Table of Contents Faculty and Professional Staff
Section of Bioengineering

M.D. Anderson Cancer Center
Department of Biomathematics

Section of Bioengineering

Staff and Activities

Staff

Dennis A. Johnston, Ph.D. (1971) Texas Tech University
Chief, Section of Bioengineering, Associate Professor of Biomathematics
Areas: Multivariate analysis; image processing; non parametric tests; statistical computer program packages.

Kuang Tang, M.S. (1975) Texas A&M University
Programmer Analyst III
Areas: Fortran and C languages; X-windows for image processing; computer karyotyping; statistical analysis on PC and UNIX machines

Activities

Staff in this Section are experienced in applied mathematics, statistics, and image processing. Research activities center in the Image Processing Laboratory Facility. Major projects are underway which involve computer analysis of DNA sequencing gels, analysis of two-dimensional polyacrylamide gels, computer karyotyping and analysis of banded and in situ hybridized cells (FISH-CGH), development of imaging features and techniques to improve diagnosis of occurrence and recurrence of disease in radiology and pathology images, and other image processing applications.

Investigator-Initiated Research

  1. Digital Image Processing (Recent Publications, # 1, 2, 5, 7, 12, 13, 14, 15, 16, 17, 20, and Submitted Publications, #1, 2, 6, 9). Dr. D. A. Johnston and Mr. K.S. Tang.
    Digital Image Processing is a collection of diverse methodologies, techniques and software used to analyze images. Cancer research and treatment produces many images which are appropriate for digital image processing. These include (1) radiographic images such as mammograms, CT and MR; (2) pathologic smears, thin sections, and fine needle aspirates to include the use of special stains and probes such as florescence in situ hybridization (FISH); and (3) biochemical preparations and extracts such a 1- and two-dimensional gels and blots (Northern, Western, Southern, and Dot) and DNA sequencing gels. Although these images represent diverse formats, the image processing software required does not differ greatly. Thus, special purpose software to analyze each type of image is not necessary during development and may only be desirable to achieve speed and throughput.
    Over the last three decades we have been developing methodology and software to process images. We are currently extending our technology to diverse platforms (PC's, Macintosh, UNIX) and expanding our techniques to include the analysis of DNA sequencing gels, FISH-CZ, full color processing, and wavelets. To permit the widespread use of the technology, we are converting many applications to run on NIH-Image, which is a Macintosh-based public domain imaging system.

  2. Nonlinear Modelling (Recent Publications, #21). Dr. D. A. Johnston.
    Cancer cell detection often is accomplished by measuring a biochemical product uniquely produced by a particular cancer. A limiting dilution assay where known concentrations of the product are diluted and then assayed to measure detection efficiency is the common method to establish the test's sensitivity, specificity and range of action. Amplification such as PCR amplification is used to detect the concentrations. Such tests produce a characteristically nonlinear sigmoid-shaped curve. The deveopment of nonlinear techniques and the development of better nonlinear inverse estimation techniques is the goal of this project. The comparison of nonlinear models both directly and by comparing coefficients is an additional goal. Once the levels of the product are estimated, their use in predicting relapse of the patient over the course of patient treatment and follow-up is a further application. These methods can be easily extended to prediction and comparison of the dosing effect of both carcinogenic and chemotherapeutic compounds on various human tissues.

    Scientific Consultations and Collaborations

    1. Automated cytogenetics. Dr. S. Zimmerman and Dr. D.A. Johnston.
    2. Texture analysis as a predictor of recurrence of breast cancer. Dr. D. Johnston, Dr. R. Dubes, Dr. S. Singletary, Dr. G. Hortobagyi, Dr. A. Buzdar, Dr. L. Moulopoulos, Dr. D. Varma, and Dr. J. Hazle.
    3. Classification and clustering of cell types in "Pap" smears and other pathological preparations. Dr. D. Johnston and Dr. R. Katz.
    4. The analysis of two-dimensional polyacrylamide electrophoresis. Dr. D. Johnston and Dr. L. Rodriguez.
    5. Probabilistic models of known olgimer sequences. Dr. M. MacLeod, Dr. R.A. White, and Dr. D.A. Johnston.
    6. Quantitative limiting dilution PCR assay to monitor residual disease in pediatric acute lymphoblastic leukemia. Dr. T. Zipf, Dr. M. Roberts, and Dr. D.A. Johnston.
    7. Analysis of olgimer response in rabbits. Dr. D. Mitchell and Dr. D.A. Johnston.
    8. The effect of UV damage as a function of depth in sea water. Dr. D. Mitchell and Dr. D.A. Johnston.
    9. Automatic DNA sequence analysis. Dr. M. LaBate, Dr. M. MacLeod, and Dr. D.A. Johnston.
    10. Genetic determinants of spontaneous cancer in rodents. Dr. J. Angel and Dr. D.A. Johnston.
    11. Association of similar genes among species. Dr. D. Morizot, Dr. R. Nairn, and Dr. D.A. Johnston.
    12. The analysis and comparison of FISH-CGH. Dr. M. Aldaz and Dr. D.A. Johnston.
    13. The association of genetic mutation with diagnostic site in bladder cancer. Dr. B. Czerniak and Dr. D.A. Johnston.
    14. The association of chromosome number, DNA index, and chromosome excess with diagnosis in bladder cancer. Dr. L. Sayage, Dr. R. Katz, and Dr. D.A. Johnston.
    15. Age adjusted PSA. Dr. R. Babaian and Dr. D.A. Johnston.
    16. Properties of DNA sequences using short periodic functions and wavelets. Dr. W. Kokolus, Dr. R.A. White, and Dr. D.A. Johnston
    17. Analysis of animal carcinogenetic trials. Dr. T. Slaga, Dr. J. DiGiovanni, Dr. C. Conti, Dr. S. Walker, and Dr. D.A. Johnston.
    18. The analysis of the beading effect in vessels imaged with CT. Dr. J. Hazle and Dr. D.A. Johnston.
    19. Image quality and wavelets. Dr. J. Hazle and Dr. D.A. Johnston.
    20. Image analysis of the distribution of intraperitoneally administered fluids in patients with ovarian cancer. Dr. V. Levenback and Dr. D.A. Johnston.
    21. Analysis of the effect of PCB's. Dr. Rodriguez, Dr. S. Safe, Dr. C. Conti, and Dr. D.A. Johnston.
    22. Analysis of 1- and 2-dimensional gels. Dr. S. Lau, Dr. L. Rodriguez and Dr. D.A. Johnston.
    23. Analysis of in situ hybridization (ISH) in sectioned preparations. Dr. K. Dhingra, Dr. W. Hittleman, and Dr. D.A. Johnston.
    24. The use of magnetic resonance imaging as a diagnostic and prognostic tool. Dr. L. Moulopoulos, Dr. D. Varma, Dr. J. Hazle, and Dr. D.A. Johnston.
    25. The use of magnetic resonance imaging in the assessment of fluid buildup. Dr. D. Varma and Dr. D.A. Johnston.
    26. The analysis of polyamines in cancer patients. Dr. J. Benvenuto, Dr. K. Nishioka, and Dr. D.A. Johnston.
    27. The effect of trauma on the brain. Dr. R. Hayes, Dr. E. Dixon, Dr. W. Taft, and Dr. D.A. Johnston.
    28. Dosage of pain medication for pediatric patients. Dr. C. Holder and Dr. D.A. Johnston.
    29. Assessment of cytotechnologist performance. Dr. N. Sneige, Dr. R. Katz, and Dr. D.A. Johnston.
    30. Analysis of multiple myeloma. Dr. R. Alexanian, Dr. N. Dimopoulos, and Dr. D.A. Johnston.
    31. The Effect of CO2 insufflation during laparoscopy. Dr. B. Feig, Dr. D. Ota, Dr. J. Daugherty, and Dr. D.A. Johnston.
    32. Study of body fat as a factor in cancer. Dr. L. Jones and Dr. D.A. Johnston.
    33. The effects of estrogen treatment. Dr. L. Jones, Mr. R. Hajek, and Dr. D.A. Johnston
    34. Liposomal-based treatment of cancer patients. Dr. E. Kleinerman, and Dr. D.A. Johnston.
    35. Analysis of treatment and progression in breast sarcoma. Dr. Pollack, Dr. H. Gutman, and Dr. D.A. Johnston.
    36. Myelodysplastic syndrome patients. Dr. M. Pallavicini, Dr. M. Andreeff, and Dr. D.A. Johnston.
    37. The use of portal films in the positioning of patients undergoing multiple radiation doses. Dr. A. Boyer and Dr. D.A. Johnston.
    38. The analysis of smoking patterns in Afro-American youth. Dr. E. Gritz and Dr. D.A. Johnston.

    Recent Publications

    1. Auger, M., Katz, R.L., Ordonez, N.G., Johnston, D.A., and Fritsche, H. Quantitation of immunocytochemical estrogen and progesterone receptor content in fine needle aspirations of breast carcinoma using SAMBA 4000 Image Analysis System. Analytical and Quantitative Cytology and Histology, 15: 274-280, 1993. (return to Research #1)
    2. Auger, M., Katz, R.L., Swan, G., Abdelatif, O. Grenko, R., Johnston, D.A., Dalton, H. and Ordonez, N.G. P-Glycoprotein and Glutathione S-Transferase expression in non-Hodgkin's lymphomas: An immunocytochemical study with image analysis quantitation. Cancer, in press. (return to Research #1)
    3. Benvenuto, J.A., Johnston, D.A. and Nishioka, K. The correlation of response with plasma pharmacokinetics and polyamine concentrations in patients with acute myelogenous leukemia receiving amonafide. Cancer Letters, 70: 175-179, 1993.
    4. Collard, S.M., McDaniel, R.K., Johnston, D., and D'Anton, E.W. The potential pathogenicity of dust generated during composite resin finishing. Journal of the American Dental Association, in press.
    5. Dhingra, K., Sneige, N., Pandita, T.K., Johnston, D.A., Lee, J.S., Emami, K., Hortobagyi, G.N. and Hittelman, W.N. Quantitative analysis of chromosome in situ hybridization signal in paraffin-embedded tissue sections. Cytometry, 16:100 112, 1994. (return to Research #1)
    6. Finkbohner, R., Johnston, D., Crawford, S., Coselli, J., and Milewicz, D.M. The Marfan Syndrome: Long-term survival and complications following aortic aneurysm repair. Circulation, in press.
    7. Fischler, D.F., Wongbunnate, S., Johnston, D.A., and Katz, R.L. DNA content by image analysis. An accurate discriminator of malignancy in pericardial effusions. Analytical and Quantitative Cytology and Histology, 16:167-173, 1994. (return to Research #1)
    8. Fujimaki, W., Itoh, K., An, T., Gano, J.B., Ross, M.I., Mansfield, P.F., Balch, C.M., Augustus,\xca L.B., Karkevitch, D.D., Johnston, D., Fidler, I.J. and Kleinerman, E.S. Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A Lipid). Cancer Biotherapy, 8:307-318, 1993.
    9. Gutman, H., Pollock, R.E., Ross, M., Benjamin, R.S., Johnston, D.A., Janjan, N. and Rohmdahl, M. Sarcoma of the breast: Implications for extent of therapy. The M. D. Anderson Experience. Surgery, 116:505-509, 1994.
    10. Hajek, R.A., Van, N.T., Johnston, D.A. and Jones, L.A. In vivo induction of increased DNA ploidy of mouse cervicovaginal epithelium by neonatal estrogen treatment. Biology of Reproduction, 49:908-917, 1993.
    11. Hug, V., Clark, J., and Johnston, D. The results of modified use of chemotherapy for patients with metastatic breast cancer. European Journal of Cancer, in press.
    12. Johnston, D.A., Tang, K.S., and Zimmerman, S. Band features as classification measures for G-banded chromosome analysis. Computers in Biology and Medicine, 23:115-129, 1993. (return to Research #1)
    13. Katz, R.L., Wojcik, E.M., El-Naggar, A.K., Ordonez, N.G., and Johnston, D.A. Proliferation markers in NHL: a comparative study between cytophotometric quantitation of Ki-67 and AO FCM proliferation index on fine needle aspirates. Analytical and Quantitative Cytology and Histology, 15:179-186, 1993. (return to Research #1)
    14. Katz, R.L., Wojcik, E.M. and Johnston, D.A. Image analysis in non-Hodgkin's lymphomas emphasizing applications in tissue procured by fine needle aspiration. IN: The Compendium on the Computerized Cytology and Histology Laboratory, pp. 241-258. Tutorials of Cytology: Chicago, IL,1994. (return to Research #1)
    15. Levenback, C., Curtin, J., Johnston, D., Rubin S.C., Yeh, S. and Hoskins, W. Image analysis of the distribution of intraperitoneally administered fluids in patients with ovarian cancer. Journal of Gynecology, in press. (return to Research #1)
    16. Moulopoulos, L.A., Dimopoulos, M.A., Varma, D.G.K., Manning, J., Johnston, D.A., Leeds, N. and Libshitz, H.I. Waldenström Macroglobulinemia: MR imaging of the spine and computed tomography of the abdomen and pelvis. Radiology, 188:669-673, 1993. (return to Research #1)
    17. Rodriguez, L.V., Gersten, D.M., Ramagli, L.S., and Johnston, D.A. Towards stoichiometric silver staining of proteins resolved in complex two dimensional goals: real time analysis of pattern development. Electrophoresis, 14: 628-637, 1993. (return to Research #1)
    18. Stephens, L.C., Robbins, M.E.C., Peters, L.J., Thames, H.D., Price, R.E., Johnston, D.A., and Ang, K.K. Radiation nephropathy in the rhesus monkey: Morphometric analysis of glomerular and tubular alterations. International Journal of Radiation, Oncology, Biology, Physics, in press, 1994.
    19. Thorp, J.A., Eckert, L.O., Ang, M.S., Johnston, D.A., Peaceman, A.M. and Parisi, V.M. Epidural analgesia and caesarean section for dystocia: Risk factors in nulliparas. American Journal of Perinatology, in press.
    20. Wojcik, E.M., Katz, R.L., Johnston, D.A., Sembera, D., and El-Naggar, A. Comparative analysis of DNA ploidy and proliferative index in fine-needle aspirates of non-Hodgkin's lymphomas by image analysis and flow cytometry. Analytical and Quantitative Cytology and Histology, 15: 151-157, 1993. (return to Research #1)
    21. Ouspenskaia, M.V., Johnston, D.A., Roberts, W.M., Estrov, Z., and Zipf, T.F. Accurate quantitation of residual B-precursor lumphoblastic leukemia by limiting dilution and a PCR-based detection system: A description of the method and the principles involved. Leukemia, in press. (return to Research #2)

    Submitted Publications

    1. Wojcik, E.M., Katz, R.L., Johnston, D.A., Fanning, T.V. and Pugh, W. Morphonuclear comparison of mantle zone and diffuse subtypes of mantle cell lymphoma. (return to Research #1)
    2. Wojcik, E.M., Katz, R L., Johnston, D., Sembera, D. and El-Naggar, A. Ploidy and proliferation in non-Hodgkin's lymphomas by image analysis and flow cytometry. A study of 78 fine needle aspirations. (return to Research #1)
    3. Kleinerman, E.S., Gano, J.B., Johnston, D.A., Benjamin, R.S. and Jaffe, N. Efficacy of liposomal muramyul tripeptide (CGP 19835A) in the treatment of relapsed osteosarcoma.
    4. del Giglio, A., O'Brien, S., Ford, Jr., R.J., Manning, J., Saya, H., Keating, M., Johnston, D., Chamone, D.F. and Deisseroth, A.B. Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL).
    5. Gutman, H., Pollock, R.E., Janjan, N.A. and Johnston, D.A. Sarcomatoid metaplasia of epithelial breast cancer: biological distinctions and therapeutic implications.
    6. Auger, M., Sneige, N., Sahin, A., Johnston, D.A., Ordonez, N.G. and El-Naggar, A. Fine needle aspiration of breast carcinoma: Comparative analysis of Ki-67 fraction by immuno-cytochemistry and proliferative activity by flow cytometry. (return to Research #1)
    7. Hug, V. and Johnston, D.A. The effects of body weight on the clinical course of breast carcinoma are not solely mediated by estrogens.
    8. Wicklund, C.L., Pauli, R.M., Johnston, D. and Hecht, J.T. Natural history study of hereditary multiple exostoses.
    9. Auger, M., Katz, R. L., and Johnston, D. The differentiating cytological features of bronchioloalveolar carcinoma from adenocarcinoma of the lung in fine needle aspirations: A statistical analysis of 27 cases. (return to Research #1)
    10. Longo, T.A., Cinque, M., Johnston, D.A., Hayes R., Frates, F.C. and Clifton, G.L. Hypovolemia, hypotension, and increased ICP in head injured children.
    11. Jones, L.A., DiPaolo, D., Insull, W., Yick, J., Galvez, C., Foreman, C., Scully, N.F., David, C., Johnston, D.A., Shallenberger, R., Mitchell, M.F., Vogel, V., Berkowitz, A., Henson, H., Brown, B. and Klish, W. Effect of a short-term low-fat diet on bioavailable estrogen levels in an ethnically diverse population.
    12. Northup, H., Etzel, F.K., Hebert, A.A., Johnston, D.A., Delgado, M.R. and Roach, E.S. Tuberous sclerosis complex: A clinical survey of 110 patients.
    13. Janjan, N.A. and Johnston, D.A. A method of scoring treatment plans for external beam radiotherapy.
    14. Ghosh, R., Taylor, J.-S., Johnston, D.A., and Mitchell, D.L. Determination of specificities of anti-UV DNA antisera using mobility shift immunoassays of oligonucleotides containing site-specific cyclobutane pyrimidine dimers and pyrimidine-pyrimidinone (6-4) photoproducts.

    Table of Contents Section of Biostatistics