National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Asthma & T cell. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Glucocorticoid Therapy in Asthma

Abstract: Glucocorticoids (GCs) are the most effective therapy we have for the treatment of asthma. Systemically administered GCs are first-line agents for acute severe asthma, whereas topical (i.e., inhaled) GCs are first line agents for the long-term management of all patients with persistent asthma. In the treatment of acute asthma exacerbations, early institution of systemic GCs can prevent further worsening of symptoms, reduce emergency room visits, and hospitalizations. Inhaled GCs are the recommended controller class of medications for all patients with persistent asthma, including children. They are the most effective class of agents in reducing symptoms, improving lung function, and decreasing bronchial hyperresponsiveness, in addition to reducing asthma morbidity and mortality. Long-term administration of oral GCs is associated with multiple adverse effects including adrenal insufficiency, weight gain, increased skin fragility, myopathy, osteoporosis, cataracts, and mood changes. Thus, in patients with chronic severe asthma who require regular systemic GC therapy, all other treatments should be maximized, and the lowest dose sufficient for control should be established through regular monitoring visits. As with oral GC therapy, high-dose inhaled GC therapy can result in systemic adverse effects. Several studies have shown that low-dose inhaled GC therapy, even when administered long term, is unlikely to result in any clinically meaningful adverse effects. By using the lowest possible effective GC dose, as well as maximizing other therapeutic modalities, adverse systemic effects from GCs can be greatly minimized.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

Abstract: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

MUC18 regulates IL-13-mediated airway inflammatory response

Abstract: To evaluate the effects of MUC18 on IL-13-mediated airway inflammatory responses in human airway epithelial cells and in mice. Primary normal human tracheobronchial epithelial (HTBE) cells, wild-type (WT) and Muc18 knockout (KO) mice, and mouse tracheal epithelial cells (mTECs) were utilized. Cultured HTBE cells treated with MUC18 siRNA or MUC18 expressing lentivirus were incubated with IL-13 (10 ng/mL) for 24 h. Mice were intranasally instilled with 500 ng of IL-13 for 3 days. mTECs were treated with IL-13 (10 ng/mL) for 3 days. PCR was used to measure mRNA expression. Western Blot and ELISAs were used to quantify protein expression. Cytospins of bronchoalveolar lavage (BAL) cells were used to obtain leukocyte differentials. MUC18 siRNA reduced IL-13-mediated eotaxin-3 (183 ± 44 vs. 380 ± 59 pg/mL, p < 0.05), while MUC18 overexpression increased IL-13-mediated eotaxin-3 (95 ± 3 vs. 58 ± 3 pg/mL, p < 0.05) in HTBE cells. IL-13-treated Muc18 KO mice had a lower percentage of neutrophils in BAL than WT mice (25 ± 3 vs. 35 ± 3%, p = 0.0565). These results implicate MUC18 as a potential enhancer of airway inflammation in a type 2 cytokine (e.g., IL-13) milieu.

Some properties of T cells in animals.

Abstract: T cells in animals have several unexpected properties. The work described here concerns two of these properties. The first property to be discussed concerns the fact that T cells divide in the apparent absence of antigen when transferred to T cell deficient mice. The second investigates the finding that memory T cells contain very large amounts of mRNA for certain chemokines. These two phenomena will be discussed in separate sections below.

Sox4 drives intestinal secretory differentiation toward tuft and enteroendocrine fates

Abstract: Intestinal stem cells (ISCs) undergo differentiation following reduction of Notch signaling and activation of Atoh1, a master regulator of secretory fate. However, recent evidence suggests that rare tuft cells may differentiate via alternative mechanisms. Here, we examine the role of Sox4 in ISC fate decisions. Loss of Sox4 results in disruption of ISC function and secretory differentiation, including decreased numbers of enteroendocrine and tuft cells. Sox4 is activated following reduction of Notch signaling and required for response to signals that induce tuft cell hyperplasia, including IL-13 and parasitic helminth infection. Subsets of Sox4+ progenitors are transcriptomically similar to both actively dividing and mature tuft cells, and dissimilar from other secretory progenitors expressing Atoh1. Our data suggest that Sox4 drives an alternative, Notch-repressed secretory differentiation pathway independently of Atoh1, and challenge the status of Atoh1 as the sole initiator of secretory fate in the intestine.