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N He

Publications and source records attributed to N He.

44 records · Page 3Linked to original sources

[Inhibition of hepatitis C virus by antisense oligodeoxynucleotide in vitro].

OBJECTIVE: To study inhibitory effect of antisense oligodeoxynucleotide (asODN) on HCV in vitro. METHODS: The H9 cells transfected by pCD-HCV, a recombinant HCV containing total HCV structural gene, were treated with two 15-mers phosphorothioate (PS) ODNs complementary (PS-ASON) and homologous (PS-ODN) to HCV core genomic region, which were labeled with digoxin (DIG). Spot blot hybridization was carried out. Treated by the two ODNs, rPS-ODN (a 15-mers PS ODN of random sequence) or PS-ASON were modified with two liposomes (DOTAP and Lipofectin) and calcium phosphate precipitation respectively. With a half-ration, the variation of level of HCV mRNA and HCV antigen expression was observed by RT-PCR and dot ELISA. 3H-TdR adding test was done to observe PS-ASON cytotoxicity. RESULTS: PS-ODN and PS-ASON were detected in the H9 cells. The target gene was hybridized to PS-ASON and PS-ODN labeled with DIG. PS-ASON cut down level of HCV mRNA and HCV antigen expression obviously. However, PS-ODN and rPS-ODN did not influence the level of the both. The time-dependent and dose-dependent inhibition of PS-ASON was observed. In contrast to free PS-ASON, both of liposomal PS-ASON showed more highly effective inhibition, but calcium phosphate precipitation-PS-ASON complex did not. The results showed PS-ASON did not influence the H9 cells growth at 10 mumol/L. CONCLUSION: PS-ASON complementary to HCV core gene is asODN and exerts antisense-inhibitory effect on the level of HCV translation obviously, but not on the level of HCV replication and transcription.

CD4-Positive T-Lymphocytes↗

Modulation of doxorubicin cytotoxicity by ethacrynic acid.

Energy-dependent membrane efflux pumps have been implicated in mediating resistance to doxorubicin (DOX). Membrane-transport mechanisms distinct from P-glycoprotein, capable of transporting DOX and glutathione conjugates have been reported in human cells. Since glutathione-conjugate-forming compounds may be candidates for modulating the cytotoxicity of certain anti-neoplastic agents transported by such transport mechanism, the present studies were performed (i) to determine whether ethacrynic acid, a glutathione-conjugate-forming diuretic, can increase DOX cytotoxicity, and (ii) to study the kinetics of DOX transport and its inhibition by the glutathione conjugate of ethacrynic acid (EA-SG) in the H69 human small-cell-lung-cancer cell line and 2 derived DOX-resistant sublines. Our results indicate that more than one DOX transport mechanism may exist in these cell lines, and that glutathione conjugates may be useful for modulating the cytotoxic effects of DOX.

ATP-Binding Cassette Transporters↗

The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype.

1. The disposition of diazepam and desmethyldiazepam was studied in 21 healthy male Chinese subjects who were phenotyped with mephenytoin. Four poor metabolizers (PM) were identified by phenotyping with mephenytoin and by genotyping for CYP2C19. 2. Serum diazepam and desmethyldiazepam concentrations were measured by high performance liquid chromatography in samples drawn up to 24 days after administration. 3. The plasma elimination half-lives of diazepam (100.8 +/- 32.3 h) and desmethyldiazepam (219.9 +/- 62.7 h) in PMs were significantly longer than those (34.7 +/- 23.0 h for diazepam, 103.1 +/- 25.9 h for desmethyldiazepam) of the 17 phenotyped extensive metabolizers (EM), and those (30.8 +/- 24.9 h for diazepam, 103.1 +/- 27.5 h for desmethyldiazepam) of the five genotyped EMs. 4. The mephenytoin S/R ratios were significantly correlated with the plasma half-lives of diazepam (r = 0.543, P < 0.05) and desmethyldiazepam (r = 0.522, P < 0.05), and with the clearance (r = -0.524, P < 0.05) of diazepam in 21 subjects. 5. These results are compatible with the conclusion that both diazepam and desmethyldiazepam are metabolized by cytochrome P450 CYP2C19 in the Chinese population. 6. The mephenytoin S/R ratios in nine EMs who drank alcohol frequently were significantly higher than those of seven EMs who were non-drinkers, but the plasma kinetics of diazepam and desmethyldiazepam were not significantly different between the two groups. The explanation for these finding is not clear.

Asian People↗

Masking by ipsilateral and contralateral maskers.

Contralateral masking occurs when the threshold of a signal in one ear is elevated by the presence of a masker in the other, contralateral ear. The classic data and theory on contralateral masking were provided by Zwislocki [J. Acoust. Soc. Am. 52, 644-659 (1972)] who observed a 3- to 18-dB threshold shift (masking) for a gated pure-tone signal in one ear when a gated pure-tone masker was presented via insert earphones to the other ear. Zwislocki referred to this phenomenon as "central masking." Here, using two psychophysical methods (Yes-No; two-interval forced-choice), Zwislocki's original results, obtained with other psychophysical methods, were successfully replicated. Similar results using several psychophysical methods suggest that contralateral masking is indicative of a sensory phenomenon rather than observer bias and other response proclivities. In a second experiment, psychophysical tuning curves were obtained using either an ipsilateral masker or a contralateral masker. Tuning curves obtained with a contralateral masker had steeper slopes on both the low- and high-frequency sides than tuning curves obtained with an ipsilateral masker. Thus, although substantially smaller in effect than ipsilateral masking, contralateral masking is more sharply tuned. The sharp tuning of contralateral masking reflects a greater compression of the input/output functions for contralateral masking than for ipsilateral masking. The closest correspondence between the tuning curves reported here for contralateral masking and those predicted by Zwislocki's theory and data (on central masking) occurred for tuning curves where the ratio of driven activity to spontaneous activity was about six. A remaining issue is the role, if any, of the efferent auditory system, especially the olivocochlear bundle, in threshold shifts measured using the Zwislocki (central masking) paradigm.

Adult↗

Experimental renal artery stenosis and angioplasty. The mechanism of the angioplasty.

The mechanism of percutaneous transluminal renal angioplasty (PTRA) was studied in 18 dogs. The dogs were divided into two groups. Seven dogs were in the early group and eleven were within 1-3 weeks after PTRA. A 4/0 resorbable chronic catgut was used to ligate subtotally the renal artery to create fibromuscular dysplasia. PTRA was performed after renal artery stenosis for 6-8 weeks. The changes of ultrastructure of renal artery were studied. A contrary orientation balance hypothesis was proposed to explain the mechanism of PTRA.

Angioplasty, Balloon↗

An antigenic recombinant fusion protein from Trichinella spiralis induces a protective response in BALB/c mice.

A previously reported recombinant lambda Ts39 fusion protein (FP) derived from Trichinella spiralis larvae was purified by affinity chromatography using an anti-beta-galactosidase antibody conjugated column and the effect of FP on induction of a protective response in mice was studied. BALB/c mice were injected three times at weekly intervals with FP emulsified in an equal volume of Freund's complete adjuvant and one week after the last injection mice were each challenged with a lethal dose of 1200 L1 larvae of Trichinella spiralis. As a result, the FP induced significant protection. Mice were also infected orally with 250 L1 larvae each after injection of the FP. On the 35th day of infection, immunized mice with the FP harboured 78% fewer muscle larvae than saline controls. Also, the numbers of adult worms in the small intestine were smaller in FP injected mice than saline controls on day 6 and 9 of the infection. These results suggest that the recombinant lambda Ts39 FP is a potentially valuable antigen for vaccine development.

Animals↗