Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects.

The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchange (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p = 0.0001), smoking (p = 0.0231), and, to a small extent (p = 0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied.     

Heat shock proteins and infection: interactions of pathogen and host.

Invasive microorganisms encounter defensive attempts of the host to starve, destroy and eliminate the infection. In experimental model systems aiming to imitate defensive actions of the host, microorganisms respond by the rapid acceleration in the rate of expression of heat shock and other stress proteins. Heat shock proteins (hsp) of most if not all pathogens are major immune targets for both B- and T-cells. Host cells involved in the defensive action cannot avoid exposure to their own reactive compounds, such as oxygen radicals, resulting in premature cell death and tissue damage. Long-term consequences to the host may include cancer. In cells in tissue culture, induction of host-specific hsps occurs upon exposure to oxidants and in viral infections. Drugs that bind to members of the hsp70 family induce peroxisome proliferation and hepatocarcinoma, but may open the way for the development of novel drugs in support of antimetabolite treatment of infections and cancer.     

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.     

Induction of hemopoietic chimerism in the caprine fetus by intraperitoneal injection of fetal liver cells

Summary Intraperitoneal injection of allogeneic liver cells from 43-day-old male fetuses into normal 60-day female goat fetuses resulted in persistent hemopoietic chimerism in surviving recipients without clinical evidence of graft-versus-host disease. Transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with -D-mannosidosis may provide an alternative strategy for evaluating hemopoietic stem cell transplantation in the treatment of human lysosomal storage diseases.     

Changes in glycosaminoglycan sulfation and protein kinase C subcellular distribution during differentiation of the human colon tumor cell line Caco-2

Summary During the spontaneous differentiation (day 5 to day 15 of the culture) of Caco-2 cells, the sulfation of cell layer glycosaminoglycans increased, whereas protein kinase C activity was concomitantly redistributed from the membrane to the cytosol. The protein kinase C activators, 4-phorbol 12-myristate, 13-acetate and 1,2-dioctanoyl-glycerol inhibited glycosaminoglycan sulfation. By contrast, 4-phorbol 12, 13 didecanoate was ineffective.These results suggest that membrane-bound PKC may exert a modulatory effect on glycosaminoglycan sulfation, and this effect is gradually attenuated as Caco-2 cell differentiation progresses.