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1.
AJNR Am J Neuroradiol ; 44(3): 317-322, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36797029

RESUMEN

BACKGROUND AND PURPOSE: Vestibular schwannomas are benign, generally slow-growing tumors, commonly presenting with hearing loss. Alterations in the labyrinthine signal are seen in patients with vestibular schwannoma; however, the association between imaging abnormalities and hearing function remains poorly defined. The purpose of this study was to determine whether labyrinthine signal intensity is associated with hearing in patients with sporadic vestibular schwannoma. MATERIALS AND METHODS: This was an institutional review board-approved retrospective review of patients from a prospectively maintained vestibular schwannoma registry imaged in 2003-2017. Signal-intensity ratios of the ipsilateral labyrinth were obtained using T1, T2-FLAIR, and postgadolinium T1 sequences. Signal-intensity ratios were compared with tumor volume and audiometric hearing threshold data including pure tone average, word recognition score, and American Academy of Otolaryngology-Head and Neck Surgery hearing class. RESULTS: One hundred ninety-five patients were analyzed. Ipsilateral labyrinthine signal intensity including postgadolinium T1 images was positively correlated with tumor volume (correlation coefficient = 0.17, P = .02). Among signal-intensity ratios, postgadolinium T1 was significantly positively associated with pure tone average (correlation coefficient = 0.28, P < .001) and negatively associated with the word recognition score (correlation coefficient = -0.21, P = .003). Overall, this result correlated with impaired American Academy of Otolaryngology-Head and Neck Surgery hearing class (P = .04). Multivariable analysis suggested persistent associations independent of tumor volume with pure tone average (correlation coefficient = 0.25, P < .001) and the word recognition score (correlation coefficient = -0.17, P = .02) but not hearing class (P = .14). No consistent significant associations were noted between noncontrast T1 and T2-FLAIR signal intensities and audiometric testing. CONCLUSIONS: Increased ipsilateral labyrinthine postgadolinium signal intensity is associated with hearing loss in patients with vestibular schwannoma.


Asunto(s)
Sordera , Oído Interno , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico , Neuroma Acústico/diagnóstico por imagen , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/etiología , Estudios Retrospectivos
2.
AJNR Am J Neuroradiol ; 42(3): 573-577, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33334855

RESUMEN

BACKGROUND AND PURPOSE: Although multishot EPI (readout-segmented EPI) has been touted as a robust DWI sequence for cholesteatoma evaluation, its efficacy in disease detection compared with a non-EPI (eg, HASTE) technique is unknown. This study sought to compare the accuracy of readout-segmented EPI with that of HASTE DWI in cholesteatoma detection. MATERIALS AND METHODS: A retrospective review was completed of consecutive patients who underwent MR imaging for the evaluation of suspected primary or recurrent/residual cholesteatomas. Included patients had MR imaging examinations that included both HASTE and readout-segmented EPI sequences and confirmed cholesteatomas on a subsequent operation. Two neuroradiologist reviewers assessed all images, with discrepancies resolved by consensus. The ratio of signal intensity between the cerebellum and any observed lesion was noted. RESULTS: Of 23 included patients, 12 (52.2%) were women (average age, 47.8 [SD, 25.2] years). All patients had surgically confirmed cholesteatomas: Six (26.1%) were primary and 17 (73.9%) were recidivistic. HASTE images correctly identified cholesteatomas in 100.0% of patients. On readout-segmented EPI sequences, 16 (69.6%) were positive, 5 (21.7%) were equivocal, and 2 (8.7%) were falsely negative. Excellent interobserver agreement was noted between reviews on both HASTE (κ = 1.0) and readout-segmented EPI (κ = 0.9) sequences. The average signal intensity ratio was significantly higher on HASTE than in readout-segmented EPI, facilitating enhanced detection (mean difference 0.5; 95% CI, 0.3-0.8; P = .003). CONCLUSIONS: HASTE outperforms readout-segmented EPI in the detection of primary cholesteatoma and disease recidivism.


Asunto(s)
Colesteatoma del Oído Medio/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Interpretación de Imagen Asistida por Computador/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
3.
AJNR Am J Neuroradiol ; 42(1): 160-166, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33154075

RESUMEN

Persistent stapedial artery is a vascular anomaly with both clinical and surgical implications. Because of its scarcity, however, it remains underrecognized on imaging. Presented here is a series of 10 cases, demonstrating characteristic CT findings associated with this vascular anomaly and its most common pathognomonic imaging signs. The variable morphologic configurations and their corresponding embryologic underpinnings are described. Clinical and surgical implications of this rare anomaly are discussed.


Asunto(s)
Arterias/anomalías , Arterias/embriología , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/embriología , Arterias/diagnóstico por imagen , Oído/irrigación sanguínea , Oído/embriología , Femenino , Humanos , Masculino , Tomografía Computarizada por Rayos X/métodos , Malformaciones Vasculares/patología
4.
AJNR Am J Neuroradiol ; 42(1): 12-21, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33184072

RESUMEN

Postoperative temporal bone imaging after surgical procedures such as ossiculoplasty, tympanomastoidectomy, cochlear implantation, and vestibular schwannoma resection is often encountered in clinical neuroradiology practice. Less common otologic procedures can present diagnostic dilemmas, particularly if access to prior operative reports is not possible. Lack of familiarity with the less common surgical procedures and expected postoperative changes may render radiologic interpretation challenging. This review illustrates key imaging findings after surgery for Ménière disease, superior semicircular canal dehiscence, temporal encephalocele repairs, internal auditory canal decompression, active middle ear implants, jugular bulb and sigmoid sinus dehiscence repair, and petrous apicectomy.


Asunto(s)
Procedimientos Quirúrgicos Otológicos/métodos , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/cirugía , Tomografía Computarizada por Rayos X/métodos , Senos Craneales/diagnóstico por imagen , Senos Craneales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía
5.
Sci Adv ; 6(40)2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32998902

RESUMEN

Staphylococcus aureus is a major human pathogen that has acquired alarming broad-spectrum antibiotic resistance. One group of secreted toxins with key roles during infection is the phenol-soluble modulins (PSMs). PSMs are amphipathic, membrane-destructive cytolytic peptides that are exported to the host-cell environment by a designated adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, the PSM transporter (PmtABCD). Here, we demonstrate that the minimal Pmt unit necessary for PSM export is PmtCD and provide its first atomic characterization by single-particle cryo-EM and x-ray crystallography. We have captured the transporter in the ATP-bound state at near atomic resolution, revealing a type II ABC exporter fold, with an additional cytosolic domain. Comparison to a lower-resolution nucleotide-free map displaying an "open" conformation and putative hydrophobic inner chamber of a size able to accommodate the binding of two PSM peptides provides mechanistic insight and sets the foundation for therapeutic design.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Humanos , Péptidos/metabolismo
6.
AJNR Am J Neuroradiol ; 41(2): 192-199, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31831467

RESUMEN

The round window serves to decompress acoustic energy that enters the cochlea via stapes movement against the oval window. Any inward motion of the oval window via stapes vibration leads to outward motion of the round window. Occlusion of the round window is a cause of conductive hearing loss because it increases the resistance to sound energy and consequently dampens energy propagation. Because the round window niche is not adequately evaluated by otoscopy and may be incompletely exposed during an operation, otologic surgeons may not always correctly identify associated pathology. Thus, radiologists play an essential role in the identification and classification of diseases affecting the round window. The purpose of this review is to highlight the developmental, acquired, neoplastic, and iatrogenic range of pathologies that can be encountered in round window dysfunction.


Asunto(s)
Ventana Redonda/patología , Femenino , Humanos , Masculino , Ventana Redonda/anomalías , Ventana Redonda/cirugía
7.
AJNR Am J Neuroradiol ; 40(12): 1987-1993, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31727744

RESUMEN

Forced exhalation against a closed glottis, known as the Valsalva maneuver, is an important clinical diagnostic and therapeutic tool due to its physiologic effects. Several unique conditions and anatomic changes can occur with repetitive or acute changes in pressure from the Valsalva maneuver. We will discuss and review various pertinent head and neck imaging cases with findings resulting from induced pressure gradients, including the Valsalva maneuver. Additionally, we will demonstrate the diagnostic utility of the Valsalva maneuver in head and neck radiology.


Asunto(s)
Cabeza/diagnóstico por imagen , Cuello/diagnóstico por imagen , Maniobra de Valsalva , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos
8.
AJNR Am J Neuroradiol ; 40(8): 1402-1405, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31296524

RESUMEN

BACKGROUND AND PURPOSE: The prevalence of patent facial nerve canals and meningoceles along the facial nerve course is unknown. This study aimed to assess the frequency of such findings in asymptomatic patients. MATERIALS AND METHODS: A retrospective review was completed of patients with high-resolution MR imaging of the temporal bone whose clinical presentations were unrelated to facial nerve pathology. Facial nerve canals were assessed for the presence of fluid along each segment and meningoceles within either the labyrinthine segment (fluid-filled distention, ≥1.0-mm diameter) or geniculate ganglion fossa (fluid-filled distention, ≥2.0-mm diameter). If a meningocele was noted, images were assessed for signs of CSF leak. RESULTS: Of 204 patients, 36 (17.6%) had fluid in the labyrinthine segment of the facial nerve canal and 40 (19.6%) had fluid in the geniculate ganglion fossa. Five (2.5%) had meningoceles of the geniculate ganglion fossa; no meningoceles of the labyrinthine segment of the canal were observed. No significant difference was observed in the ages of patients with fluid in the labyrinthine segment of the canal or geniculate ganglion compared with those without fluid (P = .177 and P = .896, respectively). Of the patients with a meningocele, one had a partially empty sella and none had imaging evidence of CSF leak or intracranial hypotension. CONCLUSIONS: Fluid within the labyrinthine and geniculate segments of the facial nerve canal is relatively common. Geniculate ganglion meningoceles are also observed, though less frequently. Such findings should be considered of little clinical importance without radiologic evidence of CSF otorrhea, meningitis, or facial nerve palsy.


Asunto(s)
Enfermedades del Nervio Facial/epidemiología , Meningocele/epidemiología , Enfermedades del Nervio Facial/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Meningocele/diagnóstico por imagen , Prevalencia , Estudios Retrospectivos , Hueso Temporal/diagnóstico por imagen
10.
AJNR Am J Neuroradiol ; 39(12): 2340-2344, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30442698

RESUMEN

BACKGROUND AND PURPOSE: Bony internal auditory canal diverticula are relatively common, occurring in approximately 5% of temporal bone CTs. Internal auditory canal diverticula have historically been considered incidental; however, a recent publication reported that internal auditory canal diverticula are associated with sensorineural hearing loss. The objective of this study was to further characterize this potential association in a large cohort of patients. MATERIALS AND METHODS: A total of 1759 patients undergoing high-resolution temporal bone CT were collected during a 6-year interval, and audiometric data were obtained from those with internal auditory canal diverticula. To assess any association of isolated internal auditory canal diverticula with sensorineural hearing loss, we excluded from further analysis patients with concomitant otosclerosis and bilateral diverticula and those without audiometric data, leaving 22 index cases. Audiometric data for the ear with a diverticulum was compared with that in the contralateral ear, to serve as an internal control. RESULTS: Of 1759 patients, 82 (4.7%) had either unilateral (n = 33, 40%) or bilateral (n = 49, 60%) internal auditory canal diverticula. The co-incidence of otosclerosis and internal auditory canal diverticula was 34% (n = 28). There was no correlation between patient age and diverticulum size on either side. Among the index cases with isolated unilateral internal auditory canal diverticula and complete audiometric data, word recognition scores and the prevalence and severity of sensorineural hearing loss were not significantly different comparing the internal auditory canal diverticulum side to its contralateral control. CONCLUSIONS: This study did not find a statistically significant association between ears with internal auditory canal diverticula and worsening sensorineural hearing loss or word recognition. Internal auditory canal diverticula most likely represent a normal anatomic variant in ears without otosclerosis.


Asunto(s)
Divertículo/epidemiología , Oído Interno/anomalías , Pérdida Auditiva Sensorineural/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/efectos adversos , Adulto Joven
11.
AJNR Am J Neuroradiol ; 39(9): 1733-1738, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30093479

RESUMEN

BACKGROUND AND PURPOSE: Evaluating abnormalities of the temporal bone requires high-spatial-resolution CT imaging. Our aim was to assess the performance of photon-counting-detector ultra-high-resolution acquisitions for temporal bone imaging and compare the results with those of energy-integrating-detector ultra-high-resolution acquisitions. MATERIALS AND METHODS: Phantom studies were conducted to quantify spatial resolution of the ultra-high-resolution mode on a prototype photon-counting-detector CT scanner and an energy-integrating-detector CT scanner that uses a comb filter. Ten cadaveric temporal bones were scanned on both systems with the radiation dose matched to that of the clinical examinations. Images were reconstructed using a sharp kernel, 0.6-mm (minimum) thickness for energy-integrating-detector CT, and 0.6- and 0.25-mm (minimum) thicknesses for photon-counting-detector CT. Image noise was measured and compared using adjusted 1-way ANOVA. Images were reviewed blindly by 3 neuroradiologists to assess the incudomallear joint, stapes footplate, modiolus, and overall image quality. The ranking results for each specimen and protocol were compared using the Friedman test. The Krippendorff α was used for interreader agreement. RESULTS: Photon-counting-detector CT showed an increase of in-plane resolution compared with energy-integrating-detector CT. At the same thickness (0.6 mm), images from photon-counting-detector CT had significantly lower (P < .001) image noise compared with energy-integrating-detector CT. Readers preferred the photon-counting-detector CT images to the energy-integrating-detector images for all 3 temporal bone structures. A moderate interreader agreement was observed with the Krippendorff α = 0.50. For overall image quality, photon-counting-detector CT image sets were ranked significantly higher than images from energy-integrating-detector CT (P < .001). CONCLUSIONS: This study demonstrated substantially better delineation of fine anatomy for the temporal bones scanned with the ultra-high-resolution mode of photon-counting-detector CT compared with the ultra-high-resolution mode of a commercial energy-integrating-detector CT scanner.


Asunto(s)
Hueso Temporal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Cadáver , Humanos , Fantasmas de Imagen , Fotones
12.
AJNR Am J Neuroradiol ; 35(1): 186-90, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23828114

RESUMEN

BACKGROUND AND PURPOSE: The prevalence of tympanic plate fractures, which are associated with an increased risk of external auditory canal stenosis following temporal bone trauma, is unknown. A review of posttraumatic high-resolution CT temporal bone examinations was performed to determine the prevalence of tympanic plate fractures and to identify any associated temporal bone injuries. MATERIALS AND METHODS: A retrospective review was performed to evaluate patients with head trauma who underwent emergent high-resolution CT examinations of the temporal bone from July 2006 to March 2012. Fractures were identified and assessed for orientation; involvement of the tympanic plate, scutum, bony labyrinth, facial nerve canal, and temporomandibular joint; and ossicular chain disruption. RESULTS: Thirty-nine patients (41.3 ± 17.2 years of age) had a total of 46 temporal bone fractures (7 bilateral). Tympanic plate fractures were identified in 27 (58.7%) of these 46 fractures. Ossicular disruption occurred in 17 (37.0%). Fractures involving the scutum occurred in 25 (54.4%). None of the 46 fractured temporal bones had a mandibular condyle dislocation or fracture. Of the 27 cases of tympanic plate fractures, 14 (51.8%) had ossicular disruption (P = .016) and 18 (66.6%) had a fracture of the scutum (P = .044). Temporomandibular joint gas was seen in 15 (33%) but was not statistically associated with tympanic plate fracture (P = .21). CONCLUSIONS: Tympanic plate fractures are commonly seen on high-resolution CT performed for evaluation of temporal bone trauma. It is important to recognize these fractures to avoid the preventable complication of external auditory canal stenosis and the potential for conductive hearing loss due to a fracture involving the scutum or ossicular chain.


Asunto(s)
Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/epidemiología , Fracturas Craneales/diagnóstico por imagen , Fracturas Craneales/epidemiología , Hueso Temporal/lesiones , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Minnesota/epidemiología , Traumatismo Múltiple/diagnóstico por imagen , Traumatismo Múltiple/epidemiología , Prevalencia , Estudios Retrospectivos , Medición de Riesgo
13.
J Evol Biol ; 17(1): 19-32, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15000644

RESUMEN

Congruence between changes in phenotypic variance and developmental noise in inter-population hybrids was analysed to test whether environmental canalization and developmental stability were controlled by common genetic mechanisms. Developmental stability assessed by the level of fluctuating asymmetry (FA), and canalization by the within- and among-individual variance, were measured on several floral traits of Dalechampia scandens (Euphorbiaceae). Hybridization affected canalization. Both within- and among-individual phenotypic variance decreased in hybrids from populations of intermediate genetic distance, and strongly increased in hybrids from genetically distant populations. Mean-trait FA differed among cross-types, but hybrids were not consistently more or less asymmetric than parental lines across traits. We found no congruence between changes in FA and changes in phenotypic variance. These results suggest that developmental stability (measured by FA) and canalization are independently controlled. This study also confirms the weak relationship between FA and the breakdown of coadapted gene complexes following inter-population hybridization.


Asunto(s)
Ambiente , Euphorbiaceae/crecimiento & desarrollo , Flores/anatomía & histología , Genética de Población , Hibridación Genética , Análisis de Varianza , Cruzamientos Genéticos , Euphorbiaceae/genética
14.
Science ; 287(5451): 308-9, 2000 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-10634786

RESUMEN

The introduction and rapid spread of Drosophila subobscura in the New World two decades ago provide an opportunity to determine the predictability and rate of evolution of a geographic cline. In ancestral Old World populations, wing length increases clinally with latitude. In North American populations, no wing length cline was detected one decade after the introduction. After two decades, however, a cline has evolved and largely converged on the ancestral cline. The rate of morphological evolution on a continental scale is very fast, relative even to rates measured within local populations. Nevertheless, different wing sections dominate the New versus Old World clines. Thus, the evolution of geographic variation in wing length has been predictable, but the means by which the cline is achieved is contingent.


Asunto(s)
Evolución Biológica , Drosophila/anatomía & histología , Drosophila/genética , Alas de Animales/anatomía & histología , Animales , Europa (Continente) , Femenino , Geografía , Masculino , América del Norte , Caracteres Sexuales , Factores de Tiempo
15.
J Reprod Fertil Suppl ; (56): 635-44, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-20681179

RESUMEN

A cytotoxic T-lymphocyte assay was used to determine whether equine chorionic girdle cells are susceptible to lysis by CD8+ cytotoxic T cells primed in vitro against allogeneic lymphocytes. Classical cytotoxic T-lymphocyte activity against fresh or cultured trophoblast targets was demonstrated using peripheral blood lymphocytes from nonpregnant mares. Lysis of allogeneic (horse) and xenogeneic (donkey) lymphocyte targets was used as a control for trophoblast lysis. The major histocompatibility complex (MHC) class I specificity of the cytotoxic T-lymphocyte reactions was determined using panels of MHC-typed target cells. The results of the present study demonstrate that the MHC class I antigens expressed on equine chorionic girdle cells are functional proteins, which can serve as targets for CD8+ allospecific cytotoxic T lymphocytes. Furthermore, these findings indicate strongly that, at least in the in vitro assay used, MHC class I positive chorionic girdle cells do not display any mechanisms that can protect them from lysis by activated maternal T cells.


Asunto(s)
Equidae/inmunología , Equidae/fisiología , Trofoblastos/inmunología , Animales , Linfocitos T CD8-positivos/fisiología , Femenino , Complejo Mayor de Histocompatibilidad/inmunología , Masculino , Embarazo
16.
J Am Podiatr Med Assoc ; 89(4): 169-73, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10220986

RESUMEN

Compensation filters allow increased visibility of detail in chest, shoulder, spine, hip, knee, and foot radiographs. This study examines use of an anatomic compensation filter to improve imaging in pedal radiographs. Anteroposterior radiographs were obtained of 25 cadaveric feet at two settings with and without the compensation filter. Densitometer readings were taken at ten forefoot anatomic sites. The compensation filter produced statistically significant reductions in densitometer readings at all anatomic sites and at both radiographic settings. Filtration improved imagery of bony structures, provided excellent soft-tissue visualization, and lowered patient exposure.


Asunto(s)
Antepié Humano/diagnóstico por imagen , Intensificación de Imagen Radiográfica/instrumentación , Cadáver , Densitometría , Estudios de Evaluación como Asunto , Humanos , Intensificación de Imagen Radiográfica/normas
17.
Biochemistry ; 35(4): 1125-36, 1996 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-8573567

RESUMEN

Experimentally, distal mutations in myoglobin substantially affect the contribution of fast and slow phases to picosecond geminate recombination of NO following flash photolysis. Earlier simulations of ligand diffusion among distal pocket mutants showed greatly differing rates of collisions between the ligands and the heme iron, suggesting that distal residues affect recombination by controlling ligand access to the iron [Gibson, Q. H., Regan, R., Elber, R., Olson, J. S., & Carver, T. (1992) J. Biol. Chem. 267, 22022-22034). In this work, molecular dynamics simulations of sperm whale myoglobin and mutations at positions 68 (E11) and 107 (G8) have been examined to investigate the structural mechanism that controls ligand diffusion and iron accessibility. Visualization of the distal ligand-accessible spaces shows a pattern of cavities (common to other hemoglobins and myoglobins) that fluctuate and interconnect due to protein motions. Access to the iron atom is highly sensitive to these fluctuations in the native structure, perhaps a reason for the strong conservation of distal residues. The positions of the helices surrounding the distal heme site were monitored to assess the involvement of more collective protein motions in ligand diffusion. Ligand migrations and collisions with the iron appear related to expansion of the distal protein matrix due to helix movements. The helices surrounding the distal site also make relative adjustments on the order of 0.5 A to accommodate the presence of a mobile diatomic ligand, suggesting a mechanism for communication between the heme site and the exterior of the protein.


Asunto(s)
Simulación por Computador , Modelos Moleculares , Mioglobina/química , Animales , Difusión , Hierro/química , Ligandos , Movimiento (Física) , Mutación , Mioglobina/genética , Ballenas
18.
Biochemistry ; 33(35): 10597-606, 1994 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-8075059

RESUMEN

Picosecond recombination of nitric oxide to the double mutants of myoglobin, His64Gly-Val68Ala and His64Gly.Val68Ile, at E7 and E11, has been studied experimentally and by computation. It is shown that distal residues have a profound effect on NO recombination. Recombination in the mutants may be explained in terms of fluctuating free volume and structure of the heme pocket. The double mutants provide insight into the effects of free volume and steric hindrance on rates of ligand rebinding following photolysis. Water molecules of the first solvation shell replace surface residues deleted by mutation and can block apparent holes in the protein structure. Thus, water molecules extend the time required for ligands to escape significantly to a nanosecond time scale, which is much longer than would be expected for an open heme pocket. Both nearly exponential (G64A68) and markedly nonexponential (native and G64I68) kinetics are observed, a result at variance with expectation from the model of Petrich et al. [Petrich, J.W., Lambry, J.C., Kuczera, K., Karplus, M., Poyart, C., & Martin, J.L. (1991) Biochemistry 30, 3975-3987], which attributes nonexponential kinetics to proximal effects.


Asunto(s)
Mioglobina/metabolismo , Óxido Nítrico/química , Secuencia de Aminoácidos , Difusión , Hemo/química , Ligandos , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Proteínas Recombinantes , Relación Estructura-Actividad
19.
Proc Natl Acad Sci U S A ; 84(21): 7686-90, 1987 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-2823271

RESUMEN

To investigate patterns of endogenous hormone release, we have proposed a biophysical model in which measured hormone concentrations at any given instant reflect the operation of a suitable cumulation function (secretory input) convolved with an appropriate elimination mechanism (metabolic clearance). The cumulation function underlying a macroscopic hormone secretory burst can be represented by a random (Gaussian) distribution of instantaneous molecular secretory rates, which are centered with some finite and determinable standard deviation about a particular moment in time. The hormone elimination mechanism is described by a mono- or biexponential clearance function. The resultant convolution integral is solved by iterative nonlinear least-squares parameter estimation, in which all plasma hormone concentrations and their variances are considered simultaneously. Experiments with human endocrine time series revealed that the spontaneous secretory patterns of any of multiple distinct anterior pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, thyrotropin, and adrenocorticotropic hormone) can be described effectively by this parsimonious model. In addition, endogenous hormone disappearance rates determined by deconvolution agreed well with those reported earlier that were determined after exogenous hormone injections. Moreover, this model predicted that durations of underlying secretory impulses are extremely brief; i.e., the standard deviations of the Gaussian distributions of instantaneous secretory rates range from 4.5 min (luteinizing hormone) to 16 min (growth hormone) compared to plasma hormone concentration peaks of 90-140 min in duration. Accordingly, we conclude that observed physiological patterns of fluctuating plasma hormone concentrations can be accounted for by distinct, highly delimited, random bursts of hormone release separated by intervals of secretory quiescence.


Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Hormona del Crecimiento/metabolismo , Hormona Luteinizante/metabolismo , Hipófisis/metabolismo , Prolactina/metabolismo , Tirotropina/metabolismo , Hormona Adrenocorticotrópica/sangre , Hormona del Crecimiento/sangre , Humanos , Hormona Luteinizante/sangre , Masculino , Periodicidad , Prolactina/sangre , Tirotropina/sangre , Factores de Tiempo
20.
J Antimicrob Chemother ; 15(5): 575-8, 1985 May.
Artículo en Inglés | MEDLINE | ID: mdl-3874200

RESUMEN

Pneumocystis carinii pneumonitis was induced using dexamethasone in male Sprague-Dawley rats. After the first death due to Pn. carinii occurred, nine rats received 50 mg/kg/day tetroxoprim and 120 mg/kg/day sulphadiazine. Four additional rats were given no therapy and served as a positive control. All the surviving rats including five negative controls were sacrificed four weeks after the last positive control rat died. All four rats in the positive control group and two of nine in the treated group developed Pn. carinii pneumonitis, whereas none of the five negative controls had evidence of Pn. carinii infection. The difference between the treated and untreated rats was significant (P = 0.05). These results suggest that combination therapy with tetroxoprim/sulphadiazine is effective in the treatment of Pn. carinii pneumonitis in this animal model.


Asunto(s)
Neumonía por Pneumocystis/tratamiento farmacológico , Pirimidinas/administración & dosificación , Sulfadiazina/administración & dosificación , Animales , Quimioterapia Combinada , Ratas , Ratas Endogámicas
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