tbuckley/cabot-search huggingface dataset:
Reduction in plasma human immunodeficiency virus ribonucleic acid after dideoxynucleoside therapy as determined by the polymerase chain reaction.
Authors: M Holodniy, D A Katzenstein, D M Israelski, T C Merigan
Journal: Journal of Clinical Investigation (1991)

Cell-free HIV RNA in plasma was detected and quantitated after antiviral therapy by the polymerase chain reaction. RNA was extracted from plasma, reverse transcribed to cDNA, amplified by polymerase chain reaction, and quantitated by absorbance based on an enzyme-linked affinity assay. 72 HIV antibody-positive subjects had one plasma sample taken. 39 who were not receiving antiretroviral therapy at the time had a mean plasma HIV RNA copy number of 690 +/- 360 (mean +/- SEM) per 200 microliters of plasma, while 33 subjects who had been receiving zidovudine therapy for a minimum of 3 mo had a mean copy number of 134 +/- 219 (P less than 0.05). 27 additional HIV antibody-positive patients had two plasma samples taken before and 1 mo after initiating dideoxynucleoside therapy. Plasma HIV RNA copy number fell from 540 +/- 175 to 77 +/- 35 (P less than 0.05). Finally, nine of these subjects had two baseline samples obtained before initiating therapy and two posttreatment samples 1 and 2 mo after therapy was begun. Mean plasma RNA copy number declined from 794 +/- 274 to less than 40 (below the lower limit of sensitivity) after 1 mo of therapy, with suppression maintained after 2 mo of therapy. These results suggest that gene amplification can be used to detect and quantitate changes in plasma HIV RNA after dideoxynucleoside therapy. Plasma HIV polymerase chain reaction may be a more sensitive marker to monitor antiviral therapy, particularly in asymptomatic patients where measurement of p24 antigen or quantitative plasma cultures are negative.
Epithelial Transport of Water-Soluble Vitamins
Authors: B B Bowman, D B McCormick, I H Rosenberg
Journal: Annual Review of Nutrition (1989)

INTRODUCTION ... . . . . . . . . . . . .. . ...... . . . . . . ......... ... ....... . .. . ...... . . . . . .. .   .. 187 HISTORICAL PERSPECTiVE  188 CONCEPTUAL ISSUES  189 METHODOLOGY ... .... .... .....     ..   190 MECHANISM OF UPTAKE  190 Initial Uptake. . . . . . . . . . . . . .. . . . . . . . . . . . .. . .... . . . . . . . . . . . . . . . . . . . . .. . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Role of Vitamin Metabolism . . . . . . . . . . . . .. ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 Cellular Disposition . . . . . . . . . . . . . . .. . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 CONCLUSION .......   ........         194
Spontaneous regression in angiocentric T-cell lymphoma
Authors: D. DE BERKER, K. WINDEBANK, L. SVILAND, D. W. KINGMA, R. CARTER, J. L. REES
Journal: British Journal of Dermatology (1996)

An 8-year-old boy presented with a 10-week history of ulcerating lesions which were histologically and immunocytochemically consistent with the diagnosis of angiocentric T-cell lymphoma. The disease was limited to the skin and resolved with no chemotherapy. Angiocentric T-cell lymphoma is commonly a disease with considerable morbidity and is often fatal. Epstein-Barr virus (EBV) could not be identified in involved tissue by immunostaining or by in situ hybridization. We consider whether the uncharacteristic absence of EBV in this case has prognostic significance.
A Trial of Antiparasitic Treatment to Reduce the Rate of Seizures Due to Cerebral Cysticercosis
Authors: Héctor H. Garcia, E. Javier Pretell, Robert H. Gilman, S. Manuel Martinez, Lawrence H. Moulton, Oscar H. Del Brutto, Genaro Herrera, Carlton A.W. Evans, Armando E. Gonzalez
Journal: New England Journal of Medicine (2004)

Neurocysticercosis is the main cause of adult-onset seizures in the developing world. Whether therapy with antiparasitic agents results in improved seizure control has been questioned because of the lack of adequate, controlled studies.We conducted a double-blind, placebo-controlled trial in which 120 patients who had living cysticerci in the brain and seizures treated with antiepileptic drugs were randomly assigned to receive either 800 mg of albendazole per day and 6 mg of dexamethasone per day for 10 days (60 patients) or two placebos (60 patients). The patients were followed for 30 months or until they had been seizure-free for 6 months after the doses of the antiepileptic drugs had been tapered. The efficacy of treatment was measured as the decrease in the number of seizures after treatment.In the albendazole group, there was a 46 percent reduction in the number of seizures (95 percent confidence interval, -74 to 83 percent) during months 2 to 30 after treatment. This reduction, which was not statistically significant, was composed of a nonsignificant reduction of 41 percent in the number of partial seizures (95 percent confidence interval, -124 to 84 percent) and a significant 67 percent reduction in the number of seizures with generalization (95 percent confidence interval, 20 to 86 percent). Most of the difference in the number of partial seizures was attributable to a few patients who had many seizures during follow-up. The proportions of patients who had partial seizures during follow-up were similar in the two groups (19 of 57 in the albendazole group and 16 of 59 in the placebo group), but the patients in the placebo group had a greater tendency to have seizures with generalization (22 of 59, vs. 13 of 57 in the albendazole group; risk ratio, 1.63; 95 percent confidence interval, 0.91 to 2.92). More of the intracranial cystic lesions resolved in the albendazole group than in the placebo group. With the sole exception of abdominal pain, side effects did not differ significantly between the two groups.In patients with seizures due to viable parenchymal cysts, antiparasitic therapy decreases the burden of parasites and is safe and effective, at least in reducing the number of seizures with generalization.
T Lymphocytes Restrain Spontaneous Metastases in Permanent Dormancy
Authors: Irene Romero, Cristina Garrido, Ignacio Algarra, Antonia Collado, Federico Garrido, Angel M. Garcia-Lora
Journal: Cancer Research (2014)

Tumor dormancy is a clinical phenomenon related to immune equilibrium during cancer immunoediting. The mechanisms involved in dormant metastases are poorly understood due to the lack of preclinical models. Here, we present a nontransgenic mouse model in which spontaneous metastases remain in permanent immunomediated dormancy with no additional antitumor treatment. After the injection of a GR9-B11 mouse fibrosarcoma clone into syngeneic BALB/c mice, all animals remained free of spontaneous metastases at the experimental endpoints (3-8 months) but also as long as 24 months after tumor cell injection. Strikingly, when tumor-bearing mice were immunodepleted of T lymphocytes or asialo GM1-positive cells, the restraint on dormant disseminated metastatic cells was relieved and lung metastases progressed. Immunostimulation was documented at both local and systemic levels, with results supporting the evidence that the immune system was able to restrain spontaneous metastases in permanent dormancy. Notably, the GR9-B11 tumor clone did not express MHC class I molecules on the cell surface, yet all metastases in immunodepleted mice were MHC class I-positive. This model system may be valuable for more in-depth analyses of metastatic dormancy, offering new opportunities for immunotherapeutic management of metastatic disease.
Critical Role of STAT3 in IL-6–Mediated Drug Resistance in Human Neuroblastoma
Authors: Tasnim Ara, Rie Nakata, Michael A. Sheard, Hiroyuki Shimada, Ralf Buettner, Susan G. Groshen, Lingyun Ji, Hua Yu, Richard Jove, Robert C. Seeger, Yves A. DeClerck
Journal: Cancer Research (2013)

Abstract Drug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R). Treatment of neuroblastoma cells with IL-6 protected them from drug-induced apoptosis in a STAT3-dependent manner because the protective effect of IL-6 was abrogated in the presence of a STAT3 inhibitor and upon STAT3 knockdown. STAT3 was necessary for the upregulation of several survival factors such as survivin (BIRC5) and Bcl-xL (BCL2L1) when cells were exposed to IL-6. Importantly, IL-6–mediated STAT3 activation was enhanced by sIL-6R produced by human monocytes, pointing to an important function of monocytes in promoting IL-6–mediated EMDR. Our data also point to the presence of reciprocal activation of STAT3 between tumor cells and bone marrow stromal cells including not only monocytes but also regulatory T cells (Treg) and nonmyeloid stromal cells. Thus, the data identify an IL-6/sIL-6R/STAT3 interactive pathway between neuroblastoma cells and their microenvironment that contributes to drug resistance. Cancer Res; 73(13); 3852–64. ©2013 AACR.
Long-term survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma.
Authors: Lawrence Kleinberg, Paul J. Catalano, Arlene A. Forastiere, Steven M. Keller, Pramila R. Anne, Al Bowen Benson
Journal: Journal of Clinical Oncology (2012)

69 Background: E1201 included operable esophageal adenocarcinoma, staged II-IVa by EUS and accrual ended Oct 2004. The primary endpoint was pathologic complete response (pCR), a surrogate endpoint generally associated with survival which did not meet criteria for further study of either arm. Long term survival results are now available. Stratification included clinical/EUS stage and ECOG performance status (PS). Methods: 81 eligible patients (pts) began treatment. Arm A was cisplatin (C) 30mg/m 2 and irinotecan (I) 50 mg/m 2 on days (d) 1, 8, 22, 29 of 45 Gy RT/5 weeks. Post-op therapy was C 30 mg/m 2 and I 65 mg/m 2 d 1, 8 q21 days x 3. Arm B therapy was C 30 mg/m 2 and paclitaxel (P) 50 mg/m 2 1 hour infusion d 1, 8, 15, 22, 29 with RT. Postoperative therapy was C 75 mg/m 2 and P 175 mg/m 2 day 1 q21 days x 3. Results: In Arm A, 26/39 have died. Median survival (S) is 35 m (months) and the 5, 6, and 7 year S was 46%, 39%, and 35%. In Arm B, 31/42 pts have died (one pt refused follow-up). Median S in arm B is 21 m. The 5, 6, and 7 year S was 27%, 27%, and 23%. Survival by EUS stage strata: For strata 1 (Stages T 2 N 0 M 0 or T 3 N 0 M 0 ), 14/20 have died. Median S is 37 m and 5 year S is 44%. In stage stratum 2 (Stages T 1-3 N 1 M 0 or T 1-3 N 0 -1M 1a ), 43/61 have died. Median S is 24 m and 5 year S is 34%. For PS Strata: Patients with PS 0, had median S 35 m and 5 year S of 37% whereas for those with PS 1, the outcomes were 20m and 35%. Survival differences for the treatments and for these strata were not statistically significant. Conclusions: Long term survival is similar for both treatment arms and does not appear superior to results achieved with 5FU based regimens. The prognostic importance of the pretreatment strata was not confirmed. These data, along with the reported pCR (15% arm A; 17% arm B) and toxicity data (&gt; =grade 3 during chemo/RT 68% arm A; 65% arm B), may have importance in aiding in the design and interpretation of ongoing and planned phase II trials adding novel agents or treatment approaches to backbones built on variations of these two regimens.
Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells
Authors: Émilie Sexton, Céline Van Themsche, Kim Leblanc, Sophie Parent, Pascal Lemoine, Eric Asselin
Journal: Molecular Cancer (2006)

Abstract Background Endometrial cancer is the fourth most prominent cancer among all feminine cancers in the Western world. Resveratrol, a natural anti-oxidant found in red wine emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on uterine cancer cells is poorly understood. At the molecular level, resveratrol has been reported to inhibit cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2 is overexpressed and confers cellular resistance to apoptosis. The aim of the present study was to determine if resveratrol could exert anti-proliferative and pro-apoptotic activity over uterine cancer cells upon inhibition of COX-2 expression and/or activity. Six different human uterine cancer cell lines were used as a model (HeLa, Hec-1A, KLE, RL95-2, Ishikawa and EN-1078D). Results and discussion High-dose of resveratrol triggered apoptosis in five out of six uterine cancer cell lines, as judged from Hoechst nuclear staining and effector caspase cleavage. In accordance, uterine cancer cell proliferation was decreased. Resveratrol also reduced cellular levels of the phosphorylated/active form of anti-apoptotic kinase AKT. Endogenous COX-2 protein levels were decreased, concomitant with a decrease in production of COX metabolites PGE2 and PGF2α, in each uterine cancer cell line expressing detectable levels of COX-1 and/or COX-2 in presence of resveratrol. Although COX expression was identified as a target of resveratrol in uterine cancer cells, inhibition of COX activity or exogenously added PGE2 did not modulate the effect of resveratrol on cellular proliferation. Conclusion High-dose of resveratrol exerts tumoricidal activity over uterine cancer cells and regulates COX expression. In these cells, resveratrol would not directly target COX activity, but possibly other enzymes involved in prostaglandin synthesis that act downstream of the COXs.
Telomeres and Telomerase in Renal Health
Authors: Lauren P. Wills, Rick G. Schnellmann
Journal: Journal of the American Society of Nephrology (2011)

The role of telomeres and telomerase in human biology has been studied since the early 1990s because telomere attrition is implicated in various diseases including cardiovascular dysfunction, carcinogenesis, and the progression of acute kidney injury. Telomeric length is a reliable indicator of intrinsic biologic age and a surrogate for the mitotic clock. Because the prevalence of chronic kidney disease increases with age, telomere length and telomerase activity may play a role in its progression.
Effects of short- and long-term exposures to ambient air pollution on COPD
Authors: Eric Garshick
Journal: European Respiratory Journal (2014)

The London fog episode in 1952 was a sentinel event that indicated that short-term exposure to ambient air pollution could adversely influence the health of persons with chronic obstructive pulmonary disease (COPD). A review of autopsy records indicated a doubling of cases with COPD as a major finding compared with other periods [1]. The association between greater levels of ambient air pollution measured in the community and an increase in subsequent short-term COPD-related mortality and hospitalisations has been confirmed by analysis of health related administrative data, including records of hospital admissions and emergency room visits in the USA, Asia and Europe [2]–[14].

There are considerably fewer studies assessing the impact of short-term air pollution exposure in COPD patients with disease documented by spirometry. Overall, these studies suggest that COPD patients experience a reduction in pulmonary function as a result of short-term exposures [15]–[20]. Remarkably, the majority of these previous studies included relatively few subjects and with one exception [21] were not designed to assess exacerbation risk. The study that assessed exacerbation risk [21] included former smokers with moderate-to-severe COPD and measured indoor levels of particles with a cut-off aerodynamic diameter of 2.5 μm (PM2.5) and NO2. Higher levels were significantly associated with more symptoms and an increased risk of experiencing an exacerbation, suggesting that measurement of indoor levels of pollutants in persons who spend considerable time indoors (such as those with significant COPD) may be a more relevant measure of exposure than outdoor levels more commonly assessed.

The most robust assessment of the effects of ambient air pollution on pulmonary function (but not limited to patients with COPD) included 3262 former and never smokers (some with repeated assessment) from the US Framingham Heart …
Cardiovascular Drugs
Authors: Dan Roden, James T. Willerson
Journal: Circulation (1998)

Review of Mechanisms and Clinical ApplicationsI n this issue and continuing on a monthly basis, Circulation will review basic mechanisms and clinical applications of the most important and relevant cardiovascular medications used to treat cardiovascular diseases in humans.Experienced physicians, knowledgeable about specific classes of medications, will contribute comprehensive reviews providing the interested reader with detailed information concerning cardiovascular medications used in the treatment of patients with selected cardiovascular problems.These reviews will identify indications, patient benefits, side effects, and possible interactions with other medications.Dr Dan Roden will serve as the Section Editor of this new series.The majority of the reviews will be invited ones, but we are also willing to consider reviews submitted by the readership of Circulation.We believe that this new series will be useful to physicians who care for patients with cardiovascular diseases.
Intensive therapy for small-cell lung cancer using carboplatin alternating with cisplatin, ifosfamide, etoposide, mid-cycle vincristine, and radiotherapy.
Authors: J Prendiville, J Radford, N Thatcher, W Steward, M Ranson, P Burt, R Stout
Journal: Journal of Clinical Oncology (1991)

Forty patients with small-cell lung cancer (31 patients with limited-stage [LS] disease, and nine patients with extensive-stage [ES] disease but of good performance status) have been treated with an intensive therapy composed of carboplatin alternating with cisplatin, ifosfamide, and etoposide with vincristine on day 14 of each carboplatin cycle. A maximum of six cycles were administered at 3 weekly intervals after the cisplatin combination and 4 weekly after the carboplatin combination. Prophylactic cranial irradiation was given with the first cycle of chemotherapy and thoracic irradiation with the third cycle. The median nadir for neutrophils was 0.47 x 10(9)/L and for platelets, 40 x 10(9)/L. Chemotherapy dosages were not reduced in response to myelosuppression, but treatment was delayed to allow blood count recovery. Sixty-eight percent of patients received all six cycles of chemotherapy, and there were four deaths associated with treatment-related neutropenia. Twenty-eight patients (70%) achieved a complete response (CR) when assessed 1 month after the end of treatment, and a further five patients (12.5%) had a partial response (PR). Median duration of CR was 16 months and of PR, 8 months. Cerebral metastases occurred in 20% of all patients and was the apparent sole site of relapse in 11% of the CR patients. The median survival of the total group was 14 months with an actual 2-year survival of 30% and a minimum follow-up of 28 months.
Phase I study of every 2- or 3-week dosing of ramucirumab, a human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2 in patients with advanced solid tumors
Authors: E.G. Chiorean, H.I. Hurwitz, R.B. Cohen, J.D. Schwartz, R.P. Dalal, F.E. Fox, L. Gao, C.J. Sweeney
Journal: Annals of Oncology (2015)
Effectiveness of quality improvement strategies on the management of diabetes: a systematic review and meta-analysis
Authors: Andrea C Tricco, Noah M Ivers, Jeremy M Grimshaw, David Moher, Lucy Turner, James Galipeau, Ilana Halperin, Brigitte Vachon, Tim Ramsay, Braden Manns, Marcello Tonelli, Kaveh Shojania
Journal: The Lancet (2012)
Evidence based policy making
Authors: S. Macintyre
Journal: BMJ (2003)

Powerful, rich, and well educated people tend to live longer and healthier lives than their less advantaged counterparts. These socioeconomic inequalities in health have been observed in a range of societies—developed, developing, market led, welfare state, and communist. Their expression, however, may vary according to how the particular society is stratified—for example, by income or wealth in the United States, by social class in the United Kingdom, or by education in Europe. They occur across a wide range of causes of death and types of illness, have been observed since accurate statistics were first available, and seem to have been increasing.1

Several governments have recently proposed strategies to reduce socioeconomic inequalities in health.2–5 An issue rendering strategy development in this field difficult is that, although a lot of information is available about the magnitude and causes of socioeconomic inequalities in health, rather less information is available about the effectiveness of policies in reducing them.6 The recent Cross-Cutting review in England noted that intervention research is scanty compared with the much larger body of observational evidence that describes inequalities.5 This is shown by the fact that the review contains six boxed lists, containing between them 50 examples …
ANTIGEN PROCESSING AND PRESENTATION BY THE CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX
Authors: Ian A. York, Kenneth L. Rock
Journal: Annual Review of Immunology (1996)

▪ Abstract Major histocompatibility complex (MHC) class I molecules bind peptides derived from cellular proteins and display them for surveillance by the immune system. These peptide-binding molecules are composed of a heavy chain, containing an antigen-binding groove, which is tightly associated with a light chain (β 2 -microglobulin). The majority of presented peptides are generated by degradation of proteins in the cytoplasm, in many cases by a large multicatalytic proteolytic particle, the proteasome. Two β-subunits of the proteasome, LMP2 and LMP7, are inducible by interferon-γ and alter the catalytic activities of this particle, enhancing the presentation of at least some antigens. After production of the peptide in the cytosol, it is transported across the endoplasmic reticulum (ER) membrane in an ATP-dependent manner by TAP (transporter associated with antigen presentation), a member of the ATP-binding cassette family of transport proteins. There are minor pathways for generating presented peptides directly in the ER, and some evidence suggests that peptides may be further trimmed in this location. The class I heavy chain and β 2 -microglobulin are cotranslationally translocated into the endoplasmic reticulum where their assembly may be facilitated by the sequential association of the heavy chain with chaperone proteins BiP and calnexin. The class I molecule then associates with the lumenal face of TAP where it is retained, presumably awaiting a peptide. After the class I molecule binds a peptide, it is released for exocytosis to the cell surface where cytotoxic T lymphocytes examine it for peptides derived from foreign proteins.