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Biomedical subjects

M Lozano

Publications and source records attributed to M Lozano.

At least 73 records · Page 4Linked to original sources
PubMed1995

Molecular characterization of a new family with alpha-thalassemia-1 (--MA mutation).

A Spanish family with alpha-thalassemia-1 (alpha-Thal-1), deletion (--MA), is described. In addition to the loss of 22 kb of DNA with a deletion of the alpha 1, alpha 2, psi alpha 2, and psi zeta 1 genes, a triplication of the zeta gene cluster in "cis" is produced. The structure of this triplication is formed by the psi zeta 1 gene, the interzeta region, and, possibly, the insertion of the psi alpha 2 fragment.

Adult↗
PubMed1995

Effect of adenosine on the management of supraventricular tachycardia by urban paramedics.

STUDY OBJECTIVE: To determine the effect of the addition of adenosine, as a standing-order medication, on the prehospital management of supraventricular tachycardia (SVT) in a large urban emergency medical services (EMS) system. DESIGN: Prospective observational case series with historical controls. SETTING: Large urban municipal EMS system staffed by paramedics and emergency medical technicians trained to operate automatic or semiautomatic defibrillators (EMT-Ds). PARTICIPANTS: We observed a consecutive sample of prehospital patients who presented with an initial ECG rhythm of SVT, as interpreted by the treating paramedics, between July 1 and December 31, 1993. We used patients from the same 6-month period in 1992 as our control group. Indications for treatment were chest pain, evidence of myocardial ischemia, or shock. Adenosine had been introduced as a first-line medication to be used under standing orders in cases of unstable SVT before a physician was contacted for medical control options. RESULTS: We studied 239 cases and 228 controls. Acceptable call reports with pretreatment and posttreatment ECGs were available for 140 (59%) of the study cases and 104 (46%) of the controls. The two groups were similar in terms of age, sex, and initial vital signs. In the control group, 75 patients had indications for treatment, and 16 were treated (21%). In the study group, 127 had indications for treatment and 103 (81.1%) were treated (odds ratio, 15.83; 95% confidence interval, 7.38-34.4). CONCLUSION: The introduction of adenosine as a standing-order medication into an urban EMS system increased the proportion of patients who received advanced life support treatment. Paramedics were able to accurately diagnose and begin treatment of SVT with adenosine without direct medical supervision.

Adenosine↗
PubMed1995

A redundant nuclear protein binding site contributes to negative regulation of the mouse mammary tumor virus long terminal repeat.

The tissue specificity of mouse mammary tumor virus (MMTV) expression is controlled by regulatory elements in the MMTV long terminal repeat (LTR). These regulatory elements include the hormone response element, located approximately between -200 and -75, as well as binding sites for NF-1, Oct-1 (OTF-1), and mammary gland enhancer factors. Naturally occurring MMTV deletion variants isolated from T-cell and kidney tumors, transgenic-mouse experiments with MMTV LTR deletions, and transient transfection assays with LTR constructs indicate that there are additional transcription regulatory elements, including a negative regulatory element (NRE), located upstream of the hormone response element. To further define this regulatory region, we have constructed a series of BAL 31 deletion mutants in the MMTV LTR for use in transient transfection assays. These assays indicated that deletion of two regions (referred to as promoter-distal and -proximal NREs) between -637 and -201 elevated basal MMTV promoter activity in the absence of glucocorticoids. The region between -637 and -264 was surveyed for the presence of nuclear protein binding sites by gel retardation assays. Only one type of protein complex (referred to as NRE-binding protein or NBP) bound exclusively to sites that mapped to the promoter-distal and -proximal NREs identified by BAL 31 mutations. The promoter-proximal binding site was mapped further by linker substitution mutations and transfection assays. Mutations that mapped to a region containing an inverted repeat beginning at -287 relative to the start of transcription elevated basal expression of a reporter gene driven by the MMTV LTR. A 59-bp DNA fragment from the distal NRE also bound the NBP complex. Gel retardation assays showed that mutations within both inverted repeats of the proximal NRE eliminated NBP binding and mutations within single repeats altered NBP binding. Intriguingly, the NBP complex was detected in extracts from T cells and lung cells but was absent from mammary gland cells. These results suggest that a factor contributing to high-level expression of MMTV in the mammary gland is the lack of negative regulation by NBP.

Animals↗
PubMed1994

Cys209 Ser mutation in the platelet membrane glycoprotein Ib alpha gene is associated with Bernard-Soulier syndrome.

Molecular genetic analysis has been performed on a patient with Bernard-Soulier syndrome (BSS). The patient had characteristically giant platelets and was deficient in the glycoprotein (GP) Ib/IX/V complex, the von Willebrand factor (vWf) receptor on platelets. Previous studies with monoclonal antibodies directed against GP Ib alpha (CD 42b) and GP IX (CD 42a) demonstrated the absence of GP Ib alpha and presence of small amounts of GP IX on the surface of the patient's platelets. In this study the presence of GP V (CD 42d) is also demonstrated. This indicates a defect in the alpha-subunit of glycoprotein Ib. Therefore polymerase chain reaction (PCR)-amplification of the genomic DNA coding for GP Ib alpha was performed. Nucleotide sequence analysis of the entire coding region of GP Ib alpha revealed a homozygous single base pair mutation T-->A, leading to a single amino acid substitution cysteine-->serine at position 209 of the mature protein. We took advantage of the Mse I target site in the mutant allele, created by the T-->A mutation, to analyse all available family members. PCR-ASRA (allele-specific restriction enzyme analysis) using the restriction enzyme Mse I, revealed the heterozygosity of the mother and the two children of the patient, whereas homozygosity of the patient for the Cys209Ser mutation was confirmed. The sister of the patient was not found to be a carrier of the mutant allele. The mutation identified in the family studied, responsible for the deficiency of the GP Ib/IX/V complex, suggests that the cysteine at amino acid position 209 may be involved in disulphide bonding.

Adult↗
PubMed1994

Suitability of low-molecular-weight heparin(oid)s and a pentasaccharide for an in vitro human thrombosis model.

There is much interest in in vitro thrombosis systems using exclusively human materials for evaluating new drugs. We have previously developed such a model using a perfusion chamber in which whole blood anticoagulated with low-molecular-weight heparin (LMWH) was circulated over the extracellular matrix of endothelial cells that had been stimulated with phorbol myristate acetate to cause tissue factor formation. Here we studied various LMWHs and a pentasaccharide to find out which was most useful in an in vitro thrombosis model. We compared unfractionated heparin, two commercial LMWHs (Fragmin and Fraxiparine), one commercial heparinoid (Orgaran), and a chemically synthesized derivative of the natural pentasaccharide (Org 31550). Blood was anticoagulated with the concentration of each glycosaminoglycan that prevented thrombin formation for at least 3 hours in the test tube (Fragmin, 20 anti-Xa U/mL; Fraxiparine, 40 anti-Xa Institute Choay U/mL; Orgaran, 15 anti-Xa U/mL; Org 31550, 200 anti-Xa U/mL; unfractionated heparin, 5 IU/mL) and recirculated over the matrix of unstimulated cells (no tissue factor in the matrix) and phorbol-stimulated endothelial cells (tissue factor in the matrix). Platelet adhesion, aggregate formation, and fibrin deposition were evaluated. In perfusions over the extracellular matrix of unstimulated cells, the highest platelet adhesion rates were observed with Orgaran. Fibrin deposition was absent with unfractionated heparin in phorbol-stimulated matrix. Increasing amounts of fibrin were observed with Orgaran, Fragmin, and Fraxiparine. Most fibrin was found with the pentasaccharide Org 31550.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMed1993

Interferon alpha 2A in the treatment of chronic myelogenous leukemia in chronic phase. Results of the Spanish Group.

Fifty-one patients with CML in chronic phase, less than two years after diagnosis, were included in one multicentric study aiming to assess the therapeutic value of interferon alpha 2a (IFN alpha 2a) in this setting. The therapeutic scheme was biphasic: The patients were first treated with hydroxyurea, and afterwards only received IFN alpha 2a, at a planned dose of 5MU/m2/day, s.c. Thirty-eight patients (81%) achieved an hematologic response, which was complete in 57% of the total group. The median time to response was of 42 days. In the last evaluation, a complete hematologic response was sustained in 21 patients (47%). Philadelphia suppression was obtained in 44% of the patients who achieved hematologic responses; major cytogenetic responses were obtained in 16% of the patients. The patients who obtained genetic responses were significantly younger and had a shorter interval from diagnosis to IFN than the patients who did not respond. At the moment of evaluation, 90% of the patients are alive, but the median follow-up of the series (217 days, range 21-1150) is too short to analyze any impact of IFN over survival. Six patients (12%) discontinued IFN because of toxicity, three of them because of severe flu-like syndrome. Leukopenia and thrombocytopenia were frequent, but rarely severe. Hypertriglyceridemia has been a very frequent finding.

Adolescent↗
PubMed1991

Treatment of early stage-B chronic lymphocytic leukemia with alpha-2b interferon after chlorambucil reduction of the tumoral mass.

Eleven patients with early CLL (two in Rai's stage 0, seven in stage I, and two in stage II) received aIFN (3 MU subcutaneously three times a week for a median of 8 months; range, 4-12) after their tumor mass had been reduced with intermittent chlorambucil. Following chlorambucil/aIFN administration, a significant reduction in blood lymphocyte counts (from 25.1 +/- 12.0 x 10(9)/l to 6.3 +/- 5.32 x 10(9)/l; p less than 0.001) and in CD 19-positive cells (from 21.0 +/- 12.0 x 10(9)/l to 3.8 +/- 2.3 x 10(9)/l; p less than 0.001) was observed. Three of seven patients with stage-I and one of two with stage-II disease moved to stage 0, and a complete response (CR) was observed in two patients with stage-I at diagnosis. Overall, there were eight patients who, after treatment, had either a CR (2 cases) or stage-0 disease (6 cases), which compares favorably with two patients with stage-0 disease before entering the study (p = 0.015). In five patients (including the two who achieved a CR) aIFN further improved the disease status achieved with chlorambucil.

Adult↗
PubMed1991

[Focal hepato-splenic mycosis caused by Trichosporon beigelii in a patient with acute leukemia].

We report a case of infection produced by Trichosporon beigelii in a patient with acute leukaemia. In spite of treatment with amphotericin B the patient died and the necropsy studies showed only involvement of liver and spleen without disseminated infection. Focal hepatosplenic fungal infection has been recognized with increasing frequency in recent years as a serious complication in immunosuppressed patients. Usually it is produced by Candida spp and this is the first case described in the literature due to the newly recognized fungus T. beigelii.

Adult↗
PubMed1990

Studies on the megakaryocytes of a patient with the Bernard-Soulier syndrome.

We have used monoclonal antibodies AP-1 (anti-GP Ib alpha). AP-2 (anti-GP IIb-IIIa) and FMC 25 (anti-GP IX) in immunofluorescence and immunocytochemical studies on megakaryocytes (MK) isolated from a Bernard-Soulier syndrome (BSS) patient whose giant platelets were characteristically deficient in GP Ib-IX complexes. Electron microscopy showed that the patient's MK were similar in size to normal MK. However, a striking feature was the variable and intermittent nature of the demarcation membrane system which was often vacuolar in appearance. Permeabilized mature MK from normal individuals were strongly positive with AP-2, AP-1 and FMC 25. Those from the BSS patient were normal for AP-2, negative for AP-1 but weakly positive with FMC 25. Binding of the monoclonal antibodies to the patient's platelets was evaluated using flow cytometry. The results confirmed the absence of GP Ib alpha from the surface membranes, but showed the presence of small amounts of GP IX distributed throughout the platelet population. Our findings confirm that the membrane lesion in BSS is also to be found in MK and further show that the defect may affect differently individual constituents of the GP-Ib-IX complex.

Adult↗