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Biomedical subjects

R Wheeler

Publications and source records attributed to R Wheeler.

At least 37 records · Page 2Linked to original sources
PubMed1994

Object-oriented model-driven control.

A monitoring and control subsystem architecture has been developed that capitalizes on the use of model-driven monitoring and predictive control, knowledge-based data representation, and artificial reasoning in an operator support mode. We have developed an object-oriented model of a Controlled Ecological Life Support System (CELSS). The model, based on the NASA Kennedy Space Center CELSS breadboard data, tracks carbon, hydrogen, and oxygen, carbon dioxide, and water. It estimates and tracks resource-related parameters such as mass, energy, and manpower measurements such as growing area required for balance. We are developing an interface with the breadboard systems that is compatible with artificial reasoning. Initial work is being done on use of expert systems and user interface development. This paper presents our approach to defining universally applicable CELSS monitor and control issues, and implementing appropriate monitor and control capability for a particular instance: the KSC CELSS Breadboard Facility.

Animals↗
PubMed1994

Retinoid modulation of biomarkers in oral leukoplakia/dysplasia.

Among the tissue, cellular, and molecular changes which take place during the development of squamous cell carcinoma (SCC) of the upper aerodigestive tract, only a limited number can be used as surrogate endpoint biomarkers (SEBs) in cancer chemoprevention trials. Molecular SEBs will be genes or gene products which can be measured accurately and reliably, are altered in intraepithelial neoplasia (dysplasia), correlate strongly with the true outcome (invasive cancer), and are modulated by a chemoprevention agent(s). To identify and modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive tract, we studied expression of the epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), and HER-2/neu genes in oral leukoplakia before, during, and after treatment with 13-cis-retinoic acid, a vitamin A derivative. Four of nine patients treated for 3 months with 1 mg/kg/day of 13-cis-retinoic acid had complete resolution of their leukoplakia. Biopsies were taken of leukoplakia and adjacent normal-appearing mucosa before, during, and after treatment. Immunohistochemistry was performed using the BioGenex Super Sensitive Biotin-Streptavidin horseradish peroxidase detection system. Pretreatment expression of EGFR, TGF-alpha, and HER-2/neu in leukoplakia was increased when compared to normal-appearing mucosa. TGF-alpha expression decreased during treatment in leukoplakia, but not in normal-appearing mucosa, suggesting that TGF-alpha may serve as an intermediate endpoint in cancer chemoprevention trials.

Anticarcinogenic Agents↗
PubMed1993

Is a surgical resection leaving positive margins of benefit to the patient with locally advanced squamous cell carcinoma of the head and neck: a comparative study using the intergroup study 0034 and the Radiation Therapy Oncology Group head and neck database.

PURPOSE: The purpose of this study was to determine whether or not for patients with squamous cell carcinomas of the head and neck, a surgical resection leaving positive margins followed by postoperative adjuvant therapy improves the outcome compared to a matched group of patients treated with definitive radiotherapy alone. METHODS AND MATERIALS: From January 1985 through January 1990 a consortium of national cooperative groups (Radiation Therapy Oncology Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Northern California Oncology Group, Southeast Group, and Southwest Oncology Group) conducted a phase III clinical trial testing the efficacy of adjuvant chemotherapy for patients with resectable, squamous cell carcinomas of the head and neck. One hundred and nine patients were excluded from this study due to positive surgical margins. These patients have been followed prospectively with regards to local/regional tumor control, development of distant metastases, and survival. The postoperative treatment of these patients was not specified by the protocol but the majority of patients received postoperative radiotherapy +/- chemotherapy. These patients were compared with a matched group of patients from the Radiation Therapy Oncology Group head and neck database of patients treated with definitive radiotherapy alone using a standard fractionation schema. Matching parameters included primary tumor site, T-stage, N-stage, Karnofsky performance status, and age. RESULTS: Actuarial curves are presented for local/regional control and survival. At 4 years the local/regional control rate is 44% for the positive margin patients compared to 24% for the patients from the data base (p = 0.007). However, there is no significant difference between the survival curves (p = 0.76) with respective median survivals being 18.1 months vs. 17.9 months and 4-year survivals being 29% vs. 25%. CONCLUSION: While an incomplete excision followed by postoperative therapy does not seem to improve survival compared to treatment with radiotherapy alone, it appears to yield significantly better local/regional control. This would argue for its applicability in selected palliative settings. A follow-up, Phase III trial for patients with advanced tumors may be warranted to test traditional resectability criteria.

Actuarial Analysis↗
PubMed1993

The role of the Mathieu repair as a salvage procedure.

Conceived as a primary single-stage procedure for coronal and subcoronal hypospadias, the Mathieu repair has not been previously described as a salvage operation in situations where other forms of hypospadias surgery have failed to give an adequate functional or cosmetic result. We describe the use of the operation as a planned salvage procedure.

Child↗
PubMed1992

The response of human decidual leukocytes to IL-2.

The phenotype of human decidual leukocytes, composed predominantly of CD3-CD16(-)-CD56bright cells, was examined after culture with IL-2 by immunofluorescence and flow cytometry. After IL-2 stimulation the phenotype became like that found on classical NK cells, with an increased proportion of cells expressing CD16. The IL-2R alpha was absent before and after IL-2 stimulation. However, the intermediate affinity receptor, IL-2R beta, was expressed by CD56bright decidual cells, but this receptor was downregulated after IL-2 stimulation. IL-2-induced proliferation of CD56+ decidual cells could be blocked using TU27, a monoclonal antibody to the IL-2R beta. These findings indicate activation of decidual leukocytes by IL-2 occurs through the IL-2R beta alone.

Antigens, CD↗
PubMed1992

Achieving and documenting closure in plant growth facilities.

As NASA proceeds with its effort to develop a Controlled Ecological Life Support System (CELSS) that will provide life support to crews during long duration space missions, it must address the question of facility and system closure. Here we discuss the concept of closure as it pertains to CELSS and describe engineering specifications, construction problems and monitoring procedures used in the development and operation of a closed plant growth facility for the CELSS program. A plant growth facility is one of several modules required for a CELSS. A prototype of this module at Kennedy Space Center is the large (7m tall x 3.5m diameter) Biomass Production Chamber (BPC), the central facility of the CELSS Breadboard Project. The BPC is atmospherically sealed to a leak rate of approximately 5% of its total volume per 24 hours. This paper will discuss the requirements for atmospheric closure in this facility, present CO2 and trace gas data from initial tests of the BPC with and without plants, and describe how the chamber was sealed atmospherically. Implications that research conducted in this type of facility will have for the CELSS program are discussed.

Atmosphere↗
PubMed1992

Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Multicenter phase II trial of brequinar sodium in patients with advanced melanoma.

Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.

Adult↗
PubMed1992

Controlled ecological life-support system. Use of plants for human life-support in space.

Scientists and engineers within NASA are conducting research which will lead to development of advanced life-support systems that utilize higher plants in a unique approach to solving long-term life-support problems in space. This biological solution to life-support, Controlled Ecological Life-Support System (CELSS), is a complex, extensively controlled, bioengineered system that relies on plants to provide the principal elements from gas exchange and food production to potable water reclamation. Research at John F. Kennedy Space Center (KSC) is proceeding with a comprehensive investigation of the individual parts of the CELSS system at a one-person scale in an approach called the Breadboard Project. Concurrently a relatively new NASA sponsored research effort is investigating plant growth and metabolism in microgravity, innovative hydroponic nutrient delivery systems, and use of highly efficient light emitting diodes for artificial plant illumination.

Aerospace Medicine↗
PubMed1990

Initial evaluation of a human immunoglobulin M monoclonal antibody (HA-1A) in humans.

A human monoclonal antibody (HA-1A) directed against bacterial endotoxin was administered to 15 patients with incurable malignant disease. No adverse effects were noted following single intravenous infusions of 0.05 to 100 mg. Pharmacokinetics were evaluated in nine patients receiving 10 mg (n = 3), 25 mg (n = 3), and 100 mg (n = 3). Seven of these patients had initial peak serum concentrations greater than 80% of predicted values with plasma disappearance curves fitting a one-compartment system and a plasma half-life of 31.5 h (range of 20.3-44.6 h). The peak serum concentrations and area under the curve values were proportional to the dose of HA-1A administered. One patient had a hypercatabolic state with low levels of serum albumin and IgM. He achieved 65% of the predicted value for peak serum concentration of HA-1A with a plasma half-life of 12.3 h. A second patient had detectable serum HA-1A for only 15 min following infusion without an adequate technical or biologic explanation. We were unable to demonstrate antibody to HA-1A in sera from these nine patients either prior to therapy or during 28 days postinfusion using a "double-antigen" radiometric assay. This study suggests that HA-1A human monoclonal antibody administration is well tolerated by patients. Phase I trials will need to be carried out to characterize further the pharmacokinetics and toxicity of HA-1A in patients with gram-negative sepsis.

Adult↗
PubMed1989

Detection of reactive free radicals in fresh coal mine dust and their implication for pulmonary injury.

Freshly ground and aged anthracite and bituminous coal samples were investigated by electron spin resonance (ESR) spectroscopy to detect the presence, concentration and reactivity of free radicals. Freshly ground anthracite coal produced greater concentration of free radicals than the bituminous coal, and the radical reactivity was also greater for the anthracite. The reactivity of the newly produced free radicals in the anthracite dust correlated with the dust's toxicity. Furthermore, similar coal-based free radicals were detected in the lung tissue of autopsied coal miners, suggestive of persistent reactivity by the embedded coal dust leading to the progressive disease process. Results of the studies on the severity of coal workers' pneumoconiosis (CWP) and free radical concentration in lung tissue support this hypothesis.

Coal↗
PubMed1989

Dissociation of cellular proliferation and c-myc expression by buttercup extract.

Buttercup extract (BE), an extract of the buttercup plant (Zanthoriza simplicissima), inhibits RNA and DNA synthesis by HL-60 promyelocytic leukemia cells. Exposure of these cells to 3% BE for 48 hours results in dramatic inhibition of RNA synthesis without loss of cell viability. The effect of BE is partially reversible over 12-24 hours with the level of RNA synthesis returning nearly to control levels during this time period. DNA synthesis is also reversibly inhibited by exposure to BE. Despite the inhibition of RNA synthesis in HL-60 cells, there is no decrease in the level of c-myc mRNA, even at high BE concentrations. The level of gene-specific mRNA for the c-Ha-ras, c-fms, and c-mos genes in these cells also remained constant during exposure to BE. Ribosomal RNA is not degraded during 24 hours of BE treatment in vitro, suggesting that BE does not maintain the relative mRNA level for these genes by selective degradation of other RNA species. The inhibition of RNA and DNA synthesis by BE without a corresponding alteration in the level of expression of the c-myc gene suggests that this agent dissociates c-myc expression and cellular proliferation in these cells.

Cell Division↗