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Biomedical subjects

W R Chen

Publications and source records attributed to W R Chen.

At least 37 records · Page 2Linked to original sources

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex.

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

2-Amino-5-phosphonovalerate↗

Photothermal effects on murine mammary tumors using indocyanine green and an 808-nm diode laser: an in vivo efficacy study.

Murine mammary tumors were treated using indocyanine green and an 808 nm diode laser, and the in vivo chromophore-enhanced photothermal effects on the tumor burden and on tumor rat survival were investigated. The power of the laser was selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent aqueous indocyanine green solution in a volume of 100-200 microliters was administered in situ, either acutely or 24 h prior to the treatment. The photothermal interaction was apparent under all our treatment conditions with a well-defined spatial containment in this study and the tumor growth was slowed after treatment. The post-treatment observation showed tumor recurrence and metastasis; no long-term survival was achieved with the single application of laser in conjunction with indocyanine green. Our results pose a question on the efficacy of the photothermal interaction even though tumor cell destruction can be achieved in a large and controlled scale. However, this highly selective photothermal impact on the tumor tissue did suggest that this method be applied repeatedly to be more effective and be used as the precursor of other modalities, such as chemotherapy, radiation therapy, immunotherapy, and surgery.

Animals↗

[A three-year follow-up study of hepatitis C virus infected individuals from Beixie village, Gu-an county, Hebel province, China].

A total number of 42 anti-HCV positive individuals from Beixie village, Gu-an county, was followed for three years to study the dynamic change of alanine aminotransminase (ALT), anti-HCV titers as well as HCV RNA in serum. Research results showed that 18.1% to 26.2% of the individuals exhibited a rise in ALT values while the positive rate of HCV RNA was 80%. The yearly negative seroconversion rate of anti-HCV was only 0.95%. The geometric mean titer (GMT) of anti-HCV was around 160 and showed no significant difference between the paired serum samples collected in 1991 and in 1994. There were no statistical associations between the GMT value of anti-HCV and ALT level as well as HCV RNA in serum.

Adult↗

Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser.

Rat mammary tumors were treated using an 808-nm diode laser in a power range of 3-15 W. Photothermolysis was selectively enhanced by the chromophore indocyanine green (ICG), which has an absorption peak corresponding to the laser wavelength. ICG, injected into neoplastic tissues 24 h before laser exposure, was retained in sufficient quantity to produce a strong photothermal reaction. With appropriate laser power and adequate irradiation duration, laser energy could inflict severe photothermal damage to the entire targeted tumor tissue while leaving the skin and other interdicted tissue undamaged. Higher laser powers (10-15 W) produced more surface damage that limited light transmission and as a result gave rise to reduced regions of thermal destruction. Post-treatment observation revealed the survival of numerous tumor cells. This finding questions the long term efficacy of the photothermal effect of a single treatment using the combination of the ICG and the diode laser, particularly in the absence of other modalities.

Animals↗

Chromophore-enhanced laser-tumor tissue photothermal interaction using an 808-nm diode laser.

A diode laser was used to irradiate tumor tissue, with indocyanine green as the chromophore. The 808-nm wavelength radiation falls within the absorption peak of the chromophore (about 780 nm). The preliminary results in this report revealed clear and significant coupling of this laser and indocyanine green in laser-tissue photothermal interaction. The chromophore targeted tissue showed laser damage while peripheral tissues remained intact. Without the chromophore, this laser inflicted no apparent tissue damage in the non-contact mode with irradiance up to 1755 J/cm2.

Animals↗

The influence of the extent of target organs on sensitivities of methods for screening rodent carcinogens.

Two hundred and thirty-three rodent carcinogens from the Carcinogenic Potency Database (CPDB) were analyzed with CASE (Computer Automated Structure Evaluation), and a comparison of the extents of target organs with the sensitivities for long-term carcinogenic bioassays in rats and mice, Salmonella assay (Sty), electrophilic substructure alert analysis (ESAA) and CASE was made. The carcinogenicity of 233 chemicals was evaluated in both rat and mouse bioassays. The present study showed that the sensitivities of the five methods for screening carcinogens were related to the extents of target organs of carcinogens. Among the carcinogens that did not induce tumors (extent = 0) in rats, the sensitivities of Sty and ESAA were 46 and 53, respectively. Among the carcinogens which induced tumors at a single organ (extent = 1) in rats, the sensitivities were 57 and 64 respectively; and 71 and 80 at multiple organs (extent > 1) respectively. The sensitivities of CASE were 76, 82, and 89 respectively at these three different extents. Similar results were obtained with these carcinogens in mice. The results indicate that mutagenic or electrophilic carcinogens are more likely to induce tumors at multiple target organs; in contrast, most carcinogens which induced tumors at only a single target organ in one species are rarely mutagenic or electrophilic. The sensitivities of Sty and ESAA were lower than that of the CASE method in these carcinogens. CASE analyzed chemical structures of many carcinogens and non-carcinogens and then established a database of key fragments, and its parameters are not only based on mutagenicity or electrophilicity of chemicals, and this resulted in a more exact detection of the carcinogenicity of chemicals with the CASE method.

Animals↗

Nicardipine enhances cytoplasmic calcium concentration in mouse thymocytes in vitro.

AIM: To study the effect of nicardipine (Nic) on the cytoplasmic free calcium concentration ([Ca2+]i) in thymocytes and on the proliferation of thymus lymphocytes from mice in vitro. METHODS: The [Ca2+]i was measured by loading cells with the fluorescent dye Fura-2. The lymphocyte proliferation was determined by [3H] thymidine incorporation. RESULTS: Nic 1-30 mumol . L-1 elevated [Ca2+]i of resting thymocytes with the percentages of its increase 43%-192% and 12%-148% in the presence and absence of extracellular Ca2+ respectively. Mitogen Con A 5 mg . L-1 also released Ca2+ from intracellular stores. Nic decreased the enhancement of [Ca2+]i induced by Con A. The IC50 (mumol . L-1) was 26.8 (95% limit: 24.8-29.0) and approximated to 10 in the presence and absence of extracellular Ca2+ respectively. Nic 1-30 mumol . L-1 did not stimulate the proliferation of resting lymphocytes from mouse thymuses (P > 0.05), but inhibited the proliferation when the lymphocytes had been stimulated by Con A (P < 0.01). CONCLUSION: Nic elevated [Ca2+]i, which decreased the response of lymphocytes to mitogen.

Animals↗

Differential expression of AE1 in renal HCO3-secreting and -reabsorbing intercalated cells.

The cortical collecting duct of the kidney contains two types of intercalated cells that transport HCO3 in opposite directions. HCO3 reabsorption takes place in the alpha-type intercalated cells, which express a Cl/HCO3 exchanger on the basolateral membrane. This exchanger is the product of the anion exchanger 1 (AE1) or band 3 gene. HCO3 secretion occurs in the beta-intercalated cells, which have a Cl/HCO3 exchanger on the apical membrane. Based on studies in an immortalized cell line, recently it was proposed that the apical anion exchanger of beta-intercalated cells is also AE1 (van Adelsberg, J. S., Edwards, J. C., and Al-Awqati, Q. (1993) J. Biol. Chem. 268, 11283-11289). In the present study we reinvestigated this issue by determining the distribution of AE1 mRNA and protein in the two intercalated cell types using cells freshly isolated from the native epithelium. Using quantitative reverse transcriptase polymerase chain reaction, we found that alpha-intercalated cells, isolated from rabbit kidney by fluorescence-activated cell sorting, have high levels of AE1 mRNA, whereas beta-intercalated cells express very low levels. The ratio of AE1 mRNA levels in alpha- versus beta-intercalated cells averaged 10.1 +/- 2.6. In addition, metabolic acidosis increased the levels of AE1 mRNA by 3-5-fold in cortical collecting duct cells. This difference was confirmed by Northern blotting. Western blotting using an antibody against rabbit AE1 revealed a major immunoreactive product with a molecular weight of approximately 110 kDa in cortical collecting duct cells. Deglycosylation reduced the size of the immunoreactive product to approximately 90 kDa, which is compatible with the presence of a truncated form of AE1. Metabolic acidosis increased the intensity of the AE1 immunoreactive band. The level of AE1-immunoreactive protein was significantly higher in alpha-intercalated cells than in beta-intercalated cells. In aggregate, these data provide evidence for the differential expression of AE1 in HCO3-reabsorbing versus HCO3-secreting renal intercalated cells both at the mRNA and at the protein level. These results give no support to the concept that AE1 functions both as a basolateral and an apical anion exchanger in cortical collecting duct cells.

Acidosis↗

[Inhibition of 5 calcium channel blockers on H2O2 release from mouse peritoneal macrophages].

After the peritoneal macrophages from mice were incubated with different concentrations of calcium channel blockers for 3 h at 37 degrees C, the macrophages were stimulated with opsonized zymosan for 1.5 h at 37 degrees C. The released H2O2 was measured by fluorescence assay. The results showed that verapamil (Ver), nifedipine (Nif), nicardipine (Nic), nimodipine (Nim), and nitrendipine (Nit) reduced the H2O2 release significantly in a dose-dependent manner. The IC50 values (mumol.L-1) were 30, 50, 49, 63, and 92 for Nic, Nif, Nim, Nit, and Ver, respectively. There was slight inhibition of dihydropyridine (Bay k 8644) 10 mumol.L-1 on H2O2 release. When Bay k 8644 at above concentration combined with Ver, Nim, and Nit 25 mumol.L-1, respectively, the inhibitions of Ver, Nim, and Nit on H2O2 release were increased 32%-40%. Above results showed that on the inhibition of H2O2 release, the effects of dihydropyridines calcium channel blockers were greater than that of Ver, and the effects of Nic and Nif were greater than those of Nim and Nit. The acting sitei of Bay k 8644 at high concentration (10 mumol.L-1 and over) was probably different from that of typical calcium channel blockers Nim, Nit, and Ver in macrophages.

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

[A computer system of automated evaluation of structure-activity relationship of chemical mutagens].

A computer automated structure evaluation (CASE) system has been established. The data base of the system consists of more than 2000 chemicals and hundreds of biophores and biophobes identified by CASE. All programs can be run in micro-computer. Thus, entry of a chemical unknown genetoxity will result in the generation of all the possible fragments. On the basis of the presence and/or absence of these descriptors, CASE can predict activity or lack of it. In addition, and independently of the above, CASE also performs spell out, please and comparison program of genetic toxicology. The CASE program can be used to predict the mutagenicity and carcinogenicity of the many untested chemicals in the ambient environment. The sensitivity and specificity of this system all exceeds 90% and therefore the system has a very good-prospect of being used for forecasting.

Carcinogens↗

A new genotype of Japanese encephalitis virus from Indonesia.

Primer-extension sequencing of the RNA template of polio, dengue, Rift Valley fever, and Japanese encephalitis (JE) viruses has provided new information on their geographic distribution, origin, and evolution. In a previous study of 46 diverse JE virus strains, we demonstrated the existence of three distinct JE genotypes in Asia. We now report the occurrence of a fourth genotype. In the present study, 19 JE virus isolates, representing various geographic regions of Asia and a 50-year time span, were compared with each other and with Murray Valley encephalitis, West Nile, and Kunjin viruses. Twelve of the JE strains from the Indonesian Archipelago and the Philippines had not been previously examined; the remainder were representatives of the three previously identified genotypes. Two hundred forty nucleotides from the pre-M gene region of the virus were used in these comparisons. Using 12% divergence as a cut-off point, the 19 JE strains fell into four distinct genotypic groups; maximum divergence across the comparison region was 21%. The newly recognized fourth genotype was comprised of five Indonesian isolates that were 7% divergent from the rest of the JE viruses.

Amino Acid Sequence↗

Preliminary report on seroepidemiology of HCV and HBV infection in northern China.

1 141 serum samples from various population groups in north China were examined for C100-3Ab by ELISA. Antibody to C100-3 antigen derived from HCV genome (C100-3A) and HBsAg were measured in 438 normal population in Beijing. The C100-3Ab positive rate was 2.1% and the HBsAg positive rate was 2.5%. There is increased occurrence with age. In 649 cases of chronic liver diseases, the HBsAg positive rate was 87.1% in chronic persistent hepatitis (CPA), 88.8% in chronic active hepatitis (CAH), 64.9% in liver cirrhosis (LC) and 67.3% in hepatocellular carcinoma (HCC). The C100-3Ab positive rate was 10.5% (CPH), 12.1% (CAH), 42.6% (LC) and 38.4% (HCC). It is noteworthy that the C100-3Ab positive rate significantly increased with disease progression from CPH to CAH, LC and HCC. Prevalence of cases positive for both C100-3Ab and HBsAg was 0% in the normal population, 6.7% in CPH, 8.4% in CAH, 31.1% in LC and 28.8% in HCC. Investigation of patients with HCV infection showed that only 36.8% had blood transfusions. HCV and HBV infection may play important pathogenic roles in CPH, CAH, LC and HCC in north China.

Adolescent↗

Seroepidemiology of HCV and HBV infection in northern China.

The HCVAb positive rate in normal population in Beijing was 2.1% and HBsAg positive rate was 2.5%. There is an increasing tendency in the aged group. Plasmapheresis might have been the major cause of HCV transmission in blood donors in the Hebei area. There was a high prevalence of HCVAb and HBsAg in chronic liver diseases in the Beijing area and the HCVAb-positive rate significantly increased corresponding to disease progression.

Adolescent↗

Similarity and diversity in sequence of HCV genome among Chinese, Japanese and American strains.

To estimate the homology between Chinese HCV strain, Japanese HCV strain and American HCV strain, we isolated and sequenced 8 clones, representing a 277-long fragment of high diversity. Chinese HCV strain was found to be homologous only in 68.6-72.6% for nucleotide sequence and in 69.6-73.9% for amino acid sequence to American HCV strain, but in 83.4-88.4% for nucleotide sequence and in 78.3-88.0% for amino acid sequence to Japanese main strain. The isolated strain may be the main strain in China, which can be divided into several substrains. This result is believed to be of paramount importance for the development of HCV detection method and vaccination as well as for the study on pathogenesis of HCV infection.

Amino Acid Sequence↗

Genetic variation of Japanese encephalitis virus in nature.

Forty-six strains of Japanese encephalitis (JE) virus from a variety of geographic areas in Asia were examined by primer-extension sequencing of the RNA template. A 240 nucleotide sequence from the pre-M gene region was selected for study because it provided sufficient information for determining genetic relationships among the virus isolates. Using 12% divergence as a cutoff point for virus relationships, the 46 isolates fell into three distinct genotypic groups. One genotypic group consisted of JE virus isolates from northern Thailand and Cambodia. A second group was composed of isolates from southern Thailand, Malaysia, Sarawak and Indonesia. The remainder of the isolates, from Japan, China, Taiwan, the Philippines, Sri Lanka, India and Nepal, made up a third group. The implications of these findings in relation to the epidemiology of JE are discussed. Results of this study demonstrate that the comparison of short nucleotide sequences can provide insight into JE virus evolution, transmission and, possibly, pathogenesis.

Animals↗

[Anti-inflammatory effects of verapamil, nifedipine and nicardipine].

Anti-inflammatory effects of calcium antagonists verapamil (Ver), nifedipine (Nif) and nicardipine (Nic) were compared. They all produced significant inhibitions in acute and chronic inflammatory models in a dose-dependent manner. The ED30 in the capillary permeability were: Ver 18, Nif 12 and Nic 8 mg/kg, respectively. In the xylene-induced swelling of mouse ears, the ED30 were: Ver 39, Nif 14, and Nic 25 mg/kg, respectively. In the carrageenan paw edema of mice, and in the acetic acid-induced pleurisy and cotton granuloma of rats these drugs inhibited inflammatory responses at 5 or 10 mg/kg. Nif showed a greater effect than Ver and Nic on the paw edema, and Ver showed greater effects than NIf and Nic on the pleurisy and granuloma. At 10 mg/kg they depressed the PGE2 content measured by radioimmunoassay in inflammatory tissues of carrageenan paw edema of mice.

Animals↗

Investigation of anti-HCV in 391 serum samples in China.

391 serum samples from healthy blood donors, HBsAg positive blood donors and patients with different kinds of liver diseases in northern China were tested for anti-HCV by ELISA. Of the healthy donors, 4.6% (7/151) were anti-HCV positive; of the HBsAg positive donors, 32.4% (24/74) were positive; and of the liver disease patients, 5.4% (9/166) were positive. Among the 24 cases of HBV-HCV double infection, 10 were assayed for serum ALT level. 40% (4/10) of them were abnormal. The causes of the surprisingly high rate of HCV infection, both in healthy donors and in HBsAg positive donors, were discussed. This is the first report on the distribution of anti-HCV in certain population in China.

Adult↗

[Influence of nicardipine on the morphology, calcium and cAMP level of immune organs in mice].

Nicardipine, 10 mg/kg sc qd x 4d, caused morphological changes of immune organs in mice. The germinal centers of lymph nodes markedly reduced. The white pulps of spleens and the cortex of thymuses atrophied slightly. In these lymphoid tissues, the small lymphocytes markedly increased and the heterochromatin of nuclei increased. In the subcellular level, nicardipine damaged the structure of mitochondria in various cells. The lymphocytes in peripheral blood and the calcium content and cAMP level in immune organs markedly decreased. These results suggest that nicardipine inhibited proliferation of lymphocytes in vivo, and this effect was probably associated with the decreasing calcium content in immune organs. Influence on the structure and functions of mitochondria may be one of the mechanisms of nicardipine inhibiting functions of immune cells.

Animals↗