tbuckley/cabot-search huggingface dataset:
NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas
Authors: Dong-Mi Shin, Daniel J. Shaffer, Hongsheng Wang, Derry C. Roopenian, Herbert C. Morse
Journal: Cancer Research (2008)

Aside from Myc-activating translocations characteristic of plasmacytomas (PCT), little is known about genetic factors and signaling pathways responsible for the development of spontaneous B-cell lineage lymphomas of mice. Here, we characterized the transcriptional profiles of PCT, centroblastic diffuse large B-cell lymphomas (CBL), and high-grade splenic marginal zone B-cell lymphoma (MZL++) using high-throughput quantitative reverse transcription-PCR. Expression profiles of CBL and MZL++ were strikingly similar and quite unlike that of PCT. Among the genes expressed at significantly higher levels by PCT were a number involved in NOTCH signaling, a finding supported by gene set enrichment analyses of microarray data. To investigate the importance of this pathway, NOTCH signaling was blocked in PCT cell lines by treatment with a gamma-secretase inhibitor (GSI) or transduction of a dominant-negative mutant of MAML1. These treatments resulted in reduced expression of NOTCH transcriptional targets in association with impaired proliferation and increased apoptosis. GSI treatment of transformed plasma cells in a primary PCT also induced apoptosis. These results integrate NOTCH activation with oncogenic signaling pathways downstream of translocated Myc in the pathogenesis of mouse PCT, two signaling pathways also implicated in development of human multiple myeloma and T-cell lymphoblastic lymphoma.
Emergency treatment of asthma.
Authors: P W Barry, C O'Callaghan
Journal: Thorax (1995)

The cholinergic component in the sympathetic innervation to the spleen was studied in dogs. This was accomplished by the use of hemicholinium (HC-3) to inhibit transmission in the chohinergic nerves and the use of reserpine and guanethidine to inhibit adrenergic function. The spleen responded normally to electrical stimulation of the splenic nerve at a time when cholinergic transmission was inhibited. These data support the concept of separate chohimiergic and adrenergic fibers in the splenic nerve rather than a cholinergic junction in the adrenergic fibers. The relationships between the cholinergic and adrenergic components associated with the splenic nerve were studied further by the use of acetylcholine and nicotine. Both of these components of this nerve were found to be involved in both the responses to nicotine and in a possible mechanism for the control of the tone of the splenic capsule. These data are dliscussed in relation to the hypothesis of local chohinergic-adrenergic interaction.
Extraskeletal Uptake of Tc-99m at Subcutaneous Injection Sites in a Diabetic Patient
Authors: MARIA GYSEN, HILDE VERLOOY, LUC MORTELMANS
Journal: Clinical Nuclear Medicine (1998)

Extraosseous Tc-99m MDP uptake is not uncommon. It has been determined from a search of the literature that this may be the first case report of abnormal soft tissue uptake of a bone-seeking agent due to subcutaneous insulin therapy in the abdominal wall.
Adjuvant Chemotherapy Is Associated with Improved Survival after Esophagectomy without Induction Therapy for Node-Positive Adenocarcinoma
Authors: Paul J. Speicher, Brian R. Englum, Asvin M. Ganapathi, Michael S. Mulvihill, Matthew G. Hartwig, Mark W. Onaitis, Thomas A. D’Amico, Mark F. Berry
Journal: Journal of Thoracic Oncology (2014)
REPORT OF CASE OF BRAIN AND OTHER ABSCESSES—FOLLOWING TONSILLAR ABSCESS AND NON-PERFORATIVE SUPPURATIVE OTITIS MEDIA.
Authors: D. MILTON GREENE
Journal: JAMA (1899)

On January 11 Dr. Vanderburg asked me to see Dr. L. V., who had been suffering from some obscure disease, for about five weeks. He had been under the care of two physicians during his illness, having changed physicians once during the five weeks. A diagnosis of tonsillitis was made in the beginning of his illness, and typhoid pneumonia later. At the time of my first visit the following history was obtained. Five weeks before he was taken with pain in his left ear, side of head and face, with extreme swelling on these parts, extending particularly into the neck and throat. He had several chills followed by fever, sore throat, swelling of the tonsils, and finally rupture and discharge of pus in the throat. His temperature fluctuated between 98 and 105 degrees, from December 15 up to three days before I saw him, when he had a severe chill.
Enhanced mobilization of circulating endothelial progenitors cells in hypercholesterolemic patients by 3-hydroxy-3-methylglutaryl Co-A reductase inhibitor: View point to two different types of endothelial progenitor cells
Authors: Kyung-Kuk Hwang, Hyo-Soo Kim, Mi-Young Nam, Jin Hur, Jin-Ho Choi, Dae-Won Sohn, Byoung-Hee Oh, Yun-Shik Choi, Young-Bae Park
Journal: Journal of the American College of Cardiology (2003)
Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle
Authors: A Nishiyama
Journal: Cardiovascular Research (1998)

Objective: Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through β-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel α-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of β-adrenergic signaling pathway in their expressions under both status. Methods: Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of l-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the β-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay. Results: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n=6, p<0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n=6, p<0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n=6, p<0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n=6, p<0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso. Conclusion: Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through β-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.
Valve strands are strongly associated with systemic embolization: A transesophageal echocardiographic study
Authors: Robin S. Freedberg, Gregory M. Goodkin, John L. Perez, Paul A. Tunick, Itzhak Kronzon
Journal: Journal of the American College of Cardiology (1995)

We attempted to determine the prevalence of strands on native and prosthetic valves, as detected by transesophageal echocardiography, and to assess the relative risk for systemic emboli associated with these strands.Fine threadlike strands, seen on native and prosthetic valves by transesophageal echocardiography, have been implicated in systemic embolization.During a 2-year period, 1,559 patients underwent transesophageal echocardiography at our center. Of these, 41 patients had strands and no other identifiable source of systemic emboli. They were matched for age, gender, history of hypertension and history of smoking with a control group of 41 patients without strands who also had no identifiable source of emboli. The risk of embolization in the two groups was compared.Of 1,559 patients studied by transesophageal echocardiography, 86 (5.5%) had strands. Strands were far more common on mitral valves than on aortic valves. Of the patients with strands, 38% had had an event consistent with a systemic embolus, whereas 62% had not. Of 597 patients with an embolic event, 63 (10.6%) had strands, whereas only 23 (2.3%) of 962 patients without emboli had strands. In the case-control study, 33 (83%) of the 41 patients with strands without another source of embolism had emboli compared with only 12 (29%) of the 41 control patients without another source (odds ratio 10.0, 95% confidence interval 3.6 to 27.8, p = 0.00001).Valvular strands visualized by transesophageal echocardiography are associated with systemic embolization.
<b>Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1</b> α <b>/COX-2 Pathway</b>
Authors: Jun He, Min Wang, Yue Jiang, Qiudan Chen, Shaohua Xu, Qing Xu, Bing-Hua Jiang, Ling-Zhi Liu
Journal: Environmental Health Perspectives (2014)

Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood.We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth.We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis.We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis.The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis.He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255-261; http://dx.doi.org/10.1289/ehp.1307545.
541. Species-Specific Characteristics in Muscle Resistance and Their Impact on In Vivo Electroporation
Authors: Amir S. Khan, Patricia A. Brown, Melissa A. Pope, Ruxandra Draghia-Akli
Journal: Molecular Therapy (2006)

Numerous investigators have outlined the effectiveness of electroporation for enhancing the uptake, and consequently, the expression of plasmids encoding antigens and therapeutic proteins in skeletal muscle in various species of mammals, from mice to men. Nevertheless, constant-voltage electroporation techniques do not measure the resistance of the tissue and may cause tissue damage, inflammation and loss of plasmid expression. In the present study, we have analyzed the muscle resistance of various mammalian species (e.g., mice, dogs, rabbits, pigs, horses and non-human primates) using a software-driven constant-current electroporator that can measure the tissue impedance before and during each electroporation pulse (over 100 measurements in a typical 52msec pulse). Also, voltage and amperage during pulses were automatically recorded and analyzed. Optimal conditions of electroporation were found to be highly dependent on the individual tissue resistance, even when the same muscle is targeted in the different species. For example, 6-week-old pigs had higher muscle resistance measured in the semimembranosus muscle (Pulse 1: 196.8±2.4 Ω, Pulse 2: 203.9±0.7 Ω, Pulse 3: 224.6±1.0 Ω with Pulse 3 versus Pulse 2: p<0.02, Pulse 1 versus Pulse 3: p<0.001) compared to 1-year-old pigs (Pulse 1: 165.1±0.4 Ω, P2: 142.8±0.5 Ω, P3: 190.5±1.3 Ω with P1 versus P2: p<0.001, P3 versus P2: p<10-5, and P1 versus P3: p<0.003), but both values were 4 to 5 times lower than the resistance of the mouse muscle (Pulse 1: 1153.9±6.3 Ω, Pulse 2: 1388.1±8.4 Ω, p<0.008). Rabbits had similar resistances to younger pigs but lower than non-human primates. One-year old pigs and horses have comparable muscle resistances, but lower than younger pigs and rabbits. The muscle resistance is also variable in function of the target muscle group and even changes during the electroporation process, with changes in muscle resistance of more than 37% from Pulse 1 to Pulse 3 in non-human primates (33% in 1-year-old pigs, 32% in rabbits, 20% in mice, and 14% in younger pigs). These results indicate that the size of the animal, muscle type and age of the animal, as well as the electroporation sequence impact the electroporation parameters in each species. Thus, muscle resistance will need to be considered for the specific target animals, and accordingly, the electroporation parameters will need to be measured and optimized for each separate species in order to achieve maximum plasmid expression in skeletal muscle.
Human and animal health agencies must cooperate to prevent spread of infections
Authors: R. Dobson
Journal: BMJ (2008)

Agencies that deal with human and animal health worldwide need to cooperate more, says a new parliamentary report, which warns that three quarters of newly emerging infections in humans come from animals.

It also wants the UK government to press for better surveillance of threats around the world that involve animal diseases, with a reporting system similar to that for monitoring diseases in humans.

The report says that with a new and potentially deadly infectious disease emerging somewhere in the world every year, more investment in international surveillance is vital if pandemics are to be avoided.

The report, from the House …
Sequestration of p27Kip1 protein by cyclin D1 in typical and blastic variants of mantle cell lymphoma (MCL): implications for pathogenesis
Authors: Leticia Quintanilla-Martinez, Theresa Davies-Hill, Falko Fend, Julia Calzada-Wack, Lynn Sorbara, Elias Campo, Elaine S. Jaffe, Mark Raffeld
Journal: Blood (2003)
Editorial: Lipid Kinases and Bone Homeostasis: Lessons Learned From Phosphoinositide 3‐Kinase Isoform–Specific Knockouts
Authors: Junjie Xing, Mary Beth Humphrey
Journal: Arthritis & Rheumatology (2014)

Bone homeostasis is maintained throughout life by coordinated osteocyte regulation of bone resorption by osteoclasts and bone formation by osteoblasts. Many pathologic bone states such as osteoporosis, inflammatory arthritis, and bone metastasis have increased numbers, survival, or function of osteoclasts resulting in enhanced bone resorption outpacing bone formation. Differentiation, survival, recruitment, and resorptive activity of osteoclasts and their precursors are highly regulated by intracellular signals stimulated by soluble mediators, extracellular matrix, and adjacent cells. In this issue of Arthritis & Rheumatology, Gyoőri and colleagues describe a specific role for the enzyme phosphoinositide 3-kinase β (PI3Kβ) in the regulation of osteoclast-mediated bone resorption (1), suggesting that a specific inhibitor of this enzyme isoform may be a novel antiresorptive agent.
Rate-pressure product and myocardial oxygen consumption during surgery for coronary artery bypass.
Authors: P L Wilkinson, J R Moyers, T Ports, K Chatterjee, D Ullyott, W K Hamilton
Journal: Circulation (1979)

Rate-pressure product (RPP) is a sensitive index of myocardial oxygen consumption (mVO2) in awake people. We wished to determine whether this relationship persisted under anesthesia and in the face of concurrent large changes in myocardial contractility and left ventricular filling pressures. In 16 patients scheduled for coronary artery bypass surgery, we inserted coronary sinus and Swan-Ganz catheters, and a central aortic catheter via the brachial artery, before induction of anesthesia with either morphine (2 mg/kg) or halothane, chosen in random order. We measured aortic, pulmonary, and venous pressures, cardiac output, systolic time intervals, and thermodilution coronary sinus flow. We calculated mVO2 as coronary sinus flow times myocardial arteriovenous oxygen content difference. We found significant correlations between mVO2 and heart rate (r = 0.57), systolic blood pressure (r = 0.52), the index delta /delta T (r = 0.53, and RPP (r = 0.78). Multiple regression of RPP and delta P/delta T against mVO2 increased their correlation (r = 0.86), while multiple regression of RPP and pulmonary wedge pressure against mVo2 did not significantly improve the correlation of RPP alone (r = 0.75). We conclude that hemodynamic changes anesthesia and surgery do not decrease the sensitivity of RPP as an index of mVO2.
Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis
Authors: S.R. Feldman, A.B. Gottlieb, M. Bala, Y. Wu, D. Eisenberg, C. Guzzo, S. Li, L.T. Dooley, A. Menter
Journal: British Journal of Dermatology (2008)

Psoriasis affects patients both physically and psychologically.To investigate the effect of comorbidities on health-related quality of life (HRQoL) and to determine whether infliximab improved HRQoL in the presence of these conditions.In this multicentre, double-blind study, 835 patients with moderate-to-severe plaque psoriasis were randomized to receive infliximab 3 or 5 mg kg(-1) or placebo at weeks 0, 2 and 6. Infliximab-treated patients were re-randomized at week 14 to receive the same treatment every 8 weeks or as needed through week 46; placebo patients crossed over to infliximab 5 mg kg(-1) at week 16. Disease severity (Psoriasis Area and Severity Index, PASI) and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health Survey, SF-36) were measured at various time points. The effect of patient comorbidities on baseline HRQoL was assessed using multiple regression models. The impact of key comorbidities on infliximab treatment effect was also assessed.Disease severity (PASI), depression and psoriatic arthritis (PsA) were predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg(-1) significantly improved physical and mental health dimensions of the SF-36 and the DLQI (all P < 0.001). Consistent improvement in HRQoL with infliximab treatment was observed regardless of baseline patient characteristics or comorbidities. Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg kg(-1) administered every 8 weeks.Disease severity, depression and PsA were significant predictors of poor HRQoL. Infliximab significantly improved HRQoL, regardless of these characteristics.
Public health exposes jargon epidemic
Authors: A. Maryon-Davis
Journal: BMJ (2008)

<h3>Abstract</h3> Genome-wide association studies have been useful in identifying common genetic variants related to a variety of complex traits and diseases; however, they are often limited in their ability to inform about underlying biology. Whilst bioinformatics analyses, studies of cells, animal models and applied genetic epidemiology have provided some understanding of genetic associations or causal pathways, there is a need for new genetic studies that elucidate causal relationships and mechanisms in a cost-effective, precise and statistically efficient fashion. We discuss the motivation for and the characteristics of the Recall-by-Genotype (RbG) study design, an approach that enables genotype-directed deep-phenotyping and improvement in drawing causal inferences. Specifically, we present RbG designs using single and multiple variants and discuss the inferential properties, analytical approaches and applications of both. We consider the efficiency of the RbG approach, the likely value of RbG studies for the causal investigation of disease aetiology and the practicalities of incorporating genotypic data into population studies in the context of the RbG study design. Finally, we provide a catalogue of the UK-based resources for such studies, an online tool to aid the design of new RbG studies and discuss future developments of this approach.
A POSTAL SURVEY OF PATIENTS WTTH DERMATITIS HERPETIFORMIS
Authors: EDWARD WYATT, SAM SHUSTER, JANET MARKS
Journal: British Journal of Dermatology (1971)

Summary.— A postal survey of patients with dermatitis herpetiformis (DH) has yielded information about 445 cases. Only just over half of these knew the name of the disease from which they were suffering. Our findings in relation to age and sex distribution of the patients are similar to those previously recorded. Patients may develop the disease at any age, including old age. Remissions are common, although we are unable to calculate the recovery rate. Dapsone is the drug most often used in treatment, and some patients seem to be taking more than they need to control their rash: a plea is made for the use of the minimal effective dose. Only a small percentage of patients are aware that they have small bowel disease, and we interpret this as indicating that small bowel mucosal biopsy is not being done as a routine in patients with DH.
THE ECONOMIC BURDEN OF OSTEOMYELITIS
Authors: CALEB S. STONE
Journal: JAMA (1933)

The suffering, the prolonged hospitalization and the great cost of osteomyelitis are obvious to those who have followed these patients through their hospital courses. There have been no studies that have brought out the marked economic loss entailed by this disease. A survey of the cases of osteomyelitis treated at the University of Virginia Hospital presents such a striking demonstration of this enormous economic burden that a presentation of the figures is thought to be worth while. It is particularly worth while if it can be felt that earlier diagnosis and treatment can help decrease the expense to the patient and to the hospital. The moral of this report will then become obvious. This study is limited to those cases of acute, pyogenic osteomyelitis of hematogenous origin, usually seen in children and most frequently caused by the staphylococcus. Other bone infections, including tuberculosis, traumatic osteitis, and osteitis originating in arthritis,
The Prevalence of Hypertension and Utilization of Antihypertensive Therapy in a District Diabetes Population
Authors: Varadarajan Baskar, Desikan Kamalakannan, Martin R. Holland, Baldev M. Singh
Journal: Diabetes Care (2002)

Hypertension and antihypertensive treatment (AHT) impact on diabetes vascular outcomes and systolic blood pressure (SBP) probably confers a greater risk than diastolic blood pressure (1,2). Recent guidelines promote low intervention thresholds and target blood pressures (<130–140/80–85 mmHg) without considering the impact on clinical service provision (3,4). Using SBP targets, we describe hypertension prevalence, AHT utilization, and efficacy in a large district diabetes population.

We studied 6,485 of 7,123 registered adults (≥18 years) who had complete SBP and AHT data. Only 4,987 (76%) had complete data …