Wilson’s disease—cause of mortality in 164 patients during 1992–2003 observation period

We studied the cause of death in a consecutive series of 164 patients with Wilson’s disease (WD) diagnosed over an 11 year period. A total of 20 [12% (95% CI 10.3–16.0)] died during the observation period. The relative survival rate of all patients in our group was statistically smaller than in Polish population. The main cause of death was the diagnosis in advanced stage of disease, but in six patients presenting with mild signs, we observed the progression of the disease despite treatment. There was no difference in mortality rate in patients treated with dpenicillamine or zinc sulphate as initial therapy.The prognosis for survival in the majority of WD patients is favourable, provided that therapy is introduced early.     

Phosphopyridoxal cyclic compounds with histamine and histidine. 7: The properties of pyridoxal and phosphopyridoxal cyclic compounds with histamine and histidine

Cyclic compounds synthesized from histamine (Hi) or histidine (His) with pyridoxal (PL)-[Hi-PL, His-PL] and Hi or His with pyridoxal 5-phosphate (PLP)-[Hi-PLP, His-PLP] were tested for stability in buffer, acid and base solutions, crude homogenates of various tissues and in the presence of enzymes which metabolize Hi or His. The cyclic pyridoxal compounds were stable in all experimental conditions, whereas phosphopyridoxal cyclic products were degraded by rat intestinal DAO and rat intestine homogenate, apparently enzymatically. In acidic and basic solutions changes in migration velocity and u.v. absorption spectrum occur. The characteristic fluorescence of these cyclic compounds is described.     

Spontaneous and concanavalin A-induced agglutination of chick-embryo neuronal cells

Concanavalin A-induced cell agglutination of different neuronal cells from the spinal cord and cerebral cortex of the chick reaches maximum values between the 9th and 11th day of embryogenesis. With further development, i.e. with increasing age, cell agglutination decreases dramatically. However, Concanavalin A binding sites were still found during the period of decreased agglutination. A pronounced difference between spontaneous and Concanavalin A-induced agglutination can be detected. The latter leads to the formation of special contact regions, where the cells develop pseudopods and remain rather motile.The results support the idea that Concanavalin A-induced agglutination, in contrast to spontaneous agglutination, is an active process of cellular interaction which is dependent on receptor mobility and related to surface movement and cell motility. Therefore this type of agglutination may be restricted to early motile stages of developing neuronal cells.     

Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical phenotype of the disease is varied. It is proposed that this variation may be a result of differential functional disruption of ATPase7B (ATP7B) resulting from mutations in the gene ATP7B. We aimed to assess the relationship between specific mutational defects in ATP7B and divergence in the phenotypic expression of WD. One hundred and forty-two patients with clinically, biochemically and genetically diagnosed WD were included in the study. The phenotypic expression of WD was compared between patients with different types of mutations in ATP7B, detected by direct sequencing of exons 1-21 of the gene. Twenty-six mutations were identified in ATP7B; eleven of them were mutations predicted to result in the absence of a full-length normal protein [frameshift/nonsense mutations; classified as 'severe' mutations (SMs)], 14 were missense mutations (MMs) and one was a splice site mutation. Patients with one or two SMs on their alleles had lower serum copper and ceruloplasmin and were younger when the first symptoms of the disease appeared, compared with individuals with two MMs. The effect of SMs on the WD phenotype was dose-dependent. It is concluded that mutations within ATP7B are very heterogeneous. Frameshift and nonsense mutations are associated with a severe phenotype of WD.     

Phosphopyridoxal complexes with histamine and histidine (3) the influence of presumed complex on activity of rat intestinal histaminase

Histamine in high concentration inhibits the rat intestinal histaminase (diamine oxidase E.C. 1.4.3.6). The apparent K_m is approximately 4.2×10^–5 M. This inhibition can be reversed by an addition of PLP.It was also found that excess of PLP inhibits enzyme activity. It is competitive inhibition.Histamine and other amines which were associated with enzyme inhibition form spectrophotometricaly demonstrable complex with PLP. The possible mechanism of the inhibitory action of PLP and complex with histamine and other amines on rat intestinal histaminase activity are discussed.     

Expression of the human erythroid Rh glycoprotein (RhAG) enhances both NH3 and NH 4 + transport in HeLa cells

The erythroid Rh-associated glycoprotein (RhAG) is strictly required for the expression of the Rh blood group antigens carried by Rh (D,CE) proteins. A biological function for RhAG in ammonium transport has been suggested by its ability to improve survival of an ammonium-uptake-deficient yeast. We investigated the function of RhAG by studying the entry of NH3/NH4+ in HeLa cells transiently expressing the green fluorescent protein (GFP)-RhAG fusion protein and using a fluorescent proton probe to measure intracellular pH (pHi). Under experimental conditions that reduce the intrinsic Na/H exchanger activity, exposure of control cells to a 10 mM NH4Cl- containing solution induces the classic pHi response profile of cells having a high permeability to NH3 (PNH3) but relatively low permeability to NH4+ (PNH4). In contrast, under the same conditions, the pHi profile of cells expressing RhAG clearly indicated an increased PNH4, as evidenced by secondary reacidification during NH4Cl exposure and a pHi undershoot below the initial resting value upon its removal. Measurements of pHi during methylammonium exposure showed that RhAG expression enhances the influx of both the unprotonated and ionic forms of methylammonium. Using a mathematical model to adjust passive permeabilities for a fit to the pHi profiles, we found that RhAG expression resulted in a threefold increase of PNH4 and a twofold increase of PNH3. Our results are the first evidence that the human erythroid RhAG increases the transport of both NH3 and NH4+.     

Anaphylactic histamine release from peritoneal mast cells of two inbred strains of rats sensitized with mouse IgE

Peritoneal mast cells from rats of BH- and DA-inbred strains were compared for their capacity to passive sensitization in vitro with mouse IgE antibodies. In identical experimental conditions mast cells of BH-rats were good receptors for mouse IgE anti-KLH fraction and released histamine when challenged with specific antigen, whereas mast cells of DA-rats were much less sensitized and released little histamine on the challenge. In contrast, mast cells of DA-rats were more susceptible to the challenge with anti-rat IgE and Concanayalin A, than were cells of BH-rats. This susceptibility correlated with total serum IgE level, which was higher in DA- than in BH-rats. These results show higher concentrations of IgE on mast cells of DA-rats. It is suggested that rat IgE present on normal mast cells may be one of the factors interfering in in vitro sensitization of the cells from DA-rats with mouse IgE antibodies.     

Neurological presentation of Wilson's disease in a patient after liver transplantation

We report of a 32‐year‐old man who showed dystonic symptoms within few days after liver transplantation (LT). The clinical, biochemical, and, finally, genetic evaluation confirmed Wilson's disease diagnosis in this patient. We suspect that extrapyramidal signs in this case could be a result of acute brain injury because of the massive copper release from liver to the circulation just before and during LT. © 2008 Movement Disorder Society