Biomedical subjects

Chia-Lin Hsu

Publications and source records attributed to Chia-Lin Hsu.

7 recordsLinked to original sources

PubMed2006

Antagonistic effect of CCAAT enhancer-binding protein-alpha and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors.

Lymphoid lineage-committed progenitors, such as common lymphoid progenitors (CLPs), maintain a latent myeloid differentiation potential, which can be initiated by stimulation through exogenously expressed cytokine receptors, including IL-2 receptors. Here we show that the transcription factor CCAAT enhancer-binding protein-alpha (C/EBPalpha) is promptly up-regulated in CLPs upon ectopic IL-2 stimulation. Enforced C/EBPalpha expression is sufficient to initiate myeloid differentiation from CLPs, as well as from proT and proB cells, even though proB cells do not give rise to myeloid cells after ectopic IL-2 stimulation. Expression of Pax5, a B lymphoid-affiliated transcription factor, is completely suppressed by enforced C/EBPalpha but not by ectopic IL-2 stimulation in proB cells. Introduction of Pax5 blocks ectopic IL-2 receptor-mediated myeloid lineage conversion in CLPs. These data suggest that C/EBPalpha is a proximal target of cytokine-induced lineage conversion in lymphoid progenitors. Furthermore, complete loss of Pax5 expression triggered by up-regulation of C/EBPalpha is a critical event for lineage conversion from lymphoid to myeloid lineage in CLPs and proB cells.

Animals↗

PubMed2005

IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF.

Cytokine receptor signals have been suggested to stimulate cell differentiation during hemato/lymphopoiesis. Such action, however, has not been clearly demonstrated. Here, we show that adult B cell development in IL-7(-/-) and IL-7R alpha(2/-) mice is arrested at the pre-pro-B cell stage due to insufficient expression of the B cell-specific transcription factor EBF and its target genes, which form a transcription factor network in determining B lineage specification. EBF expression is restored in IL-7(-/-) pre-pro-B cells upon IL-7 stimulation or in IL-7R alpha(-/-) pre-pro-B cells by activation of STAT5, a major signaling molecule downstream of the IL-7R signaling pathway. Furthermore, enforced EBF expression partially rescues B cell development in IL-7R alpha(-/-) mice. Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre-pro-B to further maturational stages.

Animals↗

PubMed2005

Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an archetypal autoimmune disease, involving multiple organ systems with varying course and prognosis. However, there is a paucity of clinical data regarding prognostic factors in SLE patients admitted to the intensive care unit (ICU). METHODS: From January 1992 to December 2000, all patients admitted to the ICU with a diagnosis of SLE were included. Patients were excluded if the diagnosis of SLE was established at or after ICU admission. A multivariate logistic regression model was applied using Acute Physiology and Chronic Health Evaluation II scores and variables that were at least moderately associated (P < 0.2) with survival in the univariate analysis. RESULTS: A total of 51 patients meeting the criteria were included. The mortality rate was 47%. The most common cause of admission was pneumonia with acute respiratory distress syndrome. Multivariate logistic regression analysis showed that intracranial haemorrhage occurring while the patient was in the ICU (relative risk = 18.68), complicating gastrointestinal bleeding (relative risk = 6.97) and concurrent septic shock (relative risk = 77.06) were associated with greater risk of dying, whereas causes of ICU admission and Acute Physiology and Chronic Health Evaluation II score were not significantly associated with death. CONCLUSION: The mortality rate in critically ill SLE patients was high. Gastrointestinal bleeding, intracranial haemorrhage and septic shock were significant prognostic factors in SLE patients admitted to the ICU.

APACHE↗

PubMed2005

Negative expiratory pressure in the assessment of bronchodilator response: comparison of spirometry and the interrupter method.

BACKGROUND AND PURPOSE: The negative expiratory pressure (NEP) method offers a simple and rapid assessment of expiratory flow limitation (EFL) during tidal respiration. This study compared the value of NEP in the assessment of the bronchodilator test (BDT) with those of spirometry and the interrupter method. METHODS: Thirty two patients referred to the lung function laboratory for BDT were investigated. All patients underwent spirometry, interrupter airway resistance (Rint) and NEP measurements in the sitting position before and after inhalation of 500 microg of terbutaline. A positive BDT was defined as an increase in the forced expiratory volume in 1 second (FEV1) of > or = 12%. RESULTS: The ratio of FEV1 to forced vital capacity (FVC) was less than 70% in 21 (65.6%) patients, but EFL as demonstrated by NEP (EFL-N) was present in only 10 patients (31.3%). The baseline EFL-N was only weakly correlated with FEV1 (r = -0.36, p = 0.04), but not with Rint or FEV1/FVC. Among the 14 patients with positive BDT results, the change in FEV1 was correlated with the change in Rint (r = -0.69, p < 0.01), but not with the change in EFL-N. CONCLUSIONS: These data suggest that, compared with spirometry and the interrupter method, NEP applied in the sitting position is not sensitive in the assessment of bronchodilator response in patients with obstructive airway disorders.

Aged↗

PubMed2004

Timing of tracheostomy as a determinant of weaning success in critically ill patients: a retrospective study.

INTRODUCTION: Tracheostomy is frequently performed in critically ill patients for prolonged intubation. However, the optimal timing of tracheostomy, and its impact on weaning from mechanical ventilation and outcomes in critically ill patients who require mechanical ventilation remain controversial. METHODS: The medical records of patients who underwent tracheostomy in the medical intensive care unit (ICU) of a tertiary medical centre from July 1998 to June 2001 were reviewed. Clinical characteristics, length of stay in the ICU, rates of post-tracheostomy pneumonia, weaning from mechanical ventilation and mortality rates were analyzed. RESULTS: A total of 163 patients (93 men and 70 women) were included; their mean age was 70 years. Patients were classified into two groups: successful weaning (n = 78) and failure to wean (n = 85). Shorter intubation periods (P = 0.02), length of ICU stay (P = 0.001) and post-tracheostomy ICU stay (P = 0.005) were noted in patients in the successful weaning group. Patients who underwent tracheostomy more than 3 weeks after intubation had higher ICU mortality rates and rates of weaning failure. The length of intubation correlated with the length of ICU stay in the successful weaning group (r = 0.70; P < 0.001). Multivariate analysis revealed that tracheostomy after 3 weeks of intubation, poor oxygenation before tracheostomy (arterial oxygen tension/fractional inspired oxygen ratio <250) and occurrence of nosocomial pneumonia after tracheostomy were independent predictors of weaning failure. CONCLUSION: The study suggests that tracheostomy after 21 days of intubation is associated with a higher rate of failure to wean from mechanical ventilation, longer ICU stay and higher ICU mortality.

APACHE↗

PubMed2003

The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens.

Microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. However, ECM components can also serve as an integral part of the innate immunity. Mice lacking expression of mindin (spondin 2), a highly conserved ECM protein, have an impaired ability to clear bacterial infection, and mindin-deficient macrophages show defective responses to a broad spectrum of microbial stimuli. Moreover, mindin binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Thus, mindin is essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens.

Amino Acid Sequence↗

PubMed2003

Diagnostic value of negative expiratory pressure for airway hyperreactivity.

STUDY OBJECTIVES: To examine the value of negative expiratory pressure (NEP) in the assessment of methacholine bronchoprovocation testing (BPT). DESIGN: Prospective, observational study. SETTING: Pulmonary function laboratory in a university hospital. PARTICIPANTS: Fifty-nine patients with chronic cough referred from outpatient clinics for methacholine BPT. METHODS: Each subject inhaled successive doubling concentrations of methacholine (from 0.049 to 25 mg/mL) until the FEV(1) decreased for > 20% or the maximum concentration of methacholine was inhaled. NEP was measured in the sitting position during tidal breathing before and after methacholine BPT. The FEV(1) and forced oscillation airway resistance (Rrs) and interrupter airway resistance (Rint) were also obtained simultaneously. A positive BPT result was defined as a fall in FEV(1) > or = 20%. RESULT: At baseline, only five patients had expiratory flow limitation as demonstrated by NEP (EFL-N). There were 39 patients with positive BPT results, and the other 20 patients had negative results. Among the BPT-positive patients, only 13 patients (33.3%) had EFL-N after methacholine challenge. The sensitivity indexes (absolute change/SD) of FEV(1), NEP, Rrs, and Rint were 16.0 +/- 9.6%, 1.1 +/- 1.6%, 3.8 +/- 4.5%, and 5.89 +/- 4.4% (mean +/- SD), respectively. The percentage changes in FEV(1) in BPT-positive patients correlated with the percentage changes in Rrs (r = 0.419, p = 0.008) and only marginally with the percentage changes in Rint (r = 0.307, p = 0.058), but not with the changes in EFL-N (r = 0.048, p = 0.77). CONCLUSION: These data suggest that NEP at sitting position is not sensitive in the assessment of methacholine bronchoprovocation as compared to FEV(1) and airway resistance measurements.

Adult↗