tbuckley/cabot-search huggingface dataset:
High-definition fiber tractography for the evaluation of perilesional white matter tracts in high-grade glioma surgery
Authors: Kumar Abhinav, Fang-Cheng Yeh, Alireza Mansouri, Gelareh Zadeh, Juan C. Fernandez-Miranda
Journal: Neuro-Oncology (2015)

Conventional white matter (WM) imaging approaches, such as diffusion tensor imaging (DTI), have been used to preoperatively identify the location of affected WM tracts in patients with intracranial tumors in order to maximize the extent of resection and potentially reduce postoperative morbidity. DTI, however, has limitations that include its inability to resolve multiple crossing fibers and its susceptibility to partial volume effects. Therefore, recent focus has shifted to more advanced WM imaging techniques such as high-definition fiber tractography (HDFT). In this paper, we illustrate the application of HDFT, which in our preliminary experience has enabled accurate depiction of perilesional tracts in a 3-dimensional manner in multiple anatomical compartments including edematous zones around high-grade gliomas. This has facilitated accurate surgical planning. This is illustrated by using case examples of patients with glioblastoma multiforme. We also discuss future directions in the role of these techniques in surgery for gliomas.
Long-Term and Late Effects of Germ Cell Testicular Cancer Treatment and Implications for Follow-Up
Authors: Hege S. Haugnes, George J. Bosl, Hink Boer, Jourik A. Gietema, Marianne Brydøy, Jan Oldenburg, Alv A. Dahl, Roy M. Bremnes, Sophie D. Fosså
Journal: Journal of Clinical Oncology (2012)

Germ cell testicular cancer (TC) represents a malignancy with high cure rates. Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5-year survival rate has increased considerably, and it is currently above 95%. Because TC is usually diagnosed before the age of 40 years, these men can expect to live for another 40 to 50 years after being successfully treated. This success, however, is hampered by an increased risk of long-term and late effects of treatment. Secondary malignant neoplasms and cardiovascular disease represent the most common potentially life-threatening late effects, typically occurring more than 10 years after treatment. Other long-term effects include pulmonary toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and psychosocial problems. The incidence and time to onset of these various adverse effects vary according to treatment type and intensity. There is still little knowledge about underlying mechanisms and genetic susceptibility of the various adverse effects. Apart from treatment burden, it is not yet possible to identify patients who are at high risk for certain late effects after TC treatment. In this clinical review, we present the current status regarding different somatic and psychosocial long-term late effects after treatment for TC, based on Medline searches and our own research. Moreover, we postulate recommendations for general medical evaluations that should begin after treatment is completed and continue during follow-up.
Circadian Timing in Cancer Treatments
Authors: Francis Lévi, Alper Okyar, Sandrine Dulong, Pasquale F. Innominato, Jean Clairambault
Journal: The Annual Review of Pharmacology and Toxicology (2010)

The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.
Association of High-Altitude Pulmonary Edema With the Major Histocompatibility Complex
Authors: Masayuki Hanaoka, Keishi Kubo, Yoshitaka Yamazaki, Takashige Miyahara, Yukinori Matsuzawa, Toshio Kobayashi, Morie Sekiguchi, Masao Ota, Hideto Watanabe
Journal: Circulation (1998)

Background —A constitutional susceptibility has been suggested in the development of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy young people, some of whom suffer recurrent episodes. We examined whether immunogenetic susceptibility is present in HAPE-susceptible subjects. Methods and Results —The frequencies of human leukocyte antigen (HLA) alleles in 28 male and 2 female subjects with a history of HAPE were compared with those in 100 healthy volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically. The pulmonary hemodynamics on admission to the hospital and the ventilatory response to hypoxia and hypercapnia were retrospectively examined in 10 of the HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects with HAPE but only 16.0% of the control subjects ( P =.0005), and HLA-DQ4 was positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control subjects ( P =.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6–positive subjects with HAPE was significantly higher than that of the HLA-DR6–negative subjects with HAPE. Conclusions —There were significant associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An immunogenetic susceptibility, which is associated with HLA class II alleles located within the major histocompatibility complex, may underlie the development of HAPE, at least in some of its forms.
Lapatinib (Tykerb, GW572016) Reverses Multidrug Resistance in Cancer Cells by Inhibiting the Activity of ATP-Binding Cassette Subfamily B Member 1 and G Member 2
Authors: Chun-ling Dai, Amit K. Tiwari, Chung-Pu Wu, Xiao-dong Su, Si-Rong Wang, Dong-geng Liu, Charles R. Ashby, Yan Huang, Robert W. Robey, Yong-ju Liang, Li-ming Chen, Cheng-Jun Shi, Suresh V. Ambudkar, Zhe-Sheng Chen, Li-wu Fu
Journal: Cancer Research (2008)

Abstract Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E217βG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic. [Cancer Res 2008;68(19):7905–14]
Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina
Authors: Stefan Blankenberg, Laurence Tiret, Christoph Bickel, Dirk Peetz, François Cambien, Jürgen Meyer, Hans J. Rupprecht
Journal: Circulation (2002)

Background — Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. Methods and Results — In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P &lt;0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend &lt;0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory variables IL-6, high-sensitive C-reactive protein, and fibrinogen, this relation remained almost unchanged, such that patients within the highest quartile of IL-18 had a 3.3-fold increase in hazard risk compared with those in the first quartile (95% CI, 1.3 to 8.4, P =0.01). This relation was observed in patients with stable angina and patients with unstable angina at baseline. Conclusions — Serum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission. This result strongly supports recent experimental evidence of IL-18–mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques.
Comprehensive Testing of Positionally Cloned Asthma Genes in Two Populations
Authors: Craig P. Hersh, Benjamin A. Raby, Manuel E. Soto-Quirós, Amy J. Murphy, Lydiana Avila, Jessica Lasky-Su, Jody S. Sylvia, Barbara J. Klanderman, Christoph Lange, Scott T. Weiss, Juan C. Celedón
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Replication of gene-disease associations has become a requirement in complex trait genetics.
Clonality in Langerhans' cell histiocytosis
Authors: R M. Egeler
Journal: BMJ (1995)

in our hospital between 1990 and 1993 and obtained similar findings; in addition we found that the satisfaction was maintained during over three years offollow up.A total of 223 women underwent endometrial resection.Five required an intraoperative hysterectomy, and the remaining 217 women were sent a questionnaire last September.Altogether 204 (94%) women replied.The mean follow up time was 25-1 months (range 9-44 months).Sixty six women had been amenorrhoeic since surgery, and a further 94 described their menstrual loss as light.We found a high degree of satisfaction associated with this operation, with 154 women describing it as having been a lot of help and a further 29 women as having been of some help.Only 21 women
Role of xanthine oxidase in the interferon-mediated depression of the hepatic cytochrome P-450 system in mice.
Authors: Gilbert J. Mannering, Laurel B. Deloria, Viola Abbott
Journal: Cancer Research (1988)

Interferon, interferon inducers, and a variety of other immunomodulators are known to depress the hepatic cytochrome P-450 drug-metabolizing system. Two concepts have been proposed to explain this phenomenon. (a) The steady-state of cytochrome P-450 is altered through decreased synthesis and increased degradation of cytochrome P-450 apoprotein. (b) Interferon induces xanthine oxidase; superoxide generated by interferon-induced xanthine oxidase destroys cytochrome P-450. The current study investigated the second concept. Administered polyribonucleotides [polyriboinosinic acid.polyribocytidylic acid (poly IC), polyriboinosinic acid.polycytidylic acid, polylysine and carboxymethylcellulose, mismatched poly IC], recombinant murine gamma-interferon, and a natural murine alpha/beta-interferon were shown to depress hepatic cytochrome P-450 and selected microsomal cytochrome P-450-dependent monooxygenase reactions and to induce hepatic xanthine oxidase activity. The feeding of tungstate in the drinking water largely depleted xanthine oxidase in mice; cytochrome P-450 levels and monooxygenase activities were not affected by tungstate treatment. Tungstate rendered the level of xanthine oxidase much below that in mice that had not received tungstate regardless of whether or not they had received poly IC or interferon; nevertheless, poly IC and interferon produced losses of cytochrome P-450 and monooxygenase activities in these tungstate-treated mice equivalent to those observed in mice that had not received tungstate. The administration of N-acetylcysteine did not prevent the loss of cytochrome P-450 induced by poly IC, as has been reported, nor did the incubation of microsomal cytochrome P-450 with buttermilk xanthine oxidase and hypoxanthine cause a loss of cytochrome P-450, which has also been reported. It is concluded from these studies that the induction of xanthine oxidase and the loss of cytochrome P-450 generated by interferon are coincidental rather than causally related phenomena.
Special interest training in respiratory medicine across Yorkshire: A web based survey
Authors: Akshay Dwarakanath
Journal: European Respiratory Journal (2011)

Introduction:  The Joint Royal Colleges of Physicians Training Board (JRCPTB) published the training curriculum for Respiratory Medicine in August 2010. It identified areas of special interest enabling the trainees to undertake additional training. However, this is not formally recognized and there is no centrally agreed funding. Current options available for such training include as Out Of Programme Experience (OOPE) or during research into the subject area concerned.   Aim:  To understand the current special areas of interest among trainees in Respiratory Medicine across Yorkshire, United Kingdom.   Method:  A web-based questionnaire was designed and all the trainees (n-75) in the Yorkshire region were invited to complete the survey.   Results:  The response rate was 52% (n-39). 69.2% (n-27) had a special area of interest.  15/27 (55.5%) agreed that a compulsory module should be implemented in the training curriculum towards pursuing a special area of interest, whilst 12/27 (44.5%) disagreed. 15/27 trainees considered 12 months as the ideal period for training, whilst 8/27 chose 6 months and 4/27 opted 3 months.   Conclusion:  Majority of the trainees wish to specialize in a specific area of interest but there seems to be a lack of funding and training opportunities in the form of fellowships. Improving the current training curriculum will lead to better patient care and service provision in the National Health Service.
Childhood Respiratory Infections: Scientific Editor: Rosalind L Smyth. UK: Oxford University Press, 2002. pound42.50. ISBN 0 1985 1624 X
Authors: P D Sly
Journal: Thorax (2003)

When opening a new book, a logical first place to start is the Table of Contents. Here one is immediately struck by the lack of logical order of the chapters. The topics covered suggest they were chosen by the authors to match their interests rather than in a concerted effort to cover subjects …
Randomized Clinical Trial of Clinic-Integrated, Low-Intensity Treatment to Prevent Deterioration of Disease Care in Adolescents With Type 1 Diabetes
Authors: Clarissa S. Holmes, Rusan Chen, Eleanor Mackey, Margaret Grey, Randi Streisand
Journal: Diabetes Care (2014)

To evaluate the efficacy of two office-based treatments designed to prevent deterioration in glycemic control in young adolescents with type 1 diabetes in a randomized clinical trial. An individualized, more intensive family teamwork Coping skills program was compared with a diabetes Education treatment.A baseline assessment was followed by four brief treatment sessions and immediate posttesting over the course of 1.5 years. Families of 226 early adolescents (ages 11-14) were randomized to receive either individualized coping skills education or diabetes education as adjunctive treatment to quarterly medical appointments. Continued follow-up occurred at 3.5-month intervals for a long-term follow-up of up to 3 years. A post hoc Usual Care group facilitated comparisons of glycemic control.Growth curve analysis showed that both treatment groups successfully prevented deterioration in adolescent disease care and simultaneously improved adolescent and parent quality of life that included indicators of more effective communication and reduced adherence barriers-without a concomitant increase in diabetes-related or general family conflict. However, contrary to expectation, the Education group was more efficacious than the Coping group in improvement of disease adherence and glycemic control over a 3-year follow-up.Low-intensity office-based quarterly treatment can maintain or improve disease care adherence in early adolescence when provided to adolescent/parent dyads. Better outcomes are achieved when treatment goals and techniques match the needs of the targeted population.
Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis
Authors: E.M. Kolibianakis, J. Collins, B.C. Tarlatzis, P. Devroey, K. Diedrich, G. Griesinger
Journal: Human Reproduction Update (2006)

This systematic review and meta-analysis aimed to answer the following clinical question: among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth per randomized patient dependent on the type of analogue used? Eligible studies were randomized controlled trials (RCTs), published as a full manuscript in a peer-reviewed journal, that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared. A literature search identified 22 RCTs comparing GnRH antagonists and GnRH agonists that involved 3176 subjects. Where live birth was not reported in a study that fulfilled the inclusion criteria, an effort was made to contact the corresponding authors to retrieve the missing information. If this was not possible, the reported outcome measure, clinical pregnancy or ongoing pregnancy was converted to live birth in 12 studies using published data (Arce et al., 2005). No significant difference was present in the probability of live birth between the two GnRH analogues [odds ratio (OR), 0.86; 95% confidence intervals (CI), 0.72 to 1.02]. This result remains stable in subgroup analysis that ordered the studies by type of population studied, gonadotrophin type used for stimulation, type of agonist protocol used, type of agonist used, type of antagonist protocol used, type of antagonist used, presence of allocation concealment, presence of co-intervention and the way the information on live birth was retrieved. In conclusion, the probability of live birth after ovarian stimulation for IVF does not depend on the type of analogue used for pituitary suppression.
Identification of unique nuclear regulatory proteins for the insulin receptor gene, which appear during myocyte and adipocyte differentiation.
Authors: A Brunetti, D Foti, I D Goldfine
Journal: Journal of Clinical Investigation (1993)

To define the molecular mechanism(s) that activate insulin receptor gene transcription during cell differentiation, we tested nuclear extracts from BC3H-1 muscle cells for their binding to the 5'-flanking region of the human insulin receptor gene. DNA binding activity of nuclear extracts was low in undifferentiated BC3H-1 cells and increased significantly during differentiation. Gel retardation assays, combined with DNase I footprinting, showed that the increased insulin receptor gene transcription occurring during differentiation was directly correlated with the appearance of DNA binding proteins that specifically interacted with two AT-rich sequences of the regulatory region of the insulin receptor gene. Fibroblast growth factor, a known inhibitor of the transcription of muscle-specific DNA binding proteins, did not inhibit the appearance of these insulin receptor DNA binding proteins. When 3T3-L1 cells differentiate from preadipocytes to adipocytes, insulin receptor gene transcription significantly increases. In differentiated adipocytes, the same two insulin receptor DNA binding proteins markedly increased. Reporter gene analysis with the two AT-rich sequences demonstrated that both of these regions of the insulin receptor gene had the characteristics of promoter rather than enhancer elements. Thus, these proteins interacting with these AT-rich sequences may have major importance in regulating the expression of the insulin receptor in target tissues.
A Double Master's Two-Step Test: Clinical, Angiographic and Hemodynamic Correlations
Authors: G. M. FITZGIBBON
Journal: Annals of Internal Medicine (1971)

One hundred and sixty men, of 41.6 years mean age, with known or suspected coronary artery disease, including, for the majority, a history of angina or myocardial infarction, or both, had double Master's two-step tests and selective coronary angiograms. Eighty-seven of these also had hemodynamic studies involving cardiac catheterization. Ninety subjects had no cardiac symptoms during the 3 months preceding study; the others had chest pain, in most cases considered to be angina. Angiographic findings were graded by degree of stenosis of major coronary arteries. Comparison of step-test results with coronary angiograms showed 16% "false positive" responses in subjects without evidence of coronary disease and 33% "false negative" tests in patients with severe obstructive coronary atherosclerosis. Relating step-test results to hemodynamic findings gave similar results. Evidence of serious coronary stenosis is found in many asymptomatic subjects, frequently in association with negative step tests. The double Master's two-step test yields an unacceptable number of "false positive" results. The prevalence of "false negative" results indicates that reliance on the test in excluding the presence of even grave coronary artery disease is unwarranted.
SPSB1 May Have MET Its Match during Breast Cancer Recurrence
Authors: Yuanbo Qin, Sandra S. McAllister
Journal: Cancer Discovery (2014)

Abstract Summary: Disease recurrence is the most common cause of death for patients with breast cancer, yet little is known about the molecular mechanisms underlying this process. Using inducible transgenic mouse model systems, Feng and colleagues identified SPSB1 as a determinant of breast cancer recurrence by virtue of its ability to protect tumor cells from apoptosis through c-MET activation. Cancer Discov; 4(7); 760–1. ©2014 AACR. See related article by Feng et al., p. 790