tbuckley/cabot-search huggingface dataset:
S36 Differentiation of tuberculosis and sarcoidosis by transcriptional profiling of immune responses in mediastinal lymph node samples
Authors: GS Tomlinson, G Hardavella, J Brown, L Succony, N Navani, N Thomas, BM Chain, SM Janes, M Noursadeghi
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Differentiating tuberculosis and sarcoidosis can be difficult, particularly in the context of mediastinal lymphadenopathy, because both diseases are characterised by overlapping clinical phenotypes and histologically similar granulomatous inflammation. Currently, diagnosis relies heavily on microbiological confirmation of tuberculosis which is only available in &lt;50% of cases. Therefore, novel diagnostic strategies are needed to prevent morbidity associated with delayed or inappropriate treatment. We tested the hypothesis that genome wide transcriptional profiling of mediastinal lymph node samples obtained by minimally invasive endobronchial ultrasound guidance could identify gene signatures that differentiate tuberculosis and sarcoidosis. <h3>Methods</h3> <i>In vivo</i> immune responses were compared in mediastinal lymph node biopsies obtained via endobronchial ultrasound guidance from patients with tuberculosis, sarcoidosis or non-granulomatous disease using genome-wide transcriptional profiling. Machine learning algorithms were used to test the discriminatory power of identified gene signatures which distinguished granulomatous from non-granulomatous disease or tuberculosis from sarcoidosis. <h3>Results</h3> Comparison of lymph node genome‑wide transcriptional profiles by principal component analysis revealed clear differences between granulomatous and non-granulomatous disease. Granulomatous profiles showed significant enrichment for genes involved in antigen presentation, inflammatory responses, innate immune responses and T cell activation, in keeping with the processes involved in granuloma generation. As expected, sarcoidosis and tuberculosis sample profiles were very similar, however, significant gene expression differences were still evident between these two groups. In particular, several genes related to development of granuloma architecture were more highly expressed in sarcoidosis samples. Next we used machine learning tools in order to test the discriminatory power of differentially expressed gene signatures and found that the support vector machines algorithm correctly classified up to 97% of granulomatous and non-granulomatous disease cases. Importantly, this technique successfully distinguished sarcoidosis from tuberculosis in up to 100% cases. <h3>Conclusions</h3> Transcriptomic analysis of lymph node samples from the site of disease identifies gene signatures that can reliably distinguish tuberculosis from sarcoidosis using computational classification tools. Our data highlight the superior discriminatory power of multiple gene expression differences over a single marker in complex disease and generate a pathway for biomarker discovery in the management of tuberculosis and sarcoidosis.
Isolation and characterization of single canine cardiac purkinje cells.
Authors: M F Sheets, C T January, H A Fozzard
Journal: Circulation Research (1983)

Single cardiac Purkinje cells should permit improved control of membrane potential during voltage clamp studies. We have developed a method for isolation of single canine Purkinje cells and studied their basic electrophysiological properties using conventional single and double microelectrode techniques. The single Purkinje cells appeared free of connective tissue, had regular striations, excluded trypan blue vital stain, and remained quiescent in solutions containing 1.8 mM calcium. Electrophysiological studies at 22 degrees C showed normal resting membrane potentials, and action potentials could be elicited by extracellular or intracellular stimulation. Plot of the upstroke velocity of the action potential (Vmax) vs. the holding potential showed a sigmoid curve with the peak mean Vmax of 167 V/sec, and voltage corresponding to half-maximal Vmax was about -70 mV. Plot of the overshoot of the action potential vs. the holding potential was similar, with maximal values of about +30 mV. The mean membrane input resistance was 21 M omega and the mean membrane capacitance was 360 pF. These experiments demonstrate that single Purkinje cells have electrical properties similar to intact Purkinje fibers and that they should be useful for more detailed electrophysiological experiments.
Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes
Authors: Hisashi Kai, Hisao Ikeda, Hideo Yasukawa, Mamiko Kai, Yukihiko Seki, Fumitaka Kuwahara, Takafumi Ueno, Kenzo Sugi, Tsutomu Imaizumi
Journal: Journal of the American College of Cardiology (1998)
Glucommander
Authors: Paul C. Davidson, R. Dennis Steed, Bruce W. Bode
Journal: Diabetes Care (2005)

Intravenous insulin is now the recommended method of diabetes management in critically ill persons in the hospital. The published methods for administering the insulin are complex and are usually limited to intensive care units with a low patient-to-nurse ratio.A computer-directed algorithm for advice on the delivery of intravenous insulin that is flexible in blood glucose timing and advises insulin dosing in a graduated manner has been developed. This software program, known as the Glucommander, has been used extensively by our group. The data were analyzed for this study.The data from 5,080 intravenous insulin runs over 120,683 h show that blood glucose levels can be safely stabilized in a target range without significant hypoglycemia by nonspecialized nurses working on any unit of a general hospital. The mean glucose level reached <150 mg/dl in 3 h. Only 0.6% of all glucose values were <50 mg/dl. The prevalence of hypoglycemia <40 mg/dl was 2.6% of all runs. No hypoglycemia was severe.This computer-directed algorithm is a simple, safe, effective, and robust method for maintaining glycemic control. It has been extensively studied and is applicable in a wide variety of conditions. In contrast to other published intravenous insulin protocols, which have been limited to intensive care units, Glucommander can be used in all units of any hospital.
Are those who quit smoking paying with their lives because of NRT's failure?
Authors: J. R. Polito
Journal: BMJ (2012)

A recent population level study, although small, found that the odds of smoking relapse in the first six months were 3.53 higher in heavily dependent quitters using nicotine replacement therapy (NRT) than in those not using NRT.1 This is why Kamerow’s reliance on the current favoured explanation for the failure of …
In-111 CYT-103 Immunoscintigraphy of Isolated Splenic Metastasis From Ovarian Carcinoma
Authors: BA D. NGUYEN, FINTAN REGAN
Journal: Clinical Nuclear Medicine (1997)

In-111 CYT-103 is a tagged monoclonal antibody directed at the tumor-related antigen TAG-23 present in ovarian cancer. It is used in the diagnostic search of ovarian metastases and appears to be helpful in the detection of pelvic and extrahepatic tumoral dissemination. The authors present a case of an uncommon solitary ovarian metastasis to the spleen. The splenic lesion was suspected on contrast-enhanced abdominal CT and elegantly shown by In-111 CYT-103 immunoscintigraphy.
Risk of Hip Fracture Among Dialysis and Renal Transplant Recipients
Authors: Adrianne M. Ball, Daniel L. Gillen, Donald Sherrard, Noel S. Weiss, Scott S. Emerson, Steve L. Seliger, Bryan R. Kestenbaum, Catherine Stehman-Breen
Journal: JAMA (2002)

Renal failure places people at particularly high risk of hip fracture. However, the possible differential impact of dialysis and renal transplantation on this risk is not well understood.To determine if patients who receive kidney transplants are at greater risk of hip fracture compared with those who continue to undergo dialysis.Cohort study of 101 039 patients with end-stage renal disease placed on the renal transplant waiting list in the United States between January 1, 1990, and December 31, 1999.Hip fractures, identified from Medicare claims data.Among the patients included in this analysis, 971 hip fractures were observed during the follow-up period of 314 767 person-years. The incidence rate of hip fracture in patients receiving dialysis was 2.9 per 1000 patients per year compared with 3.3 hip fractures per 1000 patients per year in those who had previously received a renal transplant. Initially, the relative risk (RR) of hip fracture associated with transplantation was 1.34-fold greater when compared with dialysis (adjusted RR, 1.34; 95% confidence interval [CI], 1.12-1.61) but then decreased by 1% per month (adjusted RR, 0.99; 95% CI, 0.98-0.99) until the estimated risk became equal for dialysis and transplant recipients approximately 630 days after transplantation (adjusted RR, 1.00; 95% CI, 0.87-1.15). Among transplant recipients, risk of fracture was relatively higher in persons with a prolonged period of dialysis before transplantation.The high risk of hip fracture among dialysis patients is exceeded by that among renal transplant patients during the first 1 to 3 years after transplantation.
Abstract A58: Galbanic acid isolated from <i>Ferula assafoetida</i> exerts in vivo antitumor activity in association with antiangiogenesis and antiproliferation
Authors: Sunghoon Kim, Kwanhyun Kim, Soojin Jeong, Hyojeong Lee, Junxuan Lu
Journal: Cancer Research (2012)

Abstract To investigate whether galbanic acid (GBA) exerts antiangiogenic and anticancer activities. Using human umbilical vein endothelial cell (HUVEC) model, we analyzed effects of GBA on cellular and molecular events related to angiogenesis. We tested its direct antiproliferative action on mouse Lewis lung cancer (LLC) cells and established its in vivo antiangiogenic and antitumor efficacy using LLC model. GBA significantly decreased vascular endothelial growth factor (VEGF)-induced proliferation and inhibited VEGF-induced migration and tube formation of HUVECs. These effects were accompanied by decreased phosphorylation of p38-mitogen-activated protein kinase (MAPK), c-jun N-terminal kinase (JNK), and AKT, and decreased expression of VEGFR targets endothelial nitric oxide synthase (eNOS) and cyclin D1 in VEGF-treated HUVECs. GBA also decreased LLC proliferation with an apparent G2/M arrest, but did not induce apoptosis. In vivo, inclusion of GBA in Matrigel plugs reduced VEGF-induced angiogenesis in mice. Galbanic acid given by daily i.p. injection (1 mg/kg) inhibited LLC-induced angiogenesis in an intradermal inoculation model and inhibited the growth of s.c. inoculated LLC allograft in syngenic mice. Immunohistochemistry revealed decreased CD34 microvessel density index and Ki-67 proliferative index in GBA-treated tumors. Overall, our findings suggest that GBA exerts anticancer activity in association with antiangiogenic and antiproliferative actions. Citation Format: Sunghoon Kim, Kwanhyun Kim, Soojin Jeong, Hyojeong Lee, Junxuan Lu. Galbanic acid isolated from Ferula assafoetida exerts in vivo antitumor activity in association with antiangiogenesis and antiproliferation [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A58.
Radiation-Induced Hepatitis B Virus Reactivation in Liver Mediated by the Bystander Effect from Irradiated Endothelial Cells
Authors: Chia Hung Chou, Pei-Jer Chen, Po-Huang Lee, Ann-Lii Cheng, Hui-Chen Hsu, Jason Chia-Hsien Cheng
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Hepatitis B virus (HBV) reactivation is one unique pathogenesis in Asian carriers with liver toxicity after radiotherapy for hepatobiliary malignancies. This study attempts to delineate the biological mechanism of radiation-induced HBV reactivation. Experimental Design: Primary cultures of hepatocytes (PCC) were prepared from the noncancerous liver tissue removed perioperatively from 12 HBV carriers with hepatocellular carcinoma (HCC). The conditioned medium of irradiated PCCs, HCC, and endothelial cells from patients was transferred to PCCs or HepG2.2.15 cells (a human hepatoblastoma cell line transfected with HBV DNA) before subsequent irradiation. Forty-eight hours after irradiation, HBV DNA was measured by real-time quantitative PCR. Specific cytokines were determined by cytokine array and ELISA analysis. Preradiotherapy and postradiotherapy sera from 10 HBV carriers and 16 non-HBV carriers were analyzed for viral loads and cytokine activities. Results: Radiation induced HBV DNA replication in (a) irradiated PCCs cultured with the conditioned medium from irradiated PCCs (2.74-fold; P = 0.004) and endothelial cells (9.50-fold; P = 3.1 × 10−10), but not from HCCs (1.07-fold), and in (b) irradiated HepG2.2.15 cells (17.7-fold) cocultured with human umbilical vascular endothelial cells. Cytokine assay revealed increased expression of interleukin-6 (IL-6) in conditioned medium from irradiated human umbilical vascular endothelial cells. All 16 patients with liver irradiated had the increased serum IL-6 compared with 3 of 10 patients with irradiation excluding liver (P &amp;lt; 0.001). All nine HBV carriers with liver irradiated had postradiotherapy increases in both HBV DNA and IL-6. Conclusions: Radiation-induced liver toxicity with HBV reactivation is from a bystander effect on irradiated endothelial cells releasing cytokines, including IL-6.
Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands.
Authors: I Vauhkonen, L Niskanen, E Vanninen, S Kainulainen, M Uusitupa, M Laakso
Journal: Journal of Clinical Investigation (1998)

No studies are available that have compared early defects in glucose metabolism in the offspring of insulin-deficient and insulin-resistant probands with non-insulin-dependent diabetes mellitus (NIDDM). To investigate this issue, we evaluated insulin secretion capacity with oral and intravenous glucose tolerance tests and with the hyperglycemic clamp, and insulin action with the euglycemic insulin clamp in 20 offspring of NIDDM patients with low fasting C-peptide (+/-450 pmol/liter), reflecting deficient insulin secretion (IS-group), 18 offspring of NIDDM patients with high fasting C-peptide (>/= 880 pmol/liter), reflecting insulin resistance (IR-group), and 14 healthy control subjects without a family history of NIDDM. The frequency of impaired glucose tolerance was 45.0% in the IS-group and 50% in the IR-group. The IS-group had lower insulin-glucose response at 30 min in the oral glucose tolerance test (85.2+/-10.0 pmol insulin per mmol glucose) than the control group (136.4+/-23.1 pmol insulin per mmol glucose; P < 0.05) and the IR-group (115.6+/-11.8 pmol insulin per mmol glucose; P = 0.05). Furthermore, the acute insulin response during the first 10 min of an intravenous glucose tolerance test was lower in the IS-group than in the IR-group. Maximal insulin secretion capacity evaluated by C-peptide levels during the hyperglycemic clamp did not differ between the groups. The IR-group had lower rates of whole body glucose uptake (60.1+/-4.6 micromol per lean body mass per minute) than did the control group (84.2+/-5.0 micromol per lean body mass per minute; P < 0.001) or the IS-group (82.6+/-5.9 micromol per lean body mass per minute; P < 0.01) and this was due to reduced glucose nonoxidation. To conclude, both impaired insulin secretion and insulin action seem to be inherited and could represent the primary defects in glucose metabolism in the offspring of NIDDM probands.
ABDOMINAL PAIN.ESPECIALLY PAIN IN CONNECTION WITH ILEUS.
Authors: K. G. LENNANDER
Journal: JAMA (1907)

From my published works it may be gathered that I have not been able to find any abdominal organ, innervated only by the vagus or the sympathetic nerves, which is provided with the sense of pain. Sensations of pain within the abdominal cavity are, according to my experience, transmitted only by the phrenic nerve, the lower six intercostal, the lumbar and the sacral nerves.  My former pupil, M. Ramstrom, 1 professor of anatomy at Upsala, has given us the first exact description of the course of these nerves within the diaphragm and the peritoneal lining of the anterior abdominal wall. He has shown that some of the older descriptions of the distribution of these nerves are incorrect. For instance, he has not seen any branches of the phrenic nerve running down from the diaphragm to the anterior abdominal wall, nor has he been able to trace a single branch of
Vaginal Ureteral Orifices
Authors: Winthrop M. Flagg
Journal: New England Journal of Medicine (1946)

TRUE supernumerary kidney is a rare anomaly.1 In a review of the literature Headings and Palmer2 found a total of 44 cases, of which 6 had extravesical ureteral orifices. A case reported by Shane3 and the following case bring the total number of cases of supernumerary kidney with a vaginal orifice to 8.A. G., a 7-year-old girl, was seen because of urinary incontinence, which had been present since birth but was apparent only when the child was on her feet. There had been no nocturnal enuresis since the age of 2. With the patient in the supine position there . . .
Pain management and sedation for children in the emergency department
Authors: P. Atkinson, A. Chesters, P. Heinz
Journal: BMJ (2009)

<h3>Abstract</h3> Regulated secretion of neuropeptides and peptide hormones by secretory granules (SGs) is central to physiology. Formation of SGs occurs at the trans-Golgi network (TGN) where their soluble cargo aggregates to form a dense core, but the mechanisms controlling the sorting of regulated secretory cargoes (soluble and transmembrane) away from constitutively secreted proteins remain unclear. Optimizing the use of the retention using selective hooks (RUSH) method in (neuro-)endocrine cells, we now quantify TGN budding kinetics of constitutive and regulated secretory cargoes. We further show that, by monitoring two cargoes simultaneously, it becomes possible to visualize sorting to the constitutive and regulated secretory pathways in real-time. Further analysis of the localization of SG cargoes immediately after budding from the TGN revealed that, surprisingly, the bulk of two studied transmembrane SG cargoes (phogrin and VMAT2) does not sort directly onto SGs during budding, but rather exit the TGN into non-regulated vesicles to get incorporated to SGs at a later step. This differential behavior of soluble and transmembrane cargoes suggests a more complex model of SG biogenesis than anticipated.
Abstract 4266: Potential role of reactive oxygen species in affecting tumorigenicity of glioblastoma stem cells
Authors: Feng Wang, Naima Hammodi, Shuqiang Yuan, Gang Chen, Li Feng, Sangbae Kim, Howard Colman, Ju-Seog Lee, Ruihua Xu, Peng Huang
Journal: Cancer Research (2010)

Abstract Glioblastoma multiforme (GBM) is a common and highly aggressive primary brain tumor with poor prognosis due in part to drug resistance and high incidence of tumor recurrence. The drug resistant and cancer recurrence phenotype may be ascribed to the presence of cancer stem cells, which seem to reside in special stem-cell niches in vivo and require special culture conditions including certain growth factors and serum-free medium to maintain their stemness in vitro. In this study, we used two lines of stem-like cancer cells (GSC11 and GSC23) derived from the tumor tissues of two GBM patients by classical neurosphere culture system, and showed that addition of serum (FBS) to the medium induced an increase of ROS, leading to aberrant differentiation and eventual cell death. Although both GBM stem-like cell lines showed high percentage of CD133-positive cells (20% in GSC11 and 70% in GSC23), exposure to serum only caused a moderate decrease of CD133 expression at later time points. Several methods were used to further test the role of ROS in affecting the stemness of the GSC cells and their self-renewal capacity. Addition of 5% FBS or removal of the antioxidant supplements (B27) from the culture medium caused the spheroid GSC cells to attach to the culture surface, exhibit differentiation morphology, decrease expression of certain stem-cell markers, and eventually die within two weeks. Serum exposure also resulted in a decrease of the GSC ability to form colonies in soft agar assay and to grow tumors in a mouse xenograft model. Although an increase of general cellular ROS could be detected when GSC cells were exposed to FBS, the mitochondrial superoxide appeared to be prominent and likely to be a primary event, which led to a compensatory increase of the mitochondrial SOD2 expression and upregulation of glutathione synthesis. Interestingly, addition of the antioxidant N-Acetylcysteine to the FBS-containing medium partially blocked the FBS-induced aberrant differentiation and improved cell viability and self-renewal capacity, suggesting that ROS may play an important role in affecting stemness and differentiation status of the cancer stem cells. We postulate that during tumor development, only the progeny cells that acquire the ability to counteract the impact of ROS increase induced by serum may eventually proliferate and grow as the tumor bulk, and that proper redox-modulation may be a potential novel strategy to block tumor formation and possibly kill the stem-like cancer 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 4266.
Abstract 888: Genetic variability in lipid metabolism and risk of lung cancer
Authors: Jianjun Zhang, Hideo Tanaka, Hidemi Ito, Paolo Boffetta, Keitaro Matsuo
Journal: Cancer Research (2011)

Abstract Lung cancer is the leading cause of cancer death in many countries across the world. A growing body of evidence indicates that fat (especially saturated fat) is involved in lung carcinogenesis. Lung cancer incidence is higher among countries with high intake of fat. Some, although not all, epidemiologic studies have shown that fat intake was associated with an increased risk of lung cancer. Animal studies demonstrated that fat interacted with tobacco carcinogens to influence occurrence of lung tumors. Collectively, it is possible that genetic variability in lipid metabolism may modulate the risk of lung cancer. We sought to investigate this hypothesis in a hospital-based case-control study conducted from 2000 to 2005 in Nagoya, Japan. Cases (n=230), ages 20-79, were patients pathologically diagnosed with lung cancer at the Aichi Cancer Center, and controls (n=230) were recruited from visitors to the outpatient department of the Aichi Cancer Center and matched to cases by age (within 5 years) and sex. We genotyped polymorphisms in five genes: pancreatic lipase (PNLIP, rs2915748), apolipoprotein E (APOE, rs440446), hepatic lipase (LIPC, rs1800588), fatty acid desaturase 1 (FADS1, rs174546), and FADS (rs174570). Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated with unconditional logistic regression. After adjustment for age, sex, BMI, cigarette smoking (pack-years), a promoting effect was observed for the variant allele of PNLIP rs2915748 [OR (95%CI): 1.64 (1.09-2.47) for GA/AA vs. GG]. A similar effect was found for APOE rs440446 [OR (95%CI): 1.71 (1.14-2.58) for CG/GG vs. CC)]. No significant associations were detected for other three sequence variants examined. To our knowledge, our study is among the first to suggest that genetic variations in the digestion and transport of lipids alter lung cancer risk. 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 888. doi:10.1158/1538-7445.AM2011-888