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Biomedical subjects

C Nelson

Publications and source records attributed to C Nelson.

At least 19 recordsLinked to original sources
PubMed1995

Induction of the LIM homeobox gene Lmx1 by WNT7a establishes dorsoventral pattern in the vertebrate limb.

During vertebrate limb development, the ectoderm directs the dorsoventral patterning of the underlying mesoderm. To define the molecular events involved in this process, we have analyzed the function of WNT7a, a secreted factor expressed in the dorsal ectoderm, and LMX1, a LIM homeodomain transcription factor expressed in the dorsal mesenchyme. Ectopic expression of Wnt7a is sufficient to induce and maintain Lmx1 expression in limb mesenchyme, both in vivo and in vitro. Ectopic expression of Lmx1 in the ventral mesenchyme is sufficient to generate double-dorsal limbs. Thus, the dorsalization of limb mesoderm appears to involve the WNT7a-mediated induction of Lmx1 in limb mesenchymal cells.

Animals↗
PubMed1995

Prospective study of small LDLs as a risk factor for non-insulin dependent diabetes mellitus in elderly men and women.

BACKGROUND: The excess risk of atherosclerosis among patients with non-insulin dependent diabetes mellitus (NIDDM) is well documented. However, the presence of conventional risk factors cannot fully account for this excess risk, and the underlying mechanism remains to be elucidated. The present study prospectively evaluated the role of small LDL, a known risk factor for coronary heart disease, as a risk factor for the development of NIDDM. METHODS AND RESULTS: The study was based on a nested case-control sample of 204 elderly men and women from Kuopio, Finland. LDL subclasses were characterized by size with 2% to 14% polyacrylamide gels produced by recently developed methods. Logistic regression analysis showed that subjects with a predominance of small LDL (LDL subclass phenotype B) had a greater than two fold increased risk for developing NIDDM over the 3.5-year follow-up period. This association was independent of age, sex, glucose intolerance, and body mass index but was not independent of fasting triglyceride or insulin levels. Further, an increase of 5A in LDL diameter was associated with a 16% decrease in risk of NIDDM, and a composite variable of LDL diameter and triglyceride and HDL cholesterol concentrations, identified by principal-components analysis, was also associated with NIDDM. These associations may be attributable to the role of small LDL as a marker for insulin resistance. CONCLUSIONS: This study is the first to demonstrate that a predominance of small LDL particles is a risk factor for the future development of NIDDM, and it implies that small LDL contributes to risk of coronary heart disease in prediabetics.

Aged↗
PubMed1995

Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs.

An amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx-1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF-4 and Myf-5, which are expressed in differentiated muscle and regulate muscle-specific gene activity. As anticipated, we find that Msx-1 is strongly up-regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF-4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a muscle-specific Myosin gene. In contrast Myf-5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF-4 and Myf-5 are likely to play distinct roles during regeneration. MRF-4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids.

The metabolic fate of the dietary isoflavones daidzein and genistein was investigated in human volunteers challenged with soya. Urinary diphenols, isolated by partition chromatography on Sephadex LH-20, were characterized and identified by profile capillary gas chromatography (GC) and electron ionization mass spectrometry (GC-EIMS) analysis of the trimethylsilyl ether (TMS) derivatives. Novel isoflavonic phytoestrogens found in the urine of volunteers were those of tetrahydrodaidzein, dihydrogenistein, 6'-hydroxy-O-demethylangolesin and 2-dehydro-O-demethylangolensin. Other known diphenols identified were those of equal, dehydrodaidzein, O-demethylangolensin, daidzein, genistein, glycitein, and the lignan enterolactone. Two other urinary isomers with a fragmentation pattern closely resembling that of the persilylated TMS ethers of cis/trans-isomers of tetrahydrodaidzein, were characterized based on the elucidation of fragments associated with the loss of a non-phenolic-OTMS functional group in ring-C. These are fragments presented in the persilylated mass spectra of isoflavan-4-ols and isoflav-3-ene-4-ols, demonstrated here by a combination of simple and tandem mass spectrometry study of the deuterated persilylated TMS ethers of dihydrodaidzein. In a similar study we also present the data on the structural identification and fragment elucidation of the keto/enol tautomers of the TMS ether derivatives of the dihydro derivatives of daidzein and genistein, observed in the urine of volunteers and considered probable products of the derivatization process. Finally, the GC and GC-MS data of two unknown isoflavonoids and that of a lignan-like compound are presented together with those of dihydrodaidzein, dihydrogenistein, tetrahydrodaidzein and 2-dehydro-O-demethylangolensin. The latter four were obtained here as products of small scale chemical synthesis in a preliminary study on the tentative identification of urinary isoflavonoids in human volunteers challenged with soya.

Diet↗
PubMed1995

The Pan basic helix-loop-helix proteins are required for insulin gene expression.

The rat I insulin enhancer contains two principal regulatory elements, the Nir and Far motifs of an identical 9-base pair sequence, which function both as positive and negative cis-acting elements. The Nir and Far elements are targets for DNA-binding proteins, which play a predominant role in the selective transcription of the insulin gene in endocrine beta-cells. In vitro DNA-binding studies have demonstrated the ability of several helix-loop-helix (HLH) proteins, including the Pan/E2A proteins, upstream stimulating factor, human beta-HLH factor (rat beta-HLH factor), and E2-2/ITF-2, to bind the Nir and Far enhancer motifs. The presence of the aforementioned different HLH proteins in endocrine beta-cells, all of which display similar binding affinities for the Nir and Far elements in vitro, raises the question of which HLH proteins actively participate in the transcriptional regulation of the rat insulin I gene in pancreatic endocrine beta-cells. To investigate the specific role that Pan proteins play in regulating insulin gene expression, we have created endocrine beta-cell stable integrants that constitutively express Pan antisense transcripts that selectively inhibit endogenous Pan protein synthesis in differentiated beta-cells. We demonstrate that diminished Pan protein levels in beta-cells, caused by Pan antisense transcripts, accompanies a dramatic attenuation of rat insulin gene transcription. We also show that the decrease in Pan protein expression correlates with a specific reduction of the beta-endocrine-specific Nir and Far element-binding activity, insulin enhancer factor 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The variable metabolic response to dietary isoflavones in humans.

The aim of this study was to better understand the metabolic fate of dietary estrogenic isoflavones in humans. Twelve volunteers were challenged with soya flour and urinary levels of the isoflavones daidzein (Da), genistein (Gen), and glycitein (Gly), and the isoflavonoid metabolites equol (Eq) and O-desmethylangolensin (O-Dma) determined by GC and GC-MS. Prior to challenge, Da, Gen, and Gly were present in the urine of all participants at low levels and Eq and O-Dma were present in 9/12 and 10/12 participants, respectively. Urinary levels of all five diphenols were increased in each individual on the day following challenge, returning to approximately prechallenge levels on the second or third day post-challenge. Mean post-challenge peak levels of the five diphenols compared with pre-challenge levels were Da (4x), Gen (8x), Gly (5x), Eq (45x), and O-Dma (66x). However, there was considerable individual variation in this metabolic response with peak levels of Eq showing the highest variation (1527x). An inverse relationship between Eq and O-Dma excretion was also found post-challenge suggesting individual variability in the preferred metabolic pathways of dietary isoflavones.

4-Butyrolactone↗