EXAFS study of local atomic order about iodine in thyroxine, rat, human and sheep thyroids.

Radioactive (125)I emits short-range Auger electrons and represents a human health risk when incorporated in thyroglobulin of the thyroid. Quantitative evaluation of this risk can only be realised if local atomic order about iodine in the thyroid is known. Here, extended X-ray absorption fine structure (EXAFS) has been used to probe the local structure about iodine in pure thyroid hormone, thyroxine. These data are consistent with a model where iodine is bound to a single iodinated carbon ring linked to an oxygen atom, similar to a previously published model for monoiodotyrosine, a major iodinated residue in thyroglobulin. Several structural models for the local environment of iodine from rat, human and sheep have been tested and these data are found to be compatible with a slightly modified environment with respect to that found for thyroxine. The best-fit models include the following three components: (i) iodine covalently bonded to a tyrosine ring, as found for thyroxine; (ii) iodine bonded quasi-covalently to a carbonyl ligand in partially filled (50%) sites; (iii) partially filled sites (50-40%) of carbonyl ligands, with oxygen at van der Waals distances from iodine. Advantages of using Fourier-filtered EXAFS for complex crystal structures are discussed.

Accelerated hyperfractionation in patients with non-small cell bronchogenic cancers as a cost-effective and user- and patient-friendly schedule.

We developed an accelerated hyperfractionation schedule with acceptable effect and toxicity in non-small cell bronchogenic carcinomas. An evolutionary institutional pilot was initiated in March 1995 as a modification of Radiation Therapy Oncology Group (RTOG) 9205, thrice-daily fractionation schedule. Twenty-nine patients with bronchogenic and 7 with head and neck cancers had treatment initiated and completed. A dose of 1.2 Gy was delivered to a mediastinal plus tumor field concomitantly with synchronous boost of 0.6 Gy to a limited volume of gross tumor (twice daily for 21 treatments days in 4 weeks) with a total dose being 75.60 Gy to the primary gross tumor and 50.4 Gy to the elective volume. The bronchogenic cancers were stages IB (medically unresectable, n = 3), IIB (n = 4), IIIA (n = 4), or IIIB (n = 18). Eleven patients had squamous cell cancers, 13 adenocarcinomas, 1 large cell, and 2 carcinomas not specified. With 12 months median follow-up, tolerance has been excellent without any patient complaining of at least Oncology Nursing Society (ONS) grade 3 esophagitis; treatment interruptions occurred in only one patient after 8 days. Weight loss occurred in 12 patients, averaging 4.8% for these patients and 2% overall. Seven patients had a complete response and 20 a partial response. Median survival was 12 months, 1-year survival 58%, 2-year 21%, and 3-year 18%. Seven patients with bronchogenic cancer are still alive. Seven head and neck cancer patients were treated, in which five had base of tongue tumors stage T2 to 4, N0 to N1. Pharyngitis and mucositis were problematic in at least four patients. The outcomes are comparable with other RTOG experience. Hyperfractionated synchronous concomitant boost of total tumor dose to 75.6 Gy in 4 weeks for bronchogenic patients was well tolerated and acceptable to physicians and patients.

Determination of atomic local order in thyroid hormones by extended x-ray absorption fine structure [EXAFS] for radiation dose estimates.

Dosimetry from 125I emitting Auger electrons in the follicles of the thyroid will improve when their complete interaction with the molecular structure about the Auger emitting atoms is known to Angstrom distances. Extended x-ray absorption fine structure (EXAFS) can provide this information. EXAFS experiments gave intermolecular and intramolecular distance for pure solid L-thyroxine (T4) (C15H11I4NO4) using a model based on crystalline T4 hydrochloride monohydrate (C15H11I4NO4HCl.H2O). For a solution of L-thyroxine the structure consists of the intramolecular distances found for T4 and an additional shell of four carbon atoms distances of 2.01 A. Atomic density functions from Fourier transformed EXAFS measurements are suitable for estimating very short range interactions of Auger electrons in thyroid thyroglobulin over a radial distance of 7.71 A. Examination of density functions provided a plausible argument for the difference in biological effect between 131I and 125I in the thyroid.

An iron-carboxylate bond links the heme units of malaria pigment.

The intraerythrocytic malaria parasite uses hemoglobin as a major nutrient source. Digestion of hemoglobin releases heme, which the parasite converts into an insoluble microcrystalline material called hemozoin or malaria pigment. We have purified hemozoin from the human malaria organism Plasmodium falciparum and have used infrared spectroscopy, x-ray absorption spectroscopy, and chemical synthesis to determine its structure. The molecule consists of an unusual polymer of hemes linked between the central ferric ion of one heme and a carboxylate side-group oxygen of another. The hemes are sequestered via this linkage into an insoluble product, providing a unique way for the malaria parasite to avoid the toxicity associated with soluble heme.

Vitamin B12 quality control trials.

The results of regional quality control trials of vitamin B12 assays are reported. Consideration is given to the materials suitable for such trials. The technical and clinical performance of the participants are assessed together with the methods used. The introduction of a target coefficient of variation has produced better identification of good and bad performance and the use of a reference serum has permitted comparison of assays of different methods. The linearity of most methods is suspect and indicates the need for reference sera of varying concentration. Introduction of kits has not generally improved precision and variation between laboratories shows the use of kits can be improved.