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Biomedical subjects

M Bailo

Publications and source records attributed to M Bailo.

12 recordsLinked to original sources

Target-specific action of organochlorine compounds in reproductive and nonreproductive tissues of estrogen-reporter male mice.

Organochlorines are lipophylic molecules that accumulate in the fat where they remain for years. During weight loss, they are mobilized and their concentration increases in blood. The present work tests, in transgenic estrogen-reporter mice (ERE-tK-LUC), whether this increase is sufficient to modulate the estrogen receptors (ERs) in the whole body. Three weak estrogens were studied: p,p'DDT [1,1,1-trichloro2,2-bis(p-chlorophenyl) ethane], p,p'DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], and betaBHC [beta-benzene-hexachloride]. Dose-dependent analysis of reporter expression (luciferase) were performed in tissues of acutely treated mice. A body map of ER activation was obtained. All these chemicals modulated the reporter, although with a different efficiency and depending upon the tissue analyzed. Induction was confirmed in the liver by determining the expression of the endogenous progesterone receptor (PR) gene, at the dose and time point at which the luciferase gene was maximally induced. After experimental accumulation in the fat tissue, followed by a 48-h period of fasting, we tested whether these compounds could be mobilized to reach sufficient levels to activate the ERs in selected reproductive and nonreproductive tissues (testicle, prostate, liver, and lung). This experimental setting produced results that were different than those obtained following acute treatments. In loaded mice, fasting induced betaBHC mobilization resulted in strong ER activation in the liver and the lung, which was blocked by ICI-182780. p,p'DDT mobilization had no effect in these tissues, but it acted efficiently in the prostate and testis. betaBHC inhibited the ERE-mediated reporter in the testicle and induced the reporter in the prostate. In this tissue, betaBHC action was not inhibited by the anti-estrogen ICI-182780. During fasting, betaBHC, p,p'DDT, and metabolite p,p'DDE increased in blood concentration, from 2.25 +/- 0.25, 0.51 +/- 0.09, and 0.38 +/- 0.06 microg/ml to 8.24 +/- 0.95, 4.52 +/- 0.68, and 5.06 +/- 0.57 microg/ml, respectively. The effect produced by these organochlorines in the liver correlates with the modulation of the ERalpha protein. We conclude that these organochlorines modulate differently the expression of estrogen-regulated genes in male mice. Their effect is tissue- and compound-specific and is dependent on the energetic balance.

Adipose Tissue↗

Effect of the single major proteic fractions of the liver perchloric extract UK101 on the development of oral tumours in Syrian hamsters.

Squamous cell carcinoma of the oral cavity continues to be a major clinical problem, with about 100,000 new deaths each year worldwide. There is therefore a need to search for new tools to aid oral cancer treatment. We tested the inhibitory activity on chemical carcinogenesis of the three principal protein fractions of about 50, 14, and 8.5 kDa of the mixture UK101 derived from goat liver. These are composed principally of a glycoprotein rich in mannose residues, a protein with analogy to the heat shock protein family, and ubiquitin, respectively. The animal model employed was dimethylbenzanthracene-induced hamster cheek pouch carcinoma. Number of tumours per animal, tumour mass per animal, and proliferating cell nuclear antigen (PCNA) in non-tumour mucosa were quantified: the 14-kDa fraction was the most active; this was also confirmed by testing its corresponding recombinant material. The 50-kDa fraction was inactive, while the ubiquitin showed only low inhibitory activity. It is possible that the technique described and the results obtained could lead to an interesting clinical approach to the treatment of oral cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Light and electron microscopic studies on the localization of hyaluronic acid in developing rat cerebellum.

The hyaluronic acid-binding region was prepared by trypsin digestion of chondroitin sulfate proteoglycan aggregate from the Swarm rat chondrosarcoma, and biotinylated in the presence of hyaluronic acid and link protein. After isolation by gel filtration and HPLC in 4 M guanidine HCl, the biotinylated hyaluronic acid-binding region was used, in conjunction with avidin-peroxidase, as a specific probe for the light and electron microscopic localization of hyaluronic acid in developing and mature rat cerebellum. At 1 w postnatal, there is strong staining of extracellular hyaluronic acid in the presumptive white matter, in the internal granule cell layer, and as a dense band at the base of the molecular layer, surrounding the parallel fibers. This staining moves progressively towards the pial surface during the second postnatal week, and extracellular staining remains predominant through postnatal week three. In adult brain, there is no significant extracellular staining of hyaluronic acid, which is most apparent in the granule cell cytoplasm, and intra-axonally in parallel fibers and some myelinated axons. The white matter is also unstained in adult brain, and no staining was seen in Purkinje cell bodies or dendrites at any age. The localization of hyaluronic acid and its developmental changes are very similar to that previously found in immunocytochemical studies of the chondroitin sulfate proteoglycan in nervous tissue (Aquino, D. A., R. U. Margolis, and R. K. Margolis. 1984. J. Cell Biol. 99:1117-1129; Aquino, D. A., R. U. Margolis, and R. K. Margolis. J. Cell Biol. 99:1130-1139), and to recent results from studies using monoclonal antibodies to the hyaluronic acid-binding region and link protein. The presence of brain hyaluronic acid in the form of aggregates with chondroitin sulfate proteoglycans would be consistent with their similar localizations and coordinate developmental changes.

Aggrecans↗

Serotonin and 5-hydroxyindoleacetic acid levels in discrete hypothalamic areas of the rat brain: relation to circulating corticosterone.

We examined the influence of adrenalectomy (ADX), and chronic corticosterone (CORT) replacement, on serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in discrete hypothalamic areas of the rat brain. A significant decrease in 5-HT (-25%) and 5-HIAA (-28%) content was observed in the paraventricular nucleus (PVN) 7 days following ADX. A similar decrease in 5-HT levels (-27%) was observed in the preoptic area (POM) following ADX. In contrast, 5-HT and 5-HIAA levels in the supraoptic nucleus (SON) were significantly elevated by 82% and 54%, respectively. Replacement therapy with subcutaneous CORT implants (200 mg) was effective in preventing these effects of ADX in some cases. These findings suggest that the pituitary-adrenal endocrine system may influence various physiological and behavioral functions via its action on serotonergic neurons within specific hypothalamic sites.

Adrenalectomy↗

Changes in systemic and pulmonary vascular reactivity in hypertension following nifedipine and verapamil.

Excessive vascular tone and overresponsiveness to adrenergic stimuli characterize the hemodynamics of the greater and the lesser circulation in hypertension. We tested whether calcium entry blockade with verapamil (11 cases) or nifedipine (11 cases) may improve the vascular regulation in high blood pressure. Mental arithmetic and cold were used as adrenergic activators. The former stimulus produced obvious elevation of epinephrine plasma concentration, increase of cardiac output (CO), slight systemic vasodilatation, pulmonary vasoconstriction, and rise of blood pressure in both circuits. After calcium antagonists, the epinephrine reaction to the arithmetic test was significantly attenuated, variations in CO and systemic blood pressure were unchanged, pulmonary vasoconstriction was abolished, and the pressure rise in the lesser circuit was halved. The cold pressor test increased norepinephrine plasma concentration (NE pc), systemic and pulmonary blood pressure, and vascular resistance and did not alter CO. The attained NE pc during cold was unvaried after verapamil and significantly enhanced after nifedipine; pressure and resistance responses of the two circuits were almost unchanged after the former, whereas systemic and pulmonary vascular resistance rises were importantly attenuated after the latter compound, resulting in much lower pressure reactivity. A modulation of the sympathoadrenal reaction, per se, can explain changes in the systemic and in the pulmonary vasomotion with calcium blockade during arithmetic. It would seem that after verapamil the sympathetic system was still activated during cold to such an extent as to maintain the same vasoconstrictor potency. NE pc suggests that the sympathetic discharge was not reduced by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Two CEA cross-reacting antigens: differences in absorbing the same anti-CEA serum.

A factor that cross reacts with the carcinoembryonic antigen (CEA), which we call P factor, was isolated from normal human plasma. To demonstrate the difference between this P factor and the nonspecific cross-reacting antigen (NCA), the same anti-CEA serum was absorbed in an identical manner with both the antigens. Absorption was checked by immunohistochemistry by the beta-galactosidase procedure on sections of colonic adenocarcinoma and normal colonic mucosa. The unabsorbed antiserum recognizes both tissues; after absorption with NCA the staining becomes paler on both tissues, but maintains color on the normal colonic mucosa and granulocytes. Only absorption with the P factor will give an unstained field of normal colonic mucosa, thus revealing the tumor structure. Data obtained by us suggest that the NCA (tissue extract) is an antigen that is not suitable to the absorption of anti-CEA serum for immunocytochemistry techniques, whereas the P factor (plasma extract) appears to be utilizable with good results.

Absorption↗

Anti-carcinoembryonic antigen sera acquiring higher tumor specificity by absorption with a plasma factor.

A factor reacting with antisera against carcinoembryonic antigen (CEA) was isolated from healthy donors' plasma. Ten different antiCEA sera were absorbed with this plasma factor (P-factor): the antiCEA activity was mostly, or completely, removed in 8 sera. Only 2 of these absorbed sera (here defined as type A) still presented a high CEA binding activity by radioimmunoassay and, on tissue sections, selectively stained most of the colonic adenocarcinomas and areas of severe dysplasia in neoplastic adenomas. Contrary to the behaviour of the antisera against the P-factor, of the unabsorbed antiCEA sera, of a commercially available antiserum and of a monoclonal antibody, the P-absorbed type A antiCEA sera appeared unreactive with normal colonic mucosa and granulocytes. Absorption with the P-factor allows us to obtain antiCEA sera with higher tumor specificity.

Adenocarcinoma↗

[Experience in educational information for diabetics and their families].

Experience in health education programmes for diabetics is reported. Such education is considered a priority since it is an essential aspect of treatment. Only education can prevent acute attacks and reduce the consequences of later diabetic complications. Elsewhere education programmes have been organised by Anti-diabetic Centres or group meetings. The present health education programme however was conducted at the Day Hospital. The programme was " personalized " to allow for personal control of the disease taking place in the patients' environment and attended not only by diabetics, but also by their families, subjects at risk and non-diabetics interested in this problem.

Blood Glucose↗

BCA (breast cancer antigens): different purification extraction methods.

Various types of extraction were tested to increase the immunological yield of BCA, a CEA-like primary breast cancer associated carcinoma antigen. To allow a comparison, the different extraction techniques were applied to only one breast tumour. The comparison of the various systems was based on two parameters: protein yield and immunological activity, assayed in a RIA 125I CEA-anti CEA system. The following extraction methods were described and compared in this paper: 3M KCl; 1N HClO4; neutral pH extraction (PBS) in the absence and presence of various detergents (anionic, neutral and cationic), basic pH extraction (1N NaOH) and acid pH extraction (1.5M acetic acid) in the presence of urea and various detergents. The more significant systems were applied also to the extraction of CEA, from colonic adenocarcinoma liver metastases. The best results for both the antigens studied were obtained by using neutral detergents (1% NP 40) at neutral pH.

Antigens, Neoplasm↗

Extraction and partial purification of a CEA-like BCA from a pool of pre-selected breast carcinomas.

By exploiting the cross-reaction among the antigens associated with a pool of breast carcinomas, preselected according to their antigenic content, a CEA-like BCA, with a specific activity of 1400 U/micrograms has been extracted, by means of 3M KCl, and partially purified by means of ConA Sepharose affinity chromatography and bioabsorption, employing, for the latter, a cross-reacting antiserum (anti CEA). The subsequent labelling, after Sephadex G-200 gel filtration, points out an immunological activity at the apex of the first peak versus anti CBC (or C.BCA) and anti CEA.

Absorption↗