tbuckley/cabot-search huggingface dataset:
Costimulation of T Cells
Authors: LAURENCE BUGEON, MARGARET J. DALLMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Section:ChooseTop of pageAbstract <<B7–CD28/CTLA-4 PATHWAYcd80 AND cd86 GENE PRODUC...STRUCTURE AND EVOLUTION O...WHY ARE THERE SO MANY COS...THERAPEUTIC STRATEGIES BA...CONCLUSIONReferencesCITING ARTICLES
Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.
Authors: J. G. Thornton, C. Page, G. Foote, G. R. Arthur, L. A. Tovey, J. S. Scott
Journal: BMJ (1989)

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.
Clinical Significance of the Genetic Landscape of Pancreatic Cancer and Implications for Identification of Potential Long-term Survivors
Authors: Shinichi Yachida, Catherine M. White, Yoshiki Naito, Yi Zhong, Jacqueline A. Brosnan, Anne M. Macgregor-Das, Richard A. Morgan, Tyler Saunders, Daniel A. Laheru, Joseph M. Herman, Ralph H. Hruban, Alison P. Klein, Siân Jones, Victor Velculescu, Christopher L. Wolfgang, Christine A. Iacobuzio-Donahue
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Genetic alterations of KRAS, CDKN2A, TP53, and SMAD4 are the most frequent events in pancreatic cancer. We determined the extent to which these 4 alterations are coexistent in the same carcinoma, and their impact on patient outcome. Experimental Design: Pancreatic cancer patients who underwent an autopsy were studied (n = 79). Matched primary and metastasis tissues were evaluated for intragenic mutations in KRAS, CDKN2A, and TP53 and immunolabeled for CDKN2A, TP53, and SMAD4 protein products. The number of altered driver genes in each carcinoma was correlated to clinicopathologic features. Kaplan–Meier estimates were used to determine median disease free and overall survival, and a Cox proportional hazards model used to compare risk factors. Results: The number of genetically altered driver genes in a carcinoma was variable, with only 29 patients (37%) having an alteration in all 4 genes analyzed. The number of altered driver genes was significantly correlated with disease free survival (P = 0.008), overall survival (P = 0.041), and metastatic burden at autopsy (P = 0.002). On multivariate analysis, the number of driver gene alterations in a pancreatic carcinoma remained independently associated with overall survival (P = 0.046). Carcinomas with only 1 to 2 driver alterations were enriched for those patients with the longest survival (median 23 months, range 1 to 53). Conclusions: Determinations of the status of the 4 major driver genes in pancreatic cancer, and specifically the extent to which they are coexistent in an individual patients cancer, provides distinct information regarding disease progression and survival that is independent of clinical stage and treatment status. Clin Cancer Res; 18(22); 6339–47. ©2012 AACR.
Periodica Migrainous Neuralgia
Authors: M. S. Harrison
Journal: BMJ (1964)

The interesting features of this case were:(1) that she lived to the age of 76; (2) that death was due to liver and not renal compli- cations; and (3) that the degree of portal compression by the huge cysts was sufficient to cause portal hypertension and subsequent bleeding oesophageal varices, without cir- -rhosis of the remaining compressed liver tissue.
Bioterrorism: the current threat
Authors: G R Durrant
Journal: Journal of the Royal Society of Medicine (2002)

Bioterrorism is receiving ever more attention both in the popular press and in scientific publications. In the JRSM Beale1 has discussed responses to the threat, particularly the requirement for a comprehensive vaccination programme; he also noted the remarkable fact that the UK's Public Health Laboratory Service is to be broken up. The South and West Region of the RSM, at its inaugural academic meeting held at Britannia Royal Naval College Dartmouth in June, addressed the subject in more general terms under the title ‘Bioterrorism: the current threat’.
Clinical characteristics of a series of 302 French patients with hidradenitis suppurativa, with an analysis of factors associated with disease severity
Authors: Florence Canoui-Poitrine, Jean E. Revuz, Pierre Wolkenstein, Cédric Viallette, Germaine Gabison, Florence Pouget, Florence Poli, Ousmane Faye, Sylvie Bastuji-Garin
Journal: Journal of the American Academy of Dermatology (2009)
Mutagenesis of the beta2-Adrenergic Receptor: How Structure Elucidates Function
Authors: J Ostrowski, M A Kjelsberg, M G Caron, R J Lefkowitz
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Preserving the Race in Post-war Reconstruction
Authors: T. D. Shiels
Journal: BMJ (1942)

BEDINSHfracture that can occur, including fractures of the vertebrae and hip and shoulder regions.A check is kept by the radiographer as to the x-ray dose received by the patient, and the surgeon is warned if too frequent exposures are made.In one year's experience with this method manipulations were completed long before such a warning became necessary.Finally, this method can easily be.used by resident medical officers and does not need constant control by the senior surgeon or radiologist.In all ways the method is entirely satisfactory and, being safe, should always be used in preference to screening.-Iam, etc., London, E.14.
Effectiveness of exercise training in patients with COPD: the role of muscle fatigue
Authors: Chris Burtin, Didier Saey, Melda Saglam, Daniel Langer, Rik Gosselink, Wim Janssens, Marc Decramer, François Maltais, Thierry Troosters
Journal: European Respiratory Journal (2011)

The improvement in exercise performance in response to exercise training varies greatly from one patient with chronic obstructive pulmonary disease to another. It is possible that in a portion of patients the muscle stimulus applied during exercise training is insufficient to elicit training effects. We investigated whether patients presenting quadriceps contractile fatigue after training have more favourable effects of a rehabilitation programme. 46 patients followed a 3-month high-intensity exercise training programme. Exercise capacity, quadriceps force and quality of life were measured before and after the programme. Exercise training-induced quadriceps contractile fatigue was assessed after 1 month of rehabilitation with magnetic stimulation. A fall in quadriceps force of ≥15%, 15 min after training was considered as significant fatigue. 29 (63%) out of 46 patients developed significant fatigue. Patients with fatigue had a higher increase in 6-min walk distance (median (interquartile range) 57 (47–103) m versus 17 (-7–46) m; p=0.0023) and Chronic Respiratory Disease Questionnaire score (mean± sd 22±12 points versus 14±12 points; p=0.028) after the training programme compared with patients without fatigue. Improvements in quadriceps force and maximal exercise capacity were similar in both subgroups. Patients who develop quadriceps contractile fatigue during exercise training show greater training effects in terms of functional exercise capacity and health-related quality of life.
Targeted Radiosensitization of Cells Expressing Truncated DNA Polymerase β
Authors: Sari Neijenhuis, Manon Verwijs-Janssen, Lenie J. van den Broek, Adrian C. Begg, Conchita Vens
Journal: Cancer Research (2010)

Abstract Ionizing radiation (IR) is an effective anticancer treatment, although failures still occur. To improve radiotherapy, tumor-targeted strategies are needed to increase radiosensitivity of tumor cells, without influencing normal tissue radiosensitivity. Base excision repair (BER) and single-strand break repair (SSBR) contribute to the determination of sensitivity to IR. A crucial protein in BER/SSBR is DNA polymerase β (polβ). Aberrant polβ expression is commonly found in human tumors and leads to inhibition of BER. Here, we show that truncated polβ variant (polβ-Δ)–expressing cells depend on homologous recombination (HR) for survival after IR, indicating that a considerable fraction of polβ-Δ–induced lesions are subject to repair by HR. Increased sensitization was found not to result from involvement in DNA-dependent protein kinase–dependent nonhomologous end joining, the other major double-strand break repair pathway. Caffeine and the ATM inhibitor Ku55933 cause polβ-Δ–dependent radiosensitization. Consistent with the observed HR dependence and the known HR-modulating activity of ATM, polβ-Δ–expressing cells showed increased radiosensitization after BRCA2 knockdown that is absent under ATM-inhibited conditions. Our data suggest that treatment with HR modulators is a promising therapeutic strategy for exploiting defects in the BER/SSBR pathway in human tumors. Cancer Res; 70(21); 8706–14. ©2010 AACR.
A Phase I Study of the Safety and Pharmacokinetics of the Combination of Pertuzumab (rhuMab 2C4) and Capecitabine in Patients with Advanced Solid Tumors
Authors: Joan Albanell, Clara Montagut, Eileen T. Jones, Linda Pronk, Begoña Mellado, Janette Beech, Pere Gascon, Gerhard Zugmaier, Michael Brewster, Mark P. Saunders, Juan W. Valle
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To study the safety, pharmacokinetics, and recommended dose of the combination of pertuzumab, a humanized monoclonal antibody HER2-dimerization inhibitor, and capecitabine in patients with advanced malignancies. Experimental Design: Patients that had progressed to standard treatment were treated with pertuzumab at a fixed dose of 1,050 mg given i.v. on day 1 plus capecitabine at doses of 825-1,000-1,250 mg/m2, twice daily orally on days 1 to 14 of each 21-day treatment cycle, in three sequential cohorts. The pharmacokinetics of capecitabine and pertuzumab were studied. Patients received a single dose of capecitabine in a pretreatment phase (day −7) followed by serum sampling for capecitabine and its metabolites. Results: Nineteen patients were accrued and 18 were assessable. The combination of capecitabine and pertuzumab was well tolerated at all dose levels and no dose-limiting toxicities were observed. The most frequent adverse event was asthenia, which was grade 3 in two patients. One asymptomatic pulmonary embolism occurred. No other grade 3 or 4 adverse events or cardiac or left ventricular ejection fraction events were reported. There was no apparent change in the pharmacokinetics of capecitabine and its metabolites when combined with pertuzumab. The pharmacokinetics of pertuzumab was apparently not modified when administered with capecitabine. Disease stabilization was observed in 11 patients. Conclusions: Pertuzumab and capecitabine were well tolerated at all dose levels. Escalation beyond the highest dose level tested was not planned, as this included the recommended doses of monotherapy for both drugs. In conclusion, this combination is ready for phase II testing.
The 1971 Amendment of the Illinois Statute on Confidentiality: A New Development in Privilege Law
Authors: JEROME S. BEIGLER
Journal: American Journal of Psychiatry (1972)

After reviewing the history of privilege law in psychiatry, the author describes a new Illinois statute that modifies the "patient-litigant exception" so that both patient and psychiatrist have privilege in divorce cases even though "mental cruelty" is the ground for divorce unless either the patient or psychiatrist introduces testimony concerning communications between them. He also notes that a recent Illinois appellate court ruling protects confidentiality in personal injury cases when pain and suffering are claimed.
End Points and Clinical Trial Design in Pulmonary Arterial Hypertension
Authors: Vallerie V. McLaughlin, David B. Badesch, Marion Delcroix, Thomas R. Fleming, Sean P. Gaine, Nazzareno Galiè, J. Simon R. Gibbs, Nick H. Kim, Ronald J. Oudiz, Andrew Peacock, Steeve Provencher, Olivier Sitbon, Victor F. Tapson, Werner Seeger
Journal: Journal of the American College of Cardiology (2009)
2009 Homer W. Smith Award
Authors: René J.M. Bindels
Journal: Journal of the American Society of Nephrology (2010)

The kidneys play a critical role in maintaining the systemic balance of Mg(2+) and Ca(2+) cations. The reabsorptive capacity of these divalent cations adapt to changes in their plasma concentrations. Active reabsorption of Mg(2+) and Ca(2+) takes place in the distal convoluted and connecting tubules, respectively, and is initiated by cellular transport through selective transient receptor potential (TRP) channels located along the luminal membrane and modulated by hormonal stimuli. Recent characterization of underlying molecular defects in renal Mg(2+) handling illuminate complex transport processes in the kidney and their contribution to the overall mineral balance. Likewise, studies of Ca(2+) transport proteins in null mice disclose molecular mechanisms maintaining normal plasma Ca(2+) levels and the hypercalciuria-related adaptations important in the prevention of kidney stones. Current knowledge of Mg(2+) and Ca(2+) transport is summarized here as comprehensive cellular models of the distal nephron.
Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphoblastic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate
Authors: Brenda J. Spiegler, Kimberly Kennedy, Ronnen Maze, Mark L. Greenberg, Sheila Weitzman, Johann K. Hitzler, Paul C. Nathan
Journal: Journal of Clinical Oncology (2006)

Purpose Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. Patients and Methods Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 × 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. Results Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. Conclusion Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.
New Insights into von Hippel-Lindau Function Highlighted by Investigation of the Trichloroethylene-Induced p.P81S Hotspot Mutation
Authors: L. Neckers, C. J. Ricketts, W. Marston Linehan
Journal: JNCI Journal of the National Cancer Institute (2013)

The von Hippel-Lindau gene (VHL), composed of three exons, encodes a protein, pVHL, with diverse tumor suppressor activities. Germline VHL mutations are found in patients with von HippelLindau (VHL), an autosomal dominant hereditary cancer syndrome in which affected individuals are at risk for the development of highly vascularized benign and malignant tumors including central nervous system hemangioblastomas, retinal hemangiomas, clear cell renal carcinomas (ccRCCs), pheochromocytomas, and pancreatic neuroendocrine tumors (1). Biallelic inactivation of VHL, whether via mutation or promoter methylation, is found in VHL-associated tumors and in nearly 90% of sporadic ccRCC tumors (2,3), the most common form of sporadic kidney cancer. Among its activities, pVHL functions as the substrate recognition module of a multiprotein ubiquitin ligase complex, and, by recruiting hypoxia-inducible factor (HIF) 1α and 2α to this complex, mediates their oxygen-dependent degradation (4). VHL mutations that interfere with HIF-α recognition promote aerobic glycolysis and support neoangiogenesis, perhaps the most intensively studied consequences of pVHL loss. However, regulation of HIF-α expression is unlikely to be the sole mechanism underlying the tumor suppressor function of pVHL. Given its role as the substrate recognition module of a multiprotein complex, it is reasonable to assume that pVHL has additional activities that depend on protein–protein interactions unrelated to (or perhaps complementary with) HIF stabilization, and that deregulation of one or more of these activities contributes to tumor formation, likely in a tissue-specific manner. Indeed, pVHL has been implicated in a number of cellular processes that appear to be HIF independent, including cell cycle regulation, extracellular matrix assembly, and cytoskeleton stability (5). The development of ccRCC is associated with both genetic (eg, VHL germline mutation) and environmental factors, particularly long-term exposure to the industrial solvent trichloroethylene (TCE). Although TCE exposure does not affect the histopathology of sporadic ccRCC, its onset is earlier in TCE-exposed individuals, and the VHL gene in a substantial percentage of these tumors contains a specific mutation of a cytosine to thymidine at nucleo
Improvement of Glycemic Control in Subjects With Poorly Controlled Type 2 Diabetes
Authors: Melanie Davies, Fred Storms, Simon Shutler, Monique Bianchi-Biscay, Ramon Gomis
Journal: Diabetes Care (2005)

Large prospective studies have demonstrated that optimum glycemic control is not routinely achieved in clinical practice. Barriers to optimal insulin therapy include hypoglycemia, weight gain, and suboptimal initiation and dose titration. This study compared two treatment algorithms for insulin glargine initiation and titration: algorithm 1 (investigator led) versus algorithm 2 (performed by study subjects).A prospective, multicenter (n = 611), multinational (n = 59), open-label, 24-week randomized trial in 4,961 (algorithm 1, n = 2,493; algorithm 2, n = 2,468) suboptimally controlled type 2 diabetic subjects.At baseline, mean diabetes duration was 12.3 +/- 7.2 years, and 72% of subjects were pretreated with insulin. At end point, there was no significant difference in the incidence of severe hypoglycemia between algorithms 1 and 2 (0.9 vs. 1.1%). There was a significant reduction in HbA(1c) from 8.9 +/- 1.3 to 7.8 +/- 1.2%, with a greater decrease (P < 0.001) with algorithm 2 (-1.22%) versus algorithm 1 (-1.08%). Fasting blood glucose decreased from 170 to 110 mg/dl, with a greater decrease (P < 0.001) with algorithm 2 (-62 mg/dl) versus algorithm 1 (-57 mg/dl). Mean basal insulin dose increased from 22.9 +/- 15.5 to 43.0 +/- 25.5 IU, with a significant difference (P < 0.003) between algorithm 2 (21.6 IU) and algorithm 1 (18.7 IU).Glargine is safe and effective in improving glycemic control in a large, diverse population with longstanding type 2 diabetes. A simple subject-administered titration algorithm conferred significantly improved glycemic control with a low incidence of severe hypoglycemia compared with physician-managed titration.
Virginity pledge ineffective against teen sex despite government funding, US study finds
Authors: J. Hopkins Tanne
Journal: BMJ (2008)

US teenage virgins who pledged to abstain from sex until they were married had sexual behaviour in the next five years similar to that of teenagers who had not taken an abstinence pledge, a study has shown ( Pediatrics 2009, doi:10.1542/peds.2009-0407).

But contraceptive use differed between the groups. Five years later, teenagers who had pledged virginity were less likely to protect themselves against pregnancy and sexually transmitted diseases. In addition, 84% of teenagers who had pledged virginity denied that they had ever done so. 

Teenagers should get comprehensive …