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1.
J Gen Virol ; 103(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35762858

RESUMO

Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus-free or to have only exogenous variants of KoRV with low rates of KoRV-induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV-induced disease such as lymphoma. In this study we use a combination of sequencing technologies, Illumina RNA sequencing of 'southern' (south Australian) and 'northern' (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of 'southern' (South Australian and Victorian animals) to retrieve full-length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication-competent KoRV, are not in fact KoRV-free but harbour defective, presumably endogenous, 'RecKoRV' variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV-induced disease.


Assuntos
Gammaretrovirus , Phascolarctidae , Infecções por Retroviridae , Animais , Austrália/epidemiologia , Gammaretrovirus/genética , Retroviridae/genética , Infecções por Retroviridae/veterinária
2.
Exp Brain Res ; 240(10): 2715-2723, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36074176

RESUMO

The grating orientation discrimination task (GOT) is a sensitive and reliable measure of tactile spatial resolution, or acuity. We used the GOT in three experiments to investigate the effects of hand posture and hand visibility on spatial acuity. Participant sex and experimental design were also manipulated. Healthy adult participants received brief touches to their index fingertips of grated, domed objects. Their task was to decide whether the gratings ran 'along' or 'across' their finger. Measures of the smallest grating width for which participants could reliably discriminate between orientations were recorded as threshold. Experiment 1 evaluated the effect of two- versus one-interval discrimination, hand used and participant sex. Experiments 2 and 3 evaluated the effects of hand visibility (visible or covered) and hand posture (in front or to the side). Females were better than males; the two-interval task resulted in lower thresholds than the one-interval task; and left and right hand thresholds were not significantly different. Most importantly, while hand visibility did not have a significant effect on the task, thresholds were affected by hand posture-worse when the hand was oriented to the side of the body than in front. These results replicate previously reported effects of sex (or finger size), but failed to replicate the so-called 'visual enhancement of touch' (VET) effect. We also report a meta-analysis of 27 VET studies, finding a significant effect of 'non-informative' vision on tactile perception. Our novel finding is that hand posture affects tactile acuity.


Assuntos
Percepção do Tato , Tato , Adulto , Feminino , Mãos , Humanos , Masculino , Postura , Percepção Espacial
3.
J Neurophysiol ; 123(2): 587-599, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891523

RESUMO

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala.NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.


Assuntos
Complexo Nuclear Basolateral da Amígdala/metabolismo , Neurônios GABAérgicos/metabolismo , Interneurônios/metabolismo , Plasticidade Neuronal/fisiologia , Ocitocina/fisiologia , Receptores de GABA-B/metabolismo , Receptores de Ocitocina/metabolismo , Transmissão Sináptica/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Ocitocina/administração & dosagem , Ocitocina/antagonistas & inibidores , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores de GABA-B/efeitos dos fármacos , Receptores de Ocitocina/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
4.
Proc Natl Acad Sci U S A ; 112(36): 11199-204, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26283351

RESUMO

The ability to make decisions based on data, with its inherent uncertainties and variability, is a complex and vital skill in the modern world. The need for such quantitative critical thinking occurs in many different contexts, and although it is an important goal of education, that goal is seldom being achieved. We argue that the key element for developing this ability is repeated practice in making decisions based on data, with feedback on those decisions. We demonstrate a structure for providing suitable practice that can be applied in any instructional setting that involves the acquisition of data and relating that data to scientific models. This study reports the results of applying that structure in an introductory physics laboratory course. Students in an experimental condition were repeatedly instructed to make and act on quantitative comparisons between datasets, and between data and models, an approach that is common to all science disciplines. These instructions were slowly faded across the course. After the instructions had been removed, students in the experimental condition were 12 times more likely to spontaneously propose or make changes to improve their experimental methods than a control group, who performed traditional experimental activities. The students in the experimental condition were also four times more likely to identify and explain a limitation of a physical model using their data. Students in the experimental condition also showed much more sophisticated reasoning about their data. These differences between the groups were seen to persist into a subsequent course taken the following year.


Assuntos
Tomada de Decisões/fisiologia , Estudantes/psicologia , Ensino/métodos , Pensamento/fisiologia , Algoritmos , Avaliação Educacional , Humanos , Física/educação , Reprodutibilidade dos Testes , Pesquisa/educação , Universidades
5.
Intern Med J ; 44(5): 508-11, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24816311

RESUMO

This retrospective case series identifies the largest cohort of non-O1, non-O139 Vibrio cholerae bacteraemia in an Australian population from 2000 to 2013. We examine the risk factors, epidemiology, clinical presentations and mortality of non-O1, non-O139 V. cholerae bacteraemia in Victoria and compare them with published cases in the literature. This case series highlights the pathogenic potential of non-O1, non-O139 V. cholerae and identifies possible associations with host (underlying chronic liver disease and malignancy) and environmental factors (contaminated water supply and raw seafood). Clinicians should be aware of the morbidity and mortality associated with invasive non-O1, non-O139 V. cholerae infections, particularly in immunocompromised patients.


Assuntos
Bacteriemia/microbiologia , Vibrio cholerae não O1/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Animais , Bacteriemia/epidemiologia , Comorbidade , Culinária , Suscetibilidade a Doenças , Feminino , Microbiologia de Alimentos , Gastroenterite/complicações , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Ostreidae/microbiologia , Estudos Retrospectivos , Fatores de Risco , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/microbiologia , Sorotipagem , Natação , Vibrio cholerae não O1/classificação , Vitória/epidemiologia , Microbiologia da Água , Poluição da Água
6.
Intern Med J ; 43(2): 110-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23185970

RESUMO

Vancomycin remains a clinically useful antibiotic despite the advent of several alternative drugs. Optimising vancomycin therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacodynamic parameters in the case of vancomycin, an area under the concentration time curve/minimum inhibitory concentration ratio of ≥400. Vancomycin monitoring methods can be categorised into four categories: empiric trough concentrations; linear regression analysis (one-compartment model), population methods and Bayesian estimation procedures. Although the empiric trough concentrations and population methods are easy to use and require minimal resources, there are large differences in the published vancomycin model parameters. This demonstrates that there is great variance in pharmacokinetic parameters between the models and a single vancomycin model cannot be applied to all patient populations. The linear regression and Bayesian methods recommended more accurate dosage regimens; however, they require additional resources such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offered additional advantages such as calculation of doses based on a single-serum concentration and optimisation of the patient's previous pharmacokinetic data to determine subsequent dosage regimens. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy than the empiric trough concentrations and population methods. We recommend the use of these programs providing there is appropriate expertise available to make appropriate recommendations.


Assuntos
Monitoramento de Medicamentos/métodos , Vancomicina/farmacocinética , Vancomicina/uso terapêutico , Animais , Teorema de Bayes , Monitoramento de Medicamentos/tendências , Humanos , Modelos Lineares , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/tratamento farmacológico , Resistência a Vancomicina/efeitos dos fármacos , Resistência a Vancomicina/fisiologia
7.
Musculoskelet Surg ; 107(2): 239-252, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35598252

RESUMO

INTRODUCTION: Glenoid bone loss is a commonly encountered problem in complex primary and revision shoulder arthroplasty. Addressing glenoid bone loss is critical to avoid complications like early loosening, impingement, notching and instability. A large number of techniques like bone grafting using autograft or allograft, eccentric reaming, augmented base plates, patient-specific instrumentations and custom-made implants are available to tackle bone loss. MATERIALS AND METHODS: We prospectively collected the data of all patients with glenoid defects undergoing primary or revision reverse shoulder replacement between 2004 and 2017. This included demographic data, ranges of motion, Constant-Murley score and Subjective Shoulder Value (SSV). A pre-operative CT scan was done as well to plan the surgery and calculate the glenoid version. At each follow-up, the clinical function and shoulder scores were assessed. Additionally, the radiographs were assessed for graft incorporation, evidence of lysis and calculation of glenoid version. RESULTS: Between 2004 and 2017, 37 patients underwent glenoid bone grafting during reverse shoulder arthroplasty. Average age was 72 years (range 46-88). Indications for surgery were cuff tear arthropathy (6 patients); revision of failed other prosthesis (23); primary osteoarthritis (4); rheumatoid arthritis (3); and second-stage revision for infection (1). The glenoid defect was contained in 24 patients, and therefore, impaction graft with a combination of bone graft substitute and/or humeral head autograft was performed. In 13 patients the glenoid defect was severe and uncontainable and therefore a graft-implant composite glenoid was implanted using humeral head autograft or allograft. Average follow-up was 3.6 years (range 1-10). Mean Constant score improved from 34 before surgery to 63 after surgery. Mean SSV score improved from 0.9/10 to 8.3/10. Active movements improved significantly with forward elevation increasing from 54° to 123°; abduction from 48° to 123°; external rotation from 24° to 38°; internal rotation from 57° to 70°. Radiographs at final follow-up showed no radiolucencies around the glenoid component and no evidence of loosening of the implant. In 2 cases there was a grade I notching. There was 100% survivorship at the last follow-up. CONCLUSION: Impaction bone grafting along with structural grafting when required is an effective and reproducible way of managing severe glenoid bone loss. This technique gives consistent and good clinical and radiological results.


Assuntos
Artroplastia do Ombro , Cavidade Glenoide , Articulação do Ombro , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Ombro/métodos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Transplante Ósseo/métodos , Resultado do Tratamento , Estudos Retrospectivos , Amplitude de Movimento Articular , Cavidade Glenoide/cirurgia
8.
Heredity (Edinb) ; 109(1): 19-28, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22434012

RESUMO

Seabirds are highly vagile and can disperse up to thousands of kilometers, making it difficult to identify the factors that promote isolation between populations. The endemic Hawaiian petrel (Pterodroma sandwichensis) is one such species. Today it is endangered, and known to breed only on the islands of Hawaii, Maui, Lanai and Kauai. Historical records indicate that a large population formerly bred on Molokai as well, but this population has recently been extirpated. Given the great dispersal potential of these petrels, it remains unclear if populations are genetically distinct and which factors may contribute to isolation between them. We sampled petrels from across their range, including individuals from the presumably extirpated Molokai population. We sequenced 524 bp of mitochondrial DNA, 741 bp from three nuclear introns, and genotyped 18 microsatellite loci in order to examine the patterns of divergence in this species and to investigate the potential underlying mechanisms. Both mitochondrial and nuclear data sets indicated significant genetic differentiation among all modern populations, but no differentiation was found between historic samples from Molokai and modern birds from Lanai. Population-specific nonbreeding distribution and strong natal philopatry may reduce gene flow between populations. However, the lack of population structure between extirpated Molokai birds and modern birds on Lanai indicates that there was substantial gene flow between these populations and that petrels may be able to overcome barriers to dispersal prior to complete extirpation. Hawaiian petrel populations could be considered distinct management units, however, the dwindling population on Hawaii may require translocation to prevent extirpation in the near future.


Assuntos
Aves/genética , Espécies em Perigo de Extinção , Fluxo Gênico , Variação Genética , Animais , DNA Mitocondrial/genética , Deriva Genética , Genética Populacional , Genótipo , Havaí , Repetições de Microssatélites/genética , Dados de Sequência Molecular
9.
Nanotechnology ; 23(15): 155302, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22563584

RESUMO

Anodic porous alumina nanostructures have been fabricated with tapered and cylindrical pores with a spacing of 100 and 200 nm and depth of 180-500 nm. The porous nanostructures were replicated into polymer films to create a moth-eye anti-reflecting surface by a roll-to-roll UV replication process. The angle dependent optical transmission of the resulting polymer films exhibited up to a 2% increase in transmission at a normal angle and up to a 5% increase in transmission at a 70° angle of incidence to an equivalent film with a surface replicated from polished aluminum. No significant difference was observed between the optical performance of moth-eye surfaces formed from cylindrical and tapered nano-pores.

10.
PLoS One ; 17(8): e0273337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36040903

RESUMO

Critical thinking is the process by which people make decisions about what to trust and what to do. Many undergraduate courses, such as those in biology and physics, include critical thinking as an important learning goal. Assessing critical thinking, however, is non-trivial, with mixed recommendations for how to assess critical thinking as part of instruction. Here we evaluate the efficacy of assessment questions to probe students' critical thinking skills in the context of biology and physics. We use two research-based standardized critical thinking instruments known as the Biology Lab Inventory of Critical Thinking in Ecology (Eco-BLIC) and Physics Lab Inventory of Critical Thinking (PLIC). These instruments provide experimental scenarios and pose questions asking students to evaluate what to trust and what to do regarding the quality of experimental designs and data. Using more than 3000 student responses from over 20 institutions, we sought to understand what features of the assessment questions elicit student critical thinking. Specifically, we investigated (a) how students critically evaluate aspects of research studies in biology and physics when they are individually evaluating one study at a time versus comparing and contrasting two and (b) whether individual evaluation questions are needed to encourage students to engage in critical thinking when comparing and contrasting. We found that students are more critical when making comparisons between two studies than when evaluating each study individually. Also, compare-and-contrast questions are sufficient for eliciting critical thinking, with students providing similar answers regardless of if the individual evaluation questions are included. This research offers new insight on the types of assessment questions that elicit critical thinking at the introductory undergraduate level; specifically, we recommend instructors incorporate more compare-and-contrast questions related to experimental design in their courses and assessments.


Assuntos
Estudantes , Pensamento , Humanos , Aprendizagem , Física
11.
Sci Rep ; 12(1): 10520, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732872

RESUMO

Quantum sensors based on cold atoms are being developed which produce measurements of unprecedented accuracy. Due to shifts in atomic energy levels, quantum sensors often have stringent requirements on their internal magnetic field environment. Typically, background magnetic fields are attenuated using high permeability magnetic shielding, with the cancelling of residual and introduction of quantisation fields implemented with coils inside the shield. The high permeability shield, however, distorts all magnetic fields, including those generated inside the sensor. Here, we demonstrate a solution by designing multiple coils overlaid on a 3D-printed former to generate three uniform and three constant linear gradient magnetic fields inside the capped cylindrical magnetic shield of a cold atom interferometer. The fields are characterised in-situ and match their desired forms to high accuracy. For example, the uniform transverse field, Bx, deviates by less than 0.2% over more than 40% of the length of the shield. We also map the field directly using the cold atoms and investigate the potential of the coil system to reduce bias from the quadratic Zeeman effect. This coil design technology enables targeted field compensation over large spatial volumes and has the potential to reduce systematic shifts and noise in numerous cold atom systems.

13.
Environ Sci Technol ; 45(3): 882-9, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21171562

RESUMO

The paper presents the results of a study conducted to investigate indoor air quality within residential dwellings in Lao PDR. Results from PM(10), CO, and NO(2) measurements inside 167 dwellings in Lao PDR over a five month period (December 2005-April 2006) are discussed as a function of household characteristics and occupant activities. Extremely high PM(10) and NO(2) concentrations (12 h mean PM(10) concentrations 1275 ± 98 µg m(-3) and 1183 ± 99 µg m(-3) in Vientiane and Bolikhamxay provinces, respectively; 12 h mean NO(2) concentrations 1210 ± 94 µg m(-3) and 561 ± 45 µg m(-3) in Vientiane and Bolikhamxay, respectively) were measured within the dwellings. Correlations, ANOVA analysis (univariate and multivariate), and linear regression results suggest a substantial contribution from cooking and smoking. The PM(10) concentrations were significantly higher in houses without a chimney compared to houses in which cooking occurred on a stove with a chimney. However, no significant differences in pollutant concentrations were observed as a function of cooking location. Furthermore, PM(10) and NO(2) concentrations were higher in houses in which smoking occurred, suggestive of a relationship between increased indoor concentrations and smoking (0.05 < p < 0.10). Resuspension of dust from soil floors was another significant source of PM(10) inside the house (634 µg m(-3), p < 0.05).


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Monóxido de Carbono/análise , Habitação/estatística & dados numéricos , Dióxido de Nitrogênio/análise , Material Particulado/análise , Atividades Cotidianas , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Monitoramento Ambiental , Feminino , Humanos , Laos , Masculino , Tamanho da Partícula
14.
Indoor Air ; 21(1): 25-35, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20846211

RESUMO

UNLABELLED: This article presents the results of a study on the association between measured air pollutants and the respiratory health of resident women and children in Lao PDR, one of the least developed countries in Southeast Asia. The study, commissioned by the World Health Organisation, included PM(10), CO and NO(2) measurements made inside 181 dwellings in nine districts within two provinces in Lao PDR over a 5-month period (12/05-04/06), and respiratory health information (via questionnaires and peak expiratory flow rate (PEFR) measurements) for all residents in the same dwellings. Adjusted odds ratios were calculated separately for each health outcome using binary logistic regression. There was a strong and consistent positive association between NO(2) and CO for almost all questionnaire-based health outcomes for both women and children. Women in dwellings with higher measured NO(2) had more than triple of the odds of almost all of the health outcomes, and higher concentrations of NO(2) and CO were significantly associated with lower PEFR. This study supports a growing literature confirming the role of indoor air pollution in the burden of respiratory disease in developing countries. The results will directly support changes in health and housing policy in Lao PDR. PRACTICAL IMPLICATIONS: This is the first study that investigated indoor air quality and its impact within residential dwellings in Lao PDR, which is one of the poorest and least developed countries in south-east Asia, with a life-expectancy of 56 years in 2008. While there have been other studies published on indoor air quality in other developing countries, the situation in Laos is different because the majority of houses in Laos used wood stoves, and therefore, emissions from wood burning are the dominant sources of indoor air pollution. In other countries, and studies, while emission from wood burning was investigated, wood was rarely the main or the only fuel used, as the houses used in addition (or solely) dung, kerosene or coal. The study quantified, for the first time, concentrations in houses two provinces in Laos PDR and shed light on the impact of human activities and urban design on pollutant concentrations and respiratory health. This study contributes to the accumulation of evidence to provide more reliable estimates of risk and a more informed basis for decision-making by concerned governments and communities.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Pneumopatias/etiologia , Pulmão/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Países em Desenvolvimento , Nível de Saúde , Humanos , Lactente , Laos , Razão de Chances , Testes de Função Respiratória
15.
RSC Adv ; 11(31): 19000-19011, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35478661

RESUMO

Sodium tungsten bronze (Na x WO3) is a promising alternative plasmonic material to nanoparticulate gold due to its strong plasmonic resonances in both the visible and near-infrared (NIR) regions. Additional benefits include its simple production either as a bulk or a nanoparticle material at a relatively low cost. In this work, plasmonic Na x WO3 nanoparticles were introduced and mixed into the nanoparticulate zinc oxide electron transport layer of a water processed poly(3-hexylthiophene):phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) nanoparticle (NP) based organic photovoltaic device (NP-OPV). The power conversion efficiency of NP-OPV devices with Na x WO3 NPs added was found to improve by around 35% compared to the control devices, attributed to improved light absorption, resulting in an enhanced short circuit current and fill factor.

16.
Clin Infect Dis ; 51(9): e61-4, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20868278

RESUMO

Intravascular large B cell lymphoma (IVLBCL) is a rare cause of pyrexia of unknown origin. Because of its protean clinical manifestations, diagnosis is elusive and is often made postmortem. We report here a case of IVLBCL that evaded diagnosis despite multiple investigations in vivo for pyrexia of unknown origin over a 5‐month period.


Assuntos
Febre de Causa Desconhecida/etiologia , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Neoplasias Vasculares/complicações , Neoplasias Vasculares/diagnóstico , Idoso , Antígenos CD20/análise , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células B/patologia , Microscopia , Neoplasias Vasculares/patologia
17.
Clin Infect Dis ; 50(5): 672-8, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-20121412

RESUMO

BACKGROUND: . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. METHODS: Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women. RESULTS: Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20; P= .001; mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L; P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). CONCLUSIONS: Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.


Assuntos
Deficiência de IgG/epidemiologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Influenza Humana/patologia , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
18.
J Exp Med ; 162(5): 1709-14, 1985 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-2414389

RESUMO

The major histocompatibility complex class I HLA molecules are the primary determinants recognized by allogeneic cytotoxic T lymphocytes (CTL), and serve as restricting elements for CTL recognition of viral, chemical, or minor histocompatibility antigens. HLA-Aw69 is a naturally occurring hybrid class I molecule that we have used to investigate the regions of class I antigens involved in human CTL recognition. HLA-Aw69 appears to have resulted from an exon shuffle between two closely related class I genes: the alpha 1 domain of HLA-Aw69 is identical to that of HLA-Aw68, while the alpha 2 and alpha 3 domains are identical to HLA-A2. The determinants recognized by human allogeneic CTL clones specific for HLA-A2, -Aw68, and/or -Aw69 fall into three patterns: (a) CTL determinants are located on both the alpha 1 and alpha 2 domains; (b) interaction of the alpha 1 and alpha 2 domains results in new combinatorial determinants; (c) interaction of the alpha 1 and alpha 2 domains in the hybrid molecule results in the loss of CTL determinants that are present on both parental molecules. Thus, using human CTL clones, target cells, and HLA molecules, we show that the interaction of the alpha 1 and alpha 2 domains alters CTL determinants in ways not directly predictable from primary structure.


Assuntos
Citotoxicidade Imunológica , Epitopos/análise , Antígenos HLA/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Linfócitos B/imunologia , Linhagem Celular , Células Clonais , Humanos , Relação Estrutura-Atividade
19.
J Exp Med ; 183(4): 1707-18, 1996 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8666928

RESUMO

The CD45 transmembrane glycoprotein has been shown to be a protein phosphotyrosine phosphatase and to be important in signal transduction in T and B lymphocytes. We have employed gene targeting to create a strain of transgenic mice that completely lacks expression of all isoforms of CD45. The spleens from CD45-null mice contain approximately twice the number of B cells and one fifth the number of T cells found in normal controls. The increase in B cell numbers is due to the specific expansion of two B cell subpopulations that express high levels of immunoglobulin (IgM) staining. T cell development is significantly inhibited in CD45-null animals at two distinct stages. The efficiency of the development of CD4-CD8- thymocytes into CD4+ CD8+ thymocytes is reduced by twofold, subsequently the frequency of successful maturation of the double positive population into mature, single positive thymocytes is reduced by a further four- to fivefold. In addition, we demonstrate that CD45-null thymocytes are severely impaired in their apoptotic response to cross-linking signals via T cell receptor (TCR) in fetal thymic organ culture. In contrast, apoptosis can be induced normally in CD45-null thymocytes by non-TCR-mediated signals. Since both positive and negative selection require signals through the TCR complex, these findings suggest that CD45 is an important regulator of signal transduction via the TCR complex at multiple stages of T cell development. CD45 is absolutely required for the transmission of mitogenic signals via IgM and IgD. By contrast, CD45-null B cells proliferate as well as wild-type cells to CD40-mediated signals. The proliferation of B cells in response to CD38 cross-linking is significantly reduced but not abolished by the CD45-null mutation. We conclude that CD45 is not required at any stage during the generation of mature peripheral B cells, however its loss reveals a previously unrecognized role for CD45 in the regulation of certain subpopulations of B cells.


Assuntos
Antígenos CD , Células-Tronco Hematopoéticas/imunologia , Antígenos Comuns de Leucócito/metabolismo , Linfócitos/imunologia , Transdução de Sinais , Timo/crescimento & desenvolvimento , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Animais , Antígenos de Diferenciação/metabolismo , Linfócitos B/imunologia , Antígenos CD40/metabolismo , Imunoglobulina D/biossíntese , Imunoglobulina M/biossíntese , Antígenos Comuns de Leucócito/genética , Ativação Linfocitária , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , N-Glicosil Hidrolases/metabolismo , Técnicas de Cultura de Órgãos , Receptores de Antígenos/metabolismo , Seleção Genética , Baço/citologia , Baço/imunologia , Subpopulações de Linfócitos T/imunologia , Timo/citologia
20.
J Exp Med ; 185(3): 385-91, 1997 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-9053439

RESUMO

The crucial immunological function of the classical human major histocompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptides to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molecules, HLA-E, -F, and -G, is still a mystery. The specific expression of HLA-G in placental trophoblast suggests an important role for this molecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognition by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregulation is balanced by the expression of HLA-G, thus preventing damage to the placenta. Here, we describe the partial inhibition of NK lysis of the MHC class I negative cell line LCL721.221 upon HLA-G transfection. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibition can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK inhibition by HLA-G via NKAT3 may contribute to the survival of the fetal semiallograft in the mother during pregnancy.


Assuntos
Antígenos HLA/fisiologia , Antígenos de Histocompatibilidade Classe I/fisiologia , Células Matadoras Naturais/imunologia , Receptores Imunológicos/antagonistas & inibidores , Células Cultivadas , Antígenos HLA-A/fisiologia , Antígenos HLA-B/fisiologia , Antígenos HLA-G , Humanos , Receptores KIR , Receptores KIR3DL1 , Transfecção
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