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Biomedical subjects

D A Tobin

Publications and source records attributed to D A Tobin.

15 recordsLinked to original sources

Characterization of the metal receptor sites in Escherichia coli Zur, an ultrasensitive zinc(II) metalloregulatory protein.

The Escherichia coli Zur protein is a Fur homologue that regulates expression of Zn(II) uptake systems. The zinc-loaded form of Zur is proposed to bind DNA and repress transcription of the znuABC genes. Recent in vitro data indicate that the transcriptional activity of Zur is half-maximal when free Zn(II) concentrations are in the sub-femtomolar range, making it the most sensitive Zn(II) metalloregulatory protein reported to date. Previous results indicate that Zur binds at least one zinc; however, little else is known about Zn(II) binding. We have purified E. coli Zur to homogeneity and found that it has two Zn(II) binding sites per monomer with different coordination environments. Using Zn(II) binding assays, ICP-AES analysis, and Zn EXAFS analysis, we show that one zinc is tightly bound in an S(3)(N/O) coordination environment. Both Co(II) and Zn(II) were substituted into the second metal binding site and probed by EXAFS and UV-visible absorption spectroscopy. These studies indicate that Co(II) is bound in an S(N/O)(3) coordination environment with tetrahedral geometry. The Zn(II) EXAFS of Zn(2)Zur, which is consistent with the results for both sites, indicates an average coordination environment of S(2)(N/O)(2), presumably due to one S(N/O)(3) site and one S(3)(N/O) site. These studies reveal the coordination environments that confer such exceptional zinc sensitivity and may provide the foundation for understanding the molecular basis of metal ion selectivity. A comparison of the metal binding sites in Zur with its Fe(II)-sensing homologue Fur provides clues as to why these two proteins with similar structures respond to two very different metal ions.

Amino Acid Sequence↗

Posthysterectomy megavoltage irradiation in the treatment of cervical carcinoma.

Current literature has demonstrated excellent results using postoperative megavoltage irradiation in patients who had simple hysterectomy in the presence of invasive cervical carcinoma. It has recently been suggested that total abdominal hysterectomy followed by postoperative irradiation should be used as a planned treatment for early-stage cervical carcinoma. Thirty-six cases of patients with cervical carcinoma treated with whole-pelvis irradiation following simple hysterectomy at the University of Louisville are reviewed.

Adult↗

Computed tomography and radiotherapy in the treatment of cancer.

Computed tomography (CT) has shown to be of great value in the treatment of cancer with radiation therapy. It is used more and more in the estimation of tumor volume and for treatment planning, with the aid of the computerized treatment unit. At the James Graham Brown Cancer Center, Department of Radiation Oncology, CT has been used routinely for the treatment planning. From October 1, 1981 to June 30, 1982, we performed 180 CT scans for the treatment planning, 380 simple dose calculations, 237 complex treatment plans, and 42 intracavitary dosimetry using the treatment planning unit. This is a review of our experience with some illustrations. Accurate tumor dose can be delivered with reducing the complications with the use of CT and the computerized treatment unit.

Brachytherapy↗

Management of early glottic cancer.

A detailed retrospective analysis of 136 patients with early glottic cancer treated at the University of Louisville, Radiation Center from October, 1953 to December, 1975 was done. Majority of the patients were in the age range of 55 to 74 years. Of them, 89% were male and 85% were Caucasian. The most common histological type was squamous cell carcinoma. The adjusted 5-year survival rate was 84%, with a standard error of 3%. Of these patients, 18% had local failures, and 68% of which were salvaged by surgery. The overall local control rate was 93%. The median time to recurrence was 23 months. There was no case of laryngeal necrosis, and a good function of larynx was achieved in a majority of the patients. Eighteen second cancers were diagnosed in 17 patients during the follow-up. A brief review of the literature is also done in the paper.

Adult↗

Radiation therapy of glottic carcinoma stage I.

A detailed retrospective analysis of 81 patients with a diagnosis of glottic carcinoma stage I (T1N0M0) from 1953 to 1975 has been done. Eighty-eight per cent of the patients were male and 80 per cent of the total number were white. The majority of the patients received a dose of 64 Gy in 6 1/2 weeks. The crude 5-year actuarial survival rate was 69 per cent and the adjusted 5-year actuarial survival rate was 86 per cent. Local recurrence occurred in 12 per cent and of these 80 per cent were cured by surgery. The median time of recurrence was 25.5 months. No case of laryngeal necrosis occurred, and 10 second malignant tumors were diagnosed in the follow-up.

Aged↗

Electron beam therapy in head and neck tumors.

Electron beam therapy with its high energy capabilities appears promising as a therapeutic modality in head and neck neoplasms. Over a 10-year period, 153 cases of head and neck neoplasms involving the alveolar ridge, floor of mouth, buccal mucosa, retromolar trigone, tonsil, parotid, tongue, and pharynx were treated. The pharyngeal group was removed from consideration because of the unsuitability of this lesion for single port therapy. Normal standard doses and time-dose fractions are included as a basis for treatment comparison, and the influence of stage on survival is noted. Survival and tolerance of this form of treatment is comparable to photon therapy and may in fact result in fewer complications.

Electrons↗