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1.
Clin Radiol ; 63(5): 518-28, 2008 May.
Article in English | MEDLINE | ID: mdl-18374715

ABSTRACT

PURPOSE: To examine the imaging features of non-small cell lung carcinomas (NSCLC) overlooked at digital chest radiography (dCXR), and compare general and thoracic radiologists' performance for lung carcinoma detection at dCXR. METHODS: Frontal and lateral dCXR from 30 consecutive patients with lung carcinoma overlooked during initial interpretation and 30 normal controls were independently retrospectively reviewed by two blinded thoracic radiologists and, in a separate review, three blinded general radiologists. The location, size, histopathology, borders, presence of superimposed structures, and lesion opacity were recorded. Interobserver agreement was calculated, and the detection performance between thoracic and general radiologists was compared. RESULTS: The average patient age was 67.9 years (range 47-82 years). The average size of carcinomas missed by the thoracic radiologists was 18.1mm (range 10-32 mm). Lesion margins were circumscribed in 29% (2/7), and 71% (5/7) of missed lesions were obscured by anatomical superimposition. Seventy-one percent (5/7) of missed lesions were solid nodules on computed tomography (CT) images. Forty-three percent of lesions were located in the upper lobes and 63% were adenocarcinomas. Compared with general radiologists, the seven NSCLC missed by the thoracic radiologists tended to be smaller (p=0.063), had significantly lower CT density measurements (-92.4+/-87.5 HU versus -70+/-87.2 HU, p=0.050), and more commonly had an ill-defined margin (p=0.026). The clinical stage of the overlooked lesions did not differ between the two groups (p=0.480). CONCLUSIONS: The lesion size, location, conspicuity, and histopathology impact the likelihood of lung carcinoma detection at dCXR in a fashion similar to that of conventional film-screen techniques.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Radiology/statistics & numerical data , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Diagnostic Errors/prevention & control , Diagnostic Errors/statistics & numerical data , Female , Humans , Lung Neoplasms/pathology , Male , Medical Staff, Hospital/standards , Middle Aged , Observer Variation , Radiology/standards , Retrospective Studies , Tomography, X-Ray Computed/methods
2.
Cardiovasc Intervent Radiol ; 31(4): 735-44, 2008.
Article in English | MEDLINE | ID: mdl-18427894

ABSTRACT

Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 microm, N = 9; and (B) 47-180 microm, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/8 [corrected] patients) for group A and 72.2% [corrected] for group B (13/18 [corrected] patients) (p < 0.01). [corrected] No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 microm) are superior to large ones (>180 microm).


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Heart Neoplasms/therapy , Liver Neoplasms/therapy , Neoplastic Cells, Circulating/pathology , Vascular Neoplasms/therapy , Adult , Aged , Analysis of Variance , Angiography , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/secondary , Catheterization/methods , Cohort Studies , Female , Heart Atria/pathology , Heart Neoplasms/mortality , Heart Neoplasms/secondary , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Palliative Care , Prognosis , Risk Assessment , Survival Analysis , Tomography, X-Ray Computed , Treatment Outcome , Vascular Neoplasms/mortality , Vascular Neoplasms/secondary , Vena Cava, Inferior
3.
Thorax ; 61(6): 528-34, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16517574

ABSTRACT

BACKGROUND: The role of anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies as a diagnostic marker in idiopathic pulmonary alveolar proteinosis (iPAP) remains unclear. METHODS: Anti-GM-CSF antibodies were detected in blood and bronchoalveolar lavage fluid (BAL) fluid in 13 patients with iPAP. Three patients with secondary PAP, 35 with other pulmonary disorders, and 10 subjects without lung lesions acted as controls. Blood samples only were obtained from 30 healthy medical personnel. Anti-GM-CSF antibodies were detected using immunoblotting and measured semi-quantitatively by serial dilution or concentration methods. The relationship between antibodies and reported severity indicators for iPAP was analysed. RESULTS: Anti-GM-CSF antibodies could be detected in both blood and BAL fluid samples in 12 of 13 iPAP patients and were undetectable in blood and/or BAL fluid from the other subjects studied. BAL fluid levels of anti-GM-CSF antibodies were highly correlated with the severity indicators for iPAP, including serum lactate dehydrogenase (LDH) levels, arterial oxygen tension, alveolar-arterial oxygen tension difference, (AaPO2), lung carbon monoxide transfer factor, and some lesion scores on chest radiographs and computed tomographic scans. In contrast, blood anti-GM-CSF antibodies were not significantly correlated with the severity indicators evaluated. In addition, patients with iPAP who required subsequent therapeutic lung lavage had significantly higher values of serum LDH, AaPO2, and BAL fluid anti-GM-CSF antibodies, and significantly lower values of PaO2. CONCLUSIONS: In addition to serum LDH levels, PaO2 and AaPO2, BAL fluid levels of anti-GM-CSF antibodies might reflect disease severity in patients with iPAP and predict the need for subsequent therapeutic lung lavage. These findings may expand the role of anti-GM-CSF antibodies in iPAP.


Subject(s)
Antibodies/analysis , Biomarkers/analysis , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Pulmonary Alveolar Proteinosis/diagnosis , Adolescent , Adult , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Female , Humans , Male , Middle Aged
4.
Int J Clin Pract Suppl ; (147): 12-4, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15875610

ABSTRACT

This article reports a case of transient augmentation of collateral circulation due to spontaneous coronary arterial spasm during angiography. The patient's electrocardiogram revealed ST-segment depression during vasospastic attack; this depression differs from the typical change of the ST-segment elevation in coronary spasm without collateral circulation.


Subject(s)
Collateral Circulation , Coronary Vasospasm/physiopathology , Coronary Angiography/adverse effects , Coronary Vasospasm/diagnostic imaging , Coronary Vasospasm/etiology , Humans , Male , Middle Aged
5.
Int J Clin Pract Suppl ; (147): 15-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15875611

ABSTRACT

Electrocardiogram showing Wolff-Parkinson-White (WPW) pattern in an asymptomatic patient is common, but it is difficult to assess the potential risk of sudden death in such cases. Although the incidence of sudden death in these patients is extremely low, an interventional approach is suggested for all patients despite its controversial nature. Syncope, despite being induced by various mechanisms, has been considered an alarming sign of sudden death of WPW syndrome. We describe a 16-year-old female patient with an electrocardiogram that demonstrated a WPW pattern combined with unexplained syncope. None of the examinations, including biochemical profiles, brain computed tomography, transthoracic echocardiography, head-up tilt table test and exercise electrocardiogram, clarified her syncope. Consequently, no further electrophysiologic study was performed for this patient. Unfortunately, the patient suffered sudden death while running. The case highlights the need for vigilance when unexplained syncope combined with WPW syndrome. Such cases have high risk of sudden death, and thus, further interventional study and treatment is indicated.


Subject(s)
Death, Sudden, Cardiac/etiology , Syncope/complications , Wolff-Parkinson-White Syndrome/complications , Adolescent , Electrocardiography , Fatal Outcome , Female , Humans
6.
Opt Lett ; 27(17): 1549-51, 2002 Sep 01.
Article in English | MEDLINE | ID: mdl-18026502

ABSTRACT

Thin films of Bi were grown by pulsed laser deposition on glass substrates at room temperature. The thickness and roughness of the films were characterized by grazing-incidence x-ray reflectivity, and the complex refractive indices were measured in the range from 1.5 to 4 eV by spectroscopic ellipsometry. We performed Z-scan measurements to study the third-order optical nonlinearity of the films. It was found that the Bi films exhibited an unusually large nonlinear refractive coefficient, n(I)~1.24x10(-1) cm(2)/kW and nonlinear absorption coefficient, alpha(I)~-3.97 cm/W , at low laser intensity, ~60 kW/cm(2) . This anomaly is believed to have an origin related to melting of the Bi films at the focus spot by the laser beam.

7.
Cardiology ; 95(4): 183-9, 2001.
Article in English | MEDLINE | ID: mdl-11585993

ABSTRACT

The aim of this study was to evaluate the prevalence of coronary calcification among moderate- to high-risk Chinese patients and to evaluate the ability of the coronary calcium score determined by electron beam computed tomography (EBCT) to predict angiographic coronary artery disease in this population. We enrolled 163 consecutive patients and analyzed their cardiovascular risk factors, coronary calcium scores and coronary angiogram results. One hundred and twenty-five patients (76.7%) had a positive EBCT scan result (coronary calcium score >0). The prevalence of calcification and the calcium scores showed a graded relation to the number of cardiovascular risk factors and age (p < 0.001 for trend). Coronary calcium scores showed statistically significant differences between patients with angiographic evidence of coronary artery disease and patients with normal coronary angiography (p < 0.05), but could not differentiate between patients with significant and insignificant coronary artery disease. Receiver operating characteristic curve analysis showed that a coronary calcium score >5 predicted angiographic coronary artery disease with 93% sensitivity and 86% specificity (area under the curve 0.95 +/- 0.019). Multivariate analysis showed a coronary calcium score >5 to be the strongest independent predictor of angiographic coronary artery disease (odds ratio 120.7, 95% confidence interval 21.7-671.4; p < 0.001). Coronary calcium score determined by EBCT appears to have a similar predictive value in Chinese patients as it does in other ethnic populations that have been reported to date.


Subject(s)
Calcinosis/diagnostic imaging , Coronary Artery Disease/diagnostic imaging , Adult , Aged , Aged, 80 and over , Coronary Angiography , Female , Humans , Male , ROC Curve , Sensitivity and Specificity , Statistics as Topic , Tomography, X-Ray Computed
8.
Plant J ; 27(2): 101-13, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11489188

ABSTRACT

The Arabidopsis NPR1/NIM1 gene is a key regulator of systemic acquired resistance (SAR). Over-expression of NPR1 leads to enhanced resistance in Arabidopsis. To investigate the role of NPR1 in monocots, we over-expressed the Arabidopsis NPR1 in rice and challenged the transgenic plants with Xanthomonas oryzae pv. oryzae (Xoo), the rice bacterial blight pathogen. The transgenic plants displayed enhanced resistance to Xoo. RNA blot hybridization indicates that enhanced resistance requires expression of NPR1 mRNA above a threshold level in rice. To identify components mediating the resistance controlled by NPR1, we used NPR1 as bait in a yeast two-hybrid screen. We isolated four cDNA clones encoding rice NPR1 interactors (named rTGA2.1, rTGA2.2, rTGA2.3 and rLG2) belonging to the bZIP family. rTGA2.1, rTGA2.2 and rTGA2.3 share 75, 76 and 78% identity with Arabidopsis TGA2, respectively. In contrast, rLG2 shares highest identity (81%) to the maize liguleless (LG2) gene product, which is involved in establishing the leaf blade-sheath boundary. The interaction of NPR1 with the rice bZIP proteins in yeast was impaired by the npr1-1 and npr1-2 mutations, but not by the nim1-4 mutation. The NPR1-rTGA2.1 interaction was confirmed by an in vitro pull-down experiment. In gel mobility shift assays, rTGA2.1 binds to the rice RCH10 promoter and to a cis-element required sequence-specifically for salicylic acid responsiveness. This is the first demonstration that the Arabidopsis NPR1 gene can enhance disease resistance in a monocot plant. These results also suggest that monocot and dicot plants share a conserved signal transduction pathway controlling NPR1-mediated resistance.


Subject(s)
Arabidopsis/metabolism , Fungal Proteins/physiology , Oryza/genetics , Protein Kinases , Saccharomyces cerevisiae Proteins , Signal Transduction , Xanthomonas/pathogenicity , Amino Acid Sequence , Base Sequence , DNA Primers , DNA, Complementary , Fungal Proteins/genetics , Molecular Sequence Data , Mutation , Oryza/metabolism , Oryza/microbiology , Plant Proteins/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Plants, Genetically Modified/microbiology , Sequence Homology, Amino Acid
9.
Catheter Cardiovasc Interv ; 53(3): 314-22, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11458407

ABSTRACT

We compared the acute and long-term outcomes of stentings in coronary vessels > 3.0 mm, 3.0-2.5 mm, and < 2.5 mm. A total of 1,152 patients underwent coronary stenting was divided into three groups based on the reference vessel size. Group A consisted of 598 patients (667 lesions) with a reference vessel diameter > 3.0 mm, group B 485 patients (544 lesions) with a reference vessel diameter of 3.0-2.5 mm, and group C 114 patients (119 lesions) with a reference vessel diameter < 2.5 mm. The procedural success, stent thrombosis, and in-hospital cardiac event rate were similar in the three groups. At 6-month angiographic follow-up, the lesion restenotic rate was significantly higher in the small-vessel group (14%, 22%, and 26% in groups A, B, and C, respectively; P = 0.011). These differences appeared to result from a lesser acute gain and a lesser net gain in small-vessel group; the late luminal loss was similar in the three groups. During a follow-up duration of 28 +/- 3 months, group C patients had a significantly lower rate of event-free survival than the group A and B patients (71% vs. 85% and 82%; P = 0.002). Stepwise regression analysis demonstrated that complex lesion (P = 0.032) and long lesion (P = 0.046) are independent predictors of restenosis in very-small-vessel (< 2.5 mm) stenting. In conclusion, the acute results of stenting in small coronary arteries appear safe and feasible with a high procedural success rate and a low incidence of stent thrombosis. Stenting in patients with a small coronary artery appears to have a similar in-hospital cardiac event rate, but a higher angiographic restenosis rate and a lower event-free survival rate, compared to stenting in patients with a larger coronary artery. The predictors of restenosis in very-small-vessel stenting are complex lesions and long lesions. Cathet Cardiovasc Intervent 2001;53:314-322.


Subject(s)
Coronary Disease/therapy , Coronary Vessels/surgery , Stents/adverse effects , Aged , Coronary Angiography , Coronary Disease/diagnostic imaging , Female , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
10.
Hum Biol ; 73(3): 451-60, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11459425

ABSTRACT

Apolipoprotein B (apoB, protein; APOB, gene) is the main protein component of low-density lipoprotein (LDL) and plays an important role in blood lipid metabolism. Previously, we have reported four APOB coding regions, 5' signal peptide, and 3' repeat sequence polymorphisms in our population. In this report, we further characterize other APOB genetic variations. The results illustrate that the mutation frequencies for Arg3500Gln (1/846 alleles), Arg4019Trp (2/786 alleles), -265 C/T promoter region (0/264 alleles), and intron 2 A/G (0/450 alleles) are very low. Our population showed a frequency of 68.9% for the B4311 Ser allele. The B4311 Asn allele was associated with a higher apoB level than the Ser group (p < 0.05) in normal controls. In the normal controls, a higher B4311 Asn/Asn genotype frequency was found in the group with total cholesterol (TC) > 200 mg/dL and apoB concentration > 85 mg/dL than in the group with a TC < 200 mg/dL and apoB < 85 mg/dL (p = 0.03 for TC comparison).


Subject(s)
Apolipoproteins B/genetics , Coronary Disease/genetics , Polymorphism, Genetic , Analysis of Variance , Case-Control Studies , Female , Humans , Lipids/blood , Male , Middle Aged , Taiwan
11.
Can J Cardiol ; 17(6): 667-76, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11420578

ABSTRACT

BACKGROUND: The detection of coronary artery calcification by electron beam computed tomography (EBCT) has been suggested as an indicator of atherosclerosis and coronary artery disease (CAD). There is no consensus on the correlation between coronary calcification and angiographically significant stenosis on an artery-by-artery basis. OBJECTIVE: To examine the relationship between coronary calcification score (CCS) and the presence of significant CAD on an artery-by-artery basis in patients with stable angina pectoris. METHODS AND RESULTS: EBCT and coronary angiogram (CAG) were evaluated in 71 patients with stable angina and in nine control subjects. The CCSs of each of the four major coronary arteries were highest in patients with significant CAD (n=43), followed by patients with insignificant CAD (n=5), patients with syndrome X (n=23) and control subjects, respectively. Calcification scores of the four major coronary arteries appeared to have different predictive power for significant stenosis on the same vessel. For left main (LM) and left anterior descending (LAD) coronary arteries, CCSs of vessels with significant stenoses were not different from those without significant stenoses (values expressed as medians: LM 0 versus 1; LAD 98.5 versus 70; not significant). Calcification scores of left circumflex (LCX) and right coronary arteries (RCA) were significantly higher in vessels with significant stenosis (LCX 49.5 versus 0; RCA 53 versus 1; P<0.05). CCSs appeared to be moderately useful to predict significant stenoses in these two vessels (areas under receiver operating characteristic curves: LCX 0.68+/-0.08, 95% CI 0.52 to 0.81; RCA 0.71+/-0.08, 95% CI 0.55 to 0.84). CONCLUSIONS: The CCSs of RCA and LCX arteries, but not those of LM and LAD arteries, may predict significant angiographic stenosis on an artery-by-artery basis among patients with stable angina pectoris.


Subject(s)
Angina Pectoris/complications , Calcinosis/diagnostic imaging , Coronary Disease/diagnostic imaging , Tomography, X-Ray Computed , Aged , Analysis of Variance , Calcinosis/complications , Case-Control Studies , Chi-Square Distribution , Coronary Angiography , Coronary Disease/complications , Female , Humans , Male , Middle Aged , ROC Curve , Risk Factors , Statistics, Nonparametric
12.
Chem Biol Interact ; 130-132(1-3): 193-9, 2001 Jan 30.
Article in English | MEDLINE | ID: mdl-11306043

ABSTRACT

An NAD-linked aldehyde dehydrogenase which in addition to aliphatic and aromatic aldehydes, metabolizes aminoaldehydes and betaine aldehyde, has been purified to homogeneity from male Sprague-Dawley rat liver mitochondria. The properties of the rat mitochondrial enzyme are similar to those of a rat liver cytoplasmic betaine aldehyde dehydrognase and the human cytoplasmic E3 isozyme. The primary structure. of four tryptic peptides were also similar; only one difference in primary structure was observed. The close similarity of properties of the cytoplasmic with the mitochondrial form suggest that the cytoplasmic and mitochondrial betaine aldehyde dehydrogenase may be coded for by the same nuclear gene. Investigation of the mitochondrial form by isoelectric focusing resulted in visualization of multiple forms, different from those seen in the cytoplasm suggesting that the enzyme may be processed in the mitochondria.


Subject(s)
Aldehyde Oxidoreductases/isolation & purification , Aldehyde Oxidoreductases/metabolism , Mitochondria, Liver/enzymology , Aldehyde Oxidoreductases/genetics , Amino Acid Sequence , Animals , Betaine-Aldehyde Dehydrogenase , Cytoplasm/enzymology , Humans , In Vitro Techniques , Isoelectric Focusing , Male , Peptide Fragments/chemistry , Peptide Fragments/genetics , Peptide Fragments/isolation & purification , Rats , Rats, Sprague-Dawley , Sequence Homology, Amino Acid , Tissue Distribution , Trypsin
13.
Mol Plant Microbe Interact ; 14(2): 204-13, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11204784

ABSTRACT

An 8.1-kb DNA fragment from Xanthomonas oryzae pv. oryzae that contains six open reading frames (ORF) was cloned. The ORF encodes proteins similar to flagellar proteins FlhB, FlhA, FlhF, and FliA, plus two proteins of unknown function, ORF234 and ORF319, from Bacillus subtilis and other organisms. These ORF have a similar genomic organization to those of their homologs in other bacteria. TheflhF gene product, FlhF, has a GTP-binding motif conserved in its homologs. Unlike its homologs, however, X. oryzae pv. oryzae FlhF carries two transmembrane-like domains. Insertional mutations of theflhF gene with the omega cassette or the kanamycin resistance gene significantly retard but do not abolish the motility of the bacteria. Complementation of the mutants with the wild-type flhF gene restored the motility. The X. oryzae pv. oryzae FlhF interacts with itself; the disease resistance gene product XA21; and a protein homologous to the Pill protein of Pseudomonas aeruginosa, XooPilL, in the yeast two-hybrid system. The biological relevance of these interactions remains to be determined.


Subject(s)
Bacterial Proteins , Flagella/genetics , Monomeric GTP-Binding Proteins/genetics , Operon , Xanthomonas/genetics , Amino Acid Sequence , Base Sequence , DNA Primers , Molecular Sequence Data , Monomeric GTP-Binding Proteins/chemistry , Mutation , Phenotype , Sequence Homology, Amino Acid
14.
Biochem Pharmacol ; 60(11): 1629-37, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11077045

ABSTRACT

Betaine aldehyde levels were determined in rat livers following 4 weeks of ethanol feeding, employing the Lieber-De Carli liquid diet. The results showed that the levels of betaine aldehyde are unaffected by alcohol feeding to rats. These levels in both experimental and control animals were found to be quite low, 5.5 nmol/g liver. Betaine aldehyde levels have not been determined previously in mammalian liver because of methodological difficulties. This investigation employed fast atom bombardment-mass spectroscopy to determine the levels of betaine aldehyde, betaine, and choline. The decrease in betaine levels following ethanol administration confirmed the results of other investigators. Choline levels determined during this investigation were lower than previously reported. The reason for starting this investigation was the fact that the enzyme that catalyzes betaine aldehyde dehydrogenation to betaine, which is distributed in both mitochondria and the cytoplasm, was found to also metabolize acetaldehyde with K(m) and V(max) values lower than those for betaine aldehyde. Thus, it appeared likely that the metabolism of acetaldehyde during ethanol metabolism might inhibit betaine aldehyde conversion to betaine and thereby result in decreased betaine levels (Barak et al., Alcohol 13: 395-398, 1996). The fact that betaine aldehyde levels in alcohol-fed animals were similar to those in controls demonstrates that competition between acetaldehyde and betaine aldehyde for the same enzyme does not occur. This complete lack of competition suggests that betaine aldehyde dehydrogenase in the mitochondrial matrix may totally metabolize betaine aldehyde to betaine without any involvement of cytoplasmic betaine aldehyde dehydrogenase.


Subject(s)
Betaine/analogs & derivatives , Betaine/metabolism , Choline/metabolism , Ethanol/metabolism , Liver/metabolism , Acetaldehyde/chemistry , Animals , Betaine/chemistry , Central Nervous System Depressants/pharmacology , Cytoplasm/drug effects , Cytoplasm/metabolism , Ethanol/pharmacology , Isoelectric Focusing , Kinetics , Liver/drug effects , Male , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Rats , Rats, Sprague-Dawley
15.
J Mol Biol ; 300(5): 1257-69, 2000 Jul 28.
Article in English | MEDLINE | ID: mdl-10903867

ABSTRACT

We investigated the epoxidase activity of a class mu glutathione S-transferase (cGSTM1-1), using 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as substrate. Trp209 on the C-terminal tail, Arg107 on the alpha4 helix, Asp161 and Gln165 on the alpha6 helix of cGSTM1-1 were selected for mutagenesis and kinetic studies. A hydrophobic side-chain at residue 209 is needed for the epoxidase activity of cGSTM1-1. Replacing Trp209 with histidine, isoleucine or proline resulted in a fivefold to 28-fold decrease in the k(cat)(app) of the enzyme, while a modest 25 % decrease in the k(cat)(app) was observed for the W209F mutant. The rGSTM1-1 enzyme has serine at the correponding position. The k(cat)(app) of the S209W mutant is 2. 5-fold higher than that of the wild-type rGSTM1-1. A charged residue is needed at position 107 of cGSTM1-1. The K(m)(app)(GSH) of the R107L mutant is 38-fold lower than that of the wild-type enzyme. On the contrary, the R107E mutant has a K(m)(app)(GSH) and a k(cat)(app) that are 11-fold and 35 % lower than those of the wild-type cGSTM1-1. The substitutions of Gln165 with Glu or Leu have minimal effect on the affinity of the mutants towards GSH or EPNP. However, a discernible reduction in k(cat)(app) was observed. Asp161 is involved in maintaining the structural integrity of the enzyme. The K(m)(app)(GSH) of the D161L mutant is 616-fold higher than that of the wild-type enzyme. In the hydrogen/deuterium exchange experiments, this mutant has the highest level of deuteration among all the proteins tested. We also elucidated the structure of cGSTM1-1 co-crystallized with the glutathionyl-conjugated 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) at 2.8 A resolution. The product found in the active site was 1-hydroxy-2-(S-glutathionyl)-3-(p-nitrophenoxy)propane, instead of the conventional 2-hydroxy isomer. The EPNP moiety orients towards Arg107 and Gln165 in dimer AB, and protrudes into a hydrophobic region formed by the loop connecting beta1 and alpha1 and part of the C-terminal tail in dimer CD. The phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD. We hypothesize that these two conformations represent the EPNP moiety close to the initial and final stages of the reaction mechanism, respectively.


Subject(s)
Amino Acid Substitution/genetics , Glutathione Transferase/chemistry , Glutathione Transferase/metabolism , Nitrophenols/metabolism , Oxidoreductases/chemistry , Oxidoreductases/metabolism , Animals , Binding Sites , Chickens , Crystallography, X-Ray , Deuterium/metabolism , Epoxy Compounds/chemistry , Epoxy Compounds/metabolism , Glutamine/genetics , Glutamine/metabolism , Glutathione/metabolism , Glutathione Transferase/classification , Glutathione Transferase/genetics , Hydrogen Bonding , Kinetics , Models, Molecular , Mutation/genetics , Nitrophenols/chemistry , Oxidoreductases/classification , Oxidoreductases/genetics , Protein Conformation , Protons , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Structure-Activity Relationship , Temperature , Tryptophan/genetics , Tryptophan/metabolism , Tyrosine/genetics , Tyrosine/metabolism
16.
Am J Med Sci ; 320(1): 64-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10910375

ABSTRACT

Amiodarone, an iodine-rich benzofuran derivative, is a highly effective agent for the prophylaxis and treatment of cardiac arrhythmias, but it is associated with numerous side effects. Amiodarone toxicity involving several organs simultaneously has rarely been reported heretofore. In this report, we describe a case of a 73-year-old man who developed symptomatic hypothyroidism, pulmonary toxicity, and vortex epitheliopathy of the cornea during 6 months of amiodarone therapy for frequent palpitation and angina after myocardial infarction. This case illustrates that amiodarone may cause toxicity involving several organs concurrently in a patient receiving long-term amiodarone therapy. This may be of clinical significance in managing such patients.


Subject(s)
Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Cornea/drug effects , Hypothyroidism/chemically induced , Lung/drug effects , Aged , Humans , Male
17.
Am J Clin Oncol ; 23(1): 60-4, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10683080

ABSTRACT

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Carcinoma, Non-Small-Cell Lung/secondary , Cisplatin/administration & dosage , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Survival Analysis , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
18.
Chang Gung Med J ; 23(12): 738-46, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11416894

ABSTRACT

BACKGROUND: There are no added benefits when balloon angioplasty is conducted in conjunction with thrombolytic therapy in patients with acute myocardial infarction. The purpose of this study was to determine whether or not thrombolysis has an impact on the outcome of late coronary artery stenting following acute myocardial infarction. METHODS: The outcome of late coronary artery stenting in the infarct-related artery following acute infarction was compared in patients with (68 patients, group A) and without (118 patients, group B) prior thrombolytic therapy. RESULTS: The baseline characteristics were similar in the 2 groups except that total occlusion of the infarct-related artery was more common in group B. The angiographic characteristics of the target lesion were similar in the 2 groups; the procedural success rate was 98% in both groups. There was no subacute thrombosis or other complications in either group. The 6-month follow-up coronary angiography and the restenosis rate was 18% in both groups; the reocclusion rate was 2% in group A and 4% in group B. The increment of the left ventricular ejection fraction was similar in both groups (6% versus 7%). During a follow-up duration of 18 +/- 3 months, the mortality rate was 3% versus 2%, reinfarction 0% versus 1%, recurrent angina 6% versus 4%, and target lesion revascularization by angioplasty 13% versus 13% in group A and B patients, respectively. CONCLUSION: The outcome of late coronary artery stenting following acute myocardial infarction in patients with and without prior thrombolytic therapy was comparable. Significant improvement of left ventricular function was noted in both groups.


Subject(s)
Myocardial Infarction/therapy , Stents , Thrombolytic Therapy , Adult , Aged , Coronary Angiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies
19.
Eur Radiol ; 9(9): 1835-9, 1999.
Article in English | MEDLINE | ID: mdl-10602959

ABSTRACT

Computed tomography was utilized to evaluate aberrant left brachiocephalic vein (ALBCV), an infrequently discussed congenital vascular anomaly among Chinese people. Associated vascular variation and possible embryonic correlation are discussed. Since 1990, a total of 14 cases of ALBCV have been reported in patients receiving CT scan of chest, and was mainly an incidental diagnosis. One case was confirmed angiographically and two others were confirmed by magnetic resonance imaging. Emphasis was placed on the entry of the azygos vein into the superior vena cava (SVC), the length of the SVC, and the presence of other cardiovascular abnormalities. Of the 14 cases of ALBCV, the level of azygos vein entry was higher than the origin of the SVC in 7 cases: 4 were approximately the same level and 3 were lower. The average length of the SVC was approximately 5. 6 cm shorter than that of the general population, which is approximately 7.0 cm. Three cases had associated vascular anomaly. Most cases of ALBCV had azygos vein drainage level higher than or equal to the origin of the SVC. Right-sided aorta is one of the causes giving rise to the ALBCV during embryonic development. The CT scan remains a definitive diagnostic modality for ALBCV.


Subject(s)
Brachiocephalic Veins/abnormalities , Brachiocephalic Veins/embryology , Radiography, Thoracic/methods , Tomography, X-Ray Computed , Vascular Diseases/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Azygos Vein/diagnostic imaging , Azygos Vein/embryology , Brachiocephalic Veins/diagnostic imaging , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Phlebography , Retrospective Studies , Vascular Diseases/congenital , Vena Cava, Superior/diagnostic imaging , Vena Cava, Superior/embryology
20.
Changgeng Yi Xue Za Zhi ; 22(3): 530-5, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10584431

ABSTRACT

Cardiac catheterization and percutaneous transvenous mitral commissurotomy using the Inoue technique were attempted in a 44-year-old woman with mitral stenosis. The pulmonary arterial wedge pressure was 25 mmHg, mean transmitral diastolic pressure gradient 20.3 mmHg, cardiac index 1.80 L/min/m2, and mitral valve area 0.70 cm2. After the diagnostic catheterization, the guide wire for the transseptal procedure was checked in the middle of the inferior vena cava (IVC). A 7-French end-holed Bermann catheter was then used to detect the course of the IVC. It was found that the IVC coursed along the left border of the 4th and 5th lumbar vertebrae, to the left of the abdominal aorta. At the upper border of the third lumbar vertebra, the IVC returned to the right side of the vertebra. In consideration of the inability to pass the Brockenbrough needle through the detoured infrarenal IVC and the risk of rupturing the vessel, the transseptal procedure and attempted percutaneous transvenous mitral commissurotomy were aborted. Therefore, the patient underwent open mitral commissurotomy instead.


Subject(s)
Mitral Valve Stenosis/surgery , Mitral Valve/surgery , Vena Cava, Inferior/abnormalities , Adult , Female , Humans
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