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Biomedical subjects

E Olson

Publications and source records attributed to E Olson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Activation of muscle-specific transcription by myogenic helix-loop-helix proteins.

Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.

Animals↗
PubMed1991

Differential trans-activation of a muscle-specific enhancer by myogenic helix-loop-helix proteins is separable from DNA binding.

The muscle creatine kinase (MCK) enhancer was used as a target to study the specificity of DNA binding and trans-activation by members of the helix-loop-helix (HLH) family of myogenic regulatory factors, MyoD1, myogenin, myf-5, and MRF4. Whereas all four myogenic factors bound with similar affinities to the MCK enhancer in the presence of the widely expressed HLH protein E12, only MyoD1, myogenin, and myf-5 efficiently trans-activated the enhancer in transiently transfected 10T1/2 and 3T3 cells. That MRF4 binds the MCK enhancer without activating transcription suggests that domains in addition to those required for DNA binding are important for transcriptional activation and supports the notion that the different members of the HLH family of myogenic regulatory factors may selectively regulate unique sets of muscle-specific genes.

Cells, Cultured↗
PubMed1991

Eliciting medical care preferences from nursing home residents.

We interviewed 44 residents of a nursing home to assess their preferences for care. Using case vignettes, we asked residents about resuscitation, hospital transfer, feeding tubes, and restraint use. Most were opposed to aggressive care unless the purpose was to enhance comfort or safety. However, sufficient diversity of opinions points to the need for advanced directives.

Advance Directives↗
PubMed1991

Characterization of glutathione S-transferase in cultured human keratinocytes.

The glutathione S-transferase activity and isozymic composition of cultured human keratinocytes were characterized. Keratinocytes were grown in culture and harvested at different stages of differentiation. Glutathione S-transferase activity was found in the soluble cell fraction but not in the microsomal cell fraction. The glutathione S-transferase specific activity of the soluble cell fraction was found to increase as the keratinocytes differentiated in culture. All of the enzymatic activity was found to reside with a single isozymic form that was concluded to be the pi form of the enzyme based on substrate specificity, sensitivity to inhibitors, molecular weight, and reactivity towards antibodies raised to alpha, mu, and pi forms of the enzyme. It is concluded that all of the isozymic forms of glutathione S-transferase noted in whole skin, with the exception of pi, are of extra-keratinocyte origin.

Amino Acid Sequence↗
PubMed1990

Shed tumor gangliosides and progression of human neuroblastoma.

Shedding of membrane gangliosides is characteristic of human and experimental tumors. Because some shed tumor gangliosides have potent tumor-enhancing properties, significant ganglioside shedding could influence tumor progression. We examined this possibility in a human tumor, neuroblastoma. Ganglioside shedding, measured as circulating tumor-derived GD2 ganglioside, and the outcome of 74 patients with advanced stage (III and IV) disease were studied. Progression-free survival (PFS) was inversely related to circulating GD2 levels at the time of diagnosis (P = .018). By Kaplan-Meier analysis, the quartile of patients having the highest circulating GD2 levels (greater than or equal to 568 pmol/mL) had a strikingly different outcome from the quartile of patients with the lowest (less than or equal to 103 pmol/mL) GD2 levels (P = .013): median PFS was shorter (9 v 28 months), and the long-term survival rate lower (2-year PFS of 24% v 70%). We conclude that more rapid disease progression and lower survival rate are associated with high circulating GD2 levels at diagnosis and speculate that shed neuroblastoma tumor gangliosides play a role in accelerating tumor progression.

Biomarkers, Tumor↗
PubMed1990

Myogenin is in an evolutionarily conserved linkage group on human chromosome 1q31-q41 and unlinked to other mapped muscle regulatory factor genes.

Myogenin is a member of a family of muscle-specific regulatory factors which includes MyoD1, Myf-5, and Myf-6 (also called MRF4 and herculin). Extensive regions of sequence homology in genes for these three factors suggest duplication events associated with their evolution. In the present study, the chromosomal location of the myogenin gene in humans (MYOG), mice (Myog), and Chinese hamsters (MYOG) was determined using in situ hybridization to human metaphase chromosomes as well as segregation analysis among interspecific somatic cell hybrid panels and interspecific backcrossed mice. We localize the gene encoding myogenin to human chromosome 1q31-q41 within a linkage group homologous with a region on mouse chromosome 1 and Chinese hamster chromosome 5. The results verify the nonlinkage of MYOG to MYOD1, MYF5, and MYF6 genes and indicate that events associated with the duplication of MYOG with respect to MYOD1, MYF5, or MYF6 loci were not chromosome-wide.

Animals↗
PubMed1990

The effects of freezing or freeze-drying on the biomechanical properties of the canine intervertebral disc.

The transplantation of spinal allografts to correct defects that include disc, body, or segments of both is currently under experimental investigation. A method of graft preservation that will least compromise the biomechanical integrity of the bodies or discs is required. Using a five-mode biomechanical analysis, the authors compared the change in stiffness of ten preserved canine spines. The freeze-dried specimens lost a significantly greater amount of stiffness in compression, flexion, extension, and torsion than did the frozen specimens. Therefore, from a biomechanical viewpoint, deep-freezing is superior to freeze-drying for spinal allograft preservation.

Animals↗
PubMed1988

Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair.

The human chromosomal assignments of genes of the creatine kinase (CK) family--loci for brain (CKBB), muscle (CKMM), and mitochondrial (CKMT) forms--were studied by Southern filter hybridization analysis of DNAs isolated from a human x rodent somatic cell hybrid clone panel. Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively. Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19. A probe containing canine sequences for CKMM cross-hybridized with human sequences on chromosomes 14 and 19, a result consistent with the assignments of CKBB and CKMM. A probe containing human sequences for CKMT enabled the provisional assignment of CKMT to human chromosome 15. Independent hybrids with portions of the long arm of chromosome 19 missing indicated the order of genes on the long arm of chromosome 19 as being cen-GPI-(TGFB, CYP1)-[CKMM, (APOC2-ERCC1)]-(CGB, FTL). The unexpectedly more distal location of APOC2 among the genes on the long arm--and APOC2's close association with CKMM--is discussed with respect to the close linkage relationship of APOC2 to myotonic muscular dystrophy.

Animals↗
PubMed1987

Duration of effects and tolerance of slow-release isosorbide-5-mononitrate for angina pectoris.

Isosorbide-5-mononitrate (IS-5MN) is an active metabolite of isosorbide dinitrate, but unlike its parent compound, is nearly 100% bioavailable after oral administration. Once-a-day therapy with a slow-release formulation of IS-5MN is used widely in Europe for 24-hour prophylaxis of angina pectoris. In a randomized, crossover, double-blind, placebo-controlled study, the duration of effects of 50 and 100 mg of slow-release IS-5MN were evaluated after the first dose and after once-a-day therapy for 1 week in 9 patients with stable angina pectoris. Compared with placebo values, standing blood pressure decreased (p less than 0.001) and exercise time to the onset of angina and total exercise duration increased (p less than 0.008 and p less than 0.003) at 4 hours, but not at 20 or 24 hours after first dose of 50 and 100 mg of slow-release IS-5MN. After once-a-day therapy for 1 week, no improvement in exercise duration or reduction in ST-segment depression was seen after 50 or 100 mg of slow-release IS-5MN at 4, 20 or 24 hours despite high plasma IS-5MN concentrations. Thus, despite therapeutic plasma concentrations, 50 and 100 mg of slow-release IS-5MN did not exert antianginal or anti-ischemic effects at 20 and 24 hours after the first dose and at 4, 20 and 24 hours after sustained once-a-day therapy for 1 week.

Adult↗
PubMed1986

Transdermal nitroglycerin patches in angina pectoris. Dose titration, duration of effect, and rapid tolerance.

The duration of effect of transdermal nitroglycerin patches was studied in 14 patients with angina pectoris. By titrating the dose to achieve specific circulatory effects, we chose a patch size that produced a consistent fall in systolic blood pressure of 10 mm Hg or greater for each patient (10 cm2 in 7 patients, 20 cm2 in 5, and 40 cm2 in 2; releasing 5, 10, and 20 mg of nitroglycerin per 24 hours, respectively). The effects of these individualized patches were compared with those of placebo patches. Compared with placebo, nitroglycerin patches increased exercise duration to the onset of angina (257 +/- 72 compared with 383 +/- 130 seconds, p less than 0.0001) and total exercise time (338 +/- 89 compared with 456 +/- 119 seconds, p less than 0.0001) and decreased ST segment depression (1.0 +/- 0.5 compared with 0.6 +/- 0.4 mm, p less than 0.05) at 4 hours but not at 24 and 48 hours. We conclude that nitroglycerin patches do not show objective evidence of antianginal or antiischemic effects for 24 hours. Tolerance to the circulatory and antianginal effects probably develops within 24 hours of patch application.

Administration, Topical↗
PubMed1985

Control by fibroblast growth factor of differentiation in the BC3H1 muscle cell line.

The regulation of creatine phosphokinase (CPK) expression by polypeptide growth factors has been examined in the clonal mouse muscle BC3H1 cell line. After arrest of cell growth by exposure to low concentrations of serum, BC3H1 cells accumulate high levels of muscle-specific proteins including CPK. The induction of this enzyme is reversible in the presence of high concentrations of fetal calf serum, which cause quiescent, differentiated cells to reenter the cell cycle. Under these conditions, the rate of CPK synthesis is drastically reduced. We show in the present communication that either pituitary-derived fibroblast growth factor (FGF) or brain-derived FGF are as effective as serum in repressing the synthesis of CPK when added to quiescent, differentiated cells. The decrease in the rate of synthesis of CPK occurs within 22 h after the addition of pituitary FGF to the cells. Pituitary FGF had very little effect, if any, on the rate CPK degradation. The overall rate of protein synthesis and the pattern of synthesis of the major polypeptides made by these cells was not altered by the addition of FGF. Although pituitary FGF was mitogenic for BC3H1 cells, the rate of cell growth was not absolutely correlated with the extent of repression of CPK. Brain-derived FGF fully repressed CPK induction under conditions where it showed no significant mitogenic activity. These results show that the expression of a muscle-specific protein, CPK, can be controlled by a single defined polypeptide growth factor in fully differentiated cultures, and that initiation of cell division is not required for their regulation to take place.

Animals↗
PubMed1985

Cerebral venous angiomas: MR imaging.

Seven patients with angiographically proved cerebral venous angiomas were imaged by magnetic resonance. The venous angioma was identified in all cases. The most characteristic feature was an enlarged transcerebral draining vein (86%), followed by increased signal on T2-weighted images (57%) and decreased signal on T1-weighted images (40%) in adjacent parenchyma. Mass effect was absent in all cases. T2 imaging was more successful in showing the lesions than was T1 imaging.

Adolescent↗
PubMed1984

Cerebral venous angiomas.

Several unusual cases of cerebral venous angiomas as well as some characteristic cases are reported. The characteristic angiographic feature is that of a collection of dilated medullary veins draining into a single large draining vein, which appears first in the early venous phase and persists into the late venous phase of the arteriogram. Computed tomography (CT) was abnormal in 12/13 cases. The draining vein was the most common abnormality identified on CT. Coronal and sagittal reconstruction may be helpful in demonstrating the draining vein. A case of large twin venous angiomas, a case of hemorrhage from a venous angioma, and a case of a venous angioma with an incidentally associated glioblastoma are presented.

Adolescent↗