Most human cells express two TNF and lymphotoxin (LT) membrane receptors (TNF-R), of 55 and 75 kDa. The regulatory effect of these two receptors on intercellular adhesion molecules (ICAM-1) expression was examined in various human cell lines in vitro, including human lymphokine-activated killer T cells (T-LAK) cells and HL-60 cells. Rabbit antihuman TNF-R antisera specific for each receptor were employed as probes to selectively stimulate 55- and 75-kDa TNF/LT membrane receptor production. These antisera compete with TNF/LT binding to each specific cell membrane receptor and have been found to bind to specific membrane receptors on various human cell lines in vitro. In the present study, we demonstrated biologic activity for anti-55-kDa TNF-R antiserum. For example, antibodies that bind to the 55-kDa TNF-R caused cytolysis of HeLa and ME-180 human cervical cancer cells and induced proliferation of MRC-5 human fibroblasts. In contrast, however, anti-75-kDa TNF-R antiserum demonstrated no bioactivity in these assays. In addition, no synergy or costimulation was observed when a combination of both anti-55- and anti-75-kDa TNF-R antisera were tested in these assay systems. Anti-55-kDa TNF-R antiserum up-regulated ICAM-1 expression on human HL-60, T-LAK, and THP-1 cells, whereas anti-75-kDa TNF-R antiserum had no effect. Unexpectedly, however, ICAM-1 expression was greatly enhanced by the addition of anti-75-kDa TNF-R to the anti-55-kDa TNF-R containing culture. This enhancing effect was also observed with human T-LAK cells and THP-1 monocytic leukemia cell, in vitro.

© 2015 Macmillan Publishers Limited. All rights reserved.Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates β-adrenergic-induced systemic metabolism and body weight control. Here we show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA),

Background

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry.

Methods and results

A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up.

Conclusion

Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.