tbuckley/cabot-search huggingface dataset:
Severe Diarrhea in Pneumococcal Bacteremia: Croupous Colitis
Authors: Carlos del Rio
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Greene et al<sup>1</sup>report a patient with sickle cell anemia who died of fulminant pneumococcal bacteremia and had watery diarrhea as a symptom. We recently saw a patient without sickle cell anemia but with apparent hyposplenia and pneumococcal sepsis who was initially seen with severe diarrhea. <h3>Report of a Case.—</h3> A 54-year-old black woman was admitted to the hospital with a two-day history of fever, shaking chills, nausea, and vomiting. She reported severe profuse diarrhea, with bowel movements occurring almost every hour. Her history was notable only for hypertension that was treated with thiazide diuretics. At time of admission, her temperature was 39.4°C; blood pressure, 116/60 mm Hg; pulse, 100 beats per minute; and respirations, 20/min. She was obese, lethargic, and disoriented. The neck was supple and neurological examination was nonfocal. Scattered coarse rhonchi were heard throughout her lungs and there were no heart murmurs. Results
GPs' role and recognition. GPs taken for granted ...
Authors: J H Fitton
Journal: BMJ (1993)

Smoking related to clinical diagnosisNo of controls No (o/o) of smokers No of No (%) of Age in same age in aged marked patients smokers range range controls Periductal mastitis 68 60 (88) 19-48 10 397 3955 (38O0)* Non-lactating 39 34 (87) 23-46 8 944 3441 (38-5)* Mammaryduct 32 30(94) 26-48 9 321 3504(37.6)*Duct ectasia 186 52 (28) 42-85 9 093 2722 (29 9) * p < 0 0001, XI test, comparing numbers of smokers and controls.view of Bundred and colleagues that periductal mastitis and duct ectasia are separate conditions with different clinical syndromes, different pathological features, and different aetiologies.Clinicians and pathologists should be aware of this and use appropriate terminology.
The Permian Bacterium that Isn't
Authors: Dan Graur, Tal Pupko
Journal: Molecular Biology and Evolution (2001)

There is growing evidence for the presence of viable microorganisms in geological salt formations that are millions of years old. It is still not known, however, whether these bacteria are dormant organisms that are themselves millions of years old or whether the salt crystals merely provide a habitat in which contemporary microorganisms can grow, perhaps interspersed with relatively short periods of dormancy (McGenity et al. 2000). Vreeland, Rosenzweig and Powers (2000) have recently reported the isolation and growth of a halotolerant spore-forming Bacillus species from a brine inclusion within a 250-Myr-old salt crystal from the Permian Salado Formation in New Mexico. This bacterium, Bacillus strain 2-9-3, was informally christened Bacillus permians, and a 16S ribosomal RNA gene was sequenced and deposited in GenBank under the name B. permians (accession number AF166093). It has been claimed that B. permians was trapped inside the salt crystal 250 MYA and survived within the crystal until the present, most probably as a spore. Serious doubts have been raised concerning the possibility of spore survival for 250 Myr (Tomas Lindahl, personal communication), mostly because spores contain no active DNA repair enzymes, so the DNA is expected to decay into small fragments due to such factors as the natural radioactive radiation in the soil, and the bacterium is expected to lose its viability within at most several hundred years (Lindahl 1993). In this note, we apply theproof-of-the-pudding-is-in-the-eating principle to test whether the newly reported B. permians 16S ribosomal RNA gene sequence is ancient or not. There are several reasons to doubt the antiquity of B. permians. The first concerns the extraordinary similarity of its 16S rRNA gene sequence to that of Bacillus marismortui. Bacillus marismortui was described by Arahal et al. (1999) as a moderately halophilic species from the Dead Sea and was later renamed Salibacillus marismortui (Arahal et al. 2000). The B. permians sequence differs from that of S. marismortui by only one transition and one transversion out of the 1,555 aligned and unambiguously determined nucleotides. In comparison, the 16S rRNA gene from Staphylococcus succinus, which was claimed to be ‘‘25–35 million years old’’ (Lambert et al. 1998), differs from its homolog in its closest present-day relative (a urinary pathogen called Staphylococcus saprophyticus) by 19 substitutions out of 1,525 aligned nucleotides. Using Kimura’s (1980) two-parameter model, the difference between the B. permians and S. marismortui sequences translates into 1.3
Incidence of Retinopathy and Nephropathy in Youth-Onset Compared With Adult-Onset Type 2 Diabetes
Authors: Jonathan Krakoff, Robert S. Lindsay, Helen C. Looker, Robert G. Nelson, Robert L. Hanson, William C. Knowler
Journal: Diabetes Care (2003)

OBJECTIVE—To examine the risk of retinopathy and nephropathy in participants in whom type 2 diabetes was diagnosed in youth (before 20 years of age) compared with those in whom type 2 diabetes was diagnosed at older ages. RESEARCH DESIGN AND METHODS—Subjects in whom youth-onset or adult-onset diabetes was diagnosed in the longitudinal study of health in the Pima Indians of Arizona were followed for microvascular complications. Diabetes was diagnosed in 178 subjects before 20 years of age (youth), in 1,359 subjects at 20–39 years of age (younger adults), and in 971 subjects at 40–59 years of age (older adults). Incidence rates of diabetic retinopathy diagnosed by direct ophthalmoscopy through dilated pupils and nephropathy (protein-to-creatinine ratio ≥0.5 g/g) were calculated by age at diagnosis. RESULTS—Over 25 years, nephropathy developed in 35 of the participants with youth-onset type 2 diabetes; this incidence rate was not significantly different from that in patients with adult-onset diabetes (P = 0.77). Incidence rates of retinopathy, however, were significantly lower for the youth-onset group (P = 0.007). Adjusted for sex, glycemia, and blood pressure, risk of retinopathy was lower in patients with youth-onset diabetes than in those with adult-onset diabetes (hazard rate ratio [HRR] 0.42, 95% CI 0.24–0.74, P = 0.003), but risk of nephropathy was not different (HRR 1.2, 95% CI 0.77–1.3, P = 0.38). CONCLUSIONS—In Pima Indians, the risk of nephropathy as a function of duration of diabetes is similar in all age groups. By contrast, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes.
JEvTrace: refinement and variations of the evolutionary trace in JAVA
Authors: Marcin P Joachimiak, Fred E Cohen
Journal: Genome biology (2002)

Details of functional speciation within gene families can be difficult to identify using standard multiple sequence alignment (MSA) methods. The evolutionary trace (ET) was developed as a visualization tool to combine MSA, phylogenetic and structural data for identification of functional sites in proteins. The method has been successful in extracting evolutionary details of functional surfaces in a number of biological systems and modifications of the method are useful in creating hypotheses about the function of previously unannotated genes. We wish to facilitate the graphical interpretation of disparate data types through the creation of flexible software implementations.We have implemented the ET method in a JAVA graphical interface, JEvTrace. Users can analyze and visualize ET input and output with respect to protein phylogeny, sequence and structure. Function discovery with JEvTrace is demonstrated on two proteins with recently determined crystal structures: YlxR from Streptococcus pneumoniae with a predicted RNA-binding function, and a Haemophilus influenzae protein of unknown function, YbaK. To facilitate analysis and storage of results we propose a MSA coloring data structure. The sequence coloring format readily captures evolutionary, biological, functional and structural features of MSAs.Protein families and phylogeny represent complex data with statistical outliers and special cases. The JEvTrace implementation of the ET method allows detailed mining and graphical visualization of evolutionary sequence relationships.
Automated Phylogenetic Detection of Recombination Using a Genetic Algorithm
Authors: Sergei L. Kosakovsky Pond, David Posada, Michael B. Gravenor, Christopher H. Woelk, Simon D. W. Frost
Journal: Molecular Biology and Evolution (2006)

The evolution of homologous sequences affected by recombination or gene conversion cannot be adequately explained by a single phylogenetic tree. Many tree-based methods for sequence analysis, for example, those used for detecting sites evolving nonneutrally, have been shown to fail if such phylogenetic incongruity is ignored. However, it may be possible to propose several phylogenies that can correctly model the evolution of nonrecombinant fragments. We propose a model-based framework that uses a genetic algorithm to search a multiple-sequence alignment for putative recombination break points, quantifies the level of support for their locations, and identifies sequences or clades involved in putative recombination events. The software implementation can be run quickly and efficiently in a distributed computing environment, and various components of the methods can be chosen for computational expediency or statistical rigor. We evaluate the performance of the new method on simulated alignments and on an array of published benchmark data sets. Finally, we demonstrate that prescreening alignments with our method allows one to analyze recombinant sequences for positive selection.
NKT cells get specialized
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

NFATc1 self-promotes to build boneSelf-promotion is the way to get ahead during bone development, according to Asagiri and colleagues.They show on page 1261 that the inducible transcription factor NFATc1 must turn on its own expression for bone-resorbing osteoclasts to form.NFATc1 drives osteoclast-specific gene expression and is essential for the development of these cells in vitro.But whether NFATc1 is required in vivo was unknown, as deletion of the NFATc1 gene is lethal in mice.Another open questions was whether NFATc2-NFATc1's closest relative-can drive osteoclast formation in the absence of NFATc1.Asagiri and colleagues now show that NFATc1 is indeed essential for osteoclast formation in vivo, as only NFATc1-expressing stem cells rescued osteoclast development when transferred into osteoclast-deficient mice.NFATc1-deficient stem cells failed at this task, despite having normal expression of NFATc2.Transcriptional regulation explained why only NFATc1 could do the job.Stimulation of bone marrow cells with the osteoclast growth factor RANKL (receptor activator of NF-B ligand) caused the NFATc2 protein in the cellalong with RANKL-induced NF-B proteins-to pile onto the NFATc1 promoter at the expense of the NFATc2 promoter.This binding induced the expression of NFATc1, which then bound back to its own promoter, thus amplifying NFATc1 production.The NFATc1 promoter also hoarded histone acetylases, whose DNA modifications facilitate transcription.The authors are now analyzing the chromatin structure of the two promoters, which might help explain why these proteins avoid the NFATc2 promoter.
Small intestinal CD8+TCRγδ+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease
Authors: Govind Bhagat, Afzal J. Naiyer, Jayesh G. Shah, Jason Harper, Bana Jabri, Timothy C. Wang, Peter H.R. Green, John S. Manavalan
Journal: Journal of Clinical Investigation (2008)

Intraepithelial lymphocytes (IELs) bearing the gammadelta TCR are more abundant in the small intestinal mucosa of patients with celiac disease (CD) compared with healthy individuals. However, their role in disease pathogenesis is not well understood. Here, we investigated the functional attributes of TCRgammadelta+ IELs isolated from intestinal biopsies of patients with either active celiac disease (ACD) or those on a gluten-free diet (GFD). We found that compared with individuals with ACD, individuals on GFD have a higher frequency of CD8+TCRgammadelta+ IELs that express the inhibitory NK receptor NKG2A and intracellular TGF-beta1. TCR triggering as well as cross-linking of NKG2A increased both TGF-beta1 intracellular expression and secretion in vitro. Coculture of sorted TCRgammadelta+NKG2A+ IELs, IL-15-stimulated TCRalphabeta+ IELs, and HLA-E+ enterocytes resulted in a decreased percentage of cytotoxic CD8+TCRalphabeta+ IELs expressing intracellular IFN-gamma and granzyme-B and surface NKG2D. This inhibition was partially abrogated by blocking either TGF-beta alone or both NKG2A and HLA-E. Thus, our data indicate that suppression was at least partially mediated by TGF-beta secretion as a result of engagement of NKG2A with its ligand, HLA-E, on enterocytes and/or TCRalphabeta+ IELs. These findings demonstrate that human small intestinal CD8+TCRgammadelta+ IELs may have regulatory potential in celiac disease.
Postresection CA 19-9 Predicts Overall Survival in Patients With Pancreatic Cancer Treated With Adjuvant Chemoradiation: A Prospective Validation by RTOG 9704
Authors: Adam C. Berger, Miguel Garcia, John P. Hoffman, William F. Regine, Ross A. Abrams, Howard Safran, Andre Konski, Alan B. Benson, John MacDonald, Christopher G. Willett
Journal: Journal of Clinical Oncology (2008)

Purpose CA 19-9 is an important tumor marker in patients with pancreatic adenocarcinoma. A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospective evaluation of the ability of postresectional CA 19-9 to predict survival. Methods CA 19-9 expression was analyzed as a dichotomized variable (&lt; 180 v ≥ 180) or (≤ 90 v &gt; 90). Cox proportional hazards models were utilized to identify the impact of CA 19-9 expression on overall survival (OS). Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results Three hundred eighty-five patients patients had assessable CA 19-9 levels. The majority had a CA 19-9 level lower than 180 or ≤ 90 (n = 220 and 200, respectively), while 34% were Lewis Antigen negative and 33 (9%) and 53 (14%) patients had levels higher than 180 and higher than 90. When CA 19-9 was analyzed as a dichotomized variable, there was a significant survival difference favoring patients with CA 19-9 lower than 180 (hazard ratio [HR], 3.53; P &lt; .0001). This corresponds to a 72% reduction in the risk of death for patients with a CA 19-9 lower than 180. This was also true for patients with CA 19-9 ≤ 90 (HR, 3.4; P &lt; .0001). Multivariate analyses confirmed that CA 19-9, when analyzed as both a continuous and a dichotomized variable, is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusion To our knowledge, this is the first phase III trial to perform prospective analysis of CA 19-9 levels in patients treated with adjuvant chemoradiotherapy. It definitively confirms the prognostic importance of postresectional CA 19-9 levels after surgery with curative intent in patients with pancreatic cancer.
Technology Evolution: Is It Survival of the Fittest?
Authors: Anthony Zietman, Michael Goitein, Joel E. Tepper
Journal: Journal of Clinical Oncology (2010)

New technologies are constantly being developed and introduced into medical practice. Their potential or actual use raises questions of efficacy and cost. All too often financial considerations of profit primarily determine whether a technology will be adopted. In an era in which the need to control costs has become clear, this situation is undesirable. The assessment of efficacy can, however, be very difficult, and the control of financial aspects is likewise problematic. In this article, we address these problems and suggest potential solutions, using proton radiotherapy as an example that may be relevant to the development of other medical devices.
Risk-Directed Treatment Intensification Significantly Reduces the Risk of Relapse Among Children and Adolescents With Acute Lymphoblastic Leukemia and Intrachromosomal Amplification of Chromosome 21: A Comparison of the MRC ALL97/99 and UKALL2003 Trials
Authors: Anthony V. Moorman, Hazel Robinson, Claire Schwab, Sue M. Richards, Jeremy Hancock, Christopher D. Mitchell, Nicholas Goulden, Ajay Vora, Christine J. Harrison
Journal: Journal of Clinical Oncology (2013)

To evaluate the effect on outcome of intensifying therapy for patients with acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21).We report two cohorts of patients treated on Medical Research Council ALL97 or United Kingdom (UK) ALL2003. iAMP21 was identified retrospectively in ALL97 and was not used to guide therapy. However, in UKALL2003, iAMP21 was determined prospectively, and patients were allocated to the most intensive treatment arm (regimen C), which included augmented Berlin-Frankfurt-Munster consolidation, escalating Capizzi maintenance, double delayed intensification, and an option for first remission transplantation. The presence of iAMP21 was determined by fluorescence in situ hybridization using probes specific for the RUNX1 gene.iAMP21 was identified in 2% of patients with B-cell precursor ALL treated on UKALL2003 and ALL97. The event-free survival, relapse, and overall survival rates at 5 years for iAMP21 patients treated on ALL97 and UKALL2003 were 29% and 78%, 70% and 16%, and 67% and 89%, respectively (all P < .01). Patients treated on ALL97 had an increased risk of relapse compared with patients treated on UKALL2003 (hazard ratio, 7.2; 95% CI, 2.91 to 17.87; P < .001).iAMP21 patients with ALL benefitted from receiving more intensive therapy in UKALL2003. In UKALL2011, they will continue to be treated as cytogenetic high risk, receive intensive chemotherapy (regimen C), and will only be recommended for transplantation if they do not achieve a complete remission by the end of induction therapy. This study illustrates how the discovery and characterization of disease-specific genetic aberrations can be used to tailor therapy more precisely.
Common Genetic Variation in <i>ABCA1</i> Is Associated With Altered Lipoprotein Levels and a Modified Risk for Coronary Artery Disease
Authors: Susanne M. Clee, Aeilko H. Zwinderman, James C. Engert, Karin Y. Zwarts, Henri O. F. Molhuizen, Kirsten Roomp, J. Wouter Jukema, Michel van Wijland, Marjel van Dam, Thomas J. Hudson, Angela Brooks-Wilson, Jacques Genest, John J. P. Kastelein, Michael R. Hayden
Journal: Circulation (2001)

Background —Low plasma HDL cholesterol (HDL-C) is associated with an increased risk of coronary artery disease (CAD). We recently identified the ATP-binding cassette transporter 1 ( ABCA1 ) as the major gene underlying the HDL deficiency associated with reduced cholesterol efflux. Mutations within the ABCA1 gene are associated with decreased HDL-C, increased triglycerides, and an increased risk of CAD. However, the extent to which common variation within this gene influences plasma lipid levels and CAD in the general population is unknown. Methods and Results —We examined the phenotypic effects of single nucleotide polymorphisms in the coding region of ABCA1 . The R219K variant has a carrier frequency of 46% in Europeans. Carriers have a reduced severity of CAD, decreased focal (minimum obstruction diameter 1.81±0.35 versus 1.73±0.35 mm in noncarriers, P =0.001) and diffuse atherosclerosis (mean segment diameter 2.77±0.37 versus 2.70±0.37 mm, P =0.005), and fewer coronary events (50% versus 59%, P =0.02). Atherosclerosis progresses more slowly in carriers of R219K than in noncarriers. Carriers have decreased triglyceride levels (1.42±0.49 versus 1.84±0.77 mmol/L, P =0.001) and a trend toward increased HDL-C (0.91±0.22 versus 0.88±0.20 mmol/L, P =0.12). Other single nucleotide polymorphisms in the coding region had milder effects on plasma lipids and atherosclerosis. Conclusions —These data suggest that common variation in ABCA1 significantly influences plasma lipid levels and the severity of CAD.
Amygdala-Hippocampal Volume and the Phenotypic Heterogeneity of Posttraumatic Stress Disorder
Authors: Robert H. Pietrzak, Lynnette A. Averill, Chadi G. Abdallah, Alexander Neumeister, John H. Krystal, Ifat Levy, Ilan Harpaz-Rotem
Journal: JAMA Psychiatry (2015)
CD8 T cell memory in B cell-deficient mice.
Authors: M S Asano, R Ahmed
Journal: The Journal of Experimental Medicine (1996)

Antigen presentation by B cells and persistence of antigen-antibody complexes on follicular dendritic cells (FDC) have been implicated in sustaining T cell memory. In this study we have examined the role of B cells and antibody in the generation and maintenance of CD8+ cytotoxic T lymphocyte (CTL) memory. To address this issue we compared CTL responses to lymphocytic choriomeningitis virus (LCMV) in normal (+/+) versus B cell-deficient mice. The CTL response to acute LCMV infection can be broken down into three distinct phases: (a) the initial phase (days 3-8 after infection) of antigen-driven expansion of virus-specific CD8+ T cells and the development of effector CTL (i.e., direct ex vivo killers); (b) a phase of death (between days 10 and 30 after infection) during which &amp;gt;95% of the virus-specific CTL die and the direct effector activity subsides; and (c) the phase of long-term memory (after day 30) that is characterized by a stable pool of memory CTL that persist for the life span of the animal. The role of B cells in each of these three phases of the CTL response was analyzed. We found that B cells were not required for the expansion and activation of virus-specific CTL. The kinetics and magnitude of the effector CTL response, as measured by direct killing of infected targets by ex vivo isolated splenocytes, was identical in B cell-deficient and +/+ mice. Also, the expansion of CD8+ T cells was not affected by the absence of B cells and/or antibody; in both groups of mice there was an approximately 10,000-fold increase in the number of LCMV-specific CTL and a greater than 10-fold increase in the total number of activated (CD44hi) CD8+ T cells during the first week after virus infection. Although no differences were seen during the "expansion" phase, we found that the "death" phase was more pronounced in B cell-deficient mice. However, this increased cell death was not selective for LCMV-specific CTL, and during this period the total number of CD8+ T cells also dropped substantially more in B cell-deficient mice. As a result of this, the absolute numbers of LCMV-specific CTL were lower in B cell-deficient mice but the frequencies were comparable in both groups of mice. More significantly, the memory phase of the CTL response was not affected by the absence of B cells and a stable number of LCMV-specific CTL persisted in B cell-deficient mice for up to 6 mo. Upon reinfection, B cell-deficient mice that had resolved an acute LCMV infection were able to make accelerated CTL responses in vivo and eliminated virus more efficiently than naive B cell-deficient mice. Thus, CTL memory, as assessed by frequency of virus-specific CTL or protective immunity, does not decline in the absence of B cells. Taken together, these results show that neither B cells nor antigen-antibody complexes are essential for the maintenance of CD8+ CTL memory.
Book Review Psychiatric Epidemiology: Assessment Concepts and Methods (The Johns Hopkins Series in Psychiatry and Neuroscience.) Edited by Juan E. Mezzich, Miguel R. Jorge, and Ihsan M. Salloum. 612 pp. Baltimore, Johns Hopkins University Press, 1994. $65. 0-8018-4615-3
Authors: M.R. Eastwood
Journal: New England Journal of Medicine (1994)
Cardiogenic shock after primary percutaneous coronary intervention: Effects of levosimendan compared with dobutamine on haemodynamics
Authors: Martín J. García‐González, Alberto Domínguez‐Rodríguez, Julio J. Ferrer‐Hita, Pedro Abreu‐González, Miguel Bethencourt Muñoz
Journal: European Journal of Heart Failure (2006)
Cutaneous manifestation of disseminated infection by Mycobacterium fortuitum biovariant “third group”
Authors: Sergio A. Lazo-de-la-Vega, Hugo E. Pezzarossi, Samuel Ponce-de-León, José Sifuentes, Guillermo M. Ruiz-Palacios
Journal: Journal of the American Academy of Dermatology (1987)