Heterogeneity of the genes encoding the major surface glycoprotein of Leishmania donovani.

The major surface glycoprotein of Leishmania (GP63) is present on all known species of Leishmania and likely plays an integral role during the infection of macrophages in the mammalian host. To identify regions of GP63 which may be of functional significance, the nucleotide sequence of a gene encoding GP63 of Leishmania donovani was determined and compared to the sequences reported for GP63 genes of Leishmania major and Leishmania chagasi. The GP63 nucleotide and predicted protein sequence was highly conserved among the 3 species despite their diverse geographical distribution. L. donovani GP63 is encoded by a multigene family and the gene locus contains at least 7 tandemly repeated genes and at least 3 genes which are dispersed from the tandem array. In addition, polymerase chain reaction and Southern blot analyses demonstrated that there was size heterogeneity within the pro-peptide coding regions of the multiple GP63 genes of L. donovani and that such genes were expressed concurrently in the promastigote life stage.     

Central pontine myelinolysis in liver transplantation.

Five cases of central pontine myelinolysis (CPM) were detected by neuropathological examination in a series of 50 patients coming to necropsy after liver transplantation. One patient also had extrapontine myelinolysis. In no case was the diagnosis made during life. Only two patients showed rapid rises in serum sodium concentrations. The incidence of hyponatraemia, before and after transplantation, and rapid rises in serum sodium in patients with CPM was significantly greater than in the 45 patients showing no neuropathological evidence of CPM. It is concluded that there is a high incidence of CPM after liver transplantation, that clinical diagnosis is difficult, and that there is no simple direct correlation between rapid serum sodium changes and the development of this condition. Avoidance of major electrolyte fluctuations at the time of liver transplantation is recommended but it must be emphasised that CPM may occur without any rapid rise in serum sodium concentration.     

Effects of exercise on behavioral sensitivity to carbamate cholinesterase inhibitors

The interaction between exercise and drug response has not been studied extensively. The present study examined the relationship between both acute (15 minute) and chronic (10 week) treadmill exercise and behavioral response to the carbamates physostigmine and pyridostigmine. Rats trained on an operant task under a multi-component FR30 schedule were used to evaluate the interaction between exercise and performance following drug administration. The direct effects of both 10 weeks of exercise conditioning and a moderate exercise challenge, as well as the interaction between two were assessed. Results obtained with physostigmine show that acute exercise increased behavioral sensitivity. Chronic exercise resulted in behavioral tolerance. These results are consistent with previously reported studies of centrally acting compounds. In contrast, pyridostigmine, which has little or no central activity, produced no behavioral changes. This result was constant over exercise conditions.     

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.     

Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

Mouse monoclonal antibodies against rat major histocompatibility antigens. Two Ia antigens and expression of Ia and class I antigens in rat thymus

A rat Ia (RT-1B) antigen (called Ia-A) equivalent to the mouse I-A product has been defined with mouse monoclonal antibodies (W. R. McMaster and A. F. Williams, Eur. J. Immunol. 1979. 9: 426). To identify other Ia antigens mouse monoclonal antibodies were raised against rat spleen glycoproteins depleted of the Ia-A antigen. An IgG antibody (called MRC OX17) was obtained and used to purify a molecule which had a similar structure to the Ia-A antigen and reacted with anti-Ia alloantibodies. There was no cross-reaction between the two Ia glycoproteins in assays with mouse monoclonal antibodies, alloantibodies or rabbit antibodies. In one alloantiserum almost all the detectable anti-Ia antibodies reacted with a mixture of the two Ia glycoproteins. The MRC OX17 antibody did not bind to mouse cells, but rabbit antibodies to the pure rat glycoprotein cross-reacted and recognized determinants mapping to the mouse I-E region. In the thymus the rat Ia-E antigen was on cortical epithelial and medullary reticular cells. An IgG monoclonal antibody (MRC OX18) to isotypic determinants of rat histocompatibility RT-1A antigens was also produced and used to analyze these antigens on thymus cells. The heavily labeled thymocytes were those with characteristics of mature T lymphocytes. Cortical epithelial cells and medullary dendritic-like cells were also RT-1A positive.