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Biomedical subjects

A García

Publications and source records attributed to A García.

At least 217 records · Page 12Linked to original sources

Rho prevents apoptosis through Bcl-2 expression: implications for interleukin-2 receptor signal transduction.

Here we describe a Rho-mediated apoptosis suppression pathway driven by Bcl-2 expression in the interleukin (IL)-4- or IL-2-dependent murine T cell line TS1 alpha beta. IL-2, but not IL-4, induces Bcl-2 expression through RhoA activation which is inhibited by the specific Rho family inhibitor, Clostridium difficile Toxin B, as well as by a dominant negative RhoA mutant. Using transient transfections of RhoA mutants tagged with the vesicular stomatitis virus glycoprotein, we show that a constitutively active RhoA mutant induces Bcl-2 expression and prevents apoptosis upon IL-4 withdrawal. Finally, we have identified the signaling pathway involved together with RhoA in Bcl-2 induction and show compelling evidence for the implication of phosphatidylinositol 3 kinase and protein kinase C.

Animals↗

[Extrinsic compression of the left atrium as an infrequent and fatal form of type B aortic dissection: value of ECG].

We present an infrequent case of extrinsic compression of the left atrium caused by a type B aortic dissection diagnosed by echocardiography. The transthoracic echocardiography showed the obliteration of the left atrium by a heterogeneous mass with two circular images of low echogenicity. The TEE study identified the mass as a huge hematoma surrounding the true and false lumen of the aneurysm. The case demonstrated the value of echocardiography in the diagnosis of type B aortic dissection.

Aged↗

[The usefulness of transesophageal echocardiography in the diagnosis of atypical aortic coarctation].

We report the case of a 20-year-old woman with severe hypertension diagnosed two months previously. The symptoms and physical examination suggested the diagnosis of coarctation of the aorta, but a transthoracic echocardiogram and a thoracic CT scan were normal. Nevertheless, a severe stenosis of the thoracoabdominal aorta was demonstrated by transesophageal echocardiography. The usefulness of transesophageal echocardiography for the diagnosis of atypical coarctation of the aorta is discussed.

Adult↗

The clinicopathological significance of K-RAS point mutation and gene amplification in endometrial cancer.

The aim of this study was to examine the prevalence and clinicopathological significance of K-RAS oncogene activation in endometrial carcinoma and atypical hyperplasia. We analysed K-RAS point mutation and gene amplification in 55 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism and genomic differential polymerase chain reaction. Point mutations at codon 12 of K-RAS oncogene were identified in 8 of 55 (14.5%) tumour specimens. In addition, we were unable to detect any K-RAS gene amplification in any of the endometrial carcinomas studied. No correlation was found between K-RAS gene mutation and age at onset, histological subtype, grade of differentiation, clinical stage or current patient status. We conclude that K-RAS mutation is a relatively common event in endometrial carcinomas, but with no clear prognostic value.

Aged↗

Susceptibility to endometrial cancer: influence of allelism at p53, glutathione S-transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP1A1) loci.

A case-control study was designed to identify associations between polymorphisms at p53, cytochrome P-450 (CYP1A1) and glutathione-S-transferases and endometrial cancer susceptibility. Among all polymorphisms analysed, an insertional variant in p53 (P53PIN3) and two polymorphisms in the 3'-end and exon 7 of CYP1A1 showed significant association with enhanced endometrial cancer risk.

Aged↗

B cells and monocytes are not developmentally affected in a case of reticular dysgenesis.

We report a patient with reticular dysgenesis (RD) who received an HLA-identical marrow graft and remained free of infection in spite of incomplete haematological recovery. Mixed chimerism was achieved and resulted from the presence of autologous B cells and monocytes and grafting of donor T cells. Granulocyte recovery was impaired. The B cells were CD5+ (B1 cells) and appeared to be functional, since serum immunoglobulin levels became normal after the graft. The findings described here suggest that in some cases the defect selectively affects different cell types, including the more abundant leucocyte populations, granulocytes and T lymphocytes. However, B cells and monocytes appear to be relatively spared in this case of RD. Furthermore, the present case may provide insight into the mechanism involved in the expansion of distinct B cell subpopulations (B1 and B2 cells).

B-Lymphocytes↗

AMPA receptors are coupled to the nitric oxide/cyclic GMP pathway in cerebellar astroglial cells.

In cultured rat cerebellar astroglia kainate induces cGMP formation with low potency (EC50 310 microM). In the presence of cyclothiazide, a blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor desensitization, the effect of kainate was potentiated and glutamate and AMPA elicited large increases (> 100-fold) in cGMP levels. The response to all three agonists was abolished by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine and required extracellular calcium. Uptake of Co2+ was induced by AMPA in a limited population of astroglial cells and this effect was potentiated by cyclothiazide. These results indicate that calcium-permeable AMPA receptors mediate stimulation of nitric oxide formation in cerebellar astroglia. This effect may be relevant for glutamate-dependent synaptic plasticity processes in the cerebellum.

Animals↗

Leu-M1 immunoreactivity and phaeochromocytoma.

The aim was to evaluate Leu-M1 immunoreactivity as a prognostic factor in phaeochromocytoma. Anti-Leu-M1 monoclonal antibodies were used to determine the Leu-M1 immunoreactivity in 17 histologically confirmed phaeochromocytomas from 15 patients, using an avidin-biotin technique. Ten patients had a sporadic phaeochromocytoma, and five had multiple endocrine neoplasia type 2A (MEN 2A). Malignancy was diagnosed in three patients by the presence of metastases. Leu-M1 immunoreactivity was shown in 12 (70.5%) phaeochromocytomas. Three patterns of arrangement were observed: isolated (scattered positive cells) (n = 3); focal (aggregates of positive cells) (n = 5), and diffuse patterns (dispersed positive cells) (n = 4). Two cases of malignant phaeochromocytoma were positive (one focal and one isolated pattern). All cases of MEN 2A showed immunoreactivity, although no characteristic pattern was prevalent. A diffuse pattern was observed in all phaeochromocytomas longer than 7 cm. In conclusion, Leu-M1 expression is frequent in phaeochromocytoma. However, Leu-M1 immunoreactivity seems to be useless in predicting malignant behaviour and to be influenced mainly by tumour size.

Adrenal Gland Neoplasms↗

Effectiveness of immunomodulating treatment (thymostimulin) in chronic obstructive pulmonary disease.

We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multitest or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.

Adjuvants, Immunologic↗

pp65 antigenemia as a marker of future CMV disease and mortality in HIV-infected patients.

We retrospectively evaluated the role of pp65 antigenemia (AGM) as a marker of cytomegalovirus (CMV) disease and mortality in 241 HIV-infected patients with fever. Of 225 patients in whom CD4 count was available, 189 (84%) had counts below 100/microL and 209 (92.8%) below 200/microL, 149 patients had negative AGM (AGM-) and 92 had positive AGM (AGM+), AGM+ patients were at a more advanced stage of HIV disease, as evaluated by CD4 count (p < 0.001) and prior AIDS diagnosis (p < 0.001). Overall, 29 patients (12%) presented concomitant CMV disease (18 retinitis): 24 (26%) in the AGM+ group and 5 (3.3%) in the AGM- group (p < 0.001). AGM had a negative predictive value of 96.6% but a positive predictive value of 26% which increased to 65% if a cut-off of > 10 CMV-positive cells/10(5) leukocytes was considered. The cumulative rate of future CMV disease at 3 months was 0% in AGM patients, 3% in patients with AGM 1-10/10(5) and 36% in patients with AGM > 10/10(5). In a multivariate analysis, no antiretroviral therapy, AGM+ and CMV disease were independently associated with mortality. The role of AGM as a marker of present CMV disease is limited. However, quantitative AGM may select patients at a high risk of future CMV disease. In addition, AGM may be a marker of shorter survival in severely immunosuppressed HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Description of a project for the production and evaluation of oxygen-carrying hemosubstitutes.

Scarce availability and risk of transmission of infections and diseases (HIV, hepatitis B, Chagas' disease) limit the use and benefits of homologous blood transfusions for surgical purposes. Recent trials of perfluorocarbon-based hemosubstitutes (PFC-HSs) in experimental cardiopulmonary bypass (CPB) have demonstrated their ability to improve brain oxygenation, as compared with conventional crystalloid priming solutions. The objective of the project described here is to test different formulations of PFC-HSs and optimize their formulation and dosage for use in CPB. The project includes: (1) study the feasibility of implementing a laboratory for small scale production of PFC-HSs; (2) evaluate the efficacy of use of PFC-HSs in an animal model of CPB; and (3) evaluate the safety of use of PFC-HSs in an animal model of hemorrhagic shock. Several in-house PFC-HSs and outside PFC-HSs are being evaluated. The current state of the project is: (1) the feasibility study has been completed and several PFCs, emulsifiers and surfactants are being tested; (2) and (3) the animal models have been implemented are being used to test in-house and outside PFC-HSs as priming solutions in CPB and reinfusion fluids in hemorrhagic shock respectively. Some preliminary results are presented.

Animals↗

Effects of diet on the ability to drive.

Monoamine synthesis and release depend on the availability of their precursors. Thus some individual behaviors and aptitudes can be controlled by changing the dietary supply of such amino acids. In order to determine the effects of diet on skills for a correct driving attitude, such as sleep latency, attention level, arousal and differences between sexes, we designed a crossover, double-blind trial with 50 volunteers from both sexes, aged 21-30, who ingested a protein enriched product or one composed only of carbohydrates. After 3 h, psychotechnical computerized tests were performed to assess ability to calculate speed, manual skills and vision coordination and concentration capability. No differences were seen in the performance of the tests after the ingestion of both products; thus, diet does not seem to influence behaviors involved in driving. Males performed better in tests involving space perception while females obtained higher scores in the test for visual memory.

Adult↗

Detection of clonality and genetic alterations in endometrial pipelle biopsy and its surgical specimen counterpart.

Carcinoma of the endometrium is the most frequently diagnosed gynecologic malignancy in the western world. Because endometrial carcinoma is monoclonal in origin, the small samples obtained in endometrial pipelle biopsies can be used in PCR clonal studies to distinguish cancerous from noncancerous lesions. The method used for clonal analysis was based on RFLP of the X chromosome-linked phosphoglycerokinase gene and random inactivation of one X chromosome by methylation in women. Among 50 endometrial pipelle biopsies, 26 (52%) were found to be heterozygous for the above-mentioned polymorphism. Of the samples taken from these informative (ie, heterozygous) patients, six were monoclonal including five cases of endometrial carcinoma and one of endometrial atypical hyperplasia. In each case, the same pattern of monoclonality was present in the surgical specimen counterpart. All of the remaining samples were polyclonal and, when the anatomical pathology data were contrasted, they correlated with nonmalignant endometrium (five secretory, five proliferative, seven atrophic, and three simple hyperplasias). In addition, genetic alterations study of monoclonal endometrial samples revealed a K-ras point mutation and a c-erbB2/neu gene amplification in two different endometrial carcinomas. Both alterations were also detected in the surgical specimens. In addition, a diagnosed set of 10 samples of simple hyperplasia and 5 of atypical hyperplasia were subjected to clonal assay. Among eight informative cases, the three that showed that showed the monoclonal pattern corresponded with cases of atypical hyperplasia. No other genetic alterations were detected in these samples. In conclusion, our data indicate that the detection of clonality in endometrial biopsy samples obtained by pipelle would be a useful application for the early diagnosis of endometrial cancer.

Adenocarcinoma↗

[Parapharyngeal carcinoma of the larynx: current clinical and pathological aspects and reports of a clinical case].

Schwannomas (neurilemmomas) are benign tumors of the nerve sheath arising from the Schwann cells in the neural sheath of cranial and spinal nerves. The most frequent sites are the peripheral nerves of the head and neck and the flexor surfaces of the upper extremities. Parapharyngeal schwannomas are rare, which makes them interesting for ear, nose and throat specialists. A new case of schwannoma of the parapharyngeal space is reported. Our experience with the clinical management and surgical treatment of cervical schwannomas is discussed and the literature is reviewed.

Carcinoma↗

[Keratotic neurocutaneous syndromes].

OBJECTIVE: To review current knowledge of etiologic, clinic, diagnostic and therapeutic aspects of ichthyotic diseases with neurologic manifestations. DEVELOPMENT: Classic keratotic neurocutaneous syndromes including Sjögren-Larsson syndrome, trichotyodystrophy, KID (keratitis, ichthyosis and deafness) syndrome and Rud syndrome, are reviewed. Furthermore, we pay attention to syndromes whose description and study are of current importance: cardiofaciocutaneous syndrome, neutral lipids storage disease with ichthyosis, multiple sulphatase deficiency disease and peroxisomal disorders. CONCLUSIONS: Keratotic neurocutaneous syndromes knowledge will help to improve its diagnosis and therapeutic approach.

Adrenoleukodystrophy↗