tbuckley/cabot-search huggingface dataset:
CBIO-46SPINDLE CELLS IN EARLY C6-GBM GROWTH ARE STEM CELLS - FUNCTIONAL STUDY WITH MITOCHONDRIAL VOLUME FOR THERAPEUTIC PURPOSE
Authors: Shoko Yamada, Lue Sun, Masashi Kawamoto, Shokei Yamada
Journal: Neuro-Oncology (2015)

OBJECTIVE: Recurrence of glioblastoma multiforme (GBM) after total resection is postulated to originate from precursor cells existing in surrounding brain tissue. The authors have found spindle cells in the early stage of rat C6 GBM growth, resembling spongioblasts, the origin of GBM (Bailey and Cushing, 1926). They are stem-like cells with positive CD15 staining, and should be the primary target for treatment in experimental animals (Poster at SPNO meeting in May). Currently, spindle cells are functionally evaluated by mitochondrial volume studies for future development of therapeutic tactics. METHODS: 1. C6 cells were cultured in MEM solution, and morphological cell changes were studied with and without temozolomide (TMZ) treatment. 2. Mitochondrial volume of C6 cell in these conditions was measured by mitochondrial mass specific fluorescence probe. 3. C6 cells were implanted into rat's brain and observed the growth in the normal brain tissue. RESULTS: 1. Spindle cells grew in early period, and formed syncytiums. As syncytiums multiplied, mitotic cells began to appear, and typical GBM features developed. During TMZ treatment, multiform cells were mostly destroyed, while spindle cells survived. 2. By TMZ treatment, the number of survived C6 cells decreased, but the volume of mitochondria per unit of C6 cells increased, as the concentration of TMZ increased. 3. The same cell growth pattern was identified in implanted tumor, as seen in cultured cells growth. DISCUSSION AND CONCLUSION: 1. Histologically CD15-positive spindle cells have much higher resistance for survival against TMZ than fully developed multiform cells. 2. Increased mitochondrial volume in survived C6 cells is likely related to metabolic activation of spindle cells under TMZ treatment. 3. The control of mitochondrial hyperactivity of C6 cells should be one of the important means for GBM treatment in experimental GBM, and probably in humans.
Interassociation Consensus Statement on Cardiovascular Care of College Student-Athletes
Authors: Brian Hainline, Jonathan A. Drezner, Aaron Baggish, Kimberly G. Harmon, Michael S. Emery, Robert J. Myerburg, Eduardo Sanchez, Silvana Molossi, John T. Parsons, Paul D. Thompson
Journal: Journal of the American College of Cardiology (2016)
Lack of Effect of a High-Fiber Cereal Supplement on the Recurrence of Colorectal Adenomas
Authors: David S. Alberts, María Elena Martínez, Denise J. Roe, José M. Guillén-Rodríguez, James R. Marshall, J. Barbara van Leeuwen, Mary E. Reid, Cheryl Ritenbaugh, Perla A. Vargas, A.B. Bhattacharyya, David L. Earnest, Dianne Parish, Kris Koonce, Lianne Fales, Richard E. Sampliner
Journal: New England Journal of Medicine (2000)

The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas.We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments.Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93).As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.
Plasma Clotting Factors in Chronic Hepatocellular Disease
Authors: Samuel I. Rapaport, Sara B. Ames, Solveig Mikkelsen, Joseph R. Goodman
Journal: New England Journal of Medicine (1960)

The experience of caring for a cirrhotic patient whose prothrombin time was only moderately prolonged but who bled profusely after tooth extraction prompted us to compare prothrombin times with more specific clotting-factor assays in a group of patients with chronic hepatocellular disease (primarily Laënnec's cirrhosis). We wished to learn if prothrombin times fully reflect the severity of the individual clotting-factor defects that arise in such patients and, secondly, if these defects are severe enough to account for the great difficulty frequently encountered in stopping gastrointestinal bleeding in cirrhotic patipatients.MethodsThe Quick test, the prothrombin-proconvertin (P and P) test, the . . .
The Genetic Heterogeneity of Hemophilia B
Authors: Paul E. Brown, Cecil Hougie, Harold R. Roberts
Journal: New England Journal of Medicine (1970)

At least three genetic variants of hemophilia B exist: a variant with positive crossreacting material associated with a normal oxbrain prothrombin time; one with positive material but with prolonged ox-brain prothrombin time; and one with undetectable or reduced material associated with a normal ox-brain prothrombin time. All hemophilia BM variants appear to have positive cross-reacting material, but it is not clear whether all patients with positive material are identical to the hemophilia BM variants. Our studies indicate that they are not identical since some patients with positive cross-reacting material have normal ox-brain prothrombin time. The data suggest that hemophilia B is genetically heterogeneous.
Acute Obstruction of the Small Intestine
Authors: William R. Moses
Journal: New England Journal of Medicine (1946)

HOSPITALS devoted to the care of charity patients are not usually expected to be sources of low mortality rates. The reasons for this, which are many and varied, include the generally poor state of nutrition among these patients, their advanced physiological age as compared with the chronological age and, possibly most important of all, the educational deficiencies that bring them to medical care late in the course of their diseases. When these handicaps are compounded with an illness that in the best of hands carries a formidable mortality, depressing mortality figures are to be expected.Before what might be called . . .
NSC 290205-based therapy in colon 38 adenocarcinoma in combination with adriamycin (ADR)
Authors: A. Papageorgiou, E. Stergiou, I. Stergiou, G. Geromichalos, A. Fassas
Journal: Journal of Clinical Oncology (2008)

15104 Background: NSC 290205 (A) is a hybrid synthetic antitumor ester which combines a D-lactam derivative of androsterone and nitrogen mustard. In this study cyclophosphamide in the standard CHOP chemotherapeutic regimen was replaced with NSC 290205 (AHOP) and the efficacy of these regimens against murine colon 38 adenocarcinoma was compared. Methods: Colon 38 adenocarcinoma was used in this study. It was purchased from NCI (USA). Tumor was grown in C57 Bl mice and was transplanted subcutaneously with puncture in the inguinal region. The amount of the transplanted graft was 40–50 mg fragment. The acute toxicity of the compounds was determined and the lethal dose LD10 was used as a therapeutic dose. The antitumor activity was assessed from the inhibition of tumor growth by volume in cm3 and T/C % oncostatic parameter, according to the protocol of the experimental evaluation of anticancer drugs of the NCI. Treatment was given as an intermitted dose on days 1, 5, 9. Results: Results show that treatment with steroidal derivative (A) or cyclophosphamide (C) produced almost equal borderline activity. Moreover, both CHOP and AHOP regimens showed significant and comparable antitumor effect. AHOP caused the maximum effect inhibiting tumor growth by 68.5 % and producing T/C values of 211%. CHOP was less effective producing 47.1% inhibition of tumor growth and T/C 174%. Conclusions: Although the treatment of colon adenocarcinoma with cyclophosphamide or NSC 290205 yielded equivalent results, AHOP showed higher antitumor potency than CHOP. It is very likely that the D-lactamic steroid (androstan) alkylator for A, containing the amide group -NH-CO-, combined with adriamycin which intercalates between DNA base-pairs, is the explanation for the higher activity of AHOP as compared to CHOP. Preclinical research supports that the aza-steroidal alkylator NSC 290205 demonstrates favorable acute and sub acute toxicity, as well as superior antitumor activity which in combination with adriamycin against colon 38 adenocarcinoma justifies further clinical studies. No significant financial relationships to disclose.
Abstract 333: Maturation Of ß-adrenergic Receptor (ß-AR) Signaling In Human Induced Pluripotent Stem Cell-derived Cardiomyocytes (hipsc-cms)
Authors: Gwanghyun Jung, HaoDi Wu, Giovanni Fajardo, Kazuki Kodo, Joseph Wu, Daniel Bernstein
Journal: Circulation Research (2014)

hiPSC-CMs are a novel model system for cardiovascular diseases, with proven utility in cardiac channelopathies, however, how accurately hiPSC-CMs recapitulate the signaling pathways regulating contractility and remodeling of adult cardiomyocytes remains to be determined. As ß-ARs are key regulators of both contractility and remodeling, we examined ß-AR signaling at different stages of hiPSC-CM maturation. hiPSCs, derived from healthy controls, were studied at 0, 14, 30, and 60d after cardiac induction under isoproterenol (ISO) stimulation ± ß1 or ß2 antagonists. Flag-tagged ß-ARs were transfected into hiPSC-CMs for trafficking studies. Compared to the ß1:ß2 ratio of 70:30 in adult ventricular cardiomyocytes, ß2-AR expression was higher in early stage (d14-30) hiPSC-CMs; ß1-ARs increased with maturation (d14-d60), reflective of the normal developmental pattern. Downstream signaling also matured from d14-60, regulating both function (PLB and TnI) and remodeling (ERK). The majority of cAMP generation and PKA activation at d30 was through ß2-ARs; by d60-90, ß1-AR signaling contributed equally. In contrast to studies in rodent cells, ß2-ARs did not show compartmentalization of PKA signaling. Between d30-60, components of the SR (RYR, PLB and CSQ) and caveolae (Cav3) matured, suggesting development of functional compartmentalization machinery. Finally, hiPSC-CMs showed ß2-AR downregulation and internalization in response to ISO, an important component of the normal cardiomyocyte response to pathologic stimulation. Thus, hiPSC-CM ß-AR signaling matures with time after cardiac induction, recapitulating many of the features of post-natal and several of adult cardiomyocytes. hiPSC-CM models of human cardiomyopathies are a reasonable platform for studying ß-AR signaling. Furthermore, the maturation of ß-AR signaling can be used as a read-out for hiPSC-CM maturity.
The Effect of an Endothelin-Receptor Antagonist, Bosentan, on Blood Pressure in Patients with Essential Hypertension
Authors: Henry Krum, Reuven J. Viskoper, Yves Lacourciere, Michael Budde, Vincent Charlon
Journal: New England Journal of Medicine (1998)

Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan.
Mithramycin in the Treatment of Disseminated Testicular Neoplasms
Authors: John H. Brown, B. J. Kennedy
Journal: New England Journal of Medicine (1965)

DISSEMINATED testicular neoplasms other than seminoma have not been effectively controlled by radiologic therapy or chemotherapeutic agents. In an evaluation of these tumors Whitmore1 stated that chemotherapy had no practical value in most cases because of the brevity or incompleteness of the remissions obtained. There were only 5 effective remissions in 100 treated patients. A recently introduced antibiotic, mithramycin, has demonstrated striking antitumor activity in testicular neoplasms, especially the embryonal-cell carcinoma.Except for seminoma, there is a consistently poor prognosis for testicular neoplasms of germinal origin. Dixon and Moore2 reviewed 990 testicular tumors in the United States Army population from . . .
Syndrome of Bilateral Pheochromocytoma, Medullary Thyroid Carcinoma and Multiple Neuromas
Authors: R. Neil Schimke, William H. Hartmann, Thaddeus E. Prout, David L. Rimoin
Journal: New England Journal of Medicine (1968)

Original Article from The New England Journal of Medicine — Syndrome of Bilateral Pheochromocytoma, Medullary Thyroid Carcinoma and Multiple Neuromas — A Possible Regulatory Defect in the Differentiation of Chromaffin Tissue
Loss of Vision in Gaucher's Disease and Its Reversal by Enzyme-Replacement Therapy
Authors: Stephan vom Dahl, Claus Niederau, Dieter Häussinger
Journal: New England Journal of Medicine (1998)

To the Editor: We report on an unusual manifestation of Gaucher's disease that responded to enzyme-replacement therapy. A 42-year-old woman with known type 1 Gaucher's disease who was homozygous fo...
A New Approach to the Study of Psychogenic Disturbances
Authors: F. W. Barnes, G. E. Vaillant, L. L. Havens, J. O. Barnhill
Journal: New England Journal of Medicine (1970)

Psychiatry suffers from many misunderstandings and from some of its own excursions into various schools of thought. It needs to become as realistic and meaningful as possible in terms of the doctor's grasp of the inner experience of the patient. Also, a resourceful, resilient, multifaceted approach is sought after by many. Toward these goals a realistic encounter with the primary material of human nature in its many vagaries has been designed through a specially developed use of dramatic works. As background for this, an integrated approach was used to assess the contribution of each school of thought to the development of psychiatry and its present-day potential.
P68 Phenotyping Infection Associated Asthma: A Case-Control Study
Authors: S Natarajan, R Free, A Wardlaw, S Siddiqui
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Asthmatics experiencing recurrent infective exacerbations, resembling a bacterial bronchitis, are often started on prophylactic antibiotics but this phenotype of asthma is not well understood. We sought to: a) compare asthmatics with and without recurrent infections using a case-control approach and b) phenotype asthmatics with recurrent infections to evaluate the heterogeneity within this population. <h3>Methods</h3> We reviewed Leicester difficult asthma clinic letters within two calendar years (01/01/2013–31/12/2014) and utilised an asthma database to identify matched (age, sex, BMI and GINA treatment step) controls. Case definition: a clinician diagnosis of asthma and ≥2 respiratory tract infections/preceding year requiring oral antibiotics or on prophylactic antibiotics. Control definition: a clinician diagnosis of asthma, no evidence of recurrent infections and not prescribed prophylactic antibiotics. A 1:1 case-control ratio was used. 71 cases and 71 controls were identified. The antibiotic use, physiology, CT imaging, immunoglobulins and pneumococcal serotype meta­data were evaluated. Model based cluster analysis was performed to phenotype the cases with no <i>a priori</i> assumption made on the number of clusters. Age, sex, age of onset, sputum eosinophil count and Juniper Asthma Control Score were used as the input variables (Am J Respir Crit Care Med.2008 Aug 1;178(3):218–24). <h3>Results</h3> The cases were predominately female (69%), obese with recurrent infections (mean:4.25/preceding year) and had an impaired asthma-related quality life compared to controls (p = 0.0285). Cluster analysis identified three groups. Cluster 1: male, eosinophilic, on oral corticosteroids with a low IgM, had poor lung function and bronchial wall thickening and bronchiectasis on CT. Cluster 2: female with a blood neutrophilia and preserved lung function. Cluster 3: female, non-atopic with impaired asthma control, a low IgG and air trapping on CT. 63.3% of patients on prophylactic antibiotics (n = 49) had a reduction in infective exacerbation frequency. The proportion of patients on antibiotics within each cluster and response was similar. <h3>Conclusion</h3> Three subphenotypes of asthma with recurrent infections have been identified. Further immunpathological studies to evaluate the mechanism of infection in each subphenotype, the host microbiome and response to antimicrobials are required.
Interpreting results of observational research
Authors: J Slattery, I C McManus
Journal: BMJ (1994)

obesity represents one of the worst risks for an anaesthetist and also complicates the whole obstetric episode.Its incidence is rising for various reasons, and the problem is not being addressed.Anaesthetists can improve their practice, as recommended in the report, but cannot alone counter the consequences ofpatients' self abuse.The health education message should not be blurred and needs to be directed in particular at younger patients, such as those in the obstetric population.The findings of the report represent an opportunity to promote the present benefits of weight reduction that should not be missed.
Idiopathic Cholestasis of Pregnancy
Authors: Mary Jeanne Kreek, Elliot Weser, Marvin H. Sleisenger, Graham H. Jeffries
Journal: New England Journal of Medicine (1967)

The possible role of estrogens in the pathogenesis of pruritus gravidarum and cholestatic jaundice of pregnancy was examined. 13 women of childbearing age who had been studied during at least 1 of their previous pregnancies were the subjects in the investigation. 7 of these women had symptoms during pregnancy; 3 had pruritus gravidarum and 4 cholestatic jaundice. 6 women who had been free of symptoms during pregnancy served as controls. A dose of .5 mg twice daily was given to 10 subjects; 2 received .5 mg daily, and 1, .5 mg, 3 times a day. 10 subjects recieved estrogen for 2 weeks, but in 3 who had been symptomatic during pregnancy, the development of severe symptoms or jaundice necessitated earlier cessation of hormone administration. In women with normal pregnancies the only symptom during estrogen treatment was mild early-morning nausea and liver function was not significantly impaired. In those with a history of itching or jaundice during pregnancy, ethinyl estradiol administration precipitated symptoms similar to those experienced during pregnancy. In these women liver function was significantly impaired by estrogen.
Association Of More Than One B Cell Clone Arises In Any Type Of Leukemic Chronic B Cell Disorder
Authors: Gregory Lazarian, Herve Roudot, Riham Farrah, Chadi Al Nawakil, Remi Letestu, Fanny Baran-Marszak, Virginie Eclache, Marouane Boubaya, Alain Delmer, Vincent Levy, Florence Cymbalista
Journal: Blood (2013)
Caspase-mediated proteolytic processing of Stat3: Preliminary cellular and functional analysis
Authors: James W. Darnowski, Frederick A. Goulette, Ying-Jie Guan, Y. Eugene Chin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Caspases are associated with apoptosis but have been reported to play key roles in protein processing under non-apoptotic conditions. Upon phosphorylation, STAT (signal transducer and activator of transcription) proteins regulate transcription and affect multiple cellular processes. We reported that Stat3 expression was reduced following caspase activation and biochemical analysis, conducted under cell-free conditions, revealed that caspases directly cleave this protein. We now report studies to (i) map the location of caspase cleavage sites in Stat3, and (ii) evaluate the impact of Stat3 proteolysis on transactivation. In whole cells, staurosporin (STS, 12h, 1uM) exposure resulted in Stat3 cleavage and the generation of several fragments detected with C- or N-terminal Stat3 antibodies with apparent molecular weights >40kD. Both Stat3 cleavage and fragment formation were blocked by the caspase inhibitor zVAD-FMK (40uM). Next, a series of c-Myc tagged Stat3 truncation mutants (corresponding to amino acids 1-130, 1-320, 1-688, 588-770 and 1-770) were expressed in HEK293T cells. Transfected cells then were exposed to 1uM STS (12h) and fragment cleavage patterns analyzed by Western-blot. This revealed that, with the exception of the small N-terminal (1-130) mutant, all Stat3 fragments were cleaved following STS exposure, a finding consistent with the identification of multiple caspase recognition sites in the sequence of Stat3. These findings were supported by cell-free experiments where exposure of purified full-length Stat3 to a mixture of caspases 1-10 (37ox90 mins) resulted in Stat3 disappearance that also corresponded with the formation of a fragment in the 50kD range. Experiments to sequence and identify fragment(s) generated under cell-free conditions are planned. Analysis of the functional consequence of Stat3 proteolysis employed Stat3 driven luciferase reporter assays. Initial studies examined the effect of STS (+/-zVAD) on reporter activity and revealed that STS significantly reduced luciferase activity, an effect partially blocked by zVAD and correlated with STS-induced reductions in pY705-Stat3 expression. Parallel experiments assessed the impact of Stat3 fragment expression on reporter activity in HEK293T cells under non-apoptotic conditions and revealed that the expression of all Stat3 fragments examined, except one corresponding to amino acids 1-688, slightly increased (<150%) reporter activity. In contrast, expressing the 1-688 fragment increased reporter activity ∼5-fold. These findings reveal that Stat3 contains multiple caspase cleavage sites and that caspase-mediated Stat3 proteolysis can modulate Stat3 signaling under apoptotic and non-apoptotic conditions (supported by CA-102128 and Rhode Island Hospital).