RESUMEN
La terminología hipomineralización incisivo-molar (HIM) fue descrita por primera vez en 2001 para explicar los defectos de desarrollo cualitativos demarcados del esmalte, que afectan a uno o más molares permanentes, con o sin participación de los incisivos per-manentes1. En los últimos años, las investigaciones han dado lugar a informes de lesiones comparables en segundos molares temporales hipomineralizados, sin embargo, se desconoce si la presencia de opacidades demarcadas en los caninos temporales también puede asociarse con el HIM1-3. Da Silva y cols., en 2017, son los únicos autores hasta el momento que relacionan hipomineralizaciones en segundos molares temporales (HSPM) y caninos temporales (HPC)3. La prevalencia de HSPM varía dependiendo de los países entre 2,9% a un 21,8% 3,7.Se puede esperar que las causas de los defectos de hipomineralización en los segundos molares temporales sean las mismas que en los dientes permanentes, si ocurren conco-mitantemente a la calcificación de su corona, la cual comienza alrededor de la decimooctava semana de gestación 4-7. Se presenta el caso de un paciente infantil, de 6 años, que acudió a consulta para revisión odontológica. Tras la exploración, se observó la presencia de anomalías del color y estructura en: todos los segundos molares y caninos temporales, así como en los primeros molares temporales superiores y primer molar temporal inferior izquierdo (Figuras 1-6). La posterior exploración radiográfica mostró hallazgos patológicos localizados en 54, 64, 65, 74, 75, 84, 85 (Figuras 7-9). El tratamiento supone un desafío ya que es frecuente que los dientes afectados presenten afectación pulpar, además de hipersensibilidad y descomposición post*eruptiva. Esta relación podría sugerir como factor predictivo de aparición de HIM, la presencia HSPM y HPC, así podrían implementarse las medidas de prevención y control con intervalos más frecuentes en estos pacientes
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Asunto(s)
Humanos , Masculino , Niño , Desmineralización Dental/diagnóstico por imagen , Desmineralización Dental/epidemiología , Decoloración de Dientes/etiología , Desmineralización Dental/prevención & control , Decoloración de Dientes/prevención & control , Radiografía PanorámicaRESUMEN
Droplet volume and temperature affect contact angle significantly. Phase change heat transfer processes of nanofluids - suspensions containing nanometre-sized particles - can only be modelled properly by understanding these effects. The approach proposed here considers the limiting contact angle of a droplet asymptotically approaching zero-volume as a thermophysical property to characterise nanofluids positioned on a certain substrate under a certain atmosphere. Graphene oxide, alumina, and gold nanoparticles are suspended in deionised water. Within the framework of a round robin test carried out by nine independent European institutes the contact angle of these suspensions on a stainless steel solid substrate is measured with high accuracy. No dependence of nanofluids contact angle of sessile droplets on the measurement device is found. However, the measurements reveal clear differences of the contact angle of nanofluids compared to the pure base fluid. Physically founded correlations of the contact angle in dependency of droplet temperature and volume are obtained from the data. Extrapolating these functions to zero droplet volume delivers the searched limiting contact angle depending only on the temperature. It is for the first time, that this specific parameter, is understood as a characteristic material property of nanofluid droplets placed on a certain substrate under a certain atmosphere. Together with the surface tension it provides the foundation of proper modelling phase change heat transfer processes of nanofluids.
RESUMEN
Los feocromocitomas y paragangliomas son tumores neuroendócrinos poco frecuentes y con alta morbimortalidad. Reconocer las distintas formas de presentación es el paso diagnóstico inicial. El estudio bioquímico permite determinar el exceso de catecolaminas y sus metabolitos. Sin embargo, las determinaciones disponibles ofrecen diferente precisión diagnóstica. La tomografía computada y la resonancia magnética permiten localizar estos tumores con una alta sensibilidad. Los estudios funcionales se reservan para sospecha de enfermedad metastásica y para tumores múltiples. Un tercio de los pacientes presenta una mutación genética germinal y varios genes están implicados en el desarrollo de estos tumores
Pheochromocytomas and paragangliomas are rare neuroendocrine tumours associated with high morbidity and mortality. Recognizing the clinical presentation is the first step for diagnosis. Biochemical studies may determine an excess of catecholamines and their metabolites. However, the available tests offer varying diagnosis precision. Computed tomography and magnetic resonance are highly sensitive for locating these tumours. Functional tests are reserved for when metastatic and multifocal disease are suspected. One third of the patients have a germline mutation and many genes are involved in the development of these tumours
Asunto(s)
Humanos , Paraganglioma/diagnóstico , Paraganglioma/epidemiología , Feocromocitoma/diagnóstico , Pruebas de Química Clínica/métodos , Feocromocitoma/epidemiología , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/epidemiología , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Diagnóstico Precoz , Metanefrina/análisis , Catecolaminas/metabolismo , Sensibilidad y EspecificidadRESUMEN
Pheochromocytomas and paragangliomas are rare neuroendocrine tumours associated with high morbidity and mortality. Recognizing the clinical presentation is the first step for diagnosis. Biochemical studies may determine an excess of catecholamines and their metabolites. However, the available tests offer varying diagnosis precision. Computed tomography and magnetic resonance are highly sensitive for locating these tumours. Functional tests are reserved for when metastatic and multifocal disease are suspected. One third of the patients have a germline mutation and many genes are involved in the development of these tumours.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/patología , Mutación de Línea Germinal , Humanos , Imagen por Resonancia Magnética/métodos , Paraganglioma/genética , Paraganglioma/patología , Feocromocitoma/genética , Feocromocitoma/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
A rapid and efficient enzymatic procedure for the preparation of an immobilized ß-galactosidase has been described. In a first step, soybean peroxidase was used to catalyze the polymerization of a strategically activated phenol (N-Succinimidyl 3-(4-hydroxyphenyl)propionate, known as Bolton-Hunter reagent). The phenolic support was directly employed for immobilizing ß-galactosidase from Bacillus circulans (ATCC 31382, ß-Gal-3), giving rise to a new biocatalyst subsequently applied in the synthesis of a ß-galatodisaccharide (Gal-ß(1-3)-GlcNAc and Gal-ß(1-3)-GalNAc). The reaction proceeded with high conversion rates and total regioselectivity. Reusability assays were performed with the same reaction conditions finding that the immobilized enzyme retains about 55% of its activity after eight batches. Finally and based on our results, the two-step enzymatic procedure presented here is a good and green alternative to the preparation of carbohydrates with biological activities.
Asunto(s)
Biocatálisis , Enzimas Inmovilizadas/metabolismo , Fenoles/química , Fenoles/síntesis química , Polimerizacion , beta-Galactosidasa/metabolismo , Técnicas de Química Sintética , Estabilidad de Enzimas , Enzimas Inmovilizadas/química , Glicosilación , Concentración de Iones de Hidrógeno , Temperatura , beta-Galactosidasa/químicaRESUMEN
Due to the growing demand of enantiomerically pure compounds, as well as the increasing strict safety, quality and environmentally requirements of industrial synthetic processes, the development of more sustainable, healthy and economically attractive strategies for the synthesis of chiral biologically active molecules is still an open challenge in the pharmaceutical industry. In this context, the biotransformations field has emerged as a real alternative to traditional synthetic routes, because of the exquisite chemo-, regio- and enantioselectivities commonly displayed by enzymes; thus, biocatalysis is becoming a widespread methodology for the synthesis of chiral compounds, not only at laboratory scale, but also at industrial scale. As hydrolases and oxido-reductases are the most employed enzymes, this review is focused on describing several industrial processes based on the use of these enzymes for obtaining chiral compounds useful for the pharmaceutical industry.
Asunto(s)
Industria Farmacéutica/métodos , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/síntesis química , Biotransformación , Hidrolasas/metabolismo , Oxidación-Reducción , EstereoisomerismoRESUMEN
Enzyme catalyzed reactions are commonly used at laboratory or industrial scale. Contrarily, the whole cell catalyzed reactions are restricted to special cases. The tremendous advances in the last years in Molecular Biology and more specifically in Metabolic Engineering and Directed Enzyme Evolution have opened the door to create tailor-made microorganisms or "designer bugs" for industrial purposes. Whole cell catalysts can be much more readily and inexpensively prepared than purified enzymes and the enzymes - inside the cells - are protected from the external environment and stabilized by the intracellular medium. Three situations have traditionally been considered convenient to select the use of whole cell catalyzed processes against the free enzyme catalyzed process: i) when the enzyme is intracellular; ii) when the enzyme needs a cofactor to carry out the catalytic act and iii) in the development of multienzymatic processes. Red-ox reactions represent the molecular basis for energy generation in the cell. These reactions are catalyzed by intracellular enzymes and are cofactor dependent as red-ox reactions need electron carriers as helpers in reduction reactions (gain of electrons) or oxidation (loss of electrons). In this review we present an overview of the state of the art of red-ox biotransformations catalyzed by whole cells - wild-type or genetically engineered microorganisms. Stereoselective reductions, hydroxylations of arenes and unfunctionalized alkanes, alkene monooxygenation, and Baeyer-Villiger reactions are among the processes described along the text, focusing in their chemo-, regio- and stereoselectivity.
Asunto(s)
Biocatálisis , Peroxidasas/metabolismo , Biotransformación , Hidroxilación , Oxidación-ReducciónRESUMEN
Circumsporozoite (CS) protein is a predominant surface antigen of malaria sporozoites, the infective form of the parasite, and has been used for making anti-malaria vaccines. For the first time we have examined the interaction of CS protein with various glycosaminoglycans in real time using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Heparin was the best binder among the glycosaminoglycans tested and bound to CS protein with nanomolar affinity. Using purified and structurally defined small heparin oligosaccharides, we identified a decasaccharide to be the minimum sized CS protein-binding sequence. In an indirect competition assay, this decasaccharide blocked the CS protein interaction with HepG2 cells with an ID(50) of less than 60 nM. The decasaccharide has a structure commonly found in hepatic heparan sulfate, and the same sequence has recently been shown to bind specifically to apolipoprotein E. Examination of porcine liver heparan sulfate in this indirect competition assay showed that it and heparin were the only glycosaminoglycans that could effectively block CS protein interaction with HepG2 cells in culture. These data support the hypothesis that the invasion of liver cells by the parasite shares a common mechanism with the hepatic uptake of lipoprotein remnants from the blood.
Asunto(s)
Glicosaminoglicanos/química , Heparina/química , Oligosacáridos/química , Proteínas Protozoarias/química , Animales , Conformación de Carbohidratos , Secuencia de Carbohidratos , Disacáridos/química , Glicosaminoglicanos/metabolismo , Heparina/metabolismo , Oligosacáridos/metabolismo , Plasmodium , Proteínas Protozoarias/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , PorcinosRESUMEN
Defective binding of apolipoprotein E (apoE) to heparan sulfate proteoglycans (HSPGs) is associated with increased risk of atherosclerosis due to inefficient clearance of lipoprotein remnants by the liver. The interaction of apoE with HSPGs has also been implicated in the pathogenesis of Alzheimer's disease and may play a role in neuronal repair. To identify which residues in the heparin-binding site of apoE and which structural elements of heparan sulfate interact, we used a variety of approaches, including glycosaminoglycan specificity assays, (13)C nuclear magnetic resonance, and heparin affinity chromatography. The formation of the high affinity complex required Arg-142, Lys-143, Arg-145, Lys-146, and Arg-147 from apoE and N- and 6-O-sulfo groups of the glucosamine units from the heparin fragment. As shown by molecular modeling, using a high affinity binding octasaccharide fragment of heparin, these findings are consistent with a binding mode in which five saccharide residues of fully sulfated heparan sulfate lie in a shallow groove of the alpha-helix that contains the HSPG-binding site (helix 4 of the four-helix bundle of the 22-kDa fragment). This groove is lined with residues Arg-136, Ser-139, His-140, Arg-142, Lys-143, Arg-145, Lys-146, and Arg-147. In the model, all of these residues make direct contact with either the 2-O-sulfo groups of the iduronic acid monosaccharides or the N- and 6-O-sulfo groups of the glucosamine sulfate monosaccharides. This model indicates that apoE has an HSPG-binding site highly complementary to heparan sulfate rich in N- and O-sulfo groups such as that found in the liver and the brain.
Asunto(s)
Apolipoproteínas E/metabolismo , Proteoglicanos de Heparán Sulfato/metabolismo , Animales , Apolipoproteínas E/química , Arginina/química , Sitios de Unión , Biotinilación , Encéfalo/metabolismo , Bovinos , Cromatografía de Afinidad , Relación Dosis-Respuesta a Droga , Glucosamina/química , Proteoglicanos de Heparán Sulfato/química , Heparina/química , Heparina/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Cinética , Hígado/metabolismo , Lisina/química , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Mutación , Polisacáridos/metabolismo , Unión Proteica , Serina/química , Estreptavidina/química , Resonancia por Plasmón de Superficie , Factores de TiempoRESUMEN
A structure-activity relationship study was carried out to facilitate development of inhibitors of dengue virus infectivity. Previous studies demonstrated that a highly charged heparan sulfate, a heparin-like glycosaminoglycan found on the cell surface, serves as a receptor for dengue virus by binding to its envelope protein. Interventions that disrupt this binding effectively inhibit infectivity. A competitive binding assay was developed to screen polyanionic compounds for activity in preventing binding of dengue virus envelope protein to immobilized heparin; compounds tested included drugs, excipients, and larger glycosaminoglycans and their semisynthetic derivatives. Results of this competitive binding assay were used to select agents for detailed evaluation of interactions by surface plasmon resonance spectroscopy, which afforded binding on-rates, off-rates, and dissociation constants. From these data, an understanding of the structural requirements for polyanion binding to dengue virus envelope protein has been established.
Asunto(s)
Anticoagulantes/química , Anticoagulantes/farmacología , Antivirales/síntesis química , Virus del Dengue/metabolismo , Glicosaminoglicanos/química , Glicosaminoglicanos/farmacología , Heparina/química , Heparina/farmacología , Proteínas del Envoltorio Viral/química , Antivirales/farmacología , Unión Competitiva/efectos de los fármacos , Secuencia de Carbohidratos , Cromatografía Líquida de Alta Presión , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Hialurónico/síntesis química , Ácido Hialurónico/química , Cinética , Datos de Secuencia Molecular , Peso Molecular , Oligosacáridos/síntesis química , Oligosacáridos/química , Unión Proteica , Relación Estructura-Actividad , Sulfatos/química , Resonancia por Plasmón de Superficie , Proteínas del Envoltorio Viral/antagonistas & inhibidores , Proteínas del Envoltorio Viral/biosíntesisRESUMEN
BACKGROUND: Annexin V, an abundant anticoagulant protein, has been proposed to exert its effects by self-assembling into highly ordered arrays on phospholipid membranes to form a protective anti-thrombotic shield at the cell surface. The protein exhibits very high-affinity calcium-dependent interactions with acidic phospholipid membranes, as well as specific binding to glycosaminoglycans (GAGs) such as heparin and heparan sulfate, a major component of cell surface proteoglycans. At present, there is no structural information to elucidate this interaction or the role it may play in annexin V function at the cell surface. RESULTS: We report the 1.9 A crystal structure of annexin V in complex with heparin-derived tetrasaccharides. This structure represents the first of a heparin oligosaccharide binding to a protein where calcium ions are essential for the interaction. Two distinct GAG binding sites are situated on opposite protein surfaces. Basic residues at each site were identified from the structure and site-directed mutants were prepared. The heparin binding properties of these mutants were measured by surface plasmon resonance. The results confirm the roles of these mutated residues in heparin binding, and the kinetic and thermodynamic data define the functionally distinct character of each distal binding surface. CONCLUSION: The annexin V molecule, as it self-assembles into an organized array on the membrane surface, can bind the heparan sulfate components of cell surface proteoglycans. A novel model is presented in which proteoglycan heparan sulfate could assist in the localization of annexin V to the cell surface membrane and/or stabilization of the entire molecular assembly to promote anticoagulation.
Asunto(s)
Anexina A5/química , Anexina A5/fisiología , Membrana Celular/metabolismo , Heparina/química , Oligosacáridos/química , Animales , Sitios de Unión , Biotinilación , Calcio/metabolismo , Membrana Celular/química , Cristalografía por Rayos X , Electrones , Cinética , Liposomas/química , Modelos Químicos , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Mutación , Fosfolípidos/metabolismo , Ratas , Proteínas Recombinantes/química , Estreptavidina/química , Resonancia por Plasmón de Superficie , Porcinos , Termodinámica , Factores de TiempoRESUMEN
Apolipoprotein E (apoE) is an important lipid-transport protein in human plasma and brain. It has three common isoforms (apoE2, apoE3, and apoE4). ApoE is a major genetic risk factor in heart disease and in neurodegenerative disease, including Alzheimer's disease. The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease. Here we report our studies of the interaction of the N-terminal domain of apoE4 (residues 1-191), which contains the major heparin-binding site, with an enzymatically prepared heparin oligosaccharide. Identified by its high affinity for the N-terminal domain of apoE4, this oligosaccharide was determined to be an octasaccharide of the structure DeltaUAp2S(1-->[4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S(1-->](3)4)-alpha-D-GlcNpS6S by nuclear magnetic resonance spectroscopy, capillary electrophoresis, and polyacrylamide gel electrophoresis. Kinetic analysis of the interaction between the N-terminal apoE4 fragment and immobilized heparin by surface plasmon resonance yielded a K(d) of 150 nM. A similar binding constant (K(d) = 140 nM) was observed for the interaction between immobilized N-terminal apoE4 and the octasaccharide. Isothermal titration calorimetry revealed a K(d) of 75 nM for the interaction of the N-terminal apoE fragment and the octasaccharide with a binding stoichiometry of approximately 1:1. Using previous studies and molecular modeling, we propose a binding site for this octasaccharide in a basic residue-rich region of helix 4 of the N-terminal fragment. From the X-ray crystal structure of the N-terminal apoE4, we predicted that binding of the octasaccharide at this site would result in a change in intrinsic fluorescence. This prediction was confirmed experimentally by an observed increase in fluorescence intensity with octasaccharide binding corresponding to a K(d) of approximately 1 microM.
Asunto(s)
Apolipoproteínas E/metabolismo , Heparina/metabolismo , Fragmentos de Péptidos/metabolismo , Animales , Apolipoproteína E4 , Apolipoproteínas E/química , Calorimetría , Secuencia de Carbohidratos , Cristalografía por Rayos X , Heparina/química , Cinética , Datos de Secuencia Molecular , Oligosacáridos/química , Oligosacáridos/metabolismo , Fragmentos de Péptidos/química , Espectrometría de Fluorescencia , Resonancia por Plasmón de Superficie , PorcinosRESUMEN
A heparan sulfate glycosaminoglycan chain, biotinylated at its reducing-end, was bound to a streptavidin-coated biochip. Surface plasmon resonance spectroscopy showed a low affinity interaction with antithrombin III (ATIII) when it was flowed over a surface containing heparan sulfate. ATIII bound tightly with high affinity when the same surface was enzymatically modified to using 3-O-sulfotransferase isoform 1 (3-OST-1) in the presence of 3'-phosphoadenosine 5'-phosphosulfate (PAPS). The 3-OST-1 enzyme is involved in heparan sulfate biosynthesis and introduces a critical 3-O-sulfo group into this glycosaminoglycan affording the appropriate pentasaccharide sequence capable of high affinity binding to ATIII. This experiment demonstrates the specific structural modification of a glycosaminoglycan bound to a biochip using a biosynthetic enzyme, suggesting a new approach to rapid screening glycosaminoglycan-protein interactions.
Asunto(s)
Antitrombina III/química , Heparitina Sulfato/química , Animales , Antitrombina III/metabolismo , Sitios de Unión , Heparitina Sulfato/metabolismo , Ratones , Oligosacáridos , Unión ProteicaRESUMEN
Regional effects of the chest wall on airway pressure transmission were studied during high frequency ventilation in anesthetized rabbits. We measured airway pressure (Paw), esophageal pressure (Pes), and costal pleural pressure (Ppl) by a rib capsule and flow and volume with a calibrated pneumotachograph. Using a closed circuit, pressures and flow were measured at varying frequencies (2-80 Hz) and tidal volumes (2-20 ml). Mean Pes and Ppl increased with flow amplitude above 100-250 ml/s, whereas mean Paw decreased, consistent with air trapping. Paw, Pes, and Ppl amplitudes increased monotonically with flow amplitude except above 400-500 ml/s, where the Ppl amplitude decreased suddenly. The latter occurring simultaneously with a sudden fall in mean Paw indicated airway flow limitation in costal regions. Flow instabilities during flow limitation were consistent with the large increase in the phase difference between Paw and Ppl and its variability, with frequency. By contrast, the phase difference between Paw and Pes and its variability were relatively small. These differences in Pes from Ppl responses might be caused by a difference in the impedance of the airway-mediastinum pathway or a direct transmission of tracheal pressure oscillations to the esophagus. The former suggests that constraints offered by the mediastinum and rib cage resulted in nonuniform ventilation during high frequency ventilation.
Asunto(s)
Ventilación de Alta Frecuencia , Pleura/fisiología , Mecánica Respiratoria/fisiología , Volumen de Ventilación Pulmonar , Animales , Presión , Ventilación Pulmonar/fisiología , ConejosRESUMEN
Semipurified lipase of Candida rugosa (CRSL) was subjected to chemical modification, and the activities of the modified lipase, in hydrolysis and esterification reactions, were examined. The esterification reactions were carried out in the absence and presence of isooctane. When the enzyme was modified with polyethylene glycol (PEG), two methodologies were studied. The activation of PEG with p-NO(2)-phenylchloroformate gives better biocatalysts than those obtained with cyanuric chloride-PEG. The chemical modification with PEG increases the stability of pure lipases in isooctane at 50 degrees C (extreme conditions). The chemically modified enzymes are useful for biotransformations in organic solvents. In addition the nitration of tyrosines with tetranitromethane was also studied. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 252-260, 1997.
RESUMEN
A semipurified C. rugosa lipase (LS) has been prepared from commercial lipase (LC) using an economical procedure. The presence of sugars and glycopeptides has been detected in LS and LC. Pure lipase only has covalently bonded sugars. The hydrolysis of olive oil catalyzed by LS and commercial lipase (LC) is sensitive to the presence of cations Na(I), Mg(II), Ca(II), and Ba(II) and to the nature of buffer. Highest enzyme activity is obtained with 0.1M Tris/HCl buffers and the combination of NaCl 0.11M and CaCl2 0.11M. Fluorescence spectroscopy analysis of LC, LS, and both pure isoenzymes lipases A and B, was used to analyze the interaction of the lipase with these effectors. Inorganic cations Na or Ca do not interact with pure enzyme LA but do interact with LC and LS and do so slightly with LB. The organic cations (morfolinium or tris) interact with pure lipases. We postulate that the increase in the lipase activity produced by Na(I) or Ca(II) is related with interfacial phenomena, but the increase might be more specific in the hydrolysis of olive oil in the presence of Tris-HCl or morfoline-HCl buffer, owing to enzyme-buffer interaction.
Asunto(s)
Candida/enzimología , Lipasa/química , Tampones (Química) , Cationes , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
In 10 anesthetized adult rabbits, we studied the effect of spontaneous breathing and positive pressure ventilation on pleural pressure on the costal lung surface (Ppl) and in the zone of apposition of the rib cage to the diaphragm (Papp). Ppl and Papp were measured by rib capsules installed in the 5th or 6th rib and 11th or 12th rib, respectively. Esophageal (Pes) and gastric (Pga) pressures were measured with air-filled balloons. At end expiration (functional residual capacity), Ppl was subatmospheric (-2.5 +/- 1.4 cm H2O), decreased during spontaneous inspiration, and was in phase with Pes. In contrast, Papp was above atmospheric pressure (2.1 +/- 1.8 cm H2O), increased during inspiration, and was in phase with Pga. Papp lagged Ppl by 180 degrees during spontaneous inspiration but was in phase with Ppl during mechanical ventilation. Changes in Ppl (delta Ppl) during inspiration were greater in magnitude than either delta Papp or delta Pga. Changes in transdiaphragmatic pressure in the zone of apposition (delta Pga-delta Papp) were near zero (-0.4 +/- 0.3 cm H2O), much smaller in magnitude than those (delta Pga-delta Ppl) associated with the lung (3.0 +/- 1.5 cm H2O). These results are consistent with the concept that during breathing, abdominal pressure is transmitted to the zone of apposition of the rib cage to the abdomen. During spontaneous breathing at rest, the pleural space in the zone of apposition is mechanically independent of the pleural space associated with the lung.