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Biomedical subjects

J S Yang

Publications and source records attributed to J S Yang.

At least 127 records · Page 7Linked to original sources
PubMed1989

Comparative study of metastatic behavior of a human tumor cell line in athymic (nu/nu) and beige nude mice (bg/bg-nu/nu).

In this experiment, the "nu" gene was introduced into "beige" mutant mice, which are immunodeficient in NK cell activity. The resultant beige nude mice (bg/bg-nu/nu) have combined immunodeficiency in both T and NK cell activities. The level of NK cell activity in beige nude mice is slightly higher than that in beige mice, but much lower than that in nude mice. This is consistent with other studies. In order to elucidate the role of the metastatic behavior of a human tumor cell line PAa in both athymic nude mice and beige nude mice. The PAa cell line was originally established from a human lung adenocarcinoma and maintained as a solid tumor by serial s.c. passage in nude mice. During the first 18 passages in nude mice, PAa cells were found to have metastasized spontaneously to regional lymph nodes in only 4 animals, but metastases were no longer found in subsequent passages. The total incidence of metastasis in nude mice was 9% (4/44). However, when inoculated s.c. into beige nude mice, the metastatic rate of PAa cells was 43% (9/21) to the regional lymph nodes and 10% (2/21) to the lungs in two separate experiments. We conclude from the results that NK cells may play an important, if not exclusive, role in host resistance to tumor metastasis. Beige nude mice could serve as a useful in vivo model in studies of the biology and heterogeneity of human tumor metastasis.

Adenocarcinoma↗
PubMed1989

[Studies on the chemical constituents of Aquilaria sinensis (Lour) Gilg. III. Elucidation of the structure of isobaimuxinol and isolation and identification of the constituents of lower boiling fraction of the volatile oil].

A new sesquiterpenoid, named isobaimuxinol, C15H26O2, mp 73-75 degrees C, [a]D12-68(0) (c 0.10, CHCl3), was isolated from the volatile oil of Aquilaria sinensis (Lour), Gilg. (Thymeleaceae). Based on spectral (IR, 1H-NMR, 13C-NMR and 2D-NMR as well as MS) analysis its structure was identified as isobaimuxinol. The relative stereochemistry of isobaimuxinol was determined by X-ray crystallograhy. In addition, four known compounds, benzylacetone, p-methoxybenzylacetone, anisic acid and beta-agarofuran were isolated and identified from the lower boiling fraction of the volatile oil of this plant. These compounds were obtained for the first time from this plant.

Chemical Phenomena↗
PubMed1988

A simplified high speed multicolor immunoblotting method.

We describe a simplified technique for the rapid and specific detection of antigenic determinants within a mixed population of antigens. Each determinant develops its own characteristic color in a single Western blot or dot blot. This multicolor immunostaining technique can be achieved with as little as a one-step incubation, involving a mixture of different primary and developing antibodies, and a one-step substrate reaction, involving a mixture of different substrates. The time required can be reduced to short periods of time, ranging from minutes to about 1 h. This can represent an increase in the speed of detection by one to two orders of magnitude when compared with conventional methods. The simplified protocols may facilitate the automation of routine analyses.

Antibodies↗
PubMed1988

[Route and preparation of 5-Fu administration as preoperative adjuvant chemotherapy in rectal cancer. II. Morphologic, ultrastructural and histochemical changes of the cancer cells after intrarectal and intravenous 5-Fu administration].

From March 1981 to October 1985, 5-Fu was preoperatively given to 65 Dukes B and C rectal cancer patients (intrarectal suppository 40 and emulsion 20, intravenous 5). The results indicated that after intrarectal administration, marked changes and destruction of the cancer cells in morphology were observed in 40% of the resected rectal specimens for suppository and in 45% for emulsion; marked retrograde degeneration in ultrastructure was found in 47.5% for suppository and in 50% for emulsion; DNA synthesis was obviously reduced in 63% for suppository and in 75% for emulsion. It is suggested that the emulsion be a better preparation. No obvious changes or destruction in morphology and ultrastructure were observed in cancer cells treated by intravenous drip of high dose 5-Fu though leukopenia below 4000 was found in 2/5. However, it was 0/60 by rectal administration. This implies that the intrarectal route is more rational than the conventional intravenous route. This study presents an alternate supplementary treatment in addition to radiotherapy for the reduction of postoperative local recurrence of Dukes B and C rectal cancers.

Administration, Rectal↗
PubMed1988

[In vivo metastasis of human tumor transplant in T and NK cell immune-deficient mice].

Beige-nude mice with combined T and NK cell deficiency were produced by introducing "nu" gene into the beige mice of C57BL/6 background. The beige-nude mice were characterized by morphological features, level and activity of the NK cell in spleen and peripheral blood. NK cell level of the beige-nude mice was higher than the beige mice and similar to the ordinary nude mice though its NK cell activity was markedly lower than the nude mice. Human lung adenocarcinoma (PAa) was transplanted subcutaneously to the beige-nude mice and nude mice of BALB/cA background. No metastasis was found in BALB/cA nude mice (0/7), while in beige-nude mice, spontaneous lymph node metastasis rate was 36.3% (4/11). It should be noted that the transplanted PAa metastasized to lungs, which had never been seen in BALB/cA nude mice in previous experiments. The increase of metastatic rate is correlated with the relative low NK cell activity of the beige-nude mice. Our observation is that the beige-nude mice could be a suitable experimental model for in vivo study on metastatic behavior of the human tumors.

Adenocarcinoma↗
PubMed1987

Modification of mRNA secondary structure and alteration of the expression of human interferon alpha 1 in Escherichia coli.

A plasmid (pNL015) was constructed to contain a human interferon alpha 1 (IFN-alpha 1) gene under the transcriptional control of the Escherichia coli lipoprotein promoter. The E. coli cells harboring this plasmid produce 2.8 x 10(4) units/ml of IFN. Secondary structure analysis of the transcripts produced by pNL015 showed that the coding region could base pair with the Shine-Dalgarno (SD) region with a delta G = -3.9kcal/mol. A new plasmid pNL008 was constructed by modifying pNL015 with an 11-bp deletion and a 2-bp insertion in the coding region, so that the SD region is not involved in the secondary structure. E. coli cells harboring pNL008 produce ten times more IFN activity than cells harboring pNL015. A series of experiments were carried out to show that the specific activities of IFN, differential rates of IFN transcription, protein degradation or mRNA degradation could not account for the difference observed in expression. A rigorous test on this model of translational inhibition was conducted by the construction of pNL017 with a single bp substitution which did not change the amino acid sequence of the IFN (synonymous codon substitution) but which increased the calculated energy of interaction with the SD sequence to delta G = -10.8 kcal/mol. The E. coli cells harboring pNL017 produced no detectable IFN activity.

Base Sequence↗
PubMed1987

gamma-Aminobutyric acid receptor-regulated 36Cl- flux in mouse cortical slices.

An improved neurochemical assay for gamma-aminobutyric acid (GABA) function has been developed using tracer-radioactive chloride efflux in mouse cortical slices. Careful maintenance of the brain slice viability resulted in a 3-fold stimulation of 36Cl- efflux rate by the GABA agonist muscimol (EC50 = 3 microM), comparable to electrophysiologic and other chloride flux preparations. The shape of the muscimol dose-response curve was shallow, suggestive of negative cooperativity or heterogeneous receptors, but tissue uptake of agonist, possible diffusion barriers and apparent functional desensitization complicated these results. The response to muscimol was inhibited by GABAA receptor antagonists such as RU5135 and was enhanced by barbiturates and benzodiazepines. As observed previously, barbiturates stimulated 36Cl- efflux rate on their own and potentiated the response (potency and maximal effect) to muscimol in a stereospecific and picrotoxin-sensitive manner. Benzodiazepine receptor ligands alone did not alter 36Cl- flux, but agonists such as flunitrazepam enhanced the response to muscimol, an effect sensitive to the antagonist Ro15-1788. The inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate did not inhibit muscimol-activated 36Cl- flux. The anthelminthic-insecticide avermectin B1a stimulated 36Cl- flux by itself, and this response was apparently additive with that of muscimol. This brain slice chloride flux assay is therefore suitable for the assessment of activity including dose-response curves for GABAA agonists, antagonists and modulators including benzodiazepines.

Androstanes↗
PubMed1987

gamma-Aminobutyric acid receptor binding in fresh mouse brain membranes at 22 degrees C: ligand-induced changes in affinity.

Binding of [3H]muscimol to mouse brain gamma-aminobutyric acid receptors has been assayed under more physiological conditions (never-frozen membranes, 22 degrees) than in previous studies (0-4 degrees on frozen-thawed membranes). Binding affinities were lower and agreed more closely with physiological dose response curves. In addition, heterogeneity in affinity was still present, apparently due to a mixture of non-interconvertible subpopulations and ligand-induced changes in kinetics. Super-high affinity sites (Kd less than 10 nM) observed in frozen membranes were not observed in fresh membranes under equilibrium binding conditions, and high affinity sites (Kd congruent to 25 nM) seen at 0 degree had lower affinity (Kd congruent to 250 nM) at 22 degrees. Despite an apparent best fit single-component Scatchard plot for the latter data, cold ligand displacement and association and dissociation rates demonstrated heterogeneity of affinities. Pentobarbital greatly increased the amount of high affinity sites at the expense of low affinity sites in equilibrium binding at 0 degree and slightly increased affinity at 22 degrees. The kinetics of [3H]muscimol association at 22 degrees (kapp = 1-2/min) were virtually independent of the ligand concentration, suggesting either negative cooperativity or an agonist binding-dependent receptor isomerization. Dissociation triggered by addition of excess cold ligand to membranes equilibrated with [3H]muscimol at different concentrations revealed two off-rates with t1/2 values of under 10 sec and 1-3 min; unexpectedly, the ratio of these two populations did not vary with ligand concentration but was constant at 50:50. Dissociation triggered by infinite dilution gave two off-rates, but the slowest component had a t1/2 of about 20 min; including cold muscimol in the dilution buffer increased the off-rate toward that observed in the excess cold ligand method (t1/2 = 1-2 min). The very slow off-rate was only observed following removal of agonist from a previously occupied receptor and suggests receptor isomerization into a high affinity state; this state is similar to that observed at 0 degree. Pentobarbital also favored the production of the receptor state showing very slow [3H]muscimol dissociation upon infinite dilution, opposing the action of high receptor occupancy with cold muscimol. Thus, [3H]muscimol-binding sites observed at 22 degrees with fresh membranes do not show artificially high affinity and have a Kd of 0.2-0.3 microM, closer to the EC50 for chloride channel activation (approximately 2-3 microM and 0.4 microM with pentobarbital).(ABSTRACT TRUNCATED AT 400 WORDS)

Allosteric Regulation↗