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Biomedical subjects

M Durante

Publications and source records attributed to M Durante.

At least 55 records · Page 3Linked to original sources
PubMed2001

Influence of the shielding on the space radiation biological effectiveness.

A research program in space radiobiology is described in this report. The program is focused on the effect of the shielding on the biological effects of heavy ions. Both experiments and models are included in the program. Experiments aim to determine genetic effects of heavy ions with or without shielding. Mathematical models, based on Monte Carlo codes, will be used to interpret the biological results. The final goal is to get a feasible model able to predict the radiation-induced biological damage in space, given the free-space radiation field and the space vessel shielding. The grant is supported by the Italian Space Agency (ASI), and involves Italian radiation biophysics groups (Universities of Milan and Naples, National Institute of Health in Rome), in collaboration with NASA (USA), NIRS (Japan), CERN (Switzerland), Brookhaven National Laboratories (USA), and TERA (Italy).

Chromosome Aberrations↗
PubMed2000

X-rays vs. carbon-ion tumor therapy: cytogenetic damage in lymphocytes.

PURPOSE: To measure chromosomal aberrations in peripheral blood lymphocytes from cancer patients treated with X-rays or carbon ions (C-ions). METHODS AND MATERIALS: Blood samples from patients diagnosed for esophageal or uterine cervical cancer were obtained before, during, and at the end of the radiation treatment. The novel technique of interphase chromosome painting was used to detect aberrations in prematurely condensed chromosomes 2 and 4. The fraction of aberrant lymphocytes was measured as a function of the dose to the tumor volume. For comparison, blood samples were also exposed in vitro to X-rays or to carbon ions accelerated at the HIMAC. RESULTS: C-ions were more efficient than X-rays in the induction of chromosomal aberrations in vitro. In patients with similar pathologies, tumor positions, and radiation field sizes, however, C-ions induced a lower fraction of aberrant lymphocytes than X-rays during the treatment. The initial slope of the dose-response curve for the induction of chromosomal aberrations during the treatment was correlated to the relative decrease in the number of white blood cells and lymphocytes during the treatment. CONCLUSION: C-ions induce a lower level of cytogenetic damage in lymphocytes than X-rays, reducing the risk of bone marrow morbidity.

Aged↗
PubMed2000

Complex-type chromosomal exchanges in blood lymphocytes during radiation therapy correlate with acute toxicity.

The new method of chemical-induced premature chromosome condensation combined with fluorescence in situ hybridization was used to analyze chromosomal damage in peripheral blood mononuclear lymphocytes of patients undergoing radiation treatment for esophageal cancer with high-energy X-rays or accelerated carbon ions at the National Institute of Radiological Sciences (Chiba, Japan). Total number of aberrant cells correlated with radiation field size, but no correlation was found with acute toxicity. A high frequency of complex-type exchanges were also recorded. This aberration type presented a high individual variability, and correlated well with the acute morbidity. Cytogenetic analysis by interphase chromosome painting is proposed as a useful tool for monitoring normal tissue effects during radiotherapy.

Aged↗
PubMed2000

Prediction of organic reaction products: determining the best reaction conditions

We describe some of our most recent achievements concerning the selection of the best set of reaction conditions for a specific reaction. In particular, we will concentrate on the selection of the best solvent to minimize side reactions. The solvent should favor a kinetically controlled reaction if it is a good solvent for the transition state and a bad solvent for the ground state, decreasing the activation energy. Consequently, we need the descriptions of the transition state and of the state solvation. We generally apply the principle of "similarity in solvation"; i.e., we calculate an approximate similarity between reactants, transition states, and solvent molecules. The more the former are similar to the latter, the more they are solvated. This permits the selection and the ordering of the solvents. We considered other aspects of reaction conditions that will be briefly commented on. Some results will be presented to illustrate the power of the method.

Journal Article↗
PubMed2000

Autonomic modulation of heart rate and blood pressure in normotensive offspring of hypertensive subjects.

Predominant sympathetic cardiovascular modulation in the hyperkinetic phase of arterial hypertension has been well described. Less information is available on autonomic control in persons with a family history of arterial hypertension. To investigate this question, we selected 61 normotensive subjects (mean age 30.9 +/- 1.8 years) whose mother or father or both had arterial hypertension and 30 normotensive patients (mean age 30.1 +/- 1.4 years) whose parents had not had arterial hypertension (neither mother nor father) to undergo short-term power spectral analysis of RR interval and arterial pressure variabilities. The same recordings were used to determine baroreflex sensitivity or the alpha index by means of the transfer function. Normotensive offspring of hypertensive subjects had higher diastolic blood pressures (P < .05) and left ventricular mass index (P < .05) than did normotensive offspring of non-hypertensive subjects. They also had higher spectral densities of low frequency expressed in normalized units, both for R-R intervals (P < .05) and systolic pressure variabilities (P < .05); they also had a greater ratio of low-frequency to high-frequency powers of R-R interval variability (P < .05). No difference was observed between the two normotensive groups for baroreflex sensitivity. Our spectral data indicate that normotensive persons with a positive family history of arterial hypertension have lower parasympathetic modulation than those with a negative history. In normotensive persons with a family history of arterial hypertension, normal baroreflex sensitivity could be the mechanism that buffers the tendency for pressures to increase. The gradual loss of this regulatory mechanism may favor rising arterial pressures.

Adult↗
PubMed2000

Inactivation of human normal and tumour cells irradiated with low energy protons.

PURPOSE: To analyse the cell inactivation frequencies induced by low energy protons in human cells with different sensitivity to photon radiation. MATERIALS AND METHODS: Four human cell lines with various sensitivities to photon irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours of the tongue and larynx, respectively, and the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were irradiated with y-rays and proton beams with linear energy transfer (LET) from 7 to 33 keV/microm. Clonogenic survival was assessed. RESULTS: Survival curves are reported for each cell line following irradiation with gamma-rays and with various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton effectiveness was generally greater than that of gamma-rays. In particular there was a marked increase in beam effectiveness with increasing LET for the most resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation down to 0.37 with 30 keV/microm protons. The relative biological effectiveness (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to the proton dose producing the same inactivation level as that given by 2 Gy of gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively. CONCLUSIONS: RBE for inactivation with high-LET protons increased with the cellular radioresistance to gamma-rays. The cell line with the greatest resistance to gamma-rays was the most responsive to the highest LET proton beam. A similar trend has also been found in studies reported in the literature with He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

Cell Line↗
PubMed2000

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts.

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

Cell Line↗
PubMed2000

Event-related potentials in the elderly with new mild hypertension.

Hypertension is a risk factor for cerebrovascular diseases (CVD) and cognitive impairment and the relative risk of CVD at every level of blood pressure (BP) is greater among the elderly. We submitted 20 elderly affected by new mild hypertension and 10 elderly normotensives to 24-hour ambulatory BP monitoring (ABPM), to evaluate their cognitive state using the Mini-Mental-State-Examination and to the recording of related acoustic evoked potentials (P300 and N2). We did not find significant differences for P300 latency between hypertensives and normotensives, while N2 latency recording showed a statistically significant protracted value in elderly hypertensives. In these patients we found a significant correlation between the N2 latency and systolic blood pressure values recorded by ABPM. These results demonstrated early functional alterations of cognitive state in elderly hypertensives, that are related to systolic blood pressure and future data might point to an earlier use of therapy.

Aged↗
PubMed1999

Chromatid break rejoining and exchange aberration formation following gamma-ray exposure: analysis in G2 human fibroblasts by chemically induced premature chromosome condensation.

PURPOSE: To analyse the kinetics of chromatid break induction, rejoining, and misrejoining after y-irradiation in G2 phase human cells using premature chromosome condensation induced by calyculin A. MATERIALS AND METHODS: Human fibroblast AG1522 cells were irradiated with gamma-rays and chromosomes were then prematurely condensed by calyculin A. The number of chromatid breaks and chromatid exchanges in G2 chromosomes were scored, and fitted curves were calculated. RESULTS: Calyculin A induced premature chromosome condensation in cells immediately after irradiation. Kinetics of rejoining of chromatid breaks demonstrated two exponential components with rapid and slow time constants. Within 5 min after irradiation, the number of chromatid breaks fell rapidly to about one-half, then gradually decreased. Chromatid exchanges were formed very quickly, reaching a plateau within 20 min from exposure. CONCLUSIONS: Chemically induced premature chromosome condensation technique allows a simple, rapid and precise analysis of chromatid breakage and rejoining. The rapid kinetic component was particularly well characterized.

Cells, Cultured↗
PubMed1999

Chromosome aberrations induced by light ions: Monte Carlo simulations based on a mechanistic model.

PURPOSE: To investigate the mechanisms underlying the induction of chromosome aberrations by ionizing radiation, focusing attention on DNA damage severity, interphase chromosome geometry and the distribution of DNA strand breaks. METHODS: An ab initio biophysical model of aberration induction in human lymphocytes specific for light ions was developed, based on the assumption that 'complex lesions' (clustered DNA breaks) produce aberrations, whereas less severe breaks are repaired. It was assumed that interphase chromosomes are spatially localized and that chromosome break free-ends rejoin pairwise randomly; the unrejoining of a certain fraction of free-ends was assumed to be possible, and small fragments were neglected in order to reproduce experimental conditions. The yield of different aberrations was calculated and compared with some data obtained using Giemsa or FISH techniques. RESULTS: Dose-response curves for dicentrics and centric rings (Giemsa) and for reciprocal, complex and incomplete exchanges (FISH) were simulated; the ratio between complex and reciprocal exchanges was also calculated as a function of particle type and LET. The results showed agreement with data from lymphocyte irradiation with light ions. CONCLUSIONS: The results suggest that clustered DNA breaks are a critical damage type for aberration induction and that interphase chromosome localization plays an important role. Moreover, the effect of a given particle type is related both to the number of induced complex lesions and to their spatial distribution.

Alpha Particles↗
PubMed1999

Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods.

Estimates of equivalent whole-body dose following partial body exposure can be performed using different biophysical models. Calculations should be compared with biodosimetry data, but measurements are complicated by mitotic selection induced in target cells after localized irradiation. In this paper we measured chromosomal aberrations in peripheral blood lymphocytes during radiotherapy, and estimated the equivalent whole-body dose absorbed, by using the novel technique of interphase chromosome painting. Premature chromosome condensation was induced in stimulated lymphocytes by incubation in calyculin A, and slides were hybridized in situ with whole-chromosome DNA probes specific for human chromosomes 2 and 4. Reciprocal exchanges were used to estimate the equivalent whole-body dose, based on individual pre-treatment in vitro calibration curves. Equivalent whole-body dose increased as a function of the number of fractions, and reached a plateau at high fraction numbers. Chromosomal aberration yields were dependent on field size, tumour position and concurrent chemotherapy. Results suggest that interphase chromosome painting is a simple technique able to give a reliable estimate of the equivalent whole-body dose absorbed during therapeutic partial-body irradiation.

Aged↗
PubMed1999

Autonomic modulation and QT interval dispersion in hypertensive subjects with anxiety.

Anxiety is associated with an increased risk of sudden death. QT dispersion is a marker of cardiac repolarization instability and is seen in conditions of high risk of sudden death. The purpose of this study was to evaluate autonomic nervous system control and QT dispersion in hypertensive subjects with anxiety symptoms. In a recent preliminary study, we observed that hypertensive individuals reporting high scores on a self-assessment anxiety scale had more marked left ventricular hypertrophy. In 105 hypertensive subjects divided into 3 groups according to severity of anxiety, we evaluated autonomic control by short-term power spectral analysis of RR and arterial pressure variability at rest (baseline) and during sympathetic stress (tilt test), left ventricular mass index, and heart rate-corrected QT (QTc) dispersion. At baseline, hypertensive subjects with higher anxiety symptom scores had significantly lower high-frequency RR values expressed in absolute terms (P<0.05) and in normalized units (P<0.05) than their counterparts without anxiety symptoms. Hypertensive subjects with anxiety also had a higher mean left ventricular mass index (P<0.001) and greater QTc dispersion (P<0.001). Both indexes and high frequency (P<0.05) correlated with severity of anxiety. These findings suggest that anxiety is associated with autonomic imbalance. This condition could favor an increase in left ventricular mass. Myocardial hypertrophy alone or combined with neuroautonomic imbalance may lead to QT dispersion.

Adult↗
PubMed1999

Association between G2-phase block and repair of radiation-induced chromosome fragments in human lymphocytes.

We have studied the induction of chromosomal aberrations in human lymphocytes exposed in G0 to X rays or carbon ions. Aberrations were analyzed in G0, G1, G2 or M phase. Analysis during the interphase was performed by chemically induced premature chromosome condensation, which allows scoring of aberrations in G1, G2 and M phase; fusion-induced premature chromosome condensation was used to analyze the damage in G0 cells after incubation for repair; M-phase cells were obtained by conventional Colcemid block. Aberrations were scored by Giemsa staining or fluorescence in situ hybridization (chromosomes 2 and 4). Similar yields of fragments were observed in G1 and G2 phase, but lower yields were scored in metaphase. The frequency of chromosomal exchanges was similar in G0 (after repair), G2 and M phase for cells exposed to X rays, while a lower frequency of exchanges was observed in M phase when lymphocytes were irradiated with high-LET carbon ions. The results suggest that radiation-induced G2-phase block is associated with unrejoined chromosome fragments induced by radiation exposure during G0.

Adult↗
PubMed1999

Theoretical and experimental tests of a chromosomal fingerprint for densely ionizing radiation based on F ratios calculated from stable and unstable chromosome aberrations.

In the present study, F ratios for both stable chromosome aberrations, i.e. ratios of translocations to pericentric inversions, and unstable aberrations, i.e. dicentrics and centric rings, were measured using fluorescence in situ hybridization. F ratios for stable aberrations measured after exposure to low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 1.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiation were 6.5 +/- 1.5, 4.7 +/- 1.6, 9.3 +/- 2.5 and 10.4 +/- 3.0, respectively. F ratios for unstable aberrations measured after low (2.89 Gy 60Co gamma rays) and high-LET (0.25 Gy 56Fe ions; 3.0 Gy 12C ions) radiations were 6.5 +/- 1.6, 6.3 +/- 2.3 and 11.1 +/- 3.7, respectively. No significant difference between the F ratios for low- and high-LET radiation was found. Further tests on the models for calculation of the F ratio proposed by Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) showed that the F ratio may not be straightforward as a practical fingerprint for densely ionizing radiation.

Cells, Cultured↗
PubMed1998

Effects of melanin on high- and low- linear energy transfer (LET) radiation response of human epithelial cells.

The search for effective radioprotectors is of major concern in the medical, military, environmental, and space sciences. Conventional radioprotectors are generally effective only during a single irradiation and display their radioprotective properties only at high, toxic concentrations. In addition, they reduce somatic radiation effects but are poorly efficient in protecting from hereditary stochastic radiation effects. In this respect, the pigment melanin merits attention. Experiments referring to potential melanin effects on the ionising radiation response have been carried out with different biological systems, both in vivo and in vitro. In this paper, we present results on the response to high- and low-linear energy transfer (LET) radiation of a human mammary epithelial cell line, H184B5 F5-1 M/10, supplemented by melanin. The incorporation of auto-oxidative (L-dopa) melanin was linear for concentrations from 3 to 10 micrograms/ml in the growth medium. Concentrations of up to 250 micrograms/ml did not significantly impair the cells proliferative ability. No significant protective effect of melanin on the survival of cultured cells after exposure to alpha-particles (130 keV/micron) or x-rays was observed.

Alpha Particles↗
PubMed1998

Biodosimetry of heavy ions by interphase chromosome painting.

We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

Aged↗
PubMed1998

A simple method for simultaneous interphase-metaphase chromosome analysis in biodosimetry.

PURPOSE: To find a simple protocol for measuring chromosome damage both in G1 and in G2/M chromosomes, to overcome problems related to low mitotic index and cell-cycle alterations in biodosimetric tests. MATERIALS AND METHODS: The protocol is based on the use of calyculin A to induce premature chromosome condensation in human peripheral blood lymphocytes in different phases of the cell cycle. Chromosome exchanges were measured by fluorescence in situ hybridization (chromosomes 2 and 4) in lymphocytes from four different donors. Cells were exposed to 4Gy X-rays and the results were compared to aberrations in M phase (colcemid block) and G0 (premature chromosome condensation induced by fusion to mitotic hamster cells). RESULTS: Treatment with calyculin A produced a high fraction of chromosome condensation in different phases of the cell cycle. Cells in G1 and G2/M could be scored simultaneously for biodosimetry by chromosome painting. The condensation index was 5-20 times higher than the mitotic index (colcemid alone). The calyculin A treatment did not produce a significant increase in the background of chromosomal aberrations or modify the yield of chromosomal aberrations scored after exposure to X-rays. CONCLUSIONS: Induction of chromosome condensation by calyculin A is a powerful biodosimetric tool, which provides a high number of spreads for analysis and overcomes problems related to poor in vitro growth or cell-cycle alterations.

Cell Cycle↗