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J V Turian

Publications and source records attributed to J V Turian.

3 recordsLinked to original sources

Ex vivo expansion of autologous bone marrow CD34(+) cells with porcine microvascular endothelial cells results in a graft capable of rescuing lethally irradiated baboons.

Hematopoietic stem cell (HSC) self-renewal in vitro has been reported to result in a diminished proliferative capacity or acquisition of a homing defect that might compromise marrow repopulation. Our group has demonstrated that human HSC expanded ex vivo in the presence of porcine microvascular endothelial cells (PMVEC) retain the capacity to competitively repopulate human bone fragments implanted in severe combined immunodeficiency (SCID) mice. To further test the marrow repopulating capacity of expanded stem cells, our laboratory has established a myeloablative, fractionated total body irradiation conditioning protocol for autologous marrow transplantation in baboons. A control animal, which received no transplant, as well as two animals, which received a suboptimal number of marrow mononuclear cells, died 37, 43, and 59 days postirradiation, respectively. Immunomagnetically selected CD34(+) marrow cells from two baboons were placed in PMVEC coculture with exogenous human cytokines. After 10 days of expansion, the grafts represented a 14-fold to 22-fold increase in cell number, a 4-fold to 5-fold expansion of CD34(+) cells, a 3-fold to 4-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM), and a 12-fold to 17-fold increase of cobblestone area-forming cells (CAFC) over input. Both baboons became transfusion independent by day 23 posttransplant and achieved absolute neutrophil count (ANC) >500/microL by day 25 +/- 1 and platelets >20,000/microL by day 29 +/- 2. This hematopoietic recovery was delayed in comparison to two animals that received either a graft consisting of freshly isolated, unexpanded CD34(+) cells or 175 x 10(6)/kg unfractionated marrow mononuclear cells. Analysis of the proliferative status of cells in PMVEC expansion cultures demonstrated that by 10 days, 99.8% of CD34(+) cells present in the cultures had undergone cycling, and that the population of cells expressing a CD34(+) CD38(-) phenotype in the cultures was also the result of active cell division. These data indicate that isolated bone marrow CD34(+) cells may undergo cell division during ex vivo expansion in the presence of endothelial cells to provide a graft capable of rescuing a myeloablated autologous host.

Animals↗

Matching photon and electron fields with dynamic intensity modulation.

A technique was developed to reduce the size and magnitude of the hot and cold spots in the abutting regions of photon and electron fields. The photon and electron fields were set up such that the photon field extended approximately 2 cm into the electron field in the abutting region. The region of the photon beam that overlapped the electron field was modulated using a multileaf collimator, effectively broadening the photon penumbra to make it complimentary to the electron penumbra. The computer calculations were verified using film measurements for abutting a 6 MV photon beam with a 9 MeV electron beam. A uniform dose was achieved at a prespecified depth of 2 cm, and dose uniformity was improved at the specified depth and beyond compared with unmodulated photon beams. A slight increase in dose inhomogeneity was seen at shallower depths. The overall areas of the hot and cold spots were significantly reduced. The technique also reduced the sensitivity of dose homogeneity to setup errors such that the magnitudes of the hot and cold spots were about half of those produced with unmodulated photon beam when an overlap or gap of 4 mm was introduced. The technique was applied to the treatment of a head and neck cancer and a lymphoma involving the right pleura with markedly reduced dose inhomogeneity in the abutting regions.

Computer Simulation↗

Verification of the omni wedge technique.

The optimal field shape achieved using a multileaf collimator (MLC) often requires collimator rotation to minimize the adverse effects of the scalloped dose distribution the leaf steps produce. However, treatment machines are designed to deliver wedged fields parallel or perpendicular to the direction of the leaves. An analysis of cases from our clinic showed that for 25% of the wedged fields used to treat brain and lung tumors, the wedge direction and optimal MLC orientation differed by 20 degrees or more. The recently published omni wedge technique provides the capability of producing a wedged field with orientation independent of the orientation of the collimator. This paper presents a comparison of the three-dimensional (3D) dose distributions of the omni wedged field with distributions of wedged fields produced using both the universal and dynamic wedge techniques. All measurements were performed using film dosimetry techniques. The omni wedge generated fields closely matched the conventional wedged fields. Throughout 95% of the irradiated volume (excluding the penubra), the dose distribution of the omni wedged field ranged from +5.5 to -3.5 +/- 1.5% of that of the conventionally wedged fields. Calculation of the omni wedged field is as accurate as conventional wedged field calculation when using a 3D treatment planning systems. For two-dimensional treatment planning systems, where one must assume that the omni wedged field is identical to a conventional field, the calculated field and the delivered field differs by a small amount.

Brain Neoplasms↗