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1.
Trop Anim Health Prod ; 53(3): 341, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34089388

RESUMO

Three experiments were conducted to evaluate the frequency of visits to a mineral feeder equipped with radio-frequency identification (RFID). In Exp. 1, twelve heifers (Braford, Brahman, and White Angus; n = 4/breed) were fitted with RFID ear tags and placed into a pasture with access to a RFID-equipped mineral feeder. Number of visits were greater (P ≤ 0.05) during daytime than the night period. Brahman and Braford heifers favored (P ≤ 0.05) daytime than night period. White Angus heifers did not display a specific period preference (P = 0.32). In Exp. 2, Black Angus and Brahman cows (n = 15 and 19, respectively) were placed into a pasture with access to a RFID-equipped mineral feeder. Brahman cows made more (P < 0.01) visits to the mineral feeder than Black Angus cows. There were no breed differences on the number of visits during the morning (P = 0.25) and night (P ≤ 0.25) periods, but Brahman cows made more (P ≤ 0.05) visits to the mineral feeder in the afternoon period than Black Angus cows. In Exp. 3, the location of the mineral feeder was tested using 3 groups of Bos indicus-influenced heifers (n = 12/group). The mineral feeder was moved weekly within pasture. The number of visits to the mineral feeder differed for each location (P < 0.001) with visits being greatest when mineral feeder was placed near supplement and water, followed by center of the pasture, and lastly in the shade.


Assuntos
Dispositivo de Identificação por Radiofrequência , Animais , Bovinos , Suplementos Nutricionais , Feminino , Minerais , Tecnologia
2.
Mol Psychiatry ; 23(2): 222-230, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27550844

RESUMO

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.


Assuntos
Canais de Cloreto/genética , Síndromes Epilépticas/genética , Deficiência Intelectual/genética , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Canais de Cloreto/metabolismo , Epilepsia/genética , Síndromes Epilépticas/fisiopatologia , Família , Feminino , Genes Ligados ao Cromossomo X , Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação em Linhagem Germinativa , Humanos , Deficiência Intelectual/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Oócitos , Linhagem , Fenótipo , Síndrome , Substância Branca/fisiopatologia , Xenopus laevis
3.
BMC Vet Res ; 15(1): 27, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646904

RESUMO

BACKGROUND: Producing graduates for a breadth of sectors is a priority for veterinary science programs. Undergraduate career intentions represent de-facto 'outcome' measures of admissions policy and curricula design, as intentions are strong predictors of eventual behaviour. Informed by Ajzen's Theory of Planned Behaviour, this study aimed to identify if contextually relevant attitudes and self-ratings affect student intentions for veterinary career sectors. RESULTS: Survey responses from 844 students enrolled in five Australian veterinary programs in 2014 were analysed. Intention was measured for biomedical research/academia, industry, laboratory animal medicine, public health/government/diagnostic laboratory services, mixed practice, intensive animal production, companion animal practice, not work in the veterinary profession, and business/entrepreneurship. Hierarchical multiple linear regression analysis enabled comparison of explanation of variance in intent by demographics, animal handling experience, species preference, and attitudes to aspects of veterinary work. Career sector intentions were highest for mixed or companion animal clinical practice, then business/entrepreneurship, then non-clinical sectors. Overall, intent was explained to a greater extent by species preferences than by animal experience, attitudes to aspects of veterinary work and demographics (with the exception of mixed practice intent) with gender having no significant effect. Several variables exerted negative effects on career intent for less popular career sectors. CONCLUSION: Ajzen's Theory of Planned Behaviour (TPB) provides a framework to increase understanding of and predict career sector intentions. Incorporation of attitude and self-efficacy measures in our study revealed preference for species types contributes greatly to career sector intentions for veterinary students, particularly for the more popular practice based sectors. Importantly, specific species preferences and other attitudes can have a negative effect on intent for non-aligned veterinary sectors. Further research is required to identify additional attitudes and/or beliefs to better explain variance in intent for less popular career sectors. Veterinary admissions processes may benefit from utilising the TPB framework. Identified effects revealed by this study may stimulate innovation in marketing, recruitment, admissions and curricular design, such as timing and role modelling, to utilise positive effects and mitigate against negative effects identified for sectors requiring greater representation of career intent in the student body.


Assuntos
Escolha da Profissão , Medicina Veterinária , Atitude , Austrália , Estudos Transversais , Demografia , Feminino , Humanos , Masculino , Medicina Veterinária/tendências , Recursos Humanos
4.
Anaesthesia ; 74(12): 1524-1533, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31538329

RESUMO

The recent development of electronic logbooks with secure off-device data storage provides a rich resource for research. We present the largest analysis of anaesthetic logbooks to date, with data from 494,235 cases logged by 964 anaesthetists over a 4-year period. Our analysis describes and compares the annual case-load and supervision levels of different grades of anaesthetists across the UK and Republic of Ireland. We calculated the number of cases undertaken per year by grade (median (IQR [range]) core trainees = 388 (252-512 [52-1204]); specialist trainees = 344 (228-480 [52-1144]); and consultants = 328 (204-500 [52-1316]). Overall, the proportion of cases undertaken with direct consultant supervision was 56.7% and 41.6% for core trainees and specialist trainees, respectively. The proportion of supervised cases reduced out-of-hours, for both core trainees (day 93.5%, evening 86.3%, night 78.6%) and specialist trainees (day 81.0%, evening 67.7%, night 56.4%).


Assuntos
Anestesiologistas/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Anestesiologia , Competência Clínica , Bases de Dados Factuais , Humanos , Irlanda , Estudos Retrospectivos , Reino Unido
7.
Nature ; 491(7422): 79-82, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23128227

RESUMO

The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of meteorites. Processes active in the space environment produce 'space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere, and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon and the asteroid Itokawa determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.

8.
Anaesthesia ; 73(7): 825-831, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29633251

RESUMO

We conducted a 5-year retrospective cohort study on women undergoing caesarean section to investigate factors influencing the operating room-to-incision interval. Time-to-event analysis was performed for category-1 caesarean section using a Cox proportional hazards regression model. Covariates included: anaesthetic technique; body mass index; age; parity; time of delivery; and gestational age. Binary logistic regression was performed for 5-min Apgar score ≥ 7. There were 677 women who underwent category-1 caesarean section and who met the entry criteria. Unadjusted median (IQR [range]) operating room-to-incision intervals were: epidural top-up 11 (7-17 [0-87]) min; general anaesthesia 6 (4-11 [0-69]) min; spinal 13 (10-20 [0-83]) min; and combined spinal-epidural 24 (13-35 [0-75]) min. Cox regression showed general anaesthesia to be the most rapid method with a hazard ratio (95%CI) of 1.97 (1.60-2.44; p < 0.0001), followed by epidural top-up (reference group), spinal anaesthesia 0.79 (0.65-0.96; p = 0.02) and combined spinal-epidural 0.48 (0.35-0.67; p < 0.0001). Underweight and overweight body mass indexes were associated with longer operating room-to-incision intervals. General anaesthesia was associated with fewer 5-min Apgar scores ≥ 7 with an odds ratio (95%CI) of 0.28 (0.11-0.68; p < 0.01). There was no difference in neonatal outcomes between the first and fifth quintiles for operating room-to-incision intervals. General anaesthesia is associated with the most rapid operating room-to-incision interval for category-1 caesarean section, but is also associated with worse short term neonatal outcomes. Longer operating room-to-incision intervals were not associated with worse neonatal outcomes.


Assuntos
Anestesia Obstétrica/estatística & dados numéricos , Cesárea/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Adulto , Fatores Etários , Anestesia Epidural , Anestesia Geral , Raquianestesia , Índice de Apgar , Índice de Massa Corporal , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Salas Cirúrgicas/estatística & dados numéricos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
9.
Rapid Commun Mass Spectrom ; 31(22): 1947-1956, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28857369

RESUMO

RATIONALE: The rapid screening of volatile organic compounds (VOCs) by direct analysis has potential applications in the areas of food and flavour science. Currently, the technique of choice for VOC analysis is gas chromatography/mass spectrometry (GC/MS). However, the long chromatographic run times and elaborate sample preparation associated with this technique have led a movement towards direct analysis techniques, such as selected ion flow tube mass spectrometry (SIFT-MS), proton transfer reaction mass spectrometry (PTR-MS) and electronic noses. The work presented here describes the design and construction of a Venturi jet-pump-based modification for a compact mass spectrometer which enables the direct introduction of volatiles for qualitative and quantitative analysis. METHODS: Volatile organic compounds were extracted from the headspace of heated vials into the atmospheric pressure chemical ionization source of a quadrupole mass spectrometer using a Venturi pump. Samples were analysed directly with no prior sample preparation. Principal component analysis (PCA) was used to differentiate between different classes of samples. RESULTS: The interface is shown to be able to routinely detect problem analytes such as fatty acids and biogenic amines without the requirement of a derivatisation step, and is shown to be able to discriminate between four different varieties of cheese with good intra and inter-day reproducibility using an unsupervised PCA model. Quantitative analysis is demonstrated using indole standards with limits of detection and quantification of 0.395 µg/mL and 1.316 µg/mL, respectively. CONCLUSIONS: The described methodology can routinely detect highly reactive analytes such as volatile fatty acids and diamines without the need for a derivatisation step or lengthy chromatographic separations. The capability of the system was demonstrated by discriminating between different varieties of cheese and monitoring the spoilage of meats.


Assuntos
Análise de Alimentos/métodos , Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/isolamento & purificação , Animais , Pressão Atmosférica , Aminas Biogênicas/análise , Queijo/análise , Análise por Conglomerados , Desenho de Equipamento , Ácidos Graxos/análise , Espectrometria de Massas/instrumentação , Carne/análise , Análise Multivariada , Suínos , Compostos Orgânicos Voláteis/química
10.
J R Army Med Corps ; 163(2): 140-145, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27451422

RESUMO

INTRODUCTION: The aim of this paper was to examine levels of post-traumatic growth (PTG) in a sample of the UK veterans who had received treatment for post-traumatic stress disorder (PTSD). METHODS: The study followed-up 149 UK veterans after they had completed standardised treatment for PTSD provided by Combat Stress. Data had previously been collected on a range of mental health outcomes before treatment, and then repeated 6 months after the end of treatment. For the current study, participants completed the post-traumatic growth inventory (PTGI) measure. Analysis was conducted to explore levels of PTG and whether there were any relationships between pretreatment and post-treatment ratings of mental health and PTG. RESULTS: The mean score on the PTGI was 32.6. Evidence of a treatment effect on levels of PTG was observed. There appeared to be a relationship between improvements in symptoms of PTSD and depression and higher levels of PTG. CONCLUSIONS: This study observed the presence of PTG following exposure to traumatic events within a sample of the UK veterans following their treatment for PTSD. PTG scores were moderately low in comparison to similar studies in the USA.


Assuntos
Adaptação Psicológica , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Adulto , Ira , Ansiedade/psicologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Tratamento Domiciliar , Transtornos de Estresse Pós-Traumáticos/terapia , Reino Unido
11.
Clin Genet ; 89(1): 120-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25807999

RESUMO

We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein-truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in MAOA (p.R45W). Affected males had borderline-mild ID, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of 'serotonergic' symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID with paroxysmal behavioural symptoms. It can be screened for with serum/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Deficiência Intelectual/genética , Monoaminoxidase/deficiência , Agressão , Sequência de Aminoácidos , Transtornos Disruptivos, de Controle do Impulso e da Conduta/tratamento farmacológico , Exoma , Genes Ligados ao Cromossomo X , Estudos de Associação Genética , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Loci Gênicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Terapia de Alvo Molecular , Monoaminoxidase/química , Monoaminoxidase/genética , Linhagem , Fenótipo , Conformação Proteica , Alinhamento de Sequência
12.
Clin Radiol ; 70(11): 1185-91, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26169580

RESUMO

AIM: To examine the feasibility of using automated lexical analysis in conjunction with machine learning to create a means of objectively characterising radiology reports for quality improvement. MATERIALS AND METHODS: Twelve lexical parameters were quantified from the collected reports of four radiologists. These included the number of different words used, number of sentences, reading grade, readability, usage of the passive voice, and lexical metrics of concreteness, ambivalence, complexity, passivity, embellishment, communication and cognition. Each radiologist was statistically compared to the mean of the group for each parameter to determine outlying report characteristics. The reproducibility of these parameters in a given radiologist's reporting style was tested by using only these 12 parameters as input to a neural network designed to establish the authorship of 60 unknown reports. RESULTS: Significant differences in report characteristics were observed between radiologists, quantifying and characterising deviations of individuals from the group reporting style. The 12 metrics employed in a neural network correctly identified the author in each of 60 unknown reports tested, indicating a robust parametric signature. CONCLUSION: Automated and quantifiable methods can be used to analyse reporting style and provide impartial and objective feedback as well as to detect and characterise significant differences from the group. The parameters examined are sufficiently specific to identify the authors of reports and can potentially be useful in quality improvement and residency training.


Assuntos
Radiologia/normas , Projetos de Pesquisa/normas , Osso e Ossos/diagnóstico por imagem , Competência Clínica/normas , Compreensão , Estudos de Viabilidade , Humanos , Idioma , Sistemas Computadorizados de Registros Médicos/normas , Variações Dependentes do Observador , Melhoria de Qualidade/normas , Cintilografia
13.
Anim Reprod Sci ; 262: 107433, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368654

RESUMO

Retrospective analyses were performed on a dataset of 1188 fall-calving, Brangus cow-calf pairs. Analyses 1 sorted cows according to their initial body condition score (BCS < 5 vs. ≥ 5) and whether they received (SUP) or not (NOSUP) prepartum supplementation of protein and energy. Analyses 2 sorted cows according to their calving BCS (BCS < 5 or ≥ 5) and BCS change from calving until the start of the breeding season (lost, maintained, or gained). Cows were not estrus synchronized and were assigned to natural breeding for 90 days. Prepartum supplementation increased (P = 0.04) pregnancy percentage in cows with initial BCS < 5 but not (P = 0.20) with initial BCS ≥ 5. Calf weaning weight was greatest (P ≤ 0.04) for calves born from SUP cows with an initial BCS ≥ 5 and did not differ (P ≥ 0.56) among all remaining groups. Among cows with calving BCS < 5, pregnancy percentage were less (P = 0.05) for cows that lost vs. maintained/gained BCS. Postpartum BCS change did not (P ≥ 0.16) impact pregnancy percentage of cows calving at BCS ≥ 5. Calf weaning weight increased (P < 0.01) for cows calving with BCS ≥ 5 vs. < 5 and was not impacted (P = 0.47) by postpartum BCS change. Therefore, precalving supplementation improved reproduction of cows with BCS below optimal and weaning weight of calves born from cows with BCS above optimal, whereas calving BCS was the major factor affecting postpartum BCS change and cow reproductive performance.


Assuntos
Dieta , Reprodução , Gravidez , Feminino , Bovinos , Animais , Dieta/veterinária , Estudos Retrospectivos , Parto , Ração Animal/análise , Suplementos Nutricionais , Peso Corporal
14.
Clin Anat ; 26(5): 556-63, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23408730

RESUMO

An interventional cohort comparison study with pretesting and post-testing in semesters 1 and 2 was undertaken of 159 medical students in year 3 of the MMBS course at the University of Adelaide in 2010. The intervention comprised the provision of a number of additional online resources in semester 2. Students' views on online anatomy were also sought by a questionnaire delivered at the end of semesters 1 and 2 and via a small focus group at the end of the study. Anatomy assessment results after the introduction of online anatomy were compared with a total of three control semesters in 2009 and 2010. There was >90% broad agreement before the intervention that wet specimens, tutors and discussions with other students helped students learn anatomy. After the intervention, these views remained, but there was additionally >90% broad agreement that text books helped them learn anatomy, that they had good access to anatomical specimens, and there was less agreement that lectures helped. The intervention left students' views on online anatomy largely unchanged and made no significant difference to summative assessment scores. Focus group discussions revealed that students want anatomy tutors to help direct them to reputable and relevant sites. The provision of more online resources in anatomy did not affect student views or learning outcomes. While students may need help from tutors in selecting appropriate online resources, wet specimens, textbooks, and discussions with tutors and other students remain the preferred means of learning anatomy.


Assuntos
Anatomia/educação , Sistemas On-Line , Estudos de Coortes , Avaliação Educacional , Humanos , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
15.
Spat Spatiotemporal Epidemiol ; 42: 100521, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35934330

RESUMO

Severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) continues to effect communities across the world. One way to combat these effects is to enhance our collective ability to remotely monitor community spread. Monitoring SARS-CoV-2 in wastewater is one approach that enables researchers to estimate the total number of infected people in a region; however, estimates are often made at the sewershed level which may mask the geographic nuance required for targeted interdiction efforts. In this work, we utilize an apportioning method to compare the spatial and temporal trends of daily case count with the temporal pattern of viral load in the wastewater at smaller units of analysis within Austin, TX. We find different lag-times between wastewater loading and case reports. Daily case reports for some locations follow the temporal trend of viral load more closely than others. These findings are then compared to socio-demographic characteristics across the study area.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Humanos , Análise Espaço-Temporal , Águas Residuárias
16.
Mar Pollut Bull ; 173(Pt A): 112896, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601248

RESUMO

Profiles of 33 PFAS analytes and 12 essential and non-essential trace elements were measured in livers of stranded common dolphins (Delphinus delphis) from New Zealand. PFAS concentrations reported were largely comparable to those measured in other marine mammal species globally and composed mostly of long-chain compounds including perfluorooctanesulfonic acid (PFOS), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA) and perfluorooctanesulfonamide (FOSA). PFAS profiles did not vary significantly by location, body condition, or life history. Notably, significant positive correlations were observed within respective PFAS and trace elements. However, only negative correlations were evident between these two contaminant types, suggesting different exposure and metabolic pathways. Age-associated concentrations were found for PFTrDA and four trace elements, i.e. silver, mercury, cadmium, selenium, indicating differences in the bioaccumulation biomagnification mechanisms. Overall, our results contribute to global understanding of accumulation of PFAS by offering first insights of PFAS exposure in cetaceans living within South Pacific Australasian waters.


Assuntos
Ácidos Alcanossulfônicos , Golfinhos Comuns , Fluorocarbonos , Oligoelementos , Animais , Monitoramento Ambiental , Fluorocarbonos/análise , Nova Zelândia , Oligoelementos/análise
17.
J Exp Med ; 165(5): 1237-51, 1987 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-3494806

RESUMO

Unlike parental NZB or NZW mice, (NZB X NZW)F1 mice exhibit a lupus-like disease characterized by high serum levels of IgG antinuclear antibodies and a fatal immune-complex glomerulonephritis. At least three unlinked gene loci can be distinguished in NZW mice that conceivably contribute to a T cell-dependent autoimmune disease, including the MHC (H-2z) and the T cell receptor alpha and beta chain gene complexes. We undertook an (NZB X NZW)F1 X NZB backcross to determine the relative contribution of these NZW genes to lupus-like renal disease and autoantibody production in F1 mice. The incidence of severe renal disease and elevated levels of IgG antibodies to dsDNA and histone in the backcross mice was approximately half of that observed in (NZB X NZW)F1 mice. Furthermore, there was a strong correlation between the presence of the NZW H-2z haplotype and lupus-like disease in backcross mice. Approximately 90% of backcross mice with disease carried the NZW H-2z locus compared with 16% of mice without disease; nearly 90% of H-2d/z mice expressed severe autoimmune disease. In contrast, no association was apparent between the presence of the NZW T cell receptor alpha chain gene complex or beta chain gene complex and severe renal disease or autoantibody production. Thus, the NZW MHC or gene(s) linked to this locus appear to be the only dominant NZW genetic contribution to F1 disease.


Assuntos
Camundongos Endogâmicos/genética , Alelos , Animais , Anticorpos Antinucleares/imunologia , Formação de Anticorpos , Doenças Autoimunes/genética , Genótipo , Antígenos H-2/genética , Humanos , Imunoglobulina G/imunologia , Lúpus Eritematoso Sistêmico/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Receptores de Antígenos de Linfócitos T/genética
18.
J Exp Med ; 186(11): 1933-8, 1997 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9382891

RESUMO

A single amino acid residue, Gln136, located within the connecting peptide domain of Cbeta controls the ability of the alpha/beta TCR to transmit a full signal. TCRs in which this Cbeta residue is mutated to Phe, the residue found in TCR-gamma, are unresponsive to antigenic ligands. Interestingly, this Cbeta residue is either polar or charged in every species studied thus far, including the trout and the skate. In contrast, the analogous residue in Cgamma is always hydrophobic. In spite of their compromised antigen responsiveness, the mutant TCR complex contains the CD3-gamma, -delta, -epsilon, and -zeta chains, and undergoes zeta chain phosphorylation and ZAP-70 recruitment. However, the biological response of the mutant TCR could be rescued with a calcium ionophore, implying that mutant TCRs are defective in generating a calcium-mediated signal. The implications of the differences between Cbeta and Cgamma are considered.


Assuntos
Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Transdução de Sinais/fisiologia , Sequência de Aminoácidos , Animais , Complexo CD3/fisiologia , Cálcio/fisiologia , Ionóforos/farmacologia , Mamíferos/genética , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Tirosina Quinases/metabolismo , Complexo Receptor-CD3 de Antígeno de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/química , Receptores de Antígenos de Linfócitos T gama-delta/química , Proteínas Recombinantes de Fusão/imunologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Proteína-Tirosina Quinase ZAP-70
19.
J Exp Med ; 169(4): 1405-19, 1989 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-2538552

RESUMO

We have generated an mAb, RR3-15, that recognizes murine TCRs containing the V beta 11 domain. Using this antibody to stain peripheral T cells, we have demonstrated that V beta 11-bearing T cells are largely absent from strains of mice that express the class II MHC molecule, I-E. Studies with F1 mice demonstrate that this effect is dominant, consistent with tolerance. The clonal deletion of V beta 11-bearing T cells appears to occur intrathymically, as immature but not mature V beta 11+ T cells are present in the thymus of I-E-bearing mice. Examination of B6 x DBA/2 recombinant inbred strains demonstrates that the expression of I-E molecules is necessary for the clonal deletion of V beta 11-bearing T cells, but that other non-MHC genes control the clonal deletion process, as well. Paradoxically, only a small fraction of V beta 11+ T cell hybridomas are I-E reactive.


Assuntos
Anticorpos Monoclonais/imunologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Antígenos de Histocompatibilidade Classe II/imunologia , Complexo Principal de Histocompatibilidade , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Haplótipos , Camundongos , Receptores de Antígenos de Linfócitos T alfa-beta , Timo/citologia
20.
J Exp Med ; 175(6): 1613-21, 1992 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-1316931

RESUMO

Mls-1 is an endogenous superantigen that leads to in vivo deletion and in vitro stimulation of T cell receptor (TCR) V beta 6-, 7-, 8.1-, and 9-expressing cells. The MA/MyJ mouse deletes the identical set of TCR from its mature T cell repertoire; however, it does not contain Mtv-7, the murine mammary tumor provirus (MMTV), whose sag gene encodes Mls-1. Interestingly, the superantigen activity of this mouse strain segregates with a new mammary tumor provirus, Mtv-43, not seen in other inbred strains. The predicted amino acid sequence of the sag gene of Mtv-43 was compared with that of Mtv-7. Strikingly, the COOH terminus of the two molecules is very similar, while all other MMTV-encoded superantigens differ 100% in this segment.


Assuntos
Linfócitos B/imunologia , Genes Virais , Vírus do Tumor Mamário do Camundongo/genética , Antígenos Secundários de Estimulação de Linfócitos/genética , Provírus/genética , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia , Envelhecimento , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Sequência de Bases , Deleção Cromossômica , Cruzamentos Genéticos , Camundongos , Camundongos Endogâmicos , Camundongos Mutantes , Antígenos Secundários de Estimulação de Linfócitos/análise , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Reação em Cadeia da Polimerase/métodos , Receptores de Antígenos de Linfócitos T/metabolismo , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Baço/crescimento & desenvolvimento , Baço/imunologia
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