Biomedical subjects

C Simon

Publications and source records attributed to C Simon.

At least 19 recordsLinked to original sources

PubMed2002

[Inhibition of cellular signal transduction cascades. A future anti-invasive therapeutic strategy for cancers of the head and neck region].

BACKGROUND: Squamous cell carcinomas of the head and neck are considered to be highly aggressive cancers. The 5-year survival rate of patients with this disease depends on whether a locoregional relapse occurs and if so, how early after the initial treatment. Disease was found to relapse more frequently in patients suffering from cancers with an invasive growth pattern. It was therefore concluded that cancer cell invasion influences the patient's survival. While considerable efforts are made to develop treatment regimens for relapsing disease, a novel approach consists of the prevention of the disease recurrence through the inhibition of cancer cell invasion. METHOD: Literature search. RESULTS: We summarize in this article the mechanisms of tumor invasion, focusing on the regulation of tumor proteases, which are essential for cancer invasion, and provide an overview of preliminary results with novel anti-invasive treatment strategies. CONCLUSION: Novel anti-invasive treatment regimens based on an understanding of molecular cancer invasion mechanisms may be used in the future to treat patients with head and neck cancers.

Antineoplastic Agents↗

PubMed2002

Ten-year trends of dietary intake in a middle-aged French population: relationship with educational level.

OBJECTIVE: To compare dietary intakes at a 10 y interval of a population aged 35-64 living in France. Trends in nutrient intake and food consumption were examined with a special emphasis on the relationships between educational level and dietary behaviour. DESIGN: Two independent surveys conducted in 1985-1987 (S1) and 1995-1997 (S2) in the framework of the WHO MONICA project. Dietary intake was assessed with a 3-day record method and a food frequency questionnaire. The samples analysed included 416 men and 446 women for S1, 393 men and 409 women for S2. RESULTS: A significant improvement of the quality of fat intake was observed between S1 and S2, independently of educational level, with an increase of the age adjusted P/S ratio from 0.42 to 0.50 in men (P=10(-4)) and from 0.41 to 0.50 in women (P=10(-4)), whereas the daily cholesterol intake dropped from 552.0 to 466.9 mg and from 447.2 to 384.6 mg in men and women, respectively (P=10(-4)). These variations were associated with a decrease in the consumption of high-fat foods and an increase in that of low-fat products (poultry, low-fat dairy foods, fish) in all educational classes. By contrast, the consumption of fruit and vegetables, which was highly associated with educational level, varied little over time. CONCLUSIONS: Our results indicate slight improvement in fat quality, independently of educational level, while fruit and vegetable intake, which appeared more dependent on educational level, was only poorly modified over the 10 y interval.

Adult↗

PubMed2002

Time-courses in renin and blood pressure during sleep in humans.

We previously described a strong concordance between nocturnal oscillations in plasma renin activity (PRA) and the rapid eye movement (REM) and non-REM (NREM) sleep cycles, but the mechanisms inducing PRA oscillations remain to be identified. This study was designed to examine whether they are linked to sleep stage-related changes in arterial blood pressure (ABP). Analysis of sleep electroencephalographic (EEG) activity in the delta frequency band, intra-arterial pressure, and PRA measured every 10 min was performed in eight healthy subjects. Simultaneously, the ratio of low frequency power to low frequency power + high frequency power [LF/(LF + HF)] was calculated using spectral analysis of R--R intervals. The cascade of physiological events that led to increased renin release during NREM sleep could be characterized. First, the LF/(LF + HF) ratio significantly (P < 10(-4) decreased, indicating a reduction in sympathetic tone, concomitantly to a significant (P < 10(- 3) decrease in mean arterial pressure (MAP). Delta wave activity increased (P < 10(-4) 10-20 min later and was associated with a lag of 0-10 min with a significant rise in PRA (P < 10(-4) . Rapid eye movement sleep was characterized by a significant increase (P < 10(-4) in the LF/(LF + HF) ratio and a decrease (P < 10(-4) in delta wave activity and PRA, whereas MAP levels were highly variable. Overnight cross-correlation analysis revealed that MAP was inversely correlated with delta wave activity and with PRA (P < 0.01 in all subjects but one). These results suggest that pressure-dependent mechanisms elicit the nocturnal PRA oscillations rather than common central processes controlling both the generation of slow waves and the release of renin from the kidney.

Adult↗

PubMed2001

The p38 SAPK pathway regulates the expression of the MMP-9 collagenase via AP-1-dependent promoter activation.

The invasive phenotype of cancers critically depends on the expression of proteases such as the M(R) 92,000 type IV collagenase (MMP-9). Several growth factors and oncogenes were found to increase promoter activity and as a consequence protease expression. This frequently requires the activation of the transcription factor AP-1 by signal transduction cascades such as the ERK and JNK pathways. We have previously demonstrated that the tumor promoter TPA can induce MMP-9 expression via a third signaling cascade, the p38 pathway. Considering that TPA is a potent activator of AP-1, we hypothesized that this transcription factor might also be required for p38 pathway-dependent MMP-9 regulation. While dominant negative p38 and MKK-6 mutants reduced MMP-9 promoter activity in CAT assays, a construct encoding an activating mutation in the MKK-6 protein potently stimulated it. This was mediated via 144 bp of the 5'flanking region of the wild-type promoter, which contains an AP-1 site at -79. Both point mutations in this motif and the expression of a c-jun protein lacking its transactivation domain and therefore acting as a dominant negative AP-1 mutant abrogated MKK-6-dependent promoter stimulation. Finally SB 203580, a specific p38 pathway inhibitor, reduced MMP-9 expression/secretion and in vitro invasion of cancer cells. Thus, our results provide evidence that also the third SAPK/MAPK signaling cascade, the p38 signal transduction pathway, stimulates MMP-9 expression in an AP-1-dependent fashion.

Base Sequence↗

PubMed2001

No-signaling condition and quantum dynamics.

We show that the basic dynamical rules of quantum physics can be derived from its static properties and the condition that superluminal communication is forbidden. More precisely, the fact that the dynamics has to be described by linear completely positive maps on density matrices is derived from the following assumptions: (1) physical states are described by rays in a Hilbert space, (2) probabilities for measurement outcomes at any given time are calculated according to the usual trace rule, and (3) superluminal communication is excluded. This result also constrains possible nonlinear modifications of quantum physics.

Journal Article↗

PubMed2001

Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7.

Here we show that HDAC7, a member of the class II histone deacetylases, specifically targets several members of myocyte enhancer factors, MEF2A, -2C, and -2D, and inhibits their transcriptional activity. Furthermore, we demonstrate that DNA-bound MEF2C is capable of recruiting HDAC7, demonstrating that the HDAC7-dependent repression of transcription is not due to the inhibition of the MEF2 DNA binding activity. The data also suggest that the promoter bound MEF2 is potentially capable of remodeling adjacent nucleosomes via the recruitment of HDAC7. We have also observed a nucleocytoplasmic shuttling of HDAC7 and dissected the mechanism involved. In NIH3T3 cells, HDAC7 was primarily localized in the cytoplasm, essentially due to an active CRM1-dependent export of the protein from the nucleus. Interestingly, in HeLa cells, HDAC7 was predominantly nuclear. In these cells we could restore the cytoplasmic localization of HDAC7 by expressing CaMK I. This CaMK I-induced nuclear export of HDAC7 was abolished when three critical serines, Ser-178, Ser-344, and Ser-479, of HDAC7 were mutated. We show that these serines are involved in the direct interaction of HDAC7 with 14-3-3. Mutations of these serine residues weakened the association with 14-3-3 and dramatically enhanced the repression activity of HDAC7 in NIH3T3 cells, but not in HeLa cells. Data presented in this work clearly show that the signal dependent subcellular localization of HDAC7 is essential in controlling its activities. The data also show that the cellular concentration of factors such as 14-3-3, CaMK I, and other yet unknown molecules may determine the subcellular localization of an individual HDAC member in a cell type and HDAC-specific manner.

14-3-3 Proteins↗

PubMed2001

Ferrets as a transmission model for influenza: sequence changes in HA1 of type A (H3N2) virus.

Ferrets were used as an animal model to study whether controlled transmission of type A influenza is similar to human transmission when sequence changes in HA1 are used as the outcome. Ferrets were infected initially with A/Sydney/5/97 (H3N2) or A/LA/1/87 (H3N2) intranasally, and transmission chains were established by housing infected ferrets with noninfected ferrets with no influenza antibody titer against the infecting virus. Ferrets infected with A/Sydney were seronegative for A/Sydney and A/LA; ferrets infected with A/LA were seronegative for A/LA but had hemagglutination inhibition titers against A/Sydney. Titers of naturally transmitted influenza were higher than those after direct intranasal infection, but lymphocyte counts from nasal washes diminished with transmission. Ferrets infected with A/LA had 2 amino acid differences in HA1 after transmission through 5 ferret cohorts, but those infected with A/Sydney had none. The results show the value of the ferret model. A/LA resembled the transmission of influenza in humans when under antibody pressure.

Adult↗

PubMed2001

Informed consent for pediatric leukemia research: clinician perspectives.

BACKGROUND: Good, fully informed consent is critical to the ethical conduct of clinical cancer research. The authors examined clinician perspectives on informed consent for pediatric research by surveying clinicians at five major medical centers that routinely enroll patients in Children's Cancer Group studies. METHODS: Building on a pilot study, a questionnaire was designed to elicit clinicians' general opinions, approaches, and suggestions related to informed consent in pediatric leukemia trials. Questionnaires were mailed to 132 clinicians. Eighty-nine questionnaires were returned, along with 13 nonparticipant forms notifying us of the clinician's inability to participate because of a lack of experience in pediatric informed consent. The response rate was 75%. RESULTS: Providing information so that families can decide about study entry was ranked as the most important goal of the informed consent process, whereas parents' state of shock was rated the most significant obstacle to good informed consent. Clinicians cited high levels of parental comprehension of key aspects of clinical research studies and reported information overload and increased anxiety as effects of the informed consent process on parents. Several key items were associated with clinicians' gender, race, and professional experience. Finally, one open-ended question yielded 126 suggestions for how to improve the informed consent process that were grouped into 10 meaningful categories. CONCLUSIONS: Clinicians report a range of approaches, opinions, concerns, and suggestions for improving the informed consent process. The article proposes that their views and suggestions be integrated with those of parents and patients in attempts to survey and improve informed consent in pediatric oncology.

Adult↗

PubMed2001

A new multicomponent domino reaction of 1,3-dicarbonyl compounds: one-pot access to polycyclic N/O-, N/S-, and N/N-aminals.

[reaction: see text] The first multicomponent domino transformation between 1,3-dicarbonyls 1, alpha,beta-unsaturated compounds 2, and functionalized amines 3 is described, providing a one-pot access to fused polyheterocyclic or spiropolyheterocyclic compounds 5 or 6 bearing an aminal function by formation of up to three new cycles, five novel bonds, and up to six stereogenic centers.

Acrolein↗

PubMed2001

Hidden-variable theorems for real experiments.

It has recently been questioned whether the Kochen-Specker theorem is relevant to real experiments, which by necessity only have finite precision. We give an affirmative answer to this question by showing how to derive hidden-variable theorems that apply to real experiments, so that noncontextual hidden variables can indeed be experimentally disproved. The essential point is that for the derivation of hidden-variable theorems one does not have to know which observables are really measured by the apparatus. Predictions can be derived for observables that are defined in an entirely operational way.

Journal Article↗

PubMed2001

Initial employment experiences of 1997 graduates of radiation oncology training programs.

PURPOSE: To inform the profession of current trends in the job market, the American College of Radiology (ACR) sought to detail the job-hunting experiences and outcomes of 1997 graduates of radiation oncology training programs. METHODS AND MATERIALS: In early 1998, questionnaires were mailed to all graduates; 67% responded. Results were compared with similar surveys of 1996 graduates. RESULTS: Similar to past years, immediately after graduation, 13% of residency graduates and 1 of 10 fellowship graduates encountered serious employment difficulties--that is, spent some time working locums, working outside radiation oncology, or unemployed. By 6-12 months after graduation, approximately 2% of all residency graduates were working outside the profession and approximately 3% were not working at all. Eighty-five percent of residency graduates and 7 of 8 fellowship graduates reported that their employment reasonably matched their training and individual goals. On average, graduates' actual salaries approximately corresponded to expected salaries. Eleven percent of all graduates were in nonownership-track jobs, a significant decline since 1996. For residents and fellows combined, 46% had a job with at least one characteristic some observers associate with a weak job market, but fewer than half of those with one of these characteristics actually disliked it. These percentages are similar to 1996. Women graduates were more likely than men to have spouse-related restrictions on job location but less likely to end up in a self-reportedly undesirable location. CONCLUSION: Unemployment remained low. Some other indicators of the employment market showed improvement, while others did not.

Employment↗

PubMed2001

Entanglement purification for quantum communication.

The distribution of entangled states between distant locations will be essential for the future large-scale realization of quantum communication schemes such as quantum cryptography and quantum teleportation. Because of unavoidable noise in the quantum communication channel, the entanglement between two particles is more and more degraded the further they propagate. Entanglement purification is thus essential to distil highly entangled states from less entangled ones. Existing general purification protocols are based on the quantum controlled-NOT (CNOT) or similar quantum logic operations, which are very difficult to implement experimentally. Present realizations of CNOT gates are much too imperfect to be useful for long-distance quantum communication. Here we present a scheme for the entanglement purification of general mixed entangled states, which achieves 50 per cent of the success probability of schemes based on the CNOT operation, but requires only simple linear optical elements. Because the perfection of such elements is very high, the local operations necessary for purification can be performed with the required precision. Our procedure is within the reach of current technology, and should significantly simplify the implementation of long-distance quantum communication.

Journal Article↗

PubMed2001

Molecular phylogenetic analysis of the dragonfly genera Libellula, Ladona, and Plathemis (Odonata: Libellulidae) based on mitochondrial cytochrome oxidase I and 16S rRNA sequence data.

Molecular phylogenetic relationships among members of the odonate genus Libellula (Odonata: Anisoptera: Libellulidae) were examined using 735 bp of mitochondrial COI and 416 bp of 16S ribosomal RNA gene sequences. Considerable debate exists over several relationships within Libellula, as well over the status of two putative genera often placed as subgenera within Libellula: Ladona and Plathemis. Parsimony and maximum-likelihood analyses of the separate and combined data sets indicate that Plathemis is basal and monophyletic and that Ladona is the sister clade to the remainder of Libellula sensu stricto (s.s.) (all species within the genus Libellula, excluding Plathemis and Ladona). Moreover, two European taxa, Libellula fulva and L. depressa, were found to occupy a sister group relationship within the Ladona clade. Relationships within Libellula s.s. are less well resolved. However, monophyletic lineages within the genus are largely consistent with morphologically based subgeneric classifications. Although tree topologies from each analysis differed in some details, the differences were in no case statistically significant. The analysis of the combined COI and 16S data yielded trees with overall stronger support than analyses of either gene alone. Several analyses failed to support the monophyly of Libellula sensu lato due to the inclusion of one or more outgroup species. However, statistical comparisons of topologies produced by unconstrained analyses and analyses in which the monophyly of Libellula was constrained indicate that any differences are nonsignificant. Based on morphological data, we therefore reject the paraphyly of Libellula and accept the outgroup status of Orthemis ferruginea and Pachydiplax longipennis.

Animals↗

PubMed2001

[Mechanisms of invasiveness of cancers of the head and neck region].

BACKGROUND: Squamous cell carcinomas of the head and neck region are highly aggressive cancers. Survival of these patients critically depends on the prevention of locoregional recurrences. A locoregional relapse is associated with an invasive growth pattern of the primary cancer. Thus, we need to understand regulatory mechanisms of cancer invasion to be able to develop therapeutic strategies, which may help to improve survival in this patient population. METHOD: Literature search. RESULTS: Certain tumor proteases are required for invasive growth of head and neck cancers. DISCUSSION: It is our understanding that further indepth investigation of mechanisms involved in the regulation of protease expression may help to develop treatment strategies, which improve survival by reducing the invasive capacity of head and neck cancer cells.

Carcinoma, Squamous Cell↗

PubMed2001

Inverse coupling between ultradian oscillations in delta wave activity and heart rate variability during sleep.

OBJECTIVE: We investigate the relationship between changes in heart rate variability and electroencephalographic (EEG) activity during sleep. METHOD: Nine male subjects with regular non-rapid-eye movement-rapid-eye movement (NREM-REM) sleep cycles were included in the study. They underwent EEG and cardiac recordings during one experimental night. Heart rate variability was determined over 5-min periods by the ratio of low frequency to low frequency plus high frequency power [LF/(LF+HF)] calculated using spectral analysis of R-R intervals. EEG spectra were analyzed using a fast Fourier transform algorithm. RESULTS: We found an ultradian 80-120 min rhythm in the LF/(LF+HF) ratio, with high levels during rapid eye movement (REM) sleep and low levels during slow wave sleep (SWS). During sleep stage 2 there was a progressive decrease in the transition from REM sleep to SWS, and an abrupt increase from SWS to REM sleep. These oscillations were significantly coupled in a 'mirror-image' to the overnight oscillations in delta wave activity, which reflect sleep deepening and lightening. Cardiac changes preceded EEG changes by about 5 min. CONCLUSIONS: These findings demonstrate the existence of an inverse coupling between oscillations in delta wave activity and heart rate variability. They indicate a non-uniformity in sleep stage 2 that underlies ultradian sleep regulation.

Activity Cycles↗

PubMed2001

Leisure-time physical activity and regular walking or cycling to work are associated with adiposity and 5 y weight gain in middle-aged men: the PRIME Study.

OBJECTIVE: To examine the influence of physical activity on body mass index (BMI), waist circumference (W) and body mass changes (DeltaBMI) in middle-aged men, with special regard to moderate-intensity activities. DESIGN: Longitudinal study of adults who participated in the PRIME Study. SUBJECTS: A cohort of 8865 men aged 50-59 y, free of coronary heart disease. MEASUREMENTS: BMI and W at baseline, body mass changes over a 5 y period. Detailed baseline assessment of net energy expenditure due to physical activity (PAE) in the preceding year, according to category of activity, by means of the MOSPA Questionnaire. PAE was expressed in weekly metabolic equivalent scores (MET h/week). RESULTS: After adjustment for confounders, the multiple regression analyses indicated that BMI, W and DeltaBMI were inversely associated with PAE spent in getting to work (P<10(-5), <10(-5) and 0.04, respectively) and practice of high-intensity (>or=6 MET) recreational activities (<0.01, <10(-5) and <0.01). Men who regularly spent more than 10 MET h/week in walking or cycling to work had a mean BMI, W and DeltaBMI respectively 0.3 kg/m(2), 1 cm and 0.06 kg/m(2) lower than those who did not expend energy in getting to work. In the subgroup of subjects who did not perform high-intensity activities, the level of recreational PAE was inversely associated with BMI and W but not with subsequent weight-gain. CONCLUSION: These findings indicate that, in middle-aged men, physical activities of moderate-intensity, which are probably easier to promote than more vigorous activities and, in particular, a more current daily activity, walking or cycling to work, may have a favourable effect on body fat markers and body mass gain.

Activities of Daily Living↗

PubMed2001

Allochronic speciation, secondary contact, and reproductive character displacement in periodical cicadas (Hemiptera: Magicicada spp.): genetic, morphological, and behavioural evidence.

Periodical cicadas have proven useful in testing a variety of ecological and evolutionary hypotheses because of their unusual life history, extraordinary abundance, and wide geographical range. Periodical cicadas provide the best examples of synchronous periodicity and predator satiation in the animal kingdom, and are excellent illustrations of habitat partitioning (by the three morphologically distinct species groups), incipient species (the year classes or broods), and cryptic species (a newly discovered 13-year species, Magicicada neotredecim). They are particularly useful for exploring questions regarding speciation via temporal isolation, or allochronic speciation. Recently, data were presented that provided strong support for an instance of allochronic speciation by life-cycle switching. This speciation event resulted in the formation of a new 13-year species from a 17-year species and led to secondary contact between two formerly separated lineages, one represented by the new 13-year cicadas (and their 17-year ancestors), and the other represented by the pre-existing 13-year cicadas. Allozyme frequency data, mitochondrial DNA (mtDNA), and abdominal colour were shown to be correlated genetic markers supporting the life-cycle switching/allochronic speciation hypothesis. In addition, a striking pattern of reproductive character displacement in male call pitch and female pitch preference between the two 13-year species was discovered. In this paper we report a strong association between calling song pitch and mtDNA haplotype for 101 individuals from a single locality within the M. tredecim/M. neotredecim contact zone and a strong association between abdomen colour and mtDNA haplotype. We conclude by reviewing proposed mechanisms for allochronic speciation and reproductive character displacement.

Animals↗

PubMed2001

Evaluating hypotheses on the origin and evolution of the New Zealand alpine cicadas (Maoricicada) using multiple-comparison tests of tree topology.

The statistical testing of alternative phylogenetic trees is central to evaluating competing evolutionary hypotheses. Fleming proposed that the New Zealand cicada species Maoricicada iolanthe is the sister species to the major radiation of both low-altitude and montane Maoricicada species. However, using 1,520 bp of mitochondrial DNA sequence data from the cytochrome oxidase subunit I, tRNA aspartic acid, and the ATPase subunit 6 and 8 genes, we inferred that both M. iolanthe and another low-altitude species, Maoricicada campbelli, are nested within the montane Maoricicada radiation. Therefore, we examined the stability of the inferred phylogenetic placement of these two species using the newly developed Shimodaira-Hasegawa test (SH test) implemented in a maximum-likelihood framework. The SH test has two advantages over the more commonly used Kishino-Hasegawa (KH) and Templeton tests. First, the SH test simultaneously compares multiple topologies and corrects the corresponding P: values to accommodate the multiplicity of testing. Second, the SH test is correct when applied to a posteriori hypotheses, unlike the KH test, because it readjusts the expectation of the null hypothesis (that two trees are not different) accordingly. The comparison of P: values estimated under the assumptions of both the KH test and the SH test clearly demonstrate that the KH test has the potential to be misleading when the issue of comparing of a posteriori hypotheses is ignored and when multiple comparisons are not taken into account. The SH test, in combination with a variety of character-weighting schemes applied to our data, reveals a surprising amount of ambiguity in the phylogenetic placement of M. iolanthe and M. campbelli.

Animals↗