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Biomedical subjects

A Tavares

Publications and source records attributed to A Tavares.

At least 37 records · Page 2Linked to original sources
PubMed1996

Localization of alpha 2A- and alpha 2B-adrenergic receptor subtypes in brain.

Recent studies have shown that all three subtypes of alpha2-adrenergic receptor (alpha2-AR) are found in brain. The purpose of this study was to map the subtype localization of the alpha2A- and alpha2B-ARs in brain structures. RNase protection shows that both the alpha2A- and alpha2B-ARs are detectable in cortex, cerebellum, pons-medulla, and hypothalamus. We tested probes derived from the alpha2A- and alpha2B-AR cDNAs on cell lines that express each of the alpha2-AR subtypes to establish the subtype specificity of these probes for in situ hybridization. Then we used the alpha2A- and alpha2B-AR probes for in situ hybridization on sagittal and coronal sections of rat brain. Both alpha2A and alpha2B mRNA were detected throughout the brain. Overall, there appears to be a greater expression of message for alpha2A- than alpha2B-AR in most brain areas, with the exception of the thalamus. Developing these probes for in situ hybridization is an important step for further studies on the exact role of the alpha2-AR subtypes in neurons that modulate cardiovascular function.

Animals↗
PubMed1996

[Clinical and laboratory characteristics of 62 tuberculous meningoencephalitis cases].

The authors present clinical, demographic and laboratory characteristics of 62 patients with proven tuberculous meningoencephalitis admitted at Couto Maia Hospital, reference for patients with infectious diseases in the State of Bahia. The patients' age varied from 2 months to 50 years, 59.7% of the cases with ages ranging from 0 to 4 years, no sex predominance. The time length for the disease varied from 0 to 90 days, average around 13 days. The most common signs and symptoms were fever and neck stiffness in 86.7 and 81.8% of the cases respectively. The cerebrospinal fluid showed cells varying from 4 to 1549/mm3, average of 406; glucose from 20 to 70 mg/dL, average of 37.3, protein from 30 to 500 mg/dL, average of 203; lymphocyte predominance occurred in most cases, however in 21.3% there was predominance of neutrophils.

Adolescent↗
PubMed1995

A negative regulatory element in the promoter region of the rat alpha 2A-adrenergic receptor gene overlaps an SP1 consensus binding site.

Three subtypes of alpha 2-adrenergic receptors (alpha 2A, alpha 2B and alpha 2C) have been described that differ in their primary sequence and tissue-specific expression and are encoded by three distinct genes. Previous work has shown that the human alpha 2A-adrenergic receptor gene promoter consists of a TATA-box (TATAAA), palindromic sequence (CCCACGTGGG) and GC-box (GGGGCGG) motif. Sequence analysis of the putative promoter region of the rat alpha 2A-adrenergic receptor gene showed that these promoter regions are conserved in their sequence and relative location. We analysed the transcriptional activity of these regions using RINm5F, a rat insulinoma cell line that expresses the endogenous alpha 2A-adrenergic receptor gene. These results showed that the region from -484 to -92 has a negative effect on transcription, as deletion of this region in alpha 2A-adrenergic receptor gene-chloramphenicol acetyltransferase reporter constructs increased reporter gene activity. This region included the GC-box sequence which is a consensus binding site for the nuclear factor SP1, which is a positive activator of transcription. Gel-mobility-shift assays and supershift assays with an antibody that recognizes SP1 showed binding of the SP1 nuclear factor as well as other nuclear factors to this GC-box region. Additional nuclear factors bind to the downstream palindromic region. We suggest that positive- and negative-acting nuclear factors contribute to the activity of the alpha 2-adrenergic receptor promoter.

Animals↗
PubMed1995

Characterization of a splicing mutation in the factor VIII gene at the RNA level.

Haemophilia A is an X-linked bleeding disorder caused by mutations in the coagulation factor VIII (FVIII) gene. The identification and characterization of naturally occurring disease-producing mutations allows the recognition of new mechanisms of pathogenesis in haemophilia A. Analysis of the illegitimately transcribed FVIII mRNA in a severely affected patient has revealed that the A-->G transition at position -2 of the acceptor splice site of intron 4 results in the skipping of exon 5 in 90% of the processed pre-mRNA. Another minor mRNA species arising from the skipping of exons 4 and 5 has also been observed. The skipping of exon 5 predicts the removal of the corresponding 13 amino acids from the A1 domain of FVIII. A novel missense mutation, C329S, in exon 8 of FVIII gene has been identified in another patient.

Base Sequence↗
PubMed1995

Role of bradykinin in insulin sensitivity and blood pressure regulation during hyperinsulinemia.

The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.

Animals↗
PubMed1995

Cardiovascular effects of a specific nonpeptide antagonist of substance P (NK-1) receptor in DOCA-salt hypertension.

The neurotransmitter substance P acts also as a potent vasodilator. Its participation in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt hypertension was evaluated by an acute infusion of a newly synthesized, potent, specific nonpeptide antagonist of substance P at the NK-1 receptor, the agent CP 96,345. In conscious unrestrained rats, CP 96,345 induced significant and sustained increases in mean arterial pressure of DOCA-salt rats but only small, transient, and nonsignificant rises in blood pressure of sham-treated control rats. The rise in blood pressure was not accompanied by changes in heart rate. Maximal blood pressure increase in DOCA-salt rats was 31.7 +/- 14.8 mm Hg. In a second series of experiments, the hemodynamic effects of this antagonist were evaluated under anesthesia in both DOCA-salt and sham-treated control rats by the thermodilution method. During CP 96,345 infusion, sustained increases in cardiac index and stroke volume and decreases in total peripheral resistance were observed in both DOCA-salt and control rats. In DOCA-salt rats, cardiac index rose by 79.4%, while total peripheral resistance fell by 27.9% of the baseline values. In control rats, the changes were smaller (+27.2% and -22.5%, respectively). Stroke volume changed in parallel to cardiac output in both groups. The data suggest that acute blockade of NK-1 receptors increases blood pressure in DOCA-salt rats mainly by an increase in cardiac output. We conclude that endogenous substance P tends to counteract the DOCA-salt-induced elevation of blood pressure by modulating both cardiac output and peripheral resistance.

Animals↗
PubMed1992

Severe hypertension induces disturbances of renal autoregulation.

To study if the severity of hypertension could be associated with disturbances of the autoregulation of renal blood flow and glomerular filtration, we compared the renal hemodynamic and functional responses to acute blood pressure reductions of a group of patients with moderate essential hypertension (n = 10) with those of a group of patients with severe hypertension (n = 10). Blood pressure was reduced to normal levels by a stepwise infusion of sodium nitroprusside, and effective renal blood flow (by 131I-hippuran), glomerular filtration rate (by endogenous creatinine clearance), and filtration fraction were determined. After acute blood pressure normalization, effective renal blood flow and glomerular filtration rate were significantly reduced in patients with severe hypertension (-41.6 +/- 8.3% and -44.7 +/- 6.8%, respectively; p less than 0.01 for both) but not in those with moderate hypertension (+4.9 +/- 9.1% and +6.2 +/- 13.3%, respectively; NS). Filtration fraction remained unchanged in both groups. These results show that severe but not moderate essential hypertensive patients have a displacement to the right of the lower limit of the renal autoregulation curve due to impaired vasodilation to maintain adequate renal blood flow during acute reductions of blood pressure. This impairment may be due to anatomic or functional defects of preglomerular vessels, or to both. Furthermore, the inability to maintain adequate glomerular filtration in these circumstances shows that patients with severe hypertension also have an impaired ability to adjust postglomerular vasomotor tone in the face of reductions in glomerular blood flow.

Adolescent↗
PubMed1992

[Safety in hemophilia A treatment. Viral inactivation of FVIII:C concentrates].

In the last thirty years, factor VIII concentrates have been the mainstay of hemophilia treatment, first as wet cryoprecipitate and later as dry concentrates commercially available. The evidence of a high risk of blood-born virus transmission by these products provoked the development of new methods for virus inactivation. We report these methods with special attention to their safety, and mention the new perspectives of treatment with recombinant DNA FVIII:C and ultimately by gene insertion therapy.

Factor VIII↗
PubMed1992

[Methods for preserving bone marrow for autologous transplantation].

For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.

Adolescent↗
PubMed1991

polo encodes a protein kinase homolog required for mitosis in Drosophila.

We show that mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed; normal bipolar spindles with polyploid complements of chromosomes; bipolar spindles in which one pole can be unusually broad; and monopolar spindles. We have cloned the polo gene from a mutant allele carrying a P-element transposon and sequenced cDNAs corresponding to transcripts of the wild-type locus. The sequence shows that polo encodes a 577-amino-acid protein with an amino-terminal domain homologous to a serine-threonine protein kinase. polo transcripts are abundant in tissues and developmental stages in which there is extensive mitotic activity. The transcripts show no obvious spatial pattern of distribution in relation to the mitotic domains of cellularized embryos but are specifically concentrated in dividing cells in larval discs and brains. In the cell cycles of both syncytial and cellularized embryos, the polo kinase undergoes cell cycle-dependent changes in its distribution: It is predominantly cytoplasmic during interphase; it becomes associated with condensed chromosomes toward the end of prophase; and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic.

Amino Acid Sequence↗
PubMed1991

Demonstration of three calpains in the matrix of rat liver mitochondria.

Three distinct Ca(2+)-activated proteolytic activities could be proven in rat liver mitochondria. The proteolytic activities detected in the presence of Ca2+ are different in the two mitochondrial soluble compartments, the matrix and the intermembrane space. Strikingly three Ca(2+)-activated proteolytic activities (M1, M2 and M3) appear in the matrix whereas the intermembrane space contains only two such activities. These proteolytic activities are similar to the calpains already described in the cellular cytosol with regard to their optimal pH and inhibition profiles. The Ca2+ requirements for activation of M1 and M2 correspond to those of the micromolar and millimolar Ca(2+)-requiring proteinases, whereas the concentration of Ca2+ required to activate M3 is an intermediate value.

Animals↗
PubMed1988

Pindolol, not propranolol, reverses cardiac hypertrophy in renal hypertensive rats.

Reversal of cardiac hypertrophy has been obtained by treatment with some antihypertensive drugs but has not been achieved consistently with beta blockers. To investigate whether this difference might be explained by the distinct hemodynamic actions of the drugs, we studied the effects of propranolol and pindolol, beta blockers with distinct modes of action, on cardiac hypertrophy of hypertensive male Wistar rats, two-kidney, one clip (2K1C) Goldblatt model (n = 33) and sham-operated control rats (n = 34). We also assessed the effects of such therapies on the ventricular pumping ability during open-chest, transient aortic occlusion. Four weeks after surgery, propranolol (5 mg/kg/day p.o.) was given to hypertensive (n = 8) and control rats (n = 11); pindolol was also given orally (1 mg/kg/day) to similar groups (n = 7 and n = 5, respectively). Untreated animals served as controls for both groups. Cardiac hypertrophy developed with hypertension in the untreated rats of the propranolol (3.38 +/- 0.18 vs 2.60 +/- 0.08 mg/g; p less than 0.01) and pindolol groups (3.93 +/- 0.21 vs 2.40 +/- 0.03 mg/g; p less than 0.001). Treatment reversed cardiac hypertrophy in the pindolol-treated (3.01 +/- 0.19 vs 3.93 +/- 0.21 mg/g; p less than 0.001, NS) but not in the propranolol-treated rats (3.24 +/- 0.18 vs 3.38 +/- 0.21 mg/g, NS). The maximal pressure that developed during aortic occlusion in the propranolol group was similar to that observed in the pindolol group. These results indicate that cardiac hypertrophy is reversed by pindolol but not by propranolol, and that this reversal does not interfere with left ventricular pumping ability.

Animals↗
PubMed1987

31P-NMR study of the orotate phosphoribosyltransferase equilibrium with thiopyrophosphate as substrate.

31P-nuclear magnetic resonance spectroscopy was used to directly determine the equilibrium of the reaction catalysed by yeast orotate phosphoribosyltransferase, using orotidine monophosphate and inorganic pyrophosphate as substrates. A Keq value of 0.71 was determined, in good agreement with that of 0.49 calculated by Victor, Greenberg and Sloan (J. Biol. Chem. 254 (1979) 2647-2655), from kinetic data. Substitution of thiopyrophosphate as the substrate shifted the position of the equilibrium 55-fold, to yield a Keq value of 39. Only the beta S analogue of 5-phosphoribosyl 1-diphosphate appeared to be synthesized in this reaction.

Diphosphates↗