Search PubMed⌕ Search

Biomedical subjects

Steven Clark

Publications and source records attributed to Steven Clark.

4 recordsLinked to original sources

Induction and superinduction of growth arrest and DNA damage gene 45 (GADD45) alpha and beta messenger RNAs by histone deacetylase inhibitors trichostatin A (TSA) and butyrate in SW620 human colon carcinoma cells.

Histone deacetylase (HDAC) inhibitors such as trichostatin (TSA) and butyrate have been shown to inhibit cancer cell proliferation, induce apoptosis and regulate the expression of genes involved in cell cycle. Although the precise mechanism underlying HDAC inhibitor-induced cell growth arrest is not fully understood, induction of cell cycle related genes such as p21(cip/waf), is thought to be important. Here we showed that in the SW620 human colon cancer cell line, TSA and butyrate induced the growth arrest and DNA damage gene 45alpha (GADD45alpha) and GADD45beta. Furthermore, GADD45beta and p21(cip/waf) messenger RNA were induced in the absence of protein synthesis, indicating that both genes were immediate target genes for TSA. Cyclohexamide and TSA super-induced the expression of GADD45alpha and beta, but not p21(cip/waf). Interestingly while mitogen-activated kinase (MEK) inhibitor PD98059 and p38 kinase inhibitor SB242235 were unable to affect GADD45 induction, two serine/threonine protein kinase inhibitors (H7 and H8) as well as curcumin completely blocked the super-induction. Concomitant to the inhibition of GADD45 induction, H7 and H8 also blocked TSA-induced apoptosis. Taken together, these results suggest that GADD45 induction may play important role in TSA-induced cellular effects.

Antigens, Differentiation↗

Documentation of amniotic fluid embolism via lung histopathology. Fact or fiction?

OBJECTIVE: To evaluate pulmonary histopathology for confirming amniotic fluid embolism. STUDY DESIGN: The Capra hircus (goat) model with fresh, homologous amniotic fluid was used. Raw fluid (n = 8), fluid filtered through a 5-microns filter (n = 14) and meconium-stained fluid with 1-7% solid debris (n = 7) were injected. Three hours after embolization the animals were euthanized and specimens collected. Three to five areas of lung were sampled based on the most abnormal areas visually. Traditional and special stains were utilized. The study protocol was approved by the institutional review board and animal use and care committee. Statistical analysis was by chi 2 with Yates correction. Significance was defined as P < .05. RESULTS: Amniotic fluid debris (fetal squames, mucin or foreign pigments) was found in 10 of 29 animals (34.5%). Debris was found in 7/7 (100%) of the meconium group, 2/8 (25%) of the raw fluid group and 1/14 of the filtered group (7%). The likelihood of finding debris in amniotic fluid embolism with meconium-stained fluid was greater than with raw (P < .017) or filtered amniotic fluid (P < .001). CONCLUSION: In this animal model, histopathologic confirmation of amniotic fluid embolism was an unreliable marker of the event except in cases of amniotic fluid embolism involving meconium-stained fluid.

Animals↗

Pododermatitis in turkeys.

Severe pododermatitis is a common lesion in turkeys, unlike in broiler chickens. Both dietary factors (soybean meal, biotin, methionine) and poor litter conditions (wet litter) are documented etiologies of footpad lesions. In the United States and United Kingdom both farm managers and processors monitor lesions. The United Kingdom reports an average footpad relative score higher than that of the United States. In both countries, incidence in toms is higher than in hens. There is no significant difference by country. Data support no consistent association with other lesions (i.e., breast blisters or condemnations), breed, or performance parameters (i.e., weight gain or age). The litter type used in the United Kingdom is either straw or wood shavings, whereas in the United States producers predominantly use wood shavings. In the United Kingdom, diets are formulated with a higher protein, which affects the excreta and subsequent litter conditions. British United Turkey is the predominate breed in the United Kingdom. In the United States, three breeds, British United Turkey of America, hybrid, and Nicholas, are common. Recent research has demonstrated the association between biotin levels and pododermatitis. Factors associated with pododermatitis (such as production systems, wet litter, and stocking density) are discussed. There are some indications that increased stocking density is associated with pododermatitis lesions. Further research is needed to identify what management factors are associated with pododermatitis.

Animals↗