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Biomedical subjects

L Santos

Publications and source records attributed to L Santos.

At least 55 records · Page 3Linked to original sources
PubMed2001

Role of macrophage migration inhibitory factor (MIF) in murine antigen-induced arthritis: interaction with glucocorticoids.

(MIF) is a broad-spectrum proinflammatory cytokine implicated in human rheumatoid arthritis. The synthesis of MIF by synovial cells is stimulated by glucocorticoids, and previous studies suggest that MIF antagonizes the anti-inflammatory effects of glucocorticoids. This has not been established in a model of arthritis. We wished to test the hypothesis that MIF can act to reverse the anti-inflammatory effects of glucocorticoids in murine antigen-induced arthritis (AIA). Cutaneous DTH reactions and AIA were induced by intradermal injection and intra-articular injection, respectively, of methylated bovine serum albumin in presensitized mice. Animals were treated with anti-MIF MoAbs, recombinant MIF, and/or dexamethasone (DEX). Skin thickness of DTH reactions was measured with callipers and arthritis severity was measured by blinded quantitative histological assessment of synovial cellularity. Cutaneous DTH to the disease-initiating antigen was significantly inhibited by anti-MIF MoAb treatment (P < 0.001). AIA was also significantly inhibited by anti-MIF MoAb (P < 0.02). DEX treatment induced a dose-dependent inhibition of AIA, which was significant at 0.2 mg/kg (P < 0.05). MIF treatment reversed the effect of therapeutic DEX on AIA (P < 0.001). DEX also significantly inhibited DTH reactions (P < 0.05) but rMIF had no effect on this effect of DEX. DTH and AIA are MIF-dependent models of inflammation and arthritis. The reversal of glucocorticoid suppression of AIA by MIF supports the concept that MIF is a counter-regulator of glucocorticoid control of synovial inflammation. Although DTH was observed to be MIF-dependent and glucocorticoid-sensitive, rMIF had no reversing effect on the suppression of DTH by glucocorticoids. This suggests that inflammatory processes in specific tissues may respond differently to MIF in the presence of glucocorticoids.

Animals↗
PubMed2001

'Imi Hale: establishing an inheritance for Native Hawaiians on cancer awareness, research and training.

Native Hawaiians experience disproportionate rates of cancer incidence and mortality both nationally and in their homeland, Hawai'i. 'Imi Hale--the Native Hawaiian Cancer Awareness, Research, and Training Project, a five-year project funded by the National Cancer Institute, is aimed at reducing the burden of cancer among Native Hawaiians. The project's overall goal is to reduce cancer incidence and mortality among Native Hawaiians through the establishment of a sustainable infrastructure to 1) promote cancer awareness within Native Hawaiian communities, and 2) initiate cancer research, training, and control activities. A community-based project, 'Imi Hale emphasizes community participation, respect for cultural values, and the sharing of information, as we believe that a commitment to involve Native Hawaiians in all activities of the project will help assure that the community's awareness, training, and research priorities are addressed. In the first year of operation, cancer awareness activities included the development of culturally sensitive booklets on breast cancer and the provision of cancer education and screening for members of the Association of the Hawaiian Civic Clubs. Research and training activities included focus groups to explore the perceptions and experiences of cancer survivors, surveys to assess research priorities, the identification of Native Hawaiian researchers and the development of pilot research projects. The work of 'Imi Hale is guided by the hope that Native Hawaiians can reverse the negative effects of cancer and leave a powerful legacy and inheritance for future generations based on good health and well-being. 'Imi Hale means "to establish, as a dynasty; to acquire authority, power; to seek and establish an inheritance for one's children; and to form a friendship so close that one feels welcome in the house of the other." "By using our language for a name, we are invoking and honoring our ancestors, our culture, language and restoration as a nation."

Community Participation↗
PubMed2000

Monitoring organochlorine pesticides from landfill leachates by gas chromatography-electron-capture detection after solid-phase microextraction.

Landfill leachates contain significant amounts of organic carbon, nitrogen and heavy metals as well as other specific trace organic compounds like organochlorine pesticides. In this study a simple and reliable methodology was improved to detect organochlorine pesticides in leachate samples by using a previous solid-phase microextraction procedure [with a 100 microm poly(dimethylsiloxane) fiber] and chromatographic analysis by GC-electron-capture detection. The extraction time, temperature, ionic strength of the solution and sampling of the headspace were the parameters studied. Reproducibility achieved values below 20% RSD, and standard addition was used for pesticides confirmation.

Chromatography, Gas↗
PubMed2000

Bose-einstein condensation in trapped dipolar gases

We discuss Bose-Einstein condensation in a trapped gas of bosonic particles interacting dominantly via dipole-dipole forces. We find that in this case the mean-field interparticle interaction and, hence, the stability diagram are governed by the trapping geometry. Possible physical realizations include ultracold heteronuclear molecules, or atoms with laser induced electric dipole moments.

Journal Article↗
PubMed2000

Modulation of ICAM-1 tissue expression in patients with liver transplantation (LT) and acute rejection (AR) after glucocorticoid treatment.

Acute rejection (AR) is a frequent complication following liver transplantation (LT). ICAM-1 may be involved in its pathogenesis. High doses of glucocorticoids are the standard treatment in these patients. The aim of this study was to describe corticoid effects on ICAM-1 tissue expression in liver biopsies of patients with LT and AR. The study included liver biopsies performed before and after treatment in 12 patients with LT and proven AR. In 10 patients AR was reversible and in 2, was steroid resistant. For immunohistochemistry, an indirect immunoperoxidase technique was used. Each histology section was semiquantitatively evaluated as follows: 0: < 10% staining, 1: 10-25%, 2: 25-50%, 3: > 50%. The control group comprised nine patients with LT and normal liver biopsies. In pre-treatment liver biopsy samples, ICAM-1 was markedly expressed on sinusoidal cells (2.41 +/- 0.66), and there was also expression on periportal (0.66 +/- 0.65) and perivenular hepatocytes (0.83 +/- 0.57). By contrast, in the liver tissue from the control group, sinusoidal ICAM-1 reactivity was significantly lower (0.88 +/- 0.33; P < 0.05), and hepatocytes showed no reliable ICAM-1 expression. After steroid treatment the intensity of ICAM-1 decreased significantly in sinusoids (1.5 +/- 0.67; P < 0.05) and in perivenular hepatocytes (0.25 +/- 0.86; P < 0.05). Additionally, we also observed a decreased ICAM-1 reactivity in portal hepatocytes (0.25 +/- 0.62), but these differences did not reach statistical significance. Remarkably, after treatment, hepatocytes did not show ICAM-1 reactivity in resolved AR, but in corticoid-resistant patients AR did not change or increase. In conclusion, in patients with LT and AR, ICAM-1 was expressed in hepatocytes and with more intensity in sinusoid cells. Additionally, a down-regulation of the ICAM-1 tissue expression after corticoid treatment may exist, although in corticoid-resistant AR no modulation on ICAM-1 tissue expression was observed.

Acute Disease↗
PubMed2000

Molecular structures and vibrations of m-methylaniline in the S0 and S1 states studied by laser induced fluorescence spectroscopy and ab initio calculations.

The UV fluorescence excitation and dispersed fluorescence spectra of a jet-cooled m-methylaniline have been obtained for the S1<--S0 transition, in which some of the bands have been observed for the first time. The main spectral bands have been assigned by comparison with those of other relevant substituted benzenes. It was found that the spectra exhibit an important feature which is the internal rotation of the methyl group in the electronic ground and excited states. Ab initio calculations at MP2/6-31G* and CIS/6-31G* show that the optimized structure of m-methylaniline in the ground state is not planar with the amino group having sp3 hybridation-like character due to the existence of lone-paired electrons on the nitrogen atom. Upon electronic excitation, the C-N bond exhibits a partial double bond character, indicating an enhanced interaction between the ring and the NH2 group as in the case of aniline.

Aniline Compounds↗
PubMed2000

Targets of B-cell antigen receptor signaling: the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway and the Rap1 GTPase.

In this review, we discuss the role of phosphatidylinositol 3-kinase (PI3K) and Rap 1 in B-cell receptor (BCR) signaling. PI3K produces lipids that recruit pleckstrin homology domain-containing proteins to the plasma membrane. Akt is a kinase that the BCR activates in this manner. Akt phosphorylates several transcription factors as well as proteins that regulate apoptosis and protein synthesis. Akt also regulates glycogen synthase kinase-3, a kinase whose substrates include the nuclear factor of activated T cells (NF-AT)cl and beta-catenin transcriptional activators. In addition to Akt, PI3K-derived lipids also regulate the activity and localization of other targets of BCR signaling. Thus, a key event in BCR signaling is the recruitment of PI3K to the plasma membrane where its substrates are located. This is mediated by binding of the Src homology (SH) 2 domains in PI3K to phosphotyrosine-containing sequences on membrane-associated docking proteins. The docking proteins that the BCR uses to recruit PI3K include CD19, Cbl, Gab1, and perhaps Gab2. We have shown that Gab1 colocalizes PI3K with SH2 domain-containing inositol phosphatase (SHIP) and SHP2, two enzymes that regulate PI3K-dependent signaling. In contrast to PI3K, little is known about the Rap1 GTPase. We showed that the BCR activates Rap1 via phospholipase C-dependent production of diacylglycerol. Since Rap1 is thought to regulate cell adhesion and cell polarity, it may be involved in B-cell migration.

Animals↗
PubMed2000

[Evolution of breastfeeding pattern].

OBJECTIVE: To follow the evolution of the breastfeeding practice among women in a childbirth clinic and evaluate the actions for its promotion. METHODS: Two cohorts of children born in an school hospital of Porto Alegre, Brazil, in different periods of time were compared regarding the prevalence of breastfeeding during the first six months of life, and the percentage of early cessation of breastfeeding. Both were prospective studies, including 202 children in the cohort of 1987, and 187 children in the cohort of 1994. All participants were healthy children, with birth weight of 2500g or more, were being breastfed and their parents were living in the same house. The 1987 study children were followed up through mail, and the 1994 study ones by home visits. RESULTS: Survival analysis showed similar frequencies of breastfeeding in the two cohorts. The prevalence of exclusive breastfeeding, although for a short period in both groups, was higher in the population studied in 1994, especially among children whose mothers were better educated. There was no rate difference of early cessation of breastfeeding between the two cohorts (36% for the 1987 cohort and 39% for the 1994 cohort). CONCLUSIONS: The results revealed a certain degree of apathy in regard of the promotion of breastfeeding during the studied period, giving support to actions to promote breastfeeding, especially among poor families.

Brazil↗
PubMed2000

[Application of the Portuguese version of the abbreviated instrument of quality life WHOQOL-bref].

INTRODUCTION: The need of short instruments to evaluate Quality of life determines World Health Organization Quality of Life Group (WHOQOL Group) to develop an abbreviated version of the WHOQOL-100, the WHOQOL-bref. The objective is to present the Brazilian field trial of the WHOQOL-bref. METHODS: WHOQOL-bref is composed by 26 questions divided in four domains: physical, psychological, social relationships and environment. The evaliation instrument, BDI (beck depression inventory) and BHS (beck hopelessness scale) were used in a 300 subjects sample in Porto Alegre, South Brazil. RESULTS/CONCLUSIONS: The instrument showed a good performance concerning internal consistency, discriminant validity, criterion validity, concurrent validity and test-retest reliability. The intrument allies good psychometric performance and practicity for use which puts it as an interesting option to evaluate quality of life in Brazil.

Brazil↗
PubMed2000

[Prognostic factors for survival following transarterial chemoembolization in advanced hepatocellular carcinoma].

The efficacy of transarterial chemoembolization in the palliative treatment of non-resectable hepatocellular carcinoma is controversial. To determine the possible existence of clinical and analytical variables with independent predictive value for survival related to the tumor and the treatment given, a multivariate analysis in a series of 111 patients who underwent transarterial chemoembolization was carried out. Overall actuarial survival was 54%, 31% and 24% at 1, 2 and 3 years respectively. Child-Pugh score (p < 0.05), tumor size (p < 0.05) and arterial occlusion after intraarterial chemotherapy (p < 0.05) reached independent predictive value. The group of patients in whom two or three of these factors were simultaneously present had a very poor prognosis with a survival of 20% and 0% at 1 and 2 years respectively, compared with 60%, 50% and 37% at 1, 2 and 3 years respectively in the group with one or none of these factors (p < 0.01). Grouping on the basis of these variables may be useful in the design of future controlled prospective studies that aim to determine the efficacy of transarterial chemoembolization.

Adult↗
PubMed2000

[Retinitis pigmentosa: results of rhodopsin gene analysis in the Galician population].

PURPOSE: Retinitis pigmentosa (RP) is the most prevalent inherited degeneration in the retina. The clinical manifestations are variable in terms of severity, age of onset and progression. The clinical variation is paralleled by genetic heterogeneity (more than 20 different loci have been described to date). The aim of this work was to identify mutations in rhodopsin gene and to determine the frequencies of the different genetic forms of RP in the Galician population. METHODS: 47 previously diagnosed RP patients and their relatives were studied. Genetic forms of RP were identified by recording full family history and clinical examination. DNA samples from patients with RP and control individuals were screened for point mutations in the rhodopsin gene by using PCR SSCPs (Single Strand Conformation Polymorphisms) and direct sequencing in 36 unrelated nonsyndromic RP patients. RESULTS: We report the frequency distribution of the different genetic RP forms. In the SSCPs analysis of rhodopsin gene we found different mobility shifts: one variant in the 5'-untranslated region of the gen and one variant in the third intron. Direct sequencing revealed an A269-->G and an C3982-->T transitions, respectively. Additionally, we observed a single base change in codon 160 (C-->A) of this gene. CONCLUSIONS: Polymorphisms are commom findings in the exon 1 and 3 of rhodopsin gene. They are neutral variations and do not represent a change in the protein. No significant differences in the frecuencies of A269-->G and C3982-->T polymorphisms among the three groups of RP patients (ADRP, ARRP, Esporadic RP) and normal individuals were found. There was no significant deviation from Hardy-Weinberg's equilibrium in each genotype in any group.

Adolescent↗
PubMed1999

The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase.

We have previously shown that the B cell Ag receptor (BCR) activates phosphatidylinositol (PI) 3-kinase. We now show that a serine/threonine kinase called Akt or protein kinase B is a downstream target of PI 3-kinase in B cells. Akt has been shown to promote cell survival as well as the transcription and translation of proteins involved in cell cycle progression. Using an Ab that specifically recognizes the activated form of Akt that is phosphorylated on serine 473, we show that BCR engagement activates Akt in a PI 3-kinase-dependent manner. These results were confirmed using in vitro kinase assays. Moreover, BCR ligation also induced phosphorylation of Akt of threonine 308, another modification that is required for activation of Akt. In the DT40 chicken B cell line, phosphorylation of Akt on serine 473 was completely dependent on the Lyn tyrosine kinase, while the Syk tyrosine kinase was required for sustained phosphorylation of Akt. Complementary experiments in BCR-expressing AtT20 endocrine cells confirmed that Src kinases are sufficient for BCR-induced Akt phosphorylation, but that Syk is required for sustained phosphorylation of Akt on both serine 473 and threonine 308. In insulin-responsive cells, Akt phosphorylates and inactivates the serine/threonine kinase glycogen synthase kinase-3 (GSK-3). Inactivation of GSK-3 may promote nuclear accumulation of several transcription factors, including NF-ATc. We found that BCR engagement induced GSK-3 phosphorylation and decreased GSK-3 enzyme activity. Thus, BCR ligation initiates a PI 3-kinase/Akt/GSK-3 signaling pathway.

Animals↗
PubMed1999

Cholecystectomy for suspected biliary dyskinesia in children with chronic abdominal pain.

BACKGROUND/PURPOSE: The authors reviewed their experience with a group of children with chronic abdominal pain, delayed gallbladder emptying, and no cholelithiasis. Clinical presentation, diagnostic evaluation, and effect of cholecystectomy on symptoms were investigated. METHODS: Twenty-nine children were suspected of having biliary dyskinesia. Diagnosis was based on symptoms of upper abdominal pain in conjunction with a lack of sonographically apparent gallstones, a cholecystikinin (CCK)-stimulated gallbladder ejection fraction of less that 40% at 30 minutes, and a lack of any other clear cause for symptoms. All patients underwent cholecystectomy. RESULTS: The duration of symptoms before operation was between 3 weeks and 4 years. All patients were evaluated by abdominal ultrasonography and CCK cholescintigraphy. Symptoms were relieved completely in 23 (79%) of the patients who underwent cholecystectomy. Five children had persistent pain after cholecystectomy and one had nausea. CONCLUSIONS: Symptoms suggestive of biliary colic in children without evidence for cholelithiasis frequently may represent biliary dyskinesia. CCK cholescintigraphy should be pursued in these patients. Relief of symptoms after cholecystectomy should be expected in a majority of those with an ejection fraction of less that 40%.

Abdominal Pain↗