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Biomedical subjects

A Santana

Publications and source records attributed to A Santana.

At least 19 recordsLinked to original sources
PubMed2005

[Autoimmune thyroid disease: a case report].

Autoimmune thyroid disease is the most common cause of subclinical thyroid dysfunction (hypo and hyperthyroidism) in the western countries. Autoimmune thyroid diseases with clinical relevance (Graves' disease and autoimmune hypothyroidism) are common and can present with a large clinical and laboratorial spectrum. Hypo and hyperthyroidism can exist in the same patient, on different times. Progression from Graves hyperthyroidism to chronic autoimmune thyroiditis and hypothyroidism is now well-recognized and the inverse might also occur, although being rare. We describe a case report of Graves' disease in a patient with a chronic autoimmune hypothyroidism of long course (diagnosed 21 years ago).

Aged↗
PubMed2005

From stem cells to insulin-producing cells: towards a bioartificial endocrine pancreas.

The total absence or low production of insulin by beta-cells avoids a proper control of glycemia forcing diabetic people to daily insulin injection for survival. Islet transplantation represents a hallmark in the cure of diabetes and has been successfully applied to more than 400 patients, resulting in insulin independency for periods longer than 4 years. However, transplantation trials for diabetes have to face the scarcity of islets from cadaveric donors. Therefore, the finding of renewable sources of cells could circumvent this problem. In this respect, embryonic or adult stem cells are representing an interesting alternative. Stem cells display robust proliferation and the plasticity to differentiate to other cell types, including insulin-containing cells. The current therapeutical use in the future of bioengineered insulin-secreting cells derived from stem cells needs at present to fulfill several criteria. These criteria concern to the type of stem cell to be used as starting biomaterial (embryonic or adult), the in vitro differentiation protocol applied, the functional phenotype reached for the final cell product and the transplantation associated problems (likely immune rejection and tumor formation). This review will try to focus on these different aspects in order to emphasize in the key points to consider for designing unified strategies for diabetes cell therapy.

Bioartificial Organs↗
PubMed2003

Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 --> Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 --> Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation.

Animals↗
PubMed2001

Comparison of cervical smears secured with different instruments.

BACKGROUND: In this presentation we have compared the results from cytologic samples obtained with the cervical brush and Ayre's wooden spatula, against samples obtained with Acellon Combi. METHODS: One thousand cervical smears were collected. This was a cross-sectional study, where it was decided randomly to use cervical brush for sampling of the endocervix and Ayre's wooden spatula for exocervix or Acellon Combi for both. RESULTS: The combination of the cervical brush and the wooden spatula yielded an acceptable quantity of columnar cells in 71.6% of the cases, during both endocervical and exocervical sampling, while the Acellon Combi yielded an acceptable quantity in 61.7% of the cases (p<0.01). The combination of brush/spatula yielded an acceptable quantity of squamous cells from samples of endocervix and exocervix in 87.5% cases, while with the Acellon device amounted to 77.4% (p<0.001). Highly significant differences in the state of cellular preservation of samples from endocervix obtained with cervical brush technique were found upon comparison to Acellon group. CONCLUSIONS: Henceforth, we believe that the use of the cervical brush and the Ayre wooden spatula increases the quantity and preservation of the cells retrieved during cervical smears compared to Acellon Combi.

Adolescent↗
PubMed2000

Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL.

Mild hypothermia is considered to have a protective effect during ischemic neuronal cell death. The present study provides experimental evidence for this beneficial role of mild hypothermia using reversible middle cerebral artery occlusion (MCAo) in a Sprague-Dawley (SD) rat model. MCAo was induced in rats for 1 h followed by reperfusion at different periods. Hematoxylin-eosin (HE) staining in normothermic (NT) 37 degrees C and hypothermic (HT) 33 degrees C groups of rats confirmed cerebral infarcts. The mean per cent infarct area was significantly reduced in the HT group of rats. Immunohistochemical analysis was done using anti-Fas and caspase-3 antibodies. The immunohistochemical expression of Fas and caspase-3 was demonstrable as early as 5 h after reperfusion, but the expression pattern maximized at 24 h after reperfusion. The expression of Fas and caspase-3 proteins showed a clear decrease in the HT group over the NT group. In situ detection of DNA fragmentation was done using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method (TUNEL). TUNEL-positive cells were first observed at 5h after reperfusion and progressively increased by 24h. A higher number of TUNEL-positive cells was found in the NT group, but they were significantly decreased in the HT group. Further, DNA fragmentation was confirmed by size fractionation in agarose gel. These findings demonstrate a positive relation between the expression of Fas, caspase-3 and TUNEL-positive cells.

Animals↗
PubMed1999

CD43, a molecule with multiple functions.

To initiate a specific immune response, lymphoid cells integrate a variety of signals generated through the orchestrated interaction of multiple cell surface molecules with their counter-receptors. As a result of the specific recognition of the antigen through antigen-specific receptors, and of the monitoring of their particular environment through the so-called coreceptor molecules, lymphoid cells go through elaborate processes of maturation and activation, contributing to the plasticity and sensitivity of immune response. CD43 is the major sialic acid rich protein on the surface of lymphocytes. However, the specific roles of this protein in different lymphoid cells under normal physiological conditions remain largely unknown. In this review we will mainly focus on the recent advances concerning the functions of this molecule as a coreceptor of different lymphoid cells as well as on the participation of this molecule in different pathologies.

Animals↗
PubMed1999

Late onset of subcutaneous emphysema and hypercarbia following laparoscopic cholecystectomy.

Laparoscopic surgical techniques are increasingly being applied to treat intraperitoneal abnormalities. These minimally invasive techniques potentially offer decreased operation time, decreased morbidity, and decreased length of hospitalization stays. These procedures, however are not without potential morbidity. Herein we describe two patients treated with laparoseopic cholecystectomy whose cases were complicated with subcutaneous emphysema and hyperearbia without pneumothorax. In each of these cases, carbon dioxide gas was used to induce pneumoperitoneum. In one of the cases, the hypercarbia was a late event occurring during the surgery, and in the second case, the first such description in the literature (to our knowledge), hypercarbia developed after termination of the induced pneumoperitoneum.

Aged↗
PubMed1998

Stimulus-dependent synergism of the antiapoptotic tumor necrosis factor receptor-associated factor 2 (TRAF2) and nuclear factor kappaB pathways.

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic signaling pathways. Thus, although TNF can cause apoptosis and may prove useful in the treatment of malignancies, most cells are resistant to TNF-induced cell death unless de novo protein synthesis is inhibited. Previous studies suggested that TNF activation of the nuclear factor (NF)-kappaB transcription factor family antagonizes the proapoptotic signals initiated by TNF-alpha. TNF receptor-associated factor (TRAF)2 has also been shown to mediate crucial antiapoptotic signals during TNF stimulation, yet is not essential in activation of NF-kappaB under physiologic conditions, thus raising questions about the relationship between these antiapoptotic pathways. We report here that inhibition of TRAF2 and NF-kappaB function in primary cells, by coexpression of a constitutive repressor of multiple NF-kappaB/Rel proteins (IkappaBalpha.DN) and a dominant negative form of TRAF2 (TRAF2.DN), synergistically enhanced TNF-induced apoptosis. The effects were stimulus dependent, such that neither inhibitory molecule affected Fas- and daunorubicin-induced apoptosis to the same degree as TNF-induced death. These findings indicate that the NF-kappaB and TRAF2 pathways activate independent antiapoptotic mechanisms which act in concert to suppress the proapoptotic signals induced by TNF-alpha.

Animals↗
PubMed1998

CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand.

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.

Animals↗
PubMed1997

A regulatory role for TRAF1 in antigen-induced apoptosis of T cells.

Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) and TRAF1 were found as components of the TNFR2 signaling complex, which exerts multiple biological effects on cells such as cell proliferation, cytokine production, and cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-kappaB, but the role of TRAF1 has not been previously determined. Here we show in transgenic mice that TRAF1 overexpression inhibits antigen-induced apoptosis of CD8(+) T lymphocytes. Our results demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and also support the hypothesis that the combination of TRAF proteins in a given cell type determines distinct biological effects triggered by members of the TNF receptor superfamily.

Animals↗
PubMed1997

TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival.

TRAF2 is believed to mediate the activation of NF-kappaB and JNK induced by the tumor necrosis factor receptor (TNFR) superfamily, which elicits pleiotropic responses in lymphocytes. We have investigated the physiological roles of TRAF2 in these processes by expressing a lymphocyte-specific dominant negative form of TRAF2, thereby blocking this protein's effector function. We find that the TNFR superfamily signals require TRAF2 for activation of JNK but not NF-kappaB. In addition, we show that TRAF2 induces NF-kappaB-independent antiapoptotic pathways during TNF-induced apoptosis. Inhibition of TRAF2 leads to splenomegaly, lymphadenopathy, and an increased number of B cells. These findings indicate that TRAF2 is involved in the regulation of lymphocyte function and growth in vivo.

Animals↗