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Biomedical subjects

C Fernández

Publications and source records attributed to C Fernández.

At least 37 records · Page 2Linked to original sources

IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells.

In previous studies we demonstrated that IGF-I induces proliferation of pituitary lactotrophs. In addition to its mitotrophic actions, IGF-I is known to prevent apoptosis induced by diverse stimuli in several cell types. In this study, we investigated the action of IGF-I on pituitary cell survival and the intracellular signaling transduction pathway implicated in this effect. Treatment of cultured male rat pituitary cells with IGF-I (10(-7) M) for 24 h prevented pituitary cell death induced by serum deprivation. The protective effect of IGF-I was blocked by phosphoinositide 3-kinase (PI3-kinase) inhibitor, LY294002, but was unaffected by PD98059, which inhibits MAP/ERK kinase (MEK1). IGF-I activation of PI3-kinase induced the phosphorylation and activation of the serine/threonine kinase Akt. Moreover, IGF-I increased the phosphorylation of the pro-apoptotic factor Bad and the levels of the anti-apoptotic protein Bcl-2 through the PI3-kinase pathway in primary pituitary cells.

Animals↗

[Tear function index validation for dry eye diagnosis].

PURPOSE: To develop a simple method for the clinical evaluation of tear dynamics and evaluate its usefulness in the diagnosis of dry eye syndrome. METHODS: The study includes 170 eyes from 85 adults. 102 eyes had a Schirmer's test value of less than 10 mm and subjective symptoms of dry eye. Tear function index (TFI) was calculated in all the cases using prepared drops with 0.5% fluorescein and 0.4% oxibuprocaína. Five minutes later a Schirmer strip was placed on the conjunctival fornix. Schirmer's test and tear clearance were calculated after a further five minutes. Tear clearance was measured using a table of fluorescein concentrations. TFI is the quotient between the value of the Schirmer's test and TCR. RESULTS: The cut-off value of TFI in dry eye is 74. At this point the sensitivity of this method is 74% and the specificity is 63%. The Schirmer's test results did not correlate with the tear clearance results. CONCLUSION: TFI is a rapid and sensitive method of identification of subjects with dry eye. The lack of correlation between TFI and TCR is because these methods evaluate different aspects of tear dynamics.

Adult↗

Prognostic significance of the p185 protein in colorectal cancer.

The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a role in tumor development and progression. The aim of this prospective study was to evaluate the prognostic value of p185 protein in colorectal cancer using immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens from patients who had been operated on by the same surgeon and subjected to a median follow-up of 3 years. Thirty-three per cent of patients showed p185 overexpression related to an advanced stage of the disease. In patients with adenocarcinoma tumors of the colon without distant metastases, p185 detection was found to be of clinical prognostic relevance (p = 0.06).

Adult↗

[Baroreflex failure after chemodectoma resection].

Baroreflex failure after chemodectoma resection We present a case of baroreflex failure secondary to a unilateral injury of the glossopharyngeal nerve. The patient was operated for a left-sided chemodectoma in the carotid body. Some months after surgery she started to report presyncopal episodes exacerbated by mental stress and when standing up. During these episodes, the patient presented hypertensive crises and tachycardia. However, blood pressure was below normal ranges at rest. The diagnosis was baroreflex failure secondary to unilateral injury of the glossopharyngeal nerve. The case reported herein illustrates the fact that the presence of a bilateral injury is not essential for the occurrence of this disorder.

Aged↗

Effect of freezing goat milk samples on recovery of intramammary bacterial pathogens.

With the aim of evaluating the effect of freezing goat milk samples on recovery of intramammary pathogens, 1200 milk samples from udder halves with subclinical intramammary infection were studied. Samples (20 ml) were frozen at -20 and at -80 degrees C. Thawing was carried out at room temperature at 7, 14, 21, 28, 58, 118, 178, 236 and 730 days after collection and bacteriological analyses were carried out to determine the number of colony forming units/ml (CFU/ml). Mixed model statistical analysis showed that bacterial group, temperature of storage, interaction of bacterial group and temperature of storage and the interaction of bacterial group, time and temperature of storage were statistically significant effects. For coagulase negative staphylococci (CNS), least squares means of log CFU/ml recovered at -20 and -80 degrees C were not different. Nevertheless, for Gram negative bacilli (GNB) a significant decrease was detected in samples frozen at -20 vs. -80 degrees C. At both temperatures and at different times of storage, significant increases were detected between log CFU/ml of CNS and values on day zero. At -20 degrees C, a significant decrease in GNB recovery was detected between freezing days zero and 730. This difference was not detected when goat milk samples infected by GNB were frozen at -80 degrees C. The results show that frozen milk samples can be useful in goat subclinical mastitis control programs.

Animals↗

Loss of heterozygosity and methylation of p16 in renal cell carcinoma.

To investigate the possible role of genomic aberrations of chromosome 9p21 in the tumorigenesis of human renal cell carcinoma (RCC), 40 sporadic RCCs were studied using PCR analyses. The tumours were predominantly low stage and low grade. Loss of heterozygosity (LOH) was observed in nine of 39 informative cases, but no homozygous deletion was noticed. Hypermethylation of the promoter region of p16 occurred in eight of the 40 RCCs. No correlation was found between hypermethylation of the p16 gene and LOH on 9p21. A similar level of LOH and methylation was observed in the 40 RCCS regardless of histology, grade and stage. These results suggest that inactivation of p16 and the possibility of other unknown tumour suppressor genes located on other chromosomes could be involved in the pathogenesis of RCC.

Carcinoma, Renal Cell↗

Immunoprophylaxis with Simulect (basiliximab) in kidney transplantation: results from routine clinical practice at 18 kidney transplant units.

OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.

Adrenal Cortex Hormones↗

Association between anatomopathologic graft disorders during reperfusion and vena cava sIL-2r in orthotopic liver transplantation.

UNLABELLED: Graft ischemia-reperfusion injury during orthotopic liver transplantation (OLT) is associated with anatomic and pathologic disorders in the graft, which may cause initial dysfunction. The object of this paper was to evaluate sIL-2r as an indicator of liver damage during graft reperfusion. MATERIAL AND METHODS: Blood samples were drawn from 20 consecutive patients who required OLT secondary to chronic end-stage insufficiency various sites (portal vein, vena cava, pulmonary artery) and during different surgical phases. Following centrifugation and storage at -70 degrees C, sIL-2r was quantitated by chemiluminescence (Immulite, EURO/DPC). In addition biopsies were graded from 0 to III according to the anatomic and pathologic findings. Base excess and ammonia were measured to evaluate the function of the new liver. STATISTICAL ANALYSES: Parameter associations were explored using Spearman's Rho and Kendall's Tau-b methods. RESULTS: There was a correlation between the degree of graft preservation and sIL-2R both during vena cava reperfusion (r=.0591, P=.05) and for the initial 2 hours after reperfusion (r=0.61, P=.062). CONCLUSION: sIL-2r levels drawn from the vena cava after graft reperfusion are associated with its degree of injury.

Drug Therapy, Combination↗

Automated monitoring of medical protocols: a secure and distributed architecture.

The control of the right application of medical protocols is a key issue in hospital environments. For the automated monitoring of medical protocols, we need a domain-independent language for their representation and a fully, or semi, autonomous system that understands the protocols and supervises their application. In this paper we describe a specification language and a multi-agent system architecture for monitoring medical protocols. We model medical services in hospital environments as specialized domain agents and interpret a medical protocol as a negotiation process between agents. A medical service can be involved in multiple medical protocols, and so specialized domain agents are independent of negotiation processes and autonomous system agents perform monitoring tasks. We present the detailed architecture of the system agents and of an important domain agent, the database broker agent, that is responsible of obtaining relevant information about the clinical history of patients. We also describe how we tackle the problems of privacy, integrity and authentication during the process of exchanging information between agents.

Artificial Intelligence↗

The selection between apoptosis and necrosis is differentially regulated in hydrogen peroxide-treated and glutathione-depleted human promonocytic cells.

Treatment with 0.2 mM hydrogen peroxide (H(2)O(2)) or with 0.5 mM cisplatin caused caspase-9 and caspase-3 activation and death by apoptosis in U-937 human promonocytic cells. However, treatment with 2 mM H(2)O(2), or incubation with the glutathione suppressor DL-buthionine-(S,R)-sulfoximine (BSO) prior to treatment with cisplatin, suppressed caspase activation and changed the mode of death to necrosis. Treatment with 2 mM H(2)O(2) caused a great decrease in the intracellular ATP level, which was partially prevented by 3-aminobenzamide (3-ABA). Correspondingly, 3-ABA restored the activation of caspases and the execution of apoptosis. By contrast, BSO plus cisplatin did not decrease the ATP levels, and the generation of necrosis by this treatment was not affected by 3-ABA. On the other hand, while all apoptosis-inducing treatments and treatment with 2 mM H(2)O(2) caused Bax translocation from the cytosol to mitochondria as well as cytochrome c release from mitochondria to the cytosol, treatment with BSO plus cisplatin did not. Treatment with cisplatin alone caused Bid cleavage, while BSO plus cisplatin as well as 0.2 and 2 mM H(2)O(2) did not. Bcl-2 overexpression reduced the generation of necrosis by H(2)O(2), but not by BSO plus cisplatin. These results indicate the existence of different apoptosis/necrosis regulatory mechanisms in promonocytic cells subjected to different forms of oxidative stress.

Adenosine Triphosphate↗

Acute myeloid leukemia with MLL rearrangements: clinicobiological features, prognostic impact and value of flow cytometry in the detection of residual leukemic cells.

The MLL gene, located at 11q23 band, is frequently disrupted by different chromosomal rearrangements that occur in a variety of hematological malignancies. MLL rearrangements are associated with distinct clinical features and a poor prognosis. The aim of this study was to analyze the incidence and the prognostic significance of MLL rearrangements in a consecutive series of adult AML patients and to determine the immunophenotypic features of these cases. The identification of abnormal immunophenotypes could be used for the detection of minimal residual disease (MRD). Ninety-three adult patients with de novo acute myeloid leukemia (AML) were analyzed by Southern blot in order to detect MLL rearrangements (MLL+). RT-PCR and genomic long-range PCR were performed to further characterize MLL partial tandem duplication (PTD) in those patients in whom conventional karyotype did not show 11q23 chromosomal translocations. All the patients were homogeneously immunophenotyped at diagnosis. MLL rearrangements were detected in 13 (14%) patients. Four patients (5%) showed 11q23 translocations by karyotypic conventional analysis. Nine patients (10%) revealed PTD of MLL and one patient showed a MLL cleavage pattern. The MLL+ patients usually expressed myeloid and monocytic antigens CD33 (12/13 cases), CD13 (9/13), CD117 (9/13), CD64 (11/13) and in some cases CD14 (4/11). HLA-DR was also positive in (12/13). Eight out of 13 cases expressed the stem cell marker CD34. Only one patient revealed lymphoid marker reactivity (CD7) and CD56 was expressed in 5/13 cases. All the MLL+ patients showed at least one aberrant phenotype at diagnosis, which allowed us to set out a simple panel for the MRD studies. Twenty-seven samples from eight patients in morphologic complete remission (CR) were analyzed using the aberrant immunologic combinations detected at diagnosis. Phenotypically abnormal cells were detected in all the patients who subsequently relapsed, whereas only one patient with MRD+ remained in CR. Owing to the high level of residual leukemic cells, the MLL+ patients showed a short CR duration and a poor survival. In conclusion, immunophenotyping may be a suitable approach to investigating MRD status in AML patients with PTD of the MLL gene.

Acute Disease↗

Overexpression of bcl-2 in T cells affects insulitis in the nonobese diabetic mouse.

The nonobese diabetic (NOD) mouse is a useful model for human autoimmune diabetes. The gene for the anti-apoptotic protein Bcl-2 has previously been suggested as a probable susceptibility candidate for the NOD mouse disease. In this study, we investigated how overexpression of Bcl-2 in lymphocytes might affect insulitis in NOD mice. A bcl-2 transgene expressed constitutively under the SV40-promoter and the 5'Igh enhancer, Emu, was bred onto NOD background. Two bcl-2 transgenic NOD strains were produced and analysed, one with overexpression of Bcl-2 on only B cells and the other with overexpression of Bcl-2 on both B and T cells. Subsequent to verification of expression pattern and functionality of the transgene, insulitis intensity was investigated in different backcross generations of the two transgenic strains. Overexpression of Bcl-2 on both B and T cells leads to a statistically significant protection of the mice from insulitis compared with normal littermates. Overexpression of Bcl-2 on only B cells, on the other hand, does not have any statistically significant effect on insulitis. Possible mechanisms for the effect of Bcl-2 on insulitis in NOD mice are discussed.

Animals↗

Breaking the non-responsiveness of C57BL/6 mice to the malarial antigen EB200--the role of carrier and adjuvant molecules.

Poor immunogenicity and major histocompatibility complex (MHC) restriction of immune responses to certain recombinant proteins or synthetic peptides impose problems in developing effective vaccines. EB200 is one of the vaccine candidate antigens from Plasmodium falciparum, which induces MHC-restricted immune responses in mice of different haplotypes. A way of overcoming this problem is to conjugate the antigen to an immunogenic protein carrier and to use optimal adjuvant substances. We have investigated the carrier effect of glutathione-S-transferase (GST) in CBA and C57BL/6 mice which are high and low responder to EB200, respectively. Our results reveal that the MHC restriction in C57BL/6 mice was broken by the use of GST as a carrier. Studies on the B-cell repertoires in both strains of mice immunized with GST-EB200 by preparing hybridoma cell lines indicate that the B-cell repertoires were similar in both CBA and C57BL/6 mice. However, the antibody affinity and the magnitude of the response were still lower in the low-responder C57BL/6 mice compared with that in CBA even when cholera toxin (CT) was used as adjuvant. To improve the response, the efficacy of various adjuvant substances like alum and Hsp 70 from Trypanosoma cruzi and the combination of various adjuvants was analysed. CT and Hsp 70 together act synergistically and markedly improve the immunogenicity of EB200 by increasing antibody affinity and the magnitude of the responses in C57BL/6 mice, which may be explained by the complementary effect of adjuvants. These results are of importance in the design of efficient vaccines.

Adjuvants, Immunologic↗

[Epidural anesthesia with ropivacaine vs. bupivacaine in continuous perfusion for the treatment of labor pains].

OBJECTIVE: To compare the analgesic efficacy and extent of motor block when 0.125% ropivacaine or 0.125% bupivacaine were given in continuous perfusion through an epidural catheter during labor. PATIENTS AND METHODS: We studied 60 ASA I-II women, each carrying a single fetus at full term and in spontaneous labor. The patients were distributed in 2 groups. Women in the ropivacaine group (R) (n = 30) received 8 mL of 0.2% ropivacaine for analgesic induction, followed by a continuous perfusion of 10 mL/h at 0.125%. The bupivacaine group (B) (n = 30) received bupivacaine at the same concentration and infusion rate. The objective of analgesia was to achieve a score less than 3 on a visual analog pain scale. If analgesia was inadequate, a 5 mL bolus of 0.2% ropivacaine or bupivacaine, depending on group, was administered. The motor block was evaluated on an abbreviated Bromage scale and we recorded hemodynamic stability, fetal status, type of delivery and the total dose of local anesthetic. RESULTS: Analgesia and hemodynamics were similar in both groups. Group R required a larger number of additional boluses, although the difference was not statistically significant. A motor block was observed in 8 patients in group B and 1 in group R (p < 0.05). Fetal status was similar in both groups. CONCLUSION: Both drugs were equally effective for controlling the pain accompanying labor, such that ropivacaine offered no advantage over bupivacaine in that regard. Ropivacaine's reduced motor block effect at the doses administered may offer an advantage in some situations, such as when a walking epidural is provided.

Adrenergic Agents↗