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Biomedical subjects

T Liang

Publications and source records attributed to T Liang.

At least 19 recordsLinked to original sources

Molecular dynamics simulations of peptide carboxylate hydration.

Aqueous solvation of carboxylate groups, as present in the glycine zwitterion and the dipeptide aspartylalanine, is studied employing a force-field that includes distributed multipole electrostatics and induction contributions (Amoebapro: P. Ren and J. W. Ponder, J. Comput. Chem., 2002, 23, 1497; P. Ren and J. W. Ponder, J. Phys. Chem. B, 2003, 107, 5933; J. W. Ponder and D. A. Case, Adv. Protein Chem., 2003, 66, 27). Radial and orientation distribution functions, as well as hydration numbers, are calculated and compared with existing simulation data derived from Car-Parrinello molecular dynamics (CPMD), and also distributed-charge force-fields. Connections are also made with experimental data for solvation of carboxylates in water. Our findings show that Amoebapro yields carboxylate solvation properties in very good agreement with CPMD results, significantly closer agreement than can be obtained from traditional force-fields. We also demonstrate that the influence of solvation on the conformation of the dipeptide is markedly different using Amoebapro compared with the other force-fields.

Carboxylic Acids↗

A silicon-based, sequential coat-and-etch process to fabricate nearly perfect substrate surfaces.

For many thin-film applications substrate imperfections such as particles, pits, scratches, and general roughness, can nucleate film defects which can severely detract from the coating's performance. Previously we developed a coat-and-etch process, termed the ion beam thin film planarization process, to planarize substrate particles up to approximately 70 nm in diameter. The process relied on normal incidence etching; however, such a process induces defects nucleated by substrate pits to grow much larger. We have since developed a coat-and-etch process to planarize approximately 70 nm deep by 70 nm wide substrate pits; it relies on etching at an off-normal incidence angle, i.e., an angle of approximately 470 degrees from the substrate normal. However, a disadvantage of this pit smoothing process is that it induces defects nucleated by substrate particles to grow larger. Combining elements from both processes we have been able to develop a silicon-based, coat-and-etch process to successfully planarize approximately 70 nm substrate particles and pits simultaneously to at or below 1 nm in height; this value is important for applications such as extreme ultraviolet lithography (EUVL) masks. The coat-and-etch process has an added ability to significantly reduce high-spatial frequency roughness, rendering a nearly perfect substrate surface.

Electrochemistry↗

Effect of polymorphism on expression of the neuropeptide Y gene in inbred alcohol-preferring and -nonpreferring rats.

Using animal models of alcoholism, previous studies suggest that neuropeptide Y (NPY) may be implicated in alcohol preference and consumption due to its role in the modulation of feeding and anxiety. Quantitative trait loci (QTL) analysis previously identified an interval on rat chromosome 4 that is highly associated with alcohol preference and consumption using an F2 population derived from inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats. NPY mapped to the peak of this QTL region and was prioritized as a candidate gene for alcohol-seeking behavior in the iP and iNP rats. In order to identify a potential mechanism for reduced NPY protein levels documented in the iP rat, genetic and molecular components that influence NPY expression were analyzed between iP and iNP rats. Comparing the iP rat to the iNP rat, quantitative real-time polymerase chain reaction detected significantly decreased levels of NPY mRNA expression in the iP rat in the six brain regions tested: nucleus accumbens, frontal cortex, amygdala, hippocampus, caudate-putamen, and hypothalamus. In addition, the functional significance of three previously identified polymorphisms was assessed using in vitro expression analysis. The polymorphism defined by microsatellite marker D4Mit7 in iP rats reduced luciferase reporter gene expression in SK-N-SH neuroblastoma cells. These results suggest that differential expression of the NPY gene resulting from the D4mit7 marker polymorphism may contribute to reduced levels of NPY in discrete brain regions in the iP rats.

Alcohol Drinking↗

In vitro HIV-specific CTL activity from HIV-seropositive individuals is augmented by interleukin-12 (IL-12).

IL-12 production is reduced in HIV infection, and recombinant human IL-12 (rhIL-12) augments in vitro HIV-specific proliferative responses in PBMC from HIV-seropositive individuals. To determine whether rhIL12 could also augment HIV-specific CTL responses we studied 41 HIV-seropositive individuals. Recombinant hIL-12 increased the detectable in vitro HIV-specific CD8 CTL activity of PBMC taken from HIV-seropositive individuals with CD4 counts >500 cells/microl and from some individuals with lower CD4 counts. IL-12 increased cell recovery in cultures of PBMC from HIV-seropositive individuals with CD4 counts >500 cells/microl and also increased the precursor CTL frequency. However, the increase in HIV-specific CTL activity was not due to IL-2 or IFN-gamma production or an increase in the number of cells with surface markers characteristic of CTL effector cells. This study demonstrates that rhIL-12 augments in vitro HIV-specific CTL activity and provides evidence to justify further investigation within clinical trials of this cytokine in HIV infection.

Adult↗

Growth hormone-releasing factor affects macronutrient intake during the anabolic phase of zinc repletion: total hypothalamic growth hormone-releasing factor content and growth hormone-releasing factor immunoneutralization during zinc repletion.

Growth hormone-releasing factor (GRF) is thought to perform two distinct functions within the brain. GRF synthesized in the median eminence (ME) stimulates the release of growth hormone (GH) from the pituitary, while GRF in the suprachiasmatic nucleus and median preoptic area (SCN/MPOA) may stimulate selection of dietary protein. These two functions may be coupled to regulate and enhance growth. During zinc repletion, a period characterized by increased protein intake and accelerated growth, we examined this coupling by measuring GRF peptide content in hypothalamic sites and neutralizing GRF function by infusing anti-GRF antibody into the hypothalamus during zinc repletion. Total GRF content and GRF content in the ME and SCN/MPOA were decreased in zinc-deficient (Zn-) rats compared to zinc-adequate (Zn+) rats (P < 0.05). There were no differences in GRF content during zinc repletion in either nuclei. Subsequently, we investigated the macronutrient feeding patterns of rats chronically infused with anti-GRF IgG into the lateral ventricle of the brain during zinc repletion. All Zn- and Zn+ rats administered anti-GRF IgG exhibited a reduction in protein intake during zinc repletion. The Zn- rats receiving anti-GRF-IgG consumed equal amounts of total diet compared to those receiving vehicle during the repletion period however they consumed less carbohydrate (P < 0.05) and considerably more fat (P < 0.02). There were no significant differences in carbohydrate or fat intake in Zn+ rats receiving anti-GRF antibody. These results suggest that GRF likely directs protein intake during normal growth, but may interact with additional appetite-controlling neuropeptides during zinc repletion.

Animal Nutritional Physiological Phenomena↗

Modular construction of extended DNA recognition surfaces: mutant DNA-binding domains of the 434 repressor as building blocks.

Single-chain derivatives of the 434 repressor containing one wild-type and one mutant DNA-binding domain recognize the general operator ACAA-6 base pairs-NNNN, where the ACAA operator subsite is contacted by the wild-type and the NNNN tetramer by the mutant domain. The DNA-binding specificities of several single-chain mutants were studied in detail and the optimal subsites of the mutant domains were determined. The characterized mutant domains were used as building units to obtain homo- and heterodimeric single-chain derivatives. The DNA-binding properties of these domain-shuffled derivatives were tested with a series of designed operators of NNNN-6 base pairs-NNNN type. It was found that the binding specificities of the mutant domains were generally maintained in the new environments and the binding affinities for the optimal DNA ligands were high (with K(d) values in the range of 10(-11)-10(-10) M). Considering that only certain sequence motifs in place of the six base pair spacer can support optimal contacts between the mutant domains and their subsites, the single-chain 434 repressor mutants are highly specific for a limited subset of 14 base pair long DNA targets.

Base Sequence↗

The roles of bcl-2 gene family in the pulmonary artery remodeling of hypoxia pulmonary hypertension in rats.

OBJECTIVE: To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. METHODS: Thirty rats were divided into hypoxia group (10% O2, 8 h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT-PCR were used to detect the expression level of bcl-2 and bax. RESULTS: The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bcl-2 increased whereas bax decreased significantly in the hypoxic group. CONCLUSION: The alternation in bcl-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Animals↗

The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor.

T-20, a synthetic peptide corresponding to the heptad repeat sequence of HIV-1 gp41, blocks HIV-1 entry by targeting gp41, and is currently in clinical trials as an anti-retroviral agent. We recently reported that in vitro T-20 also functions as a phagocyte chemoattractant and a chemotactic agonist at the phagocyte N-formylpeptide receptor (FPR). Here we show that T-20 is also a potent chemotactic agonist in vitro at a related human phagocyte receptor FPRL1R. To test the relative importance of FPR and FPRL1R in primary cells, we identified the corresponding mouse T-20 receptors, mFPR and FPR2, which are both expressed in neutrophils, and compared T-20 action on neutrophils from wild type and mFPR knockout mice. Surprisingly, although T-20 activates mFPR and FPR2 in transfected cells with equal potency and efficacy in both calcium flux and chemotaxis assays, neutrophils from mFPR knockout mice did not respond to T-20. These results provide genetic evidence that FPR is the major phagocyte T-20 receptor in vivo and point to the potential feasibility of studying T-20 effects on immunity in a mouse model. This may help define the cause of local inflammation after T-20 injection that has recently been reported in Phase I clinical trials.

Animals↗

Simple synthesis of 5,9-dimethylated long-chain alkanes, the sex pheromones of leaf miner moths.

Each stereoisomeric mixture of 5,9-dimethylpentadecane and 5,9-dimethylhexadecane, the major and the minor sex pheromone components of Perileucoptera coffeella, respectively, was synthesized in about 25% overall yield through 6 steps from beta-citronellol. 5,9-Dimethylheptadecane, the major sex pheromone component of Leucoptera malifoliella, was also synthesized analogously as a stereoisomeric mixture in a 22% overall yield.

Acyclic Monoterpenes↗

Synthesis of all four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth, Perileucoptera coffeella.

All of the four possible stereoisomers of 5,9-dimethylpentadecane, the major sex pheromone component of the coffee leaf miner moth (Perileucoptera coffeella), were synthesized by using the methyl esters of (S)- and (R)-3-hydroxy-2-methylpropanoic acid as chiral sources for the purpose of determining the stereochemistry of the pheromone.

Alkanes↗

Changes of transforming growth factor beta 1 in rat periodontal tissue during orthodontic tooth movement.

OBJECTIVE: To investigate the distribution and change of transforming growth factor beta 1 (TGF-beta 1) in rat periodontal tissue and understand the role of TGF-beta 1 in orthodontic tooth movement. METHODS: Force was applied on right maxillary first molars in rats, followed by the examination of the decalcified alveolodental connected tissue in different stages of tooth movement. An immunohistochemical staining technique (SP method) was used for this examination. RESULTS: TGF-beta 1 exists in normal periodontal tissue. The expression of it in periodontium increases during orthodontic tooth movement. From 5 to 10 days after applying force, the expression at the tension site was significantly greater than that at the pressure site. CONCLUSIONS: Changes in TGF-beta 1 levels play an important role in the remodeling of periodontal tissue during orthodontic tooth movement, and can powerfully promote bone formation.

Alveolar Process↗

[Interaction of Cu and Pb in accumulation process by fish].

With synthetic water, the accumulation of co-existed Ca and Pb by Paracheirodon innesvi and of Pb by Cu-tamed P. innesvi was studied. The result showed that under both conditions, there existed a significant synergistic effect on the accumulation of Cu and Pb by the fish.

Animals↗

Two cases of combined liver-kidney transplantation.

OBJECTIVES: To report the clinical experiences of simultaneous hepatorenal transplantation. METHODS: We performed simultaneous hepatorenal transplantation in one patient with liver cirrhosis of hepatitis B and uremia of chronic nephritis on February 1, 1999 and one patient with liver cirrhosis of hepatitis B complicated by hepatorenal syndrome on March 12, 1999. The donors were heart arrest cases. Rapid multiple organ harvesting techniques and UW solution infusion in situ were used. Liver and kidney transplantation were orthotopic and ordinary methods, respectively. Immunosuppressive drugs consisted of cyclosporine, Cellcept, ALG and cortstco steroids. Lamividine was used on day 50 and day 40 postoperation, respectively. RESULTS: Both transplanted organs rapidly achieved normal function postoperation and the patients recovered well but suffered mild kidney rejection day 110 postoperation in No 1 patient. In No 2 patient, acute renal function failure, mental symptoms, muscle spasm, cerebral artery thrombosis, inhalation pneumonia and chronic liver graft rejection ensured sequentially but were controlled. The patients have survived for more than nine and eight months, respectively, with normal life quality. CONCLUSIONS: Combined hepatorenal transplant is a radical treatment method for liver and kidney function failure and requires more comprehensive techniques than isolated single organ transplantation. Preventing the recurrence of hepatitis B by oral lamividine may be a key to long-term survival.

Adult↗

[Follow-up study of total condylar knee arthroplasty with three types of Chinese knee prosthetics].

OBJECTIVE: To clinical evaluate the results of total condylar knee arthroplasty using three types of Chinese knee prosthesis. METHODS: Hundred and two knees (in 92 patients) arthroplasty were performed in our department during the 14 years (April 1981-November 1995) were analyzed. The follow-up period averaged 64.4 months. Eight cases had died and 14 cases were lost of follow-up, leaving 80 knees in 70 patients for clinical evaluation. The clinical results were evaluated according to Hospital for Special Surgery Rating System. RESULTS: The average preoperative score was 47.65 and the postoperative score was 90.23. Almost all patients achieved significant pain relief after operation. Sixty-one of the 70 patients (87%) reported that they satisfied or very satisfied with the results of surgery. There were 6 failures. One was due to deep infection, one with loose patellar component, and four directly related to either improper selection or technical reasons. CONCLUSIONS: Total condylar knee arthroplasty with Chinese knee prosthetics gives a satisfactory grade of pain relief and movement of the operated knee. Chinese knee prosthetics is safety and durable.

Adult↗

Synergistic effect of copper and lead uptake by fish.

Paracheirodon innesi was exposed (simultaneously or sequentially) to copper and lead in varying concentrations in a synthetic water solution. Metal accumulations in fish gills and the fish (without gills) were measured at the end of the exposure period. Results of the exposure experiment indicated that lead seems to facilitate the uptake of copper and vice versa when the exposure process is simultaneous. In the case of sequential exposure first to copper for 7 days then to lead for 20 days, lead accumulations in the fish and the gills were enhanced by copper, indicating a possible alteration of the physiological absorption process. The synergistic effects observed during either simultaneous or sequential exposure experiments can be described using logistic equations.

Animals↗

Anabolic effect of prostaglandin E2 on cortical bone of aged male rats comes mainly from modeling-dependent bone gain.

In this study, prostaglandin E2 (3 mg/kg per day) was administered to 20-month-old male Wistar rats for 10 and 30 days. Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections. Thirty days of prostaglandin E2 (PGE2) administration increased bone formation rate/total bone surface from undetectable levels to 0.6 microm/day at the periosteal surface and from 0.5 to 2.1 microm/day at the endocortical surface. Endocortical osteoid surface area increased from 2% to 67% at day 10 and decreased to 6% at day 30; woven and lamellar bone formation started at day 0, but was most obvious at day 30, resulting in a 12% increase of total bone mass. The red to yellow marrow ratio was 0.2 in pretreatment controls, and increased to 1.6 by day 10 and 2.4 by day 30 with PGE2 administration. Intracortical cavity number and area increased after 10 days of PGE2 treatment, but with forming osteon number and area far exceeding those of resorption cavities at day 30. Endocortical modeling surface/endocortical surface was only 1.5%, and remodeling was 11.1% in pretreatment controls. PGE2 treatment increased modeling to 24.5% in the 10 day group and 93.7% in the 30 day group, whereas remodeling remained unchanged at 10 days, and decreased to 6.2% at 30 days. Osteoprogenitor cells and osteoblasts could not be detected in pretreatment controls, but increased by day 10, and returned almost to control levels by 30 days. Our data indicate that PGE2 induced periosteal and endocortical bone formation mainly by modeling-dependent bone gain, accompanied by increases in intracortical remodeling and red bone marrow, and a transient increase in the osteoprogenitor cells adjacent to the endocortical surface. These findings suggest that 20-month-old male Wistar rats were very responsive to the anabolic action of PGE2 in the tibial shaft, a site consisting mainly of cortical bone and yellow marrow.

Aging↗

Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences.

Mutations resulting in defective splicing constitute a significant proportion (30/62 [48%]) of a new series of mutations in the ATM gene in patients with ataxia-telangiectasia (AT) that were detected by the protein-truncation assay followed by sequence analysis of genomic DNA. Fewer than half of the splicing mutations involved the canonical AG splice-acceptor site or GT splice-donor site. A higher percentage of mutations occurred at less stringently conserved sites, including silent mutations of the last nucleotide of exons, mutations in nucleotides other than the conserved AG and GT in the consensus splice sites, and creation of splice-acceptor or splice-donor sites in either introns or exons. These splicing mutations led to a variety of consequences, including exon skipping and, to a lesser degree, intron retention, activation of cryptic splice sites, or creation of new splice sites. In addition, 5 of 12 nonsense mutations and 1 missense mutation were associated with deletion in the cDNA of the exons in which the mutations occurred. No ATM protein was detected by western blotting in any AT cell line in which splicing mutations were identified. Several cases of exon skipping in both normal controls and patients for whom no underlying defect could be found in genomic DNA were also observed, suggesting caution in the interpretation of exon deletions observed in ATM cDNA when there is no accompanying identification of genomic mutations.

Ataxia Telangiectasia↗

[The changes of transforming growth factor beta 1 in periodontal tissue during orthodontic tooth movement].

OBJECTIVE: To observe the distribution and change of transforming growth factor beta 1 (TGF-beta 1) in periodontal tissue and understand the role of TGF-beta 1 in orthodontic tooth movement. METHODS: Apply force on right maxillary first molars in rats, and examine the decalcified alveolodental connected tissue in different stage of tooth movement with immunohistochemical staining technique (SP method). RESULTS: TGF-beta 1 exists in normal periodontal tissue. The expression of it in periodontium increases during orthodontic tooth movement. Especially from 5 to 10 days after force application, the expression at tension side is much more than those at pressure side. CONCLUSION: TGF-beta 1 plays an important role in remodeling of periodontal tissue during orthodontic tooth movement, and can powerfully promote bone formation.

Animals↗