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Biomedical subjects

A Hernandez

Publications and source records attributed to A Hernandez.

267 records · Page 15Linked to original sources
PubMedDate not supplied

Sensitization of human colon cancer cells to TRAIL-mediated apoptosis.

TNF-related apoptosis-inducing ligand (TRAIL), a novel member of the tumor necrosis factor (TNF) family, is thought to induce apoptosis preferentially in cancer cells; however, increasing evidence suggests that a number of cancers are resistant to TRAIL treatment. FLICE-like inhibitory protein (FLIP), which structurally resembles caspase-8, can act as an inhibitor of apoptosis when expressed at high levels in certain cancer cells. The purpose of our present study was to determine whether human colon cancer cells are sensitive to TRAIL treatment and, if not, to identify potential mechanisms of resistance. Colon cancer cells of different metastatic potential (KM12C, KML4A, and KM20) were found to be resistant to the effects of TRAIL when used as a single agent. FLIP expression levels were increased in all three KM cell lines. Treatment with either actinomycin D (Act D;10 :g/ml) or cycloheximide (CHX; 10 :g/ml) decreased FLIP expression levels in all three cell lines. The decrease in cellular levels of FLIP was associated with sensitization to TRAIL-mediated apoptosis, as demonstrated by enhanced cell death and caspase-3 activity compared with either Act D or CHX alone. Our findings suggest that reduction of FLIP levels by Act D or CHX renders TRAIL-resistant human colon cancer cells sensitive to TRAIL-mediated apoptosis. The combination of TRAIL along with agents such as Act D or CHX, which target proteins that prevent cell death, may provide a more effective and less toxic regimen for treatment of resistant colon cancers.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Operative treatment of posterior shoulder dislocations by posterior glenoidplasty, capsulorrhaphy, and infraspinatus advancement.

Posterior dislocations of the shoulder are rare, comprising only 4% of shoulder dislocations. Several operative procedures have been described in treating recurrent dislocations, and results have been varied. A retrospective review of eight shoulders in eight patients treated by posterior glenoidplasty with capsulorrhaphy and infraspinatus advancement revealed generally good results. Followup ranged from 10 to 114 months, with an average of 36 months. Seven patients were classified as recurrent traumatic dislocators and one as a recurrent atraumatic voluntary dislocator. Results graded as good, fair, and failure were based on pain, range of motion, return to activities, recurrence, and roentgenograms. Six patients had good results with return to full activity, full range of motion, no pain, no recurrence, and no degenerative changes of roentgenograms. One patient, who has not returned to athletic activities and has occasional pain and limited range of motion, was graded as a fair result. The patient classified as an atraumatic voluntary dislocator has occasional feelings of instability and slight pain with strenuous activity, but has not had a recurrence and has no difficulty with activities of daily living. She was also classified as a fair result. There have been no recurrences or degenerative changes on followup radiographs. Computerized tomography performed on two patients documented a definite change in orientation of the glenoid. We feel that glenoidplasty with capsular reefing and infraspinatus advancement, if performed carefully, provides an excellent operative treatment for recurrent posterior dislocations of the shoulder.

Adolescent↗
PubMedDate not supplied

Nitric oxide synthase expression in the endothelium of pulmonary arterioles in normal and pulmonary hypertensive chickens subjected to chronic hypobaric hypoxia.

To determine whether or not exposure to chronic hypoxia and subsequent development of pulmonary hypertension syndrome (PHS) induce alterations in endothelial nitric oxide (NO) production in broiler's pulmonary vascular bed of broilers, we studied the expression of nitric oxide synthase enzyme in pulmonary endothelial cells by a nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemical staining reaction. For this purpose, 60 broilers of three different ages (17, 30, and 42 days) were used. The animals were distributed in two groups: a) 30 healthy (nonhypertensive) broilers and b) 30 chicks with PHS. All broilers in group b had fewer NADPH-diaphorase-positive endothelial cells in arterioles than did the nonhypertensive broilers. These differences were highly significant (P < 0.01). These results demonstrate for, the first time in broilers, that hypoxia-induced pulmonary hypertension is associated with a decrease of endothelial-derived NO expression in pulmonary vessels.

Animals↗
PubMedDate not supplied

The effect of agonists and antagonists on the morphology of non-transformed human smooth muscle cell in vitro.

In the present study we used scanning electron microscopy (SEM) to investigate morphological changes of non-transformed line of human bronchial smooth muscle cells (bSMC) induced by different agonists. Explants of normal bronchi were dissected and subcultured between 2 and 6 passage. In addition, smooth muscle actin content was assessed by SDS-PAGE electrophoresis, and its isoelectric point by IPG followed by immunoblotting. SMC were fixed by 2.0% paraformaldehyde and 2% glutaraldehyde and then were post-fixed by OSO4 and followed by dehydration and gold coating. Cytosolic free calcium was measured using adherent cells incubated with 500 microM Fura-2 acetoxymethylester and monitored by single excitation fluorimetry. Cultured cells possess predominantly charged actin isoforms with pI at 4.95; they respond to acetylcholine (100 microM), bradykinin (5 microM) and sulfidopeptide leukotriens (0.3-1.0 microM) with contraction, marked morphological lesions, such as widespread monolayer disorganization, extension of cell contacts. The number of microvilli on the cell surfaces was correlated with the degree of the alterations of the cellular morphology. Receptor antagonists antagonized these changes: atropine (0.3 microM), HOE 140 (1 microM) and MK 571 (1 microM). Acetylcholine and bradykinin induced a biphasic elevation of cytosolic calcium, which was antagonized by their receptor antagonists. Calcium changes in response to agonists were maintained over repetitive passages. Therefore, morphological changes seen in human bronchial SMC in culture with physiological response to various, structurally unrelated agonists can be future concern for the study the possible testing of the different pharmacological substances.

Acetylcholine↗
PubMedDate not supplied

Non-productive or thalassemic-like heavy-chain gene rearrangement in a K-chain CLL clone.

Information obtained from the study of immunoglobulin (Ig) gene rearrangement in different types of lymphoproliferative disorders has led to the suggestion that Ig gene activation obeys a precise hierarchy in which heavy-chain gene rearrangement procedes light-chain gene recombination. However no information is available on the mechanism(s) controlling this sequential activation. We report here a case of CLL which suggests that the expression of the heavy-chain genes is not necessary for light-chain gene rearrangement, or that very low amounts of heavy-chain mRNA and/or heavy chains are sufficient to activate k-chain genes.

Aged↗
PubMedDate not supplied

Hypoxic ascites in broilers: a review of several studies done in Colombia.

In Bogotá, Colombia, broilers developed ascites due to pulmonary hypertension of hypoxic origin at 2638 m above sea level. This disease has tremendous economic impact in various countries of the world and is characterized by pulmonary hypertension, hypertrophy and hyperplasia of the right ventricle of the heart, increased hematocrit and hemoglobin values, and ascites. This entity appears to be influenced by management practices and by inability of broilers to adapt to high altitude.

Altitude↗
PubMedDate not supplied

Molecular approaches applied to the epidemiology of leishmaniasis in Venezuela.

Leishmaniasis is on the increase in Venezuela (ca 30,000 new cases per year) due to deterioration in health management, increased risk groups among inmunosuppressed individuals and increased human penetration into the ecological habitats of sandfly vectors. An STD2-funded project (1989-1992) focused on the Andean state of Táchira, which showed the highest annual index of new cases (ca 200-250). The project aimed at contributing to vector/parasite identification through a combination of molecular and well established field techniques: Newly developed molecular methods distinguished among Lu. spinicrassa, Lu. youngi and Lu. townsendi. These three species of the Verrucarum group are sympatric in the Northeast of the state and could be successfully identified by CHA, DNA probes and RAPD. A Le. braziliensis specific KDNA probe used with squash blots indicated that Lu. spinicrassa is the main vector and that Le. braziliensis is the main parasite species in Táchira state, Venezuela. PCR and the Le. brasiliensis specific DNA probe, schizodemes, isoenzymes and polyclonal antibodies agreed as taxonomic criteria for classification of Leishmania isolated from parasitologically confirmed cases in Tachira. Considerable degree of antigen heterogeneity in Venezuelan Le. braziliensis complex and Le. mexicana complex isolates from Tachira suggests multiple candidate antigens for improving the specificity of immunological diagnosis. The methods developed and tested in Táchira state should be valuable in order to help solving other outstanding epidemiological problems such as following of the epidemiological impact of intervention and vector control measures in highly endemic areas. Future work (STD3 funded, 1993-1996) aims to apply these molecular techniques to a vector control pilot study in Lara state, an area showing the highest incidence of new cases in the country.

Animals↗