tbuckley/cabot-search huggingface dataset:
937. Generation of Anti-LOX-1 Cytotoxic T Lymphocytes by AAV Manipulation of Dendritic Cells towards Preventing Atherosclerosis
Authors: Jin Xie, Jay L. Mehta, Jawei Chen, Yong Liu, Paul L. Hermonat
Journal: Molecular Therapy (2005)

The ultimate goal of this study is to analyze a hypothesis that a |[ldquo]|vaccine|[rdquo]| against atherosclerosis is feasible and viable.We think that cytotoxic T lymphocytes (CTL) can target cells involved in the earliest stages of atherogenesis, thus preventing initiation of atherosclerosis.It is well-known that activation of endothelium resulting in the expression of LOX-1, an endothelium-specific receptor for oxidized low density lipoprotein (Ox-LDL) is an early event in atherogenesis. If we can selectively target the cells that express LOX-1 this may stop the first step in atherogenesis, and then, logically, stop/prevent the progression of atherogenesis. However LOX-1 is a |[ldquo]|self|[rdquo]| antigen, not a viral or bacterial antigen and T cell responders against such self antigens are much more rare than against non-self antigens. Thus our method for generating CTL must be a very good one. Dendritic cells (DC) are the key cells which initiate the CTL response by presenting antigens to naive T cells, some of which respond. To optimize CTL response against these antigens, we used Adeno-Associated Virus (AAV) gene delivery of the LOX-1 antigen into DC (also called |[ldquo]|loading|[rdquo]| DC) and T cells. This direct genetic alteration of DC and CTL should result in the continuous and stable expression of both antigen and cytokine proteins. It was found that (rAAV)-based antigen-loading of dendritic cells generated significant and rapid (one stimulation/one week) cytotoxic T lymphocyte (CTL) responses in vitro against the LOX-1 self-antigen. Killing of synthetic and natural LOX-1-positive target cells could be demonstrated. There was also no evidence of natural killer cell involvement. These data extend our earlier studies, and suggest that the rAAV-loading of DC may be a particularly good protocol for generating CTL against self-antigens which may not otherwise be considered good targets due to their low immunogenicity. We next must observe if these anti-LOX-1 CTL can limit atherogenesis in an animal model.
Preterm Delivery for Sensitized Rh-Negative Mothers
Authors: C. P. Goplerud
Journal: JAMA (1963)

Planned early delivery for selected, sensitized, Rh-negative patients to avoid fetal death or the delivery of severely anemic and hydropic infants resulted in the salvage of 59 of 73 Rh-positive infants. By previous and present experience maternal antibody titers have proved to be inadequate in predicting the severity of fetal involvement in utero. The selection of patients for early delivery was made primarily from obstetric history unless maternal hydramnios or cessation of fetal activity intervened. While this prognostic mechanism was adequate in most instances, there is obvious need for a means of accurately predicting the status of the individual fetus to prevent perinatal mortality from prematurity as well as from far-advanced hemolytic disease.
Abstract 4415: Inhibition of mammalian target of rapamycin (mTOR) signaling by Temsirolimus as a potential therapeutic strategy for esophageal cancer treatment
Authors: Munenori Takaoka, Toshio Nishikawa, Toshiaki Ohara, Yasuko Tomono, Yasuhiro Fujiwara, Yasuhiro Shirakawa, Hitoshi Nagatsuka, Takuya Fukazawa, Tomoki Yamatsuji, Xiaohong Bao, Huifang Hao, Kaori Shigemitsu, Ichiro Morita, Toshiyoshi Fujiwara, Yoshio Naomoto
Journal: Cancer Research (2011)

Abstract [Introduction] Mammalian target of rapamycin (mTOR) is an intracellular serine/threonine kinase involved in the control of translational initiation by activating its downstream molecules such as S6 kinase and 4E-BP1 and therefore plays a critical role for cell proliferation, survival and angiogenesis, each of which is infinitely activated during cancer progression. Recently, chemical inhibitors against mTOR have been synthesized and Temsirolimus, an analog of rapamycin, has been approved for clinical usage to renal cell carcinomas. Since esophageal cancer is one of the most aggressive cancers with poor prognosis, we aimed to explore a potential effectiveness of Temsirolimus as a new therapeutic option to treat esophageal cancer. [Methods] Firstly, we performed immunohistochemistry for phosphorylated mTOR in fifty-eight cases of surgically resected esophageal squamous cell carcinoma (ESCC) tissues and cultured ESCC cell lines (TE-1, TE-8, and TE-10) to compare its expression to normal esophageal epithelial tissues or primary esophageal epithelial cells. Next we treated these ESCC cells with a novel mTOR inhibitor, temsirolimus to determine its inhibitory effects on the expression of the downstream molecules and cancer cell growth. Furthermore, we administered temsirolimus weekly to nude mice with subcutaneous or orthotopic xenograft with TE-8 cells to obtain its antitumor effects and a benefit of prolonged survival. [Results] The expression of phosphorylated mTOR was increased in 46 of 58 ESCC tumors (79.3%) and appeared to get strengthened with tumor progression. All of ESCC cell lines revealed an increase of mTOR phosphorylation, accompanied with the upregulation of hypoxia inducible factor-I alpha (HIF-1α), one of the downstream effectors of mTOR. Temsirolimus treatment apparently suppressed mTOR phosphorylation and the activation of its downstream effectors, resulting in the reduced ability of ESCC cell proliferation. Finally, the weekly administration of temsirolimus significantly diminished the size of subcutaneous tumors in nude mice and effectively prolonged orthotopic esophageal cancer-bearing mice. [Conclusion] As the increased activity of mTOR signaling can be critical for ESCC progression, our study may contribute to developing an alternative therapeutic strategy for ESCC, by targeting mTOR with Temsirolimus. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4415. doi:10.1158/1538-7445.AM2011-4415
Increased p53 Level, Bax/Bcl-x<sub>L</sub> Ratio, and TRAIL Receptor Expression in Human Emphysema
Authors: Mathieu C. Morissette, Guillaume Vachon-Beaudoin, Julie Parent, Jamila Chakir, Julie Milot
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Emphysema is mainly known for the complex inflammatory processes associated with its development. In addition to lung inflammation, it is now accepted that increased alveolar cell apoptosis is also part of emphysema pathophysiology. However, little is known about the mechanisms involved in alveolar apoptosis. We postulate that oxidative stress and proinflammatory cytokines could lead to p53 accumulation, Bax/Bcl-xL ratio elevation, and higher tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) receptor levels in the emphysematous lung.Objectives: To evaluate the expression of p53, Bax, Bcl-xL, TRAIL, and TRAIL receptors in lung parenchyma from nonemphysematous nonsmokers and smokers and emphysematous smokers and ex-smokers and to determine whether H2O2 and/or TNF can modulate the expression of these apoptotic proteins.Methods: p53, Bax, Bcl-xL, and TRAIL receptor protein levels in lung parenchyma were measured by Western blot, and TRAIL mRNA levels were measured by real-time polymerase chain reaction. Changes in TRAIL receptor, Bax, Bcl-xL, and p53 protein levels after in vitro H2O2 and/or TNF stimulation of A549 cells were also assessed by Western blot.Measurements and Main Results: The p53 protein levels, the Bax/Bcl-xL ratio, and TRAIL receptors 1, 2, and 3 protein levels were significantly higher in subjects with emphysema. Moreover, they were also increased after H2O2 and TNF treatments of A549 cells.Conclusions: These findings suggest that oxidative stress and proinflammatory cytokines may be involved in the elevation of p53 levels, the Bax/Bcl-xL ratio, and TRAIL receptor levels, new mechanisms that may be implicated in the increased alveolar cell apoptosis that occurs in emphysema.
Career development centres for doctors
Authors: S. Kisely
Journal: BMJ (1998)

When the job for life is dead, reviewing career direction is vital. Steve Kisely was one of a team that piloted a three day course to help NHS doctors to plan their own futures 

Assessment and development centres have long been used in industry for the selection and career development of key staff. By contrast, the NHS places little emphasis on the career development of its staff. Although postgraduate deans, training scheme organisers, and trainers have responsibility for giving careers advice to doctors in training grades, this is not accessible to those in career grades, such as consultants, associate specialists, staff grade doctors, general practitioner principals, and community health doctors. In theory, careers advice could form part of continuing professional development (CPD), but it has not formed a prominent feature of college or faculty programmes to date. This article describes experience of a career development centre largely designed for NHS consultants.

Historically, attainment of a consultant post has been seen as a career end point. Once appointed, consultants could expect to spend 20-30 years in a stable career structure until retirement. For many, a purely clinical career sufficed, while others sought additional roles in line with their individual interests, participating in education and training, royal college or faculty activities, academic work, or medicopolitics.

Recently, a number of developments have challenged the assumption of a “job for life.” The advent of shorter, more structured postgraduate training for junior doctors means that many will be appointed as consultants earlier in their clinical career, and they may therefore seek greater diversity of experience in their consultant post. In addition, more doctors are exploring the increasing opportunities …
Studying for the MRCP---was it worth while?
Authors: W. Finckh
Journal: BMJ (1999)

When in 1996 I decided to do part of my further vocational training in Britain, I also decided to attempt the membership examination of the Royal College of Physicians. I knew it was said to be difficult, but as I was advanced in my training and always had passed examinations easily, I thought of it as a challenge.

I started studying and soon was annoyed by the multiple choice questions. So many of them were irrelevant to clinical medicine. Does it really matter whether I know all the rare associations of rare diseases? In a preparation course for part 1 I learnt that questions starting “there is a recognised association” almost always are true while questions containing the words “always” or “never” almost always are wrong. This knowledge helped me …
Quality-of-Life Changes and Hearing Impairment
Authors: Cynthia D. Mulrow
Journal: Annals of Internal Medicine (1990)

Objective: To assess whether hearing aids improve the quality of life of elderly persons with hearing loss. Setting: Primary care clinics at a Bureau of Veterans Affairs hospital. Patients: One hundred and ninety-four elderly veterans who were identified as being hearing impaired from a screening survey involving 771 consecutive clinic patients. Of the original 194, 188 (97%) completed the trial. Intervention: Subjects were randomly assigned to either receive a hearing aid (n = 95) or join a waiting list (n = 99). Main Endpoints: A comprehensive battery of disease-specific and generic quality-of-life measures were administered at baseline, 6 weeks, and 4 months. Measurements and Main Results: Persons assigned to the two groups were similar in age, ethnicity, education, marital status, occupation, and comorbid diseases. At baseline, 82% of subjects reported adverse effects on quality of life due to hearing impairment, and 24% were depressed. At follow-up, a significant change in score improvements for social and emotional function (34.0; 95% CI, 27.3 to 40.8; P < 0.0001), communication function (24.2; CI, 17.2 to 31.2; P < 0.0001), cognitive function (0.28; CI, 0.08 to 0.48; P = 0.008), and depression (0.80; CI, 0.09 to 1.51; P = 0.03) was seen in subjects who received hearing aids compared with those assigned to the waiting list. Six drop-outs (three per group), no crossovers, and no significant changes in cointerventions were seen. Average, self-reported, daily aid use in the hearing aid group was 8 hours. Conclusion: Hearing loss is associated with important adverse effects on the quality of life of elderly persons, effects which are reversible with hearing aids.
Higher Bcl‐2 levels decrease staphylococcal superantigen‐induced apoptosis of CD4<sup>+</sup> T cells in atopic dermatitis
Authors: Y. T. Lin, C. T. Wang, J. H. Lee, C. Y. Chu, W. C. Tsao, Y. H. Yang, B. L. Chiang
Journal: Allergy (2007)

Staphylococcal superantigens (SsAgs) contribute to the persistence of allergic skin inflammation in atopic dermatitis (AD). The aims of this study were to (1) determine whether there are differences between AD patients and healthy subjects in SsAg-induced caspase-3 activation and SsAg-induced changes of anti-apoptotic protein Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells; (2) investigate the effect of interleukin (IL)-4 on SsAg-induced caspase-3 activation and SsAg-induced changes of Bcl-2 and Bcl-2 mRNA levels of CD4+ T cells.Using immunofluorescence staining followed by flow cytometric analysis and real-time PCR, we analyzed peripheral blood mononuclear cells with or without staphylococcal enterotoxin B (SEB) stimulation in the presence or absence of recombinant IL-4 or anti-IL-4 neutralizing antibodies in 16 AD patients and 14 healthy subjects.SEB-reactive (TCRVbeta3+, Vbeta12+, and Vbeta17+) CD4+ T cells from AD patients were more resistant to SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA than those from healthy subjects. Exogenously added IL-4 inhibited SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from healthy subjects. Inhibition of endogenous IL-4 by using anti-IL-4 neutralizing antibodies up-regulated SEB-induced caspase-3 activation and SEB-induced decrease of Bcl-2 and Bcl-2 mRNA in SEB-reactive CD4+ T cells from AD patients.Following SsAg stimulation, IL-4 produced by T cells in AD patients down-regulates SsAg-induced caspase-3 activation and apoptosis of CD4+ T cells through inhibiting the decrease of Bcl-2. This may impair deletion of SsAg-activated T cells and resolution of allergic skin inflammation.
Relational complexity metric is effective when assessments are based on actual cognitive processes
Authors: Graeme S. Halford, William H. Wilson, Steven Phillips
Journal: Behavioral and Brain Sciences (1998)

The core issue of our target article concerns how relational complexity should be assessed. We propose that assessments must be based on actual cognitive processes used in performing each step of a task. Complexity comparisons are important for the orderly interpretation of research findings. The links between relational complexity theory and several other formulations, as well as its implications for neural functioning, connectionist models, the roles of knowledge, and individual and developmental differences, are considered.
Injury Reporting and Recording
Authors: Jess F. Kraus
Journal: JAMA (1970)

A fundamental problem associated with an epidemiologic assessment of sports-injury data is the inconsistent manner in which injury information is collected and recorded. This finding has prompted the American College of Sports Medicine, the American Standards Association, and the Joint Committee on Competitive Safeguards and Medical Aspects of Sports to institute special inquiries into methods for developing a uniform data collection system. (The National Collegiate Athletic Association and the Joint Committee on Competitive Safeguards and Medical Aspects of Sports have been involved in previous efforts to collect valid data on football injuries. The National Tackle Football Injury surveillance project is an expanded extension of that effort.) The objective of these groups is the orderly rendering of data basic to an understanding of the etiology of sports injuries. Several essential elements must be treated as prerequisite for the establishment of an injury-data collection system. The scope of these considerations is limited
The selective poly(ADP)ribose-polymerase 1 inhibitor INO1001 reduces spinal cord injury during porcine aortic cross-clamping-induced ischemia/reperfusion injury
Authors: Christian Maier, Angelika Scheuerle, Balázs Hauser, Hubert Schelzig, Csaba Szabó, Peter Radermacher, Jochen Kick
Journal: Intensive Care Medicine (2007)
Comparative sensitivity of indirect immunofluorescence to immunoblot assay for the detection of circulating antibodies to bullous pemphigoid antigens 1 and 2
Authors: R. GHOHESTANI, J. KANITAKIS, J.F. NICOLAS, E. COZZANI, A. CLAUDY
Journal: British Journal of Dermatology (1996)

The sera of 263 patients with bullous pemphigoid (BP) were tested by indirect immunofluorescence (IIF) on salt‐split skin (SSS) and immunoblot (IB) assay, in order to assess the diagnostic sensitivity of these techniques. Among the 263 sera tested. 198 sera (75%) contained antibasement membrane zone antibodies demonstrable by IIF reacting to the epidermal (98%) or both the dermal and epidermal sides (2%) of SSS. One hundred and eighty‐two of the 263 sera (69%) reacted by IB with BP antigens (Ag), most commonly the BPAgl (93 cases, 51%), and a complex of BPAgl and the 180kDa minor BP antigen (BPAg2) (47 cases, 26%). BPAg2 alone was found in 42 cases (23%). A good correlation was found between the detection of autoantibodies by IIF and labelling of BPAg1 and/or BPAg2 by IB assay, in which 152 of 198 sera with an epidermal pattern in IIF identified a BP antigen. IB analysis of the 65 sera negative by IIF yielded positive results in 30 cases (46%). Thirty‐one per cent (13 of 42) of sera recognizing by IB BPAg2, were negative by IIF, as compared with 12% (11 of 93) of those recognizing BPAg1 (P < 0.01). Comparing the sensitivity of the two tests, IIF (75%) was found to be more sensitive than IB (69%). Thirty‐five of the 263 sera (13%) remained negative by both techniques. It can be concluded from this study that IIF on SSS appears to be a sensitive and reliable assay for screening BP;IB should be performed for the sera that are negative by IIF as it may reveal circulating antibodies, particularly to BPAg2.
Lessons from a Sad Story
Authors: John Lister
Journal: New England Journal of Medicine (1979)

PHYSICIANS in Britain can still practice without too much fear of litigation, and the number of serious complaints made against doctors and hospitals is surprisingly small. Indeed, it is sometimes thought that too little is done to safeguard standards of patient care by means of monitoring, audit and peer review; it may be that the recently published report1 of a committee of inquiry into both the management and the medical and nursing care at a small 200-bed mental hospital near London will stimulate further debate on these topics.Trouble seems to have started at Normansfield psychiatric hospital several years ago . . .
Severe bleeding disorders in children with normal coagulation screening tests.
Authors: G P Taylor
Journal: BMJ (1982)

26 Lupton EW, O'Reilly PH, Testa HJ, et al. Diuresis renography and mor? phology in urinary tract obstruction. Br J Urol 1979;51:10-5. 27 Lupton EW, Testa HJ, Lawson RS, Charlton Edwards E, Carroll RNP, Barnard RJ. Diuresis renography and the results of surgery for idio pathic hydronephrosis. Br J Urol 1980;51:449-53. 28 KorT SA. Experimental validation of diagnostic methods in idiopathic hydronephrosis. In: O'Reilly PH, Gosling JA, eds. Idiopathic hydro? nephrosis. Berlin, Heidelberg and New York: Springer Verlag, 1982. 29 Lome L, Persky S, Levy L. Dynamic renal scanning in the non-visualised kidney. J Urol 1979;121:148-53. 30 Sherman RA, Blaufox MD. Clinical significance of non-visualisation with 131I hippuran renal scan. In: Hollenberg NK, Lange S, eds. Radionuclides in nephrology. Stuttgart: Georg Thieme Verlag, 1980. 31 O'Reilly PH, Lawson RS, Shields RA, Testa HJ, Charlton Edwards E. Radionuclide studies of the lower urinary tract. Br J Urol 1981 ;53: 266-70.
Predicting the Response to Nonpharmacologic Treatment in Mild Hypertension
Authors: Thomas G. Pickering
Journal: JAMA (1992)

The physician whose patient presents with blood pressure in the gray zone between normotension and hypertension faces two problems. Should treatment be prescribed, and what can be done to prevent the pressure from rising any higher? Drug treatment, while undoubtedly effective, is expensive, frequently accompanied by side effects, and minimally cost-effective for such patients. Nonpharmacologic treatment offers a potential approach, but here again there are problems. A bewildering array of treatment modalities have been proposed, ranging from dietary modification to behavioral changes, the efficacy of which is in many cases poorly substantiated. Furthermore, it is becoming increasingly clear that individual patients differ widely in the degree to which their blood pressure responds to any type of treatment, See also pp 1213 and 1221. whether pharmacologic or nonpharmacologic. Altering treatment is of no great consequence when it simply means writing a new prescription for a different medication, but many of the
After September 11: a doctor's perspective
Authors: S. Jabbour
Journal: BMJ (2002)

Since September 11, an unruly world has got worse. For us in the Arab and Muslim world, the change has touched us deeply and negatively. Firstly, there was the adventurous war on Afghanistan and unprecedented oppression in Palestine; and now there is the probability of war against Iraq. We are entering an era of massive action by a rising militarism obsessed with security and domination.

Providing humanitarian aid is not an adequate response by doctors to conflict 

Internally, we face more restrictions on political rights under the pretext of security, economic conditions continue to worsen, and religious extremism driven by hopelessness rises. People's needs—national, political, and economic—remain unaddressed, while unmatched wealth is squandered and cheap oil is exchanged for expensive arms. All this has laid the ground for more conflict. This terrible situation is not our problem alone. Because the tremendous suffering associated with ongoing conflicts has affected many communities all over the world, before, on, and …
Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients
Authors: Xingnan Li, Gregory A. Hawkins, Elizabeth J. Ampleford, Wendy C. Moore, Huashi Li, Annette T. Hastie, Timothy D. Howard, Homer A. Boushey, William W. Busse, William J. Calhoun, Mario Castro, Serpil C. Erzurum, Elliot Israel, Robert F. Lemanske, Stanley J. Szefler, Stephen I. Wasserman, Sally E. Wenzel, Stephen P. Peters, Deborah A. Meyers, Eugene R. Bleecker
Journal: Journal of Allergy and Clinical Immunology (2013)