tbuckley/cabot-search huggingface dataset:
Abstract 5608: Sipuleucel-T treatment results in sequential <i>ex vivo</i> activation of APCs and T cells during the culture step - evidence for <i>in vivo</i> immunological priming
Authors: Nadeem A. Sheikh, Corazon P. dela Rosa, Mark W. Frohlich, David L. Urdal, Nicole M. Provost
Journal: Cancer Research (2010)

Abstract Introduction. Sipuleucel-T is an investigational autologous immunotherapy for the treatment of prostate cancer. Product potency is measured in part by antigen presenting cell (APC) expression of CD54. Previous data have shown that CD54 upregulation correlates with APC activation (Sheikh 2008). This study investigated the ex vivo activation profile of T cells from men with metastatic castrate resistant prostate cancer enrolled in a Phase 3 study (D9902B, IMPACT) evaluating the safety and efficacy of sipuleucel-T treatment. Methods. Sipuleucel-T was prepared by incubating mononuclear cells isolated from leukapheresis obtained at Wks 0, 2, and 4 with PA2024 (a recombinant fusion protein comprising prostatic acid phosphatase and GM-CSF) ex vivo for 2 days, after which washed cells were infused. 512 subjects were randomized to sipuleucel-T or placebo (2:1). As part of product characterization efforts, fresh pre- and post-culture (final product - FP) T cells were evaluated in sipuleucel-T products by flow cytometry. The culture supernatant was evaluated for the production of APC and T cell activation-associated cytokines by multiplex luminex assay. Results. APC activation as measured by CD54 upregulation increased from Wk 0 to Wk 2 (P &amp;lt; 0.001) and persisted at the third dose (P &amp;lt; 0.001, Wk 0 vs Wk 4). An analysis of the culture supernatant at each week showed increases in both APC activation-associated cytokines (IL-1α, IL-1β, IL-10, IL-12p70, IL-23, IFNγ, and TNFα) and T cell activation-associated cytokines (IL-2, IL-4, IL-5, IL-10, IL-17, IFNγ, and TNFα). CD134 (OX40), CD137 (4-1BB), CD278 (ICOS), and CD279 (PD-1) expression increased in both CD4+ and CD8+ T cells at Wk 2, with expression diminished at Wk 4. Conclusion. Following The Wk 0 dose, sipuleucel-T products demonstrate evidence of increased APC and T cell activation markers as well as production of T cell activation-associated cytokines. These data provide strong evidence that sipuleucel-T activates APCs ex vivo and facilitates in vivo and ex vivo priming of T cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5608.
Chronic rejection after liver transplantation: A study of clinical, histopathological and immunological features
Authors: Deborah K. Freese, Dale C. Snover, Harvey L. Sharp, Cynthia R. Gross, Kay S. Savick, William D. Payne
Journal: Hepatology (1991)

In an effort to better understand chronic liver transplant rejection, we studied 110 children and adults who survived for at least 2 mo after the transplant procedure. Chronic rejection was defined using a combination of clinical and histopathological criteria and was diagnosed in 10 of the 110 patients for an incidence of 9.1%. All 10 patients were children with the mean age 3.4 yr vs. 21.7 yr for patients without chronic rejection (p less than .001). Males and females were equally represented, and nine received a liver from a gender-matched donor. Four patients were non-Caucasian, resulting in an incidence of 21.7% in non-Caucasian recipients vs. 6.6% in Caucasian recipients (p less than .05). All chronic rejection patients received a liver from an ABO-compatible donor. T-cell crossmatch was negative in all patients in whom it was assessed, and no significant disparity in either the class I or class II human leukocyte antigen loci was noted. Patients who had chronic rejection experienced acute rejection earlier, 11 days vs. 16 days (p less than .05), than patients who did not. In 8 of 10 patients, chronic rejection appeared to evolve directly from early episodes of acute rejection that were unresponsive to immunosuppressive therapy. Two distinct histological presentations were noted. One was progressive loss of bile ducts without hepatocellular injury (four patients), and the other was characterized by worsening ischemic hepatocellular damage and fibrosis (six patients) in addition to severe ductular injury. The first was associated with a more benign clinical course, the second with rapidly deteriorating hepatic function. Three patients recovered spontaneously 9 to 14 mo after transplant, one died awaiting a donor for retransplant, and five had retransplants. We conclude that chronic rejection after the operation is a relatively uncommon complication of liver transplantation with a variable clinical course and unpredictable outcome.
Health and Medicine in the Jewish Tradition: L'Hayyim—To Life
Authors: Allen Verhey
Journal: JAMA (1987)

<h3>Health and Medicine in the Methodist Tradition: Journey Toward Wholeness, by E. Brooks Holifield (Health/Medicine and the Faith Traditions, M. E. Marty and K. L. Vaux, eds), 198 pp, $17.95, New York, Crossroad Publishing Co, 1986.</h3><h3>Health and Medicine in the Lutheran Tradition: Being Well, by Martin E. Marty (Health/Medicine and the Faith Traditions, M. E. Marty and K. L. Vaux, eds), 178 pp, $14.95, New York, Crossroad Publishing Co, 1983.</h3><h3>Health and Medicine in the Catholic Tradition: Tradition in Transition, by Richard A. McCormick (Health/Medicine and the Faith Traditions, M. E. Marty and K L Vaux, eds), 173 pp, $15.95, New York, Crossroad Publishing Co, 1985.</h3><h3>Health and Medicine in the Anglican Tradition: Conscience, Community, and Compromise, by David H. Smith (Health/Medicine and the Faith Traditions, M. E. Marty and K. L. Vaux, eds), 103 pp, $14.95, New York, Crossroad Publishing Co, 1986.</h3><h3>Health and Medicine in the Reformed</h3>
Richard Frederic Stevens
Authors: Paul Crook, David Spooner
Journal: BMJ (2004)

An icon in the treatment of Lassa feverIn early 2000 Dr Bill Aldis, then the World Health Organization's representative in Sierra Leone, remembers getting a worried call from Geneva: "I've got an ICRC [International Committee of the Red Cross] staff member with suspected Lassa fever just evacuated from Kenema [in Sierra Leone].What do I do?" Dr Aldis replied, "The best thing you could do is put him on an airplane and get him back to Kenema-there's a hospital there with the world's greatest expert in Lassa fever, a guy named Conteh . .."Such was the reputation of Aniru Conteh, who ran the world's only Lassa fever isolation ward.Born in 1942 in Jawi Folu, Eastern Province, Sierra Leone, Aniru Conteh was the son of the local chief.At the age of 16 he left home to go to school in the country's capital, Freetown, where he went on to study chemistry and biology at Fourah Bay College.Initially he worked as a teacher, but in 1974 he enrolled as a medical student at the University of Ibadan in Nigeria, where he continued to work after qualifying, until he returned to Sierra Leone in 1979 and started working on the Lassa fever programme.Lassa fever takes its name from a small village in Nigeria, where a mysterious outbreak in a mission hospital in 1969 led to the three mission nurses becoming infected.Two of the nurses died, but the third survived and was evacuated to the Colombia Presbyterian Hospital in New York.Wilbur
Consultants of the future
Authors: J. Smith
Journal: BMJ (1995)

meetings.There is thus conflict between commitment to the service as a whole and commitment to individual patients' care.The report may be used by some managers to put further pressure on consultants to adhere inflexibly to their job plans, to operate more quickly, or to see more outpatients per session.Such moves might jeopardise the good will of the many for the sake of the few bad apples.Action, however, is going to be taken, but perhaps the report does not go far enough.Instead of tightening up on job plans should we not review the whole concept of medical finns?If shift work is appropriate for junior doctors and, incidentally, most other health care workers might it not be appropriate for senior doctors?Teams of specialists could then work together to cover all commitments, both clinical and managerial.This would ensure an equitable distribution of work among doctors.Continuity of care might suffer, but the trade off would be that patients would always be supervised by a specialist.The debate is under way.
Intramuscular Metastasis of Carcinoid Tumor
Authors: Ekaterina Tiktinsky, Tifha Horne, Svetlana Agranovich, Sophie Lantsberg
Journal: Clinical Nuclear Medicine (2008)

A 43-year-old man presented with a 2-month history of left upper lobectomy due to an atypical lung carcinoid tumor. The patient was referred to our department for further evaluation. An In-111 octreotide (Octreoscan) whole body scan and single photon emission computed tomography were performed. The scans showed slightly increased diffused tracer uptake in the apex of the left lung, most probably due to postoperative changes. A focal area of increased uptake in the right lower abdomen was also noted. Fusing octreotide tomographic construction with CT images allowed accurate determination of the area of increased uptake to be in the right transverse abdominal muscle.
Effects of Long-Term Monotherapy With Eplerenone, a Novel Aldosterone Blocker, on Progression of Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure
Authors: George Suzuki, Hideaki Morita, Takayuki Mishima, Victor G. Sharov, Anastassia Todor, Elaine J. Tanhehco, Amy E. Rudolph, Ellen G. McMahon, Sidney Goldstein, Hani N. Sabbah
Journal: Circulation (2002)

Background— In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF. Methods and Results— HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62±4 versus 68±4 mL, P &lt;0.001, and 38±3 versus 47±3 mL, P &lt;0.001, respectively), and EF decreased significantly (38±1% versus 31±2%, P &lt;0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis. Conclusions— Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.
Psychiatrist Named New Deputy Editor of JAMA, Deputy Vice President for Scientific Information
Authors: Marsha F. Goldsmith
Journal: JAMA (1989)

RICHARD M. GLASS, MD, a 45-year-old psychiatrist, has been named deputy editor of The Journal of the American Medical Association and deputy vice president for scientific information. He is the second person to fill the deputy editor's position, which was established in 1975 and was held from August of that year until her retirement in January 1988 by M. Therese Southgate, MD.  For the past 4 years, Glass has been director of Adult Psychiatry Outpatient Services at the University of Chicago Hospitals and Clinics and associate professor of psychiatry at that institution's medical school. He's been a member of the editorial board of the Archives of General Psychiatry since 1984, was assistant to the chief editor there from 1980 to 1984, and has been a consulting editor of JAMA since 1987. He is a member of several national and local professional societies, as well as of the American Association for
Regression of Atherosclerosis
Authors: Bing-Yin Wang, Hoai-Ky V. Ho, Patrick S. Lin, Severin P. Schwarzacher, Matthew J. Pollman, Gary H. Gibbons, Philip S. Tsao, John P. Cooke
Journal: Circulation (1999)

Background —We have recently found that administration of l -arginine to hypercholesterolemic rabbits induces regression of preexisting lesions. Others have previously shown that activation of the l -arginine/nitric oxide (NO) synthase pathway can induce apoptosis of vascular cells in vitro. Accordingly, the current study was designed to determine if dietary supplementation of l -arginine induces apoptosis of intimal lesions and if this effect is mediated through the NO synthase pathway. Methods and Results —Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 weeks and subsequently placed on 2.5% l -arginine HCl in the drinking water, and the cholesterol diet was continued for 2 weeks, at which time the aortas were harvested for histological studies. l -Arginine treatment increased the number of apoptotic cells (largely macrophages) in the intimal lesions by 3-fold (11.9±3.9 vs 3.9±1.4 apoptotic cells/mm 2 , P &lt;0.01). In subsequent studies, aortas were harvested for ex vivo studies. Aortic segments were incubated in cell culture medium for 4 to 24 hours with modulators of the NO synthase pathway. The tissues were then collected for histological studies and the conditioned medium collected for measurement of nitrogen oxides by chemiluminescence. Addition of sodium nitroprusside (10 −5 mol/L) to the medium caused a time-dependent increase in apoptosis of vascular cells (largely macrophages) in the intimal lesion. l -Arginine (10 −3 mol/L) had an identical effect on apoptosis, which was associated with an increase in nitrogen oxides released into the medium. These effects were not mimicked by d -arginine, and they were antagonized by the NO synthase inhibitor l -nitro-arginine (10 −4 mol/L). The effect of l -arginine was not influenced by an antagonist of cGMP-dependent protein kinase, nor was the effect mimicked by the agonist of protein kinase G or 8-BR cGMP. Conclusions —These results indicate that supplemental l -arginine induces apoptosis of macrophages in intimal lesions by its metabolism to NO, which acts through a cGMP-independent pathway. These studies are consistent with our previous observation that supplementation of dietary arginine induces regression of atheroma in this animal model. These studies provide a rationale for further investigation of the therapeutic potential of manipulating the NO synthase pathway in atherosclerosis.
Induction of cystine transport activity in mouse peritoneal macrophages.
Authors: H Watanabe, S Bannai
Journal: The Journal of Experimental Medicine (1987)

Uptake of cystine was investigated in mouse peritoneal macrophages. The rates of the uptake of cystine in resident macrophages or macrophages elicited by some irritants were very low, but a drastic increase was observed when the cells were cultured in vitro. This increase was time-dependent and required protein synthesis. In macrophages elicited by thioglycollate broth, the rate of the uptake of cystine increased by about 40-fold after 16 h in culture. Contrary to the uptake of cystine, the rates of uptake of some neutral amino acids did not change markedly during culture. We characterized the induced activity of the cystine uptake in macrophages elicited by thioglycollate broth. Cystine was taken up in an Na+-independent and pH-sensitive manner, and the uptake was potently inhibited by extracellular glutamate and the analogous anionic amino acids, but not by aspartate. The activity of the glutamate uptake was also induced during the culture in a way similar to that of cystine uptake, and the uptake of glutamate was potently inhibited by cystine. From these results we concluded that the uptake of cystine and glutamate in macrophages was mostly mediated by a single transport system similar to the ones previously reported in human fibroblasts and some other cells. As a consequence of the induction of the activity of the cystine uptake, glutathione levels in macrophages doubled during culture, and a thiol compound, presumably cysteine, was released into the culture medium and accumulated there. When the macrophages were cultured hypoxically, the induction of the cystine uptake activity was markedly depressed, suggesting an involvement of oxygen in the induction.
THE EFFECT OF LOCALISED AND GLOBALISED FATIGUE ON CENTRE OF PRESSURE EXCURSIONS IN HEALTHY AND FUNCTIONALLY UNSTABLE PARTICIPANTS FOLLOWING A SINGLE LEG DROP JUMP LANDING; ANALYSING A SUBCONSCIOUS TIME PERIOD
Authors: C Gautrey, T Watson, A Mitchell
Journal: British Journal of Sports Medicine (2014)

Background It has been reported that fatigue and stability deficits may be predispositions to musculoskeletal injury in functional ankle instability (FAI) sufferers. Analysis of subconscious time periods (initial 200 ms) may identify deficits in FAI sufferers that are not observed when analysing a conscious time frame. Objective To determine whether FAI participants suffer from subconscious neuromuscular deficits compared to healthy controls, as measured by COP excursion, following localised and globalised fatigue. Design Non-randomised experimental. Setting University biomechanics laboratory. Participants A convenience sample was used to recruit twenty males with unilateral FAI and twenty male healthy controls. Inclusion criteria included males, aged 18-25 years, who participated in semi-professional soccer and who were right leg dominant. Risk factor assessment Two localised fatigue protocols were investigated; isokinetic ankle inversion-eversion exercise and hip abduction-adduction exercise. Maximal repetitions were performed until three consecutive repetitions fell below 50% of participants 1RM. The soccer specific Drust protocol was used to elicit globalised fatigue. Three single leg drop jump landings from a 30 cm high bench onto a force platform were performed before and after fatigue. Subject group and fatigue protocols were the independent variables. Main outcome measure COP excursion in the anterior, posterior, anteroposterior, medial, lateral and mediolateral directions, following a single leg drop jump landing, before and after localised and globalised fatigue. Results The globalised soccer specific fatigue protocol caused the greatest significant increase (P &lt; .0125) in medial, lateral and mediolateral excursion in both ankles of the FAI and healthy groups. The hip and ankle localised fatigue protocols found a significant increase (P &lt; .0125) in COP excursion in the lateral and mediolateral directions in the FAI group alone. Conclusion Clinically, the results show that the fatigued individual may be at greater risk of injury, especially during more globalised prolonged exercise involving multiple joints, such as a simulated soccer protocol.
Retrotransposons and Genomic Stability in Populations of the Young Allopolyploid Species Spartina anglica C.E. Hubbard (Poaceae)
Authors: Alex Baumel, Malika Ainouche, Ruslan Kalendar, Alan H. Schulman
Journal: Molecular Biology and Evolution (2002)

Spartina × townsendii arose during the end of the 19th century in England by hybridization between the indigenous Spartina maritima and the introduced Spartina alterniflora, native to the eastern seaboard of North America. Duplication of the hybrid genome gave rise to Spartina anglica, a vigorous allopolyploid involved in natural and artificial invasions on several continents. This system allows investigation of the early evolutionary changes that accompany stabilization of new allopolyploid species. Because allopolyploidy may be a genomic shock, eliciting retroelement insertional activity, we examined whether retrotransposons present in the parental species have been activated in the genome of S. anglica. For this purpose we used inter-retrotransposon amplified polymorphism (IRAP) and retrotransposons-microsatellite amplified polymorphism (REMAP) markers, which are multilocus PCR-based methods detecting retrotransposon integration events in the genome. IRAP and REMAP allowed the screening of insertional polymorphisms in populations of S. anglica. The populations are composed mainly of one major multilocus genotype, identical to the first-generation hybrid S. × townsendii. Few new integration sites were encountered in the young allopolyploid genome. We also found strict additivity of the parental subgenomes in the allopolyploid. Both these findings indicate that the genome of S. anglica has not undergone extensive changes since its formation. This contrasts with previous results from the literature, which report rapid structural changes in experimentally resynthesized allopolyploids.
High-dimensional immunomonitoring models of HIV-1–specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control
Authors: Zaza M. Ndhlovu, Lori B. Chibnik, Jacqueline Proudfoot, Seanna Vine, Ashley McMullen, Kevin Cesa, Filippos Porichis, R. Brad Jones, Donna Marie Alvino, Meghan G. Hart, Eleni Stampouloglou, Alicja Piechocka-Trocha, Carl Kadie, Florencia Pereyra, David Heckerman, Philip L. De Jager, Bruce D. Walker, Daniel E. Kaufmann
Journal: Blood (2012)
Use of a PEG-conjugated bright near-infrared dye for functional imaging of rerouting of tumor lymphatic drainage after sentinel lymph node metastasis
Authors: Steven T. Proulx, Paola Luciani, Ailsa Christiansen, Sinem Karaman, Katrin S. Blum, Matthias Rinderknecht, Jean-Christophe Leroux, Michael Detmar
Journal: Biomaterials (2013)
Laparoscopic adrenalectomy, a safe procedure for pheochromocytoma. A retrospective review of clinical series
Authors: Giovanni Conzo, Mario Musella, Francesco Corcione, Maurizio De Palma, Fausto Ferraro, Antonietta Palazzo, Salvatore Napolitano, Marco Milone, Daniela Pasquali, Antonio Agostino Sinisi, Vittorio Colantuoni, Luigi Santini
Journal: International Journal of Surgery (2012)
Monokine induced by interferon- is induced by receptor activator of nuclear factor B ligand and is involved in osteoclast adhesion and migration
Authors: Han Bok Kwak, Soo Woong Lee, Hye Mi Jin, Hyunil Ha, Sang Ho Lee, Sunao Takeshita, Sakae Tanaka, Hyun-Man Kim, Hong-Hee Kim, Zang Hee Lee
Journal: Blood (2004)
Reappearance of epidermal Langerhans cells after PUVA therapy
Authors: P.S. FRIEDMANN, G. FORD, J. ROSS, B.L. DIFFEY
Journal: British Journal of Dermatology (1983)

Epidermal Langerhans cells (LC) disappear during photochemotherapy (PUVA) with 8-methoxypsoralen (8-MOP) and long wavelength ultraviolet (UV-A) radiation. The time course of their disappearance during treatment and their reappearance after its completion was followed. Langerhans cells lost ATPase activity before they disappeared by ultrastructural criteria: thus 90% of ATPase-stained cells had disappeared after seven treatments (2 weeks) whereas it was only after fifteen treatments (5 weeks) that they were seen to be reduced on electron microscopy. Their numbers remained low throughout the course of treatment but they had returned to normal by 3 weeks after cessation of therapy. Since PUVA lamps also emit traces of medium wavelength UV (UV-B) the separate effects of UV-A and UV-B in the presence and absence of 8-MOP were examined. Within the dose range normally used for therapy, the LC disappeared only with the combination of UV-A and 8-MOP.