tbuckley/cabot-search huggingface dataset:
A metabolic dysfunction in early murine osteoarthritis.
Authors: F P Altman
Journal: Annals of the Rheumatic Diseases (1981)

Male mice of the STR/ORT strain spontaneously develop an osteoarthritis lesion in the medial tibial condyle. The appearance of the lesion is age-related and by about 15 months has affected almost all animals. Histochemical studies of lactate dehydrogenase and succinate dehydrogenase activities have shown that a region of inactive chondrocytes appears in the cartilage of these mice before major histological evidence of degeneration. It is suggested that this may be an early metabolic dysfunction, which subsequently leads to matrix breakdown due to the lack of essential enzyme cofactors.
NK cells get helpful
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

![Graphic][1] 

IL-18–conditioned NK cells (yellow) migrate to the T cell (blue) zones of lymph nodes.On 

[page 941][2], Mailliard et al. show that natural killer (NK) cells exposed to the cytokine interleukin (IL)-18 commit to a life of helping rather than killing. According to the
Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV
Authors: Sang-Kyung Lee, Derek M. Dykxhoorn, Priti Kumar, Shahin Ranjbar, Erwei Song, Laura E. Maliszewski, Vanessa François-Bongarçon, Anne Goldfeld, N. Manjunath Swamy, Judy Lieberman, Premlata Shankar
Journal: Blood (2005)
Screening for Cardiac Dysfunction in Anthracycline-Exposed Childhood Cancer Survivors
Authors: Saro H. Armenian, Sarah K. Gelehrter, Tabitha Vase, Rajkumar Venkatramani, Wendy Landier, Karla D. Wilson, Claudia Herrera, Leah Reichman, John-David Menteer, Leo Mascarenhas, David R. Freyer, Kalyanasundaram Venkataraman, Smita Bhatia
Journal: Clinical Cancer Research (2014)

To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy.Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status.Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction.Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.
Human T cell activation. III. Rapid induction of a phosphorylated 28 kD/32 kD disulfide-linked early activation antigen (EA 1) by 12-o-tetradecanoyl phorbol-13-acetate, mitogens, and antigens.
Authors: T Hara, L K Jung, J M Bjorndahl, S M Fu
Journal: The Journal of Experimental Medicine (1986)

With human T cells activated by 12-o-tetradecanoyl phorbol-13-acetate (TPA) as immunogen, an IgG2a mAb, early activation antigen 1 (EA 1), was generated against a 60-kD protein with disulfide-linked 28-kD and 32-kD subunits. Both subunits were phosphorylated. The antigen, EA 1, was readily detected on approximately 60% of isolated and cryopreserved thymocytes, as determined by indirect immunofluorescence. A low level of EA 1 expression was detectable on 6-7% of blood lymphocytes. TPA-activated T cells expressed EA 1 as early as 30 min after activation. By 1 h, 85-90% of the T cells stained with mAb EA 1. By 3-4 h, the expression of EA 1 was detected in greater than 95% of the T cells. Although the percentages of EA 1+ T cells did not change, the intensity of staining increased slightly. After 18-24 h, both the percentage of EA 1+ cells and the intensity of staining decreased gradually. TPA-induced EA 1 expression was independent of monocytes. EA 1 expression was slightly delayed in T cells that were isolated without the rosette selection and treated with TPA. Nevertheless, greater than 85% of these T cells expressed EA 1 within 1 h, and the maximal number of EA 1+ T cells was also detected at 3-4 h. In T cell populations with 1-2% monocytes, about 50-90% of the PHA- or Con A-activated T cells expressed EA 1 with a slower kinetics. EA 1 expression preceded that of IL-2-R in these activation processes. Similarly, T cells activated by soluble antigens (tetanus toxoid and PPD) and alloantigens in MLR also expressed EA 1 after a longer incubation. Approximately 20% of the T cells stained for EA 1 at day 6. EA 1 expression was not limited to activated T cells. B cells activated by TPA or anti-IgM antibody plus B cell growth factor expressed EA 1. The kinetics of EA 1 expression was markedly slower and the staining was less intense. Repeated attempts to detect EA 1 on resting and TPA-activated monocytes and granulocytes have not been successful. However, the detection of EA 1 in nonlymphoid cell lines would indicate that EA 1 may have a broader cell distribution. EA 1 expression was due to de novo synthesis, as the induction of EA 1 was blocked by cycloheximide and actinomycin D.(ABSTRACT TRUNCATED AT 400 WORDS)
Long-term electrophysiological effects of regional cardiac sympathetic denervation of the neonatal dog
Authors: E Sosunov
Journal: Cardiovascular Research (2001)

In many cardiac arrhythmias, both a triggering factor and a favorable myocardial substrate are required. Whereas the sympathetic nervous system may trigger tachyarrhythmias, its function as a long-term modulator of the myocardial substrate is less well understood. Therefore, we tested the hypothesis that regional sympathetic denervation at birth would produce an abnormal myocardial substrate. The comparator was the substrate associated with inherited, lethal tachyarrhythmias at 5 months of age in German shepherd dogs with incomplete sympathetic innervation.Mongrel dogs underwent right cardiac stellectomy (RSX) within the first day of life and were terminally studied with control littermates at 5 months of age.On days 1-21 of life, RSX animals manifested significant QT prolongation on ECG and sudden, asystolic death. Beyond this age, QT intervals normalized and deaths did not occur. At 5 months, action potentials (AP) were recorded from Purkinje fibers (PF) and midmyocardial preparations in anteroseptal (AS) and posterobasal (PB) left ventricle. Early afterdepolarizations occurred only in left ventricular PF from RSX dogs. Isoproterenol prolonged AP duration in AS and shortened it in PB of RSX but not control dogs. The incidence of isoproterenol-initiated triggered activity and the amplitude of delayed afterdepolarizations were greater in RSX than control dogs.Five months after RSX heterogeneous alterations of LV electrophysiological properties were similar to those previously observed in animals having inherited deficits in sympathetic innervation and sudden death. This implicates the sympathetic nerves as long-term modulators of an arrhythmogenic substrate. That 5-month-old RSX dogs did not experience tachyarrhythmias or sudden death indicates that further anomalies--beyond those explicable by the substrate change--must exist to induce sudden death.
Establishment of a New Interleukin-6 (IL-6) Receptor Inhibitor Applicable to the Gene Therapy for IL-6–Dependent Tumor
Authors: Naoko Yoshio-Hoshino, Yasuo Adachi, Chieko Aoki, Alexander Pereboev, David T. Curiel, Norihiro Nishimoto
Journal: Cancer Research (2007)

Abstract Interleukin-6 (IL-6) is a key molecule involved in the pathogenesis of several inflammatory diseases and malignancies. Treatments that inhibit IL-6 mitigate the clinical conditions of such diseases. Here, we report on the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody which specifically blocks IL-6 signaling. This NRI consists of VH and VL of tocilizumab in a single-chain fragment format dimerized by fusing to the Fc portion of human immunoglobulin G1. The binding activity to IL-6 receptor and the biological activity of the purified NRI were found to be similar to those of parental tocilizumab. Because NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. We administered an adenovirus vector encoding NRI to mouse i.p. and monitored the serum NRI level and growth reduction property on S6B45, an IL-6–dependent multiple myeloma cell line, in vivo. Adequate amount of the serum NRI level to exert anti-IL-6 action could be obtained by the NRI gene introduction combined with adenovirus gene delivery, and this treatment inhibited the in vivo S6B45 cell growth significantly. These findings indicate that NRI is a promising agent applicable to the therapeutic gene delivery approach for IL-6–driven diseases. [Cancer Res 2007;67(3):871–5]
The Mechanism of Self-Perpetuated Activation of ERK1/2 in Airway Cells in the Absence of Allergen Exposure in a Mouse Model of Chronic Asthma
Authors: R. Alam, Q. Liang, N. Goplen, W. Liu, S. Rozario, R. Vepachedu, L. Guo, M.M. Gorska
Journal: Journal of Allergy and Clinical Immunology (2006)
Adenovirus Small E1A Employs the Lysine Acetylases p300/CBP and Tumor Suppressor Rb to Repress Select Host Genes and Promote Productive Virus Infection
Authors: Roberto Ferrari, Dawei Gou, Gauri Jawdekar, Sarah A. Johnson, Miguel Nava, Trent Su, Ahmed F. Yousef, Nathan R. Zemke, Matteo Pellegrini, Siavash K. Kurdistani, Arnold J. Berk
Journal: Cell Host & Microbe (2014)
Control of Hepatitis A Through Routine Vaccination of Children
Authors: Francisco Averhoff
Journal: JAMA (2001)

A CONTINUES TO BE one of the most frequently reported vaccine-preventable diseases in the United States.9][20][21] Routine vaccination of children living in small communities that had experienced recurrent hepatitis A epidemics and in which most adults are immune has been shown to be effective in helping to interrupt disease transmission. 22,23How-ever, the impact of routine childhood vaccination on disease incidence in large communities that experience recurrent epidemics, where most of the population is thought to be susceptible to the disease, has not been determined. 5We report the results of rou-
HIGH PREVALENCE OF INJURIES IN THE NORWEGIAN NATIONAL BALLET
Authors: H Fredriksen, B Clarsen
Journal: British Journal of Sports Medicine (2014)

Background Ballet dancers are both artists and athletes with extreme physical demands placed on them. Clinical experience and previous studies suggest that they are at high risk of sustaining injuries, but more high-quality prospective studies are needed. Objective To assess the prevalence of injuries and illnesses among professional ballet dancers in the Norwegian National Ballet Company, using a newly developed injury surveillance method. Information gained may provide a foundation for future prevention interventions. Design Prospective cohort study. Participants A total of 57 dancers in the National ballet company agreed to participate. During the first 32 weeks of the registration there has been 5 drop-outs. Interventions Every second week all dancers received a recently developed online questionnaire which records symptoms of illness and injury, as well as reduced participation and dancing performance due to health problems. Main outcome measurements Prevalence of injuries and illnesses. Results Preliminary results after 32 weeks. The average response rate was 81% (64–89%). The average injury prevalence was 64% (32–84%), and the average illness prevalence was 9% (4–20%). The prevalence of substantial injuries, defined as injuries leading to moderate or severe reductions in dance participation or performance, or total inability to dance, was 29% (18–45%). Thirty-four percent of injuries were located in the ankle, 18% in the lower leg, 12% in the knee and 11% in the foot. Conclusions The prevalence of injury is extremely high among dancers at the Norwegian National Ballet Company, being considerably higher than among elite athletes from Olympic sports. Future efforts to prevent injuries in this group are warranted.
Ability of Recombinant Factor VIIa to Reverse the Anticoagulant Effect of the Pentasaccharide Fondaparinux in Healthy Volunteers
Authors: Nick R. Bijsterveld, Arno H. Moons, S. Matthijs Boekholdt, Benien E. van Aken, Hein Fennema, Ron J.G. Peters, Joost C.M. Meijers, Harry R. Büller, Marcel Levi
Journal: Circulation (2002)

Background— The novel anticoagulant fondaparinux proved to be effective and safe in the postoperative prevention of venous thrombosis. Current phase III trials with this synthetic selective factor Xa inhibitor focus on its use in the treatment of patients with venous and arterial thrombosis. As with any anticoagulant therapy, there is a risk of bleeding complications; hence, a strategy to reverse the effects of fondaparinux is desirable. The aim of this study was to investigate whether recombinant factor VIIa (rFVIIa) could neutralize the anticoagulant effects of subcutaneously administered fondaparinux. Methods and Results— In a randomized, placebo-controlled design, 16 healthy male subjects received either a single subcutaneous dose of fondaparinux (10 mg) and a single intravenous bolus of rFVIIa (90 μg/kg; n=8), fondaparinux and placebo (n=4), or placebo and rFVIIa (n=4). Fondaparinux (or placebo) was administered 2 hours before rFVIIa (or placebo). Injection of rFVIIa after fondaparinux normalized the prolonged activated partial thromboplastin and prothrombin times and reversed the decrease in prothrombin activation fragments 1+2 (F 1+2 ), as observed with fondaparinux alone. Thrombin-generation time and endogenous thrombin potential, which were inhibited by fondaparinux, normalized up to 6 hours after rFVIIa injection. Conclusions— rFVIIa is capable of normalizing coagulation times and thrombin generation during fondaparinux treatment. The duration of this effect ranged from 2 to 6 hours after rFVIIa injection. These results suggest that rFVIIa may be useful to reverse the anticoagulant effect of fondaparinux in case of serious bleeding complications or need for acute surgery during treatment with fondaparinux.
Quality of life in refractory ascites: Transjugular intrahepatic portal-systemic shunting versus medical therapy
Authors: Mical S. Campbell, Colleen M. Brensinger, Arun J. Sanyal, Chris Gennings, Florence Wong, Kris V. Kowdley, Timothy McCashland, Rajender K. Reddy
Journal: Hepatology (2005)

Abstract Uncontrolled studies suggest that transjugular intrahepatic portal-systemic shunting (TIPS) may improve quality of life in patients with refractory ascites. We hypothesized that any improvement of quality of life in patients with TIPS would be matched in controls due to the competing effects of improved ascites and worsened hepatic encephalopathy. Thus, an analysis of quality of life was performed using original data from the North American Study for the Treatment of Refractory Ascites, a multicenter trial of 109 patients randomized to TIPS or repeated large volume paracentesis (LVP) for refractory ascites. Short form 36 (SF-36) surveys were completed at baseline and at 6- and 12-month follow-up. Variables analyzed were: randomization group, number of LVP performed, cumulative volume from LVP, shortness of breath, abdominal distention, abdominal pain, diuretic usage, confusion, hospitalizations, and emergency room visits. Outcomes were changes in physical component scale (PCS) and mental component scale (MCS) of SF-36 results. We constructed multivariable, mixed effects models, including randomization group and baseline MCS and PCS. Changes in PCS and MCS from baseline were similar between the two randomization groups. In multivariate analysis, PCS improvement was associated with lack of confusion, improved ascites, and lack of hospitalizations, but not directly with randomization group. Improvement in MCS was associated with randomization to TIPS and lack of confusion. In conclusion , patients with refractory ascites randomized to TIPS or repeated LVP had similar changes in quality of life. Competing effects of hepatic encephalopathy, requirement for repeated LVP, and need for hospitalizations explain similar changes in quality of life between the two groups. (Hepatology 2005.)
A Decade of Direct-to-Consumer Advertising of Prescription Drugs
Authors: Julie M. Donohue, Marisa Cevasco, Meredith B. Rosenthal
Journal: New England Journal of Medicine (2007)

Evidence suggests that direct-to-consumer advertising of prescription drugs increases pharmaceutical sales and both helps to avert underuse of medicines and leads to potential overuse. Concern about such advertising has increased recently owing to the withdrawal from the market of heavily advertised drugs found to carry serious risks. Moreover, the Food and Drug Administration (FDA) has been criticized for its weak enforcement of laws regulating such advertising.We examined industry-wide trends in spending by pharmaceutical companies on direct-to-consumer advertising and promotion to physicians during the past decade. We characterized the drugs for which such advertising is used and assessed the timing of advertising after a drug is introduced. Finally, we examined trends in the FDA's regulation of drug advertising.Total spending on pharmaceutical promotion grew from $11.4 billion in 1996 to $29.9 billion in 2005. Although during that time spending on direct-to-consumer advertising increased by 330%, it made up only 14% of total promotional expenditures in 2005. Direct-to-consumer campaigns generally begin within a year after the approval of a product by the FDA. In the context of regulatory changes requiring legal review before issuing letters, the number of letters sent by the FDA to pharmaceutical manufacturers regarding violations of drug-advertising regulations fell from 142 in 1997 to only 21 in 2006.Spending on direct-to-consumer advertising has continued to increase in recent years in spite of the criticisms leveled against it. Our findings suggest that calls for a moratorium on such advertising for new drugs would represent a dramatic departure from current practices.
An Outbreak of Type 1 Pneumococcal Pneumonia in a Men's Shelter
Authors: Alfred DeMaria
Journal: JAMA (1980)

A striking increase in blood culture isolates of<i>Streptococcus pneumoniae</i>capsular type 1 was noted at Boston City Hospital in early 1978. The increased incidence of type 1 pneumococcal bacteremia was due, at least in part, to an outbreak of disease among alcoholic, male clients of Boston's largest shelter. Residents of the shelter also were found to have a high rate of nose and throat carriage of type 1 pneumococci. This outbreak of bacteremic pneumococcal pneumonia is compared with endemic disease caused by other serotypes observed at Boston City Hospital during the same period and with previous studies of epidemic pneumococcal disease. Routine serotyping of pneumococcal isolates is important, especially in light of the emergence of pneumococci resistant to multiple antibiotics and of the renewed use of polysaccharide vaccines. (<i>JAMA</i>244:1446-1449, 1980)
Changes in Body Fat Distribution and Fitness Are Associated With Changes in Hemoglobin A1c After 9 Months of Exercise Training
Authors: Martin Sénéchal, Damon L. Swift, Neil M. Johannsen, Steven N. Blair, Conrad P. Earnest, Carl J. Lavie, Timothy S. Church
Journal: Diabetes Care (2013)

OBJECTIVE To investigate the associations between changes in body composition and fitness after exercise training and changes in hemoglobin A1c (HbA1c) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants (n = 201) were randomized to aerobic, resistance, or combined training for 9 months. HbA1c, waist circumference, total and trunk fat mass, appendicular fat mass, lean body mass, isokinetic leg muscle strength, peak O2 uptake, and estimated METs were assessed at baseline and follow-up. Change in HbA1c was evaluated across quartiles of change in body composition and fitness. RESULTS Change in HbA1c was associated with changes in body weight (r = 0.13, P = 0.052), waist circumference (r = 0.17, P = 0.013), trunk fat mass (r = 0.19, P = 0.005), and estimated METs (r = −0.16, P = 0.023). There was a trend in change in HbA1c across quartiles of waist circumference (P = 0.011), trunk fat mass (P = 0.020), and estimated METs (P = 0.011). Participants with increased estimated METs and reduced trunk fat mass had greater odds of having reduced HbA1c after training (3.48, 1.46–8.31). Finally, participants with increased estimated METs and reduced waist circumference were 2.81 (1.13–6.98) times more likely to have reduced HbA1c and type 2 diabetes medication use than those without improved fitness and central adiposity. CONCLUSIONS In patients with type 2 diabetes, a reduction in central adiposity and increase in fitness were the most prominent predictors of the change in HbA1c in response to exercise training.
Impaired Hypoxic Vasoconstriction in Intraacinar Microvasculature in Hyperoxia-exposed Rat Lungs
Authors: KOICHI SUZUKI, KATSUHIKO NAOKI, HIROYASU KUDO, KAZUMI NISHIO, NAGATO SATO, TAKUYA AOKI, YUKIO SUZUKI, KEI TAKESHITA, ATSUSHI MIYATA, HARUKUNI TSUMURA, YUKI YAMAKAWA, KAZUHIRO YAMAGUCHI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To assess the effects of exposure of the lung to hyperoxic conditions on reactivity of pulmonary microcirculation to hypoxic stimulation, we measured hypoxia-elicited overall pulmonary pressor changes (HPV) and microvascular diameter changes in intraacinar arterioles, venules, and capillaries in isolated perfused rat lungs exposed to a hyperoxic environment (90% O2). To estimate the importance of vasoactive prostaglandins and nitric oxide (NO) for HPV modification, we examined the roles of constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2) and those of NO synthase (eNOS and iNOS). Indomethacin was used for inhibiting both COX-1 and COX-2, while NS-398 was used as a selective inhibitor of COX-2. Both eNOS and iNOS were suppressed by L-NAME, whereas iNOS alone was inhibited by aminoguanidine. Microvascular diameter was measured with a real-time confocal laser scanning luminescence microscope. We found that (1) exposure to hyperoxia caused overall HPV and arteriolar constriction to be attenuated; (2) the blunted HPV was restored by L-NAME but not by aminoguanidine, indomethacin, or NS-398; and (3) arteriolar constriction was improved by either L-NAME, aminoguanidine, or indomethacin but only slightly by NS-398. In conclusion, attenuation of overall HPV in hyperoxia-exposed lungs is explicable mainly by excessive NO generated via eNOS, while impaired arteriolar constriction is caused by NO yielded by eNOS and iNOS as well as by vasodilating prostaglandin(s) produced by COX-1.