tbuckley/cabot-search huggingface dataset:
Periostin is essential for cardiac healingafter acute myocardial infarction
Authors: Masashi Shimazaki, Kazuto Nakamura, Isao Kii, Takeshi Kashima, Norio Amizuka, Minqi Li, Mitsuru Saito, Keiichi Fukuda, Takashi Nishiyama, Satoshi Kitajima, Yumiko Saga, Masashi Fukayama, Masataka Sata, Akira Kudo
Journal: The Journal of Experimental Medicine (2008)

Acute myocardial infarction (AMI) is a common and lethal heart disease, and the recruitment of fibroblastic cells to the infarct region is essential for the cardiac healing process. Although stiffness of the extracellular matrix in the infarct myocardium is associated with cardiac healing, the molecular mechanism of cardiac healing is not fully understood. We show that periostin, which is a matricellular protein, is important for the cardiac healing process after AMI. The expression of periostin protein was abundant in the infarct border of human and mouse hearts with AMI. We generated periostin−/− mice and found no morphologically abnormal cardiomyocyte phenotypes; however, after AMI, cardiac healing was impaired in these mice, resulting in cardiac rupture as a consequence of reduced myocardial stiffness caused by a reduced number of α smooth muscle actin–positive cells, impaired collagen fibril formation, and decreased phosphorylation of FAK. These phenotypes were rescued by gene transfer of a spliced form of periostin. Moreover, the inhibition of FAK or αv-integrin, which blocked the periostin-promoted cell migration, revealed that αv-integrin, FAK, and Akt are involved in periostin signaling. Our novel findings show the effects of periostin on recruitment of activated fibroblasts through FAK-integrin signaling and on their collagen fibril formation specific to healing after AMI.
Hodgkin's disease and occupational exposure to chemicals.
Authors: R T Benn, A Mangood, A Smith
Journal: BMJ (1979)

article (29 September, p 751)-never "give a moment's thought to its precise definition" are perhaps wiser than they know.Disease is one of those words best not defined.The same is true of health.What could be more fatuous than the famous definition of health made years ago by the World Health Organisation: "Health is a state of complete physical, mental, and social wellbeing, and not merely the absence of disease and infirmity"?
White Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy
Authors: Jeffrey Weber, Michael Atkins, Patrick Hwu, Laszlo Radvanyi, Mario Sznol, Cassian Yee
Journal: Clinical Cancer Research (2011)

Abstract Adoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma. A number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival. Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates. These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma. Here, we provide an overview of the current state-of-the art in T-cell–based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field. Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone are described. Finally, we provide a roadmap describing the critical steps required to test TIL therapy in a randomized multicenter setting. We suggest an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency. If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer. Clin Cancer Res; 17(7); 1664–73. ©2011 AACR.
Circadian gastric acidity in Helicobacter pylori positive ulcer patients with and without gastric metaplasia in the duodenum.
Authors: V Savarino, G S Mela, P Zentilin, M R Mele, L Lapertosa, R Patetta, E Dallorto, A Vassallo, C Mansi, S Vigneri, G Celle
Journal: Gut (1996)

BACKGROUND: The presence of gastric metaplasia allows helicobacter pylori to colonise the duodenum and this condition is thought to be acquired as a response to acid hypersecretion. This functional disorder, however, is present only in a subgroup of duodenal ulcer patients and, in addition, surface gastric metaplasia has been frequently found in the proximal duodenum of normal subjects and patients with non-ulcer dyspepsia, who cannot be certainly considered as acid hypersecretors. AIMS: To clarify the role of acid in inducing gastric type epithelium in the duodenum. This study aimed at assessing whether the pattern of circadian gastric acidity differs between H pylori positive duodenal ulcer patients with and without duodenal gastric metaplasia. PATIENTS: Seventy one patients with duodenal ulcer confirmed by endoscopy and who were found to be positive for H pylori infection by histology on antrum biopsy specimens were enrolled into this study. METHODS: Gastric type epithelium in the duodenum was found in 49 of 71 ulcer patients (69%). Continuous 24 hour gastric pH metry was performed in 50 healthy subjects and in the two subgroups of duodenal ulcer patients with and without gastric metaplasia in the duodenum. Gastric acidity was calculated for 24 hours (1700-1659), night (2000-0759) and day-time (0800-1959). RESULTS: Ulcer patients without gastric metaplasia showed a significantly higher gastric acidity (p &lt; 0.001) than controls for every time interval considered, while the ulcer subgroup with gastric metaplasia was more acid than healthy subjects (p &lt; 0.001) during the whole 24 hour period and the daytime. There was no difference between the two subgroups of duodenal ulcer patients with and without gastric metaplasia during the various time segments analysed. CONCLUSION: The findings confirm that the circadian gastric acidity of duodenal ulcer patients is higher than that of controls. As there is no difference in gastric pH between duodenal ulcer patients with and without gastric metaplasia, gastric hyperacidity is not specific to patients with duodenal gastric metaplasia. It is probable that this histological change is a non-specific response to mucosal injury resulting from various factors and not exclusively to acid.
THE CONDITIONED AVERSION TREATMENT IN CHRONIC ALCOHOLISM
Authors: J. V. EDLIN, R. H. JOHNSON, P. HLETKO, G. HEILBRUNN
Journal: American Journal of Psychiatry (1945)

Since the introduction of the aversion treatment fifteen months ago at this hospital, 15 percent of an unselected group of patients have remained abstinent for a period of five to fifteen months. An abstinence rate of 55 percent, however, was obtained in a selected group of patients with a commendable sociological background. A period of at least three months sobriety was obtained in 52 percent of all patients treated. The aversion treatment is regarded not as a therapy in itself but merely as a valuable method to interrupt the alcoholic cycle for a conjectural period of time, which should be utilized for intensive psychotherapy.
Genome-Wide Analysis of the Homeobox C6 Transcriptional Network in Prostate Cancer
Authors: Colleen D. McCabe, Demetri D. Spyropoulos, David Martin, Carlos S. Moreno
Journal: Cancer Research (2008)

Abstract Homeobox transcription factors are developmentally regulated genes that play crucial roles in tissue patterning. Homeobox C6 (HOXC6) is overexpressed in prostate cancers and correlated with cancer progression, but the downstream targets of HOXC6 are largely unknown. We have performed genome-wide localization analysis to identify promoters bound by HOXC6 in prostate cancer cells. This analysis identified 468 reproducibly bound promoters whose associated genes are involved in functions such as cell proliferation and apoptosis. We have complemented these data with expression profiling of prostates from mice with homozygous disruption of the Hoxc6 gene to identify 31 direct regulatory target genes of HOXC6. We show that HOXC6 directly regulates expression of bone morphogenic protein 7, fibroblast growth factor receptor 2, insulin-like growth factor binding protein 3, and platelet-derived growth factor receptor α (PDGFRA) in prostate cells and indirectly influences the Notch and Wnt signaling pathways in vivo. We further show that inhibition of PDGFRA reduces proliferation of prostate cancer cells, and that overexpression of HOXC6 can overcome the effects of PDGFRA inhibition. HOXC6 regulates genes with both oncogenic and tumor suppressor activities as well as several genes such as CD44 that are important for prostate branching morphogenesis and metastasis to the bone microenvironment. [Cancer Res 2008;68(6):1988–96]
How Will Changes in Health Insurance Tax Policy and Employer Health Plan Contributions Affect Access to Health Care and Health Care Costs?
Authors: M S Marquis, J L Buchanan
Journal: JAMA (1994)

To understand how changes in federal taxation of and employer contributions to health insurance benefits affect the decisions of firms to offer insurance, the willingness of households to purchase different health plans, and the resultant health expenditures.Economic policy simulation.Secondary data analysis.A total of 18,343 sampled families (representing 77 million total families throughout the United States) with a working household head from the 1988 Current Population Survey who were not covered by either Medicare, Medicaid, or CHAMPUS (Civilian Health and Medical Program of the Uniformed Services) insurance.One intervention limits the amounts of tax-free employer contributions to health insurance premiums to 80% of our estimate of the base plan in the market and assumes that employer contributions will also be limited to this maximum. A second intervention eliminates the favorable tax treatment of employer-paid premiums altogether and assumes that employees will pay the full price of insurance.Change in the number of working families offered employment-based insurance, change in insurance plan choice, and change in medical spending.Capping the favorable tax treatment and employer contributions decreases the number of families offered employment-based insurance by approximately 91,000, increases the number of families selecting the least generous insurance plan from 20% under the current situation to 33%, and reduces overall health spending by less than 2%. By eliminating the tax exemption altogether, the number of families offered employment-based insurance decreases by approximately half a million families, the number of families selecting the least generous plan goes from 20% to 40%, and overall spending falls by about $16 billion.Eliminating the tax subsidy and limiting employer-paid contributions to the low-cost plan substantially increases the number of low-income uninsured under a voluntary insurance system, decreases overall spending only modestly, but would raise tax revenues by $36 billion. These tax revenues could be used to assist low-income families to obtain insurance coverage.
Asparaginase Pharmacokinetics After Intensive Polyethylene Glycol-Conjugated L-Asparaginase Therapy for Children with Relapsed Acute Lymphoblastic Leukemia
Authors: Douglas S. Hawkins, Julie R. Park, Blythe G. Thomson, Judy L. Felgenhauer, John S. Holcenberg, Eduard H. Panosyan, Vassilios I. Avramis
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Asparaginase therapy is an important component in the treatment of children with acute lymphoblastic leukemia. Polyethylene glycol-conjugated asparaginase (PEG-ASNase) has significant pharmacological advantages over native Escherichia coli asparaginase. We investigated the pharmacokinetics of PEG-ASNase, presence of antibodies to PEG-ASNase, and concentrations of asparagine in serum and cerebrospinal fluid (CSF) in combination chemotherapy for relapsed pediatric acute lymphoblastic leukemia. Experimental Design: Twenty-eight pediatric patients with relapsed medullary (n = 16) and extramedullary (n = 11) acute lymphoblastic leukemia were enrolled at three pediatric institutions and had at least two serum and CSF samples obtained for analysis. Patients received induction therapy (including PEG-ASNase 2500 IU/m2 intramuscularly weekly on days 2, 9, 16, and 23) and intensification therapy (including PEG-ASNase 2500 IU/m2 intramuscularly once on day 7). Serum samples were obtained weekly during induction and intensification. CSF samples were obtained during therapeutic lumbar punctures during induction and intensification. Results: Weekly PEG-ASNase therapy resulted in PEG-ASNase activity of &amp;gt;0.1 IU/ml in 91–100% of patients throughout induction. During intensification, PEG-ASNase on day 7 resulted in PEG-ASNase activity &amp;gt;0.1 IU/ml in 94% and 80% of patients on days 14 and 21, respectively. Serum and CSF asparagine depletion was observed and maintained during induction and intensification in the majority of samples. PEG-ASNase antibody was observed in only 3 patients. Conclusions: Intensive PEG-ASNase therapy in the treatment of relapsed acute lymphoblastic leukemia reliably results in high-level serum PEG-ASNase activity, and asparagine depletion in serum and CSF is usually achieved. Incorporation of intensive PEG-ASNase in future trials for recurrent acute lymphoblastic leukemia is warranted.
Diltiazem-induced blockade of sympathetically mediated constriction of normal and diseased coronary arteries: lack of epicardial coronary dilatory effect in humans.
Authors: K F Hossack, B G Brown, D K Stewart, H T Dodge
Journal: Circulation (1984)

To determine mechanisms of benefit from diltiazem, 13 patients with coronary disease performed sustained isometric handgrip exercise and repeated the procedure during intravenous infusion of diltiazem (0.25 mg/kg bolus followed by 0.003 mg/kg/min). Cardiovascular responses to handgrip, diltiazem, their combination, and nitroglycerin were assessed by hemodynamic and electrocardiographic measurements and by computer-assisted measurements of normal and diseased segments of epicardial coronary arteries. Handgrip produced increases in heart rate (12%; p less than .001), pulmonary arterial pressure (19%; p less than .005), and pulmonary wedge pressure (33%; p less than .005). Diltiazem produced significant reductions in heart rate (7%; p less than .05) and aortic pressure (14%; p less than .001). Pulmonary arterial pressure and pulmonary wedge pressure were unchanged by diltiazem. Diltiazem did not prevent the increase in heart rate or in aortic or wedge pressure associated with handgrip. Diltiazem prolonged atrioventricular conduction from 0.18 +/- 0.03 to 0.20 +/- 0.03 sec (p less than .001). Compared with control values, nitroglycerin reduced aortic pressure (14%; p less than .005), pulmonary arterial pressure (38%; p less than .001), and pulmonary wedge pressure (42%; p less than .005). Heart rate was unchanged. The constriction (20%) in lumen area of normal coronary arterial segments during handgrip was effectively prevented by infusion of diltiazem (1%; p less than .001). Nitroglycerin produced a significantly greater increase (20%) in diameter of normal coronary arterial segments than diltiazem (3%; p less than .001) and tended to have a more favorable effect than diltiazem on stenosis minimum area and flow resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
PCR based method for accurate diagnosis of mycobacterial disease and description of clinical profile of disease caused by non tuberculous mycobacteria
Authors: Anoma Siribaddana, R.B. Vasanthakrishnan, S.B.P. Athauda, Dinesh Dassanayake, Manil Peiris
Journal: European Respiratory Journal (2012)

Introduction  Sri Lanka uses direct microscopy to diagnose tuberculosis. This method has relatively low sensitivity of 70% and cannot differentiate Mycobacterium Tuberculosis Complex (MtbC) and Non Tuberculous Mycobacteria (NTM).An accurate and rapid diagnosis of NTM could be made by Polymerase chain reaction.  Objective  To evaluate the use of PCR for accurate diagnosis and speciation of pulmonary disease caused by Mycobacteria and to describe clinical profile of disease caused by NTM.  Method  All patients diagnosed as pulmonary TB on the basis of positive sputum direct smear to acid fast bacilli during the 90 day period between 17-02-2009 to 19-05-2009 and placed on standard chemotherapy at a District TB clinic were included. Sputum of each patient was tested with 541-bp sequence of insertion element IS986 amplification. Samples which failed to amplify IS986 were analyzed by using 16S rRNA and six more gene loci, which are used as markers for identification of MtbC from NTM species. (Huard, et al. (2003) journal of clinical Microbiology ;41:1637-1650). Clinical profile and chest radiography of patients with NTM was recorded.  Results  Out of total study population of 44 patients 8 (18.18%) were confirmed to have disease due to NTM. Thirty six patients had disease due to mycobacterium tuberculosis. Out of 8 NTM patients one died. The other seven patients remained chronically ill.  Conclusion  PCR can rapidly and accurately differentiate NTM which causes a significant proportion of smear positive disease, who will remain chronically ill despite standard regime.
Neutralisation of muscle tumour necrosis factor alpha does not attenuate exercise-induced muscle pain but does improve muscle strength in healthy male volunteers
Authors: T L Rice, I Chantler, L C Loram
Journal: British Journal of Sports Medicine (2007)

Inflammatory mediators, such as tumour necrosis factor alpha (TNFalpha), may contribute to delayed-onset muscle soreness. The effect of neutralising TNFalpha with etanercept, a soluble TNFalpha receptor, on delayed-onset muscle soreness (DOMS) induced in the quadriceps muscle was analysed.On two separate occasions at least 6 weeks apart, etanercept 25 mg or vehicle was given subcutaneously 1 hour before unaccustomed exercise to 12 healthy men in a randomised double-blind cross-over format. To induce DOMS, subjects completed 4 sets of 15 repetitions at 80% of their one-repetition maximum (1RM), using a 45 degrees inclined leg press. Muscle soreness was assessed using a 100-mm visual analogue scale (VAS), and pressure pain threshold (PPT) on the thigh before and 24, 48 and 72 hours after exercise. Changes in the subject's muscle strength were detected by reassessing the subject's 1RM 24, 48 and 72 hours after exercise.Muscle strength decreased 24 and 48 hours after exercise regardless of agent administered (analysis of variance, p<0.001). At 72 hours after exercise, muscle strength was significantly greater (p<0.01) after etanercept than after placebo. The exercise protocol induced significant DOMS for up to 72 hours, as reflected by reduced PPT and increased VAS scores (p<0.001). Etanercept had no effect on PPT or VAS.TNFalpha does not affect muscle soreness associated with unaccustomed exercise, but may improve the recovery of muscle function.
Nelfinavir Induces Liposarcoma Apoptosis through Inhibition of Regulated Intramembrane Proteolysis of SREBP-1 and ATF6
Authors: Min Guan, Kristen Fousek, Chunling Jiang, Song Guo, Tim Synold, Bixin Xi, Chu-Chih Shih, Warren A. Chow
Journal: Clinical Cancer Research (2011)

We previously reported that nelfinavir (NFV) induces G(1) cell-cycle block and apoptosis selectively in liposarcoma cell lines due to increased SREBP-1 (sterol regulatory element binding protein-1) expression in the absence of increased transcription. We postulate that NFV interferes with regulated intramembrane proteolysis of SREBP-1 and ATF6 (activating transcription factor 6).Time-lapse, confocal microscopic studies show that NFV inhibits the nuclear translocation of full-length SREBP-1-EGFP and ATF6-EGFP fusion proteins. siRNA-mediated knockdown of site-1 protease (S1P) and/or site-2 protease (S2P) leads to inhibition of SREBP-1 intracellular trafficking to the nucleus and reduces liposarcoma cell proliferation. Treatment of LiSa-2 liposarcoma cells with 3,4-dichloroisocoumarin, a serine protease inhibitor of S1P, did not affect SREBP-1 processing. In contrast, 1,10-phenanthroline, an S2P-specific inhibitor, reproduces the molecular and biological phenotypes observed in NFV-treated cells, which implicates S2P as a target of NFV. In vivo evaluation of NFV in a murine liposarcoma xenograft model leads to inhibition of tumor growth without significant toxicity.NFV-induced upregulation of SREBP-1 and ATF6 results from inhibition of S2P, which together with S1P mediates regulated intramembrane proteolysis from their precursor to their transcriptionally active forms. The resulting endoplasmic reticulum (ER) stress and concurrent inhibition of the unfolded protein response induce caspase-mediated apoptosis.These results provide new insight into the mechanism of NFV-mediated induction of ER stress and cell death in liposarcomas and are the first to report targeting S2P for cancer therapy.
An Address ON THE OPERATION FOR REMOVAL OF THE ENTIRE RECTUM AND NEIGHBOURING LYMPHATIC AREA FOR CARCINOMA
Authors: P. L. Mummery
Journal: BMJ (1907)

ssprgeon thrusts the tip of his left index finger, up the canal, and by it he guides the end of a blunt aneurysm needle, which he, makes to traverse all three .muscleson the inner, and then on the outer, side of the canal.One suture may sometimes suffice; but, if on pulling upon its ends,.it is found that there is still more than enough room left, along the canal for the passage of the cord, the surgeon withdraws his finger a little, and passes a second, or perhaps a third, suture, by which he transfixes the conjoined tendon on the inner side, and the strong tissues just above Poupart's ligament on the outer side.All these pass, of course, in front of the cord, and, having tied them, the surgeon satisfies himself that there is enough room left at the external ring for the easy passage of the elements of the spermatic cord.After this, nothing remains but to close the surface wound and apply the dressings.As regards the material for suturing the canal, I have yet to learn that there is anything better than silk, and so also for the skin wound.The alternative to palliative treatment being, then, an operation by an open incision, the ligation and removal of the sac, and the closing of the inguinal canal by suturing, three questions may be asked:1. What are the.risks of the operation? 2. What chances are there that the radical operation may prove a failure? 3. What are the time limits as regards its early