tbuckley/cabot-search huggingface dataset:
Significant Frequencies of T Cells With Indirect Anti-Donor Specificity in Heart Graft Recipients With Chronic Rejection
Authors: Philip I. Hornick, Philip D. Mason, Richard J. Baker, Maria Hernandez-Fuentes, Loredana Frasca, Giovanna Lombardi, Kenneth Taylor, Ling Weng, Marlene L. Rose, Magdi H. Yacoub, Richard Batchelor, Robert I. Lechler
Journal: Circulation (2000)

Background —The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection. Methods and Results —Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I–derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toxoid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection. Discussion —iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.
Book Review Paediatric and Adolescent Gynaecology: A Multidisciplinary Approach Edited by Adam H. Balen, Sarah M. Creighton, Melanie C. Davies, Jane MacDougall, and Richard Stanhope. 558 pp., illustrated. New York, Cambridge University Press, 2004. $225. 0-521-80961-4
Authors: Elisabeth H. Quint
Journal: New England Journal of Medicine (2005)
Response to Letters Regarding Article, “Second Internal Thoracic Artery Versus Radial Artery in Coronary Artery Bypass Grafting: A Long-Term, Propensity Score-Matched Follow-Up Study”
Authors: Elfriede Ruttmann, Nikolaus Fischler, Adel Sakic, Orest Chevtchik, Roland Schistek, Michael Grimm, Hannes Alber, Hanno Ulmer
Journal: Circulation (2012)
KCNE2 Protein Is Expressed in Ventricles of Different Species, and Changes in Its Expression Contribute to Electrical Remodeling in Diseased Hearts
Authors: Min Jiang, Mei Zhang, Daniel G. Tang, Henry F. Clemo, Jie Liu, Dana Holwitt, Vigneshwar Kasirajan, Amber L. Pond, Erich Wettwer, Gea-Ny Tseng
Journal: Circulation (2004)

Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear.We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary (beta) subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I(Kr)) density was increased. Although the protein level of ERG (I(Kr) pore-forming, alpha, subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I(f)) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the alpha-subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude.KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.
Phase I Safety and Pharmacokinetic Study of CT-011, a Humanized Antibody Interacting with PD-1, in Patients with Advanced Hematologic Malignancies
Authors: Raanan Berger, Rinat Rotem-Yehudar, Gideon Slama, Shimon Landes, Abraham Kneller, Merav Leiba, Maya Koren-Michowitz, Avichai Shimoni, Arnon Nagler
Journal: Clinical Cancer Research (2008)

Abstract Purpose: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. Experimental Design: Seventeen patients were treated with escalating doses of CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis, blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days 7, 14, and 21. CT-011 blood levels were assessed with a specific ELISA and derived concentrations were used to calculate pharmacokinetic parameters. Activation of the immune system was assessed by measuring peripheral blood CD4+, CD8+, and CD69+ lymphocytes. Results: The study showed the antibody to be safe and well tolerated in this patient population. No single maximum tolerated dose was defined in this study. Clinical benefit was observed in 33% of the patients with one complete remission. Pharmacokinetic analyses show that serum Cmax and the AUC of CT-011 increased proportionally with dose. The median t1/2 of CT-011 ranged from 217 to 410 hours. Sustained elevation in the percentage of peripheral blood CD4+ lymphocytes was observed up to 21 days following CT-011 treatment. Conclusions: A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and well tolerated in patients with advanced hematologic malignancies.
Prevalence of lactase deficiency in British adults.
Authors: A Ferguson, D M MacDonald, W G Brydon
Journal: Gut (1984)

The prevalence of lactase deficiency in British adults is unknown. Examination of the distribution of lactase activities in single and multiple biopsies of jejunum indicated that 0.8 U/g wet weight was a suitable cut-off point to separate lactase deficient patients from others. One hundred and fifty white British adults were selected, none of whom had significant intestinal disease and all of whom had normal histopathology of a jejunal biopsy and normal activities of other disaccharidases measured in the biopsy. The prevalence of lactase deficiency in this group was 4.7%. In contrast, 15 of 20 non-white adults were lactase deficient. Lactase deficiency was found in only three of 36 patients investigated because of diarrhoea after gastric surgery, and in 16 of 200 patients with irritable bowel syndrome (8%). As the prevalence of lactase deficiency is no higher in irritable bowel syndrome than in 9normal9 individuals, lactase deficiency clearly is not a predisposing factor for irritable bowel syndrome in white British adults although the two conditions may occasionally coexist.
Suppression of secondary hyperparathyroidism in children with chronic renal failure by high dose phosphate binders: calcium carbonate versus aluminium hydroxide.
Authors: R H Mak, C Turner, T Thompson, H Powell, G B Haycock, C Chantler
Journal: BMJ (1985)

Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure.
Post Operative Analgesia for Breast Surgery: Intercostal Nerve Block Versus Subcutaneous Infiltration.
Authors: A. Syed, A. Devkaran, S. Mehta, M. Michail, H. Bradpiece
Journal: Cancer Research (2009)

Abstract BackgroundPost operative analgesia is often underestimated in breast surgery resulting in long term sequelae. Opiates and epidural analgesia may produce complications and limits early rehabilitation. We compare the effects of intercostal nerve block with subcutaneous infiltration as post operative analgesia in breast surgery.MethodsAll patients who undergo breast surgery were assigned to two groups. They either receive intercostal nerve block or subcutaneous infiltration of 0.5% bupivacaine at the end of surgery. Pain score using visual analogue scale and the total amount of morphine consumption were recorded. Personnel taking measurements were kept blind.ResultsThere were 70 patients included in the study. Of these, three patients (two from Group A and one from Group B) were excluded because of post operative haematoma and drain related complications. 33 patients had intercostal nerve block and 34 patients received subcutaneous infiltration. The groups were comparable with respect to age and type of breast surgery. There were significant differences in the visual analogue pain scores at the early post operative period in the study group (P value of &amp;lt; 0.05).Table 1Pain ScoreGroup A Median (range)Group B Median (range)No. of patientsP valueWith in 4 hr of surgery2 (1-8)2 (1-9)330.7521st post op 8am2 (1-6)3 (1-8)330.0091st post op 6pm2 (1-6)2 (1-10)330.0112nd post op 8am1 (1-5)2 (1-8)120.2442nd post op 6pm1 (1-4)1.5 (1-5)110.2213rd post op 8am1 (1-4)1 (1-6)90.1373rd post op 6pm1 (1-7)2 (1-4)90.347 ConclusionsWe have demonstrated in our study that intercostal nerve block provides effective post operative analgesia in breast surgery patients. The accessibility of intercostal nerves in the operative field makes blockade feasible. Contrary to the misconception, incidence of pneumothorax is very rare. It should therefore be used more widely in view of its simplicity. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5052.
Immunization Action Month (October)
Authors: Henri F. Wendel
Journal: JAMA (1974)

Earlier this year, St. Louis experienced an outbreak of measles—despite the fact that an effective vaccine was developed in the early 1960s. Outbreaks of diphtheria have been reported in recent years in at least four states and the number of young children immunized against poliomyelitis has been declining. Reports such as these are alarming since all of the diseases involved, as well as others such as rubella, mumps, pertussis, and tetanus, are fully preventable. Because they are, the second annual "Immunization Action Month" will be conducted this October in an effort to encourage the inoculation of as many preschool-age children as possible. These children, as a group, are most susceptible to communicable diseases; older children are less at risk, since many school systems require inoculation as a prerequisite to admission. In the case of poliomyelitis, the US Immunization Survey conducted each year by the Center for Disease Control shows that
Retinal vascular changes and immune restoration in a cohort of HIV/AIDS patients on highly active antiretroviral therapy
Authors: Ling-Jun Li, Carol Y Cheung, Petrina Tan, Tun Kuan Yeo, Rupesh Agrawal, James Ng, Tock H Lim, Tien-Yin Wong, Stephen C Teoh
Journal: The Lancet (2013)
1021-77 Diabetic patients with acute coronary syndromes were undertreated and had worse one-year outcome
Authors: Raymond T Yan, Andrew T Yan, Mary Tan, Lawrence Leiter, Chi-Ming Chow, David H Fitchett, Ronald Fowlis, Irene Janzen, Anatoly Langer, Shaun G Goodman
Journal: Journal of the American College of Cardiology (2004)
Abstract 3857: Smac mimetic TL32711 and TRAIL synergistically induce apoptosis of germinal center B lymphoma cells
Authors: Mitchell R. Smith, Indira Joshi, David E. Weng, Srinivas Chunduru, Mark A. McKinlay
Journal: Cancer Research (2012)

Abstract TL32711, a Smac mimetic in clinical testing, potently targets Inhibitor of Apoptosis Proteins (IAPs, including cIAPs and XIAP) to unblock intrinsic and extrinsic pathways, enabling caspase-dependent apoptosis via multiple signals including TRAIL (Tumor Necrosis Factor-Related Apoptosis Inducing Ligand). TL32711 also inactivates canonical and activates non-canonical NF-κB signaling through cIAPs. We investigated the pro-apoptotic effects of TL32711, alone and in combination with TRAIL to activate the extrinsic pathway, in a panel of B cell lymphoma cell lines representing germinal center/follicular (GC) vs activated B cell (ABC) histologies. We hypothesized that the efficacy of this potential combination therapeutic strategy might differ between GC and ABC lymphoma types, as ABC are reported to be NF-kB dependent. We used the following EBV negative cell lines: WSU- FSCCL t(14:18)+ follicular lymphoma (FL), FC-TxFL2 t(14:18)+ transformed FL and SU-DHL4 GC-type diffuse large B cell lymphoma (DLBCL) as examples of GC origin lymphomas. U2932 and TMD8 served as ABC-type DLBCL. Apoptosis was determined by annexin V staining after 48 hr incubation (TL32711 added 2-3 hr after TRAIL). The contribution of the different apoptotic pathways was determined by caspase-3 (common), -8 (extrinsic), and-9 (intrinsic) activity, assessed by flow cytometric methods and Western blot. TL32711 had little effect as a single agent on any of these B cell lymphoma cell lines at ≤ 100nM, though apoptosis was induced at 10-20 µM in GC types. TRAIL alone (10-25 ng/ml) induced apoptosis in the 3 GC lines, but had little effect on the 2 ABC lines. Combination of TL32711 and TRAIL at low concentrations showed marked apoptosis in GC lines, with minimal to no effect for each agent alone. In the combination-treated GC types, caspases -3, -8 and -9 were significantly induced, confirming activation of both pathways. We had previously shown in FSCCL and TxFL2 that caspase-8 induction also cleaved tBID, activating the intrinsic apoptotic pathway via caspase-9. GC subtypes, including FL, transformed FL and GC-DLBCL were sensitive to TRAIL and TL32711 at clinically achievable concentrations for TL32711, with supra-additive combination effects. ABC-type DLBCL were not sensitive to either agent alone or in combination. We are investigating whether ABC-DLBCL are truly dependent on canonical NF-κB activation for survival or have other mechanisms of resistance to TRAIL and IAP inhibition. These data suggest that clinical trials of TL32711 may focus on FL and GC lymphoma in combination with TRAIL or TRAIL-agonists. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3857. doi:1538-7445.AM2012-3857
Management of Malignant Melanoma
Authors: A. Green
Journal: BMJ (1964)

MBICALJOURNAL ment in cases of poisoning is often needlessly delayed or handicapped when the container, as is usual, is merely labelled " the tablets."Many progressive hospitals and practitioners are now asking for drug containers to be labelled with the name of the drug unless otherwise specified by the prescriber.Among many other advantages this helps in the quick identification of poisons in cases of accidental poisoning.
Successful Surgical Correction of Supravalvular Aortic Stenosis
Authors: MICHAEL E. DEBAKEY, ARTHUR C. BEALL
Journal: Circulation (1963)

Stenotic lesions in the aortic valve region may be acquired or congenital, and may be valvular, subvalvular, or supravalvular in location. As more of these patients are offered the benefits of surgical correction, cases of supravalvular aortic stenosis are being reported with increasing frequency. At least seven previous cases have been corrected successfully and another is reported. The diagnosis of supravalvular aortic stenosis usually cannot be made on clinical grounds alone. Definitive diagnostic technics are available, however, and allowed accurate delineation of the lesion in the case reported. Surgical correction consists of enlarging the aortic lumen in the area of supravalvular constriction. This usually is possible by longitudinal aortotomy through the area of constriction followed by patch angioplasty, as employed in this case in conjunction with modified endarterectomy. In most instances of supravalvular aortic stenosis, the valve itself is perfectly normal, and total correction is possible if the correct diagnosis is made.
Small RNAs Deliver a Blow to Ovarian Cancer
Authors: Andrea Kasinski, Frank J. Slack
Journal: Cancer Discovery (2013)

Targeted therapeutic approaches have seen tremendous advances in the last decade, for good reason. Specifically intervening with a disease-causing gene can revert the deleterious phenotype while eliminating the toxicity often associated with broad-spectrum agents. Unfortunately, because these selective agents hit one target in a single location, acquired resistance is often high. An arguably better treatment approach includes coupling multiple targeted agents or using an agent that hits an individual target in several independent locations and/or alters multiple relevant targets in the disease-causing pathway(s), precisely the approach taken by Nishimura and colleagues in their recent report aimed at identifying a better treatment option for ovarian cancer.
Wisconsin’s Environmental Public Health Tracking Network: Information Systems Design for Childhood Cancer Surveillance
Authors: Lawrence P. Hanrahan, Henry A. Anderson, Brian Busby, Marni Bekkedal, Thomas Sieger, Laura Stephenson, Lynda Knobeloch, Mark Werner, Pamela Imm, Joseph Olson
Journal: Environmental Health Perspectives (2004)

In this article we describe the development of an information system for environmental childhood cancer surveillance. The Wisconsin Cancer Registry annually receives more than 25,000 incident case reports. Approximately 269 cases per year involve children. Over time, there has been considerable community interest in understanding the role the environment plays as a cause of these cancer cases. Wisconsin’s Public Health Information Network (WI-PHIN) is a robust web portal integrating both Health Alert Network and National Electronic Disease Surveillance System components. WI-PHIN is the information technology platform for all public health surveillance programs. Functions include the secure, automated exchange of cancer case data between public health–based and hospital-based cancer registrars; web-based supplemental data entry for environmental exposure confirmation and hypothesis testing; automated data analysis, visualization, and exposure–outcome record linkage; directories of public health and clinical personnel for role-based access control of sensitive surveillance information; public health information dissemination and alerting; and information technology security and critical infrastructure protection. For hypothesis generation, cancer case data are sent electronically to WI-PHIN and populate the integrated data repository. Environmental data are linked and the exposure–disease relationships are explored using statistical tools for ecologic exposure risk assessment. For hypothesis testing, case–control interviews collect exposure histories, including parental employment and residential histories. This information technology approach can thus serve as the basis for building a comprehensive system to assess environmental cancer etiology.
Recognition of residual postoperative shunts by contrast echocardiographic techniques.
Authors: L M Valdes-Cruz, D R Pieroni, J M Roland, J P Shematek
Journal: Circulation (1977)

A bedside echocardiographic technique was used to detect and localize residual intracardiac shunts in 26 patients who had surgical repair of septal defects. Contrast echocardiography was performed through central venous and left atrial monitoring catheters at the same time as cardiogreen dye curves. Indicator dilution confirmed residual atrial defects in ten patients and ventricular defects in five. Contrast echocardiography indicated the presence and level of shunting in all 15 patients. Temporary flow through newly implanted septal patches was detected and differentiated from shunting across a true residual defect. The contrast echocardiographic technique using injections through the central venous and left atrial catheters as described detects and localizes right-to-left and left-to-right shunting. It is a safe and reliable method to evaluate residual intracardiac defects postoperatively.
Normalized ultraviolet (UV) induction of Langerhans cell depletion and neutrophil infiltrates after artificial UVB hardening of patients with polymorphic light eruption.
Authors: A.S. Janssens, S. Pavel, J.J. Out-Luiting, R. Willemze, F.R. de Gruijl
Journal: British Journal of Dermatology (2005)

Background Ultraviolet (UV) B hardening has been widely used as a prophylactic treatment in patients with polymorphic light eruption (PLE). Recent investigations have shown that in patients with PLE Langerhans cells (LCs) and neutrophils display less migration from and to the epidermis after an intense UVB irradiation compared with controls. Objectives To investigate the effect of UVB hardening of patients with PLE on their cell migratory responses after intense UVB exposure. Methods Thirteen patients with PLE were recruited and UVB provocation testing was performed before entering the study. Among these patients, seven developed PLE rash upon UVB provocation ('UVB‐P') and the other six did not respond ('UVB‐NP'). Eleven age/sex‐matched controls were included. Buttock skin of all included individuals was exposed to 6 minimal erythema doses (MED) of UVB (TL‐12 lamps). Biopsies were taken after 24 h and 48 h, together with one control biopsy of unirradiated skin. Patients received total‐body UVB hardening therapy consisting of 12 irradiations, on average rising from 10% to 140% of the initial MED in 6 weeks. Subsequently, MEDs were reassessed and biopsies were taken from newly irradiated (6 MED UVB) and unirradiated buttock skin. Skin sections were stained for the presence of LCs, macrophages and neutrophils. The cross‐sectional area (in percentage) of positively stained cells within the epidermis was assessed from patients before and after hardening and compared with controls. Results Before therapy, epidermal LC depletion and neutrophil influx at 48 h after 6 MED were most significantly reduced in 'UVB‐P' patients (P = 0·025 and P =0·006, respectively) when compared with controls. 'UVB‐NP' patients did not differ significantly from controls. After therapy, there were no longer any significant differences in the cell numbers among these three groups. Conclusions UVB hardening significantly improves UV‐induced cell migratory responses in patients with PLE. UVB provokability of PLE appears to be most strongly linked to reduced UVB‐induced trafficking of LCs and neutrophils, and 'UVB‐P' patients show normalization of these responses after UVB hardening.