Miracle-dz/UniFAR-FTUs huggingface dataset:
Allergen immunotherapy decreases specific allergen-induced expression of Fas and FasL on CD4+ and CD8+ cells.

UNLABELLED Apoptosis programmed cell death without induction of an inflammatory response. It is mediated by Fas--a cell surface protein which is expressed on activated lymphocytes. Interaction with its counterpart--the Fas ligand induces the apoptosis of Fas bearing cells. The mechanism underlying successful immunotherapy has not been identified. The aim of this study was to investigate whether specific immunotherapy (SIT) might affect Fas and FasL expression after stimulation with specific allergen. The study was conducted on 8 allergic subjects and 8 healthy volunteers as controls. The allergic patients were treated with conventional SIT (Pollinex). Blood samples were collected before the first day and 7 days after the last injection. Isolated CD4+ and CD8+ cells were incubated in various concentrations of specific allergen (1, 10, 100 ng/ml) or in medium alone. Indirect immunofluorescence test with rabbit IgG against human Fas and FasL was performed. The percentage of positive cells was determined under fluorescence microscope. The expression of Fas and FasL before SIT was significantly increased on CD4+ and CD8+ cells under the influence of specific allergen (10, 100 ng/ml). After SIT, significant decrease in the expression of both molecules was observed, although elimination of allergen-reactive cells was not complete and their number was still higher than in the controls. CONCLUSION The exposure of CD4+ and CD8+ cells on allergen may induce the Fas-FasL apoptotic pathway. Significant decrease in number of allergen-reactive CD4+, CD8+ cells after SIT suggests participation of the phenomenon in deletion of clones, which may be a part of the allergen tolerance mechanism achieved naturally or during SIT.
Distribution of Matrix Proteins in Perichondrium and Periosteum During the Incorporation of Meckel's Cartilage into Ossifying Mandible in Midterm Human Fetuses: An Immunohistochemical Study

Immunohistochemical localization of versican and tenascin‐C were performed; the periosteum of ossifying mandible and the perichondrium of Meckel's cartilage, of vertebral cartilage, and of mandibular condylar cartilage were examined in midterm human fetuses. Versican immunoreactivity was restricted and evident only in perichondrium of Meckel's cartilage and vertebral cartilage; conversely, tenascin‐C immunoreactivity was only evident in periosteum. Therefore, versican and tenascin‐C can be used as molecular markers for human fetal perichondrium and fetal periosteum, respectively. Meckel's cartilage underwent endochondral ossification when it was incorporated into the ossifying mandible at the deciduous lateral incisor region. Versican immunoreactivity in the perichondrium gradually became weak toward the anterior primary bone marrow. Tenascin‐C immunoreactivity in the primary bone marrow was also weak, but tenascin‐C positive areas did not overlap with versican‐positive areas; therefore, degradation of the perichondrium probably progressed slowly. Meanwhile, versican‐positive perichondrium and tenascin‐C‐positive periosteum around the bone collar in vertebral cartilage were clearly discriminated. Therefore, the degradation of Meckel's cartilage perichondrium during endochondral ossification occurred at a different rate than did degradation of vertebral cartilage perichondrium. Additionally, the perichondrium of mandibular condylar cartilage showed tenascin‐C immunoreactivity, but not versican immunoreactivity. That perichondrium of mandibular condylar cartilage has immunoreactivity characteristic of other periosteum tissues may indicate that this cartilage is actually distinct from primary cartilage and representative of secondary cartilage. Anat Rec, 297:1208–1217, 2014. © 2014 Wiley Periodicals, Inc.
Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/β-catenin signaling pathway.

Tumor necrosis factor-α (TNF-α) plays a pivotal role in malignant tumor formation in the tumor microenvironment. To investigate the role of TNF-α in esophageal squamous cell carcinoma (ESCC), we assessed expression profiles of the downstream gene TNF-α-induced protein 2 (TNFAIP2), which e previously unknown in ESCC. TNFAIP2 mRNA and protein expression levels were examined by qRT-PCR and immunohistochemical analysis in 24 fresh and 55 paraffin‑embedded specimens, respectively. The results demonstrated that TNFAIP2 mRNA and protein levels were overexpressed in tumor cells, and TNFAIP2 overexpression was significantly associated with T stage (p=0.049), N stage (p=0.019) and the International Union Against Cancer (UICC) stage (p=0.028). In vitro, TNFAIP2 was highly expressed in TNFα-stimulated Eca109, Kyse150, Kyse510 and TE-10 cells. Lentivirus-mediated RNA interference of TNFAIP2 inhibited cell proliferation, colony formation, migration, invasion and the cell cycle. Moreover, LV-RNAi-mediated TNFAIP2 was found to regulate the Wnt/β-catenin by decreasing expression of some genes downstream from β-catenin (i.e., C-myc, cyclin D1, MMP-7 and Snail), and upregulating expression of E-cadherin and p-GSK-3β. Taken together, these results show that TNFAIP2 may be a potential tumorigenesis gene in ESCC. Our data indicate that TNFAIP2 overexpression may facilitate proliferation and metastasis via activation of the Wnt/β-catenin signaling pathway in ESCC.
Deficiency of ATP-Binding Cassette Transporters A1 and G1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

Rationale: Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective: To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results: We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABCDKO mice) but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr−/− recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABCDKO BM–transplanted Ldlr−/− mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet–fed MAC-ABCDKO BM–transplanted Ldlr−/− mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusions: These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.
An epidemiological study of diabetes mellitus in dogs attending first opinion practice in the UK

This study aimed to estimate the prevalence of canine diabetes mellitus (DM) in primary-care clinics in England, to identify risk factors associated with DM and to describe the survival of affected dogs. Cases of DM were identified within the electronic patient records of 89 small-animal practices. A nested case–control study identified risk factors for the diagnosis of DM using logistic regression models. Cox proportional hazards models were used to analyse variables associated with survival. Four-hundred and thirty-nine canine DM cases were identified, giving an apparent prevalence of 0.34% (95% CI 0.31% to 0.37%). Neutered males were at an increased risk of diabetes compared with entire males, whereas neutering was not associated with DM in females. When compared with crossbred dogs, Yorkshire terriers had increased odds, whereas German shepherd dogs and golden retrievers had lower odds of DM. Being classified as overweight and having a diagnosis of pancreatitis, hyperadrenocorticism or a urinary tract infection were positively associated with DM. Older dogs and those diagnosed with pancreatitis had a higher hazard of death, whereas insured and neutered dogs had a lower hazard. This study provides an objective assessment of canine DM using primary-care veterinary practice data and is a valuable benchmark against which future epidemiological trends in DM can be assessed and improvements in the management of DM in primary-care practice can be judged.
Engagement of Glucocorticoid-Induced TNFR Family-Related Receptor on Effector T Cells by its Ligand Mediates Resistance to Suppression by CD4+CD25+ T Cells

Nonactivated CD4+CD25+ regulatory T cells constitutively express glucocorticoid-induced TNFR family-related receptor (GITR), a TNFR family member whose engagement was presumed to abrogate regulatory T cell-mediated suppression. Using GITR−/− mice, we report that GITR engagement on CD25−, not CD25+ T cells abrogates T cell-mediated suppression. Mouse APCs constitutively express GITR ligand (GITR-L), which is down-regulated following TLR signaling in vivo. Although GITR−/−CD25− T cells were capable of mounting proliferative responses, they were incapable of proliferation in the presence of physiological numbers of CD25+ T cells. Thus, GITR-L provides an important signal for CD25− T cells, rendering them resistant to CD25+-mediated regulation at the initiation of the immune response. The down-regulation of GITR-L by inflammatory stimuli may enhance the susceptibility of effector T cells to suppressor activity during the course of an infectious insult.
Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib

ABSTRACT Introduction: Idiopathic pulmonary fibrosis (IPF) is characterized by alveolitis, progressing into fibrosis. Due to the involvement of both endothelin and platelet-derived growth factor signaling in IPF, combination effects of a bosentan and imatinib were studied in mouse model of bleomycin-induced pulmonary fibrosis. Methods: Mice subjected to bleomycin instillation (0.05 U) and were administered with either bosentan (100 mg/kg) and/or imatinib (50 mg/kg). Inflammatory cell count, total protein estimation in bronchoalveolar lavage fluid, lung edema, superoxide dismutase, catalase, myeloperoxidase activities, and Hematoxylin & Eosin staining were performed on day 7. Hydroxyproline content, α-smooth muscle actin (SMA), collagens I and III gene expression analysis, immunohistochemistry, matrix metalloproteinases-9 and -2 activities, trichrome and sirius red staining were performed on day 21. Results: Combination treatment with bosentan and imatinib prevented bleomycin-induced mortality and loss of body weight more than the individual agents. On day 7, the combination therapy attenuated bleomycin-induced increase of total and differential inflammatory cell counts, total proteins, lung wet/dry weight ratio, myeloperoxidase activity, lung inflammatory cell infiltration more than individual agents alone. Bosentan but not imatinib ameliorated superoxide dismutase and catalase activities, which were lowered following bleomycin instillation. On day 21, combination therapy ameliorated bleomycin-induced increase of fibrosis score, collagen deposition, protein and gene expression of SMA, mRNA levels of collagens-I and -III, matrix metalloproteinase-9 and -2 activities more than monotherapy. Conclusion: Combination of bosentan and imatinib exerted more enhanced protection against bleomycin-induced inflammation and fibrosis than either of the agents alone.
An Immunohistochemical Algorithm to Facilitate Diagnosis and Subtyping of Rhabdomyosarcoma: The Children's Oncology Group Experience

Immunohistochemistry remains the current ancillary method of choice in the pathologic evaluation of small blue round-cell tumors. In at least 20% of cases of rhabdomyosarcoma (RMS), it is considered an essential factor in the final and/or differential diagnosis of the malignancy. Newer immunostains (antimyogenin, MyoD1) generated against intranuclear myogenic transcription factors offer pathologists the best hope for improving the sensitivity and specificity of RMS diagnosis. A large series of RMS (956) were studied consecutively from the intergroup rhabdomyosarcoma study and children's oncology group files, along with multiple other malignant, benign or reactive lesions. A panel of antibodies to muscle-related antigens (myogenin, MyoD1, desmin, muscle-specific actin) was studied using formalin-fixed, paraffin-embedded tissue, an avidin-biotin/peroxidase complex immunohistochemical technique, antigen retrieval technique as appropriate, and automated immunostaining. Myogenin and MyoD1 were equally sensitive (positive for 97% of RMS cases), with both also showing similar specificity (90% vs. 91% of cases) for the diagnosis of RMS. Myogenin and MyoD1 staining were sometimes intact in areas of coagulative tumor necrosis, but negated by B5 fixation. Isolated, rare benign myogenin-positive nuclei were seen infrequently in reactive lymph nodes. Specifically, both myogenin and MyoD1 had significantly greater extent of expression for alveolar RMS (ARMS) than embryonal RMS (ERMS) (both with P<0.001). Similarly, both myogenin (P=0.001) and MyoD1 (P<0.001) had significantly higher expression for ARMS than RMS, not otherwise specified (NOS). They were never expressed in undifferentiated sarcomas; however, reactive or regenerative myocytes did show expression. Immunostains against intranuclear myogenic transcription factors are, at present, the best available markers for confirming the diagnosis of RMS. Their differential expression in reactive myogenic lesions, variability in ARMS versus ERMS, and absence in undifferentiated sarcomas suggest new biologic questions to be explored in future studies.
Failure of calcium channel blockade to reduce platelet-mediated cyclic flow variations in dogs with coronary stenosis and endothelial injury.

Experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in blood flow to almost zero values followed by abrupt restorations to original levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet aggregation at the site of the stenosis and subsequent dislodgement of the thrombus. The present study was designed to test the efficacy of diltiazem, nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared with that of aspirin and ketanserin, two potent reference compounds effective in this model. Except for aspirin, compounds were given as a slow intravenous infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01 mg/kg/min), nifedipine (3 micrograms/kg/min), and verapamil (0.01 mg/kg/min) were totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min) abolished CFVs in 3 of 4 dogs, but serious side effects were observed [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus) caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01 mg/kg/min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel blockade alone in contrast to cyclooxygenase inhibition or 5-HT2 antagonism cannot inhibit thrombus formation in this model.
Stroke in patients with diabetes mellitus

The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer‐reviewed journals were used for analysis.
Television viewing and externalizing problems in preschool children: the Generation R Study.

OBJECTIVE To determine whether the amount, type, and patterns of television viewing predict the onset or the persistence of externalizing problems in preschool children. DESIGN Longitudinal study of a prospective population-based cohort in the Netherlands. SETTING Parents reported time of television exposure and type of programs watched by children. Externalizing problems were assessed using the Child Behavior Checklist at 18 and 36 months. PARTICIPANTS A population-based sample of 3913 children. MAIN EXPOSURE Television viewing time, content, and patterns of exposure (at 24 and 36 months) in children with and without preexisting problems to assess the incidence and persistence of externalizing problems. MAIN OUTCOME MEASURES Externalizing problems at 36 months. RESULTS Program content and time of television exposure assessed at 24 months did not predict the incidence of externalizing problems at 36 months (odds ratio, 2.24; 95% CI, 0.97-5.18). However, the patterns of exposure over time reflecting high levels of television viewing were associated with the incidence of externalizing problems (odds ratio, 2.00; 95% CI, 1.07-3.75) and the persistence of the preexisting externalizing problems (2.59; 1.03-6.55). CONCLUSIONS Our study showed that high television exposure increases the risk of the incidence and the persistence of externalizing problems in preschool children.
Nasopharyngeal pneumococcal carriage rates among HIV-infected adults following widespread pediatric use of conjugate pneumococcal vaccine-13

ABSTRACT Background: Nasopharyngeal pneumococcal carriage rates among HIV-infected adults has not been described since conjugate pneumococcal vaccine-13 (PCV13) was added to the universal infant and childhood vaccination schedule in 2010. Methods: HIV-infected adults presenting for routine health care visits to the Designated AIDS Center in Syracuse, NY between December 2013 and June 2015 were eligible for enrollment. Demographic, medical, and social history were recorded after obtaining informed consent. Nasopharyngeal samples were collected and cultured for the presence of Streptococcus pneumoniae using standard microbiologic techniques. Antibiotic susceptibility testing was performed using E-test→. Results: 707 nasopharyngeal samples were collected from 414 HIV-infected adults. 18 samples were culture positive for S. pneumoniae; 1 (6%) isolate was of vaccine-type, 9 (50%) were non-vaccine types, and 8 (44%) were non-typeable. The 18 isolates were recovered from 15 different patients (4% of those enrolled). Three patients were culture positive for pneumococcus isolated from 2 consecutive samples, with non-typeable pneumococci identified consecutively from 2 patients and serotype 35B identified consecutively from 1 patient. The most commonly identified non-vaccine serotypes were 35B and 15B/C. Identified pneumococci were penicillin and cefotaxime susceptible. Conclusion: Four percent of HIV-infected adults in our study population were colonized with S. pneumoniae. The non-vaccine serotypes 35B and 15B/C predominated.
Frontal EEG theta changes assess the training improvements of novices in flight simulation tasks

The aim of the study is to analyze the variation of the EEG power spectra in theta band when a novice starts to learn a new task. In particular, the goal is to find out the differences from the beginning of the training to the session in which the performance level is good enough for considering him/her able to complete the task without any problems. While the novices were engaged in the flight simulation tasks we recorded the brain activity by using high resolution EEG techniques as well as neurophysiologic variables such as heart rate (HR) and eye blinks rate (EBR). Results show clear changes in the EEG power spectra in theta band over the frontal brain areas, either over the left, the midline and the right side, during the learning process of the task. These results are also supported by the autonomic signals of HR and EBR, by the performances' trends and by the questionnaires for the evaluation of the perceived workload level.
Differential vesicular distribution and trafficking of MMP‐2, MMP‐9, and their inhibitors in astrocytes

Astrocytes play an active role in the central nervous system and are critically involved in astrogliosis, a homotypic response of these cells to disease, injury, and associated neuroinflammation. Among the numerous molecules involved in these processes are the matrix metalloproteinases (MMPs), a family of zinc‐dependent endopeptidases, secreted or membrane‐bound, that regulate by proteolytic cleavage the extracellular matrix, cytokines, chemokines, cell adhesion molecules, and plasma membrane receptors. MMP activity is tightly regulated by the tissue inhibitors of MMPs (TIMPs), a family of secreted multifunctional proteins. Astrogliosis in vivo and astrocyte reactivity induced in vitro by proinflammatory cues are associated with modulation of expression and/or activity of members of the MMP/TIMP system. However, nothing is known concerning the intracellular distribution and secretory pathways of MMPs and TIMPs in astrocytes. Using a combination of cell biology, biochemistry, fluorescence and electron microscopy approaches, we investigated in cultured reactive astrocytes the intracellular distribution, transport, and secretion of MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2. MMP‐2 and MMP‐9 demonstrate nuclear localization, differential intracellular vesicular distribution relative to the myosin V and kinesin molecular motors, and LAMP‐2‐labeled lysosomal compartment, and we show vesicular secretion for MMP‐2, MMP‐9, and their inhibitors. Our results suggest that these proteinases and their inhibitors use different pathways for trafficking and secretion for distinct astrocytic functions. © 2009 Wiley‐Liss, Inc.
Treatment of uncomplicated gonorrhea with rosoxacin

In a randomized, double-blind, dose-ranging study, single oral doses of rosoxacin were used to treat 126 patients with uncomplicated genital or anorectal gonorrhea. Neisseria gonorrhoeae was eradicated from 5 (28%) of 18 men treated with 100 mg, compared with 101 (94%) of 108 men and women treated with 200 mg, 300 mg, or 400 mg (P less than 0.001). Susceptibility to rosoxacin was determined for 6 pretreatment gonococcal isolates from these patients and for 194 stored clinical isolates; 296 (98.7%) of these 300 isolates, including 10 strains of penicillinase-producing N. gonorrhaeae, required a minimal inhibitory concentration of less than or equal to 0.062 microgram/ml. Urethral or cervical infection with Chlamydia trachomatis coexisted with gonococcal infection in 14 (22%) of 63 patients and persisted in 7 of 10 patients treated with rosoxacin. Postgonococcal urethritis developed in 11 (34%) of 32 men who were monitored for 12 to 30 days. Sixty-four subjects (51%) developed transient dizziness, drowsiness, altered visual perceptions, or other symptoms suggestive of central nervous system dysfunction after treatment with rosoxacin, but these symptoms were not clearly dose related. Rosoxacin in doses of greater than or equal to 200 mg appears to be effective for single-dose treatment of uncomplicated gonorrhea, but further studies of its possible central nervous system toxicity are indicated.