new-tools-to-expand-regulatory-t-cells-from-hiv-1-infected-individuals

New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals

CD4+ Regulatory T cells (Tregs) are potent immune modulators and serve an important function in human immune homeostasis. Depletion of Tregs has led to ...

Ragon Institute of MGH, MIT, and Harvard

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El prop&oacute;sito de este estudio fue determinar el cumplimiento de la vigilancia del embarazo postmolar en nuestra poblaci&oacute;n indigente.

Postmolar vigilancia en un centro de enfermedad trofobl&aacute;stica que sirve a las mujeres indigentes.

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The purpose of this study was to determine compliance with postmolar pregnancy surveillance in our indigent population.

Postmolar surveillance at a trophoblastic disease center that serves indigent women.

Le but de cette &eacute;tude &eacute;tait de d&eacute;terminer la conformit&eacute; &agrave; la surveillance de la grossesse postmolar dans notre population indigente.

Postmolar surveillance dans un centre de maladie trophoblastique qui dessert les femmes indigentes.

Postmolar &#xDC;berwachung an einem Trophoblasterkrankung Zentrum, das bed&#xFC;rftige Frauen dient.

Lo scopo di questo studio era di determinare la conformit&agrave; con sorveglianza postmolar gravidanza nella nostra popolazione indigente.

Postmolar sorveglianza presso un centro di malattia trofoblastica che serve le donne indigenti.

To identify the most effective dosing regimen for indigent patients with low-risk gestational trophoblastic neoplasia (GTN) at high risk of noncompliance.

Management of low-risk gestational trophoblastic neoplasia in indigent women.

Pour identifier le sch&eacute;ma posologique plus efficace pour les patients indigents avec faible risque la n&eacute;oplasie gestationnelle trophoblastique (GTN) &agrave; haut risque de non-conformit&eacute;.

Gestion de la n&eacute;oplasie trophoblastique gestationnelle faible risque chez les femmes indigentes.

Per identificare il regime di somministrazione pi&ugrave; efficace per i pazienti indigenti con basso rischio neoplasia trofoblastica gestazionale (GTN) ad alto rischio di non conformit&agrave;.

Gestione di basso rischio neoplasia trofoblastica gestazionale nelle donne indigenti.

The aim of this study is to evaluate the effect of oral dexamethasone in attenuating palmar-plantar erythrodysesthesias (PPE) in Doxil-treated patients for gynecologic malignancies.

Oral dexamethasone attenuates Doxil-induced palmar-plantar erythrodysesthesias in patients with recurrent gynecologic malignancies.

Le but de cette &eacute;tude est d&#39;&eacute;valuer l&#39;effet de la dexam&eacute;thasone par voie orale dans l&#39;absorption du erythrodysesthesias-plantaire (PPE) chez les patients trait&eacute;s Doxil pour les cancers gyn&eacute;cologiques.

Dexam&eacute;thasone orale att&eacute;nue erythrodysesthesias-plantaire Doxil-induite chez les patients atteints de cancers gyn&eacute;cologiques r&eacute;currentes.

Lo scopo di questo studio &egrave; valutare l&#39;effetto di Desametasone orale nell&#39;attenuare palmar-plantar erythrodysesthesias (PPE) in pazienti trattati con Doxil per neoplasie ginecologiche.

Desametasone orale attenua erythrodysesthesias palmar-plantar Doxil-indotta in pazienti con neoplasie ginecologiche ricorrenti.

In urban environments, raccoons (Procyon lotor) may act as reservoirs for an array of pathogenic organisms, presenting spillover risks for human, domestic animal, and captive (zoo) animal populations. Over 5 yr, 159 raccoons from a high-density raccoon population in St. Louis, Missouri (USA), were surveyed for exposure to canine distemper virus (CDV), canine adenovirus 1 (CAV-1); feline parvovirus (FPV; =feline panleukopenia), and several serovars of Leptospira interrogans. Exposure to each of the viruses and two Leptospira serovars (grippotyphosa and icterohemorrhagiae) was detected (prevalence of CDV = 54.1%; FPV = 49.7%; CAV-1 = 6.9%; L. interrogans icterohemorrhagiae = 8.9%; L. interrogans grippotyphosa = 6.3%). Eighty percent of raccoons showed evidence of exposure to at least one of the five primary pathogens, and 39% were positive for multiple species. Among the viruses, there was a significant co-occurrence of CDV and CAV-1. Longitudinal data on a subset of animals revealed that among individuals who were diagnosed as seropositive on first capture, 33-100% became seronegative for the pathogen of interest when reexamined at a later date. Thus, free-ranging urban raccoons have been exposed to multiple infectious agents, some of which may pose risks to humans and to nonvaccinated domestic and captive animal populations.

A serologic assessment of exposure to viral pathogens and Leptospira in an urban raccoon (Procyon lotor) population inhabiting a large zoological park.

Dans les environnements urbains, ratons laveurs (Procyon lotor) peuvent servir de r&eacute;servoirs &agrave; une diversit&eacute; d&#39;organismes pathog&egrave;nes, pr&eacute;sentant des risques de d&eacute;bordement pour homme et animal domestique en captivit&eacute; (zoo de) populations animales. Sur une p&eacute;riode de 5 ans, 159 raton laveur d&#39;une population de raton laveur haute densit&eacute; &agrave; St. Louis, Missouri (USA), ont &eacute;t&eacute; interrog&eacute;s pour l&#39;exposition au virus de la maladie de carr&eacute; (CDV), l&#39;ad&eacute;novirus 1 (CAV-1) ; parvovirose f&eacute;line (FPV; = panleucop&eacute;nie f&eacute;line) et plusieurs s&eacute;rotypes de Leptospira interrogans. L&#39;exposition &agrave; chacun des virus et des deux s&eacute;rotypes de Leptospira (grippotyphosa et icterohemorrhagiae) a &eacute;t&eacute; d&eacute;tect&eacute;e (pr&eacute;valence de CDV = 54,1 % ; FPV = 49,7 % ; CAV-1 = 6,9 % ; L. interrogans icterohemorrhagiae = 8,9 % ; L. interrogans grippotyphosa = 6,3 %). Quatre-vingt pour cent des ratons laveurs montraient des signes d&#39;exposition au moins un des cinq principaux agents pathog&egrave;nes, et 39 % &eacute;taient positifs pour plusieurs esp&egrave;ces. Parmi les virus, il y avait une importante cooccurrence de CDV et CAV-1. Les donn&eacute;es longitudinales sur un sous-ensemble des animaux a r&eacute;v&eacute;l&eacute; que parmi les personnes diagnostiqu&eacute;es comme s&eacute;ropositifs sur la premi&egrave;re capture, 33-100 % sont devenus s&eacute;ron&eacute;gatif pour le pathog&egrave;ne d&#39;int&eacute;r&ecirc;t lorsque r&eacute;examin&eacute;e &agrave; une date ult&eacute;rieure. Ainsi, &eacute;lev&eacute;es en libert&eacute; urbaines ratons laveurs ont &eacute;t&eacute; expos&eacute;s &agrave; plusieurs agents infectieuses, dont certains peuvent poser des risques pour les humains et les populations d&#39;animaux domestiques ou captifs travailleurs.

Une &eacute;valuation s&eacute;rologique d&#39;exposition aux agents pathog&egrave;nes et Leptospira dans une population urbaine raton laveur (Procyon lotor) vivant dans un grand parc zoologique.

In ambienti urbani, procioni (Procyon lotor) possono agire come serbatoi per una matrice di organismi patogeni, che presentano rischi di ricaduta per umani e animali domestici in cattivit&agrave; (zoo) delle popolazioni animali. Sono state intervistate oltre 5 yr, 159 procioni da una popolazione di procione ad alta densit&agrave; in St. Louis, Missouri (USA), per l&#39;esposizione al virus del cimurro canino (CDV), l&#39;adenovirus canino 1 (CAV-1); parvovirus felino (FPV; = panleucopenia felina) e diversi sierotipi di Leptospira interrogans. L&#39;esposizione a ognuno dei virus e due sierotipi di Leptospira (grippotyphosa e icterohemorrhagiae) &egrave; stato rilevato (prevalenza di CDV = 54,1%; FPV = 49,7%; CAV-1 = 6,9%; L. interrogans icterohemorrhagiae = 8,9%; L. interrogans grippotyphosa = 6,3%). L&#39;ottanta per cento dei procioni hanno mostrato evidenza di esposizione di almeno uno dei cinque patogeni primari, e il 39% erano positivi per molteplici specie. Tra i virus, c&#39;&egrave; stata una significativa co-occorrenza di CDV e CAV-1. Dati longitudinali su un sottoinsieme degli animali ha rivelato che tra gli individui che sono stati diagnosticati come sieropositivi sulla prima cattura, 33-100% &egrave; diventato sieronegativi per l&#39;agente patogeno di interesse quando riesaminati in una data successiva. Cos&igrave;, Stray procioni urbani sono stati esposti a pi&ugrave; agenti infettivi, alcuni dei quali possono comportare rischi per gli esseri umani e delle popolazioni animali domestiche e in cattivit&agrave; vaccinate.

Una valutazione sierologica di esposizione ad agenti patogeni virali e Leptospira in una popolazione urbana procione (Procyon lotor) che abitano un grande parco zoologico.

Vasospasmo cerebrale &egrave; delle principali cause di decesso e invalidit&agrave; dopo emorragia subaracnoidea (SAH); Tuttavia, mancano le terapie cliniche per limitare lo sviluppo di vasospasmo cerebrale. Sebbene i fattori causali sottostanti lo sviluppo di vasospasmo cerebrale sono capiti male, lo stress ossidativo contribuisce alla progressione della malattia. Nel presente studio, curcumina (150 o 300 mg/kg) protetti contro lo sviluppo di vasospasmo cerebrale e infarto cerebrale secondario limitato dopo SAH nei topi. L&#39;effetto protettivo della curcumina &egrave; stata associata con una significativa attenuazione dell&#39;espressione genica infiammatoria e la perossidazione dei lipidi all&#39;interno della corteccia cerebrale e l&#39;arteria cerebrale media. Nonostante la capacit&agrave; della curcumina di limitare lo sviluppo di vasospasmo cerebrale e infarto secondario, esito comportamentale non &egrave; stato migliorato, che indica una dissociazione tra il vasospasmo cerebrale e l&#39;esito neurologico. Insieme, questi dati indicano un ruolo romanzo per la curcumina come possibile terapia adiuvante dopo SAH, sia per prevenire lo sviluppo di vasospasmo cerebrale e per ridurre il danno ossidativo cerebrale dopo infarto secondario.

Curcumina attenua l&#39;infiammazione vascolare e vasospasmo cerebrale dopo emorragia subaracnoidea nei topi.

Cerebral vasospasm is a major cause of death and disability after subarachnoid hemorrhage (SAH); however, clinical therapies to limit the development of cerebral vasospasm are lacking. Although the causative factors underlying the development of cerebral vasospasm are poorly understood, oxidative stress contributes to disease progression. In the present study, curcumin (150 or 300 mg/kg) protected against the development of cerebral vasospasm and limited secondary cerebral infarction after SAH in mice. The protective effect of curcumin was associated with a significant attenuation of inflammatory gene expression and lipid peroxidation within the cerebral cortex and the middle cerebral artery. Despite the ability of curcumin to limit the development of cerebral vasospasm and secondary infarction, behavioral outcome was not improved, indicating a dissociation between cerebral vasospasm and neurologic outcome. Together, these data indicate a novel role for curcumin as a possible adjunct therapy after SAH, both to prevent the development of cerebral vasospasm and to reduce oxidative brain injury after secondary infarction.

Curcumin attenuates vascular inflammation and cerebral vasospasm after subarachnoid hemorrhage in mice.

Vasospasme c&eacute;r&eacute;bral est une cause majeure de d&eacute;c&egrave;s ou d&#39;invalidit&eacute; apr&egrave;s h&eacute;morragie sous-arachno&iuml;dienne (HSA) ; Cependant, des th&eacute;rapies cliniques afin de limiter le d&eacute;veloppement du vasospasme c&eacute;r&eacute;bral font d&eacute;faut. M&ecirc;me si on conna&icirc;t mal les facteurs &eacute;tiologiques sous-jacents &agrave; l&#39;&eacute;volution du vasospasme c&eacute;r&eacute;bral, le stress oxydatif contribue &agrave; la progression de la maladie. Dans la pr&eacute;sente &eacute;tude, la curcumine (150 ou 300 mg/kg) prot&eacute;g&eacute; contre le d&eacute;veloppement de vasospasme c&eacute;r&eacute;bral et l&#39;infarctus c&eacute;r&eacute;bral secondaire limit&eacute;e apr&egrave;s SAH chez la souris. L&#39;effet protecteur de la curcumine a &eacute;t&eacute; associ&eacute; &agrave; une att&eacute;nuation significative de l&#39;expression des g&egrave;nes inflammatoires et la peroxydation des lipides dans le cortex c&eacute;r&eacute;bral et l&#39;art&egrave;re c&eacute;r&eacute;brale moyenne. Malgr&eacute; la capacit&eacute; de la curcumine pour limiter le d&eacute;veloppement de vasospasme c&eacute;r&eacute;bral et d&#39;infarctus du myocarde secondaire, r&eacute;sultat comportemental n&#39;est pas am&eacute;lior&eacute;e, indiquant une dissociation entre le vasospasme c&eacute;r&eacute;bral et r&eacute;sultats neurologiques. Ensemble, ces donn&eacute;es indiquent un nouveau r&ocirc;le pour la curcumine comme une possible th&eacute;rapie adjuvante apr&egrave;s SAH, pour pr&eacute;venir le d&eacute;veloppement du vasospasme c&eacute;r&eacute;bral et pour r&eacute;duire le traumatisme cr&acirc;nien oxydatif apr&egrave;s infarctus du myocarde secondaire.

Curcumine att&eacute;nue l&#39;inflammation vasculaire et vasospasme c&eacute;r&eacute;bral apr&egrave;s une h&eacute;morragie m&eacute;ning&eacute;e chez la souris.

Increasing demand for emergency care and crowded emergency departments (EDs) lead some planners to conclude that inconvenient primary care scheduling increases the number of "unnecessary" ED visits. The reasons that the planners argue for more primary care are: to increase funding for primary care; the unfounded notion that it is less expensive to see a primary care physician (PCP) than an Emergency Physician; and the impractical goal that the ED should be used only by intellectually interesting life- or limb-threatened patients or "true emergencies."

Emergency department workload increase: dependence on primary care?

La demande croissante de soins d&#39;urgence et urgences bond&eacute;es (EDs) plomb des planificateurs pour conclure que les soins primaires incommode planification augmente le nombre de &laquo; inutile &raquo; ED visites. Les raisons qui les planificateurs plaident pour plus de soins primaires sont : pour accro&icirc;tre le financement des soins de premi&egrave;re ligne ; la notion de sans fondement qu&#39;il est moins cher pour voir un m&eacute;decin de soins primaires (PCP) qu&#39;un m&eacute;decin d&#39;urgence ; et l&#39;objectif irr&eacute;aliste que l&#39;ED doit &ecirc;tre utilis&eacute; uniquement par intellectuellement int&eacute;ressant les patients menac&eacute;s de vie ou de membre ou &laquo; vraies urgences. &raquo;

Augmentation de charge de service d&#39;urgence : la d&eacute;pendance &agrave; l&#39;&eacute;gard des soins de sant&eacute; primaires ?

Crescente domanda di cure di emergenza e affollati reparti di emergenza (EDs) piombo alcuni pianificatori per concludere quello scomodo primary care pianificazione aumenta il numero di &quot;inutili&quot; ED visite. Sono le ragioni per cui i progettisti sostengono per ulteriori cure primarie: per aumentare i finanziamenti per le cure primarie; la nozione di infondate che &egrave; meno costoso vedere un medico di assistenza primaria (PCP) rispetto a un medico di emergenza; e l&#39;obiettivo pratico che il de deve essere utilizzato solo da intellettualmente interessante vita o arto minacciato pazienti o &quot;vera emergenza&quot;.

Aumento del carico di lavoro di reparto di emergenza: dipendenza dalle cure primarie?

Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated with significant patient morbidity and death. Since the first demonstration of cerebral vasospasm nearly 60 years ago, the preponderance of research has focused on strategies to limit arterial narrowing and delayed cerebral ischemia following SAH. However, recent clinical and preclinical data indicate a functional dissociation between cerebral vasospasm and neurological outcome, signaling the need for a paradigm shift in the study of brain injury following SAH. Early brain injury may contribute to poor outcome and early death following SAH. However, elucidation of the complex cellular mechanisms underlying early brain injury remains a major challenge. The advent of modern neuroproteomics has rapidly advanced scientific discovery by allowing proteome-wide screening in an objective, nonbiased manner, providing novel mechanisms of brain physiology and injury. In the context of neurosurgery, proteomic analysis of patient-derived CSF will permit the identification of biomarkers and/or novel drug targets that may not be intuitively linked with any particular disease. In the present report, the authors discuss the utility of neuroproteomics with a focus on the roles for this technology in understanding SAH. The authors also provide data from our laboratory that identifies high-mobility group box protein-1 as a potential biomarker of neurological outcome following SAH in humans.

Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: an emerging role for neuroproteomics.

H&eacute;morragie sous-arachno&iuml;dienne (HSA) est une l&eacute;sion neurologique d&eacute;vastatrice, associ&eacute;e &agrave; la mort et la morbidit&eacute; importante de patiente. Depuis la premi&egrave;re d&eacute;monstration du vasospasme c&eacute;r&eacute;bral presque 60 ans, la pr&eacute;pond&eacute;rance de la recherche a ax&eacute; sur des strat&eacute;gies visant &agrave; limiter le r&eacute;tr&eacute;cissement art&eacute;riel et retard&eacute; une isch&eacute;mie c&eacute;r&eacute;brale suite SAH. Cependant, ces derni&egrave;res donn&eacute;es cliniques et pr&eacute;cliniques indiquent une dissociation fonctionnelle entre le vasospasme c&eacute;r&eacute;bral et r&eacute;sultats neurologiques, la n&eacute;cessit&eacute; d&#39;un changement de paradigme dans l&#39;&eacute;tude des l&eacute;sions c&eacute;r&eacute;brales apr&egrave;s SAH de signalisation. Les l&eacute;sions c&eacute;r&eacute;brales pr&eacute;coces peuvent contribuer &agrave; mauvais pronostic et mort pr&eacute;matur&eacute;e suite SAH. Toutefois, l&#39;&eacute;lucidation des m&eacute;canismes cellulaires complexes qui sous-tendent les l&eacute;sions c&eacute;r&eacute;brales pr&eacute;coces demeure un d&eacute;fi majeur. L&#39;av&egrave;nement de Neuroprot&eacute;omique moderne a avanc&eacute; rapidement de d&eacute;couverte scientifique en permettant le d&eacute;pistage &agrave; l&#39;&eacute;chelle du prot&eacute;ome de mani&egrave;re objective, de mani&egrave;re nonbiased, fournissant de nouveaux m&eacute;canismes de la physiologie du cerveau et des blessures. Dans le contexte de la neurochirurgie, l&#39;analyse prot&eacute;omique du patient d&eacute;riv&eacute; LCR permettra l&#39;identification de biomarqueurs ou des cibles de nouveaux m&eacute;dicaments qui ne peuvent &ecirc;tre connect&eacute;es de mani&egrave;re intuitive avec n&#39;importe quelle maladie particuli&egrave;re. Dans le pr&eacute;sent rapport, les auteurs discutent l&#39;utilit&eacute; de Neuroprot&eacute;omique en mettant l&#39;accent sur les r&ocirc;les pour cette technologie dans la compr&eacute;hension SAH. Les auteurs fournissent &eacute;galement donn&eacute;es dans notre laboratoire qui identifie le groupe de haute mobilit&eacute; case prot&eacute;ine-1 comme un biomarqueur potentiel de SAH issue neurologique chez l&#39;homme.

&Eacute;lucider les nouveaux m&eacute;canismes de l&eacute;sion c&eacute;r&eacute;brale suite &agrave; une h&eacute;morragie sous-arachno&iuml;dienne : un r&ocirc;le pour neuroprot&eacute;omique.

Emorragia subaracnoidea (SAH) &egrave; un devastante lesioni neurologiche associate a morte e significativa morbidit&agrave; del paziente. Poich&eacute; la prima dimostrazione di vasospasmo cerebrale quasi 60 anni fa, la preponderanza della ricerca ha focalizzato sulle strategie per limitare il restringimento arterioso e ischemia cerebrale dopo SAH in ritardo. Tuttavia, recenti dati clinici e preclinici indicano una dissociazione funzionale tra vasospasmo cerebrale e l&#39;esito neurologico, segnalando la necessit&agrave; di un cambiamento di paradigma nello studio delle lesioni cerebrali in seguito SAH. Lesione cerebrale precoce pu&ograve; contribuire a prognosi sfavorevole e morte precoce seguito SAH. Tuttavia, delucidazione dei meccanismi cellulari complessi sottostanti la lesione cerebrale precoce rimane una sfida importante. L&#39;avvento della moderna neuroproteomics ha avanzato rapidamente scoperta scientifica consentendo proteome-wide screening in modo obiettivo, modo nonbiased, fornendo nuovi meccanismi della fisiologia cerebrale e lesioni. Nel contesto della neurochirurgia, Analisi proteomic del paziente-derivato CSF permetter&agrave; l&#39;identificazione di biomarcatori e/o obiettivi farmacologici romanzo che non possono essere intuitivamente collegati con qualsiasi particolare malattia. Nella presente relazione, gli autori discutono l&#39;utilit&agrave; di neuroproteomics con un focus sui ruoli per questa tecnologia nella comprensione SAH. Gli autori forniscono anche dati dal nostro laboratorio che identifica la high-mobility group box 1 proteina come un potenziale biomarcatore dell&#39;esito neurologico dopo SAH negli esseri umani.

Chiarimento nuovi meccanismi di lesione cerebrale dopo emorragia subaracnoidea: un ruolo emergente per neuroproteomics.

Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice.

Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice.

Une h&eacute;morragie intrac&eacute;r&eacute;brale (ICH) est associ&eacute;e &agrave; une morbidit&eacute; et mortalit&eacute;. L&#39;&eacute;largissement h&eacute;matome aigu est un pr&eacute;dicteur important de l&eacute;sions neurologiques et le pronostic clinique ; mais &eacute;vacuation neurochirurgical caillot peut ne pas &ecirc;tre r&eacute;alisable chez tous les patients et les options de traitement restent largement favorables. Ainsi, de nouvelles approches th&eacute;rapeutiques pour promouvoir une r&eacute;solution h&eacute;matome sont n&eacute;cessaires. Dans la pr&eacute;sente &eacute;tude, les auteurs ont &eacute;tudi&eacute; si le curry &eacute;pice curcumin limit&eacute; neurovasculaire blessure suite ICH chez la souris.

Att&eacute;nuation de la taille de l&#39;h&eacute;matome et de l&eacute;sion neurologique avec la curcumine, suite &agrave; une h&eacute;morragie intrac&eacute;r&eacute;brale chez la souris.

Emorragia intracerebrale (ICH) &egrave; associata a significativa morbidit&agrave; e mortalit&agrave;. L&#39;allargamento ematoma acuto &egrave; un importante predittore di lesioni neurologiche e clinica prognosi; ma evacuazione del coagulo neurochirurgica potrebbe non essere fattibile in tutti i pazienti e le opzioni di trattamento rimangono in gran parte favorevole. Cos&igrave;, sono necessari nuovi approcci terapeutici per promuovere la risoluzione di ematoma. Nel presente studio, gli autori hanno indagato se la curcumina spezie curry limitata lesione neurovascolare seguito ICH nei topi.

Attenuazione della dimensione di ematomi e lesioni neurologiche con curcumina dopo emorragia intracerebrale nel topo.

Regulatory T cell frequencies do not correlate with breadth or magnitude of HIV-1-specific T cell responses.

Fr&eacute;quences de lymphocytes T r&eacute;gulateurs ne concordent pas avec la largeur ou l&#39;ampleur des lymphocytes T sp&eacute;cifiques au VIH-1.

Frequenze di cellule T regolatori non correlare con ampiezza o grandezza di HIV-1-specifiche risposte delle cellule T.

Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1-infected individuals and HIV-1 negative controls. While HIV "elite controllers" and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors.

Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissue.

Les lymphocytes T r&eacute;gulateurs (Tregs) sont des immunomodulateurs puissants, mais leur r&ocirc;le dans le virus de l&#39;immunod&eacute;ficience humaine de type 1 (VIH-1) demeure de pathog&eacute;n&egrave;se mal compris. Nous avons effectu&eacute; une analyse d&eacute;taill&eacute;e de la fr&eacute;quence et de la fonction des Tregs dans une grande cohorte de personnes infect&eacute;es par le VIH-1 et VIH-1 t&eacute;moins n&eacute;gatifs. Alors que les &laquo; Contr&ocirc;leurs d&#39;&eacute;lites &raquo; du VIH et des individus non infect&eacute;s ont des fr&eacute;quences et des num&eacute;ros de Treg semblable, le nombre absolu de Tregs a diminu&eacute; dans le sang et le tissu lympho&iuml;de associ&eacute; intestinale chez des patients pr&eacute;sentant une infection VIH-1 progressive chronique. Malgr&eacute; les changements quantitatifs en Tregs, infection &agrave; VIH-1 n&#39;&eacute;tait pas associ&eacute;e &agrave; une atteinte ex vivo fonction suppressive de Tregs flux-tri&eacute;s dans les contr&ocirc;leurs du VIH et des progresseurs chroniques non trait&eacute;es.

Conserv&eacute; la fonction des lymphocytes T r&eacute;gulateurs de l&#39;infection chronique par le VIH-1 Malgr&eacute; une diminution dans le sang et les tissus.

Cellule T regolatorie (Tregs) sono potenti modulatori immuni, ma il loro ruolo nel virus dell&#39;immunodeficienza umana tipo 1 (HIV-1) resti di patogenesi poco compreso. Abbiamo effettuato una dettagliata analisi della frequenza e la funzione di Tregs in un&#39;ampia coorte di individui infetti di HIV-1 e HIV-1 controlli negativi. Mentre l&#39;HIV &quot;elite controller&quot; e gli individui non infetti avevano Treg numeri e frequenze simili, il numero assoluto di Tregs diminuito nel sangue e tessuto linfoide intestinale nei pazienti con infezione da HIV-1 progressiva cronica. Malgrado i cambiamenti quantitativi in Tregs, infezione da HIV-1 non &egrave; stato associato a un danno dell&#39;ex vivo funzione soppressiva del flusso ordinato Tregs controller di HIV sia progressori croniche non trattate.

Conservata la funzione delle cellule T regolatorie nell&#39;infezione cronica da HIV-1, nonostante i numeri diminuiti nel sangue e nel tessuto.

Regulatory T cells (Tregs) are potent immune modulators, but their precise role in HIV pathogenesis remains incompletely understood. Most studies to date have focused on frequencies or phenotypes of 'bulk' Treg populations. However, although antigen-specific Tregs have been reported in other diseases, HIV-1 epitope-specific Tregs have not been described to date. We here report the first identification of functional HIV-1-Gag-specific regulatory T cells using human leukocyte antigen class II tetramer staining in HIV-1-infected individuals.

Identification of HIV-1-specific regulatory T-cells using HLA class II tetramers.

Les lymphocytes T r&eacute;gulateurs (Tregs) sont des immunomodulateurs puissants, mais leur r&ocirc;le pr&eacute;cis dans la pathog&eacute;n&egrave;se du VIH reste incompl&egrave;tement comprise. La plupart des &eacute;tudes &agrave; ce jour portent sur des fr&eacute;quences ou des ph&eacute;notypes de &laquo; en vrac &raquo; Treg des populations. Cependant, bien que Tregs antig&egrave;ne-sp&eacute;cifiques ont &eacute;t&eacute; signal&eacute;s dans d&#39;autres maladies, Tregs &eacute;pitope sp&eacute;cifique du VIH-1 n&#39;ont pas &eacute;t&eacute; d&eacute;crits &agrave; ce jour. Nous rapportons ici la premi&egrave;re identification de fonctionnelles sp&eacute;cifiques au VIH-1-Gag lymphocytes T r&eacute;gulateurs &agrave; l&#39;aide de human leukocyte antigen classe II t&eacute;tram&egrave;re coloration chez les personnes infect&eacute;es par le VIH-1.

Identification des lymphocytes-T r&eacute;gulateurs sp&eacute;cifiques au VIH-1 &agrave; l&#39;aide de t&eacute;tram&egrave;res HLA classe II.

Cellule T regolatorie (Tregs) sono potenti modulatori immuni, ma loro preciso ruolo nella patogenesi dell&#39;HIV rimane non completamente capito. Maggior parte degli studi fino ad oggi si sono concentrati su frequenze o fenotipi di &#39;massa&#39; Treg popolazioni. Tuttavia, sebbene Tregs antigene-specifici sono stati segnalati in altre malattie, Tregs epitopo specifico dell&#39;HIV-1 non &egrave; stata descritta fino ad oggi. Riportiamo qui la prima identificazione di funzionale dell&#39;HIV-1-Gag-specifiche cellule T regolatorie utilizzando tetramero di umano del leucocita antigen classe II colorazione in individui HIV-1-infected.

Identificazione di HIV-1-specifiche cellule T regolatorie utilizzando tetrameri II classe HLA.

Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, exhibits the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, treatment options for ICH are lacking due in part to a lack of feasible therapeutic targets. Inflammatory activation is associated with neurological deficits in pre-clinical ICH models and with patient deterioration after clinical ICH. In the present study, we tested the hypothesis that R-7050, a novel cell permeable triazoloquinoxaline inhibitor of the tumor necrosis factor receptor (TNFR) complex, attenuates neurovascular injury after ICH in mice. Up to 2h post-injury administration of R-7050 significantly reduced blood-brain barrier opening and attenuated edema development at 24h post-ICH. Neurological outcomes were also improved over the first 3 days after injury. In contrast, R-7050 did not reduce hematoma volume, suggesting the beneficial effects of TNFR inhibition were downstream of clot formation/resolution. These data suggest a potential clinical utility for TNFR antagonists as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice.

Une h&eacute;morragie intrac&eacute;r&eacute;brale (CIH), la forme la plus courante d&#39;AVC h&eacute;morragique, pr&eacute;sente la plus forte mortalit&eacute; aigu&euml; et le pronostic pire &agrave; long terme de tous les sous-types de l&#39;accident vasculaire c&eacute;r&eacute;bral. Malheureusement, les options de traitement pour ICH manquent due en partie &agrave; un manque de cibles th&eacute;rapeutiques possibles. Activation inflammatoire est associ&eacute; li&eacute;e des d&eacute;ficits neurologiques dans des mod&egrave;les pr&eacute;cliniques de ICH et avec d&eacute;t&eacute;rioration patiente apr&egrave;s clinique ICH. Dans la pr&eacute;sente &eacute;tude, nous avons test&eacute; l&#39;hypoth&egrave;se que R-7050, un inhibiteur de triazoloquinoxaline perm&eacute;able de nouvelle cellule du r&eacute;cepteur de facteur de n&eacute;crose tumorale (TNFR) complex, att&eacute;nue la l&eacute;sion de neurovasculaire apr&egrave;s ICH chez la souris. Jusqu&#39;&agrave; administration apr&egrave;s 2h de R-7050 consid&eacute;rablement r&eacute;duit la barri&egrave;re h&eacute;mato - enc&eacute;phalique d&#39;ouverture et a att&eacute;nu&eacute; le d&eacute;veloppement oed&egrave;me &agrave; post-ICH 24h. Aussi, les r&eacute;sultats neurologiques ont &eacute;t&eacute; am&eacute;lior&eacute;s pendant les 3 premiers jours apr&egrave;s une blessure. En revanche, R-7050 n&#39;abaisse pas volume de l&#39;h&eacute;matome, sugg&eacute;rant que les effets b&eacute;n&eacute;fiques de l&#39;inhibition du TNF ont &eacute;t&eacute; en aval du caillot formation/r&eacute;solution. Ces r&eacute;sultats sugg&egrave;rent une utilit&eacute; clinique potentielle pour antagonistes du TNF comme traitement d&#39;appoint de r&eacute;duire les l&eacute;sions neurologiques et d&#39;am&eacute;liorer les r&eacute;sultats pour les patients apr&egrave;s ICH.

Antagoniste des r&eacute;cepteurs du TNF-alpha, R-7050, am&eacute;liore les r&eacute;sultats neurologiques suite &agrave; une h&eacute;morragie intrac&eacute;r&eacute;brale chez la souris.

Emorragia intracerebrale (ICH), la forma pi&ugrave; comune di ictus emorragico, esibisce il pi&ugrave; alta mortalit&agrave; acuta e la prognosi a lungo termine peggiore di tutti i sottotipi di ictus. Purtroppo, le opzioni di trattamento per ICH mancano dovuta in parte alla mancanza di possibili bersagli terapeutici. Attivazione infiammatoria &egrave; associata a deficit neurologici in modelli preclinici di ICH e con paziente deterioramento dopo ICH clinico. Nel presente studio, abbiamo testato l&#39;ipotesi che R-7050, un inibitore triazoloquinoxaline permeabile cella romanzo il recettore del fattore di necrosi tumorale (TNFR) complesso, attenua la lesione neurovascolare dopo ICH nei topi. Fino a amministrazione post-infortunio di 2h di R-7050 significativamente ridotto la barriera emato - encefalica apertura e attenuato lo sviluppo di edema a post-ICH 24 ore su 24. Esiti neurologici sono stati migliorati anche oltre i primi 3 giorni dopo l&#39;infortunio. Al contrario, R-7050 non riduce volume dell&#39;ematoma, suggerendo che gli effetti benefici dell&#39;inibizione TNFR erano a valle della risoluzione/formazione del coagulo. Questi dati suggeriscono una potenziale utilit&agrave; clinica per antagonisti TNFR come terapia adiuvante per ridurre le lesioni neurologiche e migliorare i risultati per il paziente dopo ICH.

Article	Year
Postmolar surveillance at a trophoblastic disease center that serves indigent women. American journal of obstetrics and gynecology\| PubMed ID: 12748460	2003
Management of low-risk gestational trophoblastic neoplasia in indigent women. The Journal of reproductive medicine\| PubMed ID: 14628732	2003
Oral dexamethasone attenuates Doxil-induced palmar-plantar erythrodysesthesias in patients with recurrent gynecologic malignancies. Gynecologic oncology\| PubMed ID: 15297168	2004
A serologic assessment of exposure to viral pathogens and Leptospira in an urban raccoon (Procyon lotor) population inhabiting a large zoological park. Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 17469271	2007
Curcumin attenuates vascular inflammation and cerebral vasospasm after subarachnoid hemorrhage in mice. Antioxidants & redox signaling\| PubMed ID: 18752423	2009
Emergency department workload increase: dependence on primary care? The Journal of emergency medicine\| PubMed ID: 19682828	2010
Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: an emerging role for neuroproteomics. Neurosurgical focus\| PubMed ID: 20043714	2010
Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice. Journal of neurosurgery\| PubMed ID: 21417704	2011
Regulatory T cell frequencies do not correlate with breadth or magnitude of HIV-1-specific T cell responses. AIDS research and human retroviruses\| PubMed ID: 22214208	2012
Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissue. The Journal of infectious diseases\| PubMed ID: 22427677	2012
Identification of HIV-1-specific regulatory T-cells using HLA class II tetramers. AIDS (London, England)\| PubMed ID: 22874519	2012
TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice. Neuroscience letters\| PubMed ID: 23499961	2013

Melanie King

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