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Biomedical subjects

C Segura

Publications and source records attributed to C Segura.

At least 19 recordsLinked to original sources
PubMed2005

Relationship between pharmacokinetic parameters of cyclosporin and the incidence of acute rejection after heart transplantation.

Despite two decades of use, there are limited data on the best way to monitor Cyclosporine (CsA) for heart transplantation. The aim of our study was to determine the relationships between pharmacokinetic parameters and clinical outcomes after heart transplantation and to evaluate the range of CsA trough levels provided the most effective protection against graft rejection. We retrospectively analyzed the clinical outcomes of all adult patients who received a heart transplant between January 1998 and February 2005. All had routine monitoring of CsA trough levels and scheduled endomyocardial biopsies. Rejection was defined as grade > or =3, based on International Society for Heart and Lung Transplantation (ISHLT) criteria. Follow-up period was 1 year. All patients were on CsA, corticosteroids, and azathioprine/mycophenolate mofetil with or without antilymphocyte induction (eight patients with basiliximab). Data were analyzed by unpaired Student t-test, Cox regression model, and ROC curve. Among 70 patients (60 men and 10 women) who entered the study, 34 (48.6%) had at least one acute rejection episode of grade > or =3 during the first posttransplant year. Mean CsA trough level (C(0)) measured at first week posttransplant was significantly lower in the rejection than the no-rejection group (125.17 +/- 56.9 ng/mL versus 169.33 +/- 48.27 ng/mL, P = .001). C(0) was the strongest predictor of acute graft rejection (P = .000, HR = .985.) The risk decreased by 1.5% for each unit increase of the C(0) value. ROC analysis showed that C(0) of 150 ng/mL provided the optimal cutoff. Patients with mean C(0) >150 ng/mL over the first week had less incidence of acute rejection than patients with levels <150 ng/mL (30.3% versus 64.9%) (P = .009, Cochran-Mantel-Haenszel test). In conclusion, our data suggest that in heart transplant patients it may be crucial to target early trough levels above 150 ng/mL during the first days postsurgery to avoid rejection.

Adolescent↗
PubMed2005

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.

BACKGROUND: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported. OBJECTIVE: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation. METHODS: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine. RESULTS: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation. CONCLUSIONS: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.

Breast↗
PubMed2004

Analysis of the vitamin D receptor Fokl polymorphism.

In the present study we analysed the vitamin D receptor (VDR) Fokl polymorphism distribution in a Caucasian population from the North-West of Spain. This polymorphism has been associated with variation in bone mineral density levels and has been proposed as a factor for the genetic predisposition to osteoporosis. This study was performed in 60 healthy individuals by restriction fragment length polymorphism (RFLP) analysis using the endonuclease Fokl and alternatively using single strand conformation polymorphism (SSCP). The genotype distribution was: 46.7% FF homozygotes, 43.3% Ff heterozygotes, and 10% ff homozygotes. These values do not reveal significant differences in comparison with other available Caucasoid populations, but show clear differences with respect to African-American populations. The analysis of this polymorphism by SSCP reveals the existence of a novel single nucleotide polymorphism (AAT/AAC) located within the DNA binding domain of the VDR gene at position-19 codon. Thus, using a novel 109 bp hVDR gene fragment which excludes the AAT/AAC variant in the vitamin D receptor Fokl allows an easier determination by SSCP analysis of the Fokl polymorphism.

Adult↗
PubMed2003

Influence of pulsation rate on udder health and teat thickness changes in dairy ewes.

In this work on machine milking of ewes, pulsation rates of 120 and 180 cycles per min were compared, both with a pulsation ratio of 50:50 and a vacuum level of 36 kPa, comparing intramammary infection (IMI), somatic cell count (SCC) and teat end thickness changes. To this end, two groups of 20 Manchega ewes were used in a crossover experimental design with two experimental periods of 24 d for each. Bacterial exposure of all teats was increased by dipping them in a suspension of Staphylococcus simulans at four consecutive milkings of each period. Pulsation rate of 180 cycles per min, compared with 120 cycles per min, had no negative effect upon new IMI (11 and 16% of ewes infected, respectively) and SCC. No teat end lesions were observed in those animals milked with the two pulsations assayed. Also, teat thickness changes (-0.38 and -0.36 mm at 120 and 180 cycles per min, respectively) were not affected significantly. Finally, in absence of IMI, the two pulsation rates assayed did not affect the SCC.

Animals↗
PubMed2002

Pit-1/GHF-1 and GH expression in the MCF-7 human breast adenocarcinoma cell line.

GH expression in mammary tumors has been related to the increase and spreading of cell proliferation. Using the MCF-7 human breast adenocarcinoma cell line, it has been demonstrated that autocrine GH-stimulated mammary carcinoma cell proliferation decreased the apoptosis rate and enhanced cell spreading. Surprisingly, no data are available about the presence of Pit-1 (the main pituitary regulator of GH) or GH expression in this cell line. Using RT-PCR, Western blot and immunohistochemistry, we have demonstrated the presence of both mRNA coding Pit-1 and GH as well as Pit-1 and GH protein in the MCF-7 cell line. These data could imply that Pit-1 may be an adequate target to inhibit breast cell proliferation.

Adenocarcinoma↗
PubMed2001

Inefficacy of burst-suppression anesthesia in medication-resistant major depression: a controlled trial.

Burst-suppression anesthesia (BSA) has been previously compared with electroconvulsive therapy (ECT) in drug-resistant depression, with promising results. We have carried out a double-blind randomized clinical trial comparing BSA with sham-BSA in 20 patients meeting DSM-IV criteria for major depression with inadequate response to antidepressant drugs and who chose BSA as an alternative to ECT. After withdrawing antidepressant drugs, patients were randomized to receive four sessions of either BSA (induction with propofol followed by the anesthetic agent sevoflurane, achieving BSA for 1 hour) or sham-BSA (induction with propofol until loss of consciousness, followed by spontaneous awakening in 5-10 minutes). Decrease in the Hamilton Rating Depression Scale was larger with BSA (-6.0 +/- 7.3) than with sham-BSA (-2.5 +/- 4.5), but differences did not reach statistical significance ( t = -1.08, p = 0.3). In our sample, we have not found BSA to be superior to sham-BSA and therefore cannot consider BSA as an alternative to ECT.

Adult↗
PubMed2001

SHV-1 beta-lactamase is mainly a chromosomally encoded species-specific enzyme in Klebsiella pneumoniae.

The nature of the SHV-1 beta-lactamase gene was analyzed in 97 epidemiologically unrelated Klebsiella pneumoniae strains isolated from clinical samples. beta-Lactamase bands that focused at a pI of 7.6 (SHV-1-type) in 74 strains, at a pI of 7.1 (LEN-1-type) in 13 strains, and at a pI of 5.4 (TEM-1-type) in 10 strains were detected by analytical isoelectric focusing (IEF). Among the 74 SHV-1-producing strains, 40 had, in addition to the pI 7.6 band, an additional band on IEF: 20 had a band with a pI of 7.1 and 20 had a band with a pI of 5.4. Most of the 74 SHV-1-producing strains (76.7%) carried plasmids. Transfer of beta-lactam resistance by conjugation was possible in only 9.3% of the strains tested. SHV-1 gene-specific PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the chromosomal DNA was positive for 93 of the 97 strains and negative for only 4 of the 10 samples with K. pneumoniae TEM-1 producers. In an attempt to approximate the location of the SHV gene locus by endonuclease restriction analysis, RFLP analysis with Southern blotting of chromosomal DNA with a labeled SHV-1 fragment as a probe was used to study the 97 strains. A trial with EcoRI showed at least one positive hybridization band for 96 strains; two bands were detected for 8 strains. The hybridization was negative for only one TEM-1 beta-lactamase-producing strain. DNA sequence analysis showed no differences in promoter regions or extra stop-triplet sequences; only point mutations determined different allelic variants. The novel SHV-type variants are designated SHV-32 and SHV-33. As a result of the RFLP and sequencing analyses, it can be postulated that the loci for SHV-1 and LEN-1 genes are arranged in tandem. Our results strongly support the hypothesis that the ancestor of the SHV-1 beta-lactamase originated from the K. pneumoniae chromosome.

Chromosomes, Bacterial↗
PubMed2000

Activation pattern and toxicity of the Cry11Bb1 toxin of Bacillus thuringiensis subsp. medellin.

Bacillus thuringiensis protoxins undergo proteolytic processing in the midgut of susceptible insects to become active. The ability to process the Cry11Bb1 protoxin by trypsin and Culex quinquefasciatus larval gut extracts was tested. The protease activity indicated by the appearance of proteolytic products increased with an increment in pH, with the highest activity being observed at pH 10.6. A time course study showed the proteolysis of the 94-kDa Cry11Bb protein ending with the production of fragments of relative molecular mass of 30 and 35 kDa within 5 min. In vitro, gut proteases extract cleaved the solubilized toxin between Ser59 and Ile60 and between Ala395 and Asn396, generating a 30-kDa N-terminal and a 35-kDa C-terminal fragment, respectively. Similarly, mosquito larvae processed in vivo the parasporal inclusions, generating the same fragments as those observed in vitro. The Cry11Bb1 protoxin activated with trypsin or gut proteases showed larvicidal activity against C. quinquefasciatus first instar larvae. The data suggest that gut proteases participate in the activation of CryllBbl protoxin, generating at least two different fragments on which the activity could reside.

Amino Acid Sequence↗
PubMed2000

Retinoid X receptor mRNA expression in human pituitary gland.

Retinoic acid is involved in important physiological processes such as the regulation of growth and differentiation of several tissues, including the pituitary gland. These biological effects are mediated by their binding to two specific intracellular receptors termed retinoic acid and retinoid X receptors, RARs, RXR, respectively). RAR or RXR mRNA expression has been demonstrated in several tissues, but little information is available about its presence in the human pituitary gland. In this report, we demonstrate alphaRXR mRNA expression using the reverse transcription coupled to polymerase chain reaction (RT-PCR) in the human pituitary gland. These results suggest the possibility that RXR may regulate the human pituitary gene expression and hormone secretion.

Adult↗
PubMed1999

Vitamin D receptor ontogenesis in rat liver.

Vitamin D through its receptor (VDR) plays a major role in bone mineral metabolism. However, VDR is also present in a variety of cell lines as well as in numerous tissues, suggesting other functions of the hormone beyond bone metabolism and mineral homeostasis. At the liver level, it has been shown that vitamin D induces numerous changes (i.e. enzyme activity level, stimulation of some metabolic pathways and stimulation of the normal liver recovery after partial hepatectomy). However, some works did not find VDR in the liver, and also used liver tissue as a negative control of VDR gene expression. In this paper, we examined fetal, neonatal and adult rat tissues for the presence of VDR using a sensitive RT-PCR technique and immunohistochemistry. We found VDR mRNA and VDR protein in rat liver at all different periods of rat life. Thus, we suggest that some of the actions of vitamin D on liver could be mediated at the genomic level through the VDR, and that the use of this tissue as a negative control of VDR gene expression is clearly inappropriate.

Animals↗
PubMed1998

High-affinity binding sites to the vitamin D receptor DNA binding domain in the human growth hormone promoter.

The regulation of the human growth hormone (hGH) gene by 1,25(OH)2D3 is a mechanism which is poorly understood. The objective of this study was to investigate whether the hGH gene has DNA recognition elements for the DNA binding domain of the vitamin D receptor. Using gel retardation assays and footprinting techniques, two high-affinity binding sites, denominated F1 and F2, were identified in the 5'-flanking sequence of hGH. The distal site, F1, located at -59 bp is made up of an imperfect direct repeat separated by 3 bp and showed a high degree of similarity with other known vitamin D response elements (VDREs). The proximal site, F2, located at -36 bp showed a single 7-bp sequence, which is different from other known VDREs. The location of both sites (F1 near the GHF-1/Pit-1 response element, F2 contacting the TATA box) suggests that the vitamin D receptor by itself or through interference with other transcriptional factors may modulate hGH expression.

Binding Sites↗
PubMed1998

Determining the accuracy of stock and custom tray impression/casts.

A study was conducted to evaluate the accuracy of casts made from stock tray and custom tray impressions using polysiloxane impression material. The results indicate that all casts distort but that impressions made from custom trays were more accurate and consistent in reproduction than were stock tray impressions.

Acrylic Resins↗
PubMed1998

Contribution of beta-lactamases to beta-lactam susceptibilities of susceptible and multidrug-resistant Mycobacterium tuberculosis clinical isolates.

The beta-lactamases in 154 clinical Mycobacterium tuberculosis strains were studied. Susceptibilities to beta-lactam antibiotics, their combination with clavulanate (2:1), and two fluoroquinolones were determined in 24 M. tuberculosis strains susceptible to antimycobacterial drugs and in nine multiresistant strains. All 154 M. tuberculosis isolates showed a single chromosomal beta-lactamase pattern (pI 4.9 and 5.1). M. tuberculosis beta-lactamase hydrolyzes cefotaxime with a maximum rate of 22.5 +/- 2.19 IU/liter (strain 1382). Neither amoxicillin, carbenicillin, cefotaxime, ceftriaxone, nor aztreonam was active alone. Except for aztreonam, beta-lactam combinations with clavulanate produced better antimycobacterial activity.

Clavulanic Acid↗
PubMed1997

Endogenous fibronectin of blood polymorphonuclear leukocytes: immunochemical characterization and subcellular localization.

Fibronectin, a large dimeric glycoprotein synthesized and secreted by several cell types, mediates cell adherence to surfaces. In infections and inflammatory responses, blood polymorphonuclear leukocytes (PMNs) adhere to cells and matrix proteins during extravasation and accumulation at inflammatory sites. The presence of fibronectin in blood PMNs has been poorly studied, and the characteristics and subcellular localization of this endogenous adhesive molecule are practically unknown. By immunofluorescence flow cytometry, purified rabbit antibodies and a monoclonal antibody to plasma fibronectin reacted with isolated blood PMNs, only after permeabilization of the cells. By Western blot analysis, the antibodies recognized, under reducing conditions, a protein with an apparent molecular mass of 230 kDa in the cell lysate. Eleven monoclonal antibodies to common frame fibronectin epitopes, including the RGD-containing cell-binding domain, also reacted with PMN fibronectin by Western blotting. In contrast, two antibodies to ED-A, the alternatively spliced region characteristic of "cellular" fibronectin, were unreactive, but recognized platelet fibronectin. On average, 1 million PMNs contained 6.8 ng +/- 1.4 (SD) of fibronectin, as measured by sandwich ELISA. Immunogold labeling and electron microscopy studies indicated localization of most fibronectin in PMN granules. Moreover, double-immunofluorescence and digital image analysis demonstrated colocalization of fibronectin with lactoferrin, a marker of specific (secondary) granules. The results indicate that blood PMNs contain approximately 8000 molecules per cell of intact ED-A-negative fibronectin localized mainly in their specific granules.

Antibodies, Monoclonal↗