tbuckley/cabot-search huggingface dataset:
Autonomic Regulation
Authors: J. G. WIDDICOMBE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The excitatory and inhibitory nonadrenergic/noncholinergic (e-NANC, i-NANC) systems have been extensively studied. The terms excitatory and inhibitory apply to airway smooth muscle, but the neurotransmitters also act on other targets-blood vessels, glands, the epithelium-where individual actions may be the opposite. Thus, the nomenclature is unsatisfactory. Of the dozen or more putative NANC transmitters, criteria to establish their roles have been met only for vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and substance P/neurokinin A (SP/NKA). VIP and NO co-localize in vagal motor nerves, but they are also found in sympathetic and sensory nerves. In general they have similar actions on target tissues, and their relative importance may vary with species. SP/NKA, released from sensory nerves, is thought to mediate neurogenic inflammation, a process that may include airway smooth muscle contraction, at least in rodents. The evidence for neurogenic inflammation in humans is weak. On the motor side, and also possibly on the sensory, different nerves seem to contain different selections of neurotransmitters, but it is not known if there are different motor controls for these nerves. Cotransmission presents a major conceptual and experimental problem, since the two or more transmitters may give opposite instructions to the target tissue. Inevitably most of the studies on the NANC systems are on isolated rodent tissues, and although quantitative, they indicate little of what happens in vivo, and certainly not in humans. The cocktail of mediators that must be released from nerves and associated cells in airway tissues during pathophysiologic processes may refresh physiologists, but little is known about the concentrations of the ingredients or about the strength of their actions and their interactions on different target tissues in the mucosa.
Medical Shock: Abnormal Biochemical Changes in Patients with Severe, Acute Medical Illnesses, with and without Peripheral Vascular Failure
Authors: Charles S. Davidson, Jessica H. Lewis, Henry J. Tagnon, Margaret A. Adams, F. H. L. Taylor
Journal: New England Journal of Medicine (1946)

RECENT studies in the so-called "shock syndrome" in animals have definitely associated this syndrome with certain biochemical abnormalities.1 , 2 Hyperglycemia, lactacidemia, lowered alkaline reserve and changes in the partition of the nonprotein nitrogen of the blood plasma have been reported in this condition. In hemorrhagic shock, increases in the plasma alpha amino nitrogen have recently been reported.3 , 4 Anoxia has been a frequent finding in shocked animals, and furthermore, anoxic anoxia itself has been found to produce some of the biochemical changes attributed to shock.Recent reports from this laboratory have shown that in man marked biochemical changes of a similar nature . . .
NATIONAL TRENDS AND OUTCOMES IN DIALYSIS REQUIRING ACUTE KIDNEY INJURY AFTER CORONARY ARTERY BYPASS GRAFTING
Authors: Achint A. Patel, Bhavi Pandya, Girish Nadkarni, Parisha Bhatia, Amit Pawale, Pranav Garimella, Ruben Kandov, James Lafferty, Suzanne El-Sayegh
Journal: Journal of the American College of Cardiology (2016)
Intravenous Gamma Globulin
Authors: Charles A. Janeway, Ezio Merler, Fred S. Rosen, Sydney Salmon, Joan D. Crain
Journal: New England Journal of Medicine (1968)

Two types of enzymatically digested human gamma-globulin preparations, a pepsin digest and a plasmin digest, were administered to six normal persons and to six patients with agammaglobulinemia. No untoward reactions were observed. The fate of the injected material was observed by serial measurement of gamma globulin and its fragments in plasma and urine. The pepsin digest, consisting principally of an F(ab′)2S 5 fragment, had a half-time of disappearance of 10 to 14 hours. The plasmin digest, consisting mainly of an S 6.5 fragment, had a much longer half-time of disappearance: 18 to 20 days. On theoretical grounds, therefore, plasmin-digested gamma globulin appears suitable for the establishment and maintenance of passive immunity to prevent infection in agammaglobulinemic patients. It deserves further study to assess its effectiveness and safety.
Charity challenges closure of children's heart surgery unit at Leeds
Authors: C. Dyer
Journal: BMJ (2012)

Campaigners have taken the first step towards a legal challenge to the decision to close the children’s heart surgery unit at Leeds General Infirmary as part of a move to concentrate services in fewer, larger, and more specialised units in England.

A charity based at the infirmary, the Children’s Heart Surgery Fund, has sent a letter threatening judicial review proceedings in the High Court over the proposed closure.

The Leeds unit is one of three facing the axe after the Safe and Sustainable review by the joint committee of primary care trusts (JCPCT), which concluded that the number of units carrying out surgery for congenital heart defects …
Leukemia and Preleukemia after Adjuvant Treatment of Gastrointestinal Cancer with Semustine (Methyl-CCNU)
Authors: John D. Boice, Mark H. Greene, John Y. Killen, Susan S. Ellenberg, Robert J. Keehn, Eleanor McFadden, T. Timothy Chen, Joseph F. Fraumeni
Journal: New England Journal of Medicine (1983)

We evaluated the risk of acute nonlymphocytic leukemia, acute myelodysplastic syndrome, and preleukemia in 3633 patients with gastrointestinal cancer who were treated in nine randomized clinical trials. Among 2067 patients given semustine (methyl-CCNU) as adjuvant therapy, leukemic disorders developed in 14, whereas only one leukemic disorder (acute nonlymphocytic leukemia) occurred among 1566 patients given other therapies (relative risk = 12.4; 95 per cent confidence interval = 1.7 to 250). The six-year cumulative mean risk (+/- S.E.) of acquiring a leukemic disorder after treatment with semustine was 4.0 +/- 2.2 per cent; the incidence rate was 2.3 cases per 1000 persons per year. Risk increased significantly with time after treatment. The risk of leukemic disorders did not differ according to sex, race, age at treatment, or initial tumor type, nor was it enhanced by concomitant radiotherapy or immunotherapy. In addition, no excess of acute nonlymphocytic leukemia was seen in 44,370 patients treated for gastrointestinal cancer in Connecticut during the period 1935 to 1974, before the advent of nitrosourea chemotherapy. This study provides quantitative evidence that nitrosoureas are leukemogenic in human beings and confirms previous observations that adjuvant chemotherapy with alkylating agents may increase the risk of leukemia.
PTU-070 Non-adherence With Rectal Preparations In Colitic Patients. Fact Or Fiction?
Authors: B Kok, A Waters, A Jenkins
Journal: Gut (2014)

<h3>Introduction</h3> Rectal preparations containing steroids or 5-aminosalicylates are an effective treatment for distal colitis. Nonetheless, it is perceived that this therapy is associated with poor levels of adherence and that patients are not readily accepting of it. This might make gastroenterologists reluctant to prescribe rectal preparations. The patient experience and factors determining adherence with this modality of treatment have not been investigated before. The aim of our survey is to evaluate patient compliance with rectal preparations and explore the possible reasons why compliance is not always achieved. <h3>Methods</h3> A short anonymised survey was distributed over a 3-month period at general gastroenterology and IBD outpatient clinics to patients with a known diagnosis of ulcerative colitis. There were questions on baseline demographics and other details relating to compliance. A free text option was also available for suggestions that could improve compliance. <h3>Results</h3> Over the period November 2013–January 2014, a total of 59 completed surveys were received. 21 of 59 patients (36%) had never been prescribed a rectal preparation. Of the remaining 38 patients with reported experience of rectal preparations, 60% were male with a median age of 45 years. Surprisingly, 76% of these (29 patients) answered ‘Yes’ to being compliant with the preparation (s), and they had been prescribed courses ranging from once/day for 2 weeks to thrice/day long-term. 20 patients had been prescribed foam and/or liquid enemas, 8 patients a suppository, and 1 patient a suppository and foam enema. 93% of the compliant patients reported an improvement in their symptoms with the use of rectal preparations. Though compliant, 24% reported ‘Yes’ to having difficulties using the rectal preparation citing “insertion difficulties” and “difficulty retaining the fluid” and “at work” as the main reasons. When asked for suggestions to improve compliance, 62% felt reduction of treatment frequency to once/day would help, and 21% felt that better explanation about administration would help. Of the 9 patients who admitted to being noncompliant, 3 had difficulties with administration, 2 experienced pain, and the majority felt that a better explanation about administration would have improved compliance. As expected, the majority of noncompliant patients felt that the rectal preparation had made no difference to their symptoms. <h3>Conclusion</h3> Compliance with prescribed rectal preparations is surprisingly high. This is an encouragement to continue promoting its use. Compliance could be further improved by allowing for patient factors such as work hours and adjusting dosing times, and by dedicating time to explain how the medication should be administered. <h3>Disclosure of Interest</h3> None Declared.
NI-46 * THE IMPACT OF INTEGRATING VOLUMETRIC MR SPECTROSCOPIC IMAGING IN RADIATION TREATMENT PLANNING FOR GLIOBLASTOMA
Authors: S. Kandula, J. S. Cordova, E. Schreibmann, I. Crocker, C. Holder, H. Shim, H.-K. Shu
Journal: Neuro-Oncology (2014)

BACKGROUND: Magnetic resonance spectroscopic imaging (MRSI) has emerged as a molecular imaging modality which may better define active tumor compared to conventional anatomic magnetic resonance imaging (MRI). To date, using MRSI for radiation treatment (RT) planning has been challenging due to processing and resolution limitations. Here, we evaluate the feasibility of integrating 3-dimensional (3D) high-resolution full-brain MRSI into the RT planning process for glioblastoma, and determine the degree to which MRSI can modify RT targets and predict progression.

METHODS: Six patients with newly-diagnosed glioblastoma participated in our institutional study in which a pre-RT MRSI was obtained. 3D MRSI was acquired using a volumetric spin-echo EPSI sequence and parallel imaging (GRAPPA), with a 32-channel head coil on a 3T (Siemens TRIO/TIM) system, and processed to give full-brain metabolite maps with 0.108 cm3 resolution. Each MRSI voxel map, representing relative choline (Cho) to N-acetylaspartate (NAA) ratios, was registered to a corresponding T1-weighted post-contrast MRI (T1c). An MRSI-defined 60 Gray planning target volume (mrsiPTV60) was created independently by two radiation oncologists based on spatial quantitative assessment of elevated Cho/NAA ratios, and analytically compared to the RT target defined by conventional T1c abnormalities (convPTV60).

RESULTS: Using MRSI to aid target definition increased the convPTV60 by a median of 78% (range: 22%-1149%). The median dice similarity coefficient between conPTV60 and mrsiPTV60 was 0.72 (range: 0.15-0.91), indicating decreased spatial overlap. Expanded targets in two of six cases encompassed regions of tumor recurrence, which were not originally covered by the convPTV60.

CONCLUSIONS: Integration of 3D high-resolution full-brain MRSI into RT planning is feasible, resulted in considerably modified RT target volumes, and predicted post-RT recurrences. Thus, MRSI may serve as an additional treatment planning tool for improving RT target definition for the benefit of glioblastoma patients.
Abstract 5531: A bioluminescent cell viability assay optimized for 3D microtissues.
Authors: Michael P. Valley, Chad Zimprich, James J. Cali, Dan F. Lazar
Journal: Cancer Research (2013)

Abstract It has been well demonstrated that the morphology, gene expression, and overall biological response of cells assessed in 3-dimensional (3D) culture models are frequently more physiologically relevant than that of cells studied in standard 2D culture formats. In spite of rapidly growing interest, one hindrance to the use of 3D models for drug discovery and other research efforts is the lack of convenient and effective assays explicitly validated for application to 3D microtissues. Here we report on a bioluminescent ATP-detection assay comprised of both an improved formulation and an optimized protocol specifically designed to measure the viability of cells grown in 3D culture. The ability of the 3D-optimized reagent to effectively lyse cells from throughout the full thickness of 3D microtissues, including cancer cell spheroids, was clearly demonstrated by use of confocal laser fluorescent microscopy in conjunction with a fluorogenic, membrane-impermeant DNA-binding dye. Importantly, the assay's ability to accurately report the ATP content, and therefore viability, of various 3D microtissues (including a range of cancer cell line spheroids) was demonstrated by comparison to a trichloroacetic acid ATP extraction method. In scaffold-free as well as scaffold-dependent 3D models, recovery and detection of greater than 80% of ATP present was routinely observed. In contrast, another frequently used ATP-detection assay was found to have greatly reduced lytic and ATP detection properties (&amp;lt;50% recovery). This new, homogeneous 3D-assay format requires minimal sample manipulation, a brief incubation period (generally less than 30 min), and exhibits excellent sensitivity. It should be amenable to both low- and high-throughput applications and accurately report drug sensitivities of cells assayed in both 2D and 3D culture models. Citation Format: Michael P. Valley, Chad Zimprich, James J. Cali, Dan F. Lazar. A bioluminescent cell viability assay optimized for 3D microtissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5531. doi:10.1158/1538-7445.AM2013-5531
Clinical and Laboratory Factors Influencing The Probability Of Complete Remission In AML Patients With Positive Day 14 Bone Marrows
Authors: Maxim Norkin, Jan Moreb, Helen Leather, Randy A. Brown, Jack W. Hsu, John W Hiemenz, W. Stratford May, Myron N Chang, Qi An, Ying Li, Christopher R Cogle, John R Wingard
Journal: Blood (2013)
Cervical Lymphadenopathy Caused by Kikuchi Disease
Authors: ALFRED C. LIAO, YEN-KUNG CHEN
Journal: Clinical Nuclear Medicine (2003)

From the Department of Nuclear Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Received for publication August 22, 2002. Revision accepted October 1, 2002. Correspondence: Yen-Kung Chen, Department of Nuclear Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen Chang Road, Shih Lin District, Taipei, Taiwan. E-mail: [email protected]
Abstract 3895: Rational design of small molecule inhibitors that bind to an allosteric pocket on human heat shock protein 70 (Hsp70)
Authors: Tony Taldone, Pallav D. Patel, Yanlong Kang, Anna Rodina, Tanaji T. Talele, Gabriela Chiosis
Journal: Cancer Research (2012)

Abstract The 70 kDa heat shock protein (Hsp70) plays an important role in cancer and its pharmacological modulation with small molecules may represent a useful therapeutic approach. The discovery of such agents has been hampered by the lack of a full length crystal structure of human Hsp70. We constructed a homology model of the human Hsp70, which we investigated for potential druggable sites using SiteMap tool. An allosteric site in the nucleotide binding domain was identified and used to design potent Hsp70 modulators. Analysis of the Glide docking resulted in an understanding of important interactions between designed ligands, such as YK5, and the Hsp70 protein. When tested in breast cancer cells, YK5 led to depletion of onco-proteins, induced apoptosis and inhibited growth. YK5 is to our knowledge the first rationally designed small molecule inhibitor of Hsp70, and thus, represents a novel chemical tool to investigate its potential in cancer and other diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3895. doi:1538-7445.AM2012-3895
Reply to Pouw et al.
Authors: D. Adler, C. Zhou, T. Tsai, H. Lee, L. Becker, J. Schmitt, Q. Huang, J. Fujimoto, H. Mashimo
Journal: Endoscopy (2010)

We have read with great interest the comments by Pouw and Bergman regarding our recent case report on three-dimensional optical coherence tomography (3D-OCT) imaging of the normal esophagus, Barrett's esophagus, and the post-radiofrequency ablation (RFA) gastroesophageal junction (GEJ) region [1]. While we appreciate many of the points raised by the readers, we disagree with their assessment of our pilot study as biased, irrelevant, and misleading. Furthermore, we believe that it would be irresponsible to summarily disregard 3D-OCT for studying ablative therapies due to the many advantages provided by this rapidly developing visualization technique.
ET-58 * THE GENETICALLY ENGINEERED CLOSTRIDIUM NOVYI-NT IS EFFICACIOUS IN THE TREATMENT OF INTRACRANIAL GLIOBLASTOMAS
Authors: V. Staedtke, R. Bai, K. Kinzler, S. Zhou, B. Vogelstein, G. Riggins
Journal: Neuro-Oncology (2014)

Glioblastomas (GBM) exhibit a remarkable histopathologic heterogeneity with extensive necrotic regions intermixed with cell proliferation that generate local hypoxia and thus, limit the effectiveness greatly of traditional cancer therapies. The spore-forming bacterium Clostridium spp., however, has the ability to precisely target and lyse tumor cells in hypoxic environments. Here we show that Clostridium novyi-NT (C. novyi-NT), an engineered strain devoid of the lethal alpha-toxin, induces a microscopically tumor-localized response in orthotopically implanted syngeneic F98 and human xenograft 060919 rat GBM models. Both, intravenous and intratumoral, injections of C. novyi-NT spores resulted in germination within 24 hours and a rapid fall in luciferase activity, an indicator of tumor burden, in both animal models. C. novyi-NT germination was evidenced by the appearance of vegetative forms of C. novyi-NT bacteria. Strikingly, C. novyi-NT precisely localized to the tumor and micro-invasive tumor islands buried in the normal brain parenchyma, sparing adjacent normal cells only a few microns away. This bacterial "biosurgery" led to a significant survival advantage in these extremely aggressive rat models. Brain edema and increased intracranial pressure as a result of C. novyi-NT infection was common and medically managed while brain abscess formation was not clearly observed with appropriate use of antibiotics. Abscessation, however, is a potential side effect and can develop in human patients possibly requiring neurosurgical abscess drainage, a routine clinical procedure. In summary, C. novyi-NT can act as a tool to precisely eradicate GBM and significantly extend survival. Despite concerns on treatment-related toxicity, bacterial C. novyi-NT treatment may have a place in selected GBM patients in the future given the lack of alternative therapy options and dismal prognosis.
Both Native and Ectopically Transplanted Hearts Shown on FDG PET/CT in a PTLD Patient
Authors: Luke I. Sonoda, Bal Sanghera, Andrew Gogbashian, Jonathan Lambert, Wai Lup Wong
Journal: Clinical Nuclear Medicine (2012)

Posttransplant lymphoproliferative disorder (PTLD) is one of the unfortunate complications of immunosuppression after allograft transplantation. 18F-FDG PET/CT plays an important role in the diagnosis and management of PTLD. The authors report a PET/CT scan of a young woman who received a heterotopic cardiac transplant, demonstrating 2 functional hearts in the thorax. The scan also demonstrates a small-volume mediastinal lymphadenopathy caused by the PTLD/B-cell lymphoma, subsequently proven by mediastinoscopic biopsy.
Abstract B6: Revealing DAPK1 transcriptional regulation by RNA interference screening with an integrated BAC‐reporter system
Authors: Christopher C. Oakes, Yoon Jung Park, Michael Boutros, Christoph Plass
Journal: Cancer Research (2009)

Abstract High-throughput RNA interference screening has been used successfully to reveal novel gene function. Currently used expression reporter systems employ small constructs of synthetic or endogenous sequences containing pathway-specific response elements. The use of these small reporter systems does not allow for the recapitulation of the regulatory complexity that controls an individual gene of interest. Death-associated protein kinase 1 (DAPK1) is a tumor suppressor gene that is silenced in a broad variety of cancers. Specifically, we have previously found DAPK1 to be silenced in virtually all cases of chronic lymphocytic leukemia and silencing is associated with promoter DNA methylation. Although epigenetic silencing is indicative of a transcriptional defect, the basis for this silencing is unknown. Here, we have employed a novel approach to elucidate genes involved in the transcriptional regulation of DAPK1. Using BAC recombineering and stable transgene integration, we have engineered human cells to express a DAPK1-luciferase reporter under the control of approximately 180 Kb of sequence surrounding the DAPK1 transcriptional start site. By performing genome-wide siRNA high-throughout screening, we have been able to determine candidate genes involved in DAPK1 regulation. We have also performed screens in parallel using small, plasmid-based promoter reporter constructs by transient transfection and stable integration. Evaluation of these reporter systems has revealed significant drawbacks of plasmid-based reporters which include nonspecific effects arising from proximal vector backbone sequences. In conclusion, an integrated BAC-reporter system is useful for the assessment of gene-specific transcriptional regulation. Future work will involve determining the disease-specific roles for novel DAPK1 regulatory genes. Citation Information: Cancer Res 2009;69(23 Suppl):B6.