tbuckley/cabot-search huggingface dataset:
Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death
Authors: Eugene A Sosunov, Evgeny P Anyukhovsky, Alexei Shvilkin, Motoki Hara, Susan F Steinberg, Peter Danilo, Michael R Rosen, N Sydney Möise, Jocelyn Mérot, Vincent Probst, Flavien Charpentier, Yves Legeay, Hervé Le Marec
Journal: Cardiovascular Research (1999)

Objective: We tested the hypothesis that delayed afterdepolarization (DAD)-associated rhythms in German shepherd dogs with reduced anteroseptal left ventricular (LV) sympathetic innervation derive from abnormal β-adrenergic receptor effector coupling. Methods and Results: In anteroseptal LV midmyocardium of afflicted dogs, β-receptor density was greater than that in normal dogs (P<.05), with affinity being equal in both groups. Basal and maximum isoproterenol (ISO) stimulated adenylyl cyclase activity of anteroseptal LV of afflicted dogs was greater than that in normal dogs (P<.05). Isolated anteroseptal M cell preparations of afflicted dogs studied with microelectrodes showed abnormal lengthening, rather than shortening of action potential duration in response to ISO, as well as a 61% incidence of 10−7 mol/l ISO-induced triggered activity as compared to 12% in normals (P<.05). In contrast, there was no difference between afflicted and control dogs in triggered activity, β-receptors or adenylyl cyclase activity in a normally innervated region of the ventricles. Conclusion: In this model there is an increase in β-receptor density and β-adrenergic stimulation of adenylyl cyclase and of triggered activity in anteroseptal myocardium but not in a normally innervated region of the heart. Hence, abnormal β-adrenergic signal transduction appears associated with the neural abnormality identified in dogs with inherited VT.
Blood lactate as a prognostic marker in acetaminophen-induced acute liver failure
Authors: Lars E. Schmidt, Fin Stolze Larsen
Journal: Hepatology (2003)

Abstract Background: Although the King's College Hospital (KCH) selection criteria for emergency liver transplantation in paracetamol–induced acute liver failure are widely used, strategies to improve sensitivity and facilitate earlier transplantation are required. We investigated the use of arterial blood lactate measurement for the identification of transplantation candidates. Methods: In a single–centre study, we measured arterial blood lactate early (median 4 h) and after fluid resuscitation (median 12 h) in patients admitted to a tertiary–referral intensive–care unit. Threshold values that best identified individuals likely to die without liver transplantation were derived in a retrospective initial sample of 103 patients with paracetamol–induced acute liver failure and applied to a prospective validation sample of 107 patients. Predictive value and speed of identification were compared to those of the KCH criteria. Findings: In the initial sample, median lactate was significantly higher in non–surviving patients than in survivors both in the early samples (8.5 [range 1.7–21.0] vs. 1.4 [0.53–7.9] mmol/L, p&lt;0.0001) and after fluid resuscitation (5.5 [1.3–18.6] vs. 1.3 [0.26–3.2], p&lt;0.0001). Applied to the validation sample, a threshold value of 3.5 mmol/L early after admission had sensitivity 67%, specificity 95%, positive likelihood ratio 13, and negative likelihood ratio 0.35; the corresponding values for a threshold of 3.0 mmol/L after fluid resuscitation were 76%, 97%, 30, and 0.24. Combined early and postresuscitation lactate concentrations had similar predictive ability to KCH criteria but identified non–surviving patients earlier (4 [3–13] vs 10 [3.5–19.5] h, p=0.01). Addition of postresuscitation lactate concentration to KCH criteria increased sensitivity from 76% to 91% and lowered negative likelihood ratio from 0.25 to 0.10. Interpretation: Arterial blood lactate measurement rapidly and accurately identifies patients who will die from paracetamol–induced acute liver failure. Its use could improve the speed and accuracy of selection of appropriate candidates for transplantation.
Re: Luca Cindolo, Stefano Gidaro, Fabiola R. Tamburro, Luigi Schips. Laparo-Endoscopic Single-Site Left Transperitoneal Adrenalectomy. Eur Urol 2010;57:911–4
Authors: Riccardo Autorino, Robert J. Stein, Jihad H. Kaouk
Journal: European Urology (2009)
Quantitative PCR-ELAHA for the Determination of Retroviral Vector Transduction Efficiency
Authors: Ian M. Mackay, Pat Metharom, Theo P. Sloots, Ming Q. Wei
Journal: Molecular Therapy (2001)

Current methods to detect transduction efficiency during the routine use of integrating retroviral vectors in gene therapy applications may require the use of radioactivity and usually rely upon subjective determination of the results. We have developed two competitive quantitative assays that use an enzyme-linked, amplicon hybridization assay (ELAHA) to detect the products of PCR-amplified regions of transgene from cells transduced with Moloney murine leukemia virus vectors. The quantitative assays (PCR-ELAHA) proved to be simple, rapid, and sensitive, avoiding the need for Southern hybridization, complex histochemical stains, or often subjective and time-consuming tissue culture and immunofluorescence assays. The PCR-ELAHA systems can rapidly detect proviral DNA from any retroviral vector carrying the common selective and marker genes neomycin phosphotransferase and green fluorescent protein, and the methods described are equally applicable to other sequences of interest, providing a cheaper alternative to the evolving real-time PCR methods. The results revealed the number of copies of retrovector provirus present per stably transduced cell using vectors containing either one or both qPCR targets. Current methods to detect transduction efficiency during the routine use of integrating retroviral vectors in gene therapy applications may require the use of radioactivity and usually rely upon subjective determination of the results. We have developed two competitive quantitative assays that use an enzyme-linked, amplicon hybridization assay (ELAHA) to detect the products of PCR-amplified regions of transgene from cells transduced with Moloney murine leukemia virus vectors. The quantitative assays (PCR-ELAHA) proved to be simple, rapid, and sensitive, avoiding the need for Southern hybridization, complex histochemical stains, or often subjective and time-consuming tissue culture and immunofluorescence assays. The PCR-ELAHA systems can rapidly detect proviral DNA from any retroviral vector carrying the common selective and marker genes neomycin phosphotransferase and green fluorescent protein, and the methods described are equally applicable to other sequences of interest, providing a cheaper alternative to the evolving real-time PCR methods. The results revealed the number of copies of retrovector provirus present per stably transduced cell using vectors containing either one or both qPCR targets.
Alisertib is active as single agent in recurrent atypical teratoid rhabdoid tumors in 4 children
Authors: Cynthia Wetmore, James Boyett, Shaoyu Li, Tong Lin, Anne Bendel, Amar Gajjar, Brent A. Orr
Journal: Neuro-Oncology (2015)

Aurora Kinase A (AURKA) encodes a protein that regulates the formation and stability of the mitotic spindle and is highly active in atypical teratoid rhabdoid tumors (ATRT) through loss of the INI1 tumor suppressor gene. Alisertib (MLN8237) inhibits AURKA in vitro and in vivo. Given the strong preclinical data supporting the use of alisertib for ATRT patients, we sought and obtained permission to use alisertib in single patient treatment plans for 4 recurrent pediatric ATRT patients.Patients with recurrent or progressive ATRT received alisertib 80 mg/m(2) by mouth once daily for 7 days of a 21-day treatment cycle. Disease evaluation (MRI of brain and spine and lumbar puncture) was done after 2 cycles of alisertib and every 2-3 cycles thereafter for as long as the patients remained free from tumor progression.Four patients with median age of 2.5 years (range, 1.39-4.87 y) at diagnosis received alisertib 80 mg/m(2) by mouth once daily for 7 days of a 21-day treatment cycle, and all 4 patients had disease stabilization and/or regression after 3 cycles of alisertib therapy. Two patients continued to have stable disease regression for 1 and 2 years, respectively, on therapy.Single-agent alisertib produced marked and durable regression in disease burden, as detected by brain and spine MRI and by evaluation of spinal fluid cytology. Alisertib has moderate but manageable toxicities, and its chronic administration appears feasible in this pediatric population. These novel data support the incorporation of alisertib in future therapeutic trials for children with ATRT.
Abstract P1-09-06: Imaging Tests in Staging and Surveillance of Early Breast Cancer (EBC) — Changes in Routine Clinical Practice and Cost Implications
Authors: G Arpino, S Cammarota, G Ianniello, G Genua, A Febbraro, F Mastrogiacomo, R Mabilia, A Pisano, M Bianco, E Barbato, B Daniele, C Savastano, S Del Prete, L Malorni, S. De Placido
Journal: Cancer Research (2010)

Abstract Background. New imaging tests such as computed tomography [CT], [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning and magnetic resonance imaging (MRI) are not recommended for staging or follow up of asymptomatic patients with EBC according to current guidelines. However, frequently these tests are requested even in the absence of a clinical indication. Variations in practice patterns have significant cost implications and no clear impact on cancer outcomes. Aim. In the present study we analyzed how the availability of novel and more expensive imaging technique has changed staging and follow-up modalities in EBC patients and if these changes affect costs. Methods. Two thousand and five patients with EBC diagnosed between January 2005 and December 2008 were identified using clinical computerized medical records from 639 general practitioners assisting 915,689 inhabitants of the Campania, a southern region of Italy. For each year EBC incidence, the mean number of diagnostic tests per patient (N/Pt) done during the first year after the initial diagnosis and the mean costs per each year were evaluated and compared by Anova test. Results. We identified 576, 489, 474 and 497 newly diagnosed cases of EBC in 2005, 2006, 2007 and 2008 respectively. Table 1 Table 1 describes changes in the mean number of different imaging tests requested per patient in these years. Overall, there was a significant increase of the mean number of imaging tests done per patient from 2005 to 2008 (P&amp;lt;0.0001). No change of the mean number of mammograms, bone scan and chest X ray requested per patient was observed. However, importantly, the mean number of TC scan, PET scan and MRI requested per patient almost doubled from 2005 to 2008. Accordingly, the mean costs for staging and surveillance per patient also significantly increased (355 € in 2005, 378 € in 2006, 391 € in 2007 and 547 € in 2008; &amp;lt;0.0001). Conclusions. TC scan, PET scan and MRI employment for patient with EBC in daily clinical practice has been steadily growing over the past four years. However, there are no data to support their role in routine breast cancer staging or surveillance in asymptomatic patients. More studies are needed to characterize which subset of patients deserve more intensive staging and follow up procedures as costs related to these imaging test prescriptions are relevant. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-09-06.
Bacillus Calmette-Guérin Failure in Patients with Non–Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra
Authors: Gianluca Giannarini, Frédéric D Birkhäuser, Franz Recker, George N Thalmann, Urs E Studer
Journal: European Urology (2013)
REGULATION OF CELLULAR ANTIBODY SYNTHESIS
Authors: Göran Möller
Journal: The Journal of Experimental Medicine (1968)

Transfer of spleen cells from mice immunized against sheep red blood cells (SRBC) into irradiated (600 R) nonimmune, syngeneic mice in the presence of antigen resulted in excessive cellular 7S production 7 days later. The number of 7S plaque-forming cells usually exceeded 10(6) per spleen and the mean proportion varied between 1 and 70%. In occasional animals all spleen cells were producing antibodies to SRBC. Serum antibody synthesis was also excessively increased, the titers in agglutination after 2-ME treatment and in hemolysis varying between 2(15) and 2(25). The generation time of the 7S PFC was found to be 9.6 hr in the secondary hosts. It seemed possible that the excessive production of 7S PFC and antibodies in the irradiated nonimmune recipients was caused by the absence of feedback inhibition of the immune response by antibody, a mechanism which would normally function to restrict antibody synthesis. This conclusion was strengthened by the demonstration that transfer of antigen-stimulated immune cells into actively or passively immunized irradiated recipients resulted in a marked suppression of cellular 7S synthesis. Serial transfers of antigen-stimulated immune cell populations in irradiated hosts resulted in an equally high number of 7S PFC during the first four transfer generations. However, after the fifth to seventh transfer generation the number of 7S PFC rapidly declined and disappeared within one to three passages. Serum antibodies and 7S PFC declined in parallel during the last transfer generations. Further passages of antigen-stimulated spleen cells lacking 7S PFC did not lead to reappearance of PFC. Thus, antigen-sensitive cells have a limited lifespan and/or multiplication capacity. From the hypothesis that the 7S PFC developed by division from antigen-sensitive precursors it was calculated that 38-40 divisions occurred, Thus, one antigen-sensitive precursor has the potential to give rise to 10(12) 7S PFC.
Reasons for Failure and Management of Recurrence
Authors: Charles M. Norris
Journal: JAMA (1972)

Predisposing failure in the treatment of cancer of the hypopharynx and larynx are often due to late diagnosis, which stems from the following: (1) failure to recognize the importance of symptoms such as hoarseness, dysphagia, or discomfort in the throat; (2) casual examination of the larynx and pyriform sinuses on mirror laryngoscopy, or failure to do a direct examination when the mirror examination is unsatisfactory; (3) faulty interpretation of the gross findings, and neglect of biopsy as a means of proving or disproving the diagnosis; (4) poor biopsy technique; (5) failure to perform a second biopsy in some instances when the findings from initial biopsy are reported to be normal; and (6) inadequate follow up in cases where the diagnosis is not established, and in instances in which a premalignant lesion such as leukoplakia is found.<sup>41</sup> The important causes of failure in the treatment of proved cancer in these
Abstract P6-08-06: Sexual function, sexual activity and quality of life in women with breast cancer
Authors: B Beutel, I Schrof, H Rita, K Lehmann, V Kullmann, T Alexander, S Herbert, DB Andreas
Journal: Cancer Research (2013)

Abstract Background: Breast cancer (BC) is generally assumed to have an impact on sexual function and activity. Although there are several studies addressing the issue, case control studies are currently limited. Methods: We performed a cross-sectional investigation of sexual function and activity utilizing the sexual activity questionnaire, the female sexual function index, and parts of the EORTC QLQ C30. Patients with breast cancer (BC) were compared with a control group (C) of non-cancer patients. Inclusion of BC was only allowed if treatment was completed ≥ 12 months previously and patients were disease-free. This study was approved by the ethical committee of the Landesärztekammer Hessen. All consecutive patients with breast cancer who were treated at our hospital were prospectively documented in a clinical tumor registry since 2001. All patients’ records are updated annually. The control sample without any oncologic disease of 392 age-matched females was recruited in the Department of Prosthodontics, University Hospital Mainz. Results: Between December 2009 and May 2010 the questionnaires were sent out to 790 women (398 x BC and 392 x C), 21.6% of which responded. Response rates in both groups were equivalent (84 patients with BC [21.2%] and 87 control subjects [22.2%]). Median age was 57 years (C) and 62 years (BC), respectively (p = 0.005). 51.5% (C) and 60% (BC) were not sexually active, mainly owing to lack of a partner (39%) or lack of interest (21%) in controls and lack of interest (48%, p&amp;lt;0.05), self-reported physical problems (34%, p&amp;lt;0.05), and physical problems of the partner (22%, p&amp;lt;0.05) in breast cancer patients. There were significant differences between both groups in the SAQ discomfort score (p&amp;lt;0.05). We did not observe significant differences in quality of life or other scores regarding sexuality. Conclusions: About half of the women in both groups were not sexually active. However, reasons for non-activity differ. Quality of sexuality tends to be impaired in BC patients, but this seems not to influence quality of life. A shift of priority caused by substantial anxiety regarding cancer specific survival might explain our findings. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-06.
The Contribution of Professor Yujiro Ikemi to the Development of Psychosomatic Medicine in Japan
Authors: Chiharu Kubo
Journal: Psychotherapy and Psychosomatics (2000)

Accessible online at: www.karger.com/journals/pps Dr. Yujiro Ikemi, Professor Emeritus of Kyushu University, died on June 25, 1999, at age 84. With great sorrow, I write about my teacher, the late Dr. Ikemi, one of the world’s leading psychosomatists who developed new concepts, made new discoveries and gave new meaning to the expanding field of psychosomatic medicine. His contribution towards integrating Oriental wisdom into Western psychosomatic medicine and bringing forth the ancient wisdom of Asia is recognized throughout the scientific communities of the World. Dr. Ikemi was born on June 12, 1915, in Fukuoka, Japan. After graduating from Fukuoka High School, he entered the faculty of medicine of Kyushu University. During that phase of his life, he began to suffer from irritable bowel syndrome in addition to social phobia, and received various treatments without satisfactory response. Fortunately, in 1951, he went to the US as a fellow of the Institute of Tuberculosis of the Mayo Clinic in Minnesota. In the US he had a chance to study psychosomatic medicine, not only at the Mayo Clinic, but also at psychosomatic centers in America, including the Menninger Foundation. After returning to Japan, he was appointed to the position of Associate Professor of the Department of Internal Medicine at Kyushu University. He then decided to concentrate his efforts toward pioneering work in the field of psychosomatic medicine in Japan. His first important work, a special lecture on ‘Psychosomatic Aspects of the Gastrointestinal System’, came to light at the Annual Congress of the Japanese Society of Gastroenterology in 1955. He and his co-workers collected experimental evidence of functional changes in the gastrointestinal system induced by strong emotional reactions to hypnotic suggestion. Eventually, his work convinced skeptical researchers in Japan, promoting increased interest in psychosomatic medicine among physicians throughout Japan. In 1958, at the World Congress of Gastroenterology in Washington, he presented the paper ‘Experimental Studies on the Psychosomatic Disorders of the Digestive System’. This paper created tremendous interest among gastroenterologists in the US including one of the leading gastroenterologists, Professor Bockus, who invited him to contribute his work to his textbook on gastroenterology. In 1958, Professor E. Weiss, one of the pioneers of psychosomatic medicine, invited him to the Department of Comprehensive Medicine of Temple University Medical Center as an instructor. Fortunately, this association gave him a supporting hand when he built up the Department of Psychosomatic Medicine at Kyushu University School of Medicine.
ABC of antenatal care. Multiple pregnancy.
Authors: G Chamberlain
Journal: BMJ (1991)

~tMultiple pregnancy is a mixed blessing.On the one hand is the instant family, on the other are the increased perinatal mortality and morbidity as well as a much greater load for the mother after delivery. TypesMultiple pregnancy follows either the division of an oocyte fertilised by one sperm into two separate bodies (identical or monozygotic twins) or the fertilisation of more than one egg by separate sperm (non-identical or dizygotic twins).In higher multiple pregnancies than twins a combination of these two mechanisms happens.In uniovular twins division into two separate bodies was thought to occur only at a very early stage but it can in fact take place up to several days after fertilisation.Monovular and binovular twins.
Adaptive responses to pharmacological inhibition of small intestinal alpha-glucosidases in the rat.
Authors: B Lembcke, C Loser, U R Folsch, J Wohler, W Creutzfeldt
Journal: Gut (1987)

Intestinal adaptation (small intestinal weight and length, weight of the caecum and of the residual colon) to feeding different doses (0-5-50-500 mg/kg bw) of the absorbable, competitive alpha-glucosidase inhibitors BAY m 1099 and BAY o 1248 for three, seven, or 28 days was studied in rats. With the highest dose of either inhibitor, a significant and time dependent growth of the caecum was observed. Under these conditions, caecal tissue polyamine concentrations (spermidine and spermine) were slightly higher after three, unaffected after seven and slightly decreased after 28 days. Comparing the trophic effect both of BAY m 1099 and BAY o 1248 with that of the almost unabsorbed glucosidase inhibitor acarbose in fed rats showed that caecal weight was higher in response to the absorbed compounds than in response to acarbose, while total caecal carbohydrate content was unaffected by the absorbed and about nine fold increased by the unabsorbed inhibitors. These findings suggest that acarbose may partially inhibit bacterial carbohydrate degradation in the caecum.
Special features of the priming process for a secretory IgA response. B cell priming with cholera toxin.
Authors: J A Fuhrman, J J Cebra
Journal: The Journal of Experimental Medicine (1981)

Administration of cholera toxin/toxoid by either intraduodenal or parenteral routes increases the frequency of antigen-sensitive B cells in Peyer's patches (PP) and in distant lymphoid tissues greater than 50-fold. The special feature of mucosal priming with toxin is its unique effectiveness at generating secondary B cells, whose progeny express IgA exclusively, and such cells appear in highest frequency in PP and in appreciable numbers in spleen. Thus, this deliberate intraduodenal immunization seems to mimic the natural priming process induced by enteric bacterial colonization, which we have postulated to account for the high frequencies of IgA-committed cells specific for bacterial determinants in the PP of conventionally reared mice. furthermore, as a result of intraduodenal immunization, antigen-specific memory B cells are disseminated to sites distant form that of antigen application, including the lymphoid follicles associated with the respiratory mucosa. Direct antigenic stimulation of cells in the PP therefore results in effective cross-priming among mucosal and systemic sites through division, differentiation, and disemination of antigen-sensitive secondary B cells.