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Biomedical subjects

C Catena

Publications and source records attributed to C Catena.

34 records · Page 2Linked to original sources

Benign familial macrocytosis.

We have identified a 52-year-old woman and her 27-year-old daughter with macrocytosis, normal haemoglobin and mean corpuscular haemoglobin concentration. Macrocytosis could be demonstrated from the age of 40 and 25 respectively. All blood tests were normal including vitamin B12 and folic acid. Bone marrow investigation showed rare macroblasts without other abnormalities. Endoscopy of the upper gastrointestinal tract and ultrasonography of the abdomen were normal. Thus, persistent macrocytosis was present without evidence of diseases that might account for it. In these subjects, macrocytosis is likely to be related to the presence of a genetic defect.

Adult↗

Abnormalities of insulin receptors in spontaneously hypertensive rats.

Insulin resistance is present in some strains of rats with genetic hypertension. To determine whether this abnormality is present at the level of the insulin receptor, we compared insulin sensitivity, insulin receptor binding, and mRNA levels in tissues of 10-week-old spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Because we have previously demonstrated an inverse relationship between dietary sodium intake and renal insulin receptor density and mRNA levels in normal Sprague-Dawley rats, the two rat strains in the current experiment were fed either low salt (0.07% NaCl) or high salt (7.5% NaCl) chow until the SHR became hypertensive. Fasting plasma glucose and plasma insulin levels did not differ between SHR and WKY and were not affected by salt intake. When the rats were maintained on the low salt diet, the rate of glucose infusion required to main euglycemia during a hyperinsulinemic clamp was significantly lower in SHR than WKY. High salt diet decreased the rate of glucose utilization during the hyperinsulinemic clamp in WKY but not SHR. During the low salt diet, insulin infusion decreased sodium excretion in both WKY and SHR. When the rats were maintained on the high salt diet, the antinatriuretic response to insulin was blunted in WKY but not SHR. Both the density and mRNA levels of insulin receptor were comparable in the kidney of WKY and SHR, but only WKY had the previously demonstrated decrease in receptor number and mRNA levels when fed the high salt chow. Hepatic insulin receptor mRNA levels were significantly lower in SHR than WKY fed the low salt diet. High salt diet decreased significantly insulin receptor mRNA levels in the liver of WKY but not of SHR. Thus, SHR appear to have lost the feedback mechanism that normally limits insulin-induced sodium retention when extracellular volume is expanded. A decreased expression of insulin receptor in the liver of SHR provides a possible explanation for the insulin resistance and decreased insulin clearance present in this strain.

Animals↗

Micronuclei and 3AB index in X-irradiated human lymphocytes in G0 and G1 phases.

We applied the cytokines-block micronucleus assay to observe the radiobiological response of human lymphocytes after X-ray treatment in the G0 and G1 phases. In addition, we used 3-aminobenzamide (3AB) to measure the 3AB index in the two phases. The experimental results show that at 2 Gy the MN yield and the 3AB index are dependent on the cell phase and show considerable inter-individual variability. The radiation-induced MN frequency obtained for 33 subjects is 0.470 +/- 0.063 for the G0 phase and 0.689 +/- 0.139 for the G1 phase; the 3AB index values are 0.326 +/- 0.144 and 0.067 +/- 0.058 for G0 and G1 phases, respectively. At the individual level, the 3AB index for the G1 phase correlates inversely with the cytogenetic effects observed in that phase. We discuss the possibility of applying the MN test combined with the 3AB index to lymphocytes at different phases to study the individual response to radiation (individual radiosensitivity).

Adult↗

Micronuclei and 3AB index in human and canine lymphocytes after in vitro X-irradiation.

The comparative study of different species could be of interest, both applied and pure, to the field of cytogenetic damage induced by genotoxic agents. For as accurate as possible an evaluation of the inter-species response differences to radiation, we have carried out a comparison between the behaviors of human and canine lymphocytes, using the micronucleus assay (MN test) according to the cytokinesis-block method. Up to 4 Gy doses, canine lymphocytes have been found to be about three times more radiosensitive than human lymphocytes, due to blastization inhibition (binucleation failure), and, for 1 and 2 Gy doses, about 1.3 times more radiosensitive, due to MN yields. We discuss whether the differing chromosome number (dog 78 and man 46) could have any effect on the cytogenetic response. 3-Aminobenzamide, which inhibits poly(ADP-ribose)polymerase activity, is able to increase the genotoxic effect of X-rays in human lymphocytes, with a different response at the individual level. The same phenomenon with the same characteristics is also found in canine lymphocytes at the inter-individual level. Our in vitro radiobiological study confirms that the cytogenetic response obtained in blood from selected breeds of mammalian species can be utilized for applications in environmental studies.

Animals↗

Lack of effect of inhibitors of DNA synthesis/repair on the ionizing radiation-induced chromosomal damage in G2 stage of ataxia telangiectasia cells.

The relationship between the repair processes occuring at the G2 phase of the cell cycle and cytogenetic damage in ataxia telangiectasia (AT) cells was studied. Lymphoblastoid cells derived from normal, heterozygote AT (HzAT) and three AT patients were exposed to X-rays or fission neutrons and post-treated with inhibitors of DNA synthesis/repair, such as inhibitors of DNA polymerases alpha, delta and epsilon (cytosine arabinoside, ara-C; aphidicolin, APC; buthylphenylen-guanine, BuPdG) or ribonucleotide reductase (hydroxyurea, HU). A strong increase of radiation-induced chromosomal aberrations was observed in normal and HzAT cells post-treated with ara-C, APC and HU, but not in the presence of BuPdG. No enhancing effect was observed in cells derived from AT patients, except for HU post-irradiation treatment. These results suggest that the enzymes that can be inhibited by these agents are not directly involved in the repair of radiation damage induced in G2 cells from AT patients, indicating that probably the AT cells that we used lack the capability to transform the primary DNA lesions into reparable products, or that AT cells might contain a mutated form of DNA polymerase resistant to the inhibitors.

Ataxia Telangiectasia↗

Micronuclei and 3AB-index in patients receiving iodine-131 therapy.

In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for cancer, the micronucleus (MN) frequency observed in peripheral blood lymphocytes (MN-test on binucleated cells) had a weighted mean of 0.044 +/- 0.006 (SEM), which was significantly different (p < 0.001) from that observed in 93 healthy individuals (0.025 +/- 0.001). The MN frequency (F(MN)) of the patients correlated fairly well (R = 0.736) with the modified activity (Amod) calculated by the following equation: [formula: see text] where Ai is the 131I activity on a determined day, e the logarithm base, di the number of days that have passed between the determined day and the day when the blood was drawn, and k is a day coefficient, defined in this context as the "daily attenuation factor". The use of the value of 0.0003 for k allowed the following equation to be obtained: F(MN) = 7.9 x 10(-5) (+/- 1.4 x 10(-5)).Amod + 0.014 (R = 0.736) The MN frequency was used to estimate, by our DOSIME program, the dose (Gy) received at the individual level in the 131I treatment. In these subjects the calculated dose was well correlated with Amod by the relationship: DBio = 0.0009 (+/- 0.0002).Amod + 0.0675 (R = 0.755) 3-aminobenzamide (3AB), an inhibitor of the poly(ADP-ribose)polymerase enzyme involved in DNA repair, induced and increase in X-ray cytogenetic damage (MN yields), evaluated at the individual level using the 3AB-index (I-3AB). The index was obtained from the MN-yield count after x-irradiation with (MN + 3AB) and without (MN - 3AB) 3AB, using the following formula: I = 1-(MN - 3AB/MN + 3AB).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

The yield of fission neutron-induced chromatid aberrations in G2-stage human lymphocytes: effect of caffeine, hydroxyurea and cytosine arabinoside post-irradiation.

To evaluate the influence of inhibitors of DNA synthesis/repair on the yield of chromosomal aberrations in the G2 phase of the cell cycle, whole-blood cultures of human lymphocytes were exposed to various doses of fission neutrons or X-rays and treated post-irradiation during the last 2.45 h before harvesting, with 5 mM caffeine, 5 mM hydroxyurea (HU) and 0.05 mM cytosine arabinoside (ara-C). The presence of caffeine and HU strongly potentiated the yield of chromatid-type aberrations induced by both neutrons and X-rays. No potentiating effect, except at the highest dose of neutrons, was observed when irradiated cells were subsequently treated with ara-C. Since ara-C strongly potentiated the frequency of chromatid aberrations induced in G2 lymphocytes by X-rays, the results presented here indicate that fission neutrons produce a smaller proportion of lesions, the repair of which can be inhibited by ara-C, compared with the number produced by X-rays. In addition, neutron-induced mitotic delay was shortened by treatment with caffeine, mainly within the first 2 h after irradiation.

Caffeine↗

Inter-individual differences in radiation response shown by an in vitro micronucleus assay: effects of 3-aminobenzamide on X-ray treatment.

Among the methods of biological dosimetry of ionizing radiation, we propose the cytokinesis-block micronucleus assay for the measurement of the individual dose absorbed. The dose-response curve was determined for in vitro-irradiated lymphocytes from 25 individuals. The dose-response relationship, fitted by the linear-quadratic function, was F(MN) = 0.015 (+/- 0.0016) + 0.043 (+/- 0.0075).D + 0.083 (+/- 0.0045).D2. Our results are compared with those of other authors. 3-aminobenzamide (3AB) combined with X-rays were used to evaluate the micronucleus dose-response relationship in blood from 14 individuals. While it is known that 3AB inhibits poly(ADP-ribose) polymerase activity in vitro, we demonstrate that it also increases the X-ray-induced micronucleus yields. The resulting dose-response relationship varies from subject to subject. The possibility of using this approach to identify the individual radiosensitivity level is discussed.

Adult↗

[Micronuclei induced by ultraviolet radiations or X rays in mammal cells in vitro].

The effects of UV light or X rays in cultured Chinese hamster cells have been initially analyzed in terms of cell growth and colony survival. On the basis of these preliminary observations the induction of micronuclei has been studied on the same in vitro system. The increase in micronuclei yield appears to be dose-dependent, but also to vary according to the protocol used for micronuclei preparation. In general, the results confirm the hypothesis that micronucleus production is a dynamic phenomenon.

Animals↗

DNA strand break rejoining in human lymphocytes during the S phase.

Induction and repair of DNA strand breaks in asynchronous and synchronized cultures of human lymphocytes was investigated by using the alkaline DNA-unwinding technique followed by chromatography on hydroxylapatite. Strand break rejoining in exponentially growing human PHA stimulated lymphocytes, irradiated with 20 Gy of X-rays, is temperature-dependent, being fast at 37 degrees C (half-time of a few minutes), and very slow at around 4 degrees C. In synchronized cells irradiated with the same X-ray dose, the repair capacity increases during S phase reaching its maximum when DNA is entirely duplicated.

DNA Repair↗

[Effect of x-rays on the intracellular transport of thymidine in human lymphocytes stimulated by phytohemagglutinins].

The effect of X-irradiation on thymidine transport in human lymphocytes PHA stimulated was investigated. Mediated transport sistem, the predominant mechanism at low extracellular concentration of thymidine (less than 10(-7) M) in the medium is highly radiosensitive. The transport sistem was damaged considerably by high doses of X-rays (at least until 10 Krad); the decrease of thymidine uptake was a function of the time of incubation after irradiation. It suggest that repair mechanisms are not involved at high doses of X-rays within 120 minutes of incubation.

Biological Transport, Active↗

[Cytogenetic dosimetry: dose-effect curves and a methodological comparison].

When physical dosimetry is unavailable, the biological dosimetry of ionizing radiations is considered the best method for evaluating the individual absorbed dose. In order to apply this method, it is essential to know the dose-response relationship (calibration effect) regulating the phenomenon. The results obtained on human lymphocytes after in vitro X-ray treatment are presented. Two cytogenetic methods were used: the dicentric chromosomes assay in metaphase cells and the micronuclei assay in binucleated cells. The two were compared in order to verify the best utilization of each in the context of prevention and radioprotection. For the dicentric assay, 20 samples were treated with increasing doses of X-rays (from 0.5 to 2.0 Gy) and for the micronuclei assay, 25 samples were treated with doses from 0.1 to 4.0 Gy. The biological response was then evaluated. The data obtained were fitted by a second-grade polynomial regression. The dose-response relationship for the dicentric yield was F(dic) = 0.01-0.2D + 0.091D2 (regression coefficient better than 0.95); for the micronuclei yield, it was F(mn) = 0.015 + 0.043D + 0.083D2 (regression coefficient better than 0.97). The absorbed dose in exposed individuals was evaluated by the micronuclei frequency using a mathematical process (inverse prediction) that takes into account the measurement error and the 95% confidence intervals of the calibration curve. For this purpose a programme in Basic (DOSIME) was generated that was capable of estimating the dose and its variability. Since the micronuclei assay is simple and quick to carry out, it permits extensive screening and facilitates the identification of radiosensitive subjects. The estimated dose values of individuals submitted to radiotherapy are also given.

Adult↗