Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells.

Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries (Vaccinium angustifolium), on MMP activity in DU145 human prostate cancer cells in vitro. Using gelatin gel electrophoresis, MMP activity was evaluated from cells after 24-hr exposure to blueberry fractions. All fractions elicited an ability to decrease the activity of MMP-2 and MMP-9. Of the fractions tested, the proanthocyanidin-enriched fraction was found to be the most effective at inhibiting MMP activity in these cells. No induction of either necrotic or apoptotic cell death was noted in these cells in response to treatment with the blueberry fractions. These findings indicate that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may decrease overall ECM degradation. This ability may be important in controlling tumor metastasis formation.     

Fibronectin-degrading proteases from the membranes of transformed cells

The local degradation of fibronectin substrata by Rous sarcoma virus-transformed chick embryonic fibroblasts requires cell-contact-related metalloendoprotease and serine-protease activities. Using fibronectin-containing SDS gels, two large proteases with apparent molecular weights of 120K and 150K were found only in the membrane fraction of transformed cells and were absent in normal cells. Both 120K and 150K proteases were active at neutral pH, but showed preferential inhibitor sensitivities of serine and metal proteases, respectively. The 150K protease appeared to account for most of the proteolytic activity since metalloendoprotease inhibitors completely blocked proteolytic activity of the 150K in fibronectin gels, more than 80% of the fibronectin-degrading activity of solubilized membranes, and largely suppressed the appearance of fibronectin degradation spots in cultures of transformed cells.     

Dynamics of immunoglobulins and immunocompetent lymphocytes in guinea pigs with experimental ascariasis

The paper presents data on variations in the level of serous immunoglobulins (Ig M and Ig G classes), immunocompetent T- and B-lymphocytes in lymphoid organs (spleen, mesenteric, portal and mediastinal lymph nodes) and specific antiparasitic antibodies in guinea pigs during the dynamics of experimental ascariasis.     

Effect of the cytoplasm of irradiated cells on chromatin degradation in mouse thymocytes and hepatocytes

The addition of a cytoplasmic fraction, isolated from cells 3h after irradiation of mice, to exposed or intact thymocyte nuclei causes a 2- or 3-fold acceleration of chromatin degradation in the nuclei incubated in conditions optimum for activity of Ca2+,Mg2+-dependent endonuclease to be manifest. In contrast to thymocytes, no chromatin degradation products are found in liver cells of irradiated mice. The cytoplasmic fraction isolated from hepatocytes of irradiated animals fails to activate chromatin degradation in thymocyte nuclei.     

The effect of repeated administration of insulin on pain threshold and gamma-aminobutyric acid level in mouse brain

In experiments on male Albino-Swiss mice weighing 18-22 g insulin given in doses of 2 i.u./kg caused no change in the time of reaction to pain, while the same dose administered daily for 7 days potentiated the analgesic action of morphine (3 mg/kg s.c.). Glucose caused no change in this effect of insulin. After 14 days of insulin treatment the time of reaction to pain in the animals subjected to the action of morphine returned to its initial value. Twenty-four hours after the last administration of morphine the level of gamma-aminobutyric acid (GABA) was found to be decreased in the animals receiving insulin with glucose. These results suggest that the central action of insulin is dependent not only on hypoglycaemia produced by it, but may be due also to its direct action on the central structures and an indirect action mediated by its effect on other neurotransmitter systems.     

Role of motor activity in the development of hypothyroid rat pups

Studies have been made on the role of the thyroid in the development of rats. In the first group of experiments, newborn rat received within a month mercazolyl which inhibits the activity of the thyroid; in animals of the second group, mercazolyl injections were combined with cold exposures which stimulated motor activity in animals. It was found that hypothyroid rats in both groups exhibit retardation of growth as compared to normal animals. However, retardation is less significant in animals of the second group, as it is indicated by smaller changes in the protein content and total mass of skeletal muscles.     

Spontaneous mutation of the H-2b-haplotype in C57BL/10SnY mice

A new spontaneous mutation of the H-2b haplotype was found in skin graft tests with BC3 mice derived from B10.R111 (71NS) and C57BL/10SnY outcrossing. The mutation site localized in the F1 test in the H-2Kb gene is nonidentical to and noncomplementary with bm1, bm3, bm4 mutations. The novel mutation is maintained as B10.R111-H-2bm25 strain.     

Retrospective evaluation of gynecologic cytodiagnosis. II. Interlaboratory reproducibility as shown in rescreening large consecutive samples of reported cases

Two laboratories exchanged and rescreened a large sample of cases with cervicovaginal smears they had consecutively accessioned to examine the reproducibility of gynecologic cytodiagnosis under optimum conditions. At least a "working agreement" (diagnoses within +/- 1 category on a ten-category scale) was achieved in diagnoses of normal, benign reaction and squamous abnormality (from minimal dysplasia though invasive cancer) in 18,859 cases (96.8%), of endometrial abnormality in 21 cases (42%) and of "unsatisfactory" in 99 cases (20.7%). Larger differences occurred in greater than or equal to 30% of cases except in the categories of "normal" and "benign reaction," reaching a maximum of 82% for moderate dysplasia. Reexamining 382 cases decreased disagreement by category to the 20% to 65% range only in the five categories of dysplasia plus carcinoma in situ. Agreement was not predicated on the presence of endocervical cells or squamous metaplasia; the basis for "unsatisfactory" calls was not uniform. Comparison of the laboratories' diagnoses with referee diagnoses or, on 178 cases, with tissue diagnoses also demonstrated differences in diagnostic criteria.     

Diastereomers of thymidine 3'-O-(methanephosphonothioate): synthesis, absolute configuration and reaction with 3'-methoxyacetylthymidine under conditions of triester approach to oligonucleotide synthesis

Diastereomers of the title compound were obtained and absolute configuration was assigned by means of stereochemical correlation. Their reaction with 3'-O-methoxyacetylthymidine in the presence of triisopropylbenzenesulphonyl (4-nitro) triazole is neither chemo- nor stereo-selective and leads to diastereomeric pairs of dithymidyl (3',5')methanephosphonate and -methanephosphonothioate. Obtained results are discussed in terms of mechanism of activation of phosphodiesters under conditions known as "phosphotriester approach to oligonucleotide synthesis".     

Ultrastructure of the synaptic endings in nerve tissue transplants developing in the anterior chamber

Embryonic septum of hippocampus was grafted into the anterior eye chamber (AEC) of adult recipient rats. The fine structure and distribution of synaptic endings were studied in the hippocampus (HC) and septum (ST) grafts developing in oculo for 3-4 months. On the basis of the structure of postsynaptic regions, asymmetrical and symmetrical synapses are distinguished, whose distribution on the body and dendrites of hippocampal and septal neurons is basically similar with that in situ. As in vivo, axo-somatic, axo-dendrite and axo-spine forms of synaptic endings have been observed. Neuropile has, basically, normal structure, judging by the ratio of nerve and glial elements, but sometimes dendro-dendrite contacts and glomerular-like synaptic structures are observed which are not characteristic of the studied brain regions. Besides, the grafts contain an increased number of serial and tangential synapses, as well as axonal terminals with the signs of growth cones. The observed structural deviations appear to be due to incomplete tissue maturation in the absence of normal afferentation.