Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids)

BACKGROUND: Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases. OBJECTIVE: The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes. METHODS: Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch pollen-allergic donors. To determine whether the modification of natural (n)Bet v 1 with formaldehyde or maleic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional birch pollen-allergic individuals, were tested for their reactivity with these products. RESULTS: The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into allergoid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and the stimulatory potential of the allergoid was observed. Mechanisms of suppression or of anergy induction were excluded as an explanation for the non-reactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v 1 to a similar extent. CONCLUSION: These results demonstrate differences in the availability of T-cell epitopes between allergoids and unmodified allergens, which are most likely due to structural changes within the allergen molecule.     

Coupling of the human Y2 receptor for neuropeptide Y and peptide YY to guanine nucleotide inhibitory proteins in permeabilized SMS-KAN cells

This study of location information involved in information persistence used the partial-report paradigm. Six subjects were asked on 144 trials to recall positions of dots presented in a display. The subjects were instructed to maintain only information on location (but not on identity information) of the presented dots until a partial-report cue was introduced. The effects of display duration (50, 200, and 350 msec.) and cue delay (interval between the display offset and the onset of the partial-report cue: 50, 250, and 500 msec.) were examined. Analysis showed effect of cue delay on partial-report performance decreased as the duration of display increased so performance was negatively affected by the cue delay only when the subject was exposed to the presented dots for 50 msec. Contrarily, partial-report performance did not decline much for a 200-msec. duration and showed little variation in a 350-msec. duration, even though the cue delay increased. Consequently, the decay of the information on location mediating partial-report performance about dots varies with duration of display.     

Measurement of volatile organic compounds in exhaled breath as collected in evacuated electropolished canisters

A set of three complementary analytical methods were developed specifically for exhaled breath as collected in evacuated stainless steel canisters using gas chromatographic-mass spectrometric detection. The first is a screening method to quantify the carbon dioxide component (generally at 4-5% concentration), the second method measures the very volatile high-level endogenous compounds [e.g. acetone and isoprene at 500-1000 parts per billion by volume (ppbv), methanol, ethanol, dimethylsulfide at 2-10 ppbv], and the third method is designed to measure trace-level environmental contaminants and other endogenous volatile organic compounds (VOCs) (sub-ppbv) in breath. The canister-based sample format allows all three methods to be applied to each individual sample for complete constituent characterization. Application of these methods is shown to be useful in the following ways: analysis of CO2 levels indicates the approximate quantity of alveolar breath collected (as opposed to whole breath) in a sample; levels of major endogenous compounds are shown to be influenced by physical activities and subsequent recovery periods; and environmental exposures to xenobiotic VOCs can be characterized by assessment of post-exposure breath elimination curves. The instrumentation and methodology are described and example chromatograms and quantitative data plots demonstrating the utility of the methods are presented.     

Anti-B-50 (GAP-43) antibodies decrease exocytosis of glutamate in permeated synaptosomes

The involvement of the protein kinase C substrate, B-50 (GAP-43), in the release of glutamate from small clear-cored vesicles in streptolysin-O-permeated synaptosomes was studied by using anti-B-50 antibodies. Glutamate release was induced from endogenous as well as 3H-labelled pools in a [Ca(2+)]-dependent manner. This Ca(2+)-induced release was partially ATP dependent and blocked by the light-chain fragment of tetanus toxin, demonstrating its vesicular nature. Comparison of the effects of anti-B-50 antibodies on glutamate and noradrenaline release from permeated synaptosomes revealed two major differences. Firstly, Ca(2+)-induced glutamate release was decreased only partially by anti-B-50 antibodies, whereas Ca(2+)-induced noradrenaline release was inhibited almost completely. Secondly, anti-B-50 antibodies significantly reduced basal glutamate release, but did not affect basal noradrenaline release. In view of the differences in exocytotic mechanisms of small clear-cored vesicles and large dense-cored vesicles, these data indicate that B-50 is important in the regulation of exocytosis of both types of neurotransmitters, probably at stages of vesicle recycling and/or vesicle recruitment, rather than in the Ca(2+)-induced fusion step.     

Most common dermatologic problems identified by internists, 1990-1994

BACKGROUND: Internists in all settings see many patients with skin conditions. Thus, their education in dermatology is important. Information on which areas of dermatology are most commonly seen in internal medicine practices is necessary for designing effective educational programs on skin disease. OBJECTIVE: To determine what types of dermatologic problems internists most commonly diagnose. METHODS: National Ambulatory Medical Care Survey data from 1990 to 1994 were analyzed for dermatologic diagnoses. Physicians specializing in internal medicine and all its subspecialties were compared with dermatologists and with other physicians. RESULTS: The most common skin disorders diagnosed by internists were dermatitis (15.8% of all diagnoses) and bacterial skin infections (14.0% of all diagnoses). Combined, bacterial, fungal, and viral infections included 28.3% of the most common dermatologic diagnoses made by internists. The top 10 most common diagnoses accounted for 57.9% of all skin-related diagnoses and the top 20 most common diagnoses accounted for 72.8%. Internists were more likely to see patients for bacterial skin infections, herpes infection, exanthem, urticaria, and insect bites while dermatologists more commonly saw patients for actinic and seborrheic keratoses, warts, benign and malignant skin tumors, and psoriasis. CONCLUSIONS: The most common dermatologic diseases diagnosed by internists differ considerably from those diagnosed by dermatologists. Because dermatologists do much of the dermatology teaching of internal medicine residents, it is important to recognize these differences to place emphasis on the proper areas of study. Some common or serious skin conditions not often diagnosed by internists such as psoriasis and melanoma also deserve attention in internal medicine training programs.     

Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat liver and cultured rat hepatocytes

In this study the pharmacodynamics were characterized of rat hepatic cytochrome P-450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], which is metabolized further and therefore less prone to bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103, 88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values) for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-, 22-, and > or = 1-fold, respectively, compared to control values. The potencies of the three congeners for CYP2B induction appeared also to be similar, with EC50 values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51 microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or = 2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite marked differences in bioretention among the congeners.     

Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis

The efficacy of ipriflavone was investigated in a 1-year double-blind, placebo-controlled, parallel group clinical trial. Ninety-one postmenopausal women completed the study, 41 received ipriflavone and 50 placebo treatment. After six months the bone mineral density of the L2-L4 vertebral region increased in the ipriflavone-treated group (0.015 g/cm2), whereas it decreased in the placebo-treated group. The differences between the treatment groups were statistically significant. Our results support the efficacy of ipriflavone in the treatment of postmenopausal osteoporosis. Since the positive effect was more pronounced after 6 months, the possibility of an intermittent ipriflavone treatment might be taken into consideration in the future.     

The use of chemotherapy resistance in cancer treatment

It is not inconceivable that everything except the basic structure of an office building could be prefabricated in the near future. Quality and schedule are nearly always improved with prefabrication due to the simple change from an uncontrolled work environment to a controlled one. One Ludgate Place, is a 23,600 m2, ￡30,000,000 speculative commercial development in central London. This high quality office building has an exposed structural steel frame, within which are fitted prefabricated cladding panels. This paper combines the results from two research programs. The first in the area of prefabrication and the second in the management of high quality cladding construction. The writers describe the Ludgate Place project, incorporating the cladding design, testing, assembly, and installation. Factors that influenced the decision to use prefabrication are presented and evaluated, namely, cost; time; quality; past experience; design; weather joints; performance tests; site logistics; and safety. Construction interfaces and tolerances, particularly between cladding and structure, are discussed, and the future of prefabricated cladding is considered.