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Biomedical subjects

M Siegel

Publications and source records attributed to M Siegel.

At least 19 recordsLinked to original sources
PubMed2006

Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy.

Transglutaminase 2 (TG2, a.k.a. tissue transglutaminase) belongs to a family of transglutaminase enzymes that stabilize proteins by affecting covalent crosslinking via formation of amide bonds. Cell surface TG2 is directly involved as an adhesive receptor in cell-extracellular matrix (ECM) interactions. Here, we show that TG2 activity is elevated in glioblastomas compared with non-neoplastic brain. Immunofluorescent studies showed increased staining of fibronectin colocalized with TG2 in the ECM in glioblastomas. In addition, small clusters of invading human glioblastoma cells present in non-neoplastic brain parenchyma secrete high levels of TG2 and fibronectin that distinguish them from normal brain stroma. Downregulation of TG2 in U87MG glioblastoma cells with RNAi demonstrated decreased assembly of fibronectin in the ECM. Treatment with KCC009 blocked the remodeling of fibronectin in the ECM in glioblastomas in both in vitro and in vivo studies. KCC009 treatment in mice harboring orthotopic glioblastomas (DBT-FG) sensitized the tumors to N,N'-bis(2-chloroethyl)-N-nitrosourea chemotherapy, as measured by reduced bioluminescence, increased apoptosis and prolonged survival. The ability of KCC009 to interfere with the permissive remodeling of fibronectin in the ECM in glioblastomas suggests a novel target to enhance sensitivity to chemotherapy directed not only at the tumor mass, but also invading glioblastoma cells.

Animals↗
PubMed2006

Commensurability effects in superconducting Nb films with quasiperiodic pinning arrays.

We study experimentally the critical depinning current I(c) versus applied magnetic field B in Nb thin films which contain 2D arrays of circular antidots placed on the nodes of quasiperiodic (QP) fivefold Penrose lattices. Close to the transition temperature T(c) we observe matching of the vortex lattice with the QP pinning array, confirming essential features in the I(c)(B) patterns as predicted by Misko et al. [Phys. Rev. Lett. 95, 177007 (2005)]. We find a significant enhancement in I(c)(B) for QP pinning arrays in comparison to I(c) in samples with randomly distributed antidots or no antidots.

Journal Article↗
PubMed2006

Ionization of noble gases with pulses directly from a laser oscillator.

A Ti:sapphire oscillator with an extended cavity generates pulses with 0.5 microJ energy at a repetition rate of 6 MHz and pulse durations of 50 fs. Tight focusing creates peak intensities exceeding 10(14) W/cm2, which is sufficient for ionizing helium, a nonlinear process where at least 17 photons are absorbed simultaneously.

Journal Article↗
PubMed2005

High-efficiency deterministic Josephson vortex ratchet.

We investigate experimentally a Josephson vortex ratchet--a fluxon in an asymmetric periodic potential driven by a deterministic force with zero time average. The highly asymmetric periodic potential is created in an underdamped annular long Josephson junction by means of a current injector providing an efficiency of the device up to 91%. We measured the ratchet effect for driving forces with different spectral content. For monochromatic high-frequency drive the rectified voltage becomes quantized. At high driving frequencies we also observe chaos, subharmonic dynamics, and voltage reversal due to the inertial mass of a fluxon.

Journal Article↗
PubMed2005

Effect of local restaurant smoking regulations on progression to established smoking among youths.

BACKGROUND: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. OBJECTIVE: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. DESIGN, SETTING, AND SUBJECTS: A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. MAIN OUTCOME MEASURE: Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). RESULTS: Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. CONCLUSIONS: Local restaurant smoking bans may be an effective intervention to prevent youth smoking.

Adolescent↗
PubMed2004

Relation between local restaurant smoking regulations and attitudes towards the prevalence and social acceptability of smoking: a study of youths and adults who eat out predominantly at restaurants in their town.

OBJECTIVE: To examine the relation between strength of local restaurant smoking regulations and smoking related social norms among youths and adults. DESIGN: We used generalised estimating equations logistic regression analysis to examine the relation between regulation strength and youths' and adults' perceptions of adult smoking prevalence and the social acceptability of smoking in their town, while controlling for baseline anti-smoking sentiment in the town. SETTING: Each of the 351 Massachusetts towns were classified as having strong (complete smoking ban), medium (restriction of smoking to enclosed, separately ventilated areas), or weak (all others) restaurant smoking regulations. SUBJECTS: 1147 Massachusetts youths ages 12-17 years and 2116 adults who reported that they often or always eat out in their own town, drawn from a random digit dial survey. MAIN OUTCOME MEASURES: Perceived adult smoking prevalence and perceived social acceptability of smoking in restaurants, in bars, or in general. RESULTS: Compared to youths from towns with weak regulations, youths from towns with strong regulations were more likely to perceive lower adult smoking prevalence (odds ratio (OR) 1.71; 95% confidence interval (CI) 1.02 to 2.84) and social unacceptability of adult smoking (OR 2.00, 95% CI 1.29 to 3.08) in their town. Adults from towns with strong regulations were not more likely to perceive lower adult smoking prevalence, but had more than twice the odds of perceiving that smoking was unacceptable in restaurants (OR 2.19, 95% CI 1.58 to 3.02) or bars (OR 2.51, 95% CI 1.90 to 3.31). CONCLUSIONS: Strong local restaurant smoking regulations are associated with favourable smoking related social norms among youths and adults.

Adolescent↗
PubMed2003

The descriptive epidemiology of local restaurant smoking regulations in Massachusetts: an analysis of the protection of restaurant customers and workers.

OBJECTIVES: To describe the range of restaurant smoking regulations in the 351 cities and towns in Massachusetts, and to analyse the level of protection from secondhand smoke exposure guaranteed by these regulations. DESIGN: We obtained the local restaurant smoking regulations for each town, analysing them in terms of the protection of restaurant workers, bar workers, and adult and youth restaurant customers. MAIN OUTCOME MEASURE: The percentage of restaurant patrons and workers and bar workers who are protected from secondhand smoke exposure by the current smoking regulations in Massachusetts. RESULTS: As of June 2002, 225 towns had local restaurant smoking regulations. Of these, 69 (30.7%) do not allow smoking in restaurants, 10 (4.4%) restrict smoking to adult only restaurants, 64 (28.4%) restrict smoking to enclosed, separately ventilated areas, and 82 (36.4%) restrict smoking to areas that need not be enclosed and separately ventilated. Of the 174 towns that, at a minimum, restrict smoking to bar areas or separately ventilated areas, 35 (20.1%) allow variances. Overall, 60 towns, covering only 17.7% of the population, completely ban smoking in restaurants. As a result, 81.3% of adult restaurant customers, 81.2% of youth customers, 82.3% of restaurant workers, and 87.0% of bar workers are not guaranteed protection from secondhand smoke in restaurants. CONCLUSIONS: Despite the widespread adoption of local restaurant smoking regulations in Massachusetts, the majority of restaurant customers and workers remain unprotected from secondhand smoke exposure. In light of this, public health practitioners must stop compromising the protection of customers and workers from secondhand smoke exposure in restaurants.

Adolescent↗
PubMed2003

Perceived importance of being thin and smoking initiation among young girls.

BACKGROUND: Smoking among adolescents remains unacceptably high and the difference in potential risk factors for smoking initiation between male and female adolescents has been explored. Although the association between smoking initiation and dieting behaviour has been observed among girls, the mechanism of the association is unknown. OBJECTIVE: To examine prospectively the association between perceived importance of being thin at baseline and smoking initiation among girls. DESIGN: A four year prospective cohort survey including perceived importance of being thin at baseline and smoking behaviour, conducted in 1993 and 1996. SETTING AND PARTICIPANTS: 273 Massachusetts female adolescents aged 12-15 years at baseline who reported having smoked no more than one cigarette by the time of the baseline survey, drawn from households sampled by random digit dialing. MAIN OUTCOME MEASURE: Progression to established smoking, defined as having smoked 100 or more cigarettes in their lifetime. RESULTS: After adjusting for age, smoking status at baseline, and race/ethnicity, girls who valued thinness most strongly and somewhat strongly were both more likely to have become established smokers, compared to the girls who valued thinness least strongly. The odds ratios are 4.5 (95% confidence interval (CI), 1.4 to 16.7) and 3.4 (95% CI 1.04 to 10.9), respectively. CONCLUSIONS: The level of perceived importance of being thin among young female adolescents predicts future smoking initiation. Smoking prevention programmes designed for female adolescents may therefore benefit from the inclusion of content related to importance of being thin.

Adolescent↗
PubMed2003

Exposure to secondhand smoke and excess lung cancer mortality risk among workers in the "5 B's": bars, bowling alleys, billiard halls, betting establishments, and bingo parlours.

OBJECTIVE: To review existing data on exposure to secondhand smoke in bars, bowling alleys, billiard halls, betting establishments, and bingo parlours (the "5 B's") as assessed by ambient nicotine air concentration measurements and to estimate the excess lung cancer mortality risk associated with this exposure. DATA SOURCES: Using the Medline, Toxline, and Toxnet databases, the internet, and bibliographies of relevant articles, we identified studies that reported measurements of ambient nicotine concentrations in the 5 B's. STUDY SELECTION: Studies were included if they reported a mean concentration of ambient nicotine measured in at least one of the 5 B's. DATA EXTRACTION: We calculated a weighted average of nicotine concentrations in each of the 5 B's. We then estimated the working lifetime excess lung cancer mortality risk associated with this exposure, as well as with exposure at the upper and lower limits of the range of mean exposures reported in all of the studies in each establishment category. DATA SYNTHESIS: Nicotine concentrations in the 5 B's were 2.4 to 18.5 times higher than in offices or residences, and 1.5 to 11.7 times higher than in restaurants. At these exposure levels, estimated working lifetime excess lung cancer mortality risk from secondhand smoke exposure for workers in the 5 B's is between 1.0-4.1/1000, which greatly exceeds the typical de manifestis risk level of 0.3/1000. CONCLUSIONS: Workers in the 5 B's have high levels of occupational exposure to secondhand smoke and must be included in workplace smoking regulations.

Humans↗
PubMed2002

Effects of small surface tension in Hele-Shaw multifinger dynamics: an analytical and numerical study.

We study the singular effects of vanishingly small surface tension on the dynamics of finger competition in the Saffman-Taylor problem, using the asymptotic techniques described by Tanveer [Philos. Trans. R. Soc. London, Ser. A 343, 155 (1993)] and Siegel and Tanveer [Phys. Rev. Lett. 76, 419 (1996)], as well as direct numerical computation, following the numerical scheme of Hou, Lowengrub, and Shelley [J. Comput. Phys. 114, 312 (1994)]. We demonstrate the dramatic effects of small surface tension on the late time evolution of two-finger configurations with respect to exact (nonsingular) zero-surface-tension solutions. The effect is present even when the relevant zero-surface-tension solution has asymptotic behavior consistent with selection theory. Such singular effects, therefore, cannot be traced back to steady state selection theory, and imply a drastic global change in the structure of phase-space flow. They can be interpreted in the framework of a recently introduced dynamical solvability scenario according to which surface tension unfolds the structurally unstable flow, restoring the hyperbolicity of multifinger fixed points.

Journal Article↗
PubMed2001

The Master Settlement Agreement with the tobacco industry and cigarette advertising in magazines.

BACKGROUND: In 1998, the attorneys general of 46 states signed a Master Settlement Agreement with the four largest tobacco companies in the United States. The agreement prohibits tobacco advertising that targets people younger than 18 years of age. METHODS: We analyzed the trends in expenditures for advertising for 15 specific brands of cigarettes and the exposure of young people to cigarette advertising in 38 magazines between 1995 and 2000. We defined cigarette brands as "youth" brands if they were smoked by more than 5 percent of the smokers in the 8th, 10th, and 12th grades in 1998; all others were considered to be "adult" brands. We classified magazines as youth-oriented magazines if at least 15 percent of their readers or at least 2 million of their readers were 12 to 17 years old. "Reach," a standard measure of exposure to advertising, was defined as the number of young persons who read at least one issue of a magazine containing an advertisement for a particular brand of cigarette during a given year. RESULTS: In 2000 dollars, the overall advertising expenditures for the 15 brands of cigarettes in the 38 magazines were $238.2 million in 1995, $219.3 million in 1998, $291.1 million in 1999, and $216.9 million in 2000. Expenditures for youth brands in youth-oriented magazines were $56.4 million in 1995, $58.5 million in 1998, $67.4 million in 1999, and $59.6 million in 2000. Expenditures for adult brands in youth-oriented magazines were $72.2 million, $82.3 million, $108.6 million, and $67.6 million, respectively. In 2000, magazine advertisements for youth brands of cigarettes reached more than 80 percent of young people in the United States an average of 17 times each. CONCLUSIONS: The Master Settlement Agreement with the tobacco industry appears to have had little effect on cigarette advertising in magazines and on the exposure of young people to these advertisements.

Adolescent↗
PubMed2001

Penicillin-resistant Streptococcus pneumoniae endocarditis: a case report and review.

Streptococcus pneumoniae has been a rare cause of endocarditis in the postantibiotic era. The emergence of antibiotic-resistant Pneumococcus species has been accompanied by isolated reports of penicillin-resistant S. pneumoniae (PRSP) endocarditis. We report a case of bivalvular PRSP endocarditis that was treated with vancomycin and trovafloxacin, and we review the literature on this topic.

Anti-Bacterial Agents↗
PubMed2001

Detection of four human milk groups with respect to Lewis-blood-group-dependent oligosaccharides by serologic and chromatographic analysis.

Oligosaccharides from human milk samples obtained from individual donors were analyzed using high-pH anion-exchange chromatography. Three patterns of neutral oligosaccharides were detected corresponding to milk groups already described. These oligosaccharide groups correspond to the Lewis blood types Le(a-b+), Le(a+b-), and Le(a-b-). A new carbohydrate pattern was detected in a milk sample from a Le(a-b-) person in which only nonfucosylated oligosaccharides and compounds bearing alpha1,3-linked fucosyl residues were found. This finding led to the hypothesis that there exist 4 different oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood group system.

Anions↗
PubMed2001

Prenatal diagnosis of esophageal atresia using sonography and magnetic resonance imaging.

BACKGROUND: The diagnosis of esophageal atresia may be suspected on prenatal ultrasound scan in fetuses with a small or absent stomach or unexplained polyhydramnios. However, these findings are thought to have a low positive predictive value and clinical decisions affecting timing or site of delivery may be made erroneously. The authors evaluated the accuracy of fetal sonography followed by magnetic resonance imaging (MRI) for the diagnosis of this lesion. METHODS: Fetuses considered to be at risk for esophageal atresia based on detailed obstetric sonography underwent fetal MRI using a single-shot rapid-acquisition technique, and the T(2)-weighted images were evaluated prospectively. Scans were considered to be positive if the proximal esophagus was dilated, and the distal esophagus was not seen and negative if the esophagus was visualized throughout its length. RESULTS: Ten fetuses underwent MRI scanning. All had a small or absent stomach bubble with unexplained polyhydramnios. Four scans were considered to be negative for esophageal atresia; all 4 were found to have a normal esophagus after delivery. Six scans were considered to be positive; 5 had esophageal atresia (2 with tracheoesophageal fistula and 3 without), and one had a neurologic syndrome with a normal esophagus. CONCLUSIONS: Magnetic resonance imaging appears to be accurate for establishing or ruling out a prenatal diagnosis of esophageal atresia, and should be considered in fetuses who are at high risk based on ultrasound findings.

Esophageal Atresia↗
PubMed2001

The impact of involuntary job loss on subsequent alcohol consumption by older workers: findings from the health and retirement survey.

OBJECTIVE: To estimate the effect of involuntary job loss on subsequent alcohol consumption by older workers in the United States. METHODS: Using longitudinal data from the 1992 and 1994 waves of the Health and Retirement Survey, the authors estimated multivariate models to assess the impact of involuntary job loss on subsequent alcohol use. Two outcomes were investigated: reported daily alcohol consumption and onset of drinking. The analysis sample included 207 workers who experienced involuntary job loss between survey dates and a comparison group of 2,866 continuously employed workers. RESULTS: After baseline alcohol consumption and a variety of socioeconomic and illness-related covariates were controlled, involuntary job loss was not associated (p>.05) with number of daily drinks consumed at follow-up. However, among those who did not consume alcohol at baseline, individuals who suffered involuntary job loss were twice as likely as continuously employed individuals to start drinking by follow-up (OR = 2.01; CI = 1.06-3.80). The majority of those who began drinking at follow-up reported drinking less than 1 drink per day. DISCUSSION: The findings provide evidence of a significant relationship between job loss and subsequent alcohol use among baseline nondrinkers. However, the magnitude of the changes in drinking was quite modest.

Aged↗