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Biomedical subjects

R Andrade

Publications and source records attributed to R Andrade.

At least 55 records · Page 3Linked to original sources

S-100-positive T-cell lymphoproliferative disorder. A case report and review of the literature.

The authors describe a patient with a S-100-positive T-cell lymphoproliferative disorder, characterized by clinically aggressive behavior, with leukemic dissemination and death within 1 year of the onset of symptoms. The neoplastic cells had abundant amphophilic cytoplasm, suggestive of plasmacytoid differentiation, but demonstrated a mature T-cell immunophenotype characteristic of the suppressor-cytotoxic subset. In addition, the cells expressed the S-100 protein within the cytoplasm. Genotypic studies were performed by Southern blot analysis, which demonstrated beta-chain T-cell receptor gene rearrangement, further confirming the T-cell nature of this disorder. This case had features very similar to those of the seven cases previously reported. It has been proposed that the S-100-positive T-cell lymphoproliferative disorder is a distinctive clinicopathologic entity.

Adult↗

[Intracranial cavernous angioma].

Clinical, radiological and histopathological features of eight cases of symptomatic cavernous angioma are presented. Five patients were being evaluated for seizure, two for mass lesions and one for intracranial hemorrhage. CT and/or MRI detected the lesion in all cases, but there is not a characteristic image for cavernous angioma. Good results were obtained by microsurgical approach to these malformations in seven patients with only one patient suffering a worsening of neurological status after surgery.

Adolescent↗

Antagonists of 5-HT4 receptor-mediated responses in adult hippocampal neurons.

The study of serotonin-4 (5-HT4) receptors in the central nervous system has been hindered by the lack of effective, selective antagonists. However, recently, several novel compounds have been synthesized and shown to act as antagonists at 5-HT4 receptors in smooth muscle and embryonic neurons in culture. In the present study, intracellular electrophysiological recordings were used to test the effects of three of these compounds: endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-6-methoxy- 2-oxo-1H-benzimidazole-1-carboxylate (DAU 6285), [1-[2-(methylsulfonylamino)ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate (GR 113808) and 2-diethylaminoethyl-(2-methoxy-4-amino-5-chloro) benzoate (SDZ 205-557) on the 5-HT4 reduction of the afterhyperpolarization seen in adult CA1 hippocampal neurons in brain slices. GR 113808, SDZ 205-557 and DAU 6285 all functioned as competitive antagonists at these 5-HT4 receptors. Although all three compounds tested acted as effective antagonists, they differed considerably in potency. When the potency of these antagonists at the 5-HT4 receptor that mediates the reduction of the afterhyperpolarization was compared with that observed for 5-HT4 receptors in biochemical and binding assays, an excellent correlation was observed. Among the antagonists tested, GR 113808 was the most potent (pA2 = GR 113808 > SDZ 205-507 > DAU 6285). It exhibited an apparent affinity for the 5-HT4 receptors in the low nanomolar range but did not antagonize 5-HT1A, beta-adrenergic or muscarinic receptor-mediated responses when applied at concentrations two orders of magnitude higher.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobenzoic Acid↗

Unilateral pterional approach to bilateral cerebral aneurysms.

Between 1976 and 1991, we determined that 19 patients harboring bilateral supratentorial aneurysms should be approached in a single sitting through a unilateral pterional craniotomy. Using microsurgical techniques, the Sylvian cistern was opened widely to expose the aneurysms located ipsilateral to the craniotomy. These aneurysms were clipped in the usual fashion. Following clipping, a tunnel was developed over the contralateral anterior cerebral artery and over or under the contralateral optic nerve allowing access to the opposite carotid and middle cerebral arteries. The contralateral nonruptured aneurysms were clipped in a routine fashion. We were able to clip or wrap with muscle all bilateral aneurysms in 15 cases, and we have concluded that this approach can be safely employed in selected patients with bilateral supratentorial aneurysms, and thus a second craniotomy can be avoided.

Adult↗

Enhancement of beta-adrenergic responses by Gi-linked receptors in rat hippocampus.

Many excitable cells express a class of neurotransmitter receptors functionally defined by their ability to increase potassium conductance through G proteins of the Gi/G(o) class that directly activate the potassium channels. Biochemical studies have shown that these same receptors can also inhibit forskolin-stimulated adenylyl cyclase, although the functional significance of this effect remains unclear. In this study electrophysiological techniques were used to examine how activation of serotonin and gamma-aminobutyric acid receptors belonging to this class affect beta-adrenergic responses signaled through adenylyl cyclase. Surprisingly, activation of these receptors not only failed to inhibit but actually enhanced beta-adrenergic responses. These observations are consistent with evidence indicating that Gi-linked receptors can enhance the ability of Gs to stimulate certain adenylyl cyclases.

Adenylyl Cyclases↗

Pulmonary perfusion during lung transplant rejection and experimental pneumonia.

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.

Animals↗

Effect of injection sclerosis with alcohol on the rebleeding rate of gastroduodenal peptic ulcers with nonbleeding visible vessels: a prospective, controlled trial.

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.

Adult↗

Blockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus.

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.

Animals↗

Cell excitation enhances muscarinic cholinergic responses in rat association cortex.

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.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

5-Hydroxytryptamine2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association 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.

Animals↗

A common V delta 2-D delta 2-D delta 3 T cell receptor gene rearrangement in precursor B acute lymphoblastic leukaemia.

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.

Base Sequence↗