tbuckley/cabot-search huggingface dataset:
In Vivo Survival and Homeostatic Proliferation of Natural Killer Cells
Authors: Martin Prlic, Bruce R. Blazar, Michael A. Farrar, Stephen C. Jameson
Journal: The Journal of Experimental Medicine (2003)

While the specificity and development of natural killer (NK) cells have been intensely studied, little is known about homeostasis of the mature NK population. Here we show that mouse NK cells undergo homeostatic proliferation when transferred into NK-deficient Rag−/− γC−/− hosts. Normal NK functional activity is maintained during this process, although there are some changes in NK phenotype. Using cell sorting, we demonstrate that mature (Mac-1hi) NK cells undergo homeostatic proliferation in an NK-deficient environment, yet immature (Mac-1lo) NK cells also proliferate in such hosts. We find that mature NK cells survive but do not proliferate in hosts which possess an endogenous NK pool. However, we go on to show that mature NK survival is critically dependent on interleukin (IL)-15. Surprisingly, NK survival is also compromised after transfer of cells into IL-15Rα−/− mice, implying that IL-15 responsiveness by bystander cells is critical for NK maintenance. These data imply that, similar to T cells, homeostasis of the NK pool is much more dynamic than previously appreciated and this may be relevant to manipulation of NK cells for therapeutic purposes.
Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: Immunohistochemical evidence
Authors: Shotaro Sakisaka, Masahide Watanabe, Hideo Tateishi, Masaru Harada, Satoshi Shakado, Yoshihiro Mimura, Kazuhisa Gondo, Masao Yoshitake, Kazunori Noguchi, Teruko Hino, Ryuichi Nohno, Yasuo Majima, Kenji Hirai, Michio Sata, Hiroshi Yoshida, Kyuichi Tanikawa
Journal: Hepatology (1993)

Patients with hepatocellular carcinoma sometimes have erythrocytosis and high plasma erythropoietin levels. However, previous studies have not revealed direct evidence that the carcinoma cells produce the erythropoietin. To address this question, we carried out light and electron microscopic immunohistochemical studies, using a human erythropoietin antibody to the liver in three male patients with hepatocellular carcinoma and erythrocytosis. alpha-Feto-protein localization was also examined in serial liver sections by light microscopic immunohistochemistry with an antibody to alpha-fetoprotein. All three patients demonstrated high hemoglobin levels (16.7, 17.6 and 18.1 gm/dl) and high plasma erythropoietin levels (227, 266 and 280 mU/ml). In one patient the plasma erythropoietin level in the hepatic vein was significantly higher than that in the hepatic artery. The levels of plasma erythropoietin, as well as such tumor markers for hepatocellular carcinoma as serum alpha-fetoprotein and plasma des-gamma-carboxyprothrombin, were significantly reduced after treatment with an anticancer drug, cisplatin. Light microscopic immunohistochemistry showed that erythropoietin was definitely present in the cytoplasm of the hepatocellular carcinoma cells, but not in normal hepatocytes around the carcinoma lesion or in other nonparenchymal cells such as vascular endothelial cells and Kupffer cells. In electron microscopic immunohistochemistry, reaction products for erythropoietin were revealed in the cisternae of the endoplasmic reticulum in the carcinoma cells, suggesting the production of erythropoietin by these cells. Light microscopic immunohistochemistry showed that alpha-fetoprotein was localized in the hepatocellular carcinoma cells that were erythropoietin positive in the serial sections. These findings indicated that hepatocellular carcinoma cells produced erythropoietin as well as alpha-fetoprotein in these cases, leading to the complication of erythrocytosis.
Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses
Authors: M Voss
Journal: Gut (2000)

<h3>AIM</h3> To assess the feasibility and diagnostic accuracy of endoscopic ultrasound guided fine needle biopsy (EUS-FNAB) in patients with solid pancreatic masses. <h3>METHODS</h3> Ninety nine consecutive patients with pancreatic masses were studied. Histological findings obtained by EUS-FNAB were compared with the final diagnosis assessed by surgery, biopsy of other tumour site or at postmortem examination, or by using a combination of clinical course, imaging features, and tumour markers. <h3>RESULTS</h3> EUS-FNAB was feasible in 90 patients (adenocarcinomas, n = 59; neuroendocrine tumours, n = 15; various neoplasms, n = 6; pancreatitis, n = 10), and analysable material was obtained in 73. Tumour size (⩾ or &lt; 25 mm in diameter) did not influence the ability to obtain informative biopsy samples. Diagnostic accuracy was 74.4% (adenocarcinomas, 81.4%; neuroendocrine tumours, 46.7%; other lesions, 75%; p&lt;0.02). Overall, the diagnostic yield in all 99 patients was 68%. Successful biopsies were performed in six patients with portal hypertension. Minor complications (moderate bleeding or pain) occurred in 5% of cases. <h3>CONCLUSIONS</h3> EUS-FNAB is a useful and safe method for the investigation of pancreatic masses, with a high feasibility rate even when lesions are small. Overall diagnostic accuracy of EUS-FNAB seems to depend on the tumour type.
Lack of CpG Island Methylator Phenotype Defines a Clinical Subtype of T-Cell Acute Lymphoblastic Leukemia Associated With Good Prognosis
Authors: Jose Roman-Gomez, Antonio Jimenez-Velasco, Xabier Agirre, Felipe Prosper, Anabel Heiniger, Antonio Torres
Journal: Journal of Clinical Oncology (2005)

To examine cancer genes undergoing epigenetic inactivation in a set of T-cell acute lymphoblastic leukemias (T-ALLs) to obtain the CpG island methylator phenotype (CIMP) in the disease and its possible correlation with clinical features and outcome of the patients.Methylation-specific polymerase chain reaction was used to analyze methylation of the ADAMTS-1, ADAMTS-5, APAF-1, ASPP-1, CDH1, CDH13, DAPK, DIABLO, DKK-3, LATS-1, LATS-2, NES-1, p14, p15, p16, p57, p73, PARK-2, PTEN, sFRP1/2/4/5, SHP-1, SYK, TMS-1, and WIF-1 genes in samples from 50 consecutive T-ALL patients (19 children and 31 adults). Results were compared with results obtained in 286 B-cell acute lymphoblastic leukemias (B-ALLs).A total of 88% of the T-ALL samples had at least one gene methylated. According to the number of methylated genes observed in each individual sample, 12 patients (24%) were included in the CIMP- group (zero to two methylated genes), and 38 patients (76%) were included in the CIMP+ group (> two methylated genes). Clinical features and remission rate did not differ significantly among both groups of patients. Estimated disease-free survival (DFS) rate at 12 years and overall survival (OS) rate at 13 years were 100% and 91% for the CIMP- group and 20% and 17% for the CIMP+ group, respectively (P = .0006 and P = .003, respectively). Multivariate analysis demonstrated that methylation profile was an independent prognostic factor in predicting DFS (P = .05) and OS (P = .02). A group of five genes (SYK-1, ASPP-1, sFRP-2, sFRP-5, and WIF-1) showed specificity for T-ALL compared with B-ALL.Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in T-ALL.
Survival of patients with chronic myeloproliferative neoplasms and new primary cancers: a population-based cohort study
Authors: Henrik Frederiksen, Dóra Körmendiné Farkas, Christian Fynbo Christiansen, Thomas Stauffer Larsen, Hans Carl Hasselbalch, Jesper Stentoft, Henrik Toft Sørensen
Journal: The Lancet Haematology (2015)
An Outbreak of Acute Post-Cataract Surgery Pseudomonas sp. Endophthalmitis Caused by Contaminated Hydrophilic Intraocular Lens Solution
Authors: Muralidhar Ramappa, Ajit Babu Majji, Somasheila I. Murthy, Praveen K. Balne, Suma Nalamada, Chandrasekhar Garudadri, Annie Mathai, Usha Gopinathan, Prashant Garg
Journal: Ophthalmology (2012)
Factors That Influence Outcome in Diabetic Subjects With Myocardial Infarction
Authors: Stephen Fava, Joseph Azzopardi, Hugo Agius Muscat, Frederick F Fenech
Journal: Diabetes Care (1993)

OBJECTIVE To compare the outcome of acute myocardial infarction in NIDDM patients and nondiabetic control subjects. The relation of glycemic control, duration of diabetes, and major diabetic complications to the outcome of acute myocardial infarction in diabetic subjects was investigated. RESEARCH DESIGN AND METHODS This was a prospective, hospitalbased, case-control study. RESULTS One hundred and ninety-six NIDDM patients and 196 nondiabetic control subjects with acute myocardial infarction were entered into the study: 23.5% of diabetic subjects and 34.2% of control subjects received thrombolytic therapy (P &amp;lt; 0.05). Diabetic subjects showed signs of reperfusion less often than control subjects (P &amp;lt; 0.05). Mortality was higher in the diabetic group (17.3 vs. 10.2%, P &amp;lt; 0.05). Pump failure (38.3 vs. 16.8%, P &amp;lt; 0.01) and cardiogenic shock (9.7 vs. 3.6%, P &amp;lt; 0.05) also occurred more frequently in diabetic subjects. Loss of heart rate variability was correlated with both pump failure and mortality; proliferative retinopathy was correlated with pump failure. Glycemic control and other diabetic complications did not correlate with outcome. CONCLUSIONS Our findings confirm the higher mortality and incidence of pump failure in acute myocardial infarction with co-morbid diabetes. They suggest that the less frequent use of thrombolytic therapy, lower reperfusion rates, and more advanced coronary artery disease might be contributory. The presence of autonomic neuropathy and microvascular disease probably also contribute to poor outcome; other major diabetic complications and diabetic control did not influence outcome.
RAB3 AND SYNAPTOTAGMIN: The Yin and Yang of Synaptic Membrane Fusion
Authors: Martin Geppert, Thomas C. Südhof
Journal: Annual Review of Neuroscience (1998)

▪ Abstract Synaptic vesicle exocytosis occurs in consecutive steps: docking, which specifically attaches vesicles to the active zone; priming, which makes the vesicles competent for Ca 2+ -triggered release and may involve a partial fusion reaction; and the final Ca 2+ -regulated step that completes fusion. Recent evidence suggests that the critical regulation of the last step in the reaction is mediated by two proteins with opposite actions: synaptotagmin, a Ca 2+ -binding protein that is essential for Ca 2+ -triggered release and probably serves as the Ca 2+ -sensor in fusion, and rab3, which limits the number of vesicles that can be fused as a function of Ca 2+ in order to allow a temporally limited, repeatable signal.
Carruthers report calls for doctors to be more involved in NHS change
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Clinicians should be consulted before any further NHS reforms are implemented, the former head of the NHS said last week.

Sir Ian Carruthers, who was acting chief executive of the NHS for six months last year, has called for greater engagement with NHS staff on reforms in a report submitted to the Department of Health.

Sir Ian, currently the chief executive of NHS South West, was commissioned by the government to carry out a review into the process of reconfiguration in the NHS and has reported back with several recommendations.

Involving clinicians and staff in developing proposals was …
Randomized Trial of Intraportal and/or Systemic Adjuvant Chemotherapy in Patients With Colon Carcinoma
Authors: R. Labianca, R. Fossati, A. Zaniboni, V. Torri, S. Marsoni, D. Nitti, L. Boffi, M. Scatizzi, B. Tardio, N. Mastrodonato, S. Banducci, G. Consani, G. Pancera
Journal: JNCI Journal of the National Cancer Institute (2004)

5-fluorouracil-based adjuvant chemotherapy after surgical resection of colon cancer is standard treatment. However, the choice of best delivery route--that is, systemic (i.e., intravenous or oral) or regional (i.e., intraportal, intraperitoneal, or hepatic arterial infusion)--has been controversial. In a randomized clinical trial of patients with colon cancer, we compared the benefits of chemotherapy delivered by these routes individually or in combination.From April 2, 1992, through April 30, 1998, 1084 eligible patients with Dukes' stage B or C colon carcinoma were randomly assigned: 369 patients to the IP regimen (continuous portal vein infusion of 5-fluorouracil at 500 mg/m2 of body surface daily and heparin at 5000 IU daily for 7 consecutive days, beginning on the day of surgery), 358 patients to the SY regimen (six 28-day courses of systemic leucovorin at 100 mg/m2 daily on days 1 through 5 followed by systemic bolus 5-fluorouracil at 370 mg/m2 daily on days 1 through 5, with treatment initiated 15-35 days after surgery), and 357 patients to the IP+SY regimen (the IP regimen followed by the SY regimen, with the same scheduling). Primary survival was analyzed with the log-rank statistic and a Cox multivariable regression model. All statistical tests were two sided.At a median follow-up time of 99 months, 389 events (recurrences, second malignancies, or deaths) had occurred, and 361 patients died. Sites of first recurrences were similar among the three arms. At 5 years, overall and event-free survival rates were similar among those on the IP (74% and 68%, respectively), SY (78% and 71%), and IP+SY (73% and 67%) regimens. When compared with the group on the SY regimen, the risk for death associated with the IP regimen (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 0.82 to 1.36) was similar to that associated with the IP+SY regimen (HR = 1.12, 95% CI = 0.78 to 1.45) (P =.69), as were the risks for first event (HR = 1.07, 95% CI = 0.84 to 1.37 and HR = 1.10, 95% CI = 0.86 to 1.41, respectively) (P=.74).Overall and event-free survival rates were similar in all three arms. The combined regimen was no better than either single regimen alone.
Sociocultural Behavior, Sex-Biased Admixture, and Effective Population Sizes in Central African Pygmies and Non-Pygmies
Authors: Paul Verdu, Noémie S.A. Becker, Alain Froment, Myriam Georges, Viola Grugni, Lluis Quintana-Murci, Jean-Marie Hombert, Lolke Van der Veen, Sylvie Le Bomin, Serge Bahuchet, Evelyne Heyer, Frédéric Austerlitz
Journal: Molecular Biology and Evolution (2013)

Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter–gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.
Overexpression of CaMKIIδc in RyR2R4496C+/− Knock-In Mice Leads to Altered Intracellular Ca2+ Handling and Increased Mortality
Authors: Nataliya Dybkova, Simon Sedej, Carlo Napolitano, Stefan Neef, Adam G. Rokita, Mark Hünlich, Joan Heller Brown, Jens Kockskämper, Silvia G. Priori, Burkert Pieske, Lars S. Maier
Journal: Journal of the American College of Cardiology (2011)
Gastric emptying after oesophagectomy as assessed by plasma paracetamol concentrations.
Authors: P Goldstraw, P Bach
Journal: Thorax (1981)

Gastric emptying after oesophagogastrectomy may be affected by opposing influences. Truncal vagotomy of the orthotopic stomach, as used by surgeons for peptic ulcer, results in delayed gastric emptying. The emptying of such a denervated stomach is affected by position and posture and may result in gastric "incontinence", particularly if associated with drainage procedures. It is possible that postural effects may outweigh the reduced motility if the vagotomised stomach is transplanted into the chest as after oesophagogastrectomy. Despite the effect that disturbed gastric emptying may have on nutrition and drug absorption there have been few studies concerning patients who have had oesophageal resection or bypass. We report our preliminary experience of an indirect method to estimate gastric emptying after oesophageal resection and bypass, using the absorption profile of paracetamol (acetaminophen). This technique is safe and has been shown to reflect gastric emptying accurately in the innervated stomach. With this technique we have shown that, even in the absence of a concomitant drainage procedure, oesophageal resection, or bypass, using the denervated stomach to restore alimentary continuity does not result in any detectable delay in gastric emptying.
U.S. Physicians’ Perspective of Adult Vaccine Delivery
Authors: Laura P. Hurley, Carolyn B. Bridges, Rafael Harpaz, Mandy A. Allison, Sean T. O’Leary, Lori A. Crane, Michaela Brtnikova, Shannon Stokley, Brenda L. Beaty, Andrea Jimenez-Zambrano, Faruque Ahmed, Craig Hales, Allison Kempe
Journal: Annals of Internal Medicine (2014)

Adults are at substantial risk for vaccine-preventable disease, but their vaccination rates remain low.
Critical Aspects of Viral Vectors for Gene Transfer into the Kidney
Authors: DAVID FAVRE, NICOLAS FERRY, PHILIPPE MOULLIER
Journal: Journal of the American Society of Nephrology (2000)

Viral vectors have been used in vitro and in vivo for more than a decade, with some significant results in specific situations, e.g., when recombinant adeno-associated virus is used for the long-term transduction of skeletal muscle in coagulation factor IX-deficient patients. However, the kidney has been quite difficult to transduce with any viral vector currently available. When viral transduction occurs, it is often heterogeneous, transient, and eventually associated with immune and toxic side effects. However, recombinant adeno-associated virus and lentiviral vectors remain to be fully evaluated in the kidney; the former is small enough to be filtered through the glomerular basement membrane. This may be critical, because glomerular filtration is required for DNA complex-mediated transduction of tubular cells. An alternative to in situ renal gene transfer is secretion of a therapeutic protein from a distant site, such as skeletal muscle. Several examples provide evidence that this could be a clinically relevant approach. It also may allow accurate determination of the pathophysiologic mechanisms involved in the establishment and maintenance of experimental glomerulonephritis.
Why it is difficult to detect an illegally bowled cricket delivery with either the naked eye or usual two-dimensional video analysis
Authors: K D Aginsky, T D Noakes
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the influence of various anatomical and biomechanical factors on the ability to detect the magnitude of elbow extension during the cricket bowling action, with either the naked eye or from conventional two-dimensional video footage was evaluated. Design Descriptive study Setting One male bowler who had a large ℌcarrying angleℍ was studied by means of a three-dimensional biomechanical analysis using the Vicon MX13 motion analysis system when bowling at match pace. Photographs were taken from various angles during the bowling delivery action to illustrate factors influencing the visual appearance of an illegal delivery. Main outcome measures The influence of extension of the elbow joint and the elbow's anatomically fixed position, known as the “carrying angle”, on the visual perception of an illegal (“thrown”) delivery were the main outcome measures. Results The elbow joint rotates about 90° as a result of humeral rotation during the movement of shoulder circumduction produced by the bowler's delivery action. This causes the plane in which the elbow joint moves to change throughout the delivery action. This movement will also vary between bowlers. The movement of elbow planar flexion/extension can be viewed only when the viewer's eyes are at exactly 90u to the plane of elbow joint movement. Thus, a cricket umpire wishing to detect elbow extension during the bowler's delivery action would need continuously to change his viewing position as the bowler's arm moved from the horizontal to the vertical position at ball release. We show that by viewing the action from only one position, the umpire will be confused by the illusion of a “throw” produced by a large “carrying angle” in some bowlers. Conclusion It is impossible for an umpire conclusively to cite a bowler for an illegal action based only on naked eye observation. To do this the umpire would need to be in at least three different positions throughout a single delivery. Similarly, video footage shot from at least three different angles during the bowler's delivery action would need to be viewed by the match referee. By viewing the delivery from only one position, the visual illusion of a “throw” will be created by the presence of a large “carrying angle”.
The role of age in the protection of appendicectomy against ulcerative colitis
Authors: G L Adani, U Baccarani, A Risaliti
Journal: Gut (2004)

We read with great interest the article by Hallas and colleagues ( Gut 2004; 53 :351–4) investigating the protective role of appendicectomy in reducing hospital admission rates in patients with ulcerative colitis.

The population studied consisted of a cohort of 202 cases who underwent appendicectomy after their first admission for ulcerative colitis. A population of patients affected by ulcerative colitis who had not an appendicectomy was used as a reference cohort. The authors suggested that appendicectomy had no significant beneficial effect on hospital admission rates in patients with ulcerative colitis as no …