tbuckley/cabot-search huggingface dataset:
The Mexican schedule to conduct allogeneic stem cell transplantation is related to a low risk of cytomegalovirus reactivation and disease
Authors: Guillermo J. Ruiz‐Argüelles, J. David Gómez Rangel, Samuel Ponce‐de‐León, Laura González‐Déctor, Virginia Reyes‐Núñez, Javier Garcés‐Eisele
Journal: American Journal of Hematology (2004)

Abstract The prevalence of cytomegalovirus (CMV) reactivation and disease after non‐myeloablative stem cell transplantation is largely unknown. Using fludarabine combined with alemtuzumab or antithymocyte globulin in the conditioning regimen, some authors have found increased prevalences of CMV disease, whereas other authors using different schedules have observed decreased prevalences. In a group of 17 individuals allografted using the Mexican conditioning regimen, which employs fludarabine, cyclophosphamide, and busulfan, we assessed CMV reactivation, morbidity, and mortality. Before transplant, IgG anti‐CMV antibodies were found in 11 patients and in 10 donors; in 8 cases, both donor and patient had IgG anti‐CMV antibodies. In only one case (6%) was CMV mRNA identified 30 days after the allograft during grade IV acute graft‐versus‐host disease. CMV reactivation, disease, and mortality were very low using our non‐myeloablative stem cell transplantation schedule, which has been shown to be useful for allografting with minimal toxicity and reduced costs. Am. J. Hematol. 75:200–204, 2004. © 2004 Wiley‐Liss, Inc.
Retrospective investigation of patients positive for glycopeptidolipid-core antibody to mycobacterium avium complex pulmonary disease
Authors: Yasunari Oki, Tukasa Ohnishi, Sojiro Kusumoto, Yasunori Murata, Shin Ohta, Mayumi Yamamoto, Yoshio Watanabe, Shintaro Suzuki, Hiroo Ishida, Takao Shirai, Akihiko Tanaka, Takuya Yokoe, Hironori Sagara
Journal: European Respiratory Journal (2014)

Background: In recent years, the incidence of Mycobacterium avium complex pulmonary disease (MAC-PD) has been increasing. Diagnosis requires identification of pathogens on multiple occasions in addition to characteristic observation of lesions on imaging examinations, identification of pathogens on bronchoscopic examination, or other pathological evidence. As a result, the diagnosis is non-definitive in many patients who produce no sputum and do not wish to undergo bronchoscopic examination. Glycopeptidolipid (GPL)-core antibody to MAC is an easy serological test. Therefore, GPL-core antibody may be useful for diagnosing MAC-PD.

Aims : This study aimed to estimate the usefulness of GPL-core antibody for diagnosing MAC-PD by investigating patients who were positive for GPL-core antibody.

Method : A total of 66 patients who were positive for GPL-core antibody were retrospectively investigated, and their characteristics were evaluated. The cut-off value for a positive finding was 0.7 U/mL.

Results : The median GPL-core antibody titer was 2.75 U/mL. Overall, 27 patients with MAC-PD met the ATS guidelines, and 11 were positive once on sputum culture. The mean antibody titer was 5.65 U/mL with identification of pathogens and 3.61 U/ml without (p=0.089). On chest computed tomography (CCT), 48 patients showed micronodular shadows and divergent shadows, and 48 showed bronchodilation. The mean antibody titer was higher in patients with than without these shadows on CCT (p=0.0014, p<0.0001).

Conclusion : GPL-core antibody titer was higher in patients with MAC-PD when shadows were seen on CCT. Therefore, GPL-core antibody is useful for diagnosing MAC-PD.
Comparison of Two Anti-Thy 1.1-Abrin A-Chain Immunotoxins Prepared With Different Cross-Linking Agents: Antitumor Effects, In Vivo Fate, and Tumor Cell Mutants
Authors: P E Thorpe, D C Blakey, A N Brown, P P Knowles, R E Knyba, P M Wallace, G J Watson, E J Wawrzynczak
Journal: JNCI Journal of the National Cancer Institute (1987)

The A-chain of the plant toxin abrin was covalently linked to monoclonal anti-Thy 1.1 antibody (OX7) with the use of either N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) or 2-iminothiolane hydrochloride (2IT). The SPDP reagent generates a linkage containing a disulfide bond and an amide bond, whereas the 2IT reagent generates a linkage containing a disulfide bond and an amidinium bond. The two immunotoxins were powerfully and specifically toxic to Thy 1.1-expressing murine AKR-A lymphoma cells in vitro. Both reduced the rate of protein synthesis of the cells by 50% at a concentration of 10(-11) M. However, clonogenic assays revealed that about 1% of the AKR-A cells survived treatment with high concentrations of OX7-SPDP-abrin A, whereas only about 0.1% survived treatment with similar concentrations of OX7-2IT-abrin A. Several clones of the surviving cells were isolated. Of 11 clones of cells that had survived exposure to OX7-SPDP-abrin A, 10 were resistant to further treatment with OX7-SPDP-abrin A but had normal sensitivity to OX7-2IT-abrin A. These clones expressed moderate to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. In contrast, all 10 clones of cells that had survived exposure to OX7-2IT-abrin A were substantially or entirely resistant to both immunotoxins. They expressed low to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. The 2IT-linked immunotoxin was much more effective than the SPDP-linked immunotoxin at protecting nu/nu mice against the growth of AKR-A lymphoma cells in the peritoneal site. A single iv injection of 0.3 nmol OX7-2IT-abrin A eradicated at least 99.99% of the tumor cells, as judged from the extension in the median survival time of the animals, whereas OX7-SPDP-abrin A eradicated only about 99% of the cells. The tumors that developed in the animals that received OX7-2IT-abrin A were Thy 1.1-negative, whereas those in the recipients of OX7-SPDP-abrin A generally expressed normal levels of the Thy 1.1 antigen. The difference in antitumor activity of the immunotoxins was not due to differences in their in vivo fate, inasmuch as they were cleared from the bloodstream at an identical rate and broke down at the same rate to release free antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of Chemically Induced Carcinogenesis of Canine Cells In Vitro by Infection With Mouse Xenotropic Type C Virus23
Authors: Johng S. Rhim, Paul Arnstein
Journal: JNCI Journal of the National Cancer Institute (1980)

C57L mouse xenotropic type C virus infection inhibited N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced in vitro transformation of embryo cells from inbred beagles. Treatment with MNNG induced in vitro neoplastic transformation in uninfected canine cells but not in C57L virus-infected canine cells; the C57L virus-infected canine cells not treated with MNNG also remained untransformed. In this dog cell system, preinfection with a C57L mouse xenotropic type C virus inhibited in vitro neoplastic transformation induced by MNNG.
Mechanisms of Disease: Pemphigus and Bullous Pemphigoid
Authors: Christoph M. Hammers, John R. Stanley
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies.
Immunity Against MOPC 104E Plasmacytoma: Effects of Tumor Size and Time Post Therapy on In Vivo Tumor Immunity 2
Authors: R. A. Lubet, D. E. Carlson
Journal: JNCI Journal of the National Cancer Institute (1978)

BALB/c mice with the plasmacytoma MOPC 104E were cured of palpable tumors (6-15x10(7) cells) with a single injection of cyclophosphamide (10 mg/kg). Animals cured of tumor showed a considerable increase in their ability to reject secondary challenge with graded numbers of viable tumor cells. Mice with palpable subcutaneous tumors were cured therapeutically and rechallenged 22, 44, or 120 days post therapy. The ability of such animals to reject secondary tumor cell challenge was similar in all groups, which implied that in vivo tumor immunity remained relatively constant for at least 4 months post therapy. A second group of animals was treated therapeutically (10 mg cyclophosphamide/kg) 4, 11, or 20 days post tumor cell injection. These therapeutically treated animals were then rechallenged with various numbers of viable tumor cells 30 days post therapy. Mice given cyclophosphamide 4, 11, or 20 days post tumor injection rejected 6, 60, or 400 times as many tumor cells, respectively, as did control animals. These results implied that, over the range of tumor sizes investigated, exposure to greater amounts of tumor antigen resulted in increasing amounts of residual tumor immunity following cure.
Dual Role of Autophagy in Stress‐Induced Cell Death in Rheumatoid Arthritis Synovial Fibroblasts
Authors: Masaru Kato, Caroline Ospelt, Renate E. Gay, Steffen Gay, Kerstin Klein
Journal: Arthritis & Rheumatology (2013)

To investigate the role of autophagy in the regulation of cell death in rheumatoid arthritis synovial fibroblasts (RASFs).RASFs and osteoarthritis synovial fibroblasts (OASFs) were treated with thapsigargin (TG), an inducer of endoplasmic reticulum (ER) stress, and MG132, a proteasome inhibitor. Then, 3-methyladenine was used as an autophagy inhibitor and bafilomycin A1 as a lysosome inhibitor. Polyubiquitinated proteins, p62, and autophagy induction were evaluated by immunoblotting, immunofluorescence microscopy, and immunohistochemistry, respectively. OASFs were transfected with small interfering RNA targeting autophagy-linked FYVE protein (ALFY). Cell death was evaluated by flow cytometry and a caspase 3 activity assay.In RASFs, the induction of autophagy by TG and MG132 was increased compared to that in OASFs. Whereas autophagy promoted a caspase 3-independent induction of cell death under ER stress, autophagy had a protective role in apoptosis induced by proteasome inhibition. Treatment of RASFs with 3-methyladenine blocked TG-induced cell death. ER stress induced a strong accumulation of p62-positive polyubiquitinated protein aggregates, accompanied by the formation of large vacuoles in RASFs but not OASFs. Furthermore, TG-induced p62 protein expression was increased, whereas TG-induced ALFY expression was reduced, in RASFs compared to OASFs. ALFY knockdown promoted the accumulation of p62, the formation of polyubiquitinated protein aggregates, and cell death.Our data provide the first evidence of a dual role of autophagy in the regulation of death pathways in RASFs. A reduced expression of ALFY and the formation of p62-positive polyubiquitinated protein aggregates promote cell death in RASFs under severe ER stress.
Quantitative Radiosensitivity Studies of Solid Carcinomas &lt;italic&gt;In Vivo&lt;/italic&gt;: Methodology and Effect of Anoxia&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Kelly H. Clifton, Russell C. Briggs, Helen B. Stone
Journal: JNCI Journal of the National Cancer Institute (1966)

A transplantation assay method has been developed for studies of cell survival in solid adenocarcinomas of mice irradiated in vivo. The assay depends on the inverse relationship between the time from grafting until tumors are first palpable and the logarithm of the volume of viable tumor cells inoculated. In the current experiments, sources of variation in the procedure were examined, and D37 values were determined for Adenocarcinoma 755 and Adenocarcinoma MTG-B irradiated in vivo with 137Cs-γ-rays. The D37 of MTG-B tumor cells irradiated in situ indead mice was also determined. The data suggest that D37 values for such tumor cells irradiated in vivo reflect the sensitivity of a relatively resistant, anoxic fraction which comprises a minority of the tumor cell population. Radiation damage to the larger fraction of cells that were more sensitive and presumably beHer oxygenated was not reflected in the observed Da7 values, but was interpreted as affecting the lower extrapolation number of the mixed cell population. These studies demonstrate that the lcinetics of the acute cytolethal response of solid carcinoma cells irradiated in vivo are similar to those of free cell tumor and culture systems.
Regulation of expression of cd133, a colon cancer stem cell marker and other stemness genes/pathways, by celecoxib: Clues from clinical observations
Authors: Y. Deng, L. Wang, Q. Tian, C. Miller, T. Lin, A. J. Chien, C. M. Ulrich, W. M. Grady, C. A. Blau, E. H. Lin
Journal: Journal of Clinical Oncology (2009)

e15065 Background: CD133 identifies intestinal stem cells and colon CSC, the putative culprit of cancer initiation, progression and resistance. Elevated CD133 levels at protein &amp; mRNA levels predict poor outcomes in patients (pts) with colon cancer. Given that celecoxib reduces colon polyp and only maintenance capecitabine plus celecoxib lead to paradoxically high complete remission (CR) in colon cancer pts who had no resection or positive margin resection of metastases (ASCO 2007), we hypothesized that celecoxib could modulate CD133 and other stemness genes/signaling pathways. Methods: we studied the effects of celecoxib versus 5-FU on CD133, Wnt and other stemness genes/pathways using flow cytometry, immunoflurorescence, real time RT-PCR, western blot, TOP-Flash for Wnt, limiting dilution assay, and Affymetrix in colon cancer cell lines and primary colon cancer spheres. Results: Celecoxib or 5FU inhibited the growth of COX-2+ HT29 or COX-2- DLD1 that express CD133 at 80% and 30% respectively. Only celecoxib down-regulated CD133 expression at the mRNA, and protein levels in a dose and time dependent manner. This effect could not be rescued with PGE2 and may be due to Wnt inhibition. Microarray showed 4 folds down-regulation of CD133 and other stemness genes e.g. CD24, ABC transporters, and LGR4/5, findings of colon cancer sphere under differentiation. Celecoxib affected several key stem cells signaling pathway, restored RB and promote cell cycle progression (P &lt; 0.05). In contrast, 5FU affected G2M transition but had no effects on stemness genes/pathways (p &lt; 0.05). Celecoxib resulted in 6–10 folds reduction in colony size and number with 5.6–36 folds down-regulation of CD133 mRNA in primary colon cancer spheres. Pts with confirmed radiographic CR who had received &gt;6 months of maintenance capecitabine and celecoxib reached 5-year survival &gt; 90% comparable to pts who achieved pathological CR (12/19). Conclusions: Targeting colon CSC with capecitabine and celecoxib may lead to durable CR and survival and deserves further investigation. No significant financial relationships to disclose.
Interactions between adiposity and genetic polymorphisms on the risk of psoriasis
Authors: W.-Q. Li, J.-L. Han, M.-F. Zhang, A.A. Qureshi
Journal: British Journal of Dermatology (2012)

Adiposity is a known risk factor for psoriasis. Genome-wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis while the evidence on gene-environment interactions in psoriasis is very sparse.To investigate the effect modification by adiposity measures on the association between single-nucleotide polymorphisms (SNPs) from published GWAS and risk of psoriasis.Our psoriasis GWAS dataset comprised 9194 participants, including 337 individuals with psoriasis and 8857 controls from six GWAS, nested within the Nurses' Health Study (NHS), NHS II, and Health Professionals' Follow-up Study. Clinician-diagnosed psoriasis was ascertained with high validity. For stratified analyses, body mass index (BMI) was dichotomized at 25, and waist circumference was dichotomized at 30 (women) and 36 inches (men), while waist-hip ratio (WHR) was dichotomized at 0·8 (women) and 1·0 (men).Forty-one out of 44 previously reported psoriasis-related SNPs were included in our GWAS datasets. After excluding those with high linkage disequilibrium, 33 remained in the analysis. There were significant interactions between BMI and two SNPs in the IL12B (rs3212227) and IL23R (rs7530511) genes. Further analysis of these two SNPs indicated interactions between rs3212227 and waist circumference or WHR [P for interaction (P ) < 0·05], but not for rs7530511. These observations were confirmed among participants without type 2 diabetes or coronary heart disease. The interactions remained after simultaneously adjusting for BMI as a continuous variable. In addition, we did not observe a significant main effect for rs7530511.The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.
In Vivo Immunologic Selection of Proviral Gene Deletion Variants From a Nonproducer Clone
Authors: Y. Tanio, C. Talmadge, G. Dekaban, J. Hovis, S. H. Ohanian, B. Zbar
Journal: JNCI Journal of the National Cancer Institute (1986)

The mechanism by which tumors recur at sites of injection of retrovirus-infected fibrosarcoma cell lines was investigated. Previously, it was established that tumor recurrences reflect outgrowth of rare cells that lack viral antigens and are susceptible to superinfection with the homologous retrovirus. In the present study clones isolated from a retrovirus-infected cell line were evaluated as precursors for tumor recurrence. Under conditions of in vivo immunologic selection, a clone that contained a single abbreviated copy of the provirus formed variants that lacked the proviral gene. Tumor variants lacking the proviral gene grew progressively in both nonimmune and virus-immune male Sewall Wright strain 2 guinea pigs. Tumor recurrence could be prevented by superinfection of the virus-infected fibrosarcoma cell line or by superinfection of the precursor for tumor recurrence. Cell lines infected with retroviruses varied in frequency of tumor recurrence formation. This model may be useful in analyzing gene deletion as a mechanism of tumor escape from host immunologic attack.
Transmission of the Mammary Tumor Virus by the GR Mouse Strain. II. Genetic Studies2
Authors: S. Nandi, Cheryl Helmich
Journal: JNCI Journal of the National Cancer Institute (1974)

The genetic basis of congenital transmission of mammary tumor virus (MTV) by GR females was studied with F1 F2, and backcross populations of GR X BALB/c (C-) mice. All mice were foster-nursed by MTV-free C- mothers. The occurrence of 1 or more of the 3 kinds of mammary lesions (pregnancy-dependent tumors, pregnancy-independent tumors or hyperplastic nodules) in force-bred females within the first year was considered an indication of MTV infection. A mouse without mammary lesions was still considered MTV-infected if she transmitted MTV through her milk. One hundred percent of reciprocal F1 hybrids developed mammary tumors by 7 months, and the incidence of mammary tumors in (GR × C-) × GR backcrosses was also close to 100%. From the criteria used to determine MTV infection, 75% of the (GR × C-) × GR backcross females were MTV-infected. Although mammary lesions were detected in only 77% of the F2:[(GR × C-) × (GR × C-) populations, some lesion-free mice also transmitted MTV by milk. It was predicted that at least 90% of the F2 females were likely to be infected with MTV. The ratios of MTV-infected females in F1 F2, and backcross populations appeared compatible with the hypothesis that 2 independently segregating dominant genes in the GR mouse strain are involved in congenital transmission of its MTV, and that either one of these genes alone is adequate for MTV transmission.
Attitudes Toward DSM-IV Dissociative Disorders Diagnoses Among Board-Certified American Psychiatrists
Authors: Harrison G. Pope, Paul S. Oliva, James I. Hudson, J. Alexander Bodkin, Amanda J. Gruber
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The authors assessed the opinions of American psychiatrists regarding the diagnostic status and scientific validity of the DSM-IV categories of dissociative amnesia and dissociative identity disorder. METHOD: A one-page questionnaire was mailed to a random national sample of 367 board-certified American psychiatrists. RESULTS: Three hundred one responses were received—a rate of 82%. Only about one-third of respondents replied that dissociative amnesia and dissociative identity disorder should be included without reservations in DSM-IV; a larger proportion replied that these categories should be included only as proposed diagnoses. Only about one-quarter of respondents felt that diagnoses of dissociative amnesia and dissociative identity disorder were supported by strong evidence of scientific validity. CONCLUSIONS: Among board-certified American psychiatrists, there currently appears to be little consensus regarding the diagnostic status or scientific validity of dissociative amnesia and dissociative identity disorder.
Travel-related imported infections in Europe, EuroTravNet 2009
Authors: S. Odolini, P. Parola, E. Gkrania-Klotsas, E. Caumes, P. Schlagenhauf, R. López-Vélez, G.-D. Burchard, F. Santos-O'Connor, L. Weld, F. von Sonnenburg, V. Field, P. de Vries, M. Jensenius, L. Loutan, F. Castelli
Journal: Clinical Microbiology and Infection (2011)
Evidence for single limb exercise in patients with COPD or chronic heart failure - A systematic review
Authors: Andre Nyberg, Britta Lindström, Karin Wadell
Journal: European Respiratory Journal (2012)

Background : Although single limb exercise (SLE), i.e. training using one arm and/or one leg at a time, has been used in patients with COPD or chronic heart failure (CHF) the evidence for SLE has not been evaluated systematically and remains unclear.   Objectives : Our hypothesis was that SLE is beneficial for patients with COPD or CHF. The aim of this systematic review was to investigate the current evidence for SLE compared to any comparator and regarding exercise capacity, quality of life (QoL) or dyspnea in patients with COPD or CHF.   Methods : CENTRAL, PubMed and PEDro databases were searched for randomized controlled trials fulfilling inclusion criteria. Extraction of data, evaluation of study quality using the PEDro scale and the Cochrane risk of bias tool was performed by two review authors. Data and evidence for SLE were summarized in accordance with GRADE guidelines.   Results : Six RCTs, (two in COPD, and four in CHF) met the inclusion criteria. COPD: Low quality evidence indicates improved exercise capacity but no difference on dyspnea after one-legged cycling compared to two-legged cycling. CHF: Low quality evidence indicate improved exercise capacity after single limb strength training compared to a control and two-legged cycling and improved QoL compared to a control. Meters walked and some QoL outcomes improved more after two-legged knee extension compared to one-legged knee extension. No differences between regimes on other exercise capacity and QoL outcomes was found.   Conclusions : The strength of the overall evidence to support the use of SLE regimes compared to other exercise regimes or control in patients with COPD or CHF is low and further research is requested.