Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.     

Expression of specific granule markers on the cell surface of neutrophil cytoplasts

The widespread assumption that cytoplasts generated from human polymorphonuclear leukocytes (PMNs) are vesicles consisting solely of cytoplasm surrounded by plasma membrane and devoid of granule activity remains to be tested. PMN cytoplasts were prepared by centrifugation of intact cells on a Ficoll step gradient in the presence of cytochalasin B. Two granule membrane markers, Mol, a fluorometrically detectable antigen, and cytochrome b, both of which have been shown to translocate to the plasma membrane during granule release, were compared for their activity in cytoplasts and intact PMNs. We found that the amount of Mol detected on the plasma membrane of intact PMNs, as compared with other membrane markers (such as antigens LFA-1 and beta 2m), increased 1.6- fold upon exposure of PMNs to Ficoll plus cytochalasin B prior to centrifugation. Another twofold increase in Mol expression occurred upon cytoplast preparation. Release of the granule enzymes, vitamin B12- binding protein, and lysozyme were also followed and correlated well (r = .78 and .92) with the amount of Mol antigen present on the cell surface. Cytochrome b was also found to be higher (1.4-fold) on plasma membranes isolated from cytoplasts than on plasma membranes isolated from intact control cells. These results indicate that some fusion of granule membranes and plasma membranes occurred during treatment of PMNs with Ficoll plus cytochalasin b and during cytoplast preparation.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Asthma caused by potassium aluminium tetrafluoride: a case series

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF₄)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF₄ − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m³. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.     

腹腔镜手术对不孕症患者的诊断及治疗价值研究

目的探讨腹腔镜手术对不孕症患者的诊断及治疗价值。方法回顾性分析新疆医科大学第一附属医院2010年9月-2014年5月收治的319例不孕症患者的临床资料,对所有患者行腹腔镜下诊断及相应的手术治疗(包括盆腔粘连分解、输卵管造口术、输卵管灼断术等)。结果 319例患者腹腔镜术中检查与术前子宫输卵管碘油造影结果的符合率为72.1%(230/319),其中有43例术中发现子宫肌瘤,56例术中发现输卵管系膜囊肿,8例患者术中发现子宫内膜异位症,有2例患者诊断为盆腔结核,1例术中发现结肠肌瘤(术前考虑卵巢囊肿),其余为不同程度的盆腔慢性炎症。轻度粘连69例,妊娠21例,宫外孕2例,妊娠率33.33%。中重度粘连250例,其中行灼断术34例,灼断术患者后行体外受精及胚胎移植(IVF-ET),妊娠13例,妊娠率38.23%(13/34)。其余216例,失访3例,妊娠31例,宫外孕3例、妊娠率15.9%。结论腹腔镜对诊断输卵管性不孕及盆腔疾病有重要价值,子宫输卵管造影仅能初级筛查,诊断价值有限。在治疗输卵管粘连梗阻中,腹腔镜的治疗价值有待进一步探讨,临床预后与盆腔炎症的程度有关,应个体化选择手术方案。     

Differentiated Thyroid Cancer With Liver Metastases: Lessons Learned From Managing a Series of 14 Patients

Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare and usually occur in disseminated metastatic disease. The aim of this study was to review the diagnosis and management of LMDTC. Between 1995 and 2011, 14 patients with a mean age of 59.7 years (+/-10.2) were treated for LMDTC. Data were retrospectively reviewed and analyzed. Seven patients had distant metastases at diagnosis, including 2 with synchronous liver lesions. The average time of onset of LMDTC from initial diagnosis was 52.2 months (+/49.5). All LMDTC were discovered during routine radiologic monitoring. Histologic analysis confirmed LMDTC in 5 patients. Eight patients received tyrosine kinase inhibitors, 1 patient underwent resection of their LMDTC after chemotherapy. Six patients (disseminated metastases, significant comorbidities) did not receive any specific treatment. The median survival after diagnosis of LMDTC was 17.4 months (+/-3.3): 23.6 months (+/-2.9) for patients who underwent chemotherapy versus 3.9 months (+/-0.9) for patients who did not receive any specific treatment (P < 0.001). Developing DTC liver metastasis is a very poor prognostic sign. Chemotherapy by TKIs, especially, hold promise in the cure of LMDTC for selected patients.Key words: Liver metastasis, Thyroid carcinomaDifferentiated thyroid carcinoma, encompassing follicular and papillary carcinomas, has a good prognosis and long-term survival rates. Indeed, the 10-year survival rate is 80–95%. The incidence of distant metastases at the time of initial presentation of differentiated thyroid carcinoma (DTC) is 4%. During the course of treatment and follow-up, the prevalence of distant metastases ranges from 2% in low-risk patients, to 33% in high-risk patients. Distant metastases occur primarily in the lungs and, to a lesser extent, in bones. The presence of distant metastases is the most significant prognostic factor and is associated with poor outcomes. Only 50% of patients survive 10 years after a diagnosis of the metastatic DTC.^1–3Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare, with a reported frequency of 0.5%. They tend to occur during the terminal phase of the disease are a grave event. Survival ranges from 1 to 60 months after diagnosis of LMDTC in the largest series of 11 cases.⁴Because of this rarity, there is little information available on the diagnosis and management of LMDTC. We have therefore undertaken a retrospective, multicenter study on LMDTC and analyzed factors affecting survival.