Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca²⁺ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca²⁺ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Postural effect on gas exchange in patients with unilateral pleural effusions

The effect of body position (right and left lateral decubitus positions) on arterial oxygen tension (PaO2) and the relationship between this postural effect on gas exchange and pulmonary function were evaluated in 21 patients who had unilateral pleural effusions without roentgenographic and bronchoscopic evidence of bronchopulmonary disorders. Our results indicated that a positional influence on gas exchange existed in these patients. We failed to find a consistent relationship between the size of effusion estimated by chest roentgenogram and alterations in PaO2 during different positions. Postural change did affect gas exchange in the patients with unilateral pleural effusions and this postural effect on gas exchange was highly correlated with their FEV1 and FVC. This may be of clinical significance in managing such patients.     

Increased expression of MHC class II antigens in rejecting canine lung allografts

Expression of major histocompatibility complex class II antigens was investigated in the normal lungs and in lung allografts of mongrel dogs after single-lung transplantation. Cryostat sections were stained with an indirect immunoperoxidase technique that used B1F6 and 7.5.10.1 as anti-MHC class II monoclonal antibodies. In the normal lungs and native lungs of the recipient dogs after single-lung transplantation, only some cells of lymphoid tissue and macrophages/dendritic cells were MHC class II-positive. During acute rejection, increased infiltration with MHC class II-positive cells in perivascular, peribronchial, and interstitial areas and intraalveolar spaces was found in lung allografts. In addition, expression of MHC class II antigens was induced on the bronchial epithelium and vascular endothelium. Induced expression of MHC class II antigens on the bronchial epithelium and vascular endothelium in rejecting lung allografts was found as early as two days after single-lung transplantation. The intensity of MHC class II antigen expression on bronchial epithelium and vascular endothelium in graft lungs increased with the progression of rejection response and directly correlated with the bronchoalveolar lavage fluid (BALF) levels of biochemical markers, as tumor necrosis factor alpha, gamma-interferon (IFN-gamma), interleukin 2 (IL-2) and soluble interleukin 2 receptor (SIL-2R). Abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium and abnormal elevation of BALF levels of the cytokines in lung allografts could be prevented by cyclosporine (CsA) treatment. Our results suggested that MHC class II antigen expression could be induced on the bronchial epithelium and vascular endothelium of canine lung allografts during acute rejection. This abnormal expression of MHC class II antigens on bronchial epithelium and vascular endothelium of graft lungs may serve as a specific index for diagnosis of lung allograft rejection when infection as an inducing factor can be excluded. Furthermore, bronchial epithelium and vascular endothelium of lung allografts have become MHC class II-positive, and are likely to be the targets for low-grade rejection, resulting in the development of bronchiolitis obliterans and occlusive vascular disease in lung allografts.     

Intracranial ependymoma in children: analysis of prognostic factors

Summary Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25–36 Gy to the neuroaxis, 45–55 Gy to tumor bed), 12 received local field irradiation (29–60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had postradiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear. Address for offprints: Shiao Y. Woo, Department of Radiation Oncology, 6565 Fannin, M.S. DB1-37, Houston, Texas 77030, USA     

Relationship between Mandarin speech reception thresholds and pure-tone thresholds in the geriatric population.

BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement.