ABSTRACT
OBJECTIVE: This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. METHODS: Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. RESULTS: Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. CONCLUSIONS: There was no difference in survival using any treatment modality for African Americans.
Subject(s)
Black or African American , Carcinoma, Squamous Cell/ethnology , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/ethnology , Head and Neck Neoplasms/therapy , Laryngeal Neoplasms/ethnology , Pharyngeal Neoplasms/ethnology , Aged , Carcinoma, Squamous Cell/mortality , Female , Head and Neck Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/therapy , Male , Middle Aged , Pharyngeal Neoplasms/therapy , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and NeckABSTRACT
Complexes of cytochrome c oxidase and cytochrome c (Fe- or Zn-containing) have been prepared by 1-ethyl-3-[3-(dimethylamino)propyl]carbodi-imide (EDC) cross-linking. The site to which the cytochrome c covalently binds has been identified as being the same, or close to, the site occupied by cytochrome c in the electrostatic complex which may be formed between the proteins. Stopped-flow experiments, monitored either at a single wavelength or through a rapid wavelength-scan facility, showed that covalently bound Fe-containing cytochrome c cannot donate electrons to cytochrome a. Free Fe-containing cytochrome c was, however, able to transfer electrons to cytochrome a in covalent complexes containing either Fe- or Zn-containing cytochrome c. Turnover experiments showed that the complexed enzyme remains catalytically competent but with decreased (40-80%) activity. The steady-state levels of reduction of both free cytochrome c and cytochrome a in the covalent complex were higher than found in the control (uncomplexed) enzyme. These results are discussed with reference to the structure of the covalent complex and lead us to conclude that cytochrome a may accept electrons directly from free cytochrome c and that cross-linking impairs the redox properties of the CuA site.
Subject(s)
Cytochrome c Group/metabolism , Electron Transport Complex IV/metabolism , Iron/metabolism , Zinc/metabolism , Animals , Binding Sites , Cattle , Cross-Linking Reagents , Cytochrome c Group/chemistry , Electron Transport , Electrophoresis, Polyacrylamide Gel , KineticsABSTRACT
Dimeric and monomeric forms of mitochondrial cytochrome oxidase (EC 1.9.3.1) have been examined using 1H NMR spectroscopy. Paramagnetically shifted resonances were detected in spectra of the monomeric protein. Studies of this protein in a number of oxidation and ligation states have assigned these resonances to ferrihaem a. The temperature and pH dependence of this new probe of haem a environment is reported.
Subject(s)
Electron Transport Complex IV , Heme , Animals , Cattle , Hydrogen , Magnetic Resonance Spectroscopy/methods , Mitochondria, Heart/enzymology , Protein Conformation , ThermodynamicsABSTRACT
Zinc cytochrome c forms tight 1:1 complexes with a variety of derivatives of cytochrome c oxidase. On complex-formation the fluorescence of zinc cytochrome c is diminished. Titrations of zinc cytochrome c with cytochrome c oxidase, followed through the fluorescence emission of the former, have yielded both binding constants (K approximately 7 x 10(6) M-1 for the fully oxidized and 2 x 10(7) M-1 for the fully reduced enzyme) and distance information. Comparison of steady-state measurements obtained by absorbance and fluorescence spectroscopy in the presence and in the absence of cyanide show that it is the reduction of cytochrome a and/or CuA that triggers a conformational change: this increases the zinc cytochrome c to acceptor (most probably cytochrome a itself) distance by some 0.5 nm. Ligand binding to the fully oxidized or fully reduced enzyme leaves the extent of fluorescence quenching unchanged, whereas binding of cyanide to the half-reduced enzyme (a2+CuA+CuB2+-CN(-)-a3(3+)) enhances fluorescence emission relative to that for the fully reduced enzyme, implying further relative movement of donor and acceptor.
