RESUMEN
We experimentally realize the Peregrine soliton in a highly particle-imbalanced two-component repulsive Bose-Einstein condensate in the immiscible regime. The effective focusing dynamics and resulting modulational instability of the minority component provide the opportunity to dynamically create a Peregrine soliton with the aid of an attractive potential well that seeds the initial dynamics. The Peregrine soliton formation is highly reproducible, and our experiments allow us to separately monitor the minority and majority components, and to compare with the single component dynamics in the absence or presence of the well with varying depths. We showcase the centrality of each of the ingredients leveraged herein. Numerical corroborations and a theoretical basis for our findings are provided through three-dimensional simulations emulating the experimental setting and via a one-dimensional analysis further exploring its evolution dynamics.
RESUMEN
Typically, energy levels change without bifurcating in response to a change of a control parameter. Bifurcations can lead to loops or swallowtails in the energy spectrum. The simplest quantum Hamiltonian that supports swallowtails is a nonlinear 2×2 Hamiltonian with nonzero off-diagonal elements and diagonal elements that depend on the population difference of the two states. This work implements such a Hamiltonian experimentally using ultracold atoms in a moving one-dimensional optical lattice. Self-trapping and nonexponential tunneling probabilities, a hallmark signature of band structures that support swallowtails, are observed. The good agreement between theory and experiment validates the optical lattice system as a powerful platform to study, e.g., Josephson junction physics and superfluidity in ring-shaped geometries.
RESUMEN
BACKGROUND AND PURPOSE: Sensory neuronopathy is a cardinal feature of cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these patients with CANVAS and seven healthy controls. METHODS: We compared the ultrasound cross-sectional area of median, ulnar, sural and tibial nerves of 14 patients with CANVAS with 14 healthy controls and 14 age- and gender-matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross-sectional areas of patients with CANVAS and neuropathy with the reference values of our laboratory control population. RESULTS: The nerve cross-sectional area of patients with CANVAS was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites (P < 0.001). Conversely, the nerve cross-sectional areas in the upper limb were larger in neuropathy controls than healthy controls (P < 0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one patient with CANVAS. DISCUSSION: Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy.
Asunto(s)
Vestibulopatía Bilateral/diagnóstico por imagen , Ataxia Cerebelosa/diagnóstico por imagen , Nervios Periféricos/diagnóstico por imagen , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Adulto , Anciano , Anatomía Transversal , Axones/patología , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Reflejo Vestibuloocular , Trastornos de la Sensación/diagnóstico por imagen , Trastornos de la Sensación/etiología , Síndrome , UltrasonografíaRESUMEN
OBJECTIVE: The syndrome of cerebellar ataxia with bilateral vestibulopathy was delineated in 2004. Sensory neuropathy was mentioned in 3 of the 4 patients described. We aimed to characterize and estimate the frequency of neuropathy in this condition, and determine its typical MRI features. METHODS: Retrospective review of 18 subjects (including 4 from the original description) who met the criteria for bilateral vestibulopathy with cerebellar ataxia. RESULTS: The reported age at onset range was 39-71 years, and symptom duration was 3-38 years. The syndrome was identified in one sibling pair, suggesting that this may be a late-onset recessive disorder, although the other 16 cases were apparently sporadic. All 18 had sensory neuropathy with absent sensory nerve action potentials, although this was not apparent clinically in 2, and the presence of neuropathy was not a selection criterion. In 5, the loss of pinprick sensation was virtually global, mimicking a neuronopathy. However, findings in the other 11 with clinically manifest neuropathy suggested a length-dependent neuropathy. MRI scans showed cerebellar atrophy in 16, involving anterior and dorsal vermis, and hemispheric crus I, while 2 were normal. The inferior vermis and brainstem were spared. CONCLUSIONS: Sensory neuropathy is an integral component of this syndrome. It may result in severe sensory loss, which contributes significantly to the disability. The MRI changes are nonspecific, but, coupled with loss of sensory nerve action potentials, may aid diagnosis. We propose a new name for the condition: cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS).
Asunto(s)
Ataxia Cerebelosa/complicaciones , Polineuropatías/complicaciones , Trastornos de la Sensación/complicaciones , Potenciales de Acción , Adulto , Anciano , Encéfalo/patología , Encéfalo/fisiopatología , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Evaluación de la Discapacidad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Polineuropatías/patología , Polineuropatías/fisiopatología , Reflejo Anormal/fisiología , Estudios Retrospectivos , Trastornos de la Sensación/patología , Trastornos de la Sensación/fisiopatología , SíndromeRESUMEN
With the ultimate goal of developing a therapeutic cancer vaccine, we encapsulated the Her-2/neu peptide p369-377 in poly(lactide-co-glycolide) microspheres. This formulation was found to effectively elicit CD8+ cytotoxic T cell (CTL) responses in an HLA-A*0201 transgenic mouse model. In contrast, immunization with either peptide alone or peptide formulated in incomplete Freund's adjuvant (IFA) failed to elicit such CTL responses. Responses induced by the peptide-microsphere formulation were found to peak at approximately 6 weeks post-immunization, and were enhanced by delivering increased doses of peptide and with repeated administrations over time. Co-administration of the peptide-microspheres with adjuvants, including granulocyte-macrophage colony stimulating factor, MPL adjuvant and select synthetic Toll-Like Receptor 4 ligands, the aminoalkyl glucosaminide-4 phosphates, significantly augmented CTL responses. These studies provide important guidance for the design of human clinical trials of microsphere vaccines in terms of optimal peptide-microsphere formulation, vaccination regimen, vaccine dose, and adjuvant selection.
Asunto(s)
Adyuvantes Inmunológicos , Vacunas contra el Cáncer/síntesis química , Vacunas contra el Cáncer/inmunología , Citotoxicidad Inmunológica , Microesferas , Fragmentos de Péptidos/inmunología , Receptor ErbB-2/inmunología , Linfocitos T Citotóxicos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Vacunas contra el Cáncer/administración & dosificación , Células Cultivadas , Femenino , Humanos , Ratones , Ratones Transgénicos , Fragmentos de Péptidos/administración & dosificación , Poliglactina 910/administración & dosificación , Receptor ErbB-2/administración & dosificación , Bazo/citología , Bazo/inmunologíaRESUMEN
Natural blood-borne antigen-presenting cells (APCs) were tested for their ability to augment antigen presentation for SIV vaccines. Fibrocytes and monocyte-derived dendritic cells (DCs) were isolated from multiple Macaca fascicularis. Macaque fibrocytes displayed the characteristic cellular morphology and stained positive for CD34 and collagen, as observed in human and murine fibrocytes. Macaque DCs were generated from monocytes by culturing in granulocyte-macrophage colony stimulating factor and interleukin-4 (IL-4). Two days after maturation, cells were enriched for the DC marker CD83. Fibrocytes and DCs were each transfected with green fluorescence protein expression plasmids or DNA expression vectors encoding all of the SIVmne structural and regulatory genes. Autologous DCs were re-infused into macaques subcutaneously (sc) following transfection; mixing with recombinant SIV antigens or inactivated whole SIV in vitro; or mock-treatment. Autologous monocyte-derived DCs pulsed with whole inactivated SIV were re-infused and elicited cellular and/or humoral responses in vivo in eight of ten vaccinated macaques.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Formación de Anticuerpos , Células Presentadoras de Antígenos/virología , Antígenos CD , Antígenos CD34/análisis , Antígenos Virales/análisis , Células Cultivadas , Células Dendríticas/inmunología , Células Dendríticas/trasplante , Células Dendríticas/virología , Genes Reporteros , Proteínas Fluorescentes Verdes , Humanos , Inmunidad Celular , Inmunoglobulinas/análisis , Proteínas Luminiscentes/análisis , Macaca fascicularis , Glicoproteínas de Membrana/análisis , Monocitos/inmunología , Transfección , Trasplante Autólogo , Antígeno CD83RESUMEN
All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag-Pol particles (n = 4). Following intrarectal challenge with SIVmne, all macaques became infected. Three monkeys immunized with DNA alone maintained low plasma virus loads by 1 year post-challenge; the fourth exhibited high virus loads and significant CD4+ cell decline. Two of the DNA plus boost and three control macaques had high virus loads and associated CD4+ cell decline. Both vaccine protocols elicited antibodies and comparable helper T-cell proliferative responses to gp160. Cytokine mRNA levels in activated peripheral blood mononuclear cells (PBMC) taken at time of challenge suggested a dominant T helper (Th) 1 state in three DNA-immunized and one protein-boosted macaque, which correlated with low virus loads and high CD4+ cell counts post-challenge.
Asunto(s)
Vacunas contra el SIDA/inmunología , ADN Viral/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Vacunas de ADN/inmunología , Animales , Recuento de Linfocito CD4 , Clonación Molecular , Proteínas de Fusión gag-pol/genética , Proteínas de Fusión gag-pol/inmunología , Vectores Genéticos , Proteínas gp160 de Envoltorio del VIH/genética , Proteínas gp160 de Envoltorio del VIH/inmunología , Inmunización/veterinaria , Macaca fascicularis , Masculino , Ratones , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/genética , Linfocitos T Colaboradores-Inductores/inmunología , Vacunas Atenuadas/inmunología , Carga ViralRESUMEN
To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 microg recombinant gp160 plus 250 microg recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in both groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Thl responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3+ CD8+) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines.
Asunto(s)
Vacunas contra el SIDAS/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Vacunas de ADN/inmunología , Animales , Células COS , Macaca fascicularis , Carga ViralRESUMEN
Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10(-1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly.
Asunto(s)
Macaca nemestrina/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Animales , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Ensayo de Inmunoadsorción Enzimática , Femenino , Inmunohistoquímica , Ganglios Linfáticos/virología , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , Provirus/aislamiento & purificación , Proteínas de los Retroviridae/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/diagnóstico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/aislamiento & purificación , Carga Viral , Proteínas Virales/aislamiento & purificaciónRESUMEN
To gain insight into the unique pathogenicity of simian immunodeficiency virus (SIV) variant PBj14, which produces an acutely lethal enteropathic syndrome in infected pigtail macaques, we investigated the cell and tissue tropisms of a highly pathogenic biologic clone (bcl.3) of SIVsmmPBj14. To compare the relative amount of viral antigen in lymphoid organs of infected macaques we used an objective semiquantitative immunohistochemistry (sQIHC) assay. We found that in all animals viral antigen load was greater in alimentary-associated lymphoid tissues (gut-associated lymphoid tissue [GALT], tonsil, mesenteric and retropharyngeal lymph nodes) than in non-alimentary-associated lymphoid tissues (spleen, thymus, inguinal and axillary lymph nodes). Moreover, in six of nine animals examined, virus load in GALT was greater than that in any other lymphoid tissue. To determine whether the acute pathogenicity and prolific replication of SIVsmmPBj14 might be explained by a broader in vivo cell tropism than is typical of SIVs, we used cell subset separation and nested PCR. We found that the primary target cells in mesenteric lymph node for SIVsmmPBj14 were CD4+ T lymphocytes. However, the virus also infected macrophages, as well as CD8+ T cells and B cells, albeit at low frequencies. These results suggest that alimentary lymphoid tissue localization rather than unusual cell phenotype tropism distinguishes the singular pathogenesis of SIVsmmPBj14.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Animales , Axila , Linfocitos B/virología , Femenino , Citometría de Flujo , Ingle , Inmunohistoquímica , Hibridación in Situ , Intestinos , Ganglios Linfáticos/virología , Macaca nemestrina , Macrófagos/virología , Masculino , Reacción en Cadena de la Polimerasa , Provirus/aislamiento & purificación , ARN Viral/análisis , Bazo/virología , Subgrupos de Linfocitos T/virología , Timo/virología , Factores de Tiempo , Tropismo , Carga Viral , Replicación ViralRESUMEN
Evidence suggests that patients suffering from Parkinson's Disease (PD) demonstrate less sequence learning in the serial reaction time (SRT) task devised by Nissen and Bullemer (1987). One of the problems with this task is that it is motor intensive and, given the motor difficulties which characterize Parkinson's disease (e.g., tremor, impaired facility of movement, rigidity, and loss of postural reflexes), allows the possibility that patients with PD are capable of sequence learning but are simply unable to demonstrate this through a decrease in reaction time over trials. The present study examined the performance of patients with PD and healthy controls, matched for verbal fluency, on a verbal version of the SRT task where the standard button-pressing response was replaced by a spoken response. Thirteen nondementing patients with PD and 11 healthy controls were administered the SRT task. The PD group demonstrated less sequence learning than the controls and this was independent of age and severity of illness. The results add support to those studies which have found impaired sequence learning using the standard form of the SRT task.
Asunto(s)
Aprendizaje/fisiología , Enfermedad de Parkinson/psicología , Tiempo de Reacción/fisiología , Aprendizaje Seriado/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
We report on two patients each with tonic, contraversive partial ocular tilt reactions due to unilateral cerebellar lesions: one patient had had a caudal cerebellar hemorrhage, the other a posterior inferior cerebellar artery territory infarct. Both patients had tonic contraversive conjugate ocular torsion; one had skew deviation; neither had a head tilt. One patient had no specific neurologic deficit apart from the conjugate ocular torsion, which was first suspected because of a deviation of the subjective visual horizontal. These observations imply that the ocular tilt reaction (OTR), a brainstem otolith-ocular reflex of probable utricular origin, is under the inhibitory control of the ipsilateral caudal cerebellum, possibly the nodulus, and that a patient with a cerebellar infarct can present with imbalance as the only neurologic symptom and with conjugate ocular torsion as the only specific neurologic sign.
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Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/fisiopatología , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatología , Ojo/fisiopatología , Lóbulo Parietal , Anciano , Ojo/diagnóstico por imagen , Ojo/patología , Fondo de Ojo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Infection of pigtail macaques with SIVsmmPBj14, biological clone 3 (SIV-PBj14-bc13), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. We used this simian immunodeficiency virus (SIV) model as a rapid and rigorous challenge to evaluate the efficacy of two SIV Env vaccine strategies. Groups of four pigtail macaques were immunized four times over a 25-week span with either a recombinant Semliki Forest virus expressing the SIV-PBj14 Env gp160 (SFV-SIVgp160) or purified recombinant SIV-PBj14 gp120 (rgp120) in SBN-1 adjuvant. Antibody titers to SIV Env developed in all immunized animals (mean peak titers prior to challenge, 1:1,700 for SFV-SIV gp 160 and 1:10,500 for rgp120), but neither neutralizing antibodies nor SIV-specific T-cell proliferative responses were detectable in any of the vaccinees. All macaques were challenged with a 100% infectious, 75% fatal dose of SIV-PBj14-bc13 at week 26. Three of four control animals died of acute SIV-PBj14 syndrome on days 12 and 13. By contrast, all four SFV-SIVgp160-immunized animals and three of the four rgp120-immunized animals were protected from lethal disease. While all virus-challenged animals became infected, symptoms of the SIV-PBj14 syndrome were more severe in controls than in vaccinees. Mean virus titers in plasma at 13 days postchallenge were approximately 10-fold lower in vaccinated than control animals. However, there was no apparent correlation between survival and levels of peripheral blood mononuclear cell-associated culturable virus, provirus load, or any antiviral immunologic parameter examined. The results indicate that while immunization with SFV-SIVgp160 and rgp120 did not protect against virus infection, these Env vaccines did lower the virus load in plasma and protect against the lethal SIV-PBj14 challenge.
Asunto(s)
Productos del Gen env/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , Glicoproteínas de Membrana , Vacunas contra el SIDAS/inmunología , Virus de los Bosques Semliki/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Virus de la Inmunodeficiencia de los Simios/inmunología , Proteínas del Envoltorio Viral , Animales , Anticuerpos Antivirales/inmunología , Secuencia de Bases , Recuento de Linfocito CD4 , Línea Celular , Células Cultivadas , Cricetinae , ADN Viral , Femenino , Productos del Gen env/genética , Vectores Genéticos/genética , Proteína gp120 de Envoltorio del VIH/genética , Humanos , Inmunidad Celular , Macaca nemestrina , Ratones , Datos de Secuencia Molecular , Virus de los Bosques Semliki/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/mortalidad , Virus de la Inmunodeficiencia de los Simios/química , Virus de la Inmunodeficiencia de los Simios/crecimiento & desarrollo , Vacunas Sintéticas/inmunologíaRESUMEN
We compared the efficacy of immunization with either simian immunodeficiency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag-Env), or whole inactivated virus (WIV), with or without recombinant live vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone BK28. Vaccination elicited high titers of syncytium-inhibiting and anti-Env (gp120/gp160) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-immunized macaques developed anticell (HuT78) antibodies. After homologous low-dose intravenous virus challenge, we used frequency of virus isolation, provirus burden, and change in antibody titers to define four levels of resistance to SIV infection as follows. (i) No infection ("sterilizing" immunity) was induced only in WIV-immunized animals. (ii) Abortive infection (strong immunity) was defined when virus or provirus were detected early in the postchallenge period but not thereafter and no evidence of virus or provirus was detected in terminal tissues. This response was observed in two animals (one VV-Env and one Gag-Env). (iii) Suppression of infection (incomplete or partial immunity) described a gradient of virus suppression manifested by termination of viremia, declining postchallenge antibody titers, and low levels (composite mean = 9.1 copies per 10(6) cells) of provirus detectable in peripheral blood mononuclear cells or lymphoid tissues at termination (40 weeks postchallenge). This response occurred in the majority (8 of 12) of subunit-vaccinated animals. (iv) Active infection (no immunity) was characterized by persistent virus isolation from blood mononuclear cells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 10(6) cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three VV-Gag-Env-immunized animals. The results of this study restate the protective effect of inactivated whole virus vaccines produced in heterologous cells but more importantly demonstrate that a gradient of suppression of challenge virus growth, reflecting partial resistance to SIV infection, is induced by subunit vaccination. The latter finding may be pertinent to studies with human immunodeficiency virus vaccines, in which it is plausible that vaccination may elicit significant suppression of virus infection and pathogenicity rather than sterilizing immunity.
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Inmunoterapia Activa , Glicoproteínas de Membrana , Síndrome de Inmunodeficiencia Adquirida del Simio/prevención & control , Vacunación , Vacunas Sintéticas , Proteínas del Envoltorio Viral , Vacunas Virales , Animales , Anticuerpos Antivirales/sangre , Secuencia de Bases , Sangre/microbiología , Células Cultivadas , Productos del Gen gag/genética , Productos del Gen gag/inmunología , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/inmunología , Humanos , Inmunización Secundaria , Activación de Linfocitos , Macaca mulatta , Datos de Secuencia Molecular , Pruebas de Neutralización , Provirus/aislamiento & purificación , Proteínas Recombinantes/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Virus de la Inmunodeficiencia de los Simios/crecimiento & desarrollo , Virus Vaccinia/genéticaRESUMEN
We describe three patients with spontaneous pendular oscillation of the eye during funduscopy. All patients had blurred, shimmering vision or oscillopsia, exacerbated by concentration, reading, or trivial head movements, and had a history of unsteadiness. Examination revealed a fine head tremor, mild unsteadiness, absent vestibulo-ocular reflex (VOR), and otherwise normal neurologic and ocular motor findings. Rigid immobilization of the head abolished the retinal oscillations. Simultaneous precision recordings of head and eye movements showed that the eye movement was in the compensatory direction to the head tremor but that, in contrast to normal VOR, it was in phase error. We conclude that the essential head tremor was provoking oscillopsia and retinal oscillation because of the absence of VOR. Recognizing the association of head tremor with absent VOR is important since in all these patients the presence of this pendular pseudonystagmus on ophthalmoscopy raised the diagnostic possibility of brainstem disease.