tbuckley/cabot-search huggingface dataset:
Some Observations on the Clinical Approach to Metabolic Acidosis
Authors: Mitchell L. Halperin, Kamel S. Kamel
Journal: Journal of the American Society of Nephrology (2010)

The first step in the clinical approach to patients with metabolic acidosis is to deal with emergencies and to anticipate and prevent dangers associated with therapy. The traditional clinicalanalysisforthepresenceofmetabolicacidosissuffersfrom a number of limitations that at times hinders one’s ability to reach a proper diagnosis. Our aim here is to raise awareness of some of the nuanced difficulties and illustrate why other considerations add value. In patients with metabolic acidosis, analyses based on the anion gap in plasma (Panion gap) 1 or the strong ion difference 2 have major deficiencies. For example, the diagnosis of metabolic acidosis may be missed if one relies solely on pH and the concentration of bicarbonate (HCO3 ) in plasma (PHCO3) without considering changes in the content of HCO3 in the extracellular fluid (ECF) compartment. In addition, the rules of respiratory compensation, which are based solely on the arterial PCO2 rather than the more valuable PCO2 in capillary blood-draining skeletal muscle (as reflected by the venous PCO2), fail to assess the effectiveness of the bulk of the bicarbonate buffer system to remove Hand, hence, whether more H will bind to intracellular proteins in vital organs, such as the brain or the heart. 3
Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements
Authors: Francesco Albano, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Paola Casieri, Antonella Rossi, Laura Vicari, Vincenzo Liso, Mariano Rocchi, Giorgina Specchia
Journal: Molecular Cancer (2010)

The t(9;22)(q34;q11), generating the Philadelphia (Ph) chromosome, is found in more than 90% of patients with chronic myeloid leukemia (CML). As a result of the translocation, the 3' portion of the ABL1 oncogene is transposed from 9q34 to the 5' portion of the BCR gene on chromosome 22 to form the BCR/ABL1 fusion gene. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22). We report a molecular cytogenetic study of 452 consecutive CML patients at diagnosis, that revealed 50 cases identifying three main subgroups: i) cases with variant chromosomal rearrangements other than the classic t(9;22)(q34;q11) (9.5%); ii) cases with cryptic insertions of ABL1 into BCR, or vice versa (1.3%); iii) cases bearing additional chromosomal rearrangements concomitant to the t(9;22) (1.1%). For each cytogenetic group, the mechanism at the basis of the rearrangement is discussed. All breakpoints on other chromosomes involved in variant t(9;22) and in additional rearrangements have been characterized for the first time by Fluorescence In Situ Hybridization (FISH) experiments and bioinformatic analyses. This study revealed a high content of Alu repeats, genes density, GC frequency, and miRNAs in the great majority of the analyzed breakpoints. Taken together with literature data about CML with variant t(9;22), our findings identified several new cytogenetic breakpoints as hotspots for recombination, demonstrating that the involvement of chromosomes other than 9 and 22 is not a random event but could depend on specific genomic features. The presence of several genes and/or miRNAs at the identified breakpoints suggests their potential involvement in the CML pathogenesis.
Acute leukemia and myelodysplasia after adjuvant chemotherapy for breast cancer: durable remissions after hematopoietic stem cell transplantation
Authors: V. Pullarkat, M.L. Slovak, A. Dagis, V. Bedell, G. Somlo, R. Nakamura, A.S. Stein, M.R. O'Donnell, A. Nademanee, A.L. Teotico, S. Bhatia, S.J. Forman
Journal: Annals of Oncology (2009)
Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice
Authors: Yuan Zhang, Sarah R. Breevoort, Jerry Angdisen, Mingui Fu, Daniel R. Schmidt, Sam R. Holmstrom, Steven A. Kliewer, David J. Mangelsdorf, Ira G. Schulman
Journal: Journal of Clinical Investigation (2012)

Liver X receptors (LXRα and LXRβ) are important regulators of cholesterol and lipid metabolism, and their activation has been shown to inhibit cardiovascular disease and reduce atherosclerosis in animal models. Small molecule agonists of LXR activity are therefore of great therapeutic interest. However, the finding that such agonists also promote hepatic lipogenesis has led to the idea that hepatic LXR activity is undesirable from a therapeutic perspective. To investigate whether this might be true, we performed gene targeting to selectively delete LXRα in hepatocytes. Liver-specific deletion of LXRα in mice substantially decreased reverse cholesterol transport, cholesterol catabolism, and cholesterol excretion, revealing the essential importance of hepatic LXRα for whole body cholesterol homeostasis. Additionally, in a pro-atherogenic background, liver-specific deletion of LXRα increased atherosclerosis, uncovering an important function for hepatic LXR activity in limiting cardiovascular disease. Nevertheless, synthetic LXR agonists still elicited anti-atherogenic activity in the absence of hepatic LXRα, indicating that the ability of agonists to reduce cardiovascular disease did not require an increase in cholesterol excretion. Furthermore, when non-atherogenic mice were treated with synthetic LXR agonists, liver-specific deletion of LXRα eliminated the detrimental effect of increased plasma triglycerides, while the beneficial effect of increased plasma HDL was unaltered. In sum, these observations suggest that therapeutic strategies that bypass the liver or limit the activation of hepatic LXRs should still be beneficial for the treatment of cardiovascular disease.
Asymptomatic solitary papilloma of the bronchus: review of occurrence in Japan
Authors: H Miura, T Tsuchida, N Kawate, C Konaka, H Kato, Y Ebihara
Journal: European Respiratory Journal (1993)

A case of solitary papilloma of the bronchus is described, and 15 other cases occurring in Japan are reviewed. A 57 year old asymptomatic male was referred to our hospital because many squamous metaplastic cells with moderate atypia were observed in sputum cytology, twice in 3 months. The chest X-ray showed no abnormal findings. Endoscopic examination revealed a polypoid tumour at the bifurcation of the right B6a and B6b. The tumour was removed completely by endoscopic biopsy, and histological findings showed squamous papilloma. There has been no evidence of recurrence for 3 yrs. We are not aware of a previously reported case of bronchial papilloma without symptoms or abnormal shadow on chest X-ray. Considering the fact that malignant change was reported in only one case in Japan, and that there is a possibility of cancer subsequently developing at another location in the lung which might also require resection, lobectomy should be avoided if the tumour can be removed completely through endoscopy. If the lesion is limited to a small area in the bronchus, conservative treatment such as photodynamic therapy and/or yttrium aluminium garnet (YAG) laser vaporization might be sufficient to obtain a complete cure.
A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)
Authors: G. Daugaard, I. Skoneczna, N. Aass, R. De Wit, M. De Santis, H. Dumez, S. Marreaud, L. Collette, J.R.G. Lluch, C. Bokemeyer, H.J. Schmoll
Journal: Annals of Oncology (2010)
Arachidonate 15-lipoxygenase is required for chronic myeloid leukemia stem cell survival
Authors: Yaoyu Chen, Cong Peng, Sheela A. Abraham, Yi Shan, Zhiru Guo, Ngoc Desouza, Giulia Cheloni, Dongguang Li, Tessa L. Holyoake, Shaoguang Li
Journal: Journal of Clinical Investigation (2014)

Cancer stem cells (CSCs) are responsible for the initiation and maintenance of some types of cancer, suggesting that inhibition of these cells may limit disease progression and relapse. Unfortunately, few CSC-specific genes have been identified. Here, we determined that the gene encoding arachidonate 15-lipoxygenase (Alox15/15-LO) is essential for the survival of leukemia stem cells (LSCs) in a murine model of BCR-ABL-induced chronic myeloid leukemia (CML). In the absence of Alox15, BCR-ABL was unable to induce CML in mice. Furthermore, Alox15 deletion impaired LSC function by affecting cell division and apoptosis, leading to an eventual depletion of LSCs. Moreover, chemical inhibition of 15-LO function impaired LSC function and attenuated CML in mice. The defective CML phenotype in Alox15-deficient animals was rescued by depleting the gene encoding P-selectin, which is upregulated in Alox15-deficient animals. Both deletion and overexpression of P-selectin affected the survival of LSCs. In human CML cell lines and CD34+ cells, knockdown of Alox15 or inhibition of 15-LO dramatically reduced survival. Loss of Alox15 altered expression of PTEN, PI3K/AKT, and the transcription factor ICSBP, which are known mediators of cancer pathogenesis. These results suggest that ALOX15 has potential as a therapeutic target for eradicating LSCs in CML.
Alteration of Coronary Blood Flow in the Dog by Inhalation of 100 Per Cent Oxygen
Authors: Bruce J. Sobol, Stanley A. Wanlass, Edward B. Joseph, Ismail Azarshahy
Journal: Circulation Research (1962)

The administration of 100 per cent oxygen to the open-chest anesthetized dog results in a decrease in coronary blood flow. This occurs whether the animal is fully saturated on ambient air or not. It occurs as well whether or not the animal is in vascular collapse requiring pressor agents for the maintenance of its blood pressure.
Mitochondrial Genomic Rearrangements in Songbirds
Authors: Staffan Bensch, Anna H
Journal: Molecular Biology and Evolution (2000)

The organization of the mitochondrial genome is generally very conserved among vertebrates. Because of this, examination of the rare rearrangements which do occur has been suggested as offering a powerful alternative to phylogenetic analyses of mitochondrial DNA sequences. Here, we report on an avian mitochondrial rearrangement in a group of oscine passerines (warblers of the genus Phylloscopus). This rearrangement is identical to the mitochondrial organization recently identified in representatives of four orders of birds, including subsoscine Passeriformes. The rearrangement involves the movement of three genes (tRNA, NADH6, and tRNA) from their normal position in birds between tRNA and the control region (CR), to a new location between the CR and a novel, supposedly noncoding (NC), region. Our results suggest that this derived arrangement cannot be used to distinguish between suboscine and oscine passerines, as it has multiple origins both within Passeriformes and within birds as a whole. We found short stretches of DNA with high degrees of similarity between the CR and each NC region, respectively, all of which could be located in the same area of the CR. This suggests that the CR and the NC region are homologous and that the mechanism behind this mitochondrial rearrangement is a tandem duplication followed by multiple deletions. However, the similarities between the control and NC regions of each species were less pronounced than those between the control or NC regions from the different species, supporting the hypothesis of a single basal rearrangement in the Phylloscopus warblers.
Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.
Authors: J T Thigpen, J A Blessing, H Ball, S J Hummel, R J Barrett
Journal: Journal of Clinical Oncology (1994)

PURPOSE This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (&lt; 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.
Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice
Authors: Israel Gotsman, Nir Grabie, Rosa Dacosta, Galina Sukhova, Arlene Sharpe, Andrew H. Lichtman
Journal: Journal of Clinical Investigation (2007)

T lymphocyte responses promote proatherogenic inflammatory events, which are influenced by costimulatory molecules of the B7 family. Effects of negative regulatory members of the B7 family on atherosclerosis have not been described. Programmed death-ligand 1 (PD-L1) and PD-L2 are B7 family members expressed on several cell types, which inhibit T cell activation via binding to programmed death-1 (PD-1) on T cells. In order to test whether the PD-1/PD-L pathway regulates proatherogenic T cell responses, we compared atherosclerotic lesion burden and phenotype in hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice and LDLR(-/-) controls. PD-L1/2 deficiency led to significantly increased atherosclerotic burden throughout the aorta and increased numbers of lesional CD4(+) and CD8(+) T cells. Compared with controls, PD-L1/2(-/-)LDLR(-/-) mice had iliac lymphadenopathy and increased numbers of activated CD4(+) T cells. Serum levels of TNF-alpha were higher in PD-L1/2(-/-)LDLR(-/-) mice than in controls. PD-L1/2-deficient APCs were more effective than control APCs in activating CD4(+) T cells in vitro, with or without cholesterol loading. Freshly isolated APCs from hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice stimulated greater T cell responses than did APCs from hypercholesterolemic controls. Our findings indicate that the PD-1/PD-L pathway has an important role in downregulating proatherogenic T cell response and atherosclerosis by limiting APC-dependent T cell activation.
Failure to Detect, in Human Sera, Antibodies Cross-Reactive With Group-Specific Antigens of Murine Leukemia Virus
Authors: H. P. Charman, N. Kim, M. White, R. V. Gilden
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Failure to Detect, in Human Sera, Antibodies Cross-Reactive With Group-Specific Antigens of Murine Leukemia Virus Get access H. P. Charman, H. P. Charman Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Kim, N. Kim Search for other works by this author on: Oxford Academic PubMed Google Scholar M. White, M. White Search for other works by this author on: Oxford Academic PubMed Google Scholar R. V. Gilden R. V. Gilden Flow Laboratories, Inc., Rockville, Md. 20852 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 5, May 1974, Pages 1409–1413, https://doi.org/10.1093/jnci/52.5.1409 Published: 01 May 1974 Article history Received: 10 September 1973 Accepted: 09 January 1974 Published: 01 May 1974
One-Year Clinical Outcomes, Midterm Survival, and Predictors of Mortality After Carotid Stenting in Elderly Patients
Authors: Paul T.L. Chiam, Gary S. Roubin, Georgia Panagopoulos, Sriram S. Iyer, Richard M. Green, Christina Brennan, Jiri J. Vitek
Journal: Circulation (2009)

It has been demonstrated recently that carotid stenting can be performed safely in patients > or =80 years of age. However, it is uncertain whether these patients will derive benefit because longevity after revascularization is an important consideration. This study was conducted to determine survival and predictors of mortality of selected elderly patients after stenting.One hundred forty-two consecutive elderly patients who were non-high risk for stenting underwent 153 procedures. Patients had either symptomatic stenosis > or =50% or asymptomatic stenosis > or =70%. Demographics and in-hospital outcomes were entered into a database; subsequent outcomes and mortality data were obtained retrospectively. Mean+/-SD age was 83.3+/-3.1 years. Symptomatic patients accounted for 28%. Overall survival at 3 years was 76% (85% at 2 years). At 1 year, 1 fatal stroke had occurred, with 97% of survivors (n=114) free of neurological events (neurological status was undetermined in the remaining 3%). Predictors of mortality were remote (> or =6 months) transient ischemic attack or cerebrovascular accident, smoking history, and creatinine clearance (hemoglobin level showed a strong trend toward achieving significance); for the asymptomatic subgroup, predictors of mortality were smoking history, previous carotid endarterectomy, hemoglobin level, and increasing age. In particular, symptom status and sex were not independent predictors of mortality.This study demonstrates that in selected elderly patients, a high proportion (85%) survived 2 years and >75% survived 3 years after stenting. Carotid stenting may be considered a revascularization option in such patients. Better selection of patients using the predictors of mortality may help to reduce unwarranted procedures and to optimize survival likelihood.
Hospital bed utilisation in the NHS, Kaiser Permanente, and the US Medicare programme: analysis of routine data
Authors: C. Ham
Journal: BMJ (2003)

To compare the utilisation of hospital beds in the NHS in England, Kaiser Permanente in California, and the Medicare programme in the United States and California.Analysis of routinely available data from 2000 and 2001 on inpatient admissions, lengths of stay, and bed days in populations aged over 65 for 11 leading causes of use of acute beds.Comparison of NHS data with data from Kaiser Permanente in California and the Medicare programme in California and the United States; interviews with Kaiser Permanente staff and visits to Kaiser facilities.Bed day use in the NHS for the 11 leading causes is three and a half times that of Kaiser's standardised rate, almost twice that of the Medicare California's standardised rate, and more than 50% higher than the standardised rate in Medicare in the United States. Kaiser achieves these results through a combination of low admission rates and relatively short stays. The lower use of bed days in Medicare in California compared with Medicare in the United States suggests there is a "California effect" as well as a "Kaiser effect" in hospital utilisation.The NHS can learn from Kaiser's integrated approach, the focus on chronic diseases and their effective management, the emphasis placed on self care, the role of intermediate care, and the leadership provided by doctors in developing and supporting this model of care.
Cure of Helicobacter pylori Infection and Duration of Remission of Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: A. Neubauer, C. Thiede, B. Alpen, M. Ritter, B. Neubauer, G. Ehninger, A. Morgner, E. Bayerdorffer, T. Wundisch, M. Stolte
Journal: JNCI Journal of the National Cancer Institute (1997)

Low-grade B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) are most frequently localized in the gastrointestinal tract. More than 90% of gastric MALT lymphomas are diagnosed in patients with chronic, Helicobacter pylori-associated gastritis. High remission rates for these lymphomas have been observed after the cure of H. pylori infection. Data are lacking, however, with regard to the duration of the remissions. To address this question of remission duration, we have followed 50 patients in whom H. pylori infections were eradicated, and we determined whether the patients in complete remission displayed evidence of residual monoclonal B cells during follow-up.Patients were treated with amoxycillin and omeprazole for 2 weeks in an attempt to cure H. pylori infections. Follow-up included endoscopic investigations with biopsy sampling. Monoclonal B cells in biopsy specimens were detected by means of a polymerase chain reaction (PCR)-based assay.H. pylori infections were cured in all 50 patients. The median follow-up for the 50 patients is currently 24 months (729 days; range, 135-1411 days). Forty patients achieved complete remission of their lymphomas, but five have subsequently relapsed. The median time of continuous complete remission for the 40 patients was 15.4 months (468 days; range, 0-1198 days). Among six patients whose Iymphomas did not respond to H. pylori eradication, four revealed high-grade lymphomas upon surgery. PCR indicated the presence of monoclonal B cells during follow-up in 22 of 31 assessable patients in complete remission.Complete remissions of low-grade gastric MALT Iymphomas after the cure of H. pylori infection appear to be stable, although most patients display evidence of monoclonal B cells during follow-up. Whether these patients are truly cured of their Iymphomas remains to be determined.
Urotensin‐II receptor peptide agonists
Authors: Alfonso Carotenuto, Paolo Grieco, Ettore Novellino, Paolo Rovero
Journal: Medicinal Research Reviews (2004)

Abstract Urotensin II (U‐II) has been known for over 30 years as an important teleost fish hormone, but only recently has it been recognized as the endogenous ligand of a new human G‐protein‐coupled receptor (GPCR) homologous to the GPR14 orphan receptor from rat. Human U‐II was found to be a potent vasoconstrictor, widely distributed in human tissues, possibly contributing to several human cardiovascular diseases. It thus has become a major target of medicinal chemistry research. The common structural feature of U‐II peptides from different species is the C‐terminal portion, characterized by the disulfide bridged cyclic hexapeptide Cys‐Phe‐Trp‐Lys‐Tyr‐Cys. The few structure–activity relationship studies reported to date attributed a critical role to this portion, with the Trp‐Lys‐Tyr motif appearing as the key determinant of U‐II bioactivity. Consequently, this shorter cyclic peptide was used as a template for the development of several synthetic analogues, among which a superagonist, termed P5U: H‐Asp‐cyclo(Pen‐Phe‐Trp‐Lys‐Tyr‐Cys)‐Val‐OH. Conformational studies confirmed the important role of hU‐II C‐terminal cyclic portion, enabling the development of 3D pharmacophore models. These findings should lead to the design of new, potent and selective analogues, acting as agonist or antagonist at the human U‐II receptor, finally contributing to a deeper comprehension of the (patho)physiological significance of this peptide. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 5, 577–588, 2004