tbuckley/cabot-search huggingface dataset:
Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease
Authors: Katharina Lahl, Christoph Loddenkemper, Cathy Drouin, Jennifer Freyer, Jon Arnason, Gérard Eberl, Alf Hamann, Hermann Wagner, Jochen Huehn, Tim Sparwasser
Journal: The Journal of Experimental Medicine (2007)

The scurfy mutant mouse strain suffers from a fatal lymphoproliferative disease leading to early death within 3-4 wk of age. A frame-shift mutation of the forkhead box transcription factor Foxp3 has been identified as the molecular cause of this multiorgan autoimmune disease. Foxp3 is a central control element in the development and function of regulatory T cells (T reg cells), which are necessary for the maintenance of self-tolerance. However, it is unclear whether dysfunction or a lack of T reg cells is etiologically involved in scurfy pathogenesis and its human correlate, the IPEX syndrome. We describe the generation of bacterial artificial chromosome-transgenic mice termed "depletion of regulatory T cell" (DEREG) mice expressing a diphtheria toxin (DT) receptor-enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus, allowing selective and efficient depletion of Foxp3+ T reg cells by DT injection. Ablation of Foxp3+ T reg cells in newborn DEREG mice led to the development of scurfy-like symptoms with splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation. Thus, these data provide experimental evidence that the absence of Foxp3+ T reg cells is indeed sufficient to induce a scurfy-like phenotype. Furthermore, DEREG mice will allow a more precise definition of the function of Foxp3+ T reg cells in immune reactions in vivo.
Constitutive β-Catenin Activation Induces Male-Specific Tumorigenesis in the Bladder Urothelium
Authors: Congxing Lin, Yan Yin, Kristina Stemler, Peter Humphrey, Adam S. Kibel, Indira U. Mysorekar, Liang Ma
Journal: Cancer Research (2013)

Abstract The incidence for bladder urothelial carcinoma, a common malignancy of the urinary tract, is about three times higher in men than in women. Although this gender difference has been primarily attributed to differential exposures, it is likely that underlying biologic causes contribute to the gender inequality. In this study, we report a transgenic mouse bladder tumor model upon induction of constitutively activated β-catenin signaling in the adult urothelium. We showed that the histopathology of the tumors observed in our model closely resembled that of the human low-grade urothelial carcinoma. In addition, we provided evidence supporting the KRT5-positive;KRT7-negative (KRT5+; KRT7−) basal cells as the putative cells-of-origin for β-catenin–induced luminal tumor. Intriguingly, the tumorigenesis in this model showed a marked difference between opposite sexes; 40% of males developed macroscopically detectable luminal tumors in 12 weeks, whereas only 3% of females developed tumors. We investigated the mechanisms underlying this sexual dimorphism in pathogenesis and showed that nuclear translocation of the androgen receptor (AR) in the urothelial cells is a critical mechanism contributing to tumor development in male mice. Finally, we carried out global gene profiling experiments and defined the molecular signature for the β-catenin–induced tumorigenesis in males. Altogether, we have established a model for investigating sexual dimorphism in urothelial carcinoma development, and implicated synergy between β-catenin signaling and androgen/AR signaling in carcinogenesis of the basal urothelial cells. Cancer Res; 73(19); 5914–25. ©2013 AACR.
Glioblastoma Multiforme Metastasis Outside the CNS: Three Case Reports and Possible Mechanisms of Escape
Authors: Jackson D. Hamilton, Marion Rapp, Timo Marcel Schneiderhan, Michael Sabel, Anne Hayman, Axel Scherer, Patric Kröpil, Wilfried Budach, Usha Kretschmar, Peter Arne Gerber, Sujit Prabhu, Lawrence E. Ginsberg, Edwin Bölke, Christiane Matuschek
Journal: Journal of Clinical Oncology (2014)
Randomized Phase II/III Trial Assessing Gemcitabine/ Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy: Phase II—Results of EORTC Study 30986
Authors: Maria De Santis, Joaquim Bellmunt, Graham Mead, J. Martijn Kerst, Michael Leahy, Pablo Maroto, Iwona Skoneczna, Sandrine Marreaud, Ronald de Wit, Richard Sylvester
Journal: Journal of Clinical Oncology (2009)

There is no standard treatment for patients with advanced urothelial cancer who are ineligible ("unfit") for cisplatin-based chemotherapy (CHT). To compare the activity and safety of two CHT combinations in this patient group, a randomized phase II/III trial was conducted by the EORTC (European Organisation for Research and Treatment of Cancer). We report here the phase II results of the study.CHT-naïve patients with measurable disease and impaired renal function (30 mL/min < glomerular filtration rate [GFR] < 60 mL/min) and/or performance status (PS) 2 were randomly assigned to receive either GC (gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin area under the serum concentration-time curve [AUC] 4.5) for 21 days or M-CAVI (methotrexate 30 mg/m(2) on days 1, 15, and 22; carboplatin AUC 4.5 on day 1; and vinblastine 3 mg/m(2) on days 1, 15, and 22) for 28 days. End points of response and severe acute toxicity (SAT) were evaluated with respect to treatment group, renal function, PS, and Bajorin risk groups.Three of 178 patients who were ineligible or did not start treatment were excluded. SAT was reported in 13.6% of patients on GC and in 23% on M-CAVI. Overall response rates were 42% (37 of 88) for GC and 30% (26 of 87) for M-CAVI. Patients with PS 2 and GFR less than 60 mL/min and patients in Bajorin risk group 2 showed a response rate of only 26% and 20% and an SAT rate of 26% and 25%, respectively.Both combinations are active in this group of unfit patients. However, patients with PS 2 and GFR less than 60 mL/min do not benefit from combination CHT. Alternative treatment modalities should be sought in this subgroup of poor-risk patients.
MRSA as a cause of community-acquired pneumonia
Authors: A Nakou, M Woodhead, A Torres
Journal: European Respiratory Journal (2009)

taphylococcus aureus is a species of bacterium that can cause a broad variety of infections, ranging from minor skin infections to severe pneumonia and sepsis.The genetic adaptation of S. aureus has led to a multidrug-resistant pathogen, meticillin-resistant S. aureus (MRSA) after the introduction of meticillin (previously methicillin) into clinical practice in the 1960s [1].MRSA is resistant to b-lactam antibiotics, including penicillin and cephalosporins.Resistance is mediated by penicillin binding protein 2a, a penicillin binding protein encoded by the mecA gene that permits growth in the presence of meticillin.The mecA gene is situated in the staphylococcal cassette chromosome SCCmec.Initially, MRSA was only a nosocomial pathogen, i.e. healthcare-associated MRSA.It is associated with severe invasive disease [2] and tends to have multidrug resistance.It carries SCC chromosome type II (SCCmec type II) [3].
Case of Recurrent Typhlitis; Removal of Diseased Vermiform Appendix; Recovery
Authors: T. P. Teale
Journal: BMJ (1891)

only three children were examined, their ages being 3, 4, and 5 respectively.In the child of 3 years both tubes mieasured 3 centimotres in lengtlh, in that of 4 years both were 4 centi- mUtres in lengthl, but in that of 5 years the right measured 6 centimotres and tle left tube 5 centimetres.Tle tlickness of the tube at the ampulla measured 3, 4, and 5 millimetres re- spectively in the thlree children.The isthmus measured 1 nillimetre in the two younger cllildreni, and 2 millihrnitres in the older child.In all the tlhree the ostiunii abdominlale mneasured 1 millimntre in diameter.The ovariani fimbria measured 5 millimitres in the youngest chlild, and 10 inilli- metres in the other twvo.The interspace, wllichi was smootl, mneasured 5 millimC4res in the two younger, an-d 9 millimktres in the older child.II these chlildreni the isthmus was straiglit in two, and slightly wavy in the tlhird* the ampulla slhowed the same twists as in the infants, and the filmbri4e were in these children, as also in the fcetuses anid infanits, ill-developed and scantily clothed.I'ndler the microscope cilia on the
Peopling of the Americas, founded by four major lineages of mitochondrial DNA.
Authors: S Horai, R Kondo, Y Nakagawa-Hattori, S Hayashi, S Sonoda, K Tajima
Journal: Molecular Biology and Evolution (1993)

Nucleotide sequence analysis of the major noncoding region of human mitochondrial DNA from various races was extended with 72 Native Americans from 16 different local populations (nine populations from Chile, four from Colombia, and one each from Brazil and from Maya and Apache Indians). The sequences were determined directly from the polymerase chain reaction products. On the basis of a comparison of the 482-bp sequences in the 72 Native Americans, 43 different types of mitochondrial DNA sequences were observed. The nucleotide diversity within the Native Americans was estimated to be 1.29%, which is slightly less than the value of 1.44% from the total human population including Africans, Europeans, and Asians. Phylogenetic analysis revealed that most Native American lineages are classified into four major distinct clusters. Individuals belonging to each cluster share at least two specific polymorphic sites that are nearly absent in other human populations, indicating a unique phylogenetic position of Native Americans. A phylogenetic tree of 193 individuals including Africans, Europeans, Asians, and Native Americans indicated that the four Native American clusters are distinct and dispersed in the tree. These clusters almost exclusively consist of Native Americans--with only a few Asians, if any. We postulate that four ancestral populations gave rise to different waves of migration to the New World. From the estimated coalescence time of the Asian and Native American lineages, we infer that the first migration across the Bering landbridge took place approximately 14,000-21,000 years ago. Furthermore, sequence differences in all pairwise comparisons of Native Americans showed a bimodal distribution that is significantly different from Poisson. These results suggest that the ancestral Native American population underwent neither a severe bottleneck nor rapid expansion in population size, during the migration of people into the Americas.
The effect of adipose tissue derived MSCs delivered by a chemically defined carrier on full-thickness cutaneous wound healing
Authors: Dongsheng Jiang, Yu Qi, Nathan G. Walker, Anca Sindrilaru, Adelheid Hainzl, Meinhard Wlaschek, Sheila MacNeil, Karin Scharffetter-Kochanek
Journal: Biomaterials (2013)
Impaired Sphingolipid Synthesis in the Respiratory Tract Induces Airway Hyperreactivity
Authors: Tilla S. Worgall, Arul Veerappan, Biin Sung, Benjamin I. Kim, Evan Weiner, Reshma Bholah, Randi B. Silver, Xian-Cheng Jiang, Stefan Worgall
Journal: Science Translational Medicine (2013)

Decreased activity of serine palmitoyl-CoA transferase is associated with asthma.
Serum Adiponectin and Progression of Diabetic Nephropathy in Patients With Type 1 Diabetes
Authors: Markku Saraheimo, Carol Forsblom, Lena Thorn, Johan Wadén, Milla Rosengård-Bärlund, Outi Heikkilä, Kustaa Hietala, Daniel Gordin, Jan Frystyk, Allan Flyvbjerg, Per-Henrik Groop
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this study was to elucidate whether serum adiponectin is associated with progression of diabetic nephropathy in type 1 diabetic patients. RESEARCH DESIGN AND METHODS—This was a prospective follow-up study as a part of the nationwide Finnish Diabetic Nephropathy Study; 1,330 type 1 diabetic patients were followed for 5.0 ± 2.2 years. Patients were divided at baseline into three groups according to their urinary albumin excretion rate (AER) in three consecutive overnight or 24-h urine collections: 818 patients with normoalbuminuria (AER &amp;lt;20 μg/min), 216 patients with microalbuminuria (20 μg/min ≤ AER &amp;lt; 200 μg/min), and 296 patients with macroalbuminuria (AER ≥200 μg/min). Progression of albuminuria was the main outcome. Adiponectin was measured by a time-resolved immunofluorometric assay, and the values were log-transformed and adjusted for age, BMI, and sex before analysis. RESULTS—Progression either to the next albuminuria level or to end-stage renal disease (ESRD) occurred in 193 patients. No difference in adiponectin concentrations was observed between progressors and nonprogressors in patients with normoalbuminuria or microalbuminuria. In the patients with macroalbuminuria, progression to ESRD was associated with higher adiponectin in the entire group (23.4 ± 17.1 vs. 16.0 ± 8.5 mg/l, P &amp;lt; 0.001) and in men (P &amp;lt; 0.001) and women (P &amp;lt; 0.001) separately. Progression to ESRD was also associated with systolic blood pressure, insulin dose, A1C, serum cholesterol, serum triglycerides, AER, and estimated glomerular filtration rate (eGFR). When these covariates were inserted in a Cox regression analysis, A1C, triglycerides, eGFR, and adiponectin were significantly associated with progression from macroalbuminuria. CONCLUSIONS—Increased serum adiponectin levels predict the progression from macroalbuminuria to ESRD in type 1 diabetic patients.
Consideration of the linguistic characteristics of letters makes the universal model of reading more universal
Authors: Kyungil Kim, Chang H. Lee, Yoonhyoung Lee
Journal: Behavioral and Brain Sciences (2012)

Abstract We suggest that the linguistic characteristics of letters also need to be considered to fully understand how a reader processes printed words. For example, studies in Korean showed that unambiguity in the assignment of letters to their appropriate onset, vowel, or coda slot is one of the main sources of the letter-transposition effect. Indeed, the cognitive system that processes Korean is tuned to the structure of the Korean writing system.
Early-Stage, Lymphocyte-Predominant Hodgkin's Lymphoma: Patient Outcomes From a Large, Single-Institution Series With Long Follow-Up
Authors: Ronald C. Chen, Michael S. Chin, Andrea K. Ng, Yang Feng, Donna Neuberg, Barbara Silver, Geraldine S. Pinkus, Mary Ann Stevenson, Peter M. Mauch
Journal: Journal of Clinical Oncology (2009)

Purpose The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution. Patients and Methods The study population includes 113 patients with stage I or II LPHL treated between 1970 and 2005. Pathologic diagnosis for all patients was confirmed using standard criteria. Ninety-three patients received radiation therapy (RT) alone, 13 received RT with chemotherapy, and seven received chemotherapy alone. Among patients treated with RT, 25 received limited-field, 35 received regional-field, and 46 received extended-field RT. Results Median follow-up was 136 months. Ten-year progression-free survival (PFS) rates were 85% (stage I) and 61% (stage II); overall survival (OS) rates were 94% and 97% for stages I and II, respectively. PFS and OS did not differ among patients who received limited-field, regional-field, or extended-field RT. In contrast, six of seven patients who received chemotherapy alone without RT developed early disease progression and required salvage treatment. Multivariable analysis adjusting for extent of RT, clinical stage, sex, and use of chemotherapy confirmed that the extent of RT was not significantly associated with PFS (P = .67) or OS (P = .99). The addition of chemotherapy to RT did not improve PFS or OS compared with RT alone. Conclusion RT alone leads to sustained disease control and high long-term survival rates in patients with early-stage LPHL. This study supports the use of limited-field RT alone to treat this disease.
Dissociation of Microangiopathy and Macroangiopathy in Patients With Type 2 Diabetes
Authors: Maki Yamamoto, Genshi Egusa, Masamichi Okubo, Michio Yamakido
Journal: Diabetes Care (1998)

OBJECTIVE Although persistent hyperglycemia contributes greatly to the progression of diabetic micro- and macroangiopathy, microangiopathy progresses more rapidly than macroangiopathy in some type 2 diabetic patients, with the opposite being true in others. This study was conducted to identify factors responsible for such dissociation. RESEARCH DESIGN AND METHODS Patients with proliferative diabetic retinopathy and a carotid intima-media thickness (IMT) level ≤1.0 mm were classified as the microangiopathy group (MIG); those with an IMT level &amp;gt;1.1 mm and without retinopathy or with background retinopathy were assigned to the macroangiopathy group (MAG). Only middle-aged patients, 50–69 years old, were included in this study. There were 54 patients in the MIG and 68 patients in the MAG. RESULTS Patients in the MIG were significantly younger at the onset of diabetes, and those in the MAG had a significantly higher mean ratio of apoprotein (apo) B to apoAI. The percentage of patients with a family history of diabetes was significantly higher in the MIG. Maternal inheritance was common among these patients. Those with obesity, a family history of diabetes, and younger onset of hypertension were more common in the MAG. In the multiple logistic regression analyses, maternal inheritance and early onset of diabetes were independent risk factors for the acceleration of microangiopathy. A personal history of obesity and a family history of hypertension were independently related to the development of macroangiopathy. CONCLUSIONS Our results suggest that patients with early onset and maternal inheritance of diabetes may have a high risk for the progression of diabetic microangiopathy, while patients with hyperlipidemia, a history of obesity, and a family history of hypertension seem prone to the development of atherosclerosis.
Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.
Authors: K Beldjord, C Beldjord, E Macintyre, P Even, F Sigaux
Journal: The Journal of Experimental Medicine (1993)

To characterize the T cell receptor (TCR) repertoire expressed by the V delta 1+ gamma/delta T cell population, we have studied the V delta 1-J delta 1 junctional sequences from peripheral blood samples of healthy donors. We show that, surprisingly, this repertoire is restricted in most healthy adults, with a donor-specific and relatively stable pattern, whereas this repertoire remains unrestricted in infants, and is similar to that of thymocytes. These data contrast with the general assumption that the junctional repertoire of V delta 1+ gamma/delta T cells is extensive, and strongly suggest that peripheral recruitment of V delta 1+ cells bearing particular TCR occurs in humans during the postnatal stage.
Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later
Authors: Philippe Eggimann, Didier Pittet
Journal: Intensive Care Medicine (2014)

For decades, clinicians dealing with immunocompromised and critically ill patients have perceived a link between Candida colonization and subsequent infection. However, the pathophysiological progression from colonization to infection was clearly established only through the formal description of the colonization index (CI) in critically ill patients. Unfortunately, the literature reflects intense confusion about the pathophysiology of invasive candidiasis and specific associated risk factors.We review the contribution of the CI in the field of Candida infection and its development in the 20 years following its original description in 1994. The development of the CI enabled an improved understanding of the pathogenesis of invasive candidiasis and the use of targeted empirical antifungal therapy in subgroups of patients at increased risk for infection.The recognition of specific characteristics among underlying conditions, such as neutropenia, solid organ transplantation, and surgical and nonsurgical critical illness, has enabled the description of distinct epidemiological patterns in the development of invasive candidiasis.Despite its limited bedside practicality and before confirmation of potentially more accurate predictors, such as specific biomarkers, the CI remains an important way to characterize the dynamics of colonization, which increases early in patients who develop invasive candidiasis.
Identification of two distinct allergenic sites on ryegrass-pollen allergen, Lol p IV
Authors: Kuldeep S. Jaggi, Abul K.M. Ekramoddoullah, Fred T. Kisil, Jacquie M.M. Dzuba-Fischer, Edward S. Rector, Alec H. Sehon
Journal: Journal of Allergy and Clinical Immunology (1989)
European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus group (EGCCCG): Part I
Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl, Johannes Classen, Christoph Clemm, Gabriella Cohn-Cedermark, Stéphane Culine, Gedske Daugaard, Pieter H.M. De Mulder, Maria De Santis, Maike de Wit, Ronald de Wit, Hans Günter Derigs, Klaus-Peter Dieckmann, Annette Dieing, Jean-Pierre Droz, Martin Fenner, Karim Fizazi, Aude Flechon, Sophie D. Fosså, Xavier Garcia del Muro, Thomas Gauler, Lajos Geczi, Arthur Gerl, Jose Ramon Germa-Lluch, Silke Gillessen, Jörg T. Hartmann, Michael Hartmann, Axel Heidenreich, Wolfgang Hoeltl, Alan Horwich, Robert Huddart, Michael Jewett, Johnathan Joffe, William G. Jones, László Kisbenedek, Olbjørn Klepp, Sabine Kliesch, Kai Uwe Koehrmann, Christian Kollmannsberger, Markus Kuczyk, Pilar Laguna, Oscar Leiva Galvis, Volker Loy, Malcolm D. Mason, Graham M. Mead, Rolf Mueller, Craig Nichols, Nicola Nicolai, Tim Oliver, Dalibor Ondrus, Gosse O.N. Oosterhof, Luis Paz Ares, Giorgio Pizzocaro, Jörg Pont, Tobias Pottek, Tom Powles, Oliver Rick, Giovanni Rosti, Roberto Salvioni, Jutta Scheiderbauer, Hans-Ulrich Schmelz, Heinz Schmidberger, Hans-Joachim Schmoll, Mark Schrader, Felix Sedlmayer, Niels E. Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase
Journal: European Urology (2008)