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Biomedical subjects

C K Wang

Publications and source records attributed to C K Wang.

At least 37 records · Page 2Linked to original sources

Differential regulation of H- and L-ferritin messenger RNA subunits, ferritin protein and iron following focal cerebral ischemia-reperfusion.

Iron may catalyse the production of reactive oxygen species during post-ischemic reoxygenation and subsequently lead to brain damage. Ferritin, an iron sequestering and storage protein, can also be a source of iron after ischemic insult. However, its role in ischemia-reperfusion has not been carefully investigated. In the present study, we examined the temporal and spatial induction profiles of both H- and L-ferritin messenger RNA and protein in a well-defined focal cerebral ischemia model. Results of northern blot analysis showed a delayed and prolonged induction of both H- and L-ferritin messenger RNA in the ischemic cortex of rats subjected to 60min ischemic insult. A significant induction of both H- and L-ferritin messenger RNA was observed at 12h and remained elevated for up to 336h after the onset of reperfusion. At the peak level, quantitative analysis of the blot indicated a 2.5-fold and a six-fold increase in H- and L-ferritin messenger RNA, respectively, compared with the sham-operated controls. No apparent change in the levels of either messenger RNA was observed in the contralateral side. Results of in situ hybridization studies revealed constitutive expression of both H- and L-ferritin messenger RNA throughout the brain in sham-operated animals, in particular the hippocampus and the piriform cortex. Nevertheless, the signal intensity of H-ferritin messenger RNA was much higher than that of L-ferritin messenger RNA. Seventy-two hours after 60min ischemia, marked expression of H-ferritin messenger RNA was observed in the area surrounding the middle cerebral artery irrigated cortex, the medial part of the caudoputamen and in the subfield of the CA1 hippocampal region of the ipsilateral hemisphere. Similarly, a large induction of L-ferritin messenger RNA was also noted in several areas, including the middle cerebral artery irrigated cortex, the lateral part of the caudoputamen and the stratum pyramidale of the CA1 hippocampal region, which were totally different from areas where H-ferritin messenger RNA was found. At 336h after ischemia, increased expression of H-ferritin messenger RNA was observed in the peri-necrosis and ipsilateral thalamus regions, while L-ferritin messenger RNA was noted exclusively at the edge within the necrosis. Results of immunohistochemical study further revealed that ferritin immunoreactivity was present in the same areas where increased ferritin messenger RNA was found. Sixty-minute ischemia also led to iron deposition in discrete areas. Iron deposition was highly associated with the induction of ferritin, particularly in the macrophage- and microglia-positive areas where cell death or tissue necrosis was noted.In summary, our initial findings indicate that ischemic insult leads to induction of both H- and L-ferritin messenger RNA. In the present study, although the temporal induction profiles were similar, the major expression areas for these two genes were totally different. Ferritin immunoreactivity was observed in the same areas where increased ferritin messenger RNA was found. Ischemia also resulted in iron deposition, which highly associated with the ferritin immunoreactivity. The exact regulatory mechanism and pathological significance for the differential expression of H- and L-ferritin genes following ischemia/reperfusion remain to be clarified.

Animals↗

Numerical simulation of a TLD pulsed laser-heating scheme for determination of shallow dose and deep dose in low-LET radiation fields.

A new method is described to determine the depth-dose distribution in low-LET radiation fields using a thick thermoluminescent dosimeter (TLD) with a pulsed laser-heating scheme to obtain TL glow output. The computational simulation entails heat conduction and glow curve production processes. An iterative algorithm is used to obtain the dose distribution in the detector. The simulation results indicate that the method can predict the shallow and deep dose in various radiation fields with relative errors less than 20%.

Journal Article↗

Spontaneous cell sorting of fibroblasts and keratinocytes creates an organotypic human skin equivalent.

We show that an inherent ability of two distinct cell types, keratinocytes and fibroblasts, can be relied upon to accurately reconstitute full-thickness human skin including the dermal-epidermal junction by a cell-sorting mechanism. A cell slurry containing both cell types added to silicone chambers implanted on the backs of severe combined immunodeficient mice sorts out to reconstitute a clearly defined dermis and stratified epidermis within 2 wk, forming a cell-sorted skin equivalent. Immunostaining of the cell-sorted skin equivalent with human cell markers showed patterns similar to those of normal full-thickness skin. We compared the cell-sorted skin equivalent model with a composite skin model also made on severe combined immunodeficient mice. The composite grafts were constructed from partially differentiated keratinocyte sheets placed on top of a dermal equivalent constructed of devitalized dermis. Electron microscopy revealed that both models formed ample numbers of normal appearing hemidesmosomes. The cell-sorted skin equivalent model, however, had greater numbers of keratin intermediate filaments within the basal keratinocytes that connected to hemidesmosomes, and on the dermal side both collagen filaments and anchoring fibril connections to the lamina densa were more numerous compared with the composite model. Our results may provide some insight into why, in clinical applications for treating burns and other wounds, composite grafts may exhibit surface instability and blistering for up to a year following grafting, and suggest the possible usefulness of the cell-sorted skin equivalent in future grafting applications.

Animals↗

Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion.

The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.

Angiopoietin-1↗

Changes in the level of glial fibrillary acidic protein (GFAP) after mild and severe focal cerebral ischemia.

In the present study, we examined the temporal and spatial expression profiles of GFAP mRNA and protein in a focal cerebral ischemia model with ischemic injury confined to the cerebral cortex in the right middle cerebral artery (MCA) territory. Northern blot analysis showed a respective 5.5-fold and 7.2-fold increase in the GFAP mRNA in the ischemic right MCA cortex in rats subjected to 30-min (mild) or 60-min (severe) ischemia followed by 72-hr reperfusion. The GFAP mRNA signal remained elevated up to 2-week reperfusion. Interestingly, increased GFAP mRNA signal was clearly demonstrated for the first time in the left MCA cortex. A significant 1.5-fold and 5-fold increase was observed after 72-hr reperfusion following mild and severe ischemia, respectively. However, unlike the ischemic right MCA cortex, this induction was transient in the non-ischemic left MCA counterpart. In situ hybridization studies further revealed characteristic spatial induction profile following mild vs. severe ischemia. In mild ischemia, following 24-hr reperfusion, increase in GFAP mRNA was observed mainly within the ischemic right MCA cortex. Following 72-hr reperfusion, GFAP mRNA signal was observed in virtually the entire ischemic cortex, particularly the amygdala region, then gradually reduced and restricted to right MCA territory and subcortical thalamic nucleus following 2-week reperfusion. On the other hand, in severe ischemia, following 24-hr reperfusion increased GFAP mRNA signal was observed in area surrounding right MCA territory (infarct region) and outer cortical layers within the right MCA territory. Following 72-hr reperfusion, no signal was detected within right MCA cortex; however, increased GFAP signal was detected throughout the remaining ipsilateral cortex and subcortical region, as well as the contralateral cerebral cortex. GFAP mRNA signals then gradually reduced its intensity and was restricted to area surrounding necrosis and ipsilateral thalamic nucleus following 2-week reperfusion. GFAP-like immunoreactivity was also detected in area expressing GFAP mRNA. It is very likely that de novo synthesis was responsible for this increase. In summary, increased GFAP signal was noted in both ipsilateral and contralateral cerebral following mild and severe ischemia. Although the temporal induction profile for mild vs. severe ischemia was similar, the spatial induction profile was different. The mechanism leading to this differential induction and their physiological and functional significance are not clear at present. It is very likely that some local factors may involve, nevertheless, the detailed mechanisms remain to be fully explored.

Animals↗

Conformational changes in guanylyl cyclase-activating protein 1 (GCAP1) and its tryptophan mutants as a function of calcium concentration.

Guanylyl cyclase-activating proteins (GCAPs are 23-kDa Ca2+-binding proteins belonging to the calmodulin superfamily. Ca2+-free GCAPs are responsible for activation of photoreceptor guanylyl cyclase during light adaptation. In this study, we characterized GCAP1 mutants in which three endogenous nonessential Trp residues were replaced by Phe residues, eliminating intrinsic fluorescence. Subsequently, hydrophobic amino acids adjacent to each of the three functional Ca2+-binding loops were replaced by reporter Trp residues. Using fluorescence spectroscopy and biochemical assays, we found that binding of Ca2+ to GCAP1 causes a major conformational change especially in the region around the EF3-hand motif. This transition of GCAP1 from an activator to an inhibitor of GC requires an activation energy Ea = 9.3 kcal/mol. When Tyr99 adjacent to the EF3-hand motif was replaced by Cys, a mutation linked to autosomal dominant cone dystrophy in humans, Cys99 is unable to stabilize the inactive GCAP1-Ca2+ complex. Stopped-flow kinetic measurements indicated that GCAP1 rapidly loses its bound Ca2+ (k-1 = 72 s-1 at 37 degrees C) and was estimated to associate with Ca2+ at a rate (k1 > 2 x 10(8) M-1 s-1) close to the diffusion limit. Thus, GCAP1 displays thermodynamic and kinetic properties that are compatible with its involvement early in the phototransduction response.

Animals↗

Edwardsiella tarda bacteraemia--complicated by acute pancreatitis and pyomyoma.

Edwardsiella tarda (E. tarda) has recently become recognized as a pathogen in humans. Here we report a new case of E. tarda bacteraemia complicated by acute pancreatitis and pyomyoma. A 46-year-old female came to our emergency room complaining of sudden onset of left upper quadrant pain and vomiting for the previous few hours after drinking three bottles of wine. An abdominal computed tomography (CT) scan revealed multiple biliary stones, acute pancreatitis with extensive inflammatory change, and a large uterine myoma. Fever, watery diarrhoea, and mild suprapubic discomfort with vaginal spotting were noted soon after admission. The patient's blood cultures yielded E. tarda and symptoms subsided after antibiotic therapy. Fever and severe suprapubic pain with rebound tenderness developed 12 days later. Repeat abdominal CT scan revealed an enlarged uterine myoma with central necrosis. The patient subsequently underwent anterior total hysterectomy and bilateral salpingo-oophorectomy, revealing a uterine myoma with infarction and abscess formation. The patient recovered uneventfully and was discharged 1 week later.

Acute Disease↗

A new approach to film dosimetry for high-energy photon beams using organic plastic scintillators.

This study is concerned with dose measurement of photon beams, both dynamic and static, by using x-ray film. As discussed in our last study (Burch et al 1997, Yeo et al 1997), x-ray film, as an integrating dosimeter, can be an ideal candidate if the over-response problem to low-energy photons (energies below 400 keV) is solved. In summary, the problem of the over-response can be explained as follows. Because the mass energy absorption coefficient of x-ray film increases as photon energy decreases, softening of the photon spectra with depth in a phantom makes the extent of film over-response a function of phantom depth (Burch et al 1997, Yeo et al 1997). Film dosimetry is based upon (a) calibration of the film response (i.e. optical density) at some specific depth in a phantom and (b) conversion of the film density which can cover whole depths in a phantom to dose by using the calibration curve. In megavoltage dosimetry, this normally causes over-response in doses at depths greater than the calibration depth.

Dose-Response Relationship, Radiation↗

MR cholangiography in the evaluation of neonatal cholestasis.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) cholangiography in excluding biliary atresia as the cause of neonatal cholestasis. MATERIALS AND METHODS: MR cholangiography was performed on 10 control and 16 jaundiced neonates and infants aged 3 days to 5 months. Diagnosis of biliary atresia (n = 6) was confirmed with surgery and liver biopsy, with or without surgical cholangiography. Diagnosis of neonatal hepatitis (n = 9) was confirmed with clinical follow-up until jaundice resolved. In one infant, paucity of intrahepatic ducts was diagnosed at liver biopsy. MR cholangiography was performed with respiratory-triggered, heavily T2-weighted turbo spin-echo and optional inversion-recovery turbo spin-echo sequences. Diagnosis of biliary atresia was based on nonvisualization of either the common bile duct or common hepatic duct. Cholescintigraphy with technetium 99m disofenin was performed in all 16 jaundiced patients. RESULTS: In the 10 controls, the nine patients with neonatal hepatitis, and the one infant with paucity of intrahepatic ducts, MR cholangiography clearly depicted the gallbladder and common hepatic and common bile ducts. MR cholangiography was 100% accurate in excluding biliary atresia as the cause of neonatal cholestasis, while 99mTc disofenin cholescintigraphic findings were false-positive in four of 10 patients with nonobstructive cholestasis. CONCLUSION: MR cholangiography can be used to depict the major biliary structures of neonates and small infants and to exclude biliary atresia as the cause of neonatal cholestasis by allowing visualization of the biliary tract.

Biliary Atresia↗

Diagnostic efficacy of non-breath-hold magnetic resonance cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) is an emerging imaging technique for direct visualization of biliary and pancreatic ducts without the need for an invasive procedure, ionizing radiation, or iodine contrast media administration. The purpose of this study was to evaluate the efficacy of non-breath-hold MRCP in depicting normal and diseased biliary and pancreatic ducts. A retrospective analysis of 162 patients who underwent MRCP was performed, and a comparison between MRCP and direct cholangiography was made. The overall accuracy of MRCP in diagnosing malignant and benign pancreaticobiliary diseases was also calculated. MRCP depicted more than three hepatic segments in 99% of patients with dilated intrahepatic ducts and in 63% of patients with nondilated intrahepatic ducts. MRCP demonstrated the main hepatic duct, gallbladder, and cystic duct in 100%, 89%, and 72% of patients, respectively. The dilated extrahepatic duct, nondilated extrahepatic duct, dilated pancreatic duct, and nondilated pancreatic duct were visualized in 100%, 98%, 95%, and 77% of patients, respectively. The accuracy of MRCP in diagnosing hepatolithiasis, cholecystolithiasis, and choledocholithiasis was 96%, 97%, and 96%, respectively. The obstruction levels and characteristics determined by MRCP were in agreement with those determined from direct cholangiography in 98% of malignant obstructions and 89% of benign obstructions. The overall accuracy of a combination of MRCP and conventional magnetic resonance imaging in diagnosing pancreaticobiliary diseases was 81% for malignant diseases, 86% for benign diseases, and 82% for stone diseases. We conclude that non-breath-hold MRCP can reliably depict normal and diseased pancreaticobiliary ducts except for cystic ducts and nondilated pancreatic ducts.

Adolescent↗

Imaging features of simultaneous occurrence of renal and pancreatic foreign body granuloma due to chronically retained gauze: a case report.

Herein we are reporting a case of simultaneous occurrence of renal and pancreatic foreign body granuloma due to retained gauze. The different imaging features of the two lesions make correct preoperative diagnosis difficult. Foreign body granulomas due to retained surgical gauze or sponges should be considered in patients who have previous histories of operations and who also have a mass in the surgical bed. Simultaneous occurrence of foreign body granuloma away from primary surgical field is also possible.

Adult↗

Measurement of distributions of small-scale energy depositions from low-linear energy transfer particles using the superheated drop detector.

We have developed a new detection method for measuring distributions of energy depositions from particles characterized by low linear energy transfers (LETs). In particular, we have developed a detection system to measure energy depositions produced by electrons and photons on nanometer scales. The detector is based upon the operational principles of the superheated drop detector (SDD). SDDs consist of tiny droplets of superheated liquid suspended within a gel-like emulsion. The SDDs in this study are fabricated using Freon-115 and a glycerol-based gel as the superheated liquid and host medium. This SDD configuration is operated as a threshold temperature-dependent detector for measuring nanoscopic distributions of energy depositions from low-LET particles. Measured results are compared to the calculated distributions of energy depositions along an electron track. A new electron track code, ESLOW3.1, is used to perform the computational study. Measurements show good agreement with computational results in the energy deposition range of 40-200 eV.

Electrons↗

Extent of laminin-5 assembly and secretion effect junctional epidermolysis bullosa phenotype.

Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein-protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly.

Adult↗

Carbon dioxide enhanced ultrasonography of hepatic haemangiomas.

The purpose of this study was to characterize the imaging manifestations of carbon dioxide enhanced ultrasonography (CO2US) in hepatic haemangiomas. CO2US was performed for 52 haemangiomas in 25 patients and for 352 various hepatic nodules in 192 patients. Characteristic enhancement patterns for hepatic haemangiomas were noted. All 39 large haemangiomas (> 1 cm) demonstrated peripheral nodular enhancement in the early and parenchymal phases associated with delayed washout character (> 30 min). Centripetal fill-in of CO2 was noted in 82.1% of large haemangiomas. Two enhancing patterns were noted in 13 small haemangiomas (< 1 cm): peripheral nodular (69.2%) and homogeneous (30.8%). Delayed washout was also noted in all small haemangiomas. Centripetal fill-in of CO2 was hard to define in small haemangiomas. None of the other 352 hepatic nodules had the same imaging features. In conclusion we found that CO2US is valuable in differentiating hepatic haemangiomas from other liver tumours in clinically doubtful cases.

Adult↗

Alcohol-related problems in Taiwan with particular emphasis on alcoholic liver diseases.

Socioeconomic development has led to a progressive increase of alcohol consumption in Taiwan, with an accompanying increase in alcohol-related psychiatric problems, traffic accidents, and liver disease. The prevalent rates of alcohol dependence for Han Chinese and Fomosan aborigines were 0.1% and 1%, respectively in 1950. The rate of alcohol dependence increased to 23% for aborigines in 1995. The number of cases of death and serious injuries due to alcohol-related traffic accident has decreased, and the number of fatalities resulting from these accidents has decreased from third to eighth since the inception of a program of random traffic stops with alcohol breath test in 1997. Alcohol liver disease (ALD) was defined as daily alcohol consumption of 60 g, for a duration of longer than 5 years. We classified ALD patients into two groups: (1) those whose average daily consumption of alcohol exceeded 120 g for a duration longer than 15 years (group A); and (2) all other patients (group B). The case records of 33 cases of biopsy-confirmed ALD were obtained for study. The average of daily alcohol consumption in these cases was 160 g. All but one of these patients were male, age ranged from 26 to 69 years, with an average of 43.1. Clinically, ill-defined gastrointestinal symptoms were the most common presentation (61%), and hepatomegaly was the main physical sign (73%). The average mean corpuscular volume values of ALD and non-ALD patients were 102.3 +/- 10.94 and 94.5 +/- 8.1, respectively (p < 0.01). The mean corpuscular volume values of group A and group B were 102.9 +/- 9.7 vs. 96.5 +/- 9.11 (p < 0.05). Result from serum SGOT/SGPT and gamma-glutamyltransferase/alkaline phosphatase for ALD and non-ALD revealed statistically significant differences between these groups. Using the avidin-biotin complex technique, tissue IgA deposition for ALD patients was found to be different from that of non-ALD patients. Ten of 13 ALD patients vs. 2 of 13 non-ALD patients had continuous-form IgA deposition. Histologically, 45.5% of ALD patients had alcoholic cirrhosis, whereas alcoholic hepatitis was present in only 9.1% of patients. Overall, 88% of cases showed various severity of fatty metamorphosis.

Adult↗

Intra-arterial carbon dioxide-enhanced ultrasonogram of hepatocellular carcinoma treated by transcatheter arterial embolization and percutaneous ethanol injection therapy.

The purpose of this study was to investigate the value of carbon dioxide-enhanced ultrasonography (CO2-US) in the evaluation of viable hepatocellular carcinomas (HCC) which were treated by transcatheter arterial embolization (TAE), percutaneous ethanol injection (PEI), or a combination treatment (TAE and PEI). Forty-one patients with 66 HCC were included in the study. They underwent CO2-US and angiography were performed in all tumours after they were treated by TAE, PEI or a combination treatment. Forty-six tumours were positively enhanced by CO2-US and 40 of them were positive by angiography. These 46 tumours were proved to be viable tumours either by biopsy or by follow-up studies. The positive predictive value was 100% for CO2-US and 87.8% in angiography. Twenty tumours were negative by CO2-US and these were also negative by angiography. Carbon dioxide-enhanced ultrasonography is a more reliable method for detecting the viable portion of the treated HCC compared with conventional angiography.

Adult↗

Calibration and characterization of beta-particle sources for intravascular brachytherapy.

The calibration of a catheter-based system to be used for therapeutic radiation treatment to prevent restenosis following interventional coronary procedures is described. The primary dosimetry was performed ionometrically using an extrapolation chamber equipped with a 1-mm diameter collecting electrode to measure absorbed dose in tissue equivalent plastic at a depth of 2 mm. These results are compared with measurements with radiochromic dye film, which is also used to characterize sources for axial and trans-axial uniformity, and to determine dose distributions at various depths. A protocol for dose calculation based on that of AAPM TG43 is suggested for these sources, and examples of its use are given for the calculation of the enhancement effect on dose rate from a single seed source due to neighboring seeds. Monte Carlo calculations were also performed to validate the measured results.

Beta Particles↗

Anticardiolipin antibody-related Budd-Chiari syndrome: report of a case.

We report a case of a 37-year-old female who suffered from upper abdominal pain, progressive abdominal distention, shortness of breath, palpitation and pitting edema of lower legs for more than one month. Abdominal sonography showed small caliber of hepatic veins, mild hepatosplenomegaly and moderate ascites. Computed tomography of abdomen disclosed extensive thrombi in bilateral femoral veins, ovarian veins and inferior vena cava. Ascites was transudate with normal cell count. Laboratory data showed hypoalbuminemia, mild elevation of total bilirubin and iron deficiency anemia. Anti-cardiolipin antibody was positive and antinuclear antibody was negative. The histopathological features, including sinusoidal dilatation with atrophic change of adjacent hepatocytes, slight congestion and hemosiderin-like material within the cytoplasm of Kupffer cells, were compatible with the criteria of Budd-Chiari syndrome. Heparin was intravenously administered immediately to prevent further progression of thrombosis. The ascites was successfully controlled with diuretics (spironolactone and furosemide). After a two-week course of treatment, she was discharged in good condition and on warfarin anti-coagulant medication.

Adult↗