tbuckley/cabot-search huggingface dataset:
Variations in <i>HSPA1B</i> at 6p21.3 Are Associated with Lung Cancer Risk and Prognosis in Chinese Populations
Authors: Huan Guo, Qifei Deng, Chen Wu, Lingmin Hu, Sheng Wei, Ping Xu, Dan Kuang, Li Liu, Zhibin Hu, Xiaoping Miao, Hongbing Shen, Dongxin Lin, Tangchun Wu
Journal: Cancer Research (2011)

The heat shock protein Hsp70 is crucial for regulating cellular homeostasis in stressed cells. Although the tumorigenic potential and prognostic applications of Hsp70 have been widely investigated, it remains unclear whether genetic variations of the human isoforms HSPA1L, HSPA1A, and HSPA1B are associated with cancer risk and prognosis. In this study, we genotyped six tagSNPs in these genes in 1,152 paired patients with lung cancer and controls, and then validated the results in additional cohorts of 1,781 patients with lung cancer and 1,038 controls. In addition, we evaluated the associations of these tagSNPs with survival in 330 patients with advanced non-small cell lung cancer (NSCLC) with additional validation in another 331 patients with advanced NSCLC. Functions of the risk variants identified were investigated using cell-based reporter assays. We found that the HSPA1B rs6457452T allele was associated with increased lung cancer risk compared with the rs6457452C allele in both data sets and also pooled analysis (adjusted OR = 1.41; P = 2.8 × 10(-5)). The HSPA1B rs2763979TT genotype conferred poor survival outcomes for patients with advanced NSCLC in two independent cohorts and pooled analysis [adjusted hazard ratio (HR) = 1.80, 1.61, and 1.66; P = 0.013, 0.036, and 0.002, respectively]. Lastly, we also found that the rs2763979T and rs6457452T alleles were each sufficient to reduce expression of transcriptional reporter constructs, when compared with the rs2763979C and rs6457452C alleles, respectively. Taken together, our findings define that functional HSPA1B variants are associated with lung cancer risk and survival. These Hsp70 genetic variants may offer useful biomarkers to predict lung cancer risk and prognosis.
Familial mycosis fungoides
Authors: C. Baykal, N. Buyukbabani, R. Kaymaz
Journal: British Journal of Dermatology (2002)

Sir, Mycosis fungoides (MF) is a malignancy of CD4+ helper T lymphocytes, which primarily affects the skin and may later involve visceral organs. It is mainly a disease of the elderly and has only rarely been described in childhood.1 The aetiopathogenesis of MF is not well understood and its genetic basis has not been proved. To the best of our knowledge, there are only six cases of familial MF in the literature.2–5 We report a 37‐year‐old mother and her 5‐year‐old son, both of whom had MF. A 37‐year‐old woman had had plaque‐stage MF for 12 years. Psoralen plus ultraviolet (UV) A (PUVA) therapy was applied with success, although recurrence was observed. No tumours or extracutaneous involvement were recorded in 3 years of follow‐up. Her son was admitted to our clinic at 5 years of age with asymptomatic, slightly erythematous non‐infiltrated plaques with fine scales on the proximal extremities, buttocks and trunk (Fig. 1a). Mycological examination of the skin lesions was negative. He had no atopic diathesis and total IgE was normal. Other laboratory findings were normal. New lesions appeared and old ones showed no regression under treatment with topical corticosteroids and urea‐containing ointments. Skin biopsy of three plaques revealed the same findings: focal parakeratosis with mild epidermal acanthosis; a few intraepidermal lymphocytes usually seen as single cells and rarely as small collections of a few cells reminiscent of Pautrier abscesses; and mild fibrosis and perivascular lymphocytic infiltration in the papillary dermis (Fig. 1b). The histopathological picture was reminiscent of early MF. A T‐cell receptor gene rearrangement study could not be performed. Carmustine 10 mg was applied daily to the entire skin for 2 months and the lesions regressed completely. However, a recurrence characterized by a few plaques was observed during a 6‐month follow‐up period. The same topical treatment was applied to the new lesions.
Study of peroral colonic and peritoneal absorption in normal and pathological conditions using a dye
Authors: M. S. Abdou, E. Salem, G. Megahed, M. Danasoury
Journal: Gut (1966)

EDITORIAL SYNOPSIS The urinary excretion of phenol red was measured over a four-hour period following the administration of a dose of the dye by mouth, by enema, and by intraperitoneal injection.The authors used this as a test of absorption from the small intestine, colon, and peritoneum respectively.Absorption from all three sites was impaired in cirrhotics in proportion to the severity of the liver damage.Intraperitoneal absorption was grossly impaired in local diseases of the peritoneum, and colonic absorption was impaired in colitis.
THE INTRAFAMILIAL ENVIRONMENT OF SCHIZOPHRENIC PATIENTS: II. MARITAL SCHISM AND MARITAL SKEW
Authors: THEODORE LIDZ, ALICE R. CORNELISON, STEPHEN FLECK, DOROTHY TERRY
Journal: American Journal of Psychiatry (1957)

The careful scrutiny of the 14 families containing schizophrenic offspring reveals that the marital relationships of all parents were seriously disturbed. Eight of the families were split into 2 factions by the overt schism between the parents. In these schismatic families the parents repeatedly threatened to separate; one spouse sought to coerce the other to conform to rigid expectations and aroused defiance; difficulties of almost any type engendered recriminations between parents rather than mutual support. The parents derogated and undercut one another, and thus the child could not use one parent as a model for identification or as a love object without antagonizing the other parent. The other 6 couples lived together in reasonable harmony, but the family environments provided by their marriages were badly distorted or "skewed" because in each marriage the serious psychopathology of the dominant parent was accepted or shared by the other. Studies now in progress will seek to clarify further the difficulties in these marriages, the personalities involved, and the effects upon the children.
Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial
Authors: Robert Pickard, Kathryn Starr, Graeme MacLennan, Thomas Lam, Ruth Thomas, Jennifer Burr, Gladys McPherson, Alison McDonald, Kenneth Anson, James N'Dow, Neil Burgess, Terry Clark, Mary Kilonzo, Katie Gillies, Kirsty Shearer, Charles Boachie, Sarah Cameron, John Norrie, Samuel McClinton
Journal: The Lancet (2015)
Distinct gene expression profiles of human type 1 and type 2 T helper cells.
Authors: Heli Hamalainen, Hua Zhou, William Chou, Hideki Hashizume, Renu Heller, Riitta Lahesmaa
Journal: Genome biology (2001)

The development and activation of CD4+ helper T cell (Th) subsets with distinct patterns of unbalanced production of cytokines play an important part in infectious, allergic and autoimmune diseases. Human neonatal cord blood CD4+ Th cells can be polarized into type 1 or type 2-like effector cells in vitro by culturing them in the presence of interleukin (IL)-12 or IL-4, respectively. We have exploited this experimental system to identify marker genes that are differentially expressed by polarized Th1 and Th2 cells. An oligonucleotide microarray specifically designed to screen for inflammation-related candidate genes was used and the differential expression was further validated with a quantitative real-time RT-PCR method. In addition to the previously described marker genes of Th cells, we report subtle changes in the expression of several other genes that represent growth factors, receptors and other signaling molecules in polarized Th1 and Th2 cell subsets. Additionally, we describe a novel set of genes as Th1/Th2 differentiation markers for cells activated by anti-CD3 and anti-CD28 antibodies. This study demonstrates the power of the targeted use of microarrays in combination with quantitative real-time RT-PCR in identifying and validating new marker genes for gene expression studies.
Efficacy of Prophylactic Mastectomy in Women With Unilateral Breast Cancer: A Cancer Research Network Project
Authors: Lisa J. Herrinton, William E. Barlow, Onchee Yu, Ann M. Geiger, Joann G. Elmore, Mary B. Barton, Emily L. Harris, Sharon Rolnick, Roy Pardee, Gail Husson, Ana Macedo, Suzanne W. Fletcher
Journal: Journal of Clinical Oncology (2005)

We investigated the efficacy of contralateral prophylactic mastectomy (CPM) in reducing contralateral breast cancer incidence and breast cancer mortality among women who have already been diagnosed with breast cancer.This retrospective cohort study comprised approximately 50,000 women who were diagnosed with unilateral breast cancer during 1979 to 1999. Using computerized data confirmed by chart review, we identified 1,072 women (1.9%) who had CPM. We obtained covariate information for these women and for a sample of 317 women who did not undergo CPM.The median time from initial breast cancer diagnosis to the end of follow-up was 5.7 years. Contralateral breast cancer developed in 0.5% of women with CPM, metastatic disease developed in 10.5%, and subsequent breast cancer developed in 12.4%; 8.1% died from breast cancer. Contralateral breast cancer developed in 2.7% of women without CPM, and 11.7% died of breast cancer. After adjustment for initial breast cancer characteristics, treatment, and breast cancer risk factors, the hazard ratio (HR) for the occurrence of contralateral breast cancer after CPM was 0.03 (95% CI, 0.006 to 0.13). After adjustment for breast cancer characteristics and treatment, the HRs for the relationship of CPM with death from breast cancer, with death from other causes, and with all-cause mortality were 0.57 (95% CI, 0.45 to 0.72), 0.78 (95% CI, 0.57 to 1.06), and 0.60 (95% CI, 0.50 to 0.72), respectively.CPM seems to protect against the development of contralateral breast cancer, and although women who underwent CPM had relatively low all-cause mortality, CPM also was associated with decreased breast cancer mortality.
Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury
Authors: Claudia S. Robertson, H. Julia Hannay, José-Miguel Yamal, Shankar Gopinath, J. Clay Goodman, Barbara C. Tilley, Athena Baldwin, Lucia Rivera Lara, Hector Saucedo-Crespo, Osama Ahmed, Santhosh Sadasivan, Luciano Ponce, Jovanny Cruz-Navarro, Hazem Shahin, Imoigele P. Aisiku, Pratik Doshi, Alex Valadka, Leslie Neipert, Jace M. Waguspack, M. Laura Rubin, Julia S. Benoit, Paul Swank
Journal: JAMA (2014)

There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury.To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury.Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL.Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells.Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury.There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009).In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting.clinicaltrials.gov Identifier: NCT00313716.
Antigen mediation of a late-acting suppressor T-cell activity.
Authors: R W Warren, J M Davie
Journal: The Journal of Experimental Medicine (1977)

Carrier-specific suppressor T cells can suppress antibody secretion by high avidity IgG plaque-forming cells (PFC) within 90 min in vitro. This process can be blocked by the inclusion of soluble carrier in the cell mixture or by the exposure of target cells to anti-carrier antibodies or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be overcome by preincubation of the target population with a hapten-heterologous carrier before addition of heterologous carrier ATC. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody-secreting cells which serves as a target for suppressor cells or molecules.
Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck
Authors: G. Fountzilas, D. Skarlos, A. Athanassiades, A. Kalogera-Fountzila, E. Samantas, C. Bacoyiannis, A. Nicolaou, N. Dombros, E. Briasoulis, M. Dinopoulou, G. Stathopoulos, N. Pavlidis, P. Kosmidis, N. Daniilidis
Journal: Annals of Oncology (1997)
Targeting Stat3 in the Myeloid Compartment Drastically Improves the <i>In vivo</i> Antitumor Functions of Adoptively Transferred T Cells
Authors: Andreas Herrmann, Marcin Kortylewski, Maciej Kujawski, Chunyan Zhang, Karen Reckamp, Brian Armstrong, Lin Wang, Claudia Kowolik, Jiehui Deng, Robert Figlin, Hua Yu
Journal: Cancer Research (2010)

Abstract Improving effector T-cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Signal transducer and activator of transcription 3 (Stat3) in the myeloid compartment constrains Th1-type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo small interfering RNA (siRNA) delivery platform by conjugating a Toll-like receptor 9 agonist with siRNA that efficiently targets myeloid and B cells. Here, we show that either CpG triggering combined with the genetic Stat3 ablation in myeloid/B cell compartments or administration of the CpG-Stat3siRNA drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we show that both approaches are capable of increasing dendritic cell and CD8+ T-cell engagement in tumor-draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8+ T cells in vivo, upregulating effector molecules such as perforin, granzyme B, and IFN-γ. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T-cell therapies. Cancer Res; 70(19); 7455–64. ©2010 AACR.
Day and Night Closed-Loop Control in Adults With Type 1 Diabetes
Authors: Yoeri M. Luijf, J. Hans DeVries, Koos Zwinderman, Lalantha Leelarathna, Marianna Nodale, Karen Caldwell, Kavita Kumareswaran, Daniela Elleri, Janet M. Allen, Malgorzata E. Wilinska, Mark L. Evans, Roman Hovorka, Werner Doll, Martin Ellmerer, Julia K. Mader, Eric Renard, Jerome Place, Anne Farret, Claudio Cobelli, Simone Del Favero, Chiara Dalla Man, Angelo Avogaro, Daniela Bruttomesso, Alessio Filippi, Rachele Scotton, Lalo Magni, Giordano Lanzola, Federico Di Palma, Paola Soru, Chiara Toffanin, Giuseppe De Nicolao, Sabine Arnolds, Carsten Benesch, Lutz Heinemann
Journal: Diabetes Care (2013)

To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control.This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals).Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms.Both CAM and iAP algorithms provide safe glycemic control.
Influence of Chemoreflexes on Respiratory Variability in Healthy Subjects
Authors: Joost G. Van den Aardweg, John M. Karemaker
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The background of this study was the hypothesis that respiratory variability is influenced by chemoreflex regulation. In search for periodicities in the variability due to instability of the respiratory control system, spectral analysis was applied to breath-to-breath variables in 19 healthy subjects at rest. During room-air breathing, coherent oscillations in end-tidal CO2 (Pet CO2 ) and mean inspiratory flow (Vi/Ti) were found in 15 subjects with frequencies mostly below 0.15 cycles per breath. Coherent oscillations in Pet CO2 and Vi/Ti were expressed by gain (0.13 to 0.34 L/second · kPa) and phase ( − 170 ° to + 8 ° ). The oscillations in Vi/Ti were in phase with inspiratory volume (Vi). A model that describes the effects of chemoreflex feedback to noise in the system could explain these gains and phases, whereas a model without chemoreflex could not. During 100% O2 breathing, only eight subjects had coherent oscillations in Pet CO2 and Vi/Ti. The coherent oscillations in Pet CO2 and Vi/Ti were interpreted as a manifestation of chemoreflex activity. We conclude that respiratory variability is not a random process but contains information on chemoreflex properties, such as the chemoreflex gain. The analysis of respiratory variability therefore provides a new tool to study the action of the chemoreflexes without application of external stimuli.
Recent developments in the treatment of age-related macular degeneration
Authors: Frank G. Holz, Steffen Schmitz-Valckenberg, Monika Fleckenstein
Journal: Journal of Clinical Investigation (2014)

Age-related macular degeneration (AMD) is a common cause of visual loss in the elderly, with increasing prevalence due to increasing life expectancy. While the introduction of anti-VEGF therapy has improved outcomes, there are still major unmet needs and gaps in the understanding of underlying biological processes. These include early, intermediate, and atrophic disease stages. Recent studies have assessed therapeutic approaches addressing various disease-associated pathways, including complement inhibitors. Drug-delivery aspects are also relevant, as many agents have to be administered repeatedly. Herein, relevant pathogenetic factors and underlying mechanisms as well as recent and potential therapeutic approaches are reviewed.
A young man with fever, dyspnoea and nonproductive cough
Authors: B Balbi, F Fabiano
Journal: European Respiratory Journal (1996)

Case historyA 19 year old male was admitted to our hospital because of fever (39S°C), dyspnoea with tachypnoea, and nonproductive cough.His past history was unremarkable.He was a mild smoker and denied use of drugs.W e e days before admission, he had started to complain of fever and dry cough.He was given nonsteroidal anti-inflammatory drugs, but, since his shoriness of breatfi was inmasing, he decided to attend the Emergency Room of our hospital.Physical examination revealed cyanosis, bibasilar crackles and tachycardia.A chest roentgenogram is shown in figure 1. Arterial blood gas measurements on room
Etiology of hyperparathyroidism and bone disease during chronic hemodialysis
Authors: Albert E. Fournier, Claude D. Arnaud, William J. Johnson, William F. Taylor, Ralph S. Goldsmith
Journal: Journal of Clinical Investigation (1971)

Plasma concentration of immunoreactive parathyroid hormone (IPTH) was measured in 18 patients who had been on a hemodialysis program for longer than 6 months. A negative correlation was found between the predialysis plasma concentration of IPTH and the mean concentration of calcium in the dialysate previously used: plasma concentrations of IPTH were higher in patients dialyzed against a calcium concentration between 4.9 and 5.6 mg/100 ml than in patients dialyzed against a calcium concentration of 6.0 mg/100 ml or more. Plasma concentrations of IPTH also were higher in patients with bone disease than in patients without bone disease. Furthermore, a positive correlation was found between predialysis plasma concentrations of IPTH and calcium, and between mean predialysis concentration of IPTH and phosphate. To obviate the possibility that individual differences in susceptibility could have accounted for the observed effects of plasma phosphate and of dialysate calcium, a 2 × 2 factorial study was conducted in seven of these patients to examine the independent effects of perturbation of each of these factors. It was observed that plasma concentration of IPTH was lowest with the combination of high dialysate calcium and low plasma phosphate, highest with the combination of low dialysate calcium and high plasma phosphate, and intermediate with the two other combinations. It is concluded that both dialysate calcium and plasma phosphate are important determinants of parathyroid function in these patients.