tbuckley/cabot-search huggingface dataset:
Preservation and Restoration of Joint Function in Patients With Severe Burns
Authors: E. Burke Evans
Journal: JAMA (1968)

In patients with severe burns joint function may be compromised by para-articular ossification, septic arthritis, dislocation, or soft-tissue contracture. Ectopic bone forming as a sequel to burns, once excised, does not tend to recur. Septic arthritis may be dealt with as in patients without burns; but the signs and symptoms of joint sepsis are masked in burns, and the common result is ankylosis. Dislocations of otherwise intact joints may be dealt with in standard fashion; those secondary to joint destruction cannot be reduced. Whereas ectopic bone, septic arthritis, and dislocation, combined, occur in no more than 5% of severely burned patients, soft-tissue contracture occurs in almost all patients with extremity burns. Contracture is prevented by positioning, physical therapy, and splinting; it is corrected with skeletal traction or suspension alone, or in conjunction with surgery, or with surgery alone.
The rise of medical English.
Authors: R Smith
Journal: BMJ (1986)

prestigious royal college reports, research findings, and review papers struggles to persuade the public of the crucial part played in alcohol problems by factors such as the ready availability of alcohol, tolerant attitudes towards its misuse, and the fact that "drinking is a social phenomenon-it is something we both learn and practise with other people.""I 21Given the experience with tobacco and the effect of the example set by doctors in giving up smoking, is it too much to hope that many doctors would not merely read the contents of these latest alcohol reports but might actually take their lessons to heart?A useful start would be eliminating lunchtime drinking in medical settings, and consistently and readily providing soft drinks at social occasions at which alcohol is provided.Such steps are feasible and would do much to signal publicly that doctors take their drinking behaviour seriously and are not content merely to preach about other people's use of the drug.
A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes
Authors: S.M. Lim, H. Chang, M.J. Yoon, Y.K. Hong, H. Kim, W.Y. Chung, C.S. Park, K.H. Nam, S.W. Kang, M.K. Kim, S.B. Kim, S.H. Lee, H.G. Kim, I.I. Na, Y.S. Kim, M.Y. Choi, J.G. Kim, K.U. Park, H.J. Yun, J.H. Kim, B.C. Cho
Journal: Annals of Oncology (2013)
Rate of improvement of pulmonary function in sarcoidosis during treatment with corticosteroids.
Authors: D S Goldstein, M H Williams
Journal: Thorax (1986)

Serial measurements of vital capacity were obtained in 11 patients with impaired pulmonary function due to sarcoidosis during 12 courses of corticosteroid treatment. Vital capacity improved promptly and approached a maximum value in about three weeks. A three week trial is probably sufficient to show whether or not corticosteroids are effective in a patient with sarcoidosis.
Leukemia Inhibitory Factor: A Newly Identified Metastatic Factor in Rhabdomyosarcomas
Authors: Marcin Wysoczynski, Katarzyna Miekus, Kacper Jankowski, Jens Wanzeck, Salvatore Bertolone, Anna Janowska-Wieczorek, Janina Ratajczak, Mariusz Z. Ratajczak
Journal: Cancer Research (2007)

Abstract Rhabdomyosarcoma frequently infiltrates bone marrow and this process involves the stromal-derived factor-1 (SDF-1)–CXCR4 axis. Because leukemia inhibitory factor (LIF), like SDF-1, is secreted by bone marrow stroma and directs the regeneration of skeletal muscles, we examined whether the LIF–LIF receptor (LIF-R) axis affects the biology of rhabdomyosarcoma cells. We found that in rhabdomyosarcoma cells, LIF stimulates the following: (a) phosphorylation of mitogen-activated protein kinase p42/44, AKT, and signal transducers and activators of transcription 3, (b) adhesion and chemotaxis, and (c) increased resistance to cytostatics. To compare the biological effects of LIF versus SDF-1, we examined the RH30 cell line, which is highly responsive to both ligands, and found that the chemotaxis of these cells is significantly reduced when the inhibitors of both receptors (T140 for CXCR4 and gp190 blocking antibody for LIF-R) are added simultaneously. Subsequently, by using repetitive chemotaxis to LIF or SDF-1, we selected from the RH30 line subpopulations of cells that respond to LIF but not SDF-1 (RH30-L) or to SDF-1 but not LIF (RH30-S). We found that (a) RH30-L cells seed better to the bone marrow, liver, and lymph nodes of immunodeficient mice than RH30-S cells and (b) mice inoculated i.m. with the RH30-L cells had more rhabdomyosarcoma cells in the bone marrow and lung after 6 weeks. Thus, we present the first evidence that the LIF–LIF-R axis may direct rhabdomyosarcoma metastasis. Further, because we showed that the in vivo metastasis of RH30 cells is inhibited by small interfering RNA against LIF-R, molecular targeting of this axis could become a new strategy to control the metastasis of rhabdomyosarcoma. [Cancer Res 2007;67(5):2131–40]
Comment on “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model”
Authors: Jack W. Tsao
Journal: Science Translational Medicine (2012)

In their recent paper, Goldstein et al. show murine brain tau neuropathology after explosive blast with head rotation but do not present additional evidence that would delineate whether this neuropathology was principally caused by blast exposure alone or by blast exposure plus head rotational injury.
Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers
Authors: Jin Zhang, Irinoulla Scordi, Mark J. Smyth, Mathias G. Lichtenheld
Journal: The Journal of Experimental Medicine (1999)

Optimal T cell differentiation into effector cells with specialized functions requires the participation of cytokine receptor signals. In T helper cells, this process is controlled by chromatin changes and distal and proximal regulatory elements as well as specific transcription factors. Analogous events during cytotoxic T lymphocyte (CTL) differentiation remain to be identified. This process is known, however, to be crucially regulated by interleukin (IL)-2 receptor (R) signals. It is accompanied by the induction of perforin expression via a mechanism that does not entail proximal regulatory elements. In this report, transgenically expressed human perforin gene locus DNAs demonstrate that IL-2R signals target two IL-2-dependent enhancers approximately 15 and 1 kilobase upstream of the promoter. The most distal enhancer may also respond to TCR signals. In transient transfections, both enhancers required two identically spaced Stat-like elements for their activation, which was abolished by expression of a dominant negative signal transducer and activator of transcription (Stat)5 molecule, whereas a constitutively active Stat5 molecule bypassed the requirement for IL-2R signals. These results provide a molecular explanation for the activation of the perforin gene during CTL differentiation and complement the analysis of animals deficient in the activation of the IL-2R Stat signaling pathway by establishing perforin as a target gene.
Single-Agent Lenalidomide in Patients With Mantle-Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib: Phase II MCL-001 (EMERGE) Study
Authors: Andre Goy, Rajni Sinha, Michael E. Williams, Sevgi Kalayoglu Besisik, Johannes Drach, Radhakrishnan Ramchandren, Lei Zhang, Sherri Cicero, Tommy Fu, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2013)

Although dose-intensive strategies or high-dose therapy induction followed by autologous stem-cell transplantation have improved the outcome for patients with mantle-cell lymphoma (MCL), most eventually relapse and subsequently respond poorly to additional therapy. Bortezomib (in the United States) and temsirolimus (in Europe) are currently the only two treatments approved for relapsed disease. Lenalidomide is an immunomodulatory agent with proven tumoricidal and antiproliferative activity in MCL. The MCL-001 (EMERGE) trial is a global, multicenter phase II study examining the safety and efficacy of lenalidomide in patients who had relapsed or were refractory to bortezomib.Lenalidomide 25 mg orally was administered on days 1 through 21 every 28 days until disease progression or intolerance. Primary end points were overall response rate (ORR) and duration of response (DOR); secondary end points included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety.In all, 134 patients were enrolled with a median age of 67 years and a median of four prior therapies (range, two to 10 prior therapies). The ORR was 28% (7.5% CR/CR unconfirmed) with rapid time to response (median, 2.2 months) and a median DOR of 16.6 months (95% CI, 7.7 to 26.7 months). Median PFS was 4.0 months (95% CI, 3.6 to 5.6 months), and median OS was 19.0 months (95% CI, 12.5 to 23.9 months). The most common grade 3 to 4 adverse events were neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%).The MCL-001 study demonstrated durable efficacy of lenalidomide with a predictable safety profile in heavily pretreated patients with MCL who had all relapsed or progressed after or were refractory to bortezomib.
Analysis of TCR, pTα, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment
Authors: Vahid Asnafi, Kheira Beldjord, Emmanuelle Boulanger, Béatrice Comba, Patricia Le Tutour, Marie-Hélène Estienne, Frédéric Davi, Judith Landman-Parker, Pierre Quartier, Agnès Buzyn, Eric Delabesse, Françoise Valensi, Elizabeth Macintyre
Journal: Blood (2003)
Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin
Authors: Wei Wei, Mei-Sze Chua, Susan Grepper, Samuel K So
Journal: Molecular Cancer (2011)

Abstract Background There are limited therapeutic options for hepatocellular carcinoma (HCC), the most common liver malignancy worldwide. Recent studies have identified the Frizzled-7 receptor (FZD7), important for activation of Wnt-mediated signaling, as a potential therapeutic target for HCC and other cancers. Methods We hypothesized that the extracellular domain of FZD7 (sFZD7) would be a clinically more relevant therapeutic modality than previously studied approaches to target FZD7. We expressed and purified sFZD7 from E. coli, and tested its functional activity to interact with Wnt3, its ability to inhibit Wnt3-mediated signaling, and its potential for combinatorial therapy in HCC. Results sFZD7 pulled down Wnt3 from Huh7 cells, and decreased β-catenin/Tcf4 transcriptional activity in HCC cells. In vitro , sFZD7 dose-dependently decreased viability of three HCC cell lines (HepG2, Hep40, and Huh7, all with high FZD7 and Wnt3 mRNA), but had little effect on normal hepatocytes from three donors (all with low level FZD7 and Wnt3 mRNA). When combined with doxorubicin, sFZD7 enhanced the growth inhibitory effects of doxorubicin against HCC cells in vitro , and against Huh7 xenografts in vivo . Reduced expressions of c-Myc, cyclin D1, and survivin were observed in vitro and in vivo . Additionally, sFZD7 altered the levels of phosphorylated AKT and ERK1/2 induced by doxorubicin treatment in vitro , suggesting that several critical pathways are involved in the chemosensitizing effect of sFZD7. Conclusions We propose that sFZD7 is a feasible therapeutic agent with specific activity, which can potentially be combined with other chemotherapeutic agents for the improved management of HCC.
Expression of full-length p53 and its isoform Deltap53 in breast carcinomas in relation to mutation status and clinical parameters.
Authors: Lars O Baumbusch, Simen Myhre, Anita Langerød, Anna Bergamaschi, Stephanie B Geisler, Per E Lønning, Wolfgang Deppert, Irene Dornreiter, Anne-Lise Børresen-Dale
Journal: Molecular Cancer (2006)

The tumor suppressor gene p53 (TP53) controls numerous signaling pathways and is frequently mutated in human cancers. Novel p53 isoforms suggest alternative splicing as a regulatory feature of p53 activity.In this study we have analyzed mRNA expression of both wild-type and mutated p53 and its respective Deltap53 isoform in 88 tumor samples from breast cancer in relation to clinical parameters and molecular subgroups. Three-dimensional structure differences for the novel internally deleted p53 isoform Deltap53 have been predicted. We confirmed the expression of Deltap53 mRNA in tumors using quantitative real-time PCR technique. The mRNA expression levels of the two isoforms were strongly correlated in both wild-type and p53-mutated tumors, with the level of the Deltap53 isoform being approximately 1/3 of that of the full-length p53 mRNA. Patients expressing mutated full-length p53 and non-mutated (wild-type) Deltap53, "mutational hybrids", showed a slightly higher frequency of patients with distant metastasis at time of diagnosis compared to other patients with p53 mutations, but otherwise did not differ significantly in any other clinical parameter. Interestingly, the p53 wild-type tumors showed a wide range of mRNA expression of both p53 isoforms. Tumors with mRNA expression levels in the upper or lower quartile were significantly associated with grade and molecular subtypes. In tumors with missense or in frame mutations the mRNA expression levels of both isoforms were significantly elevated, and in tumors with nonsense, frame shift or splice mutations the mRNA levels were significantly reduced compared to those expressing wild-type p53.Expression of p53 is accompanied by the functionally different isoform Deltap53 at the mRNA level in cell lines and human breast tumors. Investigations of "mutational hybrid" patients highlighted that wild-type Deltap53 does not compensates for mutated p53, but rather may be associated with a worse prognosis. In tumors, both isoforms show strong correlations in different mutation-dependent mRNA expression patterns.
Efficacy and safety of calcipotriol/betamethasone dipropionate ointment for the treatment of simple onycholysis: An open-label study
Authors: Jung-Min Park, Je-Ho Mun, Seung-Wook Jwa, Margaret Song, Hoon-Soo Kim, Hyun-Chang Ko, Byung-Soo Kim, Moon-Bum Kim
Journal: Journal of the American Academy of Dermatology (2013)
MicroRNA-137 Targets Microphthalmia-Associated Transcription Factor in Melanoma Cell Lines
Authors: Lynne T. Bemis, Robert Chen, Carol M. Amato, Elizabeth H. Classen, Steven E. Robinson, David G. Coffey, Paul F. Erickson, Yiqun G. Shellman, William A. Robinson
Journal: Cancer Research (2008)

Abstract Micropthalmia-associated transcription factor (MITF) is the master regulator of melanocyte development, survival, and function. Frequent alteration in the expression of MITF is detected in melanoma, but the mechanism(s) underlying the alteration in expression have not been completely determined. In these studies, we have identified microRNA-137 (miR-137) as a regulator of MITF expression. The genomic locus of miR-137 at chromosome 1p22 places it in a region of the human genome previously determined to harbor an allele for melanoma susceptibility. Here, we show that expression of mature miR-137 in melanoma cell lines down-regulates MITF expression. Further, we have identified a 15-bp variable nucleotide tandem repeat located just 5′ to the pre-miR-137 sequence, which alters the processing and function of miR-137 in melanoma cell lines. [Cancer Res 2008;68(5):1362–8]
Defective regulatory and effector T cell functions in patients with FOXP3 mutations
Authors: R. Bacchetta
Journal: Journal of Clinical Investigation (2006)

The autoimmune disease immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is caused by mutations in the forkhead box protein P3 (FOXP3) gene. In the mouse model of FOXP3 deficiency, the lack of CD4+CD25+ Tregs is responsible for lethal autoimmunity, indicating that FOXP3 is required for the differentiation of this Treg subset. We show that the number and phenotype of CD4+CD25+ T cells from IPEX patients are comparable to those of normal donors. CD4+CD25high T cells from IPEX patients who express FOXP3 protein suppressed the in vitro proliferation of effector T cells from normal donors, when activated by “weak” TCR stimuli. In contrast, the suppressive function of CD4+CD25high T cells from IPEX patients who do not express FOXP3 protein was profoundly impaired. Importantly, CD4+CD25high T cells from either FOXP3+ or FOXP3– IPEX patients showed altered suppression toward autologous effector T cells. Interestingly, IL-2 and IFN-γ production by PBMCs from IPEX patients was significantly decreased. These findings indicate that FOXP3 mutations in IPEX patients result in heterogeneous biological abnormalities, leading not necessarily to a lack of differentiation of CD4+CD25high Tregs but rather to a dysfunction in these cells and in effector T cells.
Impact of school sports injury: Table 1
Authors: L Abernethy, D MacAuley
Journal: British Journal of Sports Medicine (2003)

Background: Most injuries in school occur during sport. Objectives: To explore the impact of sports injury in supervised school sport. Method: A prospective study of sports injury in children of secondary school age presenting to the accident and emergency department. Each patient was identified on registration, matched with medical records after discharge, and contacted later by telephone to complete a structured interview. Patients were only included if their injury was sustained during supervised school sport. Results: During the study period, 194 patients aged 11–18 attended the accident and emergency department with an injury, 51% of which occurred during school sport. Injuries occurred most commonly in rugby (43%), followed by physical education and games together (17.5%). Most injuries were x rayed (72%). Just over 12% of pupils lost no time from sport, most (71%) were back to sport within three weeks, and 2.7% were injured for more than eight weeks. Almost a third of parents needed to take time off from work to deal with the injured child. Conclusion: School sports injuries are important. They account for just over half of all injuries in secondary school children. They cause significant disruption to school and sport and have important implications for the wider family.
Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids
Authors: Marie B Condon, Damien Ashby, Ruth J Pepper, H Terence Cook, Jeremy B Levy, Megan Griffith, Tom D Cairns, Liz Lightstone
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. <h3>Methods</h3> We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)&lt;50 mg/mmol or partial remission (PR) if PCR&gt;50 mg/mmol but non-nephrotic and &gt;50% reduction. <h3>Results</h3> A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4–200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11–58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19–58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20–112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required &gt;2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. <h3>Conclusions</h3> The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.
Active Form of the Thyroid Hormone
Authors: S H Ingbar, L E Braverman
Journal: Annual Review of Medicine (1975)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Steroid Hormone Receptor Status of Mouse Mammary Stem Cells
Authors: Marie-Liesse Asselin-Labat, Mark Shackleton, John Stingl, François Vaillant, Natasha C. Forrest, Connie J. Eaves, Jane E. Visvader, Geoffrey J. Lindeman
Journal: JNCI Journal of the National Cancer Institute (2006)

The estrogen receptor alpha (ERalpha), progesterone receptor (PR), and erbB2 (Her2 in humans) are important prognostic markers of human breast cancer, and they are variably expressed in different subtypes of breast cancer. The basal subtype, for example, is negative for ERalpha, PR, and Her2 by immunohistochemistry. We investigated the expression of these signaling molecules in enriched populations of mouse mammary stem cells and luminal cells that were isolated according to their differential expression of CD24 and the alpha6beta1-integrin complex. We found that the basal population, which is enriched in mouse mammary stem cells, did not express ERalpha, PR, or ErbB2/Her2 but did express epidermal growth factor receptor (EGFR)/ErbB1, whereas the subset of cells enriched for luminal cells expressed ERalpha (37% of cells) and PR (40% of cells) but not ErbB2/Her2 or EGFR/ErbB1. Ovariectomy confirmed the importance of estrogen signaling to luminal cell proliferation but had no effect on the size of the mouse mammary stem cell-enriched population. Thus, mouse mammary stem cells were negative for ERalpha, PR, and ErbB2 and appeared to share common properties with poor-prognosis basal breast cancer.