RESUMEN
BACKGROUND AND PURPOSE: In parathyroid CT, a noncontrast phase aids discrimination of parathyroid lesions (not iodine-containing) from thyroid tissue (iodine-containing). When thyroid iodine is pathologically diminished, this differentiation is difficult with standard CT. Because the attenuation of an element is maximal near its K-edge (iodine = 33.2 keV), we hypothesized that dual-energy CT 40-keV virtual monoenergetic images will accentuate thyroid iodine relative to standard images, improving the differentiation of thyroid from parathyroid lesions. Our purpose was to test this hypothesis through quantitative assessment of Hounsfield unit attenuation and contrast-to-noise on dual-energy CT standard (70-keV) and 40-keV noncontrast images. MATERIALS AND METHODS: For this retrospective study including 20 dual-energy parathyroid CTs, we used an ROI-based analysis to assess the attenuation of thyroid tissue, parathyroid lesions, and sternocleidomastoid muscle as well as corresponding contrast-to-noise on standard and 40- keV noncontrast images. Wilcoxon signed rank tests were performed to compare differences between 70 and 40 keV. RESULTS: Absolute and percentage increases in attenuation at 40 keV were significantly greater for thyroid gland than for parathyroid lesions and sternocleidomastoid muscle (P < .001 for all). Significant increases in the contrast-to-noise of thyroid relative to parathyroid lesions (median increase, 0.8; P < .001) and relative to sternocleidomastoid muscle (median increase, 1.3; P < .001) were observed at 40 keV relative to 70 keV. CONCLUSIONS: Forty-kiloelectron volt virtual monoenergetic images facilitate discrimination of parathyroid lesions from thyroid tissue by significantly increasing thyroid attenuation and associated contrast-to-noise. These findings are particularly relevant for parathyroid lesions that exhibit isoattenuation to the thyroid on parathyroid CT arterial and venous phases and could, therefore, be missed without the noncontrast phase.
Asunto(s)
Imagen Radiográfica por Emisión de Doble Fotón , Glándula Tiroides , Medios de Contraste , Tomografía Computarizada Cuatridimensional , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos , Relación Señal-Ruido , Glándula Tiroides/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Transient loss of consciousness is commonly evaluated in the emergency department. Although typically caused by epileptic seizure, syncope, or psychogenic nonepileptic seizure, the underlying etiology is frequently misdiagnosed. Lateral tongue bites are reportedly a specific clinical finding of seizure. We have observed tongue signal abnormality suggesting bite injury on brain MR imaging after seizures. We hypothesized an association between tongue signal abnormality and seizure diagnosis among patients in the emergency department imaged for transient loss of consciousness. Our purposes were to determine the prevalence of tongue signal abnormality among this population and the predictive performance for seizure diagnosis. MATERIALS AND METHODS: For this retrospective study including 82 brain MR imaging examinations, 2 readers independently assessed tongue signal abnormality on T2-weighted and T2-weighted FLAIR images. Discrepancies were resolved by consensus, and interrater reliability (Cohen κ) was calculated. The final diagnosis was recorded. Proportions were compared using the Fisher exact test. RESULTS: Tongue signal abnormality was present on 19/82 (23%) MR imaging examinations. Interrater reliability was "substantial" (κ = 0.77). Seizure was diagnosed among 18/19 (95%) patients with tongue signal abnormality and 29/63 (46%) patients without it (P < .001). In our cohort, tongue signal abnormality conveyed 97% specificity, 95% positive predictive value, and 63% accuracy for seizure diagnosis. CONCLUSIONS: Tongue signal abnormality was observed in 23% of the study cohort and conveyed 97% specificity and 95% positive predictive value for seizure diagnosis. By assessing and reporting tongue signal abnormality, radiologists may facilitate a timely and accurate diagnosis of seizure among patients imaged for transient loss of consciousness.
Asunto(s)
Imagen por Resonancia Magnética , Convulsiones , Encéfalo/diagnóstico por imagen , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Síncope , Lengua/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Among patients undergoing serial neck CTs, we have observed variability in the appearance of the pharyngolaryngeal venous plexus, which comprises the postcricoid and posterior pharyngeal venous plexuses. We hypothesize changes in plexus appearance from therapeutic neck irradiation. The purposes of this study are to describe the CT appearance of the pharyngolaryngeal venous plexus among 2 groups undergoing serial neck CTs-patients with radiation therapy-treated laryngeal cancer and patients with medically treated lymphoma-and to assess for changes in plexus appearance attributable to radiation therapy. MATERIALS AND METHODS: For this retrospective study of 98 patients (49 in each group), 448 contrast-enhanced neck CTs (222 laryngeal cancer; 226 lymphoma) were assessed. When visible, the plexus anteroposterior diameter was measured, and morphology was categorized. RESULTS: At least 1 plexus component was identified in 36/49 patients with laryngeal cancer and 37/49 patients with lymphoma. There were no statistically significant differences in plexus visibility between the 2 groups. Median anteroposterior diameter was 2.1 mm for the postcricoid venous plexus and 1.6 mm for the posterior pharyngeal venous plexus. The most common morphology was "bilobed" for the postcricoid venous plexus and "linear" for the posterior pharyngeal venous plexus. The pharyngolaryngeal venous plexus and its components were commonly identifiable only on follow-up imaging. CONCLUSIONS: Head and neck radiologists should be familiar with the typical location and variable appearance of the pharyngolaryngeal plexus components so as not to mistake them for neoplasm. Observed variability in plexus appearance is not attributable to radiation therapy.
Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Laringe/irrigación sanguínea , Laringe/diagnóstico por imagen , Faringe/irrigación sanguínea , Faringe/diagnóstico por imagen , Adulto , Diagnóstico por Imagen , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Cuello , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Venas/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Internal auditory canal diverticula are focal lucencies along the anterior-inferior aspect of the internal auditory canal fundus. Studies in adults report conflicting data on the etiology and clinical relevance of this finding. We would expect a pediatric study to help elucidate the significance of internal auditory canal diverticula. The primary goals of this study were to determine the temporal bone CT prevalence of diverticula among pediatric patients and to assess possible hearing loss and anatomic associations. MATERIALS AND METHODS: For this retrospective study including 283 pediatric temporal bone CTs, 4 neuroradiologists independently assessed for diverticula. Discrepancies were resolved by consensus. One neuroradiologist assessed for an enlarged vestibular aqueduct, labyrinthine dysplasia, cochlear cleft, and otospongiosis. Patient demographics, audiologic data, and pertinent clinical history were recorded. One-way analysis of variance and the Fisher exact test were used to assess possible associations between diverticula and specific patient characteristics. RESULTS: Diverticula were observed in 42/283 patients (14.8%) and were more commonly bilateral. There was no significant association with age, sex, hearing loss, enlarged vestibular aqueduct, labyrinthine dysplasia, or cochlear cleft. A statistically significant association was observed with otospongiosis (P = .013), though only 1 study patient had this disease. CONCLUSIONS: Internal auditory canal diverticula are a common finding on pediatric temporal bone CT. In the absence of clinical or imaging evidence for otospongiosis, diverticula likely fall within the range of a normal anatomic variation. Familiarity with these findings may prevent neuroradiologists from recommending unnecessary additional testing in pediatric patients with isolated internal auditory canal diverticula.
Asunto(s)
Divertículo/epidemiología , Pérdida Auditiva/epidemiología , Enfermedades del Laberinto/epidemiología , Adolescente , Niño , Preescolar , Divertículo/complicaciones , Femenino , Humanos , Lactante , Enfermedades del Laberinto/complicaciones , Masculino , Prevalencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The effect of some cations on the active potassium transport system of the human red blood cell has been investigated. At low extracellular potassium concentrations, extracellular sodium competitively inhibits the active potassium influx at all sodium concentrations investigated, and tetraethylammonium behaves in a fashion similar to that of sodium. At low extracellular concentrations of potassium, ammonium at low concentrations at first stimulates the active potassium influx, but at higher concentrations inhibits it. Tetramethylammonium at most slightly stimulates the active potassium influx, and calcium is without effect. The behavior is consistent with a model in which potassium is required at more than one site before transport occurs, and the sites are indistinguishable as far as their behavior toward the ions investigated is concerned. The affinity of the alkali metal cations for the sites appears to be explicable in terms of their physical characteristics.
RESUMEN
Human red blood cells display under appropriate circumstances a ouabain-sensitive K-K exchange when the flux measurements are made using radioisotopes. Such an exchange complicates measurements of the coupling of Na outflux to K influx in cells which are partially depleted of energy sources by deprivation of glucose since the K-K exchange has been found to be increased in depleted cells. When the measurements of flux are made by estimating net cation movements chemically, it is found that glucose deprivation results in a fall in both ouabain-sensitive Na outflux and ouabain-sensitive K influx. Since both fluxes fell in concert, there is no reason for believing that the fluxes are not coupled or that the source of ATP for the Na outflux is different from that for the K influx.
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Eritrocitos/metabolismo , Potasio/sangre , Sodio/sangre , Adenosina Trifosfato , Transporte Biológico Activo , Difusión , Fructosa , Glucosa/farmacología , Glicerofosfatos , Humanos , Ouabaína/farmacología , TriosasRESUMEN
The relation between the active potassium influx in the human red blood cell and the extracellular potassium concentration does not appear to be consistent with the Michaelis-Menten model, but is adequately described by a model in which two potassium ions are required simultaneously at some site or sites in the transport mechanism before transport occurs. The same type of relation appears to exist between that portion of the sodium outflux that requires the presence of extracellular potassium and the extracellular potassium concentration. Rubidium, cesium, and lithium, which are apparently transported by the same system that transports potassium, stimulate the potassium influx when both potassium and the second ion are present at low concentrations, as is predicted by the two-site model.
Asunto(s)
Eritrocitos/metabolismo , Potasio/sangre , Transporte Biológico , Cesio/sangre , Humanos , Litio/sangre , Modelos Teóricos , Potasio/metabolismo , Rubidio/sangre , Sodio/sangreRESUMEN
The active potassium influx in the human red blood cell is inhibited by strophanthidin, ethacrynic acid, and MK-870 (a new diuretic), and the degree of inhibition is greater at low concentrations of extracellular potassium than at high. In the case of ethacrynic acid, potassium appears to diminish the rate of combination of the drug with the transport system. The kinetic behavior of the active potassium influx in the presence of the inhibitors strophanthidin and ethacrynic acid is consistent with a model in which the binding of potassium at one of the potassium-sensitive sites in the transport system reduces the affinity of the system for the drug, and binding of a second potassium ion further reduces the affinity. It is not possible to distinguish between the sites on the basis of the studies presented here.
Asunto(s)
Transporte Biológico Activo/efectos de los fármacos , Eritrocitos/metabolismo , Potasio/metabolismo , Cardanólidos/farmacología , Diuréticos/farmacología , Ácido Etacrínico/farmacología , Guanidinas/farmacología , Humanos , CinéticaRESUMEN
Evaluation of pharmacokinetic/pharmacodynamic (PK/PD) properties played an important role in the early clinical development of pembrolizumab. Because analysis of data from a traditional 3 + 3 dose-escalation design revealed several critical uncertainties, a model-based approach was implemented to better understand these properties. Based on anticipated scenarios for potency and PK nonlinearity, a follow-up study was designed and thoroughly evaluated. Execution of 14,000 virtual trials led to the selection and implementation of a robust design that extended the low-dose range by 200-fold. Modeling of the resulting data demonstrated that pembrolizumab PKs are nonlinear at <0.3 mg/kg every 3 weeks, but linear in the clinical dose range. Saturation of ex vivo target engagement in blood began at ≥1 mg/kg every 3 weeks, and a steady-state dose of 2 mg/kg every 3 weeks was needed to reach 95% target engagement, supporting examination of 2 mg/kg every 3 weeks in ongoing trials in melanoma and other advanced cancers.
Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Antineoplásicos/farmacocinética , Ensayos Clínicos Fase I como Asunto/estadística & datos numéricos , Modelos Biológicos , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Antineoplásicos/sangre , Interpretación Estadística de Datos , Estudios de Seguimiento , Humanos , Interleucina-2/antagonistas & inhibidores , Interleucina-2/sangre , InternacionalidadRESUMEN
We have examined the possibility that interaction of (alpha beta) protomers within a diprotomer is responsible for some anomalous characteristics of red cell Na,K-ATPase by examining their response to two inhibitors, FITC and H2DIDS, which bind covalently, and to ouabain, which debinds slowly from red cell pumps. The phenomena we examined were: (1) the biphasic curve relating Na,K-ATPase activity to ATP concentration, and (2) protection of Na pumps against vanadate inhibition by external Na. If interaction of (alpha beta) protomers within a diprotomer were responsible for these phenomena, random inactivation of (alpha beta) protomers should have resulted in a high proportion of (alpha beta) promtomers with an inhibited protomer as a partner, and therefore should have significantly altered the consequences of subunit interaction. With each inhibitor, 60-70% inhibition of ATPase activity did not alter the functional characteristics of the residual activity. We conclude that interaction of functional (alpha beta) protomers does not explain the phenomena which we investigated. This is consistent with our previous observation that Na,K pumps of red cell membranes exist as monomeric (alpha beta) protomers (Martin, D.W. and Sachs, V.R. (1992) J. Biol. Chem. 267, 23922-23929).
Asunto(s)
Membrana Eritrocítica/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/análogos & derivados , Ácido 4,4'-Diisotiocianostilbeno-2,2'-Disulfónico/farmacología , Adenosina Trifosfato/metabolismo , Sitios de Unión , Fluoresceína-5-Isotiocianato/farmacología , Humanos , Cinética , Ouabaína/farmacología , Fosforilación , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Vanadatos/farmacologíaRESUMEN
The interaction of extracellular Na (Na(o)), K (K(o)), and strophanthidin with the Na-K pump of the human red blood cell has been investigated. Inhibition by submaximal concentrations of strophanthidin rapidly reaches a level which does not increase further over a relatively long period of time. Under these circumstances, it is possible to apply a steady-state kinetic analysis to the interaction of Na(o), K(o), and strophanthidin with the pump. In Na-free solutions, strophanthidin increases the apparent K(1/2) of the pump for K(o), but does not change the form of the relation between the reciprocal of the active K influx ((i)M(K) (P-1)) and the reciprocal of [K(o)] ([K(o)](-1)); the relation both in the presence and absence of strophanthidin is adequately described by a straight line. In solutions containing Na, strophanthidin changes the form of the curve describing the relation between (i)M(K) (P-1) vs. [K(o)](-1); the curve becomes more parabolic in solutions containing strophanthidin. The rate of ouabain binding to K-free cells has also been measured; in the absence of K, the rate of binding is unaffected by Na(o). The data are considered in terms of a simple kinetic model. The findings can be explained if it is supposed that at low external K the form of the pump combined with one Na(o) is more likely to combine with strophanthidin than is the uncombined form of the pump. The uncombined form of the pump is more likely to combine with K even at very low K(o) than with strophanthidin.
Asunto(s)
Cardanólidos/farmacología , Eritrocitos/metabolismo , Potasio/metabolismo , Sodio/metabolismo , Humanos , Cinética , Modelos Biológicos , Ouabaína/metabolismo , Potasio/farmacología , Sodio/farmacologíaRESUMEN
K influx into resealed human red cell ghosts increases when the ghosts are swollen. The influx demonstrates properties similar to volume-sensitive K fluxes present in other cells. The influx is, for the most part, insensitive to the nature of the major intracellular cation and therefore is not a K-K exchange. The influx is much greater when the major anion is Cl than when the major anion is NO3; Cl stimulates the flux and, at constant Cl, NO3 inhibits it. Increase in the influx rate is rapid when shrunken ghosts are swollen or when NO3 is replaced by Cl. The volume-sensitive K influx requires intracellular MgATP at low concentrations, and ATP cannot be replaced by nonhydrolyzable ATP analogues. The volume-sensitive influx is inhibited by Mg2+ and by high concentrations of vanadate, but is stimulated by low concentrations of vanadate. It is not modified by cAMP, the removal of Ca2+ by EGTA, substances that activate protein kinase C, or by inhibition of phosphatidylinositol kinase. The influx is inhibited by neomycin and by trifluoperazine.
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Membrana Eritrocítica/fisiología , Eritrocitos/citología , Potasio/farmacocinética , 1-Fosfatidilinositol 4-Quinasa , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Cloruros/metabolismo , Cloruros/farmacología , Humanos , Magnesio/metabolismo , Magnesio/farmacología , Fosfotransferasas/metabolismo , Proteínas Quinasas/metabolismoRESUMEN
We have examined vanadate inhibition of the Na,K pump in the presence of external Na (Nao). Nao protects against inhibition of the Na,K pump by vanadate, but not against inhibition by phosphate or arsenate. Protection by Nao is reversed by external K (Ko). Although the site at which Na exerts its protective effect has properties similar to the two transport sites for K at the outside of the pump, it is not one of the transport sites. The data can be qualitatively accounted for if it is postulated that there is a protective site, separate from the transport sites, at which Nao and Ko compete. When the site is empty or bound to K, vanadate combines with high affinity with pumps that have two K ions bound to the transport sites, but not with pumps that have Na bound to the protective site, even if K is bound to the transport sites. The protective site has a high affinity for both Na and K; the apparent K 1/2 for external Na is less than 2 mM, which is similar to that of a previously described site at which Nao inhibits a number of the partial reactions of the pump. Nao protects against vanadate inhibition of the K-K exchange in the absence of cell Na, and against vanadate inhibition of p-nitrophenylphosphatase activity of the pump in the absence of ATP. The protective site is a manifestation of an E2 conformation of the pump. The protective effect of Nao is not changed by altering the intracellular Mg2+ concentration.
Asunto(s)
Canales Iónicos/efectos de los fármacos , Potasio/metabolismo , Sodio/metabolismo , Vanadatos/farmacología , Transporte Biológico/efectos de los fármacos , Humanos , Técnicas In Vitro , Ouabaína/farmacología , Sodio/farmacologíaRESUMEN
Red blood cells exposed to ouabain are capable of net Na outflux against an electrochemical gradient; the net outflux is inhibited by the diuretic, furosemide. In ouabain-treated cells, both the unidirectional Na outflux and the unidirectional Na influx are inhibited by furosemide. Furosemide also inhibits the ouabain-sensitive Na-Na exchange accomplished by the Na-K pump in K-free solutions. From the interaction of extracellular K, furosemide, and ouabain with the transport system, it seems possible that the ouabain-insensitive Na outflux is accomplished by the same mechanism that is responsible for the ouabain-sensitive Na-K exchange. The ouabain-insensitive Na outflux is increased by extracellular Na, and the influx increases as the intracellular Na increases. In fresh cells, high extracellular K concentrations decrease the ouabain-insensitive Na outflux and increase the ouabain-insensitive Na influx. When the rate constant for sodium outflux and the rate constant for sodium influx in ouabain-treated cells are plotted against the extracellular K concentration, the curves obtained are mirror images of each other. In starved cells, extracellular K increases the ouabain-insensitive Na outflux as does extracellular Na, and it has little effect on the Na influx.
Asunto(s)
Transporte Biológico Activo/efectos de los fármacosRESUMEN
Measurements were made of the sodium outflux rate constant, (o)k(Na), and sodium influx rate constant, (i)k(Na), at varying concentrations of extracellular (Na(o)) and intracellular (Na(c)) sodium. (o)k(Na) increases with increasing [Na(o)] in the presence of extracellular potassium (K(o)) and in solutions containing ouabain. In K-free solutions which do not contain ouabain, (o)k(Na) falls as [Na(o)] rises from 0 to 6 mM; above 6 mM, (o)k(Na) increases with increasing [Na(o)]. Part of the Na outflux which occurs in solutions free of Na and K disappears when the cells are starved or when the measurements are made in solutions containing ouabain. As [Na(o)] increases from 0 to 6 mM, (i)k(Na) decreases, suggesting that sites involved in the sodium influx are becoming saturated. As [Na(c)] increases, (o)k(Na) at first increases and then decreases; this relation between (o)k(Na) and [Na(c)] is found when the measurements are made in high Na, high K solutions; high Na, K-free solutions; and in (Na + K)-free solutions. The relation may be the consequence of the requirement that more than one Na ion must react with the transport mechanism at the inner surface of the membrane before transport occurs. Further evidence has been obtained that the ouabain-inhibited Na outflux and Na influx in K-free solutions represent an exchange of Na(c) for Na(o) via the Na-K pump mechanism.
Asunto(s)
Transporte Biológico/efectos de los fármacos , Eritrocitos/fisiología , Ouabaína/farmacología , Sodio/sangre , Humanos , Masculino , Modelos Químicos , Potasio/sangre , Isótopos de SodioRESUMEN
Volume-sensitive K-Cl cotransport occurs in red blood cells of many species. In intact cells, activation of K-Cl cotransport by swelling requires dephosphorylation of some cell protein, but maximal activity requires the presence of intracellular ATP. We have examined the relation between K-Cl cotransport activity and ATP in ghosts prepared from human red blood cells. K-Cl cotransport activity in swollen ghosts increased by ATP, and the increase requires Mg so that it almost certainly results from the phosphorylation of some membrane component. However, even in ATP-free ghosts residual volume-sensitive K-Cl cotransport can be demonstrated. This residual cotransport in ATP-free ghosts is greater in the presence of vanadate, a tyrosyl phosphatase inhibitor, and in ghosts that contain ATP cotransport is reduced by genistein, a tyrosyl kinase inhibitor. Okadaic acid, an inhibitor of serine and threonine phosphatases, inhibits K-Cl cotransport in ghosts as it does in intact cells. Experiments in which ghosts were preexposed to okadaic acid showed that the protein dephosphorylation that permits K-Cl cotransport can proceed to completion before the ghosts are swollen and K transport measured and therefore dephosphorylation is not a response to ghost swelling. In experiments with ATP-free ghosts we found that phosphorylation is not necessary to increase the cotransport rate when shrunken ghosts are swollen, nor is rephosphorylation necessary to decrease the cotransport rate when swollen ghosts are shrunken. Cotransport is greater in swollen than in shrunken ghosts even when the swollen and shrunken ghosts have the same concentration of cytoplasmic solutes. We conclude that, although phosphorylation and dephosphorylation modify the activity of the cotransporter in swollen and in shrunken ghosts, neither of these processes nor any other known messenger is involved in signal transduction between the cell volume sensor and the cotransporter as originally proposed by Jennings and Al-Rohil (Jennings, M. L., and N. Al-Rohil. 1990. Journal of General Physiology. 95: 1021-1040).
Asunto(s)
Adenosina Trifosfato/fisiología , Cloruros/sangre , Membrana Eritrocítica/metabolismo , Potasio/sangre , Transducción de Señal/efectos de los fármacos , Adenosina Trifosfato/antagonistas & inhibidores , Membrana Eritrocítica/efectos de los fármacos , Éteres Cíclicos/farmacología , Proteínas de Unión al GTP/metabolismo , Genisteína , Humanos , Técnicas In Vitro , Isoflavonas/farmacología , Magnesio/sangre , Ácido Ocadaico , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosforilación , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Sodio/sangre , Vanadatos/farmacologíaRESUMEN
The kinetic characteristics of the Na:K pump in high potassium (HK) and low potassium (LK) goat red cells were investigated after altering the intracellular cation concentrations. At low concentrations of intracellular K (K(c)), increasing K(c) at first stimulates the active K influx in HK cells, but at higher K(c) the pump is inhibited. These results suggest that in HK cells K(c) acts both at a stimulatory site at the inner aspect of the pump and by competition with intracellular Na (Na(c)) at the Na translocation sites. In LK cells, K(c) inhibits the active K influx and the sensitivity of LK cells to inhibition is much greater than the sensitivity of HK cells. Exposure of LK cells to an antibody (anti-L), raised in an HK sheep by injection of LK sheep cells, increased the active K influx at any given K(c). The effect of the antibody was greater at higher intracellular K concentrations, and in cells with very low concentrations of K the antibody had little effect on the pump rate. The failure of anti-L to stimulate the pump in low K(c) LK cells was not due to failure of the antibody to bind to the cells. Anti-L combining at the outer surface of the cell reduces the affinity of the pump at the inner surface for K at the inhibitory sites. The maximal pump rate in LK cells at optimal Na and K concentrations is less than the maximal pump rate of HK cells under the same circumstances.
Asunto(s)
Reacciones Antígeno-Anticuerpo , Eritrocitos/metabolismo , Cabras , Potasio/metabolismo , Sodio/metabolismo , Animales , Sitios de Unión de Anticuerpos , Eritrocitos/inmunología , Genética de Población , Sueros Inmunes , Cinética , Ouabaína/farmacología , Ovinos/inmunologíaRESUMEN
The characteristics of the interaction of Na-K pumps of high potassium (HK) and low potassium (LK) goat red blood cells with ouabain have been determined. The rate of inhibition by ouabain of the pump of HK cells is greater than the rate of inhibition of the pumps of LK cells. Treatment of LK cells with an antibody (anti-L) raised in HK sheep by injecting LK sheep red cells increases the rate of inhibition of the LK pumps by ouabain to that characteristic of HK pumps; reduction of intracellular K (K(c)) in LK cells increases the rate at which ouabain inhibits their pumps and exposure of these low K(c) cells to anti-L does not affect the rate of inhibition. There is considerable heterogeneity in the pumps of both HK and LK cells in the rate at which they interact with ouabain or the rate at which they pump or both. LK pumps which are sensitive to stimulation by anti-L bind ouabain less rapidly than the remainder of the LK pumps and exposure to antibody increases the rate at which ouabain binds to the sensitive pumps; the difference between the two types of pumps disappears if intracellular K is very low. The calculated number of ouabain molecules bound at 100% inhibition of the pump is about the same for HK and LK cells. Although exposure to anti-L increases the apparent number of ouabain binding sites in LK cells at normal K(c), it does not alter the apparent number of sites in LK cells when K(c) has been reduced.
Asunto(s)
Eritrocitos/metabolismo , Ouabaína/farmacología , Potasio/metabolismo , Animales , Anticuerpos , Reacciones Antígeno-Anticuerpo , Sitios de Unión , Depresión Química , Cabras , Ouabaína/metabolismo , Potasio/inmunología , Ovinos/inmunología , TritioRESUMEN
We have developed a method to characterize fluid transport through the perialveolar interstitium using micropuncture techniques. In 10 experiments we established isolated perfused rat lung preparations. The lungs were initially isogravimetric at 10 cmH2O arterial pressure, 2 cmH2O venous pressure, and 5 cmH2O alveolar pressure. Perialveolar interstitial pressure was determined by micropuncture at alveolar junctions by use of the servo-null technique. Simultaneously a second micropipette was placed in an alveolar junction 20-40 microns away, and a bolus of albumin solution (3.5 g/100 ml) was injected. The resulting pressure transient was recorded for injection durations of 1 and 4 s in nonedematous lungs. The measurements were repeated after gross edema formation induced by elevated perfusion pressure. We model the interstitium as a homogeneous linearly poroelastic material and assume the initial pressure distribution due to the injection to be Gaussian. The pressure decay is inversely proportional to time, with time constant T, where T is a measure of the ratio of interstitial tissue stiffness to interstitial resistance to fluid flow. A linear regression was performed on the reciprocal of the pressure for the decaying portion of the transients to determine T. Comparing pressure transients in nonedematous and edematous lungs, we found that T was 4.0 +/- 1.4 and 1.4 +/- 0.6 s, respectively. We have shown that fluid transport through the pulmonary interstitium on a local level is sensitive to changes in interstitial stiffness and resistance. These results are consistent with the decreased stiffness and resistance in the perialveolar interstitium that accompany increased hydration.
Asunto(s)
Resistencia de las Vías Respiratorias/fisiología , Rendimiento Pulmonar/fisiología , Animales , Técnicas In Vitro , Modelos Biológicos , Perfusión , Alveolos Pulmonares/fisiología , Edema Pulmonar/fisiopatología , Ratas , Ratas Endogámicas , Mecánica Respiratoria/fisiología , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
This study focuses on an approach for the nondestructive assessment of cartilage degeneration in vivo by quantitation of bulk material properties based on measurements made at the top surface of the tissue. A model of an electromechanical coupled poroelastic medium [Sachs and Grodzinsky (1989) Physicochem. Hydrodyn. 11, 585-614] is used to interpret the behavior of a diagnostic probe configuration suitable for such surface measurements of cartilage electromechanical and poroelastic properties via arthroscopy. The response of a planar layer of tissue to a periodic displacement imposed at the articular surface is described. This displacement produces a periodic electric streaming potential and mechanical stress in the bulk and at the surface of the tissue layer with the same frequency and wavelength as the imposed displacement. Using boundary conditions and parameter values relevant to cartilage, the results show that surface measurements of the stress and potential can be used to determine bulk material properties including tissue thickness, moduli, hydraulic permeability, and electrokinetic coupling coefficients. The relation between the temporal frequency and spatial wavelength of the surface excitation and the amplitude, phase, and penetration depth of the stress and potential is investigated numerically and asymptotically. Good agreement has been found between the long wave limit (with parameter values taken from the literature) and compression-induced streaming potential data from previous experiments in uniaxial confined compression. The results show that use of independently imposed temporal frequency and spatial wavelength may enable detection and imaging of focal regions of cartilage degeneration via nondestructive surface spectroscopy.