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Biomedical subjects

J M Sierra

Publications and source records attributed to J M Sierra.

At least 19 recordsLinked to original sources
PubMed2006

Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria.

The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes. Four norfloxacin and 20 ciprofloxacin derivatives were synthesised and tested against quinolone-susceptible and -resistant Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus strains using a microdilution test. Among the derivatives, the 4-methyl-7-piperazine ciprofloxacin derivative showed a minimum inhibitory concentration for 50% of the organisms that was 16- and 8-fold lower than ciprofloxacin for A. baumannii and S. maltophilia, respectively. When the methyl group at position 4 in the piperazine ring was substituted by ethyl, butyl or heptyl groups, activity against A. baumannii steadily decreased. The 7-(4-methyl)-piperazine ciprofloxacin derivative (UB-8902) showed very good activity against these multiresistant microorganisms including A. baumannii and S. maltophilia.

Anti-Bacterial Agents↗
PubMed2005

The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae.

Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.

Aza Compounds↗
PubMed2005

[Positron emission tomography in the diagnosis of orbital relapse of choroidal melanoma].

CASE REPORT: A 72-year-old man with a large choroidal melanoma was treated with enucleation. Three years later MRI demonstrated images compatible with recurrent tumor in the orbit. PET studies showed no focal hypermetabolic abnormalities. DISCUSSION: In patients after enucleation of choroidal melanoma, conventional imaging techniques can fail to establish differentiation between malignant from post-surgery and benign anatomic abnormalities in orbital tissue that can be detected by PET scanning.

Aged↗
PubMed2003

Integron-mediated antibiotic multiresistance in Acinetobacter baumannii clinical isolates from Spain.

OBJECTIVE: To determine whether non-epidemiologically related, antibiotic-resistant isolates of Acinetobacter baumannii from different geographical origins possess common type 1 integrons. METHODS: The epidemiologic relationships between seven A. baumannii strains recovered from different Spanish hospitals were established by pulsed-field gel electrophoresis, the presence of integrons being determined by PCR and DNA sequencing. RESULTS: Integron analysis showed the presence of four different integrons, containing six different known genes (aacC1, aacA4, aadA1, aadB, oxa21 and oxa37) plus an ORF. It was found that the same integron was present in different unrelated strains and that related strains could have different integrons. CONCLUSION: These results show the potential risk of integron dissemination among different strains of A. baumannii.

Acinetobacter Infections↗
PubMed2002

Correlation between the activity of different fluoroquinolones and the presence of mechanisms of quinolone resistance in epidemiologically related and unrelated strains of methicillin-susceptible and -resistant Staphylococcus aureus.

OBJECTIVE: To study the activity of five different fluoroquinolones against 22 epidemiologically related and unrelated strains of Staphylococcus aureus (13 methicillin-resistant (MRSA) strains and nine methicillin-susceptible (MSSA) strains) in which the mechanisms of quinolone resistance are also investigated. METHODS: The MICs of the different fluoroquinolones were determined by the microdilution method, in the presence and absence of reserpine. The quinolone resistance-determining regions of the gyrA, gyrB, grlA and grlB genes were amplified and sequenced to establish the presence of mutations. The molecular epidemiology of the 22 strains was performed by low-frequency restriction analysis of chromosomal DNA with SmaI. RESULTS: MSSA strains showed lower homology than MRSA strains, in which only two clones were seen. Trovafloxacin showed the best activity against these clinical isolates of S. aureus, since strains carrying one amino acid change in both GyrA and GrlA subunits remained susceptible to this antimicrobial agent. Furthermore, trovafloxacin did not seem to be a substrate for NorA. CONCLUSION: Trovafloxacin was the most active quinolone tested against S. aureus strains, followed by levofloxacin and sparfloxacin, whereas ciprofloxacin and norfloxacin were the least active quinolones, in both the presence and absence of reserpine. Epidemiologically related S. aureus strains presented different mechanisms of quinolone resistance, suggesting a divergent evolution of the same clone. Finally, 16 S. aureus strains with a ciprofloxacin plus reserpine MIC > or = 1 mg/L already showed a mutation in the grlA gene. This MIC may be useful as a marker of mutation in this gene, contraindicating the use of this quinolone, since a second mutation may develop during treatment.

Anti-Infective Agents↗
PubMed2001

Characterization of sparfloxacin-resistant mutants of Staphylococcus aureus obtained in vitro.

A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in increased concentrations of sparfoxacin. The presence of mutations in gyrA, gyrB, grlA and grlB genes was analyzed. The primary point mutation was located in the gyrA gene (Glu-88 to Lys). Two further mutation steps appeared in the amino acid change Ser-80 to Tyr in GrlA. No mutations occurred in the gyrB or grlB genes. Efflux pumps involved in the increase of resistance were also found to affect norfloxacin and ciprofloxacin. This effect may be related to NorA. An overexpression of NorA, may be associated with the increase of the MIC of norfloxacin from 32 mg/l to >200 mg/l in the final mutant. The MICs levels of sparfloxacin were affected by unknown mechanism.

Anti-Infective Agents↗
PubMed2001

Arachnoid cysts: entrapped collections of cerebrospinal fluid variably communicating with the subarachnoid space.

Despite decades of investigation and discussion of the mechanisms involved in the pathophysiology of arachnoid cysts, fundamental issues concerning these entities remain poorly defined and controversial. Cine-mode magnetic resonance imaging (MRI) has shown two patterns of cerebrospinal fluid (CSF) flow within the cavity in patients harbouring arachnoid cysts. Some cysts present a harmonic flow with a patent flow entry zone. All these patients had intermittent, non-progressive and non-localizing symptoms requiring no surgery according to our criteria. The second pattern of CSF flow is more chaotic and is characterized by the presence of swirls throughout the entire cardiac cycle. This pattern is associated with a more disabling clinical picture. Some of these patients required surgical treatment. During surgery, an endoscope was used for inspection purposes revealing, above all, that arachnoid cysts always and variably communicate with the subarachnoid space. The CSF enters the cyst either through a patent flow entry zone or through minute perforations in areas more loosely packed of the arachnoid network that behave as a flexible mesh able to modify the area of flowing CSF. The slipstreams of CSF within arachnoid cysts may not be channelled properly leading to possible damage of the surrounding brain parenchyma.

Adolescent↗
PubMed1999

Coexistence of primary hyperparathyroidism and thyroid disease.

Primary hyperparathyroidism (HPT) and thyroid disease are both relatively common diseases, which can coexist in the same patient. However, mere coincidence does not seem to be a satisfactory explanation for this association. Some factors like prior exposure to radiation may play a role in the association. The aim of this study was to determine the frequency of thyroid disease associated with HPT in 54 consecutive patients who underwent parathyroidectomy in our center from January 1990 to December 1997. Twenty-eight (52%) patients had thyroid disease associated to HPT. The patients had a mean age of 61+/-13 yr; they were predominantly postmenopausal women. Thyroid disease was detected preoperatively in 20 (71%) patients and during the surgical procedure in 8 (29%). Two patients had previous radiation exposure; one of them with papillary carcinoma of the thyroid. Two patients had hypothyroidism. UItrasonography was performed in the majority of patients in their preoperative evaluation. A multinodular goiter was seen to be the most frequent finding (76%). In addition to parathyroidectomy, 23 (82%) patients were also thyroidectomized. In conclusion, patients with HPT showed a high prevalence of thyroid disease, especially in postmenopausal women. Unsuspected thyroid lesions were found with sufficient frequency to warrant careful preoperative and intraoperative evaluation of both glands, in order to obviate reoperation. In experienced hands, combined surgery can be safely performed. Cervical ultrasonography is useful in the preoperative detection of nodular thyroid disease in these patients.

Adolescent↗
PubMed1999

Mechanisms of resistance to ampicillin, chloramphenicol and quinolones in multiresistant Salmonella typhimurium strains isolated from fish.

Mechanisms of antibiotic resistance and epidemiological relationships were investigated for five multiresistant strains of Salmonella typhimurium isolated from fish in India. Four strains showed resistance to nalidixic acid, chloramphenicol, tetracycline, co-trimoxazole, gentamicin and beta-lactam antibiotics. The remaining strain was susceptible to all beta-lactam antibiotics tested and to co-trimoxazole but resistant to the other antibiotics tested. Epidemiological analysis performed by REP-PCR showed that the five isolates belonged to the same clone. Resistance to nalidixic acid was related to a single mutation in the gyrA gene. Chloramphenicol resistance was related to the production of chloramphenicol acetyl-transferase. An OXA-1 beta-lactamase, located in an integron, was responsible for resistance to ampicillin. These results indicate the health hazard posed by the fact that S. typhimurium may acquire or develop several mechanisms of resistance to a variety of antibiotics, including quinolones, and can thus cause disease in humans which may be difficult to treat.

Ampicillin↗
PubMed1998

Isolation and characterization of the cDNA and the gene for eukaryotic translation initiation factor 4G from Drosophila melanogaster.

Recent evidence supports the notion that the eukaryotic polypeptide chain initiation factor (eIF)4G plays a critical bridging role in coordinating other eIF involved in eukaryotic translation initiation. Here we report the isolation and characterization of a 5621-bp cDNA encoding Drosophila eIF4G. The longest ORF predicts a polypeptide of 1666 amino acids with a molecular mass of 183,940 Da and shares 25% amino acid identity with other eIF4G. The 5' untranslated region is 386 nucleotides long and contains seven AUG codons out of frame. The in vitro transcription/translation of the cDNA yielded a major polypeptide, which was specifically immunoprecipitated with an antibody against Drosophila eIF4G. This polypeptide has the same electrophoretic mobility as eIF4G purified from Drosophila melanogaster embryos. A conserved eIF4E-binding motif was found in Drosophila eIF4G. The gene maps at the 102E region of chromosome 4 and spans a genomic region of approximately 16 kb. It was found to contain 15 introns. A single RNA transcript of approximately 5.9 kb was detected by northern blotting of poly(A)-rich RNA prepared from Drosophila adults. The sequence upstream of the transcription initiation site lacks the consensus TATA box, but contains several sequences possibly involved in the regulation of transcription.

Amino Acid Sequence↗
PubMed1997

Localization, structure and expression of the gene for translation initiation factor eIF-4E from Drosophila melanogaster.

Drosophila melanogaster contains a single copy of the gene encoding translation eukaryotic initiation factor eIF-4E, which maps in the 67A2B1 region of chromosome 3L. A genomic clone containing the entire eIF-4E gene was isolated and sequenced. Comparison of this sequence with a cDNA previously obtained in our laboratory and 5'-RACE analysis revealed the existence of three mRNAs that are generated by alternative splicing of a primary transcript. All of them have different 5' untranslated leader regions. Two of the mRNAs encode the same eIF-4E polypeptide, whose sequence has been deduced from the cDNA clone. The third mRNA species contains a new open reading frame, possibly encoding another isoform of eIF-4E, which is very similar in size to the other but has a different N-terminal sequence. Several sequences which may be involved in the regulation of transcription initiation of the eIF-4E gene, except for a consensus TATA box, were found upstream of the putative transcription initiation sites. Expression of the eIF-4E gene is spatially and temporally controlled during embryonic development. It is ubiquitously expressed during embryogenesis but transcripts preferentially accumulate in certain tissues, particularly in the pole cells, at different developmental stages.

Alternative Splicing↗
PubMed1997

Fine-needle aspiration biopsy of thyroid nodules: impact on clinical practice.

UNLABELLED: The aim of the present study was to analyze the changes in our clinical practice due to the use of FNAB in the management of nodular thyroid disease. Patients attended the thyroid unit for thyroid nodules. The study comprises three periods: First, from January 1980 to May 1984, 226 patient. Second, from June 1985 to December 1990, 166 patients. Third, from January 1991 to December 1993, 403 patients. DESIGN: retrospective the 1st period and prospective the 2nd and 3rd periods. During the 1st and 2nd periods, decision for surgery was based on clinical parameters together with results of 99Tc radionucleotide scan and B mode ultrasound studies. In the 3rd period surgical decision was based principally on cytologic results. We comparatively studied the frequency of surgical operation and frequency of malignancy in surgical thyroid specimens between the study periods. Determination of sensitivity, specificity and accuracy of the diagnostic methods was done. We observed a decrease in the frequency of patients requiring surgery, 89.9%, 67.8% and 46.6% for the 1st, 2nd and 3rd study periods, X2 = 114.7, p < 0.0001; and an increase in the frequency of malignancy in the surgical specimens, 14.7%, 24.4% and 32.9% for 1st, 2nd and 3rd periods respectively, X2 = 4.5, p < 0.05. The sensitivity 92.5% and 93.5%, the specificity 50.6% and 61.1%, and the accuracy 60.9% and 71.8% of the FNAB for the second and third periods respectively. The rates of false negative cytological specimens were 1.8% and 2.1% for 2nd and 3rd respectively, p > 0.05. Since the introduction of FNAB in the evaluation of our patients around 70% of these had a definitive preoperative diagnosis of either benign or malignant disease. Simplification in management of patients with nodular thyroid disease is the most important impact for the use of FNAB. Furthermore, a decrease in the number of patients requiring surgical treatment and an increase of malignant nodules in the specimens obtained by surgery were also observed. We think that FNAB is the most direct and accurate method in the management of patients with thyroid nodules.

Adolescent↗
PubMed1995

Translation initiation factor eIF-4E from Drosophila: cDNA sequence and expression of the gene.

A Drosophila melanogaster cDNA clone encoding the translation initiation factor eIF-4E was isolated and sequenced. The deduced polypeptide consists of 259 amino acids with a predicted molecular weight of 29,223. It shares 48%, 37% and 35% identity to its mammalian, yeast and wheat counterparts, respectively. Several residues (including eight tryptophans), which were shown to be critical for the function of mammalian and yeast eIF-4Es, are conserved in the Drosophila protein. Three transcripts of the eIF-4E gene were detected throughout Drosophila development.

Amino Acid Sequence↗
PubMed1994

Purification and characterization of eukaryotic polypeptide chain initiation factor 4F from Drosophila melanogaster embryos.

The eukaryotic polypeptide chain initiation factor 4F (eIF-4F), purified by m7GTP-Sepharose chromatography from whole extracts of Drosophila melanogaster embryos, consists of two subunits, the previously identified eIF-4E (35 kDa) (Maroto, F. G., and Sierra, J. M. (1989) Mol. Cell. Biol. 9, 2181-2190) and another of 200 kDa. Both subunits cosedimented through a sucrose density gradient containing 0.5 M KCl. In contrast to rabbit reticulocyte eIF-4F, we did not find any RNA-dependent ATPase associated with the Drosophila factor. As shown previously for eIF-4E, the p200 subunit was also required for the translation of endogenous mRNAs in cell-free systems from Drosophila embryos. Only the eIF-4E subunit was able to cross-link to the m7G cap structure. However, an efficient cross-linking of the p200 subunit to an uncapped mRNA was observed. Both subunits were phosphorylated in vitro by protein kinase C from rat brain. As an extension of our previous results (Zapata, J. M., Maroto, F. G., and Sierra, J. M. (1991) J. Biol. Chem. 266, 16007-16014) we found that the translation of the heat shock mRNAs was independent of both of the eIF-4F subunits.

Animals↗