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Biomedical subjects

M Vendrell

Publications and source records attributed to M Vendrell.

At least 19 recordsLinked to original sources

A gene expression approach to mapping the functional maturation of the hippocampus.

Previous studies have shown an association among seizures, neuronal death and the expression of cellular immediate-early genes (cIEG). To understand further the relationship between these processes, we investigated the ability of kainic acid (KAI) to induce behavioral responses and gene expression in the hippocampus of developing fos-lacZ transgenic mice. Despite the fact that KAI elicited seizure-like activity from P2 onwards, Fos-lacZ was first detected at P5 in CA3 pyramidal neurons. Thus, intense behavioral responses were not invariably associated with fos-lacZ expression. Furthermore, while adult CA3 neurons are highly susceptible to KAI toxicity, they are resistant at P5. Therefore, the presence of Fos-lacZ in CA3 neurons is not necessarily predictive of their fate. By P10, Fos-lacZ was induced in CA3 neurons and in the most mature granule neurons of the dentate gyrus (DG). Between P15 and P20, KAI induced fos-lacZ in all CA1 and CA3 pyramidal neurons and most granule neurons of the DG. This stereotypical pattern of fos-lacZ expression mirrors the ontogeny of hippocampal circuitry and glutamate signalling. Thus the fos-lacZ mice can be used to map the functional maturation of the nervous system with single cell resolution. The scope of this approach was extended by administration of additional chemoconvulsants to fos-lacZ mice and by analysis of fos-lacZ transgenic mice with mutations in their FAP site. These additional studies revealed anatomical and mechanistic differences in glutamate receptor-mediated transcriptional responses in the nervous system.

Animals

A cDNA clone highly expressed in ripe banana fruit shows homology to pectate lyases.

A cDNA clone (Ban17), encoding a protein homologous to pectate lyase, has been isolated from a cDNA library from climacteric banana fruit by means of differential screening. Northern analysis showed that Ban17 mRNA is first detected in early climacteric fruit, reaches a steady-state maximum at the climacteric peak, and declines thereafter in overripe fruit. Accumulation of the Ban17 transcript can be induced in green banana fruit by exogenous application of ethylene. The demonstrates that expression of this gene is under hormonal control, its induction being regulated by the rapid increase in ethylene production at the onset of ripening. The deduced amino acid sequence derived from the Ban17 cDNA shares significant identity with pectate lyases from pollen and plant pathogenic bacteria of the genus Erwinia. Similarity to bacterial pectate lyases that were proven to break down the pectic substances of the plant cell wall suggest that Ban17 might play a role in the loss of mesocarp firmness during fruit ripening.

Amino Acid Sequence

Characterization of specific immunoglobulin G (IgG) and its subclasses (IgG1 and IgG2) against the 23-valent pneumococcal vaccine in a healthy adult population: proposal for response criteria.

The aim of the study was to standardize an enzyme-linked immunosorbent assay (ELISA) method for the quantification of immunoglobulin G (IgG) and its subclasses (IgG1 and IgG2) against the 23-valent pneumococcal vaccine and to establish the criteria for a normal response to the vaccine. Forty healthy individuals (20 women and 20 men; mean age, 29 years) were studied. All were vaccinated with the 23-valent pneumococcal vaccine; blood samples were drawn just prior to and 3 weeks after immunization. Quantification of specific IgG and its subclasses was performed by an ELISA with the vaccine as the antigen. The linearity of the ELISA method was demonstrated by the similar slopes of the linear regression lines generated from the titration of sera with different antibody concentrations. The specificity of the antibodies against the vaccine was demonstrated by (i) an absorption test with pneumococcal vaccine, (ii) a cross-reactivity experiment with Haemophilus influenzae type b polysaccharide, and (iii) affinity chromatography with protein A-Sepharose. Response to the vaccine was defined by using the lower level of the 90% probability interval (one-tailed) for postimmunization-specific IgG, IgG1, and IgG2. By using this cutoff, responders were considered to be those with an absolute increase in antibody titers higher than 395 arbitrary units/ml for IgG, 0.350 A450 units for IgG1, and 0.314 A450 units for IgG2. Overall, 20 (50%) subjects had IgG, IgG1, and IgG2 responses, 9 (22.5%) had IgG and IgG2 responses, 4 (10%) had IgG1 responses, 3 (7.5%) had IgG and IgG1 responses, and 4 (10%) were nonresponders. Ninety percent of our population responded to the 23-valent pneumococcal vaccine. Up to 10% of healthy individuals may respond to an IgG subclass without significant increases in total IgG titers. The ELISA method that is described may be useful for evaluating the specific antibody response against polysaccharides.

Adult

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

[Theophyllines of 12- and 24-hour sustained-release. Comparative study].

To compare 24-h and 12-h delayed-release theophylline in asthmatic patients, in terms of clinical stability and respiratory function, side effects and required dose, clinical tolerance and plasma concentrations. Patients with bronchial asthma in stable phase taking theophylline every 12 h were selected. Each patient received 12-h (treatment A) and 24-h (treatment B) theophylline formulas in a prospective, cross-over study with paired data for periods of 15 days. We evaluated theophylline doses, blood levels, clinical course, lung function and side effects. Twenty patients were enrolled. No significant differences between the two treatments were observed in mean dose of theophylline per kg body weight required to obtain therapeutic plasma concentrations (treatment A: 9.36 +/- 1.88 mg/kg/day; treatment B: 9.6 +/- 1.7 mg/kg/day). Mean blood level just before administration of a the next dose was lower with the 24-h formula, but still within therapeutic margins (treatment A: 7.31 +/- 2.27 micrograms/ml; treatment B: 10.66 +/- 2.86 micrograms/ml; p = 0.002). There were no differences in side effects after the adjustment period or in FEV1 after each treatment period. Peak expiratory flow remained stable during the study. The 24-h delayed release theophylline formula was similar to the 12-h formula in dose required by asthmatic patients and in therapeutic plasma concentrations throughout the day.

Adult

IgG subclass deficiencies associated with bronchiectasis.

Only a small number of patients with IgG subclass deficiencies (IgGSD) have been observed to have bronchiectasis. Moreover, in the series of patients with bronchiectasis, IgGSD have not been found at any frequency, and the etiology of bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in 65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA test was performed to quantify subclasses 1 through 4 using subclass-specific antihuman monoclonal antibodies. IgG subclass estimation in a healthy population with age-stratified normal ranges was derived from 100 adults, 37 children aged between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum concentrations of specific IgG antibodies to Haemophilus influenzae type b capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer membrane protein complex (OMPC). Thirty-one patients (48%) had low serum concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3 deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All patients showed increased levels of total IgG, IgG1, and IgA, but this rise was significantly higher in patients without IgGSD. Patients with IgGSD showed impaired antibody response to Hib-PRP compared with patients with non-IgGSD and the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed whenever other causes of bronchiectasis have been ruled out.

Adolescent

[IgG subclasses in patients with symptomatic IgA deficiency].

BACKGROUND: Patients with IgA deficiency may be asymptomatic or may present recurrent infections mainly respiratory. A possible explanation for this variety of symptoms may be the association with a deficiency of IgG subclasses. METHODS: Twenty-five patients with a symptomatic IgA deficiency with a mean age of 18 +/- 12 years were studied. The quantification of the IgG subclasses was performed by ELISA test with antisubclass specific monoclonal murine antibodies. Serum from 100 healthy adults was collected to determine normal values of the IgG subclasses. RESULTS: Twenty-five (48%) had a deficiency of associated IgG subclasses (6 IgG2 deficiency, 1 IgG3, 3 IgG4 and 2 combined deficiency). The patient with a deficiency of associated IgG subclasses had more recurrent respiratory infections (chi 2, p < 0.03) and pneumonias (chi 2, p < 0.04). This group also had a greater FEV1 alteration (Student-t test, p < 0.04). CONCLUSIONS: Patients with symptomatic IgA deficiency frequently present IgG subclass deficiency and are more likely to have recurrent respiratory infections and greater changes in pulmonary function.

Adolescent

[The use of human gamma globulin in the treatment of common variable immunodeficiency].

BACKGROUND: The indication for treatment with human gammaglobulin in patients with primary hypogammaglobulinemia is well established. Nonetheless, there are no uniform criteria with regard to dose, periodicity and route of administration. METHODS: Twenty-seven patients with common variable immunodeficiency (CVI) who received i.m. or i.v. treatment with gammaglobulin were studied, evaluating the secondary effects, stable levels of IgG achieved, control of symptomatology, clinical evolution and the need for adjuvant therapies. RESULTS: Intravenous administration was more effective than intramuscular administration to achieve higher total IgG serum levels (5.2 +/- 1.2 vs 3.5 +/- 1.6 g/l; p = 0.07) in a shorter period of time (2.1 +/- 1.6 months vs 6.3 +/- 2.8 months; p < 0.01) and with new few secondary effects. The dose and periodicity of the treatment was individualized in each patient on the basis of the needs of consumption and the speed of metabolism of the gammaglobulin, with patients with chronic bronchial suppuration and diarrhea being those requiring the greatest doses (p < 0.0001) and a short interdosis time interval (19.2 +/- 3.1 vs 23.6 +/- 3.6 days; p = 0.01). Treatment with human gammaglobulin allowed the control of recurrent bacterial infection; however, adjuvant treatment with respiratory physical measures and antibiotics were required in patients with chronic bronchial suppuration to avoid progressive alteration of respiratory function. CONCLUSIONS: The administration of human gammaglobulin at adequate doses and frequency is effective to control infection, avoid the development of chronic bronchial disease, alteration of pulmonary function and the appearance of other complications. Intravenous route is safer and produces fewer secondary effects than intramuscular administration with the doses and period of the treatment requiring individualization for each patient.

Adolescent

Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements.

Transcription control regions of eukaryotic genes contain multiple sequence elements proposed to function independently to regulate transcription. We developed transgenic mice carrying fos-lacZ fusion genes with clustered point mutations in each of several distinct regulatory sequences: the sis-inducible element, the serum response element, the fos AP-1 site, and the calcium/cAMP response element. Analysis of Fos-lacZ expression in the CNS and in cultured cells demonstrated that all of the regulatory elements tested were required in concert for tissue- and stimulus-specific regulation of the c-fos promoter. This implies that the regulation of c-fos expression requires the concerted action of multiple control elements that direct the assembly of an interdependent transcription complex.

Animals

[The use of fibrinogen-thrombin via endoscope in the treatment of massive hemoptysis].

We assessed the efficacy of fibrinogen-thrombin instillation through the fiberoptic bronchoscope to treat massive hemoptysis in patients to whom embolization of bronchial arteries was not available, was contraindicated or had failed. The fibrinogen-thrombin solution used was Tissucol, which in addition to 2% fibrinogen and 4 U/ml of thrombin, also contained factor XIII an aprotinin. The fibrinogen-thrombin solution was instilled with the aid of the Duplojec system and a 70 cm x 2 mm 4-way catheter. In 53 of the 628 fiberoptic bronchoscopies performed during the study, the indication was hemoptysis > or = 150 ml/12 h. Of these, bronchoscopic instillation of fibrinogen-thrombin was indicated in 5 cases because bronchial artery embolization was impossible. The point of bleeding was located by bronchoscopy in all cases and fibrinogen-thrombin instillation controlled hemoptysis immediately and throughout the follow-up period, which ranged 4 to 10 months. Morning expectoration of blood (< 10 ml) was observed in only 1 patient in the 3 days after treatment. The mean time taken for bronchoscopic exploration was 3 minutes (range, 2-7). In all cases fiberoptic bronchoscopy was performed without complications that might have required the procedure to be suspended. We conclude that the local use of fibrinogen-thrombin or fibrin glue instilled through the fiberoptic bronchoscope to the point of bleeding is a simple, fast and cheap way to control massive hemoptysis on a short and long-term basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Scintigraphy, angiography and computed tomography in unilateral hyperlucent lung due to obliterative bronchiolitis.

This study examines the value of different imaging methods in assessing the anatomic structures of unilateral hyperlucent lung due to obliterative bronchiolitis. We studied 9 patients, 5 males and 4 females, suffering from UHL (mean age 49 years). Ventilation-perfusion scan (VPS) and computed tomography (CT) of the chest were performed in all, and conventional angiography or digital substraction angiography (DSA) in 7 patients. The VPS showed the characteristic pattern of a matched ventilation-perfusion defect and considerable air trapping during the washout phase. Conventional angiography and DSA displayed a smaller pulmonary artery on the affected side, with a poor peripheral vasculature. CT displayed a loss of lung volume in all cases, with diminished mean attenuation values, a markedly diminished vasculature and integrity of the main airways. In contrast to other imaging modalities, CT imaged bronchiectasis, which was the cause of the patients' clinical symptoms of bronchorrhea and hemoptysis. We conclude that CT of the chest is the most valuable imaging method for evaluating unilateral hyperlucent lung, particularly in symptomatic patients.

Adult

Continuous c-fos expression precedes programmed cell death in vivo.

The development of a multicellular organism involves a delicate balance among the processes of proliferation, differentiation and death. Naturally occurring cell death aids tissue remodelling, eliminates supernumerary cell populations and provides structural elements such as hair and skin. In the nervous system, selective cell death contributes to the formation and organization of the spinal cord and sympathetic ganglia, retina and corpus callosum. But cell death also occurs in several neuropathological conditions, such as amyelotrophic lateral sclerosis and Alzheimer's disease. Therefore an elucidation of the mechanisms responsible for cell death is critical for an appreciation of both normal development and neuropathological disorders. Using a fos-lacZ transgenic mouse, we provide evidence showing that the continuous expression of Fos, beginning hours or days before the morphological demise of the cell, appears to be a hallmark of terminal differentiation and a harbinger of death.

3T3 Cells

Proto-oncogene c-fos induction in thiamine-deficient encephalopathy. Protective effects of nicardipine on pyrithiamine-induced lesions.

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as ataxia and convulsions. Induction of proto-oncogene c-fos expression, often related to seizure activity, has been detected in the brains of thiamine-deficient rats by means of Northern blot analysis and in situ hybridization. Region-selective increases of lactate observed following thiamine deficiency development are largely coincident with histologically vulnerable regions. When thiamine-deficient rats were treated with the calcium channel blocker, nicardipine, lesions associated with thiamine deficiency did not appear and there was no induction of c-fos mRNA expression. This suggests a neurocytoprotective role of nicardipine to neuronal cell damage in thiamine-deficient encephalopathy.

Animals

Nuclear calmodulin-binding proteins in rat neurons.

By using a 125I-calmodulin overlay assay, three major high-affinity calmodulin-binding proteins, showing apparent molecular masses of 135, 60, and 50 kDa, have been detected in purified nuclear fractions isolated from rat neurons. It has been shown that after extraction of the nuclei with nucleases and high salt, all these proteins remain strongly associated with the nuclear matrix. The 60- and 50-kDa proteins have been previously identified as subunits of the calmodulin-dependent protein kinase II. We report here the immunoblot identification of the 135-kDa calmodulin-binding protein as myosin light chain kinase. We also show that the calmodulin-dependent protein phosphatase calcineurin is present in the neuronal nuclei and associated with the nuclear matrix. The nuclear localization of both calcineurin and myosin light chain kinase has been confirmed by immunocytochemical studies.

Animals