tbuckley/cabot-search huggingface dataset:
Is procalcitonin a marker of critical illness in heatstroke?
Authors: Pierre Hausfater, Margarita Hurtado, Sebastian Pease, Gaëlle Juillien, Virginie-Eve Lvovschi, Sepehr Salehabadi, Olivier Lidove, Michel Wolff, Maguy Bernard, Sylvie Chollet-Martin, Bruno Riou
Journal: Intensive Care Medicine (2008)
<i>Haemophilus Influenzae</i> in Lung Explants of Patients with End-stage Pulmonary Disease
Authors: LIEKE V. M. MÖLLER, WIM TIMENS, WIM van der  BIJ, KOR KOOI, BOB de WEVER, JACOB DANKERT, LOEK van ALPHEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

In order to determine the presence and distribution of Haemophilus influenzae in lung tissue sections, we obtained lung explants from 49 lung transplant recipients with cystic fibrosis (CF) (n = 16), chronic obstructive pulmonary disease (COPD) including emphysema (n = 16), bronchiectasis (n = 5), pulmonary hypertension (n = 9), Langerhans cell histiocytosis (n = 1), and idiopathic pulmonary fibrosis (n = 2). Analysis was done by selective culturing, immunoperoxidase (IP) staining, and by polymerase chain reaction (PCR). H. influenzae was cultured from specimens of the lung explants from one CF and one COPD patient. IP staining of tissue sections was positive in 24 patients (10 CF patients, eight COPD patients, two bronchiectasis patients, and four patients with noninfectious pulmonary diseases). IP-positive tissue sections were PCR-positive, and IP-negative sections were PCR-negative. H. influenzae was more frequently detected in tissue sections of lung explants from CF and COPD patients than from patients with bronchiectasis or noninfectious pulmonary diseases. H. influenzae was diffusely present in the epithelium, the submucosa of the bronchi, the bronchioles, the interstitium, and the alveolar epithelium. H. influenzae was localized extracellularly alone and in bacterial clusters, and was also associated with macrophages in CF patients. The results of this study demonstrate that H. influenzae is often present in the lungs of patients with end-stage pulmonary disease, especially CF and COPD patients. H. influenzae is diffusely present in the respiratory epithelium and subepithelial layers of the lungs of these patients.
Transforming Growth Factor-β Can Suppress Tumorigenesis through Effects on the Putative Cancer Stem or Early Progenitor Cell and Committed Progeny in a Breast Cancer Xenograft Model
Authors: Binwu Tang, Naomi Yoo, Mary Vu, Mizuko Mamura, Jeong-Seok Nam, Akira Ooshima, Zhijun Du, Pierre-Yves Desprez, Miriam R. Anver, Aleksandra M. Michalowska, Joanna Shih, W. Tony Parks, Lalage M. Wakefield
Journal: Cancer Research (2007)

Abstract The transforming growth factor-β (TGF-β) pathway has tumor-suppressor activity in many epithelial tissues. Because TGF-β is a potent inhibitor of epithelial cell proliferation, it has been widely assumed that this property underlies the tumor-suppressor effect. Here, we have used a xenograft model of breast cancer to show that endogenous TGF-β has the potential to suppress tumorigenesis through a novel mechanism, involving effects at two distinct levels in the hierarchy of cellular progeny that make up the epithelial component of the tumor. First, TGF-β reduces the size of the putative cancer stem or early progenitor cell population, and second it promotes differentiation of a more committed, but highly proliferative, progenitor cell population to an intrinsically less proliferative state. We further show that reduced expression of the type II TGF-β receptor correlates with loss of luminal differentiation in a clinical breast cancer cohort, suggesting that this mechanism may be clinically relevant. At a molecular level, the induction of differentiation by TGF-β involves down-regulation of Id1, and forced overexpression of Id1 can promote tumorigenesis despite persistence of the antiproliferative effect of TGF-β. These data suggest new roles for the TGF-β pathway in regulating tumor cell dynamics that are independent of direct effects on proliferation. [Cancer Res 2007;67(18):8643–52]
Survey of Conserved Alternative Splicing Events of mRNAs Encoding SR Proteins in Land Plants
Authors: Kei Iida, Mitiko Go
Journal: Molecular Biology and Evolution (2006)

The serine/arginine-rich (SR) protein family plays an important role in constitutive and alternative splicing (AS). These proteins regulate AS in a tissue-specific and stress-responsive manner. Pre-mRNAs encoding SR proteins are often alternatively spliced, and these AS events may be important for the regulation of AS events of other pre-mRNAs. In this study, we analyzed AS events of SR proteins in Arabidopsis thaliana and Oryza sativa (rice). We found three sets of AS events conserved between Arabidopsis and rice. These conserved AS events were found in the plant-novel-SR protein, SC35-like (SCL), and two-Zn-knuckles–type 9G8 subfamilies. Each member of these subfamilies has at least one RNA recognition motif (RRM) and at least one intron in the RRM-encoded region. We found that the conserved AS events occurred in these introns and, in each case, the conserved AS events resulted in mature mRNAs encoding proteins with incomplete RRMs. To search for the evolutionary origin of these AS events, we analyzed SR proteins in Physcomitrella patens (moss) in addition to those in Arabidopsis and rice. We found moss homologues of the plant-novel-SR protein, SCL, and the two-Zn-knuckles–type 9G8 subfamilies in silico, and these homologues have long introns at the same location of the conserved AS sites in Arabidopsis and rice. Such long introns are quite specific for alternatively spliced introns concerning the Arabidopsis SR protein genes. The long introns found in the moss SR protein genes strongly suggested that conserved AS events in moss SR protein genes might be similar to those in Arabidopsis and rice. We traced the evolutionary origin of the conserved AS events to 400 MYA, when plants first invaded land. These events are likely important in the regulation of whole AS events and likely contribute to the complicated transcriptome described by AS. The complicated transcriptome created by regulated AS events might have provided plants tolerance against droughts or temperature shifts and given them the ability to live on land.
Serotonin Transporter Inhibitors Protect against Hypoxic Pulmonary Hypertension
Authors: Elisabeth Marcos, Serge Adnot, Minh Hien Pham, Anne Nosjean, Bernadette Raffestin, Michel Hamon, Saadia Eddahibi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Pulmonary hypertension (PH) results from constriction and remodeling of pulmonary vessels. Serotonin contributes to both phenomena through different signaling pathways. The mitogenic effect of serotonin on pulmonary vascular smooth muscle cells is mediated by the serotonin transporter (5-hydroxytryptamine transporter [5-HTT]), whereas its constricting effect is mediated by 5-HT1B/1D and 5-HT2A receptors. Here, we investigated the respective roles of 5-HTT and 5-HT receptors on the development of chronic hypoxic PH in mice. During exposure to hypoxia (10% O2 for 2 weeks), the animals received one of the specific 5-HTT inhibitors citalopram and fluoxetine (10 mg/kg/day), the selective 5-HT1B/1D receptor antagonist GR127935 (2 and 10 mg/kg/day), or the 5-HT2A receptor antagonist ketanserin (2 mg/kg/day). Mice treated with the 5-HTT inhibitors showed less right ventricle hypertrophy (ratio of right ventricle/left ventricle + septum = 36.7 +/- 2.0% and 35.8 +/- 1.3% in citalopram- and fluoxetine-treated mice, respectively, vs. 41.5 +/- 1.5% in vehicle-treated mice) and less pulmonary vessel muscularization (p < 0.01) than those receiving the vehicle. Neither GR127935 nor ketanserin affected these parameters. These data indicate that 5-HTT plays a key role in hypoxia-induced pulmonary vascular remodeling. The effects of serotonin transporter inhibitors on PH in humans deserve investigation.
Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design
Authors: E. Gamble
Journal: European Respiratory Journal (2006)

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (<i>i.e.</i> 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.
Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in <i>Toxoplasma gondii</i>
Authors: Sethu C. Nair, Carrie F. Brooks, Christopher D. Goodman, Angelika Strurm, Geoffrey I. McFadden, Sandeep Sundriyal, Justin L. Anglin, Yongcheng Song, Silvia N.J. Moreno, Boris Striepen
Journal: The Journal of Experimental Medicine (2011)

Apicomplexa are important pathogens that include the causative agents of malaria, toxoplasmosis, and cryptosporidiosis. Apicomplexan parasites contain a relict chloroplast, the apicoplast. The apicoplast is indispensable and an attractive drug target. The apicoplast is home to a 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway for the synthesis of isoprenoid precursors. This pathway is believed to be the most conserved function of the apicoplast, and fosmidomycin, a specific inhibitor of the pathway, is an effective antimalarial. Surprisingly, fosmidomycin has no effect on most other apicomplexans. Using Toxoplasma gondii, we establish that the pathway is essential in parasites that are highly fosmidomycin resistant. We define the molecular basis of resistance and susceptibility, experimentally testing various host and parasite contributions in T. gondii and Plasmodium. We demonstrate that in T. gondii the parasite plasma membrane is a critical barrier to drug uptake. In strong support of this hypothesis, we engineer de novo drug-sensitive T. gondii parasites by heterologous expression of a bacterial transporter protein. Mice infected with these transgenic parasites can now be cured from a lethal challenge with fosmidomycin. We propose that the varied extent of metabolite exchange between host and parasite is a crucial determinator of drug susceptibility and a predictor of future resistance.
Acral lentiginous melanoma: histopathological prognostic features of 121 cases
Authors: A. Phan, S. Touzet, S. Dalle, S. Ronger-Savlé, B. Balme, L. Thomas
Journal: British Journal of Dermatology (2007)

Acral lentiginous melanoma (ALM) is the fourth histopathological subtype of malignant melanoma, accounting for < 10% of all melanomas in white-skinned populations. It is characterized by a lentiginous pattern of proliferation of the intraepidermal component of the tumour. Its individualization is still controversial, especially in regard of its prognostic value.To characterize better ALM from a pathological point of view and to assess the prognostic value of all histopathological features of ALM.We performed a review of all cases of ALM followed from 1996 to 2004 at the University Hospital Department of Dermatology, Lyon, France. We examined all haematoxylin, eosin and saffron-stained tissue sections of the primary lesions. Several pathological parameters of interest in melanoma were evaluated for disease-free and specific survival with the Kaplan-Meier method and the Cox proportional hazards regression model.Representative histological material was available for 121 patients. The mean Breslow thickness was 2.5 mm (in situ-20 mm). Fifteen lesions (12%) were in situ, nine (7%) were at Clark level II, 35 (29%) at III, 40 (33%) IV and 22 (18%) V. Extension along adnexal structures was found in almost half of the ALMs (46%), without prognostic significance. Seventeen (14%) lesions showed no microscopic pigmentation. Remnants of pre-existing naevus were found in four (3%) melanomas. The width of the 36 (30%) ulcerated lesions ranged from 1 to 20 mm (mean 7.6). Ulceration and its width were both associated with a large tumour thickness (P < 0.01), a high level of invasion (P < 0.01), the presence of vascular invasion (P < 0.01) and the lack of pigment production (P < 0.01). Among the 99 ALMs which were in the vertical growth phase (VGP), 21 showed a high mitotic rate (> 6 mitoses mm(-2)). A high mitotic rate was found to be significantly associated with the presence of ulceration (P < 0.01). The presence of microscopic satellites was noted in 10 (10%) lesions. The uncommon presence of small cells (8%) in the VGP was statistically significantly (P < 0.01) associated with a worse prognosis compared with other cell types. Multivariate analysis identified mitotic rate (P < 0.01), microsatellites (P = 0.05), Clark level (P = 0.01) and gender (P = 0.03) as independent prognostic factors for disease-free survival. Only the presence of microsatellites (P = 0.02) and a high mitotic rate (P < 0.01) were independently correlated with specific survival in ALM.This is a detailed pathological study of a large cohort with ALM, an uncommon subtype of melanoma. Mitotic activity appears to be of particular importance in predicting the outcome of ALM.
IgE Antibodies to Mammalian Allergens Are a Major Risk Factor for Prevalence, Severity, and Persistence of Asthma in Northern Sweden
Authors: Hayley R. James, Matthew S. Perzanowski, Eva Ronmark, Linnea Hedman, Anders Bjerg, Alexander J. Schuyler, Lisa J. Workman, Bo Lundback, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2015)
Fate Of Culture-Expanded Mesenchymal Stem Cells in The Microvasculature
Authors: Catalin Toma, William R. Wagner, Shivani Bowry, Abigail Schwartz, Flordeliza Villanueva
Journal: Circulation Research (2008)

Vascular delivery of mesenchymal stem cells (MSCs) following myocardial infarction is under clinical investigation. Little is known about the microvascular fate of MSCs. We used intravital microscopy of rat cremaster muscle microcirculation to track intraarterially delivered MSCs. Rat MSCs (average diameter, 23 μm) were bolused into the ipsilateral common iliac artery. Interrogation of an arteriole–venule pair revealed that 92±7% (n=6) of MSCs arrest and interrupt flow during first pass at the precapillary level, resulting in decreased flow in the feeding arteriole (velocity decreased from 6.3±1.0 to 4.6±1.3 mm/sec; P &lt;0.001). MSC deformability evaluated using filtration through polycarbonate membranes revealed that the cortical tension of MSCs (0.49±0.07 dyne/cm, n=9) was not different from that of circulating mononuclear cells (0.50±0.05 dyne/cm, n=7). When intravital microscopy was performed 3 days following injection, the number of MSCs in the cremaster further decreased to 14% of the initial number, because of cell death in situ. In vivo labeling of the basement membrane revealed that at 1 day, the surviving cells were spread out on the luminal side of the microvessel, whereas at 3 days, they integrated in the microvascular wall. Despite their deformability, intraarterially delivered MSCs entrap at the precapillary level because of their large size, with a small proportion of surviving MSCs integrating in a perivascular niche.
Hematogenous Micrometastases in Osteosarcoma Patients
Authors: Øyvind S. Bruland, Hanne Høifødt, Gunnar Sæter, Sigbjørn Smeland, Øystein Fodstad
Journal: Clinical Cancer Research (2005)

Abstract Bone marrow and peripheral blood samples from 60 patients with suspected bone sarcoma were examined for the presence and number of micrometastatic osteosarcoma cells by a sensitive immunomagnetic detection assay, using in parallel two osteosarcoma-associated antibodies. Forty-nine of the patients had osteosarcoma, and of these, as many as 31 (63%) had tumor cells in bone marrow, in many cases with a high number of cells. Only four (8%) were positive also in blood. None of 38 control bone marrow samples were positive, including 11 from patients with suspected bone sarcoma at time of sampling who later were found not to have osteosarcoma. Fifteen of 28 patients without overt metastases at primary diagnosis (54%) were positive, 12 of whom had localized high-grade primary tumors in the extremity. Four of these have relapsed compared with none of 10 negative patients. In the group of 22 patients with extremity localized nonmetastatic osteosarcoma, information was available on the histologic response to preoperative chemotherapy in 15 patients. None of the three patients in the bone marrow–negative group who had a poor response to chemotherapy have relapsed, whereas two of the four poor responders in the bone marrow–positive cohort are dead of disease. Among 12 patients with overt metastasis at primary diagnosis, 11 (92%) were positive in bone marrow with a very high number of osteosarcoma cells. The immunomagnetically isolated cells were further characterized by the use of fluorescent latex microparticles with surface-bound antibodies targeting different membrane markers. Moreover, in cases with numerous osteosarcoma cells in bone marrow attempts to grow the selected cells in vitro were successful in two of eight attempts, and in two of five cases, isolated cells produced tumors with osteosarcoma characteristics in nude mice. In conclusion, already at primary diagnosis, a very high fraction of osteosarcoma patients had malignant cells in bone marrow, and a correlation between the presence of tumor cells, clinical stage, and disease progression was found. The data show the clinical potential of this immunomagnetic method. Attempts to subgroup osteosarcoma patients for more individualized treatment based on the presence of micrometastatic cells should be studied in a larger cohort of patients.
Highly Successful Therapeutic Vaccinations Combining Dendritic Cells and Tumor Cells Secreting Granulocyte Macrophage Colony-stimulating Factor
Authors: Gregory Driessens, Malika Hamdane, Vincent Cool, Thierry Velu, Catherine Bruyns
Journal: Cancer Research (2004)

In an attempt to induce potent immune antitumor activities, we investigated, within the rat 9L gliosarcoma model, distal therapeutic vaccinations associating three therapies: dendritic cell vaccination, intratumoral granulocyte macrophage colony-stimulating factor (GM-CSF) gene transfer, and tumor apoptosis induction. Vaccines of dendritic cells coinjected with processed GM-CSF secreting 9L cells induced systemic responses, resulting in the complete regression of distant preimplanted 9L tumor masses in, with the best strategy, 94% of male rats. All of the cured rats developed a long-term resistance to a rechallenge with parental cells. The curative responses were correlated with the detection of elevated specific cytotoxic activities and a CD4+, CD8+ T cell-, and natural killer (NK) cell-mediated IFN-gamma production. The survival rate of the rat seemed more directly linked to the amount of GM-CSF secreted by the transduced tumor cells, which in turn depended on the toxicity of the apoptosis-inducing treatment, than to the level of apoptosis induced. Unexpectedly, alive GM-CSF secreting 9L cells became apoptotic when injected in vivo. Thus we documented the positive role of apoptosis in the induction of therapeutic antitumor responses by comparing, at equal GM-CSF exogenous supply, the effects of dendritic cells coinjected with apoptotic or necrotic 9L cells. The data showed the superior therapeutic efficiency of combined vaccines containing apoptotic tumor cells. In conclusion, vaccinations with dendritic cells associated with apoptotic tumor cells secreting GM-CSF show a very high therapeutic potency that should show promise for the treatment of human cancer.
Cyclooxygenase-1 and Bicistronic Cyclooxygenase-1/Prostacyclin Synthase Gene Transfer Protect Against Ischemic Cerebral Infarction
Authors: Heng Lin, Teng-Nan Lin, Wai-Mui Cheung, Gau-Ming Nian, Ping-Hui Tseng, Shu-Fen Chen, Jean-Ju Chen, Song-Kun Shyue, Jun-Yang Liou, Cheng-Wen Wu, Kenneth K. Wu
Journal: Circulation (2002)

Background — We tested the hypothesis that bicistronic cyclooxygenase-1 (COX-1)/prostacyclin synthase (PGIS) and COX-1 gene transfer reduce cerebral infarct volume by augmenting synthesis of protective prostaglandins. Methods and Results — We infused into lateral ventricle of a rat stroke model recombinant adenoviruses (rAd) containing COX-1 (Adv-COX-1), COX-1 and PGIS (Adv-COX-1/PGIS), or Adv-PGK control vector, and we determined COX-1 and PGIS protein and eicosanoid levels and infarct volume. COX-1 and PGIS proteins were increased in a time-dependent manner. Adv-COX-1/PGIS infusion selectively augmented prostacyclin levels, with reduction of other eicosanoids in ischemic cortex and a significant reduction of infarct volume, even when the rAd was administered 5 hours after ischemia. Infusion of Adv-COX-1 also increased prostacyclin, suppressed leukotriene levels, and achieved a similar degree of cerebral protection. Its neuroprotection was abrogated by treatment with a selective COX-1 inhibitor. Conclusions — COX-1/PGIS and COX-1 gene transfer reduce cerebral infarct volume by augmenting prostacyclin and suppressing leukotriene productions. COX-1–based gene transfer has potential for treating ischemic stroke.
Assisted hatching of human embryos: a systematic review and meta-analysis of randomized controlled trials
Authors: W. P. Martins, I. A. Rocha, R. A. Ferriani, C. O. Nastri
Journal: Human Reproduction Update (2011)

BACKGROUNDAssisted hatching (AH) is a manipulation of zona pellucida aiming to facilitate embryo implantation.
Resolution of Pneumocystis carinii pneumonia in CD4+ lymphocyte-depleted mice given aerosols of heat-treated Escherichia coli.
Authors: A G Harmsen, W Chen
Journal: The Journal of Experimental Medicine (1992)

Mice were thymectomized and depleted of CD4+ lymphocytes by treatment with monoclonal antibody to induce Pneumocystis carinii (PC) pneumonia (PCP). These mice were then exposed to aerosols of heat-treated Escherichia coli three times a week. Aerosol treatment for 10 d caused a slight reduction in numbers of PC nuclei in the lungs of mice, and treatment for 22 d resulted in nearly complete resolution of PCP. Large numbers of macrophages, polymorphonuclear leukocytes, and lymphocytes accumulated in lungs of aerosol-treated mice. Depletion of either CD8+ lymphocytes or asialo GM1+ cells that remained in the mice after CD4+ cell depletion had no effect on the ability of the mice to resolve PCP after E. coli aerosol treatments. However, depletion of Thy-1+ lymphocytes in these mice abrogated their ability to resolve PCP and reduced the numbers of macrophages that accumulated in the lungs. In addition, it was found that resolution of PCP induced by heat-treated E. coli aerosol treatments was also abrogated when mice were treated with polyclonal antibodies against tumor necrosis factor alpha (TNF-alpha). Thus, resolution of PCP in CD4+ lymphocyte-depleted mice by heat-treated E. coli aerosols was not dependent on either CD8+ or asialo GM1+ cells but was dependent on Thy-1+CD4-CD8- lymphocytes and on the participation of TNF. These results indicate that heat-treated E. coli aerosols can act as an immune response modifier by inducing resolution of PCP in mice by a mechanism not dependent on the presence of CD4+ lymphocytes.