tbuckley/cabot-search huggingface dataset:
Carcinoembryonic Antigen–Related Cell Adhesion Molecule 1a-4L Suppression of Rat Hepatocellular Carcinomas
Authors: Nikia A. Laurie, Meghan M. Comegys, Marie P. Carreiro, Jeanne F. Brown, Donna L. Flanagan, Kate E. Brilliant, Douglas C. Hixson
Journal: Cancer Research (2005)

Carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) is a member of the CEA family of immunoglobulin-like adhesion molecules with two major splice variants, CEACAM1(a)-4L and CEACAM1(b)-4S, differing in the length of their COOH-terminal cytoplasmic tail. Both forms are down-regulated in prostate and liver carcinomas relative to normal tissues. We have previously shown in a nude mouse xenograft model that restoration of CEACAM1(a)-4L expression in human prostate carcinoma cells (PC-3) suppresses tumorigenicity, an effect observed with carcinomas from several other tissues but never established for hepatocellular carcinomas. In this report, we have examined the effect of CEACAM1(a)-4L on tumorigenicity of 1682A, a rat hepatocellular carcinoma that grows on the omentum when injected into the peritoneal cavity. Results show that restoration of CEACAM1(a)-4L expression at levels 13- and 0.45-fold compared with negative controls or normal hepatocytes, respectively, completely suppressed the formation of 1682A tumor nodules on the omentum at 3 weeks after injection. In contrast, 1682A cells infected with CEACAM1(b)-4S or an empty retroviral vector formed multiple clusters of tumor nodules. Although tumor nodules of 1682A cells positive and negative for CEACAM1(a)-4L did not display significant differences in histologic organization, aggregates formed in vitro by 1682A-L were smaller in size and displayed enlarged intercellular spaces relative to their 1682A-V counterparts. Restoration of CEACAM1(a)-4L expression did not elevate levels of apoptosis but seemed to cause an increase in the length of G1. This is the first demonstration of CEACAM1(a)-4L-induced tumor suppression in liver carcinomas using a quantifiable i.p. syngeneic transplantation model.
DENGUE IN THE ISTHMIAN CANAL ZONE.A PRELIMINARY REPORT.
Authors: RICHARD LIGHTBURN SUTTON
Journal: JAMA (1904)

To the average North American physician, unless he be located in Mexico or in one of the extreme southern states, "breakbone fever" is so rare a disease that a case of it would probably pass unrecognized. The practitioner in the tropics, however, usually receives an early introduction to the affection and the acquaintance becomes in time an intimate one. Persons who have previously resided in a cold or temperate climate appear to be especially susceptible to the infection, and it is for this reason that it is so prevalent among fresh drafts of men sent into warmer climates for duty. It is not my intention to take up a general discussion of the disease here, such information being readily obtainable from any standard work on tropical medicine. The type usually encountered in Central America, however, I am informed by competent authorities, differs so much from
A Prospective Evaluation of X-ray Pelvimetry
Authors: Douglas W. Laube
Journal: JAMA (1981)

One hundred four consecutive patients undergoing x-ray pelvimetry were analyzed prospectively in an attempt to evaluate the efficacy of this procedure. Comparison was made between prepelvimetry and post-pelvimetry clinical management plans. Roentgenographic pelvic measurements led to prompt and significant alterations in clinical management plans in only one of 67 patients with vertex presentation and one of 37 with breech presentation. In 98% of patients, no change in immediate clinical management plan was made on the basis of x-ray pelvimetry findings.
Dexamethasone Prevents Podocyte Apoptosis Induced by Puromycin Aminonucleoside
Authors: Takehiko Wada, Jeffrey W. Pippin, Caroline B. Marshall, Sian V. Griffin, Stuart J. Shankland
Journal: Journal of the American Society of Nephrology (2005)

Nephrotic-range proteinuria is due to glomerular diseases characterized by podocyte injury. Glucocorticoids are the standard of care for most forms of nephrotic syndrome. However, the precise mechanisms underlying the beneficial effects of glucocorticoids on podocytes, beyond its general immunosuppressive and anti-inflammatory effects, are still unknown. This study tested the hypothesis that the synthetic glucocorticoid dexamethasone directly reduces podocyte apoptosis. Growth-restricted immortalized mouse podocytes in culture were exposed to puromycin aminonucleoside (PA) to induce apoptosis. Our results showed that dexamethasone significantly reduced PA-induced apoptosis by 2.81-fold. Dexamethasone also rescued podocyte viability when exposed to PA. PA-induced apoptosis was associated with increased p53 expression, which was completely blocked by dexamethasone. Furthermore, the inhibition of p53 by the p53 inhibitor pifithrin-α protected against PA-induced apoptosis. Dexamethasone also lowered the increase in the proapoptotic Bax, which was increased by PA, and increased expression of the antiapoptotic Bcl-xL protein. Moreover, the decrease in p53 by dexamethasone was associated with increased Bcl-xL levels. Podocyte apoptosis induced by PA was caspase-3 independent but was associated with the translocation of apoptosis-inducing factor (AIF) from the cytoplasm to nuclei. AIF translocation was inhibited by dexamethasone. These results show that PA-induced podocyte apoptosis is p53 dependent and associated with changes in Bcl-2–related proteins and AIF translocation. The protective effects of dexamethasone on PA-induced apoptosis were associated with decreasing p53, increasing Bcl-xL, and inhibition of AIF translocation. These novel findings provide new insights into the beneficial effects of corticosteroids on podocytes directly, independent of its immunosuppressive effects.
Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor
Authors: Vera Jankowski, Markus Tölle, Raymond Vanholder, Gilbert Schönfelder, Markus van der Giet, Lars Henning, Hartmut Schlüter, Martin Paul, Walter Zidek, Joachim Jankowski
Journal: Nature Medicine (2005)
Abstract IA13: Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: James L. Gulley, Ravi A. Madan, Kwong Y. Tsang, Caroline Jochems, William L. Dahut, Jeffrey Schlom
Journal: Cancer Research (2013)

Abstract Background: Immunotherapy is an emerging therapeutic option for mCRPC and has demonstrated improved survival. Immunologic combinations are a logical next step in the clinical development. PSA-TRICOM V, composed of poxviral vectors encoding PSA and 3 costimulatory molecules (ICAM-I, LFA-3, and B7.1), has shown evidence of clinical activity in mCRPC and is being tested in a phase III study (NCT01322490). Ipi, which blocks CTLA-4, a T-cell coinhibitory receptor, has clinical activity in mCRPC as monotherapy and has also been shown to enhance antitumor responses in combination with V in preclinical studies. Methods: We completed a phase I dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipi in combination with a fixed dose of PSA-TRICOM V. Pts with mCRPC received vaccinia PSA-TRICOM subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of fowlpox PSA-TRICOM starting on day 15. Intravenous ipi was given monthly x 6 starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. Results: We completed enrollment with 30 pts (24 of whom were chemotherapy-naïve) and did not identify any dose-limiting toxicity. 21 pts had grade ≥ 2 immune-related adverse events, including diarrhea or colitis, rash, raised aminotransferases, endocrinopathy, and neutropenia. Only 1 of the 6 pts previously treated with chemotherapy had a PSA decline from baseline. Of the 24 pts who were chemotherapy-naïve, 14 (58%) had PSA declines from baseline, of which 6 were &amp;gt; 50%. While the median predicted survival was about 18 months, based on a validated nomogram, actual median OS exceeded 34 months in this phase I study. A previous 32 pt study at the same institution of V alone in the same population (predicted survival 17.4 months) had an OS of 26.6 months. Conclusions: The use of a V targeting PSA that also enhances costimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipi. There is a suggestion of clinical activity for the combination; however, randomized trials are needed to further assess clinical outcomes of the combination of ipi and V in mCRPC. ClinicalTrials.gov registry number: NCT00113984 Ref: Madan et al., Lancet Oncology 2012. Citation Format: James L. Gulley, Ravi A. Madan, Kwong Y. Tsang, Caroline Jochems, William L. Dahut, Jeffrey Schlom. Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA13.
Assessment of Permanent Dual-Chamber Pacing as a Treatment for Drug-Refractory Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, Rick A. Nishimura, William J. McKenna, Harry Rakowski, Mark E. Josephson, Robert S. Kieval
Journal: Circulation (1999)

Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies.This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with >/=50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline (P<0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82+/-32 mm Hg to 48+/-32 mm Hg (P<0. 001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22+/-5 mm) and 12 months (21+/-5 mm; P=NS).(1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) >/= 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients.
QRS DURATION ON ELECTROCARDIOGRAPHY AND CARDIOVASCULAR MORTALITY: INSIGHTS FROM NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY-III
Authors: Vikas Singh, Nileshkumar Patel, Neeraj Shah, Ghanshyambhai Savani, Ankit Chothani, Kathan Mehta, Ankit Rathod, Abhishek Deshmukh, George Marzouka, Apurva Badheka, Raul Mitrani, Mauro Moscucci, Mauricio Cohen
Journal: Journal of the American College of Cardiology (2013)
Diabetes and Deafness
Authors: Roger G. Whittaker, Andrew M. Schaefer, Robert McFarland, Robert W. Taylor, Mark Walker, Douglass M. Turnbull
Journal: Diabetes Care (2007)

The m.3243A>G mitochondrial DNA mutation is well known to be associated with deafness and diabetes, and patients presenting with these clinical features are routinely screened for this mutation. We wanted to assess whether this is a suitable screening strategy. We retrospectively reviewed the clinical notes of 242 patients who had attended a special mitochondrial clinic in the preceding 25-year period. Of the total 29 patients with mitochondrial disease presenting with deafness and diabetes, only 21 would have been correctly diagnosed by screening for the m.3243A>G mutation in blood or urine. Of the remaining eight patients, only six had other features suggestive of mitochondrial disease. We recommend that all patients with the combination of deafness and diabetes presenting to diabetes clinics be screened for the m.3243A>G mutation. In those patients in whom this test is negative, we recommend referral to a specialist neuromuscular clinic for further investigation.

The association between maternally inherited diabetes and deafness and mitochondrial DNA (mtDNA) mutations is well recognized (1,2). Several mutations have been associated with this phenotype, including the m.3243A>G (3) and …
γ-H2AX+CD8+ T lymphocytes cannot respond to IFN-α, IL-2 or IL-6 in chronic hepatitis C virus infection
Authors: Matthew Hoare, Arun Shankar, Meera Shah, Simon Rushbrook, William Gelson, Susan Davies, Arne Akbar, Graeme J.M. Alexander
Journal: Journal of Hepatology (2012)

Age is the dominant prognostic factor influencing the natural history of hepatitis C virus (HCV) infection and treatment response. Accelerated lymphocyte telomere shortening in HCV infection correlates with adverse clinical outcomes. Critical telomere shortening generates double-stranded DNA breaks (DSB) inducing the DNA damage response, leading to replicative senescence. The phenotype and function of CD8+ T lymphocytes and the in vitro response to IFN-α in relation to the DNA damage response were investigated in patients with chronic HCV infection.CD8+ T lymphocytes with DSB were identified by expression of γ-H2AX (Ser-139) in 134 HCV-exposed subjects and 27 controls. Telomere length was determined by flow-FISH; cytokine expression by intracellular cytokine staining; in vitro responses to IFN-α, IL-2 or IL-6 by phospho-STAT1 (Y701) or phospho-STAT5 (Y694) expression.The proportion of circulating CD8+γ-H2AX+ T lymphocytes rose with increasing fibrosis stage (p=0.0023). CD8+γ-H2AX+ T lymphocytes were enriched in liver compared to blood (p=0.03). CD8+γ-H2AX+ T lymphocytes demonstrated increased IFN-γ (p=0.02) and reduced IL-2 expression (p=0.02). CD8+γ-H2AX+ T lymphocytes failed to phosphorylate STAT1 in response to IFN-α compared to unfractionated CD8+ T lymphocytes (p <0.0001). More widespread failure of Jak/Stat signalling in CD8+γ-H2AX+ T lymphocytes was suggested by impaired phosphorylation of STAT1 with IL-6 (p=0.002) and STAT5 with IL-2 (p=0.0039) compared to unfractionated CD8+ T-lymphocytes.In chronic HCV infection, CD8+γ-H2AX+ T lymphocytes are highly differentiated with shortened telomeres, are more frequent within the liver, are associated with severe fibrosis and fail to activate Jak/Stat pathways in response to IFN-α, IL-2 or IL-6, perhaps explaining treatment failure in those with severe fibrosis.
Increased connexin43 gap junction protein in hamster cardiomyocytes during cold acclimatization and hibernation
Authors: P Saitongdee
Journal: Cardiovascular Research (2000)

Objective: The physiology of hibernation is characterized by dramatic reductions of heart rate, respiration, metabolism, blood pressure and body temperature and by resistance to ventricular fibrillation. Gap junctions in the heart provide low resistance pathways, facilitating electrical and metabolic coupling between cardiac muscle cells for coordinated action of the heart and tissue homeostasis. The conductance of these junctions, and therefore their function, is likely to be affected by the physiological changes that take place during hibernation. Our objective was to quantitate gap junction protein levels in cold acclimatization, hibernation and arousal. Methods: We have used specific antibodies to connexins 43 and 40, in combination with confocal microscopy, to quantitatively analyze the expression of connexin protein in hamster (Mesocricetus auratus) left ventricles in four animal groups: normal controls at euthermy, cold controls (cold-exposed animals that did not undergo hibernation), hibernating animals and animals aroused from hibernation for 2 h. Results: Connexin40 immunostaining was not detected in ventricular cardiomyocytes in any animal group but connexin43 was found in all groups. Connexin43 expression was significantly enhanced in hibernation and cold control ventricular cardiomyocytes. Total plaque area, numerical density and plaque size were higher in the cold controls and hibernating hamsters compared to normal controls and animals aroused from hibernation. Conclusion: It is possible that the increased size and number of connexin43 gap junction plaques in the cold controls may represent a compensatory response in order to maintain sufficient gap junction communication during physiological conditions that would reduce conductance. These changes may represent a mechanism by which the hamster avoids ventricular fibrillation during hibernation and arousal.
To be or not to be NKT: Natural killer T cells in the liver
Authors: Mark A. Exley, Margaret James Koziel
Journal: Hepatology (2004)

Much of the hepatology literature to date has focused on the adaptive, antigen-specific response mediated by classical T-cell populations in both the protection and pathogenesis of liver disease. However, the liver is selectively enriched for cells representative of innate immunity, including natural killer T (NKT) cells. In particular, certain CD1d-reactive T cells are present at much higher frequencies in the liver than in the peripheral blood. Although these cells have previously been defined mostly on the basis of phenotypic markers, recent emerging literature regarding NKT cell populations has revealed considerable functional complexity. This review summarizes the recent literature regarding NKT cells, which may have important roles in a variety of liver diseases. Although there is an abundance of literature on the phenotype, distribution, and function of these cells in mice, much less is known about them in human health or liver diseases. (Hepatology 2004;40:1033-1040.)
Pneumocystis carinii pneumonia complicating low dose methotrexate treatment for rheumatoid arthritis.
Authors: A Wollner, J Mohle-Boetani, R E Lambert, J L Perruquet, T A Raffin, J L McGuire
Journal: Thorax (1991)

Low dose methotrexate has been used effectively for various rheumatic and non-rheumatic diseases. Three cases of Pneumocystis carinii pneumonia occurring during treatment of rheumatoid arthritis with low dose methotrexate are presented. Several mechanisms might contribute to impaired immunity and the rare development of opportunist lung infection with methotrexate. A high degree of suspicion may result in earlier diagnosis and treatment.
Healthcare.gov 3.0 — Behavioral Economics and Insurance Exchanges
Authors: Peter A. Ubel, David A. Comerford, Eric Johnson
Journal: New England Journal of Medicine (2015)

Interview with Dr. Peter Ubel on the influence of insurance-exchange website design on consumers' choices. (08:45)Download Now that glitch-free U.S. health insurance exchanges are presenting consumers with robust sets of health insurance choices, it's time to redesign exchange websites so as to maximize the chances that consumers will choose plans best suited to their needs and preferences.
Colonic myoelectrical activity in man: comparison of recording techniques and methods of analysis.
Authors: C J Stoddard, H L Duthie, R H Smallwood, D A Linkens
Journal: Gut (1979)

Both monopolar and bipolar recordings of human colonic myoelectrical activity have been made on 29 occasions from implanted serosal electrodes attached to either the ascending colon or transverse colon. Visual and computer analysis of the signals were made and the incidences of the two electrical rhythms present in the colon were compared for the two recording techniques, recording sites, and methods of analysis. The percentage incidence of both rhythms was similar for the mono and bipolar recording techniques in both parts of the colon. The incidence of the two rhythms in the transverse colon was approximately twice that recorded in the ascending colon, this being true for both recording techniques and methods of analysis, but neither was detected for more than 50% of the time. It is concluded that the methods of data analysis probably account for the differing incidences of electrical activity in the human colon that have been reported previously.
Parametric survival models may be more accurate than Kaplan-Meier estimates
Authors: M. May
Journal: BMJ (2003)

EDITOR—Lundin et al use Kaplan-Meier estimates of survival probabilities in their system for survival estimation in breast cancer (Finprog study, http://finprog.primed.info).1 They claim that researchers can obtain survival estimates based on actual data, rather than inferential estimates generated by a regression formula. However, any regression formula is based on actual data. More importantly, survival estimates from a regression model may be substantially more precise than Kaplan-Meier estimates …
Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer
Authors: Jih-Hsiang Lee, Elisa Giovannetti, Jin-Hyeok Hwang, Iacopo Petrini, Qiuyan Wang, Johannes Voortman, Yonghong Wang, Seth M. Steinberg, Niccola Funel, Paul S. Meltzer, Yisong Wang, Giuseppe Giaccone
Journal: Clinical Cancer Research (2011)

Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted.Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells.We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation.Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.