Asthma and the diver

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism, ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated with diving, including Henry’s law and Boyle’s law, to provide a more intimate understanding on physiological changes occurring in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in recreational diving without apparent increased risk of an asthma-related event.     

How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms.     

A luciferase expression system for Physarum that facilitates analysis of regulatory elements

We have developed a transient expression system for the protist Physarum polycephalum based on firefly luciferase. We demonstrate the utility of this system for comparing the activities of different promoters in Physarum amoebae, and also for detecting genetic elements that affect the level of gene expression. This system is likely to facilitate improvements in the stable transformation of this organism.     

Age-dependent cerebral metabolic effects of unilateral nucleus basalis magnocellularis ablation in rats

To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [14C]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalocortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease.     

EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells

Carcinomas of the prostate and other lineages often present an autocrine stimulatory loop acting via the EGF receptor (EGFR). We have recently shown that EGFR-mediated signals enhance DU-145 prostate carcinoma cell transmigration of an extracellular matrix in vitro, and that this increased invasiveness was independent of proteolytic degradation of the matrix (Xie et al., 1995, Clin Exp Metastasis, 13, 407). To determine whether up-regulated EGFR signaling promotes tumor progression in vivo and to define the EGFR-induced cell property responsible, we inoculated athymic mice with genetically-engineered DU-145 cells. Parental DU-145 cells and those transduced to overexpress a full-length wild type (WT) EGFR formed tumors and metastasized to the lung when inoculated in the prostate and peritoneal cavity. The WT DU-145 tumors were more invasive. DU-145 cells expressing a mitogenically-active, but motility-deficient (c'973) EGFR formed small, non-invasive tumors without evidence of metastasis. All three sublines demonstrated identical, EGFR-dependent rates of cell growth in vitro, suggesting that the differential invasiveness was not due to altered growth rates. To determine whether cell motility may be, in part, responsible for tumor invasiveness, we treated WT DU-145 intraperitoneal tumors with a pharmacologic agent (U73122) which blocks EGFR-mediated cell motility but not mitogenesis. Under this treatment regimen, the WT DU-145 cells formed tumors of similar numbers and size to those formed without treatment; however, these tumors were much less invasive. These data suggest that EGFR-mediated cell motility is an important mechanism involved in tumor progression, and that this cell property may represent a novel target to limit the spread of tumors.     

Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor

4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-IBB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-IBB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB.     

The neuroendocrine stress hormone norepinephrine augments Escherichia coli O157:H7-induced enteritis and adherence in a bovine ligated ileal loop model of infection

The role of the neuroendocrine environment in the pathogenesis of enteric bacterial infections is increasingly being recognized. Here we report that norepinephrine augments Escherichia coli O157:H7-induced intestinal inflammatory and secretory responses as well as bacterial adherence to intestinal mucosa in a bovine ligated ileal loop model of infection. Norepinephrine modulation of enteritis and adherence was dependent on the ability of E. coli O157:H7 to form attaching and effacing lesions.     

Spherical lesion phantoms for testing the performance of elastography systems

A set of three cubic one-litre phantoms containing spherical simulated lesions was produced for use in comparing lesion detection performance of different elastography systems. The materials employed are known to be stable in heterogeneous configurations regarding geometry and elastic contrast identical with (storage modulus of lesion material) / (storage modulus of background material), and regarding ultrasound and NMR properties. The materials mimic soft tissues in terms of elastic, ultrasound and NMR properties. Each phantom has only one value of elastic contrast (3.3, 4.6 or 5.5) and contains arrays of 1.6 mm, 2 mm, 3 mm and 4 mm diameter spherical simulated lesions. All the spheres of a given diameter are arranged in a regular array with coplanar centres. Elastograms of an array made with ultrasound allow determination of the depth range over which lesions of that diameter and elastic contrast can be detected. Two phantoms are made from agar-plus-gelatin-based materials, and one is made from oil-in-gelatin dispersions. The methods for producing the phantoms are described in detail. Lesion detection performances for two ultrasound systems, both operating at about 7.5 MHz and focused at about 5 cm, were quantified with distinctions between the two systems demonstrated. Neither system was capable of detecting any of the 1.6 mm lesions. Phantoms such as these should be useful in research labs that are refining hardware and/or software for elastography.