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Biomedical subjects

J F Schaefer

Publications and source records attributed to J F Schaefer.

12 recordsLinked to original sources

Hybridization and reproductive isolation among syntopic populations of the topminnows Fundulus notatus and F. olivaceus.

Fundulus notatus and Fundulus olivaceus are two closely related topminnow species that exhibit similar ecological niches and broad, largely overlapping, North American ranges extending throughout much of the Mississippi River drainage as well as the coastal drainages of the Gulf of Mexico. Previous studies have suggested that these two species are reproductively compatible despite cytogenetic differences and will hybridize when syntopic. We used nuclear and mtDNA loci to assess levels of hybridization and test for introgression in syntopic populations of these two species in four drainages in southern Illinois. Although hybridization was detected in all syntopic populations, an assessment of the proportion of hybrid individuals indicated a deficiency of hybrids relative to expectations under random mating. We determined that, although mtDNA introgression was prevalent and extended beyond the zones of contact, evidence of nuclear introgression was limited to the zone of sympatry.

Animals↗

FGF signaling antagonizes cytokine-mediated repression of Sox9 in SW1353 chondrosarcoma cells.

OBJECTIVE: The Sox9 transcription factor has emerged as an important determinant of chondrocyte differentiation, including the regulation of type II collagen (Col2) and aggrecan gene expression. We sought to identify a human cell line model that conserves the Sox9 regulatory pathways identified in the mouse. DESIGN: The SW1353 chondrosarcoma cell line was considered to be a candidate for Sox9 studies. The activity of a Sox9 regulated Col2a1 enhancer reporter gene was analyzed in response to treating cells with known regulators of murine Sox9 expression/activity. The effect of treatment on expression of the endogenous Sox9 gene was analyzed by real-time PCR and Western blot. RESULTS: Col2 enhancer activity was stimulated by fibroblast growth factors (FGF-1 and -2) and repressed by inflammatory cytokines (IL-1beta and TNFalpha) in SW1353 cells. These effects correlated with changes in Sox9 mRNA and protein levels. In addition, FGF-9 was shown to stimulate enhancer activity and Sox9 expression. Cotreatment studies demonstrated that FGFs functionally antagonize the cytokine-mediated repression of Sox9 expression and Col2 enhancer activity. CONCLUSIONS: SW1353 cells represent a useful human cell model as they conserve many Sox9 signaling pathways previously demonstrated in mouse chondrocytes. We identify FGF-9 as a particularly potent Sox9 agonist. The antagonism between FGFs and cytokines on Sox9 expression and Col2 enhancer activity suggests that Sox9 integrates the opposing activities of FGFs and cytokines. We also find that SW1353 cells respond to very low doses of IL-1 with Col2 enhancer activation, while increasing doses lead to repression.

Animals↗

Synergistic effect between iron and gadolinium in MRI.

Different combinations of iron glycerophosphate (Fe) and gadolinium-diethylene triamine pentaacetic acid (DTPA) (Gd) were imaged with a three-dimensional (3D) gradient-recalled echo (GRE), a 2D GRE, and a HASTE sequence on a 1.5-T MR scanner. A combination of Fe and Gd results in a synergistic effect, which improves the signal gain for selective 3D imaging of the colon and simultaneously decreases the endoluminal signal on the HASTE and 2D GRE images for better visualization of water and Gd-enhanced structures in the gut wall.

Colonic Diseases↗

Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells.

To investigate the regulation of parathyroid hormone secretion by phosphatases we examined the effect of okadaic acid, a selective inhibitor of protein phosphatases (PP)-1 and -2A, on isolated, dispersed parathyroid cells. Okadaic acid inhibited secretion from intact bovine, intact human and streptolysin-O permeabilized bovine cells. Approximately 10(-6) M okadaic acid resulted in a 50% decrease in parathyroid hormone (PTH) secretion from both intact and permeabilized cells, consistent with PP-1 being the target of inhibition. Upon subcellular fractionation, PP-1 overlapped but was not identical to either PTH, a marker of the secretory granule, or Na+/K+-ATPase, a plasma membrane marker. In summary, PP-1 activity is involved in Ca2+-dependent but not basal PTH secretion.

Animals↗

Reconstitution of calcium-regulated parathyroid hormone secretion from streptolysin-O-permeabilized parathyroid cells by guanosine 5'-O-(thio)triphosphate.

Intracellular Ca2+ levels determine the amount of PTH secretion from parathyroid cells. Dissociated calf parathyroid cells were permeabilized with streptolysin-O (SLO) to provide an in vitro model system to examine Ca(2+)-dependent regulation of hormone secretion. PTH release from these cells was energy dependent and increased by cytosolic cofactors. Guanosine 5'-O-(thio)triphosphate (GTP gamma S) increased PTH secretion from SLO-permeabilized cells in a dose-dependent manner from 0.1-100 microM. In the absence of GTP gamma S there was no relationship between the ambient Ca2+ concentration and the rate of PTH secretion. However, in the presence of GTP gamma S, intracellular Ca2+ inhibited PTH secretion with an EC50 of approximately 0.1 microM, corresponding to physiological intracellular Ca2+ levels. Thus, the addition of GTP gamma S to SLO-permeabilized parathyroid cells reconstituted the inverse relationship between extracellular Ca2+ and PTH secretion that is observed in vivo and in intact cells. The data indicate that this effect is mediated at least in part by heterotrimeric guanosine triphosphatases. In addition, calcium/calmodulin-dependent protein kinase II appears to mediate low Ca(2+)-dependent PTH secretion from these cells.

Animals↗

Characterization of cAMP-dependent protein kinase activation by CCK in rat pancreas.

This study reports on the use of a new sensitive assay of cAMP-dependent protein kinase activity to examine the effect of cholecystokinin (CCK) on the cAMP second messenger cascade in rat pancreatic acini. Treatment of acini with both low (pM) and high (nM) concentrations of CCK was associated with an increase in cAMP-dependent protein kinase activity. The increases in kinase activity were detected in the absence of phosphodiesterase inhibition, a condition required to detect a measurable increase in cellular cAMP in these cells. Furthermore, the cAMP cascade was dissociated from the secretory effects of CCK, since the CCK analogue, OPE, mediates enzyme secretion but does not increase cellular cAMP levels or kinase activity.

1-Methyl-3-isobutylxanthine↗

Clinical investigations: taking a global approach, part I.

Clinical investigations are a vital part of the development process of a medical device. A number of advantages can be gained by initiating a global approach to clinical investigation and implementing a well-designed, multinational, multicentred programme. It can mean that market approval can be accelerated and that the marketing effort is supported in specific countries, which can lead to greater market share. This article, which will be published in two parts, outlines the strategy that is required to set up and implement an effective global clinical investigation. Part I considers the elements that are involved and defines the advantages of adopting this approach.

Clinical Trials as Topic↗

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

A 38-year-old black man died from acquired immunodeficiency syndrome (AIDS) after a 15-month course. The autopsy revealed a pancolitis and a pneumonia caused by cytomegalovirus (CMV). Exceptionally, there also was a periventricular encephalitis caused by the same organism. Identification of the virus was aided by immunoperoxidase methods.

Acquired Immunodeficiency Syndrome↗

Medical ethics.

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Ethics, Medical↗