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F Guzman

Publications and source records attributed to F Guzman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Identification of the Leishmania infantum P0 ribosomal protein epitope in canine visceral leishmaniasis.

In the present work we show that a high percentage of the sera from dogs naturally affected with viscero-cutaneous leishmaniasis contain antibodies reacting with the Leishmania infantum P0 ribosomal protein. In order to map the antigenic determinants of the LiP0 protein during Leishmania-infection, the complete amino acid sequence of the protein was synthesized as overlapping 20-mer peptides. We have identified the sequence AAKEEPEESDEDDFGMG, located adjacent to the C-terminal end of the protein, as the major antigenic determinant. The anti-LiP0 antibodies present in the sera of the infected dogs do not cross-react with a relatively similar antigenic determinant of the LiP2 acidic proteins as an indication that the Leishmania P0 protein is an independent immunogenically functional antigen in the canine form of the infection.

Amino Acid Sequence↗
PubMed1995

Mapping of the linear antigenic determinants from the Leishmania infantum histone H2A recognized by sera from dogs with leishmaniasis.

Antibodies reacting against the H2A histone protein were frequently observed in the sera from dogs naturally infected with the protozoan parasite Leishmania infantum. Using synthetic peptides covering the complete sequence of the protein we have identified the amino terminal region, comprising from amino acids 1 to 20, and the carboxyl terminal region, comprising from amino acids 106 to 132, as conforming the antigenic determinants of the protein. Those regions, exposed in the nucleosome surface, are highly divergent in sequence relative to the mammalian H2A histones. The anti-H2A histone antibodies present in the sera of these dogs specifically recognize the L. infantum H2A histone and they do not react with mammalian histones. The present data indicate that, in spite of the evolutionary conservation of the H2A histone protein among eukaryotic organisms, the humoral response against this protein during natural infection is specifically triggered by the parasite protein antigenic determinants.

Amino Acid Sequence↗
PubMed1995

During active viscerocutaneous leishmaniasis the anti-P2 humoral response is specifically triggered by the parasite P proteins.

In this work we show that in the sera from dogs naturally infected with the protozoan parasite Leishmania infantum there are antibodies that react specifically against the parasite acidic ribosomal proteins LiP2a and LiP2b, and that each one of the Leishmania P proteins elicits a specific humoral immune response. Using synthetic peptides, the antigenic epitope of these proteins has been mapped in a single region located adjacent to the C-terminal domain highly conserved among the eukaryotic P proteins. The anti-P antibodies elicited during the Leishmania infection do not recognize the conserved C-terminal domain of the parasite P proteins, in contrast with the findings reported in Chagas' disease or systemic lupus erythematosus. The antigenic epitopes of the LiP2a and LiP2b are almost identical in amino acid sequence. No reactivity against Trypanosoma cruzi and human P proteins was found in sera from L. infantum-infected dogs.

Amino Acid Sequence↗
PubMed1993

Mapping of antigenic determinants of the T. cruzi hsp70 in chagasic and healthy individuals.

In the present paper we describe the analysis of the immunological recognition by sera of healthy individuals and chagasic patients of the Trypanosoma cruzi heat shock 70 kDa protein. By a Falcon Assay Screening Test, using as antigen an ATP-agarose purified T. cruzi hsp70, it has been found that the sera of infected patients as well as of that of healthy individuals show reactivity against the hsp70 protein but that the reactivity of the sera of patients is in general significantly higher than that of healthy individuals. The analysis of the reactivity of the chagasic sera against a collection of peptides covering 92% of the protein has shown that more than 50% of the peptides gave a positive response but only against a few peptides did we observe high reactivity in a wide spectrum of sera. Only four peptides (numbers 9, 12, 14 and 47) were recognized by all sera tested with high reactivity values. The sera of healthy individuals also showed reactivity against a large percentage of peptides but with lower values. It was observed that particular peptides showing high reactivity against the sera of healthy donors also show high reactivity against patients' sera. However, the general pattern of reactivity against the peptides is different in chagasic and healthy sera. The immunodominant peptides map in the highly conserved as well as in the less conserved part of the hsp70 molecule. The 1/3 C-terminal, being the least conserved part of the molecule, seems to be the least immunogenic. Mapping of the epitopes led to the identification of particular immunogenic motifs within individual peptides.

Amino Acid Sequence↗
PubMed1992

The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity.

This paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine SPf66 directed against the asexual blood stages of Plasmodium falciparum. Clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. The vaccines were grouped as high, intermediate or low responders according to their antibody titres directed against the SPf66 molecule. Two of the 185 (1.08%) SPf66-vaccinated and nine of the 214 (4.20%) placebo-vaccinated volunteers developed P. falciparum malaria. The efficacy of the vaccine was calculated as 82.3% against P. falciparum and 60.6% against Plasmodium vivax.

Amino Acid Sequence↗
PubMed1992

In human malaria protective antibodies are directed mainly against the Lys-Glu ion pair within the Lys-Glu-Lys motif of the synthetic vaccine SPf 66.

The KEK (Lysine-Glutamic acid-Lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. This motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine SPf 66, currently undergoing extensive human trials. Analysis of the antibody titres against the subunit peptides that comprise this vaccine has shown that protection is associated with high titres to the KEK-containing peptide. In this paper we examine the fine recognition of this motif by polyclonal sera from protected vaccinated individuals, demonstrating the critical role played by the interacting ion pair formed between the amino terminal lysine (K) and glutamic acid (E), which act as contact residues for an important proportion of the antibody population directed against this vaccine. This ion pair in the KEK motif constitutes perhaps one of the most important malaria epitopes involved in protection, and could explain the mechanism through which protective immunity is acquired.

Amino Acid Sequence↗
PubMed1990

Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum.

During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity. We determined the minimal infective dose of the P. falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P. falciparum strains. A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge. These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P. falciparum.

Amino Acid Sequence↗
PubMed1989

Surgery for ventricular tachyarrhythmias based on fragmentation mapping in sinus rhythm alone.

Intraoperative arrhythmia activation mapping underlies the impressive success of surgery for sustained uniform ventricular tachycardia. Unstable arrhythmias and those intraoperatively noninducible, however, are not amenable to activation mapping and strategies for dealing with them are poorly defined. We propose that fragmentation mapping in sinus rhythm can be used to direct surgery in such situation. In 21 (33%) of 64 patients operated upon at this unit, intra-operative arrhythmia mapping was impossible because of non-inducibility in 17 (27%) and unstable morphology in 4 (6%). Endocardial resection was performed in all areas showing 'fragmented' local electrograms (greater than 100 ms duration at 30-300 Hz filtering). Mean patient characteristics included: age 51 years; LV ejection fraction 32%; major arrhythmic episodes 16 (range 2-200); antiarrhythmic drug failures, 4. There were 5 (24%) early postoperative deaths (heart failure 3; sudden 1; metabolic 1) and 1 early arrhythmia recurrence. There were 3 late non-arrhythmic deaths and 1 further arrhythmia recurrence during follow-up of 23 +/- 19 months. Both patients with documented postoperative arrhythmic episodes were controlled on previously ineffective antiarrhythmic drug therapy. Fragmentation mapping in sinus rhythm successfully extends the surgical option to arrhythmias previously considered inoperable. The results compare favourably with those for arrhythmias in which surgery was directed by activation mapping.

Adolescent↗
PubMed1989

Post infarction ventricular septal defect. Review of 41 surgical cases.

Forty-one patients with ventricular septal rupture after myocardial infarction were operated over about a 4-year period. The "early" group included 17 patients operated upon within the first 24 hours and 13 of them died. A total of 29 patients were operated within the first week and 21 died. The other 12 were operated after the first week since the diagnosis was made and 11 (92%) survived. The most relevant risk factors were: cardiogenic shock, hypertension and diabetes. The initial management was based on digitalis, diuretics, inotropes (dopamine, dobutamine) and the intra-aortic balloon pump. There was no significant difference in mortality between those patients with associated procedures and those without them, except in those cases of coronary grafts with infartectomy, whose mortality was higher. Early surgical repair of ventricular septal rupture implies a very high mortality (72%), which is even worse when the operation is performed within the first 24 hours (76%).

Aged↗
PubMed1988

A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria.

We have previously shown that a mixture of three synthetic peptides (83.1, 55.1, 35.1), corresponding to fragments of the relative molecular mass 83,000 (83K), 55K and 35K Plasmodium falciparum merozoite-specific proteins, induces protection in Aotus triviroatus monkeys experimentally infected with P. falciparum. Here we describe two polymeric synthetic hybrid proteins based on these peptides that delay or suppress the development of parasitaemia in immunized human volunteers.

Adult↗
PubMed1988

Congenital left atrial wall aneurysm in a patient with neurofibromatosis.

A congenital intrapericardial aneurysmal dilatation of the left atrial wall was found in a 28 year old man who presented with atrial fibrillation after a syncopal event. The patient had cutaneous manifestations of neurofibromatosis. The diagnosis was made by cross sectional echocardiography and confirmed by angiocardiography. Surgical excision of the aneurysm resolved the symptoms.

Adult↗
PubMed1988

Beta-carbolines as antagonists of the discriminative stimulus effects of diazepam in rats.

Rats were trained to discriminate between saline and 1.0 mg/kg of diazepam in a two-choice procedure where responding was maintained under a fixed-ratio, 5-response schedule of stimulus shock termination. beta-Carboline-3-carboxylate-methyl ester (beta CCM), beta-carboline-3-carboxylate-ethyl ester (beta CCE) and beta-carboline-3-carboxylate-t-butyl ester (beta CCtB), compounds with alkylcarboxy substitutions on the 3-position of the beta-carboline ring structure, were effective antagonists of the discriminative effects of diazepam. The 3-hydroxymethyl-substituted compound (3HMC) was relatively ineffective in antagonizing the discriminative effects of diazepam. The order of potency in antagonizing the 1.0 mg/kg training dose of diazepam was beta CCtB greater than beta CCM greater than beta CCE much greater than 3 HMC. The greater potency of beta CCtB likely reflects its resistance to metabolism in vivo. beta CCE and beta CCtB produced dose-related, parallel shifts in the dose-response curve for the discriminative effects of diazepam, but the magnitude of the shifts was limited: the two highest doses of beta CCE and beta CCtB produced shifts that were not significantly different in magnitude. These latter results suggest that these beta-carbolines antagonize only a portion of the component(s) of action of diazepam in producing discriminative stimuli. In contrast, the 7-substituted beta-carbolines harmane, harmol and harmine were ineffective in antagonizing the discriminative effects of diazepam up to doses of the beta-carbolines which disrupted the ability of the animals to respond.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Candida endocarditis: report of four cases.

Four patients who developed left-sided endocarditis due to infection with Candida species are reported. Three of them had had previous prosthetic valve replacement, and the fourth one developed endocarditis on a normal valve following pancreaticoduodenectomy. The difficulties presented in diagnosis and management are discussed.

Adolescent↗
PubMed1985

Midazolam-ethanol interactions and reversal with a benzodiazepine antagonist.

The purpose of these experiments was to analyze the cerebrovascular and cerebral metabolic effects of midazolam, a short-acting water-soluble benzodiazepine, and to investigate its interaction with alcohol in rats. A benzodiazepine antagonist, 3-carbo-t-butoxy-beta-carboline (beta-CCT), was used to test the role of the benzodiazepine receptor in midazolam-alcohol effects. Experiments were carried out under 70% N2O, 30% O2 anesthesia. Rats were tested with intraperitoneal injections of 0.75-5 mg/g ethanol, intravenous infusions of 0.57, 5.75 mg/kg midazolam, and 1.15 mg/kg beta-CCT separately and in combination. Cortical cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO2) was determined from cortical CBF and arterial-sagittal sinus blood samples 20 min after ethanol treatment and/or after a 15-min drug infusion. Alcohol alone produced dose-related increases in plasma ethanol concentrations but no depression in CMRO2 except at the highest dose (5 mg/g). Midazolam infusions alone decreased cortical CBF and CMRO2 35-40%, while 2.5 mg/g alcohol (which did not depress CMRO2 alone) combined with midazolam produced a 70% depression of cortical CBF and metabolism. An infusion of beta-CCT given alone increased CMRO2 alone and reversed the depression in both cortical CBF and CMRO2 produced by midazolam plus alcohol. These results indicate that the ability of alcohol to potentiate benzodiazepine-induced sedation is not simply an additive effect but may be related to the facilitation by alcohol of benzodiazepine receptor binding. The fact that beta-CCT reversed midazolam-ethanol-induced depression suggests that the effect may be mediated through the benzodiazepine receptor.

Anesthesia, Intravenous↗
PubMed1984

beta-Carboline-3-carboxylate-t-butyl ester: a selective BZ1 benzodiazepine receptor antagonist.

The effectiveness of beta-carboline-3-carboxylate-t-butyl ester (beta CCtB) in antagonizing the anticonvulsant, ataxic and antipunishment effects of diazepam were evaluated. In mice, beta CCtB at doses of 3 and 10 mg/kg produced a dose-related antagonism of the anticonvulsant effects of diazepam against pentylenetetrazole (80 mg/kg). A dose of 30 mg/kg of beta CCtB did not produce a further shift in the diazepam dose-effect curve, apparently because beta CCtB failed to block the muscle-relaxant effects of diazepam. Further, beta CCtB (30 mg/kg) failed to antagonize the ataxic effects of diazepam in an inverted screen test. Rats responded under a multiple schedule where in one component every twentieth response (FR20) resulted in water presentation (unpunished component) and in another component every twentieth response (FR20) resulted in both shock and water presentation (punished component). Diazepam p.o. (0.1 to 10 mg/kg) first increased and then decreased rates in the punished component but only decreased rates in the unpunished component. beta CCtB had no effect on response rates when administered alone, but antagonized the rate-increasing effects of diazepam in the punished component. beta CCtB did not alter the rate-decreasing effects of diazepam in either component. Thus, beta CCtB selectively antagonized the effects of diazepam on punished behavior as well as the anticonvulsant effects of diazepam, but beta CCtB failed to antagonize the rate-decreasing and ataxic effects of diazepam. These results are consistent with the interpretation that beta CCtB is a selective BZ1 benzodiazepine receptor antagonist.

Animals↗
PubMed1984

Biomimetic approach to potential benzodiazepine receptor agonists and antagonists.

Several beta-carbolines, isoquinolines, imidazopyridines , and canthin -6-ones prepared in biomimetic fashion were tested for their ability to bind to the benzodiazepine receptor. Methyl isoquinoline-3-carboxylate, methyl 6,7- dimethoxyisoquinoline -3-carboxylate (3b) 1-phenyl-3- carbomethoxyimidazopyridine , (6B,) and canthin -6- one ( 13a ) bound with moderate affinities, while 2- carbomethoxycanthin -6- one ( 13b ) bound to benzodiazepine receptors with an affinity comparable to several pharmacologically active benzodiazepines. The potency of 13b suggests that the benzodiazepine receptor(s) can tolerate substitution at positions 1 and 9 of a beta-carboline without loss of activity if the substituents are trigonal and maintain a planar topography. Moreover, displacement of the carbonyl group by two atoms from the aromatic ring (C) of the beta-carboline skeleton caused a marked decrease in binding to the benzodiazepine receptor. This observation supports the hypothesis that maximum binding affinity of beta-carbolines is achieved when the carbonyl group at position 3 is attached directly to the aromatic pyridine ring.

Animals↗
PubMed1982

Beta-carbolines: synthesis and neurochemical and pharmacological actions on brain benzodiazepine receptors.

We have prepared a series of tetrahydro-beta-carbolines (TH beta C), beta-carbolines (beta-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic beta-C's were more potent than their corresponding TH beta C derivatives. When substituents possessing a carbonyl (CO2Me, COCH3, CHO) were introduced at the beta-C 3-position the in vitro potency was augmented. Alcohol substituents (CH2OH, CHOHCH3) demonstrated decreased in vitro potency. The importance of the carbonyl moiety was further demonstrated when beta-carboline-3-carboxylic acid was shown to bind tighter to benzodiazepine receptors at lower pH. A lower pH increases the concentration of the acid and decreases the concentration of the anion. 3-(Hydroxymethyl)-beta-carboline (24), 3-formyl-beta-carboline (25) and 3-acetyl-beta-carboline (27) were benzodiazepine antagonists in vivo. Methyl isoquinoline-3-carboxylate (31a) also had in vitro activity. The same structure-activity relationships seen in beta-C's were also observed for isoquinolines.

Animals↗