tbuckley/cabot-search huggingface dataset:
Polymorphisms in the tumor necrosis factor alpha (TNF-alpha) gene correlate with murine resistance to development of toxoplasmic encephalitis and with levels of TNF-alpha mRNA in infected brain tissue.
Authors: Y R Freund, G Sgarlato, C O Jacob, Y Suzuki, J S Remington
Journal: The Journal of Experimental Medicine (1992)

Murine resistance to development of toxoplasmic encephalitis (TE) has recently been mapped to the D region of the major histocompatibility complex (H-2). Since the gene for tumor necrosis factor alpha (TNF-alpha) is located 5' of the D region and TNF-alpha has been implicated as playing a role in neurological diseases, we were interested in determining the relationship of TNF-alpha production to TE resistance. We have demonstrated that resistance to TE in inbred mice can be correlated with specific restriction fragment length polymorphisms and microsatellite variants in the TNF-alpha gene. Mice that are susceptible to TE express elevated levels of TNF-alpha mRNA in brain tissue 6 wk after infection with the ME49 strain of Toxoplasma gondii. Resistant mice and all mice that are uninfected show no detectable TNF-alpha mRNA expression in brain tissue. Differences in the TNF-alpha gene between susceptible and resistant mice have been localized to the first intron, the promoter, and the 3' end of the TNF-alpha gene. These data implicate differences in regulation of TNF-alpha production in brain tissue as contributing to differences in susceptibility to development of TE.
Ontogenesis of the Renin-Angiotensin System in Spontaneously Hypertensive and Normal Wistar Rats
Authors: ALAN SINAIKO, BERNARD L. MIRKIN
Journal: Circulation Research (1974)

Kidney renin activity was investigated in spontaneously hypertensive and normotensive control Wistar rats. Kidneys were obtained from fetal rats after 18 and 21 days of gestation and from neonatal rats 1, 7, 14, and 21 days old. Kidney renin activity was determined by a modification of the radioimmunoassay for angiotensin I developed in this laboratory, and tissue from each age group was stained for juxtaglomerular granules. Kidney renin activity progressively increased in both strains from day 18 of fetal life until day 1 of neonatal life when a plateau level developed. In 1-day-old neonatal rats, significant differences in the kidney renin activity of the spontaneously hypertensive and the normotensive strains were initially noted. Kidney renin activity was maintained at significantly higher levels in the spontaneously hypertensive strain under 21 days of age when, because of a rise in the kidney renin activity of the normotensive control strain and a fall in the kidney renin activity of the spontaneously hypertensive strain, the difference between the two strains became statistically insignificant. In both strains, juxtaglomerular granules were first noted in 1-day-old neonatal rats and in each age group thereafter.
Tumor-Suppressive Effect of <i>Retinoid Receptor–Induced Gene-1</i> (<i>RRIG1</i>) in Esophageal Cancer
Authors: Jie Huang, Zheng D. Liang, Tsung-Teh Wu, Ashraful Hoque, Hongli Chen, Yan Jiang, Hongfu Zhang, Xiao-chun Xu
Journal: Cancer Research (2007)

Abstract We previously showed that induction of retinoid receptor–induced gene-1 (RRIG1) expression inhibited RhoA activation and tumor cell colony formation, invasion, and proliferation, and these effects are associated with the suppression of extracellular signal-regulated protein kinases 1 and 2 phosphorylation and cyclooxygenase-2 expression. To further elucidate its role in tumor cell growth, gene expression, and tumorigenesis, we determined RRIG1 expression in breast and esophageal tissue specimens and then stably transfected RRIG1 into a TE-8 esophageal squamous cell carcinoma (SCC) cell line. We found that RRIG1 was expressed in normal mammary glands (10 of 10) but not all ductal carcinoma in situ [11 of 19 (57.9%), P = 0.018] and invasive cancer [14 of 30 (46.7%), P = 0.0023] tissues. Similarly, RRIG1 was expressed in normal esophageal epithelium (22 of 22) but not all dysplastic [6 of 43 (14%), P = 0.0001] and SCC [50 of 122 (41%), P = 0.0001] tissues. Furthermore, RRIG1 expression correlated positively with tumor differentiation but inversely with lymph node metastasis of esophageal SCC. Finally, the stable transfection of RRIG1 inhibited esophageal SCC cell growth and the expression of extracellular signal-regulated protein kinases 1 and 2 and cell cycle–related genes (e.g., cyclin D1, phosphorylated Rb, and E2F). RRIG1-transfected sublines also inhibited tumor development in nude mice. The results of this study indicate that RRIG1 plays a role in suppressing tumorigenesis. [Cancer Res 2007;67(4):1589–93]
The Effect of Incentive Spirometry on Postoperative Pulmonary Function Following Laparotomy
Authors: Anna F. Tyson, Claire E. Kendig, Charles Mabedi, Bruce A. Cairns, Anthony G. Charles
Journal: JAMA Surgery (2015)

Changes in pulmonary dynamics following laparotomy are well documented. Deep breathing exercises, with or without incentive spirometry, may help counteract postoperative decreased vital capacity; however, the evidence for the role of incentive spirometry in the prevention of postoperative atelectasis is inconclusive. Furthermore, data are scarce regarding the prevention of postoperative atelectasis in sub-Saharan Africa.To determine the effect of the use of incentive spirometry on pulmonary function following exploratory laparotomy as measured by forced vital capacity (FVC).This was a single-center, randomized clinical trial performed at Kamuzu Central Hospital, Lilongwe, Malawi. Study participants were adult patients who underwent exploratory laparotomy and were randomized into the intervention or control groups (standard of care) from February 1 to November 30, 2013. All patients received routine postoperative care, including instructions for deep breathing and early ambulation. We used bivariate analysis to compare outcomes between the intervention and control groups.Adult patients who underwent exploratory laparotomy participated in postoperative deep breathing exercises. Patients in the intervention group received incentive spirometers.We assessed pulmonary function using a peak flow meter to measure FVC in both groups of patients. Secondary outcomes, such as hospital length of stay and mortality, were obtained from the medical records.A total of 150 patients were randomized (75 in each arm). The median age in the intervention and control groups was 35 years (interquartile range, 28-53 years) and 33 years (interquartile range, 23-46 years), respectively. Men predominated in both groups, and most patients underwent emergency procedures (78.7% in the intervention group and 84.0% in the control group). Mean initial FVC did not differ significantly between the intervention and control groups (0.92 and 0.90 L, respectively; P=.82 [95% CI, 0.52-2.29]). Although patients in the intervention group tended to have higher final FVC measurements, the change between the first and last measured FVC was not statistically significant (0.29 and 0.25 L, respectively; P=.68 [95% CI, 0.65-1.95]). Likewise, hospital length of stay did not differ significantly between groups. Overall postoperative mortality was 6.0%, with a higher mortality rate in the control group compared with the intervention group (10.7% and 1.3%, respectively; P=.02 [95% CI, 0.01-0.92]).Education and provision of incentive spirometry for unmonitored patient use does not result in statistically significant improvement in pulmonary dynamics following laparotomy. We would not recommend the addition of incentive spirometry to the current standard of care in this resource-constrained environment.clinicaltrials.gov Identifier: NCT01789177.
Lymphocyte culture: induction of colonies by conditioned medium from human lymphoid cell lines.
Authors: R M Galbraith, J M Goust, H H Fudenberg
Journal: The Journal of Experimental Medicine (1977)

The presence of phytohemagglutinin or pokeweed mitogen in cultures of human peripheral blood mononuclear cells in agar is known to stimulate the formation of lymphoid colonies. We now report that similar colonies can be induced in the absence of plant lectins upon addition of filtered and ultracentrifuged conditioned medium (CM) obtained from certain human lymphoblastoid cell lines. Colony formation required at least 6 X 10(5) mononuclear cells per milliliter, and optimum results were obtained at concentrations of 1 X 10(6) cells/ml in the presence of 20% CM (50-500 colonies per 10(6) cells cultured). Individual cells within colonies displayed uniform morphological characteristics of lymphoid cells, and the majority formed rosettes with sheep erythrocytes, suggesting that they were of T-cell type.
Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors
Authors: M.G. Kris, D.R. Camidge, G. Giaccone, T. Hida, B.T. Li, J. O'Connell, I. Taylor, H. Zhang, M.E. Arcila, Z. Goldberg, P.A. Jänne
Journal: Annals of Oncology (2015)
Genomic mapping of the MHC transactivator CIITA using an integrated ChIP-seq and genetical genomics approach
Authors: Daniel Wong, Wanseon Lee, Peter Humburg, Seiko Makino, Evelyn Lau, Vivek Naranbhai, Benjamin P Fairfax, Kenneth Chan, Katharine Plant, Julian C Knight
Journal: Genome biology (2014)

The master transactivator CIITA is essential to the regulation of Major Histocompatibility Complex (MHC) class II genes and an effective immune response. CIITA is known to modulate a small number of non-MHC genes involved in antigen presentation such as CD74 and B2M but its broader genome-wide function and relationship with underlying genetic diversity has not been resolved. We report the first genome-wide ChIP-seq map for CIITA and complement this by mapping inter-individual variation in CIITA expression as a quantitative trait. We analyse CIITA recruitment for pathophysiologically relevant primary human B cells and monocytes, resting and treated with interferon-gamma, in the context of the epigenomic regulatory landscape and DNA-binding proteins associated with the CIITA enhanceosome including RFX, CREB1/ATF1 and NFY. We confirm recruitment to proximal promoter sequences in MHC class II genes and more distally involving the canonical CIITA enhanceosome. Overall, we map 843 CIITA binding intervals involving 442 genes and find 95% of intervals are located outside the MHC and 60% not associated with RFX5 binding. Binding intervals are enriched for genes involved in immune function and infectious disease with novel loci including major histone gene clusters. We resolve differentially expressed genes associated in trans with a CIITA intronic sequence variant, integrate with CIITA recruitment and show how this is mediated by allele-specific recruitment of NF-kB. Our results indicate a broader role for CIITA beyond the MHC involving immune-related genes. We provide new insights into allele-specific regulation of CIITA informative for understanding gene function and disease.
Selective Activation of A <sub>3</sub> Adenosine Receptors With <i>N</i> <sup>6</sup> -(3-Iodobenzyl)Adenosine-5′- <i>N</i> -Methyluronamide Protects Against Myocardial Stunning and Infarction Without Hemodynamic Changes in Conscious Rabbits
Authors: John A. Auchampach, Ali Rizvi, Yumin Qiu, Xian-Liang Tang, Claudio Maldonado, Steffi Teschner, Roberto Bolli
Journal: Circulation Research (1997)

Abstract To examine the cardioprotective role of A 3 adenosine receptors during myocardial ischemia/reperfusion injury, we tested the effect of N 6 -(3-iodobenzyl)adenosine-5′- N -methyluronamide (IB-MECA), a potent and selective A 3 adenosine receptor agonist, in models of myocardial stunning and infarction in chronically instrumented conscious rabbits. In phase I (studies of myocardial stunning), rabbits were subjected to six 4-minute coronary occlusions, each separated by 4-minute reperfusion periods, after which the recovery of systolic wall thickening was measured (ultrasonic crystals). In phase II (studies of myocardial infarction), rabbits were subjected to a 30-minute coronary occlusion followed by 3 days of reperfusion. In both phases, IB-MECA was administered as an intravenous bolus (100 μg/kg) 10 minutes before the first coronary occlusion. This dose of IB-MECA was determined in pilot studies to have no effect on heart rate, arterial blood pressure, or plasma histamine concentration in rabbits. In phase I, IB-MECA markedly improved the recovery of wall thickening after the six occlusion/reperfusion cycles, and this effect was sustained throughout the 5-hour observation period; the total deficit of wall thickening (a measure of the overall severity of myocardial stunning) was reduced by 68% (control, 129±16 arbitrary units, n=7; IB-MECA, 41±6 arbitrary units, n=6; P &lt;.01). The protective effects of IB-MECA against stunning were completely blocked by pretreatment with the nonselective adenosine receptor antagonist 8- p -sulfophenyl theophylline or the specific protein kinase C inhibitor chelerythrine. In phase II, IB-MECA reduced myocardial infarct size by 61%; infarct size (tetrazolium staining) was 41±4% of the risk region in control animals (n=8) and 16±6% in IB-MECA–treated animals (n=8, P &lt;.01). These results demonstrate that in conscious rabbits the A 3 adenosine receptor agonist IB-MECA confers a powerful protection against both reversible (stunning) and irreversible (infarction) injury during acute myocardial ischemia and reperfusion by a protein kinase C–mediated pathway, suggesting that selective activation of A 3 receptors is an effective means of protecting the ischemic myocardium without hemodynamic changes.
Prevalence of Major Depressive Episode in Two American Indian Reservation Populations: Unexpected Findings With a Structured Interview
Authors: Janette Beals, Spero M Manson, Nancy R Whitesell, Christina M Mitchell, Douglas K Novins, Sylvia Simpson, Paul Spicer
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: American Indian populations have often been considered to be at greater risk for major depressive episode than are other groups in the United States. The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP), completed between 1997 and 1999, was designed to allow comparisons with the baseline National Comorbidity Survey (NCS), conducted in 1990–1992. The prevalence of lifetime and 12-month DSM-III-R major depressive episode was compared between the AI-SUPERPFP and NCS samples. METHOD: A total of 3,084 tribal members (1,446 in a Southwest tribe [73.7% of eligible participants] and 1,638 in a Northern Plains tribe [76.8% of eligible participants]) age 15–54 years living on or near their home reservations were interviewed. An adaptation of the University of Michigan Composite International Diagnostic Interview and the NCS algorithm for diagnosis were used to estimate the prevalence of lifetime and 12-month major depressive episode in these groups. RESULTS: The prevalence estimates for lifetime and 12-month major depressive episode were substantially lower in the American Indian samples, compared to the NCS sample. Detailed analyses indicated differential endorsement of lifetime symptoms between the American Indian groups and the NCS participants. Furthermore, American Indians were substantially less likely than NCS participants to indicate that depressive symptoms had co-occurred during an episode lasting at least 2 weeks. The lifetime prevalence estimates based on the NCS algorithm ranged from 3.8% to 7.9% for men and women in the two tribes. The analogous rates based on an adapted AI-SUPERPFP algorithm ranged from 7.2% and 14.3%. Few tribe, age, and gender differences were found. CONCLUSIONS: The findings underscore the need for careful examination of diagnostic instruments cross-culturally. Adaptation of the NCS algorithm for diagnosis appears necessary for estimation of the prevalence of major depressive episode in the American Indian populations included in this study. In striving to better reflect the clinical diagnostic process in epidemiological and services research, careful consideration of the resulting complexity becomes increasingly critical.
Medical manpower and the hospital service
Authors: A J M Cavenagh
Journal: BMJ (1976)

Incomes: vive la difference SIR,-Mr Rudolf Klein (10 July, p 126) is right.There can never be a fixed rule that previous differentials between the medical professions and other workers should always be rightly maintained-of course times change.However, to round it off he should also have said that there is no rule that the medical profession's training and expertise, sense of responsibility, and willingness to do unpaid overtime should continue without a change.These two aspects, differentials and pro- fessional standards,
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial
Authors: S Connolly, J Pogue, R Hart, M Pfeffer, S Hohnloser, S Chrolavicius, M Pfeffer, S Hohnloser, S Yusuf
Journal: The Lancet (2006)
Confirmed cancer trends in families of patients with multiple cancers including cutaneous melanoma
Authors: K. Nielsen, A. Masback, A. Bladstrom, L. Lundgren, N. Jonsson, A. Borg, C. Ingvar, H. Olsson
Journal: British Journal of Dermatology (2007)

Journal Article Confirmed cancer trends in families of patients with multiple cancers including cutaneous melanoma Get access K. Nielsen, K. Nielsen Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar A. Masback, A. Masback Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar A. Bladstrom, A. Bladstrom Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar L. Lundgren, L. Lundgren Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar N. Jonsson, N. Jonsson Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar A. Borg, A. Borg Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar C. Ingvar, C. Ingvar Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar H. Olsson H. Olsson Sections of Dermatology, *Pathology, †Oncology and Cancer Epidemiology, and ‡Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden E‐mail: kari.nielsen@med.lu.se Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 2, 1 February 2008, Pages 429–431, https://doi.org/10.1111/j.1365-2133.2007.08328.x Published: 01 February 2008
The Attitudes of Patients and Their Trainee Therapists Toward Participation in Psychiatric Board Examinations
Authors: HERBERT H. EVELOFF, CHARLES P. McCREARY
Journal: American Journal of Psychiatry (1972)

The authors examined the attitudes of patients and of trainee therapists toward the participation of patients in an examination of the American Board of Psychiatry and Neurology. Neither the therapists nor the patients reported any serious untoward consequences. The patients reported a slightly positive effect and the therapists a slightly negative one, although neither trend reached statistical significance.
Is There a Fatty Acid Taste?
Authors: Richard D. Mattes
Journal: Annual Review of Nutrition (2009)

Taste is a chemical sense that aids in the detection of nutrients and guides food choice. A limited number of primary qualities comprise taste. Accumulating evidence has raised a question about whether fat should be among them. Most evidence indicates triacylglycerol is not an effective taste stimulus, though it clearly contributes sensory properties to foods by carrying flavor compounds and altering texture. However, there is increasing anatomical, electrophysiological, animal behavior, imaging, metabolic, and psychophysical evidence that free fatty acids are detectable when non-taste cues are minimized. Free fatty acids varying in saturation and chain length are detectable, suggesting the presence of multiple transduction mechanisms and/or a nonspecific mechanism in the oral cavity. However, confirmation of "fatty" as a taste primary will require additional studies that verify these observations are taste specific. Oral exposure to free fatty acids likely serves as a warning signal to discourage intake and influences lipid metabolism.
Analysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study
Authors: Asher Chanan-Khan, Pieter Sonneveld, Michael W. Schuster, Edward A. Stadtmauer, Thierry Facon, Jean-Luc Harousseau, Dina Ben-Yehuda, Sagar Lonial, Hartmut Goldschmidt, Donna Reece, Rachel Neuwirth, Kenneth C. Anderson, Paul G. Richardson
Journal: Journal of Clinical Oncology (2008)

The aim of this subset analysis was to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus (VZV) reactivation in patients with relapsed multiple myeloma (MM).Incidence of herpes zoster was evaluated in 663 patients with relapsed MM from the phase III APEX trial comparing single-agent bortezomib with high-dose dexamethasone.Bortezomib was associated with a significantly higher incidence of herpes zoster compared with dexamethasone treatment (13%, 42 of 331 v 5%, 15 of 332; P = .0002). Most herpes zoster infections were grade 1/2; incidences of grade 3/4 events (1.8% v 1.5%) and infections considered serious adverse events (1.5% v 0.9%) were similar between treatment arms, and no herpes zoster-related deaths occurred. Neither the time to onset of the herpes event nor the patients' absolute lymphocyte counts at baseline differed significantly between arms. VZV reactivation was the only herpes viral event noted to be significantly elevated in the bortezomib treatment group compared with the dexamethasone treatment group (P = .0002). The incidence of non-VZV-related herpes viral infections was comparable between arms. No additional risk factors for herpes zoster reactivation were identified.Further studies are needed to explain these observations and their implications; however, for patients treated with bortezomib or bortezomib-containing regimens, the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis considered.