Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity

Current ideas about the mechanism of wound healing and the pathogenesis of atherosclerosis, pulmonary fibrosis and hepatic fibrosis suggest a central role for the mononuclear phagocyte in attracting and/or stimulating the proliferation of mesenchymal cells. We demonstrate here that activated human blood monocytes, but not resting monocytes, release a mediator that attracts smooth muscle cells and cooperates with other mediators to stimulate fibroblast proliferation. This mediator is very similar to platelet-derived growth factor (PDGF): its chromatographic properties and chemical stability are similar to those of PDGF, it competes with 125I-PDGF for binding to fibroblasts and it immunoprecipitates with anti-PDGF antibodies. In parallel, stimulated monocytes, but not resting monocytes, express the c-sis proto-oncogene, a gene coding for one of the PDGF chains, consistent with the concept that expression of the c-sis proto-oncogene may be involved in the ability of mononuclear phagocytes to modulate the accumulation of mesenchymal cells.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice.

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Sequence and expression of a metabotropic glutamate receptor.

The complementary DNA of a metabotropic glutamate receptor coupled to inositol phosphate/Ca2+ signal transduction has been cloned and characterized. This receptor shows no sequence similarity to conventional G protein-coupled receptors and has a unique structure with large hydrophilic sequences at both sides of seven putative membrane-spanning domains. Abundant expression of this messenger RNA is observed in neuronal cells in hippocampal dentate gyrus and CA2-3 and in cerebellar Purkinje cells, suggesting the importance of this receptor in specific hippocampal and cerebellar functions.     

Morphogenesis of human colon cancer cells with fetal rat mesenchymes in organ culture

Summary The morphogenesis and cytodifferentiation of human colon cancer cells (LS174T and HT29) were examined by combining cancer cells with fetal rat digestive-tract mesenchyme in organ culture. LS174T cells migrated into the mesenchyme to form glandular structures composed of single columnar cells with their nuclei oriented basally, while HT29 cells formed cell masses with little lumen formation. Immunohistochemical studies with antibodies against carcinoembryonic antigen and secretory components showed that the composition of cell surface glycoproteins was not necessarily reversed to the normal type, even when neoplastic cells exhibited normal glandular structures.This work was supported by grants-in-aid for Cancer Research from the Ministry of Education, Science, and Culture, Japan, and by the Veterans Administration Medical Research Service, USA. Y.S. Kim is the recipient of a Medical Investigator Award of the Veterans Administration.     

A new cell line (XTY) from a tumor of Xenopus laevis.

A new cell line (XTY) was derived from a tumor of a female Xenopus laevis. This cell line has been proliferating in standard amphibian culture medium for more than 4 years (470 generations) and has a doubling time of 75.5 h at 25 degrees C. The cells aggregate into large groups, and their stellate morphology and the expression of desmin demonstrated by immunocytochemistry suggest that their origin is not epithelial.     

A new cell line (XTY) from a tumor ofXenopus laevis

A new cell line (XTY) was derived from a tumor of a femaleXenopus laevis. This cell line has been proliferating in standard amphibian culture medium for more than 4 years (470 generations) and has a doubling time of 75.5 h at 25°C. The cells aggregate into large groups, and their stellate morphology and the expression of desmin demonstrated by immunocytochemistry suggest that their origin is not epithelial.     

Surface particle transport mechanism independent of myosin II in Dictyostelium.

Cellular locomotion could be driven by the rearward transport of membrane-bound particles observed on motile fibroblasts, keratinocytes and neuronal growth cones. A force propelling free surface particles backwards could move the cell forwards if the particles were anchored to a rigid substratum. During capping, myosin II ('double-headed' myosin) draws crosslinked membrane proteins to the rear of a cell. The mhcA- mutant of the amoebal stage of the slime mould Dictyostelium discoideum, in which the myosin II gene has been deleted, cannot cap surface particles but can crawl along the substratum. Thus, the mechanism driving capping is not essential for locomotion. We show here that the null mutant is capable of a different type of active rearward transport, independent of myosin II and distinct from capping. The transported particles on mhcA- cells follow parallel paths. In the wild-type Ax2 strain, myosin II causes particles to converge towards a focal point and significantly increases the velocity of transport behind the leading edge of the cell.     

Agglutinins from aquatic insects—tumor cell agglutination activity

Agglutinins were identified in whole body extracts of aquatic insects by means of murine tumor cell agglutination, using sarcoma 180 ascites, Ehrlich, and MM-46 cells. Screening revealed agglutinins in 5 of 10 of the larvae tested, and in 2 of 6 of the water-dwelling adult insects;Gerris paludum insularis andGyrinus japonicus. Only the agglutinin from adultG. paludum also agglutinated human erythrocytes. An ascites tumor was converted into a solid form in vivo after administration ofG. paludum agglutinin. The observation that these aquatic insect agglutinins preferentially agglutinate tumor cells has considerable implications in terms of anti-tumor effects such as inhibition of cell proliferation and metastasis.Deceased.     

An analysis of allozyme,mitochondrial DNA and morphological variation in mussel (Mytilus galloprovincialis) populations from Greece

Three populations ofM. galloprovincialis from northern Greece were investigated using isozyme analysis, discriminant analysis of morphological characteristics and analysis of restriction fragments of mtDNA. For all three types of analysis significant intra- and interpopulation differentiation was found. This differentiation is very noticeable at the mtDNA genotype frequencies. Furthermore, the restriction patterns of mtDNA were different from those reported for Atlantic populations of this species.     

Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.