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Biomedical subjects

W Huang

Publications and source records attributed to W Huang.

At least 253 records · Page 14Linked to original sources

[Vitrectomy combined with intraocular lens implantation for 103 selected cases of complicated ocular trauma].

PURPOSE: To observe the visual outcome of vitrectomy combined with intraocular lens (IOL) implantation in one operation for patients with complicated ocular trauma. METHODS: Clinical records were retrospectively reviewed in 103 patients with complicated ocular trauma (104 eyes) who underwent vitrectomy combined with IOL implantation in one operation. RESULTS: The series of cases included 35 patients with intraocular foreign body (IOFB), 37 with penetrating injury, 9 (10 eyes) with explosive injury but without IOFB, and 22 with blunt trauma. Preoperatively, visual acuity was no-light-perception to counting fingers in 88 eyes (87.1%) of 100 patients (101 eyes). Visual acuity improved in 94 eyes (93.1%) including 74 eyes (73.3%) with 0.1-1.5 postoperatively. Retinal detachment occurred in one eye during follow-up and cured with pars plana vitrectomy. CONCLUSION: Vitrectomy combined with IOL implantation in one operation can be a safe, fast and effective approach for visual recovery in selected patients with complicated ocular trauma.

Adolescent↗

[Nitric oxide and cytokines in otitis media with effusion].

OBJECTIVE: To study the role of cytokines and nitric oxide (NO) in the pathogenesis of secretory otitis media (SOM). METHODS: The content of NO, interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) in blood plasma and middle ear effusion (MEE) were measured in 58 (80 ears) patients with secretory otitis media and in 23 normal subjects, respectively. RESULTS: NO, IL-8 and TNF-alpha were found in 100%, 82.2% and 71.4% of MEE respectively. NO, IL-8 or TNF-alpha of blood plasma in the SOM group was higher than those in the normal control group (P < 0.05). The concentration of NO, IL-8 or TNF-alpha in MEE was remarkably higher than those in blood plasma (P < 0.01). It revealed that the shorter the course, the higher the concentration of IL-8 in MEE (P < 0.01), and the longer the course, the higher the concentration of NO or TNF-alpha in MEE (P < 0.05). IL-8 concentration of MEE in serous fluid group was remarkably higher than that in the mucous fluid group (P < 0.01), and the concentration of NO or TNF-alpha of MEE in the mucous fluid group was higher than that in the serous fluid group (P < 0.05). NO level of MEE was positively correlated with TNF-alpha (r = 0.696 P < 0.01). CONCLUSION: NO IL-8 and TNF-alpha might be important mediators in MEE secretion in SOM. IL-8 might participate in the defensive reaction of organism during the early stages of SOM, and play a role in serous effusion secretion. NO and TNF-alpha might be closely related to the persistence of SOM, and might be a mediator of mucin secretion in SOM.

Adolescent↗

Treatment of sodium disorders after surgery of craniopharyngioma.

OBJECTIVE: To study the treatment of the patients with blood sodium disorder after craniopharyngioma surgery. METHOD: The blood sodium in 44 patients with craniopharyngiomas was daily examined from operative to post-operative days. Hypernatremia is defined as [Na] > 145 mmol/l, and hyponatremia as [Na] < 135 mml/L. RESULTS: Of the 44 patients, 36 developed sodium disorder. Among them, simple hyponatremia was 16 patients, simple hypernatremia was 9 patients, and alternative sodium disorder was 11 patients. CONCLUSION: The blood sodium disorder in patients with craniopharyngiomas after surgery appears to present complicated changes. Three types of blood sodium disorder could be determined as simple hyponatremia, simple hypernatremia, and alternative sodium disorder. Treatment of the sodium disorder in patients with after surgery could be carried in accordance with the above three types.

Adolescent↗

[Comparison of FTIR microspectroscopy and diffuse reflectance spectroscopy for monitor of solid phase reaction].

17 FTIR micro transmission spectra of single resin beads of each sample, from polystyrene sulfonyl chloride resin changing to polystyrene sulfonyl amide resin in solid-phase reaction in water at 0 degree C, 20 degrees C, 40 degrees C, 60 degrees C, were recorded. The reaction was monitored by the means of FTIR microspectroscopy and diffuse reflectance spectroscopy upon the products. It was showed that the pressed single bead as a piece of biscuit was able to give higher quality spectrum. In comparison, 8 diffuse reflectance spectra of each sample were also collected. It seems that the diffuse reflectance spectroscopy is a more easy dealing with and effective method to control the whole reaction. However, the microspectroscopy is the first choice to check the difference between resin beads.

Ion Exchange Resins↗

[Preparation and spectroscopic characterization of hydrophobic metallic nanoparticles and their LB films].

Hydrophilic silver and gold nano-colloids were synthesized using sodium oleate as a stabilizer, and their hydrophobic nano-colloids were further obtained using tetradecanethiol as a co-stabilizer and using concentrated hydrogen chloride acid as an initiator. UV-visible spectra of the gold and silver nanoparticles at different states were recorded and compared. The spectra show that surfactant stabilized colloids are stable and monodispersed both in aqueous solution and in organic solvents. Surface pressure (pi)-area (A) curves of the nanoparticulate monolayers were measured and their LB films were constructed. IR spectra show that polar head group of the oleate was adsorbed on the surface of the nanoparticles.

English Abstract↗

Crystal structure of chondroitinase B from Flavobacterium heparinum and its complex with a disaccharide product at 1.7 A resolution.

Glycosaminoglycans (GAGs) are a family of acidic heteropolysaccharides, including such molecules as chondroitin sulfate, dermatan sulfate, heparin and keratan sulfate. Cleavage of the O-glycosidic bond within GAGs can be accomplished by hydrolases as well as lyases, yielding disaccharide and oligosaccharide products. We have determined the crystal structure of chondroitinase B, a glycosaminoglycan lyase from Flavobacterium heparinum, as well as its complex with a dermatan sulfate disaccharide product, both at 1.7 A resolution. Chondroitinase B adopts the right-handed parallel beta-helix fold, found originally in pectate lyase and subsequently in several polysaccharide lyases and hydrolases. Sequence homology between chondroitinase B and a mannuronate lyase from Pseudomonas sp. suggests this protein also adopts the beta-helix fold. Binding of the disaccharide product occurs within a positively charged cleft formed by loops extending from the surface of the beta-helix. Amino acid residues responsible for recognition of the disaccharide, as well as potential catalytic residues, have been identified. Two arginine residues, Arg318 and Arg364, are found to interact with the sulfate group attached to O-4 of N-acetylgalactosamine. Cleavage of dermatan sulfate likely occurs at the reducing end of the disaccharide, with Glu333 possibly acting as the general base.

Amino Acid Sequence↗

Development of bivalent (B/E) vaccines able to neutralize CCR5-dependent viruses from the United States and Thailand.

Recombinant envelope glycoproteins prepared from a subtype B (MN) strain and a subtype E (CM244) strain of HIV-1 were combined to create a bivalent vaccine (B/E) effective against viruses circulating in the United States and Asia. Combining the two antigens resulted in formulations that increased the breadth and potency of the inter-subtype neutralizing response. Antibodies to the bivalent vaccine formulation neutralized viruses possessing diverse phenotypes, including syncytia-inducing and non-syncytia-inducing primary isolates, viruses using either the CCR5 or the CXCR4 chemokine receptors, and viruses differing in their sensitivity to soluble CD4. These studies demonstrate for the first time that the magnitude and quality of the immune response to HIV-1 can be improved by combining recombinant envelope glycoproteins from different genetic subtypes.

AIDS Vaccines↗

Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function.

Novel organic cation transporter (OCTN2) is an organic cation/carnitine transporter, and two missense mutations, L352R and P478L, in OCTN2 have been identified as the cause for primary carnitine deficiency. In the present study, we assessed the influence of these two mutations on the carnitine transport function and the organic cation transport function of OCTN2. The L352R mutation resulted in a complete loss of both transport functions. In contrast, the P478L mutation resulted in a complete loss of only the carnitine transport function but significantly stimulated the organic cation transport function. Studies with human OCTN2/rat OCTN2 chimeric transporters indicated that the carnitine transport site and the organic cation transport site were not identical. Because carnitine transport is Na(+)-dependent whereas organic cation transport is Na(+)-independent, we investigated the possibility that the P478L mutation affected Na(+) binding. The Na(+) activation kinetics were found to be similar for the P478L mutant and wild type OCTN2. We then mutated nine different tyrosine residues located in or near transmembrane domains and assessed the transport function of these mutants. One of these mutations, Y211F, was found to have differential influence on the two transport activities of OCTN2 as did the P478L mutation. However, the Na(+) activation kinetics were not affected. These findings are of clinical relevance to patients with primary carnitine deficiency because whereas each and every mutation in these patients is expected to result in the loss of the carnitine transport function, all of these mutations may not interfere with the organic cation transport function.

Animals↗

Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant.

We report here on the cloning and functional characterization of human Na(+)-dependent vitamin C transporter 1 (SVCT1). The human SVCT1 cDNA, obtained from a Caco2 cell cDNA library, encodes a protein of 598 amino acids with 12 putative transmembrane domains. The SVCT1-specific transcript, 2.4 kb in size, is expressed in kidney, liver, small intestine, thymus and prostate. When expressed heterologously in HRPE cells, SVCT1 mediates the transport of ascorbate, the reduced form of vitamin C, in a Na(+)-dependent manner. The transporter is specific for ascorbate with a K(t) of approximately 75 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1, indicating that the transport process is electrogenic. In Caco2 cells and in normal human intestine, SVCT1 also exists as a non-functional splice variant with a four amino acid sequence inserted between E-155 and V-156. The splice variant results from the use of a donor site 12 bp downstream of the normal donor site.

Amino Acid Sequence↗

Cloning of the human thiamine transporter, a member of the folate transporter family.

We have isolated a cDNA from human placenta, which, when expressed heterologously in mammalian cells, mediates the transport of the water-soluble vitamin thiamine. The cDNA codes for a protein of 497 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is widely expressed in human tissues. When expressed in HeLa cells, the cDNA induces the transport of thiamine (K(t) = 2.5 +/- 0.6 microM) in a Na(+)-independent manner. The cDNA-mediated transport of thiamine is stimulated by an outwardly directed H(+) gradient. Substrate specificity assays indicate that the transporter is specific to thiamine. Even though thiamine is an organic cation, the cDNA-induced thiamine transport is not inhibited by other organic cations. Similarly, thiamine is not a substrate for the known members of mammalian organic cation transporter family. The thiamine transporter gene, located on human chromosome 1q24, consists of 6 exons and is most likely the gene defective in the metabolic disorder, thiamine-responsive megaloblastic anemia. At the level of amino acid sequence, the thiamine transporter is most closely related to the reduced-folate transporter and thus represents the second member of the folate transporter family.

Amino Acid Sequence↗

In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide: mechanisms of action.

Leflunomide, a novel immunomodulatory drug, has two biochemical activities: inhibition of tyrosine phosphorylation and inhibition of pyrimidine nucleotide synthesis. In the present study, we first showed that A77 1726 [N-(4-trifluoromethylphenyl-2-cyano-3-hydroxycrotoamide)], the active metabolite of leflunomide, was more effective at inhibiting the tyrosine kinase activity of platelet-derived growth factor (PDGF) receptor than that of epidermal growth factor (EGF) receptor, and had no effect on the tyrosine kinase activity of the fibroblast growth factor receptor. In the presence of exogenous uridine, A77 1726 was more effective at inhibiting the PDGF-stimulated proliferation of PDGF receptor-overexpressing C6 glioma than the EGF-stimulated proliferation of EGF receptor-overexpressing A431 cells. In vivo studies demonstrated that leflunomide treatment strongly inhibited the growth of the C6 glioma but had only a modest effect on the growth of the A431 tumor. Uridine co-administered with leflunomide did not reverse the antitumor activity of leflunomide on C6 and A431 tumors significantly. Quantitation of nucleotide levels in the tumor tissue revealed that leflunomide treatment significantly reduced pyrimidine nucleotide levels in the fast-growing C6 glioma but had no effect on the relatively slow-growing A431 tumor. Whereas uridine co-administration normalized pyrimidine nucleotide levels, it had minimal effects on the antitumor activity of leflunomide in both tumor models. Immunohistochemical analysis revealed that leflunomide treatment significantly reduced the number of proliferating cell nuclear antigen-positive cells in C6 glioma, and that uridine only partially reversed this inhibition. These results collectively suggest that the in vivo antitumor effect of leflunomide is largely independent of its inhibitory effect on pyrimidine nucleotide synthesis. The possibility that leflunomide exerts its antitumor activity by inhibition of tyrosine phosphorylation or by a yet unidentified mode of action is discussed.

3T3 Cells↗

Carnitine transport and its inhibition by sulfonylureas in human kidney proximal tubular epithelial cells.

The kidney plays an important role in the homeostasis of carnitine by its ability to reabsorb carnitine almost completely from the glomerular filtrate. The transport process responsible for this reabsorption has been investigated thus far only in laboratory animals. Here we report on the characteristics of carnitine uptake in a proximal tubular epithelial cell line derived from human kidney. The uptake process was found to be obligatorily dependent on Na+ with no involvement of anions. The process was saturable, with a Michaelis-Menten constant of 14 +/- 1 microM. The Na+:carnitine stoichiometry was 1:1. The same process also was found to be responsible for the uptake of acetylcarnitine and propionylcarnitine, two acyl esters of carnitine with potential for therapeutic use in humans. The uptake process was specific for carnitine and its acyl esters. Betaine, a structural analog of carnitine, interacted with the uptake process to a significant extent. The present studies also showed that sulfonylureas, oral hypoglycemic agents currently used in the management of type 2 diabetes, inhibited the carnitine uptake system. Among the sulfonylureas tested, glibenclamide was the most potent inhibitor. The inhibition was competitive. Glibenclamide inhibited the uptake not only of carnitine but also of acetylcarnitine and propionylcarnitine. The inhibition most likely was the result of direct interaction of the compound with the carnitine transporter because the inhibition could be demonstrated in purified rat kidney brush border membrane vesicles.

Administration, Oral↗

Cloning and expression of a b(0,+)-like amino acid transporter functioning as a heterodimer with 4F2hc instead of rBAT. A new candidate gene for cystinuria.

We have cloned a transporter protein from rabbit small intestine, which, when coexpressed with the 4F2 heavy chain (4F2hc) in mammalian cells, induces a b(0,+)-like amino acid transport activity. This protein (4F2-lc6 for the sixth member of the 4F2 light chain family) consists of 487 amino acids and has 12 putative transmembrane domains. At the level of amino acid sequence, 4F2-lc6 shows significant homology (44% identity) to the other five known members of the 4F2 light chain family, namely LAT1 (4F2-lc1), y(+)LAT1 (4F2-lc2), y(+)LAT2 (4F2-lc3), xCT (4F2-lc4), and LAT2 (4F2-lc5). The 4F2hc/4F2-lc6 complex-mediated transport process is Na(+)-independent and exhibits high affinity for neutral and cationic amino acids and cystine. These characteristics are similar to those of the b(0,+)-like amino acid transport activity previously shown to be associated with rBAT (protein related to b(0,+) amino acid transport system). However, the newly cloned 4F2-lc6 does not interact with rBAT. This is the first report of the existence of a b(0,+)-like amino acid transport process that is independent of rBAT. 4F2-lc6 is expressed predominantly in the small intestine and kidney. Based on the characteristics of the transport process mediated by the 4F2hc/4F2-lc6 complex and the expression pattern of 4F2-lc6 in mammalian tissues, we suggest that 4F2-lc6 is a new candidate gene for cystinuria.

Alanine↗

The TFB4 subunit of yeast TFIIH is required for both nucleotide excision repair and RNA polymerase II transcription.

The N-degron strategy has been used to generate a yeast strain harboring a temperature-sensitive allele of TFB4 (tfb4(td)), the gene that encodes the 37-kDa subunit of the transcription/repair factor TFIIH. The tfb4(td) strain was sensitive to UV radiation and is defective in nucleotide excision repair in vitro. The mutant strain was also found to be an inositol auxotroph due at least in part to an inability to properly induce expression of the INO1 gene. These results indicate that like other subunits of TFIIH, Tfb4 is required for both RNA polymerase II transcription and DNA repair.

Alleles↗

Effect of a single or repeated dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell subpopulations in the Long-Evans rat.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure results in adverse effects on the immune system of experimental animals. The purpose of this study was to compare the effects of a single and repeated dosing of TCDD on splenic T-cell subpopulations in Long Evans rats 9 days post-exposure to TCDD. A single dose (25 microg/kg body weight) of TCDD resulted in reduced body weight. The percentage and total number of CD4+ or CD8+ subsets and percentage of CD4+ or CD8+ cell cycling in the S and G2M phases were similar in the single dosed (25 microg/kg body weight) TCDD group compared with the vehicle control. A repeated dose (5 microg/kg/day for 5 days) of TCDD also resulted in a significant reduction in body weight. However, multiple doses of TCDD significantly decreased the percentage of the CD4+ subset and the percentage of CD4+ cells cycling in the S and G2M phases. No significant change occurred in the CD8+ cell subpopulation after single or multiple dosing with TCDD. These results demonstrated that repeated dosing of TCDD decreased the total percentage of CD4+ cells and the percentage of CD4+ cells cycling 9 days post-exposure, while an analogous single dose of TCDD failed to affect the CD4+ cell subpopulation. The difference in biological responses to a single versus 'equivalent' multiple (cumulative) dose of TCDD is discussed.

Animals↗

Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function.

We report here on the cloning and functional characterization of human SVCT2, a sodium-dependent vitamin C (ascorbate) transporter. The hSVCT2 cDNA obtained from a human placental choriocarcinoma cell cDNA library, codes for a protein of 650 amino acids with a predicted molecular mass of 70 kDa. At the level of amino acid sequence, the human SVCT2 exhibits 95% identity to its rat homolog. When functionally expressed in mammalian cells, hSVCT2 induces the transport of ascorbic acid. The transport process induced by hSVCT2 is Na(+)-dependent and is specific for ascorbate. The Michaelis-Menton constant (K(t)) for the transport of ascorbate in cDNA-transfected cells is 69 +/- 5 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1. Northern blot analysis shows that SVCT2-specific transcripts are present in heart, brain, placenta, and liver and is absent in lung and skeletal muscle. The size of the principal transcript is approximately 7.5 kb.

Amino Acid Sequence↗

Distamycin A selectively inhibits Acanthamoeba RNA synthesis and differentiation.

The effects of distamycin A on Acanthamoeba transcription, growth and differentiation were determined. Distamycin A inhibits transcription both in vitro and in vivo and can displace from DNA the transcription activator TATA binding protein promoter binding factor (TPBF). Inhibition in vivo is surprisingly selective for large rRNA precursors, 5S rRNA, profilin, S-adenosylmethionine synthetase, and extendin. Transcription from the TATA binding protein (TBP), TPBF, protein disulfide isomerase, tubulin and RNA polymerase II large subunit genes is only slightly inhibited. Moreover the rate of 5S rRNA transcription eventually recovers and exceeds that of untreated cells, while profilin transcription remains inhibited. Distamycin A inhibition is accompanied by a complex pattern of alterations to steady state levels of mRNAs. Actin, profilin and S-adenosylmethionine synthetase mRNAs are degraded, whereas mRNA encoding TBP is increased slightly in abundance. Transcription inhibition is accompanied by cessation of growth and severe morphological changes to Acanthamoeba, which are consistent with loss of production of mRNA encoding cytoskeletal proteins. Distamycin A also prevents starvation-induced differentiation of Acanthamoeba, in part due to complete prevention of cellulose production and cell wall formation.

Acanthamoeba↗