tbuckley/cabot-search huggingface dataset:
IRF-1 regulates alternative mRNA splicing of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in breast epithelial cells generating an immunoreceptor tyrosine-based inhibition motif (ITIM) containing isoform
Authors: Kenneth J Dery, Maciej Kujawski, David Grunert, Xiwei Wu, Tung Ngyuen, Celeste Cheung, John H Yim, John E Shively
Journal: Molecular Cancer (2014)

Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-γ induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter. CEACAM1 pre-mRNA undergoes extensive alternative splicing (AS) generating isoforms to produce either a short (S) cytoplasmic domain expressed primarily in epithelial cells or as an ITIM-containing long (L) isoform in immune cells. The transcriptional and molecular mechanism of CEACAM1 minigenes AS containing promoter ISREs mutations in the breast epithelial, MDA-MB-468, cell line was detected using flow cytometry. In addition, transcriptome sequencing was utilized to determine whether IRF-1 could direct the AS of other genes as well. Tumor xenografts were used to evaluate CEACAM1 isoform expression on the leading edge of breast tumor cells. In the present study, we provide evidence that CEACAM1's promoter and variable exon 7 cross-talk allowing IRF-1 to direct AS events. Transcriptome sequencing shows that IRF-1 can also induce the global AS of genes involved in regulation of growth and differentiation as well as genes of the cytokine family. Furthermore, MDA-MB-468 cells grown as tumor xenografts exhibit an AS switch to the L-isoform of CEACAM1, demonstrating that an in vivo inflammatory milieu is also capable of generating the AS switch, similar to that found in human breast cancers Mol Cancer 7:46, 2008. The novel AS regulatory activities attributed to IRF-1 indicate that the IFN-γ response involves a global change in both gene transcription and AS in breast epithelial cells.
CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens
Authors: Dalam Ly, Anne G. Kasmar, Tan-Yun Cheng, Annemieke de Jong, Shouxiong Huang, Sobhan Roy, Apoorva Bhatt, Ruben P. van Summeren, John D. Altman, William R. Jacobs, Erin J. Adams, Adriaan J. Minnaard, Steven A. Porcelli, D. Branch Moody
Journal: The Journal of Experimental Medicine (2013)

CD1c is expressed with high density on human dendritic cells (DCs) and B cells, yet its antigen presentation functions are the least well understood among CD1 family members. Using a CD1c-reactive T cell line (DN6) to complete an organism-wide survey of M. tuberculosis lipids, we identified C32 phosphomycoketide (PM) as a previously unknown molecule and a CD1c-presented antigen. CD1c binding and presentation of mycoketide antigens absolutely required the unusual, mycobacteria-specific lipid branching patterns introduced by polyketide synthase 12 (pks12). Unexpectedly, one TCR responded to diversely glycosylated and unglycosylated forms of mycoketide when presented by DCs and B cells. Yet cell-free systems showed that recognition was mediated only by the deglycosylated phosphoantigen. These studies identify antigen processing of a natural bacterial antigen in the human CD1c system, indicating that cells act on glycolipids to generate a highly simplified neoepitope composed of a sugar-free phosphate anion. Using knowledge of this processed antigen, we generated human CD1c tetramers, and demonstrate that CD1c–PM complexes stain T cell receptors (TCRs), providing direct evidence for a ternary interaction among CD1c-lipid-TCR. Furthermore, PM-loaded CD1c tetramers detect fresh human T cells from peripheral blood, demonstrating a polyclonal response to PM antigens in humans ex vivo.
Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability
Authors: Gang Liu, Beenu Kaw, Jayson Kurfis, Syed Rahmanuddin, Yashpal S. Kanwar, Sumant S. Chugh
Journal: Journal of Clinical Investigation (2003)

Neph1-deficient mice develop nephrotic syndrome at birth, indicating the importance of this protein in the development of a normal glomerular filtration barrier. While the precise subcellular localization of Neph1 remains unknown, its relationship with other components of the glomerular filtration barrier is of great interest in this field. In this paper, we localize the expression of Neph1 to the glomerular slit diaphragm by immunogold electron microscopy in rodents and describe its direct interaction with two other components of the slit diaphragm, nephrin and ZO-1. Both native and recombinant Neph1 associate with each other as dimers and multimers and interact with nephrin via their extracellular segments. Disruption of the Neph1-nephrin interaction in vivo by injecting combinations of individual subnephritogenic doses of anti-Neph1 and anti-nephrin results in complement- and leukocyte-independent proteinuria with preserved foot processes. This disruption modestly reduces Neph1 and nephrin protein expression in podocytes and dramatically reduces ZO-1 protein expression via the interaction of ZO-1 PDZ domains with the cytoplasmic tail of Neph1, independent of changes in mRNA expression of all three genes. The interaction between nephrin and Neph1 is specific and not shared by either protein with P-cadherin, another integral slit diaphragm protein. The interaction between nephrin and Neph1 therefore appears to be an important determinant of glomerular permeability.
PHYSICAL, CHEMICAL, AND BIOLOGICAL STUDIES ON THE VIRUS OF VESICULAR STOMATITIS OF HORSES
Authors: Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1927)

A taxonomic study of the virus of vesicular stomatitis is presented along with evidence additional to that already reported(1) to show the similarity of this virus to that of foot-and-mouth disease. The connection of the two is discussed and the deduction drawn that their generic relationship is close. On the contrary, the differences between these two viruses and the herpetic are sufficiently marked to indicate a lack of generic connection among the three. The results of a comparative study on the effects of particular wave-lengths and energies of monochromatic ultra-violet light on the virus and on Staphylococcus aureus reveal that the adsorption of specific energies by the two is parallel. Since the adsorption of specific energies is an index of chemical character, these experiments suggest that the virus is similar in character and chemical constitution to bacterial protoplasm.
Engraftment and Differentiation of Human Metanephroi into Functional Mature Nephrons after Transplantation into Mice Is Accompanied by a Profile of Gene Expression Similar to Normal Human Kidney Development
Authors: Benjamin Dekel, Ninette Amariglio, Naftali Kaminski, Arnon Schwartz, Elinor Goshen, Fabian D. Arditti, Ilan Tsarfaty, Justen H. Passwell, Yair Reisner, Gideon Rechavi
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Metanephroi, the embryonic precursors of the adult kidney, can be induced in vivo to grow and develop. Despite their potential clinical utility for transplantation, the ability of human metanephroi to differentiate after transplantation into functional mature nephrons is mostly unknown. To address this, 70-d human metanephroi were transplanted into NOD/SCID mice; global gene expression patterns that underlie development of human metanephric transplants were analyzed and compared with normal human kidney development. In addition, functionality of the grafts was assessed by dimercaptosuccinic acid radioisotope scans at different times after transplantation. The results of hybridization to cDNA arrays when RNA was derived from normal human kidneys at 8, 12, 16, and 20 wk gestation demonstrated that a subset of 240 genes changed substantially with time. The induced genes can be classified as cell cycle regulators, transcription and growth factors, and signaling, transport, adhesion, and extracellular matrix molecules. Strikingly, clustering analysis of global gene expression at 2, 6, and 10 wk after metanephric transplantation revealed an expression profile that characterizes normal human kidney development. Moreover, maturation of the transplants was accompanied by an increased uptake of dimercaptosuccinic acid. Nevertheless, expression levels of specific genes were mostly found to be suppressed in the transplants compared with the normal kidneys. These data provide insights into human kidney development and support the possibility of the transplantability of human metanephroi. Understanding of the molecular regulation of the transplanted developing metanephroi might lead to the development of strategies aimed at increasing the levels of specific genes, nephron endowment, and graft function.
Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.
Authors: J J Peschon, P J Morrissey, K H Grabstein, F J Ramsdell, E Maraskovsky, B C Gliniak, L S Park, S F Ziegler, D E Williams, C B Ware, J D Meyer, B L Davison
Journal: The Journal of Experimental Medicine (1994)

Interleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.
A Case of Dislocation of the Sacrum
Authors: J. T. Jones
Journal: BMJ (1878)

TPhy#ician to the General Infirmary, Leeds.[IN-Acknowledglng-the honour of his election to-the presidential chair, Dr. Clifford Alltutt spoke with warm grtitude to the profession in Yorkshire for the kindly welcome which he received on coming to Leeds -nearly twenty years ago; and for the generous confidence and friendship extended to him from that time to the present.He spoke of the sense of brotherhood existing among the medical men in the neighbourhood, which he attributed to the example of those fathers of the profession who founded the Leeds Medical School.He said, con- tinuing.]" I-can never forget the admiration with which, on my first coming to Leeds and visiting the operating theatre of
Shared Decision Making and Use of Decision Aids for Localized Prostate Cancer
Authors: Elyn H. Wang, Cary P. Gross, Jon C. Tilburt, James B. Yu, Paul L. Nguyen, Marc C. Smaldone, Nilay D. Shah, Robert Abouassally, Maxine Sun, Simon P. Kim
Journal: JAMA Internal Medicine (2015)

The current attitudes of prostate cancer specialists toward decision aids and their use in clinical practice to facilitate shared decision making are poorly understood.OBJECTIVE To assess attitudes toward decision aids and their dissemination in clinical practice.
Short­burst oxygen immediately before and after exercise is ineffective in nonhypoxic COPD patients
Authors: C.A. Lewis, T.E. Eaton, P. Young, J. Kolbe
Journal: European Respiratory Journal (2003)

Short­burst oxygen therapy (SBOT) remains an unproven treatment for reduction of exertional dyspnoea in chronic obstructive pulmonary disease (COPD). This study aimed to assess whether SBOT before exercise reduces dyspnoea or improves performance, and whether SBOT after exercise reduces dyspnoea during recovery. Twenty­two clinically stable COPD patients (mean forced expiratory volume in one second 34% predicted, mean resting saturation 94%) attended a respiratory gymnasium and undertook four 6‐min walk (6MW) tests at each of two sessions, 1 week apart. Cylinder air or oxygen was administered single­blind in random order for 5 min prior to the first two 6MW and during recovery following the final two 6MW. Dyspnoea was self­rated by subjects using the modified Borg scale. There was no significant difference in mean 6MW distance or final Borg score for air and oxygen given before exercise. There was also no significant difference in mean time­to­resting Borg score for air and oxygen given after exercise. Only two subjects demonstrated a clinically significant and consistent reduction in dyspnoea for oxygen compared with air either before or after exercise. Overall, short­burst oxygen therapy neither reduced dyspnoea nor improved performance. This study does not support the use of short­burst oxygen therapy either immediately before or after exercise.
Ten-Year Risk of Diagnostic Mammograms and Invasive Breast Procedures After Breast-Conserving Surgery for DCIS
Authors: L. Nekhlyudov, L. A. Habel, N. Achacoso, I. Jung, R. Haque, L. C. Collins, S. J. Schnitt, C. P. Quesenberry, S. W. Fletcher
Journal: JNCI Journal of the National Cancer Institute (2012)

Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known.We identified 2948 women with DCIS who were treated with BCS from 1990 to 2001 and followed for up to 10 years at three integrated health-care delivery systems. We calculated the percentages of diagnostic mammograms and ipsilateral invasive procedures following the initial breast excision to treat DCIS, estimated the 10-year cumulative incidence of these procedures, and determined hazard ratios for both types of procedures with Cox regression modeling. All statistical tests were two-sided.Over 10 years, 907 women (30.8%) had 1422 diagnostic mammograms and 1813 (61.5%) had 2305 ipsilateral invasive procedures. Diagnostic mammograms occurred in 7.3% of women in the first 6 months and continued at a median annual rate of 4.3%. Ipsilateral invasive procedures occurred in 51.5% of women in the first 6 months and continued at a median annual rate of 3.1%. The estimated 10-year cumulative risk of having at least one diagnostic mammogram after initial DCIS excision was 41.0% (95% confidence interval [CI] = 38.5% to 43.5%); at least one invasive procedure, 65.7% (95% CI = 63.7% to 67.8%); and either event, 76.1% (95% CI = 74.1% to 78.1%). Excluding events in the first 6 months following initial DCIS excision, corresponding risks were 36.4% (95% CI = 33.8% to 39.0%) for diagnostic mammograms, 30.4% (95% CI = 26.9% to 33.8%) for invasive procedures, and 49.5% (95% CI = 45.6% to 53.5%) for either event.Women with DCIS treated with BCS continue to have diagnostic and invasive breast procedures in the conserved breast over an extended period. The frequency of ongoing diagnostic breast evaluations should be included in discussions about treatment.
Long-term protection against malaria after experimental sporozoite inoculation: an open-label follow-up study
Authors: Meta Roestenberg, Anne C Teirlinck, Matthew BB McCall, Karina Teelen, Krystelle Nganou Makamdop, Jorien Wiersma, Theo Arens, Pieter Beckers, GeertJan van Gemert, Marga van de Vegte-Bolmer, André JAM van der Ven, Adrian JF Luty, Cornelus C Hermsen, Robert W Sauerwein
Journal: The Lancet (2011)
Causes of Morbidity and Mortality in Severe Pediatric Trauma
Authors: Thom Mayer
Journal: JAMA (1981)

In a two-year period, we studied 160 patients with multiple trauma (injury to at least two body areas) and graded severity of neurologic injury according to the Glasgow Coma Scale. Injuries to other body areas were categorized by the Modified Injury Severity Scale. Neurologic injury was present in nearly 80% and constituted the most severe injury in 60%. Chest (40%) and extremity (30%) injuries were next most frequently encountered. Overall mortality was 13.8%, with 11.3% disability and 74.3% of patients achieving good recovery. There was some degree of neurologic injury in all patients who died or were disabled. Among all patients with head injuries (126), mortality was 16%, vs 6% in those without head injury (34). Other deaths were caused by chest (9%) or abdominal (14.5%) injuries. (<i>JAMA</i>1981;245:719-721)
Occupational exposure to magnetic fields and the risk of brain tumors
Authors: Joseph B. Coble, Mustafa Dosemeci, Patricia A. Stewart, Aaron Blair, Joseph Bowman, Howard A. Fine, William R. Shapiro, Robert G. Selker, Jay S. Loeffler, Peter M. Black, Martha S. Linet, Peter D. Inskip
Journal: Neuro-Oncology (2009)

We investigated the association between occupational exposure to extremely low-frequency magnetic fields (MFs) and the risk of glioma and meningioma. Occupational exposure to MF was assessed for 489 glioma cases, 197 meningioma cases, and 799 controls enrolled in a hospital-based case-control study. Lifetime occupational history questionnaires were administered to all subjects; for 24% of jobs, these were supplemented with job-specific questionnaires, or "job modules," to obtain information on the use of electrically powered tools or equipment at work. Job-specific quantitative estimates for exposure to MF in milligauss were assigned using a previously published job exposure matrix (JEM) with modification based on the job modules. Jobs were categorized as < or =1.5 mG, >1.5 to <3.0 mG, and > or =3.0 mG. Four exposure metrics were evaluated: (1) maximum exposed job; (2) total years of exposure >1.5 mG; (3) cumulative lifetime exposure; and (4) average lifetime exposure. Odds ratios (ORs) were calculated using unconditional logistic regression with adjustment for the age, gender, and hospital site. The job modules increased the number of jobs with exposure > or =3.0 mG from 4% to 7% relative to the JEM. No statistically significant elevation in ORs or trends in ORs across exposure categories was observed using four different exposure metrics for the three tumor types analyzed. Occupational exposure to MFs assessed using job modules was not associated with an increase in the risk for glioma, glioblastoma, or meningioma among the subjects evaluated in this study.
Evidence for differences in erythrocyte surface receptors for the malarial parasites, Plasmodium falciparum and Plasmodium knowlesi.
Authors: L H Miller, J D Haynes, F M McAuliffe, T Shiroishi, J R Durocher, M H McGinniss
Journal: The Journal of Experimental Medicine (1977)

Human erythrocytes lacking various blood group determinants were susceptible to invasion by Plasmodium falciparum including Duffy-negative erythrocytes that are refractory to invasion by Plasmodium knowlesi. Erythrocytes treated with trypsin or neuraminidase had reduced susceptibility of P. falciparum and normal susceptibility to P. knowlesi. Chymotrypsin treatment (0.1 mg/ml) blocked invasion only by P. knowlesi. The differential effect of enzymatic cleavage of determinats from the erythrocyte surface on invasion by these parasites suggests that P. falciparum and P. knowlesi interact with different determinants on the erythrocyte surface.
Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis
Authors: J. Geddes, N. Freemantle, P. Harrison, P. Bebbington
Journal: BMJ (2000)

Objective: To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia. Design: Systematic overview and meta-regression analyses of randomised controlled trials, as a basis for formal development of guidelines. Subjects: 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or chlorpromazine) or alternative atypical antipsychotics. Main outcome measures: Overall symptom scores. Rate of drop out (as a proxy for tolerability) and of side effects, notably extrapyramidal side effects. Results: For both symptom reduction and drop out, there was substantial heterogeneity between the results of trials, including those evaluating the same atypical antipsychotic and comparator drugs. Meta-regression suggested that dose of conventional antipsychotic explained the heterogeneity. When the dose was ≤12 mg/day of haloperidol (or equivalent), atypical antipsychotics had no benefits in terms of efficacy or overall tolerability, but they still caused fewer extrapyramidal side effects. Conclusions: There is no clear evidence that atypical antipsychotics are more effective or are better tolerated than conventional antipsychotics. Conventional antipsychotics should usually be used in the initial treatment of an episode of schizophrenia unless the patient has previously not responded to these drugs or has unacceptable extrapyramidal side effects.
A Pilot Study of Interpersonal Psychotherapy for Posttraumatic Stress Disorder
Authors: Kathryn L. Bleiberg, John C. Markowitz
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This article describes pilot testing of interpersonal psychotherapy adapted for posttraumatic stress disorder (PTSD). Unlike most psychotherapies for PTSD, interpersonal psychotherapy is not exposure-based, focusing instead on interpersonal sequelae of trauma. METHOD: Fourteen consecutively enrolled subjects with chronic PTSD (DSM-IV) from various traumas received an open, 14-week interpersonal psychotherapy trial. RESULTS: Treatment was well tolerated: 13 subjects (93%) completed therapy. After 14 weeks, 12 of 14 subjects no longer met diagnostic criteria for PTSD, 69% responded (50% Clinician Administered PTSD Scale score decrement), and 36% remitted (score ≤20). Thirteen subjects reported declines in PTSD symptoms across all three symptom clusters. Depressive symptoms, anger reactions, and interpersonal functioning also improved. CONCLUSIONS: Treating interpersonal sequelae of PTSD appears to improve other symptom clusters. Interpersonal psychotherapy may be an efficacious alternative for patients who refuse repeated exposure to past trauma. This represents an exciting extension of interpersonal psychotherapy to an anxiety disorder.