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1.
PNAS Nexus ; 3(4): pgae121, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38590971

RESUMO

Little is known about the contribution of 3D surface geometry to the development of multilayered tissues containing fibrous extracellular matrix components, such as those found in bone. In this study, we elucidate the role of curvature in the formation of chiral, twisted-plywood-like structures. Tissues consisting of murine preosteoblast cells (MC3T3-E1) were grown on 3D scaffolds with constant-mean curvature and negative Gaussian curvature for up to 32 days. Using 3D fluorescence microscopy, the influence of surface curvature on actin stress-fiber alignment and chirality was investigated. To gain mechanistic insights, we did experiments with MC3T3-E1 cells deficient in nuclear A-type lamins or treated with drugs targeting cytoskeleton proteins. We find that wild-type cells form a thick tissue with fibers predominantly aligned along directions of negative curvature, but exhibiting a twist in orientation with respect to older tissues. Fiber orientation is conserved below the tissue surface, thus creating a twisted-plywood-like material. We further show that this alignment pattern strongly depends on the structural components of the cells (A-type lamins, actin, and myosin), showing a role of mechanosensing on tissue organization. Our data indicate the importance of substrate curvature in the formation of 3D tissues and provide insights into the emergence of chirality.

2.
J Clin Med ; 12(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37568385

RESUMO

It is not well established to what extent previous immunizations offer protection against infections with the SARS-CoV-2 Omicron variant in dialysis patients. We aimed to define the relevant humoral response in dialysis patients using a SARS-CoV-2 IgG chemiluminescence microparticle immunoassay (CMIA) compared to the activity of neutralizing antibodies assessed by a virus neutralization test. Next, we aimed to determine differences in humoral and cellular response levels over time among patients infected or not infected by the Omicron variant of SARS-CoV-2. Immunological parameters of cellular and humoral response to SARS-CoV-2 were analyzed at baseline and after 3 (T3), 6 (T6) and 14 months (T14). In this monocentric cohort study, we followed 110 dialysis patients (mean age 68.4 ± 13.7 years, 60.9% male) for a median of 545 days. We determined an anti-SARS-CoV-2 IgG level of 56.7 BAU/mL as an ideal cut-off value with a J-index of 90.7. Patients infected during the Omicron era had significantly lower (p < 0.001) mean antibody levels at T0 (3.5 vs. 111.2 BAU/mL), T3 (269.8 vs. 699.8 BAU/mL) and T6 (260.2 vs. 513.9 BAU/mL) than patients without Omicron infection. Patients who developed higher antibody levels at the time of the basic immunizations were less likely to become infected with SARS-CoV-2 during the Omicron era. There is a need to adjust the cut-off values for anti-SARS-CoV-2 IgG levels in dialysis patients.

3.
Leuk Res Rep ; 17: 100327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634195

RESUMO

Chronic myeloid leukemia(CML) is characterized by Philadelphia(Ph) chromosome. About 5% of cases are diagnosed in blast phase. We report a case of a 53-year-old female with no significant medical history, in B-lymphoblast crisis. Flow cytometry demonstrated B-lymphoblasts with no myeloid aberrancies, together with immature neutrophils in blood, and B-lymphoblasts in bone marrow. Cytogenetic studies identified Ph+ with complex abnormalities. Molecular analysis showed positive both for p210 and p190 transcripts in blood. ABL1 mutation analysis by Next Generation Sequencing(NGS) detected Thr315Ile mutation, which confers resistance to many tyrosine kinase inhibitors(TKIs). Eight months later she received allogeneic transplant and is doing well.

4.
Int J Surg Pathol ; 28(3): 330-335, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31631721

RESUMO

Low-grade B-cell lymphoma with immunoglobulin (IG) and interferon regulatory factor 4 (IRF4) gene rearrangement is extremely rare, with only 4 cases being previously reported. In this article, we report one additional case that arises from the skull and review the literature. The patient was a 69-year-old man who presented with recurrent and disabling vertigo and was found to have a 5.0 × 1.7 cm lesion within the left posterior parietal bone. Histological examination revealed a bone lesion with diffuse lymphoid infiltrate comprising of mostly small lymphocytes with scant cytoplasm, slightly irregular nuclei and inconspicuous nucleoli, and scattered larger cells resembling prolymphocytes and paraimmunoblasts. Immunohistochemical studies showed that the neoplastic cells were positive for CD20, CD79a, PAX5, CD23, CD43, BCL-2, BCL-6, MUM-1, LEF-1, and IgM and negative for CD5, CD10, cyclinD1, SOX11, and IgD. Flow cytometric analysis identified CD5 negative and CD10 negative monoclonal B cells with lambda light chain restriction. Fluorescence in situ hybridization analysis revealed del(13q) abnormality, but was negative for IGH/BCL2, IGH/CCND1, and BIRC3/MALT1 translocations. Next-generation sequencing identified IGK-IRF4 rearrangement and BRD4 E1113 del abnormalities. Given a low clinical stage (IE) of the disease, the patient did not receive additional treatments and was free of disease at 1 year after the diagnosis.


Assuntos
Imunoglobulinas/genética , Fatores Reguladores de Interferon/genética , Linfoma de Células B/genética , Neoplasias Cranianas/genética , Idoso , Proteínas de Ciclo Celular/genética , Humanos , Masculino , Fatores de Transcrição/genética , Translocação Genética
5.
Int J Surg Pathol ; 27(2): 166-173, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30058423

RESUMO

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (CHL) are of B-cell origin. In a small number of CHL cases, the tumor cells can express T-cell antigens. CD8 expression in this setting is extremely rare. We identified 5 cases of CHL with aberrant CD8 expression from our database. The patients included 3 men and 2 women with a median age of 33 years (range = 20-59 years). All the patients initially presented with lymphadenopathy and variable number of RS cells. Two cases were classified as mixed cellularity type that showed prominent vascular proliferation mimicking peripheral T-cell lymphoma. Two cases represented nodular sclerosis type. The tumor cells in all cases were positive for CD8 and negative for CD2, CD3, CD4, and CD7 and carried germline T-cell receptor genes. Molecular studies revealed T-cell receptor genes to be in germline configuration in 4 cases with available information. Given the morphologic overlap with peripheral T-cell lymphoma and the rarity of this type of CHL, identifying more cases will help our better understanding of this entity.


Assuntos
Antígenos CD8/biossíntese , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Células de Reed-Sternberg/imunologia , Células de Reed-Sternberg/patologia , Adulto , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Cytopathology ; 30(1): 68-73, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055110

RESUMO

BACKGROUND: Next generation sequencing (NGS) to detect actionable genetic abnormalities is standard of care in advanced stage lung adenocarcinoma. Many studies have shown that the molecular results obtained from fine needle aspiration cytology material are comparable to those obtained from formalin-fixed tissue samples. We undertook this study to validate DNA extraction from cytology material for molecular studies and to find any correlation between DNA yield, pattern of tumour cells and tumour fraction. METHODS: DNA was extracted from 34 cytology slides of pulmonary adenocarcinoma cases with predetermined EGFR mutation status. Cytology slides were reviewed for pattern of tumour distribution and tumour fraction. NGS was performed on five slides with variable DNA and compared with original results. RESULTS: There were 14 alcohol-fixed and 20 air-dried smears. The mean DNA yield was 1.74 µg and median of 0.4 µg (range, 0.02-21 µg). Tumour fractions varied from 10% to 90%. No correlation was found between tumour fraction and DNA yield (P = 0.14). The mean DNA yield was high in slides with tumour throughout the slide (sheets or scattered clusters) as compared to rare scattered clusters and/or single cells. EGFR mutation was found in four of the five cases sent for NGS lung panel while one case revealed BRAF mutation. CONCLUSIONS: DNA with good quantity and quality can be extracted from the cytology slides for NGS irrespective of type of fixation. DNA yield has better correlation with distribution pattern of tumour cells on the slides rather than tumour fraction.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Citodiagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Líquido Ascítico/patologia , Biópsia por Agulha Fina , Receptores ErbB/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
7.
JMIR Public Health Surveill ; 4(3): e59, 2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980501

RESUMO

BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

8.
Wien Med Wochenschr ; 168(11-12): 314-321, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29802493

RESUMO

The confocal laser scanning microscope (CLSM) enables the collection of images picturing selected planes in depth of thick samples, thus giving 3D information while keeping the sample intact. In this article we give an overview of our CLSM applications in bone research: (i) the characterization of osteoblasts and osteoclasts properties in cell biology, (ii) the visualization of the three dimensional (3D) osteocyte lacunar canalicular network in undemineralized plastic-embedded bone samples, (iii) the observation of tetracycline labels in bone biopsy samples from patients in combination with information on the mineralization density from quantitative backscatter electron imaging, which enables the time course of mineral accumulation in newly formed bone to be followed, (iv) the precise measurement of the thickness of thin ground bone sections, a prerequisite for the mapping of local mechanical properties by scanning acoustic microscopy.


Assuntos
Osso e Ossos/ultraestrutura , Microscopia Confocal/métodos , Osteócitos , Osso e Ossos/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Osteoblastos , Osteoclastos , Osteócitos/citologia
9.
Int J Occup Med Environ Health ; 31(2): 227-242, 2018 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29063910

RESUMO

OBJECTIVES: Limited research on the health situation of teachers on long-term sick leave is available. The aim of this study has been to describe the health status of female teachers on long-term sick leave (LSFT) in comparison to working female teachers (WFT) and to determine predictors for their state of mental health (MH) and cardiovascular fitness (CF). MATERIAL AND METHODS: Twenty-eight LSFT and 300 WFT (average age: 53±5 years old) participated in a screening diagnostic inventory. Mental health, CF, blood pressure (BP), body mass index (BMI), body fat mass (BFM), health behavior (smoking, alcohol intake, physical activity) and disease burden (DB - number of medical diagnoses) were analyzed for the purpose of characterization of the health status. The multiple linear regression analysis was performed to identify predictors for the state of MH and CF. RESULTS: Adverse values for the MH but also for CF, BFM and the DB (median of medical diagnoses: LSFT: 5; WFT: 2) among the LSFT in comparison to the WFT were confirmed. Additionally, the part of smokers among LSFT (25%) was higher (WFT: 8%). In contrast, the WFT (61%) were much more affected by an elevated BP (LSFT: 26%). Disease burden proved as the strongest predictor for MH of the female teachers. Age, BMI and DB proved as predictors for CF. CONCLUSIONS: Health-related differences between long-term sick leave and working teachers were particularized and a link between physical and mental health among teachers was quantified. Therefore, health-related concepts for teachers should equally focus on physical and psychological aspects. The relevance of regular well-structured occupational health check-ups should be brought to the attention of the profession to prevent diseases and early retirements. Int J Occup Med Environ Health 2018;31(2):227-242.


Assuntos
Doenças Cardiovasculares/epidemiologia , Nível de Saúde , Professores Escolares , Licença Médica , Adulto , Estudos Transversais , Feminino , Alemanha/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , Transtornos Mentais/epidemiologia , Saúde Mental , Pessoa de Meia-Idade , Fatores de Risco
10.
Int J Mol Sci ; 18(9)2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28914765

RESUMO

Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADP⁺/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells. Global gene expression analysis revealed that after 6 days of treatment with pharmacologic doses of the statin simvastatin and of the bisphosphonate ibandronate, simvastatin regulated more than twice as many genes as ibandronate, including many genes associated with cell cycle progression. Upregulation of starvation-markers and a reduction of metabolism and associated NADPH production, an increase in autophagy, and a concomitant downregulation of H3K27 methylation was most significant in the fast-growing cancer cell lines. This study provides possible explanations for clinical observations indicating a higher sensitivity of rapidly proliferating tumors to statins and bisphosphonates.


Assuntos
Difosfonatos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Metabolismo Energético/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Histonas , Humanos , Metilação
11.
Int J Surg Pathol ; 25(7): 599-603, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28612664

RESUMO

Primary central nervous system T-cell lymphoma (PCNSTCL) is rare, accounting for 2% of CNS lymphomas. We report the first case of PCNSTCL with aberrant expression of CD20 and CD79a in an 81-year-old man with a left periventricular brain mass. A biopsy revealed dense lymphoid infiltrate consisting of medium-sized cells in a background of gliosis and many histiocytes. The lymphoid cells were positive for CD2, CD3, CD7, CD8, T-cell intracellular antigen-1, granzyme B, CD20, and CD79a and negative for CD4, CD5, PAX-5, OCT-2, BOB-1, human herpes virus-8, and Epstein-Barr virus-encoded small RNAs. Molecular studies revealed clonal TCR-ß and TCR-γ gene rearrangements and negative immunoglobulin gene rearrangements. The patient was treated with chemotherapy (vincristine and methotrexate) and rituximab, but he died 1 month after the diagnosis. This is a unique case that emphasizes the use of a multimodal approach, including a broad immunohistochemical panel and molecular studies in lineage determination for lymphomas with ambiguous phenotype.


Assuntos
Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/patologia , Antígenos CD79/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Linfoma de Células T/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Biópsia , Encéfalo/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/virologia , Evolução Fatal , Rearranjo Gênico do Linfócito T , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/isolamento & purificação , Humanos , Imunofenotipagem , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/virologia , Masculino , RNA Viral/isolamento & purificação , Linfócitos T/patologia , Tomografia Computadorizada por Raios X
12.
Blood Coagul Fibrinolysis ; 28(1): 40-49, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26849715

RESUMO

The present study extends our previous investigation of circulating antibody/fibrinogen/C1q complexes (FgIgC) associated with thrombosis in a heterophenotypic AαR16C proband, by focusing on the molecular and functional characteristics of the FgIgC, isolated by cryoprecipitation, FgIgC components were demonstrated by SDS-PAGE and by rotary shadowing electron microscopy. Affinity chromatography was used to isolate IgG and fibrinogen from FgIgC. Thrombin-induced clots were examined by scanning electron microscopy and turbidity measurements. IgG/fibrinogen binding was measured by ELISA. Fibrinogen Aα1-19 peptides, cleaved by thrombin from fragment N-DSK, were examined by mass spectrometry. Clot stiffness, platelet release of P-selectin, and fibrinogen self-assembly were assessed by thromboelastography, flow cytometry, and atomic force microscopy, respectively. The FgIgC effects included the following: increased P-selectin release from gel-sieved platelets, finer fiber networks and decreased stiffness of its clots, and marked inhibition of fibrinogen self-assembly. The abnormal proband fibrinogen structure displayed phosphorylated AαR16C-AαR16C homodimers and AαR16C-glutathione heterodimers. ELISA measurements disclosed pronounced binding by proband fibrinogen to proband IgG, which was blocked by the IgG's Fab fragment and by proband, but not by normal plasmic fragment E1. There was appreciable, but much weaker, binding to normal fibrinogen, to its fragments E1, and D1, and to homodimeric AαR16C fibrinogen. The antibody's primary target epitope included heterodimeric AαR16C-glutathione; a secondary epitope resided in the D region. Moreover, both the enhanced platelet activation (i.e. increased P-selectin release induced by FgIgC) and the highly phosphorylated FpA (i.e. resulting in its accelerated release by thrombin) may have contributed to the thrombotic diathesis.


Assuntos
Plaquetas/metabolismo , Fibrina/metabolismo , Fibrinogênios Anormais/metabolismo , Imunoglobulina G/metabolismo , Trombose/metabolismo , Adulto , Humanos , Masculino , Ativação Plaquetária , Polimerização
14.
J Biol Chem ; 291(13): 6754-71, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-26757819

RESUMO

Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2,Col1a1,Bglap2,Sp7,Atf4, andAlpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of theTet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorptionin vivo Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/prevenção & controle , Isotiocianatos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Caspase 8/genética , Caspase 8/metabolismo , Diferenciação Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Epigênese Genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Transdução de Sinais , Fator de Transcrição Sp7 , Sulfóxidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Microtomografia por Raio-X
15.
Stress Health ; 32(3): 224-30, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25053122

RESUMO

High degrees of premature retirement among teachers warrant investigating the occupational burden and the mental health status of this profession. A sample of 1074 German teachers participated in this study. Two samples of the general population (N = 824 and N = 792) were used as comparison groups. Work distress was assessed with the Effort-Reward-Imbalance questionnaire, and mental health problems were measured with the General Health Questionnaire (GHQ-12). Teachers reported more effort-reward imbalance (M = 0.64) compared with the general population (M = 0.57), and they perceived more mental health problems (GHQ: M = 12.1) than the comparison group (M = 9.5). School type was not associated with work stress and mental health. Teachers with leading functions perceived high degrees of effort and reward, resulting in a moderate effort-reward ratio and no heightened mental health problems. Teachers working full time reported more effort than teachers working part time, but the reward mean values of both groups were similar. This results in a somewhat unfavourable effort-reward ratio of teachers working full time. Moreover, teachers working full time reported more mental health problems. The results support the appropriateness of the effort-reward conception, applied to the profession of teachers. The higher degree of effort-reward imbalance and the level of mental health problems warrant preventive measures. Copyright © 2014 John Wiley & Sons, Ltd.


Assuntos
Transtornos Mentais/epidemiologia , Doenças Profissionais/epidemiologia , Recompensa , Professores Escolares/estatística & dados numéricos , Adulto , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
16.
Appl Immunohistochem Mol Morphol ; 24(8): 589-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26371429

RESUMO

OBJECTIVES: Acquired somatic mutation Janus kinase 2 (JAK2) V617F is associated with various myeloproliferative neoplasms (MPN). Allele-specific real-time polymerase chain reaction has been widely adopted to detect mutation; however, the utility of low positive results is not well understood. The aim of this study is to investigate the clinical significance of low positivity of JAK2 V617F. MATERIALS AND METHODS: Retrospective analysis was performed for JAK2 V617F mutation tests performed using JAK2 MutaQuant kit (Ipsogen) in molecular laboratories at 2 major academic medical centers between 2010 and 2012. Cases with low positive JAK2 V617F, defined as 0.2% to 5% mutant allele, were documented. Chart review was performed for the clinical correlation. RESULTS: A total of 1697 JAK2 V617F tests was performed. Forty-five cases (2.65%) yielded a low JAK2 V617F positivity (average 1.45%), the majority of which (n=26, 62%) had <1%. Eight cases had a history of MPN. The remaining cases were related to reactive conditions without a clonal disease. Our data indicate that a low positivity of JAK2 V617F can be seen in MPN as well as reactive conditions. CONCLUSIONS: An interpretation of JAK2 V617F status should not be performed simply following some arbitrary cutoff. Any low positivity of JAK2 V617F should be reported and a correlation with clinical information is warranted for proper interpretation.


Assuntos
Janus Quinase 2/genética , Mutação , Humanos , Reação em Cadeia da Polimerase , Estudos Retrospectivos
17.
FASEB J ; 29(4): 1344-59, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25491310

RESUMO

Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis.


Assuntos
Osso e Ossos/metabolismo , Proteína Amiloide A Sérica/metabolismo , Células 3T3 , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Osso e Ossos/citologia , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Homeostase , Humanos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteócitos/citologia , Osteócitos/metabolismo , Osteogênese , Comunicação Parácrina , Filogenia , RNA Interferente Pequeno/genética , Receptores Purinérgicos P2X7/metabolismo , Homologia de Sequência de Aminoácidos , Proteína Amiloide A Sérica/antagonistas & inibidores , Proteína Amiloide A Sérica/genética , Crânio/citologia , Crânio/metabolismo
18.
Crit Rev Oncol Hematol ; 90(1): 1-16, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24183913

RESUMO

Disordered stem cell epigenetics and apoptosis-regulating mechanisms contribute essentially to the pathogenesis of myelodysplastic syndromes (MDS) and may trigger disease-progression to secondary acute myeloid leukemia (AML). Expression of apoptosis-mediators FAS (CD95) and DAPK1 the latter being also known for its association with autophagy are upregulated in neoplastic cells in patients with low-risk MDS and epigenetically silenced and downregulated in high-risk MDS and AML as confirmed by a study 50 MDS and 30 AMLs complementing this review. 5-Azacytidine (AZA) and 5-aza-2'deoxycytidine (DAC), promoted FAS and DAPK1 gene demethylation and their (re)expression as well as apoptosis in leukemic cell lines (HL-60, KG1) which can be reversed by siRNA against FAS. Thus, promoter-demethylation of FAS and DAPK1 represents a critical mechanism of drug-induced apoptosis in neoplastic cells in MDS and AML which underscores the clinical implication of epigenetically active therapies.


Assuntos
Apoptose/genética , Epigênese Genética/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Regiões Promotoras Genéticas/genética , Animais , Humanos , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/patologia
19.
Pediatr Blood Cancer ; 60(6): E10-2, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23303724

RESUMO

A 6-year-old male presented with a testicular mass, hepatosplenomegaly, and a pleural effusion while undergoing maintenance chemotherapy for treatment of T-cell acute lymphoblastic leukemia (T-ALL). He was subsequently diagnosed with a lymphoproliferative disorder that resembled hepatosplenic lymphoma (HSL). While the extranodal presentation and the protracted yet aggressive clinical course are consistent with HSL, the findings of monosomy 8 and polymorphic cell populations are unique and have not been previously described in this type of lymphoma.


Assuntos
Transtornos Linfoproliferativos/patologia , Segunda Neoplasia Primária/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Citometria de Fluxo , Humanos , Imunofenotipagem , Neoplasias Hepáticas/patologia , Linfoma/patologia , Quimioterapia de Manutenção , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Neoplasias Esplênicas/patologia
20.
Int J Occup Med Environ Health ; 26(6): 856-69, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24464565

RESUMO

OBJECTIVE: Teaching profession is characterised by an above-average rate of psychosomatic and mental health impairment due to work-related stress. The aim of the study was to identify predictors of mental health in female teachers. MATERIAL AND METHODS: A sample of 630 female teachers (average age 47 ± 7 years) participated in a screening diagnostic inventory. Mental health was surveyed with the General Health Questionnaire GHQ-12. The following parameters were measured: specific work conditions (teacher-specific occupational history), scales of the Effort-Reward-Imbalance (ERI) Questionnaire as well as cardiovascular risk factors, physical complaints (BFB) and personal factors such as inability to recover (FABA), sense of coherence (SOC) and health behaviour. RESULTS: First, mentally fit (MH(+)) and mentally impaired teachers (MH(-)) were differentiated based on the GHQ-12 sum score (MH(+): < 5; MH(-): ≥ 5); 18% of the teachers showed evidence of mental impairment. There were no differences concerning work-related and cardiovascular risk factors as well as health behaviour between MH(+) and MH(-). Binary logistic regressions identified 4 predictors that showed a significant effect on mental health. The effort-reward-ratio proved to be the most relevant predictor, while physical complaints as well as inability to recover and sense of coherence were identified as advanced predictors (explanation of variance: 23%). CONCLUSION: Contrary to the expectations, classic work-related factors can hardly contribute to the explanation of mental health. Additionally, cardiovascular risk factors and health behaviour have no relevant influence. However, effort-reward-ratio, physical complaints and personal factors are of considerable influence on mental health in teachers. These relevant predictors should become a part of preventive arrangements for the conservation of teachers' health in the future.


Assuntos
Docentes , Transtornos Mentais/epidemiologia , Saúde Mental , Estresse Psicológico/epidemiologia , Adulto , Doenças Cardiovasculares/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Recompensa , Fatores de Risco , Senso de Coerência , Inquéritos e Questionários , Ensino , Carga de Trabalho/psicologia
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