Biomedical subjects

John Tan

Publications and source records attributed to John Tan.

3 recordsLinked to original sources

PubMed2005

Pharmacodynamic properties of methotrexate and Aminotrexate during weekly therapy.

4-Amino-pteroyl-glutamic acid (Aminotrexate; AMT) has several advantages over the related antifolate methotrexate (MTX), including greater potency, complete oral bioavailability, and greater accumulation by leukemic blasts in vitro. We compared the pharmacodynamic properties of AMT (given orally at 4 mg/m2 in two divided doses per week) and MTX (100 mg/m2 in four divided doses per week) among children with acute lymphoblastic leukemia. We find AMT and MTX to have equivalent penetration into the bone marrow compartment of these patients, as indicated by the steady-state concentrations within mature red blood cells (RBCs). However, MTX concentrations in the cerebrospinal fluid after oral dosage are significantly greater than AMT. To confirm these clinical observations, mice were treated four weekly injections of AMT or MTX, at a 1:20 dosage ratio, and tissue antifolate content was then determined over the subsequent 22 days. We confirm the selective exclusion of AMT from the CNS compartment, while showing equivalent accumulation of AMT and MTX in the RBCs, liver, spleen, kidneys and testes. Finally, we demonstrate that AMT, MTX, and their predominant polyglutamate species are equipotent inhibitors of their target intracellular enzyme dihydrofolate reductase, emphasizing the critical nature of steady-state tissue accumulation in determining the relative cytotoxic potency of these two antifolates.

Aminopterin↗

PubMed2005

The analysis of golf swing as a kinematic chain using dual Euler angle algorithm.

The manner in which anatomical rotation from an individual segment contributes to the position and velocity of the endpoint can be informative in the arena of many athletic events whose goals are to attain the maximal velocity of the most distal segment. This study presents a new method of velocity analysis using dual Euler angles and its application in studying rotational contribution from upper extremity segments to club head speed during a golf swing. Dual Euler angle describes 3D movement as a series of ordered screw motions about each orthogonal axis in a streamlined matrix form-the dual transformation matrix- and allows the translation and rotation component to be described in the same moving frame. Applying this method in biomechanics is a novel idea and the authors have previously applied the methodology to clinical studies on its use in displacement analysis. The focus of this paper is velocity analysis and applications in sports biomechanics. In this study, electrogoniometers (Biometrics, UK) with a frequency of 1000 Hz were attached to a subject during the execution of the swing to obtain the joint angles throughout the motion. The velocity of the club head was then analyzed using the dual velocity which specifies the velocity distribution of a rigid body in screw motion at any point in time as the dual vector. The contributions of each segment to the club-head velocity were also compared. In order to evaluate this method, the calculated position and velocity of the club head were compared to the values obtained from video image analysis. The results indicated that there is good agreement between calculated values and video data, suggesting the suitability of using the Dual Euler method in analyzing a kinematic chain motion.

Algorithms↗

PubMed2004

Mechanotransduction at cell-matrix and cell-cell contacts.

Mechanical forces play an important role in the organization, growth, maturation, and function of living tissues. At the cellular level, many of the biological responses to external forces originate at two types of specialized microscale structures: focal adhesions that link cells to their surrounding extracellular matrix and adherens junctions that link adjacent cells. Transmission of forces from outside the cell through cell-matrix and cell-cell contacts appears to control the maturation or disassembly of these adhesions and initiates intracellular signaling cascades that ultimately alter many cellular behaviors. In response to externally applied forces, cells actively rearrange the organization and contractile activity of the cytoskeleton and redistribute their intracellular forces. Recent studies suggest that the localized concentration of these cytoskeletal tensions at adhesions is also a major mediator of mechanical signaling. This review summarizes the role of mechanical forces in the formation, stabilization, and dissociation of focal adhesions and adherens junctions and outlines how integration of signals from these adhesions over the entire cell body affects how a cell responds to its mechanical environment. This review also describes advanced optical, lithographic, and computational techniques for the study of mechanotransduction.

Animals↗