Platypnea-orthodeoxia due to aortic elongation.
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Aged↗
Biomedical subjects
E Caballero
Publications and source records attributed to E Caballero.
Effect of P64k presensitization on its efficacy as an immunological carrier in mice.
Recently, we have successfully employed the meningococcal P64k protein as a carrier for weak immunogens. Here, we study if presensitization with it can affect the murine antibody response against the hapten chemically coupled to P64k. We found that priming with 10 microg of P64k did not induce epitope-specific suppression against two out of three synthetic peptides, from viral proteins, conjugated to this carrier. Depending on the anti-carrier antibody titers elicited in the presensitized mice, we observed or not a suppressed immune response against the third peptide. Presensitization with 100 microg of P64k resulted in epitope-specific suppression when lower doses of conjugate were administered. In summary, as described for other protein carriers, P64k could induce epitope-specific suppression in mice, but it depends on the hapten and the extent of carrier-specific immunity. Furthermore, this suppression can be overcome by increasing the amount of conjugate administered per dose in the presensitized animals.
Amino Acid Sequence↗
Synthesis of imidazo[4,5-d]oxazolo[3,4-a]pyridines. New heterocyclic analogues of lignans.
The preparation of new analogues of lignans carrying an imidazole ring has been achieved. Starting from L-histidinol, cis and trans stereoisomers have been obtained. The synthesized products lack the cytotoxicity displayed by related podophyllotoxins and azatoxin.
Animals↗
Trypanosoma cruzi: inhibition of parasite growth and respiration by oxazolo(thiazolo)pyridine derivatives and its relationship to redox potential and lipophilicity.
Chagas' disease constitutes a therapeutic challenge because presently available drugs have wide toxicity to the host and are generally ineffective in the chronic stages of the disease. A series of oxazolo(thiazolo)pyridene derivatives were studied on Trypanosoma cruzi epimastigote growth and oxygen consumption and their electrochemical (redox) potentials and lipophilicity. The derivatives produced different degrees of parasite growth and respiration inhibition on CL Brener, LQ, and Tulahuen strains of T. cruzi epimastigotes. Respiratory chain inhibition appears to be a determinant of the trypanosomicidal activity of these compounds, since a significant correlation between respiration and culture growth inhibition was found. A similar correlation was found, within the different structural subfamilies, between toxic effects and the ability of the compounds to be oxidized in aqueous media. The inhibition of respiration and of parasite growth in culture increases with the lipophilicity of the substituents on the oxazolopyridine nucleus. No difference in the action of these derivatives was found among the different parasite strains. It is concluded that these compounds may have a potential usefulness in the treatment of Chagas' disease.
Animals↗
[Cor triatriatum associated with Wolff-Parkinson-White syndrome].
Several anatomic anomalies have been associated with the Wolff-Parkinson-White syndrome. However, its association with cor triatriatum has never been previously established. We present a case report on a 34-year-old woman patient with paroxysmic palpitations and data of ventricular preexcitation seen on electrocardiogram. The presence of non-obstructive cor triatriatum was observed during echocardiographic valoration prior to radiofrequency catheter ablation.
Adult↗
Safety and preliminary immunogenicity of the recombinant outer membrane protein P64k of Neisseria meningitidis in human volunteers.
P64k is a meningococcal protein from Neisseria meningitidis that has been obtained by recombinant DNA technology. Recombinant P64k has been extensively characterized by physicochemical and immunological methods. Lately this protein has been found to act as a versatile immunological carrier for weak antigens in mice. In the present work, a Phase I clinical trial was carried out in healthy volunteers who received three inoculations of either placebo or recombinant P64k (20 or 50 microg). No severe adverse events occurred during the trial. Only mild adverse events in ten volunteers were observed. At 1 month after the third dose, 15 out of 18 volunteers (83.3%) who received the recombinant antigen had a P64k-specific antibody titre > or =1:100, as detected by ELISA. A fourth dose, given 9 months after the third one, elicited a potent booster immune response in P64k vaccinees. Accordingly, these P64k formulations were considered safe and immunogenic in healthy human volunteers.
Adult↗
Anti-Pseudomonas aeruginosa antibody detection in patients with bronchiectasis without cystic fibrosis.
BACKGROUND: Pseudomonas aeruginosa is a frequent cause of infection in patients with bronchiectasis. Differentiation between non-infected patients and those with different degrees of P aeruginosa infection could influence the management and prognosis of these patients. The diagnostic usefulness of serum IgG antibodies against P aeruginosa outer membrane proteins was determined in patients with bronchiectasis without cystic fibrosis. METHODS: Fifty six patients were classified according to sputum culture into three groups: group A (n=18) with no P aeruginosa in any sample; group B (n=18) with P aeruginosa alternating with other microorganisms; and group C (n=20) with P aeruginosa in all sputum samples. Each patient had at least three sputum cultures in the 6 months prior to serum collection. Detection of antibodies was performed by Western blot and their presence against 20 protein bands (10-121 kd) was assessed. RESULTS: Antibodies to more than four bands in total or to five individual bands (36, 26, 22, 20 or 18 kd) differentiated group B from group A, while antibodies to a total of more than eight bands or to 10 individual bands (104, 69, 63, 56, 50, 44, 30, 25, 22, 13 kd) differentiated group C from group B. When discordant results between the total number of bands and the frequency of P aeruginosa isolation were obtained, the follow up of patients suggested that the former, in most cases, predicted chronic P aeruginosa colonisation. CONCLUSION: In patients with bronchiectasis the degree of P aeruginosa infection can be determined by the number and type of outer membrane protein bands indicating which serum antibodies are present.
Aged↗
[Spastic paraparesias by HTLV-1: early identification of a new case. Review of the Spanish casuistics].
This is a study of the early identification of a new case of tropical spastic paraparesis/HLTV-1-associated myelopathy in a Spanish patient not previously reported on. The patient is 48 years of age, and he has been living in Sierra Leone for the past seventeen years, where he has worked as a surgeon. On first examination, he had been suffering from symptoms of a spastic paraparesis for the previous five months. This diagnosis was confirmed using serological tests (EIA and Western-blot) on the blood and cerebrospinal fluid (CSF). We have studied the cases outlined in medical literature, paying special attention to the time elapsed between the onset of symptoms and the date on which the diagnosis was made.
Humans↗
Design, synthesis and cytotoxic activities of naphthyl analogues of combretastatin A-4.
The 3,4,5-trimethoxyphenyl and 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 are deemed optimal for its activity as antimitotic agent. The replacement of either one by a naphthalene ring results in compounds with a potency comparable to that of the parent compound. These results show that the naphthalene ring is a good surrogate for the 3,4,5-trimethoxyphenyl or the 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 and that neither of them is essential for the antitumor activity.
Antineoplastic Agents↗
Open analogues of arcyriaflavin A. Synthesis through Diels-Alder reaction between maleimides and 1-aryl-3-tert-butyldimethylsiloxy-1, 3-butadienes.
The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.
Antineoplastic Agents↗
Antihypertensive activity of substituted 2,3,8,8a-tetrahydro-7H-oxazolo[3,2-a]pyridinedicarboxylate enantiomers.
The synthesis and antihypertensive activity of racemates and enantiomers of substituted 2,3,8,8a-tetrahydro-7H-oxazolo[3,2-a]pyridinedicarboxylates have been reported.
Animals↗
Transcatheter occlusion of complex atrial septal defects.
Percutaneous device occlusion of secundum atrial septal defects (ASDs) is becoming an accepted alternative to surgical closure. This method allows us to evaluate patients with complex conditions for treatment. From a total of 70 patients with ASD evaluated for percutaneous closure, we selected for analysis 28 who had complex conditions. The mean age was 36+/-23 yr (range, 4-72). Six had heart failure, and of these six, three had atrial fibrillation. At cardiac catheterization, the pulmonary pressure was 47+/-24 mm Hg, and the QP/QS was 1.7+/-0.4; two patients had bidirectional shunt and systemic pulmonary pressure. Two patients received a buttoned device and 26 an Amplatzer septal occluder. The groups of patients with complex conditions were separated into the following groups. Group I (n = 4) underwent combined treatment of associated anomalies. Two patients had pulmonary stenosis, one had mitral stenosis, and one had an aortic root-left atrium fistula. They were treated in or during with the same procedure by combined transcatheter techniques (balloon valvuloplasty and fistula occlusion) before ASD occlusion. Group II (n = 9) had multiple defects (cribiform or two separate holes). They were treated with a single device in five instances and with two separate devices in four cases. Group III (n = 14) had large (32+/-3 mm) single defects. Nine of them underwent successful implantation using a device 33+/-3 mm in diameter; in the remaining five patients the device was removed because of instability. Group IV (n = 3) had residual defects after previous partial device occlusion. All three defects were successfully occluded with a second device. No movement or interference with the first device was observed. Group V (n = 6) had severe pulmonary hypertension (86+/-16 mm Hg). Immediately after ASD occlusion we observed significant relief in these patients (67+/-14 mm Hg; P<0.01). There were no major complications; all 23 patients with successful implants were discharged without symptoms 2-7 days later; one patient with atrial fibrillation recovered sinus rhythm. The follow-up (8+/-5 mo) Doppler echo study showed complete ASD occlusion in 22 patients and a peak pulmonary pressure of 30+/-14 mm Hg. We conclude that transcatheter occlusion of ASDs is an effective and safe treatment for patients with complex anatomic or physiopathologic conditions, as evaluated by short-term follow-up.
Adolescent↗
Effects of 3-chloro-phenyl-1,4-dihydropyridine derivatives on Trypanosome cruzi epimastigotes.
A series of 3-chloro-phenyl-1,4-dihydropyridine derivatives produced different degrees of inhibition of parasite growth and respiration on clone Brener, LQ and Tulahuen strains of Trypanosome cruzi epimastigotes. Respiratory chain inhibition appears to be a posible determinant of the trypanosomicidal activity of this compounds. No difference in the action of these derivatives was found among the different parasite strains. For comparative purposes, the inhibitory effects of felodipine and nicardipine are also reported. A good correlation between toxic effects and the easiness of oxidation of the dihydripyridine ring was found. The presence of a fused ring on the dihydropyridine moiety significantly diminished the inhibitory effects.
Animals↗
B-cell epitope mapping of the Neisseria meningitidis P64k protein using overlapping peptides.
A common meningococcal antigen designated P64k has been identified, cloned and expressed in Escherichia coli. The recombinant antigen is highly immunogenic in several animal species and its immunogenicity in healthy human volunteers is under investigation. Recently, P64k has been used as an immunological carrier for weak immunogens. To characterize the B-cell epitopes on P64k, recognized by immune sera obtained from mice, rabbits and monkeys, multiple overlapping peptides were synthesized and screened for antibody binding. Peptides covering the complete sequence of the P64k protein, 59 in all, of 20 amino acids each (overlapped by 10 residues), were synthesized. A number of continuous epitopes were detected with all sera, when immune and pre-immune bleeds were compared. For mouse and monkey sera, a few major antigenic peptides were identified, while the recognition of the rabbit serum was much more heterogeneous. Despite variation in the exact location of continuous epitopes defined by different anti-P64k sera, we found an immunogenic core region within the molecule, composed of amino acids Asp(524)-Gly(533). Consistently, in this protein segment there was an amino acid stretch located in a beta-hairpin loop, which is exposed to the solvent in the previously determined three-dimensional structure of the protein. This region is protruding and accessible to a sphere with a radius of 9 A.
Amino Acid Sequence↗
P64k meningococcal protein as immunological carrier for weak immunogens.
Previously, the P64k meningococcal protein, an antigen of 64 kDa expressed in Escherichia coli, has been extensively characterized. We have successfully conjugated several synthetic peptides and meningococcal group C polysaccharide to P64k. In three out of four model peptides, the murine humoral immune response against the homologous peptide, evaluated after three doses of conjugate, was higher in the animals immunized with the coupled peptide than in those that received free peptide. The fourth and largest was immunogenic by itself. Similarly, the antigroup C polysaccharide levels reached by conjugated polysaccharide were significantly higher than those produced against unconjugated polysaccharide. As a carrier for one of the peptides, P64k was compared with bovine serum albumin (BSA) and tetanus toxoid (TT), being able to induce slightly higher or similar antipeptide antibody levels than these well-establish protein carriers. Our results suggest that recombinant P64k protein could be a readily available immunological carrier, as efficient as other commonly used large carrier molecules.
Amino Acid Sequence↗
Prevalence of HTLV infection in pregnant women in Spain.
OBJECTIVE: To estimate the prevalence of HTLV infection among pregnant women in Spain. METHODS: A commercial ELISA incorporating HTLV-I and HTLV-II antigens was used for HTLV antibody screening. Repeatedly reactive samples were further examined by western blot. Moreover, confirmation with PCR was performed when cells were available. RESULTS: 20,366 pregnant women in 12 different Spanish cities were tested in a 3 year period (July 1996 to August 1999). 32 samples were repeatedly reactive by ELISA, and 10 of them were confirmed as positive by western blot (eight for HTLV-II and two for HTLV-I). In addition, three of 13 women who had an indeterminate western blot pattern yielded positive results for HTLV-II by PCR. All 11 HTLV-II infected women had been born in Spain, and all but one were former drug users. Seven of them were coinfected with HIV-1. One HTLV-I infected woman was from Peru, where HTLV is endemic and where she most probably was infected during sexual intercourse. CONCLUSION: The overall prevalence of HTLV infection among pregnant women in Spain is 0.064% (13/20,366), and HTLV-II instead of HTLV-I is the most commonly found variant. A strong relation was found among HTLV-II infection and specific epidemiological features, such as Spanish nationality and injecting drug use. Although HTLV-II can be vertically transmitted, mainly through breast feeding, both the low prevalence of infection and its lack of pathogenicity would not support the introduction of HTLV antenatal screening in Spain.
Blotting, Western↗
Combined percutaneous atrial septal defect occlusion and pulmonary balloon valvuloplasty in adult patients.
Severe pulmonary stenosis in association with a large atrial septal defect is uncommon. When these 2 conditions are present, significant left-to-right shunt is often prevented by the outflow obstruction, which protects the pulmonary bed until adulthood. This report shows our initial experience of percutaneous treatment of both congenital malformations, either staged or combined in the same procedure, in 2 adult patients whose treatments yielded effective atrial septal defect occlusion and right ventricular pressure relief that persisted at mid-term follow-up. Although these opposite procedures (opening and closing) have been applied as isolated methods of treatment, this preliminary experience appears to demonstrate the feasibility and effectiveness of a combined percutaneous treatment.
Adult↗
Leishmanicidal activity of combretastatin analogues and heteroanalogues.
We have investigated the in vitro leishmanicidal activity of representative members from series II-V of combretastatin analogues and heteroanalogues. Most of them exhibited different degrees of activity against various strains of Leishmania spp. The diaryl(heteroaryl)ethane system or the more complex fused heterocyclic stilbenoids, constitute useful skeletal bases to support some kind of antiparasitic activity. Particularly, the incorporation of 2-furyl substituents led to potent antileishmanial compounds, which have been selected for in vivo testing on murine models.
Animals↗