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Biomedical subjects

P Lopez

Publications and source records attributed to P Lopez.

At least 37 records · Page 2Linked to original sources

Circulating relaxin concentrations in pregnant and nonpregnant bitches: evaluation of a new enzymeimmunoassay for determination of pregnancy.

A new kit (ReproCHEK RELAXIN) intended for the diagnosis of pregnancy in bitches is now available for veterinary use. This assay measures relaxin concentrations in plasma and whole blood samples, and the presence of significant amounts of relaxin is indicative of pregnancy. A clinical trial was carried out to evaluate the performance of the test. Serial blood samples were collected on alternate days, and relaxin concentrations were determined from day 15 to day 35 after the LH surge (estimated by progesterone concentrations). Pregnancy was confirmed using ultrasonography. At the end of pregnancy, both the day of whelping and the size of the litter were recorded. Pregnancy was established in 61 bitches. The day that pregnancy was detected using the relaxin assay ranged from day 19 to day 28 after the LH surge and had a mean (+/- SD) of 25.4 +/- 2.5 days. The day of parturition was taken as a reference point, and pregnancy was detected from -46 to -38 days (mean -40.2 +/- 2.4 days) before parturition. False positives were not observed in pseudopregnant bitches (n = 16) or in the control group (30 anoestrous and ten unmated bitches). These results demonstrate that the new assay kit is an inexpensive, user-friendly and reliable technique for determining pregnancy.

Anestrus↗

Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer.

BACKGROUND: In phase II trials, paclitaxel has been shown to have antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC). However, the survival and quality-of-life (QOL) benefits of paclitaxel used as a single agent compared with supportive care alone have not been assessed in a randomized clinical trial. METHODS: A total of 157 patients with stage IIIB or IV NSCLC who had received no prior chemotherapy were randomly assigned to receive either best supportive care alone (78 patients) or paclitaxel plus supportive care (79 patients). Paclitaxel was administered as a 3-hour intravenous infusion every 3 weeks. Supportive care included palliative radiotherapy and supportive therapy with corticosteroids, antibiotics, analgesics, antiemetics, transfusions, and other symptomatic therapy as required. The primary end point of the study was survival. Time to disease progression, response rate, adverse events, and QOL were secondary end points. RESULTS: Pretreatment characteristics were evenly distributed between the two arms. Survival was statistically significantly better in the paclitaxel plus supportive care arm than in the supportive care alone arm (two-sided P =.037) (median survival = 6.8 months versus 4.8 months). Cox multivariate analysis showed paclitaxel plus supportive care to be statistically significantly associated with improved survival (two-sided P =.048). QOL was similar for both treatment arms, except for the functional activity score of the Rotterdam Symptom Checklist, where QOL data statistically significantly favored the paclitaxel plus supportive care arm (two-sided P =.043). CONCLUSION: The addition of paclitaxel to best supportive care significantly improved survival and time to disease progression compared with best supportive care in patients with advanced NSCLC and may improve some aspects of QOL.

Adult↗

Bacterial mode of replication with eukaryotic-like machinery in a hyperthermophilic archaeon.

Despite a rapid increase in the amount of available archaeal sequence information, little is known about the duplication of genetic material in the third domain of life. We identified a single origin of bidirectional replication in Pyrococcus abyssi by means of in silico analyses of cumulative oligomer skew and the identification of an early replicating chromosomal segment. The replication origin in three Pyrococcus species was found to be highly conserved, and several eukaryotic-like DNA replication genes were clustered around it. As in Bacteria, the chromosomal region containing the replication terminus was a hot spot of genome shuffling. Thus, although bacterial and archaeal replication proteins differ profoundly, they are used to replicate chromosomes in a similar manner in both prokaryotic domains.

Archaeal Proteins↗

Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving positions.

The current paradigm of eukaryotic evolution is based primarily on comparative analysis of ribosomal RNA sequences. It shows several early-emerging lineages, mostly amitochondriate, which might be living relics of a progressive assembly of the eukaryotic cell. However, the analysis of slow-evolving positions, carried out with the newly developed slow-fast method, reveals that these lineages are, in terms of nucleotide substitution, fast-evolving ones, misplaced at the base of the tree by a long branch attraction artefact. Since the fast-evolving groups are not always the same, depending on which macromolecule is used as a marker, this explains most of the observed incongruent phylogenies. The current paradigm of eukaryotic evolution thus has to be seriously re-examined as the eukaryotic phylogeny is presently best summarized by a multifurcation. This is consistent with the Big Bang hypothesis that all extant eukaryotic lineages are the result of multiple cladogeneses within a relatively brief period, although insufficiency of data is also a possible explanation for the lack of resolution. For further resolution, rare evolutionary events such as shared insertions and/or deletions or gene fusions might be helpful.

Actins↗

Increased levels of expression of an NMDARI splice variant in the superior temporal gyrus in schizophrenia.

Expression patterns of mRNAs for the NMDARI subunit (NRI) carboxy-terminus isoforms were investigated in postmortem brain tissue using isotopic in situ hybridization. Three brain regions (superior temporal, middle frontal and visual cortices) were examined in patients with schizophrenia (n = 6) and control subjects (n = 6). A 22% higher level of expression of the NRI isoform that contains neither spliced exon was observed in the superior temporal gyrus of patients with schizophrenia compared with controls (p = 0.01). No differences were observed in the expression of the other isoforms in the three regions studied. These data suggest that NRI alternative splicing might be abnormal in schizophrenia and reinforce previous findings implicating the superior temporal gyrus as a site of neural dysfunction in schizophrenia.

Adult↗

Increased renal vasoconstriction and gene expression of cyclooxygenase-1 in renovascular hypertension.

Vascular responses to arachidonic acid (AA) in the renal circulation are increased in hypertensive rats. We have suggested that these differences are related to changes in AA metabolism. In this study we investigated the mechanism involved in the increased AA-induced renal vasoconstriction. We evaluated vascular renal reactivity in the isolated perfused kidney, cyclooxygenase activity, protein content, and mRNA expression of kidneys from sham operated and aortic coarctation rats. Bolus injection of AA (1, 2, 4, and 8 microg) increased perfusion pressure in a dose-dependent manner by 20 +/- 4, 28 +/- 5, 38 +/- 6, and 44 +/- 7 mm Hg in sham-operated rats and 30 +/- 3, 55 +/- 5, 78 +/- 5, and 113 +/- 8 mm Hg in rats with aortic coarctation. Indomethacin (1 microg/ml) or the endoperoxide/thromboxane blocker SQ29548 (1 microM) prevented AA renal vasoconstriction. Cyclooxygenase activity, cyclooxygenase-1 protein content, and mRNA expression were also increased in the renal tissue from the aortic coarctation rats compared with sham-operated rats. In conclusion, we suggest that during development of hypertension, the cyclooxygenase-1 mRNA is induced, and consequently cyclooxygenase-1 activity and AA metabolism are increased, resulting in augmented production of vasoconstrictor prostaglandins that mediate the potentiated responsiveness to AA or other vascular agonists that release AA, thus increasing peripheral vascular resistance.

Animals↗

Clinical and bacteriologic efficacy of amoxycillin b.d. (45 mg/kg/day) versus amoxycillin t.d.s (40 mg/kg/day) in children with group A beta-hemolytic streptococcal tonsillopharyngitis.

This randomized, observer-blind, multicenter, parallel-group study compared the clinical and bacteriologic efficacy and safety of amoxycillin, 45 mg/kg/day b.d. and amoxycillin, 40 mg/kg/day t.d.s. after 7 days of treatment in 517 children with acute bacterial tonsillopharyngitis. At the end of treatment, a successful clinical response was recorded in more than 96% of patients in each of the treatment groups. A similar result was obtained at follow-up. Among those patients who were bacteriologically evaluable at the end of treatment, a successful bacteriologic response was achieved in more than 94% in each treatment group. Both treatments were well tolerated. Drug-related adverse events were recorded in just 12 patients (4.6%) in the b.d. group and six (2.4%) in the t.d.s. group. The study demonstrated that a twice-daily regimen of amoxycillin, 45 mg/kg/day, was as effective and as well tolerated as the standard three-times-daily regimen of amoxycillin, 40 mg/kg/day, in the treatment of acute bacterial tonsillopharyngitis in children.

Adenoids↗

A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene.

Inhibin, a member of the TGF-beta superfamily, is synthesized in the testis by Sertoli cells and exerts an endocrine regulatory function on pituitary hormone synthesis. A distinct local function has been proposed, negatively controlling cellular growth in the testis (tumor suppressor activity). A critical test for the identification of a tumor suppressor is the reversal of transformed growth properties upon re-expression of the gene in tumor-derived cell lines. Sertoli cell-derived tumoral lines were previously established from tumors that develop in elderly transgenic males which express in the testis the large T antigen of polyoma virus. Both the tumors and the cells in culture exhibited reduced levels of the inhibin alpha subunit mRNA. Stable transfectants were generated, in which this subunit was expressed from a heterologous promoter. All of them exhibited a strict inhibition of growth at confluency. On the other hand, in addition to an aging-related decrease in inhibin synthesis, the alpha subunit gene was down regulated in vivo in cells expressing the viral protein. The conjunction of these two factors accounts for the age-related occurrence of testicular cancers in the transgenic model, again pointing to inhibin as a potent cell growth regulator in the seminiferous epithelium.

Antigens, Viral, Tumor↗

Enkephalin receptors and receptor-mediated signal transduction in cultured human lymphocytes.

Enkephalins are opioid peptides that bridge the neuroendocrine and immune systems. Using flow cytometry and a fluorescein conjugate of the endogenous pentapeptide methionine-enkephalin (ME), we have identified enkephalin receptors on cultured human lymphocytes. Cell surface recognition sites that bound ME with high affinity and specificity were detected for NALM 6 (pre-B acute lymphoblastic leukemia) and Jurkat (T lymphoma) cells. Brain-like enkephalin receptors were measured for these lymphocytes using conventional radioligand-receptor assays and the highly delta opioid receptor-selective enkephalin analog [3H]DPDPE. Upon activation, the lymphocyte enkephalin receptors transmitted signals that enhanced the accumulation of intracellular cAMP. These studies provide evidence that cultured human lymphocytes of the B (NALM 6 cells) and T (Jurkat cells) lineages express functional enkephalin receptors and suggest that such receptors may be instrumental in the lymphocyte response to opioid peptides and alkaloids.

Calcium↗

The root of the tree of life in the light of the covarion model.

A few duplicated genes have been found useful to root the universal tree of life. Despite controversial results, the consensus led to locate the root in the eubacterial branch. However, we demonstrated (Philippe and Forterre 1999) that all these markers were in fact unsuitable for any firm conclusion, mainly because of their high level of mutational saturation, which masks a major part of the phylogenetic signal. But then, the very persistence of signal for events as early as the separation of the three domains becomes puzzling. This paradox was studied here for translation elongation factor proteins, EF-1alpha and EF-2, which appeared to be one of the least confusing markers. We showed that these proteins do not conform to a classical rate-across-sites pattern, as those modeled by a gamma law, but rather to a covarion-based model, because the evolutionary rate of a given position often changes between taxonomic groups. Conservation of the very ancient signal can thus be better explained by the covarion model: a substitution can occur in deep branches, and the position remains constant afterward, as "fossilized" by a change of covation. As no reconstruction method has up to now taken into account this complex model, we devised a simple method for extracting the phylogenetic signal, by considering the variability of sequence positions within predefined phylogenetic groups. We showed that noise quantitatively prevailed upon signal. Parsimony will produce erroneous topologies, because it has to minimize primarily the number of steps of the noise. In contrast, our method effectively concentrated the signal and was more suitable for inferring ancient events. We consequently found the eubacterial rooting to be presumably due to a long branch attraction artifact, because of the higher evolutionary rate of Eubacteria for these proteins. Among the two other rooting possibilities, the eukaryotic rooting appeared to be more supported, although not enough to be conclusive.

Algorithms↗

Inactivation of heat-resistant pectinmethylesterase from orange by manothermosonication.

Pectinmethylesterase of navel oranges shows two fractions greatly differing in thermostability. The most thermostable fraction accounts for approximately 10% of total activity. The thermal inactivation of this fraction follows first-order kinetics both in 5 mM, pH 3.5, citrate buffer and in orange juice at the same pH, showing a z value of 5.1 degrees C and an activation energy (E(a)) of 435 kJ mol(-)(1) K(-)(1). The heat resistance of the enzyme is approximately 25-fold higher in the juice than in citrate buffer. When ascorbic acid, sucrose, glucose, and fructose are added to the citrate buffer at the concentrations found in orange juice, the heat resistance of the enzyme increases 3-fold. The addition of pectin at 0.01% concentration multiplies it by a factor of 50. Manothermosonication (MTS), the simultaneous application of heat and ultrasound under moderate pressure (200 kPa), at 72 degrees C, increases the inactivation rate 25 times in buffer and >400 times in orange juice. MTS inactivation shows a higher z value (35.7 degrees C) and lower E(a) (56.9 kJ mol(-)(1) K(-)(1)) than simple heating.

Carboxylic Ester Hydrolases↗

Transcriptional control of the low-temperature-inducible des gene, encoding the delta5 desaturase of Bacillus subtilis.

The Bacillus subtilis des gene encodes the cold-inducible Delta5 lipid desaturase involved in the formation of unsaturated fatty acids from saturated phospholipid precursors. Here, we describe the expression pattern of the des gene in response to a temperature downshift from 37 to 20 degrees C. We found that the synthesis of des mRNA is undetectable at 37 degrees C but dramatically induced upon the temperature downshift. Decay characteristics of the des transcript as well as the in vivo decay of B. subtilis bulk mRNA were investigated. The results showed that the stability of the des transcript as well as of bulk mRNA lasted substantially longer at 20 degrees C than at 37 degrees C. Functional expression of des at 37 degrees C was achieved by exchanging its promoter with the non-cold shock spac promoter. These data provide the first direct evidence that temperature-mediated control of transcription is the major mechanism regulating the mRNA levels of the B. subtilis desaturase. The present results also demonstrate that the only component of the desaturation system regulated by temperature is the desaturase enzyme.

Bacillus subtilis↗

NTP concentration effects on initial transcription by T7 RNAP indicate that translocation occurs through passive sliding and reveal that divergent promoters have distinct NTP concentration requirements for productive initiation.

The hypothesis that active site translocation during initial transcription occurs by a passive sliding mechanism which allows the pre- and post-translocated states to equilibrate on the time scale of bond formation was tested by evaluating the effects of NTP concentration on individual transcript extension steps in the presence of translocation roadblocks created by proteins bound immediately downstream of a T7 promoter, as well as by evaluating the effects of NTP concentration on competing transcript extension pathways (iterative synthesis and "normal" extension). Results are consistent with a passive sliding mechanism for translocation which is driven by NTP binding, and are inconsistent with mechanisms in which the pre- and post-translocated states fail to equilibrate with each other on the time scale of bond formation or in which translocation is driven by NTP hydrolysis. We also find, in agreement with many previous studies, that divergence from consensus in the ITS (initially transcribed sequence) of the T7 promoter decreases productive initiation. However, this appears to be largely due to increases in the NTP concentration requirements for efficient transcription on the divergent ITSs.

Adenosine Triphosphate↗

First episode in bipolar disorder: misdiagnosis and psychotic symptoms.

BACKGROUND: This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS: It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS: A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis.

Adult↗