Thin layer chromatography of catecholamines and their metabolites

Zusammenfassung Eine einfache, schnelle und empfindliche Methode zur dünnschichtchromatographischen Trennung von 0,2–1µg Menge von Noradrenalin, Adrenalin, Normetanephrin, Metanephrin, 3,4-Dihydroxy-mandelsäure und 3-Methoxy-4-hydroxymandelsäure wird beschrieben.     

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.     

Ethanol-induced changes in plasma glucose,insulin and glucagon in fed and fasted rats

Summary Orally administered ethanol produced dose-related suppression of IRI levels and elevation of IRG levels in fed and fasting rats. Plasma glucose levels were unaffected in the fasting rats, but a moderate hyperglycemic response accompanied the decline in IRI and the rise in IRG observed in the fed rats.This research was supported in part by a grant from the National Institute on Alcohol Abuse and Alcoholism (AA-3218) and by a supplemental grant from the National Council on Alcoholism.     

Biochemical evidence for two types of noradrenaline storage particles in rabbit iris

Summary Centrifugation techniques were used to determine the subcellular distribution of noradrenaline (NA) and dopamine -hydroxylase (DH) in the rabbit iris. By application of isopycnic and differential gradient centrifugation methods 2 types of NA vesicles could be demonstrated. Of the total particle bound NA about 70% is associated with light and about 30% with heavy vesicles. For both types of vesicles the distribution of DH reflected that of NA.     

Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins.

Corticotropin-releasing factor (CRF), is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRF concentrations in the human peripheral circulation are normally low, they increase throughout pregnancy and fall rapidly after parturition. Maternal plasma CRF probably originates from the placenta, which responds to the bioactive peptide and produces the peptide and its messenger RNA. Even though CRF concentrations in late gestational maternal plasma are similar to those in rat hypothalamic portal blood and to those that can stimulate release of adrenocorticotropic hormone (ACTH) in vitro, maternal plasma ACTH concentrations increase only slightly with advancing gestation and remain within the normal range. Several groups have now reported the existence of a CRF-binding protein in human plasma which inactivates CRF and which has been proposed to prevent inappropriate pituitary-adrenal stimulation in pregnancy. The binding protein was recently purified from human plasma. We have now isolated and partially sequenced the binding protein, allowing us to clone and characterize its complementary DNA from human liver and rat brain. Expression of the cDNAs for human and rat binding protein in COS7 cells showed that these proteins bind CRF with the same affinity as the native human protein. Both rat and human recombinant binding proteins inhibit CRF binding to a CRF antibody and inhibit CRF-induced ACTH release by pituitary cells in vitro.