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1.
Science ; 376(6594): eabl5197, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549406

RESUMO

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.


Assuntos
Linfócitos B , Aprendizado de Máquina , Análise de Sequência de RNA , Análise de Célula Única , Linfócitos T , Transcriptoma , Células Cultivadas , Humanos , Especificidade de Órgãos
2.
J Immunol Methods ; 499: 113163, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34610276

RESUMO

The inflammatory response to acute brain injuries is a key contributor to subsequent outcome. The study of local central nervous system inflammatory responses is hindered by raised intracranial pressure precluding cerebrospinal fluid sampling by lumbar puncture. External ventricular drains are sited in some acute brain injury patients to divert cerebrospinal fluid and thus reduce intracranial pressure, and represent a potential route to safely gather large volumes of cerebrospinal fluid for immunological studies. In this manuscript we show that mononuclear cells can be isolated from cerebrospinal fluid collected from external ventricular drains, and that the large volumes of cerebrospinal fluid available yield sufficient mononuclear cells to allow cryopreservation. Prolonged storage of cerebrospinal fluid in the external ventricular drain collection bag can alter the phenotype of cells recovered, but the predicted effect of this can be estimated for a given flow cytometry panel by assessing the changes in peripheral blood mononuclear cells exposed to the same conditions. The described method will allow clinical studies of acute brain injuries to investigate the immunological processes occurring within the central nervous system compartment, rather than relying on changes in the peripheral circulation.


Assuntos
Lesões Encefálicas/imunologia , Líquido Cefalorraquidiano/imunologia , Criopreservação , Pressão Intracraniana/imunologia , Leucócitos Mononucleares/imunologia , Lesões Encefálicas/sangue , Lesões Encefálicas/patologia , Humanos , Leucócitos Mononucleares/patologia
3.
Oncogene ; 35(6): 671-82, 2016 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-25961921

RESUMO

The idea that tumor initiation and progression are driven by a subset of cells endowed with stem-like properties was first described by Rudolf Virchow in 1855. 'Cancer stem cells', as they were termed more than a century later, represent a subset of tumor cells that are able to generate all tumorigenic and nontumorigenic cell types within the malignancy. Although their existence was hypothesized >150 years ago, it was only recently that stem-like cells started to be isolated from different neoplastic malignancies. Interestingly, Virchow, in suggesting a correlation between cancer and the inflammatory microenvironment, also paved the way for the 'Seed and Soil' theory proposed by Paget a few years later. Despite the time that has passed since these two important concepts were suggested, the relationships between Virchow's 'stem-like cells' and Paget's 'soil' are far from being fully understood. One emerging topic is the importance of a stem-like niche in modulating the biological properties of stem-like cancer cells and thus in affecting the response of the tumor to drugs. This review aims to summarize the recent molecular data concerning the multilayered relationship between cancer stem cells and tumor-associated macrophages that form a key component of the tumor microenvironment. We also discuss the therapeutic implications of targeting this synergistic interplay.


Assuntos
Macrófagos/patologia , Terapia de Alvo Molecular/tendências , Neoplasias/imunologia , Neoplasias/terapia , Células-Tronco Neoplásicas/patologia , Animais , Humanos , Macrófagos/metabolismo , Terapia de Alvo Molecular/métodos , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Nicho de Células-Tronco/fisiologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
4.
East Mediterr Health J ; 16(6): 609-14, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20799587

RESUMO

UNRWA's noncommunicable disease screening activities were evaluated among 7762 refugees screened for hypertension and type 2 diabetes in Jordan, Syrian Arab Republic, Lebanon, Gaza Strip and West Bank in June 2007. People were referred for screening most commonly because of age (both sexes), followed by smoking (males) and family history (females). Atotal of 9% ofscreened people were diagnosed with hypertension/ diabetes. Being older than 40 years, obese or with a positive family history of diabetes or cardiovascular disease increased the risk of presenting with hypertension and/or hyperglycaemia 3.5, 1.6 and 1.2 times respectively. Differences in risk factor detection and screening outcome in relation to differences in lifestyle are discussed.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipertensão , Programas de Rastreamento/organização & administração , Refugiados/estatística & dados numéricos , Adulto , Distribuição por Idade , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Hiperglicemia/etnologia , Hiperglicemia/etiologia , Hipertensão/etnologia , Hipertensão/etiologia , Jordânia/epidemiologia , Líbano/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Oriente Médio/etnologia , Análise Multivariada , Vigilância da População , Medição de Risco , Fatores de Risco , Síria/epidemiologia , Nações Unidas
5.
(East. Mediterr. health j).
em Inglês | WHO IRIS | ID: who-117926

RESUMO

UNRWA's noncommunicable disease screening activities were evaluated among 7762 refugees screened for hypertension and type 2 diabetes in Jordan, Syrian Arab Republic, Lebanon, Gaza Strip and West Bank in June 2007. People were referred for screening most commonly because of age [both sexes], followed by smoking [males] and family history [females]. A total of 9% of screened people were diagnosed with hypertension/diabetes. Being older than 40 years, obese or with a positive family history of diabetes or cardiovascular disease increased the risk of presenting with hypertension and/or hyperglycaemia 3.5, 1.6 and 1.2 times respectively. Differences in risk factor detection and screening outcome in relation to differences in lifestyle are discussed


Assuntos
Hipertensão , Fatores de Risco , Programas de Rastreamento , Estilo de Vida , Refugiados , Hiperglicemia
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