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M Morales

Publications and source records attributed to M Morales.

At least 127 records · Page 7Linked to original sources
PubMed1997

The 5-HT3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon.

The type 3 serotonin receptor (5-HT3R) is a ligand-gated ion channel whose presence in the CNS has been established by radioligand binding, in situ hybridization, and immunohistochemical analysis. To analyze further the role of the 5-HT3R in the CNS, we used in situ hybridization and immunocytochemistry to determine that 5-HT3R-expressing neurons are mainly GABA-containing cells in the rat telencephalon. We determined that 5-HT3R/GABA-containing neurons do not exhibit somatostatin immunoreactivity but often contain cholecystokinin (CCK) immunoreactivity. 5-HT3R-expressing cells with CCK immunoreactivity were observed in the neocortex, olfactory cortex, hippocampus, and amygdala. The 5-HT3R/CCK interneurons represent between 35 and 66% of the total population of CCK-containing cells in the neocortex. Further characterization of the 5-HT3R/GABAergic neurons was based on their calcium-binding protein immunoreactivity and showed that these neurons lack parvalbumin (PV) and represent a subpopulation of calbindin (CB)-containing interneurons that were preferentially present in the CA1-CA3 subfield of the hippocampus. Although some 5-HT3R/GABAergic neurons with calretinin (CR) were found in the neocortex, olfactory cortex, hippocampus, and amygdala, these neurons were more often present in the agranular insular and piriform cortices. We conclude that the neuronal expression of the 5-HT3R is selective within the GABA neuron population in the rat telencephalon. These 5-HT3R-expressing interneurons might contain CCK, CB, and CR. We suggest that serotonin through the 5-HT3R may regulate GABA and CCK neurotransmission in the telencephalon.

Animals↗
PubMed1997

Gene cloning of rat and mouse platelet glycoprotein V: identification of megakaryocyte-specific promoters and demonstration of functional thrombin cleavage.

Platelet glycoprotein (GP) V is a major surface protein cleaved during thrombin-induced platelet activation. GPV associates noncovalently with the GPIb-IX complex to form GPIb-V-IX, a receptor for von Willebrand factor and thrombin. We describe the cloning of the genes coding for rat and mouse GPV and compare them with the human gene. The two rodent genes have a similar structure and resemble the human GPV gene with a coding sequence (approximately 1,700 nucleotides) entirely contained in one exon and a single intron (approximately 900 nucleotides) in the 5' untranslated region. Both genes have megakaryocyte-type promoters with conserved tandem Ets and GATA recognition motifs and lack a TATA box. The mature rat and mouse proteins comprise 551 amino acids, have 70% sequence identity, and contain an additional 8-amino acid intracellular segment as compared with the human protein. As in human GPV, there is an NH2-terminal leucine-rich region of 15 repeats and a thrombin cleavage recognition sequence. Whereas the rat and human thrombin cleavage sites are similar, the mouse cleavage site resembles that of the human thrombin receptor. Functionality of these sites was demonstrated by thrombin cleavage of synthetic peptides and analysis by high-performance liquid chromatography (HPLC) or mass spectrometry. Cleavage of native rat GPV was confirmed by means of a polyclonal antibody directed against the new NH2-terminal peptide exposed after thrombin cleavage. This antibody specifically recognized thrombin-activated rat platelets by fluorescence-activated cell sorting (FACS) analysis. In addition, we raised monoclonal antibodies specific for rat GPV (88 kD), which recognized the NH2-terminal soluble fragment (70 kD) liberated after thrombin cleavage. Knowledge of these rodent GPV genes and availability of species-specific peptides and antibodies will be essential to further studies aiming to define the exact in vivo function of platelet GPV using animal models of thrombosis and gene inactivation experiments.

Amino Acid Sequence↗
PubMed1997

Glutamate receptors of the kainate type and synaptic transmission.

Glutamic acid is an important excitatory neurotransmitter in the mammalian CNS. It has been established that synaptic transmission is mediated mostly by the ionotropic glutamate receptors AMPA and NMDA, with fast and slow kinetics, respectively. The recent demonstration in hippocampal neurones of a class of glutamate receptors that are activated by kainate and not by AMPA (that is, kainate-selective receptors) opens the possibility that receptors, others than those of the AMPA type, might also be involved in fast neurotransmission. The lack of specific pharmacological tools to dissect out AMPA from kainate receptors has hampered the functional study of kainate receptors. However, the recent finding that a 2,3-benzodiazepine (GYK153655) behaves as a selective antagonist of AMPA receptors allows us to address the question of the role of rapidly inactivating kainate receptors in synaptic transmission.

Animals↗
PubMed1997

Effect of bacterial lipopolysaccharide on endothelin-1 production in human vascular endothelial cells.

BACKGROUND/AIMS: The plasma levels of endothelin (ET) are 2-5 fold higher in patients with cirrhosis than in healthy subjects. It has been proposed that endotoxemia could be a mechanism responsible for this phenomenon. However, investigations in rats with cirrhosis indicate that a differential regulation for prepro ET-1 mRNA expression occurs in the liver tissue of these animals but not in the aorta or other organs. The aim of the study was to investigate the effect of bacterial lipopolysaccharide (LPS) on endothelin-1 synthesis and release in cultured human vascular endothelial cells (HUVEC). METHODS: Confluent HUVEC at passage levels 3 and 4 were exposed to increasing doses of LPS (1-1000 ng/ml) for 4 h at 37 degrees C and prepro ET-1 mRNA accumulation and big ET-1 and ET-1 concentrations in the conditioned medium were measured. RESULTS: Endotoxin had a dual effect on HUVEC. LPS at doses ranging between 250 and 1000 ng/ml induced a progressive diminution in ET-1 concentration in the culture medium. However, lower LPS concentrations dose-dependently increased big ET-1 and ET-1 release by HUVEC without altering prepro ET-1 mRNA expression. CONCLUSIONS: These results suggest that low LPS concentrations promote ET-1 release in HUVEC by a post-transcriptional mechanism located upstream of big ET-1 in the biosynthetic pathway of ET-1. These findings could explain the existence of high circulating levels of ET-1 in cirrhosis in spite of transcriptional activation of prepro ET-1 mRNA only occurring in the liver.

Cells, Cultured↗
PubMed1997

Repair of a transmandibular implant: clinical report.

The use of many currently available implant systems may be limited in patients with severe mandibular atrophy because of the lack of available bone in the symphyseal region. The transmandibular implant is a rigid box-frame structure that can distribute masticatory forces along a severely atrophied mandible with as little as 4 mm of vertical bone with an implant-borne prosthesis. Although the success rate of the transmandibular implant is favorable as compared with other systems, complications can occur after placement, including infection, partial extrusion, and fracture of a post. A case report of fractures of two posts at the necks and the bar approximately 18 months after placement is presented.

Aged↗
PubMed1997

Comparison of pressure support ventilation and assist-control ventilation in the treatment of respiratory failure.

STUDY OBJECTIVE: To assess whether pressure support ventilation (PSV) could be used as an alternative ventilatory mode to assist-control (A/C) ventilation in the treatment of respiratory failure. DESIGN: A short-term (4-h) prospective study in which the beneficial effect of PSV on respiratory mechanics, gas exchange, arterial oxygenation, cardiovascular hemodynamics, and oxygen consumption was compared with A/C ventilation. SETTING: ICU of a community hospital. PATIENTS: Forty-five patients (mean age, 62.8 [11.8] years) with respiratory failure secondary to COPD, restrictive disorders, or neuromuscular disease requiring mechanical ventilatory support in the ICU were selected for study. INTERVENTIONS: The mean duration of mechanical ventilation before the study was 7.16 (8.64) days. Patients were switched to the PSV mode of the mechanical ventilator for a period of 4 h after which conventional A/C ventilation was resumed. RESULTS: Patients supported with PSV compared with A/C ventilation showed significantly higher tidal volume, minute ventilation, and inspiratory time in association with significantly lower pressure in the airway and I:E ratio. With regard to gas exchange data, an increase in dead space/tidal volume ratio (VD/VT), decrease in PaO2, and statistically but not clinically significant alteration of arterial oxygenation indexes were noted. However, when patients with COPD, restrictive disorders, and neuromuscular disease were compared, significant changes in arterial oxygenation parameters were found only in patients with restrictive disorders. There were significant decreases in heart rate, systolic pulmonary artery pressure, and pulmonary capillary wedge pressure when PSV was applied. Oxygen transport and oxygen consumption were unchanged. CONCLUSIONS: PSV could be a possible alternative to A/C ventilation in patients with respiratory failure. PSV caused an increase in VD/VT in association with a significantly lower pressure in the airway and I:E ratio. Randomized studies are needed to define the long-term benefits of both respiratory modes and the conditions in which PSV may be a valuable alternative to A/C ventilation.

Adult↗
PubMed1997

Preserved GLP-I effects on glycogen synthase a activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats.

To search if biological effects of GLP-I on glucose metabolism in extrapancreatic tissue are present in diabetic states, we have studied the action of GLP-I and insulin on glycogen-enzyme activity, glycogen synthesis, and glucose metabolism in isolated hepatocytes and soleus muscle from adult streptozotocin (STZ)- and neonatal STZ-treated diabetic rats. This work confirms the previously reported insulin-like effects of GLP-I on glucose metabolism in both muscle and liver tissue from normal rats (control). The present study extends those observations to the muscle and liver tissue of diabetic animals. In both muscle and liver tissue, the metabolism of D-glucose, in the absence of added peptides, was more severely affected in adult STZ (IDDM model) than in neonatal STZ (nSTZ; NIDDM model) rats, and the magnitude of hormonal effect on metabolic variables was lower in diabetic rats than in control rats, as a rule. Nevertheless, in liver and muscle tissue of diabetic rats, GLP-I was able to increase glycogen synthase activity, augment the net rate of D-[U-14C]glucose incorporation into glycogen, and increase D-[5-3H]glucose utilization, D-[U-14C]glucose oxidation, and lactate production. In conclusion, GLP-I exerts insulin-like effects on D-glucose metabolism in both muscle and liver tissue in IDDM or NIDDM animal models, and present observations reinforce the view that GLP-I may represent a most promising tool in the treatment of diabetic patients.

Animals↗
PubMed1997

[Prophylaxis secondary to retinitis by CMV in patients with AIDS: the efficacy of an intermittent schedule of 3 days/week].

BACKGROUND: An approach of daily or 5 days per week treatment as maintenance therapy is mandatory among HIV patients with CMV retinitis. We evaluate the efficacy and tolerance of thrice weekly maintenance therapy for CMV retinitis in AIDS patients. METHODS: Sixty nine consecutive patients with CMV disease were eligible for a prospective open clinical trial. Thirty three completed the induction treatment of CMV retinitis, agreed on maintenance thrice weekly and were included. Twenty nine received Ganciclovir (10 mg/kg/day) and 4 foscarnet (100 mg/kg/day) thrice weekly. RESULTS: The mean age was 34 years. Twenty nine of the 33 (87%) were males and 13 (39%) drug addicts. Mean CD4+ lymphocyte count at inclusion was 44 cells per relapsed and 22 (66%) died. The median time to relapse, survival free of CMV retinitis and the median survival was 18, 14 and 34 weeks respectively. CONCLUSION: Since the outcome of our patients with thrice weekly maintenance therapy was similar to historical controls our study at least provides the rational for this hypothesis to be tested in a future randomised trial.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Weight of the normal brain of the Venezuelan adult according to sex and age].

The weight of adult brains (age range: 19-100 years) obtained from 3967 consecutive necropsies performed over a period of ten years at the Hospital General del Sur of Maracaibo, are reviewed. The analysis of the weight of 1215 g in males, whereas the men brain weight in females was 1122 g. The encephalic weight decreases with age, diminishing rapidly after age 65 in males, and age 75 un females.

Adult↗
PubMed1997

[Skin and mucous membrane hemorrhages: clinical assessment, study sequence and relative frequency of hereditary diseases of the hemostasis in a Chilean population].

BACKGROUND: Skin and mucous membrane hemorrhages are distinctive manifestations of hereditary diseases of primary hemostasis and, among them, the different types of von Willebrand disease and of platelet function disorders are the most prevalent. AIM: To know the relative frequency of these disorders and to know the clinical features of patients with mucocutaneous hemorrhages. PATIENTS AND METHODS: Five hundred eighty nine patients whose main symptom was the presence of mucocutaneous hemorrhages were studied. Bleeding time, platelet count, coagulant activity of factor VIII (FVIII:C), FvW: Ag and FvW: CoRis and ABO blood group were measured in all patients in a first stage. According to the results of these tests, further studies were decided. RESULTS: In patients younger than 13 years old, male predominated and, in older patients, females consulted with higher frequency. There was a higher proportion of individuals with O blood type than in the normal population. Bleeding time was abnormal in 330 patients (56%). One hundred ten patients (19%) had won Willebrand disease and, among them, one third had a normal bleeding time. Isolated reduction of factor WII activity was found in 66 patients (11%, 51 males) and 32 of these had normal bleeding time. Eighty one patients (14%) were considered to have an hereditary platelet function defect. A precise diagnosis was not achieved in 332 patients (56%). CONCLUSIONS: Among patients consulting for mucocutaneous hemorrhages, 19% had von Willebrand disease, 11 had an isolated reduction of factor VIII activity, 14% had platelet function defects and in 56%, a precise diagnosis was not reached.

ABO Blood-Group System↗
PubMed1996

The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus.

We used in situ hybridization and immunocytochemistry to investigate the presence of GABA in neurons that express the type 3 serotonin receptor (5-HT3R). Quantitative analysis indicated that more than 90% of 5-HT3R expressing cells are GABAergic in the neocortex and hippocampus. The co-existence of 5-HT3R and GABA in cortical and hippocampal neurons indicates that serotonin, via 5-HT3R, can affect GABA release and suggests the participation of 5-HT3R in the inhibitory regulation of forebrain neurons.

Amygdala↗
PubMed1996

Effects of tamoxifen on serum lipid and apolipoprotein levels in postmenopausal patients with breast cancer.

Serum lipids and apolipoprotein levels were measured in twenty postmenopausal women with primary breast cancer, before and three months after tamoxifen therapy (10 mg twice a day). Tamoxifen caused a significant reduction in total serum cholesterol (10%; P < 0.02), and in low-density lipoprotein cholesterol (17%; P < 0.01), and a significant 47% increase in the subclass 2 of the high density lipoprotein cholesterol (P < 0.01). In addition, tamoxifen caused a 16% increase in apolipoprotein A-I, a 12% decrease in apolipoprotein B (P < 0.05), and a 37% reduction in the serum concentration of lipoprotein (a) (P < 0.01). These results show that tamoxifen brings about an important improvement in serum lipid profile.

Aged↗
PubMed1996

Inositolphosphoglycans are possible mediators of the glucagon-like peptide 1 (7-36)amide action in the liver.

A potent glycogenic effect for GLP-1(7-36)amide has been found in rat hepatocytes and skeletal muscle, and the specific receptors detected for GLP-1(7-36)amide in these tissue membranes do not seem to be associated to adenylate cyclase. On the other hand, inositolphosphoglycan molecules (IPGs) have been implicated as second messengers in the action of insulin. In a human hepatoma cell line (HEP G-2), we have observed the presence of [125I]GLP-1(7-36)amide specific binding, and a stimulatory effect of the peptide upon glycogen synthesis, confirming the findings in isolated rat hepatocytes. Also, GLP-1(7-36)amide modulates the cell content of radiolabelled glycosylphosphatidylinositols (GPIs), in the same manner as insulin, indicating hydrolysis of GPIs and an immediate and short-lived generation of IPGs. Thus, IPGs could be mediators in the GLP-1(7-36)amide glycogenic action in the liver.

Animals↗
PubMed1996

Cellular and subcellular immunolocalization of the type 3 serotonin receptor in the rat central nervous system.

We developed and characterized 14 polyclonal antibodies against peptides whose sequences were predicted from the type 3 serotonin receptor subunit A (5-HT3R-A) cDNA. One such antiserum, 0165, raised against a peptide corresponding to the large putative intracellular loop, immunoprecipitated in vitro translated 5-HT3R-A protein and recognized both recombinant and neuronal 5-HT3R-A protein by Western blot at a high titer. Furthermore, when antiserum 0165 was used to immunolabel brain sections previously hybridized with a riboprobe specific for 5-HT3R-A transcripts, neuronal co-localization of immunoproduct and transcript was widely found throughout the brain. The study of the distribution of 5-HT3R-A-immunoreactivity in the rat central nervous system with antiserum 0165 revealed intensely immunolabeled neurons in the forebrain (isocortex, olfactory regions, hippocampal formation and amygdala), brainstem (sensory and motor nuclei and nuclei of the reticular formation) and spinal cord (dorsal and ventral horn). At the subcellular level, the 5-HT3R-A was found in endomembranes involved in translation (nuclear envelope and endoplasmic reticulum) and in the dendritic plasma-membrane. The present report is the first description of the 5-HT3R-A immunolocalization in the CNS. The wide distribution of the 5-HT3R-A in the brain and spinal cord based on ligand binding, in situ hybridization and immunolocalization studies support its participation in a large array of central nervous system functions.

Animals↗
PubMed1996

Differential compartmentalization of vasopressin messenger RNA and neuropeptide within the rat hypothalamo-neurohypophysial axonal tracts: light and electron microscopic evidence.

Arginine vasopressin messenger RNA is axonally transported in the rat hypothalamo-neurohypophysial system [for review see Mohr et al. (1993) In Vasopressin (eds Gross P., Richter D. and Robertson C. L.), pp. 119-129, John Libbey Eurotext]. Upon chronic dehydration (2% saline-feeding for seven days), vasopressin messenger RNA within this axonal compartment is dramatically increased and appears aggregated in a selected subset of axonal swellings confined to the median eminence and posterior pituitary. In this study, we analysed the axonal distribution of the vasopressin messenger RNA within the hypothalamo-neurohypophysial tracts of control and saline-fed animals, and compared this distribution to that of the vasopressin peptide. Our data further support a selective aggregation of the vasopressin messenger RNA in a subset of distal axonal swellings and/or terminals of the median eminence and posterior pituitary. The selective aggregation is observed not only in saline-fed animals, but also in control animals. Although the osmotic stimulus dramatically enhances the axonal transport of vasopressin messenger RNA, the consequent general distribution pattern of the messenger RNA in the hypothalamo-neurohypophysial system is not changed. However, the physiological perturbation does increase the number of vasopressin messenger RNA-containing swellings within the median eminence and the posterior pituitary. In both saline-fed and control animals, the level of messenger RNA label within individual swellings appeared roughly similar to that found in the perikaryal cytoplasm of extra-hypothalamic vasopressinergic neurons. A detailed comparison of the axonal compartmentalization of vasopressin messenger RNA and vasopressin peptide demonstrates that the axonal distribution of vasopressin messenger RNA does not precisely overlap that of vasopressin peptide along the hypothalamo-neurohypophysial tract. In seven-day saline-fed animals, the majority of the messenger RNA-containing swellings of the median eminence also contain detectable vasopressin peptide; however in the same animals, nearly all the messenger RNA-containing swellings of the posterior pituitary appear devoid of vasopressin peptide. Therefore, our work strongly suggests that at least in the posterior pituitary, the vasopressin messenger RNA might be selectively targeted and aggregated in a selected subset of axonal swellings containing little if any vasopressin, and hence very few neurosecretory granules. Given this evidence that vasopressin messenger RNA and neuropeptide are differentially compartmentalized in axons of magnocellular neurons, we propose that vasopressin messenger RNA and peptide probably rely on different intracellular transport systems with respect to packaging, transport and/or aggregation within these selected axonal locations.

Animals↗