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M Simons

Publications and source records attributed to M Simons.

At least 163 records · Page 9Linked to original sources
PubMed1993

Fractal landscapes and molecular evolution: modeling the myosin heavy chain gene family.

Mapping nucleotide sequences onto a "DNA walk" produces a novel representation of DNA that can then be studied quantitatively using techniques derived from fractal landscape analysis. We used this method to analyze 11 complete genomic and cDNA myosin heavy chain (MHC) sequences belonging to 8 different species. Our analysis suggests an increase in fractal complexity for MHC genes with evolution with vertebrate > invertebrate > yeast. The increase in complexity is measured by the presence of long-range power-law correlations, which are quantified by the scaling exponent alpha. We develop a simple iterative model, based on known properties of polymeric sequences, that generates long-range nucleotide correlations from an initially noncorrelated coding region. This new model-as well as the DNA walk analysis-both support the intron-late theory of gene evolution.

Actins↗
PubMed1993

A new vascular access catheter for hemodialysis.

A new vascular access catheter has been developed (Cook Critical Care, Bloomington, IN) that is suitable for both short-term and long-term hemodialysis. Designed primarily for the internal jugular vein, it emerges through a subcutaneous tunnel on the anterior chest wall. With parallel cylindrical lumens to provide blood flows of 400 mL/min, it is compressible during insertion and can be placed percutaneously in the vein through a 13-French peel-away sheath. This allows repeated insertions at different times in the same patient. In 80 catheter insertions, we have found one case of jugular vein thrombosis attributable to the catheter and no subclavian vein thrombosis. After 15 months of use, the bloodstream infection rate was one per 19.7 patient-months. Using this device, it should be possible to stop the subclavian vein damage and perforating injuries that have been the most important complications of semistiff, tapered, subclavian catheters.

Adult↗
PubMed1993

Superior vena cava stenosis associated with hemodialysis catheters.

The cases are described of four patients on long-term hemodialysis who developed stenosis of the superior vena cava (SVC) that interfered with the functioning or placement of jugular catheters for hemodialysis. All four patients had previously received multiple subclavian and/or jugular catheters inserted for hemodialysis access. In three patients, the SVC stenosis was successfully dilated by balloon angioplasty, and in one of these a stent was inserted to prevent restenosis. These three patients have subsequently been successfully dialyzed with jugular catheters. Stenosis of the SVC should be suspected when jugular catheters in the SVC give inadequate flows in the absence of thrombotic obstruction. Balloon dilatation with or without vascular stenting may allow satisfactory vascular access to be reestablished.

Aged↗
PubMed1993

Finite-size effects on long-range correlations: implications for analyzing DNA sequences.

We analyze the fluctuations in the correlation exponents obtained for noncoding DNA sequences. We find prominent sample-to-sample variations as well as variations within a single sample in the scaling exponent. To determine if these fluctuations may result from finite system size, we generate correlated random sequences of comparable length and study the fluctuations in this control system. We find that the DNA exponent fluctuations are consistent with those obtained from the control sequences having long-range power-law correlations. Finally, we compare our exponents for the DNA sequences with the exponents obtained from power-spectrum analysis and correlation-function techniques, and demonstrate that the original "DNA-walk" method is intrinsically more accurate due to reduced noise.

Animals↗
PubMed1993

Generalized Lévy-walk model for DNA nucleotide sequences.

We propose a generalized Lévy walk to model fractal landscapes observed in noncoding DNA sequences. We find that this model provides a very close approximation to the empirical data and explains a number of statistical properties of genomic DNA sequences such as the distribution of strand-biased regions (those with an excess of one type of nucleotide) as well as local changes in the slope of the correlation exponent alpha. The generalized Lévy-walk model simultaneously accounts for the long-range correlations in noncoding DNA sequences and for the apparently paradoxical finding of long subregions of biased random walks (length lj) within these correlated sequences. In the generalized Lévy-walk model, the lj are chosen from a power-law distribution P(lj) varies as lj(-mu). The correlation exponent alpha is related to mu through alpha = 2-mu/2 if 2 < mu < 3. The model is consistent with the finding of "repetitive elements" of variable length interspersed within noncoding DNA.

Base Sequence↗
PubMed1993

Effects of hypoxia and atrial natriuretic peptide on aldosterone secretion in healthy subjects.

To evaluate the inhibitory effect of hypoxia and atrial natriuretic peptide (ANP) on aldosterone secretion, 11 healthy male subjects were infused with 5 ng.kg-1 x min-1 ANP or placebo. The subjects were exposed in a stepwise fashion to incremental hypobaric hypoxia, which decreased arterial oxygen saturation to 79 +/- 2% in the placebo and 84 +/- 2% in the ANP condition (P < 0.05). In the placebo condition, the plasma ANP concentration increased from 13.8 +/- 1.0 to 19.6 +/- 2.3 pmol/l (P < 0.01) at the lowest barometric pressure. Plasma renin activity did not change, whereas the plasma aldosterone levels increased consequent to the increase of plasma adrenocorticotropic hormone (ACTH). Continuous infusion of ANP increased the plasma levels twofold (P < 0.001) and the level of guanosine 3',5'-cyclic monophosphate threefold (P < 0.001). However, the plasma aldosterone concentrations were not different in the two experimental conditions. Administration of supplementary oxygen significantly decreased ACTH to baseline values (P < 0.01) together with a decrease in aldosterone. Free water clearance (P = 0.05) but not sodium excretion (P = NS) increased during continuous ANP infusion. The data indicate that the aldosterone secretion in hypoxia is not inhibited by (patho)physiological plasma ANP levels. The inhibition of aldosterone secretion may well be explained by a direct effect of hypoxia on the adrenal cells. ACTH is a major stimulus of aldosterone secretion in hypoxia, which overrides the natriuretic effect of ANP.

Adrenocorticotropic Hormone↗
PubMed1992

Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals.

Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

Animals↗
PubMed1992

Fractal landscape analysis of DNA walks.

By mapping nucleotide sequences onto a "DNA walk", we uncovered remarkably long-range power law correlations [Nature 356 (1992) 168] that imply a new scale invariant property of DNA. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences, but not in cDNA sequences or intron-less genes. In this paper, we present more explicit evidences to support our findings.

DNA↗
PubMed1992

Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo.

Synthetic antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonucleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the blood vessel wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders.

Animals↗
PubMed1992

Long-range correlations in nucleotide sequences.

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.

Animals↗
PubMed1992

Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.

BACKGROUND: Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile phenotype) preferentially express smooth muscle myosin, proliferating smooth muscle cells (synthetic phenotype) have been shown to preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed the expression of a recently cloned isoform of human nonmuscle myosin heavy chain (MHC-B) in fresh human restenotic lesions. METHODS AND RESULTS: A total of 10 lesions, including four restenosis (three superficial femoral arterial lesions and one saphenous vein bypass lesion) and six primary (four superficial femoral arterial lesions and two coronary arterial lesions) obtained percutaneously by directional atherectomy, were processed for examination by in situ hybridization. In total, 150 tissue sections of restenotic lesions (66 sections), primary lesions (78 sections), and normal internal mammary artery (six sections) were hybridized with the nonmuscle MHC-B probe. Restenotic lesions showed intense hybridization to the nonmuscle MHC-B cRNA probe, as demonstrated by a clustering of more than 20 grains per cell nucleus in 80% of the cells examined within a high-power field (x250); in contrast, an equivalent degree of hybridization was observed in only 7% of cells within primary lesions (p less than 0.001). Results of immunocytochemistry using monoclonal antibody to smooth muscle actin indicated that cells demonstrating strong hybridization were smooth muscle in origin. CONCLUSIONS: These findings demonstrate that 1) human vascular tissue obtained by percutaneous directional atherectomy constitutes appropriate biopsy material for gene expression studies at the mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance among restenotic versus primary vascular stenoses. These observations thus provide a rational basis to explore restenotic lesions on a larger scale to identify genes that are activated in these lesions and establish potential targets for future gene therapy.

Arteriosclerosis↗
PubMed1992

Antisense nonmuscle myosin heavy chain and c-myb oligonucleotides suppress smooth muscle cell proliferation in vitro.

Smooth muscle cell (SMC) proliferation is a poorly understood process that plays a critical role in several pathological states, including atherosclerosis and hypertension. Recent work suggests that the oncogene c-myb and myosin, a ubiquitous cytoskeletal protein, may be directly involved in this process. We have used antisense nonmuscle myosin heavy chain (NMMHC) or c-myb phosphorothiolate oligonucleotides to inhibit proliferation of SMCs in vitro. The suppression of growth is accompanied by reductions in the concentrations of NMMHC and c-myb mRNAs as well as decreases in the levels of the corresponding proteins. The specificity of the antiproliferative effect is underscored by the absence of any detectable growth inhibition with sense NMMHC or c-myb phosphorothiolate oligonucleotides, an antisense c-myb mismatch phosphorothiolate oligonucleotide, or an antisense thrombomodulin phosphorothiolate oligonucleotide. Furthermore, the treatment of SMCs with antisense phosphorothiolate oligonucleotides for as little as 2 hours causes maximal inhibition of cell growth over the next 72 hours. Under these conditions, SMCs attain normal rates of growth over the following 48 hours, which shows that proliferation is suppressed in a reversible fashion by antisense phosphorothiolate oligonucleotides. These experiments indicate that both c-myb and nonmuscle myosin play critical roles in SMC proliferation and that reductions of either mRNA by antisense phosphorothiolate oligonucleotides arrest the process.

Animals↗
PubMed1992

Receiver-operating-characteristic study of chest radiographs in children: digital hard-copy film vs 2K x 2K soft-copy images.

Two methods are commonly used to visualize digital radiologic imaging data: (1) hard-copy viewing, in which the digital data are used to modulate the intensity of a laser beam that exposes an analog film and (2) soft-copy viewing, in which the digital data are converted to an analog video signal and presented on a CRT monitor. The film method allows new digital imaging systems to be easily integrated into conventional radiologic management and viewing methods. The second method, soft-copy viewing, allows digital imaging data to be managed and viewed electronically in a picture archiving and communication system (PACS). These PACS systems are hypothesized to have improved operational efficiency and enhanced image-analysis capabilities. The quality of soft-copy images is still not widely accepted. This article reports on the results of a large-scale receiver-operating-characteristic study comparing observers' performance in detecting various pediatric chest abnormalities on soft-copy 2048 x 2048K byte displays with their performance with digital laser-printed film from computed radiography. The disease categories studied were pneumothorax, linear atelectasis, air bronchogram, and interstitial disease. The selected data set included 239 images; 77 contained no proved abnormality and 162 contained one or more of the abnormalities mentioned. Seven pediatric radiologists participated in the study, two as judges and five as observers. Our results show no significant difference between viewing images on digital hard copy and soft copy for the detection of pneumothoraces and air bronchograms. A slight performance edge for soft copy was seen for interstitial disease and linear atelectasis. This result indicates that computed chest radiographs in children viewed in a soft-copy PACS environment should result in diagnoses similar to or slightly more accurate than those obtained in a laser-printed film-based environment.

Child↗
PubMed1992

Assessment of cardiovascular reflexes is of limited value in predicting maximal +Gz-tolerance.

The importance of +Gz-induced loss of consciousness as a major cause of inflight incapacitation emphasizes the need for predicting +Gz-tolerance and investigating its possible determinants. The cardiovascular changes from +Gz-stress are initially counteracted reflexly by the cardiovascular autonomic system. The integrity of neural cardiovascular reflex control can be assessed by analysing the blood pressure (BP) and heart rate (HR) responses to different maneuvers, such as the Valsalva maneuver, standing and forced respiratory sinus arrhythmia. The aim of the present study was to investigate a possible relation between the cardiovascular responses to these tests and +Gz-tolerance. In 10 healthy subjects continuous Finapres BP and HR responses to the tests have been determined and correlated with their G-levels of peripheral light loss (PLL) during centrifuge-runs (0.1 G/s). Only mean BP recovery during Valsalva maneuver correlated marginally significantly with PLL (r = 0.63, p = 0.049). Cardiovascular findings were within normal range revealing no cardiovascular autonomic dysfunction. These results indicate that intact neural cardiovascular control seems to be a condition for tolerating +Gz-stress without determining maximal +Gz-tolerance. We conclude that assessment of cardiovascular reflexes may only confirm baroreflex integrity. However, they have limited value in predicting +Gz-tolerance.

Acceleration↗
PubMed1991

Children who cross cultures.

The subject of this study is the effects of transcultural sojourn and culture shock on the psycho-social development and school achievement of Dutch children. One hundred and three Dutch children in the age range 6-17 years who stayed abroad with their parents for at least two years and returned to Holland were compared with 81 Dutch classmates of the same age and sex. The class teacher and parent(s) were the informants. The transcultural group showed more behavioural problems on the Dutch version of the Child Behavior Checklist developed by Achenbach. Parents of the transcultural group regarded their children on a modified Graham & Rutter questionnaire as less happy than the control parents. However, no differences were found for academic achievement or problem behaviour at school as assessed by the teacher version of the CBCL, the 'Teacher's Report Form' (TRF). Organizations which send their employees abroad should direct more attention to employees' children. Attention given by parents and teachers to language problems and school performance should not pre-empt close attention to the psycho-social development of children.

Adolescent↗