Interleukin 4 receptors on human bronchial epithelial cells. An in vivo and in vitro analysis of expression and function

Asthma is considered a Th2-like disease, characterized by locally increased levels of interleukin (IL) 4. The bronchial epithelium plays an important role in the initiation and perpetuation of inflammatory reactions within the airways. However, little is known about the presence of IL-4 receptors on human bronchial epithelial cells, or the effects of IL-4 on these cells. In this report, definitive evidence of IL-4 receptor expression on human bronchial epithelial cells using several methods is presented. IL-4 receptor expression on human bronchial epithelial cells in vivo was demonstrated using in situ hybridization and immunohistochemistry. No difference in IL-4 receptor protein expression was observed between bronchial biopsies of healthy subjects compared to allergic asthmatics. Cultured human bronchial epithelial cells also expressed IL-4 receptor mRNA and protein (as determined by RT-PCR analysis and flow cytometry, respectively). IL-4 receptor protein expression by bronchial epithelial cells could be increased by stimulation with PMA+calcium ionophore, whereas IL-1beta and IL-6 decreased IL-4 receptor expression. A cyclic AMP analogue and IL-4 had no effect. Finally, it is shown that the IL-4 receptor is functionally active as IL-4 stimulates the release of IL-8, monocyte chemoattractant protein 1, and particularly IL-1 receptor antagonist by human bronchial epithelial cells. It is concluded that human bronchial epithelial cells express IL-4 receptors both in vivo and in vitro. Stimulation of human bronchial epithelial cells by IL-4 may result in the release of both pro- and anti-inflammatory mediators known to be upregulated in asthmatic airways.     

Active listening to cancer patients' stories

Approximately two thirds of all Dutch cancer patients have severe emotional problems; shortly after their change from the treatment regime into the regime of medical controls. Half of them even need professional support. It is, therefore, important that a professional listens with empathy to the patient's version of the illness story. Story telling helps to overcome the existential crisis of being a cancer patient; it is an essential step in the revalidation process. Themes and open questions which structure the communication are suggested in this article.     

Clinical and research issues in breast cancer genetics

Breast cancer is the most common form of cancer in women in the U.S. The risk factors for developing breast cancer include increasing age, a family history of breast cancer, and the lack of a child by age 30. A substantial fraction of breast cancer, however, occurs in women who have no identifiable risk factors. The diagnosis, pathology, treatment, and presymptomatic testing of cancer susceptibility genes are reviewed. Syndromes with an associated risk of breast cancer are described, such as hereditary breast-ovarian cancer syndrome, Li-Fraumeni syndrome, ataxia telangiectasia, and Cowden's disease. With the localization of the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing are assuming an ever greater measure of importance. The sensitivity and specificity for molecular testing of cancer susceptibility genes, however, have not been well defined. The progress in presymptomatic genetic testing is further hampered by various factors such as the technical difficulty in distinguishing mutations from polymorphisms, the number of different mutations identified thus far and the possibility of false positive and false negative results. Laboratory quality assurance/quality control issues are of paramount importance to avoid misleading interpretations. Many issues surrounding genetic screening and testing, such as insurance and employment discrimination, privacy, and informed consent, are under active debate, and guidelines and standards are under active development. It is therefore important to proceed with caution, so that irreversible harm resulting from data misinterpretation can be avoided.     

Study of relapsing remitting experimental allergic encephalomyelitis SJL mouse model using MION-46L enhanced in vivo MRI: early histopathological correlation

Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.     

Prevalence, epidemiology and geographical distribution of Sporothrix schenckii infections in Gauteng, South Africa

Forces exerted on the right and left lingual and buccal flanges of Kennedy Type I mandibular dentures were studied using an 8 channel recording technique, during resting, swallowing, talking, reading and simulated mastication. The effects of adaptation, head position and incremental thickening of the flanges were determined. Highest forces were recorded when swallowing, with smaller differences between the other activities. Lingual forces were higher than buccal, and posterior forces higher than anterior ones. There was a highly significant relationship between increases in flange thickness of 2 and 3mm and increases in peak forces. Evidence for adaptation and effects related to head position was weaker.     

A family of fatty acid transporters conserved from mycobacterium to man

Long chain fatty acids (LCFAs) are an important source of energy for most organisms. They also function as blood hormones, regulating key metabolic functions such as hepatic glucose production. Although LCFAs can diffuse through the hydrophobic core of the plasma membrane into cells, this nonspecific transport cannot account for the high affinity and specific transport of LCFAs exhibited by cells such as cardiac muscle, hepatocytes, and adipocytes. Transport of LCFAs across the plasma membrane is facilitated by fatty acid transport protein (FATP), a plasma membrane protein that increases LCFA uptake when expressed in cultured mammalian cells [Schaffer, J. E. & Lodish, H. F. (1994) Cell 79, 427-436]. Here, we report the identification of four novel murine FATPs, one of which is expressed exclusively in liver and another only in liver and kidney. Both genes increase fatty acid uptake when expressed in mammalian cells. All five murine FATPs have homologues in humans in addition to a sixth FATP gene. FATPs are found in such diverse organisms as Fugu rubripes, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Mycobacterium tuberculosis. The function of the FATP gene family is conserved throughout evolution as the C. elegans and mycobacterial FATPs facilitate LCFA uptake when overexpressed in COS cells or Escherichia coli, respectively. The identification of this evolutionary conserved fatty acid transporter family will allow us to gain a better understanding of the mechanisms whereby LCFAs traverse the lipid bilayer as well as yield insight into the control of energy homeostasis and its dysregulation in diseases such as diabetes and obesity.     

Childhood Lead Poisoning in Russia: A Site-specific Pediatric Blood Lead Evaluation

The association between the actual status of cryoglobulins (CGs) expression in hepatitis C-related chronic liver disease (C-CLD) and different types of liver pathology, HCV-RNA titers and genotypes was investigated. Sixteen out of 1340 ordinary clinical specimens were CGs-positive (1%), and in 8 of them (50%) the patients blood was HCV-RNA positive. CGs was detected in 63% of C-CLD patients as a whole, but when compared with the histological findings in the liver, it was 88% in F3, and 92% in A3, and thus high percentages were detected in patients with progression of liver fibrosis and patients with strong activity. Serum IgG, IgM, transaminase and gamma-GTP levels were significantly higher in the patients with CGs, and their RA test and C3dCIC levels tended to be higher, but the differences were not significant, and no association was found with the anti-nuclear antibody positive level, or the HCV-RNA titers or genotypes. Based on the above, there was a clear involvement of HCV infection, especially the activity and histological progression of hepatitis in CGs formation in Japan as well, but there were few extrahepatic manifestations, suggesting differences in CGS levels and immune response to CGs from cases in Western countries.     

Dextromethorphan O-demethylation polymorphism in Jordanians

Routine transpyloric placement of feeding tubes reduces aspiration in intensive care unit patients. Spontaneous passage eliminates the need for radiologic or endoscopic intervention. It is unclear whether the addition of a weight to the end of the tube or the use of the prokinetic agent metoclopramide in the conventional dose (10 mg) improves spontaneous transpyloric placement. In a randomized, prospective trial, 39 intensive care unit patients (age > 2 years) had a total of 50 nasoenteral tubes placed after intravenous metoclopramide (20 mg in adults, 0.2 mg/kg in children). The tubes were 8 French in diameter with either a weighted end or an unweighted bullet tip. Tip position was confirmed radiographically within 4 hours after blinded placement and at 1 and 2 days if spontaneous passage had not occurred. At 4 hours, 36% of the weighted tubes and 84% of the unweighted tubes (p < .002) had passed through the pylorus. At 1 day, 48% of the weighted tubes and 86% of the unweighted tubes (p < .007) had achieved transpyloric position. At 2 days, 56% and 92% of the weighted and unweighted tubes, respectively, had passed through the pylorus (p < .009, chi 2). The occurrence of transpyloric passage and the rapidity at which it occurred was significantly greater for the unweighted tube during all time periods. A poststudy trial was conducted to evaluate the effect of the normal dose of metoclopramide (10 mg in adults and 0.1 mg/kg in children) and the transpyloric passage of the unweighted feeding tube. Twenty-five patients received 10 mg of metoclopramide before the insertion of the unweighted tube.(ABSTRACT TRUNCATED AT 250 WORDS)