Biomedical subjects

M Yin

Publications and source records attributed to M Yin.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Synthesis of a macromolecular camptothecin conjugate with dual phase drug release.

A water soluble macromolecular conjugate of camptothecin (CPT) with a new, dual phase hydrolytic drug release mechanism was prepared on the basis of a 60 kDa biodegradable hydrophilic "stealth" polyacetal, poly(1-hydroxymethylethylene hydroxy-methyl formal). Succinamido-glycinate was used as a prodrug releasing group. A model preparation with 7.5% CPT content w/w was water soluble. The lipophilic camptothecin prodrug, camptothecin-(O20)-succinimidoglycinate, was released from the conjugate with t(1/2) = 2.2 +/- 0.1 h in rodent plasma. The blood clearance in a rodent model as measured by CPT was release limited, t(1/2) = 2.1 +/- 0.2 h, while the conjugate half-life was 14.2 +/- 1.7 h. In a xenograft tumor model, the conjugate demonstrated higher antineoplastic efficacy than CPT at a less than equitoxic dose. This improved therapeutic window is in line with the modified drug pharmacokinetics and with camptothecin release in a stabilized lipophilic prodrug form. Regulation of prodrug release and hydrolysis rates through linker structure modification will open the way to further improve both pharmacokinetics and pharmacodynamics.

Adenocarcinoma↗

PubMedDate not supplied

Time lines and computer-based visual editing: new techniques for assessing exposure in epidemiologic studies.

We describe a time-line-based methodology for collecting exposure data for epidemiologic studies and for processing these data for statistical analysis with readily available software for the personal computer. The four components to this approach are: (1) collecting data in a memory-enhancing time-line format; (2) entering data from time lines into a computer database and editing them; (3) making a quantitative estimate of exposure, intake, or dose for each exposure event; and (4) creating analysis datasets by 'slicing' the quantified time lines based on desired exposure intervals or disease latent periods. Compared with fixed-format interviews, time-line-based interviews help subjects organize remembered events, thereby reducing confusion. They do not restrict responses to predetermined categorical exposure responses. The time-line methodology also facilitates the collection of supplementary data necessary for computing doses for complex exposures and the packaging of quantified exposures into analysis datasets for any time period of interest.

Child↗

PubMedDate not supplied

Hypotaurine, N-methyltaurine, taurine, and glycine betaine as dominant osmolytes of vestimentiferan tubeworms from hydrothermal vents and cold seeps.

Organic osmolytes, solutes that regulate cell volume, occur at high levels in marine invertebrates. These are mostly free amino acids such as taurine, which are "compatible" with cell macromolecules, and methylamines such as trimethylamine oxide, which may have a nonosmotic role as a protein stabilizer, and which is higher in many deep-sea animals. To better understand nonosmotic roles of osmolytes, we used high-performance liquid chromatography and (1)H-nuclear magnetic resonance (NMR) to analyze vestimentiferans (vestimentum tissue) from unusual marine habitats. Species from deep hydrothermal vents were Riftia pachyptila of the East Pacific Rise (2,636 m) and Ridgeia piscesae of the Juan de Fuca Ridge (2,200 m). Species from cold hydrocarbon seeps were Lamellibrachia sp. and an unnamed escarpid species from subtidal sediment seeps (540 m) off Louisiana and Lamellibrachia barhami from bathyal tectonic seeps (1,800-2,000 m) off Oregon. Riftia were dominated by hypotaurine (152 mmol/kg wet wt), an antioxidant, and an unidentified solute with an NMR spectrum consistent with a methylamine. Ridgeia were dominated by betaine (N-trimethylglycine; 109 mmol/kg), hypotaurine (64 mmol/kg), and taurine (61 mmol/kg). The escarpids were dominated by taurine (138 mmol/kg) and hypotaurine (69 mmol/kg). Both Lamellibrachia populations were dominated by N-methyltaurine (209-252 mmol/kg), not previously reported as a major osmolyte, which may be involved in methane and sulfate metabolism. Trunk and plume tissue of the Oregon Lamellibrachia were nearly identical to vestimentum in osmolyte composition. The methylamines may also stabilize proteins against pressure; they were significantly higher in the three deeper-dwelling groups.

Adaptation, Physiological↗

PubMedDate not supplied

CD34-positive cell selection by immunomagnetic beads and chymopapain.

BACKGROUND: Pluripotent hemopoietic stem cells, progenitors of all hemolymphopoietic lineages, and clonogenic cells from many patients with acute nonlymphocytic leukemia (ANLL) and chronic myeloid leukemia (CML) express the CD34 antigen on their surface. Isolation of these cell populations is of primary experimental and clinical importance. METHODS: Six bone marrow (BM) and 10 peripheral blood (PB) samples were obtained from 2 normal individuals, 3 patients with CML and 9 with ANLL. The CD34+ cell fraction was isolated using MY10 antibody, sheep anti-mouse immunomagnetic beads and the enzyme chymopapain. Indirect immunofluorescence and semisolid culture were employed to evaluate the percentage of CD34+ cells and that of clonogenic cells in each cell fraction. RESULTS: The frequency of CD34+ cells in the original unseparated populations was (mean +/- SE) 24.3 +/- 7.3%, and reached 85.0 +/- 2.7% in the isolated CD34-positive fractions; in the negative fractions it was only 2.7 +/- 1.7%. According to these results, the great majority of clonogenic cells was separated in the CD34-positive fractions and depleted in those CD34-negative. Moreover, chymopapain was shown to be non-toxic to the clonogenic cells. CONCLUSIONS: Positive immunoselection using My10 Ab, immunomagnetic beads and chymopapain is a method for isolating almost pure progenitors from the BM and PB of normal individuals and patients with myeloid leukemias.

Antigens, CD↗