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Biomedical subjects

G Simone

Publications and source records attributed to G Simone.

At least 55 records · Page 3Linked to original sources
PubMed1992

Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. III. Initial yield of DNA double-strand breaks in V79 cells.

The results reported form part of a series of experiments to substantiate and extend the findings by Belli et al. (1989) that protons are more biologically effective at cell killing than alpha-particles of the same LET. The irradiations were carried out using the Variable Energy Cyclotron (VEC) at the Harwell Laboratories. V79-4 Chinese hamster cells were exposed to alpha-particles and protons with LETs of 20 and 23 keV microns-1 in the dose range 40-150 Gy. X-rays were also used for comparison. Two methods were used for measurement of initial DNA double-strand breaks: sedimentation and DNA precipitation assays. The dose-response relationships were found to be well fitted by straight lines in all cases. With the sedimentation assay a slightly lower yield of dsb was found from protons than from alpha-particles of the same LET. The yield from X-rays was not significantly different from either. The precipitation assay showed similar yields of DNA damage from both particle types but significantly higher yields from X-rays. This may reflect a difference in the type of lesions scored by the two methods. Since the initial amount of dsb does not account for the observed differences in cellular response to radiations of different qualities, it is likely that these are related to the nature of the dsb (affecting reparability) or to the occurrence of other types of molecular damage.

Alpha Particles↗
PubMed1992

[Evaluation of the hereditary component in patients with essential arterial hypertension].

As is well known, genetic factors play a decisive role in the pathogenesis of essential hypertension (EH), even if they are closely related to environmental factors; it is therefore not possible to quantify with any degree of certainty the role and importance of each in the onset of hypertensive disease. The aim of the present study was to ascertain the presence of hypertensive 1st and 2nd degree ascendant, collaterals and descendants in a group of 355 out-patients with EH (167 males, 188 females; mean age: 52.9 +/- 0.7 years) using an anamnestic analysis. The results of this study confirmed the high prevalence of the hereditary component in EH: familial hypertension was found in 60.6% of the group. From a detailed analysis of the group, with regard to hypertensive ascendant, the hereditary transmission of EH by the mother was significantly higher than that by the father, both the parents and the forefathers, even if it is worth pointing out that the penetration of the genetic character was not always sex-related and was equally distributed between male and female descendents. In addition, it was observed that patients with a familial pattern of hypertension in common with collateral relatives showed significantly enhanced levels of systolic and diastolic pressure in relation to those with another hereditary component. These findings serve to underline the importance of evaluating the effective incidence of EH with regard to an entire family nucleus and not only in individual terms, in order to identify the various means of genetic transmission and possible interactions with environmental factors.

Female↗
PubMed1992

[Metabolic changes in the patient with essential hypertension].

The aim of the present study was to evaluate a number of parameters in a group of patients with essential hypertension and then compare the results with those in a group of healthy normotensive subjects. One hundred and fifty-six patients with essential hypertension (EH) in the non-complicated form (73 males, 83) females; mean age: 54.8 +/- 0.9 years) were selected and compared with 150 normotensive subjects matched for age and sex. After a 2-week period of wash-out during which patients followed a diet with normal sodium and calorie content, body mass index, systolic and diastolic arterial pressure (AP), mean arterial pressure (MAP), heart rate in clino- and orthostatism were measured and blood was collected to assay glycemia, total cholesterolemia, LDL and HDL cholesterolemia and triglycerides. In the group of patients suffering from EH all the above parameters were found to be significantly higher than in normotensive control subjects. In particular, in the hypertensive population the prevalence of obesity was 21.3%, hyperglycemia 26.9%, hypercholesterolemia 65.1% and smoking 36.4%. When the possible relation between one or more risk factors and AP values was assessed, it was found that in hypertensive patients the presence of hyperglycemia alone or in association with other metabolic disorders led to the highest MAP findings. Moreover, having studied the correlation rate of the various parameters, it was seen that in both the hypertensive and normotensive populations systolic AP measured in clinostatism positively correlated with glycemia, total cholesterolemia, and age, whereas correlations were not found between clinostatic diastolic AP and the above parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Mutation induction and RBE-LET relationship of low-energy protons in V79 cells.

The mutation induction at the HGPRT locus has been studied in V79-753B Chinese hamster cells irradiated with proton beams with energies of 3.36, 1.70 and 1.16 MeV, corresponding to average LET values of 10.6, 17.8 and 23.9 keV/microns, respectively. The mutation curve obtained with 200 kV X-rays was used for comparison. The mutation frequency induced by all the proton beams is considerably higher than that induced at the same dose by X-rays and it is linearly related to the dose. Moreover, the proton effectiveness increases with the LET. The RBEs (evaluated as the initial slope ratios) are 5.0 +/- 0.8, 5.4 +/- 0.8 and 7.7 +/- 1.2 for protons with average LETs of 10.6, 17.8 and 23.9 keV/microns, respectively. These values are higher than those reported in the literature for other ions of comparable LET. This finding parallels what we have already found for cell inactivation (for which RBEs of 3.0, 4.6 and 7.3 were obtained at the same LETs), and indicates that for mutation induction, also, the RBE-LET relationship may depend on the type of radiation.

Animals↗
PubMed1990

Tumor-proliferative activity, progesterone receptor status, estrogen receptor level, and clinical outcome of estrogen receptor-positive advanced breast cancer.

The relations among pretreatment tumor-proliferative activity, progesterone receptor (PgR) status, estrogen receptor (ER) level, and clinical outcome were analyzed in a series of 45 ER-positive advanced breast cancer postmenopausal women treated with tamoxifen (20 mg/day) until disease progression. Tritiated thymidine ([3H]dThd) Labeling Index (LI) by autoradiographic assay was utilized for proliferative activity analysis, whereas the dextran-coated charcoal method was used for ER and PgR evaluation (cutoff value, 10 fmol/mg of protein cytosol). The median [3H]dThd LI value was 1.8%; 73% of cases were PgR positive, and 53% were highly ER positive (greater than 100 fmol/mg of protein cytosol). Clinical responses were more frequently observed in slowly than in quickly proliferating tumors (86% versus 60%; P less than 0.05) but were similar for PgR-positive and -negative cases, as well as for those with high and low ER positivity. Only [3H]dThd LI was found to individualize patients with different survival rates (at 40 mo of follow-up, 78% versus 40% in slowly and quickly proliferating tumors, respectively). The [3H]dThd LI, monitored in ten patients by a second tumor biopsy after 14 days of tamoxifen therapy, was found to have a significantly lower median value (P = 0.03). These data indicate that pretreatment [3H]dThd LI provides information, which is not available in a study of PgR and ER status, on the clinical outcome of ER-positive advanced breast cancer patients treated by hormone therapy.

Breast Neoplasms↗
PubMed1990

Effects of decreased pH on membrane structural organization of Escherichia coli grown in different fatty acid-supplemented media: a 31P NMR study.

Total membranes from Escherichia coli cells grown in different fatty acid-supplemented media have been examined by 31P NMR at different pH values. The isolated inner and outer membranes were also studied and compared to the liposomes formed with the corresponding extracted lipids. While the liposomes show structures that are correlated with lipid composition, degree of fatty acid unsaturation, and pH, the membrane structure is mainly bilayer. The presence of two bilayer phases characterized by different chemical shift anisotropy values (delta nu csa) is detectable at neutral pH; a perturbation of the bilayer phase characterized by the smallest delta nu csa is produced by low pH. Moreover, an isotropic peak is always present in the membrane NMR spectra: its attribution to cardiolipin molecules is discussed on the basis of digestion experiments with phospholipase C.

Cell Membrane↗
PubMed1990

[Nuclear morphometry and estrogen receptors in infiltrating ductal carcinoma of the breast].

In this study ten cases of breast infiltrating ductal carcinoma have been considered. In all of them the content of ER has been evaluated by using monoclonal antibodies. Five of them were ER positive and five were ER negative. For the morphometric study ten nuclei of each case have been considered. By using the S.A.M. (Shape Analytical Morphometry) work-station an analytical study of the nuclear shape was performed. The first step was the extraction of fundamental shape which describes the basic shape of original contour without its irregularities. It was obtained by using two parametric equations. The second step was the evaluation of shape asymmetry by S.A.E. (Shape Asymmetry Evaluator). Finally the contour irregularities were evaluated by Fourier analysis. Along with analytical parameters, dimensions (area, perimeter and maximum diameter) were considered too. All obtained data were submitted to univariate statistical analysis (Student's T test) to compare the two groups (ER positive and ER negative tumors). Area, perimeter and maximum diameter were significatively greater in ER negative cases while analytical parameters were not discriminant between the two groups.

Breast Neoplasms↗
PubMed1989

Cell kinetics and hormonal receptor status in inflammatory breast carcinoma. Comparison with locally advanced disease.

The biological and prognostic role of hormone receptor status and proliferative activity have been studied in two series of patients affected by inflammatory breast carcinoma (IBC, 28 patients) and locally advanced breast cancer (LABC, 50 patients). Estrogen receptor (ER) and progesterone receptor (PgR) were measured by dextran-coated charcoal (DCC) method whereas proliferative activity was measured by 3H-thymidine autoradiographic labeling index (LI). The percentages of ER+ and PgR+ cases resulted lower in IBC than in LABC (ER+, 44% versus 64%; PgR+, 30% versus 51%, respectively), pertaining to both premenopausal and postmenopausal women. Inflammatory breast carcinoma showed a higher median LI value than LABC (3.5% versus 1.6%; P = 0.006). Regarding clinical aspects, time to progression (TTP) in IBC patients was not affected by hormone receptor status (19 evaluable patients) or by LI (17 evaluable patients); PgR+ status and low LI resulted important for individualizing women with a longer median overall survival (OS). Inflammatory breast carcinoma has been verified to be a heterogeneous biological entity for which hormone receptors and cell kinetics could be useful in identifying patients with different prognoses and therefore candidates for a personalized therapy.

Adult↗
PubMed1989

RBE-LET relationship for the survival of V79 cells irradiated with low energy protons.

The survival of V79 Chinese hamster cells irradiated with proton beams with energies of 0.73, 0.84, 1.16, 1.70 and 3.36 MeV, corresponding to LET values, evaluated at the cell midplane, of 34.5, 30.4, 23.9, 17.8 and 10.6 keV/micron respectively, have been studied in the dose range 0.5-6.0 Gy. As a reference, the survival curve obtained with 200 kV X-rays was used. The initial shoulder, typical of survival curves obtained with sparsely ionizing radiation, decreases as the LET increases and completely disappears at 23.9 keV/micron. This value corresponds to the maximum of the RBE, expressed as the initial slope ratio. In the energy range we have considered, the RBEs for protons are higher than those reported for other ions of comparable LET and the RBE-LET relationship results shifted to lower LET values. Our data seem to indicate that the RBE-LET curve depends on the type of radiation and this could imply that LET is not a good reference for the dose-effectiveness relationship.

Animals↗
PubMed1988

Correlation between ERICA and DCC assay in hormone receptor assessment of human breast cancer.

To study the basic relationships between estrogen receptor immunocytochemical assay (ERICA) and dextran-coated charcoal (DCC) techniques, 116 women affected by breast cancer were admitted to the study from June 1985. In 56% of cases the tumor sample came from patients with operable disease and in 44% from patients with advanced inoperable disease. We found an overall agreement of 80% between the two methods characterized by a high sensitivity (95%) and a low specificity of ERICA versus DCC. ER/ICA negative results were found in 20 out of 78 ER/DCC positive cases; on the contrary, discordant results were found in only 3 out of 38 cases described by DCC as ER negative. 29 patients with advanced disease and ER/DCC positive tumors were considered for clinical analysis and reliability of each hormone receptor assay. A clinical response was reached in 69% of ER/DCC positive patients and on 64% of ER/ICA positive ones (16/25). However, it must be noted that 4/29 cases described as negative by ERICA were clinically responsive to hormone therapy.

Breast Neoplasms↗
PubMed1986

Radiation chemical and physical mechanisms of radiosensitization of single cell systems by iothalamate.

The radiosensitizing effect of iothalamate (ITA) has been investigated in bacterial and mammalian cells in order to obtain a better understanding of the physical and radiation chemical mechanisms of sensitization displayed by the drug. In order to distinguish between the two, Escherichia coli B/r cells were irradiated with 9 MeV electrons, which allow only the radiation chemical mechanism to operate, and V79 cells with 250 KVp X-rays, which instead make possible the occurrence of both mechanisms. It has been shown that: Maximum sensitization already occurs in bacteria with 10(-2) mol dm-3 ITA (enhancement ratio (ER) 11.2 in oxygen, 2.7 in nitrogen), while in mammalian cells a concentration higher by a factor of 10 is required (ER 2.2 both in air and nitrogen). ITA sensitization is inhibited when bacteria are irradiated in growth medium instead of buffer. Such inhibition does not occur with V79 cells. Cysteine and glycerol completely cancel the sensitizing effect of ITA on bacterial cells in both gas phases. Dimethylsulphoxide (DMSO) does the same in nitrogen, while in oxygen it only reduces ITA sensitization to about 50 per cent of the level observed in control conditions. With mammalian cells, all the three scavengers do not modify significantly the enhancement produced by ITA, either in air or in nitrogen. The experimental results are consistent with both postulated mechanisms of sensitization.

Animals↗
PubMed1986

Interactions of thiyl free radicals with oxygen: a pulse radiolysis study.

A pulse radiolysis study of glutathione in aqueous solution at pH 5.5 containing N2O/O2 mixtures at various ratios indicates that oxygen rapidly adds to the thiyl glutathione radical yielding a transient absorption, with a maximum at 540 nm, whose characteristics appear to be compatible with assignment to the GSOO. radical. The reaction (Formula: see text) appears to be an equilibrium whose kinetic constants have been estimated (kf = 2.0 X 10(9) dm3 mol-1, kb = 6.2 X 10(5) s-1). Evidence for electron transfer from ascorbate to the GSOO. radical has been obtained and the respective rate constant has been determined to be 1.75 +/- 0.15 X 10(8) dm3 mol-1 s-1.

Free Radicals↗
PubMed1984

Effect of hyperthermia and gamma-radiation on Escherichia coli K1060 D-lactate dehydrogenase.

The response of E. coli K1060 D-lactate dehydrogenase (D-LDH), an enzyme located in the cytoplasmic membrane, was studied following 42.5 degrees C hyperthermia and/or gamma-irradiation. The inactivation of D-LDH following the above treatment was used as a tool to probe the role of membrane proteins in the radiation and/or heat sensitivity of cells. No correlation between loss of enzyme activity and cell killing was found, suggesting that D-LDH does not play an important role in hyperthermic cell survival. The results obtained in combined hyperthermia and gamma-irradiation treatments on loss of D-LDH activity and E. coli cell killing suggest that an interaction between heat and radiation occurs at the membrane structure level. Moreover, when cells were heated at 42.5 degrees C in the presence of 10 mM procaine-HCl, both cell killing and loss of D-LDH activity were enhanced. The involvement of membrane structure in the heat sensitivity of cells is strongly indicated by the latter observations. The opposite effect was observed when procaine was present during irradiation in oxic conditions, suggesting that procaine itself can also act as a scavenger towards OH-induced radicals.

Cell Survival↗
PubMed1983

Role of glutathione in affecting the radiosensitivity of molecular and cellular systems.

It has previously been shown that radioinduced organic radicals can be repaired by hydrogen donation from glutathione (GSH) and this repair is in competition with oxygen (damage fixation). In this paper the influence of exogenous glutathione on the radiation response of the enzyme alcohol dehydrogenase (YADH), DNA in vitro, and E. coli B/r cells has been investigated. GSH is observed to protect YADH essentially by free radical scavenging mechanisms in both presence or absence of oxygen. The same mechanism seems operate in the radioprotection afforded by GSH to DNA in vitro. E. coli B/r cells are protected at higher extent by GSH than its oxidized form (GSSG); the possibility that GSH penetrate into bacterial cells more easily that GSSG can explain their different behaviour. None of the three systems studied has provided definitive support for the occurrence of the hydrogen donation reaction in the radioprotective mechanisms of GSH versus biomolecules and bacterial cells.

Alcohol Dehydrogenase↗
PubMed1983

Lowered pH eliminates the enhanced hyperthermic killing of E. coli induced by procaine or exposure to N2 gassing.

Survival of E. coli K1060 is enhanced when they are heated at 47 degrees C in pH 6 medium as compared to pH 7.4. At pH 6 nitrogen bubbling and 10 mM procaine did not increase hyperthermic killing. The membrane content of phosphatidylethanolamine is about 80 per cent of the total of phosphatidylethanolamine, phosphatidylglycerol and cardiolipin phospholipids. The polar headgroup of this lipid is highly sensitive to pH changes in this pH range. The changes in electrostatic charge with its secondary effects on membrane-protein relationships may explain resistance to hyperthermic killing. Thus, the difference in response to lowered pH of bacterial, compared to mammalian cells may be revealing membrane-related phenomena critical to hyperthermic killing. Also increased levels of cardiolipid were observed in linolenic acid grown cells which could be an 'attempt' to stabilize their membranes.

Cell Survival↗
PubMed1977

Iodinated radiological contrast media as radiosensitizers.

This paper describes the radiosensitizing effects of diatrizoic (DA) and iothalamic (ITA) acids and of iodipamide (IP) on the survival of E coli B/r irradiated with X-rays and with high-intensity electron pulses. All compounds at concentrations between 10 and 50 mM display a strong sensitizing effect in the presence of oxygen (DMF between 0-1 and 0-3) and are much less effective in nitrogen. In N2O the degree of sensitization is intermediate between oxygen and nitrogen. The situation is the same at pH 7 or 5-6. Solutions of DA, ITA and IP irradiated at pH lower than 6 become highly toxic to bacteria added after irradiation, for several hours after X-irradiation or several minutes after pulsed irradiation. The maximum toxic effect occurs with 2 krad of X-ray and with 6-8 krad of electrons. Oxygen must be present in order to observe the bactericidal activity. This is not affected by scavenging hydrated electrons with nitrate, but is completely cancelled by scavenging OH radicals with formate. It is also cancelled by adding thiosulphate to the irradiated solutions immediately before the bacteria. In the presence of nutrient broth, the radiosensitizing effect is absent after irradiation with pulsed electrons; whereas after X-irradiation it is reduced when the concentration of sensitizers is 50 mM. The experimental data appear to be compatible with a mechanism operated by short and long-lived transients resulting from the radiolysis of iodinated contrast media.

Cell Survival↗