Cytokine-regulated expression of vascular cell adhesion molecule-1 in human glomerular endothelial cells.
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Capillaries↗
Biomedical subjects
Y H Chang
Publications and source records attributed to Y H Chang.
Incorporation of a set enumeration trees-based classifier into a hybrid computer-assisted diagnosis scheme for mass detection.
RATIONALE AND OBJECTIVES: The authors evaluated whether a hybrid classifier of two independent computer-aided diagnosis (CAD) schemes, the set enumeration (SE) trees approach and an artificial neural network (ANN), could improve the detection of masses on digitized mammograms. The potential benefits resulting from the interpretability of the SE trees model was also explored. MATERIALS AND METHODS: Two hundred thirty verified mass regions and 230 negative but suspicious regions were randomly selected from 618 digitized mammograms. Each region was represented by a 24-parameter feature vector. These features were used as input data for the SE trees and ANN-based schemes. After the positive and negative regions were randomly segmented into five exclusive partitions, a fivefold cross-validation method was applied to evaluate and compare the performance of the SE trees, ANN, and hybrid system in the identification of masses. RESULTS: The performance of the SE trees approach was comparable to that of the ANN. The average area under the receiver operating characteristic (ROC) curves for all five partitions was 0.88 (standard deviation, 0.04). Owing to the relatively low correlation between the region-based results of the SE trees and ANN methods, the hybrid classifier yielded a significantly improved performance, with an area under the ROC curve of 0.94 (standard deviation, 0.02; P < .05). CONCLUSION: The hybrid CAD scheme significantly improved performance. The amenability of the SE trees models to interpretation may aid in the assessment of the importance of specific features.
Artificial Intelligence↗
Identification of clustered microcalcifications on digitized mammograms using morphology and topography-based computer-aided detection schemes. A preliminary experiment.
RATIONALE AND OBJECTIVES: A mathematical morphology-based computer-aided detection (CAD) scheme for the identification of clustered microcalcifications was developed and tested. The potential for improving either sensitivity or specificity by combining the results with those previously reported was investigated. METHODS: The CAD scheme presented here is based on mathematical morphology and a series of simple rule-based criteria for the identification of clustered microcalcifications. A database of 105 digitized mammograms was used for training and rule setting of the scheme. A test set of 191 digitized mammograms was used to evaluate its performance. The same test set had been used to evaluate a multilayer, topography-based scheme. The results obtained by the two schemes were then combined using logical OR and AND operations. RESULTS: The morphology-based and topography-based CAD schemes performed at sensitivities of 82.9% and 89.5%, with false-positive detection rates of 1.3 and 0.4 per image, respectively. A logical OR operation resulted in 95.4% sensitivity. An AND operation achieved 76.2% sensitivity, with no false identifications on 93% of images. CONCLUSIONS: By combining the results of the morphology-based and the topography-based schemes, either sensitivity or specificity can be improved.
Algorithms↗
Force treadmill for measuring vertical and horizontal ground reaction forces.
We constructed a force treadmill to measure the vertical, horizontal and lateral components of the ground-reaction forces (Fz, Fy, Fx, respectively) and the ground-reaction force moments (Mz, My, Mx), respectively exerted by walking and running humans. The chassis of a custom-built, lightweight (90 kg), mechanically stiff treadmill was supported along its length by a large commercial force platform. The natural frequencies of vibration were >178 Hz for Fz and >87 Hz for Fy, i.e., well above the signal content of these ground-reaction forces. Mechanical tests and comparisons with data obtained from a force platform runway indicated that the force treadmill recorded Fz, Fy, Mx and My ground-reaction forces and moments accurately. Although the lowest natural frequency of vibration was 88 Hz for Fx, the signal-to-noise ratios for Fx and Mz were unacceptable. This device greatly decreases the time and laboratory space required for locomotion experiments and clinical evaluations. The modular design allows for independent use of both treadmill and force platform.
Biophysical Phenomena↗
Arterial injury by cholesterol oxidation products causes endothelial dysfunction and arterial wall cholesterol accumulation.
Cholesterol oxidation products (ChOx) have been reported to cause acute vascular injury in vivo; however, the pharmacokinetics of ChOx after administration and the mechanisms by which they cause chronic vascular injury are not well understood. To further study the pharmacokinetics and atherogenic properties of ChOx, New Zealand White rabbits were injected intravenously (70 mg per injection, 20 injections per animal) with a ChOx mixture having a composition similar to that found in vivo during a 70-day period. Total ChOx concentrations in plasma peaked almost immediately after a single injection, declined rapidly, and returned to preinjection levels in 2 hours. After multiple injections, the ChOx concentrations rose gradually to levels 2- to 3-fold above baseline levels, increasing mostly in the cholesteryl ester fraction of LDL and VLDL. Rabbit serum and the isolated LDL/VLDL fraction containing elevated ChOx concentrations were cytotoxic to V79 fibroblasts and rabbit aortic endothelial cells. At the time of killing, cholesterol levels in the aortas from ChOx-injected rabbits were significantly elevated despite the fact that plasma cholesterol levels remained in the normal range. In addition, aortas from the ChOx-injected rabbits retained more 125I-labeled horseradish peroxidase, measured 20 minutes after intravenous injection. Transmural concentration profiles across the arterial wall also showed increased horseradish peroxidase accumulation in the inner half of the media from the thoracic aorta in ChOx-injected rabbits. In conclusion, ChOx injection resulted in accumulation of circulating ChOx and induced increased vascular permeability and accumulation of lipids and macromolecules. This study reveals that even under normocholesterolemic conditions, ChOx can cause endothelial dysfunction, increased macromolecular permeability, and increased cholesterol accumulation, parameters believed to be involved in the development of early atherosclerotic lesions.
Animals↗
Sustained attention deficit and schizotypal personality features in nonpsychotic relatives of schizophrenic patients.
OBJECTIVE: The authors investigated whether nonpsychotic relatives of schizophrenic probands have an elevated risk of deficits in sustained attention as measured by the Continuous Performance Test (CPT), whether such deficits are associated with specific factors of schizotypy, and whether poor CPT performance by probands predicts poor performance by their relatives. In addition, the heritability of CPT performance in the families of schizophrenic probands was estimated. METHOD: The study subjects were 60 schizophrenic probands, 148 of their first-degree relatives, 20 normal comparison probands, and 42 of the comparison probands' first-degree relatives. Subjects completed undegraded and 25% degraded sessions of the CPT and were interviewed with use of the Chinese version of the Diagnostic Interview for Genetic Studies. Subjects' CPT sensitivity indexes, d', were standardized against those of a community sample of 345 subjects, with adjustment for age, sex, and level of education. RESULTS: On average, the d' values of the relatives of schizophrenic probands were lower than those of the relatives of comparison probands but higher than those of schizophrenic probands. Lower sensitivity indexes among the relatives of schizophrenic patients were associated with the interpersonal dysfunction and disorganization factors of schizotypy but not the cognitive/perceptual factor. When schizophrenic probands were divided into two subgroups by a cutoff of -3.0 for adjusted z score on the CPT, the d' values of relatives of probands with CPT deficits were lower than those of relatives of probands without deficits. The estimated heritability of performance on the CPT ranged from 0.48 to 0.62. CONCLUSIONS: Sustained attention deficit may be a genetic vulnerability marker for schizophrenia, and it may be more useful in linkage analysis than traditional phenotype definitions of schizophrenia.
Adult↗
Complicated urinary tract infection: analysis of 179 patients.
BACKGROUND: The aim of our study was to investigate the incidence, bacteriology, management and outcome of complicated urinary tract infections (UTIs) at the Veterans General Hospital-Taipei. METHODS: Between June, 1993, and July, 1994, medical records of 2,566 patients admitted to the Division of Urology, Veterans General Hospital-Taipei, were retrospectively reviewed. Of these patient, 1,322 had a diagnosis of benign prostatic hyperplasia (BPH), 607 were admitted for renal stones, 496 for ureteral stones, 75 for transitional cell carcinoma (TCC) of the urinary bladder, 47 for renal tumors and 19 for TCC of the ureter. Among all patients studied, 179 (6.98%) acquired a complicated UTI. Of these, 81 were admitted for BPH, 46 for renal stones, 42 for ureteral stones, five for TCC of the urinary bladder, three for renal tumors and two for TCC of the ureter. RESULTS: Of the 179 patients with complicated UTIs, 155 were men and 24 were women. The urine culture positive rate was 76.0% (136/179) and the most common bacteria were Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa. The principle mode of treatment included parenteral antibiotics and urinary diversion (percutaneous nephrostomy and Foley catheterization), when necessary. The infection control rate for these complicated UTIs was 96.3% for BPH, 95.5% for renal stone, 97.6% for ureteral stone, 80% for TCC of the urinary bladder, 100% for renal tumor and 100% for TCC of the ureter. Mortality due to complicated UTI was 3.9% (7/179). CONCLUSIONS: We concluded that the prognosis of complicated UTI is good if diagnosis and appropriate treatment are given promptly. Early drainage to relieve obstruction and intravenous antibiotics are initially necessary. Surgical intervention is required to resolve functional or structural abnormalities after the UTI has been controlled.
Adult↗
Astrocytes regulate amino acid receptor current densities in embryonic rat hippocampal neurons.
Embryonic rat hippocampal neurons were cultured in a serum-free defined medium (MEM/N3) either directly on poly-D-lysine (PDL) or on a confluent monolayer of postnatal cortical astrocytes, C6 glioma cells, or Rat2 fibroblasts. Neurons on PDL were grown in MEM/N3 or in MEM/N3 conditioned for 24 h by astrocytes or C6 cells. Membrane capacitance (Cm) and gamma-aminobutyric acid (GABA)-, glycine-, kainate-, and N-methyl-D-aspartate (NMDA)-induced currents were quantified using whole-cell patch-clamp recordings. Cm as well as the amplitude and the density of these currents in neurons cultured on astrocytes were significantly greater than those in neurons grown on PDL after 24 and 48 h. C6 cells mimicked astrocytes in promoting Cm and GABA-, glycine-, and NMDA-evoked, but not kainate-evoked, currents. Cm and currents in neurons grown on Rat2 cells were comparable to those in neurons on PDL. Astrocytes maintained in culture for 3 months were noticeably less effective than freshly prepared ones just grown to confluence. Suppression of spontaneous cytoplasmic Ca2+ (Ca[c]2+) elevations in astrocytes by 1,2-bis(2-aminophenoxy) ehane-N, N, N, N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) loaded intracellularly blocked the observed modulatory effects. Medium conditioned by either astrocytes or C6 cells mimicked the effects of direct coculture of neurons on these cells in promoting Cm and amino acid-evoked currents. Inclusion of antagonists at GABA and glutamate receptors in coculture experiments blocked the observed effects. Thus, diffusible substances synthesized and/ or secreted by astrocytes in a Ca(c)2+-dependent manner can regulate neuronal growth and aminoacid receptor function, and these effects may involve neuronal GABA and glutamate receptors.
Animals↗
A dominant negative mutation in Saccharomyces cerevisiae methionine aminopeptidase-1 affects catalysis and interferes with the function of methionine aminopeptidase-2.
Methionine aminopeptidase (MetAP) enzymes require the metal ion cobalt, but little is known about the role of cobalt in the structural stability or catalysis of these enzymes. In Escherichia coli MetAP, for which a crystal structure is available, the five amino acid residues liganding the two cobalt ions are Asp97, Asp108, His171, Glu204, and Glu235. These five amino acids are conserved in all MetAPs sequenced to date. The C-terminal domain of the yeast Saccharomyces cerevisiae MetAP1 is 41% identical to E. coli MetAP and contains these cobalt coordinating residues. Using site-directed mutagenesis on the gene coding for yeast MetAP1, we replaced Asp219 (corresponding to Asp97 in E. coli MetAP) with Asn. The yeast D219N mutant enzyme has 10(3)-fold lower catalytic activity and a different substrate specificity when compared to wild-type yeast MetAP1. These results indicate that the side-chain of Asp219 is important for catalysis. Expression of D219N-MetAP1 in yeast causes a slow-growth phenotype and interferes with wild-type MetAP1 in a dominant manner. Expression of D219N-MetAP1 also affects the function of S. cerevisiae MetAP2.
Aminopeptidases↗
5-HT1A receptor mRNA expressions differ in the embryonic spinal cord of male and female rats.
During critical periods of development, the effects of testosterone (T) on promoting androgenization of the central nervous system (CNS) are reflected not only by behavior, morphology, and hormone secretion but also by gene expression. The mechanisms involved in sexual differentiation of the CNS, however, remain incompletely defined. The current set of experiments examined with in situ hybridization the dimorphism in 5-HT1A receptor mRNA expression in the embryonic rat spinal cord and the possible role of T in the dimorphism. We found sex-related differences in expression of 5-HT1A mRNA in the spinal cord, which were altered by a single injection of T. The results suggest that this gonadal steroid is responsible for the sexual dimorphism in 5-HT1A mRNA expression occurring during the critical period.
Animals↗
Paraneoplastic elevation of serum alkaline phosphatase in renal cell carcinoma: incidence and implication on prognosis.
PURPOSE: We investigated the incidence and prognostic significance of paraneoplastic elevation of serum alkaline phosphatase in patients with renal cell carcinoma. MATERIALS AND METHODS: Clinical data of 365 pathologically proved renal cell carcinoma cases were reviewed. Serum alkaline phosphatase level greater than 100 units per 1., but without obvious conditions that may cause phosphatase elevation, including metastasis to or disease of liver or bone and pregnancy, was regarded as paraneoplastic serum alkaline phosphatase elevation. Survival was evaluated using the Kaplan-Meier method. RESULTS: Of 365 patients 77 (21.1%) had paraneoplastic serum alkaline phosphatase elevation. The respective incidence from stage I to IV cases was 9.9% (16 of 161), 31.9% (15 of 47), 34.3% (23 of 67) and 25.6% (23 of 90). Patients with stage I disease had the lowest incidence but there were no statistically significant differences among stages II, III and IV disease. Of 77 patients with elevated serum alkaline phosphatase 48 had additional paraneoplastic manifestations. The disease specific 5-year survival rate in patients with normal serum alkaline phosphatase was significantly better than in patients with isolated phosphatase elevation, which in turn was better than in patients with multiple paraneoplastic syndromes (70.7 versus 50.5 versus 30.8%). Patients with persistent or recurrent elevation of serum alkaline phosphatase after radical nephrectomy had metastatic lesion or local recurrence. In some patients serum alkaline phosphatase returned to normal after nephrectomy but metastasis developed later without recurrent phosphatase elevation. CONCLUSIONS: Paraneoplastic serum alkaline phosphatase elevation in renal cell carcinoma patients implies an unfavorable prognosis, and additional paraneoplastic syndromes further worsen the prognosis. Recurrent or persistent serum alkaline phosphatase elevation after radical nephrectomy suggests distant metastasis or residual tumor. However, the return of serum alkaline phosphatase to normal does not guarantee cure of the disease. Identification of paraneoplastic serum alkaline phosphatase elevation is valuable in the prediction of outcome and postoperative followup of renal cell carcinoma patients.
Alkaline Phosphatase↗
Characterization of cholesterol oxidation products formed by oxidative modification of low density lipoprotein.
Oxidative modification of LDL is evidenced by alterations in both the protein and lipid components of the particle. Progressive oxidation of the apoprotein is associated with loss of specific amino acids and a gradual increase in electronegativity. Electronegative LDL has been isolated from human plasma (LDL-) by several groups using liquid chromatographic techniques and appears to be oxidized based on increased lipid peroxide levels and cholesterol oxidation products (ChOx). Formation of LDL- also takes place following Cu(2+)-induced oxidation. Cu(2+)-induced oxidation caused a small fraction of the normal unoxidized LDL (n-LDL) to convert to LDL-during the oxidative lag phase while minimal increases in conjugated dienes were apparent. After the lag phase, there was a further increase in LDL-, a rapid accumulation of conjugated dienes, and another more electronegative particle was formed (LDL2-). By the end of the lag phase, approximately 30% and 12% of the total LDL converted to LDL- and LDL2-, respectively. Nearly 40% of the total ChOx formed was present by the end of the lag period, accompanied by small increases in conjugated dienes. The major products accumulating during this time were 7-ketocholesterol, cholesterol-beta-epoxide and 7-alpha-hydroxycholesterol. Accumulation of predominated during the subsequent propagation phase. At the end of propagation phase there was a six fold increase in conjugated dienes and total ChOx increased eight-fold. It appears that a subpopulation of LDL rapidly converts to LDL-, representing a mildly oxidized but oxidant sensitive LDL population. Oxidation of cholesterol accompanies these early events in LDL oxidation with formation of specific ChOx.
Adult↗
Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.
BACKGROUND: Angiogenesis, the formation of new blood vessels, is essential for tumor growth. The inhibition of angiogenesis is therefore emerging as a promising therapy for cancer. Two natural products, fumagillin and ovalicin, were discovered to be potent inhibitors of angiogenesis due to their inhibition of endothelial cell proliferation. An analog of fumagillin, AGM-1470, is currently undergoing clinical trials for the treatment of a variety of cancers. The underlying molecular mechanism of the inhibition of angiogenesis by these natural drugs has remained unknown. RESULTS: Both AGM-1470 and ovalicin bind to a common bifunctional protein, identified by mass spectrometry as the type 2 methionine aminopeptidase (MetAP2). This protein also acts as an inhibitor of eukaryotic initiation factor 2alpha (elF-2alpha) phosphorylation. Both drugs potently inhibit the methionine aminopeptidase activity of MetAP2 without affecting its ability to block elF-2alpha phosphorylation. There are two types of methionine aminopeptidase found in eukaryotes, but only the type 2 enzyme is inhibited by the drugs. A series of analogs of fumagillin and ovalicin were synthesized and their potency for inhibition of endothelial cell proliferation and inhibition of methionine aminopeptidase activity was determined. A significant correlation was found between the two activities. CONCLUSIONS: The protein MetAP2 is a common molecular target for both AGM-1470 and ovalicin. This finding suggests that MetAP2 may play a critical role in the proliferation of endothelial cells and may serve as a promising target for the development of new anti-angiogenic drugs.
Affinity Labels↗
Computer-aided detection of clustered microcalcifications on digitized mammograms: a robustness experiment.
RATIONALE AND OBJECTIVES: The authors assessed the performance of an existing computer-aided diagnosis (CAD) scheme for the detection of clustered microcalcifications in a large image database. METHODS: A previously developed, rule-based system was used to assess detectability of microcalcification clusters in a set of 386 digitized mammograms with 239 verified clusters visible on 191 images. The test was performed without any reoptimization of the scheme. None of the 386 images had been used in any previous scheme development or testing procedures. RESULTS: The CAD scheme achieved 89.5% sensitivity at an average false-positive detection rate of 0.39 per image. In 75% of all images, no false-positive findings occurred. Twenty-three of 25 false-negative findings (misses) occurred during the last two stages in the detection process. CONCLUSION: This scheme produced reasonable results in a large data set of images with a large variety of cluster characteristics.
Calcinosis↗
Adequacy testing of training set sample sizes in the development of a computer-assisted diagnosis scheme.
RATIONALE AND OBJECTIVES: The authors assessed the performance changes of a computer-assisted diagnosis (CAD) scheme as a function of the number of regions used for training (rule-setting). MATERIALS AND METHODS: One hundred twenty regions depicting actual masses and 400 suspicious but actually negative regions were selected as a testing data set from a database of 2,146 regions identified as suspicious on 618 mammograms. An artificial neural network using 24 and 16 region-based features as input neurons was applied to classify the regions as positive or negative for the presence of a mass. CAD scheme performance was evaluated on the testing data set as the number of regions used for training increased from 60 to 496. RESULTS: As the number of regions in the training sets increased, the results decreased and plateaued beyond a sample size of approximately 200 regions. Performance with the testing data set continued to improve as the training data set increased in size. CONCLUSION: A trend in a system's performance as a function of training set size can be used to assess adequacy of the training data set in the development of a CAD scheme.
Breast Neoplasms↗
The significance of serum alkaline phosphatase bone isoenzyme in prostatic carcinoma with bony metastasis.
OBJECTIVE: To evaluate the clinical significance of serum alkaline phosphatase (ALP). ALP bone isoenzyme (ALPb) and prostate specific antigen (PSA) levels in predicting bony metastasis in prostatic carcinoma. PATIENTS AND METHODS: The levels of serum ALP, ALPb and PSA were assessed in 32 patients with prostatic carcinoma and bony metastasis (group 1), 31 with prostatic carcinoma without bony metastasis (group 2), and 31 with benign prostatic hyperplasia (group 3). Bony metastases were detected using whole-body bone scintigraphy and ALPb was estimated electrophoretically before surgical or medical treatment. The levels of the three markers were compared for their ability to predict bony metastasis. RESULTS: In groups 1, 2 and 3, respectively, the mean (SD) serum levels of ALP were 304 (322.2), 76.6 (47.5) and 63.8 (14.7) IU/L, of ALPb were 79.9 (76.9), 23.6 (9.9) and 25.3 (9.0) IU/L and of PSA were 478.1 (352.2), 46.9 (32.1) and 8.1 (1.8) ng/mL. The differences in serum ALP and ALPb between groups 1 and 2, and between groups 1 and 3 were significant (P < 0.05), but not those between groups 2 and 3. The positive predictive value (PPV) for bony metastasis in patients with prostatic carcinoma was 91.3% (21/23) and 100% (18/18) and the negative predictive value (NPV) was 71.8% (28/39) and 68.9% (31/45) for ALP and ALPb, respectively. CONCLUSION: Both serum ALP and ALPb were increased significantly in patients with prostatic carcinoma with bony metastasis. The level of ALPb had a higher PPV and specificity for bony metastasis than had the level of ALP, but a lower NPV and sensitivity than ALP or PSA (at PSA levels > 20 ng/mL).
Aged↗
Activation of phosphodiesterase IV during desensitization of the A2A adenosine receptor-mediated cyclic AMP response in rat pheochromocytoma (PC12) cells.
Prolonged activation of an A2A adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A2A desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A2A desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A2A desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A2A-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A2A-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A2A desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A2A desensitization could be blocked by a protein kinase A (PKA)-selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA-dependent pathway plays a critical role in dampening the signal of the A2A receptor.
3',5'-Cyclic-AMP Phosphodiesterases↗
A clinical study on physiological response in electroacupuncture analgesia and meperidine analgesia for colonoscopy.
Fifty-nine patients underwent consecutive colonoscopic examination with premedication of electroacupuncture analgesia (EA) were compared with conventional meperidine analgesia (MA) in pain relief and changes of neurotransmitters in serum. The results showed that analgesic efficacy of both groups were the same but with less side effects in the EA group (P < 0.01) especially in regard to dizziness. Serum concentration of beta-endorphin in both groups has a similar curve change at 4 different phases during colonoscopy. Serum concentration of epinephrine, norepinephrine, dopamine and cortisol showed no significant difference between these two groups. The analgesic effect of EA and MA during colonoscopic examination may be closely related to beta-endorphin production in serum.
Acupuncture Analgesia↗