Chilton, Fertig, Fleiss, and the Task Force on Design and Analysis in Dental and Oral Research.
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American Dental Association↗
Biomedical subjects
S O Zimmerman
Publications and source records attributed to S O Zimmerman.
A model of the G1 phase of the cell cycle incorporating cyclin E/cdk2 complex and retinoblastoma protein.
A mathematical model of cyclin E, cdk2 and retinoblastoma protein control of the G1 phase of the human cell cycle is proposed. The model includes retinoblastoma (Rb) protein phosphorylation by a cyclin E/cdk2 complex and its subsequent dephosphorylation at the end of the cell cycle. The numerical solutions to this model demonstrates the cyclic behavior of the cyclin E/cdk2 complex, with and without Rb function, cell cycle. This model suggests an inhibition of cyclin E/cdk2 complex formation (or its activation) by hypophosphorylated retinoblastoma protein. The experimental results of cell cycle arrest upon injection of transforming growth factor-beta, alpha-interferon or D-erythro-sphingosine during G1 phase are reproduced. Cell cycle behavior predicted by this model for increasing the concentration of hypophosphorylated retinoblastoma protein during the G1 phase is discussed. Additional results are obtained by numerical simulation.
CDC2-CDC28 Kinases↗
Analysis of interphase cells for the Philadelphia translocation using painting probe made by inter-Alu-polymerase chain reaction from a radiation hybrid.
Fluorescence in situ hybridization (FISH) probe for the identification of the Philadelphia (Ph) translocation [t(9;22) (q34;q11)] in chronic myelogenous leukemia cells was developed by inter-Alu-polymerase chain reaction of DNA from an interspecific somatic cell hybrid containing approximately 5 Mb of human DNA covering the ABL gene region on human chromosome 9q34. This probe was large enough to be effective in identifying the genomic domains yet small enough to resolve them in more than 90% of bone marrow interphase cells. Combination of the probe with a cosmid contig probe for the BCR region of chromosome 22 in two-color FISH reduced the frequency of false-positive identification of the Ph chromosome to less than 1%. The procedure allows detection of as few as 1% Ph+ cells independent of the cycling status or BCR/ABL expression level of cells, and the quantitation of non-Ph chromosome-containing interphase nuclei in the marrow of patients judged 100% Ph+ by standard cytogenetics.
Humans↗
A model for regulation of the cell cycle incorporating cyclin A, cyclin B and their complexes.
A mathematical model for the cell cycle is proposed that incorporates the known biochemical reactions involving both cyclin A and cyclin B, the interactions of these cyclins with cdc2 and cdk2, and the controlling effects of cdc25 and weel. The model also postulates the existence of an as yet unknown phosphatase involved in the formation of maturation promoting factor. The model produces solutions that agree qualitatively with a wide variety of experimentally observed cell-cycle behaviour. Conditions under which the model could explain the initial rapid divisions of embryonic cells and the transition to the slower somatic cell cycle are also discussed.
Animals↗
Recommended revisions to American Dental Association guidelines for acceptance of chemotherapeutic products for gingivitis control. Report of the Task Force on Design and Analysis in Dental and Oral Research to the Council on Therapeutics of the American Dental Association.
This paper presents suggested revisions to the American Dental Association's 1985 guidelines for acceptance of anti-gingivitis chemotherapeutic agents. The areas of study design, choice and quality control of clinical gingivitis measurements, statistical analysis, and minimum strength of effect, are addressed. The revisions articulate certain aspects of study design which were implicit in the 1985 guidelines, clarify language on cross-over designs and independence of studies, and recommend use of a United States population in at least one trial supporting a product. Separate recording and analysis of a product's effect on gingival bleeding is proposed, and quality control of clinical measurements receives enhanced emphasis. Modestly elaborated statistical reporting guidelines and strengthened approval criteria, based on size of estimated effect as well as statistical significance, are advocated.
American Dental Association↗
Proposed guidelines for American Dental Association acceptance of products for professional, non-surgical treatment of adult periodontitis. Task Force on Design and Analysis in Dental and Oral Research.
Guidelines are suggested for determining efficacy of products to supplement scaling and root planing in professional, non-surgical treatment of adult periodontitis. They result from an extended process including a conference on clinical trials in gingivitis and periodontitis, a subsequent workshop, and commentary from industrial, academic, professional and governmental members of the periodontal research community on two drafts. Recommendations are made in the broad areas of basic study design, subject and periodontal site selection, clinical management, choice of outcome variables, statistical summarization and analysis, and criteria for acceptance. Prominent dissenting views, with justifications for positions taken here, are also provided. Groundwork is laid for possible future guidelines addressing products for primary prevention or over-the-counter uses, or for determining superiority or equivalence of competing products. However, issues are identified which require further exploration before responsible and widely acceptable recommendations can be made in these areas. The guidelines suggested here are meant to form the basis of an evolving document rather than a static standard. It is suggested that they be reviewed frequently in the light of improvement in the technology available for periodontal research, and the emergence of products representing new approaches to periodontal therapy.
Adult↗
Hodgkin's disease: study of treatment intensities and incidences of second malignancies.
BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non-Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non-Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage.
Actuarial Analysis↗
Mathematical models for the cellular concentrations of cyclin and MPF.
Several mathematical models have been proposed for regulation of the cell cycle in early embryos by cyclin and maturation-promoting factor (MPF). In this paper the previously proposed models for cyclin and MPF activity are analyzed, and the validity of those models based on the mathematical behavior of their solutions and on physical considerations are discussed. In addition, three further models are proposed that exhibit the periodic behavior necessary for modeling the mitotic clock but that do not have certain of the limitations of the other models.
Animals↗
MDA-image: an environment of networked desktop computers for teleradiology/pathology.
MDA-Image, a project of The University of Texas M. D. Anderson Cancer Center, is an environment of networked desktop computers for teleradiology/pathology. Radiographic film is digitized with a film scanner and histopathologic slides are digitized using a red, green, and blue (RGB) video camera connected to a microscope. Digitized images are stored on a data server connected to the institution's computer communication network (Ethernet) and can be displayed from authorized desktop computers connected to Ethernet. Images are digitized for cases presented at the Bone Tumor Management Conference, a multidisciplinary conference in which treatment options are discussed among clinicians, surgeons, radiologists, pathologists, radiotherapists, and medical oncologists. These radiographic and histologic images are shown on a large screen computer monitor during the conference. They are available for later review for follow-up or representation.
Clinical Laboratory Information Systems↗
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↗
Progressive resistance exercise: effect on muscle function and anthropometry of a select AIDS population.
Substantial body tissue wasting has been reported in acquired immune deficiency syndrome (AIDS) patients. The purpose of this investigation was to determine if progressive resistance exercise (PRE) would improve muscle function and increase body dimensions and mass in AIDS patients. The subjects were 24 male outpatient volunteers, status posttherapy for acute pneumocystis carinii pneumonia. Subjects were randomly assigned to control (n = 12) or experimental (n = 12) subsets. All subjects underwent muscle function testing on 12 variables of torque, force, power, and work; three variables of anthropometry were assessed. The experimental group engaged in PRE three times per week for six weeks. The control group did not exercise beyond their usual daily living activities. Both groups were retested at the end of six weeks. In comparison to the control group, the experimental group significantly increased in 13 of the 15 study variables. Thus, during the nonacute stage of AIDS, physiologic adaptation occurred that improved muscle function and increased body dimensions and mass.
Acquired Immunodeficiency Syndrome↗
Problem-solving tasks on the microcomputer: a look at the performance of students with learning disabilities.
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Child↗
The use of subchromosome-length unique band sequences in the analysis of prophase chromosomes.
Using human prophase chromosome ideograms at the 850-band stage, we previously demonstrated that the 24 prophase ideograms can be divided into a set of 94 unique band sequences, each having a recognizable banding pattern distinct from other nonhomologous chromosome portions. Using actual prophase mitotic cells in this study, we analyzed the p arm of chromosome 11 and of chromosomes 16-22 and characterized a similar set of unique band sequences on actual chromosomes. This set of unique band sequences, a statistical comparison scheme, and image-processing techniques outlined in the present report can be used to identify and distinguish banding patterns of these chromosomes and to determine band pattern abnormalities.
Chromosome Aberrations↗
Automated homologue matching of human G-banded chromosomes.
Two sets of human G-banded chromosomes were employed to test a computer algorithm for homologue matching. One set was produced at the Rigshospitalet, Copenhagen, and the other at the University of Texas M. D. Anderson Hospital. Employing a cross-correlation measure to select candidate homologue mates for each chromosome resulted in correct matches in 91.1% of the cases in the Anderson set and 93.1% in the Denmark set. To identify each chromosome and to give a measure of classification accuracy when performed by humans, five cytogeneticists were asked to independently karyotype the 49 cells in the Anderson set. Agreement between two cytogeneticists was measured by the kappa statistic. If all chromosomes that could not be identified by any given cytogeneticist were removed from the comparison, kappa values were found to be in the vicinity of 0.95. With such unidentifiable chromosomes included as a separate class, the kappa values were closer to 0.89.
Adult↗
Prophase chromosome unique band sequences: definition and utilization.
Extensive experience with the analysis of human prophase chromosomes and studies into the complexity of prophase banding patterns have suggested that at least some prophase chromosomal segments can be accurately identified and characterized independently of the morphology of the chromosome as a whole. The feasibility of identifying and analyzing specified prophase chromosome segments was thus investigated as an alternative approach to prophase chromosome analysis based on whole-chromosome recognition. Through the use of prophase idiograms at the 850-band stage (Francke, 1981) and a systematic comparison system, we have demonstrated that it is possible to divide the 24 human prophase idiograms into a set of 94 unique band sequences, each of which has a banding pattern that is recognizable and distinct from any other nonhomologous chromosome portion. The use of a unique band sequence approach in prophase chromosome analysis is expected to increase efficiency and sensitivity through more effective use of available banding information.
Chromosome Banding↗
Effect of variation of drug dosage on disease control and regional toxicity in prophylactic perfusion for Stage I extremity melanoma.
One hundred and fifty-six patients with extremity melanomas of known level or thickness who were perfused prophylactically with l-phenylalanine mustard (1-PAM) between January 1974 and December 1978 were studied retrospectively to determine the effect of variation of drug dosage and temperature on regional toxicity and disease control. The median drug dosage of 1-PAM for 57 patients undergoing axillary perfusion was 0.85 mg/kg (range 0.48-1.0 mg/kg) and the median dosage was 1.2 mg/kg (range 0.59-1.69 mg/kg) for 99 patients undergoing iliac perfusions. Sixty-five percent of patients achieved a maximum skin temperature of between 101 degrees and 102 degrees F during perfusion. Determinate survival in the entire group was 93% at 5 years; 10% of patients developed positive regional nodes; and 2.5% developed local or intransit metastases. Based on analysis of other series of patients with extremity melanoma with equivalent Clark's level 5-year determinate survival might be expected to be between 65 and 80%. The expected incidence of nodal metastases should be 19.1%-24.0% and the incidence of local and intransit metastases should be 3-6%. While this series suggests a survival advantage for a series of extremity melanomas treated by regional chemotherapy when compared to other series treated by wide excision +/- regional node dissection, the results obtained were independent of dosage of drug administered or maximal temperature attained over the range studied. This suggests consideration be given to exploring other dose ranges of drugs and heat in an effort to achieve equivalent control with lower regional toxicity.
Adolescent↗
The relationship between dental disease and radiation necrosis of the mandible.
Preirradiation panoramic radiographs of forty-six dentate patients were examined for the presence of significant dental disease. The occurrence of necrosis of the mandible after these patients received radiation therapy was then determined. Evidence of a positive association between dental disease present before radiation therapy and subsequent necrosis of the mandible was found (p = 0.09), leading to a recommendation that significant disease be eradicated before irradiation of oral tissues. Two cases are reported to illustrate the complications that can arise in dentate patients following radiation to the oral cavity. Considerable suffering results from bone necrosis, which can be reduced by careful and rational dental diagnosis and treatment.
Carcinoma, Squamous Cell↗
Multivariate considerations in the evaluation of periodontal clinical trials.
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Dental Plaque↗