Biomedical subjects

P Jacob

Publications and source records attributed to P Jacob.

At least 19 recordsLinked to original sources

PubMed2006

Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4-butanediol administration to healthy volunteers.

1,4-Butanediol (BD) is converted to gamma-hydroxybutyrate (GHB) after ingestion, and is associated with cases of dependence, coma, and death. The pharmacology of BD after oral ingestion has not been described in humans. Eight healthy volunteers (five men) were administered 25 mg/kg BD in a single oral dose after an overnight fast in a double-blinded, placebo-controlled, crossover study. Vital signs were monitored, and serial blood samples collected over 24 h for gas chromatography-mass spectrometry analysis of BD and GHB levels. Subjective mood and symptoms responses were assessed by visual analog scale. All subjects completed the study without significant adverse effects. BD was quickly absorbed and cleared, with time to maximal plasma concentration of 24+/-12 min, and elimination half-life (T(1/2)) of 39.3+/-11 min. BD was extensively converted to GHB, with a mean maximum GHB concentration of 45.6+/-19.7 mg/l reached 39.4+/-11.2 min after BD ingestion. GHB T(1/2) averaged 32.3+/-6.6 min. Some subjects exhibited slow oral clearance of BD, which tended to correlate with a variant haplotype of the alcohol dehydrogenase gene ADH-IB G143A. Mean CL/F was 151.5+/-176.5 ml/min kg for four subjects with variant haplotype versus 598.8+/-446.6 ml/min kg for four wild-type subjects (P=0.061). Subjects reported feeling less awake and alert, less able to concentrate, and more lightheaded in the first 90 min after BD ingestion. Pulse oximetry readings were lower 45 min after BD dosing with a mean oxygen saturation of 98.5% with BD versus 99.6% with placebo (P=0.031). Transient increases in mean systolic and diastolic blood pressure were observed, but other vital signs remained unchanged. BD was extensively converted to GHB after oral administration, but significant inter-individual variability in the rate of metabolism, possibly related to variants in ADH-IB, was observed. At the modest dose studied, significant clinical effects were not seen.

Administration, Oral↗

PubMed2006

Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease.

The authors studied the acute effect of caffeine on the levodopa pharmacokinetics and pharmacodynamics in 12 patients with idiopathic Parkinson disease. This double-blind, randomized, crossover study revealed that caffeine shortened the maximal plasma concentration of levodopa, decreased the latency to levodopa walking and tapping motor response, and increased the magnitude of walking response. Caffeine administered before levodopa may improve its pharmacokinetics in some parkinsonian patients.

Adult↗

PubMed2006

[Clinical pathways -- first results of a systematic IT-supported application at a surgical department of a university hospital].

BACKGROUND AND OBJECTIVE: In analogy to industrial process management, clinical pathways have been introduced for operational process organisation in orthopedic and interventional procedures as well as for conservative treatments. Within this study, introduction and continuous, systematic application of clinical pathways at a surgical department of a university hospital was investigated. METHODS: Analysis was performed by IT-based (SAP/i. s. h.med) evaluation of the registered data regarding pathway violations. Additionally, patients' records were matched with the computerized data for quality assurance of pathway documentation. RESULTS: 501 patients were entered in 16 clinical pathways (31 +/- 39 patients per pathway). The mean period from the introduction of a distinct pathway to the data acquisition of the present study ranged from 2 to 14 months (mean 7+/-7.5 months). Pathway violations correlated with the complexity, but not with the period since the pathway was introduced. Organisational reasons next to medical reasons (i. e. delayed gastric function or wound healing) were the most frequent causes for pathway violations. CONCLUSION: Clinical pathways may not only be realised for operative procedures or conservative treatments, but represent a clinical and administrative management instrument at a surgical department of a university hospital for daily work routine. They are suitable as an instrument for clinical quality and risk management, as an economic control instrument in reorganisation phases as well as in the routine of surgical clinics.

Critical Pathways↗

PubMed2006

Thyroid cancer among Ukrainians and Belarusians who were children or adolescents at the time of the Chernobyl accident.

Our objective is to assess the regional and temporal dependences of the baseline cases contributing to thyroid cancer incidence among those exposed in childhood or during adolescence in Belarus and Ukraine after the Chernobyl accident. Data are analysed for Kyiv and Sevastopol City and the 25 oblasts (regions) in Ukraine, and for Minsk and Gomel City and the 6 oblasts in Belarus. Average thyroid doses due to the Chernobyl accident were assessed for every birth year in the period from 1968 to 1985. Case data pertain to people who underwent surgical removal of thyroid cancers during the period 1986 to 2001 and who were allocated to their place of residence at the time of the accident. The 35 oblasts/cities were subdivided into an upper, middle and lower group of baseline thyroid cancer incidence. Poisson regressions were performed to estimate age, time and gender dependences of the baseline incidence rates in the three groups. The majority of oblasts/cities with high average doses and the majority of Belarusian oblasts/cities belong to the upper group of baseline thyroid cancer incidence. The baseline in the upper group is estimated to be larger than in the middle group by a factor of 2.3, and by a factor of 4.0 when compared to the lower group. The baseline incidence increases with age and with time since exposure. Estimated baseline incidence rates were found to increase from 1988 to 1999 by factors of three and two for the upper and the two lower groups respectively. The estimated thyroid cancer incidence rates in Belarus and Ukraine, and their dependences on gender and age, are consistent with observed rates found in the larger cancer registries of other countries. In conclusion, the baseline cases are found to contribute about 70% to the thyroid cancer incidence in Ukraine, and about 40% to the incidence in Belarus.

Adolescent↗

PubMed2006

Comparison of EPR occupational lifetime external dose assessments for Mayak nuclear workers and film badge dose data.

The Mayak worker cohort is one of the major sources of information on health risks due to protracted exposures to plutonium and external ionizing radiation. Electron paramagnetic resonance (EPR) measurements in tooth enamel in combination with personal dose monitoring can help to improve external dose assessment for this cohort. Here, the occupational lifetime external exposure was evaluated individually for 44 nuclear workers of three plants of the Mayak Production Association by EPR measurements of absorbed doses in collected tooth enamel samples. Analysis included consideration of individual background doses in enamel and dose conversion coefficients specific for photon spectra at selected work areas. As a control, background doses were assessed for various age groups by EPR measurements on teeth from non-occupationally exposed Ozyorsk residents. Differences in occupational lifetime doses estimated from the film badges and from enamel for the Mayak workers were found to depend on the type of film badge and the selected plant. For those who worked at the radiochemical processing plant and who were monitored with IFK film badges, the dose was on average 570 mGy larger than estimated from the EPR measurements. However, the average difference was found to be only -4 and 6 mGy for those who were monitored with IFKU film badges and worked at the reactor and the isotope production plant respectively. The discrepancies observed in the dose estimates are attributed to a bias in film badge evaluation.

Adult↗

PubMed2006

Catecholamine response to methamphetamine is related to glucocorticoid levels but not to pleasurable subjective response.

INTRODUCTION: Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. METHODS: Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. RESULTS: HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. CONCLUSION: Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.

Adult↗

PubMed2006

Thyroid cancer risk in areas of Ukraine and Belarus affected by the Chernobyl accident.

The purpose of the present study was to analyze the thyroid cancer incidence risk after the Chernobyl accident and its degree of dependence on time and age. Data were analyzed for 1034 settlements in Ukraine and Belarus, in which more than 10 measurements of the (131)I content in human thyroids had been performed in May/June 1986. Thyroid doses due to the Chernobyl accident were assessed for the birth years 1968-1985 and related to thyroid cancers that were surgically removed during the period 1990-2001. The central estimate for the linear coefficient of the EAR dose response was 2.66 (95% CI: 2.19; 3.13) cases per 10(4) PY-Gy; for the quadratic coefficient, it was -0.145 (95% CI: -0.171; -0.119) cases per 10(4) PY-Gy(2). The EAR was found to be higher for females than for males by a factor of 1.4. It decreased with age at exposure and increased with age attained. The central estimate for the linear coefficient of the ERR dose response was 18.9 (95% CI: 11.1; 26.7) Gy(-1); for the quadratic coefficient, it was -1.03 (95% CI: -1.46; -0.60) Gy(-2). The ERR was found to be smaller for females than for males by a factor of 3.8 and decreased strongly with age at exposure. Both EAR and ERR were higher in the Belarusian settlements than in the Ukrainian settlements. In contrast to ERR, EAR increases with time after exposure. At the end of the observation period, excess risk estimates were found to be close to those observed in a major pooled analysis of seven studies of childhood thyroid cancer after external exposures.

Adolescent↗

PubMed2005

Lung cancer in Mayak workers: interaction of smoking and plutonium exposure.

Lung cancer mortality among 5,058 male workers of the Mayak Production Association has been analyzed with emphasis on the interaction of smoking and radiation exposure by using the two-step clonal expansion (TSCE) model of carcinogenesis. The cohort consists of all Mayak workers with known smoking status, who were employed in the period 1948-1972, and who either had the plutonium concentration in urine measured or who worked in the reactors, where plutonium exposure was negligible. Those who died during the first two years after the first urine sampling were excluded. The follow-up extended until the end of 1998. During this time, 2,176 workers died, including 244 lung cancer cases. Mayak workers were exposed to external (gamma and neutron) radiation, and in the radiochemical and plutonium plants to plutonium. In the preferred TSCE model, internal radiation and smoking act on the clonal expansion of pre-carcinogenic clones. Assuming a plutonium radiation weighting factor of 20, the excess relative risk per lung dose was estimated to be 0.11 (95% CI: 0.08; 0.17) Sv(-1). Most of the lung cancer deaths are found to be due to smoking. The second main factor is the interaction of smoking and internal radiation. The model is sub-multiplicative in relative risks due to smoking and radiation. In a multiplicative version of the TSCE model, internal radiation acts on initiation and transformation rates. This model version agrees with conventional epidemiological risk models, because it also suggests a higher risk estimate than the preferred TSCE model. However, it fits the data less well than the preferred model.

Biophysical Phenomena↗

PubMed2005

Visual cognition: a new look at the two-visual systems model.

In this paper, we argue that no valid comparison between visual representations can arise unless provision is made for three critical properties: their direction of fit, their direction of causation and the level of their conceptual content. The conceptual content in turn is a function of the level of processing. Representations arising from earlier stages of processing of visual input have very little or no conceptual content. Higher order representations get their conceptual content from the connections between visual cognition and other parts of the human cognitive system. The two other critical properties of visual representations are their mind/world direction of fit and their mind/world direction of causation. The output of the semantic processing of visual input has a full mind-to-world direction of fit and a full world-to-mind direction of causation: it visually registers the way the world is and is caused by what it represents. The output of the pragmatic processing yields information for the benefit of intentions, which clearly have a world-to-mind direction of fit and a mind-to-world direction of causation. An intention is both the representation of a goal and a cause of the transformation of a goal into a fact. These properties segregate representations specialized for perception from those specialized for action. Perception implies comparison between simultaneously represented and analyzed objects: hence, object perception presupposes the representation of spatial relationships among objects in a coordinate system independent from the perceiver. Spatial relationships carry cues for attributing meaning to an object, so that their processing is actually part of semantic processing of visual information. These considerations lead to a re-evaluation of the role of the two classical pathways of the human visual system: the ventral and the dorsal cortical pathways. The parietal lobe, which has been identified with the dorsal pathway, cannot be considered as a unitary entity with a single function. The superior parietal lobule carries visuomotor processing, a non-lateralized process. The right inferior parietal lobule contributes to the perception of spatial relationships, a process with a mind-to-world direction of fit and a world-to-mind direction of causation. Finally, the left inferior parietal lobule contributes to still another type of representation, related to visually goal-directed action, i.e., with both a world-to-mind direction of fit and a mind-to-world direction of causation.

Brain↗

PubMed2005

Safety of gold in stapes surgery.

Gold prostheses in middle ear surgery were found to have a higher extrusion rate than prostheses made from titanium. Incidences of deafness after insertion of a gold piston into the vestibule during stapes surgery have been observed. The aim of this study was to find out to what degree gold cations can diffuse from the prosthesis piston into the perilymph. For this, gold prostheses were incubated in artificial perilymph for four months, after which the gold content of the perilymph was analysed. As gold exhibits a special behaviour in complex fluids like the perilymph, a new analysing method was developed. The results show that gold does leak out of the pistons, that it can be reliably measured and that the amount of gold reaching the perilymph depends on the contact area. As the amount of gold measured in the perilymph stays far below the toxic level, it is very unlikely that the gold cations diffusing from a stapes prosthesis into the perilymph have a toxic effect on the inner ear hair cells. Inflammatory or allergic reactions to gold induced by direct tissue contact, however, cannot be excluded.

Animals↗

PubMed2005

Photon dose conversion coefficients for human teeth in standard irradiation geometries.

Photon dose conversion coefficients for human tooth materials are computed in energy range from 0.01 to 10 MeV by the Monte Carlo method. The voxel phantom "Golem" of the human body with newly defined tooth region and a modified version of the EGS4 code have been used to compute the coefficients for 30 tooth cells with different locations and materials. The dose responses are calculated for cells representing buccal and lingual enamel layers. The computed coefficients demonstrate a strong dependence on energy and geometry of the radiation source and a weaker dependence on location of the enamel voxels. For isotropic and rotational radiation fields, the enamel dose does not show a significant dependence on tooth sample locations. The computed coefficients are used to convert from absorbed dose in teeth to organ dose or to integral air kerma. Examples of integral conversion factors from enamel dose to air kerma are given for several photon fluences specific for the Mayak reprocessing plant in Russia. The integral conversion factors are strongly affected by the energy and angular distributions of photon fluence, which are important characteristics of an exposure scenario for reconstruction of individual occupational doses.

Humans↗

PubMed2005

Post-Chornobyl thyroid cancers in Ukraine. Report 1: estimation of thyroid doses.

About 1.8 EBq of 131I was released into the atmosphere during the Chornobyl accident that occurred in Ukraine on April 26, 1986. More than 10% of this activity was deposited on the territory of Ukraine. Beginning 4-5 years after the accident, an increase in the incidence of thyroid cancer among children, believed to be caused in part by exposure to 131I, has been observed in different regions of Ukraine. A three-level system of thyroid dose estimation was developed for the reconstruction of thyroid doses from 131I for the entire population of Ukrainian children aged 1 to 18 at the time of accident: (1) At the first level, individual doses were estimated for the approximately 99,000 children and adolescents with direct measurements of radioactivity in the thyroid (so-called direct thyroid measurements) performed in May-June of 1986; (2) at the second level, group doses by year of age and by gender were estimated for the population of 748 localities (with 208,400 children aged 1-18 in 1986) where direct thyroid measurements of good quality were performed on some of the residents; and (3) at the third level, group doses by age and by gender were estimated for the population of the localities where no thyroid measurements were made in 1986. The third-level doses were then aggregated over the population of each oblast. Data, models and procedures required for each level of thyroid dose estimation are described in the paper. At the first level, individual doses were found to range up to 27,000 mGy, with geometric and arithmetic means of 100 and 300 mGy, respectively. At the second level, group doses were found to be highest for the younger children (aged 1 to 4 years); doses for the older children (aged 16 to 18 years) were 3.5 times smaller. At the third level, average population-weighted doses were found to exceed 35 mGy in the five northern oblasts closer to the Chornobyl reactor site; to be in the 14- to 34-mGy range in seven other oblasts, Kyiv city and Crimea; and to be less than 13 mGy in all other oblasts.

Adolescent↗

PubMed2004

Utility of 24-h ambulatory blood pressure measurement in a routine clinical setting of patients with chronic renal disease.

The objective of the study was to investigate the utility of 24 h ambulatory blood pressure measurement (ABPM) in patients with chronic renal disease (CRD). A retrospective audit was performed in an academic nephrology department. ABPMs obtained from 95 consecutive outpatients with nondiabetic renal disease were analysed for their power to stratify disease severity and to predict progression of renal insufficiency during 3 years follow-up. The average of 10 consecutive office blood pressure (BP) readings performed at baseline was used as a reference. Correlations and tabulated statistics were calculated. Baseline mean diurnal BP was 138/87 mmHg by ABPM and 146/92 mmHg by average office BP (56.8 vs 25.3% normotensives, P < 0.01). Mean serum creatinine was 154 +/- 109 micromol/l. Patients without a circadian BP pattern (61%) had significantly higher serum creatinine, urinary albumin excretion and subsequent progression rates of renal failure (P < 0.05). Systolic and pulse pressure ABP values correlated significantly with serum creatinine levels at baseline and 3 years thereafter, independent of daytime (r = 0.23-0.60; P < 0.05). Abnormal nocturnal systolic and mean ABP, and pulse pressure but not average day office BP were significantly associated with abnormal serum creatinine and the presence of coronary heart disease at baseline (relative risk 1.6-1.7, P < 0.05). In conclusion, physicians considered ABPM preferentially in patients with borderline-controlled BP. ABPM provided significant additional information relevant to the clinical decision making process compared with average office BP alone thereby justifying its use in specific situations.

Aged↗

PubMed2004

Bupropion in breast milk: an exposure assessment for potential treatment to prevent post-partum tobacco use.

OBJECTIVES: To assess potential infant exposure to bupropion and its active metabolites in breast milk such as would occur during treatment to prevent post-partum relapse to tobacco use, and to compare the concentrations of bupropion in urine and saliva with plasma and breast milk. DESIGN AND SETTING: Cohort study, outpatient clinical research centre. SUBJECTS: Ten healthy post-partum volunteers who agreed to take bupropion for seven days, pump and discard their breast milk, and have samples of breast milk, plasma, saliva, and urine analysed. INTERVENTION: Bupropion 150 mg a day for three days and then 300 mg a day for four days. MAIN OUTCOME MEASURES: Concentrations of bupropion and its active metabolites (hydroxybupropion, erythrohydrobupropion, threohydrobupropion) in breast milk, plasma, saliva, and urine. Determination of average infant exposure. RESULTS: The calculated average dosage of bupropion in breast milk was 6.75 microg/kg/day. Therefore, the average infant exposure is 0.14% of the standard adult dose of bupropion, corrected for the difference in body weight. Considering the sum of bupropion and its active metabolites, the average infant exposure is expected to be 2% of the standard maternal dose on a molar basis. The concentration of bupropion and its active metabolites in breast milk was not associated with age, body mass index, use of oral contraceptive pills, age of infant, or the frequency of breast feeding at the time the study was initiated. The coefficient of determination (r2) between the concentration of bupropion in breast milk and in urine was 0.77 (p < 0.01). CONCLUSIONS: Bupropion and its active metabolites are present in the breast milk of lactating women. The concentrations of bupropion in breast milk and urine were highly correlated. These results indicate that the daily dose of bupropion and metabolites that would be delivered to an infant of a woman taking a therapeutic dose of bupropion is small. These results suggest that the effectiveness of bupropion to prevent post-partum relapse to tobacco use should be evaluated without excluding women who plan to breast feed.

Adult↗

PubMed2003

On an evaluation of external dose values in the Techa River Dosimetry System (TRDS) 2000.

Absorbed doses were determined by thermoluminescence (TL) measurements for bricks from a height of 6 m from the south-western wall of the former mill in Metlino that faced the Techa river. Measurements of the internal beta-radiation and alpha-radiation in the brick samples and of radionuclide activities in soil samples from the Techa river valley were performed. The absorbed dose in bricks due to the natural radiation was derived and subtracted from the total dose in order to obtain the absorbed dose in the bricks caused by anthropogenic sources. The results were combined with results from two previous studies. The absorbed dose in the bricks due to the radiation field after relocation of the Metlino population in 1956 was derived from dose rates in air measured in front of the sampling locations in 1996/1997. Based on these dose rates the dose to bricks was calculated by means of conversion factors from the literature. The absorbed dose accumulated in the bricks in the period 1949-1956 was nearly 80% of the total dose that had been determined by TL measurements. Previously derived conversion factors were applied to obtain an estimate of the gamma dose in air at the former shore of the Techa river. An uncertainty and sensitivity analysis was performed with the program package Crystal Ball. Care was taken to treat statistical and systematic uncertainties separately and to take parameter correlations into account. The resulting distribution for the gamma dose accumulated in the period 1949-1956 at the Techa river shore has a median value of 32 Gy with a 95% confidence interval of 21-45 Gy. This study confirms the corresponding value of 26.6 Gy that is used in the Techa River Dosimetry System (TRDS) 2000.

Adsorption↗

PubMed2003

Verification of external exposure assessment for the upper Techa riverside by luminescence measurements and Monte Carlo photon transport modeling.

An area located in the Southern Urals was contaminated in 1949-1956 as a result of radioactive waste releases into the Techa river by the Mayak Production Association. The external dose reconstruction of the Techa river dosimetry system (TRDS-2000) for the exposed population is based on an assessment of dose rates in air (DRA) obtained by modeling transport and deposition of radionuclides along the river for the time before 1952 and by gamma dose rate measurements since 1952. The aim of this paper is to contribute to a verification of the TRDS-2000 external dose assessment. Absorbed doses in bricks from a 130-year-old building in the heavily exposed Metlino settlement were measured by a luminescence technique. By the autumn of 1956 the population of Metlino had been evacuated, and then a water reservoir was created at the village location, which led to a change in the radioactive source geometry. Radiation transport calculations for assumed environmental sources before and since 1957 were performed with the MCNP Monte Carlo code. In combination with TRDS-2000 estimates for annual dose rates in air at the shore of the Techa river for the period 1949-1956 and contemporary dose rate in air measurements, absorbed doses in bricks were calculated. These calculations were performed deterministically with best estimates of the modeling parameters and stochastically by propagating uncertainty distributions through the calculation scheme. Assessed doses in bricks were found to be consistent with measured values within the uncertainty bounds, while their best estimates were approximately 15% lower than the luminescence measurements.

Beta Particles↗

PubMed2003

Modelling study on the protective role of OH radical scavengers and DNA higher-order structures in induction of single- and double-strand break by gamma-radiation.

PURPOSE: To quantify the protective effects of (non-histonic) OH-radical scavengers and DNA higher-order structures in induction of single- (ssbs) and double-strand breaks (dsbs) by gamma-rays. MATERIALS AND METHODS: Spatial distributions of energy depositions by gamma-rays in liquid water were modelled with the track structure modules of the biophysical simulation code PARTRAC. Such distributions were superimposed on different DNA structure models (e.g. linear DNA, SV40 'minichromosomes' and compact chromatin), and direct energy depositions in the sugar-phosphate were considered as potential (direct) ssbs. The diffusion and interaction of the main chemical species produced in liquid water radiolysis were explicitly simulated, and reactions of *OH with the sugar-phosphate were considered as potential (indirect) ssbs. Two ssb on opposite DNA strands within 10 base pairs were considered as one dsb. Yields of ssb and dsb Gy(-1) Dalton(-1) in different DNA target structures were calculated as a function of the *OH mean lifetime, whose inverse value was taken as representative of the scavenging capacity of the DNA environment. RESULTS AND CONCLUSIONS: A further validation of the models implemented in the PARTRAC code has been provided, thus allowing a better understanding of the mechanisms underlying DNA damage. More specifically, the protection due to *OH scavengers was separately quantified with respect to that due to histones and chromatin folding, which could be 'switched off' in the simulations. As expected, for a given value of the environment scavenging capacity, linear DNA was more susceptible to strand breakage than SV40 minichromosomes, which in turn showed higher damage yields with respect to cellular DNA due to the larger accessibility offered to *OH. Furthermore, by increasing the scavenging capacity, the break yields decreased in all structures and tended to coincide with direct damage yields. Very good agreement was found with available experimental data. Comparisons with data on 'nucleoid' DNA (i.e. unfolded and histone-depleted DNA) also suggested that the experimental procedures used to obtain such structures might lower the environment scavenging capacity owing to the loss of cellular scavengers.

DNA↗

PubMed2003

Biological parameters for lung cancer in mathematical models of carcinogenesis.

Applications of the two-step model of carcinogenesis with clonal expansion (TSCE) to lung cancer data are reviewed, including those on atomic bomb survivors from Hiroshima and Nagasaki. British doctors, Colorado Plateau miners and Chinese tin miners. Different sets of identifiable model parameters are used in the literature. The parameter set which could be determined with the lowest uncertainty consists of the net proliferation rate gamma of intermediate cells, the hazard h55 at an intermediate age and the hazard h(infinity) at an asymptotically large age. Also, the values of these three parameters obtained in the various studies are more consistent than other identifiable combinations of the biological parameters. Based on representative results for these three parameters, implications for the biological parameters in the TSCE model are derived.

Cell Transformation, Neoplastic↗