tbuckley/cabot-search huggingface dataset:
Perfusion and Contractile Reserve in Chronic Dysfunctional Myocardium: Relation to Functional Outcome After Surgical Revascularization
Authors: Jeroen J. Bax, Don Poldermans, Arend F. L. Schinkel, Eric Boersma, Abdou Elhendy, Alexander Maat, Roelf Valkema, Eric P. Krenning, Jos R. T. C. Roelandt
Journal: Circulation (2002)

Chronic dysfunctional but viable myocardium may exhibit contractile reserve and/or intact perfusion. Segments with intact perfusion without contractile reserve are frequently observed inpatients with ischemic cardiomyopathy. The clinical relevance of this observation is unclear; in particular, the functional outcome after revascularization is unknown. Thus, contractile reserve (using low-dose dobutamine echocardiography) and perfusion (using resting (99m)Tc tetrofosmin) were evaluated in 114 patients with ischemic cardiomyopathy and the findings were related to functional outcome (9 to 12 months after revascularization).Patients (n=114) with ischemic cardiomyopathy undergoing surgical revascularization were evaluated for perfusion (using (99m)Tc tetrofosmin) and contractile reserve (using low-dose dobutamine echocardiography). Contractile function (two-dimensional echocardiography) was assessed before and 9 to 12 months after revascularization. In the 1 336 dysfunctional segments, perfusion was preserved in 51% of the segments and contractile reserve in 31% (P<.05); 47% of the segments with perfusion did not exhibit contractile reserve. The majority (66%) of segments with recovery of function postrevascularization had intact perfusion and contractile reserve; the majority (58%) of segments without functional recovery lacked both perfusion and contractile reserve. Interestingly, 22% of segments with functional recovery and 25% of segments without functional recovery showed intact perfusion without contractile reserve.Segments with intact perfusion/contractile reserve have a high likelihood of recovery of function postrevascularization; segments without contractile reserve/perfusion have a low likelihood of recovery and segments with intact perfusion without contractile reserve have an intermediate likelihood of recovery.
Cryptococcal virulence: beyond the usual suspects.
Authors: A. P. Mitchell
Journal: Journal of Clinical Investigation (2006)

In this issue of the JCI, the observation of the altered pathogenicity of a Cryptococcus neoformans glucosylceramide (GlcCer) mutant shines new light on the initiation of cryptococcal infection. Rittershaus and colleagues demonstrate that the cell surface glycosphingolipid GlcCer is essential for the fungus to grow in the extracellular environments of the host bloodstream and alveolar spaces of the lung, which, in contrast to the acidic intracellular environment of macrophages, are characterized by a neutral pH (see the related article beginning on page 1651). Their findings establish an unexpected connection between this glycosphingolipid and the fungal responses to physiological CO2 and pH. They also focus new attention on the therapeutic potential of anti-GlcCer antibodies found in convalescent sera.
Abstract P1-01-10: A preoperative PET/MR imaging for diagnosing malignant axillary lymph nodes in women evaluated for breast cancer
Authors: Kyung Jun Yeu, Jeong Yeong Park, Jung Eun Choi, Su Hwan Kang, Eun-Jung Kong, Ihn-Ho Cho, Soo Jung Lee
Journal: Cancer Research (2015)

Abstract Objective: We determined whether and how malignant node could be diagnosed preoperatively with simultaneous PET/MR imaging. Materials and methods:Two hundred thirty-six consecutive women with breast cancer were recruited to undergo preoperative PET/MR imaging. 52 patients were excluded; 31 DCIS, 7 neoadjuvant chemotherapy and 14 previous excisional biopsy. Thus, 184 women (51.9 ±10.2 years old) were included. Axial T1w without fat saturation, contrast enhanced image and diffusion-weighted images with simultaneous acquired PET images were analyzed by nuclear medicine physicians who were blinded the histologic findings. Visual FDG avidity, long axis and cortical thickness of axillary lymph node (ALN), morphologic feature-loss of fat hilum, cortical thickening, round shape or irregular shape- and ADC value were analyzed in most suspicious ALNs. Results:In total, 70 patients (15 patients have only micrometastasis) exhibited ALN metastasis. Mean size of breast mass was 2.1 ±1.5 cm. Macrometastatic ALN showed high FDG uptake, longer axis, thicker cortex, more frequent morphologic abnormalities, higher signal intensity at DWI and higher ADC values with statistical significance. No significant difference between micrometastatic ALN and benign ALN in PET/MR imaging. With pathologic diagnosis as the reference standard, the sensitivity, specificity and accuracy of PET for determining ALN metastasis were 84%, 58% and 68%, respectively. Those are 77%, 84% and 82% in considering both PET with morphologic change and 81%, 66% and 72% in considering PET, morphologic change and DWI, respectively. Conclusion:PET/MR imaging techniques showed high accuracy in the preoperative evaluation of axillary status in patients with breast cancer. Additional information by DWI is unlikely to be useful in predicting metastatic ALN. Citation Format: Kyung Jun Yeu, Jeong Yeong Park, Jung Eun Choi, Su Hwan Kang, Eun-Jung Kong, Ihn-Ho Cho, Soo Jung Lee. A preoperative PET/MR imaging for diagnosing malignant axillary lymph nodes in women evaluated for breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-10.
Cerebellar toxicity with high-dose cytosine arabinoside.
Authors: R H Herzig, J D Hines, G P Herzig, S N Wolff, P A Cassileth, H M Lazarus, D J Adelstein, R A Brown, P F Coccia, S Strandjord
Journal: Journal of Clinical Oncology (1987)

CNS dysfunction, especially impaired cerebellar function, is the dose-limiting toxicity associated with high-dose cytosine arabinoside, which precludes doses of greater than 48 g/m2. Four hundred eighteen patients between the ages of 2 and 74 years with leukemia or lymphoma received 36 to 48 g/m2 cytosine arabinoside either alone or with anthracycline antibiotics, 4'-(9-acridinylamino) methane sulfon-m-anisidine (m-AMSA), or total body irradiation. In only 35 of 418 patients (8%) did severe cerebellar toxicity develop; it was irreversible or fatal in four (1%) patients. The age of the patient was a critical factor in the incidence of severe cerebellar toxicity. Patients greater than 50 years old had a statistically significant greater incidence of cerebellar toxicity compared with younger patients (26/137, 19%, v 9/281, 3%; P less than .0005, chi 2). Neither the diagnosis, disease status, sex, nor the regimen altered the incidence of severe cerebellar toxicity (when corrected for age). A second course of high-dose cytosine arabinoside, administered to 62 patients, did not increase the incidence of severe cerebellar toxicity, which occurred in five (8%) of these patients. Two of the five patients had severe toxicity with the initial course. Of the 60 patients with no antecedent cerebellar dysfunction, three (5%) had severe toxicity with the second course: one of 41 patients were less than 50 years old; two of 19 patients were greater than or equal to 50 years. Since the occurrence of severe cerebellar dysfunction is greatly affected by age, reduced doses of high-dose cytosine arabinoside should be given to patients greater than 50 years old, and methods for reducing the cerebellar toxicity should be investigated in these patients.
Role of endogenous peripheral opioid mechanisms in renal function.
Authors: G F DiBona, S Y Jones
Journal: Journal of the American Society of Nephrology (1994)

The role of endogenous peripheral opioid mechanisms in renal function was evaluated in normotensive and hypertensive rats. Intravenous naloxone methylbromide, a quaternary opioid antagonist with limited ability to cross the blood-brain barrier, was used to inhibit endogenous peripheral opioid mechanisms. In normotensive rats, the opioid antagonist impaired the normal renal adaptive response to dietary sodium restriction. In spontaneously hypertensive rats, the opioid antagonist did not affect the renal functional responses to acute environmental stress. These data indicate that, depending on the nature of the intervention, a role for endogenous peripheral opioid mechanisms in the renal function responses may be identified.
Computed tomography and flexible bronchoscopy techniques for assessment of tracheomalacia in children
Authors: Gerasimos Kremmydas, Vasilios Grammeniatis, Konstantinos Douros, Michaeil Anthracopoulos, Marios Papadopoulos, Argyro Mazioti, Konstantinos Priftis, Efthimia Alexopoulou
Journal: European Respiratory Journal (2012)

Background/Aims : Tracheomalacia is not an unusual diagnosis in pediatric respiratory clinics. We tried to find the most suitable approach to the evaluation and diagnosis of “brassy”,“ barking” cough.   Methods: We performed a dynamic helical CT scan (HCT) in 15 patients (aged 5 to 14 years) suspected of tracheomalacia on the grounds of clinical symptoms (barking cough ± recurrent chest infections). All patients underwent flexible bronchoscopy (FB) under deep sedation and spontaneously breathing. Four children who suffered from various parenchymal lung diseases but no “ barking”  cough were used as controls. The ratio of anteroposterior/tranverse diameter was measured in the thoracic inlet and the carina level, in full inspiration and end expiration.   Results:  Flexible bronchoscopy confirmed the existence of tracheomalacia in all patients; in 5 out of 15, lesions were located in the upper part of the trachea as shown by FB. HCTs showed localized narrowing of the  intrathoracic trachea in 7 patients.  The measured ratios were lower in the patient group as follows: at the carina level in inspiration 0.81±0.08 and 0.97±0.08, p=0.001, and at expiration 0.66±0.13 and 0.89±0.12, p   Conclusions:  FB is valuable in the assessment of patients with extrathoracic tracheomalacia since HCTs cannot be recommended as a safe approach (radiation of the thyroid). However, CT scans provide a more accurate estimation of endothoracic tracheomalacia as it is not influenced by the effects of general anaesthesia.
Studies on poison ivy.
Authors: GILLES DUPUIS
Journal: British Journal of Dermatology (1979)

The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy.
NecroX‐5 suppresses IgE/Ag‐stimulated anaphylaxis and mast cell activation by regulating the <scp>SHP</scp>‐1‐Syk signaling module
Authors: X. Li, O. Kwon, D. Y. Kim, Y. Taketomi, M. Murakami, H. W. Chang
Journal: Allergy (2015)

IgE/Ag-stimulated mast cells release various pro-allergic inflammatory mediators, including histamine, eicosanoids, and pro-inflammatory cytokines. NecroX-5, a cell permeable necrosis inhibitor, showed cytoprotective effects in both in vitro and in vivo models. However, the anti-allergic effect of NecroX-5 has not yet been investigated. The aims of this study were to evaluate the anti-allergic activity of NecroX-5 in vivo and to investigate the underlying mechanism in vitro.The anti-allergic activity of NecroX-5 was evaluated in vitro using bone marrow-derived mast cells (BMMCs) and IgE receptor-bearing RBL-2H3 or KU812 cells and in vivo using a mouse model of passive anaphylaxis. The levels of histamine, eicosanoids (PGD2 and LTC4 ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured using enzyme immunoassay kits. The mechanism underlying the action of NecroX-5 was investigated using immunoblotting, immunoprecipitation, and gene knockdown techniques.NecroX-5 markedly inhibited mast cell degranulation and the synthesis of eicosanoids, TNF-α, and IL-6 by suppressing the activation of Syk, LAT, phospholipase Cγ1, MAP kinases, the Akt/NF-κB pathway, and intracellular Ca(2+) mobilization via the activation of phosphatase SHP-1. Oral administration of NecroX-5 effectively suppressed mast cell-dependent passive cutaneous and systemic anaphylactic reactions in a dose-dependent manner.NecroX-5 might be a potential candidate for the development of a novel anti-allergic agent that suppresses IgE-dependent mast cells signaling.
Degarelix monotherapy versus luteinizing hormone-releasing hormone (LHRH) agonists plus antiandrogen flare protection in the treatment of men with advanced prostate cancer.
Authors: Bertrand Tombal, Jan-Erik Damber, Anders Malmberg, Bo-Eric Persson, Laurence Klotz, Peter Iversen
Journal: Journal of Clinical Oncology (2014)

86 Background: Short-term antiandrogen (AA) flare protection is used to counter the testosterone surge associated with luteinising-hormone-releasing hormone (LHRH) agonist therapy. Degarelix, a gonadotrophin-releasing hormone antagonist, does not cause testosterone surge. Data from two phase III trials have been used to compare the one year efficacy of degarelix monotherapy versus combined agonist plus AA flare protection. Data has reported testosterone surge in agonist patients despite AA therapy, as well as improved prostate-specific antigen (PSA) progression-free survival (PFS) and lower mortality in degarelix patients. Here we focus on PSA PFS outcomes and serum alkaline phosphatase (S-ALP) in high risk patients (metastatic disease or PSA more than 50 ng/mL). Methods: Data were pooled from two randomised, one-year studies; CS21 compared monthly degarelix with leuprolide and CS35 compared 3 month formulations of degarelix and goserelin. AA was administered in the agonist groups at the investigator’s discretion. Analyses were performed by the Kaplan-Meier method and Log-rank test (probability of PSA PFS), Cox regression (adjusted hazard ratios [HR] for PSA PFS failure) and repeated measures ANCOVA (S-ALP). Results: Nine hundred seventy four patients received degarelix and 69 patients agonist plus AA. The agonist plus AA group contained a higher proportion of patients with Gleason score 7 to 10, metastatic disease, or baseline PSA more than 50 ng/mL compared with the degarelix group. Cox regression was used to account for these baseline differences. PSA PFS failure rate for metastatic patients and those with baseline PSA more than 50 ng/mL was significantly lower with degarelix than with agonist plus AA (HR=0.516, p=0.0198 and HR=0.490, p=0.0077, respectively). S-ALP levels in metastatic patients and those with baseline PSA more than 50 ng/mL during the year of treatment were significantly lower with degarelix (p=0.0025 and 0.0005, respectively). S-ALP fell below baseline by 2 months or less with degarelix and 7 months or less with agonist plus AA. Conclusions: This pooled analysis indicates LHRH agonist plus AA therapy flare protection may not achieve similar disease control as degarelix monotherapy during the first year of therapy in patients at high risk of symptomatic disease progression.
Adriamycin-Induced Chromosome Aberrations in Human Fibroblasts 2
Authors: Yvonne L. Newsome, L. Gayle Littlefield
Journal: JNCI Journal of the National Cancer Institute (1975)

Adriamycin (AM) induced chromosome lesions and cell division delay in human foreskin fibroblasts. Cells treated with 0.01, 0.03, and 0.05 µg AM/ml culture medium for 1 hour and evaluated 5–12 hours post treatment exhibited a wide spectrum of cytogenetic injuries, ranging from moderately damaged meta phases with predominantly simple chromatid-type lesions to heavily damaged meta phases with chromosome stickiness and fragmentation. In moderately damaged metaphases that could be scored for specific types of aberrations, we observed a paucity of chromatid exchanges and chromosome-type lesions even in cultures having a very high frequency of breakages. Further, the distribution of breaks among chromosomes within groups A-G appeared to be random, which suggested that the drug does not show breakage specificity in human fibroblasts. The number of heavily damaged metaphases increased with an increase in concentration of AM and with longer periods of recovery.
Culture of a Cell Line (NCLP-6) Derived From a Hepatocarcinoma Induced In &lt;italic&gt;Macaca mulatta&lt;/italic&gt; by &lt;italic&gt;N&lt;/italic&gt;-Nitrosodiethylamine
Authors: C. J. Dawe, Jacqueline Whang-Peng, W. D. Morgan, R. W. O'Gara, Margaret G. Kelly
Journal: JNCI Journal of the National Cancer Institute (1968)

A continuous cell culture line was established from a hepatocarcinoma induced in a rhesus monkey by N-nitrosodiethylamine. Results of intracerebral transplantation of cells of this line were described previously (J Nat Cancer Inst 39: 153–169, 1966). Line NCLP-6 has now been in continuous culture for 3½ years, through over 70 subcultures, and has been preserved frozen for as long as 28 months. A variant subline, NCLP-6-F, evolved from the parent line, NCLP-6-E, at the 26th subculture. The F subline grows more rapidly, has fibroblastoid morphology, and lacks significant cytoplasmic alkaline phosphatase. The E subline retains epithelium-like morphology and exhibits alkaline phosphatase activity in granular distribution in the cytoplasm. When retained in culture vessels after monolayer formation is complete, the E subline forms simple micropapillary and polypoid structures, with palisading of epithelium on the outer layers of cell masses. In karyotype, both the E and F sublines are subtriploid and both have a large percentage of cells with 2 marker chromosomes: 1 large metacentric and 1 small acrocentric. However, the modal number of the F subline is 56, while that of the E subline is 59. The E subline is characterized by trisomy of chromosome #20, which is disomic in subline F.
Tumorigenicity of human fibrosarcoma HT1080 cells expressing protein PA19 in either secreted or non-secreted form, as evaluated in athymic mice.
Authors: Igor Zlatkin, Sandra O’Reilly, Veronica M. Maher, J. Justin McCormick
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5571 

A profilin-like protein, PA19, common to many protozoa, was recently found to be a ligand for toll-like receptor TLR12 [Science,308,1626–1629 (2005)]. It is able to activate dendritic cells (DCs) in vitro and, when injected intraperitoneally (I.P.) in mice, to drastically reduce tumor formation by murine sarcoma S-180 [Int. J. Cancer, 114, 756–765 (2005)]. We have found that when PA19 is expressed as a transgene in human HT1080 fibrosarcoma cells, tumor formation in athymic mice is reduced [Proc. Amer. Assoc. Cancer. Res., 46, 3365 (2005)]. A report by Janke et al., (2000) showed that expression of the profilin 1 (PFN1) gene as a transgene in the human breast cancer cell line, CAL51, reduced the tumor-forming ability of these cells. This effect is believed to be the result of PFN1's interference in microfilament organization via its actin binding site [Mol. Biol. Cell, 15, 1600–1608 (2004)]. To determine whether the tumor suppressor activity of PA19 involves a mechanism similar to PFN1, we compared tumor formation by HT1080 cell lines, expressing PA19 either in an intracellular form (nPA19), or in a secreted form (sPA19). Eight cell lines stably-expressing nPA19, six expressing sPA19, five expressing an empty vector, and the parent cell line were compared. All were found to have similar growth characteristics in vitro . The expression of PA19 in the cell lines was quantified by determining the ability of the cell lysates, or conditioned media to activate DCs in in vitro assay. Mice were injected subcutaneously with 1 × 106 cells in the right or left rear flank. Blood analysis of mice injected with cell lines expressing sPA19 showed its presence as well as elevated levels of IL-12. All sites injected with parent line, or empty vector cell lines began developing tumor within 10 days after injection. On average, sites injected with cell lines expressing either form of PA19 were tumor-free for a longer period and the tumors grew more slowly than at the sites injected with the vector controls. All mice injected with cells carrying the empty vector were dead at  150 days and 40% expressing sPA19 remained tumor free for >150 days. Complete remission was observed in three mice (one injected with a cell line expressing nPA19, and two expressing sPA19). The sPA19 cell lines were less tumorigenic than the nPA19 cell lines as judged by tumor size (p=0.012) and the rate of tumor growth (p=0.027). These results support the hypothesis that the mechanisms of tumor suppression by PA19 and PFN1 are different. None of the surviving mice injected with the cell lines expressing sPA19 showed sign of immunity towards the secondary I.P. injection of the parent HT1080 cells indicating that there is no long-lasting protection involved in the observed tumor suppression mechanism. (Supported by NIH CA98305 to JJM).
Natural Occurrence of Lymphocytes Showing Cytotoxic Activity to BALB/c Radiation-Induced Leukemia RL ♂ 1 Cells
Authors: F. Sendo, T. Aoki, E. A. Boyse, C. K. Buafo
Journal: JNCI Journal of the National Cancer Institute (1975)

Spleen cells from untreated young male and female C57BL/6 and C58 mice and of male C3H/He mice showed cytotoxic activity in vitro against BALB/c X-radiation-induced leukemia RL male 1 cells by 51Cr-releasing lymphocyte-mediated cytoxicity (LMC) tests, but old mice of these strains lacked LMC activity. In contrast, spleen cells from male and female AKR, BALB/c, and DBA/2 mice, and from female C3H/He mice had no appreciable LMC activity. The proportion of active cells in spleens from young (C57BL/6 times BALB/c)F1 or reciprocal hybrid mice was higher in females than in males. The specificity of the LMC reaction of RL male 1 cells, determined by LMC inhibition assays, was somewhat different from that of previously reported serologic X.1 tests. Thus the antigen detected by LMC has been tentatively designated X.1'. The main effector cells in this system were uncharacterized cells not adherent to glass surfaces or nylon-wool columns. These findings in RL male 1 leukemia extend the evidence for the presence of naturally occurring LMC. With the single unexplained exception of strain C3H/He, the LMC activity against RL male 1 cells, exhibited by untreated mice of various strains, corresponded with a previous classification of mouse strains immunologically as X.1 responders or as X.1 nonresponders according to their ability to reject X.1-positive leukemia cells.