Characterization of contraction-mediating prostanoid receptors in human hand veins: effects of the thromboxane receptor antagonists BM13,505 and AH23848

The effects of prostaglandin F2 alpha, prostaglandin E1, prostaglandin E2 and the thromboxane A2 analogue U46619 were determined in ring segments of human hand veins. All prostanoids except prostaglandin E1 elicited contraction. The order of potency was U46619 greater than prostaglandin F2 alpha greater than prostaglandin E2. The thromboxane receptor antagonists BM13,505 and AH23848 both caused a parallel rightward displacement of the concentration-response curve for U46619 without depression of the maximum contraction, suggesting competitive antagonism. Schild plots for both antagonists yielded regression lines with slope indices not significantly different from unity. The pA2 values for BM13,505 and AH23848 were 7.9 and 8.4 respectively. Both antagonists also effectively inhibited prostaglandin F2 alpha-induced contractions. However, AH23848 significantly reduced the maximum response, and the results with BM13,505 gave no clear indication of the type of inhibition. In vein segments submaximally contracted by 5-hydroxytryptamine, prostaglandins E1 and E2 produced a biphasic response with a relaxation at low and a contraction at high concentrations. Prostaglandin F2 alpha and U46619 failed to elicit relaxation under these conditions. However, in the presence of either thromboxane receptor antagonist, prostaglandin F2 alpha but not U46619 produced a relaxation. The results are compatible with the presence of at least two prostanoid receptors in human hand veins, a contraction-mediating thromboxane receptor and an as yet unclassified receptor eliciting relaxation. U46619 was a potent agonist at the thromboxane receptor and prostaglandin E1 and E2 preferentially stimulated the relaxation-mediating receptor, whereas prostaglandin F2 alpha appeared to be active at both receptor sites.     

Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis.

The authors have used intracerebral microdialysis to develop a method for routine monitoring of disturbances in brain energy metabolism in patients in the neurosurgical intensive care unit. Microdialysis was conducted for periods ranging from 2.3 to 8.3 days in four patients (three with severe head injuries and one with severe subarachnoid hemorrhage). Altogether, 4447 chemical analyses from 587 dialysis samples were carried out. Concentrations of the energy-related metabolites lactate, pyruvate, and hypoxanthine were measured, and the lactate:pyruvate ratio was calculated. In addition, the acids glutamate, aspartate, taurine, glutamine, asparagine, and glycine were measured in one patient. The microdialysis data were matched with various clinical events, including intracranial hypertension and therapeutic interventions such as initiation or withdrawal of barbiturates and cerebrospinal fluid drainage. The present study shows that microdialysis can be used for long-term measurement of extracellular fluid (ECF) energy-related metabolites and amino acids in the frontal cortex of neurosurgical patients in a clinical setting. Fluctuations of the measured ECF energy-related substances corresponded to various clinical events presumably involving hypoxia/ischemia. The authors found a 25-fold increase in ECF glutamate, aspartate, and taurine under conditions of energy perturbation, as indicated by high levels of the lactate:pyruvate ratio, lactate, and hypoxanthine. The use of long-term intracerebral microdialysis in patients opens a new field of clinical research, with many possibilities for improving insight into intracranial dynamics in acute cerebral conditions.     

Hip fractures in urban population in Finland.

We studied prospectively the occurrence of hip fractures among the over 49-year-old urban populations (n = 88,206) in the cities Tampere, Jyv?skyl? and Kotka in 1989 and compared the results with a parallel Scandinavian multicentre study. During 1989, there were 266 inhabitants who were treated for a hip fracture, 213 of them were women. Women had in 132 cases a femoral neck fracture and in 81 cases a trochanteric fracture, and the corresponding numbers for men were 22 and 31. Among women, the total hip fracture incidence in Jyv?skyl? (n = 22) was the lowest when compared with the ones in Tampere (n = 47) and Kotka (n = 36). These incidences were on average lower than in the other Scandinavian cities studied in parallel. The all over ratio of femoral neck/trochanteric fractures was 1.1 in Tampere, 3.0 in Jyv?skyl? and 2.2 in Kotka and in Tampere, women had 9.3 times more femoral neck fractures than men. Our study showed that in Finland in three major cities the hip fracture incidence was lower than what has been similarly registered in corresponding urban populations in other Scandinavian countries. We also point out that the relative part of trochanteric fractures appears to be increasing.     

Lipoprotein lipase in guinea-pig adrenals: activity, mRNA, immunolocalization and regulation by ACTH.

Lipase activity in homogenates of guinea-pig adrenals was studied under conditions which exclude the hormone-sensitive lipase/cholesterol ester hydrolase. Antibody inhibition and chromatography on heparin-Sepharose showed that most of the activity was due to lipoprotein lipase (LPL), and that there was only a small amount of hepatic lipase activity. Northern blot analysis of total RNA demonstrated the same three adrenal LPL mRNA species (1.8, 3.1 and 3.5 kb) as were found in adipose tissue and heart. Hence, at least part of the LPL activity in adrenals is due to enzyme synthesized within the tissue. Immunolocalization showed that LPL was associated with the endothelium of blood vessels throughout the gland. In addition, there was cytoplasmic immunoreaction, suggesting that lipase was synthesized in a subpopulation of cells in the transitional zone between the fasciculata and reticularis layer of the cortex, particularly over lipid-filled cells. There was also intense immunofluorescence over scattered cells in the adrenal medulla. Treatment with an ACTH analogue depot (20 IU, i.m.) for 11 days induced a 12-fold increase in serum cortisol and increased adrenal weight 2.2-fold. The treatment induced increases in LPL mRNA (about twofold), LPL activity and in the number of cells in the adrenal cortex which gave an immunoreaction for LPL.     

Demonstration of endogenous lectins in synovial tissue.

We have recently shown that synoviocytes and extracellular matrices exhibit distinct patterns of carbohydrate expression. Their biological relevance is however not known. The purpose of the present study was to find out whether human synovial tissue would also show a specific receptor pattern for complex sugar molecules. Endogenous lectins were displayed by means of biotinylated neoglycoproteins and sulfated polysaccharides in paraffin-embedded material or cryosections. In addition to certain carbohydrate components that are known to be constituents of the carbohydrate part of cellular glycoconjugates, our panel included heparin and fucoidan, a sulfated fucose. Binding sites were shown using the avidin-peroxidase technique for light microscopy. The results were compared with immunohistochemical methods and enzyme histochemistry. Our study demonstrates that human synovial tissue contains a complex pattern of endogenous lectins depending on the different types of synovitis. The staining method we used in the investigation allows for precise localization of saccharide binding receptors and is therefore believed to be a reliable technique for further phenotypic characterization of synovial cells.     

Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins.

The lateral mobility of cell membrane glycoproteins is often restricted by dynamic barriers. These barriers have been detected by measurements of fluorescence photobleaching and recovery (FPR) and barrier-free path (BFP). To define the location and properties of the barriers, we compared the lateral mobility, measured by FPR and BFP, of wild-type class I major histocompatibility complex (MHC) membrane glycoproteins with the lateral mobility of mutant class I MHC glycoproteins truncated in their cytoplasmic domains. Mutants with 0 or 4 residues in the cytoplasmic domain were as mobile as lipid-anchored class I MHC molecules, molecules whose lateral mobility is relatively unrestricted by barriers. In contrast, mobility of class I MHC molecules with 7-residue cytoplasmic domains was as restricted as mobility of class I molecules with full-length, 31-residue cytoplasmic domains. Though some of the difference between the mobilities of mutants with 4- or 0-residue domains and the other class I molecules may be due to differences in the net charge of the cytoplasmic domain, FPR measurements of the mobility of molecules with 7-residue domains show that length of the cytoplasmic domain has an important influence on the lateral mobility. Model calculations suggest that the barriers to lateral mobility are 2-3 nm below the membrane bilayer.     

Changes in immunologic response in tonsillectomized children. I. Immunosuppression in recurrent tonsillitis.

The possible immunoregulatory role of the tonsils was studied by determining immunoglobulins IgG, A, M, E and factors C'3, C'4 and PFB of the complement system before and after tonsillectomy. The synthesis in vitro of IgG and IgM by lymphocytes stimulated with pokeweed mitogen was also measured. There were statistically significant differences between pre and post-operative levels of serum IgG, IgA and IgM, which decreased after surgery. Practically no change in the mean values of IgE and no significant differences in the levels of serum C'3, C'4, and PFB, were found. The in-vitro synthesis of both immunoglobulins (IgG, IgM) by lymphocytes increased significantly after tonsillectomy. Our results suggest that not only does tonsillectomy have no counterproductive effect on the immune system, but that, on the contrary, it seems to improve the immune response, since it appears to unblock the suppression to which the immune system was subject.