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Biomedical subjects

Kang Liu

Publications and source records attributed to Kang Liu.

At least 19 recordsLinked to original sources

Differential antigen processing by dendritic cell subsets in vivo.

Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.

Amino Acid Sequence↗

Regulation of TopBP1 oligomerization by Akt/PKB for cell survival.

Regulation of E2F1-mediated apoptosis is essential for proper cellular growth. This control requires TopBP1, a BRCT (BRCA1 carboxyl-terminal) domain-containing protein, which interacts with E2F1 but not other E2Fs and represses its proapoptotic activity. We now show that the regulation of E2F1 by TopBP1 involves the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway, and is independent of pocket proteins. Akt phosphorylates TopBP1 in vitro and in vivo. Phosphorylation by Akt induces oligomerization of TopBP1 through its seventh and eighth BRCT domains. The Akt-dependent oligomerization is crucial for TopBP1 to interact with and repress E2F1. Akt phosphorylation is also required for interaction between TopBP1 and Miz1 or HPV16 E2, and repression of Miz1 transcriptional activity, suggesting a general role for TopBP1 oligomerization in the control of transcription factors. Together, this study defines a novel pathway involving PI3K-Akt-TopBP1 for specific control of E2F1 apoptosis, in parallel with cyclin-Cdk-Rb for general control of E2F activities.

Animals↗

Transient cortical blindness after resuscitation in a child having central venous catheterization under general anesthesia.

We describe a case of chronic renal failure developing life-threatening cardiovascular collapse during the insertion of central venous catheter for hemodialysis under general anesthesia in a 7-year-old boy. With timely resuscitation, he regained his vital signs within 20 min. However, after admission to the pediatric intensive care unit, visual impairment and four limb weakness were detected on the first postoperative day. Fortunately, symptoms resolved completely with close observation, psychological support and conservative management within 72 h without sequelae.

Anesthesia, General↗

The efficacy of thoracic epidural neostigmine infusion after thoracotomy.

Few anesthesia studies have explored perioperative continuous epidural infusion of neostigmine. We examined such a regimen in thoracotomy patients. Ninety patients were randomized to one of three groups in this double-blind trial. Before anesthesia induction, an epidural catheter was inserted in all patients at T5-8 levels under local anesthesia. Pre-neo patients received bolus 500-microg epidural neostigmine before anesthesia induction followed by infusion of 125 microg/h until the end of surgery. Post-neo patients received epidural saline during the same time periods plus bolus 500-microg epidural neostigmine at end of surgery. Patients in the control group received saline placebo during all three periods. Patients in the neostigmine groups postoperatively received patient-controlled epidural analgesia with morphine 0.02 mg/mL, bupivacaine 0.08 mg/mL, and neostigmine 7 microg/mL. Control patient-controlled epidural analgesia excluded neostigmine. Data were recorded for 6 postoperative days. Daily patient-controlled epidural analgesia consumption (mL) for Pre-neo patients was significantly less than that of post-neo and control group patients for postoperative days 1-6 (at least 10% and 16% less, respectively; P < 0.05). There was a modest decrease in pain intensity on postoperative days 3-6 for pre-neo patients versus other groups (P < 0.05). These results suggest that continuous thoracic epidural neostigmine started before anesthesia provided preemptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia for these patients without increasing the incidence of adverse effects.

Adult↗

Intramyometrial injection of vasopressin causes bradycardia and cardiac arrest--report of two cases.

Vasopressin has been documented to effectively reduce blood loss in gynecologic practice. However, local infiltration of vasopressin may cause lethal cardiopulmonary complications in spite of rarity of reported cases. Severe bradycardia and cardiac arrest were encountered after intramyometrial injection of vasopressin in our two healthy patients undergoing open uterine myomectomy. We herewith discuss the associated complications and the anesthetic considerations.

Adult↗

Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells.

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex-negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid alpha-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic alphaCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted >2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance.

Adjuvants, Immunologic↗

Morphine sparing with droperidol in patient-controlled analgesia.

STUDY OBJECTIVE: To determine if droperidol has a morphine-sparing effect when coadministered with morphine via patient-controlled analgesia (PCA) for postoperative pain management. DESIGN: A randomized, double-blind clinical study. SETTING: Department of Anesthesiology, Kaohsiung Veterans General Hospital, Taiwan. PATIENTS: One hundred seventy-nine American Society of Anesthesiologists physical status 1 and 2 female patients undergoing abdominal hysterectomy. INTERVENTIONS: At the end of surgery, patients in the droperidol group received PCA, with the device programmed to deliver a bolus dose of 1 mg morphine and 50 mug droperidol on demand. Patients in the control group received 1 mg morphine on demand. For both groups, PCA lockout was 5 minutes between boluses, with a 4-hour morphine limit of 30 mg. MEASUREMENTS AND MAIN RESULTS: Pain intensity at rest or on movement and relative sedation score were evaluated and recorded at 6, 12, 24, 48, and 72 hours after surgery. Related side effects were also evaluated and recorded on postoperative days 1, 2, and 3. Morphine use was significantly lower for the droperidol group than the control group during the postoperative 72-hour period (33.9 +/- 9.8 and 54.9 +/- 12.1 mg, respectively), with significantly decreased pain intensity levels for the former relative to the latter at 48 hours (pain intensity on movement: 3.9 +/- 1.2 vs 4.3 +/- 0.9, respectively; P = .049) and 72 hours (pain intensity on movement: 3.0 +/- 1.1 vs 3.6 +/- 0.5, respectively; P = .003; pain intensity at rest: 1.3 +/- 1.0 vs 1.6 +/- 0.7, respectively; P = .033) subsequent to surgery. Control subjects demonstrated a greater frequency of postoperative nausea and vomiting than did their droperidol counterparts on postoperative day 1. CONCLUSION: Coadministration of 50 mug droperidol and 1 mg morphine on demand via PCA provides a morphine-sparing effect and reduces the frequency of postoperative nausea and vomiting.

Adult↗

Bolus injection of adenosine before cardioplegic induction improves postischemic global function in coronary artery bypass grafting.

BACKGROUND: Alternative strategies to optimize preexisting cardioplegia during myocardial preservation are currently under extensive investigation. Adenosine, an endogenous purine nucleoside, has been approved for its cardioprotective potential against ischemic-reperfusion injury. Yet, little information is available with respect to the use of adenosine for cardioplegic induction in humans. The purpose of the present study was, therefore, to assess the clinical relevance of intra-aortic administration of adenosine following aortic cross-clamping with respect to the exertion of additional protection in routine coronary artery bypass surgery. METHODS: Thirty patients to receive elective coronary artery bypass grafting under cardiopulmonary bypass (CPB) were prospectively randomized into two study groups. Immediate after aortic cross-clamping and just before the application of modified St. Thomas cardioplegic (20 mL/kg), adenosine solution (250 microg/kg) was injected into the aortic root in the study group (n = 15), while the same amount of normal saline injection was administered in the control group (n = 15). Anesthesia was carried out in all patients in a similar fashion, and all the surgeries were performed by the same team. Homodynamic change, cardiac enzyme assay, and post-bypass inotropic supplementation were recorded throughout the study period to evaluate the extent of myocardial ischemic injury. RESULTS: The mean time to asystole after aortic cross-clamping was significantly shorter for the adenosine group compared with the control group (8.1 +/- 5.9 vs. 79.0 +/- 35.3 sec, respectively; P< 0.01). To compare with the baseline value, the mean cardiac index immediately post CPB and 24 hours postoperatively was increased significantly for the adenosine group (from 2.1 +/- 0.6 to 2.6 +/- 0.6 and 3.2 +/- 0.6 L/min/m2, respectively; P < 0.05), as contrasted with the control group (from 2.3 +/- 0.5 to 2.0 +/- 0.4 and 2.5 +/- 0.4 L/min/m2). Further, the requirement for inotropic support after CPB and postoperative troponin I release were significantly less in the adenosine group. There appeared no adverse effects associated with adenosine administration. CONCLUSIONS: Immediate administration of 250 microg/kg adenosine via the aortic root following aortic cross-clamping could optimize the myocardial protective effect of conventional cardioplegia, quicken cardiac standstill, and offer better postoperative myocardial performance after CPB.

Adenosine↗

Bilateral severe bronchial obstruction after metallic tracheal stent insertion for tracheal stenosis--a case report.

Metallic wire expandable stents are increasingly used to alleviate tracheal obstruction due to malignancies. Patients usually tolerate these stents well and benefit from good to excellent palliation of their symptoms. Nevertheless, some miserable complications have also come to our notice. We report here an unfortunate case in whom severe bilateral main bronchial obstruction occurred immediately after the insertion of a Wall-stent over the tracheal stenosis.

Adult↗

Characteristics of PM2.5 in rural areas of southern Jiangsu Province, China.

To understand pollution level and possible sources of atmospheric fine particulates in rural areas of southern Jiangsu Province of China, samples of PM2.5 were collected and analyzed in Xueyan Town and Taihu Lake Station over three seasons from July 2002 to January 2003. The mass concentrations of PM2.5 and 14 principal component elements were obtained. The results showed that pollution of PM2.5 was serious and the concentration levels of S, Zn, Pb and As were similar to city. There are different seasonal distribution laws of pollutant elements in PM2.5 between two sampling sites, probably due to contribution of local sources, medium or long distance transportation of fine particulates and complicated meteorological conditions. The enrichment levels of S, Zn, Pb, As, K were high, reflecting the influence of anthropogenic activities. Particularly enrichment level of S was much higher in summer, which was probably related to meteorological condition. The result of principal components analysis showed major sources of PM2.5 included crustal resuspension, coal burning, metal processing industry or waste incineration, vehicular emission, which suggests anthropogenic activities is of important influence on PM2.5 in rural areas of southern Jiangsu Province.

Air Pollutants↗

A role for 14-3-3 tau in E2F1 stabilization and DNA damage-induced apoptosis.

Genotoxic stress triggers apoptosis through multiple signaling pathways. Recent studies have demonstrated a specific induction of E2F1 accumulation and a role for E2F1 in apoptosis upon DNA damage. Induction of E2F1 is mediated by phosphorylation events that are dependent on DNA damage-responsive protein kinases, such as ATM. How ATM phosphorylation leads to E2F1 stabilization is unknown. We now show that 14-3-3 tau, a phosphoserine-binding protein, mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. Depletion of 14-3-3 tau or E2F1, but not E2F2 or E2F3, blocks adriamycin-induced apoptosis. 14-3-3 tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage. Together, these data demonstrate a novel function for 14-3-3 tau in the regulation of E2F1 protein stability and apoptosis during DNA damage.

14-3-3 Proteins↗

The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation.

Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied alpha-galactosylceramide. This glycolipid activates innate Valpha14(+) natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40(-/-) and CD40L(-/-) mice did not elicit CD4(+) and CD8(+) T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-alpha up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40(-/-) mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation ("signal one") and costimulation ("signal two") to generate functioning CD4(+) T helper cell 1 and CD8(+) cytolytic T lymphocytes.

Animals↗

TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival.

TopBP1 (DNA topoisomerase IIbeta binding protein I) contains multiple BRCT domains and is involved in replication and the DNA damage checkpoint. Through its BRCT domain, TopBP1 interacts with and represses exclusively E2F1 but not other E2F factors. This regulation of E2F1 transcriptional activity is mediated by a pRb-independent, but Brg1/Brm-dependent mechanism. TopBP1 recruits Brg1/Brm, a central component of the SWI/SNF chromatin-remodeling complex, to E2F1-responsive promoters and represses the activities of E2F1, but not E2F2 or E2F3. This regulation is crucial in the control of E2F1-dependent apoptosis during normal cell growth and DNA damage. Interestingly, TopBP1 is induced by E2F and interacts with E2F1 during G1/S transition. Thus, TopBP1 functions as a critical modulator and serves as a negative feedback regulator of E2F1 by inhibiting E2F1-dependent apoptosis during G1/S transition as well as DNA damage to promote cell survival.

Apoptosis↗

Dendritic cell function in vivo during the steady state: a role in peripheral tolerance.

The avoidance of autoimmunity requires mechanisms to actively silence or tolerize self reactive T cells in the periphery. During infection, dendritic cells are not only capturing microbial antigens, but also are processing self antigens from dying cells as well as innocuous environmental proteins. Since the dendritic cells are maturing in response to microbial and other stimuli, peptides will be presented from both noxious and innocuous antigens. Therefore it would be valuable to have mechanisms whereby dendritic cells, prior to infection, establish tolerance to those self and environmental antigens that can be processed upon pathogen encounter. In the steady state, prior to acute infection and inflammation, dendritic cells are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. These immature cells are not inactive, however. They continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature dendritic in vivo silence T cells either by deleting them or by expanding regulatory T cells. In this way, it is proposed that the immune system overcomes at least some of the risk of developing autoimmunity and chronic inflammation. It is proposed that dendritic cells play a major role in defining immunologic self, not only centrally in the thymus but also in the periphery.

Animals↗

Regulation of E2F1 by BRCT domain-containing protein TopBP1.

The E2F transcription factor integrates cellular signals and coordinates cell cycle progression. Our prior studies demonstrated selective induction and stabilization of E2F1 through ATM-dependent phosphorylation in response to DNA damage. Here we report that DNA topoisomerase IIbeta binding protein 1 (TopBP1) regulates E2F1 during DNA damage. TopBP1 contains eight BRCT (BRCA1 carboxyl-terminal) motifs and upon DNA damage is recruited to stalled replication forks, where it participates in a DNA damage checkpoint. Here we demonstrated an interaction between TopBP1 and E2F1. The interaction depended on the amino terminus of E2F1 and the sixth BRCT domain of TopBP1. It was specific to E2F1 and was not observed in E2F2, E2F3, or E2F4. This interaction was induced by DNA damage and phosphorylation of E2F1 by ATM. Through this interaction, TopBP1 repressed multiple activities of E2F1, including transcriptional activity, induction of S-phase entry, and apoptosis. Furthermore, TopBP1 relocalized E2F1 from diffuse nuclear distribution to discrete punctate nuclear foci, where E2F1 colocalized with TopBP1 and BRCA1. Thus, the specific interaction between TopBP1 and E2F1 during DNA damage inhibits the known E2F1 activities but recruits E2F1 to a BRCA1-containing repair complex, suggesting a direct role of E2F1 in DNA damage checkpoint/repair at stalled replication forks.

Apoptosis↗

Anesthetic management of laparoscopic surgery in a patient with a ventriculoperitoneal shunt.

With advanced knowledge of management of hydrocephalus, patients with ventriculoperitoneal shunts are expected to enjoy a longer lifetime. Developments in both instrumentations and surgical techniques have led to increasing popularity of laparoscopic surgery in many surgical subspecialties. Therefore, it is not a surprising event that a patient with a ventriculoperitoneal shunt is scheduled for a laparoscopic surgery under anesthesia. Until now, there is no uniformized protocol for anesthetic management of a patient with a ventriculoperitoneal shunt undergoing laparoscopic surgery. Increased intracranial pressure may occur intraoperatively and be a major concern. We report here our experience in anesthetic management of such a patient and discuss the anesthetic considerations and the potential complications.

Aged↗

Inferior vena cava tear during posterior spinal fusion surgery.

Inferior vena cava tear is a rare but potentially lethal event associated with spinal surgery. Early recognition and repair are mandatory to minimize morbidity and mortality. Here we report a case of inferior vena cava tear which occurred during posterior spinal fusion surgery. Without marked bleeding from the surgical field, the patient was suddenly seized with a profound shock. Abdominal distension was found after resumption of the supine position from prone. Emergent exploratory laparotomy disclosed inferior vena cava tear. After repairing of the torn vessel, the patient was transferred to ICU. Unfortunately, patient expired two weeks later due to multiple-organ failure.

Female↗