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Biomedical subjects

A Sierra

Publications and source records attributed to A Sierra.

At least 37 records · Page 2Linked to original sources
PubMed2000

Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer.

We have examined whether the extended life span of cells induced by Bcl-2 in T(1) ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c-Myc, c-erbB-2 and epidermal growth factor receptor by immuno-histochemistry in a group of 142 T(1) (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl-2 over-expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl-2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl-2-positive tumors (trend test, p = 0.03), p53-mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl-2-positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53-negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl-2-positive tumors (trend test, p = 0.03). In human T(1) ductal breast carcinoma, over-expression of Bcl-2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53-negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl-2- and p53-dependent mechanisms.

Antibodies, Monoclonal↗
PubMed2000

Inhibitory control of the GABAergic transmission in the rat neostriatum by D2 dopamine receptors.

The aim of the study was to determine the role of dopamine on the GABAergic input to striatal projection neurons. Accordingly, the effect of the activation of dopamine D2-like receptors on GABA-mediated depolarizing postsynaptic potentials evoked in striatal slices by local stimulation was studied. Conventional intracellular recording techniques were used to record the synaptic responses. The experiments were done in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM) and (+)-2-amino-5-phosphonovaleric acid (40 microM) to block the participation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate and N-methyl-D-aspartate receptors in the synaptic response. The GABAergic nature of the response was assessed by its potentiation by pentobarbital (50 microM) and by its elimination by bicuculline or picrotoxin. At 100 nM, a concentration already maximal, dopamine inhibited by 55% the GABAergic synaptic response. The inhibitory effect was totally blocked by the selective antagonist of D2-like receptors, sulpiride (100 nM). The dopamine inhibition was observed only in one-third of the studied neurons and was concentration dependent (IC50 = 14 nM). The inhibition was not associated with changes in the input resistance or any other membrane property. In addition, dopamine (50 nM) reduced the frequency but not the amplitude of spontaneous, bicuculline-sensitive depolarizing postsynaptic potentials. The D2-like receptor agonist quinpirole also dose-dependently (IC50 = 10 nM) inhibited the GABAergic synaptic response. As with dopamine, the inhibition did not change the membrane properties of the studied neurons. In addition, the quinpirole induced inhibition of the GABA response was accompanied by increased paired-pulse facilitation. The results indicate that D2-like receptors located on intrinsic GABAergic terminals in the rat striatum exert an inhibitory control of the GABAergic input to striatal projection neurons. The dopaminergic effect would be translated in facilitation of the firing of the neurons upon the arrival of the cortical input.

Animals↗
PubMed2000

Bcl-xL promotes metastasis of breast cancer cells by induction of cytokines resistance.

Metastasis is a highly complex process involving the survival of tumor cells, both in the blood stream and within specific organs. Cell-death and survival are determined by a number of gene products from an expanding family of the Bcl-2 gene, either promoting or preventing apoptosis. Furthermore, the survival of tumor cells may favor the accumulation of additional genetic alterations causing further growth and invasive opportunities which may lead to metastasis. To examine whether the prevention of cell-death influences the metastatic behavior, we transfected a human breast cancer cell line MDA-MB-435 with the Bcl-xL cDNA and then studied metastatic ability of the selected clones in vivo. Our results show that Bcl-xL-clones had a decreased tumor growth latency and an increased metastatic ability. Apoptosis-resistance to cytokines was induced in 435 cells by Bcl-xL-expression with minor modifications in their proliferation rates. These cells also showed diminished adhesion to extracellular matrix proteins and a survival advantage in suspension over 435/Neo cells. Moreover, to determine survival in blood stream and in cells lodged in the lungs, we injected 435/Bcl-xL and 435/Neo cells at 1:3 proportion i.v., and animals were killed at intervals of 15' to 16 h after injection. Tumor cells were recovered from the lungs and Southern-blot analysis revealed the presence of exogenous Bcl-xL cDNA. These results showed that 435/Bcl-xL cells had a survival advantage in circulation over 435/Neo cells. This advantage in vivo was attributable to Bcl-xL expression. We conclude that Bcl-xL expression in breast cancer cells can increase metastatic activity. This advantage could be created by inducing resistance to apoptosis against cytokines, increasing cell survival in circulation, and enhancing anchorage-independent growth.

Animals↗
PubMed2000

Reclassification as supervised clustering.

In some branches of science, such as molecular biology, classes may be defined but not completely trusted. Sometimes posterior analysis proves them to be partially incorrect. Despite its relevance, this phenomenon has not received much attention within the neural computation community. We define reclassification as the task of redefining some given classes by maximum likelihood learning in a model that contains both supervised and unsupervised information. This approach leads to supervised clustering with an additional complexity penalizing term on the number of new classes. As a proof of concept, a simple reclassification algorithm is designed and applied to a data set of gene sequences. To test the performance of the algorithm, two of the original classes are merged. The algorithm is capable of unraveling the original three-class hidden structure, in contrast to the unsupervised version (K-means); moreover, it predicts the subdivision of one of the original classes into two different ones.

Algorithms↗
PubMed2000

Influence of human wet cerumen on the growth of common and pathogenic bacteria of the ear.

The available data on the effect of human wet cerumen on bacterial growth are not conclusive. Nevertheless it is widely accepted that cerumen has a bactericidal effect. In this study the activity of human wet cerumen on bacterial growth was assessed by applying cerumen suspensions to bacterial cultures. Bacterial counts were performed before and after application of cerumen suspensions. A total of 383 assays was carried out with 73 pools of cerumen that were tested against cultures of Staphylococcus aureus, Staphylococcus epidermidis, Corynebacterium spp., Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens. An increase in growth occurred much more frequently than a decrease in growth in almost every microrganism tested, with the mean increase percentage being much higher than the mean decrease percentage, except in the case of S. aureus. The largest average growth increase was obtained with E. coli. The largest average decrease in bacterial growth was recorded with S. marcescens. Our study does not support the conception of a decrease in bacterial growth produced by humen wet cerumen. In vitro, the most observable effect was in fact an increase in microbial growth.

Adolescent↗
PubMed2000

[Energy and nutrient intake and risk of inadequate intakes in Canary Islands (1997-98)].

OBJECTIVES: To evaluate the consumption of energy and nutrients and to identify the risk of inadequate intakes in the Canary Island population (1997-98). DESIGN: Cross-sectional epidemiological study. METHODS: A dietary survey was conducted in a representative sample of the Canary Island population (n = 1747; 821 men and 926 women) aged 6 to 75 years. Two 24-hour recalls were utilised as the dietary survey instrument, carried out over non-consecutive days. Spanish Food Composition Tables were used and data was adjusted for intraindividual variability. RESULTS: The mean daily intakes were 1760 kcal for energy, 73 g for protein, 228 g for carbohydrates, 15 g for fibre and 62 g for fat (24 g SFA, 25 g MUFA and 8 g PUFA). Energy and nutrient consumption decreased with age excluding vitamins A. C and folate. Nutrient density increased with age, with the lowest intakes seen in children and adolescents. As for social class, decreased calorie intake was observed in the lowest category, with the highest income level showing the greatest intakes for vitamin A, B12, niacin and folate. Noteworthy findings include an overall low calorie intake, and elevated risks of inadequate intakes (percentages of the population with intakes below 2/3 of the RDI) for vitamins D (92.5%), E(87.4%), A(74%), folate(44.7%), iron(30.1%) magnesium (14.9%) and vitamin C (5.4%). Risk for inadequate protein intake was not observed.

Adolescent↗
PubMed1999

Neuroprotective effects of estradiol in the adult rat hippocampus: interaction with insulin-like growth factor-I signalling.

We have previously shown that 17-beta-estradiol protects neurons in the dentate gyrus from kainic acid-induced death in vivo. To analyse whether this effect is mediated through estrogen receptors and through cross-talk between steroid and insulin-like growth factor (IGF) systems, we have concomitantly administered antagonists of estrogen receptor (ICI 182,780) or the IGF-I receptor (JB1) with estradiol. In addition, we have also administered IGF-I with or without the estrogen receptor antagonist. JB1 (20 microg/ml), ICI 182,780 (10(-7) M), and IGF-I (100 microg/ml) were delivered into the left lateral ventricle of young ovariectomized rats via an Alzet osmotic minipump (0.5 microl/hr) for 2 weeks. All rats received kainic acid (7 mg/Kg b.w.) or vehicle i.p. injections at day 7 after minipump implant. Also on day 7, rats treated i.c. v.with only ICI 182,780 or JB1 received a single i.p. injection of 17-beta-estradiol (150 microg/rat) or vehicle. On day 14 after minipump implant, the rats were killed, brains processed, and the number of surviving hilar neurons estimated by the optical disector technique. Both IGF-I and estradiol treatments resulted in over 90% survival of hilar neurons. The neuroprotective action of estradiol was blocked by ICI 182,780 and by JB1. Furthermore, IGF-I enhancement of neuronal survival was significantly reduced by ICI 182,780. These results indicate that in this model of hippocampal lesion, the neuroprotective effect of estradiol depends both on estrogen receptors and IGF-I receptors, while the protection exerted by IGF-I depends also on estrogen receptors. In conclusion, an interaction of estrogen receptor and IGF-I receptor signalling may mediate neuroprotection in the adult rat hippocampus.

Animals↗
PubMed1999

Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal rebleeding after recent variceal hemorrhage.

Variceal hemorrhage continues to be a major cause of morbidity and mortality in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is gaining wide acceptance as a treatment for several complications of portal hypertension. The aim of the current randomized study was to compare the transjugular shunt and endoscopic sclerotherapy (ES) for the prevention of variceal rebleeding (VB) in cirrhotic patients. Forty-six consecutive cirrhotic patients with variceal bleeding were randomly allocated to receive either transjugular shunt (22 patients) or ES (24 patients) 24 hours after control of bleeding. VB (50% vs. 9%) and early (first 6 weeks) VB (33% vs. 5%) were significantly more frequent in sclerotherapy patients; the actuarial probability of being free of VB was higher in the shunt group (P <.002). Eight patients (33%) of the sclerotherapy group and 3 patients (15%) of the shunt group died; the actuarial probability of survival was higher for the shunted patients (P <.05); 6 patients in the sclerotherapy group and none in the shunt group died from VB (P <.05). No difference was found in the proportion of patients with clinically evident hepatic encephalopathy (HE). These results show that the transjugular shunt is more effective than sclerotherapy in the prevention of both early and long-term VB. Moreover, a significant improvement in survival was found in the shunt group.

Adolescent↗
PubMed1999

A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms.

A randomized blinded clinical trial was performed in 53 patients bitten by Bothrops sp. and Porthidium sp. in Antioquia and Chocó, Colombia, in order to compare the efficacy and safety of two antivenoms made of whole IgG obtained by either ammonium sulphate (monovalent anti-B. atrox) or caprylic acid (polyvalent) fractionation. Additionally, antivenoms were compared by electrophoretic and chromatographic analyses and anticomplementary activity in vitro. With a protocol of 2, 4 and 6 antivenom vials for the treatment of mild, moderate and severe envenomings, respectively, both antivenoms were equally efficient to neutralize the most relevant signs of envenoming and to clear serum venom levels in patients from the first hour and later on. Three patients with severe envenoming and initially treated with less than six vials on admission had persistent or recurrent venom antigenemia within 12-48 h. Monovalent antivenom fractionated by ammonium sulphate precipitation had higher amounts of protein aggregates and nonimmunoglobulin proteins than polyvalent antivenom fractionated by caprylic acid precipitation. Both antivenoms presented anticomplementary activity in vitro, being higher in the monovalent product. In agreement, monovalent antivenom induced a significantly higher incidence of early antivenom reactions (52%) than polyvalent antivenom (25%).

Adolescent↗
PubMed1999

Nosocomial infection, indices of intrinsic infection risk, and in-hospital mortality in general surgery.

The objectives of this paper are to assess whether two indices of intrinsic infection risk (the SENIC and the NNIS index) predict in-hospital mortality and the attributable in-hospital mortality due to nosocomial infection in surgical patients. A prospective study on 4714 patients admitted to three hospitals has been carried out. The relative risk and its 95% confidence interval (CI) were estimated. Multiple-risk factors adjusted for odds ratios (OR) were yielded by logistic regression analysis. Overall, 119 patients (2.5%) died before hospital discharge. Both the SENIC and the NNIS indices were related to in-hospital mortality in crude data. After controlling for several variables (age, sex, ASA score, cancer, renal failure, diabetes mellitus, stay at the ICU), the SENIC index did not show any significant trend with mortality (P = 0.252), whereas the trend was significant for the NNIS index (P < 0.001). Risk of death in patients with one nosocomial infection was 7.5%, and in patients developing more than one nosocomial infection was 17.1%. After adjusting for several confounding variables, the development of an organ/space surgical site infection was significantly related to mortality (OR = 4.5, 95% CI 1.5-15.6) as was blood infection (OR = 17.3, 95% CI 3.5-87.0). The association of a surgical site infection and either a respiratory tract infection or a blood infection also increased significantly the risk of in-hospital mortality (OR = 3.3, 95% CI 1.2-8.7). In conclusion, the NNIS index is a good predictor of in-hospital mortality. Patients developing an organ/space surgical site infection and/or a blood infection have an increased risk of in-hospital mortality.

Adult↗
PubMed1999

Expression of dopamine receptors in the subthalamic nucleus of the rat: characterization using reverse transcriptase-polymerase chain reaction and autoradiography.

We analysed the expression of dopamine receptor subtypes in the subthalamic nucleus by means of reverse transcriptase-polymerase chain reaction. We also studied, using autoradiography, all pharmacologically characterized dopamine receptors in four subregions of the subthalamic nucleus. For comparison, dopamine receptor subtypes were also evaluated in brain regions where they are more abundant and well characterized. The radioligands used were: [3H]SCH-23390, [3H]emonapride and [3H]2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene for dopamine D1, D2 and D3 receptors, respectively; and [3H]YM-09151-2 in the presence of raclopride for dopamine D4 receptors. Finally, we also evaluated the effect of unilateral 6-hydroxydopamine injection into the medial forebrain bundle on dopamine receptor levels expressed in the ipsilateral subthalamic nucleus. The lesion was estimated by decrease in the binding of [3H]WIN-35428, a specific dopamine transporter label. D1, D2 and D3 receptor messenger RNAs and binding sites were present in the subthalamic nucleus, but no messenger RNA for D4 receptors was found, although specific binding sites for these receptors were observed. As compared to the intact side, the 6-hydroxydopamine lesion did not change D1 receptors, increased D2 receptors, and decreased D3 receptors and the dopamine transporter. The results suggest that postsynaptic D1, D2 or D3 receptors can mediate the effect of dopamine on subthalamic nucleus neuronal activity. D4 receptors would mediate exclusively presynaptic effects. These results reinforce the idea that dopamine receptors in the subthalamic nucleus may play an important role in the physiology of the basal ganglia and in the pathophysiology of Parkinson's disease.

Animals↗
PubMed1999

Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas.

The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n = 142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (chi2 test, p = 0.008). Moreover, very large associations (pOR = 6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR = 8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR = 2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.

Adult↗
PubMed1999

Gonadal hormones affect neuronal vulnerability to excitotoxin-induced degeneration.

The role of endogenous gonadal secretions in neuroprotection has been assessed in a model of hippocampal degeneration induced by the systemic administration of kainic acid to adult male and female rats. A low dose of kainic acid (7 mg/Kg b.w.) induced a significant loss of hilar dentate neurons in castrated males and did not affect hilar neurons in intact males. The effect of kainic acid on hilar neurons in female rats was different depending on the day of the estrous cycle in which the neurotoxin was administered; while no significant effect of kainic acid was observed when it was injected in the morning of estrus, there was a significant loss of hilar neurons when it was injected in the morning of proestrus as well as when it was injected into ovariectomized rats. Estradiol or estradiol plus progesterone prevented hilar neuronal loss when injected simultaneously with kainic acid in ovariectomized rat. Progesterone by itself did not prevent neuronal loss induced by kainic acid and estogen was only effective when it was injected either 24 h before or simultaneously with kainic acid and not when it was injected 24 h after the administration of the toxin. These findings indicate that endogenous gonadal hormones protect hippocampal hilar neurons from excitotoxic degeneration. In addition, the timing of exposure to ovarian hormones and the natural fluctuation of ovarian hormones during the estrous cycle may influence the vulnerability of hilar neurons to excitotoxicity. These findings are relevant to possible modifications in neurodegenerative risk in humans as endogenous levels of gonadal hormones change during the menstrual cycle and during aging.

Animals↗
PubMed1999

The effect of frequency of chart review on the sensitivity of nosocomial infection surveillance in general surgery.

OBJECTIVE: To assess the sensitivity of different frequencies of nosocomial infection surveillance (NIS) in general surgery. DESIGN: Data obtained with a prospective daily NIS are compared with those of hypothetical cross-sectional studies carried out with different frequencies (from one weekly visit up to one visit every other day). SETTING: General surgery services at three hospitals. MAIN OUTCOME MEASURE: Sensitivity in the detection of nosocomial infection (overall and stratified by site), compared to a gold standard of prospective surveillance of every patient's complete medical record daily from the first day after surgery until discharge and once more after discharge. PATIENTS: 5,859 patients. RESULTS: 837 nosocomial infections were detected by the gold standard (58.8% were surgical-site infections [SSI]). The sensitivity of weekly NIS for all infections was 74.5% (95% confidence interval [CI95], 71.4%-77.5%) and varied from 65.1% (CI95, 56.2%-73.3%) for urinary tract infection to 83.3% (CI95, 62.6%-95.3%) for respiratory tract infection; it was 76.4% (CI95, 72.4%-80.1%) for SSI. As expected, sensitivity increased with the frequency of NIS. Performing NIS every 4 days improved sensitivity significantly, to 82.3% (CI95, 79.5%-84.8%) for all infections and 83.3% (CI95, 79.7%-86.5%) for SSI. One visit every other day increased the sensitivity for all infections by another 4.9%, mainly due to increased detection of urinary tract and other less severe infections. CONCLUSIONS: The sensitivity of two visits a week exceeded that of one weekly visit by approximately 8%, and one visit every other day added another 5% increase. Results varied according to duration of infection and postdischarge hospital stay.

Bacterial Infections↗
PubMed1999

Localization of estrogen receptor beta-immunoreactivity in astrocytes of the adult rat brain.

Estrogen receptors are direct regulators of transcription that function by binding to specific DNA sequences in promoters of target genes. The two cloned forms of estrogen receptors, alpha and beta, are expressed in the central nervous system by different neuronal populations. Astrocytes in vitro are also reported to express estrogen receptor alpha; however, this expression has not been confirmed in the rat brain in vivo. The apparent absence of estrogen receptors in glia in vivo contrasts with the well-known effects of this hormone on astrocytes of different brain areas, including the hippocampal formation. In this study, the expression of estrogen receptors in the hippocampal formation of adult male rats has been assessed by confocal microscopy. Estrogen receptor alpha-immunoreactivity was localized in neuronal nuclei in the pyramidal cell layer of CA1-CA3 fields. Estrogen receptor beta-immunoreactivity was observed in the perikarya, apical dendrites, and cell nuclei of pyramidal neurons in CA1 and CA2. Furthermore, estrogen receptor beta-immunoreactive glia were observed in CA1, CA2, CA3, and in the hilus of the dentate gyrus of male and female rats. Estrogen receptor beta-immunoreactivity was localized in glial processes and perikarya and, in some cases, in glial cell nuclei. Double immunocytochemical labeling of estrogen receptor beta and the specific astroglial marker glial fibrillary acidic protein revealed that estrogen receptor beta-immunoreactive glial cells were astrocytes. Estrogen receptor alpha was not co-localized with glial fibrillary acidic protein. The presence of estrogen receptor beta in astrocytes of adult male and female rats demonstrates a possible mechanism by which estrogen can directly modulate gene expression in these cells.

Animals↗
PubMed1998

Estradiol prevents kainic acid-induced neuronal loss in the rat dentate gyrus.

The neuroprotective role of 17beta-estradiol in the hippocampal dentate gyrus of adult rats treated with kainic acid has been investigated. The systemic injection of a single low dose (7 mg/kg) of kainic acid to ovariectomized rats produced a marked loss of Nissl-stained and somatostatin-immunoreactive hilar neurons. A single simultaneous systemic dose of estradiol (150 microg per animal) prevented the kainic acid-induced decrease in Nissl-stained and somatostatinergic hilar neurons. These results indicate that estradiol may protect adult hilar neurons in vivo from neurotoxic-induced cell death.

Animals↗