tbuckley/cabot-search huggingface dataset:
Human inter-individual variability in metabolic pathways and genotoxic response to zidovudine
Authors: Ofelia A. Olivero, Irma L. Vazquez, Catherine Cooch, Jessica M. Ming, Ainsley Weston, Miriam C. Poirier
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4451 

Patients infected with the human immunodeficiency virus (HIV-1) undergo extensive therapy with antiretroviral nucleoside analog drugs, among which Zidovudine® (AZT) is used the most frequently. The genotoxicity of AZT, a DNA replication chain terminator, has been documented in experimental models, but inter-individual variability in human genotoxic response has not been well studied. Here we used 19 different strains of normal human mammary epithelial cells (NHMECs) cultured from breast tissue obtained at reduction mammoplasty and representing human inter-individual variability. Cells, at passage 6, were exposed to either 0 or 200 μM AZT for 24 hr, and incorporation of AZT into DNA was analyzed by radioimmunoassay using anti-AZT antiserum. Of the 19 cell strains, 7 had no detectable AZT-DNA incorporation, 8 had 6–50 molecules of AZT/106 nucleotides, 2 had 51–100 molecules of AZT/106 nucleotides, and 2 had >100 molecules of AZT/106 nucleotides. exposure to the direct-acting DNA damaging agent bleomycin indicated that these responses were specific for the AZT exposures and not general responses to DNA damage. Further studies were therefore focused on AZT metabolism, and Western blots of all 19 NHMEC strains were performed for thymidine kinase 1 (TK1), the first enzyme phosphorylating AZT on the pathway to DNA incorporation. The 7 NHMEC strains showing no AZT-DNA incorporation had no measurable TK1 before AZT exposure, while 3 of these strains had AZT-inducible TK-1 at 24 hr. Of the 12 strains showing AZT-DNA incorporation, 9 had functional or AZT-inducible TK1. Taken together these data suggest that there may be a metabolic specificity underlying human sensitivity/resistance to AZT. Whereas the patients having high levels of TK1 may sustain more organ genotoxicity as a result of AZT exposure and incorporation, those with lower levels or inducible TK1 still have sufficient enzyme for the antiretroviral properties of the drug, but may be less susceptible to host genotoxic effects.
Biochemical and Molecular Genetic Analysis of Hormone-Sensitive Adenylyl Cyclase
Authors: G F Casperson, H R Bourne
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
CA-125: a tumor marker in non-Hodgkin's lymphomas?
Authors: T Pabst, C Ludwig
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.7.1827 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7602374 CA-125: a tumor marker in non-Hodgkin's lymphomas? T PabstxT PabstSearch for articles by this author , C LudwigxC LudwigSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.7.1827 PDF "CA-125: a tumor marker in non-Hodgkin's lymphomas?." Journal of Clinical Oncology, 13(7), pp. 1827–1828© 1995 by American Society of Clinical Oncology
Rapid Optical Cavity PCR
Authors: Jun Ho Son, SoonGweon Hong, Amanda J. Haack, Lars Gustafson, Minsun Song, Ori Hoxha, Luke P. Lee
Journal: Advanced Healthcare Materials (2015)

Recent outbreaks of deadly infectious diseases, such as Ebola and Middle East respiratory syndrome coronavirus, have motivated the research for accurate, rapid diagnostics that can be administered at the point of care. Nucleic acid biomarkers for these diseases can be amplified and quantified via polymerase chain reaction (PCR). In order to solve the problems of conventional PCR—speed, uniform heating and cooling, and massive metal heating blocks—an innovative optofluidic cavity PCR method using light‐emitting diodes (LEDs) is accomplished. Using this device, 30 thermal cycles between 94 °C and 68 °C can be accomplished in 4 min for 1.3 μL (10 min for 10 μL). Simulation results show that temperature differences across the 750 μm thick cavity are less than 2 °C and 0.2 °C, respectively, at 94 °C and 68 °C. Nucleic acid concentrations as low as 10 –8 ng μL –1 (2 DNA copies per μL) can be amplified with 40 PCR thermal cycles. This simple, ultrafast, precise, robust, and low‐cost optofluidic cavity PCR is favorable for advanced molecular diagnostics and precision medicine. It is especially important for the development of lightweight, point‐of‐care devices for use in both developing and developed countries.
Visual Motion Processing and Sensory-Motor Integration for Smooth Pursuit Eye Movements
Authors: S G Lisberger, E J Morris, L Tychsen
Journal: Annual Review of Neuroscience (1987)

The function of smooth pursuit is to keep the fovea pointed at a small visual target that moves smoothly across a patterned background. Chemical lesions, single cell recordings, and behavioral measures have shown that the cortical motion processing pathways form the afferent limb for pursuit. Important areas include at least the striate cortex and the middle temporal visual area, and probably the medial superior temporal visual area and the posterior parietal cortex. We argue that the visual inputs are transmitted through a simple sensory motor interface in the pons, to the efferent limb in the brain stem and cerebellum. The efferent limb uses neural velocity memory to maintain pursuit automatically. We present evidence that the velocity memory is provided, at least in part, by eye velocity positive feedback between the flocculus of the cerebellum and the brain stem. Finally, we use a computer model to show how the maintenance of pursuit can be simulated on a millisecond time scale. The structure and internal elements of the model are based on the biological experiments reviewed in our paper. In the past five years, progress on the neural basis of pursuit eye movements has been rapid. Several areas of research have made substantial contributions, by using combinations of new and conventional methods. Many of the pathways that contribute to pursuit have been identified, and their physiological activity and functions are becoming understood. Continuing progress promises to yield an understanding of one specific form of visually guided movement, at the level of neuronal circuits and behavior, in the primate.
How concerns and experiences with medical malpractice affect dermatopathologists' perceptions of their diagnostic practices when interpreting cutaneous melanocytic lesions
Authors: Patricia A. Carney, Paul D. Frederick, Lisa M. Reisch, Stevan Knezevich, Michael W. Piepkorn, Raymond L. Barnhill, David E. Elder, Berta M. Geller, Linda Titus, Martin A. Weinstock, Heidi D. Nelson, Joann G. Elmore
Journal: Journal of the American Academy of Dermatology (2015)
Calmodulin: a potential target for cancer chemotherapeutic agents.
Authors: W N Hait, J S Lazo
Journal: Journal of Clinical Oncology (1986)

Calmodulin is a ubiquitous, calcium-binding protein that is responsible for many of the intracellular actions of calcium. Recent evidence suggests that calmodulin may regulate cellular proliferation and that its function may be altered in malignancy. The discovery that drugs such as phenothiazines antagonize the action of calmodulin led to the study of these antagonists against tumor cells. It is now appreciated that calmodulin antagonists are cytotoxic, can restore the sensitivity of resistant cells to drugs such as doxorubicin and vincristine, and can augment the cytotoxicity of bleomycin. This report addresses the possibility of developing new forms of chemotherapeutic agents that work by disrupting the function of this intriguing molecule.
Food Poisoning Due to Vibrio Parahaemolyticus
Authors: W H Barker, E J Gangarosa
Journal: Annual Review of Medicine (1974)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Clinicopathologic analysis of <scp>TAFRO</scp> syndrome demonstrates a distinct subtype of <scp>HHV</scp>‐8‐negative multicentric Castleman disease
Authors: Noriko Iwaki, David C. Fajgenbaum, Christopher S. Nabel, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Isao Yoshida, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Kosei Matsue, Mitsutoshi Kurosawa, Masao Hagihara, Akio Saito, Masataka Okamoto, Kenji Yokota, Shinichiro Hiraiwa, Naoya Nakamura, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato
Journal: American Journal of Hematology (2015)

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed.
Dissociation and posttraumatic stress disorder in Vietnam combat veterans
Authors: J D Bremner, S Southwick, E Brett, A Fontana, R Rosenheck, D S Charney
Journal: American Journal of Psychiatry (1992)

This study compared current dissociative symptoms and dissociation at the time of specific traumatic events in Vietnam combat veterans with posttraumatic stress disorder (PTSD) and Vietnam combat veterans without PTSD.Vietnam combat veterans who sought treatment for PTSD (N = 53) were compared to Vietnam combat veterans without PTSD (N = 32) who sought treatment for medical problems. Dissociative symptoms were evaluated with the Dissociative Experiences Scale. Dissociation at the time of a combat-related traumatic event was evaluated retrospectively with the modified Dissociative Experiences Questionnaire. The Combat Exposure Scale was used to measure level of combat exposure.There was a significantly higher level of dissociative symptoms, as measured by the Dissociative Experiences Scale, in patients with PTSD (mean = 27.0, SD = 18.0) than in patients without PTSD (mean = 13.7, SD = 16.0). This difference persisted when the difference in level of combat exposure was controlled with analysis of covariance. PTSD patients also reported more dissociative symptoms at the time of combat trauma, as measured retrospectively by the Dissociative Experiences Questionnaire (mean = 11.5, SD = 1.6) than non-PTSD patients (mean = 1.8, SD = 2.1).Dissociative symptoms are an important element of the long-term psychopathological response to trauma.
Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study
Authors: Maura Harrigan, Brenda Cartmel, Erikka Loftfield, Tara Sanft, Anees B. Chagpar, Yang Zhou, Mary Playdon, Fangyong Li, Melinda L. Irwin
Journal: Journal of Clinical Oncology (2015)

Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers.One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months.The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05).Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care.
Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group.
Authors: P Hesketh, R Navari, T Grote, R Gralla, J Hainsworth, M Kris, L Anthony, A Khojasteh, E Tapazoglou, C Benedict, W Hahne
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the comparative antiemetic efficacy of single-dose intravenous (IV) dolasetron mesylate and ondansetron in preventing cisplatin-induced nausea and vomiting. PATIENTS AND METHODS Cancer patients (n = 609) receiving first-course cisplatin chemotherapy were randomized to one of three treatments: 1.8 or 2.4 mg/kg dolasetron mesylate salt (equivalent to 1.3 and 1.8 mg/kg dolasetron base, respectively) or 32 mg ondansetron. Each treatment was infused over 15 minutes, 30 minutes before cisplatin administration. Patients were stratified to cisplatin doses of &gt; or = 70 and less than 91 mg/m2 (n = 368) or &gt; or = 91 mg/m2 (n = 241), administered over &lt; or = 3 hours. Protocol-defined efficacy criteria included complete response (zero emetic episodes and no rescue medication), major response (1 to 2 emetic episodes and no rescue medication), and patients' report of nausea severity and satisfaction recorded on a 100-mm visual analog scale (VAS). RESULTS The three treatments met protocol-specified criteria for equivalence. Complete response rates for dolasetron mesylate 1.8 mg/kg, 2.4 mg/kg, and ondansetron, respectively, were 49.2%, 45.6%, and 50.4% for patients in the lower cisplatin stratum (mean, 74.7 mg/m2) and 36.8%, 31.3%, and 31.8% in the higher cisplatin stratum (mean, 100.6 mg/m2). No significant differences were observed in the extent of nausea with either dolasetron dose compared with ondansetron. Less nausea was noted with 1.8 mg/kg dolasetron compared with the 2.4 mg/kg dose (P = .044) All three antiemetic treatments were well tolerated. Asymptomatic electrocardiogram changes were recorded with both dolasetron and ondansetron. CONCLUSION A single IV dose of dolasetron mesylate (1.8 or 2.4 mg/kg) has comparable safety and efficacy to a single 32-mg IV dose of ondansetron in patients receiving cisplatin chemotherapy.
Former health secretary takes on another advisory role in private health sector
Authors: G. Iacobucci
Journal: BMJ (2015)

The former health secretary for England, Andrew Lansley, has taken on a role advising the drug company Roche, prompting fresh concerns over the “revolving door” between the government and industry.

Lansley, who was appointed to the House of Lords last month after stepping down as an MP in May 2015, has declared in his register of interests that he is advising the company on pharmaceutical supply and pricing issues in Europe until the end of November 2015.1

Roche was one of the main beneficiaries of the Cancer Drugs Fund that Lansley set up in 2010 and was recently in dispute with the NHS in England over the price of the breast cancer drug Kadcyla. The UK National Institute for …
Stepped care for depression and anxiety in visually impaired older adults: multicentre randomised controlled trial
Authors: Hilde P A van der Aa, Ger H M B van Rens, Hannie C Comijs, Tom H Margrain, Francisca Gallindo-Garre, Jos W R Twisk, Ruth M A van Nispen
Journal: BMJ (2015)

Is stepped care compared with usual care effective in preventing the onset of major depressive, dysthymic, and anxiety disorders in older people with visual impairment (caused mainly by age related eye disease) and subthreshold depression and/or anxiety?265 people aged ≥50 were randomly assigned to a stepped care programme plus usual care (n=131) or usual care only (n=134). Supervised occupational therapists, social workers, and psychologists from low vision rehabilitation organisations delivered the stepped care programme, which comprised watchful waiting, guided self help based on cognitive behavioural therapy, problem solving treatment, and referral to a general practitioner. The primary outcome was the 24 month cumulative incidence (seven measurements) of major depressive dysthymic and/or anxiety disorders (panic disorder, agoraphobia, social phobia, and generalised anxiety disorder). Secondary outcomes were change in symptoms of depression and anxiety, vision related quality of life, health related quality of life, and adaptation to vision loss over time up to 24 months' follow-up.62 participants (46%) in the usual care group and 38 participants (29%) from the stepped care group developed a disorder. The intervention was associated with a significantly reduced incidence (relative risk 0.63, 95% confidence interval 0.45 to 0.87; P=0.01), even if time to the event was taken into account (adjusted hazard ratio 0.57, 0.35 to 0.93; P=0.02). The number needed to treat was 5.8 (3.5 to 17.3). The dropout rate was fairly high (34.3%), but rates were not significantly different for the two groups, indicating that the intervention was as acceptable as usual care. Participants who volunteered and were selected for this study might not be representative of visually impaired older adults in general (responders were significantly younger than non-responders), thereby reducing the generalisability of the outcomes.Stepped care seems to be a promising way to deal with depression and anxiety in visually impaired older adults. This approach could lead to standardised strategies for the screening, monitoring, treatment, and referral of visually impaired older adults with depression and anxiety.Funded by ZonMw InZicht, the Dutch Organisation for Health Research and Development-InSight Society. There are no competing interests. Full dataset and statistical code are available from the corresponding author.Study registration www.trialregister.nl NTR3296.
High-dose cisplatin in hypertonic saline in refractory ovarian cancer.
Authors: R F Ozols, Y Ostchega, C E Myers, R C Young
Journal: Journal of Clinical Oncology (1985)

Nineteen previously treated refractory ovarian cancer patients, including 17 who had received standard-dose cisplatin regimens, were treated in a phase II trial with high-dose cisplatin (40 mg/m2 daily for five days with cycles administered every 28 to 35 days). Objective responses were achieved in 6/19 (32%) patients while eight patients had minor responses or stable disease. The median duration of survival from the start of salvage chemotherapy was 12 months for all patients, and 16 months for responding patients. The dose-limiting toxicity was peripheral neuropathy with 37% of patients having severe paresthesias or ataxia. These results indicate that the dose of cisplatin may be an important factor in improving survival in ovarian cancer patients.
Ageing costs
Authors: T. Richards
Journal: BMJ (1998)

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Providing and paying for long term care for Britain's ageing population is an urgent issue. The fastest growing sector of the population is the over 80 year olds. By 2030 a third of the population will be of pensionable age.1 Last December the government set up a royal commission to produce costed options for the next 50 years and report back. The commission has accumulated a mountain of opinion and evidence from some 2000 individuals and special interest groups concerned with care of the elderly. Last week it held its final public hearing to give them the opportunity to hammer home their messages.

Much consensus was evident. Radical organisational change and new methods of financing are needed to reverse the effects of policies which have left old and vulnerable people hostage to confusing, inadequate, inequitable, and poorly coordinated services. The onus on elderly people to demonstrate what they can't do rather than what they can in order to get help is …

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In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin-2 and LAK cell therapy.
Authors: J H Phillips, B T Gemlo, W W Myers, A A Rayner, L L Lanier
Journal: Journal of Clinical Oncology (1987)

Patients with advanced metastatic cancer were given combined autologous lymphokine activated killer (LAK) cell and recombinant interleukin-2 (rIL-2) therapy on a National Cancer Institute extramural phase II trial. Systemic administration of rIL-2 resulted in pronounced lymphocytopenia. Within two days after completion of in vivo rIL-2 therapy, there was a dramatic increase in absolute numbers of circulating lymphocytes, and cytotoxic activity against tumor cell targets was mediated by peripheral blood lymphocytes, indicating in vivo generation of LAK activity. Patients were leukapheresed and cells cultured for three to four days in rIL-2. rIL-2 cultured cells from all patients demonstrated cytotoxic activity. In order to characterize the effector cell, T cells and natural killer (NK) cells were isolated to greater than 95% purity by flow cytometry. Cytotoxic activity was mediated by rIL-2--activated NK cells, whereas T cells demonstrated no substantial activity. The circulating in vivo cytotoxic effectors detected after in vivo rIL-2 therapy were also shown to be rIL-2--activated NK cells. Results from these studies demonstrate that all patients were capable of generating a cytotoxic response, and that the cytotoxic effector cells were rIL-2--activated NK cells, identified by the phenotype CD3--, Leu 19+.