tbuckley/cabot-search huggingface dataset:
Nodular lymphoid hyperplasia with hypogammaglobulinaemia
Authors: A. B. Ajdukiewicz, G. R. Youngs, I. A. D. Bouchier
Journal: Gut (1972)

A patient with nodular lymphoid hyperplasia, who manifested defects in cellular immunity, is presented. The clinical course is discussed and a review included of the 23 patients thus far reported with nodular lymphoid hyperplasia and hypogammaglobulinaemia.
Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis
Authors: J Hescheler
Journal: Cardiovascular Research (1997)

Time for primary review 20 days.

In order to study cardiac myocyte development different approaches were established during the last decades. The main purpose of these studies was the differentiation of cardiac precursor cells into specialized, differentiated cell types, as well as the development of functional properties such as Ca2+ handling, rhythm generation and excitation-contraction coupling of cardiomyocytes during development. Although considerable data exist about skeletal myogenesis [1–3], limited knowledge is available with regard to the origin of the commitment and differentiation of cardiac cells. A comprehensive, morphological study on the cytodifferentiation from mesenchymal cells into cardiac myocytes is described in the embryonic murine heart [4]: According to the authors, different stages of myofibrillogenesis are present during embryological myocardial development. Cells with no or only little myofibrillar arrangement develop to myocardial cells with orientated myofibrils [5, 6]. A number of morphological studies have investigated heart development on embryonic, neonatal and adult isolated cardiomyocytes also from different species [7–16].

Although the ultrastructure during cardiac development has been thoroughly investigated [17], still relatively little is known on the development of excitability of the mammalian heart, most importantly: (1): The relation between expression of cardio-specific genes (see review [23]), the formation of cardiac phenotypes and the functional expression of different types of ion channels; (2): The regulation and genetic control of expression of ion channels (e.g. by growth factors, hormones, extracellular matrix); (3): The development of the regulation of ion channels and morphological correlates. The progress in this field is hampered by the inability to study cardiomyocytes from early, embryonal hearts because of their very small size and because of the lack of cardiac cell lines that mimic various stages of cardiac development. The development of ion currents has been studied in cardiomyocytes prepared from mammalian embryos … 

* Corresponding author. Tel.: (+49-221) 4786960; Fax: (+49-221) 4786965.
A Unique Spectrum of Somatic <i>PIK3CA</i> (p110α) Mutations Within Primary Endometrial Carcinomas
Authors: Meghan L. Rudd, Jessica C. Price, Sarah Fogoros, Andrew K. Godwin, Dennis C. Sgroi, Maria J. Merino, Daphne W. Bell
Journal: Clinical Cancer Research (2011)

The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC).We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wild type and mutant constructs in U2OS cells and measuring levels of AKT(Ser473) phosphorylation.Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1-7 and half were in exons 9 and 20. The exons 1-7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110α. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93, and Lys111 formed mutation hotspots. The p110α-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKT(Ser473) compared to wild-type p110α. Overall, 62% of exons 1-7 PIK3CA mutants and 64% of exons 9-20 PIK3CA mutants were activating; 72% of exon 1-7 mutations have not previously been reported in endometrial cancer.Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110α; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway.
Effect of manual lymph drainage in addition to guidelines and exercise therapy on arm lymphoedema related to breast cancer: randomised controlled trial
Authors: N. Devoogdt, M.-R. Christiaens, I. Geraerts, S. Truijen, A. Smeets, K. Leunen, P. Neven, M. Van Kampen
Journal: BMJ (2011)

<b>Objective</b> To determine the preventive effect of manual lymph drainage on the development of lymphoedema related to breast cancer. <b>Design</b> Randomised single blinded controlled trial. <b>Setting</b> University Hospitals Leuven, Leuven, Belgium. <b>Participants</b> 160 consecutive patients with breast cancer and unilateral axillary lymph node dissection. The randomisation was stratified for body mass index (BMI) and axillary irradiation and treatment allocation was concealed. Randomisation was done independently from recruitment and treatment. Baseline characteristics were comparable between the groups. <b>Intervention</b> For six months the intervention group (n=79) performed a treatment programme consisting of guidelines about the prevention of lymphoedema, exercise therapy, and manual lymph drainage. The control group (n=81) performed the same programme without manual lymph drainage. <b>Main outcome measures</b> Cumulative incidence of arm lymphoedema and time to develop arm lymphoedema, defined as an increase in arm volume of 200 mL or more in the value before surgery. <b>Results</b> Four patients in the intervention group and two in the control group were lost to follow-up. At 12 months after surgery, the cumulative incidence rate for arm lymphoedema was comparable between the intervention group (24%) and control group (19%) (odds ratio 1.3, 95% confidence interval 0.6 to 2.9; P=0.45). The time to develop arm lymphoedema was comparable between the two group during the first year after surgery (hazard ratio 1.3, 0.6 to 2.5; P=0.49). The sample size calculation was based on a presumed odds ratio of 0.3, which is not included in the 95% confidence interval. This odds ratio was calculated as (presumed cumulative incidence of lymphoedema in intervention group/presumed cumulative incidence of no lymphoedema in intervention group)×(presumed cumulative incidence of no lymphoedema in control group/presumed cumulative incidence of lymphoedema in control group) or (10/90)×(70/30). <b>Conclusion</b> Manual lymph drainage in addition to guidelines and exercise therapy after axillary lymph node dissection for breast cancer is unlikely to have a medium to large effect in reducing the incidence of arm lymphoedema in the short term. <b>Trial registration</b> Netherlands Trial Register No NTR 1055.
Exemestane for Breast Cancer Prevention: A Critical Shift?
Authors: Andrea DeCensi, Barbara K. Dunn, Matteo Puntoni, Alessandra Gennari, Leslie G. Ford
Journal: Cancer Discovery (2012)

Abstract The Mammary Prevention 3 (MAP.3) placebo-controlled randomized trial in 4,560 high-risk postmenopausal women showed a 65% reduction in invasive breast cancer with the use of exemestane at 35 months median follow-up. Few differences in adverse events were observed between the arms, suggesting a promising risk:benefit balance with exemestane for use in chemoprevention. Yet, the MAP.3 design and implementation raise concerns regarding limited data maturity and not prospectively including key bone-related and other toxicities as study end points. Exemestane for prevention is juxtaposed against selective estrogen receptor modulators and the other aromatase inhibitors. Additional issues for prevention, including the influence of obesity, alternative dosing, and biomarker use in phase III trials, are addressed. Significance: The recently completed MAP.3 trial of exemestane for breast cancer prevention offers a potential new standard for pharmaceutical risk reduction in high-risk postmenopausal women. In addition to describing key findings from the publication of MAP.3 and related trials, our review undertakes a detailed analysis of the strengths and weaknesses of MAP.3 as well as the implications for future prevention research. Cancer Discovery; 2(1); 25–40. ©2012 AACR.
Absent ileal uptake of IF-bound vitamin B12 in vivo in the Imerslund-Grasbeck syndrome (familial vitamin B12 malabsorption with proteinuria).
Authors: J F Burman, W J Jenkins, J A Walker-Smith, A D Phillips, N A Sourial, C B Williams, D L Mollin
Journal: Gut (1985)

A Syrian family is described with three children who had inherited selective vitamin B12 malabsorption associated with proteinuria. (Imerslund-Grasbeck syndrome). Although inherited the defect was apparently not present at birth. A third child had less severe vitamin B12 malabsorption, was not vitamin B12 deficient and had no proteinuria. Studies on two of the affected children with subcellular fractionation of the uptake of radioactive vitamin B12 by ileal tissue in vivo indicate a defect in the ileal receptors for IF-bound vitamin B12. These findings are different from the single in vitro experiment on a patient with this condition that has been previously reported.
SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes)
Authors: Daisuke Kokuryo, Yasutaka Anraku, Akihiro Kishimura, Sayaka Tanaka, Mitsunobu R. Kano, Jeff Kershaw, Nobuhiro Nishiyama, Tsuneo Saga, Ichio Aoki, Kazunori Kataoka
Journal: Journal of Controlled Release (2013)
Increased Renal Vascular Endothelial Growth Factor and Angiopoietins by Angiotensin II Infusion Is Mediated by Both AT1 and AT2 Receptors
Authors: Bishoy Rizkalla, Josephine M. Forbes, Mark E. Cooper, Zemin Cao
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. A link between angiotensin II and cell proliferation has previously been reported. However, there remains controversy as to the role of the individual angiotensin II receptor subtypes in mediating these effects and their link to angiogenic cytokines and their receptors. Male Sprague-Dawley rats were infused with either angiotensin II or vehicle for 14 d at a dose of 58.3 ng/min. Angiotensin II–infused rats received no treatment, an AT1 receptor antagonist valsartan (30 mg/kg per d), or an AT2 receptor antagonist PD123319 (830 ng/min). Gene expression of vascular endothelial growth factor (VEGF) and receptor VEGF-R2, as well as Tie-2 and its ligands angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) were assessed by reverse transcription–PCR. Protein expression was assessed by Western blotting and immunohistochemistry. Gene and protein expression of VEGF, Ang-1, and Ang-2 were increased by angiotensin II infusion. Valsartan and PD123319 attenuated angiotensin II–associated increases in VEGF gene and protein expression. Ang-1 and Ang-2 gene but not protein expression were reduced by both treatments. These changes occurred in the context of attenuation of angiotensin II–induced glomerular cell proliferation by both valsartan and PD123319. In situ hybridization and immunohistochemical studies localized VEGF, Ang-1, and Ang-2 expression to the epithelial cells of the glomerulus, and VEGF-R2 and Tie-2 receptors to the endothelial cells of the kidney. These findings extend the increasing evidence that the AT2 receptor, in addition to the AT1 receptor subtype, plays an important role in mediating the proliferative actions of angiotensin II in the kidney.
Vessel Size and Long-Term Outcome After Coronary Stent Placement
Authors: Shpend Elezi, Adnan Kastrati, Franz-Josef Neumann, Martin Hadamitzky, Josef Dirschinger, Albert Schömig
Journal: Circulation (1998)

The role of coronary stenting in the treatment of patients with small vessels is not well defined. The purpose of this study was to investigate the influence of vessel size on long-term clinical and angiographic outcome after coronary stent placement.The study comprised 2602 patients with successful stent implantation for symptomatic coronary artery disease. Patients were subdivided into 3 equally sized groups (tertiles) according to vessel size, with respective ranges of <2.8, 2.8 to 3.2, and >3.2 mm. Event-free survival at 1 year was 69.5% in the group with smaller vessels, 77.5% in the second group, and 81% in the group with larger vessels (P<0.001). Late lumen loss was similar between the 3 groups (1.12+/-0.73, 1.12+/-0.79, and 1.09+/-0. 88 mm, respectively). Angiographic restenosis rate was significantly higher in the small-vessel group (38.6%, 28.4%, and 20.4% in groups 1, 2, and 3, respectively; P<0.001). The analysis identified subgroups with different risk for restenosis even among patients with small vessels. Within this group, the restenosis rate may be as low as 29.6% in patients without additional risk factors and as high as 53.5% in patients with diabetes and complex lesions.Patients with small vessels present a higher risk for an adverse outcome after coronary stent placement because of a higher incidence of restenosis. However, the unusually high risk for restenosis is confined to those patients with small vessels who have concomitant risk factors such as diabetes and complex lesions.
Potential antitumor phenoxazines
Authors: Noboru Motohashi, Lester A. Mitscher, Roger Meyer
Journal: Medicinal Research Reviews (1991)

From the various studies cited, spanning more than forty years, it is clear that some members of the phenoxazine and benzophenoxazine dye family selectively stain certain tumors and, when given in suitable concentrations in the feed, can prolong life and shrink tumors. In addition, some use has been made of these compounds as carriers for other antitumor agents based upon the idea of selective accumulation into tumor tissue. Although many analogs have been made and examined, the work has been done in a relatively unfocused manner and the field could benefit from a systematic study of the effect of structure on biological activity. None of the synthetic materials prepared and tested to date has the potency of the outstanding antitumor natural products bearing the ring system of the actinomycins. Advances in our understanding of the molecular mode of action of the actinomycins, based in large measure upon x-ray studies, suggest some avenues for future exploitation. To date, attempts to prepare simplified actinomycins or elaborate phenoxazines to accomplish this have been disappointing.
A Role for Tumor Necrosis Factor Receptor Type 1 in Gut-associated Lymphoid Tissue Development: Genetic Evidence of Synergism with Lymphotoxin β
Authors: Pandelakis A. Koni, Richard A. Flavell
Journal: The Journal of Experimental Medicine (1998)

Lymphotoxin α (LTα) signals via tumor necrosis factor receptors (TNFRs) as a homotrimer and via lymphotoxin β receptor (LTβR) as a heterotrimeric LTα1β2 complex. LTα-deficient mice lack all lymph nodes (LNs) and Peyer's patches (PPs), and yet LTβ-deficient mice and TNFR-deficient mice have cervical and mesenteric LN. We now show that mice made deficient in both LTβ and TNFR type 1 (TNFR1) lack all LNs, revealing redundancy or synergism between TNFR1 and LTβ, acting presumably via LTβR. A complete lack of only PPs in mice heterozygous for both ltα and ltβ, but not ltα or ltβ alone, suggests a similar two-ligand phenomenon in PP development and may explain the incomplete lack of PPs seen in tnfr1−/− mice.
<i>MCP-1</i> Promoter Polymorphism at −2518 Is Associated with Metastasis of Nasopharyngeal Carcinoma after Treatment
Authors: Ka-Po Tse, Nang-Ming Tsang, Kung-Den Chen, Hsin-Pai Li, Ying Liang, Chuen Hsueh, Kai-Ping Chang, Jau-Song Yu, Sheng-Po Hao, Ling-Ling Hsieh, Yu-Sun Chang
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We herein examined whether the single nucleotide polymorphism (SNP) at −2518 of the MCP-1 gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients. Experimental Design: The study population consisted of 411 NPC patients without metastasis at diagnosis. All patients were treated at the Chang Gung Memorial Hospital from March 1994 to November 2004. The MCP-1 SNP−2518 genotype of each patient was determined by TaqMan genotyping kit. Statistical analyses were conducted to compare disease-specific survival (DSS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) of patients according to genotype. MCP-1 expression in tumor biopsies was examined by immunohistochemistry. Results: Among 411 NPC patients, carriers of AA and AG genotypes were prone to distant metastasis than that of GG genotype (hazard ratio, 2.21; P = 0.017, and hazard ratio, 2.23; P = 0.005, for AA and AG genotype, respectively) after initial radiotherapy. No genotype-specific significant difference was found in DSS, PFS, and LRFS. Furthermore, immunohistochemistry revealed that MCP-1 expression level was higher in NPC tumor cells from GG carriers compared with those from AA and AG carriers. Conclusions: MCP-1 SNP−2518 may be a valuable genetic marker for assessing the risk of developing distant metastasis after the radiotherapy in NPC patients. Carriers of A allele may require more aggressive chemotherapy implicating a potential marker for personalized medicine. We speculate that a regulatory SNP may be associated with the distant metastasis of NPC. Validation studies are warranted.
Functional DNA quantification guides accurate next-generation sequencing mutation detection in formalin-fixed, paraffin-embedded tumor biopsies
Authors: Sachin Sah, Liangjing Chen, Jeffrey Houghton, Jon Kemppainen, Adam C Marko, Robert Zeigler, Gary J Latham
Journal: Genome Medicine (2013)

The formalin-fixed, paraffin-embedded (FFPE) biopsy is a challenging sample for molecular assays such as targeted next-generation sequencing (NGS). We compared three methods for FFPE DNA quantification, including a novel PCR assay ('QFI-PCR') that measures the absolute copy number of amplifiable DNA, across 165 residual clinical specimens. The results reveal the limitations of commonly used approaches, and demonstrate the value of an integrated workflow using QFI-PCR to improve the accuracy of NGS mutation detection and guide changes in input that can rescue low quality FFPE DNA. These findings address a growing need for improved quality measures in NGS-based patient testing.
Extensive diversity in the recognition of influenza virus hemagglutinin by murine T helper clones.
Authors: K H Mills, J J Skehel, D B Thomas
Journal: The Journal of Experimental Medicine (1986)

A panel of H-2k class II-restricted Th clones were established from individual CBA mice primed by infection with X31 influenza virus. 27 clones, which showed specific recognition of the HA surface glycoprotein, were all H3N2 subtype specific, in contrast to a T cell line which was crossreactive and which may have other specificities. 20 distinct HA-specific clones recognized a tryptic cleavage fragment of X31 consisting of residue 28-328 of HA1 (tops) which includes all the Ab-combining regions of the HA molecule. Seven other HA-specific clones failed to respond to either tops or to aggregate (the remainder of the virus after tryptic cleavage of tops). The specificity of these clones has been mapped, tentatively, to a conformational determinant in the interface antibody-binding region of the HA trimer. Analysis of the fine specificity of the HA-specific clones against a panel of H3N2 natural variant viruses isolated from major virus epidemics from 1968 to 1984 revealed a hitherto unrecognized diversity in T cell recognition of a HA. A total of 12 specificity groupings were evident, and varied from groups of clones that recognized all natural variants to one clone that responded only to isolates from 1968 to 1972. Six out of eight clones from a major specificity group, which failed to recognize variants TX/77, BK/79, or CN/84, responded to two overlapping peptides (48-68 and 53-87), corresponding to a region of HA1 that includes part of two antibody combining sites. An examination of the amino acid sequences of natural variant viruses from this region of HA revealed that residues Asn53 and Asn54 and/or Ile62 were critical for recognition by these clones. We conclude that recognition of HA by Th cells is not restricted to a limited number of epitopes in the conserved regions of the molecule, but is extremely diverse and includes specificities that map to variable antibody-combining regions of the molecule. In addition, the sensitivity of the T cell clones to the amino acid substitutions occurring in HA1 of natural variant viruses suggests that Th may play a role in the immune pressure for antigenic variation in the HA molecule.
In vitro generation of antigen-specific helper T cells that collaborate with cytotoxic T-cell precursors.
Authors: L L Baum, L M Pilarski
Journal: The Journal of Experimental Medicine (1978)

Antigen-specific helper T cells are required in the generation of cytotoxic T cells from thymocyte precursors. We have demonstrated that these alloantigen-specific helper cells can be generated in vitro and that both the quantity and quality of the helpers appear to be superior to the help obtained from unprimed spleen cells. Optimal helper cell activity is produced at day two of culture when CBA splenic helper precursors are stimulated by irradiated allogeneic spleen cells. Helper cell precursors are antigen-specific cells which cannot be instructed to express forbidden receptor specificities and bear theta antigen on their surface. The helper effectors are radioresistant, theta-bearing, and antigen-specific cells.
Decisions, Decisions … SRF Coactivators and Smooth Muscle Myogenesis
Authors: Mark W. Majesky
Journal: Circulation Research (2003)

mooth muscle-restricted gene transcription depends on a highly conserved cis-regulatory element termed a CArG box [CC(A/T) 6 GG].The CArG box binds serum response factor (SRF), an evolutionarily conserved MADS (MDM1, agamous, deficiens, SRF) domain-containing protein that is required for specification of smooth, cardiac, and skeletal muscle lineages from early mesoderm. 1SRF is a multifunctional protein that not only binds DNA but also provides docking surfaces within the conserved core MADS domain for interaction with a wide variety of accessory cofactors.Most, but not all, smooth muscle cell (SMC) marker genes examined to date require SRF interactions with pairs of CArG-like elements that often contain single G/C substitutions in the AT-rich core region.However, SRF-CArG interactions alone are not sufficient to produce the diversity of smooth muscle subtypes found within the vascular system.A report by Yoshida et al in this issue of Circulation Research confirms and extends previous work by Wang et al, 2,3 Chen et al, 4 and Du et al, 5 suggesting that myocardin is a potent SRF-dependent coactivator for smooth muscle differentiation.