tbuckley/cabot-search huggingface dataset:
Inhibition of fatty acid synthase induces anti-tumor effect in multiple myeloma
Authors: Y. Okawa, T. Hideshima, H. Ikeda, N. Raje, S. Vallet, T. Kiziltepe, S. Enatsu, S. Pozzi, P. G. Richardson, K. C. Anderson
Journal: Journal of Clinical Oncology (2008)

19522 Background: Fatty acid synthase (FAS) is a key metabolic enzyme that catalyzes the terminal steps in the synthesis of long-chain fatty acids. Several reports have shown that FAS is expressed at significantly higher levels in a variety of human cancers, and FAS inhibitors inhibit tumor cell growth and induce apoptosis in various human cancers both in vitro and in vivo. In this study, we investigate the biological significance of inhibition of FAS in multiple myeloma (MM) cells using the small molecule inhibitor Cerulenin. Methods: FAS expression were analyzed by western blotting (WB) and immunohistochemical analysis. Cell growth was assesed by MTT assay or 3H uptake analysis. Apoptosis was evaluated by Flow cytometric analysis using Apo2.7 staining and WB. ER stress response was analyzed by WB. Assesement of combination effects with Cerulenin and other agents was performed by MTT assay and isobologram analysis. Results: FAS protein is more highly expressed in MM than normal cells. Cerulenin triggers growth inhibition in both MM cell lines and MM patient cells, as well as overcomes the survival and growth advantages conferred by IL-6, IGF-1 and bone marrow stromal cells (BMSC). It induces apoptosis in MM cell lines with only modest activation of caspase-8,-9,-3 and PARP. Moreover, the pan-caspase inhibitor Z- VAD-FMK does not significantly inhibit Cerulenin-induced apoptosis and cell death. In addition, treatment of MM cells with Cerulenin primarily up- regulates both AIF and Endo G, mediators of caspase-independent apoptosis. Importantly, Cerulenin also induces ER stress response via up- regulation of Grp78/IRE1α/JNK pathway. Although C-Jun-NH2-terminal kinase (JNK) inhibitor SP600215 blocks Cerulenin- induced cytotoxicity, it does not inhibit apoptosis and caspase cleavage triggered by Cerulenin. Furthermore, Cerulenin triggers synergistic cytotoxicity with Bortezomib, Melphalan and Doxorubicin, which induce apoptosis via activation of caspase. Conclusions: Our results indicate that inhibition of FAS by Cerulenin triggers primarily non-caspase-dependent apoptosis and JNK-dependent cell death in MM. This is the first report to demonstrate that inhibition of FAS has anti-tumor activity against MM cells, suggesting that it represents a novel therapeutic target in MM. No significant financial relationships to disclose.
Low Doses of Dopamine Agonists in the Long-Term Treatment of Macroprolactinomas
Authors: Antonio Liuzzi, Daniela Dallabonzana, Giuseppe Oppizzi, Giuseppe Giorgio Verde, Renato Cozzi, Piergiorgio Chiodini, Giovanni Luccarelli
Journal: New England Journal of Medicine (1985)

To evaluate the long-term effects of dopamine agonists in the treatment of macroprolactinoma, we studied prolactin levels and tumor size for 30 to 88 months (57 +/- 14, mean +/- S.D.) in 38 patients treated with bromocriptine or lisuride. Elevated prolactin levels became normal in 30 patients, and the tumor shrank in 29. After two years of treatment, we attempted to reduce the maintenance dose (5 to 20 mg of bromocriptine per day or 0.4 to 0.8 mg of lisuride per day); in 21 patients no changes in prolactin levels or tumor size were observed over 6 to 52 months with 0.625 to 10 mg of bromocriptine per day or 0.05 mg of lisuride per day. However, it was possible to withdraw the drug in only one patient. We conclude that dopamine agonists are usually effective treatments for macroprolactinoma and that after a response has been obtained, it can be maintained in many patients with a greatly reduced dose.
P248 Self-reported activity levels, barriers and facilitators to exercise in severe asthma
Authors: A Clarke, AH Mansur
Journal: Thorax (2015)

<h3>Introduction and aim</h3> The association between physical inactivity and increased morbidity is well documented.<sup>1</sup> It is widely recognised that patients with respiratory disease often have decreased exercise capacity, and therefore may be at increased risk of co morbidities such as cardiovascular disease, depression and obesity. The latter have been found to be highly prevalent within severe asthma populations. In recent years there has been a greater emphasis placed on co-production and service user involvement in shaping interventions for patients with chronic diseases.<sup>2</sup> The aim of this study was to gather self-reported activity levels of severe asthma patients and to determine barriers and facilitators to exercise, in order to focus future interventions. <h3>Method</h3> Fifty two patients (40 females) aged 18 to 65 years with a confirmed diagnosis of severe asthma following systematic multidisciplinary assessment took part in this study. Patients completed an activity questionnaire anonymously during their clinic visits. The questionnaire included a mixture of open and closed questions that assessed the level and attitudes to physical activities and exercise. <h3>Results</h3> 48/51 (94%) of respondents rated themselves as less active than their peers, and 21/49 (43%) did not participate in any exercise. There was a strong theme of fear of exercise induced exacerbation and breathlessness in 21/52 (40%) of patients, with 21/52 (40%) reporting feeling unsafe to exercise, and 33/52 (63%) reporting exercise induced worsening of their asthma symptoms. 45/52 (87%) wanted to become more active. Patients reported a strong preference for exercising alone or with a health professional present as opposed to group activities or classes. Swimming and walking were the activities patients were most likely to show an interest in. <h3>Conclusion</h3> This data suggests the main barrier to increasing physical exercise in severe asthma was fear/anxiety of worsening asthma symptoms particularly breathlessness. More research is required to investigate the relationship between this fear of exercise and objective measures of asthma worsening. <h3>References</h3> 1 Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence.<i> CMAJ</i> 2006;<b>174</b>:801–809 2 National Voices. <i>Policy position on coordinated care</i> [Online]. Available at: http://www.nationalvoices.org.uk/sites/www.nationalvoices.org.uk/files/policy_position_coordinated_care_v.final_.pdf, 2012
Chronic Disability in Mild Cases of Trench Foot
Authors: Franklin K. Paddock
Journal: New England Journal of Medicine (1946)

Relatively little study has been made of the persistent signs and symptoms of trench foot and immersion foot, most papers on this disorder dealing with their acute manifestations.1 , 2 According to my experience, however, these symptoms may be disabling for at least one year and are apparently not alleviated by any of a variety of therapeutic measures, including psychiatric treatment. At the present time, with relatively large numbers of patients with this condition awaiting disposition at military hospitals in this country, such a study appears timely.During February and March, 1945, in Italy, an opportunity was presented to study with special . . .
Long-Term Complications of Diabetes Mellitus
Authors: David M. Nathan
Journal: New England Journal of Medicine (1993)

Diabetes mellitus is a disease of metabolic dysregulation, most notably abnormal glucose metabolism, accompanied by characteristic long-term complications. The complications that are specific to diabetes include retinopathy, nephropathy, and neuropathy. Patients with all forms of diabetes of sufficient duration, including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), are vulnerable to these complications, which cause serious morbidity (Table 1 and Table 2). Retinopathy is so characteristic of diabetes that its presence has been incorporated into the nosologic definition of NIDDM. Only hyperglycemia of sufficient magnitude to be associated with retinopathy is classified as NIDDM, while lower levels of hyperglycemia that are . . .
Single-cell profiling of lncRNAs in the developing human brain
Authors: Qing Ma, Howard Y. Chang
Journal: Genome biology (2016)

Single-cell RNA-seq in samples from the human neocortex demonstrate that long noncoding RNAs (lncRNAs) are abundantly expressed in specific individual brain cells, despite being hard to detect in bulk samples. This result suggests that the lncRNAs might have important functions in specific cell types in the brain. Please see related Research article: www.dx.doi.org/10.1186/s13059-016-0932-1
Case 5-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Denise J. Strieder, Eugene J. Mark
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of a cough.She was well until eight months earlier, when she began to have a nonproductive cough and exertional dyspnea. An x-ray film of the chest was normal. During the two months before admission she experienced vague epigastric distress. X-ray films of the gallbladder and an upper gastrointestinal series were normal. Six weeks before admission a repeated x-ray film of the chest (Fig. 1) showed a bilateral linear and finely nodular infiltrate that involved both lungs and was most prominent in the lower lobes; no hilar lymphadenopathy . . .
Use of fermented mistletoe (viscum album L.) extract from oak tree (quercus) as supportive treatment for patients with pancreatic cancer
Authors: G. M. Stauder, H. Matthes, W. E. Friedel, P. R. Bock
Journal: Journal of Clinical Oncology (2009)

e15656 Background: To evaluate safety and efficacy of supportive treatment with fermented mistletoe extract Iscador Qu (from oak tree, quercus) (ISC-Qu) in a cohort of patients that received conventional adjuvant chemo- and/or radiotherapy (conv-th) alone (control) or additionally ISC-Qu (test group). Methods: Multicenter, comparative, non- interventional cohort study with parallel groups. Unselected, standardized, anonymized data from medical records meeting the eligibility criteria were followed until last visit or death. All endpoints were adjusted to baseline imbalance, therapy regimen and other confounders. Results: 270 patients (75 ISC-Qu/195 control) from 17 oncological centers. The treatment with ISC-Qu started before (16.7%), during (75.0%), or after (8.3%) the conv-th (mainly with gemcitabine) and usually lasted until last visit or death. The period of aftercare was median 20.3 (test group) and 10.1 months (control). Isc-Qu was applied by sequential dose escalation from 0.01 mg up to 20 mg, 2–3 injections per week (s.c.). Safety: Only 14.7% of the patients developed local ADR to ISC-Qu, there was no life- threatening ADR. Efficacy: There was a significant and relevant prolongation of overall survival: hazard ratio, HR (95% CI) = 0.35 (0.21- 0.58), p &lt; 0.001; estimated relative risk reduction = 65%. The number of ADR to conv-th (odds ratio, OR = 0.20, p = 0.006, risk reduction 80%) and the estimated risk for disease or therapy related symptom persistence were significantly reduced in the test group with ISC-Qu. Conclusions: The results show reliable safety and an important effect of supportive ISC-Qu treatment on overall survival in patients with pancreatic cancer of any stage. [Table: see text]
Response to “Comment on ‘Exposure to Road Traffic Noise and Behavioral Problems in 7-Year-Old Children: A Cohort Study’”
Authors: Dorrit Hjortebjerg, Anne Marie Nybo Andersen, Jeppe Schultz Christensen, Matthias Ketzel, Ole Raaschou-Nielsen, Jordi Sunyer, Jordi Julvez, Joan Forns, Mette Sørensen
Journal: Environmental Health Perspectives (2016)
Epstein–Barr Virus–Associated B-Cell Proliferations of Diverse Clonal Origins after Bone Marrow Transplantation in a 12-Year-Old Patient with Severe Combined Immunodeficiency
Authors: William T. Shearer, Jerome Ritz, Milton J. Finegold, I. Celine Guerra, Howard M. Rosenblatt, Dorothy E. Lewis, Marilyn S. Pollack, Larry H. Taber, Ciro V. Sumaya, F. Carl Grumet, Michael L. Cleary, Roger Warnke, Jeffrey Sklar
Journal: New England Journal of Medicine (1985)

Original Article from The New England Journal of Medicine — Epstein–Barr Virus–Associated B-Cell Proliferations of Diverse Clonal Origins after Bone Marrow Transplantation in a 12-Year-Old Patient with Severe Combined Immunodeficiency
Calcified Mass in a Patient on Long-Term Hemodialysis
Authors: P Lazowski, D S Goldfarb
Journal: New England Journal of Medicine (1998)

Figure 1. A 46-year-old man with end-stage renal disease due to diabetic nephropathy had been undergoing hemodialysis for almost two years. Fourteen months after beginning dialysis, he reported pain below the right antecubital fossa, the site of an arteriovenous graft. A plain radiograph showed a nonpalpable calcification measuring 2 cm by 3 cm in the soft tissue. The patient had not been compliant in taking aluminum-containing phosphate binders and had been treated intermittently with intravenous calcitriol. His calcium–phosphate product (with both substances measured in milligrams per deciliter) ranged from 74 to 116 in the ensuing nine months (mean, 93). At . . .
The Long-Term Course of Lyme Arthritis in Children
Authors: Ilona S. Szer, Elise Taylor, Allen C. Steere
Journal: New England Journal of Medicine (1991)

The natural history of Lyme disease is not completely known. We studied the long-term course of Lyme arthritis in 46 children in whom the onset of the disease occurred between 1976 and 1979 and who received no antibiotic therapy for at least the first four years of the illness.
Distinctive Patterns of Proliferative Activity in Kidney Cell Cultures Derived From Normal, Dimethylnitrosamine-Treated, and Renal Tumor-Bearing Rats 2
Authors: Bernard W. Stewart, Gordon C. Hard
Journal: JNCI Journal of the National Cancer Institute (1977)

Administration of a single dose of the renal carcinogen dimethylnitrosamine (DMN) to rats 24 hours prior to isolation and culture of cells from the target organ is known to result in the growth of cells with characteristics radically different from those of cells cultured from the kidneys of an untreated animal; after five subcultures, cells isolated from DMN-treated rats become morphologically transformed. The examination of cell multiplication and rates of thymidine (TdR) incorporation suggested that the cells transformed by exposure to DMN in vivo were similar in culture to cells isolated from DMN-induced renal mesenchymal tumors. Following the isolation of renal cells from control and DMN-treated rats, rates of TdR incorporation were compared at each subculture. Distinction between the two cell populations was possible at the third subculture because of increasing incorporation by the carcinogen-exposed cells. Morphologic transformation of the carcinogen-exposed cells occurred by the fifth subculture and corresponded with the establishment of a high rate of TdR incorporation relative to that by earlier cultures of these cells; this high rate was maintained uniformly in subsequent subcultures. Thus increased TdR incorporation was a further characteristic expressed at the time of morphologic transformation and, in this experimental system, was a quantitatively more responsive parameter than cell number determinations.
In Vivo Induction and Reversal of Nitroglycerin Tolerance in Human Coronary Arteries
Authors: David C. May, Jeffrey J. Popma, William H. Black, Saul Schaefer, Howard R. Lee, Benjamin D. Levine, L. David Hillis
Journal: New England Journal of Medicine (1987)

The mechanism by which tolerance to the clinical effects of organic nitrates develops has not been elucidated. This study was done to determine whether an intravenous infusion of nitroglycerin induces tolerance in the coronary vascular bed and whether such tolerance is reversed by the sulfhydryl-group donor N-acetylcysteine. We studied 19 subjects--17 with coronary artery disease and 2 without it--who had a mean age (+/- SD) of 54 +/- 9 years. Coronary sinus blood flow, which approximates blood flow to the left ventricle, was measured before and during intracoronary injections of nitroglycerin (10, 25, 50, and 100 micrograms). The patients then received a 24-hour intravenous infusion of saline (n = 7) or of nitroglycerin, 45 +/- 13 micrograms per minute (n = 12), after which the responses of coronary sinus flow to the same doses of intracoronary nitroglycerin used earlier were measured. In the seven patients given saline, the four doses of intracoronary nitroglycerin caused similar percentage increases in coronary sinus flow before and after the saline infusion. In the 12 patients given intravenous nitroglycerin, the four intracoronary doses caused percentage increases in coronary flow before the infusion of 30 +/- 9, 35 +/- 14, 41 +/- 12, and 52 +/- 15, respectively. After the infusion, the same doses of nitroglycerin caused smaller (P less than 0.05) percentage increases (16 +/- 6, 21 +/- 11, 23 +/- 12, and 27 +/- 11, respectively), indicating the development of partial tolerance. Subsequently, 7 of the 12 patients received N-acetylcysteine, after which intracoronary nitroglycerin caused percentage increases in coronary sinus flow similar to the values measured before the intravenous nitroglycerin was given (34 +/- 13, 32 +/- 8, 38 +/- 11, and 44 +/- 16, respectively). We conclude that the coronary vasodilator effect of nitroglycerin is attenuated by an intravenous infusion of nitroglycerin (that is, partial tolerance develops) and that tolerance to the agent can be reversed by administration of the sulfhydryl-group donor N-acetylcysteine. The mechanism by which N-acetylcysteine reverses tolerance will require further investigation.
Response of Two Rodents, &lt;italic&gt;Mastomys natalensis&lt;/italic&gt; and &lt;italic&gt;Mystromys albicaudatus&lt;/italic&gt;, to the Pancreatic Carcinogen Azaserine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: B D Roebuck, D S Longnecker
Journal: JNCI Journal of the National Cancer Institute (1979)

The response of two rodents to azaserine carcinogenicity for the pancreas was evaluated. Mystromys albcaudatus was not responsive; however, Mastomys natalensis developed large numbers of atypical acinar cell nodules and several adenomas in a 6-month study. Mastomys is the most responsive of several animals in which azaserine has been studied as a pancreatic carclnogen.
A Comparison of Angioplasty with Medical Therapy in the Treatment of Single-Vessel Coronary Artery Disease
Authors: Alfred F. Parisi, Edward D. Folland, Pamela Hartigan
Journal: New England Journal of Medicine (1992)

Despite the widespread use of percutaneous transluminal coronary angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We compared the effects of PTCA with those of medical therapy on angina and exercise tolerance in patients with stable single-vessel coronary artery disease.
Occupational Risks for Pleural Mesothelioma in Sweden, 1961–79
Authors: H S Malker, J K McLaughlin, B K Malker, B J Stone, J A Weiner, J L Erickson, W J Blot
Journal: JNCI Journal of the National Cancer Institute (1985)

From national population-based registries linking cancer incidence from 1961 to 1979 with 1960 census data on industry and occupation for all employed individuals in Sweden, a systematic assessment was made of pleural mesothelioma occurrence according to occupational and industrial classifications. There were 318 cases of pleural mesothelioma recorded during the 19-year follow-up period among males employed in 1960, with significant variation by industrial and occupational categorizations. The observed number of pleural mesotheliomas for men employed in the sugar refining, cellulose, wood and pulp, shipbuilding, and railroad equipment manufacturing industries was more than three times the number expected. Occupations with at least twofold excess of mesotheliomas included the craftsman categories of plumbers, mechanics and repairmen, electricians, painters, tire makers, and stationary equipment operators. Our findings are consistent with available data relating mesothelioma to occupational asbestos exposure in other countries, although unexpected associations were found that deserve further epidemiologic study.
Unrecognized Emboli to the Lungs with Subsequent Cor Pulmonale
Authors: William R. Owen, Wilbur A. Thomas, Benjamin Castleman, Edward F. Bland
Journal: New England Journal of Medicine (1953)

IN recent years interest in pulmonary embolization has centered largely about preventive measures, with emphasis on leg-vein ligation and anticoagulant therapy.1 , 2 The principal cause for concern has been the acute syndrome of pulmonary infarction with its all too familiar picture of chest pain, hemoptysis and sometimes sudden death. It is well known, however, that pulmonary emboli may occur without clinical recognition,3 4 5 and the incidental post-mortem finding of organized emboli involving scattered vessels is not uncommon.There is a special group of patients, however, in whom the emboli are so extensive that they ultimately result in serious obstruction to the flow . . .
Phase I JAVELIN solid tumor trial of avelumab (MSB0010718C), an anti-PD-L1 antibody: Safety and pharmacokinetics
Authors: H.-T. Arkenau, K. Kelly, M.R. Patel, B. Neuteboom, I. Speit, K. Chin, C.R. Heery, J.L. Gulley
Journal: Annals of Oncology (2015)
Cisplatin plus pirarubicin chemotherapy and combination ifomide, etoposide, pirarubicin, and carboplatin chemotherapy for hepatoblastoma.
Authors: E. Hiyama, A. Kamimatsuse, N. Kamei, K. Watanabe, T. Hishiki, T. Tajiri, K. Ida, M. Yano, S. Kondo, F. Sasaki
Journal: Journal of Clinical Oncology (2010)

9534 Background: The Japanese Study Group for Pediatric Liver Tumor is running cooperative treatment studies on hepatoblastoma (HB) since 1991. The main aim in JPLT-1 study was to evaluate the efficacy of cisplatin/pirarubicin. A total of 145 cases were registered and their 6-year overall survival (OS) and event-free survival (EFS) were 73.4% and 66%, respectively (J Pediatr Surg 37: 851-6, 2002). Since the outcomes of advanced HB cases remained poor, JPLT-2 protocol was launched in 1999 to evaluate the cure rate of risk-stratified HB: standard risk HB (a tumor involving three or fewer sectors of the liver) and high risk HB (a tumor involving all sectors of the liver or with metastasis). Methods: In JPLT-2, children with HB who were younger than 15 years of age were eligible for inclusion in the study. The cisplatin/pirarubicin regimen (CITA) is kept as the first line and the second line regimen consisting of ifomide, etoposide, pirarubicin, and carboplatin (ITEC) is recommended for the tumors resistant to CITA. For high risk HB cases, high dose chemotherapy with stem cell transplantation (SCT) was carried out. Results: Until 2007, 245 hepatoblastoma cases have been registered in JPLT-2, and 203 cases have completed the protocol including 69 cases (18%) with metastatic tumors. The 3-year OS and EFS of the cases with standard risk HB were 96% and 76%, while that of the cases with high risk HB was 54% and 34%. Among 34 high risk HB cases (30 with metastatic HB and 4 with unresectable HB) who underwent high dose regimen with SCT, only 21 cases (57%) were cured, indicating that high dose chemotherapy with SCT is not so effective in advanced tumors. With this regimen, 5 cases suffered treatment-related death. And the late phase complications were 3 cases with maldevelopment, 13 with cardiac complications, 20 with ototoxicity and 4 with second malignancies. Conclusions: As compared with other regimens, CITA regimens achieved similar or superior rates of survival among children with standard-risk HB. ITEC regimens and high dose chemotherapy with SCT is not so effective in high- risk HB. More promising strategies including liver transplantation and new targeting drugs should be developed for high risk HB. No significant financial relationships to disclose.