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Biomedical subjects

T Su

Publications and source records attributed to T Su.

At least 19 recordsLinked to original sources

Direct role of hydrogen in the Staebler-Wronski effect in hydrogenated amorphous silicon.

We report a hydrogen-related defect that establishes the direct role of hydrogen in stabilizing the silicon dangling bonds created in the Staebler-Wronski effect in hydrogenated amorphous silicon. A specific NMR signal due to paired hydrogen atoms occurs only after optical excitation, exists at an intensity that is consistent with the density of optically induced silicon dangling bonds, and anneals at temperatures that are consistent with the annealing of the optically induced silicon dangling bonds. At this defect the hydrogen atoms are 2.3+/-0.2 A apart.

Journal Article↗

Design and synthesis of glycolic and mandelic acid derivatives as factor Xa inhibitors.

A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 microM plasma concentration following intravenous administration.

Acetanilides↗

Study on the degeneracy of antisense peptides using affinity chromatography.

The degeneracy of antisense peptides was studied by high-performance affinity chromatography. A model sense peptide (AAAA) and its antisense peptides (CGGG, GGGG, RGGG, SGGG) were designed and synthesized according to the degeneracy of genetic codes. An affinity column with AAAA as the ligand was prepared. The affinity chromatographic behaviors of antisense peptides on the column were evaluated. The results indicated that model antisense peptides have clear retention on the immobilized AAAA affinity column. RGGG showed the strongest affinity interaction. Similar result was obtained from another experiment that Arg-substituted antisense peptide of fusion peptide (1-11) of influenza virus A was also shown the highest affinity binding to immobilized fusion peptide.

Amino Acid Sequence↗

Discovery of transition state factor Xa inhibitors as potential anticoagulant agents.

Factor Xa is an attractive biological target in the discovery and development of either parenteral or orally active anticoagulant agents. Several strategies have been utilized at COR Therapeutics in the pursuit of tri-peptide based transition state mimetic factor Xa inhibitors with high aqueous solubility. Some of these inhibitors have displayed excellent in vitro potency in inhibiting factor Xa in the prothrombinase complex. More importantly, these compounds showed strong in vivo antithrombotic efficacy without significant bleeding complications in several animal thrombosis models. These results demonstrated that small molecule factor Xa inhibitors could be advantageous over Warfarin and LMWH. For the discovery and development of orally active anticoagulant agents, small organic molecules as reversible factor Xa inhibitors were explored. From a medicinal chemistry perspective, significant insight has been gained regarding the in vivo antithrombotic efficacy and pharmacokinetic behaviors of each class of factor Xa inhibitors. This review will focus on the design and discovery of transition state factor Xa inhibitors as potential parenteral anticoagulant agents. Several excellent comprehensive review articles on factor Xa inhibitors have appeared recently [1-4].

Animals↗

Effects of nutritional factors and soil addition on growth, longevity and fecundity of the tadpole shrimp Triops newberryi (Notostraca: Triopsidae), a potential biological control agent of immature mosquitoes.

The notostracan tadpole shrimp (TPS) Triops newberryi Packard has potential to be used as a biocontrol agent of immature mosquitoes. Eggs, nymphal or adult shrimps are considered to be the stages for field introduction. To yield good growth of the shrimp and high production of shrimp eggs under artificial conditions, nutritional requirements of TPS for growth, survival and fecundity need to be elucidated. In the laboratory, we evaluated various nutritional and edaphic regimens, such as soil alone, mosquito larvae or rabbit pellets alone and various combinations of these three components for culturing. These factors influenced the growth, longevity and egg production profoundly. It was shown that the simulated natural conditions, i.e. full combination of all three factors, yielded the largest TPS with longest survival and highest egg production, followed by the combinations of any two components. Any single component, soil, mosquito larvae, or rabbit pellets, did not result in good growth, survival and egg production. By formulating optimal rearing substrates, this species of TPS will yield large numbers of all stages for experimentation and field introductions. Under optimal conditions, they mature in 7-8 days and survive for about one month. Each TPS is capable of producing up to 1,000 eggs during its lifetime. These studies developed nutritional regimens for TPS mass culturing procedures, where the eggs, nymphal and adult TPS can be mass cultured for field introduction and stocking in mosquito developmental sites.

Animal Feed↗

Effects of temperature on development, mortality, mating and blood feeding behavior of Culiseta incidens (Diptera: Culicidae).

Culiseta incidens Thomson is distributed over most of the western USA and Canada northward to Alaska. Because this mosquito is difficult to colonize, its biology has not been well investigated. We colonized this species in 1998 and studied the effects of temperature on various aspects of its life cycle. The time required for egg melanization and the duration of the egg stage were negatively correlated with temperature. The proportion of fertile egg rafts was temperature-independent. An inverse relationship existed between temperature and egg hatch. Molting and stadium duration after hatching were temperature-dependent, with higher temperature accelerating development and molting. Larvae and pupae experienced lower mortality and higher molting success at lower temperatures. Survivorship of adult mosquitoes fed on sugar solution was inversely proportional to temperature, lethal times for 50% mortality (LT50) were greater at the lower temperature than at the higher temperature. Females survived longer than did males at all test temperatures. Because this species is eurygamous, mating only occurred in large cages. Mating success was also affected by temperature. At the test temperatures, 20 degrees C, 25 degrees C and 30 degrees C, mating started from 3-5 days after emergence and reached a peak on days 13-15 after emergence. Maximum mating rates at 20 degrees C and 25 degrees C were higher than at 30 degrees C. Blood feeding, as indicated by cumulative feeding rates, was affected by cage size, mosquito age and temperature. Mosquitoes in large cages exhibited a much higher feeding rate than in small cages. With age, the cumulative blood feeding rate increased, with the highest rate at 25 degrees C, followed by 20 degrees C and 30 degrees C. At all temperatures tested, most of the blood fed females were mated.

Age Factors↗

Mosquito larval control with Bacillus sphaericus: reduction in adult populations in low-income communities in Nonthaburi Province, Thailand.

During 1999 and 2000 several larvicidal treatments of Bacillus sphaericus strain 2362 water dispersible granular (WDG) formulations were made at 50 to 200 mg/m2 in mosquito developmental sites in low-income communities in Nonthaburi Province, Thailand to determine whether larviciding dense populations would results in a noticeable reduction of adult mosquitoes in small treated areas. In the treated area in 1999 (Soi Jumpa), immature populations were suppressed to extremely low levels for extended periods, especially at the higher dosages. This decline in immature populations was followed by a substantial decline in adult mosquitoes. There was a lag of 7 to 14 days post-larval treatments before maximum decline in adults was noted. Adults that emerged prior to treatments survived for 7-14 days or longer, thus no drastic reduction was noted soon after treatments. Despite a slight resurgence in adult mosquitoes during the middle of the experimental period, adult female mosquitoes (over 98% Cx quinquefasciatus), remained low during the 5-month period of trials. During the last 2 weeks (17 days post last treatment) of the experimental period, female populations reached the pre-treatment level. During the 2000 tests at Wat Pikul reduction in larvae was 87-98% for 7 weeks after first treatment at 200 mg/m2, resulting in a reduction of 24 to 73% (2 and 7 days post-treatment respectively) and 87 to 98 (2-6 weeks) in the adults. In the second and third treatments at 50 mg/m2, larval control and subsequent adult reduction were lower and shorter-lived than at the high dosage, and the fourth treatment at 100 mg/m2 did not yield a high level of reduction in the larvae (18 to 33%), but reduction of adults was still 80%. The final fifth treatment at 200 mg/m2 yielded only 18% control of larvae, suggesting tolerance to B. sphaericus at this site. It was shown that at both treated sites repeated treatments with a larvicide such as B. sphaericus could result in substantial reduction in adult mosquitoes. Vigilance for detection of resistance development should be practiced, as resistance could emerge in certain populations following a few treatments.

Animals↗

Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

The human CYP2A subfamily comprises three genes, CYP2A6, CYP2A7, and CYP2A13. CYP2A6 is active toward many carcinogens and is the major coumarin 7-hydroxylase and nicotine C-oxidase in the liver, whereas CYP2A7 is not functional. The function of CYP2A13 has not been characterized. In this study, a CYP2A13 cDNA was prepared by RNA-PCR from human nasal mucosa and was translated using a baculovirus expression system. In a reconstituted system, the expressed CYP2A13 was more active than CYP2A6 in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, and N-nitrosomethylphenylamine but was much less active than CYP2A6 in coumarin 7-hydroxylation. Of particular interest, CYP2A13 was highly active in the metabolic activation of a major tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, with a catalytic efficiency much greater than that of other human cytochrome P450 isoforms examined previously. The tissue distribution of CYP2A13 was determined with isoform-specific RNA-PCR. CYP2A13 mRNA was detected in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle. Quantitative PCR analysis further revealed that CYP2A13 mRNA is expressed at the highest level in the nasal mucosa, followed by the lung and the trachea. Together, these findings suggest that CYP2A13 plays important roles in xenobiotic toxicity and tobacco-related tumorigenesis in the human respiratory tract.

Adolescent↗

Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity.

High levels of cytochrome P450 are present in the olfactory mucosa (OM) in mammalian animals and contribute to the known tissue-selective toxicity of numerous chemical compounds. Olfactory toxicity in the perinatal period may have a greater impact on behavior, growth, and development than in adults. To establish a molecular basis for determining the risk of developmental toxicity in OM, the expression of several cytochrome P450 enzymes, as well as NADPH-cytochrome P450 reductase and microsomal epoxide hydrolase, was examined in hepatic and nasal microsomes prepared from human fetal tissues at gestational day 91-125. The relative microsomal concentrations of these biotransformation enzymes were determined on immunoblots. Expression of CYP2A, CYP2J2, the reductase, and epoxide hydrolase was detected in both OM and liver. The microsomal levels of these enzymes were generally lower in OM than in liver of the same fetuses, except for the CYP2A-related proteins, which were expressed in OM at much higher levels. OM expression of CYP2A6, CYP2A13, CYP2B6, and CYP2J2 mRNAs was detected using RNA-PCR. These results document, for the first time, prenatal expression of xenobiotic-bioactivating cytochrome P450 enzymes in human OM and suggest that the human fetal OM may be a preferred target tissue for the toxicity of maternally derived chemical compounds that are activated by the CYP2A enzymes.

Biotransformation↗

Cloning and characterization of DIP1, a novel protein that is related to the Id family of proteins.

Using human cyclin D1 as the "bait" in a yeast two-hybrid system, together with a HL60 cDNA library, we identified a novel human nuclear protein designated DIP1. This protein is expressed in a variety of cell types, and in fibroblasts its level remains constant throughout the cell cycle. However, the level of this protein increases severalfold during the differentiation of HL60 cells. The DIP1 protein can be phosphorylated in vitro by a cellular kinase and this activity reaches its maximum in extracts obtained from cells in the G1 phase of the cell cycle. DIP1 contains a helix-loop-helix motif but lacks an adjacent basic DNA-binding domain, thus resembling the Id family of proteins. The dip1 gene is located on human chromosome 16p11.2-12, a locus that is amplified in several types of human cancer. These results suggest that DIP1 may be involved in the control of gene expression and differentiation, but its precise function remains to be determined.

Amino Acid Sequence↗

Chin-Shan Community Cardiovascular Cohort in Taiwan-baseline data and five-year follow-up morbidity and mortality.

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Adult↗

Relationships between DNA incorporation, mutant frequency, and loss of heterozygosity at the TK locus in human lymphoblastoid cells exposed to 3'-azido-3'-deoxythymidine.

3'-Azido-3'-deoxythymidine (AZT), a thymidine analogue widely used in the treatment of AIDS patients and for prevention of the onset of AIDS in HIV-seropositive individuals, causes tumors in mice exposed as adults or in utero. The purpose of this study was to investigate the potential mechanisms of AZT mutagenicity and carcinogenicity by quantifying the incorporation of AZT into cellular DNA, measuring AZT-induced thymidine kinase (TK) mutant frequencies (Mfs), and determining the percentage of loss of heterozygosity (LOH) in spontaneous or AZT-induced TK mutants in the human lymphoblastoid cell line, TK6. Cells were exposed to 300 microM AZT for 0, 1, 3, or 6 days, or to 0, 33, 100, 300, or 900 microM AZT for 3 days (n = 5 flasks/group). The effects of exposure concentration on incorporation of AZT into cellular DNA were evaluated by an AZT radioimmunoassay, and the effects of duration and concentration of AZT exposure on the TK Mfs were assessed by a cell-cloning assay. AZT was incorporated into DNA in a dose-related manner at concentrations up to 300 microM, above which no further increase was observed. TK Mf increased with the extended duration and with incremental concentrations of AZT exposure. There was a positive correlation (P = 0.036, coefficient = 0.903) between AZT-DNA incorporation and AZT-induced TK Mfs, suggesting that AZT incorporation into cellular DNA has a direct role in the genotoxicity of AZT. Southern blot analyses indicated that 84% (6.2 x 10(-6)/7.4 x 10(-6)) of AZT-induced mutants were attributable to LOH, consistent with the known mechanism of AZT as a DNA chain terminator. Considering the importance of LOH in human carcinogenesis, AZT-induced LOH warrants further study.

Anti-HIV Agents↗

Delivery of lipoplexes for genotherapy of solid tumours: role of vascular endothelial cells.

The cells constituting a solid tumour may vary considerably due to biological disparities, but for a solid tumour to pose as a threat to its host, an adequate blood supply has to be established. Although neovascularisation may have dire consequences for the host, it provides a common route by which tumours in general may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue means that selective delivery of drugs may be achieved. A closer examination of the role played by the cells making up the tumour vascular bed, vascular endothelial cells (VECs), is required to facilitate design of ways for enhancing drug delivery to solid tumours via the vascular route. VECs have two major roles in the body, barrier and transport, both of which are highly pertinent to drug delivery. This review discusses the factors regulating VEC function, and how these cells may be manipulated in-vivo to improve the selective delivery of lipoplexes, carriers for gene therapy constructs, to solid tumours. It also discusses how genotherapeutic drugs may be targeted against tumour VECs on the premise that by killing these cells, the tumour itself will perish.

Drug Carriers↗

Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart.

We have recently shown that rat CYP2J4 is inducible by pyrazole in liver, small intestine, and olfactory mucosa. The aim of the present study was to determine whether mouse CYP2Js are also inducible by pyrazole, which was known to induce CYP2A5 in mouse liver and kidney, but not in lung or olfactory mucosa. CYP2J proteins were detected in mouse liver, lung, kidney, heart, eye, olfactory mucosa, and small intestine by immunoblot analysis with an anti-CYP2J4 antibody. The microsomal level of the CYP2J4-related P450s in various mouse tissues ranked in the order of small intestine > olfactory mucosa > liver > kidney > or = heart > lung > eye. Induction of the CYP2J proteins was observed in the eye, liver, lung, kidney, olfactory mucosa, and small intestine, but not in the heart, after daily i.p. injection of pyrazole at 120 or 200 mg/kg for 3 days. CYP2J proteins were induced similarly in C57BL/6 and DBA/2 mice. CYP2A5 was detected in the small intestine in addition to liver and olfactory mucosa; however, treatment with pyrazole induced CYP2A5 in the liver, but not in the olfactory mucosa or the small intestine. Induction of CYP2J mRNAs was also observed by RNA blot analysis with a CYP2J4 cDNA probe. RNA-polymerase chain reaction analysis showed that, in both untreated and pyrazole-treated mice, CYP2J5 was expressed in the kidney and liver, but not in the other tissues examined, whereas CYP2J6 was detected in all tissues examined. The different tissue selectivities in CYP2A5 and CYP2J induction by pyrazole suggest involvement of different regulatory mechanisms.

Animals↗

[The relationship between GPx activity in gingival fluid and clinical parameters of adult periodontitis].

OBJECTIVE: To study the relationship of glutathione peroxidase (a natural FR scavenger) in gingival cervical fluid (GCF) of patients with periodontitis. METHODS: GCF was collected from 44 sites of 23 patients with adult periodontitis. The volume of GCF was measured with Periotron 8000. GCF-GPx activity was determined by DTNB methods before and after treatment, and the periodontal parameters GI, PD and AL were recorded. RESULTS: GCF-GPx activity was negatively correlated with PD and AL (P < 0.01, P < 0.005), but was not correlated with GI (P > 0.05). After treatment, clinical parameters decreased while GCF-GPx activity increased (P < 0.001), but the increment of GCF-GPx activity showed no correlation with the base level and the changes of clinical parameters. CONCLUSION: The imbalance between FR's production and scavenging might be an important pathological factor of periodontal diseases, and GCF-GPx might be a promising indicator of periodontal status.

Adult↗

[The effect of intra-articular injection of sodium hyaluronate and prednisolone on rabbits' temporomandibular joints].

OBJECTIVE: To evaluate the different effects of sodium hyaluronate and prednisolone on the surface of rabbits' temporomandibular joints. METHODS: 20 juvenile Japanese large ear rabbits were divided into 5 groups, including one control group and the other 4 experimental groups. In these groups, half of their right inferior cavity of temporomandibular joints were injected with sodium hyaluronate(25 mg/ml, 0.1 ml), while others were injected with prednisolone(1%, 0.1 ml), then the rabbits were killed on the 1st, 3rd, 7th, and 14th days after injection. The specimens were evaluated by scanning electron microscope (SEM) to compare the different effects on the inferior superfacial structure of the articular disc and the surface of the condyle. RESULTS: Prednisolone could change the uniform distribution of the agglutinating substance on the inferior superfacial of the articular disc and the surface of the condyle. In the 1st-day and the 3rd-day groups, the agglutinating substance decreased in some areas and gathered in other areas. In the 7 th-day group, the distribution of the agglutinating substance on the inferior superfacial of the articular disc and the surface of the condyle were more regular than that of the 1st-day and the 3rd-day groups. In the 14th-day group, the distribution of the agglutinating substance were almost as the same as that of the control group. But sodium hyaluronate didn't change the uniform distribution of the agglutinating substance in every group. CONCLUSION: Prednisolone can change the uniform distribution of the agglutinating substance on the inferior superfacial of the articular disc and the surface of the condyle, while sodium hyaluronate don't have this effect.

Animals↗

Cytochrome P450 and steroid hydroxylase activity in mouse olfactory and vomeronasal mucosa.

The aims of this study are to identify the sex steroid-metabolizing cytochrome P450 enzymes of the vomeronasal organ (VNO) and to determine the activities of VNO microsomes to metabolize estradiol, progesterone, and testosterone. Several P450 isoforms, including CYP1A2, CYP2A, CYP2B, CYP2C, CYP2G1, and CYP3A, NADPH P450-reductase, and microsomal epoxide hydrolase were detected in mouse VNO, although their expression levels were much lower than those in the main olfactory epithelium. VNO microsomes were active toward the three steroid hormones, producing metabolite profiles similar to those seen with olfactory mucosal microsomes. Thus, the mammalian VNO, a steroid hormone target tissue, contains multiple steroid-metabolizing P450 isoforms and is capable of metabolic disposition of the three major sex steroid hormones. These findings support the proposed roles of olfactory mucosal and VNO microsomal P450 enzymes in maintaining cellular hormonal homeostasis and other perireceptor processes associated with olfactory chemosensory function.

Animals↗