Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM)

Two antibodies, BT14 and L101, detect a tumor-associated cell surface glycoprotein (gp130) whose properties in normal and diseased skin were assessed, and whose molecular identity was determined in this study. In normal skin, gp130 was constitutively expressed on dermal blood vessels and epidermal appendages, but not in interfollicular epidermis. Marked induction was detected within benign and malignant tumors of various origins including viral warts, basal cell carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell lymphomas. In vitro studies confirmed the general upregulation of gp130 expression in malignantly transformed cells. Surprisingly, gp130 was also induced in inflammatory skin diseases including psoriasis and allergic contact dermatitis. Halting proliferation of transformed keratinocytes through cytostatic drugs or increasing the Ca2+ concentration in the medium resulted in increased gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of gp130. When the protein was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential immunoprecipitations and western blot analyses confirmed the identity of the antigen. Thus, both expression pattern and regulation characteristics of the now-known glycoprotein gp130 extended beyond previously published data regarding MUC18, thus shedding some new light on a supposedly well-known antigen.     

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.     

Effects of ethnicity and gender on motion sickness susceptibility

INTRODUCTION: Susceptibility to motion sickness (MS) is known to be affected by gender and ethnic origin, but whether gender and ethnicity are interacting is unknown. METHODS: We investigated MS development in healthy Caucasian subjects (n = 227), and in subjects of Chinese origin (n = 82). All subjects were exposed to nausea-inducing body rotations in a rotation chair, and rotated around the yaw axis for 5 x 1 min, while they were instructed to move their heads. Prior to rotation, subjects had to fill out a motion-sickness susceptibility questionnaire (MSSQ). Total rotation tolerance time (RT) was noted. Symptom ratings (SR) were performed at the beginning, and immediately after the end of each rotation, and 15 and 30 min later. RESULTS: The average RT was significantly higher in Caucasian (163 +/- 6 s) than in Chinese subjects (111 +/- 7 s) (F = 24.84, p < 0.0001). The adult MSSQ score was significantly lower in Caucasians (17.8 +/- 1.1) than in Chinese volunteers (24.2 +/- 2.1) (F = 6.05, p = 0.014). Maximal SR post rotation was similar in Chinese and Caucasian subjects. RT was highly predictable from the MSSQ scores, but separate for both genders. CONCLUSION: Susceptibility to MS is affected by both ethnic origin and by gender in a rather complex fashion. The most reliable prediction of RT can be based on the individual's history as assessed by the MSSQ.     

Use of primary prevention services among male adults with cerebral palsy, multiple sclerosis, or spinal cord injury in managed care and fee-for-service

Future research needs to clarify the biases in clinical practice and potential barriers that may exist at both the provider and health plan levels that exclude men with physical disabilities from routine preventive services. As the population of people with disabilities ages and lives longer, it is necessary that routine preventive services are accessible and made available to them, regardless of gender, disability, or health insurance type.     

Influence of propofol on neuronal damage and apoptotic factors after incomplete cerebral ischemia and reperfusion in rats: a long-term observation

BACKGROUND: Propofol reduces neuronal damage from cerebral ischemia when investigated for less than 8 postischemic days. This study investigates the long-term effects of propofol on neuronal damage and apoptosis-related proteins after cerebral ischemia and reperfusion. METHODS: Male Sprague-Dawley rats were randomly assigned as follows: group 1 (n = 32, control): fentanyl and nitrous oxide-oxygen; group 2 (n = 32, propofol): propofol and oxygen-air. Ischemia (45 min) was induced by carotid artery occlusion and hemorrhagic hypotension. Pericranial temperature and arterial blood gases were maintained constant. After 1, 3, 7, and 28 postischemic days, brains were removed, frozen, and sliced. Hippocampal eosinophilic cells were counted. The amount of apoptosis-related proteins Bax, p53, Bcl-2, and Mdm-2 and neurons positive for activated caspase-3 were analyzed. RESULTS: In propofol-anesthetized rats, no eosinophilic neurons were detected, whereas in control animals, 16-54% of hippocampal neurons were eosinophilic (days 1-28). In control animals, the concentration of Bax was 70-200% higher after cerebral ischemia compared with that in animals receiving propofol over time. Bcl-2 was 50% lower in control animals compared with propofol-anesthetized rats during the first 3 days. In both groups, a maximal 3% of the hippocampal neurons were positive for activated caspase-3. CONCLUSIONS: These data show sustained neuroprotection with propofol. This relates to reduced eosinophilic and apoptotic injury. Activated caspase-3-dependent apoptotic pathways were not affected by propofol. This suggests the presence of activated caspase-3-independent apoptotic pathways.