tbuckley/cabot-search huggingface dataset:
Lymphocyte senescence in COPD is associated with loss of glucocorticoid receptor expression by cytotoxic/ pro-inflammatory lymphocytes
Authors: Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul Reynolds, Sandra Hodge
Journal: European Respiratory Journal (2014)

Glucocorticoid (GC) resistance is a major barrier in the treatment of COPD and the reason for this unknown. We have shown that COPD is associated with an increase in cytotoxic/pro-inflammatory T and NKT-like cells particularly CD8+ subsets. Loss of the co-stimulatory molecule CD28 (lymphocyte senescence) from these cells was associated with a further increase in their cytotoxic/ pro-inflammatory potential and resistance to GC. We hypothesized that lymphocyte senescence is associated with downregulation of the GC receptor (GCR) from these cells.  Blood was collected from 10 COPD and 10 healthy aged-matched controls. Cytotoxic/pro-inflammatory cytokine profiles, expression of CD28 and GCR and binding of Dexamethasone-Fluorescene were determined in lymphocyte subsets using flow cytometry.  Loss of CD28 was associated with an increase in the percentage of T and NKT-like cells producing granzyme b, IFNγ and TNFα in all subjects studied. Loss of CD28 was associated with a loss of GCR and Dex-Fluor staining. There was a significant loss of GCR in CD8+CD28null compared with CD4+CD28null cells in both groups. There was a significant negative correlation between GCR expression and the percentage of T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R= -.763, p  Lymphocyte senescence in COPD is associated with loss of GCR in CD28null T and NKT-like cytotoxic/pro-inflammatory cells and a fall in lung function, suggesting that alternative treatment options to GCS are required to inhibit these pro-inflammatory/cytotoxic cells.
Transplantable Primate Tumors Induced by Rous Sarcoma Virus. I. Induction of Tumors Transplantable Into Young Marmosets<xref ref-type="fn" rid="FN1">2</xref>
Authors: B Marczynska, R J Massey
Journal: JNCI Journal of the National Cancer Institute (1986)

The tumors induced in white-lipped marmosets (Saguinus fuscicollis, S. nigricollis) by Rous sarcoma virus (RSV) of chicken origin (RSV-SR) were not transplantable to allogeneic hosts. In contrast, RSV rescued from these tumors (RSV-M) induced sarcomas that were transplantable to young but not to adult marmosets. The tumors induced by RSV-M and the transplants rapidly enlarged, metastasized to various organs, and killed the recipients 29-59 days post inoculation. Cell lines were readily established from all transplantable sarcomas. No virus expression was detected in transplantable tumor cell lines by electron microscopy or by biochemical and biological assays. However, RSV of the same subgroup as RSV-SR was rescued from both short-term and long-term tumor cell cultures by cocultivation with chicken embryo fibroblasts (CEF). The rescued viruses transformed marmoset cells 100-fold more efficiently than CEF cells, although CEF cells remained permissive for virus replication. Cytogenetic studies revealed extensive chromosome abnormalities in tumor transplants but not in RSV-M-induced sarcomas. All cell lines were hyperploid and contained structurally abnormal, large metacentric and telocentric chromosomes. Immunologic studies failed to detect group-specific (gs) antigen of the avian sarcoma-leukemia complex in either RSV-M-induced, transformed cells or tumor transplants. By complement-dependent cytotoxicity assays, with the use of marmoset anti-gs serum, RSV-associated antigen could be detected on the surfaces of tumor cells. No differences in the expression of this antigen existed between transplantable and nontransplantable marmoset sarcomas. All transplantable cell lines contained abnormal amounts of lipids and glycogen in comparison to RSV-SR-induced tumors and normal marmoset cell lines. The glycogen was associated with unique cytoplasmic membrane complexes and was surrounded by either single- or double-membraned vesicles.
Avoidance of base runs in switch regions of immune-system genes.
Authors: Pascale Perrin, Richard Grantham
Journal: Molecular Biology and Evolution (1988)

Mouse immunoglobulin (Ig) switch-region sequences are anti-"runny"; that is, they have a smaller amount of their total bases in homonucleotide tracts ("runs") than would be expected if each nucleotide in the sequence were a random selection from a pool of the composition of the region. The switch sequences involve the first intron of rearranged Ig heavy-chain genes; this intron differs strikingly from the succeeding ones, which are "runny" (have more bases than expected in runs). Switch regions are the only category of sequences so far found to be antirunny by statistical test. This sequence characteristic is related to the presence in switch sequences of repeating heteronucleotides. We suggest that the resulting base dispersion and increased complexity favor more specific interactions between sequences, which may be advantageous in recombinational processes such as switching and translocation.
Abstract 14887: Short-Term Costimulatory Molecule Blockade Promotes Long-Term Engraftment of Transplanted Human Embryonic Stem Derivatives and Improves Cardiac Recovery
Authors: Bruno C Huber, Julia D Ransohoff, Katherine J Ransohoff, Patricia E de Almeida, Joseph D Gold, Robert C Robbins, Joseph C Wu
Journal: Circulation (2012)

Introduction: Transplantation of human embryonic stem cells (hESC) and their derivatives offers great promise in preventing cardiac failure following acute myocardial infarction. However, transplantation requires effective long-term immunosuppression which is problematic due to toxicity of traditional drugs, e.g. Cyclosporine A (CsA). Here, we test the hypothesis that briefly blocking costimulatory molecule signaling with two agents (CTLA4-Ig and anti-LFA-1) promotes cell survival and improves functional outcome of transplanted hESC-derived endothelial cells (hESC-ECs) after myocardial infarction. Methods/Results: Human ESC-ECs were stably transduced with GFP-Fluc for fluorescence and bioluminescence imaging (BLI). 2×106 cells were injected into the left ventricle of immunocompetent (FVB) and immunodeficient (SCID) mice following LAD ligation. Animals were randomized to receive either no immunosuppression, a standard approach (CsA and prednisone), or a short course of costimulatory blocking agents. In the...
India makes strides in some, but not all, health goals, finds WHO
Authors: C. Travasso
Journal: BMJ (2015)

India has successfully met targets to reduce the spread of HIV and improve the availability of drinking water but has a long way to go in improving sanitation facilities and providing universal access to reproductive healthcare, the latest World Health Statistics report has found.

Findings showed that although the proportion of Indians using improved sources of drinking water rose from 70% in 1990 to 93% in 2012, the proportion of the population using improved sanitation facilities rose from 18% to only 36% over the same period.1

India made progress in controlling HIV and tuberculosis. Prevalence of HIV/AIDS fell from 222 per 100 000 in 2001 to 166 per 100 000 in 2013. However, only 36% of those …
Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Switzerland: sampling only invasive isolates does not allow a representative description of the local diversity of clones† †This study was presented in part at the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), London, UK, April 2012.
Authors: L. Senn, P. Basset, G. Greub, G. Prod'hom, R. Frei, R. Zbinden, V. Gaia, C. Balmelli, G.E. Pfyffer, K. Mühlemann, G. Zanetti, D.S. Blanc
Journal: Clinical Microbiology and Infection (2013)
Hodgkin's disease presenting below the diaphragm: a review.
Authors: J G Krikorian, C S Portlock, P M Mauch
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.10.1551 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3531425 Hodgkin's disease presenting below the diaphragm: a review. J G KrikorianxJ G KrikorianSearch for articles by this author , C S PortlockxC S PortlockSearch for articles by this author , P M MauchxP M MauchSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.10.1551 First Page PDF © 1986 by American Society of Clinical Oncology
Late stage of experimental pulmonary fibrosis is modulated by collagen V
Authors: Alexandre Todorovic Fabro, Mozar Suzigan de Almeida, Igor O. Minatel, Erika C. Prado, Claudia Aparecida Rainho, P.R. Teodoro Walcy, Edwin R. Parra Cuentas, Vera Capelozzi, Helmut Popper
Journal: European Respiratory Journal (2012)

Background: The IPF is a disease with high morbi-mortality. Several experimental models of pulmonary fibrosis (PF) has been proposed, however, a later stage of these models tend to go for the resolution of the fibrosis, but in different degrees of intensity depending on the strain. Thus these mechanisms in certain strains may participate in the progression of PF.  Aims: To study the immune-fibrotic pattern in different models of PF in the late stage (21d).  Methods: We used the models of Bleomycin-Balb/c (BLM), Paraquat-Balb/c, Bleomycin-C57BL/6 and BLM-IL17RA-KO-C57BL/6. We analyzed the amounts of total collagen (TC) and collagen V (Col5) through the morphometric evaluation by the picrosirius and IF. These data were validated by RT-PCR of Col5.  Results: The peribronchiolar TC by PPM did not differ between the treated groups, but the peripheral interstitial TC was higher in the C57BL/6, independent of the absence of IL-17RA. The protein expression of Col5 was higher in IL-17RA-KO (75,5±9% X 52,7±13%; p=0,01) and lower in BLM-Balb/c (69,8±3,4% X 53,3±14,3%; p  Conclusion: The perpetuation of PF in fibrosis-susceptible mice is related to expression of Col5 in a IL-17-independent manner and this suggests that Col5 is an important component responsible for the development of PF.
Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome
Authors: O Marrone, A Stallone, A Salvaggio, F Milone, V Bellia, G Bonsignore
Journal: European Respiratory Journal (1991)

The spectrum of breathing events during sleep in patients with obstructive sleep apnoea syndrome (OSAS) after the abolition of obstructive apnoeas has been extensively studied in tracheostomized patients, but has received much less attention in patients submitted to continuous positive airway pressure (CPAP). We analysed the breathing pattern during sleep in forty patients while CPAP was administered. A regular breathing pattern throughout the sleep study was observed in 15 patients. In the remaining 25 subjects, one or more of the following events was observed: central apnoeas, hypopnoeas, periodic breathing, prolonged oxyhaemoglobin desaturations. Central apnoeas during non-rapid eye movement (NREM) sleep appeared almost exclusively after arousals or wakefulness periods; their prevalence did not significantly differ between subjects who showed and who did not show similar events before CPAP. Central apnoeas in rapid eye movement (REM) sleep had a random occurrence. Hypopnoeas were found only in REM sleep, and, like central apnoeas, occurred randomly; in one patient they had a prolonged duration (up to 110 s). Periodic breathing was observed in only two subjects, one of whom had congestive heart failure: it was limited to NREM sleep and was not associated with arousals or shifts in sleep stage. Prolonged oxyhaemoglobin desaturations were found mainly in REM sleep; most subjects with such abnormalities had daytime blood gas alterations. In conclusion, abnormalities of the breathing pattern of patients with OSAS can be observed during CPAP and after tracheostomy, but periodic breathing is less common than is reported after tracheostomy, and is probably caused by different mechanisms.
Whose data are they anyway?
Authors: I. Oswald, A J M Slovak, C Kalman, N F Davies, G Mayho, R Wood, J T Winkler
Journal: BMJ (1997)

# Access to raw data would need legislation {#article-title-2} Editor—Tony Delamothe argues that there should be universal access to the raw data of medical research.1 I agree, subject to practicality: some records are very bulky and cannot be kept indefinitely. Contrary to Delamothe's assertion, electronic files rarely are raw data—they are data that have been processed, and in the handling they have been open to error and filtering. Delamothe does not mention that legislation would be required in the United Kingdom and the United States, because lobbying by the pharmaceutical industry has ensured that the raw data of their treatment trials have to remain secret unless a litigant can obtain a court order. The Freedom of Information Act in the United States does not give access to those copies of raw data from drug companies that are held within the Food and Drug Administration. For the past decade those copies have in any case been limited to the records of patients who died or entered hospital during a treatment trial. 1. 1.↵1. Delamothe T .Whose data are they anyway?BMJ1996; 312:1241–2. (18 May.) [OpenUrl][1][FREE Full Text][2] # Datasharing would cause problems in nuclear industry {#article-title-4} Editor—The article by Tony Delamothe advocating researchers' unrestricted access to anonymised raw data1 might lead one to think the author naive, arrogant, and authoritarian. We do not hold such views, but we nevertheless … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DDelamothe%26rft.auinit1%253DT.%26rft.volume%253D312%26rft.issue%253D7041%26rft.spage%253D1241%26rft.epage%253D1242%26rft.atitle%253DWhose%2Bdata%2Bare%2Bthey%2Banyway%253F%26rft_id%253Dinfo%253Apmid%252F8634604%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=312/7041/1241&atom=%2Fbmj%2F314%2F7082%2F749.2.atom
Validation of hepatitis B virus–related hepatocellular carcinoma prediction models in the era of antiviral therapy
Authors: Kyu Sik Jung, Seung Up Kim, Kijun Song, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim, Kwang‐Hyub Han
Journal: Hepatology (2015)

Several risk prediction models have been created to predict hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) occurrence, with promising results. However, their prognostic performances need to be validated in the era of antiviral therapy. From 2006 to 2011, patients with chronic HBV infection were recruited and those with a history of HCC or hepatic decompensation were excluded. At enrollment, liver stiffness (LS) was measured using transient elastography. We assessed the performances of conventional HCC prediction models (CU-HCC, GAG-HCC, REACH-B, and LSM-HCC scores) and the modified REACH-B (mREACH-B) score where LS values were incorporated into REACH-B score instead of serum HBV-DNA levels. Of 1,308 subjects analyzed, the median age was 50.0 years (883 men). During the follow-up (median, 75.3 months), HCC developed in 125 (9.6%) patients. mREACH-B score had the highest areas under the receiver operating characteristic curves (AUROCs) for the prediction of HCC development at 3/5 years (0.828/0.806), compared with LSM-HCC (0.777/0.759), GAG-HCC (0.751/0.757), REACH-B (0.717/0.699), and CU-HCC (0.698/0.700) scores, respectively, with statistical significances (all P values <0.05 vs. mREACH-B). When serum HBV-DNA levels were excluded from the formula for REACH-B score, AUROCs for HCC development at 3/5 years improved paradoxically (from 0.717/0.699 to 0.757/0.732, respectively). In patients with antiviral therapy (n = 848), mREACH-B score had the better prognostic performances for HCC development at 3/5 years, compared to other prediction models. However, in patients without antiviral therapy (n = 460), it had the prognostic performances comparable to those of other prediction models.Prognostic performances of mREACH-B score seemed better compared to conventional models. In the era of antiviral therapy, incorporation of serum HBV-DNA level should be applied cautiously and individual risks should be assessed effectively based on the fibrotic burden.
Haemodynamic effects of short-term nasal continuous positive airway pressure therapy in sleep apnoea syndrome: monitoring by a finger arterial pressure device
Authors: E Sforza, V Capecchi, E Lugaresi
Journal: European Respiratory Journal (1992)

We have evaluated the effects of short-term nasal continuous positive airway pressure (nCPAP) therapy on systemic blood pressure and heart rate in patients with obstructive sleep apnoea syndrome. Twenty five consecutive patients were examined during baseline conditions (No-CPAP) and during one night of nCPAP treatment (CPAP). The mean value and the variation coefficient of cardiovascular variables, examined by a finger arterial pressure device (Finapres), were determined in wakefulness and sleep. Without nCPAP an increase in blood pressure from wakefulness to sleep was observed in all patients from 138 +/- 3 mmHg to 146 +/- 3 and 155 +/- 4 mmHg, and from 80 +/- 1 mmHg to 82 +/- 2 and 84 +/- 2 mmHg, respectively, for systolic and diastolic values in non rapid eye movement (NREM) and rapid eye movement (REM) sleep. Conversely, heart rate decreased from 75 +/- 2 beats.min-1 to 70 +/- 2 and 69 +/- 2 beats.min-1. In addition, variability of heart rate and blood pressure was greatly increased compared with the awake state. Short-term nCPAP therapy significantly reduced systolic pressure from 144 +/- 3 mmHg to 137 +/- 3 and 143 +/- 4 mmHg during NREM and REM sleep, respectively, associated with a decrease in heart rate (from 69 +/- 2 to 65 +/- 2 beat.min-1). In total sleep and in all sleep stages a significantly reduced variability (p less than 0.001) was found. No changes were observed for diastolic pressure during CPAP night compared with baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer.
Authors: M Fukuoka, H Niitani, A Suzuki, M Motomiya, K Hasegawa, Y Nishiwaki, T Kuriyama, Y Ariyoshi, S Negoro, N Masuda
Journal: Journal of Clinical Oncology (1992)

PURPOSE Camptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. To evaluate the effectiveness of CPT-11 in patients with non-small-cell lung cancer (NSCLC), a phase II study was conducted between April 1989 and February 1990. PATIENTS AND METHODS Seventy-three patients were entered onto the study. All patients had had no previous therapy and had measurable disease. Their median age was 67 years (range, 34 to 75 years). Fifty-four patients had a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, and 19 had a PS of 2. CPT-11 was given at a dose of 100 mg/m2 by intravenous 90-minute infusion once a week. The dose of CPT-11 was modified based on the WBC count obtained on the day of drug administration. RESULTS Of 72 assessable patients, 23 (31.9%) showed a partial response (95% confidence interval, 20.2% to 43.6%). Of 40 patients with a stage IV disease, 13 (32.5%) responded. Response rates for patients with PS 0 or 1 and those with PS 2 did not differ (34.0% and 26.3%, respectively). The median duration of response in patients showing a PR was 15 weeks. The median survival time for all patients was 42 weeks. The major toxicities were leukopenia and diarrhea. Grade 3 or 4 leukopenia and diarrhea occurred in 18 patients (25%) and 15 patients (21%), respectively. These toxicities were unpredictable. Other toxicities of greater than or equal to grade 3 included nausea/vomiting (22%), anemia (15%), alopecia (4%) and pneumonitis (3%). One patient died of pulmonary toxicity (interstitial pneumonitis). CONCLUSIONS CPT-11 is a very active agent for NSCLC with acceptable toxicities. Further trials in combination with other agents for this disease are warranted.
Abstract 1373: Postnatal Ectopic Overexpression of Bmp10 in Ventricular Myocardium Disrupts Cardiac Developmental Hypertrophic Growth
Authors: Hanying Chen, Weidong Yong, Weihua Shen, Yongzheng He, Weinian Shou
Journal: Circulation (2006)

Cardiac hypertrophies have traditionally been classified into physiological and pathological hypertrophy and regarded as adaptive responses to hemodynamic load in postnatal heart when cardiomyocyte...
Combination of Tumor Necrosis Factor α and Interleukin‐6 Induces Mouse Osteoclast‐like Cells With Bone Resorption Activity Both In Vitro and In Vivo
Authors: Kazuhiro Yokota, Kojiro Sato, Takashi Miyazaki, Hideki Kitaura, Hisako Kayama, Fumihiko Miyoshi, Yasuto Araki, Yuji Akiyama, Kiyoshi Takeda, Toshihide Mimura
Journal: Arthritis & Rheumatology (2013)

Objective To clarify the function of osteoclast‐like multinuclear cells differentiated from bone marrow–derived macrophages (BMMs) by a combination of tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6), and to investigate the molecular mechanisms underlying the differentiation. Methods BMMs were stimulated by TNFα and/or IL‐6. The cells were then compared with conventional osteoclasts differentiated in vitro by RANKL. An in vitro pit formation assay on dentine slices and an in vivo resorption assay of calvarial bones were performed. We also evaluated the activities and expression levels of NF‐κB, c‐Fos, and NF‐ATc1, which are essential to the differentiation of conventional osteoclasts. Small interfering RNA was used to knock down c‐Fos. The effects of genetic ablation of STAT‐3 and pharmacologic inhibitors of NF‐AT, JAK, and ERK were also studied. Results Osteoclast‐like cell differentiation depended on TNFα and IL‐6 and was not inhibited by osteoprotegerin. These differentiated cells were associated with both in vitro and in vivo bone resorption activity. TNFα and IL‐6 had a synergistic effect on the activity and expression of c‐Fos. Knockdown of c‐Fos inhibited the expression of NF‐ATc1 and the differentiation of osteoclast‐like cells. All of these inhibitors blocked differentiation of the cells in vitro, but surprisingly, the conditional knockout of STAT‐3 did not. Tofacitinib also inhibited the bone destruction caused by TNFα and IL‐6 in vivo. Conclusion Our results demonstrate that a combination of the inflammatory cytokines TNFα and IL‐6 can induce osteoclast‐like cells that have in vitro and in vivo bone‐resorptive activity.