tbuckley/cabot-search huggingface dataset:
Biochemical and trichological characterization of diffuse alopecia in women
Authors: D.H. RUSHTON, I.D. RAMSAY, K.C. JAMES, M.J. NORRIS, J.J.H. GILKES
Journal: British Journal of Dermatology (1990)

Journal Article Biochemical and trichological characterization of diffuse alopecia in women Get access D.H. RUSHTON, D.H. RUSHTON School of Pharmacy and Biomedical Sciences, Portsmouth Polytechnic, U.K. Dr D.H.Rushton, Philip Kingsley Trichological Clinic, 54 Green Street, London W1Y3RH, U.K. Search for other works by this author on: Oxford Academic Google Scholar I.D. RAMSAY, I.D. RAMSAY North Middlesex Hospital, London N18, U.K. Search for other works by this author on: Oxford Academic Google Scholar K.C. JAMES, K.C. JAMES Welsh School of Pharmacy, University of Wales College of Cardiff, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.J. NORRIS, M.J. NORRIS School of Pharmacy and Biomedical Sciences, Portsmouth Polytechnic, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.J.H. GILKES J.J.H. GILKES Bloomsbury Dermatology Department, Middlesex Hospital, London W1, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 2, 1 August 1990, Pages 187–197, https://doi.org/10.1111/j.1365-2133.1990.tb01846.x Published: 01 August 1990
Heavy LIFting: tumor promotion and radioresistance in NPC
Authors: Micah Luftig
Journal: Journal of Clinical Investigation (2013)

The epithelial-derived nasopharyngeal carcinoma (NPC) is a rare tumor in most of the world; however, it is common in southern China, northern Africa, and Alaska. NPC is often left undiagnosed and untreated until a late stage of disease. Furthermore, while radiation therapy is effective against this tumor, local recurrence due to radioresistance is an important clinical problem. In this issue, Liu et al. report on their identification of the IL-6 family cytokine leukemia inhibitory factor (LIF) as a serum predictor of local NPC recurrence following radiation therapy. The authors developed this initial finding to discover a role for the LIF/LIFR/mTORC1 signaling axis in NPC tumor cell growth as well as radioresistance.
Macrophage deactivation. Altered kinetic properties of superoxide-producing enzyme after exposure to tumor cell-conditioned medium.
Authors: S Tsunawaki, C F Nathan
Journal: The Journal of Experimental Medicine (1986)

Incubation of activated mouse peritoneal macrophages with tumor cell-conditioned medium (TCM) results in their deactivation, as measured by ability to release reactive oxygen intermediates and kill protozoal pathogens. The mechanism of suppression by macrophage deactivation factor (MDF) was studied. Inhibition of H2O2 release could not be overcome by increasing the concentration of phorbol diesters used to trigger the respiratory burst. Deactivated macrophages consumed H2O2 at the same rate as activated cells (t1/2, 35-40 min for 25 nmol H2O2 per 10(6) peritoneal cells). They transported glucose with the same kinetics (Km, 1 mM; Vmax, approximately 100 nmol per 6 min per milligram cell protein), and maintained similar intracellular concentrations of NADPH and NADP (approximately 0.62 mM and approximately 0.11 mM, respectively), as measured by enzymatic cycling methods and determinations of the volume of cell water (3.6 microliter/mg cell protein). To study the kinetics of the PMA-triggered NADPH oxidase in cell lysates, mixed detergents were used (deoxycholate and Tween 20). These stabilized the oxidase for approximately 3.3-fold longer than deoxycholate alone, which was used in previous studies. Incubation of activated macrophages in MDF resulted in a marked increase in the Km of the oxidase for NADPH, from 0.06 mM to 0.67 mM. The Vmax fell approximately 1.7-fold. These kinetic changes, together with the measured intracellular concentration of NADPH, account quantitatively for the suppression of H2O2 release by deactivated macrophages, and are nearly the mirror image of the kinetic changes observed during macrophage activation.
S108 Expert consensus on diagnostic criteria and tertiary service requirements for bronchiectasis
Authors: J. Holme, S. Bianchi, I. Clifton, A. De-Soyza, F. Edenborough, D. Peckham, O. Pirzada, P. Walker, M. Walshaw, R. Niven
Journal: Thorax (2011)

<h3>Introduction</h3> There are no agreed diagnostic criteria for bronchiectasis and no stated minimum requirements for a tertiary service. The Northern Bronchiectasis Group aimed to use the validated RAND technique to form consensus opinions on these issues. <h3>Method</h3> Following literature review, a questionnaire was devised containing 89 statements relevant to the topics above. Eight expert members rated their level of agreement with the statements from 1 (not relevant) to 9 (mandatory). Following a group debate about these statements, the experts re-structured some statements then re-rated the questionnaire. Consensus agreement, indifference or disagreement was reached if 7/8 members9 scores were in the 7–9, 4–6 or 1–3 ranges respectively. <h3>Results</h3> There was consensus agreement for 31/89, consensus indifference for 5/89 and consensus disagreement for 12/89 statements. Consensus was not reached for 41/89 statements. It was agreed daily sputum production would prompt investigation for bronchiectasis, CT was always necessary, and the following factors, support the diagnosis: bronchoarterial ratio &gt;1.0, non-tapering bronchi, thickened airway walls, irreversible changes. It was agreed that a tertiary service should provide: access to HRCT, spirometry, routine and fungal sputum cultures, ciliary function testing; functional antibodies and immunoglobulins for all, antibiotic &amp; hypertonic saline nebuliser challenges, nebuliser loan and maintenance, home iv antibiotic service (preferably by patients in their own homes), portacath insertion, physiotherapy at least annually, access to a dietician, immunologist, microbiologist with an interest in bronchiectasis and pulmonary rehabilitation. Specialist nurses could see selected patients and separate clinics are desirable for patients colonised with pseudomonas. There was indifference to the availability of telephone consultations, posted sputum analysis, iv antibiotic service based in the community (not in patients9 home), a patient support group and patient educational sessions. Consensus was not reached regarding if respiratory infection, bronchoarterial ratios of &gt;1.5 or &gt;2.0 or abnormal spirometry are necessary to diagnose bronchiectasis; or if a consultant should see patients at most visits, iv antibiotics could be given by a nurse in the patients home and if access to palliative care was necessary in a tertiary service. <h3>Conclusion</h3> Comprehensive consensus statements regarding the diagnostic criteria for bronchiectasis and tertiary service requirements have been formed.
The Proteasome Inhibitor Carfilzomib Functions Independently of p53 to Induce Cytotoxicity and an Atypical NF-κB Response in Chronic Lymphocytic Leukemia Cells
Authors: Sneha V. Gupta, Erin Hertlein, Yanhui Lu, Ellen J. Sass, Rosa Lapalombella, Timothy L. Chen, Melanie E. Davis, Jennifer A. Woyach, Amy Lehman, David Jarjoura, John C. Byrd, David M. Lucas
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The proteasome consists of chymotrypsin-like (CT-L), trypsin-like, and caspase-like subunits that cleave substrates preferentially by amino acid sequence. Proteasomes mediate degradation of regulatory proteins of the p53, Bcl-2, and nuclear factor-κB (NF-κB) families that are aberrantly active in chronic lymphocytic leukemia (CLL). CLL remains an incurable disease, and new treatments are especially needed in the relapsed/refractory setting. We therefore investigated the effects of the proteasome inhibitor carfilzomib (CFZ) in CLL cells. Experimental Design: Tumor cells from CLL patients were assayed in vitro using immunoblotting, real-time polymerase chain reaction, and electrophoretic mobility shift assays. In addition, a p53 dominant-negative construct was generated in a human B-cell line. Results: Unlike bortezomib, CFZ potently induces apoptosis in CLL patient cells in the presence of human serum. CLL cells have significantly lower basal CT-L activity compared to normal B and T cells, although activity is inhibited similarly in T cells versus CLL. Co-culture of CLL cells on stroma protected from CFZ-mediated cytotoxicity; however, PI3K inhibition significantly diminished this stromal protection. CFZ-mediated cytotoxicity in leukemic B cells is caspase-dependent and occurs irrespective of p53 status. In CLL cells, CFZ promotes atypical activation of NF-κB evidenced by loss of cytoplasmic IκBα, phosphorylation of IκBα, and increased p50/p65 DNA binding, without subsequent increases in canonical NF-κB target gene transcription. Conclusions: Together, these data provide new mechanistic insights into the activity of CFZ in CLL and support phase I investigation of CFZ in this disease. Clin Cancer Res; 19(9); 2406–19. ©2013 AACR.
Measuring Oncogenic Signaling Pathways in Cancer with PET: An Emerging Paradigm from Studies in Castration-Resistant Prostate Cancer
Authors: Michael J. Evans
Journal: Cancer Discovery (2012)

Abstract As parallel advances in cancer biology and drug development continue to elevate the role of targeted therapies in oncology, the need for imaging biomarkers that systematically measure the biology associated with therapeutic intervention has become more urgent. Although the molecular imaging community has a commitment to develop technologies to this end, few investigational radiotracers directly measure the biology of common oncogenic signaling pathways often addressed by targeted therapies. Visible progress has been achieved with a handful of radiotracers rationally designed to intercalate the pathobiology of prostate cancer, a molecularly heterogeneous disease nevertheless broadly defined by a fairly small repertoire of recurrent oncogenic lesions. Significance: That variable treatment responses or emergent resistance phenotypes are often documented in humans argues strongly for diagnostic technologies that can be realistically applied posttherapy to capture the dynamic patterns of disease response. The purpose of this review is to describe a collection of radiotracers developed to measure the pathobiology of prostate cancer for improved treatment monitoring, placing particular emphasis on the biologic rationale for their preparation. A chronologic description of radiotracer development programs is outlined, primarily to stress how an ongoing dialectic between earlier and more contemporary imaging technologies has accelerated discovery. Cancer Discov; 2(11); 985–94. ©2012 AACR.
The metabolic syndrome
Authors: N. Unwin
Journal: Journal of the Royal Society of Medicine (2006)

It has long been known that certain cardiovascular and metabolic risk factors tend to cluster together.For example, in the 1940s the French clinician, Vague, described the diabetic and atherogenic risk associated with android (upper body) obesity.The relatively recent concept of a metabolic syndrome suggested that the clustering represents a discrete entity due to a single underlying aetiology (insulin resistance).Yet, despite several definitions and its own International Classification of Diseases code its validity and utility remains unclear.The evidence does not fully support the existence of a single underlying aetiology, and most, but not all, evidence suggests that the syndrome as currently defined appears to have little value in predicting cardiovascular disease risk over other approaches that consider individual risk factors.At present there is no specific treatment for the syndrome other than targeting the individual risk factors.It is concluded that at this time its main utility is as a reminder to the clinician that certain risk factors tend to cluster, and as an indicator of the public health importance of the risk factor clustering associated with obesity and physical inactivity.
Diesel Exhaust, Solvents, and Other Occupational Exposures as Risk Factors for Wheeze among Farmers
Authors: Jane A. Hoppin, David M. Umbach, Stephanie J. London, Michael C. R. Alavanja, Dale P. Sandler
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Farmers engage in activities that result in exposure to diesel exhaust, solvents, welding fumes, and other respiratory irritants. Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina, we evaluated the odds of wheeze associated with nonpesticide occupational exposures. We used logistic regression models controlling for age, state, smoking, and history of asthma or atopy to evaluate odds of wheeze in the past year among the 20898 farmers who provided complete information on all covariates. Driving diesel tractors was associated with elevated odds of wheeze (odds ratio = 1.31; 95% confidence interval = 1.13, 1.52); the odds ratio for driving gasoline tractors was 1.11 (95% confidence interval = 1.02, 1.21). A duration-response relationship was observed for driving diesel tractors but not for driving gasoline tractors. Activities involving solvent exposure, including painting and use of solvents for cleaning, were associated with an increased odds of wheeze in a duration-dependent fashion. The highest odds of wheeze for farm activities were for daily painting (odds ratio = 1.82; 95% confidence interval = 0.89, 3.73), an indication of daily solvent exposure. These results add to the growing body of evidence of adverse respiratory effects of diesel exposure on the lung and suggest exposure to solvents may contribute as well.
Effect of Hyperthermia on the Functional Activity of Cytotoxic T-Lymphocytes 2
Authors: H. Robson MacDonald
Journal: JNCI Journal of the National Cancer Institute (1977)

The effect of hyperthermia on the functional activity of murine cytotoxic thymus-derived lymphocytes (CTL's) has been investigated. CTL's were generated in vitro in mixed leukocyte cultures (MLC's) and assayed for cytotoxicity on 51Cr-labeled allogeneic P-815 mastocytoma cells. Exposure of MLC cells to temperatures of 43° C or above rapidly inactivated CTL function. The degree of inactivation depended on temperature and time of exposure to heat. CTL function was much more sensitive to hyperthermia than was the reproductive capacity of tumor target cells (assessed by a cloning assay), and the heat sensitivity of CTL's appeared to depend on their stage of differentiation. CTL function dramatically increased when MLC cells were incubated at 37° C after exposure to hyperthermia or when a total exposure to heat was split into two equal fractions separated by an interval at 37° C. These latter findings were operationally analogous to the repair of potentially lethal and sublethal radiation damage, respectively, and suggested that further studies are required to assess the complex interrelationships between hyperthermia, cell-mediated immunity, and tumor cell survival.
Allergy and Allergic Diseases
Authors: A.B. Kay
Journal: New England Journal of Medicine (2001)

Allergic rhinitis, asthma, and atopic eczema are among the commonest causes of chronic ill health. These diseases are increasing in prevalence, and they add considerably to the burden of health care costs. In Sweden, for example, the number of children with allergic rhinitis, asthma, or eczema roughly doubled over a 12-year period,1 and in the United States the annual cost of treating asthma is about $6 billion.2 The term “allergy” was introduced in 1906 by von Pirquet, who recognized that in both protective immunity and hypersensitivity reactions, antigens had induced changes in reactivity.3 With the passage of time the word . . .
An Essential Requirement for the SCAP/SREBP Signaling Axis to Protect Cancer Cells from Lipotoxicity
Authors: Kevin J. Williams, Joseph P. Argus, Yue Zhu, Moses Q. Wilks, Beth N. Marbois, Autumn G. York, Yoko Kidani, Alexandra L. Pourzia, David Akhavan, Dominique N. Lisiero, Evangelia Komisopoulou, Amy H. Henkin, Horacio Soto, Brian T. Chamberlain, Laurent Vergnes, Michael E. Jung, Jorge Z. Torres, Linda M. Liau, Heather R. Christofk, Robert M. Prins, Paul S. Mischel, Karen Reue, Thomas G. Graeber, Steven J. Bensinger
Journal: Cancer Research (2013)

Abstract The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of fatty acid synthase activity from stearoyl-CoA desaturase 1 (SCD1)–mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. Cancer Res; 73(9); 2850–62. ©2013 AACR.
Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis
Authors: Kazuyoshi Kuwano, Naoki Hagimoto, Masayuki Kawasaki, Takehiro Yatomi, Norio Nakamura, Shigekazu Nagata, Takashi Suda, Ritsuko Kunitake, Takashige Maeyama, Hiroyuki Miyazaki, Nobuyuki Hara
Journal: Journal of Clinical Investigation (1999)

The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.
Cardiopulmonary, blood metabolite and rating of perceived exertion responses to constant exercises performed at different intensities until exhaustion
Authors: Flávio O Pires, Timothy D Noakes, Adriano E Lima-Silva, R Bertuzzi, Carlos Ugrinowitsch, Fabio S Lira, Maria Augusta P D M Kiss
Journal: British Journal of Sports Medicine (2011)

This study analysed cardiopulmonary, metabolic and rating of perceived exertion (RPE) responses during exercise bouts performed below, at and above the second lactate threshold (LT2) intensity.10 healthy men performed constant workloads to exhaustion at the first lactate threshold (LT1), LT2 and 25% of the difference between LT2 and maximal aerobic power output (TW(25%)) identified during an incremental test. The time to exhaustion (TE) was 93.8 (18.0), 44.5 (16.0) and 22.8 (10.6) min at LT1, LT2 and TW(25%), respectively (p < 0.001). Metabolic and cardiopulmonary parameters and RPE data were time normalised to the exercise bout duration. The correlation between the slope of these variables and TE was calculated.Differences were found for respiratory exchange ratio (RER), RPE and potassium at LT1; RER, RPE, norepinephrine and potassium at LT2; and ventilation, respiratory rate (RR), RPE, lactate and potassium at TW(25%). Except for RR, no cardiopulmonary or metabolic parameter increased significantly after 50% of the exercise duration, indicating a physiological steady state. VO₂, heart rate and lactate at exhaustion in all exercise bouts were significantly lower than values reached in the maximal incremental test. The slope of most metabolic variables was not correlated to TE in LT1, LT2 and TW(25%), whereas the slope of RPE was significantly correlated to TE (r = -0.72 to -0.84; p < 0.05) for the three exercise intensities.Contrary to traditional suggestions, exercise at LT1, LT2 and TW(25%) intensities is performed and terminated in the presence of an overall physiological steady state.
Meat and Fat Intake as Risk Factors for Pancreatic Cancer: The Multiethnic Cohort Study
Authors: Ute Nöthlings, Lynne R. Wilkens, Suzanne P. Murphy, Jean H. Hankin, Brian E. Henderson, Laurence N. Kolonel
Journal: JNCI Journal of the National Cancer Institute (2005)

Meat intake has been associated with risk of exocrine pancreatic cancer, but previous findings have been inconsistent. This association has been attributed to both the fat and cholesterol content of meats and to food preparation methods. We analyzed data from the prospective Multiethnic Cohort Study to investigate associations between intake of meat, other animal products, fat, and cholesterol and pancreatic cancer risk.During 7 years of follow-up, 482 incident pancreatic cancers occurred in 190,545 cohort members. Dietary intake was assessed using a quantitative food frequency questionnaire. Associations for foods and nutrients relative to total energy intake were determined by Cox proportional hazards models stratified by gender and time on study and adjusted for age, smoking status, history of diabetes mellitus and familial pancreatic cancer, ethnicity, and energy intake. Statistical tests were two-sided.The strongest association was with processed meat; those in the fifth quintile of daily intake (g/1000 kcal) had a 68% increased risk compared with those in the lowest quintile (relative risk = 1.68, 95% confidence interval = 1.35 to 2.07; Ptrend < .01). The age-adjusted yearly incidence rates per 100,000 persons for the respective quintiles were 41.3 and 20.2. Intakes of pork and of total red meat were both associated with 50% increases in risk, comparing the highest with the lowest quintiles (both Ptrend < .01). There were no associations of pancreatic cancer risk with intake of poultry, fish, dairy products, eggs, total fat, saturated fat, or cholesterol. Intake of total and saturated fat from meat was associated with statistically significant increases in pancreatic cancer risk but that from dairy products was not.Red and processed meat intakes were associated with an increased risk of pancreatic cancer. Fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism because the findings for fat from meat and dairy products differed. Carcinogenic substances related to meat preparation methods might be responsible for the positive association.