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Biomedical subjects

G Doria

Publications and source records attributed to G Doria.

At least 55 records · Page 3Linked to original sources
PubMed1994

Melatonin restores immunodepression in aged and cyclophosphamide-treated mice.

Melatonin, the main hormone of the pineal gland, when chronically injected into young mice or mice immunodepressed by aging or by cyclophosphamide treatment, was able to enhance the antibody response to a T-dependent antigen. The enhancement of antibody response was associated with increased induction of T helper cell activity and IL-2 production as evidenced in mice immunodepressed by aging or by cyclophosphamide treatment. These observations suggest that melatonin may be successfully used in the therapy of immunodepressive conditions.

Adjuvants, Immunologic↗
PubMed1994

Murine recombinant interleukin-3 induces recovery of T and B cells in irradiated mice.

Injection of murine recombinant interleukin-3 (IL-3) into (C57BL/10 x DBA/2)F1 mice, sublethally irradiated with 300 cGy and killed 14 days later, induced in the thymus recovery of the cell number and mitotic responsiveness to concanavalin A (Con A), as well as an increase in number of double-negative CD4-CD8-, double-positive CD4+ CD8+, and single-positive CD4+CD8- and CD4-CD8+ cells. Also in the spleen, the cell count and mitotic responsiveness to Con A and lipopolysaccharide were increased to normal levels by IL-3 treatment. If the assays were performed 21 or 28 days after irradiation, IL-3 treatment was able to restore thymus and spleen cell counts as well as T- and B-cell mitotic responsiveness, even when mice were exposed to 400 or 500 cGy, respectively. These results altogether indicate that IL-3 induces differentiation and growth of thymocytes and recovery of T- and B-cell functions in mice exposed to sublethal irradiation.

Animals↗
PubMed1994

Ageing and genetic control of immune responsiveness.

Ageing is associated with a progressive decline of immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focussed on the mechanisms of the immunologic features of ageing. Alterations in cellular components of the immune system rather than in the extracellular milieu seem to account for most of the variations of immune competence in ageing.

Aging↗
PubMed1994

Genetics of chemical carcinogenesis--II. Papilloma induction and malignant conversion in susceptible (Car-s) and resistant (Car-R) lines of mice produced by bidirectional selective breeding and in their (Car-S X Car-R) F1 hybrids.

Susceptible (Car-S) and resistant (Car-R) lines of mice separated by 10 consecutive generations of bidirectional selective breeding present a very large difference in responsiveness to two-stage skin carcinogenesis. Car-S mice initiated with 0.5 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA) and promoted with 0.25 micrograms 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 77 days showed a papilloma incidence of 88% and a tumour multiplicity of 3.2 +/- 0.4 (mean +/- SE), with a tumour induction rate of 0.415. Car-R mice initiated with larger DMBA and TPA doses (50 micrograms and 20 micrograms respectively) and promoted for 111 days gave a comparable papilloma response: incidence 65%, tumour multiplicity 3.2 +/- 0.6 and tumour induction rate 0.288. The difference in papilloma response between the two lines is due to the interaction of genetic and environmental factors. In order to overcome the genetic effect with environmental factors and induce in Car-R a papilloma response comparable to that of Car-S, the DMBA dose had to be increased up to 100 times, that of TPA 40 times and the promotion time augmented by 44%. Papilloma to carcinoma conversion 112 days after the end of promotion depends on the DMBA and TPA doses applied. The number of carcinomas induced in Car-S mice and in (Car-S X Car-R) F1 hybrids was larger than that induced in Car-R mice, but the ratio of carcinoma conversion was lower, therefore a larger proportion of the small number of papillomas induced in the Car-R mice progressed to malignancy. The dominance effect measured in (Car-S X Car-R) F1 hybrids demonstrated that the susceptibility to papilloma induction was an incomplete dominant character (d/a = 0.38), whereas for carcinoma conversion the resistance was incompletely dominant (d/a = -0.49).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Hypertension and ischemic heart disease. Role of dipyridamole echocardiography test.

The aim of this study is to try to evaluate the relationship between arterial hypertension and ischemic heart disease (IHD) in the light of the physiopathologic response pattern to the dipyridamole echocardiography test (DET) in hypertensive patients, in pharmacologic washout, without any electrocardiographic ST segment depression during exercise tests or at rest. Sixty patients affected by mild to moderate asymptomatic essential arterial hypertension were studied: the subjects had a sitting diastolic blood pressure > or = 95 < or = 114 mmHg; there were 38 men and 22 women with a mean age of 49.8 +/- 7.6 years (range twenty-nine to sixty-eight). All patients had undergone high-dose DET (0.84 mg/kg in ten minutes). No patients developed side effects or asynergy in cardiac contractility during the test. In the absence of any significant coronary artery obstruction assessed angiographically, 18 patients (30%) showed ST segment depression > 1.0 mV during DET, sometimes with the presence of ventricular and/or supraventricular extrasystoles. In this group of patients the left ventricular mass index (LVMI) and duration of hypertension (in months) were higher as compared with those of the other 42 patients (respectively: 160.2 +/- 5.1 vs 129.2 +/- 9.2 g/m2, P < 0.02; and 30 +/- 4.8 vs 9 +/- 5.4 months, P < 0.007). In conclusion it is reasonable to speculate from these data that the ischemic-like" dipyridamole-induced ST segment depression, like that shown by patients affected by Syndrome X, might involve a worse prognosis in hypertensive patients. This may be because of increased coronary resistance due to structural modification or anatomic background.

Adult↗
PubMed1993

Effect of recombinant IL-3 on lymphocyte populations in irradiated mice.

Administration of murine recombinant interleukin 3 (IL-3) to sublethally irradiated mice induced in the thymus recovery of the cell count and mitotic responsiveness to Con A, as well as a decrease in CD4-CD8- cells concomitant with an increase in single positive cells. Also in the spleen, the cell count and mitotic responsiveness to Con A and lipopolysaccharide (LPS) were recovered by IL-3 treatment. These findings show that IL-3 induces differentiation and growth of thymocytes and recovery of T and B cell functions in sublethally irradiated mice.

Animals↗
PubMed1993

Melatonin increases antigen presentation and amplifies specific and non specific signals for T-cell proliferation.

Our preceding results have shown that melatonin administration to normal and immunodepressed mice increases significantly the antibody response. We also found that melatonin is able to restore the impaired T-helper cell activity in immunodepressed mice. The present study shows that melatonin enhances antigen presentation by splenic macrophages to T-cells. This effect is concomitant with an increase in the expression of MHC class II molecules and production of IL-1 and TNF-alpha. Considering the role of antigen presentation and cytokine production in the initiation of the immune response, the present findings provide evidence for relevant mechanisms that may account for the regulatory role of the pineal gland in immunoregulation.

Animals↗
PubMed1992

Effect of in vivo hyperthermia on thymocyte maturation and selection.

Two-month-old male mice were exposed to whole-body hyperthermic treatment in a circulating water bath. After 1 h exposure to 41 degrees C, mice were kept at room temperature for 24, 48, 72, and 96 h before thymus examination. The total thymocyte number progressively decreased after 24 and 48 h, reached a minimum value at 72 h, and returned to almost normal value after 96 h. Similar changes occurred in the CD4+CD8+ cell subset. Conversely, the percentage of CD4-CD8- cells rose to a maximum at 48 h and then declined to normal value at 96 h. The percentage of CD4-CD8+ and CD4+CD8- cell subsets increased to a maximum at 48 h and then declined to normal value at 96 h. These variations in single positive cell subsets correlated well with similar changes in the thymocyte mitotic response to concanavalin A. The observed effects on thymocytes were heat dose dependent, and suggest that hyperthermia induces the development of the most primitive thymocytes and positively selects mature T cells with high mitotic responsiveness. It is proposed that heat shock proteins might be involved in the hyperthermia-induced alterations of thymocyte maturation and selection.

Animals↗
PubMed1992

Effect of synthetic thymic humoral factor (THF-gamma 2) on T cell activities in immunodeficient ageing mice.

Immunodeficient ageing (C57BL/10 x DBA/2)F1 mice were treated by a single injection of synthetic thymic hormones and 4 days later their thymus and spleen cells were assayed in vitro for T cell activities. A few nanograms of THF-gamma 2 were found to raise the frequency of mitogen-responsive T cells in thymus and spleen cell populations as well as the frequency of cytokine-producing splenic T cells, up to the levels observed in young mice. Moreover, injection of THF-gamma 2 was found to restore T cell growth factor (TCGF) production by mitogen-stimulated spleen cells. Also, the helper activity of spleen cells was enhanced by this treatment and increased with increasing the THF-gamma 2 dose over a wide range. Similarly, the effects of thymopentin and thymosin-alpha 1 on T helper cell activity increased with increasing the injected dose, but the efficiencies of THF-gamma 2 and thymopentin were, respectively, 400-fold and eight-fold greater than that of thymosin-alpha 1.

Aging↗
PubMed1991

Radiation protection and restoration by the synthetic 163-171 nonapeptide of human interleukin 1 beta.

We have previously reported that the synthetic nonapeptide VQGEESNDK, position 163-171 of human interleukin 1 (IL-1 beta), when injected in immunodepressed mice, shows immunorestorative activity similar to that of the whole protein, but with no IL-1-like inflammatory effects [Frasca et al., J. Immunol. 141, 2651-2655 (1988)]. In the present study we have compared the protective and restorative activities of the nonapeptide and human recombinant (hur) IL-1 beta on the survival of lethally irradiated mice. When mice were given a single injection of different doses of the nonapeptide or hurIL-1 beta 20 h before total-body irradiation, both molecules increased the percentage survival of mice exposed to 750 or 850 cGy, but not to 950 cGy. The nonapeptide, however, is less effective than hurIL-1 beta and displays a different dose-response relationship, suggesting that the two molecules act through different radioprotective pathways. When mice were injected with the nonapeptide or hurIL-1 beta immediately after exposure to 850 cGy, the percentage survival was also increased but restoration was lower than protection in both cases. The nonapeptide was also less effective than hurIL-1 beta in restoration, but the two molecules displayed a comparable dose-response relationship as if they shared similar mechanisms. These findings indicate that the 163-171 nonapeptide is able to protect from lethal radiation injury and to restore viability. The nonapeptide appears less effective than hurIL-1 beta but does not exhibit the IL-1-like side effects of the whole molecule.

Adjuvants, Immunologic↗
PubMed1990

Genetics of chemical carcinogenesis. 1. Bidirectional selective breeding of susceptible and resistant lines of mice to two-stage skin carcinogenesis.

Six generations of a bidirectional selective breeding model for producing lines of mice susceptible (Car-S) and resistant (Car-R) to two-stage skin carcinogenesis are described. Initiation was with 9,10-dimethyl-1,2-benzanthracene (DMBA single application), and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA twice weekly). The selective breeding was initiated with a highly genetically polymorph foundation population, produced by the intercrossing of eight inbred mouse strains. The Car-S line was produced by assortative mating of the mice presenting the largest number of tumors induced by low DMBA and TPA doses, the Car-R line by mating tumorless mice or mice showing the smallest number of tumors induced by large DMBA and TPA doses. The character investigated was expressed as per cent tumor incidence and as tumor multiplicity per mouse. The mean heritability of the susceptibility character for the two first generations was 0.84 for tumor incidence and 1.3 for tumor multiplicity; these values decreased to 0.53 and 0.44 respectively for the two consecutive generations. The heritability of the resistance character maintained a constant value of 0.29 +/- 0.04 for tumor incidence, and 0.53 +/- 0.08 for tumor multiplicity. The progressive response to selection indicates that the characters investigated are subject to polygenic regulation, even though some genes may have a major effect on the susceptibility character. The interline separation in F5, challenged with the same initiation and promotion schedule, is very large. In the Car-S line, tumor incidence was 82.5% and tumor multiplicity 4.9/mouse on promotion day 49, whereas the corresponding values for the Car-R line were 4.5% and 0.1/mouse on promotion day 81.

9,10-Dimethyl-1,2-benzanthracene↗