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.     

Report on a conference on organic solvents and the nervous system.

At two scientific conferences in 1985, one in Copenhagen sponsored by the Nordic Council of Ministers and the World Health Organization (WHO), the other in Raleigh, NC, it was concluded that chronic toxic encephalopathy may develop following long-term occupational exposure to organic solvents (1,2). The terms organic affective syndrome, mild and severe chronic toxic encephalopathy were suggested for this condition describing increasing severity. In May 1990, a conference on organic solvents and the nervous system was held in Copenhagen sponsored by the Commission of the European Communities and the Danish Ministry of the Environment (3). Scientists and representatives from the governments, industries, and labour organisations from the EEC and US participated.     

Has smoking changed the epidemiology of ulcerative colitis?

The influence of smoking on the risk of developing ulcerative colitis is well documented. Compared with lifetime non-smokers, the risk is reduced in smokers and increased in ex-smokers. During the past 50 years general smoking habits have changed considerably. The proportions of smokers and ex-smokers among men and women have undergone significant changes and, consequently, probably also their risk of ulcerative colitis. A review of 56 earlier epidemiologic studies of ulcerative colitis from 1930 to 1990 showed that the sex distribution in ulcerative colitis has changed from an earlier female predominance that has now been replaced by a male predominance. In contemporary pediatric studies no such changes were seen. We propose that these changes in adults are not related to the disease per se but to an extrinsic factor affecting adults but not children--namely smoking.     

Does damage of perivascular astrocytes in multiple sclerosis plaques participate in blood-brain barrier permeability?

In six young and two senile MS cases perivascular astrocytes within demyelination lesions were evaluated immunocytochemically. The peroxidase-antiperoxidase method of Sternberger et al. (1970) was used for visualization of glial fibrillary acidic protein (GFAP). In all cases very weak immunoreactivity of perivascular astrocytes was noted. Accumulation of perivascular glial fibers, and infrequently their fragmentation were observed both within active and old demyelination plaques. Clasmatodendrosis, Rosenthal's fibers and prominent regressive changes of astrocyte perikarya were found only in old plaques. A lack of immunoreactivity of perivascular astrocytes was noted within old demyelination lesions. The background of the latter was often immunonegative to GFAP. It is suggested that secondary damage of perivascular astrocytes influences vascular permeability within demyelination lesions including old plaques.     

Susceptibility to endometrial cancer: influence of allelism at p53, glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP1A1) loci.

A case-control study was designed to identify associations between polymorphisms at p53, cytochrome P-450 (CYP1A1) and glutathione-S-transferases and endometrial cancer susceptibility. Among all polymorphisms analysed, an insertional variant in p53 (P53PIN3) and two polymorphisms in the 3''-end and exon 7 of CYP1A1 showed significant association with enhanced endometrial cancer risk.     

Chromosome mapping of Rett syndrome: a likely candidate region on the telomere of Xq.

Rett syndrome (RS) is a disease of neurological development. First reported 30 years ago in 1966, its biological and genetic basis remains obscure. RS is commonly thought of as an X linked dominant disorder lethal to hemizygous males. The few familial cases would arise through mosaicism or because of occasional females failing to manifest the disorder through skewed X inactivation in relevant cell types. We have one family where the mother and daughter are affected with RS, and which can be explained according to this hypothesis. If the alternative proposal of Thomas (1996) is correct, that the lack of males affected by such disorders is the result of a high male to female ratio of germline mutations rather than of gestational lethality, then the RS gene should be located on the grandpaternal chromosome. Genomic screening with markers covering the whole X chromosome has been performed. Studies using multiple informative markers indicate that the RS locus is likely to be located close to one of the X chromosome telomeres. Further investigations in eight additional families suggest the most likely region for the RS gene to be is the distal part of Xq (Xq28).