tbuckley/cabot-search huggingface dataset:
Evidence for a stepwise program of extrathymic T cell development within the human tonsil
Authors: Susan McClory, Tiffany Hughes, Aharon G. Freud, Edward L. Briercheck, Chelsea Martin, Anthony J. Trimboli, Jianhua Yu, Xiaoli Zhang, Gustavo Leone, Gerard Nuovo, Michael A. Caligiuri
Journal: Journal of Clinical Investigation (2012)

The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34⁺CD38dimLin⁻ cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34⁺CD38brightLin⁻ cells; (c) CD34⁺CD1a⁺CD11c⁻ cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34⁻CD1a⁺CD3⁻CD11c⁻ cells, which resemble CD4⁺CD8⁺ double-positive T cells in the thymus; and (e) CD34⁻CD1a⁺CD3⁺CD11c⁻ cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT⁺ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre-T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development.
CD44 Expression Predicts Local Recurrence after Radiotherapy in Larynx Cancer
Authors: Monique C. de Jong, Jimmy Pramana, Jacqueline E. van der Wal, Martin Lacko, Carine J. Peutz-Kootstra, Jos M. de Jong, Robert P. Takes, Johannes H. Kaanders, Bernard F. van der Laan, Jasper Wachters, Jeroen C. Jansen, Coen R. Rasch, Marie-Louise F. van Velthuysen, Reidar Grénman, Frank J. Hoebers, Ed Schuuring, Michiel W. van den Brekel, Adrian C. Begg
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329–38. ©2010 AACR.
Inhibition and Promotion of Differentiated-Like Phenotype of a Human Lung Carcinoma in Athymic Mice by Natural and Recombinant Forms of Transforming Growth Factor-beta
Authors: D. R. Twardzik, J. E. Ranchalis, J. M. McPherson, Y. Ogawa, L. Gentry, A. Purchio, E. Plata, G. J. Todaro
Journal: JNCI Journal of the National Cancer Institute (1989)

Both structurally related forms of transforming growth factor-beta (TGF-beta types I and II) are potent inhibitors of tumor cell growth in vitro and can also modulate the differentiation of some cells in culture. In this study, we describe the effects of natural and recombinant TGF-betas on the growth and differentiation of a xenograft of human lung adenocarcinoma A549 in male athymic BALB/c mice. Subcutaneous, peritumoral injection of both forms of TGF-beta inhibited, in a dose-dependent manner, the growth of established human lung tumors. Histologically, tumors inhibited by TGF-beta appeared more differentiated, as judged by reduced mitotic activity and a predominance of highly specialized mucus-secreting goblet-like cell types. These findings suggest that TGF-betas can be useful in the development of novel, perhaps less cytotoxic, cancer therapeutic strategies.
Trefoil peptides promote epithelial migration through a transforming growth factor beta-independent pathway.
Authors: A Dignass, K Lynch-Devaney, H Kindon, L Thim, D K Podolsky
Journal: Journal of Clinical Investigation (1994)

The trefoil peptides, a recently recognized family of protease-resistant peptides, expressed in a regional specific pattern throughout the normal gastrointestinal tract. Although these peptides have been hypothesized to act as growth factors, their functional properties are largely unknown. Addition of recombinant trefoil peptides human spasmolytic polypeptide (HSP), rat and human intestinal trefoil factor (RITF and HITF) to subconfluent nontransformed rat intestinal epithelial cell lines (IEC-6 and IEC-17), human colon cancer-derived cell lines (HT-29 and CaCO2) or nontransformed fibroblasts (NRK and BHK) had no significant effect on proliferation. However addition of the trefoil peptides to wounded monolayers of confluent IEC-6 cells in an in vitro model of epithelial restitution resulted in a 3-6-fold increase in the rate of epithelial migration into the wound. Stimulation of restitution by the trefoil peptide HSP was enhanced in a cooperative fashion by the addition of mucin glycoproteins purified from the colon or small intestine of either rat or man, achieving up to a 15-fold enhancement in restitution. No synergistic effect was observed by the addition of nonmucin glycoproteins. In contrast to cytokine stimulation of intestinal epithelial cell restitution which is mediated through enhanced TGF beta bioactivity, trefoil peptide, and trefoil peptide-mucin glycoprotein stimulation of restitution was not associated with alteration in concentrations of bioactive TGF-beta and was not affected by the presence of immunoneutralizing anti-TGF beta antiserum. Collectively, these findings suggest that the trefoil peptides which are secreted onto the lumenal surface of the gastrointestinal tract may act in conjunction with the mucin glycoprotein products of goblet cells to promote reestablishment of mucosal integrity after injury through mechanisms distinct from those which may act at the basolateral pole of the epithelium.
Prognostic Significance of Blasts in the Cerebrospinal Fluid Without Pleiocytosis or a Traumatic Lumbar Puncture in Children With Acute Lymphoblastic Leukemia: Experience of the Dutch Childhood Oncology Group
Authors: D. Maroeska W.M. te Loo, Willem A. Kamps, Anna van der Does-van den Berg, Elisabeth R. van Wering, Siebold S.N. de Graaf
Journal: Journal of Clinical Oncology (2006)

To determine the significance of blasts in the CSF without pleiocytosis and a traumatic lumbar puncture in children with acute lymphoblastic leukemia (ALL).We retrospectively studied a cohort of 526 patients treated in accordance with the virtually identical Dutch protocols ALL-7 and ALL-8. Patients were classified into five groups: CNS1, no blasts in the CSF cytospin; CNS2, blasts present in the cytospin, but leukocytes less than 5/microL; CNS3, blasts present and leukocytes more than 5/microL. Patients with a traumatic lumbar puncture (TLP; > 10 erythrocytes/mL) were classified as TLP+ (blasts present in the cytospin) or TLP- (no blasts).Median duration of follow-up was 13.2 years (range, 6.9 to 15.5 years). Event-free survival (EFS) was 72.6% (SE, 2.5%) for CNS1 patients (n = 304), 70.3% (SE, 4.7%) for CNS2 patients (n = 111), and 66.7% (SE, 19%) for CNS3 patients (n = 10; no significant difference in EFS between the groups). EFS was 58% (SE, 7.6%) for TLP+ patients (n = 62) and 82% (SE, 5.2%) for TLP- patients (n = 39; P < .01). Cox regression analysis identified TLP+ status as an independent prognostic factor (risk ratio, 3.5; 95% CI, 1.4 to 8.8; P = .007). Cumulative incidence of CNS relapses was 0.05 and 0.07 in CNS1 and CNS2 patients, respectively (not statistically significant).In our experience, the presence of a low number of blasts in the CSF without pleiocytosis has no prognostic significance. In contrast, a traumatic lumbar puncture with blasts in the CSF specimen is associated with an inferior outcome.
Serum type I and type III procollagen peptide levels in sarcoidosis
Authors: L Bacchella, C Tinelli, LS Gile, V Peona, C Aprile, M Gorrini, L Pasturenzi, G Cetta, M Luisetti
Journal: European Respiratory Journal (1996)

Type I and type III are the most abundant collagens in the lung. The aim of our study was to compare type I and III procollagen peptides in sera of sarcoid patients. Sixty eight patients with sarcoidosis were studied (19 with newly recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in stable remission). Thirty healthy volunteers served as controls. The levels of procollagen I and III peptides were determined by radioimmunoassay. Angiotensin-converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In patients with newly recognized sarcoidosis, both serum procollagen I and III peptide levels were increased with respect to controls (p=0.0014 and p<0.00001, respectively). There was a poor correlation between levels of procollagen I and III (r=0.26), whereas there was a closer correlation between procollagen III and ACE (r=0.69). Procollagen I peptide level did not identify patients in roentgenological stage III. In conclusion, in patients with newly recognized sarcoidosis there is a significant increase in the serum level of procollagen I peptide. However, procollagen I peptide is not a marker of sarcoid patients with fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than that of procollagen III peptide.
Hydrolytically Degradable Hyperbranched PEG‐Polyester Adhesive with Low Swelling and Robust Mechanical Properties
Authors: Hong Zhang, Tianyu Zhao, Patrick Duffy, Yixiao Dong, Aisling Ní Annaidh, Eoin O'Cearbhaill, Wenxin Wang
Journal: Advanced Healthcare Materials (2015)

Photocrosslinkable and water soluble hyperbranched PEG‐polyester polymers (HPEGDA) have been developed as robust degradable adhesives. The HPEGDA polymers have been synthesized from controlled homopolymerization of poly(ethylene glycol) diacrylate (PEGDA 700 ) via in situ deactivation enhanced atom transfer radical polymerization (DE‐ATRP). By introducing a high initiator‐to‐monomer ratio, the obtained HPEGDA polymer is composed of extremely short carbon–carbon backbones interconnected together by the long PEG chains as well as pendent photocrosslinkable acrylate moieties. Due to the extremely short C–C backbone, the long PEG chains can therefore be seen as the main chain, thus, HPEGDA polymers behave more like polyester which is a category of polymers that contain the ester functional group in their main chain. Photo‐cured HPEGDA can be readily adhered to tissue forming a patch with robust mechanical and adhesive strengths. The degradation profile by hydrolysis of polyester blocks as well as a significantly low swelling ratio of HPEGDA gels in an aqueous environment allow them to have great potential for sealing and repair of internal tissue. Furthermore, HPEGDA gels appear to have minor significant cytotoxicity in vitro. These unique properties indicate that the reported HPEGDA polymers are well poised for the development of adhesive tissue engineering matrixes, wound dressings, and sealants.
CTLA-4 ligation blocks CD28-dependent T cell activation.
Authors: T L Walunas, C Y Bakker, J A Bluestone
Journal: The Journal of Experimental Medicine (1996)

CTLA-4 is a CD28 homologue believed to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction of apoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition of IL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28-mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL-2 to the cultures restored IL-2 receptor expression and T cell proliferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production.
Fertility preservation in girls during childhood: is it feasible, efficient and safe and to whom should it be proposed?
Authors: P. Jadoul, M.-M. Dolmans, J. Donnez
Journal: Human Reproduction Update (2010)

In prepubertal and adolescent girls, fertility may be impaired by gonadotoxic treatments, repeat ovarian surgery or genetic disorders. Cryopreservation of ovarian cortex is an existing option to preserve fertility in these young girls at risk of premature ovarian failure (POF). The efficacy, feasibility and risks of ovarian cryopreservation in children must be assessed in order to validate the technique. Here, we conducted a review of ovarian cryopreservation in adults and, more specifically, in children using the PubMed databases. In addition, our own experience with ovarian cryopreservation in children was evaluated and compared with the literature. Analysis of the literature and six published series on ovarian cryopreservation in children, as well as our own series of 58 cases, show that there is no reason to doubt its efficacy in this young population. However, no consensus has yet been reached on the indications for the technique. Indeed, with existing models, the real risk of POF may be over- or underestimated. Our review suggests that ovarian cortex cryopreservation is feasible and as safe as comparable operative procedures in children. Although no births have yet resulted from freeze-thawing of prepubertal ovarian cortex, the results of this approach in adults are encouraging. However, the absence of consensus on the indications for fertility preservation, as well as the optimal timing and quantity of ovarian cortex for cryopreservation, should be taken into consideration when discussing fertility issues with girls at risk of POF and their parents.
Nitro-oleic acid and epoxyoleic acid are not altered in obesity and Type 2 diabetes: reply
Authors: F. J. Schopfer, B. A. Freeman, N. K. H. Khoo
Journal: Cardiovascular Research (2014)

We appreciate the interest in our recent study of the in vivo signalling actions of electrophilic fatty acid nitroalkenes,1 including the commentary from Tsikas et al. This study is based on a high-fat diet (HFD)-induced obesity murine model that displays the canonical features of metabolic syndrome, including glucose tolerance, vascular dysfunction, increased inflammation, adipokine dysfunction, and most notably development of pulmonary hypertension. We tested the pharmacological actions of synthetic 10-nitro-octadec-9-enoic acid (OA-NO2) and reported potent protective actions of OA-NO2 in this murine model of HFD-induced obesity and pulmonary hypertension. First and foremost, we stress that under no circumstance did we state or imply the existence of any link between obesity and decreased OA-NO2 biosynthesis. This is an incorrect and misleading interpretation of the data presented in our manuscript.

The …
The Addition of Interleukin-6 Soluble Receptor and Transforming Growth Factor Beta<sub>1</sub> Improves a Preoperative Nomogram for Predicting Biochemical Progression in Patients With Clinically Localized Prostate Cancer
Authors: Michael W. Kattan, Shahrokh F. Shariat, Ben Andrews, Kuichun Zhu, Eduardo Canto, Kazumasa Matsumoto, Masatoshi Muramoto, Peter T. Scardino, Makoto Ohori, Thomas M. Wheeler, Kevin M. Slawin
Journal: Journal of Clinical Oncology (2003)

Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1).Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance.In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75.We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.
Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome
Authors: Josep Brugada, Luis Aguinaga, Lluı́s Mont, Amadeu Betriu, Jaume Mulet, Ginés Sanz
Journal: Journal of the American College of Cardiology (2001)
Renovascular Hypertension in Mice With Brain-Selective Overexpression of AT1a Receptors Is Buffered by Increased Nitric Oxide Production in the Periphery
Authors: Eric Lazartigues, Andrew J. Lawrence, Fred S. Lamb, Robin L. Davisson
Journal: Circulation Research (2004)

We recently established a new transgenic mouse model with brain-restricted overexpression of angiotensin II (Ang II) type 1a receptors (NSE-AT(1a)) to unmask the role of the brain renin-angiotensin system in hypertension. To test the hypothesis that these mice would exhibit an early exacerbation of renovascular hypertension, NSE-AT(1a) and nontransgenic (NT) mice underwent 2-kidney-1-clip (2K1C) surgery and blood pressure (BP) and heart rate (HR) were recorded continuously by radiotelemetry for 28 days. Results show that NSE-AT(1a) mice developed hypertension much more rapidly than NT, and this was not attributable to genotype-related differences in plasma or brain Ang II levels. A marked bradycardia accompanied this early increase in BP in NSE-AT(1a) mice, as did a substantial cardiovascular region-specific downregulation of AT(1) receptor binding in brain but not in kidney. As BP reached its plateau in NT ( approximately 1 week after clip), hypertension began to abate and eventually stabilized at significantly lower levels in NSE-AT(1a) mice despite marked elevations in Ang II levels in brain stem and hypothalamus at these later time points. This hypertension reversal and the bradycardia were prevented by chronic infusion of the nitric oxide synthase (NOS) blocker l-NAME. These data, along with evidence showing enhanced NOS expression and NO-mediated compensatory responses in 2K1C NSE-AT(1a) peripheral arteries during this later phase, suggest that activation of endogenous NO systems plays an important role in buffering the maintenance of hypertension caused by overexpression of AT(1a) receptors in the brain.
Volume Replacement in Critically Ill Patients with Acute Renal Failure
Authors: MAXIMILIAN J. R. RAGALLER, HERMANN THEILEN, THEA KOCH
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Maintenance and restoration of intravascular volume are essential tasks of critical care management to achieve sufficient organ function and to avoid multiple organ failure in critically ill patients. Inadequate intravascular volume followed by impaired renal perfusion is the predominate cause of acute renal failure. Crystalloid solutions are the first choice to correct fluid and electrolyte deficits in these patients. However, in case of major hypovolemia, particularly in situations of increased capillary permeability, colloid solutions are indicated to achieve sufficient tissue perfusion. Whereas albumin should be avoided for correction of intravascular hypovolemia, synthetic colloids can restore intravascular volume and stabilize hemodynamic conditions. In addition to a faster, more effective and prolonged restoration of intravascular volume, colloid solutions are able to improve microcirculation. Of the synthetic colloids, hydroxyethyl starch (HES) solutions with a low in vivo molecular weight, such as HES 200/0.5, offer the best risk/benefit ratio. These solutions are safe with respect to effects on coagulation, platelets, reticuloendothelial system, and renal function, if used below their upper dosage limits. For patients with acute renal dysfunction, daily monitoring of renal function is necessary if colloids are required to stabilize hemodynamic conditions. In these patients, measurement of the colloidal osmotic pressure and adequate amounts of crystalloid solutions will reduce the risk of hyperoncotic renal failure. Of all colloids, gelatin and HES solutions with low in vivo molecular weight are preferred in these cases. In the very specific situation of kidney transplantation, colloid solutions should be administered in a restricted manner to organ donors and kidney recipients.