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P Fuchshuber

Publications and source records attributed to P Fuchshuber.

9 recordsLinked to original sources
PubMed1998

Flt3 ligand promotes the generation of a distinct CD34(+) human natural killer cell progenitor that responds to interleukin-15.

Interleukin-15 (IL-15) is produced by human bone marrow (BM) stromal cells and can induce CD34(+) hematopoietic progenitor cells (HPCs) to differentiate into CD56(+)CD3(-) natural killer (NK) cells in the absence of stromal cells. IL-15 mediates its effects by signaling through the beta and gammac chains of the IL-2/15 receptor (R). The c-kit ligand (KL), also produced by stromal cells, enhances the expansion of NK cells from CD34(+) HPCs in the presence of IL-15, but alone has no ability to differentiate NK cells. Mice deficient in KL do not appear to have a quantitative deficiency in NK cells, suggesting that other stromal cell factors may contribute to NK cell expansion. Flt3 ligand (FL) is also produced by BM stromal cells and has homology with KL. Furthermore, mice with a targeted disruption of the FL gene have reduced numbers of NK cells. We evaluated here the effects of FL on human NK cell development and expansion from CD34(+) HPCs. Like KL, FL significantly enhanced the expansion of NK cells from CD34(+) HPCs in the presence of IL-15, compared with IL-15 alone. However, FL alone had no effect on NK cell differentiation. We therefore explored the mechanism by which FL promotes IL-15-mediated NK cell development. FL was found to induce IL-2/15Rbeta (CD122) expression on CD34(bright) HPCs. The CD34(bright) CD122(+) cell coexpressed CD38, but lacked expression of CD7, CD56, NK cell receptors (NKRs), or cytotoxic activity in the absence of IL-15. Using limiting dilution analysis in the presence of IL-15 alone, we demonstrated that the FL-induced CD34(bright)CD122(+) HPCs had an NK cell precursor frequency 20- to 60-fold higher than the CD34(dim/neg)CD122(-) HPCs and 65- to 235-fold higher than fresh CD34(+) HPCs. KL had similar effects as FL, but induced a significantly lower percentage of CD34(bright)CD122(+) cells (P </=.01). Both FL and KL also increased IL-15R transcript in CD34(+) HPCs. Culture of CD34(+) HPCs in FL or KL, followed by culture in IL-15 alone, induced expression of both C-type lectin and Ig-superfamily NKRs on CD56(+) cells. These data collectively support a role for FL in early human NK cell development. FL or KL generate a unique CD34(bright) CD122(+)CD38(+) human NK cell intermediate from CD34(+) HPCs that lacks NK features yet is IL-15-responsive. IL-15 is then required for the induction of CD56 and NKRs, LGL morphology, cytotoxic activity, and the ability to produce abundant cytokines and chemokines.

Adult↗
PubMed1998

Differentiated thyroid carcinoma: risk group assignment and management controversies.

In this review, we provide a framework for clinical decision-making in the treatment of differentiated thyroid cancer. The clinical discussion and treatment recommendations are relevant to an adult population (> 16 years of age). The natural history, pathogenesis, diagnostic tools, and treatment controversies in the management of this disease are explored. The roles of radioiodine therapy and thyroid-stimulating hormone (TSH) suppression and the treatment of locoregional disease are reviewed. This discussion provides a comprehensive assessment of management and treatment issues in differentiated thyroid cancer.

Adult↗
PubMed1990

Lytic units reconsidered: pitfalls in calculation and usage.

51Chromium release-derived cytotoxicity data yield curvilinear plots when the x axis displays the effector:target ratio and the y axis displays the percentage of cytotoxicity. To facilitate data analysis, several biomathematical models (simple linear regression, exponential fit, and Von Krogh) have been used to express these cytotoxicity curves as a single numerical value, termed the lytic unit. Other than using raw cytotoxicity data, the lytic unit has been the most common method of data presentation in human and animal tumor immune studies involving natural killer cells, lymphokine-activated killer cells, and cytotoxic T cells. Unfortunately, the models for determining lytic unit values incorporate assumptions and methods of calculation that can result in inaccurate model-predicted cytotoxicity in comparison with the actual observed cytotoxicity data. Even when the model is accurate in predicting cytotoxicity values (i.e., the nonlinear regression-calculated three-parameter Von Krogh model), comparisons between donors of minimally different or highly different cytotoxicity are still fraught with potential error due to statistically verifiable violations of assumptions of parallelism. Although more cumbersome, donor cytotoxicity comparisons using a range of effector:target ratios are not subject to the above problems. Researchers may therefore want to reconsider the use of lytic units when evaluating and reporting cytotoxicity data.

Chromium Radioisotopes↗
PubMed1990

Immunologic and clinical aspects of natural killer cells in human leukemia.

We have studied peripheral-blood, splenic and bone marrow natural killer (NK) activity in patients with leukemia. These studies demonstrated that leukemic patients displayed defective NK activity in all of these tissues. However, NK defect could be corrected by culture of effector cells with interleukin-2 (IL-2). The phenotypic analysis of IL-2 cultures showed clearly the heterogeneity of lymphocyte subsets. The characterization studies demonstrated that CD56+, CD3- NK cells manifested most potent lysis of leukemia, CD56+, CD3+ T cells mediated some, but low, antileukemia activity and CD56-, CD3+ T lymphocytes were devoid of cytotoxicity.

Bone Marrow Cells↗
PubMed1989

A parametric study of the force/moment systems produced by T-loop retraction springs.

This study considers the effects of several parameters on the force/moment systems produced by T-loop retraction springs. The springs are studied by using the finite element method and by experimentally measuring the forces and moments from the various designs. The results show that varying the spring height can produce larger moment to force ratios as the height increases. Changes in the preactivation bends result in unsymmetric moment characteristics and also produce large intrusive/extrusive forces. The addition of helices at the bends did little to alter the springs' mechanical characteristics.

Computer Simulation↗
PubMedDate not supplied

A mathematical model for metastatic growth illustrated by in vivo and in vitro growth of a transplantable mammary carcinoma in mice.

We analysed the growth pattern of metastases in C3H-mice produced by i.v. injection (tail vein) of tumor cell suspensions of mammary carcinoma HB. Although the ordinary Gompertz equation generally corresponds well to tumor growth in animals and men, we found it inadequate to describe the growth of lung metastases in our model. The morphometric analysis and growth kinetics (LI/GF) of the metastases show a biphasic pattern. The first phase is characterized by a strictly avascular growth and nutrition by diffusion, the second phase is initiated by tumor angiogenesis. To analyze these observations we developed a new mathematical equation which fits particularly well to the metastatic growth curve. We conclude that the present model is appropriate for the analysis of tumor angiogenesis, especially to study factors, which influence the development of a tumor specific vascular system.

Animals↗