI forms a specific structure by dimerization that is necessary for the binding of this receptor to collagen fibrils. The binding of m-Fab-F to platelets directly demonstrates that GPVI is present as a functionally relevant dimer on the platelet surface.

So far we have developed Emergency Telemedicine System (ETS) which is a robust system using heterogeneous networks. In disaster areas, however, ETS cannot be used if the primary network channel is disabled due to damages on the network infrastructures. Thus we designed network management software for disaster communication network by combination of Mobile Ad hoc Network (MANET) and Wireless LAN (WLAN). This software maintains routes to a Backbone Gateway Node in dynamic network topologies. In this paper, we introduce the proposed disaster communication network with management software, and evaluate its performance using ETS between Medical Center and simulated disaster areas. We also present the results of network performance analysis which identifies the possibility of actual Telemedicine Service in disaster areas via MANET and mobile network (e.g. HSDPA, WiBro).

Multispecialist teleconsultation systems can be particularly useful in obtaining a second opinion from remote medical specialists. In this paper, a multispecialist teleconsultation (MST) system was designed by using multiple unicasting to enable operability over the existing Internet infrastructure and the support of reliable data transmission. The MST was tested over Asynchronous Digital Subscriber Line (ADSL), Very high speed Digital Subscriber Line (VDSL), Wireless Local Area Network (WLAN), and the hospital Local Area Network (LAN) to demonstrate the operability of the designed system over popularly deployed networks that together make up the current Internet. Also, subjective evaluation using induced delay and low quality video coding of sample brain surgery testing videos and two cases of clinical experimentations demonstrated the limiting factors of the MST in terms of quality and delay differences as well as the feasibility of the MST in a real clinical setting.

Background: Blood vessels contain different types of collagen, with types I and III being the major components of vascular collagen. Platelet adhesion under high shear stress has been suggested to depend on the binding of von Willebrand factor (VWF) to collagen., Objective: We analyzed the collagen type specificity for the interaction with VWF and high shear stress platelet adhesion., Methods: VWF binding to different types of immobilized collagen and effects of antibodies against glycoprotein Ib (gpIb) and integrin alpha(2)beta(1) on platelet adhesion to type I and III collagens under high shear were analyzed., Results: VWF showed high-affinity, selective binding to human and bovine type III collagens, but weak or no affinity for types I, II, IV and V under static conditions. Anti-integrin alpha(2)beta(1) markedly inhibited adhesion to type I collagen, but did not affect that to type III collagen. Anti-gpIb antibody significantly inhibited adhesion to type III collagen. Adding both antibodies abrogated the adhesion to either type I or III collagen., Conclusions: Both the gpIb-VWF interaction and the integrin alpha(2)beta(1)-collagen interaction contribute to platelet adhesion to collagen under high shear stress, and integrin alpha(II)beta(1) makes a greater contribution to adhesion to type I collagen because less VWF is bound to it.

Background: There have been only seven reported cases of glycoprotein (GP) VI deficiency. However, the pathogenesis of this disorder has not been well-elucidated., Objectives: We characterized a novel patient with GPVI deficiency and used these platelets to investigate the role of GPVI in normal hemostasis., Patient: A 31-year-old female with immune thrombocytopenic purpura who had been suffering from mild bleeding diathesis even after recovery from thrombocytopenia., Results and Conclusion: The patient's platelets did not aggregate in response to either convulxin or collagen-related peptide. Immunoblotting revealed complete absence of the GPVI molecule, whereas a significantly reduced but substantial amount of Fc receptor (FcR) gamma-chain was expressed. Platelet stimulation with convulxin did not induce tyrosine-phosphorylation of FcR gamma-chain, indicating a defect in GPVI-mediated signaling. Concerning the underlying pathogenesis, we found normal level of GPVI-mRNA expression, no aberration of the sequence of the entire coding region of GPVI, and presence of degraded GPVI in her plasma. However, no anti-GPVI autoantibody was detected either by the binding assay to GPVI-Fc2 fusion protein or by immunoblotting/immunoprecipitation using the patient's immunoglobulin. We thus consider that either a short-time exposure to anti-GPVI autoantibody or a continuous exposure to low titers of the autoantibody has resulted in persistent GPVI deficiency. Under high shear flow, the patient's platelets could not form large aggregates, although initial platelet attachment was obviously observed. These results suggest that GPVI deficiency in this patient resulted in defective platelet thrombi development, manifesting as bleeding diathesis. Furthermore, our observations indicate that coordination of GPVI with integrin alpha2beta1 is essential for physiological platelet thrombus formation.

Although cardiac tamponade is an important and emergent complication of systemic lupus erythematosus (SLE), purulent pericarditis is rare despite the high frequency of pericardial effusion in SLE. We describe the first SLE case of Haemophilus influenzae type-f pericarditis with cardiac tamponade with SLE as the initial presentation. The pathophysiology and therapy are discussed.

Apoptosis, or programmed cell death, is now recognised as an important cellular event during both normal development and specific disease progression. Apoptosis has been suggested to play a critical role in several cardiovascular diseases, but has not yet been identified as a major influence in primary cardiac tumours. A retrospective review of the achieved material at Chang Gung Memorial Hospital revealed seven patients with cardiac myxoma and one with a tumour originating from the crista terminalis, from January 2002 to December 2002. The medical chart, surgical pathology reports and microscopic slides were available in all cases. All patients, including eight cardiac myxomas and one tumour from crista terminalis, were assessed for apoptosis by terminal deoxynucleotidyl transferase nick-end labelling assay. In this study, apoptosis is well documented in all seven myxoma and has even been reported in tumour from the crista terminalis. Interestingly, apoptosis appears related to the nature of the cell properties rather than the incidence of embolism. In conclusion, apoptosis is important in the progression of the primary cardiac tumours, but the mechanism of cardiac tumour regression still remains uncertain.

Myxopapillary ependymoma is a variant of ependymoma occurring almost exclusively in the conus medullaris or filum terminale. Myxopapillary ependymoma found primarily in the brain is extremely rare. Two such cases appearing at the 4th ventricle and cerebral falx are reported. The imaging features of such tumors are a primary cystic mass with strong enhancement at its solid part. Myxopapillary ependymoma should be a possible differential diagnosis when an intracranial cystic tumor is found.

Objectives: Hemodynamic derangement during displacement of beating heart in off-pump coronary artery bypass graft (OPCAB) surgery might be related with right ventricular (RV) dysfunction. We evaluated RV function and hemodynamic alterations using a thermodilution pulmonary artery catheter., Methods: The study included 30 patients undergoing OPCAB, using single pericardial suture and tissue stabilizer. A thermodilution pulmonary artery catheter for continuous monitoring of the cardiac output (CO), right ventricular ejection fraction (RVEF) and RV volume was inserted before anesthesia. The hemodynamic variables were measured after the induction of anesthesia, 5 min after the heart was positioned for each coronary anastomosis and after the sternum was closed., Results: There was no significant change in the RVEF and cardiac index during anastomosis of the left anterior descending artery and right coronary artery. However, the significantly reduced RVEF accompanied by an increase in RV afterload and decrease in the CO was observed during anastomosis of the obtuse marginal (OM) artery. RV volumes did not significantly change during anastomoses, though the right atrial pressure increased during anastomoses of all coronary arteries., Conclusions: The displacement of beating heart for positioning during anastomosis of the graft to OM artery caused significant derangement of RV function and decrease in CO. A thermodilution catheter continuously measuring the CO and RVEF was useful to monitor the change in RV function and volume during OPCAB.

Myxoma is the most common benign neoplasm of the heart. This work is the first to present an unusual left atrium and mitral valve cardiac myxoma which cannot be completely resected. This cardiac myxoma was also associated with abundant mucopolysaccharidic matrix, including mucin. Mucin gene expression is cell- and tissue-specific, with variations during cell differentiation and inflammation, and is altered during carcinogenesis. The expression of mucin genes in cardiac myxoma has never been elucidated previously. Detailed immunohistochemical analysis of MUC1, MUC2 and MUC5AC has been performed in this left atrium and mitral valve myxoma. Notably, the expressions of mucins in cardiac myxoma must be further evaluated.

Recurrent endometrial cancer with both local and distant metastasis is very difficult to treat. A 55-year-old endometrial adenocarcinoma patient with bulky central recurrences and pelvic and inguinal lymph node metastases underwent laparotomy and paraaortic, pelvic and inguinal lymphadenectomy followed by concurrent chemoradiation (with cisplatin) to the paraaortic and inguinal lymph nodes as well as the whole pelvis. Neck and mediastinal lymph node metastasis emerged during treatment. Neck-node radiation and epirubicin was added followed by paclitaxel and carboplatin. Complete remission was achieved. Ten months later, isolated central re-recurrence happened and total pelvic exenteration was performed. The patient has survived without further recurrence for more than five years after the exenteration. Therefore, a multimodality approach with a combination of radical resection (even pelvic exenteration), radiotherapy and chemotherapy could be offered to well-selected patients with recurrent endometrial cancer despite out-of-field progression during therapy and in-field local failure to initial salvage treatment.