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Biomedical subjects

A Lacroix

Publications and source records attributed to A Lacroix.

At least 127 records · Page 7Linked to original sources
PubMed1983

Metabolism of [11-3H]retinyl acetate in liver tissues of vitamin A-sufficient, -deficient and retinoic acid-supplemented rats.

A study was conducted on the incorporation of [11-3H]retinyl acetate into various retinyl esters in liver tissues of rats either vitamin A-sufficient, vitamin A-deficient or vitamin A-deficient and maintained on retinoic acid. Further, the metabolism of [11-3H]retinyl acetate to polar metabolites in liver tissues of these three groups of animals was investigated. Retinol metabolites were analyzed by high-performance liquid chromatography. In vitamin A-sufficient rat liver, the incorporation of radioactivity into retinyl palmitate and stearate was observed at 0.25 h after the injection of the label. The label was further detected in retinyl laurate, myristate, palmitoleate, linoleate, pentadecanoate and heptadecanoate 3 h after the injection. The specific radioactivities (dpm/nmol) of all retinyl esters increased with time. However, the rate of increase in the specific radioactivity of retinyl laurate was found to be significantly higher (66-fold) than that of retinyl palmitate 24 h after the injection of the label. 7 days after the injection of the label, the specific radioactivity between different retinyl esters were found to be similar, indicating that newly dosed labelled vitamin A had now mixed uniformly with the endogenous pool of vitamin A in the liver. The esterification of labelled retinol was not detected in liver tissues of vitamin A-deficient or retinoic acid-supplemented rats at any of the time point studied. Among the polar metabolites analyzed, the formation of [3H]retinoic acid from [3H]retinyl acetate was found only in vitamin A-deficient rat liver 24 h after the injection of the label. A new polar metabolite of retinol (RM) was detected in liver of the three groups of animals. The formation of 3H-labelled metabolite RM from [3H]retinyl acetate was not detected until 7 days after the injection of the label in the vitamin A-sufficient rat liver, suggesting that metabolite RM could be derived from a more stable pool of vitamin A.

Animals↗
PubMed1983

Effect of 2-alkanols on the separation of geometric isomers of retinol in non-aqueous high-performance liquid chromatography.

The effects of 2-alkanols as mobile phase modifiers on the resolution of 11-cis-, 13-cis-, 9-cis- and all-trans-retinol in high-performance liquid chromatography were studied. Partisil-10-ODS and Zorbax CN columns were used in series. The retentions of 9-cis-and all-trans-retinol were significantly influenced by the presence of long-chain 2-alkanols in the mobile phase. Baseline separation of 9-cis-and all-trans-retinol was achieved when 1% 2-heptanol in hexane was used as the eluent. On the other hand, the separation of 11-cis-from 13-cis-retinol required 5% dioxane in hexane. The method is applicable to the separation of retinol isomers present in biological samples. Analysis of normal rat liver lipids showed the presence of a small amount of 13-cis-retinol in addition to all-trans-retinol.

Animals↗
PubMed1983

Separation and estimation of retinyl fatty acyl esters in tissues of normal rat by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatography system for the complete separation of naturally occurring retinyl fatty acyl esters (RFAE) is described. The sensitivity of the method allows the detection of as little as 40 pmol of the various RFAE. The procedure was applied to the separation and estimation of endogenous RFAE present in tissues of normal rats; in addition, the incorporation of [3H]retinyl acetate into RFAE was also investigated. Retinyl palmitate is the major fatty acyl ester (79%) present endogenously in various tissues. However, eight other RFAE were also present in some tissues. At 24 hours after the injection of the label, radioactivity present in retinol and its metabolites was recovered mainly in liver tissue followed by kidneys, adrenals, lungs, intestine, trachea, testis, blood, heart and spleen. However, it was found that, in liver tissue, the specific radioactivity (dpm/nmol) of several RFAE was greater than that of retinyl palmitate (retinyl laurate 66-fold, retinyl pentadecanoate 5-fold, retinyl palmitoleate 4-fold).

Animals↗
PubMed1983

Restoration of anchorage regulation in transformed cells by retinoic acid (RA) is independent of the presence of cytoplasmic RA-binding proteins.

In an attempt to analyse the cause-effect relationship between anchorage-independent growth (a property which correlates best with in vivo tumorigenicity) and a set of other common transformation-related properties, the effect of retinoic acid (RA) treatment on six unrelated transformed cell lines (including DNA tumor virus, retrovirus, and spontaneously transformed cells) were studied. The data show that the changes in morphology and cellular orientation in culture, loss of cell surface fibronectin, disruption of actin microfilaments, increased hexose uptake, loss of density-dependent growth, and decreased binding of EGF, properties which are often associated with oncogenic transformation of cells, are dissociable from one another and from anchorage-independent growth. RA appears to interfere with anchorage-independent growth of all the retrovirus and spontaneously transformed cell lines (responsive cells) that we examined; however, such treatment failed to inhibit anchorage-independent growth in both of the DNA tumor virus-transformed cell lines (non-responsive cells) that we used in the present study. The presence of RA-binding proteins in both responsive and non-responsive cells suggests that the mechanism of RA action for the inhibition of anchorage-independent growth in transformed cells may be independent of the presence of such cytoplasmic proteins. Finally, the present study clearly indicates that the use of RA treatment, like partial transformation mutants of oncogenic viruses, can be a novel approach in analysing the general mechanism by which transformed cells grow without anchorage.

Actins↗
PubMed1983

[Variations in the plasma concentration of prolactin, LH and FSH and in testicular activity during the first year of life in the roe deer (Capreolus capreolus L.)].

Plasma prolactin, LH, FSH, testosterone patterns, and spermatogenic activity were determined during the first year of life in roe deer. A high gonadotrophic activity was observed a few months after birth, in autumn, along with an increase of testis volume and spermatogenic activity. Some spermatozoa could be seen in seminiferous tubules in December. A second increase of pituitary gonadotrophic activity appears in early spring when testicular volumes comparable to the adult are achieved. The first period of gonadotrophic activity coincides with the autumnal decrease in photoperiod, whereas the second coincides with the progressive increase in day length. It is suggested that the precocious LH and FSH release induces the first pubertal testicular activity.

Animals↗
PubMed1982

Phase II trial of 13-cis-retinoic acid in metastatic breast cancer.

Studies have suggested that both natural and synthetic retinoids have extensive chemopreventive activity against a variety of carcinogens in vivo and in vitro. We have previously shown that growth of human breast cancer cells can be inhibited by retinoids, and retinoic acid-binding proteins have been demonstrated in these cell lines and tumor biopsies. We studied the activity of 13-cis-retinoic acid in the treatment of 18 patients with advanced breast cancer refractory to standard cytotoxic and/or endocrine therapy. Patients began on 0.5 mg/kg and escalated to 8 mg/kg over a one-month period unless toxicity (dry skin, dry mucosa, cheilitis, conjunctivitis) forced dose reduction. All these toxicities responded promptly to dose reduction. Four patients exhibited drug related hypercalcemia, 2 complained of severe earache and several had nausea, vomiting and abdominal cramping. There were no objective responses as defined by standard criteria. One patient with thrombocytopenia secondary to documented marrow involvement demonstrated a recovery of platelet count from 9000 to 110,000. 13-cis-Retinoic acid is not of apparent value in women with heavily pretreated breast cancer.

Breast Neoplasms↗
PubMed1981

The pituitary-thyroid axis after hemithyroidectomy in euthyroid man.

The pathogenesis of euthyroid goiter is assumed to be TSH dependent, but most studies have not demonstrated elevation of serum TSH. To elucidate the early events involved in thyroid growth, we studied thyroid function in eight euthyroid patients subjected to hemithyroidectomy for solitary cold nodules preoperatively and 2, 15, 60, and 90 days and 36 months, postoperatively. Although within the euthyroid range, serum T4 decreased at 30 days and thereafter up to 90 days (P less than 0.01). Basal serum TSH rose significantly by the 30th day and remained elevated for the entire 90-day period (P less than 0.001). The serum TSH response to TRH was exaggerated from days 15-90 (P less than 0.001). Thirty-six months postoperatively, all parameters of thyroid function were similar to control values, with the exception of one patient who showed an exaggerated response of serum TSH to TRH. We conclude that 1) the dynamic phase of recuperation post hemithyroidectomy is TSH dependent, 2) the serum TSH increase occurs within normal limits and is a temporary event, and 3) 3 yr postoperatively, a new steady state is achieved with normal parameters of thyroid function. Thus, we believe that TSH plays a dominant role in the genesis of goiter.

Adult↗
PubMed1980

Binding of retinoids to human breast cancer cell lines and their effects on cell growth.

Vitamin A and its analogues (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, we examined the model system of human breast cancer cell lines in long-term tissue culture for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 muM retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [(3)H]retinoic acid and [(3)H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [(3)H]retinoic acid binding was present, but no binding of [(3)H]retinol was detectable. This study reveals that retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.

Breast Neoplasms↗