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J T Huang

Publications and source records attributed to J T Huang.

At least 37 records · Page 2Linked to original sources
PubMed1991

Adenovirus inhibition of cellular protein synthesis involves inactivation of cap-binding protein.

Adenovirus (Ad) infection results in a marked inhibition of cellular protein synthesis that initiates during the late phase of the viral infectious cycle. We show that the mechanism used for suppression of cellular protein synthesis during cell cycle progression is exploited by Ad to repress host and enhance late viral mRNA translation. Discrimination between cellular and late Ad mRNAs and inhibition of host protein synthesis are shown to involve viral-mediated underphosphorylation of cap-binding protein (CBP) and subsequent inactivation of CBP complex, a large enzymatic complex required for cap-dependent mRNA translation. Late Ad mRNAs, like those of poliovirus, possess the unique ability to translate independent of a normal cap recognition process and do not require the activity of CBP complex. Inhibition of cellular translation by these two viruses is quite similar, except that whereas CBP complex is proteolytically degraded by poliovirus, it is functionally inactivated by Ad.

Adenoviruses, Human↗
PubMed1991

An opioid pancreatic peptide produces ileal muscle inhibition and naloxone-reversible analgesia.

The opioid activity of immunoreactive beta-endorphin-like peptide extracted from pork pancreas duplicates the effects of morphine and synthetic beta-endorphin when measured by inhibition of isolated guinea pig ileal muscle response to electro-stimulation in vitro and by morphine-like analgesia following intravenous injection in the mouse. These responses are reversed by the opiate antagonist naloxone, indicating that a potent opioid mu receptor binding ligand is present in pancreatic extract. These findings imply a pancreatic source of plasma immunoreactive beta-endorphin that may explain a number of physiological and behavioral effects generally attributed to hypophyseal beta-endorphin alone.

Analgesics↗
PubMed1991

Fluorinated sugar analogues of potential anti-HIV-1 nucleosides.

In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3' -difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2',3'-didehydro-2' -fluorothymidine (25), 3'-azido-2',3'-dideoxy-2'-fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2',3'-dideoxy-5-methyluridine (31), and 2'3'-dideoxy-2' -fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents.

Animals↗
PubMed1990

Adenovirus inhibition of cellular protein synthesis is prevented by the drug 2-aminopurine.

Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.

2-Aminopurine↗
PubMed1990

Translation by the adenovirus tripartite leader: elements which determine independence from cap-binding protein complex.

The adenovirus tripartite leader is a 200-nucleotide-long 5' noncoding region which facilitates translation of viral mRNAs at late times after infection. The tripartite leader also confers the ability to initiate translation independent of the requirement for cap-binding protein complex or eIF-4F without any requirement for adenovirus gene products. To elucidate the manner by which the tripartite leader functions, the primary determinants of leader activity were investigated in vivo by testing a series of mutations expressed from transfected plasmids. The results of these experiments indicate that the tripartite leader does not promote internal ribosome binding, at least in a manner recently described for picornavirus mRNAs. In addition, despite an unusual arrangement of sequences complementary to the 3' end of 18S rRNA in the tripartite leader, we could find no evidence for involvement in its translation activity. Instead, our results are consistent with a model in which much of the first leader is maintained in an unstructured conformation which determines the ability of the tripartite leader to facilitate translation and bypass a normal requirement for eIF-4F activity. Several possible translation models are discussed, as well as the implications for translation of late viral mRNAs.

Adenoviruses, Human↗
PubMed1989

Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purines and their biological activities.

Seven purine nucleosides containing the 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl moiety were synthesized and tested for their antitumor activity. Direct condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (1) with N6-benzoyladenine in CH2Cl2 followed by saponification of the product afforded the adenine nucleoside (I, 2'-F-ara-A). Deamination of I with NaNO2 in HOAc gave the hypoxanthine analogue (II, 2'-F-ara-H). The 6-thiopurine nucleoside (III, 2'-F-ara-6MP) was prepared by condensation of 1 with 6-chloropurine by the mercury procedure followed by thiourea treatment and saponification of the product. Methylation of III gave the 6-SCH3 analogue (IV). Raney Ni desulfurization of III afforded the unsubstituted purine nucleoside (V, 2'-F-ara-P). Condensation of 1 with 2-acetamido-6-chloropurine by the silyl procedure afforded the protected 2-acetamido-6-chloropurine nucleoside which served as the precursor for both the guanine and 6-thioguanine nucleosides (VI, 2'-F-ara-G and VII, 2'-F-ara-TG, respectively). Thus, alkaline hydrolysis of the precursor gave VI. Thiourea treatment prior to alkaline hydrolysis gave VII. The new nucleoside, 2'-F-ara-G (VI) is found to be selectively toxic to human T-cell leukemia CCRF-CEM.

Animals↗
PubMed1988

Effects of noise exposure and task demand on cardiovascular function.

Cardiovascular effects under various noise-exposure and task-demand conditions were studied among 40 senior highschool students. The subjects consisted of 20 males and 20 females with a mean age of 16.7 +/- 0.7 years. All subjects had equivalent abacus performance ratings. Each subject was tested with a random sequence of six sessions. The time limit set for each session was 33 min. Six experimental sessions were constructed by a random combination of noise exposure (60, 85 or 90 dB (A] white noise) and task demand (task presence or task absence) variables. Blood pressure measures were taken at the beginning and ending phases of each session. A task-demand variable was defined as a conjoint of mental arithmetic (3 min) and abacus arithmetic (30 min). The results from the present study show that the effect of noise exposure on task performance is remarkable. Only noise exposure tended to influence the performance of male students in abacus arithmetic. The effect of task demand on blood pressure was higher than that of noise exposure. No interaction effect (noise exposure x task demand) on blood pressure, was found via analyses of within-subjects two-way ANOVA.

Adolescent↗
PubMed1988

Anti-fertility and other actions of gossypol analogues.

From a series of gossypol derivatives studied, we conclude that the carbonyl groups of gossypol are needed for inhibition of erythrocyte anion transport and the hydroxy groups affect but are not essential to that inhibition. In an in vitro mouse erythroleukemia cytocidal assay, the most active compounds were gossypol and apogossypol. The latter was not active in the inhibition of erythrocyte anion transport or in a spermicidal assay. Of the more simple structures related to gossypol, those that were active in the cytocidal and spermicidal assays were bi-aromatic, linked by a 1- and not a 4-carbon chain and had free phenolic hydroxyl groups. These results are included in a discussion of the specificity and mechanism of action of gossypol.

Animals↗
PubMed1988

Chemical synthesis and biological activities of 5-deazaaminopterin analogues bearing substituent(s) at the 5- and/or 7-position(s).

Condensation of cyanothioacetamide (4) with ethyl alpha-(ethoxymethylene)acetoacetate (5b), ethyl 4-ethoxy-2-(ethoxymethylene)-3-oxobutanoate (5c), ethyl 2-(ethoxymethylene)-3-oxo-4-phenylpropanoate (5d) afforded exclusively the corresponding 6-substituted pyridines (6b-d). Cyclization of 4 with 3-carbethoxybutane-2,4-dione (5e) gave 3-cyano-5-(ethoxycarbonyl)-4,6-dimethylpyridine-2(1H)-thione (6e), whereas reaction of 4 with 3-carbethoxy-1-phenylpropane-1,3-dione (5f) yielded two products, 3-cyano-5-(ethoxycarbonyl)-4-methyl-6-phenylpyridine-2(1H)-thione (6f) and the 6-methyl-4-phenyl isomer 6g. The structural assignments for 6f and 6g are made on the basis of 1H and 13C NMR spectral analyses of the 2-(methylthio)nicotinates (7f,g) prepared from 6f and 6g by treatment with MeI/K2CO3. Nicotinates 7b,d-g were converted into their corresponding 2,4-diaminopyrido[2,3-d]pyrimidines 12b,d-g in five steps, via reduction, protection, oxidation, condensation with guanidine, and deprotection. The 7-mono- and 5,7-disubstituted-5-deazaaminopterins (1b,d-g) were prepared from the respective pyrido[2,3-d]pyrimidines 12b,d-g. Preliminary biological studies showed that 7-methyl and 5,7-dimethyl analogues (1b and 1e) were less active than methotrexate against human leukemic HL-60 and murine L-1210 cells in tissue culture. Compound 1e produced an ILS of 71% at 100 mg/kg per day X 5 (ip) in BDF mice inoculated ip with 10(6) L-1210 cells.

Aminopterin↗
PubMed1987

5-substituted 2'-fluoro-arabinonucleosides as potential antiviral agents.

In order to study the electronic effects of 5-substituents of 2'-fluoro-ara-U on antiviral activity, eight nucleosides were synthesized and screened for their activity. Preliminary in vitro studies revealed that 5-thiocyano-, 5-hydroxy- and 5-formyl-ara-U are moderately active against HSV-1, HSV-2 and VZV, but they are also cytotoxic. None of these showed significant activity against CMV.

Animals↗
PubMed1986

Synthesis and biological activities of 5-deaza analogues of aminopterin and folic acid.

N-[p-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl] amino]benzoyl]-L-glutamic acid (1a, 5-deazaaminopterin) and the 5-methyl analogue (1b) were synthesized in 14 steps from 5-cyanouracil (4a) and 5-cyano-6-methyluracil (4b), respectively, by exploitation of the novel pyrimidine to pyrido[2,3-d]pyrimidine ring transformation reaction. The 5-cyanouracils 4 were treated with chloromethyl methyl ether to the 1,3-bis(methoxymethyl)uracils (5, which were treated with malononitrile in NaOEt/EtOH to give the pyrido[2,3-d]pyrimidines 6. Diazotization of 6 in concentrated HCl afforded the 7-chloro derivatives 8 in high yield. After reduction of 8, the 7-unsubstituted products 9 were reduced in the presence of Ac2O and the products, 6-(acetamidomethyl)pyridopyrimidines 10, were converted into the 6-acetoxymethyl derivatives 12 via nitrosation. After removal of the N-methoxymethyl groups from 12, the 6-(acetoxymethyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones 14 were converted into 2,4-diamino-6-(hydroxymethyl)pyrido[2,3-d]pyrimidine (15a) and its 5-methyl analogue 15b by the silylation-amination procedure. Compounds 15 were brominated to the 6-bromomethyl derivatives 16, which were treated with diethyl (p-aminobenzoyl)-L-glutamate, and the products 17 were saponified to afford 5-deazaaminopterin (1a) and its 5-methyl analogue 1b. Compound 1b was also prepared by an alternative procedure in 10 steps from cyanothioacetamide and ethyl beta-(ethoxymethylene)acetoacetate via 2,4-diamino-6-(hydroxymethyl)-5-methylpyrido[2,3-d]pyrimidine (15b). 5-Deaza-5-methylfolic acid (2) was also prepared in four steps from 15b. The aminopterine analogues 1 showed significant anticancer activity in vitro and in vivo, whereas the folic acid analogue 2 did not exhibit any significant toxicity.

Aminopterin↗
PubMed1985

Effect of some smooth muscle stimulants and trypsin on the contraction of vas deferens of aging rats.

Contractions of vas deferentia induced by KCI or field stimulation were not different between mature and old rats. The effect of trypsin or BaCl2 but not bradykinin or carbachol on contraction induced by field stimulation was significantly different between mature and old rats. The increase of twitching contractions by trypsin may be due to its effect on presynaptic alpha-adrenoceptors. Trypsin treatment did not qualitatively alter the responses produced by agonists in the vas deferentia of mature and old rats.

Aging↗
PubMed1984

In situ formation of immune complexes in the choroid plexus of rats by sequential injection of a cationized antigen and unaltered antibodies.

The deposition of cationized human serum albumin (HSAED) in the choroid plexus of rats was compared to deposition in renal glomeruli. Initial deposition in the choroid plexus required a higher dose of antigen than deposition in glomeruli. The optimal dose for deposition in the choroid plexus was 50 mg/kg of HSAED. With this dose the antigen was still present in the choroid plexus at eight days after injection, whereas the glomeruli became largely negative by one day. Immune complex formation and persistence was examined in the choroid plexus by injecting rabbit antibodies to HSA at varying times after the injection of HSAED. When a limited amount of antibody was injected, it localized preferentially to glomeruli as compared to the choroid plexus. When sufficient antibodies were injected, the antigen and antibodies persisted in a comparable manner in the choroid plexus and glomeruli. By the eighth day after injection of foreign proteins, rat IgG deposited in both organs, indicating an endogenous immune response. The formed deposits were still present at 28 days, containing HSA, rabbit IgG, and rat IgG, but not rat C3. These results indicate that immune deposits readily form in the choroid plexus after injecting a cationized antigen. Differences, however, exist in the formation of immune deposit in the choroid plexus and the glomeruli.

Animals↗
PubMed1982

Accumulation of peptide Tyr-D-Ala-Gly by choroid plexus during ventriculocisternal perfusion of rat brain.

Accumulation of Tyr-D-Ala-Gly (TAG) in choroid plexus was studied with ventriculocisternal perfusion of anesthetized rats. The choroid plexus of the lateral ventricles and the fourth ventricle accumulated TAG against a concentration gradient with regards to cerebrospinal fluid (CSF) but not plasma. This accumulation was inhibited by some metabolic inhibitors and peptides which had the same effect on accumulation of TAG in isolated choroid plexus. These results indicate that the active transport of TAG is present in the epithelium facing CSF. This active accumulation was affected by morphine. Reserpine, which is a chemical denervation of sympathetic nerves has no effect on the active accumulation of TAG. Thus, all these results suggest that, in vivo accumulation of TAG in choroid plexus during ventriculocisternal perfusion is similar to in vitro accumulation of TAG in isolated plexus.

2,4-Dinitrophenol↗
PubMed1982

Purification and partial characterization of hyaluronidase from five pace snake (Agkistrodon acutus) venom.

A hyaluronidase (EC 3.2.1. 35) was isolated and purified from Agkistrodon acutus venom. The purification procedure included CM-Sephadex C-50 chromatography, gel-filtration on Sephadex G-75 and CM-Sephadex C-25 chromatography. The purified preparation of the enzyme was homogeneous on polyacrylamide gel electrophoresis at pH 4.3, a 45-fold purification being obtained. The hyaluronidase was a glycoprotein (positive PAS staining) with a molecular weight of 33,000 and a pI of 10.3. No hemorrhagic activity was found. The hyaluronidase had an optimum pH of 3.5-5.0 and an optimum temperature of 37 degrees C. It was heat sensitive, was more stable in the acidic than in the neutral region, and lost its activity in the alkaline region. Fe2+, Cu2+ and heparin inhibited the venom hyaluronidase. The Km value for hyaluronic acid was 6.2 X 10(-3) mg/ml.

Animals↗