Angiostatin K1‐3 induces E‐selectin via AP1 and Ets1: a mediator for anti‐angiogenic action of K1‐3

Summary. Background: Angiostatin, a circulating angiogenic inhibitor, is an internal fragment of plasminogen and consists of several isoforms, K1‐3 included. We previously showed that K1‐3 was the most potent angiostatin to induce E‐selectin mRNA expression. The purpose of this study was to identify the mechanism responsible for K1‐3‐induced E‐selectin expression and investigate the role of E‐selectin in the anti‐angiogenic action of K1‐3. Methods and results: Quantitative real time RT‐PCR and Western blotting analyses confirmed a time‐dependent increase of E‐selectin mRNA and protein induced by K1‐3. Subcellular fractionation and immunofluorescence microscopy showed the co‐localization of K1‐3‐induced E‐selectin with caveolin 1 (Cav1) in lipid rafts in which E‐selectin may behave as a signaling receptor. Promoter‐driven reporter assays and site‐directed mutagenesis showed that K1‐3 induced E‐selectin expression via promoter activation and AP1 and Ets‐1 binding sites in the proximal E‐selectin promoter were required for E‐selectin induction. The in vivo binding of both protein complexes to the proximal promoter was confirmed by chromatin immunoprecipitation (ChIP). Although K1‐3 induced the activation of ERK1/2 and JNK, only repression of JNK activation attenuated the induction of E‐selectin by K1‐3. A modulatory role of E‐selectin in the anti‐angiogenic action of K1‐3 was manifested by both overexpression and knockdown of E‐selectin followed by cell proliferation assay. Conclusions: We show that K1‐3 induced E‐selectin expression via AP1 and Ets‐1 binding to the proximal E‐selectin promoter (?356/+1), which was positively mediated by JNK activation. Our findings also demonstrate E‐selectin as a novel target for the anti‐angiogenic therapy.     

A longitudinal study of immunological status in Chinese haemophiliacs: importance of the heat viral inactivation of factor concentrates. I. Immunological associations with the consumption of factor concentrates

Summary . Twenty-four of 117 cases of haemophilia A (20.5%) and none of 18 cases of haemophilia B reported in this study had an antibody to the human immuno-deficiency virus (HIV). Both groups of patients showed similar immunological alterations. HIV-seropositive haemophilia A patients had an increased CD8 cell count and a similarly decreased CD4/CD8 ratio as compared to HIV-seronegative haemophilia A patients. Multiple regression analysis for the association of CD4/CD8 ratio with HIV infection status and dosage of plasma products in haemophilia A and B patients, respectively, revealed that there was a significant negative association of ln(CD4/CD8) with dosage of factor VlII concentrates (P = 0.0435) and factor IX concentrates (P = O.O028), respectively. N o association occurred between CD4/CD8 ratio and HIV infection as well as dosage of other plasma products. These data indicate that the immunological abnormalities of our haemophilia A and B patients in their early years were primarily caused by various viral infections and/or a suppressive effect of allogeneic protein through infusion of factor concentrates and not caused simply by HIV infection.     

Tumour-infiltrating lymphocytes in non-small cell lung cancer are activated T lymphocytes

This study was carried out in order to investigate the local immune reaction of tumour-infiltrating lymphocytes (TILs) in the primary tumours of non-small cell lung carcinomas. Thirty non-small cell lung cancer (NSCLC) patients were included. The tumour tissue was taken at thoracotomy and monocellular suspension of the tumour was obtained by mechanical disaggregation. Dual-coloured flow cytometric analysis of TILs and their corresponding peripheral blood lymphocytes (PBLs) was performed. Tumour-infiltrating lymphocytes contained significantly higher proportions of CD3(+) T lymphocytes and CD8(+) T lymphocytes than the corresponding PBLs (82.0%±13.9% vs 66.3%±10.6% for CD3, P <0.001; 39.0%±18.4% vs 26.4%±5.2% for CD8, P <0.001). Tumour-infiltrating lymphocytes contained significantly higher proportions of activated memory lymphocytes than PBLs did (9.8%±8.6% vs 1.3%±1.5% for CD25, P <0.001; 40.5%±30.2% vs 10.2%±14.8% for CD71, P <0.001; 75.5%±11.9% vs 28.6%±9.8% for HLA-DR, P <0.001). These findings were also found in both CD4(+) TILs and CD8(+) TILs. The TILs of NSCLC contained higher proportions of T lymphocytes and CD8(+) lymphocytes than their corresponding peripheral bloods. The proportions of activated memory lymphocytes were also significantly higher in the TILs, both in CD4(+) TILs and CD8(+) TILs, than the corresponding PBLs.     

Hyperventilation Facilitates Induction of Supraventricular Tachycardia: A Novel Method and the Possible Mechanism

INTRODUCTION: Hyperventilation has been demonstrated to alter autonomic function. Sympathomimetic drugs (isoproterenol) and parasympatholytic drugs (atropine) may be needed to facilitate induction of supraventricular tachycardia (SVT). The aim of this study was to test the clinical utility and mechanisms of hyperventilation to facilitate SVT initiation. METHODS AND RESULTS: Fourteen patients with clinically documented SVT (9 AV nodal reentrant tachycardia and 5 AV reciprocating tachycardia) but noninducible during baseline electrophysiologic study were included. Immediately after hyperventilation test (at least 30 respirations/min) for 2 minutes, systolic blood pressure, sinus cycle length, anterograde and retrograde 1:1 conduction, and induced SVT were measured. Arterial blood gas, pH, and heart rate variability before and after hyperventilation were measured. Seven of nine patients with AV nodal reentrant tachycardia and 3 of 5 patients with AV reciprocating tachycardia could be induced immediately after the hyperventilation test. After hyperventilation, anterograde AV and retrograde VA 1:1 conduction were improved, sinus cycle length was decreased, and heart rate variability were decreased in both groups. CONCLUSION: Hyperventilation can facilitate induction of SVT. Improvement of conduction properties and changes of autonomic function are the possible mechanisms.     

Treatment Outcome of Overactive Bladder Patients Receiving Antimuscarinic Therapy for More than One Year

Objectives

Details on the therapeutic effects of long‐term antimuscarinic therapy have not been reported. Thus, the aim of this study is to evaluate the detailed long‐term therapeutic effect of antimuscarinic therapy.

Methods

All consecutive patients who visited the urologic outpatient clinics of a medical center for treatment of overactive bladder syndrome and received antimuscarinic therapy of 12 months or more were retrospectively reviewed. All medical records, including the Overactive Bladder Symptom score (OABSS), the modified Indevus Urgency Severity Scale and the International Prostate Symptoms score (IPSS) questionnaires, and uroflowmetry parameters were reviewed at each visit.

Results

A total of 140 patients had received 12 months or more of antimuscarinic therapy. Sustained therapeutic effects were observed by persistent decreases of IPSS‐storage score, IPSS‐total score and OABSS score. Moreover, the maximum flow rate did not change over time. A temporary increase in postvoid residual volume and decrease in voiding efficiency were found, but these parameters improved over long‐term visits. Side‐effects were observed in 81 patients (57.9%) and included dry mouth (n = 58, 41.4%), constipation (n = 48, 34.3%) and blurred vision (n = 4, 2.9%); all side‐effects were tolerable. Patients aged 75 years or more (n = 94) had a higher comorbidity rate (n = 46, 48.9%) before treatment but generally exhibited similar therapeutic effects as overall patients; elderly patients could also tolerate side‐effects.

Conclusion

Sustained therapeutic effects were observed in patients who received 12 months or more of antimuscarinic therapy, even in elderly patients. In addition, side‐effects in patients receiving long‐term therapy were also common but tolerable.     

经皮肝穿刺胆道引流口发生渗漏患者使用美皮康吸收性敷料的效果观察

目的 探讨美皮康吸收性敷料在经皮肝穿刺胆道引流口发生渗漏患者中的应用效果.方法 经皮肝穿刺胆道引流术后患者留置引流管期间发生渗漏患者98例,采用随机数字表法分成对照组和观察组各49例.对照组采用无菌纱布联合防漏膏换药,观察组使用美皮康吸收性敷料联合防漏膏换药.观察比较2组患者置管期间舒适度、周围刺激性皮炎及意外脱管发生情况.结果 观察组患者置管期间舒适度高于对照组(P<0.05),观察组患者刺激性皮炎发生率低于对照组(P<0.05),2组患者意外脱管发生率的比较差异无统计学意义(P>0.05).结论 使用美皮康吸收性敷料处理经皮肝穿刺胆道引流口发生渗漏患者,可提高患者舒适度,减少刺激性皮炎的发生,值得临床借鉴使用.     

Regressed Subungual Melanoma Simulating Cellular Blue Nevus: Managed with Sentinel Lymph Node Biopsy

BACKGROUND: Subungual melanoma, a not uncommon presentation of cutaneous melanoma in Asian populations, is easily overlooked as benign and thus is improperly treated. OBJECTIVE: To present two cases with clinical suspicion of subungual melanoma. Skin biopsies failed to demonstrate the diagnostic features of malignancy. METHODS: Lymphoscintigraphy and sentinel lymph node (SLN) biopsies were performed to determine regional lymph node status. RESULTS: Both hematoxylin-eosin and HMB45 staining revealed melanoma cells in the SLN of the patient. The second patient's SLN was negative for malignant cells, but her excised primary lesion showed extensive regressed melanoma. CONCLUSION: Regression phenomena are not uncommon for subungual melanoma. An extention biopsy techniques are useful for determining nodal basin status in regressed subungual melanoma.     

Acyclovir-induced acute renal failure

SUMMARY: Acyclovir is an effective antiviral agent in the treatment of herpes simplex and varicella-zoster viral infections. the best known side-effects of this drug are significant nephrotoxicity and neurotoxicity. We report on a diabetic patient with acute retinal necrosis who developed non-oliguric acute renal failure during the administration of high doses of intravenous acyclovir (500 mg/m² intravenous infusion every 8h). No obvious uremic symptoms or signs were noted. No obvious haematuria, proteinuria or crystalluria were noted in the urine. After discontinuing the acyclovir administration, renal function partially recovered. In this paper, we also review the mechanism of acyclovir-induced acute renal failure, and the precipitating factor of acyclovir-induced acute renal failure. Finally, we must once again emphasize the importance of hydration and routine check ups for renal function in preventing acyclovir-induced acute renal failure.