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Biomedical subjects

F Lopez

Publications and source records attributed to F Lopez.

At least 55 records · Page 3Linked to original sources

SAmBA: an interactive software for optimizing the design of biological macromolecules crystallization experiments.

SAmBA is a new software for the design of minimal experimental protocols using the notion of orthogonal arrays of strength 2. The main application of SAmBA is the search of protein crystallization conditions. Given a user input defining the relevant effectors/variables (e.g., pH, temperature, salts) and states (e.g., pH: 5, 6, 7 and 8), this software proposes an optimal set of experiments in which all tested variables and the pairwise interactions between them are symmetrically sampled. No a priori restrictions on the number and range of experimental variables is imposed. SAmBA consists of two complementary programs, SAm and BA, using a simulated annealing approach and a backtracking algorithm, respectively. The software is freely available as C code or as an interactive JAVA applet at http:/(/)igs-server.cnrs-mrs.fr.

Algorithms↗

Pharyngeal wall vibration detection using an artificial neural network.

An artificial-neural-network-based detector of pharyngeal wall vibration (PWV) is presented. PWV signals the imminent occurrence of obstructive sleep apnoea (OSA) in adults who suffer from OSA syndrome. Automated detection of PWV is very important in enhancing continuous positive airway pressure (CPAP) therapy by allowing automatic adjustment of the applied airway pressure by a procedure called automatic positive airway pressure (APAP) therapy. A network with 15 inputs, one output, and two hidden layers, each with two Adaline-nodes, is used as part of a PWV detection scheme. The network is initially trained using nasal mask pressure data from five positively diagnosed OSA patients. The performance of the ANN-based detector is evaluated using data from five different OSA patients. The results show that on the average it correctly detects the presence of PWV events at a rate of approximately 92% and correctly distinguishes normal breaths approximately 98% of the time. Further, the ANN-based detector accuracy is not affected by the pressure level required for therapy.

Adult↗

The difficulty of identifying genes in anonymous vertebrate sequences.

The identification of genes in newly determined vertebrate genomic sequences can range from a trivial to an impossible task. In a statistical preamble, we show how "insignificant" are the individual features on which gene identification can be rigorously based: promoter signals, splice sites, open reading frames, etc. The practical identification of genes is thus ultimately a tributary of their resemblance to those already present in sequence databases, or incorporated into training sets. The inherent conservatism of the currently popular methods (database similarity search, GRAIL) will greatly limit our capacity for making unexpected biological discoveries from increasingly abundant genomic data. Beyond a very limited subset of trivial cases, the automated interpretation (i.e. without experimental validation) of genomic data, is still a myth. On the other hand, characterizing the 60,000 to 100,000 genes thought to be hidden in the human genome by the mean of individual experiments is not feasible. Thus, it appears that our only hope of turning genome data into genome information must rely on drastic progresses in the way we identify and analyse genes in silico.

Amino Acid Sequence↗

Lemierre's syndrome.

Lemierre's syndrome is an acute medical condition characterized by anaerobic oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein. The illness is often complicated by septic pulmonary emboli and distant metastatic infections. Treatment consists of surgical drainage of purulent collections and long-term intravenous antibiotic therapy. Although Lemierre's syndrome is rare, it is potentially fatal and remains an important entity for clinicians to recognize and treat appropriately.

Abscess↗

Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS: Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION: Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.

Adult↗

p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma.

BACKGROUND: Mutations in the tumor suppressor gene p53 have been associated with resistance to ionizing radiation and chemotherapy. Paclitaxel and concurrent radiation (paclitaxel/RT) achieve high response rates with locally advanced nonsmall cell lung carcinoma (NSCLC). In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC. METHODS: Thirty patients with Stage IIIA or IIIB NSCLC who participated in Brown University Oncology Group protocols utilizing paclitaxel/RT had tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis of exons 5 through 8 of the p53 gene, and confirmed by direct sequencing. RESULTS: Mutations in p53 were found in 12 of 30 patients (40%). The response rates (complete plus partial) of 75% for patients with tumors with p53 mutations, and 83% for patients with wild-type p53, did not differ significantly (P = 0.70). CONCLUSIONS: p53 mutations do not predict response of patients with NSCLC to paclitaxel/RT. This finding is in striking contrast to results with other chemotherapeutic agents and ionizing radiation. These clinical data support in vitro data and animal studies regarding the unique mechanism of the action of paclitaxel. Further investigation is needed to determine the mechanism of lung tumor cell death after paclitaxel/RT. These results suggest that paclitaxel/RT may be an active regimen for patients with other locally advanced neoplasms with high rates of p53 gene mutations.

Aged↗

Molecular mechanisms of antiproliferative effect of somatostatin: involvement of a tyrosine phosphatase.

A protein of 66 kd immunoreactive to anti-tyrosine phosphatase (PTP1C) antibodies coeluted with, and so may be associated with, somatostatin receptors (ssts) from rat pancreatic membranes. Also, anti-PTP1C antibodies immunoprecipitated functional ssts from pancreatic membranes, suggesting a PTP1C protein can associate with ssts at the membrane level. Somatostatin analog RC 160 had good affinity for sst2,3 and sst5 (IC50 = 0.2, 0.1, and 21 nmol/L) and low affinity for sst1 and sst4 (IC50 = 200 and 620 nmol/L), and induced rapid dose-dependent stimulation of PTP activity (maximal at 1 nmol/L and half maximal at 5 pmol/L) in NIH3T3 and CHO cells expressing sst2, with similar results for sst1, but no stimulation with sst3,4 or sst5. Treatment of cells expressing sst2 with RC 160 for 24 hours inhibited serum- or growth factor-induced cell proliferation dose-dependently (maximal at 1 nmol/L, half maximal at 6 to 53 pmol/L RC 160). In cells expressing sst1, weak inhibition of fibroblast growth factor 2-induced NIH3T3 cell proliferation was provoked by somatostatin analogs (> 10 nmol/L). The good correlation between inhibition of somatostatin binding, stimulation of PTP activity, and inhibition of cell proliferation implicates a PTP in growth inhibition mediated by sst2 and sst1.

3T3 Cells↗

Method of recording cerebrospinal fluid pressure at three anatomic places in conscious and unrestrained adult wistar rats.

There does not appear to be a consensus on the normal values of cerebrospinal fluid pressure (Pcsf) in rats because of the different conditions in which each experiment has been done. Anaesthesia, restraint or recordings from different anatomical places and the use of simultaneous infusions could produce a great variability in the obtained results and because of that the average Pcsf in rats has been reported to be between 2 and about 18.5 cm H2O. The aim of this study is to provide new information about the normal values of Pcsf in adult, conscious rats by carrying out long-term measurements, for 3 consecutive days, from different anatomical places. Thirty male Wistar rats divided in three experimental groups of ten animals each were used. A catheter of silicone was implanted into the lateral ventricles in group I, the cisterna magna in group II, and the lumbar subarachnoid space in group III to record the Pcsf values. This catheter was attached to a swivel system to allow unrestrained and free behaviour in the rats. Mean values of normal Pcsf values were 13.03 +/- 0.73 cm H2O from the lateral ventricles, 15.9 +/- 0.73 cm H2O from the cisterna magna, and 16.73 +/- 1.14 cm H2O from the lumbar subarachnoid space.

Anesthesia↗

Analgesic effect of two calcitonins and in vitro interaction with opioids.

1. When the analgesic effect of salmon-calcitonin (S-CT) and of eel-calcitonin (E-CT), as well as their influence on the morphine-analgesia were compared, no significant differences were found. 2. While on isolated tissues, E-CT induced a significant increase on the effect of bremazocine, [D-Pen2,D-Pen5]enkephalin and [Met5]enkephalin and no changes were observed on the effect of DAMGO, suggesting that E-CT increases the effects of opioids acting on delta or kappa receptors but not on mu receptors. 3. These findings corroborate the possibility of interactions between calcitonin and the opioid system.

Analgesics↗

Development of a clinically applicable high-speed flow cytometer for the isolation of transplantable human hematopoietic stem cells.

A high-speed cell sorter capable of a throughput speed 4-5-fold greater than commercially available systems was developed and evaluated as a processing tool for isolating purified hematopoietic stem cell grafts. The clinical high-speed sorter (CHSS) serves as a single-pass, multiparameter processing tool that provides the means to isolate a highly purified population of cells from starting cell populations with extremely low frequencies. The sorter incorporates environmental barriers to create a sterile environment for cell processing. Monoclonal antibodies and reagents produced under good manufacturing practices (GMP) are used to isolate hematopoietic stem cells by means of the CHSS. Using this technology, the CD34+Thy-1+Lin- hematopoietic stem cell population has been isolated from normal adult bone marrow and mobilized peripheral blood. The sorted cells have been shown to be sterile and viable and to retain hematopoietic function.

Cell Separation↗

Microsurgical anatomy of the posterior choroidal arteries.

In this study, we analysed the microanatomy of the medial and lateral posterior choroidal arteries, which supply vital central nervous system structures to the brainstem and choroids plexus. We traced the anatomical course of the medial and lateral posterior choroid arteries, their origin, diameter, number of branches, length, and anatomical variations. Twenty-six human unfixed brains were injected through the vertebral and carotid arteries with silicon rubber. Fifty-one out of a total of 129 vessels were medial posterior, and 78 were lateral posterior choroidal arteries. We divided the medial posterior choroidal artery into three segments: around the brainstem, quadrigeminal-pineal, and choroidal. The mean length of the medial posterior choroidal artery was 77.6 +/- 15 mm on the right side, and 77.1 +/- 15 mm on the left; the mean outer diameter observed was 0.8 +/- 0.5 mm on the right side, and 0.8 +/- 0.4 mm on the left. The number of branches arising from the medial posterior choroidal arteries averaged 25 +/- 9. In the lateral posterior group, the mean length observed was 49.5 +/- 26 mm on the right, and 58.0 +/- 23 mm on the left. There were instances of duplication and triplication of the lateral posterior choroidal vessels. The outer diameter averaged 0.72 mm on the right, and 0.6 mm on the left. The posterior choroidal arteries are clearly an important vascular component. A comprehensive knowledge of their anatomy will aid the neurosurgeon during surgery of the brainstem, pineal region, and third ventricle, and will limit complications resulting from injury to these arteries.

Arteries↗

Involvement of central serotonergic pathways in analgesia elicited by salmon calcitonin in the mouse.

The contribution of central serotonergic pathways to the analgesic activity induced by salmon calcitonin in the writhing test was investigated. Salmon calcitonin was administered to mice after lesioning of the ascending and descending serotonergic pathways by means of i.p. administration of p-chloroamphetamine (40 mg/kg, for 2 days) or p-chlorophenylalanine (300 mg/kg, for 3 days). The analgesic effect induced by salmon calcitonin at the doses of 10 and 20 IU/kg was not evident in mice previously treated with p-chloroamphetamine or p-chlorophenylalanine. However, the analgesic effect of salmon calcitonin 40 IU/kg was not significantly modified by p-chloroamphetamine or p-chlorophenylalanine pretreatment. Salmon calcitonin did not alter the depletion of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid after p-chloroamphetamine or p-chlorophenylalanine administration. Similarly, this hormone did not change the NSD 1015-induced accumulation of 5-hydroxytryptophan or the tranylcypromine-induced accumulation of 5-HT. These results indicate that although salmon calcitonin does not influence the synthesis and metabolism of 5-HT, it does require the integrity of the serotonergic system in order to cause analgesia.

Analgesics↗

The labelling of proliferating cells by Ki67 and MIB-1 antibodies depends on the binding of a nuclear protein to the DNA.

The antigen Ki-67 Ag, regarded as a marker for proliferating cells, was identified as a protein(s) (pKi-67) which can exist free or associated with DNA as evidenced by DNA digestion of cells before or after immunolabeling with Ki-67. The dual nature of this antigen was also supported by reconstitution of Ki-67 Ag from purified DNA and nuclear proteins extracted from the K562 cell line. The immunoreactivity of the resulting complexes was examined in solution using Ki-67 and MIB-1 antibodies. The interaction between Ki-67 or MIB-1 antibodies and pKi-67 was enhanced in the presence of undegraded ds DNA, indicating that ds DNA modulates the conformation of pKi-67 and that the altered conformation of pKi-67 is more reactive than the pure protein to both Ki-67 and MIB-1 antibodies.

Antibodies↗

Flow cytometric study of idarubicin and daunorubicin accumulation and the effect of verapamil in leukemic cell lines and fresh cells from patients with acute non-lymphoblastic leukemia.

By using flow cytometry, the intracellular accumulation (Acc) of idarubicin (IDA) and daunorubicin (DNR) and the effect of verapamil (VRP) on both anthracycline accumulation (VRP index) were studied in leukemic cell lines (K562 and HL60 and their two DNR-resistant subclones) and fresh leukemic cells. IDA accumulated more than DNR in both parental (K562: p < 0.03 and HL60: 0.09) and resistant cell lines (p < 0.01 for both cell lines) irrespective of whether or not they were treated with VRP. VRP index was higher for DNR than for IDA (p < 0.05). Similar results were observed in fresh leukemic blasts from 25 patients with ANLL (IDA Acc superior to DNR Acc: p < 0.0001; higher VRP index for DNR than for IDA: p < 0.01). The higher Acc of IDA than DNR seen in fresh leukemic cells could explain the better clinical efficacy of IDA reported in patients with ANLL.

Adolescent↗

Geographic independence of HTLV-I and HTLV-II foci in the Andes highland, the Atlantic coast, and the Orinoco of Colombia.

To clarify the ethnic specificity of human T cell leukemia virus type I (HTLV-I) and type II (HTLV-II) carriers among Colombian native Indians, we investigated the geographic distribution of HTLV-I and HTLV-II seroprevalence among the isolated ethnic groups of Mongoloid origin in the Andes highlands and the Atlantic coast of Colombia. HTLV-I carriers were found in 1.6% (1/62 samples) of Inga, 8.5% (5/59) of Kamsa, and 0% (0/55) of Cumbal Indians who live in the Andes highlands at 3000 m above sea level. On the other hand, HTLV-II carriers were found in 4.1% (5/123) of Wayuu Indians, who live in the Guajira region of the Atlantic coast of Colombia at a distance of 1000 km from the Andes highlands. This ethnic specificity of HTLV-II was similarly observed among Guahibo Indians in the Orinoco. The seroprevalence of HTLV-I and HTLV-II was mutually exclusive among Inga, Kamsa, and Wayuu Indians. These results suggest that HTLV-I and HTLV-II may have evolved among Mongoloid populations and been independently transmitted among two different lineages of Colombian native Indians, Andes highlanders and Atlantic coast lowlanders.

Adolescent↗