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Biomedical subjects

C Arias

Publications and source records attributed to C Arias.

At least 37 records · Page 2Linked to original sources
PubMed1997

The Pit-1 gene is regulated by distinct early and late pituitary-specific enhancers.

The differentiation of three anterior pituitary cell types is regulated by the tissue-specific POU domain factor Pit-1, which is initially expressed on Embryonic Day 13.5-14 in mice. The Pit-1 gene remains continuously, highly expressed in the somatotrope, thyrotrope, and lactotrope cells of the adult. Using the Pit-1-defective Snell dwarf as a genetic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene activation and for subsequent autoregulation (required for maintenance of expression) and that Pit-1-dependent activation of the distal enhancer can be mediated in the absence of the early enhancer. These two distinct enhancers provide the basis for temporally specific regulation by discrete pituitary-specific factors, events likely to be prototypic for regulation of other classes of genes encoding transcription factors controlling terminal differentiation.

Animals↗
PubMed1997

Neuronal damage and MAP2 changes induced by the glutamate transport inhibitor dihydrokainate and by kainate in rat hippocampus in vivo.

Neurotoxicity mediated by glutamate is thought to play a role in neurodegenerative disorders, and alterations in cytoskeletal proteins are possibly involved in the mechanisms of neuronal death occurring in Alzheimer's disease. In the present work we studied the neurotoxic effects of the intrahippocampal injections of the glutamate transport inhibitor dihydrokainate as compared to those of kainate, as well as the concomitant changes in the microtubule-associated protein MAP2. Neuronal alterations were assessed at 3, 12, 24, and 48 h by Nissl staining and immunocytochemistry of MAP2. At 3 h, both compounds induced neuronal damage that was correlated with loss of dendritic MAP2 immunoreactivity. Neuronal damage was more evident at 12 h and 24 h after drug injection, and at these times an accumulation of MAP2 in the somata of pyramidal neurons was observed. The effects of dihydrokainate were restricted to the CA1 region and totally prevented by the N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), but not by the non-NMDA receptor antagonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f)-quinoxaline (NBQX). In contrast, kainate-induced alterations included CA1, CA3, and CA4 subfields, and the changes in CA1 were prevented by NBQX, while MK-801 was ineffective. These results suggest that early MAP2 disruption may be a marker of the excitotoxicity due to activation of different glutamate receptors located in discrete hippocampal regions.

Animals↗
PubMed1997

Transient emotional changes elicited by intraperitoneal saline injection: effect of naloxone and flumazenil.

The effect of the intraperitoneal (i.p.) saline injection was assessed by using the defensive burying (DB) and the elevated plus-maze (EPM) anxiety paradigms in rats. Animals were handled gently by the body, injected i.p. with saline solution, 2 ml/kg, and tested independently in the defensive burying as well as in the elevated plus-maze test at different times after the i.p. injection: 1.5, 3, 5, 10, 15, and 30 min. A transient effect of i.p. saline injection was observed (i.e., increased DB in animals tested 1.5 min after injection) and a decrease in this parameter when studied 3 min after the injection. No changes at 5, 10, 15, and 30 min after the injection were found. To discriminate the putative participation of the opiate peptide and benzodiazepine receptors in the actions of the i.p. injection, flumazenil (5 mg/kg) and nalozone (1 mg/kg) were administered. The increase in DB at 1.5 min was masked by double injection, an effect blocked by naloxone, but not by flumazenil, while both of them reverted the decrease in DB response in animals tested 3 min after injection. A partial action of the i.p. in the animals tested in the elevated plus-maze test was found. Present results are discussed on the basis of behavioral and pharmacological evidence.

Animals↗
PubMed1996

[Transient osteoporosis of the hip and magnetic nuclear resonance].

The authors evaluated the diagnostic importance of MRI in a woman who presented with transient osteoporosis of both hips, over an interval of three years. The diagnosis was made only during the second episode with the aid of MRI. The patient recovered without sequelae.

Adult↗
PubMed1995

beta-Amyloid peptide fragment 25-35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices.

beta-Amyloid protein (beta AP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that beta AP, particularly its fragment 25-35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25-35 on the release of endogenous amino acids from hippocampal slices of young adult (3-3.5-month-old) and aged (23-25-month-old) rats, under basal, K(+)-depolarization, and post-depolarization conditions, in the presence and absence of Ca2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1-hr preincubation of slices from young animals with 10 microM 25-35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control-stimulated release. These effects were strictly dependent on external Ca2+. Neither the K(+)-stimulated release of gamma-amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25-35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25-35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K(+)-induced release of both aspartate and glutamate was also higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1995

p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors.

p53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non-invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S-phase of the tumours, disease-free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53-positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low-grade dysplasias and 5 of 10 (50 per cent) high-grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease-free nor overall survival showed differences between p53-positive and p53-negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progression of the tumours.

Adult↗
PubMed1995

Evidence for short-loop feedback effects of ACTH on CRF and vasopressin expression in parvocellular neurosecretory neurons.

Immuno- and hybridization histochemical methods were used to examine a possible role for adrenocorticotropic hormone (ACTH) in regulating the expression of corticotropin-releasing peptides in rat hypothalamus. Densitometric assessments of relative levels of mRNAs encoding corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX) and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable increases in relative levels of CRF and AVP transcripts in the parvocellular PVH; no effects on OT mRNA in this compartment were evident. In a second experiment, ACTH or saline vehicle were administered systemically via osmotic minipump for seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement doses of ACTH reduced the number of detectable AVP-immunoreactive (AVP-ir) cells in the parvocellular PVH to 53% of that seen in vehicle-treated HYPOX/ADX controls; the number of CRF-IR cells was not significantly affected. Higher doses of ACTH resulted in counts of AVP- and CRF-IR neurons that were reduced to 32% and 70%, respectively, of control values. Staining patterns for the two peptides in the external lamina of the median eminence generally followed the cell count data. Neither densitometric nor combined immunohistochemical (for CRF-ir) and hybridization histochemical (for AVP mRNA) assays revealed any marked effect of ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The results indicate that ACTH is capable of inhibiting corticotropin-releasing peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms underlying these effects remain to be fully clarified.

Adrenocorticotropic Hormone↗
PubMed1993

Okadaic acid induces early changes in microtubule-associated protein 2 and tau phosphorylation prior to neurodegeneration in cultured cortical neurons.

Microtubules and their associated proteins play a prominent role in many physiological and morphological aspects of brain function. Abnormal deposition of the microtubule-associated proteins (MAPs), MAP2 and tau, is a prominent aspect of Alzheimer's disease. MAP2 and tau are heat-stable phosphoproteins subject to high rates of phosphorylation/dephosphorylation. The phosphorylation state of these proteins modulates their affinity for tubulin and thereby affects the structure of the neuronal cytoskeleton. The dinoflagellate toxin okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A. In cultured rat cortical neurons and a human neuroblastoma cell line (MSN), okadaic acid induces increased phosphorylation of MAP2 and tau concomitant with early changes in the neuronal cytoskeleton and ultimately leads to cell death. These results suggest that the diminished rate of MAP2 and tau dephosphorylation affects the stability of the neuronal cytoskeleton. The effect of okadaic acid was not restricted to neurons. Astrocytes stained with antibodies to glial fibrillary acidic protein (GFAP) showed increased GFAP staining and changes in astrocyte morphology from a flat shape to a stellate appearance with long processes.

Animals↗
PubMed1992

The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization.

In addition to a nonadecapeptide homologous to the teleost melanin-concentrating hormone (MCH), the amino acid sequence predicted from a rat prepro-MCH (ppMCH) cDNA suggested that at least one (neuropeptide EI, or NEI), and possibly a second (NGE), additional neuropeptide may be encoded by this precursor. Cross-reactivity with epitopes of NEI or NGE can account for reported localization of alpha-MSH, rat CRF, and human GRF in rat dorsolateral hypothalamic neurons. We have used antisera raised against rat MCH and NEI in immunohistochemical studies at the light and electron microscopic levels, along with hybridization histochemical localization of ppMCH mRNA, to define the organization of this system. As expected, ppMCH mRNA is prominently expressed in cells in the lateral hypothalamic area and zona incerta. The MCH and NEI peptides were extensively colocalized in neurons in both of these areas. In addition, smaller cell groups in the olfactory tubercle and pontine tegmentum were also positively hybridized for ppMCH mRNA and immunostained for MCH and NEI. Fibers stained for MCH and NEI were similarly, and very broadly, distributed throughout the central nervous system in patterns that generally conformed with known projection fields of the lateral hypothalamic area and zona incerta. A differential distribution was seen in at least one region, the interanterodorsal nucleus of the thalamus, which contained a prominent terminal field stained for MCH but not NEI. At the electron microscopic level, MCH-stained perikarya displayed a prominent staining associated with the Golgi apparatus; this was not encountered in NEI-stained cells. Both peptides were distributed similarly in terminals in the lateral hypothalamic area and median eminence, with staining associated principally with dense-cored vesicles. The results suggest that ppMCH-derived peptides may serve as neurotransmitters or modulators of prominence in a surprisingly expansive projection field of incerto-hypothalamic neurons. The terminal distributions of this system seem most compatible with functional roles in generalized arousal and sensorimotor integration, processes previously implicated as being subject to modulation by the lateral hypothalamic area.

Animals↗
PubMed1992

Inhibition of brain glutamate decarboxylase activity is related to febrile seizures in rat pups.

Because previous work showed that in the newborn brain, but not in the adult brain, glutamate decarboxylase (GAD) is notably susceptible to heat, we have studied the possible involvement of GAD inhibition in febrile convulsions and the related changes in gamma-aminobutyric acid (GABA) content. Rats of different ages were subjected to hyperthermia, and GAD activity was determined in brain homogenates by measuring the release of 14CO2 from labeled glutamate and by measuring the formation of GABA. The latter method gave considerably lower values than the former in the youngest rats, and was considered more reliable. With this method, we found a 37-48% inhibition of GAD activity in rat pups 2-5 days old, which showed febrile seizures at progressively higher body temperatures, whereas in 10- and 15-day-old animals, which did not show convulsions, GAD activity was not affected by hyperthermia. Whole-brain GABA levels, however, did not change at any age. In contrast to GAD, choline acetyltransferase and lactic dehydrogenase activities were not altered by hyperthermia at any of the ages studied. These results suggest that a decreased efficiency of the inhibitory neurotransmission mediated by GABA, consequent to the inhibition of GAD activity, may be a factor related to febrile convulsions.

Animals↗
PubMed1992

Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics.

Immunohistochemical and in situ hybridization localization of peptides derived from, and mRNAs encoding, prepro-somatostatin (ppSS) and prepro-growth hormone-releasing factor (ppGRF) was carried out on hypothalami from rats flown on biosatellites COSMOS 1887 and 2044 to investigate possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion. Results from the COSMOS 1887 mission indicated that both SS and GRF immunostaining in the median eminence were diminished in flight animals relative to controls; no differences between groups in staining for other peptidergic neurosecretory systems were apparent. Animals flown on COSMOS 2044 displayed a more pronounced depletion of GRF than SS immunoreactivity from neurosecretory terminals in the median eminence. In addition, flight animals displayed significant 46-50% reductions in the number and signal intensity of presumed hypophysiotropic cells in the arcuate nucleus expressing ppGRF mRNA; positively hybridized cells in the region surrounding the ventromedial nucleus were less markedly affected. Both indexes of ppSS mRNA levels in the anterior periventricular nucleus were similar in flight and control rats. An additional group of animals that experienced hindlimb suspension, a manipulation that mimics the effects of weightlessness on several parameters, did not differ from controls in any of the above measures. These data suggest that exposure to microgravity results in a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impaired GH secretion described previously in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.

Animals↗
PubMed1992

[Use of standard protocols in the evaluation of voice disorders].

The purpose of this paper is to present a protocol for the use of standard forms in the evaluation of laryngeal structure and function in patients with voice disorders. The forms are designed to cover all the essential parameters needed to reach an accurate descriptive diagnosis which allows us to have an appropriate therapy plan according to the individual's detailed observations. It also gives us a consistent standardized evaluation form to measure changes after therapy whether behavioral, medical or surgical, and to compare different observations across patients. Reporting observations in this consistent manner will make characteristic patterns of different vocal behaviors readily obvious to the researcher or the clinician and reduce the possibility of missing any important details. The protocols are: indirect laryngoscopy, video-stroboscopic-evaluation form, functional voice and auditory perceptual voice evaluation.

Adult↗
PubMed1991

Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant.

Most of the transcriptional effects of cyclic AMP are mediated by the cAMP response element binding protein (CREB). After activation of cAMP-dependent protein kinase A, the catalytic subunits of this enzyme apparently mediate the phosphorylation and activation of CREB. As cAMP serves as a mitogenic signal for anterior pituitary somatotrophic cells, we investigated whether CREB similarly regulates proliferation of these cells. We prepared transgenic mice expressing a transcriptionally inactive mutant of CREB (CREBM1), which cannot be phosphorylated, in cells of the anterior pituitary. If CREB activity is required for proliferation, the overexpressed mutant protein would effectively compete with wild-type CREB activity and thereby block the response to cAMP. As predicted, the CREBM1 transgenic mice exhibited a dwarf phenotype with atrophied pituitary glands markedly deficient in somatotroph but not other cell types. We conclude that transcriptional activation of CREB is necessary for the normal development of a highly restricted cell type, and that environmental cues, possibly provided by the hypothalamic growth hormone-releasing factor, are necessary for population of the pituitary by somatotrophic cells.

Amino Acid Sequence↗
PubMed1991

[Management of unilateral vocal cord paralysis].

The phoniatric analysis evaluates the importance of the vocal disorder and the appearance of the larynx what permets to find five clinical cases. For each one, there is a precise treatment: no treatment, rehabilitation with precises exercises in each case, collagen injection, early or secondary to rehabilitation. The rehabilitation will be intensive and done as soon as possible. It is based on a well known body proprioception. Intrinsic laryngeal muscles work, breathing exercises, exercises aimed at restoring the laryngeal sphincter will precede the pure vocal work. Author's experience shows that the results are good if rehabilitation is well indicated from the beginning and the patient with good motivations.

Humans↗
PubMed1991

Microalbuminuria in clinical practice.

Albumin excretion rate measured by new immunoassays and semiquantitative tests is advocated as a means for early detection of diabetic nephropathy. We determined albumin excretion rate in 276 patients. Albumin excretion rate was normal in 66%, within the microalbuminuric range in 27%, and within the macroproteinuric range in 7%. Significant predictors of albumin excretion rate included presence of hypertension and glycosylated hemoglobin level in type I diabetes mellitus, and years since diagnosis in type II diabetes mellitus. A semiquantitative test was deemed to be of limited diagnostic value. We conclude that testing for early diabetic nephropathy in routine clinical practice gives valuable information and that determination by a quantitative immunoassay based on a single 24-hour urine sample is preferable. The optimal frequency of screening and the levels that determine progressive renal disease have yet to be established.

Adult↗
PubMed1990

Inhibin beta, somatostatin, and enkephalin immunoreactivities coexist in caudal medullary neurons that project to the paraventricular nucleus of the hypothalamus.

Concurrent and sequential dual immunohistochemical labeling methods were used in combination, along with retrograde tracing techniques, to determine the extent to which inhibin beta (I beta), somatostatin-28 (SS-28), and enkephalin (ENK) immunoreactivity (IR) might be jointly expressed in neurons centered in the caudal part of the nucleus of the solitary tract (NTS) that project to the paraventricular nucleus of the hypothalamus (PVH). The results indicate that at least 65% of I beta-stained neurons in the NTS also express SS-28 IR, and at least 33% are ENK-positive. At least 25% of the I beta IR population stains positively for all three peptides. A substantial number of cells stained with markers for two, or all three, peptide families, could be retrogradely labeled following tracer deposits centered in the PVH. Prominent I beta and SS-28 IR projections from the caudal medulla to the hypothalamus have been described and include a preferential input to oxytocinergic (OT) compartments of the magnocellular neurosecretory system. The present results suggest that these arise in large measure from a common pool of neurons, a subset of which also shows ENK IR. Implications for the control of OT secretion, and for the processing of sensory information through the NTS, are discussed.

Animals↗