tbuckley/cabot-search huggingface dataset:
Genetic Control of Cancer Metastasis
Authors: I. J. Fidler, R. Radinsky
Journal: JNCI Journal of the National Cancer Institute (1990)

Cancer is a complex of many types of malignant neoplastic growths, and each cancer of each organ exhibits numerous subsets. Despite this heterogeneity, malignant neoplasms have a uniform characteristic—the ability to invade host tissues and produce metastases. The most fearsome aspect of cancer is metastasis. This fear is well based. There have been great improvements in diagnosis, general patient care, surgical techniques, and local and systemic adjuvant therapies, but most deaths from cancer are still due to metastases that are resistant to conventional therapies. Continual empiricism is unlikely to produce significant improvement. Rather, a better understanding of the metastatic process and the development of biologic heterogeneity in neoplasms should provide a basis for new approaches to more effective therapy. Identification of specific properties unique to metastatic cells is an obvious prerequisite.
Silencing PP2A Inhibitor by Lenti-shRNA Interference Ameliorates Neuropathologies and Memory Deficits in tg2576 Mice
Authors: Gong-Ping Liu, Wei Wei, Xin Zhou, Hai-Rong Shi, Xing-Hua Liu, Gao-Shang Chai, Xiu-Qing Yao, Jia-Yu Zhang, Cai-Xia Peng, Juan Hu, Xia-Chun Li, Qun Wang, Jian-Zhi Wang
Journal: Molecular Therapy (2013)

Deficits of protein phosphatase-2A (PP2A) play a crucial role in tau hyperphosphorylation, amyloid overproduction, and synaptic suppression of Alzheimer's disease (AD), in which PP2A is inactivated by the endogenously increased inhibitory protein, namely inhibitor-2 of PP2A (I2(PP2A)). Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration. By infusion of lentivirus-shRNA targeting I2(PP2A) (LV-siI2(PP2A)) into hippocampus and frontal cortex of 11-month-old tg2576 mice, we demonstrated that expression of LV-siI2(PP2A) decreased remarkably the elevated I2(PP2A) in both mRNA and protein levels. Simultaneously, the PP2A activity was restored with the mechanisms involving reduction of the inhibitory binding of I2(PP2A) to PP2A catalytic subunit (PP2AC), repression of the inhibitory Leu309-demethylation and elevation of PP2AC. Silencing I2(PP2A) induced a long-lasting attenuation of amyloidogenesis in tg2576 mice with inhibition of amyloid precursor protein hyperphosphorylation and β-secretase activity, whereas simultaneous inhibition of PP2A abolished the antiamyloidogenic effects of I2(PP2A) silencing. Finally, silencing I2(PP2A) could improve learning and memory of tg2576 mice with preservation of several memory-associated components. Our data reveal that targeting I2(PP2A) can efficiently rescue Aβ toxicities and improve the memory deficits in tg2576 mice, suggesting that I2(PP2A) could be a promising target for potential AD therapies.
Commentary: Consent and confidentiality in publishing--the view of the BMJ's ethics committee
Authors: A. J Newson, J. Sheather
Journal: BMJ (2008)

Two years ago four paediatricians and an ethicist submitted to the <i>BMJ</i> a case study as an ethical debate which the <i>BMJ</i> decided not to publish because the authors had not obtained the consent of the patient's parents for publication. The authors submitted it elsewhere, and the article was published last year.
Innate production of tumour necrosis factor and interleukin 10 is associated with radiological progression of knee osteoarthritis
Authors: S Botha-Scheepers, I Watt, E Slagboom, A J M de Craen, I Meulenbelt, F R Rosendaal, F C Breedveld, T W J Huizinga, M Kloppenburg
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Inflammation may contribute to progression of knee osteoarthritis (OA). Therefore, we investigated whether innate differences in the inflammatory response regarding cytokine production were associated with radiological progression of knee OA. <h3>Methods:</h3> Symptomatic patients with knee OA (n = 89) were included. Standardised posteroanterior knee radiographs were obtained at baseline and after 24 months. Medial and lateral tibiofemoral joint space narrowing (JSN) was graded with the Altman atlas. Radiological progression was defined as an increase of at least one score in JSN total scores. Whole blood samples were stimulated with lipopolysaccharide (LPS) (10 ng/ml). Relative risks (RR) with 95% CIs of OA progression in relation to quartiles of innate ex vivo production of interleukin (IL)1β, tumour necrosis factor (TNF)α, IL1 receptor antagonist (Ra) and IL10 were calculated. <h3>Results:</h3> Progression of JSN was present in 29 (33.7%) of 86 followed patients after 2 years. Patients in the highest quartile of TNFα production had a sixfold increased risk of JSN progression (age, sex and body mass index adjusted RR 6.1, 95% CI 1.4 to 9.8) and patients in the highest quartile of IL10 production had a fourfold increased risk of JSN progression (age, sex and body mass index adjusted RR 4.3, 95% CI 1.7 to 6.2), both in comparison with those patients in the lowest quartile. No significant associations were found between variations in IL1β and IL1Ra production and JSN progression. <h3>Conclusion:</h3> The innate capacity to produce TNFα and IL10 upon LPS stimulation is associated with radiological progression of knee OA, even over a relatively short follow-up period of 2 years.
A Case-Management System for Coronary Risk Factor Modification after Acute Myocardial Infarction
Authors: Robert F. DeBusk
Journal: Annals of Internal Medicine (1994)

Objective: To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification. Design: Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction. Setting: 5 Kaiser Permanente Medical Centers in the San Francisco Bay area. Patients: 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction. Intervention: In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy. Outcome: Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction. Results: In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 ± 0.69 mmol/L and 3.41 ± 0.90 mmol/L (107 ± 30 mg/dL and 132 ± 30 mg/dL) (P = 0.001), and functional capacities were 9.3 ± 2.4 METS and 8.4 ± 2.5 METS (P = 0.001), respectively. Conclusion: In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.
Swedish Rectal Cancer Trial: Long Lasting Benefits From Radiotherapy on Survival and Local Recurrence Rate
Authors: Joakim Folkesson, Helgi Birgisson, Lars Pahlman, Bjorn Cedermark, Bengt Glimelius, Ulf Gunnarsson
Journal: Journal of Clinical Oncology (2005)

To evaluate the long-term effects on survival and recurrence rates of preoperative radiotherapy in the treatment of curatively operated rectal cancer patients.Of 1,168 randomly assigned patients in the Swedish Rectal Cancer Trial between 1987 and 1990, 908 had curative surgery; 454 of these patients had surgery alone, and 454 were administered preoperative radiotherapy (25 Gy in 5 days) followed by surgery within 1 week. Follow-up was performed by matching against three Swedish nationwide registries (the Swedish Cancer Register, the Hospital Discharge Register, and the Cause of Death Register).Median follow-up time was 13 years (range, 3 to 15 years). The overall survival rate in the irradiated group was 38% v 30% in the nonirradiated group (P = .008). The cancer-specific survival rate in the irradiated group was 72% v 62% in the nonirradiated group (P = .03), and the local recurrence rate was 9% v 26% (P < .001), respectively. The reduction of local recurrence rates was observed at all tumor heights, although it was not statistically significant for tumors greater than 10 cm from the anal verge.Preoperative radiotherapy with 25 Gy in 1 week before curative surgery for rectal cancer is beneficial for overall and cancer-specific survival and local recurrence rates after long-term follow-up.
PNEUMOCOCCIC ARTHRITIS FOLLOWING ACUTE PNEUMONIA
Authors: W. S. Richardson
Journal: BMJ (1914)

CASES of pneueiococcic infection of a joint folloWing acute pneumionia are rare, and the literatture on the subject is certainly not volumiiinous.For these reasons the following notes nlay prove of interest.The older writers on the colmiplications of plneumlaonia imlention "I rheumatic joints" as somiietilues following this lisease.Quain and Osler both record the fact that art'liritis miay follow an acute attack of pneumonia.Sticliler, of Philadelplhia, collected records of 11,846 cases of pneumonia from various clines, and found joint complicationis in about 800, that is, about 14 per cenit.He does not indicate wlhether alny suppurative forms occurred.In the Epitome of the issue of tlle BRITISH MEDICAL JOURNAL for June 13th, 1914, Buckley is quoted (No. 339) as collecting 172 records of pneumococcic artlhritis, and as having reported a case of his own in the Annals of Surgery.The shoulder-joint was involved in a child 11 montlhs old, and the trouble supervenied upon left lobar pneuimonia.The notes of m-iy own case are as follows; history.A mliale, aged 49, spenit his 50th birthday in a lnursing home coinvalescing from pneumococcic infection of the left ankle-
Effect of Laparotomy on Clearance and Cytokine Induction in<i>Staphylococcus aureus</i>–infected Lungs
Authors: Michal A. Olszewski, Nicole R. Falkowski, Rishi Surana, Joanne Sonstein, Anne Hartman, Bethany B. Moore, Gary B. Huffnagle, Galen B. Toews
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Staphylococcus aureus is a major pathogen complicating postsurgical care.To test the effect of sterile laparotomy (LAP) on pulmonary clearance of S. aureus in a murine model.Control and LAP mice were infected intranasally with 10(8) cfu of S. aureus. Microbial clearance, pulmonary leukocyte recruitment, and cytokine profiles were compared between the groups. Antibody neutralization or cytokine gene knockout mice were used to evaluate the role of cytokines.Laparotomy resulted in a 10-fold increase in S. aureus lung colony-forming units on Days 2 and 3 postinfection. Both groups cleared the infection by Day 4. No defect in leukocyte recruitment into the lungs was observed in infected LAP animals; however, an increase in the number of Mac-3-positive cells and a significant decrease of cells with high surface expression of Fc-gammaR suggest suboptimal activation of leukocytes in the lungs of infected LAP animals. Infected LAP mice had decreased expression of interferon (IFN)-gamma and increased expression of mRNA for IL-13 in the lungs on Day 1 postinfection and decreased levels of IL-6, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage at Day 2 postinfection. Neutralization of IFN-gamma mimicked the effect of LAP with impaired clearance on Day 2.Sterile LAP induced temporary deactivation of innate immune responses to pulmonary S. aureus challenge. Impaired microbial clearance was accompanied by altered cytokine expression and suboptimal activation of pulmonary leukocytes. Lack of early IFN-gamma induction in the infected lungs of LAP animals is a likely mechanism contributing to the observed phenotype.
Macrophages From Cancer Patients: Analysis of TRAIL, TRAIL Receptors, and Colon Tumor Cell Apoptosis
Authors: Jean-Philippe Herbeuval, Claude Lambert, Odile Sabido, Michèle Cottier, Pierre Fournel, Michel Dy, Christian Genin
Journal: JNCI Journal of the National Cancer Institute (2003)

Tumor-infiltrating macrophages secrete cytokines, including Fas ligand, tumor necrosis factor-alpha (TNF-alpha), and TNF-related apoptosis-inducing ligand (TRAIL). TRAIL induces apoptosis in tumor cells but not in normal cells; however, regulation of TRAIL and its receptors in cancer patients is relatively uncharacterized. We investigated whether macrophages from cancer patients produce TRAIL and whether apoptosis in cultured colon adenocarcinoma cells involves TRAIL and its receptors.Macrophages isolated from pleural effusions of nine cancer patients and five control patients with congestive heart failure (whose effusions contained no tumor cells) were cultured. Levels of TRAIL, TNF-alpha, interferon alpha, and Fas ligand in conditioned medium were measured by enzyme-linked immunosorbent assays. Apoptosis of human colon adenocarcinoma cell lines, including Colo 205, was determined by the Annexin V method and terminal deoxynucleotidyltransferase-mediated deoxyuridine 5'-triphosphate nick-end labeling (TUNEL). Cell-surface TRAIL receptors were measured by flow cytometry.Conditioned culture medium from macrophages isolated from pleural effusions containing 1%-5% tumor cells (CM-A) contained TRAIL at 980-1300 pg/mL, whereas that from macrophages from pleural effusions containing more than 50% tumor cells or containing no tumor cells (CM-B) contained TRAIL at 0-50 pg/mL. When cultured with medium containing 50% CM-A, 40% (95% confidence interval [CI] = 30% to 50%) of Colo 205 cells underwent apoptosis; when cultured with 50% CM-B, 8% (95% CI = 3% to 13%) underwent apoptosis. When Colo 205 cells were cultured with 50% CM-A, cell-surface expression of TRAIL death receptors DR5 and DR4 increased 13-fold and sixfold, respectively, compared with that of untreated Colo 205 cells. Recombinant TRAIL induced 90% (95% CI = 85% to 95%) of Colo 205 cells to undergo apoptosis and acted synergistically with TNF-alpha to induce apoptosis.Macrophages from cancer patients appear to be activated by tumor cells to produce TRAIL and to increase the expression of TRAIL death receptors DR4 and DR5 on tumor cells.
Referral rates for colposcopy.
Authors: W P Soutter
Journal: BMJ (1990)

the agents gave advice on relevant immunisations and malaria prophylaxis.Nineteen agents recog- nised that there was a risk of acquiring HIV infection in Bangkok, but only four of these advised customers of that risk.The Department of Health booklet The Travel- lers Guide to Health contains information on HIV infection and the measures to take to avoid infection.2This booklet was available in 18 of the agencies: for reference only in two, on request in 11, and given to all booking customers in five.We were concerned to discover that two commonly quoted reference sources ABC Guide to Inter- national Travel1 and World Travel Guide' did not mention the risk of HIV infection to travellers.We recommend that the Department of Health book- let should be readily available to all travellers.Though we recognise worldwide distribution of HIV and that the risk of infection relates to particular activities and not to the area per se, perhaps known high risk areas should be identified specifically.Clearly, travel agents already assume some responsibility for providing health informa- tion to travellers.We suggest that this should be extended to include advice about the risks of contracting HIV while abroad and ways to minimise this risk.
Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.
Authors: E S Connolly, C J Winfree, T A Springer, Y Naka, H Liao, S D Yan, D M Stern, R A Solomon, J C Gutierrez-Ramos, D J Pinsky
Journal: Journal of Clinical Investigation (1996)

Acute neutrophil (PMN) recruitment to postischemic cardiac or pulmonary tissue has deleterious effects in the early reperfusion period, but the mechanisms and effects of neutrophil influx in the pathogenesis of evolving stroke remain controversial. To investigate whether PMNs contribute to adverse neurologic sequelae and mortality after stroke, and to study the potential role of the leukocyte adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of stroke, we used a murine model of transient focal cerebral ischemia consisting of intraluminal middle cerebral artery occlusion for 45 min followed by 22 h of reperfusion. PMN accumulation, monitored by deposition of 111In-labeled PMNs in postischemic cerebral tissue, was increased 2.5-fold in the ipsilateral (infarcted) hemisphere compared with the contralateral (noninfarcted) hemisphere (P < 0.01). Mice immunodepleted of neutrophils before surgery demonstrated a 3.0-fold reduction in infarct volumes (P < 0.001), based on triphenyltetrazolium chloride staining of serial cerebral sections, improved ipsilateral cortical cerebral blood flow (measured by laser Doppler), and reduced neurological deficit compared with controls. In wild-type mice subjected to 45 min of ischemia followed by 22 h of reperfusion, ICAM-1 mRNA was increased in the ipsilateral hemisphere, with immunohistochemistry localizing increased ICAM-1 expression on cerebral microvascular endothelium. The role of ICAM-1 expression in stroke was investigated in homozygous null ICAM-1 mice (ICAM-1 -/-) in comparison with wild-type controls (ICAM-1 +/+). ICAM-1 -/- mice demonstrated a 3.7-fold reduction in infarct volume (P < 0.005), a 35% increase in survival (P < 0.05), and reduced neurologic deficit compared with ICAM-1 +/+ controls. Cerebral blood flow to the infarcted hemisphere was 3.1-fold greater in ICAM-1 -/- mice compared with ICAM-1 +/+ controls (P < 0.01), suggesting an important role for ICAM-1 in the genesis of postischemic cerebral no-reflow. Because PMN-depleted and ICAM-1-deficient mice are relatively resistant to cerebral ischemia-reperfusion injury, these studies suggest an important role for ICAM-1-mediated PMN adhesion in the pathophysiology of evolving stroke.
Association of hidradenitis suppurativa disease severity with increased risk for systemic comorbidities
Authors: J.J. Crowley, J.R. Mekkes, C.C. Zouboulis, N. Scheinfeld, A. Kimball, M. Sundaram, Y. Gu, M.M. Okun, F. Kerdel
Journal: British Journal of Dermatology (2014)

DEAR EDITOR, I read with interest the recent report by Haus et al. 1 about a patient who developed two lesions of lymphomatoid papulosis (LyP) on the red parts of a tattoo.However, their report deserves a few comments.Many reported pseudolymphomas on tattoos involve T cells or both T and B cells, and are not attributed 'mainly' to B cells, as described in the manuscript. 2,3 To date, Sangueza et al. 4 in 1992 have published the only well-documented report of the malignant transformation of a T-cell pseudolymphoma into a monoclonal B-cell lymphoma related to a chronic tattoo reaction.It is widely accepted that mercury has disappeared from red ink manufacturing. 5Despite withdrawal of mercury, red tattoo reactions, including pseudolymphoma, still occur, raising the question of the culprit component or by-product leading to such reactions.Beyond the nosological issues that the authors try to discuss (LyP or pseudolymphoma), the present case illustrates an increasingly frequent situation due to the popularity of tattoos, namely the occurrence of coincidental dermatological conditions in tattooed individuals.Indeed, in the vast majority of cases of both pseudolymphoma and other 'allergic' reactions, tattoos display either a complete infiltration of the whole culprit colour or an infiltration made by more or less distinct papules or nodules restricted to one colour. 2,3A tattoo 'allergy' does not present as one, two or three single lesions on a very little part of the culprit colour.It is hard to conceive that a chronic stimulation of a clonal subset of lymphocytes against a specific component of the colour would be responsible for only an extremely limited reaction on two distant parts of such a wildly coloured area as reported by Haus et al.Besides, despite being rare, localized LyP happens more often among the young. 6 It seems rather likely that this patient developed a localized LyP on a fortuitous tattooed area.One could argue the possible presence of specific impurities located specifically on both areas that could have selected a monoclonal population, but it is pushing the speculation rather far, especially as the reaction spontaneously resolved after 2 months and the patient has now been disease free for the past 1Á5 years.Pseudolymphomas on tattoos may indeed regress spontaneously, 2 but they usually follow a protracted course in the absence of any treatment.The number of anecdotal reactions on tattoos 7 will keep on increasing with the popularity of tattoos and the ageing of the tattooed population, due to a fortuitous coexistence of a skin condition and the tattoo.LyP on a tattoo seems to be one of them.
Trace amounts of sporadically reappearing HCV RNA can cause infection
Authors: Naga Suresh Veerapu, Su-Hyung Park, Damien C. Tully, Todd M. Allen, Barbara Rehermann
Journal: Journal of Clinical Investigation (2014)

Successful hepatitis C virus (HCV) treatment is defined as the absence of viremia 6 months after therapy cessation. We previously reported that trace amounts of HCV RNA, below the sensitivity of the standard clinical assay, can reappear sporadically in treatment responders. Here, we assessed the infectivity of this RNA and infused 3 chimpanzees sequentially at 9-week intervals with plasma or PBMCs from patients who tested positive for trace amounts of HCV RNA more than 6 months after completing pegylated IFN-α/ribavirin therapy. A fourth chimpanzee received HCV RNA-negative plasma and PBMCs from healthy blood donors. The 3 experimental chimpanzees, but not the control chimpanzee, generated HCV-specific T cell responses against nonstructural and structural HCV sequences 6-10 weeks after the first infusion of patient plasma and during subsequent infusions. In 1 chimpanzee, T cell responses declined, and this animal developed high-level viremia at week 27. Deep sequencing of HCV demonstrated transmission of a minor HCV variant from the first infusion donor that persisted in the chimpanzee for more than 6 months despite undetectable systemic viremia. Collectively, these results demonstrate that trace amounts of HCV RNA, which appear sporadically in successfully treated patients, can be infectious; furthermore, transmission can be masked in the recipient by an extended eclipse phase prior to establishing high-level viremia.