tbuckley/cabot-search huggingface dataset:
Human keratinocytes release the endogenous beta-galactoside-binding soluble lectin immunoglobulin E (IgE-binding protein) which binds to Langerhans cells where it modulates their binding capacity for IgE glycoforms.
Authors: A Wollenberg, H de la Salle, D Hanau, F T Liu, T Bieber
Journal: The Journal of Experimental Medicine (1993)

A better understanding of the pathophysiological role of Langerhans cells (LC) in atopic diseases is dictated by the characterization of the structures involved in immunoglobulin (IgE)-binding on their cell surface. We previously reported that human LC express the high affinity receptor for IgE (Fc epsilon RI), as well as the low affinity receptor for IgE (Fc epsilon RII/CD23). In the present study, we document the presence of a third IgE-binding structure on human LC, the IgE-binding protein (epsilon BP), an endogenous soluble beta-galactoside binding lectin. Immunohistochemical studies performed on normal human skin revealed an anti-epsilon BP reactivity in the cytoplasm of keratinocytes and in that of acinous cells of eccrine sweat glands. epsilon BP was also found on the cell surface of LC, as shown by anti-epsilon BP/anti-CD1a double labeling and flow cytometric analysis. Anti-epsilon BP binding to the surface of LC was completely abolished by preincubation with lactose and restored by addition of recombinant human epsilon BP, indicating that epsilon BP binds to LC surface by virtue of its lectin property. Immunoblot analysis of anti-epsilon BP-reactive material in keratinocytes and purified LC disclosed a protein with an apparent molecular weight of 33,000 consistent with epsilon BP. Interestingly, mRNA transcripts for epsilon BP were detected only in keratinocytes but not in purified LC isolated from normal skin. epsilon BP was found to be released in culture supernatants of keratinocytes. Incubation of LC with these supernatants resulted in epsilon BP-binding to LC surface via protein-carbohydrate interaction. Most importantly, we could show that binding of human myeloma IgE to LC was inhibited by epsilon BP. In contrast, neuraminidase-treated human myeloma IgE binds to LC only in the presence of epsilon BP. In situ binding studies revealed that keratinocytes, although containing epsilon BP intracytoplasmatically, failed to exhibit any IgE-binding properties. Collectively, our results suggest that human keratinocytes produce the beta-galactoside-binding lectin epsilon BP, which subsequently binds to the surface of LC where it is functional in modulating their binding capacity for IgE glycoforms.
Percutaneous Intramyocardial Delivery of Mesenchymal Stem Cells Induces Superior Improvement in Regional Left Ventricular Function Compared with Bone Marrow Mononuclear Cells in Porcine Myocardial Infarcted Heart
Authors: Bo Tao, Mingliang Cui, Chen Wang, Sai Ma, Feng Wu, Fu Yi, Xing Qin, Junting Liu, Haichang Wang, Zhe Wang, Xiaowei Ma, Jie Tian, Yundai Chen, Jing Wang, Feng Cao
Journal: Theranostics (2014)

To investigate the efficacy and feasibility of percutaneous intramyocardial injection of bone marrow mesenchymal stem cells (MSC) and autologous bone marrow-derived mononuclear cells (BMMNC) on cardiac functional improvement in porcine myocardial infarcted hearts.Acute myocardial infarction (AMI) was induced in 22 minipigs by temporary balloon occlusion of the left anterior descending coronary artery for 60 min.Two weeks post AMI, BMMNC (n = 7, 245 ± 98 × 10(6)), MSC (n = 8, 56 ± 17 × 10(6)), or phosphate buffered saline (PBS; n = 7) were injected intramyocardially. Cardiac function and myocardial perfusion were analyzed by echocardiography and gated single-photon emission computed tomography/computed tomography (SPECT/CT) at 1 week before AMI and 2 and 10 weeks after AMI. Cell engraftment, proliferation, vascular density, and cardiac fibrosis were evaluated by histology analysis. In all groups, the echocardiography revealed no significant change in the left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), or left ventricular end-diastolic volume (LVEDV) at 10 weeks after AMI compared with those at 2 weeks after AMI. However, the wall motion score index (WMSI) and left ventricular systolic wall thickening (WT%) were significantly improved at 10 weeks compared with those at 2 weeks after AMI in the MSC group (WMSI 1.55 ± 0.06 vs. 1.87 ± 0.10, WT 33.4 ± 2.3% vs.24.8 ± 2.7%,p < 0.05) but not in the BMMNC group. In addition, myocardial perfusion quantified by SPECT/CT was improved in both the MSC and BMMNC groups, whereas the MSC group showed a superior improvement in vascular density and collagen volume fraction (p < 0.05).This preclinically relevant study suggests that when delivered by percutaneous (transcatheter) intramyocardial injection, MSC might be more effective than BMMNC to improve ischemia and reperfusion after AMI.
Tamoxifen <i>versus</i> Aromatase Inhibitors for Breast Cancer Prevention
Authors: Wei Yue, Ji-Ping Wang, Yuebai Li, Wayne P. Bocchinfuso, Kenneth S. Korach, Prabu D. Devanesan, Eleanor Rogan, Ercole Cavalieri, Richard J. Santen
Journal: Clinical Cancer Research (2005)

Abstract Long-term exposure to estradiol is associated with an increased risk of breast cancer, but the mechanisms responsible are not firmly established. The prevailing theory postulates that estrogens increase the rate of cell proliferation by stimulating estrogen receptor (ER)–mediated transcription, thereby increasing the number of errors occurring during DNA replication. An alternative theory suggests that estradiol is metabolized to quinone derivatives, which directly remove base pairs from DNA through a process called depurination. Error-prone DNA repair then results in point mutations. We postulate that both processes act in an additive or synergistic fashion. If correct, aromatase inhibitors would block both processes, whereas antiestrogens would only inhibit receptor-mediated effects. Accordingly, aromatase inhibitors would be more effective in preventing breast cancer than antiestrogens. Our initial studies showed that catechol-estrogen metabolites are formed in MCF-7 human breast cancer cells in culture. We then used an animal model that allows dissociation of ER-mediated function from the effects of estradiol metabolites and showed formation of genotoxic estradiol metabolites. We also examined the incidence of tumors formed in these ERα knockout mice bearing the Wnt-1 transgene. The absence of estradiol markedly reduced the incidence of tumors and delayed their onset. In aggregate, our results support the concept that metabolites of estradiol may act in concert with ER-mediated mechanisms to induce breast cancer. These findings support the possibility that aromatase inhibitors might be more effective than antiestrogens in preventing breast cancer.
Free thiomalate levels in rheumatoid arthritis.
Authors: T M Jefferies, D H Llewellyn, L J Notarianni
Journal: Annals of the Rheumatic Diseases (1985)

associated with fenclofenac.'Apart from the well known gastrointestinal adverse reactions of the non-steroidal anti-inflammatory drugs it has become increasingly appa- rent that these agents can cause a number of adverse renal effects, for example, acute renal failure, chronic renal damage, nephrotic syndrome and interstitial nephritis, and also abnormalities of water, sodium, and potassium homeostasis.2We would like to report our experience with a 66-year- old male patient suffering from rheumatoid arthritis for three years who was taking piroxicam for his arthritis and Moduretic for ankle oedema.As his arthritis was de- teriorating piroxicam was stopped and instead he was started on diclofenac 50 mg three times a day and also penicillamine 125 mg a day.Before introduction of these drugs the laboratory investigations showed: white cell count 9-5x109/l, haemoglobin 10-9 g/dl, erythrocyte sedi- mentation rate 108 mm/h, serum urea 10-3 mmolUl, serum creatinine 96 ,mol/l, electrolytes and bicarbonate within normal limits.About 10 days later the patient complained of nausea and malaise and his urinary output fell to 500 ml in 24 hours.Investigations revealed normal urinary microscopy, no proteinuria, serum urea 22-3 mmol/l, serum creatinine 160 ,umol/l, and serum potassium 5-2 mmol/l, but the other electrolytes were within normal limits.A straight x-ray of the abdomen showed no abnormality of the renal outlines.Both penicillamine and diclofenac were stopped, after which the serum urea, creatinine, and potassium gradually fell and returned to normal levels in five days.Our patient developed uraemia after only 10 days' treatment with diclofenac and penicillamine.Adverse reactions on the kidneys due to penicillamine are usually late events and appear initially with proteinuria.3We cannot absolutely rule out penicillamine as the offending drug in our patient, but it seems unlikely.A more obvious suspect is diclofenac, as a number of non-steroidal anti-inflammatory drugs have now been reported to cause renal impairment believed due to inhibition of prostaglan- dins' action in the kidneys.2In any patient who develops unexplained uraemia, especially in the presence of pre- vious renal impairment or during the use of diuretics, a full drug history should be taken, and any non-steroidal anti-inflammatory drug should be withdrawn for a period to see if renal impairment improves, before resorting to further renal work up which may be necessary.Due caution should be exercised in prescribing these drugs to patients who may be liable to renal complications, in particular patients with chronic renal insufficiency, hepatic cirrhosis, cardiac failure, and intravascular volume con- traction as a result of either nephrotic syndrome or the use of diuretics.
IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation
Authors: Önder Alpdogan, Stephanie J. Muriglan, Jeffrey M. Eng, Lucy M. Willis, Andrew S. Greenberg, Barry J. Kappel, Marcel R.M. van den Brink
Journal: Journal of Clinical Investigation (2003)

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor α chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into lethally irradiated hosts suggested that recent thymic emigrants can undergo homeostatic proliferation and acquire a memory-like phenotype. We found by BrdU pulse-chase, cell cycle, and annexin V analyses that IL-7 administration has significant proliferative and antiapoptotic effects on posttransplant peripheral T cells. We conclude that homeostatic expansion is important for T cell reconstitution after allogeneic BMT and involves both transferred mature T cells and recent thymic emigrants. Apart from its thymopoietic effects, IL-7 promotes peripheral T cell reconstitution through its selective proliferative and antiapoptotic effects on nonalloreactive and de novo–generated T cells, but has no effect on alloreactive T cells.
Conjugation of a brain-penetrant peptide with neurotensin provides antinociceptive properties
Authors: Michel Demeule, Nicolas Beaudet, Anthony Régina, Élie Besserer-Offroy, Alexandre Murza, Pascal Tétreault, Karine Belleville, Christian Ché, Alain Larocque, Carine Thiot, Richard Béliveau, Jean-Michel Longpré, Éric Marsault, Richard Leduc, Jean E. Lachowicz, Steven L. Gonias, Jean-Paul Castaigne, Philippe Sarret
Journal: Journal of Clinical Investigation (2014)

Neurotensin (NT) has emerged as an important modulator of nociceptive transmission and exerts its biological effects through interactions with 2 distinct GPCRs, NTS1 and NTS2. NT provides strong analgesia when administered directly into the brain; however, the blood-brain barrier (BBB) is a major obstacle for effective delivery of potential analgesics to the brain. To overcome this challenge, we synthesized chemical conjugates that are transported across the BBB via receptor-mediated transcytosis using the brain-penetrant peptide Angiopep-2 (An2), which targets LDL receptor–related protein-1 (LRP1). Using in situ brain perfusion in mice, we found that the compound ANG2002, a conjugate of An2 and NT, was transported at least 10 times more efficiently across the BBB than native NT. In vitro, ANG2002 bound NTS1 and NTS2 receptors and maintained NT-associated biological activity. In rats, i.v. ANG2002 induced a dose-dependent analgesia in the formalin model of persistent pain. At a dose of 0.05 mg/kg, ANG2002 effectively reversed pain behaviors induced by the development of neuropathic and bone cancer pain in animal models. The analgesic properties of ANG2002 demonstrated in this study suggest that this compound is effective for clinical management of persistent and chronic pain and establish the benefits of this technology for the development of neurotherapeutics.
Interaction of α <sub>1</sub> -Adrenoceptor Subtypes With Different G Proteins Induces Opposite Effects on Cardiac L-type Ca <sup>2+</sup> Channel
Authors: Jin O-Uchi, Hiroyuki Sasaki, Satoshi Morimoto, Yoichiro Kusakari, Hitomi Shinji, Toru Obata, Kenichi Hongo, Kimiaki Komukai, Satoshi Kurihara
Journal: Circulation Research (2008)

We examined the effect of alpha(1)-adrenoceptor subtype-specific stimulation on L-type Ca2+ current (I(Ca)) and elucidated the subtype-specific intracellular mechanisms for the regulation of L-type Ca2+ channels in isolated rat ventricular myocytes. We confirmed the protein expression of alpha(1A)- and alpha(1B)-adrenoceptor subtypes at the transverse tubules (T-tubules) and found that simultaneous stimulation of these 2 receptor subtypes by nonsubtype selective agonist, phenylephrine, showed 2 opposite effects on I(Ca) (transient decrease followed by sustained increase). However, selective alpha(1A)-adrenoceptor stimulation (> or =0.1 micromol/L A61603) only potentiated I(Ca), and selective alpha(1B)-adrenoceptor stimulation (10 mumol/L phenylephrine with 2 micromol/L WB4101) only decreased I(Ca). The positive effect by alpha(1A)-adrenoceptor stimulation was blocked by the inhibition of phospholipase C (PLC), protein kinase C (PKC), or Ca2+/calmodulin-dependent protein kinase II (CaMKII). The negative effect by alpha(1B)-adrenoceptor stimulation disappeared after the treatment of pertussis toxin or by the prepulse depolarization, but was not attributable to the inhibition of cAMP-dependent pathway. The translocation of PKCdelta and epsilon to the T-tubules was observed only after alpha(1A)-adrenoceptor stimulation, but not after alpha(1B)-adrenoceptor stimulation. Immunoprecipitation analysis revealed that alpha(1A)-adrenoceptor was associated with G(q/11), but alpha(1B)-adrenoceptor interacted with one of the pertussis toxin-sensitive G proteins, G(o). These findings demonstrated that the interactions of alpha(1)-adrenoceptor subtypes with different G proteins elicit the formation of separate signaling cascades, which produce the opposite effects on I(Ca). The coupling of alpha(1A)-adrenoceptor with G(q/11)-PLC-PKC-CaMKII pathway potentiates I(Ca). In contrast, alpha(1B)-adrenoceptor interacts with G(o), of which the betagamma-complex might directly inhibit the channel activity at T-tubules.
Unraveling a Revealing Paradox
Authors: Remy Bosselut, Terry I. Guinter, Susan O. Sharrow, Alfred Singer
Journal: The Journal of Experimental Medicine (2003)

The mechanism by which T cell receptor specificity determines the outcome of the CD4/CD8 lineage decision in the thymus is not known. An important clue is the fact that major histocompatibility complex (MHC)-I-signaled thymocytes paradoxically appear as CD4+8lo transitional cells during their differentiation into CD8+ T cells. Lineage commitment is generally thought to occur at the CD4+8+ (double positive) stage of differentiation and to result in silencing of the opposite coreceptor gene. From this perspective, the appearance of MHC-I-signaled thymocytes as CD4+8lo cells would be due to effects on CD8 surface protein expression, not CD8 gene expression. But contrary to this perspective, this study demonstrates that MHC-I-signaled thymocytes appear as CD4+8lo cells because of transient down-regulation of CD8 gene expression, not because of changes in CD8 surface protein expression or distribution. This study also demonstrates that initial cessation of CD8 gene expression in MHC-I-signaled thymocytes is not necessarily indicative of commitment to the CD4+ T cell lineage, as such thymocytes retain the potential to differentiate into CD8+ T cells. These results challenge classical concepts of lineage commitment but fulfill predictions of the kinetic signaling model.
Tumor Detection by Imaging Proteolytic Activity
Authors: Molly R. Darragh, Eric L. Schneider, Jianlong Lou, Paul J. Phojanakong, Christopher J. Farady, James D. Marks, Byron C. Hann, Charles S. Craik
Journal: Cancer Research (2010)

The cell surface protease membrane-type serine protease-1 (MT-SP1), also known as matriptase, is often upregulated in epithelial cancers. We hypothesized that dysregulation of MT-SP1 with regard to its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1), a situation that increases proteolytic activity, might be exploited for imaging purposes to differentiate malignant from normal tissue. In this study, we show that MT-SP1 is active on cancer cells and that its activity may be targeted in vivo for tumor detection. A proteolytic activity assay with several MT-SP1-positive human cancer cell lines showed that MT-SP1 antibodies that inhibit recombinant enzyme activity in vitro also bind and inhibit the full-length enzyme expressed on cells. In contrast, in the same assay, MT-SP1-negative cancer cell lines were inactive. Fluorescence microscopy confirmed the cell surface localization of labeled antibodies bound to MT-SP1-positive cells. To evaluate in vivo targeting capability, 0.7 to 2 nmoles of fluorescently labeled antibodies were administered to mice bearing tumors that were positive or negative for MT-SP1. Antibodies localized to MT-SP1-positive tumors (n = 3), permitting visualization of MT-SP1 activity, whereas MT-SP1-negative tumors (n = 2) were not visualized. Our findings define MT-SP1 activity as a useful biomarker to visualize epithelial cancers using a noninvasive antibody-based method.
The Dutch hypothesis (chronic non-specific lung disease) revisited
Authors: HJ Sluiter, GH Koeter, JG de Monchy, DS Postma, K de Vries, NG Orie
Journal: European Respiratory Journal (1991)

In 1961 the hypothesis (later referred to as the Dutch Hypothesis (DH)) was put forward that asthma, chronic bronchitis and emphysema should be considered as different expressions of one disease entity, in which both endogenous (host) and exogenous (environmental) factors play a role in the pathogenesis. A hereditary predisposition to develop allergy and bronchial hyperreactivity were considered to be important denominators of disease susceptibility. Complications and complicating diseases would also contribute to the ultimate phenotype of the patient. In the present paper we discuss the relevance of this hypothesis in 1990. Until now it has not been refuted; circumstantial evidence in its favour has accumulated, but formal proof is still lacking. Further research should pay more attention to the genetic aspects of the disease. Arguments are presented against the use of the terms asthma, chronic bronchitis, and emphysema as indicators of disease entities, and in favour of the use of an umbrella-term, e.g. chronic non-specific lung disease (CNSLD), provided that, in addition, every patient is characterized using so-called defining criteria.
ACUTE POLIOMYELITIS: WITH SPECIAL REFERENCE TO THE OUTBREAK IN PLYMOUTH, STONEHOUSE, AND DEVONPORT
Authors: A. B. Soltau
Journal: BMJ (1911)

ACUTE POLIOMYELITIS.r TMDzILnTTJOUNAL 11T -I.DW L4URXAL XTCtisling cf and his colleagues caimie to the conclusion fro mio-st laborious and carefutl investigations that the anterior loble was the essential eleimient in tlhe gland; that if it was coimlpletely remioved death miiust follow very rapidly (in the aduilt withlini a few days).This coneltusioni we cannot con- fitrn, for tlhree of our animals (Cat No. 11, DogJ No. 121, Monlkey No. 169) survived in-health.anid yet the pans, anterior was completely remloved.In these catses it is (lear that survival could only be attributed to the preserva- tioii of the acini of the pars internedlia infundibuli if the gland( is albsolutely esselntial to life.We aro not prepared to myiake finial conclusion,s onl suichl a (lifficult subject from a fewv experimients, anid it is clear tlhat scientific opinioi munust be reserved oIn the qtuestion ai whetlher viability in the hypophyseoprival cond(lition (lel)ends oIn the pars intermedia.Ourmiiiaterial enables lus to imaleCcoimineuts, oil certainl subordinate points.1. Condition of 11lenwinls of Glbnl in Iipci,fect x'xti1)- pratio.-Welhave obtained a conLsiderable numiber of comii- plete suirvivals in all the classes of aninisals examinied- that is.cats, dogs,.andmnonkeys--and in w ltolm-po.stotow t(cm?? ininute fragments of onie or otlher of tile parts; of the glaind were found enclosed in tlhe fibrouis scar occupying the initer- peduinclar region.These for the iiost part preserve the normial appearance of tlheir constitnent ells.Occasionally thley are atrophie(l.The fuill discu-ission of their histo- logical chaniges will be given later, butt it is clcarthat in solne cases the remiiains foundl cani lilrdly v with justicef 1) accredited with the survival.2. Contlition of the Inftuib a lio .-ThePhy-siolog;ical iluportanec of the pars anterior may be considered in conijulletion witlh the hypothesis that it furnishles lhormones for subsequent treatment by tile rest of tlhe glanid.Sucil a view lhas beeni supported by the considerationi byHerring and others of the importance of the infuandihlum-thi as a (luct and chaninel of transferenice of the pirodticts of tlhe really active lobe, thlc pars posterior.Ouir experiments s1low tilat tllcse view,-s must be re- garded very closely before tllev are accep)ted.since wve have lnot onily divided tlhe infunedibuluni \w-itlhotut causing (leatlh, but we lhave also completely occltude(d it cicatricially in cases whlere also infinitesimal rnemainis of other palrts of tile glandl were fouind imbedded in tile suar.: 3. Glycostria.-We liave observed tile occurrence of sliglit glycosuria in two instances ouLt of seveni cases of complete or almost colmtplete extirpatioll.4. Relatiton7z of the .Fiypoplhsis to Othe} lu/cr)iedl ,S'(re- lito'i (llands.-Weliave not observe( clhanes in otller initernial secretioll glands which colul(l be w-lth certainty attributed to tilie lesiolls of the lIypopliysis.'Tui4 p)oint -will als be dealt with in tlle full Ipa)M' by Di.Ilandelsmiianii.