Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.394
Filtrar
1.
Medicine (Baltimore) ; 99(5): e18927, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000406

RESUMO

Cytomegalovirus (CMV) gastritis is a rare opportunistic infection with diverse clinical manifestations. Our study aimed to investigate the clinical features of Chinese patients with CMV gastritis.Six inpatients diagnosed with CMV gastritis were retrospectively enrolled, based on the finding of inclusion bodies in routine hematoxylin and eosin staining or positive anti-CMV monoclonal antibodies under immunohistochemistry in the gastric biopsy. Data, including demographics, diagnostic measurements, and medications, were collected.Abdominal pain was the most frequently reported symptom, occurring in 4 patients. Five patients were immunocompromised with associated underlying diseases, and 3 patients had decreased leukocyte differentiation antigen 4 positive (CD4) T lymphocyte counts. Only 3 patients had either positive cytomegalovirus (CMV)-immunoglobulin (Ig) M or increased copies of CMV-DNA peripherally. All patients had gastric lesions in the antrum of the stomach, including ulcers or erosions observed by gastroscopy. All patients received ganciclovir by intravenous injection (IV) as the first line anti-CMV therapy, and attained complete (4) or partial remission (2) during the follow-up.CMV gastritis should be taken into consideration in patients with immunocompromised status who have abdominal pain, nausea, or vomiting. Gastroscopy and necessary biopsy are the major diagnostic methods for CMV gastritis. Early diagnosis leads to a better prognosis for these patients.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Gastrite/diagnóstico , Gastrite/epidemiologia , Dor Abdominal/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/epidemiologia , Dor Abdominal/etiologia , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Feminino , Gastrite/tratamento farmacológico , Gastrite/patologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/diagnóstico , Náusea/tratamento farmacológico , Náusea/epidemiologia , Náusea/etiologia , Prognóstico , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/patologia , Centros de Atenção Terciária , Vômito/diagnóstico , Vômito/tratamento farmacológico , Vômito/epidemiologia , Vômito/etiologia
2.
PLoS Pathog ; 16(2): e1007968, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32059027

RESUMO

Human cytomegalovirus (HCMV) infection is the leading non-genetic cause of congenital birth defects worldwide. While several studies have addressed the genetic composition of viral populations in newborns diagnosed with HCMV, little is known regarding mother-to-child viral transmission dynamics and how therapeutic interventions may impact within-host viral populations. Here, we investigate how preexisting CMV-specific antibodies shape the maternal viral population and intrauterine virus transmission. Specifically, we characterize the genetic composition of CMV populations in a monkey model of congenital CMV infection to examine the effects of passively-infused hyperimmune globulin (HIG) on viral population genetics in both maternal and fetal compartments. In this study, 11 seronegative, pregnant monkeys were challenged with rhesus CMV (RhCMV), including a group pretreated with a standard potency HIG preparation (n = 3), a group pretreated with a high-neutralizing potency HIG preparation (n = 3), and an untreated control group (n = 5). Targeted amplicon deep sequencing of RhCMV glycoprotein B and L genes revealed that one of the three strains present in the viral inoculum (UCD52) dominated maternal and fetal viral populations. We identified minor haplotypes of this strain and characterized their dynamics. Many of the identified haplotypes were consistently detected at multiple timepoints within sampled maternal tissues, as well as across tissue compartments, indicating haplotype persistence over time and transmission between maternal compartments. However, haplotype numbers and diversity levels were not appreciably different between control, standard-potency, and high-potency pretreatment groups. We found that while the presence of maternal antibodies reduced viral load and congenital infection, it had no apparent impact on intrahost viral genetic diversity at the investigated loci. Interestingly, some minor haplotypes present in fetal and maternal-fetal interface tissues were also identified as minor haplotypes in corresponding maternal tissues, providing evidence for a loose RhCMV mother-to-fetus transmission bottleneck even in the presence of preexisting antibodies.


Assuntos
Anticorpos Antivirais/farmacologia , Infecções por Citomegalovirus , Citomegalovirus/metabolismo , Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez , Animais , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/patologia , Feminino , Macaca mulatta , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia
3.
PLoS One ; 15(1): e0226182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929537

RESUMO

People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD), and immunity against cytomegalovirus (CMV) may be a contributing factor. We hypothesized that enhanced T-cell responses against CMV and CMV-IgG antibody-levels are associated with higher arterial blood pressure in PLHIV. We assessed serum CMV-IgG, systolic- (SBP) and diastolic- (DBP) blood pressure, pulse pressure (PP), traditional risk factors, activated CD8+ T-cells (CD38+HLA-DR+), senescent CD8+ T-cells (CD28-CD57+) and interleukin-6 (IL-6) in 60 PLHIV and 31 HIV-uninfected controls matched on age, gender, education and comorbidity. In PLHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65 and CMV-gB. Associations between CMV-specific immune responses and hypertension, SBP, DBP or PP were assessed by multivariate logistic and linear regression models adjusted for appropriate confounders. The median age of PLHIV was 47 years and 90% were male. Prevalence of hypertension in PLHIV was 37% compared to 55% of HIV-uninfected controls. CMV-specific CD8+ T-cell responses were independently associated with higher PP (CMV-pp65; ß = 2.29, p = 0.001, CMV-gB; ß = 2.42, p = 0.001) in PLHIV. No significant differences were found with regard to individual measures of SBP and DBP. A possible weak association was found between CMV-IgG and hypertension (ß = 1.33, p = 0.049) after adjustment for age, smoking and LDL-cholesterol. HIV-related factors, IL-6, CD8+ T-cell activation or CD8+ T-cell senescence did not mediate the associations, and no associations were found between CMV-specific CD4+ T-cell responses and blood pressure in PLHIV. In conclusion, increased arterial blood pressure in PLHIV may be affected by heightened CMV-specific CD8+ T-cell responses.


Assuntos
Pressão Sanguínea , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/imunologia , Infecções por HIV/patologia , Adulto , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Senescência Celular , Citomegalovirus/metabolismo , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Feminino , Infecções por HIV/complicações , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/patologia , Interleucina-2/análise , Interleucina-6/sangue , Modelos Logísticos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Proteínas da Matriz Viral/imunologia
4.
Exp Oncol ; 41(4): 300-303, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31868329

RESUMO

The review analyzes in detail the data on cytomegalovirus (CMV) as the cause of the development of malignant brain tumors. The use of modern methods of immunohistochemistry and polymerase chain reaction makes it possible to detect both individual proteins and CMV genes in tumor tissue, while virus cannot be isolated from tumor tissue using classical virological methods. The paper discusses the theories of "hit-and-run" and "microinfections", which explain the mechanism of action of CMV. The data on various molecular mechanisms of transformation of normal cells into tumor cells under the action of CMV are presented. The presence of CMV was shown not only in tumor cells, but also in neural stem cells, monocytes and macrophages. The possibility of using immunotherapy with T-lymphocytes and CMV-based dendritic cellular vaccines for the treatment of cancer patients is discussed in detail. Clinical data on their effectiveness are presented. Three possible mechanisms of the action of immunotherapeutic drugs containing CMV antigens are considered.


Assuntos
Neoplasias Encefálicas/virologia , Infecções por Citomegalovirus/complicações , Citomegalovirus/fisiologia , Animais , Encéfalo/patologia , Encéfalo/virologia , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/patologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Células-Tronco Neurais/patologia , Células-Tronco Neurais/virologia
5.
Diagn Cytopathol ; 47(11): 1194-1196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31322837

RESUMO

Liver transplant recipients are prone to several infections, including lung infections, which can lead to substantial morbidity and mortality. Bronchoalveolar lavage (BAL) cytology is a rapid and sensitive diagnostic tool to identify the etiologic agents. We report a rare case of a 24-year-old male, post Live donor liver transplantation for autoimmune chronic liver disease, who presented with cough, fever, weight loss, and cavitatory lesion in lung. BAL cytology revealed Leishmania donovani (LD) and Pneumocystis jirovecii/carinii (PCP). Cytomegalovirus deoxyribonucleic acid polymerase chain reaction (CMV DNA PCR) test showed markedly raised levels. Patient was put on treatment for these multiple infections and showed significant improvement. Thus, rapid diagnosis of infections through BAL cytology is crucial in transplant recipients to institute timely therapy and avoid undesirable empirical treatments. Moreover, this case highlights a rare finding of LD bodies along with PCP in BAL cytology.


Assuntos
Líquido da Lavagem Broncoalveolar , Lavagem Broncoalveolar , Infecções por Citomegalovirus , Leishmania donovani/genética , Leishmaniose Visceral , Transplante de Fígado , Pneumocystis carinii/genética , Pneumonia por Pneumocystis , Reação em Cadeia da Polimerase , Adulto , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/parasitologia , Líquido da Lavagem Broncoalveolar/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/patologia , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/genética , Leishmaniose Visceral/patologia , Doadores Vivos , Masculino , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/genética , Pneumonia por Pneumocystis/patologia
6.
PLoS One ; 14(6): e0218471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216320

RESUMO

BACKGROUND: Human cytomegalovirus (CMV) has been emerged as one of the causes of acute recurrent or chronic hypertensive anterior uveitis in immunocompetent. In hypertensive anterior uveitis, human trabecular meshwork (TM) cells are considered a focus of inflammation. We investigated the effects of losartan, a selective angiotensin II receptor antagonist, on CMV infection in human TM cells. METHODS: Human TM cells were infected with CMV AD169. Virus infected and mock-infected cells were treated with losartan or dexamethasone or ganciclovir with or without transforming growth factor (TGF)-ß1. Viral DNA accumulation and host cell response were analyzed using real-time PCR. Levels of secreted TGF-ß1 were measured by determining its concentration in conditioned medium using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: CMV infection significantly increased the concentrations of the secreted TGF-ß1 at 3, 5, and 7 day post infection in TM cells. Treatment with dexamethasone or losartan significantly decreased the levels of TGF-ß1, whereas treatment with ganciclovir did not affect TGF-ß1 levels. TM cells treated with TGF-ß1 along with the presence of losartan for 48 hours showed marked decrease in the expression of α-smooth muscle actin (SMA), lysyl oxidase (LOX), connective tissue growth factor (CTGF), fibronectin and collagen-1A, compared with cells treated with TGF-ß1 alone. CMV-infected TM cells stimulated by TGF-ß1 significantly increased the expression of α-SMA and CTGF, which were attenuated by additional treatment with losartan. CONCLUSION: Losartan inhibited the expression of TGF-ß1 and fibrogenic molecules in human TM cells. Thus, losartan has the potential to decrease TM fibrosis in patients with CMV-induced hypertensive anterior uveitis.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Fibrose/tratamento farmacológico , Losartan/farmacologia , Malha Trabecular/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Actinas/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Ensaio de Imunoadsorção Enzimática , Fibrose/patologia , Fibrose/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína-Lisina 6-Oxidase/genética , Malha Trabecular/patologia
8.
PLoS Pathog ; 15(5): e1007785, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083700

RESUMO

Memory T cell inflation is a process in which a subset of cytomegalovirus (CMV) specific CD8 T cells continuously expands mainly during latent infection and establishes a large and stable population of effector memory cells in peripheral tissues. Here we set out to identify in vivo parameters that promote and limit CD8 T cell inflation in the context of MCMV infection. We found that the inflationary T cell pool comprised mainly high avidity CD8 T cells, outcompeting lower avidity CD8 T cells. Furthermore, the size of the inflationary T cell pool was not restricted by the availability of specific tissue niches, but it was directly related to the number of virus-specific CD8 T cells that were activated during priming. In particular, the amount of early-primed KLRG1- cells and the number of inflationary cells with a central memory phenotype were a critical determinant for the overall magnitude of the inflationary T cell pool. Inflationary memory CD8 T cells provided protection from a Vaccinia virus challenge and this protection directly correlated with the size of the inflationary memory T cell pool in peripheral tissues. These results highlight the remarkable protective potential of inflationary CD8 T cells that can be harnessed for CMV-based T cell vaccine approaches.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Memória Imunológica/imunologia , Muromegalovirus/imunologia , Receptores Imunológicos/imunologia , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Imunológicos/metabolismo
9.
Ann Hematol ; 98(8): 1877-1883, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144019

RESUMO

Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.


Assuntos
Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/virologia , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Ativação Viral/imunologia , Adolescente , Adulto , Idoso , Antígenos CD34/imunologia , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/virologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Haploidêntico
10.
Med Microbiol Immunol ; 208(3-4): 475-485, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31065796

RESUMO

Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, yet there are no established treatments for preventing maternal-fetal transmission. During first trimester, HCMV replicates in basal decidua that functions as a reservoir for virus and source of transmission to the attached placenta and fetal hemiallograft but also contains immune cells, including natural killer cells, macrophages, and T cell subsets, that respond to pathogens, protecting the placenta and fetus. However, the specific cellular and cytokine responses to infection are unknown, nor are the immune correlates of protection that guide development of therapeutic strategies. Here we survey immune cell phenotypes in intact explants of basal decidua infected with a clinical pathogenic HCMV strain ex vivo and identify specific changes occurring in response to infection in the tissue environment. Using 4-color immunofluorescence microscopy, we found that at 3 days postinfection, virus replicates in decidual stromal cells and epithelial cells of endometrial glands. Infected cells and effector memory CD8+ T cells (TEM) in contact with them make IFN-γ. CD8+ TEM cells produce granulysin and cluster at sites of infection in decidua and the epithelium of endometrial glands. Quantification indicated expansion of two immune cell subtypes-CD8+ TEM cells and, to a lesser extent, iNKT cells. Approximately 20% of immune cells were found in pairs in both control and infected decidua, suggesting frequent cross-talk in the microenvironment of decidua. Our findings indicate a complex immune microenvironment in basal decidua and suggest CD8+ TEM cells play a role in early responses to decidual infection in seropositive women.


Assuntos
Infecções por Citomegalovirus/patologia , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/imunologia , Decídua/patologia , Imunidade Celular , Placenta/patologia , Linfócitos T CD8-Positivos/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Células T Matadoras Naturais/imunologia , Técnicas de Cultura de Órgãos , Gravidez , Células Estromais/patologia , Células Estromais/virologia
11.
Malays J Pathol ; 41(1): 75-78, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31025643

RESUMO

We report a case of congenital cytomegalovirus and Herpes simplex virus infection suspected via ultrasound indicated by the presence of fetal cerebral abnormalities. The pregnancy was electively terminated at 31 weeks of gestation. The postmortem examination of the foetus showed brain with lissencephaly. The histopathological examination revealed numerous enlarged cells containing cytomegalic inclusions and multinucleated giant cells in multiple fetal organs and placenta. Documented evidence of histopathological detection of cytomegalovirus inclusions in multiple organs are very sparse in literature. This case highlights the causal relationship of viral infections in early pregnancy and abnormalities of the central nervous system.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/patologia , Feto/patologia , Herpes Simples/congênito , Herpes Simples/patologia , Complicações Infecciosas na Gravidez/patologia , Feminino , Feto/virologia , Humanos , Lisencefalia/patologia , Lisencefalia/virologia , Gravidez
12.
Clin J Gastroenterol ; 12(5): 407-413, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30945123

RESUMO

Ulcerative colitis has hypercoagulable state and high risk of thrombosis; so mucosal disturbance of microcirculation may be mediate and amplify the inflammation of ulcerative colitis. A 56-year-old female patient was admitted in hospital for discontinuously mucous bloody stool for more than 1 year. Ulcerative colitis was determined after colonoscopy and pathologic examination. Mesalazine was effective during the year, but her symptoms recurred three times due to her bad compliance. One month before admission, the patient had severe recurrence after mesalazine withdrawal. At this time, the result of quantitative fluorescence PCR of colonic histic CMV-DNA was 1.6 × 104 copies/mL positive, CMV colitis was accompanied. After 4 weeks of ganciclovir and 6 weeks of mesalazine usage and nutrition support, the symptoms of diarrhea and abdominal cramp did not improve; stool frequency was more than twenty times a day. Probe-based confocal laser endomicroscopy revealed local microcirculation disturbance. Papaverine 90-mg slow drip for at least 10 h a day was added. The symptoms dramatically disappeared after 3 days of papaverine treatment. The patient had yellow mushy stool 2-3 times a day. Pathological findings showed diffuse submucosal hemorrhage and transparent thrombosis in capillaries. Treatment of microcirculatory disturbance in severe UC is a promising adjuvant therapy. Confocal laser endomicroscopy may be an effective method for microcirculation judgment.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Infecções por Citomegalovirus/complicações , Papaverina/uso terapêutico , Vasodilatadores/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Colo/irrigação sanguínea , Colo/patologia , Colonoscopia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/fisiopatologia , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Microcirculação/efeitos dos fármacos , Microscopia Confocal , Pessoa de Meia-Idade
13.
Arch Virol ; 164(5): 1249-1257, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30888562

RESUMO

Malignant gliomas are the most common types of incurable primary brain tumours. Therefore, to better clarify the aetiology and pathogenesis of the disease and analyse the risk factors involved, several researchers have highlighted a possible link to human cytomegalovirus (HCMV). Regarding this potential link, the numbers of studies and controversies concerning the relationship between HCMV infections and malignant gliomas have significantly increased. Therefore, we conducted a meta-analysis of observational studies to summarize and pool the available results on the association of HCMV in patients with glioma. Our meta-analysis was based on the PRISMA algorithm, using fixed/random models through STATA IC 13.1 software. Thus, 32 studies were included with a total of 2,190 participants/specimens (glioma, n = 1,871; non-glioma, n = 319). The overall estimate of combined HCMV frequency in patients with glioma was 63% (95% confidence interval [CI]: 56-70). There was an association between HCMV infection and glioma (adjusted OR = 3, 95% CI: 1.7-5.3). The pooled subgroup analysis of viral markers also showed a positive association between the pp65 protein (OR = 3.1, 95% CI: 1.8-5), and gB nucleic acids (OR = 3.1, 95% CI: 1.1-8). For the viral marker IE1-72 protein, the pooled frequency and association results were higher. However, there was no correlation of higher viral association according to the histological subtypes and low/high grade of gliomas. In conclusion, the available evidence suggests an association between HCMV and glioma. Consequently, precautions should be taken, as discussed in this report.


Assuntos
Neoplasias Encefálicas/virologia , Infecções por Citomegalovirus/patologia , Citomegalovirus/isolamento & purificação , Glioma/virologia , Neoplasias Encefálicas/patologia , Citomegalovirus/genética , Glioma/patologia , Humanos , Proteínas Imediatamente Precoces/genética
14.
J Virol ; 93(9)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30814291

RESUMO

Chromatin-based modifications of herpesviral genomes play a crucial role in dictating the outcome of infection. Consistent with this, host cell multiprotein complexes, such as polycomb repressive complexes (PRCs), were proposed to act as epigenetic regulators of herpesviral latency. In particular, PRC2 has recently been shown to contribute to the silencing of human cytomegalovirus (HCMV) genomes. Here, we identify a novel proviral role of PRC1 and PRC2, the two main polycomb repressive complexes, during productive HCMV infection. Western blot analyses revealed strong HCMV-mediated upregulation of RING finger protein 1B (RING1B) and B lymphoma Moloney murine leukemia virus insertion region 1 homolog (BMI1) as well as of enhancer of zeste homolog 2 (EZH2), suppressor of zeste 12 (SUZ12), and embryonic ectoderm development (EED), which constitute the core components of PRC1 and PRC2, respectively. Furthermore, we observed a relocalization of PRC components to viral replication compartments, whereas histone modifications conferred by the respective PRCs were specifically excluded from these sites. Depletion of individual PRC1/PRC2 proteins by RNA interference resulted in a significant reduction of newly synthesized viral genomes and, in consequence, a decreased release of viral particles. Furthermore, accelerated native isolation of protein on nascent DNA (aniPOND) revealed a physical association of EZH2 and BMI1 with nascent HCMV DNA, suggesting a direct contribution of PRC proteins to viral DNA replication. Strikingly, substances solely inhibiting the enzymatic activity of PRC1/2 did not exert antiviral effects, while drugs affecting the abundance of PRC core components strongly compromised HCMV genome synthesis and particle release. Taken together, our data reveal an enzymatically independent, noncanonical function of both PRC1 and PRC2 during HCMV DNA replication, which may serve as a novel cellular target for antiviral therapy.IMPORTANCE Polycomb group (PcG) proteins are primarily known as transcriptional repressors that modify chromatin and contribute to the establishment and maintenance of cell fates. Furthermore, emerging evidence indicates that overexpression of PcG proteins in various types of cancers contributes to the dysregulation of cellular proliferation. Consequently, several inhibitors targeting PcG proteins are presently undergoing preclinical and clinical evaluation. Here, we show that infection with human cytomegalovirus also induces a strong upregulation of several PcG proteins. Our data suggest that viral DNA replication depends on a noncanonical function of polycomb repressor complexes which is independent of the so-far-described enzymatic activities of individual PcG factors. Importantly, we observe that a subclass of inhibitory drugs that affect the abundance of PcG proteins strongly interferes with viral replication. This principle may serve as a novel promising target for antiviral treatment.


Assuntos
Infecções por Citomegalovirus/metabolismo , Citomegalovirus/fisiologia , Replicação do DNA , DNA Viral/biossíntese , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Replicação Viral , Células Cultivadas , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/terapia , DNA Viral/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 2/genética
15.
Dermatol Online J ; 25(1)2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30710895

RESUMO

The possible presentations of cytomegalovirus (CMV) are vast not only in its systemic manifestations, but also in the various cutaneous lesions that may result. Cutaneous cytomegalovirus is rarely reported in the literature because the clinical and pathologic features can be difficult to identify. Its identification, however, is vital as cutaneous human CMV infection can signal systemic disease and an unfavorable prognosis. The objective of this study is to aid in recognition, diagnosis, and treatment of CMV according to dermatological evidence. A complete literature search was performed within PubMed, resulting in the inclusion of 58 patient cases. The most common dermatologic manifestation was perianal or oral ulcers, but the locations and types of lesions noted throughout the review were numerous. Treatment is often simple, yet incorrect diagnoses along with concurrent illnesses can often complicate management. It is imperative for CMV to be detected early in its course to prevent mortality, especially in the immunocompromised. Dermatological presentations are often the first sign of this deadly virus' activity and it is essential that these diagnoses are made more efficient and accurate.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Dermatopatias Virais/diagnóstico , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Órgãos , Dermatopatias Virais/tratamento farmacológico , Dermatopatias Virais/imunologia , Dermatopatias Virais/patologia
16.
BMJ Case Rep ; 12(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739086

RESUMO

A 42-year-old woman with a history of cholangiocarcinoma on adjuvant chemotherapy with capecitabine presented with painless haematochezia. She was found to have an isolated twenty-five mm ulcer in the ascending colon. Biopsies of the ulceration demonstrated typical cytomegalovirus (CMV) inclusions and her peripheral blood CMV PCR was significantly elevated. This is an unusual case of a solitary proximal colon ulcer. Non-steroidal anti-inflammatory drugs, inflammatory bowel disease and malignancy, are the most frequent causes of isolated ulcers in the proximal colon. Gastrointestinal (GI) CMV disease most commonly causes CMV colitis and is considered rare outside of the transplant population and other severely immunosuppressed patient groups. Patients who have received chemotherapy may also be at risk for GI CMV disease. The diagnosis should be suspected in patients who present with haematochezia or watery diarrhoea within a broad window of time after receiving chemotherapy.


Assuntos
Colite/diagnóstico , Colo Ascendente/patologia , Infecções por Citomegalovirus/diagnóstico , Úlcera/diagnóstico , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Antivirais/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Capecitabina/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Colangiocarcinoma/tratamento farmacológico , Colite/complicações , Colite/patologia , Colite/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/patologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Pancreaticoduodenectomia , Fatores de Risco , Úlcera/complicações , Úlcera/patologia , Úlcera/virologia , Valaciclovir/uso terapêutico
17.
Comp Med ; 69(1): 55-62, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30704552

RESUMO

Cytomegalovirus (CMV) is a common chronic herpesvirus found in humans and numerous other mammalian species. In people, chronic viruses like CMV can alter overall health and immunity and pose a serious risk for those with an inadequate immune system. In addition, CMV plays an important role in animal health, and could affect the health of vulnerable populations, like endangered species. Previous studies found a high rate of CMV seropositivity among adult baboons (Papio anubis), and results from our laboratory revealed that baboon CMV (BaCMV) seropositivity was correlated with altered immune cell populations. In the current study, we further characterized BaCMV infection in normal, adult baboons. Analysis of blood samples from baboons (age, 6 to 26 y) revealed a low overall prevalence of detectable of BaCMV DNA, with a higher detection rate in aged baboons (older than 15 y). Furthermore, data suggest that individual baboons maintain similar rates of recurrence and levels of BaCMV shedding in saliva over time. Finally, we evaluated multiple commercially available assays for antihuman CMV IgG and IgM for use with baboon sera. Results of this study will improve our understanding of BaCMV and may be directly relevant to other closely related species.


Assuntos
Infecções por Citomegalovirus/veterinária , Doenças dos Macacos/patologia , Papio anubis , Fatores Etários , Animais , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , DNA Viral/sangue , Doenças dos Macacos/sangue , Doenças dos Macacos/imunologia , Saliva/virologia , Eliminação de Partículas Virais
18.
BMC Gastroenterol ; 19(1): 3, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616563

RESUMO

BACKGROUND: Many reports have documented the increasing impact of Clostridium difficile infection (CDI) in patients with ulcerative colitis (UC). We conducted a retrospective study to determine the incidence, clinical characteristics, risk factors and prognosis of CDI in patients with UC. METHODS: We studied patients with UC, hospitalized between January 2010 and December 2015 in a tertiary hospital in China. Stool samples were tested for C. difficile toxins A and B (CDAB) by enzyme immunoassays in UC patients with disease flare. CDI in UC patients was diagnosed by clinical symptoms and positive CDAB test, and each case was matched with CDAB-negative patients in a 1:2 ratio. Univariate and binary logistic regression analyses were used to measure the differences between patients with and without CDI. RESULTS: Thirty-four (8.92%) of 381 patients with UC were CDAB positive. Antibiotic exposure within 3 months prior to the study (P = 0.004), hospitalization within 1 month prior to the study (P = 0.025), systemic use of steroids (P = 0.002) and active cytomegalovirus (CMV) infection (P = 0.001) were higher in CDI than non-CDI patients. Binary logistic regression analysis revealed that CMV infection was associated with CDI (odds ratio = 13.502, 95% confidence interval 1.307-139.512, P = 0.029). UC patients with C. difficile and CMV co-infection had more severe colonoscopic features. CONCLUSIONS: Recent use of antibiotics, prior hospitalization and systemic use of steroids increased the risk of CDI. CMV infection was an independent risk factor of CDI in patients with UC.


Assuntos
Infecções por Clostridium/epidemiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/microbiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/patologia , Coinfecção , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Colonoscopia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/patologia , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária
19.
Arch Pathol Lab Med ; 143(5): 639-642, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30500287

RESUMO

In the United States, cytomegalovirus is the most common congenital viral infection and the number 1 cause of nonhereditary sensorineural hearing loss. The vast majority of infants may be asymptomatic, especially if cytomegalovirus is contracted later in the pregnancy, and some symptoms may have a delayed onset. Therefore, it is important for the pathologist to identify the common histologic findings to help confirm the diagnosis so the child can be followed for late sequelae. Histologic examination of the placenta is important in live births and in cases of intrauterine fetal demise. Chronic lymphoplasmacytic villitis and fibrotic, avascular villi are the most common findings. When present, Cowdry A intranuclear and basophilic intracytoplasmic inclusions are characteristic. Immunohistochemistry for cytomegalovirus can highlight these inclusions as well as the associated eosinophilic debris. In addition, polymerase chain reaction or viral culture on placental or fetal samples can be performed for confirmation.


Assuntos
Infecções por Citomegalovirus/patologia , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Complicações Infecciosas na Gravidez/patologia , Feminino , Humanos , Gravidez
20.
Ann Hematol ; 98(1): 67-72, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30255313

RESUMO

Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n = 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P = 0.01). Ferritin > 5000 ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P = 0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P = 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.


Assuntos
Síndrome de Imunodeficiência Adquirida , Linfo-Histiocitose Hemofagocítica , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/microbiologia , Síndrome de Imunodeficiência Adquirida/patologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Medula Óssea/metabolismo , Medula Óssea/microbiologia , Medula Óssea/patologia , Medula Óssea/virologia , Criptococose/epidemiologia , Criptococose/microbiologia , Criptococose/patologia , Criptococose/virologia , Cryptococcus neoformans , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/microbiologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Feminino , HIV-1 , Humanos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/microbiologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Mycobacterium , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/patologia , Infecções por Mycobacterium/virologia , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA