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1.
Opt Express ; 28(19): 27316-27323, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32988028

ABSTRACT

Investigation of photodarkening (PD) in Yb-doped fibers tandem-pumped at 1018 nm is reported. For a homemade Yb-doped aluminosilicate double-clad fiber (YADF), the transmitted power of a 633 nm probe beam is reduced by 2.4% over 2 hours for the tandem pumping configuration at 1018 nm, which is significantly smaller than 33.3% for a laser diode (LD) pumping at 976 nm. A tandem-pumped Yb fiber amplifier also shows a much smaller decrease in the amplified output power over time than a LD-pumped Yb fiber amplifier. Based on fluorescence spectra of the YADF, we can not only associate PD of the YADF to intrinsic oxygen deficiency centers or Tm3+ impurities but also confirm the impact of the excited Yb3+ ion density on PD. The benefits of the tandem pumping in a high-power Yb fiber laser system will be discussed.

2.
Article in English | MEDLINE | ID: mdl-27726224

ABSTRACT

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.


Subject(s)
Patient Navigation/methods , Perioperative Care/methods , Thyroid Neoplasms/surgery , Adolescent , Adult , Aged , Case-Control Studies , Continuity of Patient Care , Female , Humans , Male , Middle Aged , Needs Assessment , Patient Satisfaction , Program Evaluation , Young Adult
3.
Anaesthesia ; 71(9): 1070-6, 2016 09.
Article in English | MEDLINE | ID: mdl-27440234

ABSTRACT

In this retrospective case-control study, we evaluated peri-operative dental injury risk factors following tracheal intubation. Ninety-four of 290,415 patients experienced dental injury following tracheal intubation over a 10-y period. A control group was matched for surgery type and intubating anaesthetist. The incidence of dental injury was 0.03%. Univariate analysis revealed that previous and current difficult intubation, male gender, hepatitis, neurological disease, anticonvulsant use, pre-existing poor dentition and the use of airway devices (other than a laryngoscope) were associated with dental injury. Multivariate analysis revealed that predictors of dental injury were: history of hepatitis, odds ratio (95% CI) 10.1 (1.02-100.3); poor dentition, 8.8 (3.9-20.0); alternative airway device use, 3.1 (1.2-8.0); and intubation difficulty, 3.7 (1.0-13.3). As well as confirming previously reported risk factors for dental injury during tracheal intubation, this study also suggests hepatitis and the use of alternative airway devices as additional risk factors.


Subject(s)
Intubation, Intratracheal/adverse effects , Tooth Injuries/etiology , Adult , Case-Control Studies , Equipment Design , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Sex Factors
4.
Acta Anaesthesiol Scand ; 59(8): 1068-75, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25903742

ABSTRACT

BACKGROUND: Nefopam has been used as an adjuvant to opioid analgesia after operation. We investigated the efficacy of nefopam as an adjunct to fentanyl-based intravenous patient-controlled analgesia (IV PCA) on post-operative pain relief in patients undergoing renal transplantation. METHODS: Ninety-eight patients undergoing elective renal transplantation were randomised into two groups: nefopam or control groups. The former received nefopam (160 mg in 200 ml at a rate of 4 ml/h) whereas the latter received normal saline during the first 48 h after reperfusion of grafted kidney. Pain intensity scores, cumulative dose of fentanyl, and the incidence of adverse events were assessed at 1, 6, 12, 24, and 48 h post-operatively. Serum creatinine and estimated glomerular filtration rate were evaluated on post-operative days 1, 2, 4, and 7. RESULTS: The cumulative fentanyl consumption during the first 48 h after operation was 19% less in the nefopam group than that in the control group (1005 ± 344 µg vs. 1246 ± 486 µg, mean ± SD; P = 0.006). Pain intensity scores at rest and on coughing were significantly lower in the nefopam group throughout the first 12 and 48 h after operation, respectively. Adverse events and early graft function were comparable between the groups, except a significantly lower incidence of drowsiness observed in the nefopam group (4% vs. 21%, P = 0.027). CONCLUSION: In combination with fentanyl PCA, nefopam reduced post-operative fentanyl consumption with superior analgesia after renal transplantation.


Subject(s)
Analgesia, Patient-Controlled/methods , Analgesics, Non-Narcotic/therapeutic use , Kidney Transplantation , Nefopam/therapeutic use , Pain, Postoperative/drug therapy , Administration, Intravenous , Adult , Analgesics, Non-Narcotic/administration & dosage , Female , Humans , Male , Middle Aged , Nefopam/administration & dosage , Treatment Outcome , Young Adult
5.
Anaesthesia ; 70(9): 1052-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25919658

ABSTRACT

The purpose of this study was to investigate the effects of dexmedetomidine on biventricular systolic and diastolic function using transoesophageal echocardiography. Cardiac function was assessed in 30 healthy patients who received total intravenous anaesthesia with propofol and remifentanil. The echocardiographic examinations were performed just before and 20, 40 and 60 min after dexmedetomidine or saline administration. Patients who received dexmedetomidine, compared with saline after 20 min, had a lower mean (SD) heart rate (56.7 (5.2) vs. 67.1 (7.1) beats.min(-1) ), higher systolic blood pressure (125.7 (18.9) vs. 109 (7.9) mmHg), and lower cardiac output (2.9 (0.5) vs. 3.7 (1.0) l.min(-1) ), respectively (all p < 0.05). In contrast, no changes were observed in biventricular systolic and diastolic indices in either group, and there were no inter-group differences at any time point. Dexmedetomidine, as an adjuvant to total intravenous anaesthesia, does not impair biventricular systolic and diastolic function in healthy patients, but decreases cardiac output by reducing heart rate.


Subject(s)
Anesthesia, Intravenous , Dexmedetomidine/pharmacology , Echocardiography, Transesophageal/methods , Hypnotics and Sedatives/pharmacology , Adult , Cardiac Output/drug effects , Echocardiography, Transesophageal/statistics & numerical data , Female , Heart Rate/drug effects , Humans , Male
6.
Acta Anaesthesiol Scand ; 58(2): 168-76, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24261345

ABSTRACT

BACKGROUND: This study was done to investigate how nicardipine, remifentanil and dexmedetomidine affect the balance of the autonomic nervous system in patients receiving controlled hypotension under general anaesthesia by evaluating heart rate variability indices. METHODS: Sixty-two patients were randomly allocated to either the nicardipine-sevoflurane (Group N, n = 21), remifentanil-sevoflurane (Group R, n = 21) or dexmedetomidine-sevoflurane (Group D, n = 20) group for controlled hypotension during orthognathic surgery. Electrocardiogram data acquisition was done after vital sign stabilization following anaesthesia induction (T1) and 30 min after controlled hypotension was induced (T2). RESULTS: Total power and low frequency (LF) power was significantly decreased at T2 compared with T1 in all groups, while a decrease in high frequency (HF) power was only observed in Group N (P < 0.001). LF/HF ratios of Group R and D were significantly suppressed at T2 compared with T1 (P = 0.001 and P < 0.001, respectively), but was increased Group N (P = 0.009). The LF/HF ratio of Group N was significantly higher than Group R and D at T2 (P < 0.001 in both), with Group D showing a significantly lower LF/HF ratio compared with Group R (P < 0.001). CONCLUSIONS: Remifentanil and dexmedetomidine did not have sympathetic nervous system-stimulating effects during controlled hypotension, while remifentanil seemed to be superior in preserving the overall balance in autonomic nervous system activity. Nicardipine was found to stimulate the sympathetic nervous system, which may be problematic in patients vulnerable to disturbances in the autonomic nervous system.


Subject(s)
Anesthetics, Intravenous/pharmacology , Antihypertensive Agents/pharmacology , Dexmedetomidine/pharmacology , Heart Rate/drug effects , Hypnotics and Sedatives/pharmacology , Hypotension, Controlled/methods , Nicardipine/pharmacology , Piperidines/pharmacology , Anesthesia, General , Anesthetics, Inhalation , Consciousness Monitors , Electrocardiography/drug effects , Female , Humans , Male , Methyl Ethers , Orthognathic Surgical Procedures , Prospective Studies , Remifentanil , Sample Size , Sevoflurane , Young Adult
7.
J Eur Acad Dermatol Venereol ; 26(9): 1149-53, 2012 Sep.
Article in English | MEDLINE | ID: mdl-21929552

ABSTRACT

BACKGROUND: Prurigo pigmentosa is a rare inflammatory disease of unknown origin. It is characterized by the sudden onset of pruritic erythematous papules, usually involving the trunk and neck, which coalesce to form reticulated, mottled patches. METHODS: We studied 16 patients with prurigo pigmentosa. The patients were selected from those attending the outpatient Department of Dermatology at the Kyung Hee University Hospital from January 2002 to January 2010. All clinical information was retrospectively collected from medical records. The serum concentrations of ketones (acetoacetic acid, 3-hydroxybutyrate acid [3-OHBA]) were examined in four patients, and a test for ketone in the urine was performed in 10 patients. RESULTS: The age at the time of diagnosis ranged from 18 to 36 years (mean age: 23.5 years), and the female : male ratio was 14 : 2. Skin lesions were almost always characterized by recurrent pruritic erythematous papules that had resolved, leaving a peculiar, reticulate hyperpigmentation. Eight of 16 patients showed a chronological relationship between a prurigo pigmentosa appearance of skin lesions and dieting or fasting. Histopathological findings were either of fully developed lesions (4/16) or late lesions (12/16). Most patients responded well to minocycline treatment. Ketosis was observed in six patients. CONCLUSIONS: In conclusion, we propose that ketosis was caused by fasting, and that diet may contribute to the pathogenesis of prurigo pigmentosa. Thus, physicians need to warn that excessive fasting can cause prurigo pigmentosa.


Subject(s)
Pigmentation Disorders/pathology , Prurigo/pathology , Adolescent , Adult , Female , Humans , Male , Pigmentation Disorders/drug therapy , Prurigo/drug therapy , Treatment Outcome , Young Adult
8.
Food Microbiol ; 29(1): 80-7, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22029921

ABSTRACT

(-)-Epigallocatechin-3-gallate (EGCG), a main constituent of tea catechins, affects Gram-positive and Gram-negative bacteria differently; however, the underlying mechanisms are not clearly understood. Atomic force microscopy (AFM) was used to compare morphological alterations in Gram-positive and Gram-negative bacteria induced by EGCG and by H(2)O(2) at sub-minimum inhibitory concentrations (MICs). EGCG initially induced aggregates in the cell envelopes of Staphylococcus aureus and eventually caused cell lysis, which was not observed in cells treated with H(2)O(2). It initially induced nanoscale perforations or microscale grooves in the cell envelopes of Escherichia coli O157:H7 which eventually disappeared, similar to E. coli cells treated with H(2)O(2). An E. coli O157:H7 tpx mutant, with a defect in thioredoxin-dependent thiol peroxidase (Tpx), was more severely damaged by EGCG when compared with its wild type. Similar differing effects were observed in other Gram-positive and Gram-negative bacteria when exposed to EGCG; it caused aggregated in Streptococcus mutans, while it caused grooves in Pseudomonas aeruginosa. AFM results suggest that the major morphological changes of Gram-negative bacterial cell walls induced by EGCG depend on H(2)O(2) release. This is not the case for Gram-positive bacteria. Oxidative stress in Gram-negative bacteria induced by EGCG was confirmed by flow cytometry.


Subject(s)
Catechin/analogs & derivatives , Escherichia coli O157/cytology , Microscopy, Atomic Force/methods , Plant Extracts/pharmacology , Staphylococcus aureus/cytology , Camellia sinensis/chemistry , Catechin/pharmacology , Escherichia coli O157/drug effects , Escherichia coli O157/metabolism , Hydrogen Peroxide/pharmacology , Microbial Viability/drug effects , Oxidative Stress/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism
10.
J Nanosci Nanotechnol ; 9(2): 901-4, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19441418

ABSTRACT

We have introduced in-situ growth of Ge2Sb2Te5 (GST) nanoparticles with 10 nm of average diameter by pulsed laser ablation directly on Pt/Ir-coated AFM tips and investigated their microstructure and phase formation using scanning and transmission electron microscopy. In addition, Fourier transform analysis of electron micrographs discloses the crystal structure of the Ge2Sb2Te5 phase which has a lattice constant with approximately 6 A like bulk value of face-centered cubic and hexagonal structure.

11.
Ultramicroscopy ; 108(10): 1124-7, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18571856

ABSTRACT

In this study, we characterized the two-dimensional lattice of bovine serum albumin (BSA) as a chemical and physical barrier against bacterial adhesion, using fluorescence microscopy and atomic force microscopy (AFM). The lattice of BSA on glass surface was fabricated by micro-contact printing (microCP), which is a useful way to pattern a wide range of molecules into microscale features on different types of substrates. The contact-mode AFM measurements showed that the average height of the printed BSA monolayer was 5-6 nm. Escherichia coli adhered rapidly on bare glass slide, while the bacterial adhesion was minimized on the lattices in the range of 1-3 microm(2). Especially, the bacterial adhesion was completely inhibited on a 1 microm(2) lattice. The results suggest that the anti-adhesion effects are due by the steric repulsion forces exerted by BSA.


Subject(s)
Bacteria/metabolism , Bacterial Adhesion , Microscopy, Atomic Force/methods , Serum Albumin, Bovine/chemistry , Animals , Cattle , Microscopy, Fluorescence , Serum Albumin, Bovine/metabolism , Surface Properties
12.
Anaesthesia ; 63(12): 1314-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19032299

ABSTRACT

This study compared cerebral blood flow-carbon dioxide (CBF-CO2) reactivities in the supine and modest Trendelenburg position under pnemoperitoneum during sevoflurane anaesthesia. After induction of anaesthesia in 25 patients, mechanical ventilation was adjusted to increase Paco2 from 4.7 (T1) to 6.0 kPa (T2) in the supine position, and the change in jugular bulb oxygen saturation was measured as an index of CBF. Then, after establishment of pneumoperitoneum and 30 degrees Trendelenburg position, the CO(2) step and measurement of CBF were repeated. The CBF-CO2 reactivity was 7.5 (3.3) %xkPa(-1) (% change in jugular bulb oxygen saturation per unit change in Paco2) in the supine position and 6.8 (2.3) %xkPa(-1) in the 30 degrees Trendelenburg-pneumoperitoneum condition (p = 0.086). We conclude that CBF-CO2 reactivity is unchanged by the modest Trendelenburg position under pneumoperitoneum during sevoflurane anaesthesia.


Subject(s)
Anesthetics, Inhalation/pharmacology , Cerebrovascular Circulation/drug effects , Head-Down Tilt , Methyl Ethers/pharmacology , Pneumoperitoneum, Artificial , Adult , Aged , Anesthesia, Inhalation/methods , Carbon Dioxide/blood , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Oxygen/blood , Partial Pressure , Prostatectomy , Sevoflurane , Supine Position
13.
Ultramicroscopy ; 107(10-11): 869-74, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17544218

ABSTRACT

Biofilms are complex microbial communities that are resistant against attacks by bacteriophages and removal by drugs and chemicals. In this study, biofilms of Escherichia coli O157:H7, a bacterial pathogen, were investigated using atomic force microscopy (AFM) in terms of the dynamic transition of morphology and surface properties of bacterial cells over the development of biofilms. The physical and topographical properties of biofilms are different, depending on nutrient availability. Compared to biofilms formed in a high nutrient medium, biofilms form faster and a higher number of bacterial cells were recovered on glass surface in a low nutrient medium. We demonstrate that AFM can obtain high-resolution images and the elastic information about biofilms. As E. coli biofilm becomes mature, the magnitude of the force between a tip and the surface of the biofilm gets stronger, suggesting that extracellular polymeric substances (EPSs), sticky components of biofilms, accumulate over the surface of cells upon the initial attachment of bacterial cells to surfaces.


Subject(s)
Biofilms/growth & development , Escherichia coli O157/physiology , Microscopy, Atomic Force/methods , Bacterial Adhesion , Culture Media , Escherichia coli O157/ultrastructure
14.
Ultramicroscopy ; 107(10-11): 954-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17570592

ABSTRACT

Relaxor ferroelectric PbMg(1/3)Nb(2/3)O(3)(65%)-PbTiO(3)(35%) (PMN-35PT) thin films were grown by a sol-gel method on Pt(111)/TiO(2)/SiO(2)/Si(100) substrates. Piezoresponse and poling behavior appear to have a relation with the relaxor behavior of the materials. Piezoelectric images were studied in a number of regions on the films with subsequent statistical analysis of the obtained data using the contact mode of scanning force microscopy. Hysteresis loops were observed with external field applied over a wide range of the vibration frequency. The piezoelectric coefficient, d(33), and the crystallographic electrostrictive constant, Q(33), were also determined as 100pm/V and 2.8x10(-3)C(-2)m(4), respectively.

15.
Ann Nucl Med ; 21(10): 585-92, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18092135

ABSTRACT

OBJECTIVE: This study was performed to evaluate the effects of intravenous (i.v.) contrast agent on semi-quantitative values and lymph node (LN) staging of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with lung cancer. METHODS: Thirty-five patients with lung cancer were prospectively included. Whole-body PET and nonenhanced CT images were acquired 60 min following the i.v. injection of 370 MBq 18F-FDG and subsequently, enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated contrast agent without positional change. PET images were reconstructed with both nonenhanced and enhanced CTs, and the maximum and average standardized uptake values (SUVmax and SUVave) calculated from lung masses, LNs, metastatic lesions, and normal structures were compared. To evaluate the effects of the i.v. contrast agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs; SUVmax=3.5, SUVave=3.0). RESULTS: The mean differences of SUVmax in normal structures between enhanced and nonenhanced PET/CT were 15.23%+/-13.19% for contralateral lung, 8.53%+/-6.11% for aorta, 5.85%+/-4.99% for liver, 5.47%+/-6.81% for muscle, and 2.81%+/-3.05% for bone marrow, and those of SUVave were 10.17%+/-9.00%, 10.51%+/-7.89%, 4.95%+/-3.89%, 5.66%+/-9.12%, and 2.49%+/-2.50%, respectively. The mean differences of SUVmax between enhanced and nonenhanced PET/CT were 5.89%+/-3.92% for lung lesions (n=41), 6.27%+/-3.79% for LNs (n=76), and 3.55%+/-3.38% for metastatic lesions (n=35), and those of SUVave were 3.22%+/-3.01%, 2.86%+/-1.71%, and 2.33%+/-3.95%, respectively. Although one LN status changed from benign to malignant because of contrast-related artifact, there was no up- or down-staging in any of the patients after contrast enhancement. CONCLUSIONS: An i.v. contrast agent may be used in PET/CT without producing any clinically significant artifact.


Subject(s)
Artifacts , Fluorodeoxyglucose F18 , Iopamidol/analogs & derivatives , Lung Neoplasms/diagnosis , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Contrast Media/administration & dosage , Female , Humans , Iopamidol/administration & dosage , Lung/diagnostic imaging , Lung/drug effects , Male , Middle Aged , Radiopharmaceuticals , Subtraction Technique
16.
Ultramicroscopy ; 106(8-9): 779-84, 2006.
Article in English | MEDLINE | ID: mdl-16675118

ABSTRACT

Retention behavior and local hysteresis characteristics in Pb(Zr(0.52)Ti(0.48))O(3) (PZT) thin films on Pt electrodes have been investigated by electrostatic force microscopy (EFM). A sol-gel method is used to synthesize PZT thin films and drying conditions are carefully explored over a wide range of temperature. Decay and retention mechanisms of single-poled and reverse-poled regions of the ferroelectric thin films are explained by space charge redistribution. Trapping behavior of space charges is dependent on the nature of interface between ferroelectric thin films and bottom electrodes. Local measurement of polarization-electric field curves by EFM shows inhomogeneous space charge entrapment.

17.
Ultramicroscopy ; 106(8-9): 775-8, 2006.
Article in English | MEDLINE | ID: mdl-16650933

ABSTRACT

Optical response and topography of fluorescent latex beads both on flat self-assembled monolayer and on a micron-patterned surface with poly(dimethylsiloxane) are studied. Scanning near-field optical microscopy and atomic force microscopy were utilized together for detecting fluorescence and imaging topography of the patterned latex beads, respectively. As a result, the micro-patterned latex beads where a specific chemical binding occurred show a strong signal, whereas no signals are observed in the case of nonspecific binding. With fluorescein isothiocyanate (FITC), it is convenient to measure fluorescence signal from the patterned beads allowing us to monitor the small balls of fluorescent latex.

18.
Neoplasma ; 53(1): 30-6, 2006.
Article in English | MEDLINE | ID: mdl-16416010

ABSTRACT

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Carcinoma, Non-Small-Cell Lung/mortality , Cisplatin/therapeutic use , Combined Modality Therapy , Etoposide/therapeutic use , Humans , Ifosfamide/therapeutic use , Lung Neoplasms/mortality , Retrospective Studies , Survival Analysis , Treatment Outcome
19.
Cell Death Differ ; 23(2): 333-46, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26206088

ABSTRACT

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase and its dysregulation is implicated in neurodegenerative diseases. Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5-mediated phosphorylation disrupts the interaction between CHIP and truncated apoptosis-inducing factor (tAIF) without affecting CHIP's E3 ligase activity, resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral transduction assay shows that knockdown of Cdk5 or overexpression of CHIP(S20A), but not CHIP(WT), attenuates tAIF-mediated neuronal cell death induced by hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP negatively regulates its neuroprotective function, thereby contributing to neuronal cell death progression following neurotoxic stimuli.


Subject(s)
Apoptosis Inducing Factor/physiology , Apoptosis , Cyclin-Dependent Kinase 5/physiology , Neurons/physiology , Ubiquitin-Protein Ligases/metabolism , Animals , Cyclin-Dependent Kinase 5/chemistry , Hydrogen Peroxide/pharmacology , Male , Mice, Transgenic , Neurons/drug effects , Phosphorylation , Proteasome Endopeptidase Complex/metabolism , Proteolysis , Ubiquitin-Protein Ligases/chemistry , Ubiquitination
20.
Cell Death Dis ; 7(6): e2240, 2016 06 02.
Article in English | MEDLINE | ID: mdl-27253404

ABSTRACT

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration.


Subject(s)
Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Nerve Tissue Proteins/metabolism , Proteolysis , 1-Methyl-4-phenylpyridinium , Aging/metabolism , Animals , Calpain/metabolism , Cell Death , Cell Line , Disease Models, Animal , Dopaminergic Neurons/metabolism , Down-Regulation , Mesencephalon/metabolism , Neuroprotection , Parkinson Disease/metabolism , Parkinson Disease/pathology , Postmortem Changes , Rats, Sprague-Dawley , Substantia Nigra/metabolism , Substantia Nigra/pathology , Tyrosine 3-Monooxygenase/metabolism , Ubiquitin/metabolism
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