Infusion of guanine nucleotides through recording electrodes for studies on G-protein regulation of ion currents and channels.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Andrade.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Six left lung allotransplants were performed in healthy mongrel dogs. Immunosuppression was established with cyclosporine (15 mg/kg/day p.o.) from the day of transplantation for 30 days. Another group of animals (n = 3) was used to produce acute experimental pneumonia by instilling 4-6 ml of a 10(8) CFU suspension of Pseudomonas aeruginosa into the right lower lobe. Dynamic perfusory lung scintigraphy (DPLS) was performed before transplant/pneumonia (control), during acute rejection/pneumonia as detected radiologically, and after treatment with methylprednisolone (1 g/day for 3 days i.v.) (transplant group) or antibiotics (pneumonia group). Seroalbumin macroaggregates (5-8 McI) marked with 99-mTc were injected into the cephalic vein and the percentage of perfusion to each lung was determined. Eight acute rejection episodes were detected. DPLS showed similar perfusion to each lung, whereas during acute rejection perfusion was significantly reduced by almost 30%. Perfusion was reestablished to control levels after treatment with methylprednisolone. Reduction in perfusion correlated with radiological rejection grading. No reduction in left lung perfusion was detected in pneumonia animals. In conclusion, acute rejection reduces perfusion to the transplanted lung as measured by DPLS. Treatment restores normal perfusion.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To assess the efficacy of injection therapy with alcohol on prevent rebleeding and emergency surgery in patients with gastroduodenal ulcers and nonbleeding visible vessels, we have performed a prospective controlled trial involving 39 patients who were classified into two groups according to the time of the day on which emergency endoscopy was performed: group 1 (25 patients) in which endoscopic hemostasis with absolute alcohol was performed, and group 2 (14 patients) in which conventional therapy was applied (blood transfusions, antacids, and ranitidine). The two groups were comparable with regard to age, sex, and type of bleeding. The rebleeding rate/emergency surgery rate of 8%/4%, respectively, for group 1 was lower than the 57%/50% for group 2 (p less than 0.001). Our results suggest that endoscopic hemostasis with alcohol should be considered as the initial treatment of choice in patients who present with major upper gastrointestinal hemorrhage and are found to have an ulcer with a nonbleeding visible vessel.
Intracellular injection of QX-314 blocked the ability of baclofen and 5-carboxyamidotryptamine to hyperpolarize cells in the rat hippocampus. This effect was not associated with a reduction in the effects of norepinephrine on these cells nor a blockade of the potassium channels underlying the calcium-dependent afterhyperpolarization responsible or significant changes in membrane potential. These results suggest that QX-314 is an effective blocker of G-protein-gated potassium channels in this region.
The cerebral cortex receives a prominent cholinergic innervation which is thought to play an important role in regulating its normal function. Electrophysiological studies have shown that activation of cholinergic receptors results in a marked enhancement of excitatory stimuli onto cortical neurons and it has been suggested that this effect is secondary to the blockade of several voltage- and calcium-dependent potassium conductances in these cells. It is reported here that, in addition to these effects, activation of muscarinic receptors in the prefrontal cortex elicits the appearance of a slow calcium-dependent inward current in response to the generation of action potentials. This inward aftercurrent produces a slowly decaying depolarizing afterpotential which, when activated by stimulation of the cell, can summate with the carbachol-induced depolarization greatly increasing its magnitude. As a result the ability of muscarinic receptor to elicit a depolarization and excite cells in this region can be dramatically potentiated by evoked cell activation. This effect expands the range of mechanisms by which muscarinic receptors can facilitate excitatory inputs and provides a mechanism by which the association of brief excitatory stimuli to cholinergic stimulation can selectively enhance muscarinic responses among discrete cell populations in the cerebral cortex.
The effects of serotonin on pyramidal cells of layer V of the medial prefrontal cortex were examined using intracellular recording techniques in rat brain slices in vitro. Bath administration of serotonin (0.3-100 microM) produced two distinct responses which could be differentiated physiologically and pharmacologically. The first of these responses was a membrane hyperpolarization. This effect of serotonin was associated with a decrease in input resistance and was independent of the transmembrane chloride gradient, suggesting that it was mediated by an increase in potassium conductance. The ability of serotonin to induce a hyperpolarization was mimicked by (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and was blocked by BMY 7378 and spiperone but not by ketanserin, indicating that it was mediated by the activation of receptors of the 5-hydroxytryptamine1A subtype. The second response to serotonin involved a membrane depolarization, the replacement of the afterhyperpolarization that follows a burst of spikes in these cells by a slow depolarizing afterpotential, and a decrease in spike frequency accommodation. These effects were mimicked by 4-bromo-2,5-dimethoxyphenyl-isopropylamine and antagonized by ketanserin and by low concentrations of spiperone, indicating that they were mediated by the activation of 5-hydroxytryptamine2 receptors. Interestingly, qualitatively identical responses could be elicited in these cells by activation of muscarinic and alpha 1-adrenergic receptors suggesting that 5-hydroxytryptamine2, muscarinic and alpha 1-adrenergic receptors converge onto a common set of membrane mechanisms to increase cellular excitability. Although 5-hydroxytryptamine1A and 5-hydroxytryptamine2 receptors mediated opposing effects on membrane excitability, most pyramidal neurons appeared to express both receptor subtypes on their membrane surface. The coactivation of both receptor subtypes resulted in a selective enhancement of responsiveness to strong excitatory stimuli with little effect on weaker stimuli. The paradoxical presence of two serotonin receptors mediating opposite effects on membrane excitability in the same cell provides a flexible mechanism by which serotonin might regulate how pyramidal neurons encode incoming excitatory stimuli onto firing activity.
Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) alpha, beta and gamma chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, delta, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the delta chain gene locus, using probes of the variable, joining, and constant regions of the delta chain gene. The majority of precursor B cell ALLs in this series (25/32, 78%) showed rearrangement or deletion of one or more TCR delta genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR delta gene rearrangements were detected. An unusual TCR delta rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR delta rearrangements. In contrast to the utilization ov V delta 1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of J delta segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive V delta 2-D delta 2-D delta 3 recombination in this precursor B ALL. We conclude that the TCR delta chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL.
Explore the source record for details and available documents.
318 records of male workers, 169 Spanish and 149 Arab were retrospectively studied in 1987 at the "Gabinete de Seguridad e Higiene en el Trabajo" (Council for Safety and Hygiene in the Workplace) in Ceuta in order to prove the hypothesis that 2 different ethnic groups living in the same geographic area have a non-equal distribution of cardiovascular risk factors. The Spanish group showed a higher prevalence in blood hypertension, diabetes, glucose intolerance, obesity and alcohol intake, compared to the Arab group. Smoking and high levels of seric cholesterol were similar in both groups, however, medium levels of seric cholesterol were lower in the Arab group. Family histories of cardiovascular disease were very rare in the latter mentioned group. These observations suggested a major predisposition to ischemic cardiopathy in the Spanish group.
Hippocampal pyramidal neurons of the CA1 region express 5-hydroxytryptamine (serotonin, 5-HT) receptors which, upon activation, elicit a slow membrane depolarization and a decrease in the calcium-activated afterhyperpolarization present in these cells. Previous electrophysiological studies have shown that this receptor(s) exhibits a pharmacological profile similar to that of the 5-HT1p, 5-HT3 and 5-HT4 subtypes. In the present study, intracellular recordings in rat brain slices were used in order to examine the effects of a variety of compounds that distinguish between these receptor subtypes. Administration of 5-HT in the presence of a 5-HT1A receptor antagonist elicited a depolarization and a concentration-dependent reduction in the amplitude of the afterhyperpolarization. These effects were mimicked by 5-methoxytryptamine and 5-carboxyamidotryptamine but not by 2-methyl-5-HT or phenylbiguanide. Administration of the benzamides BRL 24924, zacopride and cisapride blocked the responses to 5-HT with micromolar affinity although, in a small proportion of the cells tested, BRL 24924 was found to exhibit some agonist activity. This suggests that these compounds function as weak partial agonists in the rat hippocampus. These results establish clear differences between the 5-HT receptor(s) mediating the depolarization and reduction in the afterhyperpolarization in the hippocampus and the 5-HT3 and 5-HT1p receptors and suggest its classification in the 5-HT4 class. Thus, 5-HT4 receptors appear capable of mediating slow excitatory responses to 5-HT in the brain.
Administration of serotonin (5-hydroxytryptamine, 5-HT) to pyramidal cells of the CA1 region of the hippocampus results in a hyperpolarizing response which is followed by a rebound depolarization and a decrease in the calcium-activated afterhyperpolarization (AHP). While the hyperpolarizing response has been previously shown to be mediated by receptors of the 5-HT1A subtype, the identity of the receptor(s) involved in the depolarizing response and decrease of the AHP have not been identified. In the present study the effectiveness of a series of 5-HT receptor antagonists in blocking the membrane depolarization and reduction of the AHP was assessed. While a variety of 5-HT1 and 5-HT2 antagonists were found to be ineffective, the substituted benzamide BRL 24924 was found to be a potent and selective antagonist of the 5-HT-induced depolarization and decrease in the AHP in this region. This effect however appeared unrelated to the ability of this compound to block 5-HT3 receptors, as ICS 205-930 and MDL 72222 were markedly less efficacious in blocking these effects of 5-HT. Upon blockade of 5-HT1A receptors, 5-HT elicits a depolarization which is accompanied by a marked increase in excitability. These effects were also dose-dependently antagonized by BRL 24924. The present results thus suggest the presence in the CA1 region of the hippocampus of a novel 5-HT receptor at which BRL 24924 functions as a selective antagonist and which is capable of mediating slow excitatory responses in central neurons.
The rearranging antigen receptor genes of lymphoid cells serve as unique clonal markers of lymphoid neoplasms. Gene rearrangement analysis is a highly sensitive and reproducible tool which is useful in the diagnosis and classification of malignant lymphoma/leukemia. Although clonality can often be determined among B cell neoplasms by virtue of immunoglobulin isotype analysis, no such phenotypic marker of clonality exists for T cells. Therefore, clonality of T lymphoproliferative processes is most readily determined by rearrangement analysis of the T cell antigen receptor genes. The alpha, beta, gamma, and delta genes of the T cell receptor gene family encode heterodimeric surface antigen receptors and undergo rearrangement early in T cell differentiation. Identification of rearrangement of T cell antigen receptor genes provides valuable diagnostic information concerning cellular lineage, clonality and classification of T cell neoplasms. This molecular approach is applicable to the diagnosis of occult disease, relapse, and resolution of diagnostic dilemmas in any type of tissue sample including fluids and needle aspirations.
The distribution of apoprotein E phenotypes in a randomly chosen population sample of Málaga was compared to other published studies performed in other countries, observing minimal differences in Caucasian populations but significant differences with oriental ethnic groups. Cholesterol and triglyceride plasma levels were not significantly different in the different apo E phenotypes. A high proportion of subjects (26%) with hydrocarbon metabolism abnormalities (diabetic and glucose intolerant) was observed in phenotype E4/3 and very low (4.7%) in phenotype E3/2. The study of plasma triglyceride levels which were higher in the diabetic group, revealed a greater increase in phenotype E4/3 than in E3/3. These results support the idea about the complex relationship that exists between apo E phenotypes and some cardiovascular risk factors.
We analyzed the gene rearrangements associated with the newly described delta T-cell receptor (TCR) gene from a series of 19 consecutive precursor T-cell (lymphoblastic) neoplasms that represent discrete stages surrounding the TCR gene rearrangement process. Significantly, the delta TCR gene showed rearrangement in most (13 of 19) of these T cells, and in addition it was rearranged in two cells displaying no rearrangement for any other TCR gene. Our survey showed three types of delta gene rearrangements associated with cell-surface TCR expression that presumably represent usage of three V delta genes. This analysis demonstrates (1) a major subclass of human precursor T-cell neoplasms belonging to the gamma/delta T-cell receptor-rearranging subtype; (2) a narrow repertoire of human V delta gene usage; and (3) the utility of delta gene rearrangements as a diagnostic clonal marker in precursor T lymphoblastic neoplasms.