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Biomedical subjects

F Muñoz

Publications and source records attributed to F Muñoz.

At least 55 records · Page 3Linked to original sources

Increased activity of eukaryotic initiation factor 2B in PC12 cells in response to differentiation by nerve growth factor.

Translational rates, and activities and levels of initiation factors 2 and 2B were assessed in rat pheochromocytoma cells upon nerve growth factor (NGF) treatment. Two or 5 days of exposure to NGF caused significant quantitative increases in protein synthesis rate that are deemed necessary for neuronal differentiation. Changes in initiation factor 2 activity, as measured by its capacity to form a ternary complex, occur parallel to the observed changes in protein synthesis. Nevertheless, neither the intracellular levels of the initiation factor 2 nor the degree of phosphorylation of its alpha subunit can justify this increased activity. Interestingly, initiation factor 2B activity increases parallel to the neurite outgrowth, being significantly higher after 5 days of exposure to NGF, and could be responsible for the elevated rate of protein synthesis. No significant changes in the levels of eukaryotic initiation factor 2B, as determined with two different antibodies against the gamma and epsilon subunits of the factor, were observed, implying that the increased activity should be regulated by factors other than its cellular concentration. Our results support the hypothesis that initiation factor 2B may play a role in the biochemical events controlling the differentiative growth factor-induced signaling pathway in these cells.

Animals↗

Localization of eukaryotic initiation factor 2 in neuron primary cultures and established cell lines.

Eukaryotic initiation factor 2 (eIF-2) is a heterotrimeric protein with subunits alpha, beta and gamma that forms a ternary complex with Met-tRNA and GTP. It promotes the binding of Met-tRNA to ribosomes and controls translational rates via phosphorylation/dephosphorylation mechanisms. By means of immunofluorescence and post-embedding immunocytochemistry of intact cells and quantitative immunoblotting of cell extracts, the cellular distribution of the initiation factor has been examined in primary neuronal cultures as well as in two established cell lines: PC12 phaeochromocytoma cells and rat pituitary GH4C1 cells. Our results indicated that the initiation factor is located not only in the cytoplasm but also in the nuclei of the cultured neurons and cell lines. In the cytoplasm, immunocytochemical studies reveal that the factor is present mainly in those areas that are rich in ribosomes. In the nucleus, the immunolabelling of eukaryotic initiation factor 2 verified the presence of gold particles in both nucleolar and extranucleolar areas. The specific distribution of this factor on both sides of the nuclear envelope suggests that it might have some nuclear-related function(s) besides its already known role in the control of translation.

Animals↗

Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C. The Hepatitis/HIV Spanish Study Group.

OBJECTIVES: The factors influencing the histological severity of chronic hepatitis C (CHC) have not been well established. We therefore investigated the effect of hepatitis C virus (HCV) genotypes and human immunodeficiency virus (HIV) infection on histological liver damage in a cohort of intravenous drug users with CHC. METHODS: We analyzed the histological activity score and the HCV genotypes in 59 HCV-RNA-positive patients with biopsy-proven CHC. Forty-eight (81%) of them had concomitant HIV infection with a CD4+ cell count above 200 x 10(6) cells/L and an absence of AIDS-defining conditions. Multivariate analysis was performed to determine the features associated with the histological severity. RESULTS: Minimal/mild hepatitis was found in 16 patients (27%), moderate chronic hepatitis in 29 (49%), and severe chronic hepatitis in 14 (24%). Patients with HCV subtype 1b had a higher histological score than others (8.7 +/- 3.3 vs. 6.5 +/- 3.2, p = 0.012), either as single or mixed infections. In multivariate analysis, HIV-infected individuals had a higher score of piecemeal necrosis (OR = 21.7, p = 0.002) and a higher stage of fibrosis (OR = 17.9, p = 0.004) than patients without HIV infection. HIV infection and HCV genotype 1b were found to be independent factors of histological severity. CONCLUSIONS: Liver damage in patients with CHC seems to be directly influenced by HCV subtypes. Infection by HCV subtype 1b is closely associated with more severe forms of liver pathology. Furthermore, the presence of HIV infection is an independent factor associated with more aggressive histological damage. In these patients, higher degrees of piecemeal necrosis and fibrosis are commonly seen.

Adult↗

[Importance of pre-analytical variables in the quality of arterial blood gas determination].

BACKGROUND: Several frequent errors in the measurement of arterial blood gases, shed doubts on their real usefulness. AIM: To identify sampling, manipulation and transport errors in the measurement of arterial blood gases. MATERIALS AND METHODS: Three hundred and nine consecutive arterial blood samples received at the central laboratory of a public hospital were analyzed. Patient data in the order form, reception conditions at the laboratory, transport media, time of arrival and analysis of each sample were recorded. RESULTS: Five percent of orders informed the hour of sampling, 0.6% the patient's temperature and 18.1% the inspired oxygen fraction. Bubbles or clots were present in 12.9% and 3.2% of samples respectively, 87.3% of samples were well sealed and the amount of blood withdrawn in relation to the syringe capacity was optimal in 47.2% of cases. Ninety three percent of syringes were transported with ice cubes that did no cover the syringe and 5.8% of samples were received at room temperature. The delay in analysis, since the time of reception at the laboratory, ranged from 0 to 55 min (mean 12.9 min). CONCLUSIONS: Several deficiencies in pre analytical variables in blood gas analysis were identified, most caused by neglect and susceptible of correction. Quality controls for this determination should be performed frequently.

Blood Gas Analysis↗

Changes in the phosphorylation of eukaryotic initiation factor 2 alpha, initiation factor 2B activity and translational rates in primary neuronal cultures under different physiological growing conditions.

Phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF-2) is one of the best known mechanisms regulating protein synthesis in a wide range of eukaryotic cells, from yeast to human. To determine whether this mechanism operates in primary neuronal cells, we have cultured primary neuronal cells for 7 days under two optimal growing conditions, complete medium (containing 15% serum) and serum-free medium, and determined the protein synthesis rate, eukaryotic initiation 2 and 2B (eIF-2B) activities, as well as the level of phosphorylation of eIF-2. Cells cultured in serum-free medium exhibited a lower rate of protein synthesis (75%), concomitant to a decreased eIF-2 activity (71%), and slightly higher eIF-2(alpha P) levels (from 10 to 16% of total eIF-2) with respect to cells cultured in complete media. eIF-2B activity, as measured at saturating eIF-2. GDP concentrations (assay independent on the presence of eIF-2(alpha P)) was similar under the two culture conditions. When neurons cultured in serum-free medium are exposed to complete medium for only 24 h, there is a clear decrease in the phosphorylation of eIF-2 alpha (16-3%). This decrease correlates in time with an increase in the protein synthesis rate (154%), as well as eIF-2 activity (236%). The increased levels of eIF-2(alpha P), a competitive inhibitor of eIF-2B in the guanine-exchange reaction, are responsible for the decreased eIF-2B activity found in the neurons cultured in serum-free medium. Additionally, eIF-2(alpha P) is accountable for the lower effect of exogenous eIF-2B in ternary complex formation from preformed eIF-2. GDP in the serum-free media. These changes in phosphorylation of eIF-2 alpha in normal mammalian cells in response to changes in the extracellular medium are reported here for the first time.

Animals↗

[Morbidity and mortality associated with chronic viral hepatopathy in patients infected with the human immunodeficiency virus].

BACKGROUND: Hepatitis B, C and D virus infection is frequent in HIV-infected individuals, particularly in drug addicts. However, chronic liver disease of viral etiology has been little studied in AIDS. METHODS: The impact of infection by hepatotropic viruses on hospital morbidity/mortality was analyzed in a group of HIV positive (HIV+) patients over the period from October 1991 to April 1994. RESULTS: Viral liver disease was the cause of hospitalization in 94 (8.6%) out of 1,082 HIV+ patient admissions. Only 4 admissions were for severe or fulminant cases of acute viral hepatitis. Complicated (gastrointestinal bleeding, and spontaneous bacterial infection) or decompensated (ascites, jaundice and encephalopathy) viral liver disease was the diagnosis in the 90 remaining cases. Death directly associated to liver diseases was observed in 9 (9.5%) of these patients, globally representing 4.3% (9 out of 207) of the causes of hospital mortality during the study period, and the fifth in order of frequency. Hospital stay was significantly longer in patients admitted for decompensated or complicated chronic viral liver disease in comparison with the remaining patients (27.9 +/- 9 versus 18.4 +/- 8 days) (p < 0.05). Infection by the hepatitis C virus was observed in 88% (80 out of 90) of the hospital admissions for chronic liver disease although half presented coinfection by B or delta viruses. CONCLUSIONS: Chronic liver disease of viral etiology, mainly by the hepatitis C virus, represents an important cause of hospital morbidity and mortality in Spanish HIV+ patients.

AIDS-Related Opportunistic Infections↗

Leukemia after true histiocytic lymphoma: another type of acute monocytic leukemia with histiocytic differentiation (AML-M5c)?

The case of a 44-year-old man diagnosed of a true histiocytic lymphoma who, after autologous bone marrow transplantation, developed leukemia with histiocytic cells is reported. Morphologic, cytochemical, immunophenotypic and genotypic characteristics of malignant cells are described, and the literature about this and related entities is reviewed. In addition, comparison with a recent report of malignant histiocytosis with leukemic involvement is established and its inclusion in the recently proposed subtype of monocytic leukemia with histiocytic differentiation (M5c), suggested.

Adult↗

[Gastrointestinal disease due to cytomegalovirus in patients infected with the human immunodeficiency virus].

OBJECTIVE: To describe all the clinical settings, endoscopic findings and response to therapy in a series of HIV-positive patients with biopsy proven gastrointestinal CMV disease. PATIENTS: We retrospectively reviewed the medical records of all HIV-infected patients who underwent digestive endoscopies at our Hospital from June 1990 to October 1993. RESULTS: Twelve (7.5%) of 158 HIV-positive patients had gastrointestinal CMV disease. Sites of prove infection included the esophagus (n = 6, 50%), stomach (n = 2, 17%), duodenum (n = 4, 33.3%), ileum (n = 1, 8.5%) and colon (n = 2, 17%). The most common endoscopic findings were focal or diffuse mucosal ulcers. Three patients had pseudotumoral mucosal lesions. Cytomegalic cells were observed in 11 patients (91.6%) and immunohistochemical staining was positive in 9 (81.8%) of 11 patients tested. Eight patients completed a course of treatment with ganciclovir or foscarnet and all of them showed clinical improvement. The median survival time of our AIDS patients with CMV gastrointestinal disease was 7 weeks (range 1-39 weeks). CONCLUSIONS: Gastrointestinal CMV disease may damage any site of the digestive tract in AIDS patients. Routine histopathologic examination was better than immunohistochemical staining for the diagnosis. Treatment improves the clinical situation in most of them. The mean survival is low and it is related to the degree of immunosuppression.

AIDS-Related Opportunistic Infections↗

[Cytomegalovirus colitis in a patient carrying the human immunodeficiency virus: the endoscopic image similar to pseudomembranous colitis].

Endoscopically detected ulcers and submucous haemorrhage are common findings related to cytomegalovirus infection. We report a case of cytomegalovirus colitis in a patient seropositive for human immunodeficiency virus. Endoscopic findings showed elevated, white-yellowish, small size plaques with an erythematous central depression, resembling those found in pseudomembranous colitis.

AIDS-Related Opportunistic Infections↗

[Characteristics of chronic delta hepatitis in patients wih HIV infection].

BACKGROUND: Hepatitis Delta virus (HDV) induces severe liver disease in HBsAg carriers. In regions such as Spain, drug addicts make-up a large part of the HIV-positive population and they are at risk of HDV infection. Natural history of chronic hepatitis D is not well known in HIV-infected patients. METHODS: We reviewed the clinical charts of 37 patients attending our institution from 1989 to 1993, fulfilling the criteria for chronic hepatitis D. We compared all clinical, epidemiological, serological and histological findings between both HIV-positive and HIV-negative patients. RESULTS: All the following parameters showed significant statistical differences between the both groups: mean ALT levels (175 vs 79 respectively, p < 0.05), previous episodes of hepatic decompensation (37% vs 10%, p < 0.01), the circulating Delta antigen (26% vs 10%, p < 0.05), the presence of HBeAg in serum (41% vs 0%, p < 0.01) and the HCV coinfection (85% vs 20%, p < 0.01). Histological findings were not significantly different comparing both groups, as chronic active hepatitis with cirrhosis was the most common diagnosis. CONCLUSION: Chronic hepatitis D may present a more severe course in HIV-infected patients. The higher replication of HDV and the presence of HCV coinfection could explain this worst outcome.

Adult↗

[Paraneoplastic myelopathy, probably necrotizing myelopathy: apropos of a case associated with anaplastic small cell carcinoma].

We comment a case of necrotizing myelopathy, a rare neurological paraneoplastic syndrome, that it was the first manifestation of a microcit anaplastic carcinoma. The diagnostic was made with the clinical and radiological base, after we deprive another diseases with similar clinical manifestations and the result of the Magnetic resonance image of the nervous system. We didn't obtain permise for the necropsic study.

Aged↗

Alkaline hydrolysis of cefotaxime. A HPLC and 1H NMR study.

A kinetic study on the alkaline hydrolysis of cefotaxime at pH 10.5 and 37 degrees C has been carried out by using HPLC and 1H NMR. The main resulting degradation products have been isolated and identified. These include, apart from the well-known deacetylcefotaxime, the exocyclic methylene derivative, the 7-epimer of cefotaxime and the 7-epimer of deacetylcefotaxime. The kinetic constants involved in the process have been determined and according to the experimental results the attack of the hydroxyl group on the ester function bonded to the 3'-carbon is the fastest step in the proposed kinetic scheme. It should be emphasized that the base-catalyzed epimerization of the hydrogen at the 7 position clearly depends on the presence of a good electron-withdrawing group at C(3'). On the other hand, no hydrolysis of the amide at position 7 was detected.

Cefotaxime↗