tbuckley/cabot-search huggingface dataset:
Re: The Association Between Statins and Cancer Incidence in a Veterans Population
Authors: Elizabeth A. Platz
Journal: JNCI Journal of the National Cancer Institute (2008)

I was pleased to read the article by Farwell et al. ( 1 ) reporting on statins and cancer. By comparing cancer incidence rates in statin users (irrespective of antihypertensive drug use) and antihypertensive drug users, the investigators likely limited detection bias that can arise in studies in which opportunity for exposure and outcome detection both depend on accessing medical care. For prostate cancer, detection bias has become of particular concern in epidemiological studies after the introduction of prostatespecific antigen (PSA) screening. Detection bias could arise when men who seek medical care are screened for both elevated cholesterol and PSA: compared with men who test negative, men who test positive for elevated cholesterol are more likely to be prescribed a statin, and men who test positive for elevated PSA are more likely to undergo biopsy examination. Consequently, men with prostate cancer who take a statin would be more likely diagnosed when their disease is organ confined, whereas men with prostate cancer who do not take a statin would be more likely diagnosed when their disease is advanced. Thus, statin use would appear associated positively with total and early disease and inversely with advanced disease. Farwell et al. ( 1 ) reported a slight inverse association between statins and prostate cancer (relative risk = 0.90, 95% confi dence interval = 0.81 to 0.99) but no trend across dose. These fi ndings are somewhat different than for lung and colorectal cancers, which were moderately inversely associated ( 1 ). I am concerned that Journal readers may be left with the impression that there is little, if any, evidence that statins infl uence the development of prostate cancer. What Farwell et al. ( 1 ) did not address is
The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1
Authors: Saad Z Usmani, Robert D Bona, Gabriela Chiosis, Zihai Li
Journal: Journal of Hematology & Oncology (2010)

Heat shock protein 90 (HSP90) inhibitors have emerged as a promising class of anti-cancer drugs in both solid and hematologic malignancies. The HSP90 family includes the cytosolic HSP90 (HSP90AA1), the ER paralogue gp96 (HSP90B1) and the mitochondrial member TRAP1 (HSP90L). We evaluated the in vitro anti-tumor activity and mechanism of action of PU-H71, a novel purine scaffold HSP90 inhibitor in human multiple myeloma cell lines. Multiple human myeloma cell lines including cells that are resistant to corticosteroids and bortezimab were treated with PU-H71, followed by analysis of cell viability, cell cycle progression and apoptosis, by flow cytometry and caspase 3 immunoblot. Induction of unfolded protein response was studied by XBP-1 s immunoblot. The role of gp96 was further assessed by small hairpin RNA knockdown of gp96 before treatment with PU-H71. PU-H71 has potent in vitro anti-myeloma activity in both drug-sensitive and drug-resistant cell lines. PU-H71 activates the unfolded protein response and induces caspase-dependent apoptosis. The stable gp96 knockdown human myeloma cell line was found to be more resistant to PU-H71 and other HSP90 inhibitors including 17-AAG and 17-DMAG, even though these cells are more sensitive to conventional anti-myeloma drugs. We conclude that PU-H71 is a promising drug for the treatment of myeloma. Our finding further suggests that PU-H71 and the geldanamycin analogues work in part by inhibiting the endoplasmic reticulum gp96 along with the cytosolic HSP90.
INTERFERENCE BETWEEN THE INFLUENZA VIRUSES
Authors: James E. Ziegler, George I. Lavin, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1944)

Influenza A or influenza B virus rendered non-infective by ultraviolet radiation was found to be capable of producing interference with the multiplication of active influenza viruses in the chick embryo. Certain temporal and quantitative relationships affecting the interference phenomenon with this host-virus system were studied. An hypothesis of the mechanism of interference between the influenza viruses is proposed and discussed.
Protection of Wistar Furth Rats from Chronic Renal Disease Is Associated with Maintained Renal Nitric Oxide Synthase
Authors: Aaron Erdely, Laszlo Wagner, Veronica Muller, Attila Szabo, Chris Baylis
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Wistar Furth (WF) rats do not develop renal injury after severe reduction of renal mass. Because clinical and animal studies suggested that nitric oxide (NO) deficiency occurs and may contribute to chronic renal disease (CRD), the status of the NO system in WF versus Sprague Dawley (SD) rats was examined with the 5/6 renal ablation/infarction (A/I) model of CRD. Eleven weeks after A/I, SD rats developed proteinuria, severe kidney damage, decreased renal function, and marked decreases in total and renal NO synthase (NOS), specifically neuronal NOS. In contrast, WF rats exhibited elevated baseline and maintained post-A/I total NO production, with no decrease in renal cortex NOS activity despite a decrease in remnant neuronal NOS abundance. When low-dose chronic Nω-nitro-L-arginine methyl ester treatment was added for WF A/I-treated rats, rapid progression of CRD was observed. In conclusion, elevated NO production in WF rats was associated with protection from the progression of CRD after renal mass reduction. The protection might be attributable to greater total and renal NO-generating capacity and increased nephron number, compared with SD rats. NOS inhibition rendered WF rats susceptible to progression, suggesting a possible critical threshold for NO production, below which renal injury occurs. E-mail: [email protected]
Widespread cutaneous necrosis occurring in association with the antiphospholipid syndrome: a report of two cases
Authors: D. Creamer, B.J. Hunt, M.M. Black
Journal: British Journal of Dermatology (2000)

Abstract The antiphospholipid syndrome is an acquired prothrombotic state where thrombosis and/or pregnancy loss is related to the presence of antiphospholipid antibodies. Cutaneous necrosis secondary to intravascular thrombosis of small dermal vessels is a recognized but rare association with antiphospholipid syndrome. We report two patients with high circulating levels of anticardiolipin antibodies who developed widespread cutaneous necrosis as the first clinical manifestation of the antiphospholipid syndrome. The exact mechanism by which antiphospholipid antibodies mediate thrombosis is uncertain; however, proposed mechanisms of activity include endothelial cell activation, altered endothelial production of prostacyclin, activation of platelets, and modulation of the protein C and S pathways.
A case of Reiter's disease complicated by fulminating colitis.
Authors: P Hickling, M F Martin, S Brooks
Journal: Annals of the Rheumatic Diseases (1982)

We describe a patient who, 6 months after the onset of Reiter9s disease associated with a destructive peripheral arthritis and keratodermia blenorrhagica, developed fulminating colitis. The possible relationship between Reiter9s disease and ulcerative colitis is discussed, and the need for further family studies to assess its validity is stressed.
<i>CUL7</i> Is a Novel Antiapoptotic Oncogene
Authors: Sam S. Kim, Mary Shago, Lilia Kaustov, Paul C. Boutros, James W. Clendening, Yi Sheng, Grace A. Trentin, Dalia Barsyte-Lovejoy, Daniel Y.L. Mao, Robert Kay, Igor Jurisica, Cheryl H. Arrowsmith, Linda Z. Penn
Journal: Cancer Research (2007)

Abstract Using an expression cloning approach, we identify CUL7, a member of the cullin family, as a functional inhibitor of Myc-induced apoptosis. Deregulated expression of the Myc oncogene drives cellular proliferation yet also sensitizes cells to undergo p53-dependent and p53-independent apoptosis. Here, we report that CUL7 exerts its antiapoptotic function through p53. CUL7 binds directly to p53, and small interfering RNA–mediated knockdown of CUL7 results in the elevation of p53 protein levels. This antiapoptotic role of CUL7 enables this novel oncogene to cooperate with Myc to drive transformation. Deregulated ectopic expression of c-Myc and CUL7 promotes Rat1a cell growth in soft agar, and knockdown of CUL7 significantly blocks human neuroblastoma SHEP cell growth in an anchorage-independent manner. Furthermore, using public microarray data sets, we show that CUL7 mRNA is significantly overexpressed in non–small cell lung carcinoma and is associated with poor patient prognosis. We provide experimental evidence to show CUL7 is a new oncogene that cooperates with Myc in transformation by blocking Myc-induced apoptosis in a p53-dependent manner. [Cancer Res 2007;67(20):9616–22]
Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors
Authors: Katherine C Murray, Aya Nakae, Marilee J Stephens, Michelle Rank, Jessica D'Amico, Philip J Harvey, Xiaole Li, R Luke W Harris, Edward W Ballou, Roberta Anelli, Charles J Heckman, Takashi Mashimo, Romana Vavrek, Leo Sanelli, Monica A Gorassini, David J Bennett, Karim Fouad
Journal: Nature Medicine (2010)
Amifostine Protects Against Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma
Authors: Maryam Fouladi, Murali Chintagumpala, David Ashley, Stewart Kellie, Sridharan Gururangan, Tim Hassall, Lindsey Gronewold, Clinton F. Stewart, Dana Wallace, Alberto Broniscer, Gregory A. Hale, Kimberly A. Kasow, Thomas E. Merchant, Brannon Morris, Matthew Krasin, Larry E. Kun, James M. Boyett, Amar Gajjar
Journal: Journal of Clinical Oncology (2008)

To determine the role of amifostine as a protectant against cisplatin-induced ototoxicity in patients with average-risk (AR) medulloblastoma treated with craniospinal radiotherapy and four cycles of cisplatin-based, dose-intense chemotherapy and stem-cell rescue.
Light Chain Distribution in Immune Deposits on Glomeruli of Kidneys in Human Renal Disease*
Authors: Roger C. Herdman, Richard Hong, Alfred F. Michael, Robert A. Good
Journal: Journal of Clinical Investigation (1967)

The gammaG-immunoglobulin (IgG) deposited on glomeruli of 32 percutaneous renal biopsies from 30 patients with various forms of renal disease was examined by fluorescent techniques to determine its light chain composition. Serum kappa: lambda light chain ratios were determined on 17 serum samples from 16 of the 30 patients. Glomerular IgG staining with only antikappa antiserum, only antilambda antiserum, and with both antisera was demonstrated. No correlation of serum kappa: lambda light chain ratios with the type or types of light chains demonstrable on the glomeruli was observed. We concluded that the IgG deposited on glomeruli of patients with various forms of renal disease is not a nonspecific sample of the circulating immunoglobulin pool but may well reflect more specific selection, as in the deposition of specific antibody formed against exogenous or endogenous antigens during the development of the renal lesion.
Functional Status Changes Following Medical or Surgical Treatment for Cerebral Ischemia
Authors: R. Brian Haynes
Journal: JAMA (1987)

To determine the value of extracranial-intracranial arterial anastomosis (EC/IC bypass), we randomly allocated 1377 patients with symptomatic atherosclerosis of the internal carotid or middle cerebral arteries to medical care alone or to EC/IC bypass with continuing medical care. As previously reported, surgery did not reduce--or significantly increase--the risk of stroke. Functional status data collected during the trial provide new information. Six weeks following entry, surgical patients showed greater dysfunction in the following activities: fluency of speech, getting in and out of bed, sitting down and standing up, toileting, cutting food and pouring beverages, and dressing and undressing. At 4.5 months, surgical patients still exhibited greater dysfunction in toileting, with nonsignificant trends in several other activities. From six months onward, there were no significant differences between the groups. Thus, EC/IC bypass results in transient worsening of functional status beyond the immediate perioperative period.
Overview: viral agents and cancer.
Authors: N Mueller
Journal: Environmental Health Perspectives (1995)

Substantial evidence indicates that several common viruses are clearly or probable causal factors in the etiology of specific malignancies. These viruses either normally establish latency or can become persistent infections. Oncogenesis is probably linked to an enhanced level of viral activation in the infected host, reflecting heavy viral dose or compromised immune control. The major virus-malignancy systems include hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatocellular carcinoma; human lymphotropic virus-type 1 (HTLV-1) and adult T-cell leukemia/lymphoma (ATL); Epstein-Barr virus (EBV) and endemic Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease; and human papilloma virus (HPV) and cervical cancer. Of these, a vaccine is available only for HBV. These malignancies tend to occur in early to mid-life and account for a substantial amount of morbidity and person-years lost. They are also likely to occur as "opportunistic malignancies" among individuals infected with human immunodeficiency virus type-1, particularly among those who experience prolonged survival.
Further evidence that FeNO directed therapy reduces asthma exacerbations
Authors: Jorgen Syk, James Donohue, Kjell Alving, Nancy Herje, Glenn Crater
Journal: European Respiratory Journal (2014)

Introduction:  Fractional Exhaled Nitric Oxide (FeNO) has been shown to reduce asthma exacerbations in adults when used to guide the dosing of inhaled corticosteroids (ICS) in a recent meta-analysis (Donohue, J. et.al. Respir Med 2013). These studies focused on care delivered by specialists whereas a more recent study looked at the impact of FeNO directed ICS therapy in a primary care setting (Syk, J. et.al. J Allergy Clin Immunl Pract 2013).   Objective:  To compare a recently published clinical trial to a meta-analysis of asthma exacerbation rates in adult studies evaluating asthma managed using FeNO versus standard clinical parameters alone.   Methods:  Data from 3 adult studies by Shaw, Smith & Powell and the new adult study by Syk were analyzed in a meta-analysis.   Results:  Across the 4 studies, there were a total of 302 subjects in the FeNO management group and 296 subjects in the control management group. Asthma exacerbation rates ranged from 0.22-0.49 and 0.41-0.9 across the FeNO and control management groups, respectively, and the exacerbation rate was significantly reduced in favor of the FeNO based management (-0.26 [-0.38, -0.15]). When these data were expressed as a relative rate, the rate of exacerbations was 44% lower with the FeNO-based asthma management strategy compared with the control asthma management strategy (0.56 [0.42, 0.74]).   Conclusion:  Data from the Syk study are consistent with findings from the Shaw, Smith & Powell studies published in the Donohue meta-analysis. Across the 4 studies asthma exacerbations were reduced, providing evidence that FeNO directed therapy reduces asthma exacerbation.
THE NOSOLOGICAL POSITION OF PANIC REACTIONS
Authors: Oskar Diethelm
Journal: American Journal of Psychiatry (1934)

Panic reactions—i. e., maximal fear states which result from prolonged tension and insecurity, occur in certain constitutional make-ups as a reaction to specific life situations. Panics develop as a climax of a tension depression, or they may form an important and prolonged phase in depressions with uneasiness and anxiety. This latter group has been described as an anxiety psychosis (Wernicke). I distinguish these two groups of leading panics from mere incidental panics, which may occur in any psychosis or psychoneurosis. A thorough discussion of the literature shows the development of the concept of panic in psychiatry and reviews especially the attitude to the impure affects of anxiety, fear, panic and fright. Impure affects have to be studied from a genetic-dynamic point of view. This leads to the recognition of their far-reaching influence. Much of what has been diagnosed schizophrenic admixtures can be explained by impure affects. The term tension depression which is used in this paper does not coin a new disease entity, but describes reactions of an attack type in which tension and its symptoms are the outstanding complaint and in which the depressive affect seems to play a subordinate rOle. Because of their course and their close relation to depressions, tension depressions are considered to belong to the affective reaction type. From a formal point of view we distinguish between paranoid and disorganizing panics. Their relation to paranoic and schizophrenic reactions is fully discussed.
Selective deletion of leptin receptor in neurons leads to obesity
Authors: Paul Cohen, Connie Zhao, Xiaoli Cai, Jason M. Montez, S. Christy Rohani, Paul Feinstein, Peter Mombaerts, Jeffrey M. Friedman
Journal: Journal of Clinical Investigation (2001)

Animals with mutations in the leptin receptor (ObR) exhibit an obese phenotype that is indistinguishable from that of leptin deficient ob/ob mice. ObR is expressed in many tissues, including brain, and the relative importance of leptin's effects on central versus peripheral sites has not been resolved. To address this, we generated mice with neuron-specific (ObR(SynI)KO) and hepatocyte-specific (ObR(Alb)KO) disruption of ObR. Among the ObR(SynI)KO mice, the extent of obesity was negatively correlated with the level of ObR in hypothalamus and those animals with the lowest levels of ObR exhibited an obese phenotype. The obese mice with low levels of hypothalamic ObR also show elevated plasma levels of leptin, glucose, insulin, and corticosterone. The hypothalamic levels of agouti-related protein and neuropeptide Y RNA are increased in these mice. These data indicate that leptin has direct effects on neurons and that a significant proportion, or perhaps the majority, of its weight-reducing effects are the result of its actions on brain. To explore possible direct effects of leptin on a peripheral tissue, we also characterized ObR(Alb)KO mice. These mice weigh the same as controls and have no alterations in body composition. Moreover, while db/db mice and ObR(SynI)KO mice have enlarged fatty livers, ObR(Alb)KO mice do not. In summary, these data suggest that the brain is a direct target for the weight-reducing and neuroendocrine effects of leptin and that the liver abnormalities of db/db mice are secondary to defective leptin signaling in the brain.
Prevalence of the Metabolic Syndrome Among Omani Adults
Authors: Jawad A. Al-Lawati, Ali J. Mohammed, Halima Q. Al-Hinai, Pekka Jousilahti
Journal: Diabetes Care (2003)

OBJECTIVE—To estimate the prevalence of the metabolic syndrome by age and sex in the Omani population as defined by the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) of North America. RESEARCH DESIGN AND METHODS—We analyzed data from a cross-sectional survey conducted in 2001 containing a probability random sample of 1,419 Omani adults aged ≥20 years living in the city of Nizwa. The metabolic syndrome, defined by the ATP III, was defined as having three or more of the following abnormalities: waist circumference &amp;gt;102 cm in men and &amp;gt;88 cm in women, serum triglycerides ≥150 mg/dl (1.69 mmol/l), HDL cholesterol &amp;lt;40 mg/dl (1.04 mmol/l) in men and &amp;lt;50 mg/dl (1.29 mmol/l) in women, systolic blood pressure ≥130 mmHg and/or diastolic ≥85 mmHg or on treatment for hypertension, and fasting serum glucose ≥110 mg/dl (6.1 mmol/l) or on treatment for diabetes. RESULTS—The age-adjusted prevalence of the metabolic syndrome was 21.0%. The crude prevalence was slightly lower (17.0%). The age-adjusted prevalence was 19.5% among men and 23.0% among women (P = 0.236). Low HDL cholesterol was the most common component (75.4%) of the metabolic syndrome among the study population followed by abdominal obesity (24.6%). Abdominal obesity was markedly higher in women (44.3%) than in men (4.7%). CONCLUSIONS—The prevalence of the metabolic syndrome in Oman is similar to that in developed countries. Future prevention and control strategies should not overlook the importance of noncommunicable disease risk factors in rapidly developing countries.
Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus
Authors: P. E Westerweel, R. K M A C Luijten, I. E Hoefer, H. A Koomans, R. H W M Derksen, M. C Verhaar
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Systemic lupus erythematosus (SLE) is associated with a high prevalence of cardiovascular disease. Circulating endothelial progenitor cells (EPCs) contribute to vascular regeneration and repair, thereby protecting against atherosclerotic disease. EPCs are derived from CD34+ haematopoietic stem cells (HSCs), which have an increased propensity for apoptosis in the bone marrow of patients with SLE. <b>Aim:</b> To determine whether circulating HSCs and EPCs are reduced in SLE, contributing to an increased cardiovascular risk. <b>Methods:</b> Progenitor cells were sampled from 15 female patients with SLE in prolonged clinical remission from their disease and 15 matched healthy controls. HSC and CD34+KDR+ EPCs were quantified by flow cytometry. Annexin V staining was used to identify apoptotic cells. <b>Results:</b> Patients with SLE had reduced levels of circulating CD34+ HSCs and CD34+KDR+ EPCs, associated with increased HSC apoptosis. Compared with controls, the fraction of HSCs that could be identified as EPCs was higher in patients with SLE, consistent with a primary defect of HSCs. EPC outgrowth from mononuclear cells, which depends mainly on CD34− cells, was unaffected. <b>Conclusions:</b> Patients with SLE have lower levels of circulating HSCs and EPCs, even during clinical remission. The data suggest that increased HSC apoptosis is the underlying cause for this depletion. These observations indicate that progenitor cell-mediated endogenous vascular repair is impaired in SLE, which may contribute to the accelerated development of atherosclerosis.