tbuckley/cabot-search huggingface dataset:
A Procedure for Culture of Cells From Mouse Tail Biopsies: &lt;italic&gt;Brief Communication&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M R Lander, B Moll, W P Rowe
Journal: JNCI Journal of the National Cancer Institute (1978)

A simple technique was developed for production of cell cultures from mouse tails. The use of mouse tail tissue for biopsies made repeated sampling of animals possible without their health or breeding performance being jeopardized. The procedure proved to be particularly useful in studies of murine leukemia viruses, because it allowed virus induction and Fv-1 gene-typing tests to the done on biopsy tissue from adult animals.
Risks of Vesicoureteric Reflux in the Transplanted Kidney
Authors: Timothy H. Mathew, Priscilla Kincaid-Smith, Poroor Vikraman
Journal: New England Journal of Medicine (1977)

The risk to the transplanted kidney of vesicoureteric reflux was evaluated in 150 consecutive first cadaveric renal allografts surviving for over three months. Of the 119 (79 per cent) allografts studied by micturating cystography 29 (24 per cent) were shown to reflux. The presence of reflux was associated with urine leakage and reoperation, and with ureteric insertion involving a short intramural tunnel. Graft failure (graft nephrectomy or death from renal failure) occurred in 14 of 29 refluxing grafts as compared to 14 failures in 90 nonrefluxing grafts (P less than 0.01). Graft failure in the refluxing group was typically slow, and commonly associated with proteinuria, microscopic hematuria, hypertension and a biopsy appearance of mesangiocapillary glomerular change. Urinary infection, though frequent (69 per cent), was not more common in the group with than in that without reflux. Vesicoureteric reflux is an important cause of late renal-graft failure.
Transfection of dendritic cells (DCs) with mRNA encoding IL-12p70 enhances anti-tumor immunity in melanoma patients
Authors: K. Minkis, D. Kavanagh, D. O'Neill, G. Alter, S. Sunderji, S. Adams, B. Walker, A. C. Pavlick, R. Gandhi, N. Bhardwaj
Journal: Journal of Clinical Oncology (2008)

22217 Background: DCs are widely used in experimental immune-based therapies for melanoma. Prior to injection, DCs are matured with a cocktail of recombinant cytokines and PGE-2, which preserves the ability of DCs to migrate to draining lymph nodes. However, PGE-2 also suppresses the ability of DCs to express IL-12p70. To overcome this paradox, we transfected mature DCs with synthetic mRNA encoding IL-12p70 and evaluated both their innate and adaptive immune functions in vitro. Methods: DCs from healthy donors and melanoma patients were cultured in vitro and transfected with IL-12p70 mRNA. The ability of these DCs to secrete bioactive IL-12p70 was tested by ELISA. Bioactivity of the secreted IL-12 was tested using NK cell assays and allogeneic MLRs. T cell assays were also performed to assess TH1 skewing towards melanoma antigens: T cells from healthy donors and melanoma patients were isolated and stimulated with autologous DCs previously transfected with MART-1 and IL-12p70 mRNA. The quantity and quality of the primed MART-1 specific T cells was determined. For comparison, melanoma tumor-infiltrating T cells (TILs) isolated from a resected tumor were used to examine TH phenotype. Results: IL-12p70-transfected DCs produced bioactive IL-12p70, and enhanced the response of NK cells to MHC class I-negative tumor targets. IL-12p70 transfected DC skewed TH responses away from TH2 in allogeneic MLRs. Cotransfection of DCs derived from the blood of healthy donors with IL-12p70 and MART-1 enhanced in vitro priming of melanoma- specific CD8 T cells, enhanced their capacity to secrete IFNγ and inhibited the production of the TH2 cytokines IL-4 and IL-5, compared to MART-1 alone. In contrast, TILs from resected tumor exhibited a strong TH2 phenotype. T cell lines primed in vitro from the blood of melanoma patients by autologous DCs also showed strong TH2 skewing that was reversed by IL-12p70 transfection. Conclusions: Clinical DC preparations may be improved by IL-12p70 transfection, which enhances both innate and antigen-specific anti-tumor immune responses in vitro. This approach can be applied in vivo, thereby contributing to effective immune-based therapy against melanoma. No significant financial relationships to disclose.
Abstract 286: Structural Determinants Of Thermodynamic Stability And Actin-binding Function Of Dystrophin And Utrophin
Authors: Krishna Mallela, Swati Bandi, Surinder Singh
Journal: Circulation Research (2013)

Muscular dystrophy (MD) is an incurable disease, and affects all types of muscles. The decreased function of heart muscles causes heart problems such as cardiomyopathy and congestive heart failure. A deficiency in functional dystrophin protein in muscle cells triggers the onset of Duchenne MD and Becker MD. Utrophin is the closest homologue of dystrophin and is being tested as a protein drug to replace the loss of functional dystrophin in human patients. However, utrophin is less stable and binds to actin through a different mode of contact when compared with dystrophin. To optimize utrophin as the protein drug, we first need to understand how its molecular structure controls its stability and function. Utrophin and dystrophin bind to actin using tandem calponin-homology (CH) domains at their N-terminus. Individual CH domains of utrophin and dystrophin are very similar in amino acid sequence and their three dimensional structures. The major difference is in their relative orientation around the linker region that connects the two CH domains. To determine the role of the linker, we designed constructs with linkers switched between utrophin and dystrophin. Our results indicate that the tandem CH domain of utrophin with dystrophin linker (UDL) is more stable than that of utrophin but less stable than that of dystrophin. Similarly, tandem CH domain of dystrophin with utrophin linker (DUL) is less stable than that of dystrophin but more stable than that of utrophin. Kinetic folding and unfolding studies suggest that the linker predominantly affects the folding rate rather than the unfolding rate. In addition to stability and folding, the linker also controls protein aggregation. UDL is more prone to aggregation when compared with that of utrophin, whereas DUL is less prone to aggregation when compared with that of dystrophin. These results indicate that the linker plays a major role in controlling the stability and function of tandem CH domains, and further suggests that it is possible to engineer utrophin to behave precisely like dystrophin based on their molecular structures.
Barriers against split-dose bowel preparation for colonoscopy
Authors: F Radaelli, S Paggi, A Repici, G Gullotti, P Cesaro, G Rotondano, L Cugia, C Trovato, C Spada, L Fuccio, P Occhipinti, F Pace, C Fabbri, A Buda, G Manes, G Feliciangeli, M Manno, L Barresi, A Anderloni, P Dulbecco, F Rogai, A Amato, C Senore, C Hassan
Journal: Gut (2016)

<h3>Objective</h3> Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients9 attitude towards split regimen and patient-related factors associated with its uptake. <h3>Design</h3> In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. <h3>Results</h3> Of the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p&lt;0.001, χ<sup>2</sup> for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service &gt;1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). <h3>Conclusion</h3> Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. <h3>Trial registration number</h3> NCT02287051; pre-result.
Tuberculous Meningitis in Patients Infected with the Human Immunodeficiency Virus
Authors: Juan Berenguer, Santiago Moreno, Fernando Laguna, Teresa Vicente, Magdalena Adrados, Arturo Ortega, Juan González-LaHoz, Emilio Bouza
Journal: New England Journal of Medicine (1992)

Tuberculosis is a frequent complication of human immunodeficiency virus (HIV) infection. We describe the clinical manifestations and outcomes of tuberculous meningitis in patients with HIV infection, and compare them with those in non—HIV-infected patients. We reviewed the records from 1985 through 1990 at two large referral hospitals in Madrid for patients who had Mycobacterium tuberculosis isolated from cerebrospinal fluid.
Artificial Insemination with Fresh Donor Semen
Authors: Ronald C. Strickler, David W. Keller, James C. Warren
Journal: New England Journal of Medicine (1975)

A total of 141 patients received donor insemination during a 2 1/2-year period. Pregnancy was achieved by 57 per cent of these patients. When patients who were inseminated for less than three cycles are excluded, the pregnancy rate is 77 per cent. The mean conception time was three treatment cycles. In 69 pregnancies, the occurrence of abortion was that of the general population, and an increased male-to-female ratio was observed in the 36 live-born infants. Questionnaires sent to all couples and returned by 81 per cent indicated that donor insemination was not emotionally harmful to their marriage. Heterologous insemination is a safe, effective therapeutic alternative to adoption for selected couples. (N Engl J Med 293:848–853, 1975)
Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder
Authors: R W Lam, C P Gorman, M Michalon, M Steiner, A J Levitt, M R Corral, G D Watson, R L Morehouse, W Tam, R T Joffe
Journal: American Journal of Psychiatry (1995)

The authors investigated the efficacy and safety of fluoxetine in the treatment of winter seasonal affective disorder.Sixty-eight outpatients who met the DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern, were randomly assigned to 5 weeks of treatment with fluoxetine, 20 mg/day (N = 36), or placebo (N = 32). The outcome measures included the 29-item modified Hamilton Depression Rating Scale, administered by experienced clinicians, and the self-rated Beck Depression Inventory; adverse events and safety data were also recorded. Clinical response was defined as a greater than 50% reduction in depression score between baseline and study termination.Both groups showed significant improvement. The fluoxetine group had lower depression scores at termination than the placebo group, but these differences did not achieve statistical significance. However, the rate of clinical response in the fluoxetine group (59%) was superior to that in the placebo group (34%). Post hoc analyses showed that the greatest fluoxetine responses were in the most markedly depressed patients and that overall response was greater for patients studied later in the season. Fluoxetine was well tolerated, and few subjects dropped out because of adverse events.On the basis of clinical response rate, fluoxetine appears to be an effective, well-tolerated treatment for seasonal affective disorder. Because the differences between fluoxetine and placebo in the continuous outcome measures did not reach statistical significance, further studies with larger study groups and longer treatment periods are required to conclusively demonstrate efficacy of fluoxetine for seasonal affective disorder.
Abstract 1944: NFκB: Activation by EGF requires TLR4 and activation by LPS requires EGFR
Authors: Sarmishtha De, Hao Zhou, Xiaoxia Li, George Stark
Journal: Cancer Research (2015)

Abstract In normal cells, quiescent NFκB is activated by inflammatory stimuli, whereas the abnormal constitutive activation of NFκB is important for the survival of most cancer cells. NFκB activation is regulated by several different pathways. Recently we showed that EGFR is an important mediator of NFκB activation, in both non-malignant and malignant cells. We now provide additional mechanistic insight into this pathway by further investigating whether signaling to NFκB in response to EGF depends solely on EGFR, or involves another receptor known to activate NFκB. Knockdown experiments revealed that TLR4 and two downstream components in the canonical TLR4 pathway, MYD88 and TAK1, are all required for EGF-dependent NFκB activation. Conversely, the ability of TLR4 to activate NFκB in response to LPS was impaired by down regulating EGFR expression or by use of the EGFR inhibitor erlotinib. PP2, a general inhibitor of SRC-family kinases, blocked EGF-induced NFκB activation, and the SRC family member LYN became bound to EGFR upon LPS stimulation. Erlotinib blocked this LPS-dependent association, indicating a key role for LYN in EGFR-TLR4 cross signaling. In mice, erlotinib blocked the LPS-induced, NFκB-dependent expression of TNFα and IL-6, indicating that EGFR is essential for LPS-induced NFκB activation in vivo. Citation Format: Sarmishtha De, Hao Zhou, Xiaoxia Li, George Stark. NFκB: Activation by EGF requires TLR4 and activation by LPS requires EGFR. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1944. doi:10.1158/1538-7445.AM2015-1944
Studies of the Familial Nature of Celiac Sprue Using Biopsy of the Small Intestine
Authors: W. C. MacDonald, W. O. Dobbins, C. E. Rubin
Journal: New England Journal of Medicine (1965)

IT is now generally accepted that celiac disease in children and idiopathic steatorrhea (nontropical sprue) in adults are phases of the same disease.1 For convenience we refer to this entity as celiac sprue.2 It has long been recognized that this disease has a familial tendency, cases being reported in parents and children,3,4 siblings5 and twins.6,7 Davidson et al.8 recorded steatorrhea in 5 members of 1 family. Davidson and Fountain9 obtained a history of steatorrhea in another family member in 9.2 per cent of 130 cases of celiac disease and in 4 per cent of 75 cases of idiopathic . . .
Hsp70 preventing thrombosis: benefit without burden?
Authors: Daniel Duerschmied, Christoph Bode
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Hsp70 protects from stroke in atrial ﬁbrillation patients by preventing thrombosis without increased bleeding risk’ by M. Allende et al ., pp. 309–318. 

Thromboembolism is a major killer worldwide and is also involved in debilitating chronic ischaemic disease of heart and brain. Most cases of myocardial infarction, stroke, and pulmonary embolism are caused by a thrombus that contains fibrin and activated platelets. Antithrombotic therapy targets both the coagulation process of fibrin formation and platelet activation. However, any antithrombotic agent that effectively prevents thrombus formation increases the risk for bleeding, because both coagulation and platelets are required for haemostasis. Clinicians generally accept this paradigm as an unavoidable trade-off. Many researchers however refuse to accept this and have tried to …
Case 22-1966
Authors: Henning Pontoppidan, John B. Blennerhassett
Journal: New England Journal of Medicine (1966)

Presentation of Case First admission. A seventy-two-year-old man entered the hospital because of dyspnea.He had been well until nine years previously, when an aneurysm of the abdominal aorta was found in the course of a suprapubic prostatectomy. X-ray films of the chest showed minimal elongation of the thoracic portion of the aorta but were otherwise normal; an electrocardiogram was within normal limits. Several weeks later the aneurysm was resected, and an aortic homograft was inserted. Thereafter, he experienced mild exertional dyspnea, with little progression during the next few years. Three years before admission x-ray films of the chest . . .
Death by Prescription
Authors: George J. Annas
Journal: New England Journal of Medicine (1994)

Society and physicians in the United States remain unable to accept death and thus unable to deal with the physical, psychological, and spiritual approach of death. The hour of death itself “is commonly tranquil,” but “the serenity is usually bought at a fearful price -- and the price is the process by which we reach that point”1 -- a process that has been described as “a purgatory that may last for weeks.”1 Suicide has been seen as a rational way to avoid that purgatory, especially as a response to end-stage cancer and AIDS, and proposals to “legalize” physician-assisted suicide in . . .
P176 Epidermal Growth Factor Receptor (EGFR) Mutation Testing and Treatment Choice in Advanced Non-small Cell Lung Cancer (NSCLC): UK Findings from a Global Survey
Authors: J Spicer, B Tischer, M Peters
Journal: Thorax (2015)

<h3>Introduction</h3> International and UK guidelines recommend EGFR mutation testing should be performed for advanced non-squamous NSCLC and results should guide treatment decisions. This testing is an important component of standard care because matching mutations to specific TKI treatment can extend survival and improve quality of life compared to first-line chemotherapy. <h3>Objectives</h3> To assess the prevalence of EGFR mutation testing, attitudes and barriers to testing, and how results affect choice of therapy among prescribers in the UK and internationally. <h3>Methods</h3> We conducted an online representative survey of 562 prescribers in 10 countries (Canada, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, UK and US) between December 2014 and January 2015, including 51 oncologists in the UK (Annals of Oncology, Volume 26, Supplement 1, 2015). <h3>Results</h3> In the UK, prescribers stated that 77% of newly diagnosed patients with advanced NSCLC were tested for EGFR mutations, the same proportion as in Europe (77%) and North America (76%), but less than in Asia (92%). The stated reasons for not testing included: histology, insufficient tissue to perform the test, poor performance status, and long turnaround time for results. Despite the relatively high rate of EGFR testing claimed in the UK, respondents said that 21% of patients for whom a test was ordered were started on first-line treatment before results were available, nearly double the rate in Asia (12%). Further, 67% of UK of oncologists, compared to 51% of all respondents, reported that treatment decisions were not affected by EGFR mutation subtype. <h3>Conclusion</h3> Despite the high levels of EGFR mutation testing in the UK, the survey found that more than one in five patients with advanced NSCLC do not receive treatment personalised for cancer type and mutation subtype, even though evidence shows this improves survival and quality of life. These findings suggest there is incomplete implementation of UK guidelines. Further research is needed to discover what factors contribute to oncologists not following established guidelines in the UK. These data were originally presented at the European Lung Cancer Conference, 2015. Annals of Oncology, Volume 26, Supplement 1, 2015. <h3>Reference</h3> 1 Spicer J, Tischer B, Peters M. EGFR mutation testing and oncologist treatment choice in advanced NSCLC: global trends and differences. <i>Annals of Oncology</i> 2015;<b>26</b>(supplement 1):i57–i61
Discontinuation of ventilation after brain stem death
Authors: R Khanna, M A Chaudhry, D. Michaeli
Journal: BMJ (1999)

Editor—We were interested in the educational debate concerning withdrawal of ventilatory support after confirmation of brain stem death.1 Clearly if ventilatory support is withdrawn without the agreement of the family, although such action may be medically and legally correct, the potential for sensationalised unfavourable headings in tabloid newspapers must be considered.

Although the medicolegal and ethical aspects of the issue have been discussed, the scientific aspects have not been. Unlike in the persistent vegetative state, brain stem death is followed by a series of profound changes in the autonomic and hormonal mechanisms regulating the cardiovascular system. Complete cardiovascular and autonomic uncoupling has been shown in humans after brain stem death.2 In validated animal models of brain stem death a catecholamine surge was consistently observed after brain stem death, followed rapidly by decreases in vasopressin, adrenocorticotrophic hormone, thyroxine, and glucagon concentrations.3 Inotropic and vasoactive treatment is therefore frequently required to maintain organ function for potential donation.

It has been established that, despite full cardiovascular support, most deeply comatose patients (97% of 140) will develop asystole in a week.4 Clearly, the time for developing asystole is likely to be shorter in patients with brain stem death, especially if full cardiovascular support is not attempted. We suggest that in such cases it would be reasonable to continue ventilatory and circulatory support without further manipulation. In almost all cases managed in this way rapid cardiac death will ensue.

Although we have no satisfactory answer to the central question raised as to whom the duty of care is greatest—the grieving family or another critically ill patient—we believe that nature should be allowed to take its own course and end the dilemma.