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Biomedical subjects

A Maggi

Publications and source records attributed to A Maggi.

At least 91 records · Page 5Linked to original sources
PubMed1992

Nucleotide sequence of estrogen receptor cDNA from Sprague-Dawley rat.

The cDNA of the Sprague-Dawley rat estrogen receptor was sequenced. With respect to the published Wistar rat estrogen receptor sequence, a single amino acid difference (tryptophan instead of asparagine) was found in the hormone binding site. Since tryptophan was found at the same position in chicken, human and mouse estrogen receptors, it is proposed that the Wistar rat could represent an interesting natural mutant for estrogen receptor studies.

Amino Acid Sequence↗
PubMed1992

Induction of mutations in V79-4 mammalian cells under hypoxic and aerobic conditions by the cytotoxic 2-nitroimidazole-aziridines, RSU-1069 and RSU-1131. The influence of cellular glutathione.

Incubation of the 2-nitroimidazole-aziridine, RSU-1069 [1-(2-nitro-1-imidazolyl)-3-(1-aziridinyl)-2-propanol], and its monomethylaziridine analogue, RSU-1131 [1-(2-nitro-1-imidazolyl)-3-(1-(2-methylaziridinyl))-2-propanol], with V79-4 mammalian cells for 2 hr under aerobic or hypoxic conditions induces mutations as measured at the hypoxanthine phosphoribosyl transferase locus. The ability of these agents to induce mutations is increased by a factor of 12-14 under hypoxic conditions. The increased cytotoxicity of these agents under hypoxic conditions was confirmed following a 2 hr incubation period. Decreasing the glutathione (GSH) content of the cells with buthionine-(S,R)-sulphoximine to < 1% of the control generally results in an increase in the cytotoxicity and mutagenicity of these agents under both aerobic and hypoxic conditions. Since these agents do not modify the cellular GSH levels, it is inferred that the thiols partially detoxify through removal of a reactive metabolite of the agents, under hypoxic conditions, or removal of known DNA adducts, and not through their interaction with the agents themselves. Under aerobic conditions, the formation of mutations is consistent with the established monofunctional action of these agents whereas under hypoxic conditions the bifunctional action predominates for mutation induction, based upon the large differential aerobic:hypoxic effect. From a comparison of the number of mutations per lethal event, the effect of thiol depletion is more pronounced for cytotoxicity than for mutation induction by these agents. In summary, these agents are considered to be weak mutagens towards V79-4 cells under aerobic conditions when compared with other DNA alkylating agents, although they are more potent under anoxic conditions.

Animals↗
PubMed1992

Determinants of non-attendance to mammographic screening. Analysis of a population sample of the screening program in the District of Florence.

The characteristics associated with non-attendance to mammographic breast cancer screening were studied by interviewing a random sample (213 attenders, 121 non-attenders in the 1989 screening) of residents in one of the municipalities of the Florence District Program, where screening has been ongoing since 1970. The overall attendance rate was 60%, and it was dependent on age (40-49 years, 66.5%; 50-59 years, 62.5%; 60-70 years, 55.5%), whereas a significant association with socio-economic status, educational level and health-behavior reported in other programs was not confirmed in the study. This finding suggests that determinants of non-attendance may vary and should be evaluated in each local setting. The belief that screening is useless, fear of cancer being detected, postponement and laziness were the most common motivations of refusal stated by non-attenders, and such a negative attitude towards screening was rather strong since most non-attenders stated they would not like to be informed or stimulated to attend future screenings. Rapid improvement of attendance rates in such a context might be achieved only by putting special pressure on women aimed to change their negative attitude towards screening and their opinion about the benefits of early breast cancer detection. This might be regarded as unacceptable and however would involve high costs and a major organization effort.

Age Factors↗
PubMed1992

Estrogen induction of cytochrome c oxidase subunit III in rat hippocampus.

Differential screening of a cDNA library prepared from mRNA of the hippocampus of estrogen-stimulated ovariectomized female rats led to the identification of a single estrogen-induced clone. Analysis of the sequence identified this cDNA as the gene coding for subunit III of the enzyme cytochrome c oxidase. Cytochrome c oxidase subunit III mRNA levels significantly increased as early as 3 h following the administration of a single dose of hormone. This effect was visible in the hippocampus and in the hypothalamus, but not in the other brain areas examined. Because subunit III of the cytochrome c oxidase is of mitochondrial origin, the mechanism involved in the estrogenic effect is still unknown. The observation that the activity of cytochrome c oxidase can also be induced by estrogens in the hippocampus indicates that this induction may be secondary to the increased expression of the other subunits of cytochrome c oxidase or to the general increase of neuronal activity.

Amino Acid Sequence↗
PubMed1992

Estrogen receptor in rat brain: presence in the hippocampal formation.

A series of studies was done in order to fully characterize the estrogen receptor (ER) expressed in the hippocampus of adult female rat. The structural identity among the ER mRNAs expressed in the hippocampus, hypothalamus and uterus was established by polymerase chain reaction amplification of the ER cDNA. Subsequently, the ER of the hippocampus was proved to bind DNA and beta-estradiol with the same affinity as the hypothalamic receptor. Finally, it was demonstrated that systemic administration of beta-estradiol determines the nuclear increase of ER levels with a time course which appears to be almost superimposable in the hippocampus and hypothalamus. On the basis of the above-mentioned evidence, it is concluded that the ER expressed in the hippocampus is structurally and functionally indistinguishable from the receptor expressed in the other hormone target tissues.

Animals↗
PubMed1991

A rapid method for the quantitation of estrogen receptors in small amounts of tissue.

A rapid and highly reproducible protocol which permits the detection of quantities of estrogen receptor as low as 5 fmol/mg protein is described. The separation of free and receptor-bound hormone is achieved by specific immunoprecipitation of the hormone-receptor complex. This procedure can be performed without perturbing the equilibrium of the binding reaction.

Animals↗
PubMed1991

Relationships between cell killing, mutation induction and DNA damage in X-irradiated V79 cells: the influence of oxygen and DMSO.

The relationships between cell killing, mutation induction and DNA double (dsb) and single (ssb) strand breaks have been studied in V79 cells irradiated with X-rays under oxic and anoxic conditions in the presence and in the absence of dimethylsulphoxide (DMSO). Curvilinear relationships were found between all pairs of endpoints, except for dsb versus ssb. Statistical analysis of experimental data has shown that in the absence of DMSO there is evidence of good correlations between cell killing, mutation induction and dsb in oxic and anoxic conditions. However, when DMSO was present, no significant correlation was found. In the presence of oxygen DMSO always exerts a protective effect while in anoxia it is generally much less protective and induces a strong sensitization with respect to mutation induction. Possibly DMSO acts not only as a radical scavenger but also as an agent inducing chromatin relaxation and/or under anoxia, forming highly mutagenic short-term radicals. The present data suggest that lethal and mutational events are at least partially independent and not proportional to the initial number of DNA breaks. This may imply that either other kinds of lesions are involved in cell lethality and mutability, or dose-dependent repair mechanisms of dsb have to be considered.

Animals↗
PubMed1991

Hypothalamic-pituitary somatotropic function in prepubertal hypothyroid rats: effect of growth hormone replacement therapy.

The effect of thyroid hormone deficiency and growth hormone (GH) treatment on hypothalamic GH-releasing hormone (GHRH)/somatostatin (SS) concentrations, GHRH/SS mRNA levels, and plasma GH and somatomedin-C (IGF-I) concentrations were studied in 28- and 35-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Hypothyroid rats, at both 28 and 35 days of life, had decreased hypothalamic GHRH content and increased GHRH mRNA levels, unaltered SS content and SS mRNA levels, and reduced plasma GH and IGF-I concentrations. Treatment of hypothyroid rats with GH for 14 days completely restored hypothalamic GHRH content and reversed the increase in GHRH mRNA, but did not alter plasma IGF-I concentrations. These data indicate that, in hypothyroid rats, the changes in hypothalamic GHRH content and gene expression are due to the GH deficiency ensuing from the hypothyroid state. Failure of the GH treatment to increase plasma IGF-I indicates that the feedback regulation on GHRH neurons is operated by circulating GH and/or perhaps tissue but not plasma IGF-I concentrations. Presence of low plasma IGF-I concentrations would be directly related to thyroid hormone deficiency.

Analysis of Variance↗
PubMed1991

[The prognosis of the patient with heart failure: an analysis of the most significant clinical and instrumental parameters].

Despite the progress of the medical and surgical therapy of cardiac failure, the prognosis of this syndrome remains severe. We studied in a group of cardiac failure patients (n = 203; 18-74 years old) admitted in our division from 1982 to 1987 the most significant clinical and instrumental parameters of prognostic importance. The clinical parameters considered were: age, sex, heart rate, blood pressure, NYHA class, presence of mitral insufficiency, episodes of acute heart failure. The instrumental parameters were: presence of complete left bundle branch block (LBBB), atrial fibrillation, episodes of ventricular tachycardia, cardiothoracic index (C/T), end-diastolic and end-systolic diameters, ejection fraction (EF). Statistical analysis was performed in order to correlate single parameters with mortality. The total survival at 5 years was 50%, being higher in patients with coronary artery disease than in patients with primary dilated cardiomyopathy. The parameters worsening the prognosis were: mitral insufficiency, III-IV NYHA class, occurrence of repeated episodes of acute heart failure in the last year, complete LBBB, C/T greater than 0.55 and EF less than 20%. In conclusion, considering instrumental parameters high risk patients are detected with a precision of 80%.

Adolescent↗
PubMed1990

Regulation of progesterone receptor gene expression.

The levels of progesterone receptor (PR) mRNA, PR protein, and [3H]R5020 binding activity were measured in parallel experiments conducted on a T47D subline expressing the estrogen receptor. A significant increase of PR mRNA levels could be detected within 6 h of exposure of the cells to estradiol (10(-8) M). The changes in mRNA, however, did not lead to any variation of PR protein levels of [3H]R5020 binding activity. A parallel analysis of PR mRNA and [3H]R5020 binding was then performed in a series of tumor biopsies. In estrogen receptor-positive and PR-positive tissues a correlation among the two values was found. It is postulated that the above mentioned data could reflect the existence of a difference in the mechanisms controlling the numerous steps of the PR synthesis in the various hormone-responsive tissues. This variability could allow an organ-specific response to the cyclic changes of circulating hormone.

Blotting, Northern↗
PubMed1990

c-fos induction by estrogen in specific rat brain areas.

The present study was undertaken to determine whether estrogen modulates the expression of the c-fos gene in the CNS of rats. The analysis of the levels of c-fos mRNA was performed by slot blot assay. Administration of estradiol to ovariectomized rats determined a rapid and transient increase in the levels of c-fos mRNA in rat mid-brain and hippocampus, but not in the cerebellum (a brain area which does not express estrogen receptors). Such a change in the levels of c-fos mRNA was not observed after administration of alpha-estradiol or other steroid hormones. The presence of an estrogen responsive element-like sequence, revealed in the 5' flanking region of the murine c-fos gene, strengthens the hypothesis that c-fos gene transcription is directly enhanced by the interaction of the estrogen receptor complex with the promoter region of the proto-oncogene.

Animals↗
PubMed1990

Effects of progesterone on [35S] t-butylbicyclophosphorothionate binding in some forebrain areas of the female rat and its correlation to aggressive behavior.

The antiaggressive effects of progesterone (P) were evaluated in association with alterations in [35S] t-butylbicyclophosphorothionate (TBPS; chloride ion channel antagonist) binding in some forebrain sites of the female rat using in vitro quantitative autoradiography. The administration of 4 mg P was followed by a reduction in the frequency of different aggressive behaviors such as circling, nose-to-nose and fighting (mostly of the defensive nature) in ovariectomized (OVX) sexually mature rats, housed in pairs, during male-female encounters. Quantitative autoradiography data revealed that the same P dose, at the forebrain level, was responsible for low [35S] t-butylbicyclophosphorothionate binding levels in the medial preoptic area, lateral and basolateral amygdala nucleus and oriens-pyramidalis hippocampus CA1 layer, with even lower values being obtained following the in vitro addition of the potent P metabolite 5 alpha-pregnan-3 alpha-ol-20-one. These results suggests that the probable antiaggressive role of P during heterosexual encounters may be regulated by a local potent metabolite acting at the membrane site of the GABA complex.

Aggression↗
PubMed1990

Changes in the hypothalamic-pituitary somatotropic function of infant hypothyroid rats.

The effects of the perturbation of the pituitary-thyroid axis induced during development on the functional activity of the growth hormone (GH) regulatory neuronal systems, GH-releasing hormone (GHRH), and somatostatin (SS) were studied in 14- and 21-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Infant hypothyroid rats, both at 14 and 21 days of life, had elevated plasma thyroid-stimulating hormone levels and decreased pituitary and plasma GH levels. Simultaneous determination of hypothalamic GHRH/SS-like immunoreactivity (LI) and GHRH/SS mRNA levels did not reveal any difference in 14-day-old hypothyroid rats when compared with age-matched controls. In contrast, 21-day-old hypothyroid rats had decreased GHRH-LI content and a striking rise in GHRH mRNA levels, whereas SS-LI content and SS gene expression remained unaltered. These data indicate that in infant hypothyroid rats, changes in the functional activity of the GHRH neuronal system occur later than changes in GH secretion and are probably dependent on the GH deficiency. The functional activity of SS neurons was apparently unaltered in these hypothyroid rats, pointing to a lesser sensitivity of this system to the perturbation of the pituitary-thyroid axis.

Animals↗
PubMed1989

Differential modulation of [3H]flunitrazepam binding in female rat brain by sex steroid hormones.

Quantitative autoradiographic analysis revealed changes in [3H]flunitrazepam (a benzodiazepine agonist) binding in the anterior hypothalamus nucleus, the medial preoptic area and the cortico-medial amygdala nucleus following in vivo estradiol. The administration of 4 mg of progesterone, but not 1 mg, increased the binding of [3H]flunitrazepam in the basolateral amygdaloid nucleus and in the oriens-pyramidalis CA1 layer of the hippocampus. Exposure of brain sections in vitro to the potent, naturally occurring progesterone metabolite, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, induced GABA-dependent changes in flunitrazepam binding, similar to the changes induced by progesterone, thus suggesting that different steroid mechanisms are implicated in the control of flunitrazepam binding.

Animals↗
PubMed1989

Estrogen-induced proteins in rat hypothalamus.

The identification of estrogen-inducible genes in specific regions of the central nervous system (CNS) will give information about the mechanisms by which this steroid modulates nervous activity. Two-dimensional gel analysis of the proteins synthesized in vitro from mRNA isolated from control or estrogen-treated rats indicated that the levels of mRNA were increased in the estrogen-treated animals. The levels of mRNA were elevated only in those brain regions that express estrogen receptors.

Animals↗
PubMed1989

Hippocampus: a target for estrogen action in mammalian brain.

An analysis of the distribution of estrogen receptor (ER) via immunoenzymatic assay in the brain of ovariectomized rats reveals the presence of large amounts of ER-like immunoreactive material in the cytosol of the hippocampus: a brain area described to contain little estrogen-binding activity. The protein detected in the hippocampus by the specific antibody is indistinguishable from the rat ER in its response to hormonal treatments and in its electrophoretic mobility. The presence of elevated amounts of ER in such an important part of the limbic system creates new possibilities for interpreting the role played by this sex hormone in the central nervous system of rat.

Animals↗
PubMed1989

The role of thiols in lethal and mutational radiation damage.

Over the last few decades, free radicals have been increasingly implicated in biological processes including radiation effects, ageing, carcinogenesis, initiation and progression of various diseases, toxicity of chemicals and drugs. In this field Radiation Biology has played an important role in the development of both technical and cultural background, because it was very soon recognized the radical nature of processes following exposure to ionizing radiation. Several studies have pointed out the importance of both radicals, reacting with cellular targets, and endogenous thiols, mainly represented by glutathione, in controlling radiation responses of living cells. Experimental supports for such a role mainly rest on observations made on cell lines depleted of glutathione content because of a genetic defect or as result of a pharmacological manipulation. We present a study on the influence of endogenous and exogenous thiols on the correlation between lethal and mutational damage in mammalian cells. Survival (S) and induction of HPRT- mutation (M) were measured in cells irradiated with X-rays either after treatment with BSO or in the presence of MEA or GSH. In control experiments log of S is linearly correlated to M. Incubation with 1 mM BSO reduces cellular GSH content and produces an increase in radiosensitivity with regard to both lethal and mutagenic effects. In the presence of MEA a concentration dependent radioprotective effect can be observed on both end-points. GSH added to cells immediately or 90 min before irradiation only displays a slight protective effect on lethality. The yield of mutant cells is not significantly affected when GSH is added immediately before irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗