Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases

The presence of epidermal-growth-factor receptors (EGFR) and of its ligands (TGFalpha and amphiregulin) in breast-cancer tissues suggests that they play a paracrine/autocrine role in tumor growth or progression. This hypothesis was tested on 3 cell lines, S2T2, NS2T2A and NS2T2A1. These epithelial cells are derived from a normal human breast-epithelial-cell culture transformed by SV40-T Ag, are of the same clonal origin, have respectively increasing levels of EGFR, TGFalpha, amphiregulin and of thymidine-kinase activity associated with increasing tumorigenic potential in nude mice (tumor intake and tumor volume). The monoclonal antibody MAb 425, which blocks ligands interaction with EGFR, reduced by more than 90% anchorage-independent growth of the most tumorigenic cells, NS2T2A1. Another anti-EGFR MAb, 528, reduced to 25% of controls the mean tumor mass after NS2T2A1 grafting in mice. Anti-sense RNA expression of EGFR in these cells confirmed the importance of this receptor in tumor progression, since it reduced significantly the tumor volume and tumor weight of NS2T2A1 cells to 16% of those in mock-transfected control cells.     

Chromosome mapping of low-temperature induced Wcs120 family genes and regulation of cold-tolerance expression in wheat

Low-temperature (LT) induced genes of the Wcs120 family in wheat (Triticum aestivum) were mapped to specific chromosome arms using Western and Southern blot analysis on the ditelocentric series in the cultivar Chinese Spring (CS). Identified genes were located on the long arms of the homoeologous group 6 chromosomes of all 3 genomes (A, B, and D) of hexaploid wheat. Related species carrying either the A, D, or AB genomes were also examined using Southern and Western analysis with the Wcs120 probe and the WCS120 antibody. All closely related species carrying one or more of the genomes of hexaploid wheat produced a 50 kDa protein that was identified by the antibody, and a Wcs120 homoeologue was detected by Southern analysis in all species. In the absence of chromosome arm 6DL in hexaploid CS wheat no 50 kDa protein was produced and the high-intensity Wcs120 band was missing, indicating 6DL as the location of Wcs120 but suggesting silencing of the Wcs120 homoeologue in the A genome. Levels of proteins that cross-reacted with the Wcs120 antibody and degrees of cold tolerance were also investigated in the Chinese Spring/Cheyenne (CS/CNN) chromosome substitution series. CNN chromosome 5A increased the cold tolerance of CS wheat. Densitometry scanning of Western blots to determine protein levels showed that the group 5 chromosome 5A had a regulatory effect on the expression of the Wcs120 gene family located on the group 6 chromosomes of all three hexaploid wheat genomes.     

Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese

The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation. This process protects against cold and regulates energy balance. Manipulation of thermogenesis could be an effective strategy against obesity. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after treatment with a beta3-adrenergic-receptor agonist and that they are sensitive to cold, indicating that their thermoregulation is defective. However, this deficiency caused neither hyperphagia nor obesity in mice fed on either a standard or a high-fat diet. We propose that the loss of UCP may be compensated by UCP2, a newly discovered homologue of UCP; this gene is ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.     

A first locus for isolated autosomal recessive optic atrophy (ROA1) maps to chromosome 8q

In contrast to the frequent dominant optic atrophies (DOAs) in which the neuropathy is usually an isolated event, isolated recessive optic atrophies (ROAs) are very uncommon and have been described as severe congenital or early infantile conditions. To date, two loci for isolated DOA have been mapped, of which one was ascribed to mutations in the OPA1 gene. Conversely, no isolated autosomal ROA locus had previously been localised. Here, we report a large multiplex consanguineous family of French origin affected with an early onset but slowly progressive form of isolated OA. A genome-wide search for homozygosity allowed the localisation of the disease-causing gene to chromosome 8q21-q22 (Zmax of 3.41 at theta=0 for D8S270), in a 12 Mb interval flanked by markers D8S1702 and D8S1794. This localisation excludes allelism of the disease with both isolated DOAs, on one hand, or all known syndromic forms of ROA, on the other hand, supporting the mapping of a first gene for isolated autosomal ROA (ROA1) on the long arm of chromosome 8.     

Human immunodeficiency virus type 2 envelope glycoprotein binds to CD8 as well as to CD4 molecules on human T cells

We report here that human immunodeficiency virus type 2 (HIV-2) envelope glycoprotein (gp105), but not HIV-1 gp120, can bind to CD8 molecules as well as to CD4 molecules on human T cells. This phenomenon may lead to differences in the life cycles of HIV-1 and HIV-2, and it may be related to the differences in disease manifestations of HIV-1 and HIV-2 infection, including longer survival of HIV-2-infected patients.     

Society stress and peptic ulcer perforation

To examine the relationship between society stress and peptic ulcer perforation, time-trend analysis was performed on the annual incidence of perforated peptic ulcer per 100,000 population in Hong Kong during the years 1962-85, when Hong Kong, as a developing city, went through significant socio-economic and political changes, and the trend was correlated with specially designed and validated society stress scores estimated annually during the same period. The society stress scores were derived independently by two expert panels blinded to the purpose of the study, one selecting and categorizing negative news events for Hong Kong during this period, and the other weighing the categories and scoring the impact of the news on Hong Kong. The incidence of perforation increased significantly during the years and manifested three distinct peaks, which coincided with the worst economic recession in Hong Kong, the influx of mainlander Chinese and Vietnamese boat people, and the Sino-British negotiation on the sovereignty of Hong Kong after 1997. Both linear and autoregression analysis, the latter taking into consideration point fluctuations in rates, showed that perforation rates correlated significantly with the society stress scores (r = 0.57, P < 0.002). The peak effects and the significant correlations indicate that an association exists between society stress and peptic ulcer perforation, and suggest that chronic society stress plays an important role in the aetiology of this condition, although the relatively low r value also suggests the presence of other aetiological factors.     

Ser752 mutation to Pro or Ala in the beta3 integrin subunit differentially affects the kinetics of cell spreading to von Willebrand factor and fibrinogen

The beta3 cytoplasmic domain of the alpha v beta3 integrin is essential for intracellular signals required for cytoskeletal rearrangements. Expression of beta3Ser752Pro mutation in heterologous cells profoundly affects cell spreading and beta3 localization into focal contacts. However, the beta3Ser752Ala substitution mostly restores normal integrin functions, suggesting that the presence of Pro is responsible for the receptor's loss of function. To further assess the role of the Ser752 of the beta3 cytoplasmic domain in the cytoskeletal organization of adherent cells, we developed a computer-assisted method of image analysis allowing the automatic classification of spread cells according to the quantitative analysis of their cell morphology. We compared adhesion and spreading to von Willebrand factor (vWF) or fibrinogen (Fg) of cells expressing beta3 wild type, beta3Ser752Pro or beta3Ser752Ala mutated integrin subunit as a chimeric alpha v beta3 receptor. The beta3Ser752Ala substitution did not impair the general ability of cells to spread, but resulted in a delayed and reduced spreading on both vWF and Fg. Moreover, the beta3Ser752Ala mutation produced modifications of the morphology of spread cells, suggesting a disorganization of their cytoskeleton. Attachment studies showed that the beta3Ser752Ala mutation did not modify the capacity of cells to attach to the substrate, indicating no change in the ligand binding affinity of the alpha v beta3 integrin. Furthermore, we identified a slight defect of beta3Ser752Pro cell attachment to vWF and Fg, beside their impairment of spreading. Taken together, these results suggest a role of Ser752 of the beta3 cytoplasmic domain in the optimal cytoskeletal organization of adherent cells.     

Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar. This confirms a previous conclusion about the prevalence of A/C serotype among intravenous narcomaniacs in the former USSR.     

Membrane association of active plasmid partitioning protein A in Escherichia coli

QsopA and SopA, proteins essential for stable maintenance of low copy number plasmids and encoded on plasmid QpH1 of Coxiella burnetii and the F plasmid of Escherichia coli, respectively, are shown to be membrane associated using three independent approaches: isolation of hybrid protein A-PhoA proteins that display PhoA (bacterial alkaline phosphatase) activity indicating a periplasmic location, biochemical fractionation by flotation gradient centrifugation, and subcellular localization by immunoelectron microscopy. These data provide insight into the mechanism by which partitioning protein A spatially directs plasmids into daughter cells at bacterial division.