Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
2.
Cerebellum ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363498

RESUMO

Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Our results (i) confirmed SCA6 being considered as a pure cerebellar grey matter disease, (ii) emphasise the involvement of cerebellar white matter in the neuropathology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

3.
Res Sq ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38014351

RESUMO

Background: Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Methods: Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Results: Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Conclusion: Our results (i) confirmed SCA6 being considered as a pure cerebellar gray matter disease, (ii) emphasise the involvement of cerebellar white matter in the neurophatology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

4.
Front Cell Infect Microbiol ; 13: 1277522, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868348

RESUMO

Chimaeribacter arupi (heterotypic synonym: "Nissabacter archeti") is a facultative anaerobic, newly described Gram-negative rod and belongs to the Yersineacea family. Here, we report the case of a 19-month-old female infant patient who presented to the emergency unit with somnolence and fever. C. arupi was isolated from a positive blood culture, taken via an implanted Broviac catheter, proving a bloodstream infection by the pathogen. The objective of this study was to utilize whole genome sequencing to assess the genes encoding potential virulence associated factors, which may play a role in host tropism, tissue invasion and the subsequent stages in the pathogenesis of a bloodstream infection with C. arupi. The genome of the isolate was completely sequenced employing Illumina MiSeq and Nanopore MinION sequencing and the presumptive virulence associated factors and antimicrobial resistance genes were investigated in more detail. Additionally, we performed metabolic profiling and susceptibility testing by microdilution. The presence of predicted TcfC-like α-Pili suggests that C. arupi is highly adapted to humans as a host. It utilizes flagellar and type IV pili-mediated motility, as well as a number of γ1-pili and a σ-pilus, which may be used to facilitate biofilm formation and adherence to host epithelia. Additionally, long polar fimbriae may aid in tissue invasion. The bacterium possesses antioxidant factors, which may enable temporary survival in phagolysosomes, and a capsule that potentially provides protection from phagocytosis. It may acquire iron ions from erythrocytes through the type 6 secretion system and hemolysins. Furthermore, the isolate exhibits beta-lactamase-mediated penicillin and aminopenicillin resistance. Based on the analysis of the whole genome, we conclude that C. arupi possesses virulence factors associated with tissue invasion and may thus be a potential opportunistic pathogen of bloodstream infections.


Assuntos
Fímbrias Bacterianas , Sepse , Humanos , Feminino , Lactente , Fímbrias Bacterianas/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Bactérias Gram-Negativas/genética , Sequência de Bases , Sepse/metabolismo
5.
Front Microbiol ; 14: 1169829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213500

RESUMO

Extended spectrum beta-lactamases (ESBL) are frequently found in Enterobacterales isolates from Western Africa. However, information on the molecular epidemiology of regional ESBL-positive Enterobacterales strains is scarce. In order to provide epidemiological information, ESBL-positive Escherichia coli isolates from stool samples of European soldiers with diarrhea deployed to a field camp in Mali were subjected to whole-genome sequencing (Illumina MiSeq and Oxford Nanopore MinION) and antimicrobial susceptibility testing. With two exemptions, sequence-based analysis suggested an absence of transmission events between soldiers as indicated by a high genetic diversity of isolates and sequence types, confirming previous rep-PCR results. Third-generation cephalosporin resistance was associated with the presence of blaCTX-M-15 genes with (n = 14) and without (n = 5) co-occurring blaTEM-1b genes. Between 0 and 6 virulence and resistance plasmids per isolate were recorded. The detected resistance plasmids could be categorized into five types, which, in turn, share different sequence-identical segments, representing particular antimicrobial resistance gene-associated mobile genetic elements (MGEs). Phenotypic resistance rates within the 19 assessed isolates that showed distinguishable colony morphologies were 94.7% (18/19) against ampicillin-sulbactam and trimethoprim/sulfamethoxazole, 68.4% (13/19) against moxifloxacin, 31.6% (6/19) against ciprofloxacin, 42.1% (8/19) against gentamicin, 31.6% (6/19) against tobramycin, and 21.1% (4/19) against piperacillin-tazobactam and fosfomycin. Virulence-associated genes mediating infectious gastroenteritis were rarely detected. The gene aggR, which is characteristic for enteroaggregative E. coli, was only detected in one single isolate. In summary, we found a variety of different strains and clonal lineages of ESBL-carrying E. coli. Transmission either between soldiers or from common contaminated sources was demonstrated in two cases and played only a minor role in this military field camp, while there were indications that resistance gene bearing MGEs had been exchanged between antimicrobial resistance gene-(ARG-)carrying plasmids.

6.
Front Cell Dev Biol ; 10: 1063692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578787

RESUMO

The Raf/MEK/ERK signaling pathway plays a key role in regulating cellular proliferation, differentiation, apoptosis, cytokine production, and immune responses. However, it is also involved in diseases such as cancer, and numerous viruses rely on an active Raf/MEK/ERK pathway for propagation. This pathway, and particularly MEK1/2, are therefore promising therapeutic targets. Assessment of target engagement is crucial to determine pharmacodynamics or the efficacy of a MEK1/2 inhibitor. In the field of infectious diseases, this is usually first determined in clinical trials with healthy volunteers. One method to detect MEK1/2 inhibitor target engagement is to assess the degree of ERK1/2 phosphorylation, as ERK1/2 is the only known substrate of MEK1/2. As healthy subjects, however, only feature a low baseline MEK1/2 activation and therefore low ERK1/2 phosphorylation in most tissues, assessing target engagement is challenging, and robust methods are urgently needed. We hence developed a method using PBMCs isolated from whole blood of healthy blood donors, followed by ex vivo treatment with the MEK1/2 inhibitor zapnometinib and stimulation with PMA to first inhibit and then induce MEK1/2 activation. As PMA cannot activate MEK1/2 upon MEK1/2 inhibition, MEK1/2 inhibition results in impaired MEK1/2 activation. In contrast, PMA stimulation without MEK1/2 inhibition results in high MEK1/2 activation. We demonstrated that, without MEK1/2 inhibitor treatment, MEK1/2 stimulation with PMA induces high MEK1/2 activation, which is clearly distinguishable from baseline MEK1/2 activation in human PBMCs. Furthermore, we showed that treatment with the MEK1/2 inhibitor zapnometinib maintains the MEK1/2 activation at approximately baseline level despite subsequent stimulation with PMA. As our protocol is easy to follow and preserves the cells in an in vivo-like condition throughout the whole handling process, this approach can be a major advance for the easy assessment of MEK1/2 inhibitor target engagement in healthy probands for clinical drug development.

7.
Front Cardiovasc Med ; 9: 901260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811695

RESUMO

Background: Family-Centered Care is a useful framework for improving care for hospitalized children with congenital heart disease. The EMpowerment of PArents in THe Intensive Care-30 (EMPATHIC-30) questionnaire is a widely accepted tool to measure parental satisfaction with Family-Centered Care. Psychometric properties of the EMPATHIC-30 have been evaluated in neonatal and pediatric intensive care units, but not in pediatric cardiac care units. Therefore, our aim was to assess the psychometric properties of the German EMPATHIC-30 in an intermediary/general pediatric cardiology unit. Methods: We used data from a quality management survey comprising the German EMPATHIC-30, a sociodemographic questionnaire and four general satisfaction items. Data were collected at the intermediary/general pediatric cardiology unit of a specialized heart center in Germany (n = 366). We split the data randomly into two subsets. In the first subset, we assessed internal consistency reliability with McDonald's omega and Cronbach's alpha, and convergent validity using Spearman's rank correlation. Furthermore, we explored the internal structure with Principal Component Analysis (PCA). In the second subset, we validated the resulting structure using Confirmatory Factor Analysis (CFA). Results: The reliability estimates exceeded 0.70 for all five domain scores and 0.90 for the full-scale score. Convergent validity between EMPATHIC-30 domain scores/ the full-scale score and the four general satisfaction items was adequate (rs = 0.40-0.74). The PCA suggested three components, accounting for 56.8% of the total variance. Cross-validation via CFA showed poor model fit (χ2 = 1545.78, χ2/df = 3.85, CFI = 0.70, TLI = 0.66, RMSEA = 0.13), indicating that the EMPATHIC-30 shows no clear and generalizable factor structure in this sample. Discussion: The German version of the EMPATHIC-30 exhibited reasonable psychometric properties in an intermediary/general pediatric cardiology unit. Follow-up studies should investigate the factor structure of the EMPATHIC-30 in other pediatric inpatient care settings.

8.
Dtsch Arztebl Int ; 115(13): 213-219, 2018 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-29669676

RESUMO

BACKGROUND: Lower-limb endoprosthetic operations and spinal operations are among the more common types of orthopedic procedures. Postoperative woundhealing disturbances and infections can lead to longer periods of hospital stay and recovery as well as to higher morbidity and mortality. METHODS: 209 patients who had been judged to have an indication for a primary knee or hip endoprosthesis or for a primary spinal operation were included in this randomized trial (ClinicalTrials.gov: NCT01988818) over the period June 2014- February 2015. After randomization, patients in the intervention group were given a trial dressing (Mepilex-Border Post-Op) and those in the control group were given a conventional adhesive dressing (Cosmopor). The primary endpoint was blister formation. RESULTS: In the overall study population, only a single case of blister formation was seen. The affected patient belonged to the intervention group but was mistakenly given a control dressing and developed blisters on the 6th day after surgery. Dressings were changed less frequently in the intervention group, and this difference was statistically significant (p<0.001). The patients, nurses, and physicians all expressed greater satisfaction with the trial dressings than with the control dressings (p<0.001). CONCLUSION: The intervention group did not differ from the control group with respect to the primary endpoint, postoperative blister formation. The patients, nurses, and physicians all judged the dressing used in the intervention group more favorably than the conventional dressing.


Assuntos
Absorventes Higiênicos/normas , Bandagens/normas , Cicatrização/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Bandagens/tendências , Vesícula/etiologia , Vesícula/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Neuro Oncol ; 18(2): 173-83, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26627848

RESUMO

BACKGROUND: A major hallmark of malignant progression in human astrocytomas is the formation of new blood vessels. Antiangiogenic therapy using the anti-vascular endothelial growth factor (VEGF)-antibody bevacizumab leads to increased progression-free survival in glioblastoma patients but does not influence their overall survival. To date, it is unclear why antiangiogenic therapy fails in many glioblastoma patients, while a small subpopulation profits considerably from this treatment. METHODS: The aim of our study was to determine the expression of VEGF-A and its (co-) receptors by immunohistochemistry and to test the association with patient survival in 350 glioma patients. Additionally, VEGF-A expression was analyzed by in-situ hybridization. In 18 patients, the protein expression was compared with the bevacizumab response according to extended and modified RANO criteria. RESULTS: We found a heterogeneous expression pattern of VEGF and its receptors in glioblastoma patients with significantly lower levels in WHO grade II and III tumors and normal-appearing brain tissue (P < .001). Pilocytic astrocytomas (WHO grade I) showed significantly higher VEGFR-1, -2 and neuropilin-1 levels as compared to WHO grade II and III astrocytomas (P < .01) but at lower levels than glioblastomas. The expression of neuropilin-2 was low in all tumors. There was neither a significant correlation between protein expression and patient survival nor between protein levels and bevacizumab response after modified RANO criteria. CONCLUSION: Since our data indicate that beneficial response to bevacizumab treatment is independent of the expression of VEGF-A and its (co-) receptors, further investigation is needed to decipher the underlying mechanisms of antiangiogenic treatment response.


Assuntos
Astrocitoma/tratamento farmacológico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neuropilina-1/metabolismo , Neuropilina-2/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Astrocitoma/metabolismo , Astrocitoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
10.
Trials ; 16: 81, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25873529

RESUMO

BACKGROUND: Postoperative wound infection is a preventable risk. One potential postoperative complication is blistering, which leads to increased pain, delayed healing, and higher care costs. The incidence of wound blisters has been reported to be between 6 and 24%. The aim of this study is to assess whether the risks of postoperative blistering and wound infections within the first 6 days postsurgery will be reduced using a special dressing compared to a standard one. METHODS/DESIGN: This is a randomized clinical trial in a University hospital. Patients presenting for knee or hip arthroplasty or spine procedures will be assessed against study inclusion and exclusion criteria. After giving written informed consent, patients will be randomized to participate in the 7-day study during hospitalization. One hundred patients will be randomized per group. The primary outcome measure is blistering incidence from day 0 to day 6 postsurgery. Photo documentation will be evaluated in a blinded manner by the Clinical Evaluation Committee (CEC). DISCUSSION: A new dressing will be compared to the standard wound dressing regarding the risk of postoperative blistering, wound infection, and patient comfort. This study will assess the potential advantages of a modern wound dressing. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01988818 (Entered 13 November 2011).


Assuntos
Bandagens , Vesícula/prevenção & controle , Materiais Revestidos Biocompatíveis , Procedimentos Ortopédicos/efeitos adversos , Silicones , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Cicatrização , Adesividade , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Vesícula/diagnóstico , Vesícula/microbiologia , Protocolos Clínicos , Desenho de Equipamento , Alemanha , Hospitais Universitários , Humanos , Teste de Materiais , Satisfação do Paciente , Projetos de Pesquisa , Fatores de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo , Resultado do Tratamento
11.
Mol Biol Evol ; 31(10): 2689-96, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25053804

RESUMO

Cooperation requires communication; this applies to animals and humans alike. The main communication means differ between taxa and social insects (ants, termites, and some bees and wasps) lack the cognitive abilities of most social vertebrates. Central to the regulation of the reproductive harmony in insect societies is the production of a royalty scent which signals the fertility status of the reproducing queen to the nonreproducing workers. Here, we revealed a central genetic component underlying this hallmark of insect societies in the termite Cryptotermes secundus. Communication between queens and workers relied upon the expression of a gene, Neofem4, which belongs to the cytochrome P450 genes. We inhibited Neofem4 in queens by RNA interference. This resulted in the loss of the royalty scent in queens and the workers behaved as though the queen were absent. The queen's behavior was not generally affected by silencing Neofem4. This suggests that the lack of the royalty scent lead to workers not recognizing her anymore as queen. P450 genes are known to be involved in the production of chemical signals in cockroaches and their expression has been linked to a major fertility regulator, juvenile hormone. This makes P450 genes, both a suitable and available evolutionary substrate in the face of natural selection for production of a queen substance. Our data suggest that in an organism without elaborate cognitive abilities communication has been achieved by the exploitation of a central gene that links the fertility network with the chemical communication pathway. As termites and social Hymenoptera seem to share the same class of compounds in signaling fertility, this role of P450 genes might be more widespread across social insects.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Isópteros/enzimologia , Comunicação Animal , Animais , Técnicas de Silenciamento de Genes , Humanos , Isópteros/genética , Feromônios/metabolismo , Seleção Genética , Comportamento Social
12.
Blood ; 119(17): 3975-86, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22403256

RESUMO

Beyond providing a scaffold for immune cells, recent studies indicate that lymph node stromal cells provide potent regulatory capacities that affect the quality of adaptive immune responses. In this study, we provide evidence that neonatal lymph node stromal cells (nnLNSCs) consistently promote the differentiation of macrophage dendritic cell progenitors as well as mature and immature dendritic cells into a distinct population of CX3CR1(+) CD11b(+)F4/80(+) regulatory macrophages (regMΦ). These cells possess remarkably low levels of T cell costimulatory molecules as well as MHC class II molecules. regMΦ do not interfere with early T-cell activation but, via nitric oxide secretion, efficiently suppress T-cell proliferation. Furthermore, CD4(+) T cells proliferating in the presence of regMΦ gain immunosuppressive capacity and MΦ isolated from day 3 nnLNs are T-cell immunosuppressive. Adoptive transfer of antigen-loaded regMΦ induce a profound antigen-specific immune suppression in vivo. Together our data show that nnLNSCs skew the differentiation of dendritic cells and their progenitors toward regMΦ, thus revealing a novel mechanism for local immune regulation.


Assuntos
Antígeno B7-1/metabolismo , Antígeno CD11b/metabolismo , Linhagem da Célula , Células Dendríticas/imunologia , Linfonodos/imunologia , Macrófagos/imunologia , Células Mieloides/imunologia , Receptores de Quimiocinas/metabolismo , Células Estromais/imunologia , Animais , Animais Recém-Nascidos , Receptor 1 de Quimiocina CX3C , Proliferação de Células , Células Cultivadas , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/imunologia , Linfonodos/citologia , Linfonodos/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/citologia , Células Mieloides/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenótipo , Células Estromais/citologia , Células Estromais/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
13.
J Insect Physiol ; 58(3): 376-83, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22245373

RESUMO

Termites are social cockroaches and this sociality is founded on a high plasticity during development. Three molting types (progressive, stationary and regressive molts) are fundamental to achieve plasticity during alate/sexual development, and they make termites a major challenge to any model on endocrine regulation in insect development. As the endocrine signatures underpinning this plasticity are barely understood, we studied the developmental dynamics and their underlying juvenile hormone (JH) titers in a wood-dwelling termite, Cryptotermes secundus, which is characterized by an ancestral life style of living in dead wood and individuals being totipotent in development. The following general pattern elements could be identified during winged sexual development (i) regressive molts were accompanied by longer intermolt periods than other molting types, (ii) JH titers decreased gradually during the developmental transition from larva (immatures without wing buds), to nymph (immatures with wing buds), to winged adult, (iii) in all nymphal stages, the JH titer rose before the next molt and dropped thereafter within the first week, (iv) considerable variation in JH titers occurred in the midphase of the molting cycle of the 2nd and 3rd nymphal instar, inferring that this variation may reflect the underlying endocrine signature of each of the three molting types, (v) the 4th nymphal instar, the shortest of all, seems to be a switch point in development, as nymphs in this stage mainly developed progressively. When comparing these patterns with endocrine signatures seen in cockroaches, the developmental program of Cryptotermes can be interpreted as a co-option and repetitive use of hormonal dynamics of the post dorsal-closure phase of cockroach embryonic development.


Assuntos
Isópteros/crescimento & desenvolvimento , Isópteros/metabolismo , Hormônios Juvenis/metabolismo , Muda , Animais , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo
14.
Nat Immunol ; 12(9): 879-87, 2011 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-21841786

RESUMO

Little is known about the molecular mechanisms that determine the entry into the lymph node and intranodal positioning of lymph-derived cells. By injecting cells directly into afferent lymph vessels of popliteal lymph nodes, we demonstrate that lymph-derived T cells entered lymph-node parenchyma mainly from peripheral medullary sinuses, whereas dendritic cells (DCs) transmigrated through the floor of the subcapsular sinus on the afferent side. Transmigrating DCs induced local changes that allowed the concomitant entry of T cells at these sites. Signals mediated by the chemokine receptor CCR7 were absolutely required for the directional migration of both DCs and T cells into the T cell zone but were dispensable for the parenchymal entry of lymph-derived T cells and dendrite probing of DCs. Our findings provide insight into the molecular and structural requirements for the entry into lymph nodes and intranodal migration of lymph-derived cells of the immune system.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Quimiocinas CC/imunologia , Células Dendríticas/imunologia , Linfonodos/imunologia , Receptores CCR7/imunologia , Migração Transcelular de Célula/imunologia , Migração Transendotelial e Transepitelial/imunologia , Animais , Linfócitos T CD4-Positivos/citologia , Quimiocinas CC/metabolismo , Células Dendríticas/citologia , Citometria de Fluxo , Humanos , Injeções Intralinfáticas , Linfa/imunologia , Linfonodos/citologia , Vasos Linfáticos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptores CCR7/deficiência , Receptores CCR7/genética
15.
Eur J Immunol ; 41(3): 611-23, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21341262

RESUMO

Deficiency of transplant recipients for the chemokine receptor CCR7 was originally described to slightly increase the survival time of vascularized solid organ grafts, probably due to a reduced priming of alloreactive T cells. Using a model of allotolerance induction by donor-specific splenocyte transfusion (DST) in combination with anti-CD40L mAb-mediated costimulation blockade (CSB), we show here a striking failure of CCR7-deficient (CCR7(-/-) ) recipients to tolerate cardiac allografts. Furthermore, in addition to the recently described lack of Treg, CCR7(-/-) mice were found to harbor significantly reduced numbers of plasmacytoid dendritic cells (pDCs) within peripheral as well as mesenteric lymph nodes (LNs), but not the bone marrow or spleen. pDCs had previously been suggested to function as tolerogenic APC during allograft transplantation, and a single transfer of syngeneic WT pDCs, but not conventional DCs, was indeed sufficient to rescue graft survival in DST+CSB-treated CCR7(-/-) recipients in a dose-dependent manner. We therefore conclude that the nearly complete absence of pDCs within LNs of CCR7(-/-) mice prevents the successful induction of DST+CSB-mediated allotolerance, leading to the observed acute rejection of cardiac allografts under tolerizing conditions.


Assuntos
Transplante de Coração/imunologia , Receptores CCR7/deficiência , Tolerância ao Transplante/imunologia , Transferência Adotiva , Animais , Anticorpos Monoclonais/administração & dosagem , Ligante de CD40/antagonistas & inibidores , Células Dendríticas/imunologia , Células Dendríticas/transplante , Sobrevivência de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Transplante de Coração/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Modelos Animais , Receptores CCR7/genética , Receptores CCR7/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo , Transplante Isogênico
16.
Science ; 324(5928): 758, 2009 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-19423819

RESUMO

A major transition in evolution is the origin of a division between reproduction and work among individuals. Nowhere is this divide more striking than in social insects, where workers rarely produce offspring even though they are often capable of reproduction should the queen or king die. The molecular mechanisms that control worker reproduction remain largely unknown. We used a combination of behavioral assays and RNA interference (RNAi) to identify a gene required for the reproductive division of labor between the queen and the workers.


Assuntos
Genes , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Isópteros/genética , Isópteros/fisiologia , Animais , Comportamento Animal , Evolução Molecular , Feminino , Isópteros/enzimologia , Interferência de RNA , Reprodução/genética , Comportamento Social
17.
J Immunol ; 182(11): 6861-9, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19454682

RESUMO

Murine gamma-herpes virus 68 is a natural rodent pathogen closely related to the human gamma-herpes viruses Kaposi's sarcoma-associated herpes virus and EBV. By intranasally infecting wild-type and CCR7-deficient mice, we investigated whether CCR7 is necessary for viral clearance from the lung and the establishment of latency. We found during the lytic phase of infection that inflammation in lungs of CCR7(-/-) mice was more severe and viral load significantly higher compared with wild-type littermates. In addition, activation of T cells was delayed and clearance of the inflammation was retarded in mutant lungs, demonstrating that CCR7 is necessary for a rapid and efficient immune response. However, for the establishment of splenomegaly and latency, the presence of CCR7 was dispensable. Finally, by microdissecting BALT, we could demonstrate that these ectopic lymphoid structures are a place in the lung where virus resides during latency.


Assuntos
Brônquios/virologia , Pulmão/virologia , Receptores CCR7/imunologia , Rhadinovirus/imunologia , Latência Viral , Animais , Inflamação , Pulmão/imunologia , Ativação Linfocitária , Camundongos , Rhadinovirus/fisiologia , Linfócitos T/imunologia , Carga Viral
18.
Evol Dev ; 11(3): 269-77, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19469854

RESUMO

Wood-dwelling termites are characterized by an extremely high and unique developmental flexibility that allows workers, which are immatures, to explore all caste options. The endocrine signatures underlying this flexibility are only vaguely understood. We determined juvenile hormone (JH) and ecdysteroid hemolymph titers during postembryonic development and in terminal instars of the drywood termite Cryptotermes secundus using field and laboratory colonies. Postembryonic development is characterized by a drop in JH titers at the transition from larval (individuals without wing buds) to nymphal (individuals with wing buds) instars. JH titers were low in winged sexuals and reproducing primary reproductives (<200 pg/microl) but were by an order of magnitude higher in neotenic replacement reproductives. The unique regressive molts of termites seem to be characterized by elevated JH titers, compared with progressive or stationary molts. Ecdysteroid titers were generally low in nymphal instars and in primary reproductives (<50 pg/microl). It was only during the third and fourth nymphal instars and in winged sexuals where some individuals showed elevated ecdysteroid titers. These results are the most comprehensive endocrinological data set available for any lower termite, with the potential to serve as baseline for understanding the extreme developmental flexibility underlying the evolution of social life in termites.


Assuntos
Glândulas Endócrinas/crescimento & desenvolvimento , Isópteros/crescimento & desenvolvimento , Animais , Ecdisteroides/metabolismo , Isópteros/metabolismo , Morfogênese , Radioimunoensaio
19.
Naturwissenschaften ; 96(2): 315-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19034403

RESUMO

In social insects, it is assumed that signals of the queen inform nestmates about her reproductive status. Thus, workers forego their own reproduction if the queen signals high fertility. In hemimetabolous termites, little is known about reproductive inhibition, but evidence exists for a royal-pair control. Workers of lower termites exhibit a high developmental flexibility and are potentially able to become reproductives, but the presence of a fertile reproductive restrains them from reaching sexual maturity. The nature of this control, however, remains unknown. Here, we report on qualitative differences in cuticular hydrocarbon profiles between queens and workers of the basal drywood termite Cryptotermes secundus. Queens were characterized by a shift to long-chained and branched hydrocarbons. Most remarkably, similar chemical patterns are regarded as fertility cues of reproductives in social Hymenoptera. This might suggest that both groups of social insects convergently evolved similar chemical signatures. The present study provides deeper insights into how termites might have socially exploited these signatures from sexual communication in their cockroach-like ancestor.


Assuntos
Hidrocarbonetos/análise , Isópteros/fisiologia , Reprodução/fisiologia , Animais , Feminino , Hidrocarbonetos/isolamento & purificação , Comportamento de Nidação , Comportamento Social , Madeira/parasitologia
20.
ASAIO J ; 49(3): 340-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12790387

RESUMO

An increase in the number of patients with end stage heart failure is leading to increased use of ventricular assist devices (VAD). However, sometimes the optimal time point for implantation of left ventricular or biventricular support remains unclear. Data analysis using an electronic database may help to make the decision making process more precise and thus improve outcome. However, it is not easy to find a balance between sufficient comprehensiveness of the data, which are selected from a huge amount of available information, and practicability of database maintenance and data analysis. We developed the Assist Database based on Access for Windows. The Assist Database consists of five main parts: (1) demographic and admission data, diagnosis, goal, and type of VAD; (2) preoperative period; (3) postoperative period up to 30 days; (4) follow-up period; and (5) statistical evaluation. The preoperative and postoperative parts include hemodynamic data; ventilatory support; laboratory results; results from echocardiographic, neurologic, pathologic, and other examinations; medication; and complications. The follow-up part documents readmissions, complications, and outcome. From April 1987 to October 2002, eight different types of VAD were implanted in 654 patients in our institution. Their data were retrospectively added to the Assist Database using medical records and different previously used electronic databases. Since the Assist Database came into routine use, it has been supplied daily with selected data of current patients. On the data entry level, the data arising from medical records are entered either manually via standard forms or automatically from other electronic documentation systems used in our hospital in routine patient care to collect laboratory results, demographic data, blood transfusion data, and operative data and from electronic patient charts via interfaces. The structure of the database is designed to facilitate the data analysis level. The database presented is one of three databases united to form a network. The structure of the Assist Database facilitates comprehensive, time saving data collection, which allows different online data analyses. These analyses may affect the decision making process and thus improve outcome. However, achieving a balance between the volume of available information, the time consumed, and the relevance of the data for further analysis remains difficult. The Assist Database should include information relevant for the decision making process and for the prediction of outcome. In particular, data collection should be focused on patients' preoperative condition and on postoperative organ function and quality of life. Further, different databases (for patients with congestive heart failure, assist device patients, and transplanted patients) should be unified to form a network to avoid the repeated collection of identical data, to save time, and to increase the quality of analysis. In the long-term, multicenter use of the Assist Database could be considered.


Assuntos
Bases de Dados Factuais , Coração Auxiliar , Sistemas Computadorizados de Registros Médicos , Coleta de Dados/métodos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/estatística & dados numéricos , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA