Biomedical subjects

Yen-Ta Lu

Publications and source records attributed to Yen-Ta Lu.

12 recordsLinked to original sources

PubMed2006

Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease.

BACKGROUND: Triggering receptor expressed on myeloid cells (TREM)-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses. The aim of this study was to investigate the expression of TREM-1 in pleural effusions of various causes. METHODS: For this cross-sectional, observational study conducted between February and August 2005 in Taiwan, 74 patients with pleural effusions of varying etiology were investigated. Soluble TREM-1 (sTREM-1) was measured in pleural fluid samples, and cells in the fluid were assessed for surface expression of TREM-1. RESULTS: Concentrations of sTREM-1 were significantly higher in infectious and neoplastic pleural effusions (189.1+/-36.7 and 69.9+/-22.8ng/ml, mean+/-sem) than in transudates (10.1+/-5.3ng/ml; P<0.001). Among infectious effusions, the sTREM-1 levels were significantly higher in parapneumonic than in tuberculous effusions (301.8+/-49.8 vs. 38.9+/-17.3ng/ml; P<0.001). TREM-1 was expressed on a portion of the myeloid (CD11b positive) cells in each type of effusion, without significant differences among them (transudative, 34.7%; neoplastic, 36.0%; parapneumonic, 27.7%; tuberculous, 21.2%; P=0.861). Non-myeloid cells expressed very little TREM-1 (transudative, 6.3%; neoplastic, 0.5%; parapneumonic, 1.0%; tuberculous, 0.7%; P=0.192). CONCLUSIONS: sTREM-1 expression in pleural fluids is highest in parapneumonic and neoplastic effusions but low in transudates. In infectious effusions, a high concentration of sTREM-1 may exclude tuberculous pleurisy.

Aged↗

PubMed2006

Silencing of p29 affects DNA damage responses with UV irradiation.

Human p29 is a newly identified nuclear protein whose function is largely undetermined. We found that p29 associated with chromatin, interacted with MCM3, and localized with proliferating cell nuclear antigen foci in the S phase. Silencing of p29 using small interfering RNA duplexes reduced DNA synthesis and increased the expression of p107, a member of the RB family, and of cyclin-dependent kinase inhibitor p21, accompanied with a decreased expression of DNA polymerase alpha. Lethal events consisting of premature chromatin condensation with a reduced Chk1 phosphorylation were observed in p29-depleted cells in response to UV irradiation. Intriguingly, the phosphorylation of ataxia telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated cells. Taken together, these results reveal a novel function of p29 in the regulation of DNA replication checkpoint responses.

Apoptosis↗

PubMed2006

Viral load and outcome in SARS infection: the role of personal protective equipment in the emergency department.

This study was conducted to evaluate the effectiveness of personal protective equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non-HCWs were studied. We compared the initial viral load by nasopharyngeal swabs, clinical progression, and outcome of this cluster. The HCWs had a lower viral load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation, and a higher incidence of intubation and death. Secondary household transmission developed in three of the non-HCWs' families. One month after discharge, non-HCWs had more signs of fibrosis on high resolution computed tomography (HRCT) scan and an impaired pulmonary function test. Although most of the PPE do not confer absolute protection against SARS, it seems that they may lower exposure to the virus, leading to a lower risk of secondary transmission, and be associated with relatively mild disease and a better early outcome.

Adolescent↗

PubMed2006

Preparation and characterization of monoclonal antibody against protein TREM-like transcript-1 (TLT-1).

TREM-like transcript-1 (TLT-1) was initially characterized as the putative inhibitory receptor within the TREM locus on chromosome 6 and was suggested to play a critical role in modulating TREM-associated immunity. Recently, TLT-1 was found not to function as an inhibiting member of the TREM family; however, it may play a significant role in maintaining vascular hemostasis, coagulation, and inflammation at sites of injury through its location in platelets. In this study, we have successfully generated a monoclonal antibody that can be applied to assays, including enzyme-linked immunosorbent assay (ELISA), Western immunoblotting, immunofluorescence, and Fluorescence-Activated Cell Sorter (Becton-Dickinson) (FACS), for the study of TLT-1 functions in physiological and pathological conditions.

Animals↗

PubMed2006

Colonization of severe acute respiratory syndrome-associated coronavirus among health-care workers screened by nasopharyngeal swab.

STUDY OBJECTIVES: To report the efficacy and findings of a large-scale preventive screening program for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using amplification of the virus from a nasopharyngeal swab (NPS) obtained from the health-care workers (HCWs). DESIGN: A prospective observational study. SETTING: A medical center in Taiwan. PARTICIPANTS: Two hundred thirty HCWs. INTERVENTION: NPS examination for the presence of SARS-CoV by two nested reverse transcription-polymerase chain reaction (RT-PCR) assays. MEASUREMENTS AND RESULTS: During the outbreak of severe acute respiratory syndrome (SARS), NPS polymerase chain reaction screening of HCWs for SARS-CoV was performed. SARS-CoV was examined by two nested RT-PCRs and a quantitative RT-PCR. Serum-specific antibodies were assessed by enzyme immunoassay and indirect immunofluorescence. We monitored 230 HCWs, including 217 first-line HCWs and 13 non-first-line HCWs. One hundred ninety first-line HCWs and 13 non-first-line HCWs had negative results in both nested RT-PCR assays. Two first-line HCWs who were positive on both nested RT-PCR assays had SARS. They had 16,900 +/- 7,920 copies (mean +/- SD) of RNA per milliliter in the NPS and had detectable anti-SARS antibodies. The remaining 25 first-line HCWs were negative for the first nested RT-PCR but positive for the second nested RT-PCR. Their corresponding titers were 338 +/- 227 copies of RNA per milliliter; antibodies developed in none of these 25 HCWs. The expression and function of angiotensin-converting enzyme-2 were not different among these HCWs. This study shows that colonization of SARS-CoV occurred in 25 of 217 well-protected first-line HCWs on a SARS-associated service, but they remained seronegative. CONCLUSION: With the second RT-PCR assay more sensitive than the first RT-PCR assay, we are able to show that approximately 11.5% of well-protected HCWs exposed to SARS patients or specimens may have colonization without seroconversion. Only those with significant clinical symptoms or disease would have active immunity. Thus, regular NPS screening for nested RT-PCR assays in conjunction with a daily recording of body temperature in all first-line HCWs may provide an effective way of early detection.

Adult↗

PubMed2005

Comparative study of patients with and without SARS who fulfilled the WHO SARS case definition.

To differentiate severe acute respiratory syndrome (SARS) from non-SARS illness, we retrospectively compared 53 patients with probable SARS and 31 patients with non-SARS who were admitted to Mackay Memorial Hospital from April 27 to June 16, 2003. Fever (> 38 degrees C) was the earliest symptom (50/53 SARS vs. 5/31 non-SARS, p < 0.0001), preceding cough by a mean of 4.5 days. The initial chest X-ray study was normal in 22/53 SARS cases versus 5/31 non-SARS cases. SARS patients with an initially normal chest X-ray study developed infiltrates at a mean of 5 +/- 3.44 days after onset of fever (21/22 SARS vs. 0/5 non-SARS). Rapid radiographic progression of unifocal involvement to multifocal infiltrates was seen in 22 of 24 SARS vs. 0 of 26 non-SARS patients (p < 0.0001). Pleural effusion was not present in any SARS patients but was seen in 6 of 26 non-SARS cases (p < 0.0001). Initial lymphopenia, thrombocytopenia, and elevated lactate dehydrogenase were all more common in SARS than non-SARS (p < 0.0001). They may help differentiate SARS from non-SARS if a reliable and rapid diagnostic test is not available.

Adult↗

PubMed2005

Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers.

STUDY OBJECTIVES: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS). DESIGN: A retrospective observational study. SETTING: Two medical centers in Taiwan. PATIENTS: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin. MEASUREMENTS AND RESULTS: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001). CONCLUSIONS: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Adult↗

PubMed2005

Neutralizing antibody response and SARS severity.

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

Adult↗

PubMed2004

Antibody detection of SARS-CoV spike and nucleocapsid protein.

Early detection and identification of SARS-CoV-infected patients and actions to prevent transmission are absolutely critical to prevent another SARS outbreak. Antibodies that specifically recognize the SARS-CoV spike and nucleocapsid proteins may provide a rapid screening method to allow accurate identification and isolation of patients with the virus early in their infection. For this reason, we raised peptide-induced polyclonal antibodies against SARS-CoV spike protein and polyclonal antibodies against SARS-CoV nucleocapsid protein using 6x His nucleocapsid recombinant protein. Western blot analysis and immunofluorescent staining showed that these antibodies specifically recognized SARS-CoV.

Amino Acid Sequence↗

PubMed2004

Clinical and laboratory features of severe acute respiratory syndrome vis-a-vis onset of fever.

STUDY OBJECTIVES: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. DESIGN: Retrospective observational study. SETTING: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. PATIENTS: Fifty-three patients with SARS seen between April 27 and June 16, 2003. RESULTS: Fever (ie, temperature > 38 degrees C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (+/- SD) time of 4.5 +/- 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 +/- 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 +/- 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 +/- 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. CONCLUSIONS: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.

Adolescent↗

PubMed2002

Time course of lung ischemia-reperfusion-induced ICAM-1 expression and its role in ischemia-reperfusion lung injury.

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is an important mechanism underlying ischemia-reperfusion (I/R) induced neutrophil activation and tissue injury in other organs. However, I/R of the lungs has not been shown to upregulate ICAM-1 expression. We determined the time course profile of lung I/R-induced ICAM-1 expression and assessed the role of ICAM-1 in mediating neutrophil sequestration, transmigration, and I/R injury in the isolated blood-perfused rat lungs. I/R had a biphasic effect on ICAM-1 expression, an early downregulation and a late-phase upregulation. Superoxide dismutase and neutrophil depletion prevented the early ICAM-1 downregulation. The late-phase ICAM-1 upregulation coincided with the I/R-induced increase in pulmonary microvascular leakage index. ICAM-1 monoclonal antibody (MAb) reversed the I/R-induced increase in pulmonary microvascular leakage index, with control antibody being ineffective. Neither I/R nor ICAM-1 MAb affected lung MPO activity and circulating neutrophil count. Lung I/R significantly increased bronchoalveolar lavage fluid neutrophil count and the GSSG-to-(GSSG+GSH) ratio. ICAM-1 MAb blocked the I/R-induced increase in GSSG-to-(GSSG+GSH) ratio but had no effect on bronchoalveolar lavage fluid neutrophil count. Our results demonstrated that lung I/R up- and downregulates ICAM-1 expression depending on the duration of reperfusion. ICAM-1 upregulation is an important mechanism of I/R-induced pulmonary endothelial injury.

Animals↗

PubMed2002

GTPCH is not a rate-limiting factor for hemorrhagic shock-induced hepatic nitric oxide biosynthesis.

BACKGROUND: Hemorrhagic shock upregulates inducible nitric oxide (NO) synthase (iNOS) expression and the resultant NO overproduction. Liver is one of the major organs that is responsible for increased NO production after trauma-hemorrhage and resuscitation. Guanosine triphosphate cyclohydrolase I (GTPCH) is the rate-limiting enzyme for the synthesis of tetrahydrobiopterin (BH4), a necessary co-factor for iNOS activity. Very little is known about the effects of hemorrhagic shock on hepatic GTPCH expression. METHODS: Fifteen male Sprague-Dawley rats were randomly assigned to one of three groups, i.e. a sham instrumented (Sham) group, a sustained hemorrhagic shock (HS) group, and a hemorrhagic shock with resuscitation (HS/RES) group (n = 5 in each group). Controlled hemorrhagic shock was induced and the mean arterial pressure (MAP) was kept between 40-45 mmHg for sixty minutes in both HS and HS/RES groups. Then resuscitation with infusion of shed autologous blood and normal saline was performed in HS/RES group. Microdialysis probes were put in the liver and the right atrium for collection of serial samples. NO concentrations in dialysate samples were measured using chemiluminescence. Hepatic iNOS and GTPCH mRNA concentrations were analyzed using semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Hemorrhagic shock induced both the hepatic and circulating NO biosynthesis as well as hepatic iNOS mRNA expression. Resuscitation with shed blood/normal saline normalized this upregulation. However, no difference was found in mean hepatic GTPCH mRNA concentrations between groups in this experiment. CONCLUSIONS: We provide the evidence that hemorrhagic shock-induced NO biosynthesis involves upregulation of iNOS transcription in liver tissue and GTPCH transcription is unaffected by either hemorrhagic shock or resuscitation. Furthermore, microdialysis is an ideal technique for serial sampling and that events can be followed.

Animals↗