tbuckley/cabot-search huggingface dataset:
Appendicitis Manifested as Lumbar Plexus Neuritis
Authors: Alfred M. Lerner
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Appendicitis commonly afflicts 7% of the population. With classic symptoms, it poses no diagnostic puzzle. However, since a delay in appropriate treatment produces substantial mortality, internists have been cautioned to be aware of highly atypical manifestations of appendicitis.<sup>1-4</sup>We report a case of appendicitis manifested as a lumbar plexus neuritis. <h3>Report of a Case.—</h3> A 72-year-old man was admitted to the hospital with complaints of pain and weakness of the right lower extremity. Four days before admission, he awoke at midnight with burning pain over his right anterior and medial thigh, which recurred intermittently over the next four days. He had no fevers, chills, anorexia, nausea, vomiting, change in bowel habits, dysuria, or abdominal pain. On admission, he was afebrile. His abdominal examination results were unremarkable. There was a notable weakness of the right iliopsoas muscle and mild right quadriceps muscle weakness. There was a patchy
Relevance of Different UGT1A1 Polymorphisms in Irinotecan-Induced Toxicity
Authors: Elisabeth Rouits, Michèle Boisdron-Celle, Agnès Dumont, Olivier Guérin, Alain Morel, Erick Gamelin
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We wanted to assess polymorphisms in the uridine diphosphoglucuronosyl transferase 1A1 (UGT 1A1) gene: the TATA box polymorphism and UGT 1A1 G71R and Y486D mutations in the coding sequence, the main mutations characterizing Gilbert’s syndrome, as predictors of severe toxic event occurrence after irinotecan (CPT-11) administration. Therefore, we set up a rapid, sensitive, and reliable technique in routine practice to detect before CPT-11 treatment, the at-risk patients. Experimental Design: Seventy-five patients with advanced colorectal cancer and treated with CPT-11 and 5-fluorouracil, entered the study. We used the Pyrosequencing technology a real-time sequencing method, to detect the UGT 1A1 TATA box polymorphisms and mutations in the coding regions. Patients were also assessed for both biochemical and clinical evaluation and tolerance to treatment. Results: No G71R and Y486D mutations were found in our population. Frequencies for UGT 1A1 TATA box polymorphisms were 41, 47, and 9% for wild-type 6/6, heterozygous 6/7, and Gilbert’s syndrome 7/7, respectively. Tolerance to treatment decreased with increased number of TA repeat with 71% of the patients in 7/7 group who experienced grade 3/4 toxicity. Conclusions: The method we set up is suitable for the detection of UGT 1A1 polymorphism in routine practice before irinotecan treatment. It could help to detect the patients homozygous or heterozygous for Gilbert’s syndrome, at-risk of CPT 11-induced toxicity, and thus could help to individualize the dose to optimize efficacy and limit toxicity.
Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib
Authors: Siquan Chen, Jonathan L. Blank, Theodore Peters, Xiaozhen J. Liu, David M. Rappoli, Michael D. Pickard, Saurabh Menon, Jie Yu, Denise L. Driscoll, Trupti Lingaraj, Anne L. Burkhardt, Wei Chen, Khristofer Garcia, Darshan S. Sappal, Jesse Gray, Paul Hales, Patrick J. Leroy, John Ringeling, Claudia Rabino, James J. Spelman, Jay P. Morgenstern, Eric S. Lightcap
Journal: Cancer Research (2010)

Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen to evaluate the genetic determinants that confer sensitivity to bortezomib (Velcade (R); PS-341). This screen identified 100 genes whose knockdown affected lethality to bortezomib and to a structurally diverse set of other proteasome inhibitors. A comparison of three cell lines revealed that 39 of 100 genes were commonly linked to cell death. We causally linked bortezomib-induced cell death to the accumulation of ASF1B, Myc, ODC1, Noxa, BNIP3, Gadd45alpha, p-SMC1A, SREBF1, and p53. Our results suggest that proteasome inhibition promotes cell death primarily by dysregulating Myc and polyamines, interfering with protein translation, and disrupting essential DNA damage repair pathways, leading to programmed cell death.
Bus Therapy
Authors: Smita Das, Sebastien C. Fromont, Judith J. Prochaska
Journal: JAMA Psychiatry (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Modeling the CD8+ T Effector to Memory Transition in Adoptive T-Cell Antitumor Immunotherapy
Authors: Cleo E. Rolle, Roberto Carrio, Thomas R. Malek
Journal: Cancer Research (2008)

Abstract Adoptive T-cell therapy with CD8+ CTLs is often characterized by poor persistence of the transferred T cells and limited effector responses. Improved persistence and therapeutic efficacy have been noted when antigen-activated CD8+ T cells express properties of memory cells. The current study was undertaken to more precisely characterize the development of memory-like CD8+ T cells from short-term CTLs in vitro and upon transfer in vivo, including their antitumor activity. Ovalbumin (OVA)–specific OT-I CTLs acquired phenotypic and functional properties of memory cells 2 to 3 days later either by lowering the concentration of antigen to a level that does not support primary responses and providing a survival signal through transgenic Bcl-2 in vitro or simply by transferring early day 3 CTLs to antigen-free lymphoid-replete mice. In lymphoid-replete mice, established OVA-expressing E.G7 tumor was rejected by short-term CTLs that simultaneously acquired memory-like properties in secondary lymphoid tissues, where tumor antigen level remained low. Collectively, these data indicate that CTLs readily converted to memory-like cells upon lowering antigen to a concentration that selectively supports memory responses and suggest that such conversion predicts successful adoptive immunotherapy. [Cancer Res 2008;68(8):2984–92]
Toll-Like Receptor 4 in Butylated Hydroxytoluene–Induced Mouse Pulmonary Inflammation and Tumorigenesis
Authors: Alison K. Bauer, Darlene Dixon, Laura M. DeGraff, Hye-Youn Cho, Christopher R. Walker, Alvin M. Malkinson, Steven R. Kleeberger
Journal: JNCI Journal of the National Cancer Institute (2005)

Because chronic pulmonary diseases predispose to lung neoplasia, the identification of the molecular mechanisms involved could provide novel preventive, diagnostic, and therapeutic strategies. Toll-like receptors (TLRs) transduce exogenous and endogenous signals into the production of inflammatory cytokines to coordinate adaptive immune responses. To determine the role of Tlr4 in chronic lung inflammation, we compared lung permeability, leukocyte infiltration, and nuclear factor kappa B (NFkappaB) and activator protein 1 (AP-1) DNA binding in butylated hydroxytoluene (BHT)-treated (four weekly injections of 125-200 mg/kg each) inbred mouse strains with functional Tlr4 (OuJ and BALB) and mutated Tlr4 (HeJ and BALB(Lps-d)). We also measured primary tumor formation in these mice after single-carcinogen injection (3-methylcholanthrene; 10 microg/kg), followed by BHT treatment (six weekly injections of 125-200 mg/kg each). Mice with functional Tlr4 had reduced lung permeability, leukocyte inflammation, and primary tumor formation (BALB(Lps-d), mean = 22.3 tumors/mouse, versus BALB, mean = 13.9 tumors/mouse, difference = 8.4 tumors/mouse, 95% confidence interval = 4.6 to 12.1 tumors/mouse; P = .025) compared with mice with mutated Tlr4. NFkappaB DNA binding activity was higher in OuJ than in HeJ mice; however, AP-1 activity was elevated in HeJ mice. To our knowledge, this is the first model to demonstrate a modulatory role for Tlr4 in chronic lung inflammation and tumorigenesis.
Higher Relative Risk for Multiple Sclerosis in a Pediatric and Adolescent Diabetic Population: Analysis From DPV Database
Authors: Susanne Bechtold, Astrid Blaschek, Klemens Raile, Axel Dost, Clemens Freiberg, Meik Askenas, Elke Fröhlich-Reiterer, Esther Molz, Reinhard W. Holl
Journal: Diabetes Care (2013)

OBJECTIVE Type 1 diabetes and multiple sclerosis (MS) are typical autoimmune diseases in children and young adults. We assessed the co-occurrence of type 1 diabetes and MS by estimating the relative risk (RR) for MS in a pediatric and adolescent diabetic population and looked for possible influencing factors. RESEARCH DESIGN AND METHODS Within the Diabetes Patienten Verlaufsdokumentation (DPV)-Wiss Project, from January 1995 to October 2012, data from 56,653 patients with type 1 diabetes were collected in 248 centers in Germany and Austria. Published data on German and Mid-European MS prevalence were taken for comparison. Multivariable regression analysis was used to identify confounders for co-occurrence of type 1 diabetes and MS. RESULTS The RR for MS in patients with type 1 diabetes was estimated at 3.35-4.79 (95% CI 1.56-7.21 and 2.01-11.39, respectively). Immigration status in all patients (P < 0.05) and the presence of thyroid antibodies in male patients only (P = 0.05) were identified as influencing factors on MS incidence within the DPV database. The month-of-birth pattern revealed that risk was higher during the spring and summer months in the population with type 1 diabetes and MS in comparison with the population with type 1 diabetes. CONCLUSIONS The present cohort study demonstrates a higher risk of co-occurrence of MS in a pediatric and adolescent diabetic population. Immigration status and thyroid antibodies in male patients were independent risk indicators for the incidental rate of MS. Diabetic patients born during spring and summer had a higher risk for the development of MS. We suggest that environmental factors modulate the individual's risk for the co-occurrence of both diseases.
p38MAPK Plays a Crucial Role in Stromal-Mediated Tumorigenesis
Authors: Elise Alspach, Kevin C. Flanagan, Xianmin Luo, Megan K. Ruhland, Hui Huang, Ermira Pazolli, Maureen J. Donlin, Timothy Marsh, David Piwnica-Worms, Joseph Monahan, Deborah V. Novack, Sandra S. McAllister, Sheila A. Stewart
Journal: Cancer Discovery (2014)

Abstract Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood. Here, we address a key unanswered question: how the SASP is sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus controls their stability. The importance of this regulatory mechanism is underscored by our findings that stromal-specific p38MAPK inhibition abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Our data suggest that targeting SASP mRNA stability through inhibition of p38MAPK will significantly aid the development of clinical strategies to target the TME. Significance: The TME plays a key role in tumorigenesis. We demonstrate that p38MAPK governs a posttranscriptional mechanism that sustains the protumorigenic SASP. Inhibition of p38MAPK abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Thus, p38MAPK is a TME-specific Achilles' heel that may be exploited as a new therapeutic target. Cancer Discov; 4(6); 716–29. ©2014 AACR. See related commentary by Isacke and Barcellos-Hoff, p. 637 This article is highlighted in the In This Issue feature, p. 621
Multiple Myeloma Regression Mediated by Bruceantin
Authors: Muriel Cuendet, Konstantin Christov, Daniel D. Lantvit, Yunfan Deng, Samad Hedayat, Lawrence Helson, James D. McChesney, John M. Pezzuto
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Bruceantin has been shown to induce cell differentiation in a number of leukemia and lymphoma cell lines. It also down-regulated c-MYC, suggesting a correlation of down-regulation with induction of cell differentiation or cell death. In the present study, we focused on multiple myeloma, using the RPMI 8226 cell line as a model. Experimental Design: The effects of bruceantin on c-MYC levels and apoptosis were examined by immunoblotting, 4′,6-diamidino-2-phenylindole staining, evaluation of caspase-like activity, and 3,3′-dihexyloxacarbocyanine iodide staining. The potential of bruceantin to inhibit primary tumor growth was assessed with RPMI 8226 xenografts in SCID mice, and apoptosis in the tumors was evaluated by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: c-MYC was strongly down-regulated in cultured RPMI 8226 cells by treatment with bruceantin for 24 h. With U266 and H929 cells, bruceantin did not regulate c-MYC in this manner. Apoptosis was induced in the three cell lines. In RPMI 8226 cells, apoptosis occurred through proteolytic processing of procaspases and degradation of poly(ADP-ribose) polymerase. The mitochondrial pathway was also involved. Because RPMI 8226 cells were the most sensitive, they were used in a xenograft model. Bruceantin treatment (2.5–5 mg/kg) resulted in a significant regression of tumors without overt toxicity. Apoptosis was significantly elevated in tumors derived from animals treated with bruceantin (37%) as compared with the control tumors (14%). Conclusions: Bruceantin interferes with the growth of RPMI 8226 cells in cell culture and xenograft models. These results suggest that bruceantin should be reinvestigated for clinical efficacy against multiple myeloma and other hematological malignancies.
Effects of propranolol and diltiazem alone and in combination on the recovery of left ventricular segmental function after temporary coronary occlusion and long-term reperfusion in conscious dogs.
Authors: L R Bush, L M Buja, G Tilton, M Wathen, P Apprill, J Ashton, J T Willerson
Journal: Circulation (1985)

We evaluated the ability of propranolol and diltiazem alone and in combination to enhance the recovery of left ventricular (LV) segmental function during 1 month of reperfusion after two temporary occlusions of the left anterior descending coronary artery (LAD) in conscious dogs instrumented with ultrasonic crystals for the measurement of regional net systolic wall thickening (NET). LV segments were classified according to their contractile function after 1 hr of LAD occlusion: class 1, greater than 67% of preocclusion (control) NET; class 2, 0% to 66.9%; class 3, less than 0% (paradoxical systolic wall thinning). Propranolol (1 mg/kg iv) or diltiazem (20 micrograms/kg/min) was given 65 min after LAD occlusion in dogs that had 2 (group I) or 4 hr (group II) of LAD occlusion. Diltiazem plus propranolol (same doses) were given to another group of dogs that underwent 4 hr (but not 2) of LAD occlusion. Untreated control dogs received 25 ml of saline and underwent 2 or 4 hr of LAD occlusion. The NET of class 2 and 3 segments in group I control dogs increased significantly during 1 month of reperfusion, from 32 +/- 5% and -43 +/- 6% to 66 +/- 9% and 26 +/- 9%, respectively (p less than .05). Neither diltiazem nor propranolol enhanced the long-term recovery of these segments in group I dogs. However, diltiazem prevented further deterioration of contractile dysfunction observed in control dogs immediately after reperfusion in both segment classes. The NET of class 2 segments in group II control dogs after 4 weeks of reperfusion remained at levels observed during LAD occlusion: 30 +/- 4% to 37 +/- 12%. Class 3 NET increased from -33 +/- 5% to 12 +/- 12% with 1 month of reperfusion, but these segments were essentially akinetic. Propranolol or diltiazem alone did not produce significant overall increases in NET, but diltiazem again prevented further declines in NET of class 2 and 3 segments during early reperfusion. However, the combination of diltiazem and propranolol significantly enhanced overall recovery of class 2 NET in group II dogs (44 +/- 3% to 88 +/- 7%) and prevented the worsening of NET associated with early reperfusion. Compared with untreated dogs, propranolol plus diltiazem also significantly decreased the extent of histologic necrosis in class 2 and 3 segments as well as the macrohistochemically determined infarct size in group II dogs.(ABSTRACT TRUNCATED AT 400 WORDS)
Ranitidine reduced clinically important gastrointestinal bleeding in patients who required mechanical ventilation
Authors: C J HINDS, S N FLETCHER
Journal: Gut (1999)

QuestionIn patients who require mechanical ventilation, what is the eYcacy and safety of sucralfate compared with ranitidine for preventing upper gastrointestinal bleeding? DesignRandomised, triple blind, controlled trial with follow up to hospital discharge or death.Setting 16 intensive care units (ICUs) in Canada.Patients 1200 patients (mean age 59 y, 60% men) who were admitted to ICUs and were expected to require mechanical ventilation for >48 hours.Exclusion criteria were gastrointestinal bleeding or pneumonia at admission, gastrectomy, poor prognosis, previous randomisation in a trial, or previous open label prophylactic treatment.Follow up was complete. InterventionPatients were allocated to intravenous bolus ranitidine (Zantac, Glaxo Wellcome), 50 mg every 8 hours (n=596), or sucralfate (Sulcrate, Hoechst Marion Roussel) suspension through a nasogastric tube or given orally, 1 g every 6 hours (n=604).Ranitidine doses were adjusted for patients with creatinine clearance rates of 25-50 ml/minute (50 mg every 12 h) or <25 ml/minute (50 mg every 24 h) and for patients dependent on dialysis (50 mg every 12 h). Main outcome measuresClinically important gastrointestinal bleeding, ventilator associated pneumonia, length of stay in the ICU, and mortality. Main resultsAnalysis was by intention to treat.More patients allocated to sucralfate than to ranitidine had clinically important bleeding (p=0.02)(table).No diVerences existed between groups for ventilator associated pneumonia, mortality (table ), or length of stay in the ICU (median 9 days for both groups). ConclusionsIn patients who required mechanical ventilators, ranitidine led to less gastrointestinal bleeding than did sucralfate.Ventilator associated pneumonia, mortality, and length of stay in the ICU did not diVer between treatment groups.
Why Human Disease-Associated Residues Appear as the Wild-Type in Other Species: Genome-Scale Structural Evidence for the Compensation Hypothesis
Authors: Jinrui Xu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2014)

Many human-disease associated amino acid residues (DARs) appear as the wild-type in other species. This phenomenon is commonly explained by the presence of compensatory residues in these other species that alleviate the deleterious effects of the DARs. The general validity of this hypothesis, however, is unclear, because few compensatory residues have been identified. Here we test the compensation hypothesis by assembling and analyzing 1,077 DARs located in 177 proteins of known crystal structures. Because destabilizing protein structures is a primary reason why DARs are deleterious, we focus on protein stability in this analysis. We discover that, in species where a DAR represents the wild-type, the destabilizing effect of the DAR is generally lessened by the observed amino acid substitutions in the spatial proximity of the DAR. This and other findings provide genome-scale evidence for the compensation hypothesis and have important implications for understanding epistasis in protein evolution and for using animal models of human diseases.
US judge again rules that ban on partial birth abortion is unconstitutional
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

[Editor's note: Originally, our headline for this story was wrong. It was corrected on 17 September 2004.] 

The federal law banning “partial birth abortions” is heading, very slowly, to the Supreme Court. Three judges in separate jurisdictions ruled it unconstitutional and unenforceable because it did not include an exception to protect a woman's health. The Department of Justice said it would appeal.

Pro-choice advocates fear that, years from now, a more conservative Supreme Court will uphold the law as constitutional, thus outlawing most abortions.

The law was passed by Congress and signed by President Bush last year ( BMJ 2003;327:1009). It was immediately challenged by five organisations involved with family planning, …
Detection of Minimal Residual Disease: Relevance for Diagnosis and Treatment of Human Malignancies
Authors: Cheryl Hirsch-Ginsberg
Journal: Annual Review of Medicine (1998)

Minimal residual disease (MRD) is the tumor burden that is present after a course of treatment that has resulted in clinical remission. For hematopoietic malignancies, techniques for detection of this minimal tumor burden are being used to monitor MRD. These involve methods that are capable of identifying very low numbers of neoplastic cells in an otherwise normal marrow or lymph node. Patients with demonstrable residual neoplastic cells tend to do worse than patients without detectable cells; however, results depend on the timing of the assay and whether the detectable neoplastic cells appear to be increasing in number with subsequent assays. For bone marrow transplantation, assays incorporating chimerism analyses, cytogenetics, and morphology are used to regulate therapy.