tbuckley/cabot-search huggingface dataset:
T cell receptor beta chain gene rearrangements in lymphoproliferative disorders of large granular lymphocytes/natural killer cells.
Authors: A Rambaldi, P G Pelicci, P Allavena, D M Knowles, S Rossini, R Bassan, T Barbui, R Dalla-Favera, A Mantovani
Journal: The Journal of Experimental Medicine (1985)

Twelve cases of T gamma LPD (lymphoproliferative disorders of Fc gamma receptor-bearing T cells) involving an expansion of large granular lymphocyte/natural killer (LGL/NK) cells were investigated for the expression of LGL/NK-associated markers and for T beta gene rearrangement. All the cases selected were classified as T gamma LPD on the basis of morphology, function, and phenotype of the circulating cells. 10 to 12 cases displayed clonal rearrangements of the T beta locus and expression of the T3 antigen, whereas the 2 remaining cases displayed the germline configuration of the T beta gene and no expression of the T3 antigen. T8, Mol, B73.1, and N901 antigens were variably expressed among both T beta+T3+ and T beta-T3- T gamma LPD cases. We suggest that individual T gamma LPD cases represent the clonal expansion of cells frozen at different stages of differentiation/activation within an individual hematopoietic LGL/NK lineage.
Multiparameter flow cytometry for staging of solitary bone plasmacytoma: new criteria for risk of progression to myeloma
Authors: Bruno Paiva, Mauricio Chandia, Maria-Belen Vidriales, Enrique Colado, Teresa Caballero-Velázquez, Fernando Escalante, Alfonso Garcia de Coca, Maria-Carmen Montes, Ramon Garcia-Sanz, Enrique M. Ocio, Maria-Victoria Mateos, Jesus F. San Miguel
Journal: Blood (2014)
Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis
Authors: Berend Isermann, Ilya A Vinnikov, Thati Madhusudhan, Stefanie Herzog, Muhammed Kashif, Janusch Blautzik, Marcus A F Corat, Martin Zeier, Erwin Blessing, Jun Oh, Bruce Gerlitz, David T Berg, Brian W Grinnell, Triantafyllos Chavakis, Charles T Esmon, Hartmut Weiler, Angelika Bierhaus, Peter P Nawroth
Journal: Nature Medicine (2007)
Faecal flora of patients with ulcerative colitis during treatment with salicylazosulphapyridine.
Authors: E M Cooke
Journal: Gut (1969)

Blood agar was Oxoid proteose peptone 2 g, Oxoid Lab- Lemco beef extract 10 g, NaCI 5 g, MgCl2 1 g, water 1 litre, to which, after adjustment to pH 7 5, New Zealand agar 9 g, and, when sufficiently cooled, defibrinated horse blood, 50 ml, were added.The blood agar was poured in
Direct G Protein Modulation of Ca<sub>v</sub>2 Calcium Channels
Authors: H. William Tedford, Gerald W. Zamponi
Journal: Pharmacological Reviews (2006)

The regulation of presynaptic, voltage-gated calcium channels by activation of heptahelical G protein-coupled receptors exerts a crucial influence on presynaptic calcium entry and hence on neurotransmitter release. Receptor activation subjects presynaptic N- and P/Q-type calcium channels to a rapid, membrane-delimited inhibition—mediated by direct, voltage-dependent interactions between G protein βγ subunits and the channels—and to a slower, voltage-independent modulation involving soluble second messenger molecules. In turn, the direct inhibition of the channels is regulated as a function of many factors, including channel subtype, ancillary calcium channel subunits, and the types of G proteins and G protein regulatory factors involved. Twenty-five years after this mode of physiological regulation was first described, we review the investigations that have led to our current understanding of its molecular mechanisms.
Mitochondrial DNA from Prehistoric Canids Highlights Relationships Between Dogs and South-East European Wolves
Authors: Fabio Verginelli, Cristian Capelli, Valentina Coia, Marco Musiani, Mario Falchetti, Laura Ottini, Raffaele Palmirotta, Antonio Tagliacozzo, Iacopo De Grossi Mazzorin, Renato Mariani-Costantini
Journal: Molecular Biology and Evolution (2005)

The question of the origins of the dog has been much debated. The dog is descended from the wolf that at the end of the last glaciation (the archaeologically hypothesized period of dog domestication) was one of the most widespread among Holarctic mammals. Scenarios provided by genetic studies range from multiple dog-founding events to a single origin in East Asia. The earliest fossil dogs, dated ≈17–12,000 radiocarbon (14C) years ago (YA), were found in Europe and in the Middle East. Ancient DNA (a-DNA) evidence could contribute to the identification of dog-founder wolf populations. To gain insight into the relationships between ancient European wolves and dogs we analyzed a 262-bp mitochondrial DNA control region fragment retrieved from five prehistoric Italian canids ranging in age from ≈15,000 to ≈3,000 14C YA. These canids were compared to a worldwide sample of 547 purebred dogs and 341 wolves. The ancient sequences were highly diverse and joined the three major clades of extant dog sequences. Phylogenetic investigations highlighted relationships between the ancient sequences and geographically widespread extant dog matrilines and between the ancient sequences and extant wolf matrilines of mainly East European origin. The results provide a-DNA support for the involvement of European wolves in the origins of the three major dog clades. Genetic data also suggest multiple independent domestication events. East European wolves may still reflect the genetic variation of ancient dog-founder populations.
CARCINOMA OF THE RECTUM COMPLICATED BY PREGNANCY: Two Cases Treated by Excision
Authors: R. C. B. Maunsell
Journal: BMJ (1925)

THrE DEaITna 826MAY 29 1925TM RENACY MEICL ouE-Cases which attended regularly anid.had a full -course of treatment showed in--ge'neral a steady fall, in units to6 a stal1e legatiee weaction, but cases whiichl attended regularly at-d had an incomplete course of treatmeent were liable to become resistantto arsenic, the number of units often .rellaininigstationary when treatment was resumed.3. As regards the effect of treatment in the tertiary .stage:Onily 3 out of 106 cases became negative; at the beginning of observation these cases had a low-number of, units, 'and lhad receivedimuch previou's treatment.Of the remaining cases the units fell in about-one-fifth of the -cases, fell and then:remained unchanged in one-third, of the cases, and remained unchanged through6ut in one-third.In 3 cases-a rise of units was observed, and in 2 of these cases the rise was associated with a visible increased activity of the disease.,It is probable that in the majority of.tertiarycases the Sigma units fall to a .-certainlevel:as 'a result of treatment and that it is difficult to cause a,..firtlier fall in UD its.This level is usually between 2 and 15 Sigma units.The -most effective dose of --N.A.B. was 0.9 gram.No substanital effect was observed in the number of units, if thwe injeetions of N.A.B. were given at intervals of three wveeks or longer-, Intravenous injections of mercuric perebloride were given to 24 stationary caees, and produced a fall in units in about 50 per cent.of-these, but,-no case becamne negative.About 90 per cent. of cases -showed-'no change' in their unDitage during rest or during oral treatment following courses of N.A.B.The renmaining 10 per tent.showed a rise and fall of units-in equal proportions.The number of units-in the blood corresponds toa certain (legree, with the visible extent of the activity of the disease.in-43 per cent. of cases a fall of units was associated wiith clinical improvement, but in 15.6 per cent.the units re--nained uichlanged althouglh there was improvement * liIlicahlyt.
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs
Authors: Fernando Cruz-Guilloty, Matthew E. Pipkin, Ivana M. Djuretic, Ditsa Levanon, Joseph Lotem, Mathias G. Lichtenheld, Yoram Groner, Anjana Rao
Journal: The Journal of Experimental Medicine (2009)

Activation of naive CD8+ T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.
Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.
Authors: G Tsoulfa, G A Rook, J D Van-Embden, D B Young, A Mehlert, D A Isenberg, F C Hay, P M Lydyard
Journal: Annals of the Rheumatic Diseases (1989)

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn9s disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn9s disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat.
Hypertrophic Pulmonary Osteo-arthropathy as First Symptom of Neoplasm
Authors: J. W. Craig
Journal: BMJ (1937)

PULMONARY OSTEO-ARTHROPATHY AND NEOPLASM MTHEBRITIS}{ undetected carcinoma of the cervix will lead to certain death.The task is very difficult.Even Victor Bonney states: "Nor have I observed that patients in more recent years present themselves earlier in spite of modern propa- ganda."Lastly, the work of cancer investigation cannot be complete unless substantial help and co-operation come from the corporation and the Government.
Levels of target activation predict antifibrotic responses to tyrosine kinase inhibitors
Authors: Britta Maurer, Alfiya Distler, Clara Dees, Korsa Khan, Christopher P Denton, David Abraham, Renate E Gay, Beat A Michel, Steffen Gay, Jörg HW Distler, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To assess whether the discrepancy between the strong antifibrotic effects of tyrosine kinase inhibitors (TKIs) in animal models and the inconsistent results in clinical studies might be related to the activation levels of drug targets. Methods Skin sections of bleomycin, TSK1, Fra-2 transgenic mice, SSc patients and controls were analysed by histology and immunohistochemistry. Subgroups of mice were treated with the TKIs nilotinib or imatinib. Differences in the activation levels of the TKI targets p-PDGFRβ (platelet derived growth factor β) and p-c-abl were assessed. Results In bleomycin and TSK1 mice, expression of activated p-PDGFRβ (platelet derived growth factor receptor β) and p-c-abl was ubiquitous with strong upregulation compared with controls. Treatment with TKIs resulted in successful target inhibition and consequently reduced dermal fibrosis. In the Fra-2 model, the activation levels of p-PDGFRβ and p-c-abl were much lower than in the bleomycin and the TSK1 models. Accordingly, nilotinib did not prevent dermal fibrosis and target inhibition was unsuccessful. Notably, in skin biopsies of SSc patients, the mean activation levels of TKI targets were only moderate and in the majority of patients resembled those of the non-responsive Fra-2 model. Conclusions Animal models for proof-of-concept studies should be selected based on a similar activation level and expression pattern of drug targets as in human SSc.
Angiotensin II Type 1 Receptor Blockade Inhibits the Development and Progression of HIV-Associated Nephropathy in a Mouse Model
Authors: Noriyuki Hiramatsu, Keiju Hiromura, Tetsuya Shigehara, Takashi Kuroiwa, Hiroshi Ideura, Noriyuki Sakurai, Shigeru Takeuchi, Mai Tomioka, Hidekazu Ikeuchi, Yoriaki Kaneko, Kazue Ueki, Jeffrey B. Kopp, Yoshihisa Nojima
Journal: Journal of the American Society of Nephrology (2007)

HIV-associated nephropathy (HIVAN) is characterized by a collapsed glomerular capillary tuft with hyperplasia and hypertrophy of podocytes. Recently generated were conditional transgenic mice (podocin/Vpr) that express one of the HIV-1 accessory genes, vpr, selectively in podocytes using podocin promoter and Tet-on system. These transgenic mice developed renal injury similar to HIVAN when treated with doxycycline for 8 to 12 wk. This study demonstrated that nephron reduction by heminephrectomy markedly enhanced phenotypic changes of podocytes and led to severe FSGS within 4 wk. Nephrotic-range proteinuria was observed already at 2 wk, together with dedifferentiation and dysregulation of podocytes, indicated by decreased expression of nephrin, synaptopodin, and Wilms' tumor 1 protein and increased expression of Ki-67. The acceleration of phenotypic changes of podocytes, proteinuria, and subsequent glomerulosclerosis by heminephrectomy was almost completely inhibited by angiotensin II type 1 receptor (AT1R) blocker olmesartan. In contrast, the renoprotective effect of the calcium channel antagonist azelnidipine was minimal, although it lowered systemic BP to the same level as olmesartan, demonstrating that the inhibitory effect of AT1R blocker was independent of systemic BP. Olmesartan also reduced proteinuria and prevented glomerulosclerosis even by the delayed treatment, which was initiated after the podocyte injury appeared. These data suggest that nephron reduction exaggerates podocyte injury and subsequent glomerulosclerosis, possibly through glomerular hypertension, in the mouse model of HIVAN. AT1R blockade could be beneficial in the treatment of HIVAN by ameliorating podocyte injury by avoiding the vicious cycle of nephron reduction and glomerular hypertension.
Oxygen Deprivation Triggers Upregulation of Early Growth Response-1 by the Receptor for Advanced Glycation End Products
Authors: Jong Sun Chang, Thoralf Wendt, Wu Qu, Linghua Kong, Yu Shan Zou, Ann Marie Schmidt, Shi-Fang Yan
Journal: Circulation Research (2008)

Myocardial infarction, stroke, and venous thromboembolism are characterized by oxygen deprivation. In hypoxia, biological responses are activated that evoke tissue damage. Rapid activation of early growth response-1 in hypoxia upregulates fundamental inflammatory and prothrombotic stress genes. We probed the mechanisms mediating regulation of early growth response-1 and demonstrate that hypoxia stimulates brisk generation of advanced glycation end products (AGEs) by endothelial cells. Via AGE interaction with their chief signaling receptor, RAGE, membrane translocation of protein kinase C-βII occurs, provoking phosphorylation of c-Jun NH 2 -terminal kinase and increased transcription of early growth response-1 and its downstream target genes. These findings identify RAGE as a master regulator of tissue stress elicited by hypoxia and highlight this receptor as a central therapeutic target to suppress the tissue injury–provoking effects of oxygen deprivation.
Dietary advice in systemic sclerosis: the dangers of a high fibre diet
Authors: A Gough, T Sheeran, P Bacon, P Emery
Journal: Annals of the Rheumatic Diseases (1998)

Systemic sclerosis frequently aVects the gastrointestinal tract. 1 However, information on large bowel involvement and dietary advice for patients is scarce.Even the most recent and comprehensive rheumatological text discusses colonic involvement but gives no information on dietary advice or management. 2 It is widely felt and advertised that a high fibre diet is "good for all".We report on four cases, three of whom required emergency admission after receiving such advice. Case reportsA 48 year old woman was admitted with a 10 day history of severe abdominal pain and distension.She had a four year history of diVuse systemic sclerosis and was taking penicillamine and indomethacin.Two weeks before admission she had recounted some diYculty with infrequent bowel motions to a friend, who had advised a high fibre diet.She obtained a high fibre breakfast cereal.Within three days she developed abdominal distension and colicky pain.This lead to colonic atony with no bowel action for 10 days before admission.She was treated with daily picolax and discharged three days later.A barium enema did not reveal any obstructive lesion.She has remained well on her normal low residue diet and has had no similar problems or investigations since.
Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma
Authors: A. Estrada-Bernal, K. Palanichamy, A. Ray Chaudhury, J. R. Van Brocklyn
Journal: Neuro-Oncology (2012)

FTY720 is a sphingosine analogue that down regulates expression of sphingosine-1-phosphate receptors and causes apoptosis of multiple tumor cell types, including glioma cells. This study examined the effect of FTY720 on brain tumor stem cells (BTSCs) derived from human glioblastoma (GBM) tissue. FTY720 treatment of BTSCs led to rapid inactivation of ERK MAP kinase, leading to upregulation of the BH3-only protein Bim and apoptosis. In combination with temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, FTY720 synergistically induced BTSC apoptosis. FTY720 also slowed growth of intracranial xenograft tumors in nude mice and augmented the therapeutic effect of TMZ, leading to enhanced survival. Furthermore, the combination of FTY720 and TMZ decreased the invasiveness of BTSCs in mouse brains. FTY720 is known to cross the blood-brain barrier and recently received Food and Drug Administration approval for treatment of relapsing multiple sclerosis. Thus, FTY720 is an excellent potential therapeutic agent for treatment of GBM.
Long-term efficient gene delivery using polyethylenimine with modified Tat peptide
Authors: Seiichi Yamano, Jisen Dai, Shigeru Hanatani, Ken Haku, Takuto Yamanaka, Mika Ishioka, Tadahiro Takayama, Carlo Yuvienco, Sachin Khapli, Amr M Moursi, Jin K Montclare
Journal: Biomaterials (2013)
To proliferate or not to proliferate
Authors: Y. Lee
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Cardiomyocyte cell cycle control and growth estimation in vivo —an analysis based on cardiomyocyte nuclei’ by S. Walsh et al ., pp. 365–373, this issue. 

Cardiomyocytes in mammalian hearts undergo significant reduction in their cell proliferation capacity soon after birth, which is not disputed. However, it remains uncertain whether the adult heart contains a limited capacity for cell proliferation. Through the use of immunohistochemical staining methods, it has been reported that adult mouse cardiomyocytes can re-enter the cell cycle and duplicate.1,2 However, the origin of the cell-cycle-positive cells was not determined. Others reported permanent inhibition of cell-cycle progression in adult cardiomyocytes in mice.3 With advances in lineage tracing technology, a recent genetic labelling study demonstrated that stem or precursor cells did not contribute significantly to the formation of cardiomyocytes during normal ageing up to 1 year in the mouse. In contrast, precursor cells may participate in the formation of new cardiomyocytes after cardiac injury.4 In humans, high myocyte proliferation rates that could result in the exchange of all cardiomyocytes within 5 years have been reported by employing immunostaining technology on sections of human patients who died of acute myocardial infarction.5 In contrast, using 14C dating analyses in humans, Bergmann et al .6 reported that cardiomyocytes are renewed with a gradual decrease from …
Diabetes and retinopathy11The following letter addresses an article that appeared in the January 2000 issue of the Journal: Bresnick GH, Mukamel DB, Dickinson JC, Cole DR. A screening approach to the surveillance of patients with diabetes for the presence of vision-threatening retinopathy. (Ophthalmology 2000;107:19–24)
Authors: James F Vander, Allen C Ho, J.Arch McNamara, Carl D Regillo, Gary C Brown, William E Benson, William Tasman
Journal: Ophthalmology (2000)
HIV Develops Indirect Cross-resistance to Combinatorial RNAi Targeting Two Distinct and Spatially Distant Sites
Authors: Priya S Shah, Nhung P Pham, David V Schaffer
Journal: Molecular Therapy (2012)

Resistance to existing HIV therapies is an increasing problem, and alternative treatments are urgently needed. RNA interference (RNAi), an innate mechanism for sequence-specific gene silencing, can be harnessed therapeutically to treat viral infections, yet viral resistance can still emerge. Here, we demonstrate that HIV can develop indirect resistance to individual and combinatorial RNAi-targeting protein-coding regions up to 5,500 nucleotides (nt) downstream of the viral promoter. We identify several variants harboring mutations in the HIV promoter, and not within the RNAi targets, that produce more fully elongated transcripts. Furthermore, these variants are resistant to the RNAi, potentially by stoichiometrically overwhelming this cellular mechanism. Alarmingly, virus resistant to one short hairpin RNA (shRNA) also exhibits cross-resistance to a different shRNA, which targets a distinct and spatially distant region to which the virus has not been previously exposed. To our knowledge, this is the first example of HIV "cross-resistance" to viral inhibitors targeting different loci. Finally, combining anti-HIV RNAi with a small molecule enhancer of RNAi can inhibit the replication of an indirectly resistant mutant. These results suggest that indirect resistance to RNAi is a general mechanism that should be considered when investigating viral resistance and designing combinatorial RNAi therapies.