tbuckley/cabot-search huggingface dataset:
Dynamic Antigen-specific T-Cell Responses after Point-Source Exposure to<i>Mycobacterium tuberculosis</i>
Authors: Katie Ewer, Kerry A. Millington, Jonathan J. Deeks, Lydia Alvarez, Gerry Bryant, Ajit Lalvani
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The kinetics of Mycobacterium tuberculosis-specific Th1-type T-cell responses after M. tuberculosis infection are likely to be important in determining clinical outcome.To investigate the kinetics of T-cell responses, in the context of a point-source school tuberculosis outbreak, in three groups of contacts who differed by preventive treatment status and tuberculin skin test (TST) results: 38 treated TST-positive students, 11 untreated TST-positive staff, and 14 untreated students with negative or borderline TST results.We used the ex vivo IFN-gamma enzyme-linked immunospot assay (ELISpot) to track T cells specific for two region of difference 1 (RD1) antigens, early secretory antigenic target 6 and culture filtrate protein 10, for 18 mo after cessation of tuberculosis exposure.The treated TST-positive students had an average 68% decline in frequencies of RD1-specific IFN-gamma-secreting T cells per year (p < 0.0001) and 6 of 38 students had no detectable RD1-specific T cells by 18 mo. No change in frequencies of these cells was observed in the untreated TST-positive staff (p = 0.38) and none were ELISpot-negative at 18 mo. Of the 14 untreated students, 7 were persistently ELISpot-positive (all of whom had borderline TST results), and 7 became ELISpot-negative (all but one had negative TST results) during follow-up.The decrease in M. tuberculosis-specific T cells and their disappearance in a proportion of treated students likely reflect declining antigenic and bacterial load in vivo induced by antibiotic treatment. The observed disappearance of M. tuberculosis-specific T cells in the untreated TST-negative contacts suggests that an acute resolving infection may occur in some contacts.
Effect of subcentimeter nonpositive resection margin on hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases. Evidences from 663 liver resections
Authors: J. Figueras, F. Burdio, E. Ramos, J. Torras, L. Llado, S. Lopez-Ben, A. Codina-Barreras, S. Mojal
Journal: Annals of Oncology (2007)

To elucidate if a nonpositive <1-cm resection margin has any effect on hepatic recurrence in patients undergoing liver resection for colorectal liver metastases.Six hundred and nine patients underwent 663 liver resections. Patients with positive margin were excluded from the analysis. Two groups were studied: group A, <1-cm resection margin and group B, > or =1-cm resection margin.A total of 545 liver resections in 523 patients were carried out with nonpositive resection margins. With a median follow-up of 25 months, the 5-year cumulative hepatic recurrence reached 54% in group A (n = 206) and 41% in group B (n = 339). Factors associated with hepatic recurrence were synchronic metastases (P = 0.0015), bilobar (P < 0.001), two or more metastases (P < 0.001), margin <1 cm (P = 0.0123) and extrahepatic disease (P = 0.0037). A strong correlation between resection margin and number of metastases was confirmed (P < 0.001). At multivariate analysis only two factors were independent predictors of hepatic recurrence: multinodular disease in the liver specimen [> or =4 metastases hazard ratio (HR) = 3.45; 95% confidence interval (CI): 2.2-5.38; P < 0.001] and extrahepatic disease at hepatectomy (HR = 1.58; 95% CI: 1.58-3.32).Subcentimeter nonpositive resection margins do not directly influence hepatic recurrence in patients undergoing hepatectomy for colorectal liver metastases.
Superior Antitumor<i>In vitro</i>Responses of Allogeneic Matched Sibling Compared with Autologous Patient CD8+ T Cells
Authors: Sandra Kausche, Thomas Wehler, Elke Schnürer, Volker Lennerz, Walburgis Brenner, Sebastian Melchior, Mark Gröne, Marion Nonn, Susanne Strand, Ralf Meyer, Elena Ranieri, Christoph Huber, Christine S. Falk, Wolfgang Herr
Journal: Cancer Research (2006)

Allogeneic cell therapy as a means to break immunotolerance to solid tumors is increasingly used for cancer treatment. To investigate cellular alloimmune responses in a human tumor model, primary cultures were established from renal cell carcinoma (RCC) tissues of 56 patients. In three patients with stable RCC line and human leukocyte antigen (HLA)-identical sibling donor available, allogeneic and autologous RCC reactivities were compared using mixed lymphocyte/tumor cell cultures (MLTC). Responding lymphocytes were exclusively CD8(+) T cells, whereas CD4(+) T cells or natural killer cells were never observed. Sibling MLTC populations showed higher proliferative and cytolytic antitumor responses compared with their autologous counterparts. The allo-MLTC responders originated from the CD8(+) CD62L(high)(+) peripheral blood subpopulation containing naive precursor and central memory T cells. Limiting dilution cloning failed to establish CTL clones from autologous MLTCs or tumor-infiltrating lymphocytes. In contrast, a broad panel of RCC-reactive CTL clones was expanded from each allogeneic MLTC. These sibling CTL clones either recognized exclusively the original RCC tumor line or cross-reacted with nonmalignant kidney cells of patient origin. A minority of CTL clones also recognized patient-derived hematopoietic cells or other allogeneic tumor targets. The MHC-restricting alleles for RCC-reactive sibling CTL clones included HLA-A2, HLA-A3, HLA-A11, HLA-A24, and HLA-B7. In one sibling donor-RCC pair, strongly proliferative CD3(+)CD16(+)CD57(+) CTL clones with non-HLA-restricted antitumor reactivity were established. Our results show superior tumor-reactive CD8 responses of matched allogeneic compared with autologous T cells. These data encourage the generation of antitumor T-cell products from HLA-identical siblings and their potential use in adoptive immunotherapy of metastatic RCC patients.
In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia
Authors: Ilaria Iacobucci, Andrea Ghelli Luserna Di Rorà, Maria Vittoria Verga Falzacappa, Claudio Agostinelli, Enrico Derenzini, Anna Ferrari, Cristina Papayannidis, Annalisa Lonetti, Simona Righi, Enrica Imbrogno, Silvia Pomella, Claudia Venturi, Viviana Guadagnuolo, Federica Cattina, Emanuela Ottaviani, Maria Chiara Abbenante, Antonella Vitale, Loredana Elia, Domenico Russo, Pier Luigi Zinzani, Stefano Pileri, Pier Giuseppe Pelicci, Giovanni Martinelli
Journal: Journal of Hematology & Oncology (2015)

Although progress in children, in adults, ALL still carries a dismal outcome. Here, we explored the in vitro and in vivo activity of PF-00477736 (Pfizer), a potent, selective ATP-competitive small-molecule inhibitor of checkpoint kinase 1 (Chk1) and with lower efficacy of checkpoint kinase 2 (Chk2). The effectiveness of PF-00477736 as single agent in B-/T-ALL was evaluated in vitro and in vivo studies as a single agent. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B-/T-ALL cell lines. Finally, the action of PF-00477736 was assessed in vivo using leukemic mouse generated by a single administration of the tumorigenic agent n-ethyl-n-nitrosourea. Chk1 and Chk2 are overexpressed concomitant with the presence of genetic damage as suggested by the nuclear labeling for γ-H2A.X (Ser139) in 68 % of ALL patients. In human B- and T-ALL cell lines, inhibition of Chk1/2 as a single treatment strategy efficiently triggered the Chk1-Cdc25-Cdc2 pathway resulting in a dose- and time-dependent cytotoxicity, induction of apoptosis, and increased DNA damage. Moreover, treatment with PF-00477736 showed efficacy ex vivo in primary leukemic blasts separated from 14 adult ALL patients and in vivo in mice transplanted with T-ALL, arguing in favor of its future clinical evaluation in leukemia. In vitro, ex vivo, and in vivo results support the inhibition of Chk1 as a new therapeutic strategy in acute lymphoblastic leukemia, and they provide a strong rationale for its future clinical investigation.
Radiation from CT and perfusion scanning in pregnancy
Authors: J Valmai Cook, John Kyriou
Journal: BMJ (2005)

EDITOR—In her news article Eaton notes that most of the rise in medical radiation exposure is due to computed tomography.1 However, the whole body effective dose given for computed tomography may not reflect the increased risk to individual exposed body areas.

Last year we assessed the risks for pregnant women undergoing investigation for possible pulmonary embolism.2 The British Thoracic Society guidelines 2003 recommend computed tomography …
Evidence for familial aggregation of hand, hip, and spine but not knee osteoarthritis in siblings with multiple joint involvement: the GARP study
Authors: N Riyazi
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To evaluate whether familial aggregation of osteoarthritis differs by joint site in a sibling pair study (GARP) of patients with osteoarthritis at multiple sites. <b>Subjects:</b> White Dutch probands aged 40 to 70 years and their siblings with primary osteoarthritis at multiple sites. <b>Methods:</b> The diagnosis of knee, hip, and spine osteoarthritis was based on a combination of pain or stiffness on most days of the previous month and osteophytes or joint space narrowing on <i>x</i> ray. Hand osteoarthritis was defined by ACR criteria. Odds ratios (OR) were calculated for siblings and probands sharing disease in the same joints. <b>Results:</b> 191 sibling pairs were included (85% women; mean age 60 years). In the probands, osteoarthritis was present in spine (76%), hands (77%), knees (37%), and hips (26%). The most common combinations in probands were spine–hand (59%), spine–knee (27%), and hand–knee (25%). The OR adjusted for age, sex, and body mass index for siblings to be affected in the same joint sites as the proband were increased in osteoarthritis of the hand (OR = 4.4 (95% confidence interval, 2.0 to 9.5)), hip (OR = 3.9 (1.8 to 8.4)), spine (OR = 2.2 (1.0 to 5.1)), hip–spine (OR = 4.7 (2.1 to 10.4)), and hand–hip (OR = 3.4 (1.1 to 10.4)). Siblings of probands with osteoarthritis in the knee did not have an increased likelihood of knee osteoarthritis. <b>Conclusions:</b> In middle aged patients with familial osteoarthritis at multiple sites, familial aggregation of osteoarthritis was most striking for hand and hip but remarkably absent for the knee.
Myocardial Ultrasound Tissue Characterization in Patients with Chronic Renal Failure
Authors: Massimo Salvetti, Maria Lorenza Muiesan, Anna Paini, Cristina Monteduro, Bianca Bonzi, Gloria Galbassini, Eugenia Belotti, Ezio Movilli, Giovanni Cancarini, Enrico Agabiti-Rosei
Journal: Journal of the American Society of Nephrology (2007)

The objective of this study was to detect ultrastructural changes in myocardium related to collagen content by ultrasound tissue characterization in patients with chronic kidney disease (CKD) and in uncomplicated hypertensive control subjects. In 25 hemodialysis (HD) patients, in 25 patients with moderate to severe chronic renal failure (CRF), and in 10 patients with essential hypertension (EH) and normal renal function matched for age, BP, and left ventricular mass index, left ventricular anatomy and function were evaluated by conventional echocardiography, and integrated backscatter signal (IBS) was analyzed by acoustic densitometry. IBS mean reflectivity increased from 48% in patients with EH to 56% in patients with CRF to 62% in HD patients (ANOVA P < 0.01). IBS mean cyclic variation was progressively increased from 4.35 +/- 1.2 dB in HD patients to 5.27 +/- 0.90 in patients with CRF to 6.50 +/- 1.6 dB in patients with EH (ANOVA P < 0.01). At multivariate analysis, IBS mean reflectivity was positively related to age and serum creatinine (beta 0.351, P = 0.036; and beta = 0.408, P = 0.016, respectively). IBS mean cyclic variation was inversely related to age and serum creatinine (beta = -0.274, P = 0.025; and beta = -0.262, P = 0.025, respectively) and positively related to left ventricular midwall fractional shortening and transmitral E/A ratio (beta = 0.269, P < 0.05; and beta = 0.314, P < 0.001, respectively). The data support the hypothesis that interstitial collagen deposition may appear early in the course of CKD and suggest that acoustic densitometry may represent a useful tool for the assessment of myocardial tissue changes in patients with CKD.
Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study
Authors: Simon R Harris, Edward JP Cartwright, M Estée Török, Matthew TG Holden, Nicholas M Brown, Amanda L Ogilvy-Stuart, Matthew J Ellington, Michael A Quail, Stephen D Bentley, Julian Parkhill, Sharon J Peacock
Journal: The Lancet Infectious Diseases (2012)

The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages of MRSA means that it is necessary to understand transmission dynamics in terms of hospitals and the community as one entity. We assessed the use of whole-genome sequencing to enhance detection of MRSA transmission between these settings.We studied a putative MRSA outbreak on a special care baby unit (SCBU) at a National Health Service Foundation Trust in Cambridge, UK. We used whole-genome sequencing to validate and expand findings from an infection-control team who assessed the outbreak through conventional analysis of epidemiological data and antibiogram profiles. We sequenced isolates from all colonised patients in the SCBU, and sequenced MRSA isolates from patients in the hospital or community with the same antibiotic susceptibility profile as the outbreak strain.The hospital infection-control team identified 12 infants colonised with MRSA in a 6 month period in 2011, who were suspected of being linked, but a persistent outbreak could not be confirmed with conventional methods. With whole-genome sequencing, we identified 26 related cases of MRSA carriage, and showed transmission occurred within the SCBU, between mothers on a postnatal ward, and in the community. The outbreak MRSA type was a new sequence type (ST) 2371, which is closely related to ST22, but contains genes encoding Panton-Valentine leucocidin. Whole-genome sequencing data were used to propose and confirm that MRSA carriage by a staff member had allowed the outbreak to persist during periods without known infection on the SCBU and after a deep clean.Whole-genome sequencing holds great promise for rapid, accurate, and comprehensive identification of bacterial transmission pathways in hospital and community settings, with concomitant reductions in infections, morbidity, and costs.UK Clinical Research Collaboration Translational Infection Research Initiative, Wellcome Trust, Health Protection Agency, and the National Institute for Health Research Cambridge Biomedical Research Centre.
Radial Artery Tonometry Demonstrates Arterial Stiffness in Children With Type 1 Diabetes
Authors: Michael J. Haller, Margaret Samyn, Wilmer W. Nichols, Todd Brusko, Clive Wasserfall, R. Fletcher Schwartz, Mark Atkinson, Jonathan J. Shuster, Gary L. Pierce, Janet H. Silverstein
Journal: Diabetes Care (2004)

OBJECTIVE—To determine if children with type 1 diabetes have increased arterial stiffness by estimating augmentation index with the simple noninvasive technique of radial artery tonometry. RESEARCH DESIGN AND METHODS—We studied 98 type 1 diabetic children and 57 healthy control subjects, ages 10–18 years, matched for age, sex, race, and BMI, generating 43 matched pairs. Radial artery tonometry was performed, and blood was collected for analysis of fasting lipids, HbA1c, glucose, and cytokines in all children. RESULTS—Children with diabetes had a significantly higher augmentation index corrected to a heart rate of 75 (AI75) than their matched control subjects. Mean AI75 in type 1 diabetic subjects was 1.11 ± 10.15 versus −3.32 ± 10.36 in control subjects. The case-control difference was 5.20 ± 11.02 (P = 0.0031). CONCLUSIONS—Children with type 1 diabetes have increased arterial stiffness compared with healthy control subjects. Radial artery tonometry is a simple noninvasive technique that could be added to the armamentarium of tests used to provide cardiovascular risk stratification in children with type 1 diabetes.
Trypanosoma cruzi. Factors modifying ingestion and fate of blood form trypomastigotes.
Authors: N Nogueira, S Chaplan, Z Cohn
Journal: The Journal of Experimental Medicine (1980)

Blood form trypomastigotes of the Y and CL strains of Trypanosoma cruzi were tested for their ability to enter and infect mouse peritoneal macrophages. Both strains failed to enter macrophages in appreciable numbers, whereas metacyclic trypomastigotes purified from acellular cultures were ingested with ease. Macrophage parasitization was enhanced manyfold after the removal of an antiphagocytic substance by trypsinization. This occurred without modification of parasite viability. Opsonization with hyperimmune mouse serum also enhanced the uptake of blood form trypomastigotes by macrophages. This effect was mediated by the macrophage Fc receptor. The effects of serum and trypsinization were additive at high parasite:cell ratios. Neither trypsin-mediated nor antibody-dependent opsonization of the organisms modified the fate of either strain within resident macrophages. However, lymphokine-activated macrophages were capable of destroying both strains, and antibody opsonization further enhanced this process.
Abnormal Automaticity in Canine Purkinje Fibers Focally Subjected to Low External Concentrations of Calcium
Authors: Toyomi Sano, Tohru Sawanobori
Journal: Circulation Research (1972)

The false tendon was isolated from the dog heart and mounted under a partition plate in the center of a chamber which was filled with Tyrode's solution. Two microelectrodes were positioned closely on either side of the plate and inserted into the false tendon. The partition did not alter repolarization of the action potential in normal Tyrode's solution. When EDTA was added to one side of the preparation, a low-plateau potential appeared after repolarization on the other side, which contained normal Tyrode's solution. This change occurred concurrently with a prolongation of the action potential in the calcium-free Tyrode's solution. The low-plateau potential was a reflection of the electrotonic potential from the nearby cells whose action potentials were prolonged. Repetitive firing of the action potential was frequently observed when abrupt differences in repolarization were recorded at close interelectrode distances. These results suggest that differences in repolarization of closely apposed cells can initiate arrhythmias.
Disseminated Cutaneous Infection of Mycobacterium Colombiense with Myelodyspalstic Syndrome: a Case Report
Authors: Yuichiro Inagaki, Tatsuya Ito, Satomi Sahashi, Kotaro Miyao, Toko Saito, Takanobu Morishita, Hiroki Mizuno, Yoshitaka Ono, Masashi Sawa, Kazuhisa Inuzuka
Journal: Annals of Oncology (2014)
Childhood Asphyxiation by Food
Authors: Carole Stallings Harris, Susan P. Baker, Gary A. Smith, Richard M. Harris
Journal: JAMA (1984)

Data on all identified food-related asphyxiations of infants and children aged 0 to 9 years in 41 states from 1979 to 1981 were analyzed by type of food and age of child. Nationally, one death occurred approximately every five days. More than 90% occurred in infants and children younger than 5 years and 65% in infants younger than 2 years. Round foods were most often mentioned of the 103 foods specifically identified on death certificates. Most frequently cited were hot dog products (17 cases, 17%), candy, ten; nuts, nine; and grapes, eight. Hot dogs caused deaths from infancy through 3 years (more than two thirds of all deaths from meat products) and seven of ten deaths in 3-year-olds. Characteristics of foods, children, and environment can be related to three phases of food asphyxiation: penetration, occlusion, and expulsion. Preventive measures include product modification, warning labels, and dissemination of information on high-risk foods.
A case of ‘<i>ego embolisation per consilium</i>' of gastrointestinal bleeding: Figure 1
Authors: Ramesh P Arasaradnam, Kashmiri Dabenik, Vishal Verma, Olu Adesanya, Chuka U Nwokolo
Journal: Gut (2010)

A 53-year-old man initially presented with recurrent episodes of acute-on-chronic pancreatitis with no obvious cause identified. Subsequently, over the ensuing months, these episodes settled but then presented with recurrent episodes of haematemesis. Repeated upper and …
A Clinical Study of LSD Treatment in Alcoholism
Authors: ARNOLD LUDWIG, JEROME LEVINE, LOUIS STARK, ROBERT LAZAR
Journal: American Journal of Psychiatry (1969)

One hundred seventy-six male alcoholic patients participated in a controlled investigation of the differential efficacy of three LSD treatment procedures and a "no therapy," or milieu treatment, condition. Half of each group was also assigned to disulfiram after discharge from the hospital to determine whether any of these techniques could be enhanced by its use. Although significant improvement was shown within all treatment groups as measured by a number of clinical assessments in the post-treatment and follow-up periods, no one treatment condition proved to be superior. The authors conclude that the dramatic claims for the efficacy of LSD treatment in alcoholism are unjustified.
IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and Contributes to Cigarette Smoke–induced Lymphoid Neogenesis
Authors: Abraham B. Roos, Caroline Sandén, Michiko Mori, Leif Bjermer, Martin R. Stampfli, Jonas S. Erjefält
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

End-stage chronic obstructive pulmonary disease (COPD) is associated with an accumulation of pulmonary lymphoid follicles. IL-17A is implicated in COPD and pulmonary lymphoid neogenesis in response to microbial stimuli. We hypothesized that IL-17A is increased in peripheral lung tissue during end-stage COPD and also directly contributes to cigarette smoke-induced lymphoid neogenesis.To characterize the tissue expression and functional role of IL-17A in end-stage COPD.Automated immune detection of IL-17A and IL-17F was performed in lung tissue specimens collected from patients with Global Initiative for Chronic Obstructive Lung Disease stage I-IV COPD, and smoking and never-smoking control subjects. In parallel, Il17a(-/-) mice and wild-type control animals were exposed to cigarette smoke for 24 weeks, and pulmonary lymphoid neogenesis was assessed.Tissue expression of IL-17A and IL-17F was increased in COPD and correlated with lung function decline. IL-17A was significantly elevated in severe to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease III/IV) compared with both smokers and never-smokers without COPD. Although CD3(+) T cells expressed IL-17A in very severe COPD, most IL-17A(+) cells were identified as tryptase-positive mast cells. Attenuated lymphoid neogenesis and reduced expression of the B-cell attracting chemokine C-X-C motif ligand (CXCL) 12 was observed in cigarette smoke-exposed Il17a(-/-) mice. CXCL12 was also highly expressed in lymphoid follicles in COPD lungs, and the pulmonary expression was significantly elevated in end-stage COPD.IL-17A in the peripheral lung of patients with severe to very severe COPD may contribute to disease progression and development of lymphoid follicles via activation of CXCL12.