tbuckley/cabot-search huggingface dataset:
The Relationship between Global Methylation Level, Loss of Heterozygosity, and Microsatellite Instability in Sporadic Colorectal Cancer
Authors: Koji Matsuzaki, Guoren Deng, Hirofumi Tanaka, Sanjay Kakar, Soichiro Miura, Young S. Kim
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The relationship between global hypomethylation, chromosomal instability (CIN), and microsatellite instability (MSI) remains unclear in colorectal cancer. The aim of this study was to investigate the relationship between global methylation status, loss of heterozygosity (LOH), and MSI in sporadic colorectal cancer. Experimental Design: We determined global methylation levels in 80 sporadic colorectal cancers, 51 adjacent normal tissues, and 20 normal tissues using the long interspersed nucleotide elements–combined bisulfite restriction analysis method. We also analyzed 80 colorectal cancers for MSI status and LOH at chromosomes 5q21, 8p12-22, 17p13, and 18q21. Results: We identified 14 cases of MSI (17.5%) and 58 cases of LOH (72.5%). LOH was observed more frequently in microsatellite stable (MSS) cancers than in MSI cancers at all loci. Colorectal cancers showed significantly lower global methylation levels than did normal tissues (41.0 ± 9.7% versus 54.3 ± 6.5%; P &amp;lt; 0.001). MSS cancers showed significantly lower global methylation levels when compared with MSI cancers (39.5 ± 9.4% versus 48.2 ± 8.2%; P = 0.003). Tumors with global hypomethylation (with ≤40% of methylation levels) had a significantly increased number of chromosomal loci with LOH than did tumors without global hypomethylation (1.9 versus 0.9; P &amp;lt; 0.001); 11 tumors (13.9%) lacked both MSI and LOH. This subgroup had significantly higher global methylation levels (46.8 ± 8.7%) than did MSS cancers with LOH (38.0 ± 9.0%; P = 0.006). Conclusions: These data showed a significant association between global hypomethylation and chromosomal instability in sporadic colorectal cancer. This suggests that global hypomethylation plays an important role in inducing genomic instability in colorectal carcinogenesis.
Risk factors for facial melasma in women: a case–control study
Authors: A.C. Handel, P.B. Lima, V.M. Tonolli, L.D.B. Miot, H.A. Miot
Journal: British Journal of Dermatology (2014)

Background Melasma is a localized chronic acquired hypermelanosis, common in adult women and which has an important impact on their life quality. Its pathology is unknown, despite some recognized triggering factors. Objective To evaluate risk factors for developing facial melasma in women. Methods This was a case–control study involving adult women with or without facial melasma, paired by age. Variables were grouped into hierarchical levels: personal characteristic data, exposure variables, links to hormonal stimuli and the State-Trait Anxiety Inventory questionnaire, Brazilian version. The data were analysed using conditional multiple logistic regression. Results We evaluated 207 patients and 207 controls. The mean age was 38 years. Cases differed from controls for phototype, Amerindian ancestry [odds ratio (OR) 2·59], years of beach or rural residence (OR 1·06), time exposed to sun at work (OR 1·65), time exposed to sun in leisure activities (OR 1·04), antidepressant/anxiolytic use (OR 4·96), menstrual irregularity (OR 3·83), pregnancy history (OR 3·59), years of oral contraceptive use (OR 1·23) and anxiety scores (OR 1·08). A family history of melasma was reported in 61% of cases and 13% of controls (OR 10·40). Conclusions Facial melasma is independently associated with elements linked to pigmentation capacity, family ancestry, chronic sun exposure, sexual hormone stimuli, psychotropics and anxiety traits.
Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Authors: E.M. Olson, N.U. Lin, P.J. DiPiro, J.S. Najita, I.E. Krop, E.P. Winer, H.J. Burstein
Journal: Annals of Oncology (2011)
Inhibition of human blood platelet aggregation by photochemotherapy in vitro and in vivo*
Authors: D. VELLA BRIFFA, M.W. GREAVES
Journal: British Journal of Dermatology (1979)

Irradiation of human blood platelets with UV-A in vitro impairs their ability to aggregate after challenge with collagen. There also appears to be mild and transient inhibition of platelet aggregability in psoriatics during the fourth week of photochemotherapy.
Circulating Tumor Cells As Prognostic Markers in Neuroendocrine Tumors
Authors: Mohid S. Khan, Amy Kirkwood, Theodora Tsigani, Jorge Garcia-Hernandez, John A. Hartley, Martyn E. Caplin, Tim Meyer
Journal: Journal of Clinical Oncology (2012)

Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells. Results Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of &lt; one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P &lt; .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.
Autoregulation of Cerebral Blood Flow
Authors: KOUZO YOSHIDA, JOHN S. MEYER, KO SAKAMOTO, JYOJI HANDA
Journal: Circulation Research (1966)

Changes in blood flow through the internal carotid, vertebral and external carotid arteries were measured by electromagnetic flowmeters during and after acute hypertension induced by closing a clamp around the thoracic aorta in anesthetized monkeys. The internal carotid and vertebral arterial system showed both rapid and delayed autoregulatory responses to rapid increases in blood pressure; the rapid (primary) responses occurred within seconds, the progressive (delayed) within 3 to 4 minutes. In contrast, the flow response within the external carotid system appeared to be passive. Cervical sympathetic innervation and myogenic reflexes (Bayliss reflex) both appear to play a part in the rapidly occurring (primary) regulation of cerebral blood flow. The mechanism responsible for delayed and progressive (secondary) autoregulation in the cerebral vasculature appeared to be metabolic, since it was predominantly influenced by changes in blood Pco 2 . Changes in intracranial pressure did not seem to be involved in autoregulation.
Flow through collapsible tubes at high Reynolds numbers.
Authors: C K Lyon, J B Scott, D K Anderson, C Y Wang
Journal: Circulation Research (1981)

The pressure-flow relationships of collapsible tubes were studied utilizing the Starling resistor model. Reynolds numbers much higher than previously reported were used to simulate high cardiac output states. Alterations which occur in vivo, including longitudinal tension, stretch, tubing diameter, length, and outflow resistance were also simulated and systematically investigated. The pressure-flow curves showed an initial rising phase, a plateau phase, as well as a late-rising phase which has not been reported previously. Self-induced oscillations occurred during the plateau phase and persisted throughout the late-rising phase. These perturbations were markedly increased by longitudinal tension and stretch, but were attenuated by increased diameter, length, and outflow pressure. These instabilities may prove to be an explanation for the "venous hum."
Cooperative and individualistic functions of the microRNAs in the miR-23a~27a~24-2 cluster and its implication in human diseases
Authors: Ravindresh Chhabra, Richa Dubey, Neeru Saini
Journal: Molecular Cancer (2010)

The small RNA molecules of about 19-22 nucleotides in length, aptly called microRNAs, perform the task of gene regulation in the cell. Interestingly, till the early nineties very little was known about them but eventually, the microRNAs have become forefront in the area of research. The huge number of microRNAs plus each one of them targeting a vast number of related as well as unrelated genes makes them very interesting molecules to study. To add to the mystery of miRNAs is the fact that the same miRNA can have antagonizing role in two different cell types i.e. in one cell type; the miRNA promotes proliferation whereas in another cell type the same miRNA inhibits proliferation. Another remarkable aspect of the microRNAs is that many of them exist in clusters. In humans alone, out of 721 microRNAs known, 247 of them occur in 64 clusters at an inter-miRNA distance of less than 5000 bp. The reason for this clustering of miRNAs is not fully understood but since the miRNA clusters are evolutionary conserved, their significance cannot be ruled out. The objective of this review is to summarize the recent progress on the functional characterization of miR-23a~27a~24-2 cluster in humans in relation to various health and diseased conditions and to highlight the cooperative effects of the miRNAs of this cluster.
Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America
Authors: Luis Villar, Gustavo Horacio Dayan, José Luis Arredondo-García, Doris Maribel Rivera, Rivaldo Cunha, Carmen Deseda, Humberto Reynales, Maria Selma Costa, Javier Osvaldo Morales-Ramírez, Gabriel Carrasquilla, Luis Carlos Rey, Reynaldo Dietze, Kleber Luz, Enrique Rivas, Maria Consuelo Miranda Montoya, Margarita Cortés Supelano, Betzana Zambrano, Edith Langevin, Mark Boaz, Nadia Tornieporth, Melanie Saville, Fernando Noriega
Journal: New England Journal of Medicine (2014)

In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development.In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection.A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events.The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).
HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN TWO COHORTS OF HOMOSEXUAL MEN: NEUTRALISING SERA AND ASSOCIATION OF ANTI-GAG ANTIBODY WITH PROGNOSIS
Authors: JonathanN. Weber, RobinA. Weiss, Carol Roberts, Ian Weller, RichardS. Tedder, PaulR. Clapham, David Parker, Julian Duncan, Christopher Carne, AnthonyJ. Pinching, Rachanee Cheingsong-Popov
Journal: The Lancet (1987)
Nonmelanoma Skin Cancer and Risk for Subsequent Malignancy
Authors: J. Chen, I. Ruczinski, T. J. Jorgensen, G. Yenokyan, Y. Yao, R. Alani, N. J. Liegeois, S. C. Hoffman, J. Hoffman-Bolton, P. T. Strickland, K. J. Helzlsouer, A. J. Alberg
Journal: JNCI Journal of the National Cancer Institute (2008)

Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study. In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18 405) a personal history of NMSC (total n = 19 174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided. The crude incidence rate (per 10 000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups ( P for interaction = .022). This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors.
REPRESENTATION ON THE COUNCIL OF THE SOCIETY OF MEDICAL OFFICERS OF HEALTH
Authors: T. R. Bailey
Journal: BMJ (1925)

<h3>Abstract</h3> Current methods for tuberculosis (TB) treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during TB treatment as biomarkers. Plasma MMP-1, -8 and -10 significantly decreased during treatment. Plasma MMP-8 was increased in sputum <i>Mycobacterium tuberculosis</i> culture positive relative to culture negative participants, prior to (median 4609 pg/ml, IQR 2353-9048 vs 775 pg/ml, IQR 551-4920, p=0.019) and after 6 months (median 3650, IQR 1214-3888 vs 720, IQR 551-1321, p=0.008) of TB treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance TB treatment monitoring and screen for possible culture positivity.
Distinct requirements for T-bet in gut innate lymphoid cells
Authors: Giuseppe Sciumé, Kiyoshi Hirahara, Hayato Takahashi, Arian Laurence, Alejandro V. Villarino, Kentner L. Singleton, Sean P. Spencer, Christoph Wilhelm, Amanda C. Poholek, Golnaz Vahedi, Yuka Kanno, Yasmine Belkaid, John J. O'Shea
Journal: The Journal of Experimental Medicine (2012)

Interleukin (IL)-22-producing innate lymphoid cells (ILCs; ILC22) comprise a heterogeneous population of cells that are dependent on the transcription factor retinoid-related orphan γt (RORγt) and are critical for barrier function of the intestinal mucosa. A distinct ILC22 subset expresses the natural cytotoxicity receptor NKp46 (NKp46+ ILC22); however, the factors that contribute to the generation of this population versus other subsets are largely unknown. Herein, we show that T-bet (encoded by Tbx21) was highly expressed in NKp46+ ILC22, a feature shared by all NKp46+ cells present in the intestine but not by other IL-22-producing populations. Accordingly, the absence of T-bet resulted in loss of NKp46+ ILC22 in the intestinal lamina propria. The residual NKp46+ ILC22 present in Tbx21(-/-) mice showed a marked reduction of Rorγt expression and impairment in IL-22 production. Generation and functions of gut NK1.1+ cells were also altered. Bone marrow chimera experiments revealed a cell-intrinsic requirement for T-bet in these subsets and competitive reconstitution experiments revealed roles for T-bet in multiple ILC subsets. Thus, T-bet has a general importance for ILC in the gut and plays a selective and critical role in the generation of NKp46+ ILC22.
Glomerular Hyperfiltration in Experimental Diabetes Mellitus
Authors: VOLKER VALLON, KERSTIN RICHTER, ROLAND C. BLANTZ, SCOTT THOMSON, HARTMUT OSSWALD
Journal: Journal of the American Society of Nephrology (1999)

Abstract. An increase in Na + /glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e. , the luminal Na + , Cl - , and K + concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na + , Cl - , and K + were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na + , Cl - , and K + by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na + /glucose cotransport, elicited ( 1 ) a greater reduction in absolute and fractional reabsorption of Na + , Cl - , and K + up to the early distal tubule, and ( 2 ) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na + /glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.
Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination
Authors: Cheng-Gang Jiang, Ling Lv, Fu-Rong Liu, Zhen-Ning Wang, Fu-Nan Liu, Yan-Shu Li, Chun-Yu Wang, Hong-Yan Zhang, Zhe Sun, Hui-Mian Xu
Journal: Molecular Cancer (2011)

Abstract Background Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P &lt; 0.05). Patients with positive CTGF expression had significantly lower cumulative postoperative 5 year survival rate than those with negative CTGF expression (22.9% versus 48.1%, P &lt; 0.001). We demonstrated that knockdown of CTGF expression significantly inhibited cell growth of gastric cancer cells and decreased cyclin D 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.
Tumours of the mononuclear phagocyte system: A review of clinical and pathological features
Authors: Bruce F. Burns, William K. Evans
Journal: American Journal of Hematology (1982)

Abstract Cells of the mononuclear‐phagocyte system (MPS) may give rise to a wide variety of tumours of diverse morphology ranging from acute leukemia to small benign tumours of the skin. This review of tumours of the MPS was prompted by recent advances in understanding of tumour morphology and immunologic features. It is now possible to differentiate tumours of the MPS more precisely from tumours of lymphoid origin with which they have often been confused; however, controversy still exists as to the origin of the malignant cell of Hodgkin disease. Current evidence is reviewed which favours the view that the malignant cell of Hodgkin disease is of monocyte origin. A classification of MPS tumours based on organ system of origin and disease extent is presented.
The DNA Damage-Regulated Autophagy Modulator DRAM1 Links Mycobacterial Recognition via TLR-MYD88 to Autophagic Defense
Authors: Michiel van der Vaart, Cornelis J. Korbee, Gerda E.M. Lamers, Anouk C. Tengeler, Rohola Hosseini, Mariëlle C. Haks, Tom H.M. Ottenhoff, Herman P. Spaink, Annemarie H. Meijer
Journal: Cell Host & Microbe (2014)