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Biomedical subjects

A Ferrer

Publications and source records attributed to A Ferrer.

At least 91 records · Page 5Linked to original sources
PubMed1997

Cloning and characterization of the Arabidopsis thaliana SQS1 gene encoding squalene synthase--involvement of the C-terminal region of the enzyme in the channeling of squalene through the sterol pathway.

Squalene synthase (SQS) catalyzes the first committed step of the sterol biosynthetic pathway. A full-length Arabidopsis thaliana SQS cDNA has been isolated by combining library screening and PCR-based approaches. Arabidopsis SQS is encoded by a small gene family of two genes (SQS1 and SQS2) which are organized in a tandem array. SQS1 and SQS2 have an identical organization with regard to intron positions and exon sizes and encode SQS isoforms showing a high level of sequence conservation (79% identity and 88% similarity). The isolated cDNA has been assigned to the SQS1 gene product, SQS1. RNA blot analysis has shown that the 1.6-kb SQS1 mRNA is detected in all plant tissues analyzed (inflorescenses, leaves, stems and roots) although the transcript is especially abundant in roots. Arabidopsis SQS1 isoform is unable to complement the SQS-defective Saccharomyces cerevisiae strain 5302, although SQS activity was detected in the microsomal fraction of the transformed yeast strain. However, a chimeric SQS resulting from the replacement of the 66 C-terminal residues of the Arabidopsis enzyme by the 111 C-terminal residues of the Schizosaccharomyces pombe enzyme was able to confer ergosterol prototrophy to strain 5302. Labeling studies using [3H]farnesyl-P2 and microsomal fractions obtained from yeast strains expressing either Arabidopsis SQS1 or chimeric Arabidopsis/S. pombe SQS derivatives indicated that the C-terminal region of the enzyme is involved in the channeling of squalene through the yeast sterol pathway.

Amino Acid Sequence↗
PubMed1997

Three spinach leaf nitrate reductase-3-hydroxy-3-methylglutaryl-CoA reductase kinases that are regulated by reversible phosphorylation and/or Ca2+ ions.

In spinach (Spinacea oleracea L.) leaf extracts, three protein kinases (PKI, PKII and PKIII) were identified each of which phosphorylated spinach nitrate reductase on serine-543, and inactivated the enzyme in the presence of nitrate reductase inhibitor, 14-3-3. PKIII was also very active in phosphorylating and inactivating Arabidopsis (Landsberg erecta) 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (HMGR1). PKI and PKII phosphorylated HMGR1 more slowly than PKIII, compared with their relative rates of phosphorylation of nitrate reductase. HMGR1 identical with those that are seen after phosphorylation of serine-577 by the sucrose non-fermenting (SNF1)-like PK, 3-hydroxy-3-methylglutaryl-Co A reductase kinase A (HRK-A), from cauliflower [Dale, Arró, Becerra, Morrice, Boronat, Hardie and Ferrer (1995) Eur. J. Biochem. 233, 506-513]. PKI was Ca2+-dependent when prepared in the absence of protein phosphatase (PP) inhibitors, and largely Ca2+-dependent when prepared in the presence of PP inhibitors (NaF and EGTA). The Ca2+-independent portion of PKI was inactivated by either PP2A or PP2C, while the Ca2+-dependent portion of PKI became increasingly activated during storage, which we presume was mimicking the effect of an unidentified PP. These findings indicate that PK1 is regulated by two functionally distinct phosphorylations. PKI had a molecular mass of 45 kDa on gel filtration and was active towards substrate peptides that terminated at the +2 residue from the phosphorylation site, whereas PKIII was inactive towards these peptides. PKII was Ca2+-stimulated under all conditions tested. PKIII was Ca2+-indepdented, inactivated by PP2A or PP2C, had a requirement for a hydrophobic residue in the +4 position of peptide substrates, had a molecular mass by gel filtration of approximately 140 kDa, and an antibody against the rye SNF1-related PK (RKIN1) recognized a 58 kDa subunit in fractions containing PKIII. These properties of PKIII are identical with those reported previously for the SNF1-like enzyme, HRK-A. Our results indicate a considerable complexity of kinase cascades mediating the regulation of assimilatory and biosynthetic pathways in response to environmental stimuli in plants.

Amino Acid Sequence↗
PubMed1997

The Arabidopsis thaliana FPS1 gene generates a novel mRNA that encodes a mitochondrial farnesyl-diphosphate synthase isoform.

The enzyme farnesyl-diphosphate synthase (FPS; EC 2.5.1.1./EC 2.5.1. 10) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. FPS is considered to play a key role in isoprenoid biosynthesis. We have reported previously that Arabidopsis thaliana contains two differentially expressed genes, FPS1 and FPS2, encoding two highly similar FPS isoforms, FPS1 and FPS2, (Cunillera, N., Arró, M., Delourme, D., Karst, F., Boronat, A., and Ferrer, A. (1996) J. Biol. Chem. 271, 7774-7780). In this paper we report the characterization of a novel Arabidopsis FPS mRNA (FPS1L mRNA) derived from the FPS1 gene. A cDNA corresponding to the FPS1L mRNA was cloned using a reverse transcription-polymerase chain reaction strategy. Northern blot analysis showed that the two FPS1-derived mRNAs are differentially expressed. The FPS1L mRNA accumulates preferentially in inflorescences, whereas the previously reported FPS1 mRNA (FPS1S mRNA) is predominantly expressed in roots and inflorescences. FPS1L mRNA contains an in-frame AUG start codon located 123 nucleotides upstream of the AUG codon used in the translation of the FPS1S isoform. Translation of the FPS1L mRNA from the upstream AUG codon generates a novel FPS1 isoform (FPS1L) with an NH2-terminal extension of 41 amino acid residues, which has all the characteristics of a mitochondrial transit peptide. The functionality of the FPS1L NH2-terminal extension as a mitochondrial transit peptide was demonstrated by its ability to direct a passenger protein to yeast mitochondria in vivo and by in vitro import experiments using purified plant mitochondria. The Arabidopsis FPS1L isoform is the first FPS reported to contain a mitochondrial transit peptide.

Alkyl and Aryl Transferases↗
PubMed1997

From clinical trials to clinical practice: oral anticoagulation among patients with non-rheumatic, atrial fibrillation.

OBJECTIVES: The aim of the present study was to evaluate the impact of the results of clinical trials on the prophylactic treatment of non-rheumatic atrial fibrillation with oral anticoagulants. METHODS: Retrospectively, we studied a random sample of 375 patients discharged from our hospital with a diagnosis of non-rheumatic atrial fibrillation between 1991 and 1993. Information about diagnoses, other clinical variables and treatments prescribed at discharge was obtained from the hospital medical records. RESULTS: During the whole study period, 14% of patients were prescribed an oral anticoagulant agent and 17% were prescribed acetylsalicylic acid. A non-significant increase in the proportion of patients prescribed oral anticoagulant drugs, from 9% to 17%, was observed. Multivariate analysis showed that a history of stroke (OR = 5.96) and younger age were significantly associated with the prescription of oral anticoagulants. ASA prescription was strongly associated with a history of concomitant vascular disease (OR = 5.8), but not with other risk factors for stroke. Sixty-five percent of patients had one or more risk factors for stroke, did not present any contraindications to anticoagulant agents, but nevertheless were not prescribed one of these drugs. CONCLUSIONS: Anticoagulant agents and acetylsalicylic acid were largely underprescribed to patients with non-rheumatic atrial fibrillation, and oral anticoagulants were not prescribed according to the individual patients' risk of stroke.

Acenocoumarol↗
PubMed1997

Photochemistry of water-soluble quinones. Production of a water-derived spin adduct.

The photolyses of phosphate-buffered (pH 7) air- and nitrogen-saturated solutions containing the water-soluble quinones, 1,4-benzoquinone (BQ), 2-methyl-1,4-benzoquinone (MBQ), sodium 1,4-naphthoquinone-2-sulfonate (NQ2S), 9,10-anthraquinone-2-sulfonate (AQ2S) or 9,10-anthraquinone-1,5-disulfonate (AQDS), and the spin trap 5,5-dimethylpyrroline-1-oxide (DMPO) produce a DMPO-OH adduct. Electron paramagnetic resonance spectroscopy of the photolyzed samples in 17O-enriched water demonstrates that this adduct derives almost exclusively from water. With the exception of BQ, quantum yields for the formation of DMPO-OH are larger in air than in nitrogen-saturated samples, thus supporting the idea of the formation of air-oxidized intermediates that enhance the DMPO hydroxylation reaction rate. Evidence has been obtained which suggests that BQ and MBQ, but not AQDS, are able to photooxidize water, with the consequent production of the free OH radical.

Cyclic N-Oxides↗
PubMed1997

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease.

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.

Acute Disease↗
PubMed1997

Empiric treatments impair the diagnostic yield of BAL in HIV-positive patients.

OBJECTIVE: To investigate the influence of empiric treatments prior to fiberoptic bronchoscopy (FOB) on the diagnostic yield of BAL in HIV-positive patients with respiratory symptoms. METHOD: We studied 123 consecutive FOBs with BAL in HIV-positive patients; 101 of these patients (82%) had received previous antimicrobial treatment from 1 to 60 days. Diagnostic yield of BAL for Pneumocystis carinii, Mycobacterium tuberculosis, and bacterial pneumonia was compared between patients with and without previous empiric treatments. RESULTS: A diagnosis was obtained in 85 patients (69%), of whom 17 (20%) had multiple infections. Diagnostic yield was higher in patients without previous treatment, 91% (20/22) compared with 64% (65/101), p < 0.03. Diagnostic yield was also higher for bacterial pneumonia: seven isolations from 22 patients not receiving previous empiric treatment (32%), compared with 11 of those who had (11%; p < 0.02). The duration of empiric treatment against P carinii in patients in whom it was isolated was significantly shorter than in those in whom P carinii was not detected (3.5 +/- 1.8 days compared with 5.2 +/- 2.4 days; p = 0.003). FOB permitted a change in treatment in 62% of patients with a final diagnosis. CONCLUSION: This study demonstrates that empiric treatments prior to FOB significantly impair the diagnostic yield of BAL in detecting common pathogens in HIV-infected patients with respiratory symptoms.

AIDS-Related Opportunistic Infections↗
PubMed1997

Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature.

Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Light microscopic changes in Plasmodium falciparum from Gabonese children treated with artemether.

The changes in Plasmodium falciparum in four Gabonese children suffering from severe malaria and treated with pure artemether were observed in thin blood smears fixed and stained with Giemsa and examined by light microscopy. Peripheral blood samples were taken every 8 hr up to 72 hr from three children and every 3 hr up to 9 hr from the other child. The morphologic changes involved all development stages (trophozoites, schizonts, and gametocytes); they were first seen 3 hr after the start of treatment and all parasites were abnormal after 24 hr. After two days of treatment, all infected erythrocytes disappeared except for a few with necrotic trophozoites. The morphologic changes were similar to the ultrastructural changes previously described in vivo and in vitro in experimental models. They confirm the rapid effect of artemisinin derivatives on parasite clearance and clinical recovery, particularly in cases of cerebral malaria.

Animals↗
PubMed1997

High prevalence of mollusc shell hypersensitivity pneumonitis in nacre factory workers.

Following the discovery of hypersensitivity pneumonitis caused by the inhalation of mollusc shell dust in two workers from a nacre-button factory, the health status of 26 workers employed in sawing mollusc shells was investigated. The evaluation included the administration of two questionnaires and radiological, functional and immunological assessments of all workers at the outset and 1 year later, when hygienic and therapeutic measures had been taken. Six workers, in whom specific inhalation challenge test was positive, were diagnosed with mollusc shell hypersensitivity pneumonitis, thus yielding a prevalence of 23%. Evidence of diffuse lung disease and systemic symptoms was found in these patients. Nonspecific bronchial hyperreactivity was also found more frequently in patients with mollusc shell hypersensitivity pneumonitis. Specific immunoglobulin G (IgG) level and specific skin testing failed to differentiate patients with mollusc shell hypersensitivity pneumonitis from other exposed workers; whereas, nonspecific skin testing, which was impaired in the patients, did differentiate. Bronchoalveolar lavage and transbronchial biopsy performed in patients with mollusc shell hypersensitivity pneumonitis were consistent with the disease. Removal from an environment containing mollusc shell dust was followed by regression of clinical, radiological and functional changes. The clinical picture of the 20 workers who did not present mollusc shell hypersensitivity pneumonitis remained unchanged, but functional decline was observed despite improvement in the environmental conditions of the factory. This report describes the first series of patients with mollusc shell hypersensitivity pneumonitis studied, and underlines the importance of careful follow-up of workers occupationally-exposed to mollusc shell dust.

Adult↗
PubMed1997

Pulmonary abscess as a complication of transarterial embolization of multinodular hepatocellular carcinoma.

Hepatic transarterial embolization has been widely used in the treatment of hepatocellular carcinoma and other liver tumors. Despite being a safe treatment, some complications associated with this procedure have been described. The most frequent adverse effect of transarterial embolization is postembolization syndrome, whereas infections account for only 3.4% of complication. We report the first case of lung abscess as a complication of transarterial embolization used in the treatment of multinodular hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1996

Arabidopsis thaliana contains two differentially expressed farnesyl-diphosphate synthase genes.

The enzyme farnesyl-diphosphate synthase (FPS; EC 2.5.1.1/EC 2.5.1.10) catalyzes the synthesis of farnesyl diphosphate (FPP) from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). This reaction is considered to be a rate-limiting step in isoprenoid biosynthesis. Southern blot analysis indicates that Arabidopsis thaliana contains at least 2 genes (FPS1 and FPS2) encoding FPS. The FPS1 and FPS2 genes have been cloned and characterized. The two genes have a very similar organization with regard to intron positions and exon sizes and share a high level of sequence similarity, not only in the coding region but also in the intronic sequences. Northern blot analysis showed that FPS1 and FPS2 have a different pattern of expression. FPS1 mRNA accumulates preferentially in roots and inflorescences, whereas FPS2 mRNA is predominantly expressed in inflorescences. The cDNA corresponding to the FPS1 gene was isolated by functional complementation of a mutant yeast strain defective in FPS activity (Delourme, D., Lacroute, F., and Karst, F. (1994) Plant Mol. Biol. 26, 1867-1873). By using a reverse transcription-polymerase chain reaction strategy we have cloned the cDNA corresponding to the FPS2 gene. Analysis of the FPS2 cDNA sequence revealed an open reading frame encoding a protein of 342 amino acid residues with a predicted molecular mass of 39,825 Da. FPS1 and FPS2 isoforms share an overall amino acid identity of 90.6%. Arabidopsis FPS2 was able to rescue the lethal phenotype of an ERG20-disrupted yeast strain. We demonstrate that FPS2 catalyzes the two successive condensations of IPP with both DMAPP and geranyl diphosphate leading to FPP. The significance of the occurrence of different FPS isoforms in plants is discussed in the context of the complex organization of the plant isoprenoid pathway.

Alkyl and Aryl Transferases↗
PubMed1996

[Pleural cryptococcosis in patients with human immunodeficiency virus infection].

Four cases of pleural cryptococcosis as the form of onset of cryptococcosis in patients with human immunodeficiency virus (HIV) infection are reported. In two out of the four cases cryptococci were simultaneously isolated in other localizations (blood and meninges). In the two remaining patients the pleura was the only site of the disease, with serum determination of the cryptococci antigen being negative in one. The four patients evolved favourably, with three being exclusively treated with fluconazol. Pleuritis is an infrequent manifestation in cryptococcosis although it may be the form of onset and the only localization of the disease. Only 10 cases have been reported in patients with HIV infection. The present four cases represent 11% of the authors' series of cryptococcosis in AIDS patients. The diagnostic possibility of cryptococcosis should be considered in patients with human immunodeficiency virus infection presenting pleural effusion.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Visual function in pseudophakic eyes with poly(methyl methacrylate), silicone, and acrylic intraocular lenses.

PURPOSE: To evaluate the quality of visual function after cataract surgery and intraocular lens (IOL) implantation with three lens materials. SETTING: Klinik Dardenne, Bonn Bad Godesberg, Germany. METHODS: In a prospective, randomized study, 55 patients having uncomplicated phacoemulsification received IOLs made of three materials: 16 received acrylic IOLs, 20 received silicone IOLs, and 19 received poly(methyl methacrylate) (PMMA) IOLs. Pseudophakic patients with accompanying eye diseases were excluded. Visual acuity, glare sensitivity, contrast sensitivity, and mesopic acuity were evaluated 6 weeks postoperatively. RESULTS: Postoperatively, best corrected visual acuity was excellent in all three lens groups. Acuity under bright light conditions and contrast sensitivity were low in all groups; mesopic acuity was extremely low in 73% of patients. Glare and contrast sensitivity were significantly better with PMMA and acrylic IOLs. CONCLUSION: The visual quality achieved in pseudophakic eyes with three different lens materials was lower than expected. The results of individual visual function tests were better for PMMA and acrylic IOLs than for silicone IOLs.

Acrylates↗
PubMed1996

[Cryopreservation of isolates of Toxoplasma gondii in cell culture].

For a better preservation and identification of Toxoplasma gondii isolates, we propose a new method of freezing of toxoplasma growth in THP-1 cell culture. A cystogenic strain isolated from foetal blood has been grown in these cells and frozen in liquid nitrogen. After thawing, toxoplasma recover the same growth rate and morphology in vitro and the same capacity to form brain cysts into mice compared to the initial strains. The freezing of the cell suspension provides a simple and appropriate method for preservation of Toxoplasma gondii within "bank" isolates.

Animals↗
PubMed1996

Ventilation-perfusion response after fenoterol in hypoxemic patients with stable COPD.

BACKGROUND: The effects of vasoactive drugs, including bronchodilators, on vascular and pulmonary dynamics are interrelated, complex and difficult to measure, but important because of potential deleterious effects on gas exchange. METHODS: To assess the effects of fenoterol at both high and low dose on pulmonary gas exchange in 24 hypoxemic patients with stable COPD: fenoterol, 5 mg; fenoterol, 1 mg and ipratropium bromide, 0.5 mg; ipratropium bromide, 0.5 mg; or matched placebo were nebulized in a double-blind, placebo-controlled fashion. Spirometry, ventilation, systemic hemodynamics, and respiratory and inert gases were measured before and 15, 60, and 120 min after each treatment. RESULTS: Compared with placebo, heart rate (p < 0.002) and cardiac output (p = 0.05) increased after high-dose fenoterol therapy to return to baseline values by 120 min. Following fenoterol at high dose, mean maximum PaO2 change from baseline decreased by 6.3 +/- 1.1 mm Hg (SD) and both alveolararterial oxygen pressure difference (P[A-a]O2), by 8.3 +/- 4.0 mm Hg, and ventilation-perfusion (VA/Q) mismatching increased, as evidenced by increments of the dispersion of pulmonary blood flow, without reaching significance; likewise, low-dose fenoterol therapy increased VA/Q inequalities while both PaO2 and P(A-a)O2 remained unchanged. CONCLUSIONS: In this population of COPD patients, high-dose fenoterol therapy [corrected] significantly increased heart rate and cardiac output resulting in minor adverse consequences on arterial oxygenation and VA/Q relationships.

Adrenergic beta-Agonists↗