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.     

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.     

Immunohistochemical evidence of p53 overexpression in gastric epithelial dysplasia.

Molecular abnormalities of the p53 gene in chromosome 17p may be among the most commonly observed in human cancer. Their role in gastric carcinogenesis is suggested by their frequent detection in invasive adenocarcinomas. To investigate the chronology with which these abnormalities appear in the gastric carcinogenesis process, the expression of p53 proteins was investigated in late stages of the process, namely dysplasia, and in superficial carcinomas. A polyclonal antibody, CM-1, against both wild-type and mutant proteins was applied to paraffin-embedded biopsy and gastrectomy specimens previously fixed in buffered formalin. Positive nuclear stain was obtained in 36.4% of 33 cases of gastric epithelial dysplasia, corresponding to 19% of mild, 27.3% of moderate, and 64.3% of severe dysplasias. Eight of 13 (61.5%) invasive carcinomas showed positive stain. The data indicate an increased incidence of p53 abnormalities in the late stages of gastric carcinogenesis.     

YKL-40 expression is associated with poorer response to radiation and shorter overall survival in glioblastoma.

PURPOSE: YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response. EXPERIMENTAL DESIGN: Patients (n=147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set (n=140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease. RESULTS: In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined (n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss. CONCLUSIONS: The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.     

Long-Term Psychological Outcome of Workers After Occupational Injury: Prevalence and Risk Factors

Introduction This study aimed to examine the prevalence rates of both post-traumatic stress disorder (PTSD) and major depression at 12 months in workers experiencing different types of occupational injury in Taiwan. Demographic and injury-related risk factors for psychological symptoms were also evaluated. Methods Our study candidates were injured workers in Taiwan who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance program. A two-staged survey study was conducted. A self-reported questionnaire including the Brief Symptom Rating Scale and Post-traumatic Symptom Checklist was sent to workers at 12 months after injury. Those who met the criteria were recruited for the second-stage phone interview with a psychiatrist using the Mini-international Neuropsychiatric Interview (MINI). Results A total of 1,233 workers completed the questionnaire (response rate 28.0 %). Among them, 167 (13.5 %) fulfilled the criteria for the MINI interview and were invited. A total of 106 (63.5 %) completed the phone interview. The estimated rate of either PTSD/PPTSD or major depression was 5.2 %. The risk factors for psychological symptoms were female gender, lower education level, loss of consciousness after occupational injury, injury affecting physical appearance, occupational injury experience before this event, life experience before and after this injury, length of hospital stay, self-rated injury severity, and percentage of income to the family. Conclusions These results showed that occupational injury can cause long-term psychological impact in workers. Key demographic and injury characteristics may enhance the identification of at-risk occupational injured workers who would benefit from targeted screening and early intervention efforts.     

Measurements of components of resistance to breathing

Total respiratory resistance (Rrs), pulmonary resistance (RL), and airway resistance (Raw) of 12 male patients with chronic obstructive lung disease were measured by the partial occlusion method, intraesophageal balloon technique, and body plethysmography, respectively. Chest wall resistance (Rew) and lung tissue resistance (Rti) were computed. Percentages of Rew/Rrs, RL/Rrs, Raw/Rrs, Rti/Rrs, Raw/RL, and Rti/RL were calculated. The magnitude of the components of resistance to breathing of this study and the data appearing in the literature are compared. Wide variation between the data reported by various authors was observed. The possible causes of these variations are discussed.