tbuckley/cabot-search huggingface dataset:
Fluctuations in serum cytokine levels in the patient with cyclic neutropenia
Authors: T. Yujiri, K. Shinohara, F. Kurimoto
Journal: American Journal of Hematology (1992)

Abstract The fluctuations of the levels of serum cytokines in a patient with cyclic neutropenia were studied. The greatest fluctuation was found in granulocyte colony‐stimulating factor (G‐CSF). Tumor necrosis factor‐α level fluctuated inversely with fluctuation of G‐CSF, and oscillation of interleukin (IL)‐6 level preceded that in G‐CSF level. It is likely that the variations of the levels of cytokines play a significant role in regulating hematopoiesis in cyclic neutropenia. Our results suggested that the stage of the granulocyte‐committed stem cell is the major step of the defect, and the defect at the stage of the multipotent stem cell or bone marrow microenvironment was also suggested.
Kin term diversity is the result of multilevel, historical processes
Authors: Fiona M. Jordan, Michael Dunn
Journal: Behavioral and Brain Sciences (2010)

Abstract Explanations in the domain of kinship can be sought on several different levels: Jones addresses online processing, as well as issues of origins and innateness. We argue that his framework can more usefully be applied at the levels of developmental and historical change, the latter especially. A phylogenetic approach to the diversity of kinship terminologies is most urgently required.
High Fluorodeoxyglucose Uptake on Positron Emission Tomography in Patients with Advanced Non–Small Cell Lung Cancer on Platinum-Based Combination Chemotherapy
Authors: Kyung-Hun Lee, Se-Hoon Lee, Dong-Wan Kim, Won Jun Kang, June-Key Chung, Seock-Ah Im, Tae-You Kim, Young Whan Kim, Yung-Jue Bang, Dae Seog Heo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To evaluate response and survival for platinum-based combination chemotherapy in chemonaive patients with non–small cell lung cancer (NSCLC) according to pretreatment standardized uptake values (SUV) by fluorodeoxyglucose positron emission tomography. Experimental Design: Patients with advanced NSCLC who had not previously received chemotherapy were eligible. Response rates and survivals were analyzed according to maximal SUVs [low (≤7.5) versus high (&amp;gt;7.5), where 7.5 was the median value] before the first cycle of chemotherapy. Results: Eighty-five consecutive patients were included in the retrospective study. Patients with high SUV tumors exhibited significantly higher response rates (34.1% for low SUVs versus 61.0% for high SUVs; P = 0.013). Other factors, including sex, age, histology, performance status, number of involved organs, regimens used, and disease stage, did not affect response. However, high SUVs were related with a shorter response duration (279 days for low SUVs versus 141 days for high SUVs; P = 0.003) and time to progression (282 days for low SUVs versus 169 days for high SUVs; P = 0.015). Overall survival was unaffected by maximal SUVs (623 days for low SUVs versus 464 days for high SUVs; P = 0.431). Conclusions: Patients having NSCLC with high maximal SUVs showed a better response to platinum-based combination chemotherapy but had a shorter time to progression. Tumor glucose metabolism, as determined by SUVs on fluorodeoxyglucose positron emission tomography, was found to discriminate NSCLC subsets with different clinical and biological features.
Atopy: a prostaglandin E precursor- and receptor-dependent defect in T-cell maturation and function?
Authors: B.C. Melnik, G. Plewig
Journal: British Journal of Dermatology (1990)

Journal Article Atopy: a prostaglandin E precursor‐ and receptor‐dependent defect in T‐cell maturation and function? Get access B.C. Melnik, B.C. Melnik Lipid Research Laboratory, Department of Dermatology, University of Dusseldorf, Moorenstrasse 5, D‐4000 Dusseldorf, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar G. Plewig G. Plewig Lipid Research Laboratory, Department of Dermatology, University of Dusseldorf, Moorenstrasse 5, D‐4000 Dusseldorf, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 1, 1 July 1990, Pages 126–128, https://doi.org/10.1111/j.1365-2133.1990.tb01834.x Published: 01 July 1990
No Clear Link Between Passive Smoking and Lung Cancer
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2013)

MRI every 6 months was associated with an absence of interval cancers and with high sensitivity/specificity for detecting tumors smaller than 1 cm.Led by Olufunmilayo I. Olopade, MD, a hematologist-oncologist at the University of Chicago Hospitals, the authors concluded that their results "support this screening strategy as a viable alternative to prophylactic mastectomy."According to Domchek, women under surveillance at the Perelman School of Medicine get staggered mammograms and MRI 6 months apart.When women complete (or forgo) child rearing, chemoprevention alone or in combination with oophorectomy may also offer an alternative to mastectomy.But according to Davidson, the evidence for chemoprevention benefits in BRCA-positive women derives almost entirely from studies showing that agents such as tamoxifen and raloxifene reduce the risk of tumors in the other breast in women who have already had breast cancer.In 2000, for instance, Steven Narod, MD, a fellow of the Royal Society of Canada in Toronto, published findings in The Lancet showing that tamoxifen halves the risk of cancer in the opposite breast in women with BRCA1 and BRCA 2 mutations.And this year, Kelly-Anne Phillips, MD, of the Peter MacCallum Cancer Centre in Victoria, Australia, published virtually identical risk reductions in the Journal of Clinical Oncology.Davidson said that scientists have tried to look at primary prevention of the first tumor in BRCApositive individuals (for instance, through the National Surgical Adjuvant Breast and Bowel Project's P1 trial), but since the mutations are so rare, the results so far lack statistical power.Still, Davidson asserted that
Movement of Norepinephrine through the Media of Rabbit Aorta
Authors: JOHN A. BEVAN, JOZEF TöRöK
Journal: Circulation Research (1970)

The entry and movement of norepinephrine through the media of the isolated rabbit thoracic aorta has been investigated using an isotopic frozen section technique. After 1-minute exposure of the intimal surface of a helical strip to Krebs bicarbonate solution containing tritiated norepinephrine ( 3 H-NE), the 3 H material was distributed throughout the thickness of the wall. The highest concentration occurred at the innermost layer of the media and gradually decreased toward the adventitial side. The shape of the tritium distribution curves was not significantly changed by previous treatment of aortic strips with either cocaine, phenoxybenzamine or the MAO and COMT inhibitors, pargyline and tropolone, respectively. Temperature reduction to 27°C had no significant effect on the tritium distribution curves. The apparent diffusion coefficient for 3 H-NE calculated for movement into the extracellular (inulin) space of the media was 7.29 x 10 -7 cm 2 /sec. This relatively slow rate of diffusion is probably due to physical barriers such as elastic lamellae within the tunica media.
Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.
Authors: G F Pierce, J E Tarpley, J Tseng, J Bready, D Chang, W C Kenney, R Rudolph, M C Robson, J Vande Berg, P Reid
Journal: Journal of Clinical Investigation (1995)

Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-beta receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB.
Barriers to referral in patients with angina: qualitative study Commentary: Generalisability and validity in qualitative research
Authors: K. Gardner, A. Chapple, J. Green
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To explore barriers to patients being referred for possible revascularisation. <b>Design:</b> Qualitative study using semi-structured interviews. <b>Participants:</b> 16 patients aged under 75 years with stable angina and their doctors. <b>Setting:</b> General practice in Toxteth, Liverpool. <b>Results:</b> Fear of both hospitals and medical tests was common and largely hidden from the doctors. Patients felt they were old, had low expectations of treatment, viewed angina as a chronic illness, and knew little about new developments in angina treatment. Patients and doctors had difficulty in recognising angina symptoms that were not textbook definitions amid multiple comorbidity. Patients saw doctors as busy and did not want to bother them with their condition. Cultural gaps and communication difficulties existed despite all but one patient having English as their first language. <b>Conclusions:</b> Listening to patients is vital to address inequitable access to health services: how patients are treated by doctors today affects acceptability of referral tomorrow. Primary care groups in deprived areas should work with communities to address local fears. This will involve collaboration between primary, secondary, and tertiary care Cultural gaps exist between patients and doctors in deprived areas, and diagnostic confusion can occur particularly in the presence of other psychological and physical morbidity. Adequate time and resources—for example, education for doctors and patients and provision of interpreters—need to be provided if inequitable access to revascularisation procedures is to be addressed. <h3>Key messages</h3> In different communities and patient groups different myths and fears operate and need to be addressed, as experiences of hospital can profoundly affect patients9 confidence Patients in deprived areas with high mortality rates perceive themselves as "old" at a young age, and expectations of treatment are limited Angina symptoms in inner city primary care may not be the same as those in a textbook, and this has implications for care of patients Cultural gaps exist even between committed doctors and their patients in deprived areas—time and resources are needed to address these gaps Qualitative studies are necessary to understand quantitative evidence of inequitable access to specialist health services
Anti-TNF antibody therapy in Crohn's disease: the risk of a switch
Authors: Elena Ricart, Ingrid Ordás, Julián Panés
Journal: Gut (2011)

The efficacy of infliximab and adalimumab for the treatment of Crohn's disease has been shown in randomised controlled trials and corroborated in observational studies. However, one of the most worrying aspects of biological therapies for patients and clinicians is the variable but relevant proportion of patients on long-term treatment in whom there is a loss of response. From studies evaluating the incidence of loss of response to infliximab in patients with Crohn's disease (including more than 2000 patients and more than 6000 patient-years of follow-up), it is estimated that approximately 40% will lose response to infliximab, and the annual risk for loss of response to infliximab is calculated to be about 13% per patient-year of treatment.1 Similarly, data from a systematic review on the loss of response and need for adalimumab dose intensification in adult and paediatric patients with Crohn's disease showed that the mean percentage of patients who lost response to adalimumab was 18.2% among a total of 955 primary responders, with a calculated annual risk of 20.3% per patient-year. The mean percentage of patients who needed escalation of the adalimumab dose was 21.4% and the annual risk was 24.4% per patient-year.2 Loss of response and intolerance are the main reasons for switching from one anti-tumour necrosis factor (TNF) agent to another. However, constraints in hospital budgets or changes in the personal situation of patients may also lead to consideration of a change in treatment from an intravenous to a subcutaneously administered drug.

In their paper published in Gut , Van Assche …
Updated meta-analysis of non-melanoma skin cancer rates reported from prospective observational studies in patients treated with tumour necrosis factor inhibitors
Authors: Xavier Mariette, Alan Vaughan Reynolds, Paul Emery
Journal: Annals of the Rheumatic Diseases (2012)

We recently published a meta-analysis of malignancy rates reported from prospective observational studies in patients treated with tumour necrosis factor inhibitors (TNF-I).1 While there was no increase in the rates of all-site malignancy or lymphoma, there was an increased risk of non-melanoma skin cancer (NMSC) (1.45, 95% CI 1.15 to 1.76).

The skin cancer analysis included data from an abstract from the British Society for Rheumatology Biologics Register (BSRBR)2 that has since been published as a full paper with different …
Amyloidogenic peptide oligomer accumulation in autophagy-deficient β cells induces diabetes
Authors: Jinyoung Kim, Hwanju Cheon, Yeon Taek Jeong, Wenying Quan, Kook Hwan Kim, Jae Min Cho, Yu-Mi Lim, Seung Hoon Oh, Sang-Man Jin, Jae Hyeon Kim, Moon-Kyu Lee, Sunshin Kim, Masaaki Komatsu, Sang-Wook Kang, Myung-Shik Lee
Journal: Journal of Clinical Investigation (2014)

Islet amyloid accumulation is a hallmark of human type 2 diabetes (T2D). In contrast to human islet amyloid polypeptide (hIAPP), murine islet amyloid polypeptide (mIAPP) does not exhibit amyloidogenic propensity. Because autophagy is important in the clearance of amyloid-like proteins, we studied transgenic mice with β cell–specific expression of hIAPP to evaluate the contribution of autophagy in T2D-associated accumulation of hIAPP. In mice with β cell–specific expression of hIAPP, a deficiency in autophagy resulted in development of overt diabetes, which was not observed in mice expressing hIAPP alone or lacking autophagy alone. Furthermore, lack of autophagy in hIAPP-expressing animals resulted in hIAPP oligomer and amyloid accumulation in pancreatic islets, leading to increased death and decreased mass of β cells. Expression of hIAPP in purified monkey islet cells or a murine β cell line resulted in pro-hIAPP dimer formation, while dimer formation was absent or reduced dramatically in cells expressing either nonamyloidogenic mIAPP or nonfibrillar mutant hIAPP. In autophagy-deficient cells, accumulation of pro-hIAPP dimers increased markedly, and pro-hIAPP trimers were detected in the detergent-insoluble fraction. Enhancement of autophagy improved the metabolic profile of hIAPP-expressing mice fed a high-fat diet. These results suggest that autophagy promotes clearance of amyloidogenic hIAPP, autophagy deficiency exacerbates pathogenesis of human T2D, and autophagy enhancers have therapeutic potential for islet amyloid accumulation-associated human T2D.
Transcellular transport of organic anions in the isolated perfused rat liver: The differential effects of monensin and colchicine
Authors: Nankei Aoyama, Toshihide Ohya, Kimberly Chandler, Susan Gresky, Thomas R. Holzbach
Journal: Hepatology (1991)

Nonbile salt cholephiles and bile salts are two classes of organic anions that are efficiently taken up and excreted by the liver. Recent evidence suggests that a microtubular system-dependent, colchicine-sensitive transcellular pathway may transport both classes of these ligands. The relationship of this pathway to flux rates, however, remains unclear. Some structural evidence suggests an important role for a Golgi-associated vesicular system. Monensin, like colchicine, is a perturbing agent that is believed to target primarily Golgi and related organelles. The effects of a minimal effective dose of both colchicine (0.06 mg to 0.12 mg/100 gm body wt) and monensin (0.6 mg/100 gm body wt) were examined in the isolated perfused rat liver in a single-pass mode. The nonbile salt cholephile, phenol red, was studied at two doses: 1 nmol and 5 mumol. Sodium taurocholate was studied at three doses: 2 nmol, 1 mumol and 5 mumol. Colchicine affected the transcellular transport for both classes of organic anions equally. Partially inhibitory effects on both anions occurred only at high ligand flux rates. In contrast, monensin greatly impaired the transport of nonbile salt cholephiles but had no influence on transcellular bile salt flux. We conclude that the monensin effect appears to define a distinct transcellular transport pathway for each of the two classes of organic anions.
Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies
Authors: C.M. Maybury, Z.K. Jabbar-Lopez, T. Wong, A.P. Dhillon, J.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2014)

Journal Article Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies Get access C.M. Maybury, C.M. Maybury St John's Institute of Dermatology Division of Genetics and Molecular Medicine King's College London London U.K https://orcid.org/0000-0001-5860-3785 Search for other works by this author on: Oxford Academic Google Scholar Z.K. Jabbar‐Lopez, Z.K. Jabbar‐Lopez Dermatological Sciences Institute of Cellular Medicine Newcastle University Newcastle upon Tyne U.K Search for other works by this author on: Oxford Academic Google Scholar T. Wong, T. Wong Department of Gastroenterology Guy's and St Thomas' NHS Foundation Trust London U.K Search for other works by this author on: Oxford Academic Google Scholar A.P. Dhillon, A.P. Dhillon Department of Cellular Pathology UCL Medical School Royal Free Campus London U.K Search for other works by this author on: Oxford Academic Google Scholar J.N. Barker, J.N. Barker St John's Institute of Dermatology Division of Genetics and Molecular Medicine King's College London London U.K Search for other works by this author on: Oxford Academic Google Scholar C.H. Smith C.H. Smith St John's Institute of Dermatology Division of Genetics and Molecular Medicine King's College London London U.KSt John's Institute of Dermatology Guy's and St Thomas' NHS Foundation Trust London U.K Correspondence Catherine Smith. E‐mail: catherine.smith@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 1, 1 July 2014, Pages 17–29, https://doi.org/10.1111/bjd.12941 Published: 01 July 2014
In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment.
Authors: M Sykes, M L Romick, K A Hoyles, D H Sachs
Journal: The Journal of Experimental Medicine (1990)

Previous work from this laboratory has demonstrated that T cell-depleted (TCD) syngeneic marrow can delay, but not prevent, the mortality from acute graft-vs.-host disease (GVHD) caused by MHC-mismatched lymphoid cells administered to lethally irradiated mice. We demonstrate here that a protective effect against GVHD is also observed after in vivo treatment with IL-2. Administration of 10,000-50,000 U of IL-2 twice daily for the first 5 d after bone marrow transplantation markedly reduced the mortality from both acute and chronic GVHD induced across complete MHC barriers in lethally irradiated mice, and frequently led to long-term survival. Complete allogeneic reconstitution was demonstrated in all long-term survivors of this treatment regimen. While either IL-2 or TCD syngeneic marrow administered alone was protective in some experiments, the maximal protective effect was observed after administration of both IL-2 and TCD syngeneic marrow, especially when the effects of IL-2 were suboptimal. The timing of IL-2 administration was critical to this beneficial effect, since a delay of 7 d in commencing IL-2 treatment was associated with accelerated GVHD mortality. This new approach to the prevention of GVHD permits the administration of allogeneic T cells, and may therefore avoid the increased incidence of graft failure and loss of antileukemic effects associated with the T cell depletion of allogeneic marrow, which is otherwise required for the prevention of GVHD.
The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB
Authors: Jo-David Fine, Robin A.J. Eady, Eugene A. Bauer, Johann W. Bauer, Leena Bruckner-Tuderman, Adrian Heagerty, Helmut Hintner, Alain Hovnanian, Marcel F. Jonkman, Irene Leigh, John A. McGrath, Jemima E. Mellerio, Dedee F. Murrell, Hiroshi Shimizu, Jouni Uitto, Anders Vahlquist, David Woodley, Giovanna Zambruno
Journal: Journal of the American Academy of Dermatology (2008)
New scoring charts for GPs are too crude, say doctors' leaders
Authors: A. O'Dowd
Journal: BMJ (2012)

GPs and their practices are to be scored out of 10 for how their patients rate their experiences under new data being published in England for the first time.

Doctors’ leaders, however, have described the data as too simplistic, lacking detail, and creating a risk of overwhelming patients with information.

From 7 June, the Department of Health will be publishing data online about various issues such as appointments, communication skills, and waiting times at GP practices in England.

This patient experience information, which has been gathered from patients’ responses to the annual GP Patient Survey, will be available on the NHS Choices website (www.nhs.uk/Pages/HomePage.aspx) and the idea is that it will allow patients to …