tbuckley/cabot-search huggingface dataset:
B7‐1, B7-2 and class II MHC molecules in idiopathic pulmonary fibrosis and bronchiolitis obliterans-organizing pneumonia
Authors: Y. Kaneko, K. Kuwano, R. Kunitake, M. Kawasaki, N. Hagimoto, N. Hara
Journal: European Respiratory Journal (2000)

Interstitial lung diseases are thought to be associated with the infiltration of activated T-lymphocytes. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with major histocompatibility complex (MHC) molecules to T-lymphocytes but also express B7 molecules. Therefore, the expression of B7-1, B7-2 and class II MHC molecules was investigated in lung tissues from patients with idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans-organizing pneumonia (BOOP), and in normal lung parenchyma as a control, using immunohistochemical localization. B7-1 and B7-2 were aberrantly expressed in bronchiolar and alveolar epithelial cells, and class II MHC molecules were also aberrantly expressed in bronchiolar epithelial cells in IPF. B7-1 was aberrantly expressed in bronchiolar epithelial cells in BOOP. There was no significant difference in the expression of these proteins in alveolar macrophages between IPF and control subjects. However, B7-2 and class II MHC molecule expression in alveolar macrophages was decreased in BOOP compared with that in control subjects. Expression of CD28 and CTLA4, receptors for B7 molecules, was detected in infiltrating lymphocytes in lung tissues in IPF and BOOP. It was concluded that bronchiolar and alveolar epithelial cells may actively participate in the pathophysiology of idiopathic pulmonary fibrosis through the aberrant expression of B7 and class II major histocompatibility complex molecules. The dysregulation of these molecules in epithelial cells may lead to the activation of autoreactive T-lymphocytes, which might contribute to the pathogenesis of fibrosing lung diseases.
Pulmonary function during pregnancy in normal women and in patients with cardiopulmonary disease
Authors: K. Gazioglu, N. L. Kaltreider, M. Rosen, P. N. Yu
Journal: Thorax (1970)

Pulmonary function studies were carried out during pregnancy in 8 normal women, in 8 patients with valvular (either mitral or aortic) heart disease, and in 8 patients with chronic pulmonary disease (either emphysema or sarcoidosis). In healthy pregnant women, changes in lung volumes and maximal expiratory flow rates were not significant. Diffusing capacity tended to decrease associated with unchanged pulmonary capillary blood volume. In patients with valvular heart disease, ventilation and oxygen consumption increased toward the term. The patients with mitral valve lesions showed a significant decrease in diffusing capacity with an increase in pulmonary capillary blood volume. In patients wth emphysema, characteristic changes were increasing obstructive functional abnormalities associated with an increase in pulmonary diffusing capacity and pulmonary capillary blood volume. None of these patients, however, had clinical evidence of deterioration of their disease. Patients with sarcoidosis had no appreciable alteration in pulmonary function tests. The influence of various factors, such as increased ovarian hormones, ventilation-perfusion relationships, intra-abdominal distension, and cardiac haemodynamics, are discussed in relation to the change in pulmonary diffusing capacity and pulmonary capillary blood volume. From the standpoint of pulmonary function studies we think that patients with mitral heart disease and those with pulmonary emphysema tolerate pregnancy less favourably than normal subjects and patients with sarcoidosis.
Coeliac disease and birth defects in offspring Reply
Authors: K K HOZYASZ
Journal: Gut (2001)

Editor,—I read with interest the paper by Martinelli et al (Gut 2000; 46 :332–335) and letter by Unsworth et al (Gut 2000; 47 :598) which stress the high prevalence of coeliac disease in anaemic pregnant women. Untreated coeliac disease can adversely affect the reproductive system and result in infertility, multiple abortions, low birth weight babies, and short breast feeding periods.1 2 A low plasma level of folic acid is a common finding in newly diagnosed patients3: there are good theoretical reasons for hypothesising that coeliac disease could also be a maternal risk factor for birth defects.4 5 The seven coeliac women identified in the study of Martinelli et al had a further pregnancy and reached term. One of them had a boy with a major cardiac malformation; she was the only one on a gluten containing diet.

I examined sera from 40 …
Three cases of nalbuphine hydrochloride dependence associated with anabolic steroid use.
Authors: A J McBride, K Williamson, T Petersen
Journal: British Journal of Sports Medicine (1996)

Three case reports are presented of nalbuphine hydrochloride dependence meeting DSM IIIR and ICD10 criteria for opioid dependence. Nalbuphine hydrochloride is being obtained from illicit sources and used by those using performance enhancing drugs. In some cases this leads to opioid dependence. There is a potential risks of crossover between the misuse of drugs of performance and the misuse of psychoactive drugs by injection. Further research into the dependence potential of nalbuphine and the extent of the crossover between steroid misuse and other psychoactive drug misuse is required. The legal status of nalbuphine should be reviewed in the light of its availability on the black market.
Identification of proteoglycans as the APRIL-specific binding partners
Authors: Karine Ingold, Adrian Zumsteg, Aubry Tardivel, Bertrand Huard, Quynh-Giao Steiner, Teresa G. Cachero, Fang Qiang, Leonid Gorelik, Susan L. Kalled, Hans Acha-Orbea, Paul D. Rennert, Jürg Tschopp, Pascal Schneider
Journal: The Journal of Experimental Medicine (2005)

B cell activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) are closely related ligands within the TNF superfamily that play important roles in B lymphocyte biology. Both ligands share two receptors—transmembrane activator and calcium signal–modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA)—that are predominantly expressed on B cells. In addition, BAFF specifically binds BAFF receptor, whereas the nature of a postulated APRIL-specific receptor remains elusive. We show that the TNF homology domain of APRIL binds BCMA and TACI, whereas a basic amino acid sequence (QKQKKQ) close to the NH2 terminus of the mature protein is required for binding to the APRIL-specific “receptor.” This interactor was identified as negatively charged sulfated glycosaminoglycan side chains of proteoglycans. Although T cell lines bound little APRIL, the ectopic expression of glycosaminoglycan-rich syndecans or glypicans conferred on these cells a high binding capacity that was completely dependent on APRIL's basic sequence. Moreover, syndecan-1–positive plasma cells and proteoglycan-rich nonhematopoietic cells displayed high specific, heparin-sensitive binding to APRIL. Inhibition of BAFF and APRIL, but not BAFF alone, prevented the survival and/or the migration of newly formed plasma cells to the bone marrow. In addition, costimulation of B cell proliferation by APRIL was only effective upon APRIL oligomerization. Therefore, we propose a model whereby APRIL binding to the extracellular matrix or to proteoglycan-positive cells induces APRIL oligomerization, which is the prerequisite for the triggering of TACI- and/or BCMA-mediated activation, migration, or survival signals.
Genome sequence of the cultivated cotton Gossypium arboreum
Authors: Fuguang Li, Guangyi Fan, Kunbo Wang, Fengming Sun, Youlu Yuan, Guoli Song, Qin Li, Zhiying Ma, Cairui Lu, Changsong Zou, Wenbin Chen, Xinming Liang, Haihong Shang, Weiqing Liu, Chengcheng Shi, Guanghui Xiao, Caiyun Gou, Wuwei Ye, Xun Xu, Xueyan Zhang, Hengling Wei, Zhifang Li, Guiyin Zhang, Junyi Wang, Kun Liu, Russell J Kohel, Richard G Percy, John Z Yu, Yu-Xian Zhu, Jun Wang, Shuxun Yu
Journal: Nature Genetics (2014)

Yu-Xian Zhu, Jun Wang, Shuxun Yu and colleagues report sequencing and assembly of the genome of cultivated cotton, Gossypium arboreum. Comparison with the Gossypium raimondii genome sequence provides insights into genome evolution and speciation, and identifies two shared whole-genome duplication events occurring before the speciation event around 2–13 million years ago. The complex allotetraploid nature of the cotton genome (AADD; 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled the Gossypium arboreum (AA; 2n = 26) genome, a putative contributor of the A subgenome. A total of 193.6 Gb of clean sequence covering the genome by 112.6-fold was obtained by paired-end sequencing. We further anchored and oriented 90.4% of the assembly on 13 pseudochromosomes and found that 68.5% of the genome is occupied by repetitive DNA sequences. We predicted 41,330 protein-coding genes in G. arboreum. Two whole-genome duplications were shared by G. arboreum and Gossypium raimondii before speciation. Insertions of long terminal repeats in the past 5 million years are responsible for the twofold difference in the sizes of these genomes. Comparative transcriptome studies showed the key role of the nucleotide binding site (NBS)-encoding gene family in resistance to Verticillium dahliae and the involvement of ethylene in the development of cotton fiber cells.
Type 1 Diabetes Mellitus and Cardiovascular Disease
Authors: Sarah D. de Ferranti, Ian H. de Boer, Vivian Fonseca, Caroline S. Fox, Sherita Hill Golden, Carl J. Lavie, Sheela N. Magge, Nikolaus Marx, Darren K. McGuire, Trevor J. Orchard, Bernard Zinman, Robert H. Eckel
Journal: Circulation (2014)
Anti-EGFR Antibody Cetuximab Enhances the Cytolytic Activity of Natural Killer Cells toward Osteosarcoma
Authors: Jens H.W. Pahl, S. Eriaty N. Ruslan, Emilie P. Buddingh, Susy J. Santos, Karoly Szuhai, Massimo Serra, Hans Gelderblom, Pancras C.W. Hogendoorn, R. Maarten Egeler, Marco W. Schilham, Arjan C. Lankester
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Osteosarcoma and Ewing's sarcoma are the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease have a poor prognosis, illustrating the need for alternative therapies. Sarcoma cells are susceptible to the cytolytic activity of resting natural killer (NK) cells which can be improved by interleukin (IL)-15 stimulation. In this study, we explored whether the cytolytic function of resting NK cells can be augmented and specifically directed toward sarcoma cells by antibody-dependent cellular cytotoxicity (ADCC). Experimental Design: Epidermal growth factor receptor (EGFR) expression was examined on osteosarcoma and Ewing's sarcoma cell lines by flow cytometry and in osteosarcoma biopsy and resection specimens by immunohistochemistry. Cetuximab-mediated ADCC by NK cells from osteosarcoma patients and healthy controls was measured with 4-hour 51Cr release assays. Results: EGFR surface expression was shown on chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cells (12/12), most primary osteosarcoma cultures (4/5), and few Ewing's sarcoma cell lines (2/7). In the presence of cetuximab, the cytolytic activity of resting NK cells against all EGFR-expressing sarcoma cells was substantially increased and comparable with that of IL-15–activated NK cells. Surface EGFR expression on primary osteosarcoma cultures correlated with EGFR expression in the original tumor. The cytolytic activity of osteosarcoma patient-derived NK cells against autologous tumor cells was as efficient as that of NK cells from healthy donors. Conclusion: Our data show that the cytolytic potential of resting NK cells can be potentiated and directed toward osteosarcoma cells with cetuximab. Therefore, cetuximab-mediated immunotherapy may be considered a novel treatment modality in the management of advanced osteosarcoma. Clin Cancer Res; 18(2); 432–41. ©2011 AACR.
Extracellular Protease<i>ADAMTS9</i>Suppresses Esophageal and Nasopharyngeal Carcinoma Tumor Formation by Inhibiting Angiogenesis
Authors: Paulisally Hau Yi Lo, Hong Lok Lung, Arthur Kwok Leung Cheung, Suneel S. Apte, Kwok Wah Chan, Fung Mei Kwong, Josephine Mun Yee Ko, Yue Cheng, Simon Law, Gopesh Srivastava, Eugene R. Zabarovsky, Sai Wah Tsao, Johnny Cheuk On Tang, Eric J. Stanbridge, Maria Li Lung
Journal: Cancer Research (2010)

ADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we evaluated the hypothesized antiangiogenic and tumor-suppressive functions of ADAMTS9 in ESCC and NPC, in stringent tumorigenicity and Matrigel plug angiogenesis assays. ADAMTS9 activation suppressed tumor formation in nude mice. Conversely, knockdown of ADAMTS9 resulted in clones reverting to the tumorigenic phenotype of parental cells. In vivo angiogenesis assays revealed a reduction in microvessel numbers in gel plugs injected with tumor-suppressive cell transfectants. Similarly, conditioned medium from cell transfectants dramatically reduced the tube-forming capacity of human umbilical vein endothelial cells. These activities were associated with a reduction in expression levels of the proangiogenic factors MMP9 and VEGFA, which were consistently reduced in ADAMTS9 transfectants derived from both cancers. Taken together, our results indicate that ADAMTS9 contributes an important function in the tumor microenvironment that acts to inhibit angiogenesis and tumor growth in both ESCC and NPC.
The Kringle 1 Domain of Hepatocyte Growth Factor Has Antiangiogenic and Antitumor Cell Effects on Hepatocellular Carcinoma
Authors: Zan Shen, Zhen Fan Yang, Yi Gao, Ji Cheng Li, Hai Xiao Chen, Ching Chiu Liu, Ronnie T.P. Poon, Sheung Tat Fan, John M. Luk, Kong Hung Sze, Tsai Ping Li, Ren Bao Gan, Ming Liang He, Hsiang Fu Kung, Marie C.M. Lin
Journal: Cancer Research (2008)

The kringle 1 domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial cell proliferation, suggesting that it might be an antiangiogenic molecule. Here, we evaluated the in vivo efficacy of a recombinant adenoassociated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model and explored its molecular mechanisms in vitro in both endothelial and tumor cells. We first showed that rAAV-HGFK1 treatment significantly prolonged the survival time of rats transplanted with tumor cells. Treatment with rAAV-HGFK1 inhibited tumor growth, decreased tumor microvessel density, and completely prevented intrahepatic, lung, and peritoneal metastasis in this in vivo model. In vitro, rAAV-HGFK1 exhibited both antiangiogenic and antitumor cell effects, inhibiting the proliferation of both murine microvascular endothelial cells (MEC) and tumor cells, and inducing apoptosis and G(0)-G(1) phase arrest in these cells. To our surprise, rAAV-HGFK1 did not act through the hepatocyte growth factor/hepatocyte growth factor receptor pathway. Instead, it worked mainly through epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling, with more minor contributions from vascular endothelial growth factor/vascular endothelial growth factor receptor and beta fibroblast growth factor (bFGF)/beta fibroblast growth factor receptor (bFGFR) signaling. In both MECs and tumor cells, rAAV-HGFK1 acted through two pathways downstream of EGFR, namely inhibition of extracellular signal-regulated kinase activation and stimulation of p38 mitogen-activated protein kinase/c-Jun-NH(2)-kinase activation. These results suggest for the first time that HGFK1 exerts both antiangiogenic and antitumor cell activities mainly through EGF/EGFR signaling, and may thus be considered as a novel therapeutic strategy for the treatment of HCC.
Chronic one-kidney hypertension in rabbits. III. Renopressin, a new hypertensive substance.
Authors: L T Skeggs, J R Kahn, M Levine, F E Dorer, K E Lentz
Journal: Circulation Research (1977)

The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the discovery of a hypertensive substance which we have named renopressin. Subcutaneous injection of the new substance into normal rabbits produces a delayed, slow increase in blood pressure, and after a few days the development of a moderate hypertension which persists indefinitely. The response of the blood pressure to renopressin is totally unlike that to renin. While the pressor action of renin can be blocked by an angiotensin II antagonist, the hypertension caused by renopressin cannot. Renin can increase the blood pressure of hypertensive rabbits; renopressin has no effect. The blood pressure of hypertensive rabbits and of normal rabbits made hypertensive by injection of renopressin can be lowered to normal by passive immunization with the same antibody preparation. The evidence is consistent with the possibility that renopressin and the agent causing the elevation of blood pressure in hypertensive rabbits are similar or identical.
Functional proteomics characterization of residual breast cancer after neoadjuvant systemic chemotherapy
Authors: A.M. Gonzalez-Angulo, S. Liu, H. Chen, M. Chavez-MacGregor, A. Sahin, G.N. Hortobagyi, G.B. Mills, K.-A. Do, F. Meric-Bernstam
Journal: Annals of Oncology (2012)
Characteristics of salt and water transport in superficial and juxtamedullary straight segments of proximal tubules.
Authors: S Kawamura, M Imai, D W Seldin, J P Kukko
Journal: Journal of Clinical Investigation (1975)

The purpose of the present studies was to characterize the nature of salt and water transport out of the superficial (SF) and juxtamedullary (JM) straight segments of rabbit proximal tubules as examined by in vitro microperfusion techniques. When the perfusate consisted of a solution simulating ultrafiltrate of plasma, there were no differences between SF and JM straight tubules in either net reabsorption of fluid (SF=0.47 nl/mm per min; JM=0.56 nl/mm per min) or in transtubular potential difference (PD) (SF=-2.1 mV; JM=-1.8 mV). Removal of glucose and alanine from the perfusate had no effect on the magnitude of the PD in either straight segment. Ouabain decreased both the net reabsorptive rates and the PD. Isosmolal replacement of NaCL by Na-cyclamate (a presumed impermeant anion) in the perfusate and the bath caused an increase in luminal negativity in both segments wheras similar substitution of NaCL by choline-CL (nontransported cation) changed the PD TO NEAR ZERO. These studies, therefore, suggest that sodium is transported out of the proximal straight tubules by an active noncoupled process that generates a PD (electrogenic process). When the perfusate consisted of a solution with a high chloride concentration (resulting from greater HCO3 than CI reabsorption in the proximal convoluted tubule), different PDs in SF and JM tubules were generated: SF=+1.6 plus or minus 0.2 mV; JM=-1.3 plus or minus 0.3 mV. This difference in PD was attributed to relative differences in Na and CI permeabilities in these two segments. Electrophysiological and isotopic estimates of the chloride to sodium permeability revealed that the SF tubule is about twice as permeant to chloride than to sodium whereas the JM tubules are approximately twice as permeant to sodium than to chloride. It is concluded that the mechanism of active sodium transport in the straight segment of proximal tubule differs from that of the convoluted segment and that both the SF and JM straight segments differ from each other with respect os sodium and chloride permeability.
Mitochondrial import of PKCε is mediated by HSP90: a role in cardioprotection from ischaemia and reperfusion injury
Authors: Grant R. Budas, Eric N. Churchill, Marie-Hélène Disatnik, Lihan Sun, Daria Mochly-Rosen
Journal: Cardiovascular Research (2010)

Protein kinase C epsilon (PKCε) is critical for cardiac protection from ischaemia and reperfusion (IR) injury. PKCε substrates that mediate cytoprotection reside in the mitochondria. However, the mechanism enabling mitochondrial translocation and import of PKCε to enable phosphorylation of these substrates is not known. Heat shock protein 90 (HSP90) is a cytoprotective protein chaperone that participates in mitochondrial import of a number of proteins. Here, we investigated the role of HSP90 in mitochondrial import of PKCε. Using an ex vivo perfused rat heart model of IR, we found that PKCε translocates from the cytosol to the mitochondrial fraction following IR. Immunogold electron microscopy and mitochondrial fractionation demonstrated that following IR, mitochondrial PKCε is localized within the mitochondria, on the inner mitochondrial membrane. Pharmacological inhibition of HSP90 prevented IR-induced interaction between PKCε and the translocase of the outer membrane (Tom20), reduced mitochondrial import of PKCε, and increased necrotic cell death by ∼70%. Using a rational approach, we designed a 7-amino acid peptide activator of PKCε, derived from an HSP90 homologous sequence located in the C2 domain of PKCε (termed ψεHSP90). Treatment with this peptide (conjugated to the cell permeating TAT protein-derived peptide, TAT47–57) increased PKCε–HSP90 protein–protein interaction, enhanced mitochondrial translocation of PKCε, increased phosphorylation and activity of an intra-mitochondrial PKCε substrate, aldehyde dehydrogenase 2, and reduced cardiac injury in ex vivo and in vivo models of myocardial infarction. Our results suggest that HSP90-mediated mitochondrial import of PKCε plays an important role in the protection of the myocardium from IR injury.
Production of the Pseudomonas aeruginosa neuraminidase is increased under hyperosmolar conditions and is regulated by genes involved in alginate expression.
Authors: G Cacalano, M Kays, L Saiman, A Prince
Journal: Journal of Clinical Investigation (1992)

The pathogenesis of Pseudomonas aeruginosa infection in cystic fibrosis (CF) is a complex process attributed to specific characteristics of both the host and the infecting organism. In this study, the properties of the PAO1 neuraminidase were examined to determine its potential role in facilitating Pseudomonas colonization of the respiratory epithelium. The PAO1 neuraminidase was 1000-fold more active than the Clostridium perfringens enzyme in releasing sialic acid from respiratory epithelial cells. This effect correlated with increased adherence of PAO1 to epithelial cells after exposure to PAO1 neuraminidase and was consistent with in vitro studies demonstrating Pseudomonas adherence to asialoganglioside receptors. The regulation of the neuraminidase gene nanA was examined in Pseudomonas and as cloned and expressed in Escherichia coli. In hyperosmolar conditions neuraminidase expression was increased by 50% (P less than 0.0004), an effect which was OmpR dependent in E. coli. In Pseudomonas the osmotic regulation of neuraminidase production was dependent upon algR1 and algR2, genes involved in the transcriptional activation of algD, which is responsible for the mucoid phenotype of Pseudomonas and pathognomonic for chronic infection in CF. Under the hyperosmolar conditions postulated to exist in the CF lung, nanA is likely to be expressed to facilitate the initial adherence of Pseudomonas to the respiratory tract.