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Biomedical subjects

A Marti

Publications and source records attributed to A Marti.

At least 91 records · Page 5Linked to original sources
PubMed1997

Milk accumulation triggers apoptosis of mammary epithelial cells.

Continuous milk production is a consequence of a complex interplay of lactogenic hormones and it depends on the suckling stimulus during lactation. Involution is associated with a massive engorgement of the gland with milk followed by apoptosis of secretory epithelial cells and a restructing of the gland. Sealing of a single gland during lactation is sufficient to induce an initial engorgement and a subsequent collapse of alveolar structures and massive epithelial cell death while the other glands of the same animal remain morphologically and functionally in a lactating state. Many markers of involution such as sulfated glycoprotein-2, protein kinase A, transcription factor AP-1 and most notably stromelysin are induced in sealed glands. These findings suggest a cell death pathway which is independent of the systemic levels of lactogenic hormones but which is triggered by an accumulation of apoptosis-inducing factors in the milk, in the lobulo-alveolar structures or by a physical distortion of secretory epithelial cells generated by the engorgement.

Animals↗
PubMed1996

Regulation of a physiological apoptosis: mouse mammary involution.

Continuous milk production during lactation is dependent on a complex interplay of lactogenic hormones and the suckling stimulus exerted by the young. Involution can be initiated in the mouse mammary gland at any stage of lactation by removing the pups; involution then remains reversible for about 30 to 36 h. Involution in the mouse mammary gland is characterized by a massive loss of secretory epithelial cells from programmed cell death. The nuclear activation of protein kinase A and transcription factor activator protein 1 precede the irreversible phase of involution that is characterized by internucleosomal DNA fragmentation. Activation of activator protein 1 and fragmentation of chromosomal DNA can be prevented by lactogenic hormone treatment in explant cultures derived from mammary tissue at lactation. The elevation in activator protein 1 coincides with the epithelial expression of sulfated glycoprotein 2, a potential target gene of activator protein 1. Programmed cell death in the mammary gland is associated with the expression of the growth arrest gene, gas-1, and the integrin-associated protein gene, IAP, which codes for a putative Ca2+ channel that is dependent on integrin. Their potential roles during involution are discussed.

Animals↗
PubMed1996

Lung-angiodysplasia and von Willebrand's disease in a family with Rendu-Osler disease. A case report.

A young woman suffering from sideropenic anemia, bleeding disorders related to von Willebrand's disease and pulmonary vascular telangiectasias presented at our observation. Laboratory findings, genetic and hemostatic studies revealed platelet aggregation defect while in her father and grandfather lung angiodysplastic lesions without platelet aggregation defect. The association between bleeding disorders and pulmonary angiodysplasia has rarely presented in literature and deficiency of von Willebrand factor might increase the risk of bleeding in patients with coexisting angiodysplastic disease.

Anemia, Iron-Deficiency↗
PubMed1995

Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland.

Milk production during lactation is a consequence of the suckling stimulus and the presence of glucocorticoids, prolactin, and insulin. After weaning the glucocorticoid hormone level drops, secretory mammary epithelial cells die by programmed cell death and the gland is prepared for a new pregnancy. We studied the role of steroid hormones and prolactin on the mammary gland structure, milk protein synthesis, and on programmed cell death. Slow-release plastic pellets containing individual hormones were implanted into a single mammary gland at lactation. At the same time the pups were removed and the consequences of the release of hormones were investigated histologically and biochemically. We found a local inhibition of involution in the vicinity of deoxycorticosterone- and progesterone-release pellets while prolactin-release pellets were ineffective. Dexamethasone, a very stable and potent glucocorticoid hormone analogue, inhibited involution and programmed cell death in all the mammary glands. It led to an accumulation of milk in the glands and was accompanied by an induction of protein kinase A, AP-1 DNA binding activity and elevated c-fos, junB, and junD mRNA levels. Several potential target genes of AP-1 such as stromelysin-1, c-jun, and SGP-2 that are induced during normal involution were strongly inhibited in dexamethasone-treated animals. Our results suggest that the cross-talk between steroid hormone receptors and AP-1 previously described in cells in culture leads to an impairment of AP-1 activity and to an inhibition of involution in the mammary gland implying that programmed cell death in the postlactational mammary gland depends on functional AP-1.

Animals↗
PubMed1995

Expression and activity of cell cycle regulators during proliferation and programmed cell death in the mammary gland.

In the mammary gland distinct phases of proliferation, differentiation and programmed cell death of epithelial cells occur at defined stages of development. Here we show that the expression and activity of cell cycle regulators during normal and preneoplastic proliferation and programmed cell death are remarkably similar. In all cases we found elevated levels of a protein kinase A activity and of transcription factor AP-1, cFos and JunD being the major components of the AP-1 DNA binding complex. A correlation between cFos and JunD expression and chromosomal DNA fragmentation during programmed cell death was observed. Several genes associated with G1, including cyclin D1, D2 and D3 and c-fos, c-jun, junB, JunD, c-myc and p53, are induced in proliferating and in apoptotic mouse mammary tissue. Whereas the expression of these genes correlated with active proliferation of epithelial cells in terminal end buds during puberty, very little proliferation or DNA synthesis, but, instead, extensive apoptosis of epithelial cells, was observed during involution. Our results suggest that a G1-like state is associated with programmed cell death of mammary epithelial cells in vivo and that apoptosis occurs without S-phase induction.

Journal Article↗
PubMed1994

Prostaglandin E2 accelerates enzymatic and morphological maturation of the small intestine in suckling rats.

The effect of prostaglandin E2 (PGE2) injection on the postnatal maturation of the 16-day-old rodent small intestine was studied. Previous studies have shown that 16,16-dimethyl PGE2 induced several morphological and biochemical parameters in the small intestine of 11-day-old rats. PGE2 was given subcutaneously daily at doses of 2 and 4 mg/kg body weight on postnatal days 11-15. After treatment there was a rise in the mean activities of sucrase, maltase, lactase and aminopeptidase. In rats receiving 4 mg/kg PGE2, sucrase activity was strongly stimulated (p < 0.001) in the proximal and the distal small bowel. In the duodenum, PGE2 treatment (4 mg/kg body weight) produced a significant increase in crypt depth (35%, p < 0.001), although villus height was not modified. Serum corticosterone levels were significantly increased in PGE2-treated rats. The results seem to indicate that PGE2 accelerates enzymatic and morphological intestinal maturation and this effect could be mediated by an increase in corticosterone.

Animals↗
PubMed1994

Effect of lindane on galactose and leucine transport in chicken enterocytes.

Lindane (gamma-hexachlorocyclohexane) influence on the in vitro intestinal transport of D-galactose and L-leucine has been studied in isolated chicken enterocytes. Animals were injected i.p. with 30 mg/kg b.w. of the pesticide over 7 days. Total uptake of D-galactose and L-leucine was significantly decreased by lindane action. There was no alteration in the non-mediated component, but the mediated transport was markedly inhibited in both cases. Furthermore, the exit of D-galactose across the basolateral membrane, as well as (Na(+)-K+)-ATPase activity, was significantly decreased in pesticide-treated chickens.

Animals↗
PubMed1994

Effect of misoprostol on the enzyme ontogeny of the rat intestine.

The effect of Misoprostol (an analog of PGE1) on the biochemical changes in the small intestine of suckling rats was studied. Misoprostol increases sucrase activities in the proximal and the distal small intestine. Jejunal aminopeptidase N activity is higher in Misoprostol-treated rats than in the control rats. This drug also modifies the relative weight of the small intestine and the mucosal ratio of DNA to RNA. Misoprostol effects appear to be mediated by corticosterone release.

Animals↗
PubMed1994

Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells.

At weaning the mammary gland undergoes a reductive remodelling process (involution) which is associated with the cessation of milk protein gene expression and programmed cell death of milk-producing epithelial cells. Elevated nuclear protein kinase A (PKA) activity was observed from one day post-lactation, paralleled by increased c-fos, junB, junD and to a lesser extent c-jun mRNA levels. AP-1 DNA binding activity was transiently induced and the AP-1 complex was shown to consist principally of cFos/JunD. Oct-1 DNA binding activity and Oct-1 protein were gradually lost from the gland over the first 4 days of involution, whereas Oct-1 mRNA levels remained unchanged. Comparing nuclear extracts from normal mammary glands with nuclear extracts from glands which had been cleared of all epithelial cells 3 weeks after birth, revealed that PKA activation, AP-1 induction and Oct-1 inactivation all are dependent on the presence of the epithelial compartment. The increased Fos/Jun expression and the inactivation of Oct-1 may be consequences of the increased PKA activity. A similar induction of AP-1 (cFos/JunD) was also observed in the involuting rat ventral prostate pointing to a possible role for AP-1 in programmed cell death.

Animals↗
PubMed1993

Sustained release phenylpropanolamine hydrochloride from ATO 888 matrix.

Sustained release phenylpropanolamine HCl tablets were prepared with compritol as a retardant material. The effects of varying wax levels and methods of matrix formation on drug release were investigated. Also the compaction profiles were recorded for all formulations. The amount of drug in the formula was held constant (10% w/w), while the wax level was varied from 10% to 50% w/w. Two methods were used for the preparation of drug: wax systems; physical mixture and solid dispersion. The drug release from tablets containing 10% Compritol and prepared by solid dispersion was 97% after six hours of testing dissolution. Tablets prepared with 30% wax released 72% of the drug, while tablets containing 50% wax released only 30% of the drug after six hours. Tablets prepared by physical mixture gave higher drug release than tablets prepared by solid dispersion method. The incorporation of Compritol decreased the ejection forces of tablets during compaction. The drug release from tablets prepared by solid dispersion followed the diffusion controlled model described by Higuchi for inert porous matrix.

Chemistry, Pharmaceutical↗
PubMed1993

Physicochemical characterization of acetaminophen-ethylcellulose solid dispersion.

In this study, ethylcellulose was evaluated as a carrier for the preparation of sustained release of acetaminophen via solid dispersion technique. Physical mixture at the same level of acetaminophen and ethylcellulose was prepared. Differential scanning calorimetry and scanning electron microscope were used to characterize the physical properties of the various systems and to determine if there is possible interaction between acetaminophen and ethylcellulose.

Acetaminophen↗
PubMed1992

Granule containing cells in the crayfish third abdominal ganglion.

1. Four of the 850 neuron cell bodies of the crayfish third abdominal ganglion contain large dense secretory granules. 2. The processes of these cells form a neurohemal organ in the dorsal perineurium/neurilemma in the ganglion. 3. None of the immunocytochemically identified peptides accounts for the observed distribution of granules.

Abdomen↗
PubMed1992

Overexpression of Mos, Ras, Src, and Fos inhibits mouse mammary epithelial cell differentiation.

Mammary epithelial cells terminally differentiate in response to lactogenic hormones. We present evidence that oncoprotein overexpression is incompatible with this hormone-inducible differentiation and results in striking cellular morphological changes. In mammary epithelial cells in culture, lactogenic hormones (glucocorticoid and prolactin) activated a transfected beta-casein promoter and endogenous beta-casein gene expression. This response to lactogenic hormone treatment was paralleled by a decrease in cellular AP-1 DNA-binding activity. Expression of the mos, ras, or src (but not myc) oncogene blocked the activation of the beta-casein promoter induced by the lactogenic hormones and was associated with the maintenance of high levels of AP-1. Mos expression also increased c-fos and c-jun mRNA levels. Overexpression of Fos and Jun from transiently transfected constructs resulted in a functional inhibition of the glucocorticoid receptor in these mouse mammary epithelial cells. This finding clearly suggests that glucocorticoid receptor inhibition arising from oncogene expression will contribute to the block in hormonally induced mammary epithelial cell differentiation. Expression of Src resulted in the loss of the normal organization and morphological phenotype of mammary epithelial cells in the epithelial/fibroblastic line IM-2. Activation of a conditional c-fos/estrogen receptor gene encoding an estrogen-dependent Fos/estrogen receptor fusion protein also morphologically transformed mammary epithelial cells and inhibited initiation of mammary epithelial differentiation-associated expression of the beta-casein and WDNM 1 genes. In response to estrogen treatment, the cells displayed a high level of AP-1 DNA-binding activity. Our results demonstrate that high cellular AP-1 levels contribute to blocking the ability of mammary epithelial cells in culture to respond to lactogenic hormones. This and other studies indicate that the oncogene products Mos, Ras, and Src exert their effects, at least in part, by stimulating cellular Fos and probably cellular Jun activity.

Animals↗
PubMed1992

Ethylcellulose as a carrier for controlled-release acetaminophen tablets.

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.

Acetaminophen↗
PubMed1978

Unilateral forelimb deafferentation in the monkey: purposive movement.

Monkeys with unilateral dorsal rhizotomy C2-T3 used their denervated limbs to retrieve unseen food pellets when movements of the intact contralateral limb were rendered ineffective by enclosure of the hand within a container. Even after protracted use in this condition, however, the deafferented limb ceased to be used in the test situation when the intact arm was released. These findings cast doubt on interpretations of lack of use of a unilaterally dorsal rhizotomized limb as being due to cross-spinal inhibition or to learned disuse.

Afferent Pathways↗