tbuckley/cabot-search huggingface dataset:
High-dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma.
Authors: D Cunningham, L Paz-Ares, S Milan, R Powles, M Nicolson, T Hickish, P Selby, J Treleavan, C Viner, J Malpas
Journal: Journal of Clinical Oncology (1994)

PURPOSE We report the results of intensive chemotherapy with high-dose melphalan (HDM) following conventional-dose cytoreductive chemotherapy in previously untreated patients with myeloma. PATIENTS AND METHODS From 1986 to 1991, 53 previously untreated patients with myeloma received HDM 200 mg/m2 plus methylprednisolone 1.5 g daily (MP) for 5 days with autologous bone marrow transplantation (ABMT) after cytoreductive chemotherapy. RESULTS At the time of HDM administration, responses to induction therapy were complete remission (CR) in nine patients, partial remission (PR) in 38, and no response (NR) in six. Following HDM, all but one patient responded, with 40 patients achieving a CR (75%). There was one treatment-related death following HDM. The median time to reach a WBC count more than 1,000/microL and platelet count more than 25,000/microL was 19 days (range, 13 to 30) and 24 days (range, 15 to 55), respectively. The median duration of response has not been reached at 20 months, and it is significantly longer for patients in CR than for those in PR (P &lt; .025). Currently, with a median follow-up duration of 31 months (range, 6 to 58), 12 patients are dead and 40 are alive, and the estimated probability of survival at 54 months is 63%. Multivariate analysis found hemoglobin (Hb) more than 10 g/dL (P = .012), and stage A disease (P = .001) at diagnosis to be favorable indicators for survival. CONCLUSION Myeloma patients who are able to receive HDM plus ABMT following conventional chemotherapy achieve a high proportion of CRs, which may be associated with prolonged survival.
Tuberculosis and Legionella pneumophila pneumonia in a patient receiving anti-tumour necrosis factor-α (anti-TNF-α) treatment
Authors: G. Mancini, L. Erario, R. Gianfreda, A. Oliva, A.P. Massetti, C.M. Mastroianni, V. Vullo
Journal: Clinical Microbiology and Infection (2007)
Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.
Authors: C Hesdorffer, J Ayello, M Ward, A Kaubisch, L Vahdat, C Balmaceda, T Garrett, M Fetell, R Reiss, A Bank, K Antman
Journal: Journal of Clinical Oncology (1998)

Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy.Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy.High-level MDR transduction of erythroid burst-forming unit (BFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM) derived from transduced CD34+ cells was shown posttransduction and prereinfusion. However, only two of the five patients showed evidence of MDR transduction of their marrow at a low level at 10 weeks and 3 weeks, respectively, posttransplantation. The cytokine-stimulated transduced cells may be out-competed in repopulation by unmanipulated normal cells that are reinfused concomitantly. The MDR retroviral supernatant that was used was shown to be free of replication-competent retrovirus (RCR) before use, and all tests of patients' samples posttransplantation were negative for RCR. In addition, no adverse events with respect to marrow engraftment or other problems related to marrow transplantation were encountered.These results indicate the feasibility and safety of bone marrow gene therapy with a potentially therapeutic gene, the MDR gene.
The evaluation of renal transplant candidates
Authors: B L Kasiske, E L Ramos, R S Gaston, M J Bia, G M Danovitch, P A Bowen, P A Lundin, K J Murphy
Journal: Journal of the American Society of Nephrology (1995)

Kasiske, B L; Ramos, E L; Gaston, R S; Bia, M J; Danovitch, G M; Bowen, P A; Lundin, P A; Murphy, K J
Abstract 3759: Enhanced External Counterpulsation Arrests the Progression of Atherosclerosis by Regulating Cellular Apoptosis and Proliferation Signaling Pathway
Authors: Yan Zhang, Hong Ma, Xiaohong He, Guifu Wu, Xiaolin Chen, Donghong Liu, Zhimin Du, Yugan Dong, Yafei Jin, Wen He, Kuijian Wang, Jinyun Luo, Yan Xiong, William E Lawson, John C Hui, Zhensheng Zheng
Journal: Circulation (2008)

Shear stress may be the most crucial local factor affecting atherogenesis. Enhanced External Counterpulsation (EECP) has been documented to increase arterial wall shear stress in vivo. We hypothesize that chronic exposure to increased pulsatile shear stress by EECP arrests the progression of atherosclerosis due to hypercholesterolemia. Forty-eight pigs were randomized to usual diet (n = 7), high-cholesterol diet (n = 18), and high-cholesterol diet plus EECP (34±2 hours, n = 23). At week 15, the left anterior descending coronary arteries (LAD) were collected for HE staining, transmission electron microscopy examination, immunohistochemical analysis of AKT, caspase- 3 and TUNEL assay. Expression and localization of NK- κB was assessed by immunofluorescence and confocal laser scanning microscope. The aortas were isolated for Sudan staining and Western-blot analysis. Blood lipids, viscosity, Doppler ultrasound flow examination was performed. Statistical analysis was by Kruskal-Wallis and Mann-Whitney tests. During EECP, the peak diastolic arterial wall shear stress in the right brachial artery increased significantly compared with baseline (53.18±3.81 dynes/cm 2 versus 23.92±2.02 dynes/cm 2 , p&lt;0.001), as well as the mean arterial wall shear stress (27.46±2.22 dynes/cm 2 versus 20.43±1.87 dynes/cm 2 , p &lt; 0.001). High-cholesterol diet induced remarkable atherosclerotic lesions with excessive cellular proliferation and apoptosis. In comparison, hypercholesterolemic animals receiving EECP showed ameliorated atherosclerotic lesions in LADs ( lesion/medial area ratio: 19.71±3.79 % versus 7.32±1.59 %, p = 0.001) and aortas (percentage of plaque area: 9.95±1.81 % versus 5.16±1.08 %, p = 0.011), coupled with decreased TUNEL positive staining (64±2.08 % versus 49±2.27 %, p &lt; 0.001), reduced caspase- 3 protein expression, AKT and NF- κB activity. This study demonstrates that EECP administration leads to reduced atherosclerotic lesions, coupled with dual inhibitory effects on vascular cellular proliferation and apoptosis. Its mechanisms are related to chronic increased shear stress by EECP suppressing the over-activation of the AKT/NF-κB signaling pathway.
Co-infections with hepatitis B and C viruses in human immunodeficiency virus-infected patients in Morocco
Authors: K. Rebbani, A. Ouladlahsen, A. Bensghir, A. Akil, H. Lamdini, H. Issouf, I. Brahim, B. Kitab, F.Z. Fakhir, L. Wakrim, K. Marhoum El Filali, H. Himmich, S. Ezzikouri, S. Benjelloun
Journal: Clinical Microbiology and Infection (2013)
Changes in Levels of Phosphorus Metabolites in Temporal Lobes of Drug-Naive Schizophrenic Patients
Authors: Hiroshi Fukuzako, Tsuyoshi Fukuzako, Tomo Hashiguchi, Satoshi Kodama, Morikuni Takigawa, Toshiro Fujimoto
Journal: American Journal of Psychiatry (1999)

The authors examined phospholipids and high-energy phosphorus metabolism in the temporal lobes of drug-naive schizophrenic patients.In vivo 31P magnetic resonance spectroscopy was performed on 17 first-episode, drug-naive schizophrenic patients and 17 age- and gender-matched healthy subjects.Patients showed higher levels of phosphodiesters and lower levels of phosphomonoesters than the comparison group. Phosphocreatine levels were increased in the left temporal lobes of patients.The results suggest disturbed membrane phospholipid metabolism in both temporal lobes and decreased energy demands in the left temporal lobes of drug-naive schizophrenic patients.
Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma
Authors: Richard G. Everson, Joseph P. Antonios, Dominique N. Lisiero, Horacio Soto, Rudi Scharnweber, Matthew C. Garrett, William H. Yong, Ning Li, Gang Li, Carol A. Kruse, Linda M. Liau, Robert M. Prins
Journal: Neuro-Oncology (2015)

BackgroundImmunotherapy is an ideal treatment modality to specifically target the diffusely infiltrative tumor cells of malignant gliomas while sparing the normal brain parenchyma. However, progress in the development of these therapies for glioblastoma has been slow due to the lack of immunogenic antigen targets that are expressed uniformly and selectively by gliomas.
Bone Marrow Stromal Cell-Derived Exosomes Facilitate Multiple Myeloma Cell Survival Through Inhibition Of The JNK Pathway
Authors: Jinheng Wang, An Hendrix, Elke De Bruyne, Els Van Valckenborgh, Eddy Himpe, Nathan De Beule, Olivier De Wever, Karin Vanderkerken, Eline Menu
Journal: Blood (2013)
Rational Use of Cytotoxic Chemotherapy for Recurrent Ovarian Cancer
Authors: Joyce Liu, Ursula Matulonis
Journal: Journal of the National Comprehensive Cancer Network (2006)

Ovarian cancer remains the leading cause of death among women with gynecologic malignancies, and the fifth leading cause of cancer mortality in women in the United States. Although many patients respond to first-line platinum-based therapy, most will experience disease recurrence. The role of further therapy in the setting of recurrent ovarian cancer is palliative, and large randomized phase III trials on treatment options for recurrent ovarian cancer are rare. Controversies exist as to the optimal timing and duration of treatment, and many issues regarding treatment of recurrent disease remain.
Exhaled breath condensate in chronic cough.
Authors: Morice A, Everett Cf, Mulrennan Sa, Chung Kf
Journal: Thorax (2005)

We read with interest the recent article by Niimi et al reporting low levels of exhaled breath condensate (EBC) pH in patients with chronic cough.1 We and others have described low EBC pH in association with airway inflammation in allergic asthma, cystic fibrosis, and chronic obstructive pulmonary disease.2–4 In these studies there is a relatively close association between inflammation and low pH which is shown by the further fall in pH during exacerbations.2 However, in non-asthmatic chronic cough, while there is a low grade inflammation present in some subjects, this is much less than would be required to invoke inflammation as the major cause of airway acidification.

It is unclear from the description of the …
Origins of Bladder Cancer
Authors: Bogdan Czerniak, Colin Dinney, David McConkey
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy.
A controlled pilot study of high-dose methotrexate as postsurgical adjuvant treatment for primary osteosarcoma.
Authors: J H Edmonson, S J Green, J C Ivins, G S Gilchrist, E T Creagan, D J Pritchard, W A Smithson, D C Dahlin, W F Taylor
Journal: Journal of Clinical Oncology (1984)

Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised (37 amputations, one limb sparing procedure) were allocated at random to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate (HDMTX) regimen or regular follow-up without primary adjuvant chemotherapy. Although the vincristine, HDMTX, leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2, delayed methotrexate excretion limited dosage escalations in 25%. An estimated 52% of the 38 patients were surviving five years after randomization and an estimated 42% remained continuously relapse-free after five years. No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent; however, power to detect differences was low. Furthermore, no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed. Approximately 20% of these failing patients appear to have been salvaged for long-term survival. This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma.
Late-breaking abstract: Discordant intra-individual upper and lower airway responses following simultaneous nasal and bronchial allergen challenge
Authors: Graham Clarke, Leonidas Carayannopoulos, Chris Chung, Jennifer McCarthy, Carin Mordin, Matthew Gill, Faizah Haider, Margaret Rainer, Leonard Siew
Journal: European Respiratory Journal (2014)

To measure the within-subject correlation between cytokine production in the nasal and bronchial airways in response to simultaneous allergen challenge (AC)at both anatomic sites, both with and without pretreatment with systemic steroids.  Methods:  Ten patients with allergic rhinitis and asthma enrolled in a randomized, placebo-controlled, three-period study. Period 1 was a run-with patients receiving placebo pretreatment followed by nasal and inhaled allergen challenges. Those with a late airways responses (LAR) were admitted to study periods 2 & 3,during which allergen challenges were preceded by treatment with 25mg oral prednisone and placebo. Sputum and Nasal exudates were obtained at pre-dose and 8 hrs post challenge and bronchoscopy for BAL and epithelial brushings collection at 24 hrs post challenge, to assess cytokine and mRNA profiles.  Results:  AC significantly reduced LAR FEV1 following pbo pretreatment (-27% mean nadir;p 8.5 fold {p 0.07 being ∼0.08 --similarly for IL-13.  Conclusions:  Within given patients , nasal and bronchial cytokine responses can be discordant. High nasal response selectivity of key subject phenotypes is required for what remains to be an attractive proof of biology tool.
Ischemic Stroke Subtype Incidence Among Whites, Blacks, and Hispanics
Authors: Halina White, Bernadette Boden-Albala, Cuiling Wang, Mitchell S.V. Elkind, Tanja Rundek, Clinton B. Wright, Ralph L. Sacco
Journal: Circulation (2005)

Background— Stroke incidence is greater in blacks than in whites; data on Hispanics are limited. Comparing subtype-specific ischemic stroke incidence rates may help to explain race-ethnic differences in stroke risk. The aim of this population-based study was to determine ischemic stroke subtype incidence rates for whites, blacks, and Hispanics living in one community. Methods and Results— A comprehensive stroke surveillance system incorporating multiple overlapping strategies was used to identify all cases of first ischemic stroke occurring between July 1, 1993, and June 30, 1997, in northern Manhattan. Ischemic stroke subtypes were determined according to a modified NINDS scheme, and age-adjusted, race-specific incidence rates calculated. The annual age-adjusted incidence of first ischemic stroke per 100 000 was 88 (95% CI, 75 to 101) in whites, 149 (95% CI, 132 to 165) in Hispanics, and 191 (95% CI, 160 to 221) in blacks. Among blacks compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42 to 7.13); lacunar stroke, 3.09 (95% CI, 1.86 to 5.11); and cardioembolic stroke, 1.58 (95% CI, 0.99 to 2.52). Among Hispanics compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80 to 3.63); lacunar stroke, 2.32 (95% CI, 1.48 to 3.63); and cardioembolic stroke, 1.42 (95% CI, 0.97 to 2.09). Conclusions— The high ischemic stroke incidence among blacks and Hispanics compared with whites is due to higher rates of all ischemic stroke subtypes.
Protection of Mice Against X Irradiation by Plasma Proteins
Authors: Agnes N. Stroud, Austin M. Brues, Mildred M. Summers
Journal: JNCI Journal of the National Cancer Institute (1955)

Protection of Mice Against X Irradiation by Plasma Proteins Get access Agnes N. Stroud, Agnes N. Stroud Division of Biological and Medical Research, Argonne National Laboratory, Lemont, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar Austin M. Brues, Austin M. Brues Division of Biological and Medical Research, Argonne National Laboratory, Lemont, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mildred M. Summers Mildred M. Summers Division of Biological and Medical Research, Argonne National Laboratory, Lemont, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 1109–1123, https://doi.org/10.1093/jnci/15.4.1109 Published: 01 February 1955 Article history Received: 08 November 1954 Published: 01 February 1955
Abstract 4275: <i>TGFBR2</i> Mutations Reduce Expression of Contractile Proteins in Aortic Smooth Muscle Cells and Predispose Individuals to Thoracic Aortic Aneurysms and Dissections
Authors: Sakiko Inamoto, Callie Kwartler, Andrea Lafont, Yao Yun Liang, Van Tran Fadulu, Senthil Duraisamy, Marcia Willing, Anthony Estrera, Hazim Safi, Mark Hannibal, John Carey, John Wiktorowicz, Filemon Tan, Xin-Hua Feng, Hariyadarshi Pannu, Dianna Milewicz
Journal: Circulation (2008)

Mutations in the TGF-β receptor type II gene ( TGFBR2 ) cause thoracic aortic aneurysms and dissections (TAAD). Studies have suggested a gain of function effect for these mutations, leading to increased TGF-β signaling in the aortic media and resulting in vascular disease. We sought to characterize the phenotype of smooth muscle cells (SMCs) harboring heterozygous missense TGFBR2 mutations and our data suggest that instead of a gain of function, TGFBR2 mutations cause TAAD as a result of a loss of function resulting in defective SMC differentiation. Using primary aortic SMCs from patients harboring TGFBR2 mutations (n=4), we show a global decrease in expression of SMC contractile proteins ( ACTA2 , MYH11 , CNN1 , SMTN , TPM1 , TPM2 , p &lt;0.001) by quantitative PCR analysis when these cells are compared with age and gender matched control SMCs (n=4), along with no change in the expression of cytoskeletal proteins. Consistent with the decreased expression of contractile proteins in the mutant cells, there was increased expression of S100A4, a marker of de-differentiated SMCs (p&lt;0.001). Analysis of fixed and frozen aortas from patients with TGFBR2 mutations (n=3) confirmed decreased in vivo expression of SMC contractile proteins when compared to control aortas (n=3). In control SMCs, addition of TGF- β significantly increased the expression of the SMC contractile proteins but the TGFBR2 SMCs showed no significant increase in expression of these proteins with TGF-β stimulation. We found that fibroblasts explanted from patients with TGFBR2 mutations (n=8) consistently fail to transform into myofibroblasts as assessed by expression of SMC contractile proteins after TGF-β stimulation, when compared with age and gender matched control fibroblasts (n=8). Finally, introduction of TGFBR2 missense mutations into a mouse mesenchymal embryonic cell line that is used as a model of SMC differentiation (10T1/2 cells) disrupts the expression of contractile proteins in these cells when assessed post-differentiation. These data suggest that TGFBR2 mutations disrupt differentiation of SMCs and myofibroblasts. This is the first genetic defect identified to lead to defective SMC differentiation.
Biological assays for interleukin 1 detection
Authors: L. Remvig, J. Vibe‐Petersen, M. Svenson, C. Enk, K. Bendtzen
Journal: Allergy (1991)

Various biological assays are used for qualitative and quantitative measurements of interleukin 1 (IL‐1) in supernatants from cell cultures. The purpose of the present study was to compare the specificity and variability of three cellular IL‐1 bioassays: the PHA co‐stimulatory human T lymphocyte proliferation assay, the PHA co‐stimulatory murine thymocyte (THY) proliferation assay, and the 2‐step NOB‐1 conversion assay. Three different ways of IL‐1 unit calculation, based on a semi‐logarithmic plot, a double‐logarithmic plot, or a probit‐analysis plot were also compared. The T lymphocyte assay can be used only to demonstrate qualitative differences in IL‐1‐like activity, whereas the THY assay is excellent as a semi‐quantitative assay, with a low intra‐assay variability, but also with a low specificity. The NOB‐1 assay is probably more specific with respect to IL‐1 measurement, although, with a high intra‐assay variance. The THY and the NOB‐1 assays both have a high inter‐assay variability, and measurement of samples from longitudinal clinical studies must be done in one and the same analysis if quantitative differences are to be illustrated, Probit analysis for unit calculation is recommended. To generate a consensus view as to assay performance, collaborative laboratory studies are needed.