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Biomedical subjects

C H Chen

Publications and source records attributed to C H Chen.

At least 289 records · Page 16Linked to original sources

A newly discovered function for C1 inhibitor, removal of the entire C1qr2s2 complex from immobilized human IgG subclasses.

A new function for C1 inhibitor (C1 INH) is reported. C1 inhibitor dislodged the entire activated C1 complex (C1qr2s2) from immobilized human IgG. C1 binding to doses of immobilized human IgG3, IgG1, or IgG2 was quantified as a function of time. When human serum, as a source of C1qr2s2, was added to relatively low doses of immobilized IgG, C1q binding peaked at 1.0 min then gradually decreased. However when purified C1q was applied to immobilized IgG, C1q binding did not diminish with time. The removal of C1q was duplicated by adding purified C1 INH to C1qr2s2 which had been bound to immobilized IgG. The dislodgement of C1q from immobilized IgG required the presence of intact C1qr2s2 and of C1 INH. This removal of C1q by purified C1 INH was prevented when activated C1s was used to neutralize C1 INH function or when relatively high levels of IgG were immobilized.

Binding, Competitive↗

Cloning and characterization of a general amino acid control transcriptional activator from the chestnut blight fungus Cryphonectria parasitica.

We have cloned and characterized a homologue of the Neurospora crassa general amino acid control gene cpc-1 from the chestnut blight fungus Cryphonectria parasitica. The deduced amino acid sequence of C. parasitica CPC1 (cpCPC1) contains regions with significant homology to the transcriptional activation, DNA binding, and dimerization domains previously defined for N. crassa CPC1 (ncCPC1) and the equivalent "b-ZIP" transcription factor from Saccharomyces cerevisiae, GCN4 (scGCN4). Treatment of C. parasitica with low levels of the protein synthesis inhibitor cycloheximide caused cpc-1 transcript levels to undergo a rapid, transient increase similar to that reported for the mammalian b-ZIP transactivators, c-Jun and c-Fos. Northern analysis also revealed that amino acid starvation of C. parasitica elicits an increase in cpc-1 transcript levels. Hypovirus infection did not affect this increase, although transcript accumulation for several amino acid biosynthetic genes was slightly diminished in the hypovirus-containing strain. Recombinant cpCPC1 specifically bound to the consensus DNA binding element (AP-1), 5'-A/GTGACTCAT-3', also located upstream of the C. parasitica cpc-1 coding region. Constitutive transgenic expression of a DNA binding defective cpCPC1 mutant impaired the ability of C. parasitica to adjust to amino acid starvation. Moreover, these transformants showed reduced ability to grow on host chestnut tissue. Our results define a general amino acid control transactivator in a plant pathogenic fungus and suggest that functional modulation of this factor can influence fungal virulence.

Amino Acid Sequence↗

Simultaneous anterior dislocation of the shoulder and fracture of the ipsilateral humeral shaft. Two case reports.

Two patients with anterior dislocation of the shoulder and ipsilateral fracture of the shaft of the humerus have been studied and the mechanism of their injuries has been documented. Closed reduction of the dislocations was performed under anaesthesia during surgery for humeral fixation with a dynamic compression plate. The fractures and dislocations healed without any problems at 6 to 9 months postoperatively. At recent follow-up, one patient had returned to work and regained normal mobility. The other patient had the sequelae of a brachial plexus injury. The literature on this subject is reviewed.

Adult↗

Cementless Roy-Camille femoral component.

From 1984 to 1987, a complete, single-layered, porous-coated femoral component (Roy-Camille type) was used for primary cementless total hip replacement in 80 patients. Seventy-two patients (77 hips) with a minimal follow-up of 5 years (mean 7.2 years) were assessed clinically and radiographically. Thigh pain occurred in 4 hips. Osteolysis appeared in 5 hips. Cortical thinning around the femoral component was significant at the proximal and middle levels. In total, 6 femoral components failed, which led to reoperation due to aseptic loosening (4 hips) and septic loosening (2 hips). The hip rating score (modified d'Aubigne and Postel rating system) in the surviving hips progressed from 9.0 (range 6-10) preoperatively to 16.3 (range 12-18) points at the latest follow-up. From this study, we found that the complete, single-layered, porous-coated stem had a low loosening rate after 5 years. Bone ingrowth into the porous coating was found in most of the cases. A lower stress shielding effect in comparison with the complete, multi-layered, porous-coated prosthesis was also noted.

Adult↗

Chromosomal fragile site expression in lymphocytes from patients with schizophrenia.

Schizophrenia is a common complex mental disorder. The lifetime prevalence of this disease is about 1% across different populations. The etiology is still unknown despite decades of intensive study. This report is aimed at studying the relationship between chromosomal fragile sites and the etiology of schizophrenia. Lymphocytes of 72 schizophrenic patients and 66 healthy controls were cultured in M medium, which is deficient in folic acid, and in medium RPMI 1640 with distamycin A. G-banding was carried out on 100 metaphases of each individual. Fragile sites were characterized as specific chromosomal bands that exhibit nonrandom gaps or breaks. Culture in M medium resulted in significant differences in the total number of chromosomal lesions and the total number of cells with chromosomal lesions between patients and controls (P<0.001), while no difference was noted after exposure to distamycin A. In the case of M medium, 17 bands in both patients and controls were recognized as expressing fragile sites nonrandomly using a statistical method based on the relationship of the binomial and F distributions. Further analysis using Fisher's exact test revealed a significant excess of expression of a rare fragile site at 2q11.2 among patients compared with controls (P<0.05). In the case of distamycin A induction, 13 bands were identified as having nonrandom expression of fragile sites using the same statistical method. A significant excess expression of a fragile site at 9q12 was identified among patients compared with controls by applying Fisher's exact test (P<0.001). Thus, our data suggest that chromosomal bands 2q11.2 and 9q12 are interesting regions that may harbor important genes associated with schizophrenia.

Adult↗

Impaired adaptive vascular growth in hypercholesterolemic rabbit.

Occlusive arterial disease stimulates compensatory growth of pre-existent and new arterial channels which help to maintain organ perfusion. Previous studies characterizing compensatory or collateral vascular growth have been performed in normocholesterolemic animals. Because hyperlipidemic states alter vascular regulation, it remains to be demonstrated that the capacity of the vasculature to undergo compensatory growth is preserved in the presence of dyslipidemic vascular injury. To assess effects of hypercholesterolemia on vascular growth, arterial supply to the ear of rabbits with (n = 13) or without hypercholesterolemia (n = 14) was surgically restricted. Compensatory growth of residual arteries and distal microvessels was evaluated using quantitative angiographic and microanatomic methods. Lumen-expanding hyperplasic arterial remodeling and distal microvascular proliferation induced by arterial restriction were assessed by independent techniques including in vivo microangiography, laser Doppler flowmetry, quantitative histometry, and thymidine incorporation. Compared with controls, hypercholesterolemic rabbits exhibited depressions in all arterial and capillary growth indexes. Microvascular proliferation in hypercholesterolemic rabbits was less than 20% of control. Results demonstrate for the first time that an atherogenic dyslipidemia may limit compensatory macro- and microvascular growth in response to arterial restriction, a phenomenon that could play an important role in the pathophysiology of atherosclerotic occlusive artery disease.

Adaptation, Physiological↗

Evidence for the internal location of actin in the pseudorabies virion.

Pseudorabies virions were purified by sucrose gradient and virion-associated proteins were examined. Cytoskeleton actin was found to be a component of virion preparation. In addition, abundant virion-associated actin was detected even after the virion preparation was treated with trypsin digestion or the viral envelope was removed by Triton X-100. This finding indicated that the location of actin is inside the pseudorabies virion. Furthermore, the possible involvement of actin in the life cycle of pseudorabies virus was studied by using cytochalasin D, an F-actin binding drug, and the result showed that cytochalasin D reduced the number of plaques and the size of the plaque of pseudorabies virus.

Actins↗

Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma.

BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). METHODS: HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. RESULTS: The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. CONCLUSIONS: These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.

Aged↗

Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly.

OBJECTIVES: We tested the hypothesis that age-related arterial stiffening is matched by ventricular systolic stiffening, and that both enhance systolic pressure sensitivity to altered cardiac preload. BACKGROUND: Arterial rigidity with age likely enhances blood pressure sensitivity to ventricular filling volume shifts. Tandem increases in ventricular systolic stiffness may also occur and could potentially enhance this sensitivity. METHODS: Invasive left ventricular pressure-volume relations were measured by conductance catheter in 57 adults aged 19 to 93 years. Patients had normal heart function and no cardiac hypertrophy and were referred for catheterization to evaluate chest pain. Twenty-eight subjects had normal coronary angiography and hemodynamics, and the remaining had either systolic hypertension or coronary artery disease without infarction. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded systolic and diastolic left ventricular chamber and effective arterial stiffness and pulse pressure. RESULTS: Left ventricular volumes, ejection fraction and heart rate were unaltered by age, whereas vascular load and stiffening increased (p < 0.008). Arterial stiffening (Ea) was matched by increased ventricular systolic stiffness (Ees): Ees=0.91 x Ea + 0.53, (r=0.50, p < 0.0001), maintaining arterial-heart interaction (Ea/Ees ratio) age-independent. Ventricular systolic and diastolic stiffnesses correlated (r=0.51, p < 0.0001) and increased with age (p < 0.03). Both ventricular and vascular stiffening significantly increased systolic pressure sensitivity to cardiac preload (p < 0.006). CONCLUSIONS: Arterial stiffening with age is matched by ventricular systolic stiffening even without hypertrophy. The two effects contribute to elevating systolic pressure sensitivity to altered chamber filling. In addition to recognized baroreflex and autonomic dysfunction with age, combined stiffening could further enhance pressure lability with diuretics and postural shifts in the elderly.

Adult↗

Infrequent mutations and no methylation of CDKN2A (P16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan.

CDKN2A (p16INK4A/MTS1) and CDKN2B (p15INK4B/MTS2) have recently been shown to be potent inhibitors of the cyclin D/cyclin-dependent kinase-4 complex. Both genes are candidates for the putative tumour suppressor genes located at chromosome 9p21 and are frequently inactivated in many human cancers through homozygous deletion. More recently, another reported pathway of inactivation involves loss of transcription associated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 hepatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) amplification, sequence analysis and Southern blot. Homozygous deletions of P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygous deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%). Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of these specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data suggest that the p16/MTS1 gene has a limited role in HCC. However, deletions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC.

Adult↗

Telomerase activity and telomere length in human hepatocellular carcinoma.

Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters.

Adult↗

Scission of DNA at a preselected sequence using a single-strand-specific chemical nuclease.

BACKGROUND: We were interested in developing a protocol for cleaving large DNAs specifically. Previous attempts to develop such methods have failed to work because of high levels of nonspecific background scission. RESULTS: R-loop formation was chosen for sequence-specific targeting, a method of hybridization whereby an RNA displaces a DNA strand of identical sequence in 70% formamide using Watson-Crick base-pairing, leading to a three-stranded structure. R-loops are stabilized in aqueous solution by modifying the bases with chemical reagents. The R-loop was cleaved using a novel nuclease prepared from the Thr48-->Cys mutant of the single-strand-specific M-13 gene V protein (GVP), which was alkylated with 5-(iodoacetamido-beta-alanyl)1,10-phenanthroline. The cleavage products of the pGEM plasmid were cloned in to the pCR 2.1-TOPO vector. Adenovirus 2 DNA (35.8 kb; tenfold larger than the pGEM plasmid) was also cleaved quantitatively at a preselected sequence. CONCLUSIONS: A new method for cleaving duplex DNA at any preselected sequence was developed. The cleavage method relies on the chemical conversion of M-13 GVP into a nuclease, reflecting GVP's specificity for single-stranded DNA. The GVP chimera is the first example of a semisynthetic secondary structure specific nuclease. The chemical nuclease activity of 1,10-phenanthroline-copper is uniquely suited to this technique because it oxidizes the deoxyribose moiety without generating diffusible intermediates, providing clonable DNA fragments. The protocol could be useful in generating large DNA fragments for mapping the contiguity of probes or defining the exon-intron structure of transcription units.

Adenoviridae↗

Thymic function can be accurately monitored by the level of recent T cell emigrants in the circulation.

Expression of the avian chT1 thymocyte antigen persists on a subpopulation of peripheral T cells enriched in the DNA deletion circles created by alphabeta and gammadelta TCR gene rearrangements. The chT1+ cells are evenly distributed among all of the peripheral T lymphocyte compartments. The levels of chT1+ T cells in the periphery gradually decline in parallel with age-related thymic involution, and these cells disappear following early thymectomy. Experiments in which variable numbers of the 14 thymic lobes are removed in young chicks indicate a direct correlation between the levels of circulating chT1+ cells and residual thymic mass. Measurement of recent thymic emigrants in the periphery thus provides an accurate indication of thymic function.

Aging↗

C1 inhibitor removes the entire C1qr2s2 complex from anti-C1Q monoclonal antibodies with low binding affinities.

Evidence is presented for a new C1 Inhibitor (C1 INH) function. C1 INH was capable of dislodging the entire C1qr2s2 complex from C1-activating substances that bound weakly to the globular heads of C1q. Two different mouse IgG1 monoclonal antibodies with different affinities for C1q globular heads were compared for their complement-activating properties in the presence of normal human serum. As expected the higher affinity monoclonal antibody (Qu) was more effective in binding C1q and causing C1-mediated C4b deposition. Unexpectedly, time responses of C1 (C1q) binding to immobilized 3C7 reached a peak then gradually decreased. However, C1q remained constantly bound to immobilized Qu. These results indicated that after C1 activation in human serum, the entire C1 complex (including C1q) was dislodged from 3C7, but not from immobilized Qu. The addition of purified C1 INH to purified C1, which had bound to immobilized 3C7, resulted in removal of C1 (C1q). Removal of the entire C1qr2s2 did not occur when C1 INH preparations were first neutralized by the addition of purified activated C1s. In summary, it is suggested that C1 INH plays a prominent role in dislodging the entire C1qr2s2 from immunoglobulin preparations which have a low binding affinity for the globular heads of C1q.

Animals↗

P300 in response to the subject's own face.

The P300 event-related potentials in response to self-relevant stimuli has been reported to be different from those to non-target stimuli under a passive attention condition. In the present study the P300 in response to the subject's own face was examined. Twelve right-handed volunteers served as subjects. In two separate conditions, deviant (subject's own face and red square; 30%), non-target (two unfamiliar faces; 30% each), and target (famous face; 10%) stimuli were randomly presented on a computer screen. P300 amplitudes in response to the red square were larger than those to the unfamiliar faces, but were significantly lower than those to the subject's own face. The subject's own face in normal population may have an intense relevance to the subjects which has an additional effect over the simple orienting response.

Adult↗

Optimal preload adjustment of maximal ventricular power index varies with cardiac chamber size.

BACKGROUND: Maximal left ventricular power (PWRmax) can index contractile function and reserve; however, its marked preload dependence mandates load adjustment to yield a more cardiac-specific measurement. Prior studies have used varying methods, but supporting data have generally been lacking. We hypothesized that the optimal approach for preload adjustment varies with ventricular volume (particularly end-systolic volume) and is significantly different for dilated hearts with reduced left ventricular function compared with small to normal-sized hearts with normal systolic function. METHODS: Left ventricular pressure-volume relations were measured by the conductance catheter method in 36 patients, with preload altered by inferior vena cava obstruction. Patients with normal ventricles (n = 16), hypertrophy or mitral stenosis (n = 12), and dilated cardiomyopathy (n = 8) were divided into three groups based on resting end-diastolic volume: group 1, 66.3 +/- 12; group 2, 118.1 +/- 20; and group 3, 218.2 +/- 48 ml. PWRmax was the maximal product of simultaneous left ventricular pressure and rate of volume change. PWRmax end-diastolic volume (EDV) data were fit to a power function, PWRmax = alphaEDVbeta (where alpha is a scaling factor and beta is the power coefficient), and the preload sensitivity of beta and PWRmax/EDVbeta ratios (beta = 1, 2, or best fit) were compared. RESULTS: Beta varied directly with chamber size: 0 = 0.004 x (EDV + 0.56), r = 0.65, p < 0.0001. However, it was equally well approximated by 1.0 in groups 1 and 2 (ESV <75 ml, EF >40%), whereas beta = 2 was more appropriate in group 3. CONCLUSION: PWRmax/EDV provides adequate preload independence in all but dilated hearts with reduced LV function, whereas PWRmax/EDV2 is required in the latter. These data should help clinical application of a noninvasive PWRmax index for assessing chamber contractility and contractile reserve in human beings.

Adult↗

Clinical impact of screening first-degree relatives of patients with hepatocellular carcinoma.

Family history is a risk factor for hepatocellular carcinoma (HCC). However, the risk of first-degree relatives is not known. To investigate the risk of HCC among the first-degree relatives of probands and whether screening can lead to early diagnosis of HCCs in these relatives, we conducted a screening program. The probands' first-degree relatives who were >20 years old were included. Serum aminotransferase, hepatitis viral marker, alpha-fetoprotein, and abdominal sonography were done. HCCs were found in 20 (1.9%) of the 1,046 first-degree relatives, especially in the male siblings. Eighty-five percent of these 20 HCC patients were hepatitis B virus carriers. Forty percent of these 20 HCC patients had tumors <5 cm. Approximately 55% of these 20 HCCs were resectable. The 1-year survival rate in these 20 HCC patients with resectable HCCs was 72.7%. However, the overall 1-year survival rate was only 40%. We found HCC in 1.9% of the first-degree relatives of HCC patients. The male relatives, especially the older brothers, were the group at highest risk. The familial HCCs were closely related to the hepatitis B virus infection. To detect HCCs early, initial screening should be done as early as possible on the HCC family members.

Adult↗

A method to correct for scatter, spillover, and partial volume effects in region of interest analysis in PET.

Scatter and spatial resolution effects degrade the accuracy of radioactivity concentration estimates obtained from positron emission tomography (PET) data. We present and evaluate a methodology for region quantification which accounts for these degradations. The method is based on analysis of sinogram data and does not require dynamic data sequences to be reconstructed. Moreover, estimates of region variance are also produced which may be used to define weights for model analyses that use weighted least squares minimization in order to obtain unbiased parameter estimates. We evaluate the method using both simulation and measured data and find that, with an appropriate model of scatter and spatial resolution effects, it is unbiased and capable of quantifying myocardial concentration with no more than a 5% error in accuracy for myocardium as thin as 10 mm.

Adrenergic beta-Antagonists↗