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Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 217 records · Page 12Linked to original sources

Long-term contribution to the myeloid compartment by lineage-committed stem cells.

The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived myeloid-committed stem cell population(s) that continuously replenishes the mature myeloid lineage for at least 9 months. After myeloid-specific retroviral-mediated gene transfer, the exogenous gene could be detected in thioglycollate-induced macrophages and granulocytes by Southern blot analysis and by in situ polymerase chain reaction on an individual cell basis. The targeted stem cell population does not repopulate the bone marrow in secondary recipients and did not give rise to cells other than cells of the myeloid lineage. It therefore represents the first nonpluripotential stem cell population capable of replenishing a hemopoietic lineage for a long period of time. The ability to target a myeloid-specific stem cell could facilitate gene therapy of congenital disorders of the myeloid system such as lysosomal storage diseases. It also offers a unique opportunity to assess the immunologic consequences of expressing an exogenous gene of choice exclusively in the myeloid lineage.

Animals↗

A sensory neuron-specific, proton-gated ion channel.

Proton-gated channels expressed by sensory neurons are of particular interest because low pH causes pain. Two proton-gated channels, acid-sensing ionic channel (ASIC) and dorsal root ASIC (DRASIC), that are members of the amiloride-sensitive ENaC/Degenerin family are known to be expressed by sensory neurons. Here, we describe the cloning and characterization of an ASIC splice variant, ASIC-beta, which contains a unique N-terminal 172 aa, as well as unique 5' and 3' untranslated sequences. ASIC-beta, unlike ASIC and DRASIC, is found only in a subset of small and large diameter sensory neurons and is absent from sympathetic neurons or the central nervous system. The patterns of expression of ASIC and ASIC-beta transcripts in rat dorsal root ganglion neurons are distinct. When expressed in COS-7 cells, ASIC-beta forms a functional channel with electrophysiological properties distinct from ASIC and DRASIC. The pH dependency and sensitivity to amiloride of ASIC-beta is similar to that described for ASIC, but unlike ASIC, the channel is not permeable to calcium, nor are ASIC-beta-mediated currents inhibited by extracellular calcium. The unique distribution of ASIC-beta suggests that it may play a specialized role in sensory neuron function.

Acid Sensing Ion Channels↗

Protein kinase C eta mediates lipopolysaccharide-induced nitric-oxide synthase expression in primary astrocytes.

The signaling pathway involved in protein kinase C (PKC) activation and role of PKC isoforms in lipopolysaccharide (LPS)-induced nitric oxide (NO) release were studied in primary cerebellar astrocytes. LPS caused a dose- and time-dependent increase in NO release and inducible NO synthase (iNOS) expression. The tyrosine kinase inhibitor, genestein, the phosphatidylcholine-phospholipase C inhibitor, D609, and the phosphatidate phosphodrolase inhibitor, propranolol, attenuated the LPS effects, whereas the PI-PLC inhibitor, U73122, had no effect. The PKC inhibitors (staurosporine, Ro 31-8220, Go 6976, and calphostin C) also inhibited LPS-induced NO release and iNOS expression. However, long term (24 h) pretreatment of cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) did not affect the LPS response. Previous results have shown that TPA-induced translocation, but not down-regulation, of PKCeta occurs in astrocytes (Chen, C. C., and Chen, W. C. (1996) Glia 17, 63-71), suggesting possible involvement of PKCeta in LPS-mediated effects. Treatment with antisense oligonucleotides for PKCeta or delta, another isoform abundantly expressed in astrocytes, demonstrated the involvement of PKCeta, but not delta, in LPS-mediated effects. Stimulation of cells for 1 h with LPS caused activation of nuclear factor (NF)-kB in the nuclei as detected by the formation of a NF-kB-specific DNA-protein complex; this effect was inhibited by genestein, D609, propranolol, or Ro 31-8220 or by PKCeta antisense oligonucleotides, but not by long term TPA treatment. These data suggest that in astrocytes, LPS might activate phosphatidylcholine-phospholipase C and phosphatidylcholine-phospholipase D through an upstream protein tyrosine kinase to induce PKC activation. Of the PKC isoforms present in these cells, only activation of PKCeta by LPS resulted in the stimulation of NF-kB-specific DNA-protein binding and then initiated the iNOS expression and NO release. This is further evidence demonstrating that different members of the PKC family within a single cell are involved in specific physiological responses.

Animals↗

Cutaneous reflexes in patients with acute lacunar infarctions.

Cutaneous reflex (CR) was measured in 15 patients with acute lacunar stroke and in 15 age- and sex-matched normal subjects. EMG activities were recorded from the first dorsal interosseous muscle with surface electrodes, rectified and averaged. Intensity of the stimulation on the index finger was four times the sensory threshold. Aided by audio- and visual-feedback monitoring, the subjects abducted the index finger. Side-to-side comparison was made on all the subjects. CR abnormalities were found in all of our patients. The early inhibitory (I1) and second excitatory (E2) components were attenuated in 11 of 15 patients. The I1-E2 interpeak amplitude (A2) was significantly reduced in all the patients. Prolonged latency of I1-E2 components was found to be pronounced in six of eight patients with sensory symptoms. Eight patients were followed up 1 month later. By that time, the abnormal CR had reversed to some degree in all of them. CR alternation was still present in two fully recovered patients. Our results implied a thalamic relay in the afferent limb of the CR. CR could be a valuable adjunct for assessing long tract dysfunction and monitoring functional recovery.

Aged↗

Magnolol induces cytosolic-free Ca2+ elevation in rat neutrophils primarily via inositol trisphosphate signalling pathway.

In the present study, we describe the role of inositol trisphosphate in the signalling pathway that leads to the elevation of cytosolic-free Ca2+ in rat neutrophils stimulated with magnolol, a compound isolated from the cortex of Magnolia officinalis. Magnolol increased [Ca2+]i, by stimulating Ca2+ release from internal stores and Ca2+ influx across the plasma membrane, in a concentration-dependent manner. Ni2+ and [6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H -pyrrole-2,5-dione (U73122), but not pertussis toxin, inhibited the magnolol-induced Ca2+ influx. Measurement of cellular levels of inositol trisphosphate showed a clear increase upon exposure to magnolol. U73122 but not ryanodine suppressed the Ca2+ release from internal stores caused by magnolol. Pretreatment of cells with formyl-Met-Leu-Phe (fMLP) or cyclopiazonic acid greatly reduced the [Ca2+]i changes caused by the subsequent addition of magnolol. Collectively, these findings suggest that a pertussis toxin-insensitive inositol trisphosphate signalling pathway is involved in the magnolol-induced [Ca2+]i elevation in rat neutrophils.

Animals↗

A unique high-performance wide-range (10-1500 eV) spherical grating monochromator beamline.

A wide-spectral-range high-performance 6 m-spherical grating monochromator (6 m-SGM) beamline has been designed and is under construction at SRRC. Two different entrance slits, instead of additional mirrors, are used to optimize the overall performance. Six gratings are used to cover photon energies from 10 to 1500 eV. Movable entrance slits and bendable vertical focusing mirrors are used to enhance further the beamline performance. A bendable horizontal focusing mirror is used to improve the resolution and to focus the photon beam at the experimental station immediately after the exit slit. Several end-stations can be installed at the same time to utilize the beam time fully. The expected energy-resolving power, with both slit openings set at 10 micro m, is up to 15 000 and 40 000 for the high- and low-energy branches, respectively. A photon flux of 1 x 10(11) photons s(-1) can be obtained with an energy-resolving power of 20 000.

Journal Article↗

A high-performance wide-range beamline for elliptically polarized undulator source.

A high-performance wide-range beamline has been designed for monochromatizing circularly polarized photons with energies from 10 to 1400 eV. A grazing SGM-based beamline with two entrance slits has been employed to optimize the performance. The degree of the circular polarization affected by the beamline optics has been analysed. The horizontal and vertical refocusing mirrors have been specially arranged to improve greatly the polarization degree in the low-energy region. By connecting this beamline to a high-efficiency elliptically polarized undulator, this beamline should be able to provide, in the entire energy range, intensive and high-resolution photons of a high degree of circular polarization.

Journal Article↗

Application of solid-phase microextraction and gas chromatography-mass spectrometry for the determination of chlorophenols in urine.

This study investigated the feasibility of applying solid-phase microextraction (SPME) combined with gas chromatography-mass spectrometry to analyze chlorophenols in urine. The SPME experimental procedures to extract chlorophenols in urine were optimized with a polar polyacrylate coated fiber at pH 1, extraction time for 50 min and desorption in GC injector at 290 degrees C for 2 min. The linearity was obtained with a precision below 10% R.S.D. for the studied chlorophenols in a wide range from 0.1 to 100 microg/l. In addition, sample extraction by SPME was used to estimate the detection limits of chlorophenols in urine, with selected ion monitoring of GC-MS operated in the electron impact mode and negative chemical ionization mode. Detection limits were obtained at the low ng/l levels. The application of the methods to the determination of chlorophenols in real samples was tested by analyzing urine samples of sawmill workers. The chlorophenols were found in workers, the urinary concentration ranging from 0.02 microg/l (PCP) to 1.56 microg/l (2,4-DCP) depending on chlorophenols. The results show that trace chlorophenols have been detected with SPME-GC-MS in the workers of sawmill where chlorophenol-containing anti-stain agents had been previously used.

Chlorophenols↗

Characterization of the antiplatelet effects of (2S)-5-methoxy-6-methylflavan-7-ol from Draconis Resina.

(2S)-5-methoxy-6-methylflavan-7-ol (MMF) was purified from Draconis Resina and its in vitro effects on various aspects of platelet reactivity were examined. Results indicated that MMF dose dependently inhibited aggregation of washed rabbit platelets induced by collagen, arachidonic acid, ADP, U46619 or platelet-activating factor (PAF), with IC50) values of 17.2, 49.8, 179.8, 109.6, and 189.2 microM, respectively. Concomitantly, MMF also dose dependently suppressed ATP release by platelets activated by these stimulants. The increase in intracellular free calcium ([Ca2+]i), elicited by these activating agents, was inhibited by MMF as reflected by fura-2 fluorescence measurements. However, MMF had no effects on the cyclic AMP level of platelets. In addition, MMF inhibited the arachidonic acid-induced thromboxane B2 and prostaglandin D2 formation in intact platelet suspensions or homogenized platelet lysates. This study provided evidence that MMF is an antiplatelet agent whose activity is likely related to cyclooxygenase inhibition and suppression of [Ca2+]i increase.

Adenosine Triphosphate↗

The paired Ig-like receptor PIR-B is an inhibitory receptor that recruits the protein-tyrosine phosphatase SHP-1.

An emerging family of cell surface inhibitory receptors is characterized by the presence of intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM). These ITIM-bearing inhibitory receptors, which are typically paired with activating isoforms, associate with Src homology domain 2-containing phosphatases following ITIM tyrosine phosphorylation. Two categories of phosphatases are recruited by the ITIM-bearing receptors: the protein-tyrosine phosphatases, SHP-1 and SHP-2, and the polyphosphate inositol 5-phosphatase, SHIP. The dynamic equilibrium of B cell activation is partially controlled by two well known ITIM-bearing receptors, CD22 and FcgammaRIIB, a low affinity receptor for IgG. We describe here that a murine ITIM-bearing molecule, PIR-B, can also negatively regulate B cell activation. Tyrosine-phosphorylated ITIMs allow PIR-B to associate with SHP-1 but not with SHIP. Engagement of PIR-B thereby initiates a SHP-1-dependent inhibitory pathway that may play an important role in regulating B lymphocyte activation.

Amino Acid Sequence↗

In situ detection of Epstein-Barr virus in breast cancer.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and some lymphoepithelioma-like carcinomas from other anatomic sites. This study investigates the presence of EBV in breast cancer. Immunohistochemistry for EBV proteins (EBV nuclear antigen-2 and latent membrane protein-1) and in situ hybridization for EBV-encoded small nuclear RNAs (EBER-1 and -2) were performed in 60 invasive breast cancers. None of the 60 breast cancer samples showed detectable EBV. These results suggest that EBV may not play a significant role in the etiology of breast cancers in Taiwan.

Adult↗

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.

Adult↗

ATP-induced arachidonic acid release in cultured astrocytes is mediated by Gi protein coupled P2Y1 and P2Y2 receptors.

ATP-induced arachidonic acid (AA) release was studied in [3H]AA-prelabeled cultured astrocytes. To characterize the P2 purinoceptor-mediated effect of ATP, the subtype-specific agonists 2-methylthio ATP (2-MeSATP) and UTP were compared. ATP, UTP, or 2-MeSATP induced a dose-dependent increase of [3H]AA release, with EC50 values of 22.7 microM, 29.4 microM, and 1.68 microM, respectively; alpha,beta-methyleneATP and adenosine had no effect. The order of potency was ATP = UTP > or = 2-MeSATP, indicating that ATP interacted with both P2Y1 and P2Y2 receptors to mediate AA release in astrocytes. The effect of ATP, UTP, or 2-MeSATP was markedly inhibited by pretreatment of cells with pertussis toxin. Ca2+ ionophore-A23187 and PKC activator-TPA mimicked the effects of these three agonists to stimulate AA release. ATP, UTP, and 2-MeSATP induced a rapidly initial rise of [Ca2+]i and a sustained [Ca2+]i increase. The AA release was blocked in the external Ca2+ free in condition the sustained [Ca2+]i increase was abolished. Both A23187- and TPA-induced AA release were also blocked in this condition. Furthermore, inorganic Ca2+ channel blocker Co2+ inhibited ATP, UTP, or 2-MeSATP induced AA release as well. Long-term (24 h) treatment of cells with TPA resulted in an attenuation of three agonists, TPA or A23187 response. Similarly, ATP or TPA promoted AA release was inhibited by the mitogen-activated protein kinase (MAPK) cascade inhibitor PD 98059. ATP, TPA, or A23187 induced an increase in the activity and tyrosine phosphorylation of p42 MAPK, as well as a molecular weight shift, consistent with phosphorylation, of cytosolic phospholipase A2 (cPLA2). ATP- and TPA-stimulated activation of p42 MAPK activity and tyrosine phosphorylation were inhibited by long-term TPA treatment, while A23187-stimulated effects were completely blocked. Furthermore, tyrosine phosphorylation and activation of p42 MAPK and mobility shift of cPLA2 induced by A23187 were reversed in the absence of external Ca2+, suggesting the involvement of PKCalpha in MAPK activation and mobility shift of cPLA2. Taken together, ATP-stimulated AA release was secondary to the activation of P2Y1 and P2Y2 receptors/PLC pathway. Ca2+ and PKC interact to regulate this response. Elevation of intracellular Ca2+, the mechanism involving extracellular Ca2+ influx, might act partly through PKCalpha activation and in turn MAPK might be activated, leading to cPLA2 phosphorylation and AA release.

Adenosine Triphosphate↗

Pyogenic liver abscess complicating a ventriculoperitoneal shunt.

Pyogenic liver abscess is a rare complication of ventriculoperitoneal (VP) shunting. We report a 4-month-old female with this complication who was successfully treat ed by computed tomography-guided percutaneous transhepatic catheter drainage, shunt externalization, and parenteral antibiotics. Liver abscess is a possible intra-abdominal complication of VP shunting, and imaging studies are good adjuncts in making the clinical diagnosis.

Female↗

Anorectal function and endopelvic dissection in patients with repaired imperforate anus.

Fifty-eight patients with anorectal malformations were closely followed up for postoperative anorectal function. Constipation was noted shortly after anorectoplasty in 10 of 28 low anomalies (35.7%) treated with limited sagittal anorectoplasty (LSARP), in 18 of 25 high or intermediate anomalies (72.0%) treated with posterior sagittal anorectoplasty (PSARP), but in none of 5 high or intermediate anomalies treated with Rehbein's mucosa-stripping endorectal pull-through and anterior sagittal perineal anorectoplasty (R-ASAP). The constipation resolved mostly within 1-2 years after repair under conservative management, but persisted beyond 2 years after repair in 3/25 children with LSARP and 10/25 with PSARP. Anal soiling was noted in 1/23 (4.3%) LSARP and 6/22 (27.3%) PSARP patients, but normal anorectal function was attained in 20/23 LSARP (86.9%) and 11/12 PSARP patients (50.0%) by the time of toilet training. Manometric studies disclosed that the resting rectal pressure (RRP) was lower and the anorectal pressure gradient (ARPG) higher in the constipated than the non-constipated children, while the RRP was higher and the ARPG lower in the soiled than the non-soiled patients. The ARPG after R-ASPA was close to that of non-constipated and in between that of the constipated and soiled patients. The rectoanal sphincter inhibitory reflex was not related to defecation status or surgical procedures, but showed a tendency toward positive conversion with time or after exclusion of esctatic terminal bowel in the severely constipated. It is concluded that anorectal function in patients with repaired imperforate anus seems to be more affected by the extent of endopelvic dissection than by preservation of the terminal bowel or sphincter muscles.

Anal Canal↗

Prenatal and neonatal intussusception.

Intussusception found in the 1st month of life is rare and usually discussed as one entity, neonatal intussusception, but in fact, includes the intussusceptions occurring both prenatally and neonatally, of which the clinical presentations and results are different. Four full-term babies with prenatal intussusception presenting as intestinal atresia (IA) and three premature babies with neonatal intussusception mimicking necrotizing enterocolitis (NEC) are presented. Prenatal intussusception, as one of the causes of IA produces prominent signs of intestinal obstruction immediately after birth. Preoperative evaluation usually fails to yield a definitive diagnosis, but surgery is usually performed in time and is successful. In neonatal intussusception, full-term infants usually have a pathological lead point and the colon is almost always involved. A barium enema is thus useful in diagnosis. Premature babies, on the other hand, rarely have a colonic component, and the clinical features are insidious and similar to NEC. This results in diagnostic confusion that may lead to a dangerous delay in appropriate surgical correction. A high level of suspicion about this condition in cases diagnosed presumptively with NEC is important. Serial abdominal sonograms may be helpful in the early diagnosis of neonatal intussusception.

Fatal Outcome↗

Hepatocellular carcinoma in children: clinical review and comparison with adult cases.

BACKGROUND: Hepatocellular carcinoma (HCC) in children was rarely reported and usually included with hepatoblastoma in most studies of pediatric liver malignancies despite different clinical behaviors. The authors report their experience in pediatric HCC and discuss its differences from adult HCC. METHODS: A retrospective review of radiographic, laboratory, pathological, and therapeutic data in 55 children with HCC was performed. The liver function was graded by modified Child's classification. Kaplan-Meier survival curves in various therapeutic and Child's groups were plotted, and log-rank test was used to detect differences among survival curves. RESULTS: Although children with HCC mostly presented with advanced disease at diagnosis, disturbances of liver function were unremarkable. Sixty-eight percent of cases concurred with liver cirrhosis. The median survivals for resectable, chemotherapeutic, and untreated HCCs were 23, 3, and 2 months, respectively. Resectable HCC significantly posed a much better prognosis. However, the resectability was unsatisfactory (18.2%). Resection was limited because of anatomic unfeasibility including bilateral involvement (62.5%), portal vein thrombi (41.7%), distant metastasis (29.1%), para-aortic lymphadenopathy (18.8%), inferior vena cava thrombi (16.7%), and hilar invasion (6.3%). Distant metastasis was the most ominous for survival in children with unresectable HCC. CONCLUSIONS: HCC behaved somewhat differently between children and adults. Surgical resection represented the best hope of long-term survival. The outcome in children could not keep up with that in adults because of a diagnostic delay. Hence, alpha-fetoprotein and sonography screening in carrier children should be worthwhile.

Adolescent↗

Successful arterial switch operation in a low-birth-weight neonate who had transposition of the great arteries and advanced necrotizing enterocolitis.

A low-birth-weight (LBW; 1,940 g) girl was born at the gestational age of 36 weeks without any perinatal insult. Transposition of the great arteries (TGA) with a large patent ductus arteriosus (PDA) and interatrial shunt was detected. Stage IIIB necrotizing enterocolitis (NEC) developed 46 hours after birth. She received ileostomy and drainage. Arterial switch operation was successfully performed at 23 days of age when her weight was 1,900 g. The enterostomy was successfully repaired at 104 days of age.

Ductus Arteriosus, Patent↗