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Biomedical subjects

M Simons

Publications and source records attributed to M Simons.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes.

We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In aggreement with previously reported results using avian tissues, we show that the mRNAs encoding the two myosin heavy chain isoforms are differentially expressed in rat nonmuscle and muscle tissues as well as in a number of human cell lines. The cDNA sequence encoding the 5' portion of the NMMHC-A isoform completes the previously published 3' cDNA sequence encoding a human myosin heavy chain, thus providing the cDNA sequence encoding the entire NMMHC-A amino acid sequence. Comparison of this sequence to cDNA clones encoding the amino-terminal one third of the NMMHC-B sequence (amino acids 58-718) shows them to be 89% identical at the amino acid level and 74% identical at the nucleotide level.

Amino Acid Sequence↗
PubMed1990

Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region.

The frequency of nasopharyngeal carcinoma is nearly 100-fold higher in southern Chinese than in most European populations. Earlier studies have suggested that an increased risk of nasopharyngeal carcinoma is associated with specific haplotypes in the HLA region: relative risks slightly over twofold were found for haplotypes A2, Bw46 and the antigen B17. We now report a linkage study based on affected sib pairs which suggests that a gene closely linked to the HLA locus confers a greatly increased risk of nasopharyngeal carcinoma. The maximum likelihood estimate is of a relative risk of approximately 21. The relationship between this suspected disease susceptibility gene (or genes) and known viral and environmental aetiological factors remains to be elucidated.

China↗
PubMed1990

Multiple hepatic abscesses: cholangiographic changes simulating sclerosing cholangitis and resolution after percutaneous drainage.

A 59-yr-old man developed multiple hepatic abscesses following an episode of diverticulitis. A percutaneous transhepatic cholangiogram (PTC) showed changes typical of sclerosing cholangitis complicated by multiple hepatic abscesses. No biliary tract stones were seen either on ultrasound or PTC. A single drain left in the right biliary tree and a course of intravenous antibiotics resulted in complete normalization within 14 days of the previously involved biliary tree.

Bacteroides Infections↗
PubMed1975

Measurement of gastric blood flow with radioactive microspheres.

The validity of using radioactive microspheres (15 +/- 5-mum diameter) to measure gastric blood flow and its partition between gastric wall layers was investigated in anesthetized dogs with a chambered segment of gastric corpus. Total flow measured by a venous effluent technique demonstrated close correlation with microsphere-measured flow (r = 0.98, slope = 0.95) in 12 dogs given histamine, gastrin, or isoproterenol. In 12 histamine-stimulated dogs, mucosal flow measured by aminopyrine clearance and by microspheres also showed good agreement (r = 0.96, slope = 0.83). No evidence was found to indicate that microspheres altered hemodynamic or gastric function. In all experiments less than 1% of the total gastric radioactivity passed through arteriovenous shunts. The mucosa always contained a statistically adequate number of spheres (greater than 400), but the submucosa and muscularis frequently did not. Microspheres of all sizes mixed adequately in large arteries, but a significant difference was found in the distribution of 16- and 26 mum spheres between mucosa and submucosa, presumably because of streaming of the larger spheres past mucosal arteries. It was concluded that, with the techniques developed in our laboratory, microspheres could be a highly useful tool for quantitating gastric regional blood flow under a variety of experimental conditions.

Aminopyrine↗
PubMed1975

Effect of p-chloromercuribenzene sulfonate on gastric parietal and surface cell function in the dog.

p-Chloromercuribenzene sulfonate, a polar organic mercurial which presumably penetrates cell membranes with great difficulty, led to a profound decrease in acid recovered from exteriorized segments of dog gastric fundus stimulated by exogenous histamine. Trapping of secreted hydrogen ions by Tris buffer did not significantly reduce the back-diffusion component of apparent inhibition. Sodium-for-hydrogen exchange was close to unity before and after inhibition.

Animals↗