tbuckley/cabot-search huggingface dataset:
2nd International Symposium on Triglycerides and HDL
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2005)

This is the first of two articles summarizing the 2nd International Symposium on Triglycerides and HDL, organized by the Giovanni Lorenzini Medical Foundation and held in New York, New York, 14–17 July 2005.

Anthony Gotto (New York, NY) gave an overview of the “evolving story” of HDL and triglycerides in cardiovascular disease (CVD) prevention. He noted that statins only reduce clinical events by approximately one-third (although subsequent speakers suggested that with more aggressive LDL targets events may be reduced by half), and recommended targeting HDL and triglyceride in addition to LDL cholesterol to achieve greater degrees of risk reduction. There is as yet, however, no direct evidence of clinical benefit with this approach. In the early 1950s, the higher level of HDL cholesterol in women and the association of low HDL with CVD was first described, with the Framingham Heart Study recognizing low HDL as the “major potent lipid risk factor” in 1977 (1), and with recognition that each 1-mg/dl decrease in HDL is associated with a 2–3% increase in CVD risk later proposed by this group. Triglyceride also has been shown to be associated with CVD, although this is more controversial. In a meta-analysis of 17 population-based prospective studies of 46,413 men and 10,864 women, adjusting for HDL cholesterol and other risk factors, there were increases of 16 and 42% in CVD end points in men and in women, respectively, for every 100-mg/dl increase in triglyceride level (2). The National Cholesterol Education Program Adult Treatment Panel III (ATP III) recommended use of non-HDL cholesterol as a target of therapy if the triglyceride level exceeded 200 mg/dl. Triglycerides were recommended as a “secondary target” if levels exceeded 200 mg/dl, with nicotinic acid and fibrates useful pharmacologic approaches, and specific HDL cholesterol targets were not recommended (3). Using the ATP III …
Skin Prick Test Reactivity to Common Allergens in Finnish Adolescents
Authors: Tari Haahtela, Fred Bjorkstéan, Maija Heiskala, Ilpo Suoniemi
Journal: Allergy (1980)

We studied 708 adolescents aged 15–17 years in the 9th grade of school in Imatra. Of the eligible population born in 1962 77% were included. All were skin prick tested with 16 extracts from two manufacturers with 12 common allergens, which included pollens, epithelia, mite, house dust and fish. At least one positive, immediate reaction (weal diameter 3 mm or larger) occurred in 49% and at least two positive reactions in 43% of those studied. The boys were observed to be significantly more reactive than the girls. The allergen preparations to which positive reactions were most prevalent were house dust, cat and horse epithelium, and mite extract. Large differences in the prevalence of positive reactions were observed with different preparations of the same allergen. Pollen allergens tended to cause the largest positive weal reactions, and the weal size distribution with some pollens was distinctly bimodal. A scheme for calculating allergen potency in histamine‐equivalent‐prick (HEP) units is presented. It is noted that the result is greatly dependent on the population group chosen for testing.
Periodontal Status and A1C Change
Authors: Ryan T. Demmer, Moïse Desvarieux, Birte Holtfreter, David R. Jacobs, Henri Wallaschofski, Matthias Nauck, Henry Völzke, Thomas Kocher
Journal: Diabetes Care (2010)

OBJECTIVE Infection may be a type 2 diabetes risk factor. Periodontal disease is a chronic infection. We hypothesized that periodontal disease was related to A1C progression in diabetes-free participants. RESEARCH DESIGN AND METHODS The Study of Health in Pomerania (SHIP) is a population-based cohort in Germany including 2,973 diabetes-free participants (53% women; aged 20–81 years). Participants were categorized into four groups according to increasing baseline periodontal disease levels (percentage of sites per mouth with attachment loss ≥5 mm, determined a priori); sample sizes for each respective category were 1,122, 488, 463, and 479 (241 participants were edentulous). Mean absolute changes (year 5 minus baseline) in A1C (ΔA1C) were regressed across periodontal categories while adjusting for confounders (e.g., age, sex, smoking, obesity, physical activity, and family history). RESULTS Across baseline periodontal disease categories, ΔA1C ± SEM values were 0.023 ± 0.02, 0.023 ± 0.02, 0.065 ± 0.03, and 0.106 ± 0.03 (Ptrend = 0.02), yielding an approximate fivefold increase in the absolute difference in ΔA1C when dentate participants in the highest versus lowest periodontal disease category were compared; these results were markedly stronger among participants with high-sensitivity C-reactive protein ≥1.0 mg/l (Pinteraction = 0.01). When individuals who had neither baseline periodontal disease nor deterioration in periodontal status at 5 years were compared with individuals with both poor baseline periodontal health and longitudinal periodontal deterioration, mean ΔA1C values were 0.005 vs. 0.143% (P = 0.003). CONCLUSIONS Periodontal disease was associated with 5-year A1C progression, which was similar to that observed for a 2-SD increase in either waist-to-hip ratio or age in this population.
G protein–coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population
Authors: Yan Feng, Xiumei Hong, Lin Wang, Shanqun Jiang, Changzhong Chen, Binyan Wang, Jianhua Yang, Zhian Fang, Tonghua Zang, Xiping Xu, Xin Xu
Journal: Journal of Allergy and Clinical Immunology (2006)
Comparison of Hi-C results using in-solution versus in-nucleus ligation
Authors: Takashi Nagano, Csilla Várnai, Stefan Schoenfelder, Biola-Maria Javierre, Steven W. Wingett, Peter Fraser
Journal: Genome biology (2015)

Chromosome conformation capture and various derivative methods such as 4C, 5C and Hi-C have emerged as standard tools to analyze the three-dimensional organization of the genome in the nucleus. These methods employ ligation of diluted cross-linked chromatin complexes, intended to favor proximity-dependent, intra-complex ligation. During development of single-cell Hi-C, we devised an alternative Hi-C protocol with ligation in preserved nuclei rather than in solution. Here we directly compare Hi-C methods employing in-nucleus ligation with the standard in-solution ligation. We show in-nucleus ligation results in consistently lower levels of inter-chromosomal contacts. Through chromatin mixing experiments we show that a significantly large fraction of inter-chromosomal contacts are the result of spurious ligation events formed during in-solution ligation. In-nucleus ligation significantly reduces this source of experimental noise, and results in improved reproducibility between replicates. We also find that in-nucleus ligation eliminates restriction fragment length bias found with in-solution ligation. These improvements result in greater reproducibility of long-range intra-chromosomal and inter-chromosomal contacts, as well as enhanced detection of structural features such as topologically associated domain boundaries. We conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.
A synthetic peptide from transforming growth factor- 1 type III receptor prevents myocardial fibrosis in spontaneously hypertensive rats
Authors: N. Hermida, B. Lopez, A. Gonzalez, J. Dotor, J. J. Lasarte, P. Sarobe, F. Borras-Cuesta, J. Diez
Journal: Cardiovascular Research (2008)

We investigated whether P144, a synthetic peptide from transforming growth factor-beta(1) (TGF-beta(1)) type III receptor betaglycan, exhibits cardiac antifibrotic properties.The study was carried out in one group of 10-week-old normotensive Wistar-Kyoto rats treated with vehicle (V-WKY), one group of 10-week-old spontaneously hypertensive rats treated with vehicle (V-SHR), and one group of 10-week-old SHR treated with P144 (P144-SHR) for 12 weeks. Two more groups of 10-week-old untreated WKY and SHR were used to assess baseline values of the parameters tested. In addition, the effects of P144 on rat cardiac fibroblasts stimulated with TGF-beta(1) were also studied. Compared with V-WKY, V-SHR exhibited significant increases in the myocardial expression of phosphorylated Smad2, 38 and 42 kDa connective tissue growth factor (CTGF) isoforms, procollagen alpha1 (I) mRNA, and collagen type I protein, as well as in the expression of lysyl oxidase (LOX) mRNA and protein, collagen cross-linking and deposition. P144 administration was associated with significant reduction in all these parameters in P144-SHR. TGF-beta(1)-stimulated fibroblasts exhibited significant increases in phosphorylated Smad2, 38 and 42 kDa CTGF proteins, and procollagen alpha(1) (I) mRNA compared with control fibroblasts. No significant differences were found in these parameters between fibroblasts incubated with TGF-beta(1) and P144 and control fibroblasts.These results show that P144 inhibits TGF-beta(1)-dependent signalling pathway and collagen type I synthesis in cardiac fibroblasts. These effects may be involved in the ability of this peptide to prevent myocardial fibrosis in SHR.
Looking Beyond Historical Patient Outcomes to Improve Clinical Models
Authors: Chih-Chun Chia, Ilan Rubinfeld, Benjamin M. Scirica, Sean McMillan, Hitinder S. Gurm, Zeeshan Syed
Journal: Science Translational Medicine (2012)

Clinical models can be improved by decreasing the importance assigned to fitting historical patient outcomes in often small and imperfectly characterized derivation cohorts.
Eag1: An Emerging Oncological Target
Authors: Luis A. Pardo, Walter Stühmer
Journal: Cancer Research (2008)

Abstract Emerging evidence indicates that ion channels act in a variety of physiologic and pathologic processes beyond electronic signal transmission, including in cancer. We recently found that the potassium channel Eag1 can mediate cancer progression and that a monoclonal antibody, which inhibits Eag1 action, can effectively restrict cancer cell proliferation. We discuss how Eag1 targeting may be useful in diagnostic or therapeutic settings. [Cancer Res 2008;68(6):1611–3]
Pediatric Brain Tumor Survivors, Physicians, and Researchers Face Long-Term Challenges
Authors: Renee Twombly
Journal: JNCI Journal of the National Cancer Institute (2009)

Living 5 years after a cancer diagnosis is an event many patients celebrate — for some it signifies the transition from cancer patient to cancer survivor, suggesting a future life free of the disease and its effects. But new research makes it clear that no reliable benchmark exists for those treated for pediatric central nervous system (CNS) malignancies, most of which are brain cancers. According to a study in this issue of the Journal, more than 25% of former patients will die within 30 years of their diagnosis — due primarily to recurrence and/or progression of primary disease. In addition, 82% of survivors reported having at least one chronic medical condition, 38% of which were deemed serious or life threatening. The researchers also found considerable cognitive impairment among survivors. Those treated with radiation had lower rates of employment and marriage or had emotional problems. The study, which
DIETARY TREATMENT OF HYPERTENSION. II. SODIUM DEPLETION AS RELATED TO THE THERAPEUTIC EFFECT 1
Authors: Vincent P. Dole, Lewis K. Dahl, George C. Cotzias, Dominic D. Dziewiatkowski, Cecilia Harris
Journal: Journal of Clinical Investigation (1951)

Abnormal accumulations of sodium have been demonstrated by direct analysis of the tissues of dogs (1) and rats (2) that had been made hypertensive by renal ischemia. These observations are of special interest because of the reductions of blood pressure in hypertensive patients that may be induced by means of extreme restriction of the dietary sodium. Taken together, these facts suggest that the benefit experienced by the patients might be due to the removal of excess sodium.
Rituximab Using A Thrice Weekly Dosing Schedule in B-Cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Demonstrates Clinical Activity and Acceptable Toxicity
Authors: John C. Byrd, Timothy Murphy, Robin S. Howard, Margaret S. Lucas, Amy Goodrich, Kathy Park, Michael Pearson, Jamie K. Waselenko, Geoffrey Ling, Michael R. Grever, Antonio J. Grillo-Lopez, Jay Rosenberg, Lori Kunkel, Ian W. Flinn
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule. PATIENTS AND METHODS: Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m 2 ) and cohort II (n = 7; 375 mg/m 2 ) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort III (n = 23; 375 mg/m 2 ) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter. RESULTS: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P = .02) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+). CONCLUSION: Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.
Prognostic factors for subdiaphragmatic involvement in clinical stage I–II supradiaphragmatic Hodgkin’s disease: A retrospective analysis of the GHSG
Authors: U. Rueffer, M. Sieber, A. Josting, K. Breuer, F.J. Grotenhermen, H. Bredenfeld, H. Tesch, H. Nisters-Backes, A. Engert, V. Diehl
Journal: Annals of Oncology (1999)
Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment
Authors: Morten Lebech, Ole Andersen, Niels Christian Christensen, Jens Hertel, Hans Erik Nielsen, Birgit Peitersen, Catherine Rechnitzer, Severin Olesen Larsen, Bent Nørgaard-Pedersen, Eskild Petersen
Journal: The Lancet (1999)
Diabetes and the Risk of Infection-Related Mortality in the U.S.
Authors: Alain G. Bertoni, Sharon Saydah, Frederick L. Brancati
Journal: Diabetes Care (2001)

OBJECTIVE—To determine whether diabetes predicts infection-related mortality and to clarify the extent to which this relationship is mediated by comorbid conditions that may themselves increase risk of infection. RESEARCH DESIGN AND METHODS—We performed a retrospective cohort study using the Second National Health and Nutrition Examination Survey Mortality Study of 9,208 adults aged 30–74 years in 1976–1980. We defined demographic variables, diabetes, cardiovascular disease (CVD), and smoking by self-report; BMI, blood pressure, and serum cholesterol from baseline examination; and cause-specific mortality from death certificates. RESULTS—Over 12–16 years of follow-up, 36 infection-related deaths occurred among 533 adults with diabetes vs. 265 deaths in 8,675 adults without diabetes (4.7 vs. 1.5 per 1,000 person-years, P &amp;lt; 0.001). Diabetes (RR 2.0, 95% CI 1.2–3.2) and congestive heart failure (2.8, 1.6–5.1) were independent predictors of infection-related mortality after simultaneous adjustment for age, sex, race, poverty status, smoking, BMI, and hypertension. After subdividing infection-related deaths into those with (n = 145) and without (n = 156) concurrent cardiovascular diagnoses at the time of death, diabetic adults were at risk for infection-related death with CVD (3.0, 1.8–5.0) but not without CVD (1.0, 0.5–2.2). CONCLUSIONS—These nationally representative data suggest that diabetic adults are at greater risk for infection-related mortality, and the excess risk may be mediated by CVD.
Risk factors for pulmonary Mycobacterium avium-intracellulare complex disease deterioration in immunocompetent patients
Authors: Satoshi Watanabe, Yuichi Tambo, Yuko Waseda, Ryo Matsunuma, Hazuki Takato, Kanako Inuzuka, Akihito Okazaki, Nobuyuki Katayama, Masahide Yasui, Kazuo Kasahara, Masaki Fujimura
Journal: European Respiratory Journal (2012)

Backgrounds and objectives: Pulmonary Mycobacterium avium-intracellulare complex (MAC) disease has become increasingly observed in immunocompetent patients without any underlying lung diseases. Disease progression is variable and its natural history is not well understood. We investigated possible risk factors for deterioration of pulmonary MAC disease.

Methods: A case-control study was done for 61 patients with pulmonary MAC disease who had no underlying lung diseases and were not immunosuppressed. Patients were divided into two groups: disease deterioration (Cases; N=32) and no disease deterioration (Controls; N=29). At their first visit, we examined patient characteristics, symptoms, chest CT findings, bacteriological and hematological test results, and respiratory function test results.

Results: At their first visit, Cases were more often symptomatic than Controls (90.6% vs. 37.9%; p<0.001). Cases had advanced radiological changes (CT scores 8.2 vs. 4.3; p<0.001), and more Cases than Controls had cavitation (28.1% vs. 3.4%; p=0.009), and enlarged mediastinal lymph nodes (71.9% vs. 24.1%, p<0.001). Erythrocyte sedimentation rates (ESR) and fibrinogen levels were significantly increased in Cases. No significant differences were found between these groups for age, BMI, environmental exposure, nutritional status, immune status, or respiratory function.

Conclusions: Increased symptoms incidence, advanced radiological changes, increased ESR and high fibrinogen levels are risk factors for pulmonary MAC disease deterioration. These factors might be useful not only to predict disease deterioration but for decisions regarding the timing of introducing treatment.
Is there a doctor in the house? An analysis of the practice of physicians' treating their own families
Authors: J. La Puma
Journal: JAMA (1992)

THE PRACTICE of physicians' caring medically for their families is not new and appears to be common. In the only published empirical data on this subject,<sup>1</sup>83% of 465 practicing physicians in a community teaching hospital had prescribed medications for family members; 80% had diagnosed illnesses; 72% had examined family members; 17% had attended family members in the hospital; and 11% had operated on family members. Most (59%) had previously refused a family member's request for medical care; 48% had referred the patient for whom they had made their "most important diagnosis."1 Incidence, quality effects, process and outcome of care, and the utility and effectiveness of the physician-patient relationship when physician and patient are family remain unknown. The practice of physicians' treating their own families raises ethical concerns, including when to breach confidentiality or obtain advance directives; how to secure informed consent, assess decisionmaking capacity, or give end-of-life care;
Reduced Antiretroviral Drug Susceptibility Among Patients With Primary HIV Infection
Authors: Susan J. Little
Journal: JAMA (1999)

ContextThe transmission of drug-resistant human immunodeficiency virus (HIV) has been documented, but the prevalence of such transmission is unknown.ObjectiveTo assess the spectrum and frequency of antiretroviral susceptibility among subjects with primary HIV infection.Design, Setting, and PatientsRetrospective analysis of 141 subjects identified from clinical research centers in 5 major metropolitan areas, enrolled from 1989 to 1998, with HIV seroconversion within the preceding 12 months and no more than 7 days' prior antiretroviral (ARV) therapy.Main Outcome MeasuresPhenotypic and genotypic ARV susceptibility of HIV from plasma samples.ResultsThe transmission of drug-resistant HIV as assessed by a greater than 10-fold reduction in ARV susceptibility to 1 or more drugs was observed in 3 (2%) of 141 subjects, including to a nonnucleoside reverse transcriptase inhibitor in 1 patient and to a nucleoside reverse transcriptase inhibitor and a protease inhibitor in 2 patients. Population-based sequence analysis of these 3 samples identified multidrug-resistance mutations in reverse transcriptase (M184V, T215Y, K219K/R) and protease (L10I/V, K20R, M36I, M46I, G48V, L63P, A71T, V77I, V82T, I84V, L90M) in the 2 latter patient samples, along with numerous polymorphisms. A reduction in susceptibility of greater than 2.5- to 10-fold to 1 or more drugs was observed in viral isolates from 36 patients (26%). Sequence analysis of these 36 samples identified well-characterized drug resistance mutation in reverse transcriptase and protease in only 1 of these patients.ConclusionsReductions in drug susceptibility of more than 10-fold were rare among this cohort of recently HIV-infected subjects and were distributed among each of the 3 major classes of ARV drugs tested. Reductions in susceptibility of more than 2.5- to 10-fold to certain ARV drugs of unknown clinical significance were highly prevalent among newly infected patients. Resistance testing may be warranted to monitor the frequency of drug resistance over time and to assess the potential for geographic variability.
In Vivo Modulation of Thymus-Leukemia Antigens on Mouse Leukemia Cells and Thymocytes: Retention of Modulating Antibody on the Cell Surface&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Janet B. Jacobson, Stefan Galuska, Christopher W. Stackpole
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article In Vivo Modulation of Thymus-Leukemia Antigens on Mouse Leukemia Cells and Thymocytes: Retention of Modulating Antibody on the Cell Surface Get access Janet B. Jacobson, Janet B. Jacobson 3Donald S. Walker Laboratory, Sloan-Kettering Institute for Cancer Research, 145 Boston Post Rd., Rye, N.Y. 10580. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefan Galuska, Stefan Galuska 3Donald S. Walker Laboratory, Sloan-Kettering Institute for Cancer Research, 145 Boston Post Rd., Rye, N.Y. 10580. Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher W. Stackpole Christopher W. Stackpole 4 3Donald S. Walker Laboratory, Sloan-Kettering Institute for Cancer Research, 145 Boston Post Rd., Rye, N.Y. 10580. 4Address reprint requests to Dr. Stackpole. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 3, September 1978, Pages 819–825, https://doi.org/10.1093/jnci/61.3.819 Published: 01 September 1978 Article history Received: 16 November 1977 Accepted: 03 April 1978 Published: 01 September 1978