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Biomedical subjects

L Tan

Publications and source records attributed to L Tan.

At least 145 records · Page 8Linked to original sources

[Determination of ethmozine in human plasma by high performance liquid chromatography and its pharmacokinetics].

Following detailed study, a rapid and sensitive assay for ethmozine in human plasma has been developed using reversed phase high performance liquid chromatography (HPLC). Plasma samples were prepared for analysis by addition of internal standard (5-chloro-2-amino-benzophenone) followed by protein precipitation using acetonitrile. Analytical column was a C18 Spherisorb. The mobile phase consisted of mathanol-water-triethylamine (70:30:0.4, v/v/v, pH 6.5). The column effluent was monitored at 268 nm. The calibration curve was linear in the range from 20 ng/ml to 4000 ng/ml with r = 0.9994. The detection limit of this method was 3 ng/ml. The method showed good precision and the analytical recovery of ethmozine from plasma was 90-105%. The relative standard deviations for within-day and between-day were 2.4-6.3% and 4.5-10.2% respectively. The plasma drug concentration-time course in man after oral administration of 400 mg after conformed to a 1-compartment open model with a first order absorption phase. Mean T1/2 value was 1.75 +/- 0.45 h.

Adult↗

A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42.

The Ras-related Rho subfamily of GTP-binding proteins (p21s), which includes Rho, Rac and Cdc42Hs, is implicated in different aspects of cytoskeletal organization. These proteins behave like Ras (p21ras) in that their active GTP-bound form is inactivated by intrinsic hydrolysis of the nucleotide gamma-phosphate, which can be stimulated by GTPase-activating proteins (GAPs). We have previously shown that there is a diversity of GAPs that recognize this subfamily, including n-chimaerin, which is enriched in the hippocampus; we also detected proteins that bind these p21 proteins and seem to inhibit GTP hydrolysis. We now report the characterization of a hippocampal complementary DNA encoding a tyrosine kinase that specifically binds Cdc42Hs in its GTP-bound form. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain and inhibits both the intrinsic and GAP-stimulated GTPase activity of Cdc42Hs. Our findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway.

Amino Acid Sequence↗

Concanavalin A enhances ATP resynthesis via de novo pathway in postischemic rat hearts.

Acute post-ischemic cardiac failure was studied in isolated rat hearts. Xylitol, glutamine, aspartic acid and glycine were added during reperfusion, resulting in no inotropic effect. Concanavalin A had a moderate inotropic effect. When concanavalin A added with xylitol, glutamine, aspartic acid and glycine, a rapid recovery of myocardial function and high-energy phosphate was achieved.

Adenosine Triphosphate↗

The subclass IgG responses of mice to influenza surface proteins formulated into liposomes.

Unprimed mice and mice primed by prior infection with an H1N1 subtype of influenza virus were used to assess the total and subclass IgG serum antibody responses to influenza virus A/Sichuan/2/87 (H3N2) surface haemagglutinin and neuraminidase proteins incorporated into four different formulations of liposomes. Only one of these liposome preparations, DSPC(B), induced greater total IgG, and subclass IgG1 and IgG2a antibody levels, in sera from both primed and unprimed mice than the aqueous A/Sichuan surface preparations alone administered at equivalent levels of haemagglutinin protein. The same DSPC(B) liposome formulation of A/Sichuan antigens was also the only preparation found to elicit levels of IgG2b and IgG3 subclass antibodies above baseline values in these animals.

Animals↗

Mass spectrometric analysis of the fragments produced by cleavage and reduction of rat prolactin: evidence that the cleaving enzyme is cathepsin D.

The site(s) at which mammary tissue enzymatically cleaves rat (r) PRL, and the possibility that the cleaving activity is cathepsin D, were investigated using mass spectrometry and enzyme inhibitors. Cleavage of intact rPRL [22,566 atomic mass units (amu)] by either mammary gland-conditioned medium or cathepsin D (both at pH 3) reduced the mass of the molecule by 397 amu. Subsequent reduction of the large rPRL fragment cleaved by either method generated two fragments of 16,364 and 5808 amu. The mass of the smaller fragment is consistent with the report of Vick et al. (Biochim Biophys Acta 931: 196-204, 1987) that its amino-terminal residue is Ser149. These results indicate that both enzyme preparations cleave rPRL by excision of the tripeptide Leu-Val-Trp (mass = 397 amu) between residues 145 and 149. The ability of both enzyme preparations to cleave rPRL at pH3 was inhibited by pepstatin A but not by phenylmethane sulfonyl fluoride, and both preparations were essentially inactive at pH7. Accordingly, the PRL-cleaving activity of rat mammary tissue is probably cathepsin D.

Amino Acid Sequence↗

Transjugular intrahepatic portosystemic shunt: a case report.

Of the various methods currently available to manage potentially life threatening bleeding from oesophagogastric varices, surgical portosystemic shunts are recognised to have the lowest incidence of rebleeding though surgery is associated with high morbidity and mortality. Recently, a promising non-surgical technique has been developed to create an intrahepatic portosystemic shunt via a percutaneous transjugular route. This paper presents a case report of this region's first transjugular intrahepatic portosystemic shunt procedure and briefly reviews the development and preliminary results of this technique.

Catheterization↗

[Highperformance liquid chromatographic assay for lomefloxacin in plasma and its pharmacokinetics in healthy volunteers].

A sensitive and simplified high performance liquid chromatographic procedure has been developed for quantification of lomefloxacin in human plasma. The recovery of lomefloxacin was 95 to 102%. The relative standard deviation was 2.1 to 7.8%. The calibration curve was linear in the range from 0.125 micrograms/ml to 5.012 micrograms/ml with r = 0.9998. The detection limit of the method is 25 ng/ml. The plasma drug concentration-time course after medication conformed to a 1-compartment open model with a first order absorption. Mean t1/2 value was 5.5 h.

Anti-Infective Agents↗

Plasma beta-endorphin concentration and xanthine treatment in apnea of prematurity.

Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/- SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased.

Apnea↗

Peliosis hepatis: a case report.

A 54-year-old man who presented with marked hepatomegaly and a liver scan suggestive of an infiltrative malignancy was found to have peliosis hepatis caused by androgenic steroids. A detailed and repeated drug history is necessary for making the correct diagnosis. Withdrawal of the offending drug is indicated and may result in reversal of this serious form of hepatic toxicity.

Androgens↗

Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells.

The infiltration of the glomerulus by monocyte-derived macrophages is an important step in the pathogenesis of glomerular injury. The factors regulating glomerular leukocyte traffic remain unknown. We postulated that the glomerular mesangial cell (MC) may participate in the development of glomerular inflammation through the production of the monocyte-specific chemotactic factor, monocyte chemoattractant protein-1 (MCP-1). Using a cell culture system, we found that human MC produced a basal level of monocyte chemotactic activity, which was significantly increased by the inflammatory cytokines IL-1 beta and TNF-alpha. This increase in bioactivity correlated with the increased expression of MCP-1 mRNA by cytokine-conditioned MC. The total chemotactic activity of MC-conditioned supernatants was reduced by more than 80% after immunoadsorption with a specific anti-MCP-1 antibody. Thus, MC could play a role in inflammatory glomerular conditions through the production of MCP-1.

Cells, Cultured↗

Liposomes enhance the immunogenicity of reconstituted influenza virus A/PR/8 envelopes and the formation of protective antibody by influenza virus A/Sichuan/87 (H3N2) surface antigen.

Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration-rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used.

Adjuvants, Immunologic↗

Processing of rat prolactin by rat tissue explants and serum in vitro.

Previous work has shown that enzymes from rat liver or mammary gland can cleave rat (r) PRL to form a two-chain derivative that yields approximately 16- and 7-kilodalton (kDa) fragments upon reduction. Both cleaved rPRL and the purified 16-kDa fragment have maintained biological activity. Thus, cleavage may be of physiological significance. To determine whether rPRL can be cleaved by intact cells, and to evaluate the extent to which rPRL processing is tissue specific and varies with physiological state, rPRL was incubated with slices of different tissues from cycling, midpregnant, or 15-day lactating rats. The molecular mass and relative abundance of rPRL and fragments of the hormone in the medium were determined using reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with an antiserum to the 16-kDa fragment of rPRL. Parenthetically, the fragment that was previously identified as having a molecular mass of 16 kDa had the same mobility on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis as the form that we designate as having a molecular mass of 14 kDa. Kidney, spleen, mammary gland and liver explants from pregnant rats processed PRL in qualitatively and quantitatively different ways. Mammary gland from lactating rats produced more of a 14-kDa fragment than liver or kidney slices from lactating rats, and the capacity to produce 14-kDa PRL by mammary gland from rats in different physiological states was as follows: pregnant greater than cycling greater than lactating. Fragments of 11 and 16 kDa were also produced, but only by mammary gland from lactating rats, and the latter only after 3 h of incubation. After a 2-h incubation, PRL-like immunoreactivity in lactating mammary gland medium was composed of 23-, 14-, and 11-kDa forms in the following relative amounts: 65 +/- 9, 17 +/- 1, and 10 +/- 5%, respectively. These results suggest that PRL is cleaved in a manner that varies with different tissues and physiological states; and thus, forms are produced that might be important mediators of PRL's biological actions on different target tissues. Medium conditioned by preincubation with mammary gland from lactating rats and clarified by 15,000 x g centrifugation had no PRL-cleaving activity at pH 7.4, but gained activity when the pH was lowered, with maximal activity at pH 2.6-3.0. When heated to 85 C for 15 min, such medium had no activity at pH 3.0.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Recombinant human tumor necrosis factor-beta entrapped in liposomes formed by a modification of the dehydration-rehydration method retains potent cytotoxic activity on L929 cells in vitro.

Recombinant human tumor necrosis factor-beta (rhTNF-beta) may be encapsulated with high efficiency in phosphatidylcholine and distearoylphosphatidylcholine liposomes, with entrapment values of 93.4% and 92.3%, respectively, by first entrapping the substance in multilamellar vesicles using a high solute-to-phospholipid ratio followed by freeze-drying and then rehydration. The entrapped cytokine retains potent cytotoxic activity on L929 cells in vitro, causing 100% cytotoxicity, equal to that of free rhTNF-beta at a concentration of about 5 x 10(-8) g/ml.

Animals↗

[Atmosphere pollution by sulfur dioxide during processing of zirantong].

This paper reports the colorimetric determination of total SO2 in Zirantong by the method of rosaniline hydrochlorid. Samper of processed Zirantong from the pharmacy have been analyzed and the quality specifications established. Optimum conditions for processing have been chosen and a procedure has been proposed for the recovery of the poisonous matter SO2 which is then transformed into a beneficial material.

Air Pollution↗