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E Bone

Publications and source records attributed to E Bone.

9 recordsLinked to original sources

A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice.

Bone resorption is a dominant feature of many bone metastases and releases factors from the bone matrix that can promote the expression of the metastatic phenotype in cancer cells. Since proteolytic enzymes, including matrix metalloproteinases (MMPs) contribute to bone destruction by metastatic tumour cells and host cells, we have examined the effect of a MMP inhibitor, batimastat, on the ability of MDA-MB-231 cells to degrade bone in vitro and to form bone metastases in BalbC nu/nu mice. In vitro, the neoplastic cells produced MMP-2 and MMP-9, degraded [3H]-proline-labelled osteoblast matrices, and formed resorption pits in cortical bone. These phenomena were inhibited by < or = 20 microM batimastat. To induce vertebral and long bone metastases in vivo, 1x10(5) MDA-MB-231 cells were injected into the arterial circulation of BalbC nu/nu mice. Test groups were also given 30 mg/kg batimastat intraperitoneally (i.p.). After 21 days, the long bone metastases were characterised by a 67% reduction of metaphyseal medullary bone and complete replacement of marrow by tumour. In tumour-bearing mice that had been treated with 30 mg/kg batimastat i.p., the tumour volume decreased 8-fold, osteolysis was inhibited by 35%, and replacement of the bone marrow by tumour was inhibited by 65%. Similar effects were observed in the vertebral metastases. These data provide evidence that MDA-MB-231 cells can degrade osteoblast matrices and mineralised bone in vitro and support the hypothesis that MMPs are involved in the pathogenesis of osteolytic bone metastases in vivo. They demonstrate that an agent which inhibits proteolysis can retard the development of osteolytic bone metastases in this model.

Animals↗

Trends and rates of microevolution in plants.

Evidence for rapid evolutionary change in plants in response to changing environmental conditions is widespread in the literature. However, evolutionary change in plant populations has not been quantified using a rate metric that allows for comparisons between and within studies. One objective of this paper is to estimate rates of evolution using data from previously published studies to begin a foundation for comparison and to examine trends and rates of microevolution in plants. We use data gathered from studies of plant adaptations in response to heavy metals, herbicide, pathogens, changes in pH, global change, and novel environments. Rates of evolution are estimated in the form of two metrics, darwins and haldanes. A second objective is to demonstrate how estimated rates could be used to address specific microevolutionary questions. For example, we examine how evolutionary rate changes with time, life history correlates of evolutionary rates, and whether some types of traits evolve faster than others. We also approach the question of how rates can be used to predict patterns of evolution under novel selection pressures using two contemporary examples: introductions of non-native species to alien environments and global

Adaptation, Biological↗

Chemotropic and contact responses of phytophthora sojae hyphae to soybean isoflavonoids and artificial substrates

We have investigated the role of the isoflavones daidzein and genistein on the chemotropic behavior of germinating cysts of Phytophthora sojae. Hyphal germlings were shown to respond chemotropically to daidzein and genistein, suggesting that hyphal tips from zoospores that have encysted adjacent to the root may use specific host isoflavones to locate their host. Observations of the contact response of hyphal germlings were made on several different substrates in the presence and absence of isoflavones. Hyphal tips of germlings detected and penetrated pores in membranes and produced multiple appressoria on smooth, impenetrable surfaces. Hyphae that successfully penetrated the synthetic membrane were observed to grow away from the membrane surface. The presence of isoflavones in the medium surrounding the hyphal germlings did not appear to alter any of those habits. Daidzein and genistein did not inhibit germination or initial hyphal growth at concentrations up to 20 &mgr;M.

Journal Article↗

Matrix metalloproteinases degrade myelin basic protein.

Matrix metalloproteinases (MMPs) are a group of enzymes responsible for the degradation of interstitial connective tissue and basement membrane. The coding sequences for five of the human MMPs, viz. interstitial collagenase, 72 kDa gelatinase, stromelysin-1, matrilysin and 92 kDa gelatinase, were cloned and expressed in Chinese hamster ovary cells, and the proteins purified. The enzymes were compared for their ability to digest myelin basic protein, the major extrinsic membrane protein of central nervous system myelin. The most active on this substrate was 72 kDa gelatinase, followed by stromelysin-1; interstitial collagenase, matrilysin and 92 kDa gelatinase were of comparable but lesser activity. Production of these enzymes by glia or infiltrating inflammatory cells could therefore contribute to demyelination in neuroinflammatory disease.

Animals↗

Thyroglobulin gene activation by thyrotropin and cAMP in hormonally depleted FRTL-5 thyroid cells.

Thyroglobulin gene control by cAMP and thyrotropin has been compared in FRTL-5 thyroid cells maintained in the absence of serum, insulin, cortisol, and thyrotropin for 7 days. Readdition of thyrotropin induces an increase in the expression of the thyroglobulin gene with little effect on total RNA synthesis. In contrast, addition of 8-bromo cyclic AMP and cholera toxin stimulate total RNA synthesis as well as thyroglobulin gene expression. The same non-selective effect of cyclic AMP on the thyroglobulin gene was observed when transcriptional activity was measured in permeabilized FRTL-5 cells.

8-Bromo Cyclic Adenosine Monophosphate↗

Quantitative estimates of beta-lactam residues in raw milk around a reference standard: collaborative study.

A collaborative study was conducted to determine the reliability of a Bacillus stearothermophilus disc assay method for differentiating various concentrations of penicillin in raw milk. Participating laboratories tested 10 different samples (including one negative) in blind duplicate. Triplicate standards were alternated with triplicate unknowns around the periphery of each of 5 different plates. Zone diameters were measured and the difference in zone size of pairs of adjacent standard and unknown samples were analyzed by a paired t-test. Penicillin concentrations 0.003 IU/mL different from the reference concentrations were consistently distinguishable at a 95% confidence level. Such discriminatory power was determined to be possible with as few as 3 plates (9 replicates) per unknown. The method has been adopted official first action.

Animals↗

The production of urinary phenols by gut bacteria and their possible role in the causation of large bowel cancer.

Epidemiological evidence is presented to relate the amount of dietary meat to the risk of large bowel cancer; it has been suggested that this may be due to the production of cocarcinogenic volatile phenols by intestinal bacteria from tyrosine. This paper describes preliminary experiments to test this suggestion. In vitro, aerobic bacteria tended to produce phenol from tyrosine while anaerobic bacteria produced p-cresol. Urine from 10 normal healthy persons contained a mean of 9.8 mg phenol/day and 51.8 mg p-cresol/day. Results from studies on patients with ileostomy, colostomy, and diverticular disease indicated that p-cresol is largely produced by the anaerobic flora of the left colon while phenol was produced in the ileum (when colonized) and cecum. In patients with familial polyposis the activity of the aerobic flora was apparently normal but there was greatly reduced amounts of p-cresol produced. The amounts of urinary volatile phenols in six patients with newly diagnosed large bowel cancer were not different from the normal values, indicating that cocarcinogenic phenols were unlikely to be a major cause of the disease.

Adult↗

Gut bacteria and their metabolic activities in familiar polyposis.

Earlier work had suggested that patients with large-bowel cancer can be characterized by carriage of clostridia capable of dehydrogenating the nucleus of steroids and by high faecal bile-acid concentrations. Familial polyposis is an inherited disease which untreated, will progress to cancer of the large bowel, and those affected might be expected to have these metabolic characteristics. However, enviromental factors seem to play no part in polyposis. Investigation of as yet unaffected children of known polyposis patients revealed that the gut flora of half of them did not degrade cholesterol in vivo andnor did flora from patients in whom polyposis had already been diagnosed. The reason for this is unknown, but if the same patients develop polyposis (i.e., they carry the abnormal gene) we would have a simple diagnostic test which could replace the continuing follow-up now required for the siblings and children of patients with polyposis.

Adult↗