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Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 883 records · Page 49Linked to original sources

Comparison of low-pressure versus standard-pressure fixation Carpentier-Edwards bioprosthesis.

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.

Actuarial Analysis↗

CABG in octogenarians: early and late events and actuarial survival in comparison with a matched population.

BACKGROUND: With important demographic changes in cardiac surgical practice, more older patients are undergoing complex cardiac operations. Controversy exists as to whether the expenditure of healthcare resources on the growing elderly populations represents an effective approach in maintaining a meaningful quality of life. METHODS: From January 1982 through April 1991, 121 consecutive octogenarians underwent a surgical procedure that included coronary artery bypass grafting. Retrospective review of patient medical records was performed; follow-up information was obtained via telephone contact with the patient, the patient's family, or the patient's physician. RESULTS: There were 67 men (55%) and 54 women (45%). Mean age was 82.1 years (range, 80 to 89 years). Sixty-nine percent of the patients were having class III or IV symptoms. There were 11 hospital deaths (9.1%); risk factors included longer cardiopulmonary bypass time (p = 0.01), higher preoperative left ventricular end-diastolic pressure (p = 0.02), advanced age (p = 0.05), history of renal disease (p = 0.02), and myocardial infarction (p = 0.04). Late death occurred in 34 patients (30.9%) at a mean of 27 months postoperatively; univariate risk factors included chronic obstructive pulmonary disease (p = 0.009), higher left-ventricular end-diastolic pressure (p = 0.03), and recent myocardial infarction (p = 0.03). Actuarial survival, including hospital death, was 32.8% at 80 months, compared with 37.6% for an age; sex; and race-matched population (p > 0.3). Most late survivors (84%) were in New York Heart Association class I or II. CONCLUSIONS: We conclude that coronary artery bypass grafting can be performed in octogenarians with an acceptable, although increased risk. Hospital survivors have a good late functional status but are at risk for pulmonary and other atherosclerosis-related events, which impair overall survival.

Aged↗

Perioperative events in patients with failed mechanical and bioprosthetic valves.

From 1963 through 1991, 1037 patients underwent reoperative valvular procedures. The 478 patients having reoperations for either failed bioprosthetic (n = 212) or mechanical (n = 266) valves were evaluated. There were 210 male (44%) and 268 female (56%) patients. The mean age at reoperation of the patients in the bioprosthesis group was 59.7 years and and that in the mechanical valve group was 56.1 years (p = 0.0006). The mean interval to the time of reoperation was 84.7 months in the mechanical valve group and 74 months in the bioprosthesis group. There was no difference between the two groups in the functional class at reoperation. More severe mitral valve stenosis and incompetence, more severe aortic valve stenosis, and higher right ventricular and pulmonary arterial pressures were noted in the bioprosthesis group than in the mechanical valve group. Hemolysis (p = 0.05) was more prevalent in the patients with mechanical valves than in the ones with bioprostheses. A longer aortic occlusion time (p = 0.0001) and longer cardiopulmonary bypass time (p = 0.0001) were required for the reoperations in the bioprosthesis group. The operative mortality was 13.2% for the bioprosthesis patients and 12.4% for the mechanical valve patients. The risk factors for hospital death included the cross-clamp time (p = 0.0001), the functional class (p = 0.00001), the presence of ascites (p = 0.02), hepatomegaly (p = 0.002), and decreasing ejection fraction (p = 0.05). We conclude that mechanical valve failures do not produce catastrophic events resulting in poor reoperative results.

Adolescent↗

Cloning of a human kappa opioid receptor from the brain.

By using a rat kappa opioid receptor cDNA as a probe to screen a human brain cDNA library, we isolated a 4.0-kb clone (z115) which encompasses a major portion of a human kappa opioid receptor (hkor), extending from the amino acid residue #6 to the 3'-untranslated region. The extreme 5'-region 232-bp fragment of z115 was used as a probe to screen a human genomic DNA library. A 1.6-kb fragment (d2) of one positive clone was found to extend from 5'-untranslated region to beyond the exon/intron junction at residue Arg86. The genomic DNA fragment d2 and the cDNA clone z115 were assembled to generate a clone (d2-z115) containing the entire coding sequence of hkor. Clone d2-z115 has an open reading frame of 1140 bp, which encodes for a 380-amino acid protein. The deduced amino acid sequence has 93.9% and 93.2% identity to rat and mouse kappa receptors, respectively. It also displays approximately 60% identity to both human mu and delta receptors. Northern blot analysis showed that in the human brain there was a single hkor mRNA transcript of 6.0 kb. Among brain regions examined, the amygdala, caudate nucleus, hypothalamus and subthalamic nucleus contained high levels of hkor mRNA. Hkor was cloned into the expression vector pBK-CMV and transiently expressed in COS-1 cells. Hkor had high affinity for [3H] diprenorphine, a nonselective opioid antagonist, and displayed stereospecific binding to naloxone. kappa selective ligands (U50,488H and nor-BNI) had high affinities, whereas mu and delta selective ligands bound with much lower affinities. Dynorphin A (1-17) and alpha-neoendorphin, both endogenous kappa peptides, bound with high affinities. These binding characteristics confirmed that hkor is a kappa receptor, most likely kappa 1 type. Cloning of the human kappa receptor allows investigation of interactions of compounds with the human receptor, instead of rodent receptors, for development of better therapeutic agents.

Amino Acid Sequence↗

The enzyme and inhibitors of 4-ene-3-oxosteroid 5 alpha-oxidoreductase.

Since evidence of 5 alpha-reductase activity in rabbit liver homogenate was discovered in 1954, the presence of this enzyme has been demonstrated in many other organs and tissues of mammalian species. 5 alpha-Reductase selectively transforms a 4-ene-3-oxosteroid (e.g., testosterone) irreversibly to the corresponding 5 alpha-3-oxosteroid (e.g., 5 alpha-dihydrotestosterone) in the presence of NADPH as an essential coenzyme at an optimal pH. However, excessive production of 5 alpha-dihydrotestosterone is the major cause of many androgen-related disorders, such as prostate cancer, benign prostatic hyperplasia, acne, female hirsutism, and male pattern baldness; therefore, inhibition of androgenic action by 5 alpha-reductase inhibitors is a logical treatment. During the past two decades, research has focused on understanding the biological functions and effects of 5 alpha-reductase and its 5 alpha-reduced metabolites: purification of the enzyme, substrates, and metabolites; characterization of their physical, chemical, and biochemical properties; analysis of the amino acid sequence of the enzyme; synthesis of various classes of molecules as potential inhibitors; and examination of the biological activity of the inhibitors in vitro and/or in vivo. This review summarizes the biochemical studies on this enzyme, suggests the mechanisms of action of the enzyme or inhibitors, and discusses the chemistry necessary for the preparation, structure-activity relationships, and in vitro and/or in vivo data obtained from the evaluation of nonsteroidal and steroidal compounds that have been tested as inhibitors of 5 alpha-reductase. In particular, IC50 and Ki values for relevant compounds will be compared according to molecular class. This review could function as a comprehensive working reference of what research has been accomplished so far and what problems remain to be solved in the future for those engaged in this interesting field.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

ATP modulation of L-type calcium channel currents in guinea pig outer hair cells.

Ca2+ channel currents and their modulation by adenosine 5'-triphosphate (ATP) in acutely isolated guinea pig outer hair cells (OHCs) were investigated using the whole-cell patch-clamp technique. The current-voltage (I-V) relation of OHCs indicated that the Ca2+ channel opened near -30 mV, and the current reached a maximum at +10 and 0 mV in 20 mM Ca2+ and Ba2+ external solutions, respectively. BayK 8644 (BayK, 2 microM) caused a 3.5-fold increase in peak Ca2+ currents and shifted the I-V curves toward more negative potentials. These results suggest that the majority of Ca2+ channels in OHCs have L-type characteristics. The effects of ATP on Ca2+ channels of OHCs were heterogenous. ATP (100 microM) decreased Ca2+ channel currents by 31.7 +/- 5.6% at 0 mV and shifted Ca2+ tail activation curves toward more depolarized potentials in some cells (N = 6). By contrast, in others, ATP enhanced the currents by 43.5 +/- 12.5% at +10 mV (N = 6). In the presence of BayK, however, ATP-induced inhibition or enhancement of Ca2+ channel currents was attenuated. In addition, 100 microM ATP produced little effect on Ca2+ channel currents in another subpopulation of cells (N = 12). This heterogenous neuromodulation of Ca2+ channel currents by ATP may reflect a functional diversity among OHCs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Nitroprusside suppresses cochlear potentials and outer hair cell responses.

Biochemical and pharmacological evidence supports a role for nitric oxide (NO) in the cochlea. In the present experiments, we tested sodium nitroprusside (SNP), an NO donor, applied by intracochlear perfusions on sound-evoked responses of the cochlea (CM, cochlear microphonic; SP, summating potential; EP, endocochlear potential; CAP, compound action potential) and in vitro on outer hair cell (OHC) voltage-induced length changes and current responses. In vivo application of SNP in increasing concentrations (10, 33, 100, 330 and 1000 microM) reduced all sound-evoked responses starting at about 300 microM. The responses continued to decline after a postdrug wash. At 1 mM SNP decreased EP slowly (approximately 80 min) whereas at 10 mM it reduced EP more rapidly (approximately 20 min). Ferricyanide (1 mM) and S-nitroso-N-acetylpenicillamine (SNAP; 1 mM) had no effect on sound-evoked cochlear potentials. Ferricyanide (1 mM and 10 mM) and ferrocyanide (10 mM) had no effect on EP. In vitro, SNP (10 mM) significantly reduced both OHC voltage-induced length changes and whole-cell outward currents. Results suggest that SNP, possibly acting by released NO, influences cochlear function through effects at the stria vascularis and at the OHCs.

Acoustic Stimulation↗

Noise exposure alters the response of outer hair cells to ATP.

The outer hair cells (OHCs) are one target of noise-induced effects. To date there are few studies which examine changes in the function of OHCs induced by noise exposure. There is increasing evidence that ATP may be a neuromodulator acting on OHCs. Therefore, we examined the possibility that the response to ATP may be altered by low-level noise exposure. ATP was tested on cation currents recorded from outer hair cells (OHCs) isolated from chronic noise-exposed guinea pigs and compared to currents recorded from normal control animals. The whole-cell variant of the patch-clamp technique was used. The incidence of response to 100 microM ATP was decreased in OHCs from noise-exposed animals as compared to controls when normal internal and external solutions were employed. When K+ was substituted by N-methyl-glucamine (NMG+) in the pipette solution, there were significant differences in the magnitudes of ATP-evoked currents between cells from noise-exposed and control animals. This was observed in both normal and 20 mM Ba2+ external solutions. In addition, the response to ATP exhibited a dependency on OHC length. In short OHCs (< 65 microns) from noise-exposed animals the magnitude of the response to ATP was significantly reduced. By contrast, the response in long OHCs (> 65 microns) from noise-exposed animals was increased. Results suggest that low-level noise exposure induces changes in OHCs which affect the response of the cell to ATP.

Acoustic Stimulation↗

Immunoglobulin heavy chain gene replacement: a mechanism of receptor editing.

We have generated a site-directed transgenic (sd-tg) mouse model in which the JH locus has been replaced with a rearranged VDJ coding for the heavy chain of an anti-DNA antibody. In these mice, B cells expressing the anti-dsDNA specificity are negatively regulated. We observe a novel mechanism for B cell tolerance, receptor editing at the heavy chain locus. In most sd-tg B cells, the inserted anti-DNA VH gene has been replaced by the upstream endogenous VH, or DH, or both genes through recombination with the heptamer embedded at the 3' end of most VH genes. Three types of recombination events have been identified. VH-to-VDJ, DH-to-VDJ, and VH-to-DH-VDJ. Analysis of the junctional sequences revealed features of classical V(D)J rearrangement, namely N sequence addition and nucleotide deletion. A conserved nonamer was found 12 bp upstream of the embedded heptamer. This nonamer may represent a novel recombination signal sequence used for VH editing. The sd-tg model thus provides direct evidence for secondary rearrangement at VH-D-JH. This process may play a role in tolerance by editing autoreactive receptors and may also serve to diversify the VH repertoire.

Amino Acid Sequence↗

Heat shock protein (HSP 72) expression in patients undergoing cardiac operations.

The major mammalian stress-inducible protein, heat shock protein 72, protects cells from certain stresses and rapidly accumulates in cells after ischemia. Heat shock protein 72 is rapidly synthesized in the myocardium of various species in response to ischemia, but it has not been investigated in human heart. To determine if heat shock protein 72 accumulated in the ischemic myocardium of patients undergoing cardiac operations, we obtained sequential right atrial biopsy specimens from 12 patients undergoing repair at three intervals: before bypass, after reperfusion, and after bypass. Immunoblot analysis for heat shock protein 72 demonstrated a high expression in the human heart compared with other mammalian hearts, p (Binomial) = 0.01. Compared with before bypass, heat shock protein 72 contents after reperfusion and after bypass were 98.2% +/- 8.9%, p (signed-rank) = 0.65, and 87.6% +/- 17.1%, p (signed-rank) = 0.28, respectively. Although heat shock protein 72 concentration was unchanged in hearts after reperfusion and after bypass, the initial prebypass level of heat shock protein 72 was high. The high heat shock protein 72 level detected in human hearts may reflect preoperative disease and drug therapy, or inherently high levels may be usual in the human myocardium. These findings indicate that the myocardium of patients undergoing cardiac operations contains relatively high concentrations of heat shock protein 72, which are not increased during the surgical procedure.

Adolescent↗

Boundary layer infusion of heparin prevents thrombosis and reduces neointimal hyperplasia in venous polytetrafluoroethylene grafts without systemic anticoagulation.

PURPOSE: Recently, we designed and characterized a novel polytetrafluoroethylene-based local drug delivery device that selectively concentrates infused pharmacologic agents specifically within those blood layers adjacent to the graft wall and at downstream anastomotic sites. In this study we locally administered heparin with this approach and evaluated its effect on graft patency and neointimal hyperplasia formation in a rabbit model of inferior vena cava replacement. METHODS: Twelve animals were evenly assigned either to a control group infused with saline solution or to a treatment group infused with heparin for 14 days. Bromodeoxyuridine labeling was used to assess vascular cell proliferation. RESULTS: All grafts in the control group were occluded at 14 days. All grafts in the heparin-treated group remained patent, although there was no significant difference in systemic activated partial thromboplastin time measurements taken before and during the infusion of heparin (p > 0.5). In the treatment group, heparin reduced neointimal thickness, neointimal area, and the bromodeoxyuridine labeling index by 88%, 95%, and 72%, respectively (p < 0.01), at the locally treated downstream anastomosis as compared with the untreated upstream anastomosis. CONCLUSION: These data demonstrate that the local boundary layer infusion of heparin significantly increases overall inferior vena cava graft patency (p = 0.014) and markedly reduces downstream anastomotic neointimal hyperplasia and cell proliferation. This approach may represent an attractive strategy for antithrombotic therapy in venous replacement with synthetic graft materials.

Animals↗

Artificial neural network method for discriminating coding regions of eukaryotic genes.

This paper describes the application of artificial neural networks to discriminating the coding system of eukaryotic genes. We choose > 300 genes from eight eukaryotic organisms: human, mouse, rat, horse, ox, sheep, soybean and rabbit, from which we build up different discrimination models relevant to their promoter regions, poly(A) signals, splice site locations of introns and noose structures. The results shows that as long as the coding length is definite, the only correct coding region can be chosen from the large number of possible solutions discriminated by neural networks.

Animals↗

Detection of putative periodontal pathogens in subgingival specimens by 16S ribosomal DNA amplification with the polymerase chain reaction.

The utility of the 16S ribosomal RNA-based polymerase chain reaction (PCR) for detection of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Campylobacter rectus, Eikenella corrodens, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola was examined and compared with that of anaerobic culture. Primer pairs consisting of 20-27 nucleotides amplified 404- to 688-bp regions of 16S ribosomal RNA genes of these organisms. This method had a lower detection limit of 50 target cells in a background of 10(7) cells. Its specificity for B. forsythus, P. gingivalis, and T. denticola seemed high. The primers for A. actinomycetemcomitans, C. rectus, and P. intermedia cross-reacted with some closely related species but did not reveal amplification products in tests with more distantly related organisms. The primers for E. corrodens did not seem to cross-react with oral organisms. This PCR technique was sensitive, reproducible, and easy to perform. PCR-based amplification may prove valuable for the detection of some periodontal pathogens in crude subgingival specimens.

Adult↗