tbuckley/cabot-search huggingface dataset:
Resistance to artemisinin of malaria parasites (Plasmodium falciparum) infecting alpha-thalassemic erythrocytes in vitro. Competition in drug accumulation with uninfected erythrocytes.
Authors: S Kamchonwongpaisan, G Chandra-ngam, M A Avery, Y Yuthavong
Journal: Journal of Clinical Investigation (1994)

Plasmodium falciparum infecting hemoglobin (Hb)H and/or Hb Constant Spring erythrocytes has higher resistance to artemisinin in vitro than when infecting normal erythrocytes. This is due to low drug accumulation of infected erythrocytes resulting from competition with uninfected variant erythrocytes, which have a higher accumulation capacity than genetically normal cells. Drug accumulation of the parasite was shown to be saturable and dependent on metabolic energy. The 50% inhibitory concentrations (IC50's) for the parasite in HbH/Hb Constant Spring erythrocytes were decreased when normal erythrocytes were added to the infected cells, and correspondingly, the IC50's in normal erythrocytes were increased when HbH/Hb Constant Spring erythrocytes were added to the infected cells. The changes of IC50 corresponded to the variation in drug accumulation of mixtures of normal and variant erythrocytes of different compositions. The IC50's for the parasite in variant erythrocytes were also greatly decreased when the hematocrit of the culture was lowered, while the IC50's in normal erythrocytes were independent of the hematocrit. The increase in IC50 values for the parasites infecting variant erythrocytes was also related to the decrease in parasite accumulation, indicating that drug accumulation capacity of the parasite also has a role in determining drug sensitivity. Artemisinin sensitivity therefore is determined by its accessibility to the parasite, which is decreased in infected variant erythrocytes.
Endotoxin in inner-city homes: Associations with wheeze and eczema in early childhood
Authors: Matthew S. Perzanowski, Rachel L. Miller, Peter S. Thorne, R. Graham Barr, Adnan Divjan, Beverley J. Sheares, Robin S. Garfinkel, Frederica P. Perera, Inge F. Goldstein, Ginger L. Chew
Journal: Journal of Allergy and Clinical Immunology (2006)
Dilation of Benign Strictures Following Low Anterior Resection Using Savary - Gilliard Bougies
Authors: None Werre, None Mulder, None van Heteren, None Spillenaar Bilgen
Journal: Endoscopy (2000)

Background and Study Aims: Benign anastomotic strictures occur in up to 22 % of patients after colorectal resections. Initially, treatment for these strictures was surgical, but nowadays endoscopic dilation techniques are preferred. This study was conducted to assess the efficacy of dilation using Savary-Gilliard bougies.
Posttraumatic Stress Disorder After Severe Traumatic Brain Injury
Authors: Richard A. Bryant, Jeno E. Marosszeky, Jenelle Crooks, Joseph A. Gurka
Journal: American Journal of Psychiatry (2000)

This study indexed the profile of posttraumatic stress disorder (PTSD) after severe traumatic injury to the brain.Patients who sustained a severe traumatic brain injury (N=96) were assessed for PTSD 6 months after the injury with the PTSD Interview, a structured clinical interview based on DSM-III-R criteria.PTSD was diagnosed in 26 (27.1%) of the patients. While only 19.2% (N=5) of the patients with PTSD reported intrusive memories of the trauma, 96.2% (N=25) reported emotional reactivity. Intrusive memories, nightmares, and emotional reactivity had very strong positive predictive values for the presence of PTSD.These findings indicate that PTSD can develop after severe traumatic brain injury. The predominance of emotional reactivity and the relative absence of traumatic memories in patients with PTSD who suffered impaired consciousness during trauma suggest that traumatic experiences can mediate PTSD at an implicit level.
Developmental and tissue-specific regulation of rabbit skeletal and cardiac muscle calcium channels involved in excitation-contraction coupling.
Authors: A M Brillantes, S Bezprozvannaya, A R Marks
Journal: Circulation Research (1994)

Two types of calcium channels signal excitation-contraction (E-C) coupling in striated muscle: dihydropyridine receptors (DHPRs, voltage-gated L-type calcium channels on the transverse tubule) and ryanodine receptors (RyRs, calcium release channels on the sarcoplasmic reticulum). Sarcolemmal depolarization activates the DHPR; subsequently, the RyR is activated and releases calcium that activates muscle contraction. We show in the present study that expression of the E-C coupling calcium channels is upregulated during myogenic development in the rabbit. Skeletal and cardiac muscle isoforms of the following genes were examined: the DHPR alpha 1, alpha 2, beta, and gamma subunits and the RyR. Distinct cardiac and skeletal muscle-specific cDNAs were isolated, encoding each of the DHPR subunits and the RyR. The skeletal muscle DHPR alpha 1, alpha 2, beta, and gamma subunits and the cardiac DHPR alpha 1 subunit mRNA levels increased on the day of birth and at the adult stage compared with fetal levels. The skeletal and cardiac RyR mRNA levels increased on the day of birth and at adult stages compared with fetal levels. Ryanodine binding sites increased in both skeletal and cardiac muscle. We now provide a molecular explanation for the physiological "maturation" of the E-C coupling apparatus observed at the day of birth and during early postnatal development in both skeletal and cardiac muscles. Low levels of calcium channel expression in fetal cardiac and skeletal muscle make these tissues more sensitive to pharmacological therapy with calcium channel blockers, a phenomenon that has been reported in human neonates.
Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.
Authors: S R Heller, S A Amiel, P Mansell
Journal: Diabetes Care (1999)

OBJECTIVE: To measure the effectiveness of insulin lispro, a fast-acting insulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy. RESEARCH DESIGN AND METHODS: In 11 diabetes outpatient clinics in the U.K., 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen. Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level. RESULTS: A total of 135 patients were randomized, with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction. Glycemic control was equally tight during treatment with human regular insulin (HbA1c, 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04). This difference was chiefly because of a reduced number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group. CONCLUSIONS: The use of a fast-acting insulin analog, insulin lispro, as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy.
Progress towards fewer inappropriate attempts at cardiopulmonary resuscitation
Authors: E. J. Hall, N. Sykes, D. Swann
Journal: BMJ (2011)

Despite preparation by health professionals, relatives sometimes call an ambulance to someone near to death, but this does not need to result in attempted resuscitation.1 Locally, much work has gone into implementation of written do not resuscitate orders that can be left in the patient’s house, with their consent.

But even without a written order, paramedics …
Watson-Jones Fractures and Joint Injuries
Authors: Kingsbury G. Heiple
Journal: JAMA (1977)

The new edition of an old and familiar work like<i>Watson-Jones Fractures and Joint Injuries</i>is always welcome, and one looks forward to such a product with enthusiasm, but also with some trepidation lest an old favorite will lose some of the inherent qualities that has made it such a standby. Fortunately, Dr Wilson and his collaborators have been maintaining much of the flavor and quality of this classic work while managing to update it reasonably well, at least regarding current British practice. As with the previous editions, the work remains a two-phased approach to the management of trauma, with the first volume concentrating generally on principles and the second volume serving as a regional atlas of injuries that will be more useful for immediate reference. The material in volume 1 on the repair of fractures, joint stiffness, and the systemic effects of injury is excellent. The latter is an
Novel Zoom Endoscopy Technique for Diagnosis of Small Flat Gastric Cancer: A Prospective, Blind Study
Authors: Kenshi Yao, Akinori Iwashita, Hiroshi Tanabe, Takashi Nagahama, Toshiyuki Matsui, Toshiharu Ueki, Suketo Sou, Yosuke Kikuchi, Makoto Yorioka
Journal: Clinical Gastroenterology and Hepatology (2007)
Conformational Changes in Myocardial Nuclei of Rats
Authors: S. BLOOM, P. A. CANCILLA
Journal: Circulation Research (1969)

Myocardial nuclei have been found to undergo a dramatic change in nuclear conformation during the contraction-relaxation cycle. This was demonstrated with electron micrographs of longitudinally and transversely oriented nuclei in contracted and relaxed fibers of rat myocardium. The contracted fibers had a mean sarcomere length of l.7µ ± 0.1µ (±1 SD), and extended fibers had a mean sarcomere length of 2.1µ ± 0.3µ. The amount of membrane wrinkling was quantified by comparing a straight-line distance of 6.64µ between two points on the nuclear membrane to the distance along the membrane (NML) between the same points. The degree of wrinkling was expressed as "redundancy" which is [(NML - 6.64)/6.64] x 100. Longitudinal sections showed a marked difference in mean length and width in the two populations of nuclei, with an axial ratio of 2.2 in the contracted, and 4.8 in the extended fibers. The most obvious difference between the two populations, however, was the nuclear membrane redundancy, which was 2.1% and 27.0% for the extended and contracted fibers, respectively. Although a difference in nuclear membrane redundancy was clear in longitudinal sections, it was not apparent in transverse sections. It is concluded that during systole myocardial nuclei become longitudinally compressed with folding of the membrane perpendicular to the long axis. The correlation of the change in sarcomere length with the change in nuclear length and membrane redundancy suggests a coupling of the nuclear membrane to some sarcomere segment.
Abstract 3007: Down-regulation of HOXC6 in serous ovarian cancer.
Authors: David L. Tait, Zahra Bahrani-Mostafavi, Carol Vestal, Christine Richardson, M. Taghi Mostafavi
Journal: Cancer Research (2013)

Abstract Objective: The Homeobox (HOX) family of genes consists of 39 genes encoding transcription factors important to morphogenesis and cell differentiation. Usually inactive in normal differentiated tissues, dysregulation of HOX genes has been reported in several malignancies. HOX genes have been linked to genes important in malignant transformation including vascular endothelial growth factor, Ras, interleukin-8, and fibroblast growth factor. We have previously reported up-regulation of HOXA2, HOXA7 and HOXB7 in ovarian cancer. Little is known about HOXC6 gene expression in ovarian cancer. In this study we evaluated HOXC6 expression in normal and malignant human ovarian tissue to characterize expression of HOXC6 in serous ovarian cancer. Methods: Microarray analysis of mRNA from LCM captured cells from human ovarian tissues was performed on 11 samples of normal, and malignant ovarian tissues. These samples were analyzed using the Affymetrix Human EXON 1.0 ST microarray to distinguish the differential pattern of mRNA expression between malignant and normal samples. Real-time reverse transcription PCR was utilized to confirm down-regulation of HOXC6 genes as determined by microarray analysis. HOXC6 protein in tissue was evaluated by immunohistochemistry. Results: Microarray analysis demonstrated significant down-regulation of the HOXC6 gene in malignant serous ovarian tumor samples compared to normal ovarian epithelial cells of control samples. RT-PCR and immunohistochemistry confirmed HOXC6 down-regulation in malignant samples. A 115-fold difference in malignant and normal primary tissue samples and cell lines was seen in the RT-PCR analysis. By immunohistochemistry nuclear staining of HOXC6 protein was seen in the nuclei of normal ovarian surface epithelial tissues but significantly reduced or absent in malignant ovarian samples. Conclusion: HOXC6 is significantly differentially expressed comparing normal ovarian tissue and serous malignant ovarian tissue based on both tissue mRNA and protein analysis. This finding of HOXC6 down-regulation in ovarian cancer is unique and opposite of the up-regulation of other HOX genes previously reported. Down-regulation of HOXC6 in serous ovarian cancer may be an important finding relative to oncogenic pathways and biomarker development. This suggests dysregulation of HOXC6 genes may be an early event in malignant transformation and additional studies to validate the role of the HOXC6 gene in ovarian cancer are warranted. Citation Format: David L. Tait, Zahra Bahrani-Mostafavi, Carol Vestal, Christine Richardson, M. Taghi Mostafavi. Down-regulation of HOXC6 in serous ovarian cancer. [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 3007. doi:10.1158/1538-7445.AM2013-3007
Experimental Myocardial Infarction in the Dog
Authors: J. RUSSELL REES, V. J. REDDING
Journal: Circulation Research (1969)

Control measurements of myocardial blood flow were made in intact dogs by a method of 133 Xe clearance, using a catheter positioned radiographically in the circumflex artery. Acute myocardial infarction was then caused by tying the anterior descending artery. A small catheter was inserted distally beyond the obstructed artery into the infarct, and another proximally toward the anterior ventricular artery supplying adjacent left ventricular muscle. Their ends were brought out as the chest was closed. 133 Xe in solution was injected serially over 4 hours to determine myocardial blood flow within the infarct, in adjacent muscle, and in more distant muscle supplied by the circumflex artery. Myocardial blood flow in the circumflex artery usually fell as a result of infarction. A constant finding was that adjacent flow exceeded the more distant flow by 6% up to 43% (mean 20%) regardless of either spontaneous or induced changes in blood pressure. The difference was not related to the collateral flow rate and was abolished by dipyridamole. Perfusion of muscle adjacent to the infarct was less homogenous than that of more distant muscle. In the normal dog rates of myocardial blood flow in the distribution of the circumflex and anterior descending branches of the left coronary artery were the same, contrasting with lower rates for the right.
Bifunctional RNAs Targeting the Intronic Splicing Silencer N1 Increase SMN Levels and Reduce Disease Severity in an Animal Model of Spinal Muscular Atrophy
Authors: Erkan Y Osman, Pei-Fen Yen, Christian L Lorson
Journal: Molecular Therapy (2011)

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of survival motor neuron-1 (SMN1). A nearly identical copy gene, SMN2, is present in all SMA patients. Although the SMN2 coding sequence has the potential to produce full-length SMN, nearly 90% of SMN2-derived transcripts are alternatively spliced and encode a truncated protein. SMN2, however, is an excellent therapeutic target. Previously, we developed antisense-based oligonucleotides (bifunctional RNAs) that specifically recruit SR/SR-like splicing factors and target a negative regulator of SMN2 exon-7 inclusion within intron-6. As a means to optimize the antisense sequence of the bifunctional RNAs, we chose to target a potent intronic repressor downstream of SMN2 exon 7, called intronic splicing silencer N1 (ISS-N1). We developed RNAs that specifically target ISS-N1 and concurrently recruit the modular SR proteins SF2/ASF or hTra2β1. RNAs were directly injected in the brains of SMA mice. Bifunctional RNA injections were able to elicit robust induction of SMN protein in the brain and spinal column of neonatal SMA mice. Importantly, hTra2β1-ISS-N1 and SF2/ASF-ISS-N1 bifunctional RNAs significantly extended lifespan and increased weight in the SMNΔ7 mice. This technology has direct implications for SMA therapy and provides similar therapeutic strategies for other diseases caused by aberrant splicing.
Positive Geometric Vascular Remodeling Is Seen After Catheter-Based Radiation Followed by Conventional Stent Implantation but Not After Radioactive Stent Implantation
Authors: I. Patrick Kay, Manel Sabaté, Marco A. Costa, Ken Kozuma, Mariano Albertal, Willem J. van der Giessen, Alexander J. Wardeh, Jurgen M. R. Ligthart, Veronique M. A. Coen, Peter C. Levendag, Patrick W. Serruys
Journal: Circulation (2000)

Background —Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. Methods and Results —We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm 3 ) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm 3 ) compared with low-activity radioactive stent implantation (NIH 21.2 mm 3 ) and conventional stent implantation (NIH 20.8 mm 3 ) ( P =0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. Conclusions —Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.
Rupture of the spleen in rheumatoid arthritis.
Authors: R W Marcus
Journal: Annals of the Rheumatic Diseases (1985)

to establish a possible relationship between these two diseases.Finally, though we did not find the same high prevalence of cheiroarthropathy in NIDD as did Fitzcharles et al.,' we do agree that there is an association between microvascular derangement and diabetic cheiroarthropathy which is independent of glycaemic control.
Abstract 3269: Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery .
Authors: Cristian Rodriguez-Aguayo, Haifa Shen, Vianey Gonzalez-Villasana, Guodong Zhang, Xiaoyong Deng, Burcu Aslan, Xuewu Liu, Jason Sakamoto, Arturo Chavez-Reyes, Hee-Dong Han, Anil K. Sood, Mauro Ferrari1, Gabriel Lopez-Berestein
Journal: Cancer Research (2013)

Abstract RNA interference has the potential to specifically knock down the expression of target genes, and thereby transform cancer therapy. However, lack of effective delivery of small inhibitory RNA (siRNA) has dramatically limited its in vivo applications. We have developed a multistage vector (MSV) system, composed of discoidal porous silicon particles loaded with siRNA oligos packaged in dioleoyl phosphatidylcholine (DOPC) nanoliposomes, that directs effective delivery and sustained release of siRNA in tumor tissues. Tumor accumulation of siRNA was observed after i.v. administration of MSV/siRNA, and sustained release of siRNA from DMSV maintained high levels of siRNA in tumor for over one week after a single dose of DMSV/siRNA. Treatment of SKOV3ip2 tumor mice with DMSV carrying siRNA oligos specific for the human EphA2 gene (MSV/EphA2) biweekly for 6 weeks resulted in dose-dependent (5, 10 and 15 μg/mice) reduction of tumor weight (36%, 64%, and 83%) and number of tumor nodules compared with the control groups. In addition, tumor growth was completely inhibited when mice were treated with MSV/EphA2 in combination with paclitaxel. Furthermore, combination treatment with MSV/EphA2 and docetaxel inhibited growth of HeyA8-MDR tumors, which were otherwise resistant to docetaxel treatment. Taken together, MSV/EphA2 merits further development as a therapeutic approach for ovarian cancer. Citation Format: Cristian Rodriguez-Aguayo, Haifa Shen, Vianey Gonzalez-Villasana, Guodong Zhang, Xiaoyong Deng, Burcu Aslan, Xuewu Liu, Jason Sakamoto, Arturo Chavez-Reyes, Hee-Dong Han, Anil K. Sood, Mauro Ferrari1, Gabriel Lopez-Berestein. Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery . [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 3269. doi:10.1158/1538-7445.AM2013-3269
Reprogrammed Foxp3+ Regulatory T Cells Provide Essential Help to Support Cross-presentation and CD8+ T Cell Priming in Naive Mice
Authors: Madhav D. Sharma, De-Yan Hou, Babak Baban, Pandelakis A. Koni, Yukai He, Phillip R. Chandler, Bruce R. Blazar, Andrew L. Mellor, David H. Munn
Journal: Immunity (2010)