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C K Chen

Publications and source records attributed to C K Chen.

At least 37 records · Page 2Linked to original sources

Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1.

Timely deactivation of the alpha-subunit of the rod G-protein transducin (Galphat) is essential for the temporal resolution of rod vision. Regulators of G-protein signalling (RGS) proteins accelerate hydrolysis of GTP by the alpha-subunits of heterotrimeric G proteins in vitro. Several retinal RGS proteins can act in vitro as GTPase accelerating proteins (GAP) for Galphat. Recent reconstitution experiments indicate that one of these, RGS9-1, may account for much of the Galphat GAP activity in rod outer segments (ROS). Here we report that ROS membranes from mice lacking RGS9-1 hydrolyse GTP more slowly than ROS membranes from control mice. The Gbeta5-L protein that forms a complex with RGS9-1 was absent from RGS9-/- retinas, although Gbeta5-L messenger RNA was still present. The flash responses of RGS9-/- rods rose normally, but recovered much more slowly than normal. We conclude that RGS9-1, probably in a complex with Gbeta5-L, is essential for acceleration of hydrolysis of GTP by Galphat and for normal recovery of the photoresponse.

3',5'-Cyclic-GMP Phosphodiesterases↗

Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH.

In man high levels of aneuploidy are seen in spontaneous abortions. Very few autosomal trisomies survive to birth, the three most common being those for chromosome 13, 18 and 21 giving rise to the syndromes named Patau, Edwards and Down respectively. Since the majority of these spontaneously abort, what makes the survivors different from the aborters? Could it be that they have tissue specific mosaicism with the additional normal cell line supporting survival? In this study fluorescence in situ hybridisation was used as a convenient way to detect trisomy in interphase cells. To study the level of mosaicism across gestation, different tissues from 21 trisomic foetuses were analysed using probes for chromosome 13, 18, 21, X and Y. Two trisomy 18 foetuses exhibited mosaicism. Two others, one trisomy 13 and one trisomy 18 had mosaic placentas. There was no clear association between the limited mosaicism seen and severity of the phenotype. We conclude that at least for this sample set, tissue-specific mosaicism was not likely to be responsible for potential survival to birth.

Adult↗

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population.

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.

Adult↗

Small hepatocellular carcinoma: safety and efficacy of single high-dose percutaneous acetic acid injection for treatment.

PURPOSE: To evaluate the safety and efficacy of single high-dose percutaneous acetic acid injection (PAI) for treatment of small (<3-cm-diameter) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighteen patients with HCC (22 nodules; diameter range, 1.5-3.0 cm) underwent single PAI. With ultrasonographic or computed tomographic (CT) guidance, 4-11 mL of 50% acetic acid was slowly injected into the center of the nodule through a skinny multiple-side-hole needle. Follow-up was performed with helical contrast material-enhanced CT. Complications of high-dose PAI were recorded. RESULTS: Seventeen nodules showed no local recurrence (follow-up, 6-29 months) after single PAI. At a mean follow-up of 15.6 months, mean tumor diameter was 2.1 cm and mean injected volume was 6.4 mL. Four nodules showed residual tumor (mean tumor diameter, 2.6 cm; mean injected volume, 5.8 mL). The mean ratio of injected to estimated volume of acetic acid was 1.21 in cases of successful single PAI and 0.72 in cases of local recurrence (P < .001). One patient with preexistent right portal venous thrombosis died of hepatic failure 37 days after PAI. Other complications included severe pain (11%), high fever (4%), and segmental wedge infarction (4%). CONCLUSION: Single high-dose PAI is safe and effective for treatment of small HCC.

Acetic Acid↗

Carpal tunnel syndrome caused by tophaceous gout: CT and MR imaging features in 20 patients.

OBJECTIVE: The objective of this study is to describe the CT and MR imaging findings of gouty tophi in the wrist and present this entity as a cause of carpal tunnel syndrome. MATERIALS AND METHODS: Retrospective review of the CT (n = 18) and MR imaging (n = 20) studies of the wrist in patients with a documented diagnosis of gout who presented with gout-related carpal tunnel syndrome was performed; images of 24 wrists were collected over a 5-year period. Patient population included 20 men, who ranged in age from 35 to 76 years. All images were reviewed by two musculoskeletal radiologists who reached a consensus opinion. Surgical correlation was available in 12 patients. RESULTS: Tophi were found in the floor of the carpal tunnel (n = 18), carpal bones (n = 17), radiocarpal joint (n = 17), and extensor tendons or tendon sheaths (n = 16) of the wrist. All tophi showed similar signal characteristics (from low to intermediate signal intensity on T1-weighted images with heterogeneous signal intensity on T2-weighted images) with the exception of tophi in the floor of the carpal tunnel (low signal intensity on T2-weighted images). Varying degrees of calcification were noted on CT and MR imaging studies. Gadolinium-enhanced MR studies showed heterogeneous enhancement. CONCLUSION: Gouty tophi should be entertained as a cause of carpal tunnel syndrome in the appropriate patient population. Familiarity with this entity and its imaging characteristics may prove helpful in diagnosis and preoperative planning.

Adult↗

Amino-terminal cysteine residues of RGS16 are required for palmitoylation and modulation of Gi- and Gq-mediated signaling.

RGS proteins (Regulators of G protein Signaling) are a recently discovered family of proteins that accelerate the GTPase activity of heterotrimeric G protein alpha subunits of the i, q, and 12 classes. The proteins share a homologous core domain but have divergent amino-terminal sequences that are the site of palmitoylation for RGS-GAIP and RGS4. We investigated the function of palmitoylation for RGS16, which shares conserved amino-terminal cysteines with RGS4 and RGS5. Mutation of cysteine residues at residues 2 and 12 blocked the incorporation of [3H]palmitate into RGS16 in metabolic labeling studies of transfected cells or into purified RGS proteins in a cell-free palmitoylation assay. The purified RGS16 proteins with the cysteine mutations were still able to act as GTPase-activating protein for Gialpha. Inhibition or a decrease in palmitoylation did not significantly change the amount of protein that was membrane-associated. However, palmitoylation-defective RGS16 mutants demonstrated impaired ability to inhibit both Gi- and Gq-linked signaling pathways when expressed in HEK293T cells. These findings suggest that the amino-terminal region of RGS16 may affect the affinity of these proteins for Galpha subunits in vivo or that palmitoylation localizes the RGS protein in close proximity to Galpha subunits on cellular membranes.

Acylation↗

Negative regulation of atonal in proneural cluster formation of Drosophila R8 photoreceptors.

atonal (ato) encodes a basic helix-loop-helix protein and is required for the specification of R8 photoreceptor cells in Drosophila. In the eye imaginal discs, expression of Ato protein is initially in a dorsoventral stripe of cells anterior to the morphogenetic furrow (MF). In the MF, this stripe expression is resolved into regularly spaced clusters of Ato-positive cells, the proneural clusters, which are intervened with Ato-negative cells. Another basic helix-loop-helix protein, Daughterless (Da), dimerizes with Ato and is expressed at an enhanced level in Ato-expressing cells. Here we show that during the late stages of proneural clusters, the mitogen-activated protein kinase (MAPK) is activated in proneural clusters. Normal ato or da activity is required for maintenance of MAPK activation. Furthermore, in ato or da mutants, Ato expression is expanded to all cells in the MF, suggesting that ato and da are required for Ato repression in cells between proneural clusters. By changing the MAPK activity in proneural clusters, we show that MAPK activation mediates Ato repression nonautonomously. Consistently, hyperactivation of the MAPK in a stripe of cells posterior to or overlapping the Ato stripe eliminates the formation of proneural clusters. Taken together, these results suggest that a negative regulatory loop involving MAPK activation and Ato repression is required for the generation of evenly spaced proneural clusters.

Animals↗

Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase.

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the single-photon response to become larger and longer lasting than normal. These results demonstrate that RK is required for normal rhodopsin deactivation. When the photon responses of RK-/- rods did finally turn off, they did so abruptly and stochastically, revealing a first-order backup mechanism for rhodopsin deactivation. The rod outer segments of RK-/- mice raised in 12-hr cyclic illumination were 50% shorter than those of normal (RK+/+) rods or rods from RK-/- mice raised in constant darkness. One day of constant light caused the rods in the RK-/- mouse retina to undergo apoptotic degeneration. Mice lacking RK provide a valuable model for the study of Oguchi disease, a human RK deficiency that causes congenital stationary night blindness.

Animals↗

Regulators of G-protein signalling: a novel protein family involved in timely deactivation and desensitization of signalling via heterotrimeric G proteins.

In a variety of signalling pathways heterotrimeric guanine-nucleotide-binding proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli. Receptor-induced GDP/GTP exchange activates G proteins by dissociating G-protein alpha-subunits from the betagamma-dimers. Both alpha-subunits and betagamma-dimers are involved in effector regulation. The deactivation of these active forms is controlled by the hydrolysis of GTP bound to alpha-subunits, allowing the inactive heterotrimer to reform. Termination of G-protein-mediated signalling in vivo is 10- to 100-fold faster than the in vitro rate of GTP hydrolysis by alpha-subunits, suggesting that in analogy to the GTPases of the Ras-superfamily, GTPase-activating proteins (GAPs) are required to achieve timely deactivation. Recently, members of a novel protein superfamily, known as "regulators of G-protein signalling" (RGS), were identified as potent GAPs for at least one subset of heterotrimeric G-protein alpha-subunits. In this review, we intend to discuss the proposed mechanism by which RGS proteins exert GAP activity for G-protein alpha-subunits as well as their specificities. The role of RGS proteins in desensitization and temporal resolution in certain signalling pathways will also be addressed.

Animals↗

Intra-articular gouty tophi of the knee: CT and MR imaging in 12 patients.

OBJECTIVE: To define the imaging characteristics of intra-articular tophi of the knee. DESIGN AND PATIENTS: Twelve patients with intra-articular tophi in the knee were studied with routine MR imaging, gadolinium (Gd)-enhanced MR imaging, and CT over a 4-year period. There were 11 men and one woman, 25-82 years of age (mean age 48 years). Four patients did not have a documented history of gout at the time of the MR examination. The diagnosis of intra-articular tophi was provided by arthroscopy and histological examination (5 patients), by microscopic study of joint fluid (5 patients), or by characteristic clinical, laboratory and imaging findings (2 patients). RESULTS: In 15 MR examinations the tophi were located purely intra-articularly in 10 knees. In the remaining five MR studies, periarticular soft tissues or bone, or both, were involved. All the intra-articular tophi manifested low to intermediate signal intensity on both T1- and T2-weighted images. All five Gd-enhanced MR examinations demonstrated a heterogeneous peripheral enhancement. All 10 CT scans showed varying degrees of stippled calcifications within the tophi. The nature of the calcifications was confirmed on histological examination in three patients. CONCLUSION: Presenting clinical manifestations of gout may relate to intra-articular tophaceous deposits. Such deposits present as masses on MR images with low to intermediate signal intensity on both T1- and T2-weighted images and a characteristic enhancement pattern following intravenous Gd administration. These features relate primarily to internal calcifications, which are most evident on CT images. MR evaluation (including Gd administration) supplemented, in some cases, with CT scanning allows accurate diagnosis of intra-articular tophaceous deposits.

Adult↗

Active cancellation system of acoustic noise in MR imaging.

In this paper, we introduce a new neural-network architecture for reducing the acoustic noise level in magnetic resonance (MR) imaging processes. The proposed neural network (NN) consists of two cascaded time-delay NN's (TDNN's). This NN is used as the predictor of a feedback active noise control (ANC) system for reducing acoustic noises. Experimental results with real MR noises show that the proposed system achieved an average noise power attenuation of 18.75 dB, which compares favorably with previous studies. Preliminary results also show that with the proposed ANC system installed, acoustic MR noises are greatly attenuated while verbal communication during MRI sessions is not affected.

Algorithms↗

Effect of acetate on molecular and physiological aspects of Clostridium beijerinckii NCIMB 8052 solvent production and strain degeneration.

The addition of sodium acetate to chemically defined MP2 medium was found to increase and stabilize solvent production and also increase glucose utilization by Clostridium beijerinckii NCIMB 8052. RNA and enzyme analyses indicated that coenzyme A (CoA) transferase was highly expressed and has higher activity in C. beijerinckii NCIMB 8052 grown in MP2 medium containing added sodium acetate than in the microorganism grown without sodium acetate. RNA analysis suggested the existence of a sol operon and confirmed the presence of a ptb-buk operon in C. beijerinckii NCIMB 8052. In addition to CoA transferase, C. beijerinckii NCIMB 8052 grown in MP2 medium containing added acetate demonstrated higher acetate kinase- and butyrate kinase-specific activity than when the culture was grown in MP2 medium containing no added acetate. Southern blot analysis with chromosomal DNA isolated from solventogenic and degenerated C. beijerinckii NCIMB 8052 indicated that C. beijerinckii NCIMB 8052 strain degeneration does not involve loss of the CoA transferase genes. The addition of acetate to MP2 medium may induce the expression of the sol operon, which ensures solvent production and prevents strain degeneration in C. beijerinckii NCIMB 8052.

Journal Article↗

T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies.

The activation status of T lymphocytes and the presence of various cytokines in ascitic fluid were examined to test peritoneal immunity in women with ovarian malignancies. Peripheral blood and peritoneal fluid were collected from 12 patients with primary ovarian cancer with ascites and 27 normal control subjects during laparoscopic examination. Lymphocyte subpopulations and the expression of activation markers on T lymphocytes were analyzed by dual-color flow cytometry. The concentrations of various cytokines and soluble interleukin (IL)-2 receptor-alpha were measured. CD8 T lymphocytes were the main component of peritoneal lymphocytes. CD69 and HLA-DR, but not CD25, were highly expressed on peritoneal T lymphocytes compared to those in peripheral blood. In ascitic fluid of ovarian malignancies, CD4 T lymphocyte concentrations were further decreased, resulting in a decreased CD4/CD8 ratio. Decreased expression of CD69 and CD25 was also noted on T lymphocytes from ascites compared with T lymphocytes in normal peritoneal fluid. IL-1b, tumor necrosis factor-alpha, IL-6, and soluble IL-2 receptor-alpha concentrations were increased significantly in the ascitic fluid of women with ovarian cancer. The decrease in activation markers on T lymphocytes is suggestive of an immunosuppressive state, despite the presence of abundant stimulatory cytokines. The immunosuppression may be multifactorial, attributed, in part, to the increased concentrations of soluble IL-2 receptor-alpha and other inhibitors.

Ascitic Fluid↗

Characteristics of hospitalized heroin smokers and heroin injectors in Taiwan.

BACKGROUND: Heroin usage in Taiwan has been under-investigated. Use of the same drug by different routes provides an opportunity for examination of drug behavior and complications related to the drug itself and to the different routes of administration. METHODS: A sample of 245 hospitalized heroin users received semi-structured interviews, drug screen urine tests, serological screens for hepatitis B infection, and liver function tests. The sample was divided into a smokers group and an injectors group for comparison. RESULTS: The heroin injectors had lower educational status, spent less money on day-to-day heroin usage, but had longer drug-using careers than the heroin smokers. There was a trend for injectors to have a higher rate of abnormal liver function than the smokers although there was no significant difference in the prevalence of hepatitis B infection. CONCLUSION: Major differences exist between heroin smokers and heroin injectors. Therefore harm reduction intervention for heroin users should take account of the different routes of administration. A comprehensive survey of risk factors relating to hepatic dysfunction in heroin addicts in Taiwan is indicated.

Adolescent↗

Imaging diagnosis of insufficiency fracture of the sacrum.

BACKGROUND: Insufficiency fracture of the sacrum has been recognized as a major cause of lower back pain, especially in elderly osteoporotic patients with or without underlying malignancy and/or prior pelvic radiotherapy. Its diagnosis cannot be readily made from its nonspecific clinical features. Consequently some cases may be mistaken for bone metastases, causing patients to receive inappropriate diagnostic measures and management. Recognition of the spectrum of imaging features is the basis of correct diagnosis and treatment. METHODS: The imaging studies of 14 cases (12 women and 2 men; age range, 60-84 years; mean age, 70 years) of sacral insufficiency fracture were reviewed retrospectively. These included 14 radiographs, six bone scintigraphs, eight computerized tomography (CT) scans and 12 magnetic resonance (MR) imaging studies. Six patients had a history of malignancy. Diagnosis was made by characteristic imaging findings, and clinical and radiographic follow-up for one to 3.5 years. RESULTS: Five cases of sacral insufficiency fracture were suspected based on radiographic findings of fracture lines (2 cases) and focal sclerosis (3 cases). Seven cases were diagnosed by CT findings of linear fractures (7 cases) and focal sclerosis (2 cases). Nine MR examinations demonstrated characteristic vertical bands of marrow edema. A hypointense fracture line was identified in eight cases. The remaining two MR imaging studies disclosed nonspecific focal marrow edema. An early case, which appeared normal on CT scan, showed marrow edema on MR imaging. The positive and diagnostic rates were both 36% for plain radiographs, 88% for CT scans, and 100% and 83%, respectively, for MR images. CONCLUSIONS: Plain radiographs are often unrewarding. Although MR imaging is the most sensitive tool, fracture lines are best demonstrated and diagnosed using CT. Due to the better diagnostic rate, popularity and cost effectiveness, CT is recommended as the definitive modality for confirming diagnosis of insufficiency fracture of the sacrum.

Aged↗

Fatal hyperkalemia during rapid and massive blood transfusion in a child undergoing hip surgery--a case report.

We report a girl who developed severe and fatal hyperkalemia following rapid and massive blood transfusion during surgery. She was 7-year-old, 20-kg in weight, and received wide resection of the femoral bone with custom prosthesis implant because of malignant femoral osteosarcoma. During the procedure, bleeding was active and profuse and amounted to about 3,000 mL in 4 h, eventuating in shock. Despite rapid transfusion with 15 units of packed red blood cells (RBC) still she remained hypotensive and hypovolemic. When we switched to give her whole blood, actually 100 mL having been given, widening of QRS complex followed immediately by cardiac arrest developed. Cardiopulmonary resuscitation although started at once was unsuccessful. At this juncture, arterial blood gas analysis showed acidosis and severe hyperkalemia (10.3 mmol/L), possibly resulting from transfusion of blood of older storage. The case reminded us once again the importance and necessity of the use of potassium-low blood component (fresh, saline-washed RBCs) in case of massive and rapid blood transfusion especially in pediatric patients with hypovolemia and low cardiac output.

Bone Neoplasms↗

Autophosphorylation and ADP regulate the Ca2+-dependent interaction of recoverin with rhodopsin kinase.

Recoverin is a 23 kDa myristoylated Ca2+-binding protein that inhibits rhodopsin kinase. We have used surface plasmon resonance to investigate the influences of Ca2+, myristoylation, and adenine nucleotides on the recoverin-rhodopsin kinase interaction. Our analyses confirmed that Ca2+ is required for recoverin to bind RK. Myristoylation had little effect on the affinity of recoverin for the kinase, but it raised the K0.5 for Ca2+ from 150 nM for nonacylated recoverin to 400 nM for myristoylated recoverin. Finally, our studies also revealed two separate and previously unreported effects of adenine nucleotides on the recoverin-rhodopsin kinase binding. The interaction is weakened by autophosphorylation of the kinase, and it is strengthened by the presence of ADP.

Adenosine Diphosphate↗