Regulation of endothelial permeability by beta-adrenoceptor agonists: contribution of beta 1- and beta 2-adrenoceptors

The barrier function of cultured, macrovascular endothelial cells derived from bovine aorta was analyzed using confluent monolayers of cells and measuring the exchange of fluorescein dextrans of different molecular masses. The effects of beta-adrenoceptor agonists with different selectivity for beta 1- and beta 2-adrenoceptors (AR) were investigated. Formoterol, a novel high-affinity agonist for beta 2-AR recently introduced in the treatment of bronchial asthma, showed a significant reduction of cell permeability with subnanomolar concentrations, whereas the catecholamines (-)-isoproterenol and (-)-norepinephrine only showed significant effects with micromolar concentrations. In order to elucidate if this difference in potential to regulate cell permeability is related to appropriate changes in the selectivity and affinity of the agonists for beta 2 AR, we investigated the beta AR-coupled adenylate cyclase (AC) in membranes from endothelial cells and compared AC stimulation with the binding of agonists to the receptors using [125I](-)-iodopindolol as radioligand. beta-Adrenoceptors revealed to be closely coupled to AC as assessed by a similar magnitude of effects by receptor agonists in comparison to GTP analogues and direct stimulants of AC activity. AC activity was increased by formoterol in parallel to its receptor occupancy of beta 2AR with nanomolar concentrations which were 50-fold higher than those used for the regulation of cell permeability indicating the existence of spare receptors. In contrast to formoterol, the catecholamines (-)-isoproterenol and (-)-norepinephrine stimulated AC activity through both beta 1AR and beta 2AR. From the overproportional high contribution of beta 1AR to AC stimulation (42%) in comparison to its low fraction (13%) in receptor binding we calculated that beta 1AR is 3-4-fold more effectively coupled to AC than beta 2 AR.     

High dietary calcium level decreases colonic phytate degradation in pigs fed a rapeseed diet

The degradation of phytate (inositol hexaphosphate) in rapeseed meal diet not containing phytase activity was studied in 15 growing ileum-fistulated pigs. Stomach and small intestinal degradation and total gastrointestinal degradation were compared. The effect of addition of calcium carbonate to the rapeseed meal diet at two levels (9.2 and 18.5 g/kg diet) was investigated. A commercial barley-wheat-soybean diet with intrinsic phytase activity was used as reference. Phytate and its hydrolysis products in diets, ileal digesta and feces were determined by HPLC ion-pair chromatography. Hydrolysis of phytate in the stomach and small intestine was 35-45% in pigs fed the rapeseed meal diet independent of calcium addition, and 65% in pigs fed the reference diet. Total gastrointestinal degradation of phytate in pigs fed the rapeseed diet was 97, 77 and 42% (P < 0.001) when calcium intakes were 4.5, 9.9 and 15 g/d, respectively; total gastrointestinal degradation was 72% in pigs fed the reference diet. The intestinal phytate degradation pattern, when rapeseed diet was fed, indicated the activity of an unspecific phosphatase, whereas that of the reference diet indicated intrinsic dietary phytase activity. We conclude that dietary supplementation of calcium carbonate decreases the phytate degradation in the colon of pigs, but not in the stomach and small intestine.     

Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study

We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.     

Isolation and characterization of three Dictyostelium myosin-I isozymes

Using ion exchange chromatography and an ATP-dependent actin precipitation step, we have isolated three myosin-I isozymes that, together, account for most of the K+EDTA-ATPase activity recovered from extracts of Dictyostelium. The two major myosin-I isozymes, present in approximately equal amounts, had apparent molecular masses of 125 kDa on SDS gels and have been identified by amino acid sequence analysis as the products of the Dictyostelium myosin-IB (DMIB) and myosin-ID (DMID) genes. DMIB, with a specific K+EDTA-ATPase activity 10-fold higher than DMID, was responsible for most of the activity in cell extracts. The third isozyme, present in low amounts, had an apparent molecular mass of 137 kDa on SDS gels and is too large to be the product of any of the known myosin-I genes. DMIB eluted from DE53 cellulose columns as two distinct peaks (II and III). Addition of the phosphatase inhibitor okadaic acid to the extraction buffer increased the fraction of DMIB recovered from growth phase cells in peak III from 35 to 70%. DMIB isolated from peak III, but not from peak II, displayed a significant level of actin-activated MgATPase activity. These results indicate that peak III represents a phosphorylated, actin-activatable form of DMIB.     

Swenson's operation for neonatal Hirschsprung's disease

OBJECTIVE: To describe our experience with Swenson's operation for Hirschsprung's disease done during the neonatal period. DESIGN: Retrospective study. SETTING: University department of paediatric surgery. SUBJECTS: 10 Neonates with Hirschsprung's disease. INTERVENTIONS: Rectosigmoidectomy and pull through (Swenson's operation), with covering transverse colostomy. MAIN OUTCOME MEASURES: Mortality, morbidity, and continence. RESULTS: The median age at definitive operation was 25 days (range 15-35). There was one late death three weeks after discharge from hospital of respiratory and cardiac failure. Two patients presented with caecal perforation and two with intestinal obstruction; in all four Hirschsprung's disease was diagnosed on frozen section, a transverse colostomy was done, and the Swenson's operation was done electively. The other six were diagnosed by barium enema examination and biopsy, and underwent total bowel irrigation followed by Swenson's operation and transverse colostomy. The colostomies were closed three to four weeks later. There were no postoperative complications. All nine surviving patients were continent (3-4 stools/day), at a mean (SD) follow up of 21 (5) months. CONCLUSION: With the current high standards of anaesthesia and neonatal intensive care, and an experienced surgeon, Swenson's operation for neonatal Hirschsprung's disease is safe and the procedure of choice for this condition.     

Factor XIIIa immunoreactivity in primary and secondary tumours of the meninges

Occasionally variants of meningeal hemangiopericytomas (HPC) may be confused with primary and secondary tumours of the meninges by virtue of their features and patterns of growth. Until now, a specific immunohistochemical marker for HPC could not be identified. HPC are reported to express factor XIIIa (F XIIIa) in the cytoplasm of the tumour cells. In an effort to assess the diagnostic value of F XIIIa for meningeal HPC, we investigated 38 primary meningeal tumours (6 HPC, 28 meningiomas of various subtypes, 4 meningeal sarcomas) and 23 secondary meningeal tumors (8 metastatic carcinomas, 6 gliosarcomas, 9 anaplastic gliomas) with anti-F XIIIa antibody. All HPC revealed 5%-20% of F-XIIIa-positive neoplastic cells. Malignant fibrous histiocytomas and gliosarcomas with MFH-like structures also exhibited multiple F-XIIIa-positive cells. Most of the F-XIIIa-positive cells in meningiomas were identified as macrophages. Furthermore, there was a population of small dark cells of uncertain histogenesis. Cells with positive immunoreactivity for F-XIIIa in metastatic carcinomas and gliomas apparently were of macrophage lineage. Though, in some cases, it would have been difficult to distinguish reactive from neoplastic cells without simultaneous immunohistochemical investigation with antibodies for macrophages, cytokeratin, EMA and GFAP. Because of these uncertainties, wo believe that the potential of F XIIIa-antibody in obtaining precise differential diagnostic information is limited.     

Coincident indices of exons and introns

In this paper, the coincident index, proposed by W. F. Friedman in cryptology, is made use of in DNA sequence analysis and exon prediction. The coincident index of exons exceeds that of introns by many times, and is mainly affected by window length, which is correlated negatively with the coincident index. An optimal exon prediction scheme was obtained by experimental analysis with an orthogonal table. Besides exons, many other special sites such as tandem repeats can be identified by using the coincident index approach. The application of this approach to the ARV-2 (AIDS associated retrovirus 2) genome found three new possible coding regions and some unusual base composition regions which are probably related to definite biological functions.     

The femur-tibia control system of stick insects--a model system for the study of the neural basis of joint control

In a form of top-down analysis, the femur-tibia control system of stick insects is investigated. Open-loop experiments show that it is mainly velocity-sensitive with an extremely low velocity-threshold, that it possesses a very high gain and that it has only a very small phase reserve and thus works close to instability. The closed-loop system generates catalepsy. The system consists of a single sense organ with approximately 80 sense cells with known characteristics, a small number of interneurones (mainly non-spiking ones) and a small number of motor neurones. The characteristics of the whole system can quantitatively be attributed to the characteristics of its elements. The gain of the loop is state-dependent and the system is 'switched off' during active movements and replaced by a control system with different attributes. It is discussed that most of the characteristics of this system are, at least qualitatively, similar to joint control systems in other animals. Because the described system can be more easily investigated than other systems (especially in vertebrates) it can serve as a model against which more complicated joint control loops may be compared.     

The neu-oncogene product in serum and tissue of patients with breast carcinoma

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'.