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Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 181 records · Page 10Linked to original sources

[Hepatitis C epidemiology in the central area of Portugal. Prevalence of anti-HCV in the population of the district of Coimbra].

Anti-hepatitis C virus antibody (anti-HCV) screening was performed in a sample of the adult population of the Coimbra District. 657 persons were included (267 male and 390 female, mean age of 42.7 +/- 13.1 years), aleatorily chosen from four characteristic councils. Anti-HCV was detected using an ELISA-2 test and all positive sera were also tested with RIBA-2. General prevalence of anti-HCV was 0.46%. All positive patients live in urban areas and presented risk factors for HCV infection. Anti-HCV was found in 33.3% of intravenous drug abusers, in 1.8% of transfused individuals, in 1.33% of alcoholics (higher than 80 g/d alcohol ingestion), in 1% of cases with history of surgical operations, and in 0.65% of persons who lived in risk regions for hepatitis B. We conclude that anti-HCV prevalence is low in our region. We think it is important to perform other studies in larger samples of general population and to study risk groups.

Adult↗

Thyroid hormone up-regulates NGFI-A gene expression in rat brain during development.

NGFI-A is an immediate-early response gene induced by signals that initiate growth and differentiation. Its mRNA encodes a sequence-specific transcriptional activator possibly implicated in the control of brain developmental processes. Due to the essential role of thyroid hormone for a correct brain development, we have now investigated the possible regulation by 3,5,3'-triiodo-L-thyronine (T3) of NGFI-A gene expression during maturation of the central nervous system. Our results indicate that expression of mRNA encoding NGFI-A transcription factor is about 8-fold decreased in the brain of neonatal hypothyroid rats. No changes were seen when hypothyroidism was induced in adult life. T3 treatment increased NGFI-A mRNA within 1 h, suggesting that thyroid hormone effect is likely to be a direct one. These data indicate a strong regulation by thyroid hormone of the expression of the growth factor inducible gene NGFI-A during brain development, making this gene a suitable model to study T3 action in the early developing nervous system.

Animals↗

Effects of analogs of 1,25(OH)2 vitamin D3 on the proliferation and differentiation of the human chronic myelogenous leukemia cell line, RWLeu-4.

We evaluated the proliferative and differentiative effects of analogs of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] on a chronic myelogenous leukemia cell line, RWLeu-4, which is growth-inhibited and differentiates in response to 1,25(OH)2D3 (ED50 = 3-10 nM). Side-chain-fluorinated analogs were more potent (ED50 = 0.7-2 nM) while most of those with altered saturation of the D ring or side-chain carbon-carbon bonds were equally or less effective than 1,25(OH)2D3. However, the two analogs with either two additional double bonds or an extra double and triple bond in the D ring had greater antiproliferative activity [1,25(OH)2-16,23-diene D3 (ED50 = 2.7 nM) and 1,25(OH)2-16-ene-23-yne D3 (ED50 = 0.7 nM)]. Since the latter of these has been reported to be less potent at mobilizing calcium than 1,25(OH)2D3, it (or a similar compound) may be a candidate for clinical use as an antineoplastic agent.

Antigens, CD↗

Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome.

The Denys-Drash syndrome is characterised by a typical nephropathy, genital abnormalities and also predisposes to the development of Wilms' tumor. These patients eventually go into end stage renal failure. A candidate Wilms' tumor gene, WT1, from the 11p13 chromosome region has recently been cloned. We have analysed the DNA sequence in constitutional cells from eight patients and have shown heterozygous mutations in six of them. Four of the mutations were in exon 9, all resulting in missense mutations. Three were at nucleotide position 1180 resulting in an arg > trp amino acid change. The other was at position 1186 converting an asp > asn in the predicted resultant protein. One patient had a missense mutation in exon 8, converting an arg > his. A single base pair insertion at nucleotide position 821 in exon 6 resulted in the generation of a premature stop codon in the last patient. We were unable to find a mutation in one patient despite complete sequencing of the genomic sequence of the gene. The last patient carried a constitutional deletion of the 11p13 region and no additional mutation was found. There was no obvious correlation between the type of mutation and phenotypic expression. These results further demonstrate that the WT1 gene is important in both the development of the kidney and the genito-urinary system.

Base Sequence↗

4'-epidoxorubicin versus mitomycin C intravesical chemoprophylaxis of superficial bladder cancer.

The authors report the preliminary data concerning a phase III study comparing the chemoprophylactic effects of mitomycin C and epirubicin in Ta-T1 primary and recurrent superficial bladder tumors. 60 patients were treated, 32 with epirubicin and 28 with mitomycin C, with a medium follow-up of 17.7 and 16.2 months, respectively. There were no systemic side effects. The remission rate was 62.5% in the epirubicin group and 64.2% in the mitomycin C group. Both drugs were equally useful in the chemoprophylaxis of superficial bladder cancer.

Administration, Intravesical↗

Bacterial single-chain antibody fragments, specific for carcinoembryonic antigen.

We have produced single-chain antibody (scFv) fragments in bacteria specific for carcinoembryonic antigen (CEA). Polymerase chain reaction (PCR) was used for the cloning and modification of the heavy and light variable regions (VH and VL) of the mouse monoclonal antibody (MAb) CB-CEA.1. A 14-amino acid linker was used in the synthesis of the scFv gene. The VH and VL regions were amplified from cDNA by PCR using 5' end FR1 and 3' end constant region primers, and then sequenced. VH was then amplified by PCR using an exact 5' end FR1 primer, and a phosphorylated (PP) 3' end primer for J2 that also encoded the first 7 amino acids of the linker. VL was amplified with a PP 5' end primer for FR1, also encoding the remaining 7 amino acids of the linker, and a 3' end primer for J5, plus a stop codon and a BglII restriction site. The fragments were ligated and reamplified with the PP VH 5' and VL 3' end primers. The VH-linker-VL structure was blunt-cloned into expression vectors bearing the tryptophan promoter and pelB or ompA signal peptide sequences. Culture supernatant, bacteria pellet and periplasm preparations were assayed in Western blot and a protein of about 27 kDa was identified with rabbit antibodies specific for the Fab of CB-CEA.1. Bacterial supernatant and periplasm preparations also inhibited the recognition of CEA by HRP-labeled CB-CEA.1 in enzyme-linked immunosorbent assay (ELISA). Periplasm preparations were purified by affinity chromatography with specific anti-idiotypic MAbs. The Western blot of the eluates identified a protein of approximately 27 kDa that blocked the recognition of CEA by HRP-labeled CB-CEA.1 in ELISA. The VH-linker-VL structure was cloned into a vector bearing the lacZ promoter and the pelB signal peptide. The recombinant bacterial clones also expressed about 27 kDa scFv, specific for CEA.

Amino Acid Sequence↗

[Usefulness of studies of susceptibility of ampicillin, carbenicillin, cefalotin and colistin as a presumptive identification system for the Aeromonas sp. group].

We have studied the restricted antibiotic susceptibility tests for 180 strains belonging to mesophilic Aeromonas sp. isolated from stools samples. Strains has been identified as follows: A. caviae (64.6%), A. hydrophila (17.7%) and A. sobria (17.7%). Antibiotics tested were ampicillin (10 micrograms), carbenicillin (100 micrograms), cephalotin (30 micrograms) and colistin (10 micrograms), by means of agar diffusion tests (disk-plate). We identified four different patterns of antibiotic susceptibility. The most frequent pattern (pattern #1) (77.8%) is characterized by susceptibility only to colistin, and was predominant among A. caviae strains (80%). Pattern #2 (susceptibility to cephalotin and colistin) was found in 18.9% of strains, being predominant in A. sobria (88.2%). We confirm the higher susceptibility of A. sobria sp. to cephalotin as well as the possibility that these different patterns might be used as screening method for species identification among mesophilic group of Aeromonas.

Aeromonas↗

Independent expression of the alpha and beta c-erbA genes in developing rat brain.

Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.

Age Factors↗

Genotypic dependency of spontaneous yawning frequency in the rat.

By inbreeding we have obtained two sublines of Sprague-Dawley rats which differ significantly in spontaneous mean yawning frequency (MYF). In generation F21 of the high-yawning (HY) subline MYF was 21.5 yawns/h (y/h) in males and 1.95 y/h in females, at the age of 2 months. In the low-yawning (LY) subline, in generation F16 the MYF was 0.9 y/h in males and only 0.5 y/h in females. During the first 15 days there are no differences in yawning frequency between HY and LY rats. Thereafter yawning increases with age, more steeply in the HY subline. The results of reciprocal crosses between both sublines indicate that the LY character is partially dominant over the HY one.

Age Factors↗

[Arterial hypertension associated with hyperlipoproteinemia].

Hypertension and serum cholesterol levels are strongly interrelated as cardiovascular risk factors. The Framingham study showed that the risk of both ischaemic heart disease and brain infarction doubles in presence of mild hypertensive status and triplicates in presence of a definitive hypertension. The systolic pressure showed to be the best predictor of both ischaemic heart disease and cerebral infarction particularly in persons aged more than 65 years. In terms of physiopathology we point out several mechanisms by which hypertension could interact with hypercholesterolemia on the arterial wall causing endothelial lesion, enhancing the penetration of arterial wall by lipoproteins, calcium accumulation on smooth subendothelial muscle and suppression of the relaxation factor produced by endothelial cells. In relation to the dietetic treatment, we must restrict more rigorously the ingestion of salt, saturated fatty acids, and total calories. In terms of anti-hypertensive drugs, we should: Avoid thiazide diuretics in case of cholesterol levels of moderate to high risk. Avoid beta blockers in patients with high levels of triglycerides, low HDL and low ratio total cholesterol/HDL. Consider to choose a calcium antagonist, a converting enzyme or an alpha blocker.

Humans↗