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Biomedical subjects

M Bartolome

Publications and source records attributed to M Bartolome.

13 recordsLinked to original sources
PubMed2001

Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat.

In response to moderately increased dietary fat content, melanocortin-4 receptor-null mutant (MC4R-/-) mice exhibit hyperphagia and accelerated weight gain compared to wild-type mice. An increased feed efficiency (weight gain/kcal consumed) argues that mechanisms in addition to hyperphagia are instrumental in causing weight gain. We report two specific defects in coordinating energy expenditure with food intake in MC4R-/- mice. Wild-type mice respond to an increase in the fat content of the diet by rapidly increasing diet-induced thermogenesis and by increasing physical activity, neither of which are observed in MC4R-/- mice. Leptin-deficient and MC3R-/- mice regulate metabolic rate similarly to wild-type mice in this protocol. Melanocortinergic pathways involving MC4-R-regulated neurons, which rapidly respond to signals not requiring changes in leptin, thus seem to be important in regulating metabolic and behavioral responses to dietary fat.

Adipose Tissue, Brown↗
PubMed1999

[Development of cell cultures in basic research on renal carcinoma].

OBJECTIVE: The development of in vitro cell tissue culture techniques has provided most of the current knowledge on the physiology of both normal and tumor cells. The results of cell culture studies using nephrectomy specimens are presented. METHODS: Surgical specimens from 7 patients (3 males, 42.9%; 4 females, 57.1%) aged 43-79 years (mean 62.14), who had undergone nephrectomy for renal adenocarcinoma between April 1997 and February 1998 were utilized. The tumor cell samples were obtained during surgery, after the kidney had been excised. The samples were cut, washed in a balanced saline solution and enzymatically dissociated in a trypsin solution (0.1% Hank's solution) for 30 minutes at 37 degrees, centrifuged, placed in Multiwell plates, covered with 0.1 mg/ml polylysine (ICN) or 3 mg/ml collagen S (Boehringer) and cultured in RPMI 1640 (Sigma) supplemented with 5% fetal calf serum (reagent), which was changed every 2-3 days for one month. After the culture had developed, samples were fixed in 70% ethanol and stained with hematoxylin-eosin for cell identification. Cell types were identified by cytokeratin analysis. RESULTS: The histological types were: clear cell renal adenocarcinoma in three cases (42.9%), renal oncocytoma in two (28.6%), mixed cells renal adenocarcinoma in one (14.3%) and papillary carcinoma in one case (14.3%). Polylysine and collagen were found to be good substrates for normal and tumor cell culture. Polylysine was found to be a better substrate for epithelial cells; there were less epithelial and more mesangial cells in the collagen substate. The positive cytokeratin expression (a marker for intermediate filaments) corroborates the well-known epithelial origin of renal cell carcinoma. Epithelial cells from normal kidney grew well in the culture medium. Mean cell survival was 30.83 days (range 15-50). To evaluate the viability of the culture, positivity for a neutral red stain was used as marker for good metabolic activity after one month. All cultures that survived for more than one month (5 of 7) stained positively. CONCLUSIONS: The study and development of human cell lines is useful to analyze the metabolic aspects of renal carcinoma. Cell cultures permit conducting genetic and molecular studies and investigating the radio and chemosensitivity of renal carcinoma in vitro.

Adenocarcinoma↗
PubMed1994

Thioether excretion, urinary mutagenicity, and metabolic phenotype in smokers.

In 81 healthy individuals (51 smokers and 30 nonsmokers) biological indicators of internal exposure to electrophiles derived from tobacco smoke through metabolism were evaluated. Subgroups of smokers have been established in relation to the amount and type of tobacco smoked. Acetylator and hydroxylator phenotypes have been used as biomarkers of genetically determined susceptibility to cancer development. Urinary concentrations of thioethers (UT) and mutagenicity, with S9 mix for microsomal activation (MI-S9), were higher in smokers in relation to the level of tobacco consumption, but not to the type of tobacco. The "Slow acetylators-rapid oxidizers" category was not significant from the "rapid acetylators-rapid oxidizers" for values of UT and MI-S9. Data suggest that the biomarkers of exposure used in this study lack the necessary specificity to ascertain genetically determined susceptibility to cancer induced by tobacco smoking.

Acetylation↗
PubMed1990

Dose-dependent effect of prenatal dexamethasone treatment on beta-adrenergic receptor coupling to ornithine decarboxylase and cyclic AMP.

Glucocorticoids regulate the coupling of beta-adrenergic receptors to cell function. In the current study, the potential role of these agents in the development of adrenergic responses was evaluated in the offspring of pregnant rats given 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19. We examined the postnatal development of beta-receptors coupling to ornithine decarboxylase in heart and kidney throughout neonatal life into young adulthood; this enzyme is involved in transduction of neural signals controlling cellular replication and differentiation. Dexamethasone exposure perturbed the basal pattern of cardiac ornithine decarboxylase activity and attenuated the response of the enzyme in both heart and kidney to acute challenge with the beta-agonist, isoproterenol. Subsensitivity persisted into the postweaning period. This dosage regimen of dexamethasone also suppressed renal cyclic AMP responses to isoproterenol, but exposure to a lower dose (0.2 mg/kg) enhanced the response. Thus, although low doses of glucocorticoids foster development of the coupling of beta-receptors to cellular transduction mechanisms, higher doses such as those used to stimulate lung function may lastingly obtund adrenergic sensitivity.

Aging↗
PubMed1989

Role of sympathetic neurons in development of beta-adrenergic control of ornithine decarboxylase activity in peripheral tissues: effects of neonatal 6-hydroxydopamine treatment.

Sympathetic neurons are thought to regulate the development of their postsynaptic targets. In the current study, we examined the effects of sympathectomy with 6-hydroxydopamine in neonatal rats on the ontogeny of beta-receptor binding sites and their linkage to both cyclic AMP production and ornithine decarboxylase activity. Cardiac norepinephrine levels and turnover were used to confirm the completeness and permanence of the lesion. The ability of isoproterenol, a beta-adrenergic agonist, to stimulate ornithine decarboxylase (a growth-related enzyme) in heart, lung and kidney, was reduced by neonatal sympathectomy; the effect persisted into young adulthood. The effect represented a selective uncoupling of enzyme activity from receptor activation, as receptor binding capabilities were unaffected and the linkage of beta-receptors to cyclic AMP was enhanced. Comparison of the effects of peripheral sympathectomy with those of central lesions (intracisternal 6-hydroxydopamine) confirmed the importance of sympathetic nerve terminals in determining the coupling of the receptors to ornithine decarboxylase. These data suggest that sympathetic neurons program their target organs to specific trophic responses during development.

Animals↗
PubMed1988

Trophic control of lung development by sympathetic neurons: effects of neonatal sympathectomy with 6-hydroxydopamine.

The onset of peripheral sympathetic neuronal function is thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we examined the effects on lung development of neonatal sympathectomy with 6-hydroxydopamine. The completeness of the lesion and effectiveness in reducing sympathetic input to the tissue were confirmed by direct measurement of norepinephrine levels and turnover. Despite the denervation, no evidence of beta-receptor up-regulation was found; in fact, receptor binding sites tended to be reduced throughout development. The cyclic AMP response to isoproterenol challenge was initially suppressed in the lesioned animals, but became supersensitive even in the face of reduced receptor binding capabilities. Evidence was also obtained for ontogenetic abnormalities in the ornithine decarboxylase/polyamine system, which is partially controlled by beta-adrenergic input and which regulates macromolecule synthesis in replicating and differentiating cells. Eventually, the alterations were reflected in aberrant developmental patterns of DNA, RNA and protein in the lung. These results indicate that sympathetic neurons influence the biochemical development of the lung and may serve to program permanently the relationships among receptor sites, receptor coupling to cellular function, and control of cell maturation.

Animals↗
PubMed1986

Effects of neonatal methylmercury exposure on adrenergic receptor binding sites in peripheral tissues of the developing rat.

Neonatal exposure to methylmercury produces changes in patterns of tissue growth and function, in part, due to alterations in adrenergic neuronal input. To explore the mechanisms by which these changes come about, newborn rats were exposed to methylmercury (1 or 2.5 mg/kg per day) throughout the preweaning stage and the ontogeny of adrenergic receptor binding sites evaluated in liver, kidney, heart and lung, using [3H]prazosin (alpha 1-receptors), [3H]rauwolscine (alpha 2-receptors) and [125I]pindolol (beta-receptors). In the kidney, methylmercury caused decreases in beta- and alpha 1-receptor binding and increases in alpha 2-binding; previous work has shown that beta-receptor-mediated responses are generally enhanced in methylmercury-exposed pups, and the down-regulation of beta-receptor binding thus probably represents a compensatory action secondary to alterations in post-receptor coupling mechanisms. The effects of methylmercury on hepatic adrenergic receptors were different from those seen in the kidney, with substantial elevations in beta- and alpha 1-receptor binding apparent in the preweaning stage; this agrees also with the differences in effects of the mercurial on trophic reactivity and growth in the 2 tissues. Despite the fact that methylmercury causes activation of neonatal cardiac sympathetic nerves, beta-receptor binding sites in the heart were unaffected by methylmercury exposure; the failure to down-regulate cardiac postsynaptic receptors in the face of increased nerve activity again represents an anomaly of synaptic regulatory function. These results indicate that methylmercury alters adrenergic responsiveness, in part, through actions on the development of receptor binding sites, and further, that the organ-specificity and receptor subtype-selectivity are consistent with subsequent effects of the organomercurial on adrenergic participation in target organ growth; however, changes in receptor binding alone do not account for all of the effects of methylmercury on synaptic activity or trophic responses.

Aging↗
PubMed1986

Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms.

The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions of urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. In addition, the reactivity of the kidney to challenge with desmopressin was altered coincidentally with the appearance of the effects on basal clearance mechanisms. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs. postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

Animals↗
PubMed1985

Postnatal methyl mercury exposure: effects on ontogeny of renal and hepatic ornithine decarboxylase responses to trophic stimuli.

The effects of postnatal methyl mercury exposure on the ontogeny of renal and hepatic responsiveness to trophic stimuli were examined. Increased ornithine decarboxylase (ODC) activity was used as an index of tissue stimulation. In the rat, renal ODC responsiveness to growth hormone, angiotensin, vasopressin, isoproterenol, and serotonin was absent at birth and matured 3 to 4 weeks later. However, pups exposed to methyl mercury showed marked, ODC responses to these same agents as early as 10 to 19 days of postnatal age, accompanied by a significant renal hypertrophy. In contrast to the kidney, the liver of normally developing rats was responsive to trophic factors even in the neonate. In this tissue, there was no consistent effect of neonatal methyl mercury treatment on ODC responses at any developmental stage tested; although absolute liver weights were reduced, liver/body weight ratio was not affected. These results demonstrate that postnatal methyl mercury exposure causes a precocious onset of ODC responses to trophic agents specifically in the kidney. Altered responsiveness may mediate some of the effects of this organomercurial on overall renal development and function.

Animals↗
PubMed1984

Effect of chronic methadone administration on neuroendocrine function in developing rats.

This paper reports the effects of chronic postnatal methadone administration on basal hormone levels and on the endocrine response to methadone. Chronic postnatal methadone administration delayed normal developmental increases in serum T4 (decrease on day 5), corticosterone (CS) (days 15 and 20) and growth hormone (GH) (day 25). In addition, marked tolerance to methadone effects on GH, CS, thyroid-stimulating hormone (TSH) and prolactin (PRL) secretion developed during chronic postnatal administration, and effects on PRL and TSH secretion persisted after drug withdrawal.

Age Factors↗
PubMed1982

Norepinephrine content of the rat kidney during development: alterations induced by perinatal methadone.

The concentration and the total content of norepinephrine (NE) in the kidney were measured in Sprague-Dawley rats from 3 to 120 days after birth. Renal NE concentration was relatively low until the end of the second week, when it rose abruptly to adult levels; total NE content per kidney increased steadily throughout development. The effects of perinatal methadone treatment on renal NE development were examined by administering the drug either directly to the pups from 1 to 19 days after birth, or to the mother from 10 days of gestation to 20 days after birth. Both treatments resulted in significant deficits of body weight and kidney weight. Maternal methadone caused a significant deficit in renal NE which was most pronounced at two weeks of postnatal age; direct methadone had less effect on renal NE. These results suggest that renal sympathetic neurotransmission may become mature two weeks after birth and indicate further that maternal methadone interferes with this maturation.

Animals↗