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Biomedical subjects

Y Huang

Publications and source records attributed to Y Huang.

At least 181 records · Page 10Linked to original sources
PubMed2001

Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans.

Augmentation of selective serotonin reuptake inhibitors (SSRIs) therapy by the 5-HT(1A) receptor agent pindolol may reduce the delay between initiation of antidepressant treatment and clinical response. This hypothesis is based on the ability of pindolol to block 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN) and to potentiate the increase in 5-HT transmission induced by SSRIs. However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors during treatment with pindolol controlled release (CR) in nine healthy volunteers with Positron Emission Tomography and [11C]WAY 100635. Subjects were studied four times: at baseline, following one week of pindolol CR 7.5 mg/day (4 and 10 hrs post dose), and following one dose of pindolol CR 30 mg(4 hrs post dose). Occupancy of the DRN was 40 +/- 29% on scan 2, 38 +/- 26% on scan 3, and 64 +/- 15% on scan 4. The average occupancy in all other regions was significantly lower at each doses (18 +/- 5% on scan 2, 12 +/- 3% on scan 3, and 42 +/- 4% on scan 4). These results suggest that the blockade in the DRN reached in clinical studies (7.5 mg/day) might be too low and variable to consistently augment the therapeutic effect of SSRIs. However, these data indicate that pindolol exhibits in vivo selectivity for the DRN 5-HT(1A) autoreceptors. As DRN selectivity is desirable for potentiation of 5-HT function, this observation represents an important proof of concept for the development of 5-HT(1A) agents in this application.

Adult↗
PubMed2001

CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus.

Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKbeta/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKbeta/Pyk2, and administering CAKbeta/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKbeta/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKbeta/Pyk2-stimulated enhancement of synaptic AMPA responses was prevented by blocking NMDARS, chelating intracellular Ca(2+), or blocking Src. Thus, activating CAKbeta/Pyk2 is required for inducing LTP and may depend upon downstream activation of Src to upregulate NMDA receptors.

Animals↗
PubMed2001

Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3).

Using the PCR primers generated from human expressed sequence tag (EST), the cDNA of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene family, was cloned from the human fetal brain mRNA. The predicted amino acid sequence of the hLOXL3 gene was highly homologous to mLOR2. Bioinformatics analysis shows that hLOXL3 protein is also a member of the scavenger receptor cysteine-rich family, which contains a 25 amino acids signal peptide. The hLOXL3 gene was mapped to human 2p13 locus by BLAST search and at least 14 exons were found. Expression of the hLOXL3 gene was detected in several human tissues and especially high in spleen and testis.

Amino Acid Oxidoreductases↗
PubMed2001

Characterization of antioxidants present in hawthorn fruits.

Hawthorn fruit extract has been shown to have many health benefits including being cardiovascular protective, hypotensive and hypocholesterolemic. The present study was carried out to characterize further the antioxidants of hawthorn fruit and their effect on the oxidation of human low density lipoprotein (LDL) and alpha-tocopherol. The dry hawthorn fruit was extracted successively with ether, ethyl acetate, butanol and water. The ethyl acetate fraction was only effective in inhibition of Cu(+2)-mediated LDL oxidation. The column chromatographic separation led to isolation of eight pure compounds; namely, ursolic acid, hyperoside, isoquercitrin, epicatechin, chlorogenic acid, quercetin, rutin and protocatechuic acid. All of these phenolic compounds, except ursolic acid, were protective to human LDL from Cu(+2)-mediated LDL oxidation. They were also effective in preventing the peroxy free radical-induced oxidation of alpha-tocopherol in human LDL. The inhibitory effect of these compounds on oxidation of LDL and alpha-tocopherol was dose-dependent at concentrations ranging from 5 to 40 µM. In addition, supplementation of 2% hawthorn fruit powder significantly elevated serum alpha-tocopherol by 18-20% in rats fed a 30% polyunsaturated canola oil diet, as compared with the control. The present results suggest that part of the mechanism for cardiovascular protective effects of hawthorn fruit might also involve the direct protection to human LDL from oxidation or indirect protection via maintaining the concentration of alpha-tocopherol in human LDL.

Journal Article↗
PubMed2001

Estrogen pyrazoles: defining the pyrazole core structure and the orientation of substituents in the ligand binding pocket of the estrogen receptor.

Previously, we reported that certain tetrasubstituted 1,3,5-triaryl-4-alkyl-pyrazoles bind to the estrogen receptor (ER) with high affinity (Fink, B. E.; Mortenson, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205-219; Stauffer, S. R.; Katzenellenbogen, J. A. J. Comb/. Chem. 2000, 2. 318 329; Stauffer, S. R.: Coletta, C. J.: Sun, J.; Tedesco, R., Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med. Chem. 2000, submitted). To investigate how cyclic permutation of the two nitrogen atoms of a pyrazole might affect ER binding affinity, we prepared a new pyrazole core isomer, namely a 1,3,4-triaryl-5-alkyl-pyrazole (2), to compare it with our original pyrazole (1). We also prepared several peripherally matched core pyrazole isomer sets to investigate whether the two pyrazole series share a common binding orientation. Our efficient, regioselective synthetic route to these pyrazoles relies on the acylation of a hydrazone anion, followed by cyclization, halogenation, and Suzuki coupling. We found that the ER accommodates 1,3,4-triaryl-pyrazoles of the isomeric series only somewhat less well than the original 1,3,5-triaryl series, and it appears that both series share a common binding mode. This preferred orientation for the 1,3,5-triaryl-4-alkyl-pyrazoles is supported by binding affinity measurements of analogues in which the phenolic hydroxyl groups were systematically removed from each of the three aryl groups, and the orientation is consistent, as well, with molecular modeling studies. These studies provide additional insight into the design of heterocyclic core structures for the development of high affinity ER ligands by combinatorial methods.

Animals↗
PubMed2001

Synthesis of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole analogues and their binding affinities for dopamine D(2) and D(3) receptors.

A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D(2) and D(3) receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D(2) and D(3) receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D(3) receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D(3) receptor affinity of 21nM and a 7-fold selectivity for D(3) versus D(2) receptors. The binding affinity for sigma(1) and sigma(2) receptors was also measured, and the results showed that several analogues were selective sigma(1) receptor ligands.

Animals↗
PubMed2001

[[(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl) acetamide for imaging the sigma receptor status of tumors: comparison with [(18)F]FDG, and [(125)I]IUDR.

A series of biodistribution studies were conducted with the radiotracer, [(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl)acetamide, [(18)F]1 in nude mice bearing tumor xenografts of the mouse mammary adenocarcinoma, line 66. This radiotracer has a high affinity for both sigma(1) and sigma(2) receptors. In vivo studies were also conducted in order to assess the effect of blocking sigma(1) receptors on tumor uptake and the tumor:background ratio of this radiotracer. The results of these studies revealed that blocking the sigma(1) receptor so that only the sigma(2) receptors are labeled in vivo, results in a higher tumor:background ratio with only a small reduction in the tumor uptake of the radiotracer relative to the no-carrier-added (i.e., nonselective) conditions. Comparative in vivo studies were also conducted with the anatomic and metabolic imaging agent, [(18)F]FDG, and a radiolabeled DNA precursor, [(125)I]IUdR. Both of these radiolabeled compounds represent classes of agents that have been proposed for imaging the proliferative status of solid tumors. The results of these studies indicated that a sigma(2)-selective imaging agent may be, 1) a better anatomic imaging agent for breast cancer than [(18)F]FDG, and 2) a better functional imaging agent than the radiolabeled DNA precursors, [(123/124)I]IUdR and [(11)C]thymidine, for measuring the proliferative status of breast tumors with PET and SPECT. However, additional studies will be needed to compare sigma(2)-selective imaging agents with [(18)F]FLT in order to determine which is the more appropriate imaging agent for measuring the proliferative status of breast tumors with PET.

Acetamides↗
PubMed2001

Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA.

We have uncovered a novel function for two members of the SR protein family in mRNA export. Using UV cross-linking, transient transfection, and Xenopus oocyte microinjection, we find that the nucleocytoplasmic shuttling proteins SRp20 and 9G8 interact specifically with a 22-nt RNA element from the histone H2a gene to promote the export of intronless RNAs in both mammalian cells and Xenopus oocytes. Antibodies to SRp20 or 9G8 eliminate RNA binding and significantly inhibit the export of RNAs carrying the element from oocyte nuclei. Our observation that SRp20 and 9G8 can be UV cross-linked to polyadenylated RNA in both the nucleus and cytoplasm of HeLa cells suggests a more general role for these SR proteins in mRNA export.

Active Transport, Cell Nucleus↗
PubMed2001

Cloning and characterization of a novel human TEKTIN1 gene.

Tektins comprise a family of filament-forming proteins that are known to be coassembled with tubulins to form ciliary and flagellar microtubules. A new member of the tektin gene family was cloned from the human fetal brain cDNA library. We hence named it the human TEKTIN1 gene. TEKTIN1 cDNA consists of 1375 bp and has a putative open reading frame encoding 418 amino acids. The predicted protein is 48.3 kDa in size, and its amino acid sequence is 82% identical to that of the mouse, rat, and dog. One conserved peptide RPNVELCRD was observed at position number 323-331 of the amino acid sequence, which is a prominent feature of tektins and is likely to represent a functionally important protein domain. TEKTIN1 gene was mapped to the human chromosome 17 by BLAST search, and at least eight exons were found. Northern blot analysis indicated that TEKTIN1 was predominantly expressed in testis. By in-situ hybridization analysis, TEKTIN1 mRNA was localized to spermatocytes and round spermatids in the seminiferous tubules of the mouse testis, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗
PubMed2001

A high pressure FT-IR spectroscopic study of phase transitions in 1-chloro- and 1-bromoadamantane.

The infrared spectra of two orientationally disordered adamantane derivatives, 1-chloro- and 1-bromoadamantane, have been obtained as a function of pressure by use of a diamond anvil cell. Phase transitions were detected from the splittings of vibrational bands and from changes in the slopes on plots of frequency versus pressure. In 1-chloroadamantane, a disorder-order phase transition was detected at approximately 5 kbar. This high-pressure phase is identical to the ordered phase obtained at low temperature. A second phase transition at high pressure was identified, for the first time, at approximately 17 kbar. The new high-pressure phase is an ordered phase. For 1-bromoadamantane, a semi-ordered to ordered phase transition was detected at about 5 kbar, and no other transitions were observed up to a pressure of 35 kbar. For both derivatives, the phase changes were reversible.

Adamantane↗
PubMed2001

The calpain family and human disease.

The number of mammalian calpain protease family members has grown to 14 on last count. Overactivation of calpain 1 and calpain 2 (and their small subunit) has long been tied to acute neurological disorders (e.g. stroke and traumatic brain injury) and recently to Alzheimer's disease. Loss-of-function mutations of the calpain 3 gene have now been identified as the cause of limb-girdle muscular dystrophy 2A. Calpain 10 was recently identified as a susceptibility gene for type 2 diabetes, whereas calpain 9 appears to be a gastric cancer suppressor. This review describes our current understanding of the calpain family members and their mechanistic linkages to the aforementioned diseases as well as other emerging pathological conditions.

Alzheimer Disease↗
PubMed2001

Degradation of green tea catechins in tea drinks.

Green tea cateachins (GTC). namely (-) epicatechin (EC), (-) epicatechin gallate (ECG), (-) epigallocatechin (EGC), and (-) epigallocatechin gallate (EGCG), have been studied extensively for their wide-ranging biological activities. The goal of the present study was to examine the stability of GTC as a mixture under various processing conditions. The stability study demonstrated that GTC was stable in water at room temperature. When it was brewed at 98 degrees C for 7 h, longjing GTC degraded by 20%. When longjing GTC and pure EGCG were autoclaved at 120 degrees C for 20 min, the epimerization of EGCG to (-) gallocatechin gallate (GCG) was observed. The relatively high amount of GCG found in some tea drinks was most likely the epimerization product of EGCG during autoclaving. If other ingredients were absent, the GTC in aqueous solutions was pH-sensitive: the lower the pH, the more stable the GTC during storage. When it was added into commercially available soft drinks or sucrose solutions containing citric acid and ascorbic acid, longjing GTC exhibited varying stability irrespective of low pH value. This suggested that other ingredients used in production of tea drinks might interact with GTC and affect its stability. When canned and bottled tea drinks are produced, stored, and transported, the degradation of GTC must be taken into consideration.

Beverages↗
PubMed2001

Detection of sodium chloride in cured salmon roe by SW-NIR spectroscopy.

Salt and moisture content of cured salmon roe (ikura) was determined using short-wavelength-near-infrared (SW-NIR) reflectance spectroscopy (600-1100 nm). SW-NIR can be used to measure chloride species. Calibrations for salt in bulk samples of high-quality roe (R(2) = 0.904, SEP = 0.421%, RPD = 3.21) and average-quality roe (R(2) = 0.711, SEP = 1.13%, RPD = 1.81), crushed eggs (R(2) = 0.857, SEP = 0.509%, RPD = 2.62), and individual eggs (R(2) = 0.731, SEP = 0.698%, RPD = 1.98) were developed using partial least squares (PLS) regression models. The heterogeneous distribution of lipid and moisture in the individual eggs limit the sensitivity of this method; however, this method provides a rapid nondestructive method for high-value food products where destructive testing is expensive or impractical and for process control applications.

Animals↗
PubMed2001

Antioxidative activities of phenylethanoid glycosides from Ligustrum purpurascens.

Tea and kudingcha (bitter tea) are the two most popular beverages consumed in China. Tea derived from the leaves of Camellia sinensis has been well studied for its various health benefits, but there are very limited data on the biological activities of bitter tea derived from the leaves of Ligustrum purpurascens (LP). The present study was carried out to characterize the antioxidants present in the bitter tea brewed from the leaves of LP. It was found that the crude glycoside fraction possessed strong protection against oxidation of human low-density lipoprotein (LDL). The column chromatographic separation led to the isolatation of five phenylethanoid glycosides, namely, acteoside, ligupurpuroside A, cis-ligupurpuroside B, trans-ligupurpuroside B, and osmanthuside B. When acteoside was heated in the boiling water, it was isomerized to form isoacteoside. Acteoside, isoacteoside, and ligupurpuroside A purified from LP were protective, whereas cis-ligupurpuroside B, trans-ligupurpuroside B, and osmanthuside B exhibited no protection to human LDL from Cu(2+)-medicated oxidation. Acteoside, isoacteoside, and ligupurpuroside A were also effective in preventing the peroxyl free radical-induced oxidation of alpha-tocopherol in human LDL. The antioxidant activities of acteoside, isoacteoside, and ligupurpuroside A were comparable to that observed for a green tea antioxidant, (-)-epicatechin gallate. The inhibitory effect of these three phenylethanoid glycosides on oxidation of human LDL and alpha-tocopherol was dose-dependent at concentrations of 5-40 microM. The present results suggest that the bitter tea beverage derived from LP contains effective antioxidants that may have an equal benefit as a green tea beverage.

Antioxidants↗
PubMed2001

Circumdatin G, a new alkaloid from the fungus Aspergillus ochraceus.

The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G. The structure of circumdatin G was determined by spectroscopic analysis.

Alkaloids↗
PubMed2001

Cloning and characterization of KLHL5, a novel human gene encoding a kelch-related protein with a BTB domain.

Most kelch family proteins contain two conserved domains, the BTB domain and the kelch repeat domain. Here we describe the cloning and characterization of a novel human KLHL5 gene. The 3488 bp cDNA encodes a kelch family protein homologous to the Drosophila kelch protein. It also contains the two conserved domains. Northern blot analysis reveals a single transcript. It is abundantly expressed in ovary, adrenal gland, and thyroid and less abundantly expressed in trachea, prostate, testis, lymph node, and spinal cord. KLHL5 was mapped to 4p13-4p15.1.

Amino Acid Sequence↗
PubMed2001

Dependence of permeability transition pore opening and cytochrome C release from mitochondria on mitochondria energetic status.

The dependence of Ca2+-induced permeability transition pore (PTP) opening and cytochrome c (Cyt. c) release from mitochondria on mitochondria energetic status was investigated. Results of test the PTP opening and Cyt. c release of isolated rat liver mitochondria with different mitochondrial respiratory substrates, electron transport inhibitors and uncoupler by spectrophotometry and western blotting showed that, Cyt. c release from mitochondria by PTP opening. PTP opening and Cyt. c release showed more sensitive and responsive with FADH-linked succinate than with NADH-linked glutamate plus malate as substrate. Partial or full inhibition of electron flow with electron flow inhibitors resulted in partial or full inhibition of PTP opening and Cyt. c release, respectively. Partial recovery of electron flow with electron sponsors resulted in partial recovery of PTP opening and Cyt. c release. PTP opening and Cyt. c release were completely interrupted by uncoupler. These results indicated PTP opening and Cyt. c release are characterized by respiratory substrate selectivity, electron flow dependence and energy coupling reliance. Hence, PTP opening and Cyt. c release tightly depend on mitochondria energetic status. These findings suggested also that it is possible to regulate apoptosis by altering mitochondrial energetic status to alter PTP opening and Cyt. c release.

Animals↗