tbuckley/cabot-search huggingface dataset:
Deficiency of C5aR Prolongs Renal Allograft Survival
Authors: Qijun Li, Qi Peng, Guolan Xing, Ke Li, Naiyin Wang, Conrad A. Farrar, Lucy Meader, Steven H. Sacks, Wuding Zhou
Journal: Journal of the American Society of Nephrology (2010)

Interaction between C5a, a product of complement activation, and its receptor (C5aR) upregulates antigen-specific T cell responses by modulating the activation of antigen-presenting cells and T cells. Whether this C5a-C5aR interaction contributes to the immune responses that promote renal allograft rejection is unknown. Here, we found that deficiency of C5aR in both graft and recipient reduced allospecific T cell responses and prolonged renal allograft survival. In addition, lack of C5aR impaired the function of donor and recipient antigen-presenting cells and inhibited the response of recipient T cells to allostimulation. Furthermore, deficiency of C5aR in both graft and recipient reduced early inflammation in the grafts, with less cellular infiltration around the vessels and fewer F4/80 positive cells in the peritubular interstitium. These data demonstrate that C5aR is critical for a full adaptive immune response and mediates renal allograft rejection. Engagement of C5aR on dendritic cells and T cells modulates their function, enhancing allospecific T cell responses that lead to allograft rejection. Targeting C5a signaling may have therapeutic potential for T cell-mediated graft rejection.
Porcine liver sinusoidal endothelial cells contribute significantly to intrahepatic ammonia metabolism
Authors: Geir I. Nedredal, Kjetil Elvevold, Lars M. Ytrebφ, Ole-Martin Fuskevåg, Ingvild Pettersen, Peter A. G. McCourt, Kjell Bertheussen, Bård Smedsrφd, Arthur Revhaug
Journal: Hepatology (2009)

Ammonia metabolism in the liver has been largely credited to hepatocytes (HCs). We have shown that liver nonparenchymal cells that include liver sinusoidal endothelial cells (LSECs) produce ammonia. To address the limited knowledge regarding a role for LSECs in ammonia metabolism, we investigated the ammonia metabolism of isolated LSECs and HCs under three different conditions: (1) bioreactors containing LSECs (LSEC-bioreactors), (2) bioreactors containing HCs (HC-bioreactors), and (3) separate bioreactors containing LSECs and HCs connected in sequence (Seq-bioreactors). Our results showed that LSEC-bioreactors released six-fold more ammonia (22.2 nM/hour/10(6) cells) into the growth media than HC-bioreactors (3.3 nM/hour/10(6) cells) and Seq-bioreactors (3.8 nM/hour/10(6) cells). The glutamate released by LSEC-bioreactors (32.0 nM/hour/10(6) cells) was over four-fold larger than that released by HC-bioreactors and Seq-bioreactors (<7 nM/hour/10(6) cells). LSEC-bioreactors and HC-bioreactors consumed large amounts of glutamine (>25 nM/hour/10(6) cells). Glutaminase is known for catalyzing glutamine into glutamate and ammonia. To determine if this mechanism may be responsible for the large levels of glutamate and ammonia found in LSEC-bioreactors, immunolabeling of glutaminase and messenger RNA expression were tested. Our results demonstrated that glutaminase was present with colocalization of an LSEC-specific functional probe in lysosomes of LSECs. Furthermore, using a nucleotide sequence specific for kidney-type glutaminase, reverse-transcription polymerase chain reaction revealed that this isoform of glutaminase was expressed in porcine LSECs.LSECs released large amounts of ammonia, perhaps due to the presence of glutaminase in lysosomes. The ammonia and glutamate released by LSECs in Seq-bioreactors were used by hepatocytes, suggesting an intrahepatic collaboration between these two cell types.
Azathioprine in the management of enteropathy in cystic fibrosis
Authors: Hui-Leng Tan, Neil Shah, Ranjan Suri
Journal: Journal of the Royal Society of Medicine (2011)

While respiratory complications remain the main cause of morbidity and mortality in patients with cystic fibrosis (CF), gastrointestinal (GI) problems are also a significant cause of morbidity. CF research has concentrated on the inflammation in the airways, but there is now increasing evidence of inflammation in the GI tract as well, leading some clinicians to coin the term CF enteropathy. The cause of this inflammation and the best therapeutic options are still to be determined. We describe a case of a 16-year-old boy with CF and enteropathy which was treated with azathioprine.
Abstract 4561: Preclinical characterization of MT112/BAY 2010112, a novel PSMA/CD3-bispecific BiTE antibody for the treatment of prostate cancer
Authors: Ralf Lutterbuese, Matthias Friedrich, Roman Kischel, Doris Rau, Patrick Hoffmann, Evelyn Ebert, Dieter Zopf, Ricarda Finnern, Peter Mueller, Patrick A. Baeuerle, Andreas Wolf, Benno Rattel, Tobias Raum, Peter Kufer
Journal: Cancer Research (2011)

Abstract Prostate-specific membrane antigen (PSMA) has been frequently selected as target antigen for antibody-based therapy of prostate cancer. Here, we recombinantly constructed a PSMA/CD3-bispecific BiTE antibody, called MT112/BAY 2010112. The BiTE antibody was produced in Chinese hamster ovary cells as a secreted protein of 55 kDa, showing high serum and thermal stability. MT112/BAY 2010112, purified as homogenous monomeric protein, bound at low nanomolar concentrations to defined epitopes on PSMA and CD3 antigens of human and macaque origin, respectively. In cell culture studies bispecific binding of MT112/BAY 2010112 selectively redirected human T cells against several PSMA-positive human prostate cancer cell lines as well as PSMA cDNA-transfected cell lines and potently induced specific target cell lysis with EC50 values ranging from 1 to 50 pM using non-stimulated human peripheral blood mononuclear cells as effector cells. EC50 values correlated with the number of PSMA molecules on the cell surface ranging from 37,000-500,000 molecules per cell among the cell lines analyzed. The anti-tumor activity of MT112/BAY 2010112 was assessed in several SCID mouse models bearing subcutaneous xenografts derived from the human prostate cancer cell lines LNCaP, PC3 and 22Rv1. The BiTE antibody completely inhibited growth of tumors at doses as low as 0.005 mg/kg administered daily intravenously when human T cells and tumor cells were co-inoculated. Transient regression of tumors were observed in a model where human T cells were adoptively transferred into the peritoneal space of mice with subcutaneously established tumors. These data suggest that the PSMA/CD3-bispecific antibody MT112/BAY 2010112 has high therapeutic potential for treatment of prostate cancer. Its cross-reactivity with human and macaque PSMA and CD3 antigens will greatly facilitate assessment of pharmacology, pharmacokinetics and safety during further pre-clinical development. 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 4561. doi:10.1158/1538-7445.AM2011-4561
The delivery of thrombi-specific nanoparticles incorporating oligonucleotides into injured cerebrovascular endothelium
Authors: Wei Shi, Heng Mei, Jun Deng, Chen Chen, Huafang Wang, Tao Guo, Bo Zhang, Zhiqing Pang, Xinguo Jiang, Xuxia Wang, Hao Lei, Yu Hu
Journal: Biomaterials (2013)
Transfer of Autologous Gene-modified T Cells in HIV-infected Patients with Advanced Immunodeficiency and Drug-resistant Virus
Authors: Jan van Lunzen, Tobias Glaunsinger, Ingrid Stahmer, Volker von Baehr, Christopher Baum, Andrea Schilz, Klaus Kuehlcke, Sonja Naundorf, Holger Martinius, Felix Hermann, Tsanan Giroglou, Sebastian Newrzela, Ingrid Müller, Francis Brauer, Gunda Brandenburg, Alexander Alexandrov, Dorothee von Laer
Journal: Molecular Therapy (2007)

Drug toxicity and viral resistance limit the long-term efficacy of antiviral drug treatment for human immunodeficiency virus (HIV) infection. Thus, alternative therapies need to be explored. We tested the infusion of T lymphocytes transduced with a retroviral vector (M87o) that expresses an HIV entry-inhibitory peptide (maC46). Gene-modified autologous T cells were infused into ten HIV-infected patients with advanced disease and multidrug-resistant virus during anti-retroviral combination therapy. T-cell infusions were tolerated well, with no severe side effects. A significant increase of CD4 counts was observed after infusion. At the end of the 1-year follow-up, the CD4 counts of all patients were still around or above baseline. Gene-modified cells could be detected in peripheral blood, lymph nodes, and bone marrow throughout the 1-year follow-up, and marking levels correlated with the cell dose. No significant changes of viral load were observed during the first 4 months. Four of the seven patients who changed their antiviral drug regimen thereafter responded with a significant decline in plasma viral load. In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus.
The Allocation of Organs Donated by Altruistic Strangers
Authors: David Steinberg
Journal: Annals of Internal Medicine (2006)

In many transplant centers, organ retrieval from altruistic strangers is accepted practice; patients use Internet Web sites and other public media to locate strangers willing to give them an organ. It is argued that altruistic strangers should be permitted to select the recipients of their organs because 1) personal relationships are morally important; 2) it increases the number of available organs; and 3) no one is hurt by the process. Nonetheless, using public media to obtain organs may undermine equity in organ allocation. Organs donated by altruistic strangers do not go necessarily to patients who have the best immunologic match or the most urgent need or who have waited the longest. A publicly chartered organization should be established to coordinate live organ donation, including donation by altruistic strangers. Altruistic strangers should be educated to allocate their donated organs according to a prudent balance of equity and utility rather than their emotional response to a particular patient's plight, identity, or circumstances.
A double blind randomised trial of low power laser treatment in rheumatoid arthritis.
Authors: J.K. Heussler, G Hinchey, E Margiotta, R Quinn, P Butler, J Martin, A.D. Sturgess
Journal: Annals of the Rheumatic Diseases (1993)

To define the value of low power laser treatment in small joint rheumatoid arthritis. Twenty five women with active disease were recruited. The metacarpophalangeal and proximal interphalangeal joints of one hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser. The other hand received a sham laser treatment designed so that neither therapist nor patient could distinguish the active laser from the sham laser. Each patient received 12 treatments over four weeks. The following parameters were measured: pain as assessed by visual analogue scale; range of joint movements; grip strength; duration of early morning stiffness, joint circumference, Jebsen's hand assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement Scales; three phase bone scans; haematological and serological tests. A total of 72% of patients reported pain relief but this reduction was reported equally in both hands. No significant changes were seen in other clinical, functional, scintigraphic, or laboratory features. Neither patients nor staff were able to detect which hand was treated with the active laser. When this specific laser and dose regimen was used, low power laser treatment had no objective effect on patients with rheumatoid arthritis. It did appear to produce analgesia through a powerful placebo effect.
8-hydroxy-2'-deoxyguanosine, a major mutagenic oxidative DNA lesion, and DNA strand breaks in nasal respiratory epithelium of children exposed to urban pollution.
Authors: L Calderón-Garcidueñas, L Wen-Wang, Y J Zhang, A Rodriguez-Alcaraz, N Osnaya, A Villarreal-Calderón, R M Santella
Journal: Environmental Health Perspectives (1999)

Southwest metropolitan Mexico City children are repeatedly exposed to high levels of a complex mixture of air pollutants, including ozone, particulate matter, aldehydes, metals, and nitrogen oxides. We explored nasal cell 8-hydroxy-2'-deoxyguanosine (8-OHdG), a major mutagenic lesion producing G-->T transversion mutations, using an immunohistochemical method, and DNA single strand breaks (ssb) using the single cell gel electrophoresis assay as biomarkers of oxidant exposure. Nasal biopsies from the posterior inferior turbinate were examined in children in grades one through five, including 12 controls from a low-polluted coastal town and 87 Mexico City children. Each biopsy was divided for the 8-OHdG and DNA ssb assays. There was an age-dependent increase in the percentage of nasal cells with DNA tails > 10 microm in Mexico City children: 19 +/- 9% for control cells, and 43 +/- 4, 50 +/- 16, 56 +/- 17, 60 +/- 17 and 73 +/- 14%, respectively, for first through fifth graders (p < 0.05). Nasal ssb were significantly higher in fifth graders than in first graders (p < 0.05). Higher levels (2.3- to 3-fold) of specific nuclear staining for 8-OHdG were observed in exposed children as compared to controls (p < 0.05). These results suggest that DNA damage is present in nasal epithelial cells in Mexico City children. Persistent oxidative DNA damage may ultimately result in a selective growth of pr eneoplastic nasal initiated cells in this population and the potential for nasal neoplasms may increase with age. The combination of 8-OHdG and DNA ssb should be useful for monitoring oxidative damage in people exposed to polluted atmospheres.
Islet transplantation in type 1 diabetes
Authors: H. d. Kort, E. J. d. Koning, T. J. Rabelink, J. A. Bruijn, I. M. Bajema
Journal: BMJ (2011)

#### Summary points

A clinical review in the BMJ in 2001 anticipated that by 2010 transplantation of islets of Langerhans would be the treatment of choice for most patients with type 1 diabetes.1 Currently, islet transplantation is an option for a specific group of patients with type 1 diabetes only—those with severe glycaemic lability, recurrent hypoglycaemia, and hypoglycaemia unawareness. Patients with type 1 diabetes—who must deal with daily subcutaneous insulin injections, regular finger pricks for glucose measurements, and worries about hypoglycaemic episodes and long term complications of diabetes, hope for a cure for their disease and may ask their doctors about islet transplantation. Therefore, doctors who treat such patients should understand the potential benefits of islet transplantation as well as the hurdles that need to be overcome before it is widely used (box 1).

#### Sources and selection criteria

We searched PubMed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier, and ScienceDirect using the keyword “islet transplantation”. We limited our search to the English language and to human studies. We found no randomised controlled trials, and most publications lacked an appropriate control group that was intensively managed by insulin using modern treatment regimens. Data were mainly derived from case series, follow-up …
Oral Contraceptives and Alopecia Areata
Authors: M. G. P. Fisher
Journal: BMJ (1965)

When the diathermy is applied to the thorax or neck of an insulated patient the shortest electrical path is through the anaes- thetic tubing and machine or the anaesthetist, who usually has bare hands and conducting boots.When patients are intubated, the endotracheal tube is non-conducting when dry, and electrical contact is first made with the metal connector, which can easily make contact with the skin of the face but is often
Neuromedin S-Producing Neurons Act as Essential Pacemakers in the Suprachiasmatic Nucleus to Couple Clock Neurons and Dictate Circadian Rhythms
Authors: Ivan T. Lee, Alexander S. Chang, Manabu Manandhar, Yongli Shan, Junmei Fan, Mariko Izumo, Yuichi Ikeda, Toshiyuki Motoike, Shelley Dixon, Jeffrey E. Seinfeld, Joseph S. Takahashi, Masashi Yanagisawa
Journal: Neuron (2015)
Lung Cancer in Swedish Iron Miners Exposed to Low Doses of Radon Daughters
Authors: Edward P. Radford, K. G. St. Clair Renard
Journal: New England Journal of Medicine (1984)

In a retrospective study, we investigated lungcancer mortality from 1951 to 1976 in 1415 Swedish iron miners exposed to short-lived radioactive daughters of radon gas at concentrations leading to annual doses close to the currently accepted occupational limits. Fifty deaths from lung cancer were observed, as compared with 12.8 expected; expected rates were determined by a smoking-specific analysis based on data from a random sample of the Swedish male population. Among nonsmokers 18 deaths were observed, as compared with 1.8 expected; among current smokers and recent exsmokers 32 deaths were observed and 11.0 were expected. The effects of smoking and exposure to alpha radiation from radon daughters were nearly additive. Comparison of lung-cancer risk coefficients from this study and from other cohort studies of underground miners showed good agreement. Exposure to radon daughters is a major medical problem in underground metal mining, but our results also indicate that exposure to radon daughters at home accounts for an appreciable number of cases of lung cancer in the general population. (N Engl J Med 1984; 310:1485–94.)
New subtype of apical hypertrophic cardiomyopathy identified with nuclear magnetic resonance imaging as an underlying cause of markedly inverted T waves
Authors: Jun-ichi Suzuki, Fumiyoshi Watanabe, Katsu Takenaka, keiko Amano, Wataru Amano, Tsutomu Igarashi, Toshiro Aoki, Takashi Serizawa, Tsuguya Sakamoto, Tsuneaki Sugimoto, Jun-ichi Nishikawa
Journal: Journal of the American College of Cardiology (1993)
The Tragic Events of April 1996
Authors: Jack Coulehan
Journal: Annals of Internal Medicine (2000)

In the early 19th century, Port Arthur, Tasmania, was the site of a notorious prison in a land at the end of the world. In 1996, Port Arthur was also the site of the worst mass murder in modern Australian history. A gunman with a semiautomatic weapon stepped into a tourist coffee shop and systematically shot dead 35 men, women, and children. Throughout Australia, an outpouring of grief, shame, and anger followed this tragic event and led quickly to more stringent gun control legislation. Several years later, Australians still remember the mass murder at Port Arthur with shame and horror as a personal affront, rather than simply a historical event. In the more violent society of the United States, many Americans perceive themselves as helpless victims or detached observers, rather than as persons who are responsible for promoting change.
Diagnosing SAPHO Syndrome in Suspected Metastatic Bone Tumors
Authors: Ivana M. Abuhid, Luciana C. Silva, Gabriela P. Martins, Nilton A. de Rezende
Journal: Clinical Nuclear Medicine (2010)

A previously healthy 44-year-old woman who had been followed at different health care facilities for symptoms which had begun 3 years earlier was referred to our service for clinical evaluation. Her problems during the initial examination were pain in the sternoclavicular and sacroiliac joints as well as plantar pustulitis. Based on previous x-ray hyperostosis findings, metastatic bone tumors to the spine and first costocondral junctions bilaterally were suspected. A biopsy of the sternoclavicular lesion showed a nonspecific inflammation pattern. On the first physical examination we found a nontender swelling of the sternoclavicular junctions, necrosis of the plantar epidermis and pain at the sacroiliac joints. The patient was referred for bone scintigraphy and positron emission tomography-computed tomography (PET-CT) scan. The whole body bone scintigraphy using Tc-99m MDP showed increased accumulation of the radiotracer in the anterior chest wall and in the right sacroiliac joint. Metastatic bone tumor was not suggested, although exclusion of bone metastases was difficult. The PET-CT with F-18 FDG showed areas with low metabolic activity in the anterior chest wall (SUV Max: 1.96) and in the right sacroiliac joint (SUV Max: 2.18) making the diagnosis of malignancy and acute infection unlikely. The clinical symptoms, the typical skin lesions involving the soles of the feet and low hypermetabolic lesions on PET-CT made the final diagnosis of SAPHO syndrome.
Psychological complications after stillbirth--influence of memories and immediate management: population based study
Authors: I. Radestad, G. Steineck, C. Nordin, B. Sjogren
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To identify factors that may predict long term psychological complications among women who have had a stillborn child. <b>Design</b>: Nationwide population based study using epidemiological methods. <b>Subjects</b>: 380 subjects and 379 controls who had had a stillborn or non-deformed live child in Sweden in 1991. <b>Results</b>: Information was provided by 636 (84%) women. The ratio (95% confidence interval) of proportions of women with symptoms related to anxiety above the 90th centile for women who had had a stillborn child compared with those who had not was 2.1(1.2 to 3.9). An interval of 25 hours or more from the diagnosis of death in utero to the start of delivery gave a ratio of 4.8 (1.5 to 15.9). The ratio was 2.3 (1.1 to 5.3) for not seeing the child as long as the mother had wished and 3.1 (1.6 to 6.0) for no possession of a token of remembrance. <b>Conclusion</b>: It is advisable to induce the delivery as soon as feasible after the diagnosis of death in utero. A calm environment for the woman to spend as much time as she wants with her stillborn child is beneficial, and tokens of remembrance should be collected. <h3>Key messages</h3> This study used an anonymous postal question- naire to 636 women to assess mothers9 needs It shows that it is advisable to induce the delivery as soon as feasible after the diagnosis of death in utero A calm environment, with the mother able to spend as much time as she wants with her dead newborn child, is beneficial, as are tokens of remembrance of the child Rather than enforcing mourning rituals, flexibil- ity should be shown towards the mother9s own needs