tbuckley/cabot-search huggingface dataset:
Abstract 3183: Modulation of NLRP3 by chemotherapeutics: Potential application in mesothelioma treatment
Authors: Arti Shukla, Catherine Westbom, Joyce Thompson, Maximilian MacPherson, Stacie Beuschel
Journal: Cancer Research (2014)

Abstract Malignant mesothelioma (MM) is a deadly cancer and inflammation plays an important role in this carcinogenesis. In about 80% of cases, asbestos is the cause of MM development. We have previously shown that asbestos-induced NLRP3 priming and activation plays a significant role in MM development. We have also demonstrated that MM cells and tumor tissues show decreased levels of NLRP3 and caspase-1 activity as compared to normal mesothelial cells or tissue. Here using various human MM lines and two chemotherapeutic agents, doxorubicin and cisplatin, we show that chemotherapeutic agents can prime and activate NLRP3 in various MM cell lines, resulting in caspase-1 activation which may help in reducing drug resistance and increase tumor toxicity. The process of NLRP3 priming/activation was in part based on reactive oxygen species generated by these chemotherapeutic agents, as N-acetyl cysteine (NAC) was able to block these responses partly but significantly. The process of NLRP3 activation by these drugs also resulted in the release of pro-inflammatory cytokine IL-1β and IL-18. Our current studies are focused on blocking IL-1 receptor by an antagonist to find out if this can attenuate the release of IL-1-related cytokines like IL-6, IL-8 and VEGF. If successful, the combination of chemotherapeutic drugs and IL-1 receptor antagonists may have potential in MM treatment. This work is supported by NIH RO1 grant and a fellowship from the Department of Pathology, UVM. Citation Format: Arti Shukla, Catherine Westbom, Joyce Thompson, Maximilian MacPherson, Stacie Beuschel. Modulation of NLRP3 by chemotherapeutics: Potential application in mesothelioma treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3183. doi:10.1158/1538-7445.AM2014-3183
Psychosomatic Consultation-Liaison Service in a Medical Out-Patient Department
Authors: Antje Haag
Journal: Psychotherapy and Psychosomatics (1984)

A sample of 103 patients was chosen at random from those attending the Hamburg University medical out-patient clinic. As well as undergoing the usual diagnostic procedures, these patients were interviewed to establish whether psychosomatic factors were also involved. The results show that a high percentage of the patients was willing to accept that psychological and/or social factors played a role in their illness. There was, however, a significant negative correlation between this willingness and the length of time the illness had persisted. In 50% of the patients the clinical diagnostic procedures revealed no signs of a pathological organic condition. Approximately one quarter of the patients were suffering from psychosomatic disorders in the strict sense of the word. Almost a third of the patients received psychotherapeutic help after the diagnostic procedures had been completed. The vital importance of cooperation from the outset between medical clinicians and psychotherapists is discussed in the light of empirical findings on iatrogenic chronification and its financial and personal implications for the medical services and their patients.
Suicide in doctors while under fitness to practise investigation
Authors: K. Hawton
Journal: BMJ (2015)

GMC review contains wide ranging proposals

Doctors have long been known to be at risk of suicide; in several countries their rates of suicide are higher than those for certain other professions and the general population.1 2 3 Some studies have found the main risk to be among female doctors.4 5 Several factors contribute to this problem, including mental disorder, substance misuse, work problems,6 and awareness of and easy access to methods of suicide.3 7 Doctors have higher rates of mental health disorders, including depression, anxiety, substance misuse, and “burn out,” than other occupational groups yet getting help may be undermined by lack of willingness to access services.8 9 Some 10-20% of doctors are thought to become depressed at some point in their careers .10

Doctors facing fitness to practise and other investigations understandably find them particularly stressful.11 They may experience challenges to both their professional and personal identities and may feel isolated, stigmatised, and angry. For many doctors their work is their main source of self esteem, making investigation threatening, especially when the process is prolonged. When these circumstances are compounded by lack of support (perceived or otherwise), depression, and …
Myocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects
Authors: F Calabrese
Journal: Cardiovascular Research (2003)

Myocarditis is an inflammatory disease of the myocardium associated with cardiac dysfunction. The natural history of myocarditis is frequently characterised by the evolution in dilated cardiomyopathy. Due to its variable clinical manifestation from latent to very severe clinical forms, such as acute congestive heart failure and sudden death, its prevalence is still unknown and probably underestimated. In spite of the development of various diagnostic modalities, early and definite diagnosis of myocarditis still depends on the detection of inflammatory infiltrates in endomyocardial biopsy specimens according to the Dallas criteria. Routine application of immunohistochemistry, used for identification and characterisation of inflammatory cell populations, has now significantly increased the sensistivity of the diagnosis of inflammatory cardiomyopathy. Various molecular techniques, such as PCR, gene sequencing and real-time PCR, often applied on the same endomyocardial specimen, have become an essential part of the diagnostic armamentarium for rapid, specific and sensitive identification of infective agents. The correct application of molecular techniques will allow increasingly more information to be obtained: new epidemiology, new patient risk stratification and overall more appropriate medical treatment.
Role of nitric oxide in intestinal water and electrolyte transport
Authors: F H MOURAD, J L TURVILL, M J G FARTHING
Journal: Gut (1999)

2][3][4] The eVect of NO on the intestinal epithelium, the local microcirculation, the enteric nervous system, and inflammatory cascades has implicated it as a potential mediator of intestinal water and electrolyte transport. 5Data produced by diVerent groups over the past few years have been contradictory, some showing NO as an absorbagogue and others as a secretagogue. Biology of nitric oxide and its source in the intestineIn biological systems, NO has a half life of less than 5 seconds, rapidly degrading to nitrite and nitrate in the presence of oxygen and water. 1 Being soluble in both water and lipid, it freely traverses cell membranes and passes into adjacent target cells. 6The potential sources of NO in the gut are the endothelial cells, the intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neurones), residing and infiltrating leucocytes (neutrophils and monocytes), reduction of luminal gastric nitrates, and to a lesser extent denitrification by commensal intestinal bacteria. 5itric oxide is formed from L-arginine by the action of a stereospecific group of enzymes called nitric oxide synthases (NOS). 7][10][11][12] Nitric oxide can be produced by enterocytes through both the constitutive and the inducible NOS. 13 14 Nitric oxide has been considered as a regulator of basal intestinal water transport, as a mediator of pathological conditions where disturbance in water transport plays a role, and as an eVector substance in both laxatives and antidiarrhoeal agents. Role of nitric oxide in basal water transportOur understanding of the physiological action of NO comes from studies on the eVects on water and electrolyte movement of substances that inhibit NOS and thus prevent NO release.Serosal addition of the NOS inhibitors N G -methyl-L-arginine (L-NMA) or N G -nitro-L-arginine (L-NNA) (0.01-0.3 mM) to unstripped mouse ileum mounted in Ussing chambers resulted in an increase in short circuit current (Isc) which was reversed by L-arginine (0.1-10 mM) implying a net proabsorptive eVect for NO on ion transport. 15However, Rolfe et al and Eutamene et al found no eVect of NOS inhibition on water transport in rat ileum in vitro and in rat colon in vivo, respectively. 16 17Oth-on August 19,
Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification
Authors: L. Pasqualucci, A. Liso, M. P. Martelli, N. Bolli, R. Pacini, A. Tabarrini, M. Carini, B. Bigerna, A. Pucciarini, R. Mannucci, I. Nicoletti, E. Tiacci, G. Meloni, G. Specchia, N. Cantore, F. Di Raimondo, S. Pileri, C. Mecucci, F. Mandelli, M. F. Martelli, B. Falini
Journal: Blood (2006)
Intimal Thickening Develops Without Humoral Immunity in a Mouse Aortic Allograft Model of Chronic Vascular Rejection
Authors: Lawrence H. Chow, Susanna Huh, Jifu Jiang, Robert Zhong, J. Geoffrey Pickering
Journal: Circulation (1996)

Background The major threat to the long-term survival of cardiac allograft recipients is the development of diffuse intimal thickening in the allograft coronary arteries through mechanisms that are poorly understood. Although antidonor antibodies have been associated with the development of this condition, a causal relationship has not been established. Methods and Results To determine whether humoral immune responses are necessary for the development of graft vascular disease, we performed abdominal aortic allografts from normal donor mice into different immunodeficient recipient mice: those lacking all donor-specific immune responses (severe combined immunodeficient [SCID] mice and recombination activating gene-1 [RAG-1]–deficient mice) and those lacking humoral immune responses alone owing to a targeted deletion of the joining region (J H ) gene segments for the immunoglobulin heavy chain. At 6 to 9 weeks after transplantation, aortic allografts in normal immunocompetent recipients showed concentric intimal thickening extending the full length of the graft (percent luminal reduction, [%LR], 31.2±9.1 [mean±SD] and 38.5±3.6 in different donor-recipient strain combinations). In contrast, syngeneic (histocompatible) aortic grafts showed a normal-appearing vessel wall (%LR, 1.6±0.7). In both SCID and RAG-1–deficient recipients, aortic allografts showed a virtual absence of neointimal formation (%LR, 3.7±2.1 and 3.8±1.6 in SCID and RAG-1–deficient recipients, respectively), indicating a critical etiological role for alloimmune responses in this model. Importantly, allografts in J H -deficient mice showed marked intimal thickening (%LR, 35.7±7.9), with an appearance histologically indistinguishable from that of normal immunocompetent recipients. Conclusions Neointimal formation in graft vascular disease is critically dependent on alloimmune responses of the host. Humoral effector mechanisms, however, may not be required.
New doctors' group challenges medical bodies' opposition to assisted dying
Authors: Z. Kmietowicz
Journal: BMJ (2010)

UK doctors have set up a new group for health professionals to challenge the BMA and a number of royal colleges in their stance against assisted dying for terminally ill people and to push for a change in the law.

The group, called Dignity in Dying: Healthcare Professionals for Change, was set up by Ann McPherson, who is dying of pancreatic cancer, after an article she wrote in the BMJ last year generated interest in giving people who are dying the option of help to end their lives when they chose ( BMJ 2009;339:b2827 doi:10.1136/bmj.b2827).

Dr McPherson, who is a fellow of …
ON THE HAEMAGGLUTININ REACTION AS A TEST OF THE TOXICITY OF VARIOUS ANTISEPTIC REAGENTS, AND ON THE ASSOCIATION (IF ANY) BETWEEN THE HAEMAGGLUTININ CONTENT OF THE BLOOD SERUM AND PUS, AND CAPACITY TO RESIST INFECTION
Authors: C. J. Bond
Journal: BMJ (1917)

1'TkLE HAEMAGGLUTININ.REACTION.[ TIazEazU 75B Dxc.~~~~8 ,11,IZICLJUA 5 some instances.These pulmonary lesions probably possess some siginificance in relation to the frequent occurrcnce of dys'pnoea.For the supply of clinical records and patlhological material we must tliank collectively a very large number of officers througlhout the armies in France.We are especially grateful to Surgeon-General W, W. Pilie, whlo placed all the records of cases of nepliritis in hlis army at our disposal, and to Colonel Sir Wilmot Herringlham, wvlo htas all along taken the greatest interest in the work a,nd given us much valuable assistance and advice.
Insulin Receptor A and IGF-1R in AML – Letter
Authors: Nicolas Chapuis, Catherine Lacombe, Jerome Tamburini, Didier Bouscary, Patrick Mayeux
Journal: Cancer Research (2010)

In support of the recent article by Wahner Hendrickson and colleagues (1), we wish to share our data on the implication of insulin-like growth factor-1(IGF-1)/IGF-1 receptor (IGF-1R) signaling in acute myelogenous leukemia (AML). Indeed, we recently reported that a constitutively activated IGF-1R is expressed in AML cells (2). The authors hypothesize that an autocrine/paracrine stimulation of IGF-1R or insulin receptor isoform A (IR-A) could explain the overactivation of phosphoinositide-3-kinase (PI3K)/Akt and ERK/MAPK signaling in AML cells, thereby providing a rationale for dual IGF-1R/IR-A inhibition. In fact, in our previous works, we clearly established the existence of an IGF-1 autocrine production (3) and its critical role in PI3K deregulation in a cohort of 40 primary AML samples (2). Our results suggest that this PI3K/Akt activation is mediated through the IGF-1R rather than the IR-A, as specific inhibition of IGF-1R signaling with a neutralizing anti–IGF-1R antibody (αIR3) markedly inhibits the Akt constitutive phosphorylation in 70% of AML samples with deregulated PI3K activity (2). Interestingly, according to Wahner Hendrickson's data, IR-A signaling might potentially be implicated in PI3K deregulation in αIR3-resistant patients. Conversely, we assume that deregulation of ERK1/2 does not occur downstream of the IGF-1R, as αIR3 does not decrease ERK1/2 phosphorylation (2). The implication of IR-A in ERK1/2 constitutive activity is unlikely because, in our experiments, exogenous IGF-1 stimulation, which also triggers IR-A activation (1), never led to an increase of ERK1/2 phosphorylation (2). Finally, a constitutive ERK1/2 phosphorylation is detectable even in samples without constitutive PI3K activity, thereby suggesting that both deregulations proceed from different mechanisms (2).Altogether, Wahner Hendrickson and colleagues suggest that targeting IGF-1R and IR could have a significant therapeutic value in AML. Accordingly, we found that αIR3 inhibits the proliferation of primary AML cells but does not induce apoptosis (2). Interestingly, dual IGF-1R and IR-A inhibition may have stronger activity in AML, as suggested by the induction of apoptosis by BMS-536924 (1), thereby underlying a potential contribution of IR-A signaling to the survival of AML cells. However, it cannot be ruled out that other kinases involved in cell survival are also inhibited by BMS-536924, as the specificity of tyrosine kinase inhibitors is generally uncertain. Furthermore, generalized IR inhibition might induce more serious side effects than blocking IGF-1R alone, especially towards the glucose metabolism. Indeed, insulin resistance and compensatory hyperinsulinemia have been reported in mice treated with BMS-554417, another dual IGF-1R/IR inhibitor (4). Finally, how to introduce these new strategies in the arsenal of AML therapy remains an ongoing challenge.See the Response, p. 7010.No potential conflicts of interest were disclosed.
Response to Chan et al.: Hyperhomocysteinemia and Macroangiopathy in Type 2 Diabetes
Authors: M. Buysschaert, M.P. Hermans
Journal: Diabetes Care (2001)

We thank Chan et al. (1) for their interest in our work (2) and their relevant comments. We agree that there is still much to be learned about the relationship between homocysteine and atherosclerosis, as was recently stressed by Christen et al. (3). We also agree that homocysteine metabolism is altered for a few days after acute ischemic events, as reported by Egerton et al. (4) and Lindgren et al. (5). Therefore, patients with acute cardiovascular events were excluded from our analysis and could not interfere with the interpretation of our results.

Chan et al. (1) pertinently mention the role of fibrates and metformin as potential confounders of homocysteine …
Effect of Cortisone on Gastric Secretion in Adrenalectomized Dogs
Authors: Demetre M. Nicoloff
Journal: JAMA (1961)

THERE HAS BEEN increasing interest in the hormonal aspects of peptic ulcer. Various reports have implicated hormonal substances from the pancreas, 1 gonads, 2 pituitary, 3 and the adrenals. 3 Whether there is any direct relationship between the activity of these glands and peptic ulceration still remains controversial.  A brief resume of the literature shows conflicting reports as to the effect of cortisone on gastric secretion in various experimental situations. Plainos and Philippu 6 gave 60 mg. of prednisone daily to pouch dogs with intact adrenals and noticed a 412% increase in hydrochloric acid (HCl) and a 365% increase in pepsin secretion. Zubiran et al. 7 gave dogs with intact adrenals and different types of pouches 100 mg. of cortisone daily and produced a 30% to 209% increase in hydrochloric acid secretion. Wiederanders et al. 8 gave 300 mg. of cortisone to dogs with Heidenhain pouches and intact adrenals and
The Effect of Nitroglycerine on the Ballistocardiogram of Persons with and without Clinical Evidence of Coronary Heart Disease
Authors: ISAAC STARR, ELAINE PEDERSEN, ALDO N. CORBASCIO
Journal: Circulation (1955)

Nitroglycerine has been given to a series of patients and its effect on the ballistocardiogram oserved. Attacks of angina pectoris are accompanied by great deterioration of the record; if nitroglycerine is given at such a time, the record improves as pain passes off. Given between attacks to patients having coronary heart disease with abnormal ballistocardiograms, nitroglycerine is often followed by improvement in the record. Also given to older patients who have abnormal ballistocardiograms but no clinical evidence of coronary heart disease, nitroglycerine is often followed by improvement in the record, a fact consistent with the view that coronary heart disease is present in such cases. However, nitroglycerine is sometimes followed by deterioration of the ballistocardiogram, the possible reasons for this unexpected finding are discussed; attention is called to recent evidence indicating that serious toxic effects may follow exposure to nitrites in industry.
Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene.
Authors: D Del Bufalo, A Biroccio, S Soddu, N Laudonio, C D'Angelo, A Sacchi, G Zupi
Journal: Journal of Clinical Investigation (1996)

Lonidamine, a dichlorinated derivative of indazole-3-carboxylic acid, was shown to play a significant role in reversing or overcoming multidrug resistance. Here, we show that exposure to 50 microg/ml of lonidamine induces apoptosis in adriamycin and nitrosourea-resistant cells (MCF-7 ADR(r) human breast cancer cell line, and LB9 glioblastoma multiform cell line), as demonstrated by sub-G1 peaks in DNA content histograms, condensation of nuclear chromatin, and internucleosomal DNA fragmentation. Moreover, we find that apoptosis is preceded by accumulation of the cells in the G0/G1 phase of the cell cycle. Interestingly, lonidamine fails to activate the apoptotic program in the corresponding sensitive parental cell lines (ADR-sensitive MCF-7 WT, and nitrosourea-sensitive LI cells) even after long exposure times. The evaluation of bcl-2 protein expression suggests that this different effect of lonidamine treatment in drug-resistant and -sensitive cell lines might not simply be due to dissimilar expression levels of bcl-2 protein. To determine whether the lonidamine-induced apoptosis is mediated by p53 protein, we used cells lacking endogenous p53 and overexpressing either wild-type p53 or dominant-negative p53 mutant. We find that apoptosis by lonidamine is independent of the p53 gene.
Cubital Tunnel Syndrome
Authors: Charles B. Clark
Journal: JAMA (1979)

The symptoms of cubital tunnel syndrome in 118 patients were mainly those of muscular atrophy, but they also included sensory disturbances in the ring and little fingers and pain in the ulnar side of the forearm. The syndrome occurs equally in men and women, with no particular age preference in adults. Seven tests are useful in diagnosing the condition. Treatment consists of excising the band, which constricts the ulnar nerve at the elbow. Sensory recovery is usually complete, but muscular atrophy may not recover in older patients. In my series of 561 nerve decompressions, ulnar nerve decompression was carried out eight times more often at the elbow than at the wrist. (<i>JAMA</i>241:801-802, 1979)
A DIFFERENTIAL SIGN IN ABDOMINAL RIGIDITY
Authors: C. Fremont Vale
Journal: JAMA (1923)

Abdominal signs and symptoms in diaphragmatic pleurisy have been emphasized times innumerable. Let us add chest injury to the pleurisy. There are few internists who have not placed the lesion in the peritoneal cavity, and few surgeons who have not operated in such cases for appendicitis or other acute abdominal condition—all of which means that the differential diagnosis is often extremely difficult. It is hoped that the simple sign here described may be of value to some in such cases when rigidity is present. So far as I have been able to learn, it has not been mentioned in the literature. When the lesion is intrathoracic, the rigidity of the abdominal muscles momentarily relaxes at the end of expiration. This is typical, and is not present regularly at any other period of the respiratory excursion. When the lesion is intraperitoneal, the rigidity is usually constant; but, if intermittent, is not
Air Contamination: A Respiratory Hazard
Authors: Seymour M. Farber
Journal: JAMA (1962)

Health hazards due to contamination of the atmosphere are not limited to the immediate effects of severe episodes. Air pollution plays an important role in the etiology of lung cancer and is linked to cancer of other sites. It is a major cause of bronchitis and can be implicated in many other diseases of the respiratory tract. Continued study of the mechanisms involved demonstrate that these effects are not due to single factors in most situations but to multiple components differing widely from one city to another. Statistical and experimental studies of chronic exposure to common ambient levels of air pollution clearly demonstrate the serious health hazard represented by air contamination.
Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma
Authors: Elodie Bégué, Francette Jean-Louis, Martine Bagot, Sébastien Jauliac, Jean-Michel Cayuela, Liliane Laroche, Nathalie Parquet, Hervé Bachelez, Armand Bensussan, Gilles Courtois, Laurence Michel
Journal: Blood (2012)