tbuckley/cabot-search huggingface dataset:
An <i>In vitro</i> Multistep Carcinogenesis Model for Human Cervical Cancer
Authors: Mako Narisawa-Saito, Yuki Yoshimatsu, Shin-ichi Ohno, Takashi Yugawa, Nagayasu Egawa, Masatoshi Fujita, Setsuo Hirohashi, Tohru Kiyono
Journal: Cancer Research (2008)

Human papillomaviruses (HPV) are believed to be the primary causal agents for development of cervical cancer, and deregulated expression of two viral oncogenes E6 and E7 in basal cells, mostly by integration, is considered to be a critical event for disease progression. However, lines of evidence suggest that, besides expression of E6 and E7 genes, additional host genetic alterations are required for cancer development. To directly test this hypothesis, we first transduced HPV16 E6 and E7 with or without hTERT into several lines of normal human cervical keratinocytes (HCK) from independent donors and then searched for additional alterations required for carcinogenesis. Oncogenic Hras(G12V) (Hras) provided marked tumor forming ability in nude mice and ErbB2 or c-Myc (Myc) endowed weaker but significant tumor forming ability. Combined transduction of Myc and Hras to HCKs expressing E6 and E7 resulted in the creation of highly potent tumor-initiating cells. These results show that only one or two genetic changes occurring after deregulated expression of high-risk HPV oncogenes might be sufficient for development of cervical cancer.
Tracheal distensibility in cystic fibrosis
Authors: P Lebecque, G Liistro, C Veriter, D Stanescu
Journal: European Respiratory Journal (1996)

Size and distensibility of large airways have important implications for flow limitation and the efficacy of coughing. From radiological and functional data, some authors have suggested an increased size and distensibility of the trachea in cystic fibrosis (CF). Using computed tomography (CT) we compared size and distensibility of the trachea in 5 cystic fibrosis patients and five age- and height-matched healthy volunteers. Tracheal cross-sectional area was measured 25 mm below the cricoid cartilage. CT recordings were made at functional residual capacity, at 0 and +20 cmH2O mouth pressure. Inductive plethysmography was used to check that during these manoeuvres lung volume did not change and that the glottis remained open. Tracheal cross-sectional area and derived indices of tracheal distensibility were similar in the two groups. This study does not support the concept of an increased size and distensibility of the trachea in cystic fibrosis.
Pulsatile Stretch Stimulates Superoxide Production and Activates Nuclear Factor-κB in Human Coronary Smooth Muscle
Authors: Keiichi Hishikawa, Barry S. Oemar, Zhihong Yang, Thomas F. Lüscher
Journal: Circulation Research (1997)

Abstract There is increasing evidence that oxidative stress is of pathophysiological importance in cardiovascular disease. Mechanical forces such as pulsatility may also contribute. Using human coronary artery smooth muscle cells (HCAS), we tested the hypothesis that stretch-induced cell proliferation is associated with oxidative stress. Stretch induced DNA synthesis in HCAS, and this was prevented by the antioxidants N -acetylcysteine and pyrrolidinedithiocarbamate (PDTC). Pulsatile stretch also increased superoxide production from HCAS in a time- and stretch-dependent manner. Stretch-induced superoxide production was inhibited by diphenyleneiodoniumchloride, an NADPH oxidase inhibitor, and p -chloromercuriphenylsulfonic acid, an NADH oxidase inhibitor, but not by the xanthine oxidase inhibitor oxypurinol or the cyclooxygenase inhibitor indomethacin. In electrophoretic mobility shift assays, tumor necrosis factor-α activated nuclear factor-κB (NF-κB) with a peak at ≈3 hours, whereas pulsatile stretch showed sustained activation during stimulation for up to 24 hours. The sustained activation of NF-κB was abolished by cotreatment with N -acetylcysteine or PDTC. Furthermore, treatment of HCAS with antisense p65 and p50 oligodeoxynucleotides of NF-κB inhibited stretch-induced DNA synthesis. We propose that pulsatile stretch increases oxidative stress and, in turn, promotes DNA synthesis via NF-κB in cultured human coronary artery smooth muscle cells.
Idiotope regulation by isotype switch variants of two monoclonal antiidiotope antibodies.
Authors: C E Müller, K Rajewsky
Journal: The Journal of Experimental Medicine (1984)

Previous work has shown that the injection of antiidiotope antibodies specific for idiotopes of the germline-encoded anti-(4-hydroxy-3-nitro-phenyl) acetyl (NP) antibody B1-8 enhanced or suppressed the expression of B1-8 idiotopes in subsequent humoral anti-NP responses, depending on the dose and perhaps also the isotype of the injected antibody. To formally answer the question of whether the isotype of an antiidiotope determines its effector function in this type of idiotypic control, we have performed regulatory experiments with isotype switch variants selected from two hybridomas secreting anti-B1-8 idiotopes of CBA (Ighj) and C57BL/6 (Ighb) origin. The antibodies of each variant family differ from each other only in the constant region of the heavy chain. The results show that, irrespective of whether an antiidiotope antibody belongs to the IgG1, IgG2b, IgG2a, or IgE class, a 10-ng dose enhances idiotope expression whereas a dose of 10 micrograms exerts a suppressive effect. It emerges from the present and parallel data that the expression of antibody V regions resembling idiotypically that of antibody B1-8 can be enhanced and suppressed by any of four antiidiotope antibodies that recognize distinct idiotopes on those V regions. This suggests that the initial step in the regulatory process induced by an antiidiotope is its binding to antibody V regions carrying the target idiotope. The antiidiotopes preferentially regulate the expression of antibodies that coexpress with the target idiotope other B1-8 idiotopes, despite the fact that some B1-8 idiotopes are also expressed independently of each other in anti-NP responses of idiotypically unmanipulated mice. This finding may reflect high affinity binding of the antiidiotopes to the target against which they were originally raised (i.e., antibody B1-8) or, more likely, a preferential recognition of B1-8-like V regions by regulatory T cells.
Letter: Vinyl chloride and cancer.
Authors: F J Roe
Journal: BMJ (1974)

Bauer's view, but a subsequent trial in Paki- stan6 failed to demonstrate a statistically sigicant effect.In addlition Rao et al.7 in a controlled and supervised trial with a closely related compound, shown to be high- ly effective in the laboratory, were able to show only a minimal prophylactic effect.If the thiosemicarbazones are really as effec- tive against variola virus in man, as Dr. Bauer claims, it is surprising that they have no appreciable effect on the success rate of vaccination with the closely related vaccinia ViruS.4 7Until more conclusive evidence is pre- sented in favour of hyperimmune ganxmaglobulin and antiviral drus of the thiosemicarbazone series we oDnsider that vaccination with all its limitations must re- main the first line of defence in containing outbreaks of smallpox.In our view this should 'be combined with hyperimmune gammaglobulin for those at particular risk.At the present time we do not believe that thiosemicarbazones have a part to play in -the routine prophylaxis of szulipox.-Weare, etc.
Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor- , in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study
Authors: G. R. Burmester, E. Feist, M. A. Sleeman, B. Wang, B. White, F. Magrini
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of mavrilimumab, a human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, in subjects with rheumatoid arthritis (RA). <h3>Methods</h3> A randomised, double-blind, placebo-controlled, dose-escalating phase I study in subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment. Subjects received single intravenous escalating doses of mavrilimumab (0.01–10.0 mg/kg) or placebo. <h3>Results</h3> 32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg were followed by five sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg, respectively). Adverse events were mild or moderate and were reported with similar frequency across all treatment cohorts. One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment. Systemic clearance of mavrilimumab approached that of endogenous IgG at doses &gt;1.0 mg/kg; pharmacodynamic activity was confirmed in the 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts. In exploratory analyses, reductions of acute phase reactants were observed in subjects with elevated C-reactive protein (&gt;5 mg/l) and erythrocyte sedimentation rate (≥20.0 mm/h) at baseline. No significant change in Disease Activity Score 28-joint assessment (DAS28) was seen in any of the cohorts. In mavrilimumab-treated subjects (n=15) with baseline DAS28 &gt;3.2, mean disease activity (DAS28) was significantly reduced at 4 weeks. <h3>Conclusion</h3> In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. Importantly, the safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA. Trial registration number: NCT00771420.
In renal transplantation blood cyclosporine levels soon after surgery act as a major determinant of rejection: Insights from the MY.S.S. Trial
Authors: Norberto Perico, Piero Ruggenenti, Eliana Gotti, Flavio Gaspari, Dario Cattaneo, Umberto Valente, Maurizio Salvadori, Giuseppe Segoloni, Donato Donati, Silvio Sandrini, Maria Ganeva, Borislav D Dimitrov, Giuseppe Remuzzi
Journal: Kidney International (2004)
The cyclic GMP-dependent protein kinase II gene associates with gout disease: identified by genome-wide analysis and case-control study
Authors: S-J Chang, M-H Tsai, Y-C Ko, P-C Tsai, C-J Chen, H-M Lai
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To identify the position of a gout susceptibility gene. <h3>Methods:</h3> A genome-wide scan was performed using 382 random polymorphic microsatellite markers spread across 22 autosomes in a Taiwanese family with gout to screen for the gout susceptibility genetic marker. Its association with gout by 33 single nucleotide polymorphisms (SNP) in 148 matched case–control subjects was confirmed. The family with gout comprised eight patients with gout and 10 gout-free subjects; case–control subjects were 74 male patients with gout and 74 healthy controls matched by age. <h3>Results:</h3> Analysis of the genome-wide scan results by a non-parametric linkage method found that chromosome 4q21 contains a locus significantly linked with gout (D4S3243 at 81 289 553 bp; p = 0.004; LOD score = 5.13). In SNP genotyping analysis at the neighbourhood regions of marker D4S3243 for the case–control subjects, the polymorphisms rs7688672 and rs6837293, located on the cGMP-dependent protein kinase II (cGK II) gene, were found to relate significantly to gout disease in a recessive model after adjustment of hyperuricaemia (OR = 2.89, 95% CI 1.19 to 7.02 and OR = 2.72, 95% CI 1.13 to 6.54, respectively). <h3>Conclusions:</h3> This study suggests that the cGK II gene on chromosome 4q21 is most likely to harbour gout disease independently of hyperuricaemia and is inherited recessively.
THE BIOLOGICAL AND THE SEROLOGICAL REACTIONS OF INFLUENZA BACILLI PRODUCING MENINGITIS
Authors: T. M. Rivers, Lawrence A. Kohn
Journal: The Journal of Experimental Medicine (1921)

1. An attempt has been made to standardize the cultural and the serological work on influenza bacilli. As technique and knowledge improve cultural and serological characteristics may be shown to be different from those reported here. The results are constant enough for comparison as they were obtained under as nearly similar conditions as possible. 2. Of thirteen meningitic strains of Bacillus influenzæ isolated by different workers during a period of 7 years, eleven are alike culturally and fall into two groups by absorption of agglutinin tests; seven are in Group 1, three in Group 2, with one intermediate strain. Two strains stand alone culturally and serologically. 3. Four blood culture strains from children with pneumonia differ from each other culturally and serologically. When these strains show a relation culturally to members of the meningitic group this is not confirmed by serological reactions. When more respiratory strains are studied there may be found among them some similar culturally and serologically to the meningitic group. 4. Evidence has been set forth in favor of the possibility that a certain group of influenza bacilli may have risen to a level of pathogenicity to produce a disease picture known as influenzal meningitis. If this be true an attempt should be made to obtain a potent serum for treatment.
Temperature corrections in routine spirometry.
Authors: D Cramer, A Peacock, D Denison
Journal: Thorax (1984)

Forced expiratory volume (FEV1) and forced vital capacity (FVC) were measured in nine normal subjects with three Vitalograph and three rolling seal spirometers at three different ambient temperatures (4 degrees C, 22 degrees C, 32 degrees C). When the results obtained with the rolling seal spirometer were converted to BTPS the agreement between measurements in the three environments improved, but when the Vitalograph measurements obtained in the hot and cold rooms were converted an error of up to 13% was introduced. The error was similar whether ambient or spirometer temperatures were used to make the conversion. In an attempt to explain the behaviour of the Vitalograph spirometers the compliance of their bellows was measured at the three temperatures. It was higher at the higher temperature (32 degrees C) and lower at the lower temperature (4 degrees C) than at the normal room temperature. These changes in instrument compliance could account for the differences in measured values between the two types of spirometer. It is concluded that the ATPS-BTPS conversion is valid and necessary for measurements made with rolling seal spirometers, but can cause substantial error if it is used for Vitalograph measurements made under conditions other than normal room temperature.
Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working Group
Authors: Patrick Y. Wen, David R. Macdonald, David A. Reardon, Timothy F. Cloughesy, A. Gregory Sorensen, Evanthia Galanis, John DeGroot, Wolfgang Wick, Mark R. Gilbert, Andrew B. Lassman, Christina Tsien, Tom Mikkelsen, Eric T. Wong, Marc C. Chamberlain, Roger Stupp, Kathleen R. Lamborn, Michael A. Vogelbaum, Martin J. van den Bent, Susan M. Chang
Journal: Journal of Clinical Oncology (2010)

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.
Preventing neural tube defects in Europe: population based study
Authors: Araceli Busby, Lenore Abramsky, Helen Dolk, Ben Armstrong
Journal: BMJ (2005)

Folic Acid Working GroupEach year, more than 4500 pregnancies in the European Union are affected by neural tube defects.Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing neural tube defects has been available since 1991, 1 and improving folate status sufficiently could result in the prevention of more than two thirds of all neural tube defects.We report on trends in the prevalence of neural tube defects up to 2001
Targeting sclerostin as potential treatment of osteoporosis
Authors: S. E. Papapoulos
Journal: Annals of the Rheumatic Diseases (2011)

In recent years, study of rare bone diseases has led to the identification of signalling pathways that regulate bone formation and provided targets for the development of novel therapeutic agents to stimulate bone formation in patients with osteoporosis. Studies of two bone sclerosing dysplasias, sclerosteosis and van Buchem disease led to the identification of sclerostin, a negative regulator of bone formation. Sclerostin binds to LRP5/6 and inhibits Wnt signalling, but its precise molecular mechanism of action is not yet known. Its expression is restricted in the skeleton to osteocytes and is modified by mechanical loading and parathyroid hormone treatment. Sclerostin deficiency reproduces the findings of the human diseases in mice, while sclerostin excess leads to bone loss and reduced bone strength. An antibody to sclerostin increased bone formation dramatically at all bone envelopes in ovariectomised rats and intact monkeys, without affecting bone resorption and improved bone strength. In initial human studies, a single injection of the antibody to postmenopausal women increased serum P1NP and transiently decreased serum CTX. Clinical phase II studies with this antibody are currently underway.
Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor
Authors: Edward Weir, Qiuyan Chen, Marie C. Defrances, Aaron Bell, Rebecca Taub, Reza Zarnegar
Journal: Hepatology (1994)

Liver regeneration factor belongs to the leucine-zipper family of transcription factors. It was originally cloned and characterized through differential screening of a regenerating rat liver cDNA library. The mRNA for liver regeneration factor-1 is barely detectable in normal rat liver but is dramatically induced after two-thirds hepatectomy, with a peak 1 to 3 hr after surgery. The nature of the signaling molecule(s) for this rapid induction is not known. It has been suggested that the liver regeneration factor-1 protein product, through complex interactions with other transcription factors such as c-Jun and Jun-B, controls expression of genes that are required during the G1 phase of hepatic growth. Hepatocyte growth factor has been shown to be the most potent mitogen for hepatocytes in vitro and in vivo. Plasma levels of hepatocyte growth factor rapidly (within 30 min) increase after loss of hepatic parenchyma induced by partial hepatectomy or carbon tetrachloride treatment. It has been postulated that hepatocyte growth factor plays a crucial role in stimulating the hepatocyte to enter the cell cycle. In this communication, we report that addition of pure hepatocyte growth factor to primary cultures of rat hepatocytes in the absence of serum and insulin results in rapid and transient induction of liver regeneration factor-1 mRNA (more than 20-fold) with a peak of expression 1 hr after treatment. The levels of jun-B and c-fos mRNAs, which are also known to be induced during the early hours of liver regeneration, were also increased after treatment of isolated hepatocytes with hepatocyte growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Silencing of Apoptosis-Inducing factor and poly (ADP-ribose) glycohydrolase reveals novel roles in breast cancer cell death after chemotherapy
Authors: Xiaoxing Feng, Yiran Zhou, Alicia M Proctor, Mandi M Hopkins, Mengwei Liu, David W Koh
Journal: Molecular Cancer (2012)

Abstract Background Cell death induced by poly(ADP-ribose) (PAR) and mediated by apoptosis-inducing factor (AIF) is well-characterized in models of ischemic tissue injury, but their roles in cancer cell death after chemotherapy are less understood. Methods Here we investigated the roles of PAR and AIF by RNA interference (RNAi) in MDA-MB-231 and MCF-7 breast adenocarcinoma cells after chemotherapy. Differences in effects were statistically tested by analysis-of-variance and unpaired student’s t-test. Results Silencing of AIF by RNAi led to decreased MDA-MB-231 and MCF-7 breast cancer cell death after chemotherapy, which demonstrates a critical role for AIF. RNAi silencing of PAR glycohydrolase (PARG), the primary enzyme that catalyzes the hydrolysis of PAR, led to increased PAR levels but decreased cell death. Further investigation into the possible role of PAR in apoptosis revealed decreased caspase-3/7/8/9 activity in PARG-null cells. Interestingly, the pharmacologic inhibition of caspase activity in PARG-silenced breast cancer cells led to increased cell death after chemotherapy, which indicates that an alternative cell death pathway is activated due to elevated PAR levels and caspase inhibition. AIF silencing in these cells led to profound protection from chemotherapy, which demonstrates that the increased cell death after PARG silencing and caspase inhibition was mediated by AIF. Conclusions The results show a role for AIF in breast cancer cell death after chemotherapy, the ability of PAR to regulate caspase activity, and the ability of AIF to substitute as a primary mediator of breast cancer cell death in the absence of caspases. Thus, the induction of cell death by PAR/AIF may represent a novel strategy to optimize the eradication of breast tumors by activating an alternative cell death pathway.
(2) Erythema induratum: a clinical and histological review
Authors: M. Rademaker, D.G. Lowe, D.D. Munro
Journal: British Journal of Dermatology (1988)

Journal Article (2) Erythema induratum: a clinical and histological review Get access M. Rademaker, M. Rademaker Departments of Dermatology, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar D.G. Lowe, D.G. Lowe Departments of Histopathology, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar D.D. Munro D.D. Munro Departments of Dermatology, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue s33, 1 July 1988, Page 41, https://doi.org/10.1111/j.1365-2133.1988.tb05376.x Published: 01 July 1988