Characterization of GPRA, a novel G protein-coupled receptor related to asthma

We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth.     

Time course of the effect of intravenous dimetindene maleate

Summary In order to evaluate the time course of its effects, dimetindene maleate has been investigated in a histamine provocation model in man. Eight healthy male volunteers were treated i. v. with 4 mg dimetindene maleate or sodium chloride solution in a double blind, cross over study. Intracutaneous histamine injections were given at –1, 2, 5, 14, 17, 20, 23, 26, and 29 h following drug administration and the areas of flares and wheals were measured after 5, 10, 20, and 30 min. There was strong inhibition of the development both of flares and wheals, which was more pronounced for the former. Baseline adjusted areas under the curve differed significantly following drug and placebo treatment. The maximum effect was observed at 2 h.The mean residence time of the inhibitory effect was calculated to be 13 h compared to the mean residence time of dimetindene in blood of 5 h, which indicates a non-linear relationship between blood level and effect.     

CT in malignancy grading and prognostic prediction of non-Hodgkin's lymphoma

PURPOSE: The presence of tumor inhomogeneities in MR images of non-Hodgkin's lymphoma (NHL) provides information about malignancy grade and prognosis. The aim of this study was to determine whether CT images are also informative in these respects. MATERIAL AND METHODS: Sixty-three CT examinations in patients with NHL (32 high-grade and 31 low-grade tumors) were reviewed retrospectively by two senior radiologists. The tumor patterns were classified subjectively as homogeneous, slightly inhomogeneous or severely inhomogeneous and their relations to malignancy grade, clinical characteristics and prognosis were determined. RESULTS: Sixteen out of 17 patients with a severely inhomogeneous tumor pattern had high-grade NHL tumors while 21 out of 29 patients with a homogeneous tumor appearance had low-grade NHL tumors. Among chemotherapy-treated patients, those with the highest degree of inhomogeneity had a significantly worse prognosis (9 out of 11 patients died). This relationship was not found in patients treated with radiotherapy. CONCLUSION: A severely inhomogeneous tumor pattern on CT images was found to be associated with a high malignancy grade in NHL. This CT pattern was also compatible with a poor prognosis in patients treated with chemotherapy.     

Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers

Summary O-(-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period.There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (90 arbitrary units i.e. 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (–1.1, –5.9, and –7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.     

Morphologisch-experimenteller Beitrag zur Kenntnis der Vorgänge bei der Verpflanzung von autologer Beckenkammspongiosa bei Hunden

Die Einheilung von autologer Beckenkammspongiosa in einem durch Plattenosteosynthese stabilisierten Kontinuitätsdefekt eines Röhrenknochens wurde an 20 erwachsenen Boxerhunden unter Verwendung der Semidünnschnittechnik untersucht. Die Durchsicht der Semidünnschnitte des transplantierten Knochengewebes, welches 1, 2, 4 und 8 Wochen nach der Transplantation entnommen wurde, ergab folgende Ergebnisse:

[18F] FDG PET in Gastric Non-Hodgkin's Lymphoma

The possibility of using [¹⁸F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 Iow-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [¹⁸F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [¹⁸F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [¹⁸F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [¹⁸F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.     

Cell Envelope and Shape of Escherichia coli K12

Rod-shaped "ghosts" that are free of murein have been isolated from E. coli. The shape of these "ghosts" is maintained by a unit membrane soluble in sodium dodecyl sulfate. Ghosts consist of about 20-30% phospholipid (almost exclusively phosphatidylethanolamine) and 50-60% protein; a large fraction of the remaining material is lipopolysaccharide. Sodium dodecyl sulfate-gel electrophoresis reveals 4-5 different bands corresponding to molecular weights between 10,000 and 40,000. Treatment of ghosts with Pronase reduces this number to 3, and the rod shape still is not lost. Results of treatment of ghosts with a crude extract from Dictyostelium discoideum have supplied tentative evidence that at least one of these proteins is involved in the maintenance of rod shape. It does not appear too unlikely that these polypeptide chains are the final products of the genetic information specifying cellular shape.     

The global distribution of average volume of alcohol consumption and patterns of drinking

AIMS: To make quantitative estimates on a global basis of exposure of disease-relevant dimensions of alcohol consumption, i.e. average volume of alcohol consumption and patterns of drinking. DESIGN: Secondary data analysis. MEASUREMENTS: Level of average volume of drinking was estimated by a triangulation of data on per capita consumption and from general population surveys. Patterns of drinking were measured by an index composed of several indicators for heavy drinking occasions, an indicator of drinking with meals and an indicator of public drinking. Average volume of consumption was assessed by sex and age within each country, and patterns of drinking only by country; estimates for the global subregions were derived from the population-weighted average of the countries. For more than 90% of the world population, per capita consumption was known, and for more than 80% of the world population, survey data were available. FINDINGS: On the country level, average volume of alcohol consumption and patterns of drinking were independent. There was marked variation between WHO subregions on both dimensions. Average volume of drinking was highest in established market economies in Western Europe and the former Socialist economies in the Eastern part of Europe and in North America, and lowest in the Eastern Mediterranean region and parts of Southeast Asia including India. Patterns were most detrimental in the former Socialist economies in the Eastern part of Europe, in Middle and South America and parts of Africa. Patterns were least detrimental in Western Europe and in developed countries in the Western Pacific region (e.g., Japan). CONCLUSIONS: Although exposure to alcohol varies considerably between regions, the overall exposure by volume is quite high and patterns are relatively detrimental. The predictions for the future are not favorable, both with respect to average volume and to patterns of drinking.     

Intrinsic skeletal muscle alterations in chronic heart failure patients: a disease-specific myopathy or a result of deconditioning?

Chronic heart failure (CHF) patients frequently experience impaired exercise tolerance due to skeletal muscle fatigue. Studies suggest that this in part is due to intrinsic alterations in skeletal muscle of CHF patients, often interpreted as a disease-specific myopathy. Knowledge about the mechanisms underlying these skeletal muscle alterations is of importance for the pathophysiological understanding of CHF, therapeutic approach and rehabilitation strategies. We here critically review the evidence for skeletal muscle alterations in CHF, the underlying mechanisms of such alterations and how skeletal muscle responds to training in this patient group. Skeletal muscle characteristics in CHF patients are very similar to what is reported in response to chronic obstructive pulmonary disease (COPD), detraining and deconditioning. Furthermore, skeletal muscle alterations observed in CHF patients are reversible by training, and skeletal muscle of CHF patients seems to be at least as trainable as that of matched controls. We argue that deconditioning is a major contributor to the skeletal muscle dysfunction in CHF patients and that further research is needed to determine whether, and to what extent, the intrinsic skeletal muscle alterations in CHF represent an integral part of the pathophysiology in this disease.