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Biomedical subjects

F Fernández

Publications and source records attributed to F Fernández.

At least 55 records · Page 3Linked to original sources
PubMed2000

Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation.

Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graft-versus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Immune hemolytic anemia induced by 6-mercaptopurine.

BACKGROUND: Myelosuppression is the main hematotoxic effect of 6-mercaptopurine (6-MP), which is an antimetabolite chemotherapy drug. Immune hemolytic anemia associated with this drug has not been previously reported. CASE REPORT: A 67-year-old man with chronic myelomonocytic leukemia presented with anemia 2 weeks after 6-MP therapy had been initiated. Additional tests provided laboratory evidence of hemolysis. When treatment was stopped, the patient's condition and laboratory results showed a progressive improvement. RESULTS: The direct antiglobulin test was positive for IgG. The eluate and the serum were not reactive with panel red cells but reacted with 6-MP-treated red cells, while the normal serum pool was unreactive. The direct antiglobulin test was no longer positive by 20 days after the cessation of 6-MP therapy. CONCLUSION: This drug, 6-MP, should be added to the list of drugs that have been reported to cause immune hemolytic anemia by means of the so-called hapten mechanism.

Aged↗
PubMed2000

Liver insulin-like growth factor-I mRNA is not affected by diet composition or ration size but shows diurnal variations in regularly-fed gilthead sea bream (Sparus aurata).

Nutritional regulation of insulin-like growth factor-I (IGF-I) mRNA was assessed in liver of gilthead sea bream (Sparus aurata). As in mammals, starvation lowered the IGF-I mRNA content, which was recovered by refeeding. However, in contrast to previous observations in rats, neither diet composition nor ration size significantly affected hepatic IGF-I mRNA. Although fish growth depended on the quantity of diet supplied, no relationship was found between growth and liver IGF-I mRNA levels, a fact that challenges the importance, at least in fish, of liver-derived IGF-I on body growth attributed by the classical somatomedin hypothesis. In addition, diurnal modulation of mRNA levels occurred following food intake, suggesting that the intake of food may play a key role in the regulation of the short-term anabolic effects of IGF-I.

Animals↗
PubMed2000

Personal-computer-based system for three-dimensional anatomic-physiological correlations during stereotactic and functional neurosurgery.

This paper describes the automatic three-dimensional (3D) graphic possibilities that are supplied by the Neurosurgical Deep Recording System (NDRS) to facilitate anatomic-physiological targeting during stereotactic and functional neurosurgery using depth recording. This software has been developed to substitute the complex electronic equipment ordinarily used for deep brain electrical recording, display and processing by a personal computer. It may also help to improve on-line graphic analysis, automatic management of the recorded information and flexibility to implement different forms of signal analysis. It can automatically show a 2D or 3D representation of the electrode track, with the electrophysiological findings superimposed as well as the corresponding sagittal, coronal and axial views of a brain atlas using automatic scaling. The NDRS has already successfully been applied during more than 300 neurosurgeries in Spain and Cuba, enabling improved targeting accuracy and safety.

Brain Mapping↗
PubMed2000

Comparison of several ELISA tests for detecting the presence of IgG and IgM against herpes simplex viruses.

Four enzyme-linked immunosorbent assays designated test 1 (ETI-HSVK-G 1/2); test 2 (ETI-HSVK-M 1/2); test 3 (ETI-HSVK-G 2), and test 4 (BioElisa HSV2 IgG) were studied to evaluate different stages of herpes simplex virus (HSV) infection. Samples (50 sera and 14 cerebrospinal fluid) were included in four groups. Group 1 consisted of samples from patients with primary HSV infections; group 2 comprised samples from patients with recurrent HSV infections; group 3 were samples nonreactive to HSV; and group 4 were samples from patients with infections by other herpes viruses (4a, chickenpox; 4b, herpes zoster; and 4c, infectious mononucleosis by Epstein-Barr virus). The percentages of agreement between tests 1 and 2 were 100 and 72.1%, respectively. The total diagnostic values of tests 1 and 2 were: 100 and 50% sensitivity, respectively; and 100 and 89% specificity, respectively. Few positive results for HSV-2 infection were found, and so, tests 3 and 4 were not evaluated. The results of tests 3 and 4 for a chickenpox patient, and a herpes zoster patient were not in agreement.

Antibodies, Viral↗
PubMed2000

[False resistance to imipenem in gram negative bacilli with and automatized system].

BACKGROUND: The aim of this study was to evaluate the reliability of MIC values of imipenem against gramnegative rods obtained with the automated system WalkAway-98 (MicroScan, Dade, USA). MATERIAL AND METHODS: One-hundred and seventy three consecutive clinical isolates of Gram-negative rods for which the MIC of imipenem were > or = 4 mg/l (Urine-Combo 6I panels, U6I) or > or = 8 mg/l (Neg-Combo 6I panels, N6I) were evaluated, including 104 non-fermenting gram-negative rods (NFGNR) and 69 enterobacteria. Panels were inoculated and read according to manufacturer's instructions. Microdilution, according to NCCLS guidelines, was used as the method of reference. MIC of imipenem determined by WalllAway-96 and microdilution differing > or = 2 dilution steps from those obtained with mirodilution were considered as discrepant results. Discrepancies in clinical categories were also evaluated by calculating three types of errors: very major (false susceptibility), major (false resistance) and minor (either susceptible or resistant by one method and intermediate by the other one). RESULTS: The percentages of discrepancies in the MIC of imipenem determined with U6I panels were 74% and 84% for NFGNR and enterobacteria, respectively. No very major errors were detected. Major errors were observed for 6% and 12% of the strains with U6I panels in NFGNR and enterobacteria, respectively, and in 12% (NFGNR) and 50% (enterobacteria) with N61 panels. With U61 panels minor errors were observed in 11% and 25% of NFGNR and enterobacteria, respectively, while with N61 panels minor error were observed in 39% and 45% of both groups, respectively. CONCLUSIONS: MIC of imipenem > or = 4 mg/l obtained with the WalkAway-96 system against gramnegative rods, particularly in the case of enterobacteria, should be confirmed with a reference susceptibility method.

Drug Resistance, Microbial↗
PubMed1999

Genetic evidence for the heterodimeric structure of glucosidase II. The effect of disrupting the subunit-encoding genes on glycoprotein folding.

It has been proposed that in rat and murine tissues glucosidase II (GII) is formed by two subunits, GIIalpha and GIIbeta, respectively, responsible for the catalytic activity and the retention of the enzyme in the endoplasmic reticulum (ER). To test this proposal we disrupted genes (gls2alpha(+) and gls2beta(+)) encoding GIIalpha and GIIbeta homologs in Schizosaccharomyces pombe. Both mutant cells (gls2alpha and gls2beta) were completely devoid of GII activity in cell-free assays. Nevertheless, N-oligosaccharides formed in intact gls2alpha cells were identified as Glc(2)Man(9)GlcNAc(2) and Glc(2)Man(8)GlcNAc(2), whereas gls2beta cells formed, in addition, small amounts of Glc(1)Man(9)GlcNAc(2). It is suggested that this last compound was formed by GIIalpha transiently present in the ER. Monoglucosylated oligosaccharides facilitated glycoprotein folding in S. pombe as mutants, in which formation of monoglucosylated glycoproteins was completely (gls2alpha) or severely (gls2beta and UDP-Glc:glycoprotein:glucosyltransferase null) diminished, showed ER accumulation of misfolded glycoproteins when grown in the absence of exogenous stress as revealed by (a) induction of binding protein-encoding mRNA and (b) accumulation of glycoproteins bearing ER-specific oligosaccharides. Moreover, the same as in mammalian cell systems, formation of monoglucosylated oligosaccharides decreased the folding rate and increased the folding efficiency of glycoproteins as pulse-chase experiments revealed that carboxypeptidase Y arrived at a higher rate but in decreased amounts to the vacuoles of gls2alpha than to those of wild type cells.

Animals↗
PubMed1999

In vivo antitumor activity of choline kinase inhibitors: a novel target for anticancer drug discovery.

Transformation by some oncogenes is associated with increased activity of choline kinase (ChoK), resulting in elevated constitutive levels of phosphorylcholine, a proposed second messenger required for DNA synthesis induced by growth factors. Here we describe the characterization of ChoK inhibitors with antiproliferative properties against human tumor-derived cell lines. The new molecules were tolerated in mice at doses that showed in vivo antitumor activity against human tumor xenografts derived from HT-29 and A431 cell lines implanted s.c. in nude mice. This first generation of inhibitors provides in vivo evidence that blockade of phosphorylcholine production is a valid strategy for the development of new anticancer agents, opening a new avenue for the development of antitumor drugs with a novel mechanism of action.

Adenocarcinoma↗
PubMed1999

[Changes in the long arm of chromosome 3 (3q) in malignant myeloid hemopathies. A study of 10 cases].

BACKGROUND: Abnormalities of the long arm of chromosome 3 (3q) involving bands 3q21 and/or 3q26 occur in 2-6% of myeloid malignancies. Trilineage myelodysplasia, especially in the megakaryocytic line, is a characteristic feature. Additional abnormalities of chromosomes 5 and 7 are usually present. The response to treatment and prognosis are poor. PATIENTS AND METHODS: The main clinical, cytologic (bone marrow aspirate and biopsy) and cytogenetic characteristics as well as the response to the treatment in 10 patients with 3q abnormalities diagnosed in a single hospital in a period of 8 years are referred. RESULTS: Eight patients had acute non-lymphoblastic leukemia, being de novo in five of them. The median value of hemoglobin was 87 g/l (range: 51-148), white blood cells count 5.8 x 10(9)/l (1.2-47.1) and platelet count 34 x 10(9)/l (5-182). The morphological findings in the study of the bone marrow were: dyserythropoietic features (7 patients), dysgranulopoietic abnormalities (5 patients) and small-sized megakaryocytes with hypolobulated nuclei (8 patients). Fibrosis was observed in the 4 cases in which a bone marrow biopsy was performed. In addition to the 3q alteration, abnormalities of chromosomes 7 (4 patients), 5q (2 patients) and +8 (2 patients) were present. Four patients received intensive chemotherapy and in two of them a complete remission was achieved, but relapse occurred at 3 and 5 months, respectively. All patients have died, the median survival being 7 months. CONCLUSIONS: 3q abnormalities define a subtype of myeloid malignancies with characteristic clinical and morphological features. The response to therapy and survival are poor.

Adult↗
PubMed1999

Molecular cloning of a cDNA encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from liver of Sparus aurata: nutritional regulation of enzyme expression.

A cDNA clone encoding full-length 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF-2-K/Fru-2, 6-P2ase) was isolated and sequenced from a Sparus aurata liver cDNA library. The 2527 bp nucleotide sequence of the cDNA contains a 73 bp 5'-untranslated region (5'-UTR), an open reading frame that encodes a 469 amino acid protein and 1041 bp at the 3'-UTR. The deduced amino acid sequence is the first inferred 6PF-2-K/Fru-2, 6-P2ase in fish. The kinase and bisphosphatase domains, where the residues described as crucial for the mechanism of reaction of the bifunctional enzyme are located, present a high degree of homology with other liver isoenzymes. However, within the first 30 amino acids at the N-terminal regulatory domain of the fish enzyme a low homology is found. Nutritional regulation of the 6-phosphofructo-2-kinase activity, together with immunodetectable protein and mRNA levels of 6PF-2-K/Fru-2,6-P2ase, was observed after starvation and refeeding. In contrast to results previously described for rat liver, the decrease in immunodetectable protein and kinase activity caused by starvation was associated in the teleostean fish to a decrease in mRNA levels.

Amino Acid Sequence↗
PubMed1999

Synthesis and antiviral and cytostatic activities of carbocyclic nucleosides incorporating a modified cyclobutane ring. Part 1: Guanosine analogues.

Five new carbocyclic nucleosides were prepared by constructing a guanine (compounds 3, 5) or 8-azaguanine (compounds 4, 6, and 7) base on the amino group of (1'S,3'R)-3-(3'-amino-2',2'-dimethylcyclobutyl)propan-1-ol (8), and their activities against a variety of viruses and tumor cell lines were determined. Only compounds 3 and 7 showed a detectable activity at subtoxic concentrations against some viruses tested.

Antineoplastic Agents↗
PubMed1999

Prospective clinical and microbiological study of pleural effusions.

A prospective clinical microbiological study of pleural fluid samples was conducted to investigate the etiology of pleural effusions and to evaluate two different methods for transport and culture of these samples. A total of 245 pleural fluid specimens were inoculated into a transport vial, an aerobic and an anaerobic blood culture vial, and a sterile tube. One hundred nine samples were from infectious patients and 128 from noninfectious patients. Gram stain had a sensitivity of 48% and a specificity of 100% as compared to culture. Of the total, 15.5% of the samples were positive for microorganisms, and 60% of the positive samples were nonpurulent pleural fluid. Single-organism growth was found in 23 samples (60.5%). Sixty-three microorganisms were isolated: 25 (39.7%) aerobic, 22 (35%) anaerobic, 13 (20.6%) mycobacteria, and three (4.7%) fungi. Of the 25 positive samples, excluding those samples that grew mycobacteria, nine (36%) were positive exclusively in the blood culture vials. Twelve organisms were isolated, only one of which did not grow in the anaerobic vial. Two (8%) samples were positive by conventional culture only, and 14 (56%) were positive by both methods. The microorganism isolation rate obtained with use of blood culture vials was significantly greater than that obtained with the conventional method of transport and culture. Sixty-three percent of the empyema patients had an associated underlying pathology, pneumonia being the most frequent. In conclusion, for microbiological study of pleural fluid, it seems appropriate to inoculate all samples, including nonpurulent samples, into both a sterile tube and an anaerobic blood culture vial.

Adolescent↗
PubMed1999

Cathepsin D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma.

AIMS: To determinate the relationship between tumoral angiogenesis and cathepsin D (CD) expression in tumour and host stromal cells of invasive breast carcinoma, and to examine its association with classical prognostic factors such as lymph node status, histological grade, tumour size, mitotic rate, peritumoral lymphovascular invasion and oestrogen receptor (ER) status. METHODS AND RESULTS: Sections from 102 invasive breast carcinoma were cut from the archival formalin-fixed, paraffin-embedded tissue blocks and stained using immunohistochemistry for the endothelial cell adhesion molecule (CD31) and CD. Microvessel density was assessed by counting vessels in the three most vascular areas at x400 field. The counts were expressed as the highest counts within any x400 field. The evaluation of immunostaining for CD was performed separately in both the parenchymal and stromal cells. Microvessel density was correlated positively with histological grade and peritumoral lymphovascular invasion, and correlated inversely with ER status. Positive CD staining of tumour cells was more frequent in positive ER tumours and was not significantly associated with the other classical prognostic factors. However, moderate to strong staining of host cells was correlated with higher histological grade, higher mitotic index and lack of ER protein. There was a statistically significant association between CD expression of host stromal cells and higher vessel count. CONCLUSIONS: CD in host stromal cells is associated with more aggressive tumours and with a higher intratumoral microvessel density. Evaluation of CD in combination with angiogenic activity may be of some help in more accurately predicting the biological behaviour of breast carcinoma.

Adult↗
PubMed1999

Relationship between haemolysis production and resistance to fluoroquinolones among clinical isolates of Escherichia coli.

The activities of ampicillin, amoxycillin-clavulanic acid, gentamicin, tetracycline, nalidixic acid, ciprofloxacin, pefloxacin and trovafloxacin against 207 consecutive clinical isolates of Escherichia coli were determined. Fifty-six (27.3%) isolates were haemolytic. The percentages of resistance to quinolones and tetracycline, but not to other agents, among haemolytic isolates were significantly lower (P < 0.05) than among non-haemolytic isolates. Ciprofloxacin-resistant mutants obtained from ciprofloxacin-susceptible haemolytic isolates still produced haemolysis. It is concluded that most quinolone-resistant clinical isolates of E. coli are non-haemolytic, although haemolysis is produced by quinolone-resistant mutants derived from haemolytic quinolone-susceptible strains.

Amoxicillin↗
PubMed1999

Synthesis and antiviral and antineoplastic activities of some novel carbocyclic guanosine analogues with a cyclobutane ring.

Cyclobutyl nucleoside analogues containing guanine and 8-azaguanine (compounds 5-10) were prepared from (1R,cis)-3-aminomethyl-2,2-dimethylcyclobutylmethanol (1). All were evaluated as antiviral and antitumoral agents in a variety of assay systems. Compounds 6 and 7 showed a noteworthy activity against a respiratory syncytial virus and compound 10 was moderately active against vaccinia virus. Only compound 5 showed some cytostatic activity.

Antineoplastic Agents↗