Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin-3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor antagonist

The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and vascular endothelial cells, where it transduces IL-3- dependent signals leading to cell activation. Although IL-3R activation may play a role in hematopoiesis and immunity, its aberrant expression or excessive stimulation may contribute to pathologic conditions such as leukemia, lymphoma, and allergic reactions. We describe here the generation and characterization of a monoclonal antibody (MoAb), 7G3, which specifically binds to the IL-3R alpha-chain and completely abolishes its function. MoAb 7G3 immunoprecipitated and recognized in Western blots the IL-3R alpha-chain expressed by transfected cells and bound to primary cells expressing IL-3R alpha. MoAb 7G3 bound the IL-3R alpha-chain with a kd of 900 pmol/L and inhibited 125I-IL-3 binding to high- and low-affinity receptors in a dose-dependent manner. Conversely, IL-3 but not granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibited 125I-7G3 binding to high- and low-affinity IL- 3Rs, indicating that MoAb 7G3 and IL-3 bind to common or adjacent sites. In keeping with the inhibition of IL-3 binding, MoAb 7G3 antagonized IL-3 biologic activities, namely stimulation of TF-1 cell proliferation, basophil histamine release, and IL-6 and IL-8 secretion from human endothelial cells. Two other anti-IL-3R alpha-chain MoAbs failed to inhibit IL-3 binding or function. Epitope mapping experiments using truncated IL-3R alpha-chain mutants and IL-3R alpha/GM-CSFR alpha chimeras revealed that 31 amino acids in the N-terminus of IL-3R alpha were required for MoAb 7G3 binding. MoAb 7G3 may be of clinical significance for antagonizing IL-3 in pathologic conditions such as some myeloid leukemias, follicular B-cell lymphoma, and allergy. Furthermore, these results implicate the N-terminal domain of IL-3R alpha in IL-3 binding. Since this domain is unique to the IL-3/GM- CSF/IL-5 receptor subfamily, it may represent a novel and common binding feature in these receptors.     

Pharmacomechanical Thrombectomy in Paget–Schroetter Syndrome

Purpose

The purpose of the study was to evaluate feasibility of pharmacomechanical thrombectomy (PMT) in the treatment of Paget–Schroetter syndrome (PSS) followed by thoracoscopic or open surgical decompression of the subclavian vein.

Methods

Twenty-two out of 27 consecutive patients with PSS received PMT using the Trellis-8 peripheral infusion system (Covidien) between 2010 and 2014. Subsequent surgery was performed in 18 of those patients, 9 patients were treated with thoracoscopic, 7 patients with subclavicular, and 2 patients with transaxillary first rib resection, 4 patients were treated with PMT and anticoagulation alone. Technical success, complications, and patency were registered.

Results

PMT was successful in 21 (95 %) patients; 1 patient with unsatisfactory lysis received further catheter-directed thrombolysis, which, however, did not improve the result. The mean endovascular procedure time was 105 ± 33 min (range 70–200 min), and the required median amount of thrombolytic agent was 500,000 international unit (IU; range 250,000–1,000,000 IU). Adjunctive balloon venoplasty and aspiration were used in 18 (82 %) and 7 (32 %) cases, respectively. One patient had an intimal tear of the subclavian vein that was discovered and repaired during surgery. There were no other complications related to the endovascular procedure. At follow-up, 18 of 21 patients (86 %) with follow-up imaging available had patent subclavian vein, and all except 1 of the 22 patients were asymptomatic. The mean follow-up time was 25 ± 17 months.

Conclusions

In experienced hands, PMT is effective for early thrombus removal in PSS. Surgical decompression must be considered after PMT.

     

Adenocarcinoma of the Esophagus and the Esophagogastric Junction: Positron Emission Tomography Improves Staging and Prediction of Survival in Distant but Not in Locoregional Disease

In adenocarcinoma of the esophagus and esophagogastric junction for prognostication and treatment allocation, one prerequisite is accurate pretreatment staging. This staging, we hypothesized, would be improved by the use of positron emission tomography (PET). After 55 patients suitable for radical esophageal resection were staged with PET, spiral computed tomography (CT), and endoscopic ultrasonography (EUS), results were compared with histopathology and with survival. Accuracy in detecting locoregional lymph node metastasis did not differ significantly between EUS (72%), PET (60%), and CT (58%). Adding PET to standard staging failed to improve the accuracy of N staging (P = 0.250). In M staging, accuracy between CT (75%) and PET (76%) did not differ. The accuracy of combined studies of CT and PET and of EUS, CT, and PET were 87% (P = 0.016 versus CT) and 91% (P = 0.031 versus EUS and CT), respectively. Of the 55 patients, 19 (35%) had metastatic lesions. By combined use of CT and EUS and by combined use of CT, EUS, and PET, 8 and 14 (P = 0.031), respectively, could be detected. In nodal disease without distant metastases, PET did not improve the prediction of survival. However, positive PET for distant metastasis by either positive EUS or CT predicts well the poor survival of these patients. The staging value of PET by itself in adenocarcinoma of the esophagus is limited because of low accuracy for nodal and the lack of specificity for distant disease prognosis. Adding PET to standard staging does, however, improve detection of stage IV disease and its associated poor survival. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (poster presentation).     

彩色多普勒超声诊断肾恶性循环肿瘤的价值(附20例分析)

目的:评价彩色多普勒超声诊断肾常见恶性肿瘤的价值。方法:分析20例手术病理证实为肾恶性肿瘤的超声表现。结果:肾恶性肿瘤的灰阶超声各异,彩色多普勒超声表现为抱球型和丰富血流型的肾脏肿瘤,术前均定性诊断正确(9/9)。对于星点型、少血流型的肾脏肿瘤,诊断符合率分别为75%(3/4),85.7%(6/7)。超声定性诊断与术后病理符合率为90%。结论:肾恶性肿瘤的回声多种多样,无特异性,彩色血流丰富和抱球型的肿瘤,多考虑恶性。超声诊断对血供丰富的肾肿瘤意义更大,可作为肾恶性肿瘤患者术前首选的检查方法。     

Pneumonectomy: post-operative quality of life and lung function

BACKGROUND: Pneumonectomy is associated with high morbidity and mortality. After pneumonectomy, data on health-related quality of life (HRQoL) or its correlation with dyspnea and lung function are scarce. Our main aim was to evaluate long-term HRQoL after pneumonectomy. METHODS: In a retrospective one-center cross-sectional study, we investigated 31 of 98 patients who underwent pneumonectomy between January 1997 and October 2003 due to primary lung cancer. Pre- or postoperative chemotherapy or radiotherapy was applied according to hospital protocol. In June 2004, all patients alive received the generic HRQoL instrument (15D), as well as the Baseline Dyspnea Index (BDI). Results of the 15D were compared with those for an age- and gender-standardized general population. In April 2005, 20 patients participated in follow-up spirometric pulmonary function tests. RESULTS: The 15D total score and its various dimensions were significantly lower after pneumonectomy than in the general population. Females both in 15D score and in the BDI had more dyspnea (p<0.05). No difference appeared between right and left pneumonectomy patients, except for more prominent dyspnea in women with right-sided pneumonectomy. CONCLUSIONS: Pneumonectomy had a negative impact on patients' HRQoL. The use of a broad HRQoL instrument like the 15D, which covers multiple dimensions of HRQoL, yields a more accurate evaluation than did a single-dimension HRQoL instrument. Possibilities for sleeve-resection should be considered thoroughly before any pneumonectomy. SUMMARY: Quality of life (QoL) after pneumonectomy, as measured with a generic QoL instrument, the 15D, was compared in an age- and gender-standardized population. QoL after pneumonectomy was significantly lower, especially in women after right-sided pneumonectomy.