Protein Information Resource: a community resource for expert annotation of protein data.

The Protein Information Resource, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the most comprehensive and expertly annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database. To provide timely and high quality annotation and promote database interoperability, the PIR-International employs rule-based and classification-driven procedures based on controlled vocabulary and standard nomenclature and includes status tags to distinguish experimentally determined from predicted protein features. The database contains about 200,000 non-redundant protein sequences, which are classified into families and superfamilies and their domains and motifs identified. Entries are extensively cross-referenced to other sequence, classification, genome, structure and activity databases. The PIR web site features search engines that use sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. The PIR-Inter-national databases and search tools are accessible on the PIR web site at http://pir.georgetown.edu/ and at the MIPS web site at http://www.mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.

iProClass: an integrated, comprehensive and annotated protein classification database.

The iProClass database is an integrated resource that provides comprehensive family relationships and structural and functional features of proteins, with rich links to various databases. It is extended from ProClass, a protein family database that integrates PIR superfamilies and PROSITE motifs. The iProClass currently consists of more than 200,000 non-redundant PIR and SWISS-PROT proteins organized with more than 28,000 superfamilies, 2600 domains, 1300 motifs, 280 post-translational modification sites and links to more than 30 databases of protein families, structures, functions, genes, genomes, literature and taxonomy. Protein and family summary reports provide rich annotations, including membership information with length, taxonomy and keyword statistics, full family relationships, comprehensive enzyme and PDB cross-references and graphical feature display. The database facilitates classification-driven annotation for protein sequence databases and complete genomes, and supports structural and functional genomic research. The iProClass is implemented in Oracle 8i object-relational system and available for sequence search and report retrieval at http://pir.georgetown.edu/iproclass/.

PIR: a new resource for bioinformatics.

UNLABELLED: The Protein Information Resource (PIR) has greatly expanded its Web site and developed a set of interactive search and analysis tools to facilitate the analysis, annotation, and functional identification of proteins. New search engines have been implemented to combine sequence similarity search results with database annotation information. The new PIR search systems have proved very useful in providing enriched functional annotation of protein sequences, determining protein superfamily-domain relationships, and detecting annotation errors in genomic database archives. AVAILABILITY: http://pir.georgetown.edu/. CONTACT: mcgarvey@nbrf.georgetown.edu

Registration of planar emission images with reprojected CT data.

UNLABELLED: Planar gamma-camera imaging is still widely used clinically. Alignment of planar images with images from tomographic modalities, such as CT, or with other planar images would be desirable. Here, we present and evaluate a method for such an alignment, using planar transmission images acquired with the emission images and reprojection of the 3-dimensional CT data. This method permits determination of which CT slice corresponds to a particular row of pixels in the gamma-camera image and which column of pixels in that CT slice corresponds to a particular pixel in the emission data. METHODS: A method based on maximization of the correlation coefficient, previously used for 3-dimensional datasets, was modified to permit 2-dimensional registrations. Planar transmission measurements were obtained using a collimated 99mTc flood source in conjunction with planar emission studies. The CT data were first reprojected to permit the 2-dimensional registration. The registration method was evaluated for its accuracy and reproducibility. RESULTS: For phantom data, the registration errors were -0.1 +/- 1.0 mm for x-translations, 1.0 +/- 1.3 mm for y-translations, and -0.2 +/- 0.3 degrees for rotations. For patient data, the errors were 1.6 +/- 0.8 mm for x-translations, 1.3 +/- 1.0 mm for y-translations, and 0.5 +/- 0.5 degrees for rotations. An examination of the need for rescaling of the attenuation data (to compensate for the different photon energies used in the respective attenuation measurements) showed no significant impact on registration error. When 5 different regions of interest were used for the correlation coefficient calculation, the mean errors attributable to region-of-interest choice alone were 1.0 mm for x-translations, 2.0 mm for y-translations, and 1.2 degrees for rotations. CONCLUSION: In almost all instances, translational registration errors were kept to subpixel levels (pixel size, 2.6 mm) and rotational errors to 1 degrees or less. The 1 exception was in the easily avoidable case of "pitch" rotations of the patient of 2 degrees or more. The modified registration method provides a simple yet reliable way to provide cross-modality evaluation of planar emission data.

Recombinant human thyrotropin for the diagnosis and treatment of a highly functional metastatic struma ovarii.

The optimal treatment of metastatic thyroid cancer that produces high amounts of thyroid hormone has not been well defined. A 46-yr-old woman presented with a follicular thyroid carcinoma arising from a struma ovarii with hepatic metastases. After the removal of both the struma and the thyroid gland, the liver metastases showed evidence of a high degree of hormonogenesis. Brain, chest, abdomen, and bone imaging was negative for additional metastases. Because iodine uptake by most thyroid carcinomas is quite low in the absence of high levels of ambient TSH, we used recombinant human TSH (rhTSH) (Thyrogen) to achieve a concentration of 131I activity in the tumor high enough for a significant cytotoxic effect. After rhTSH administration (0.9 mg im daily for 2 consecutive days), a 131I diagnostic whole body scan confirmed the existence of 17 discrete hepatic foci of 131I uptake. To calculate the amount of 131I that would deliver an absorbed radiation dose that would be optimally cytotoxic to the metastases (>8000 rad/lesion) and not to the normal liver, we performed lesion dosimetry. Analysis of dosimetric data showed that 15 of 17 lesions would receive an adequate radiation dose following the administration of 65 mCi of 131I. Additionally, we performed whole body dosimetry to assure that this dose would not cause bone marrow toxicity. The patient was reevaluated 6 months after therapy; the liver metastases showed significant, but partial, response. In conclusion, we used the combination of rhTSH with lesional and whole body dosimetry for the treatment of highly functional metastases from follicular thyroid carcinoma arising within a struma ovarii. This strategy can be applied to determine a safe and effective dose of 131I for the treatment of any thyroid cancer metastases that produce enough TH to preclude stimulation of endogenous pituitary TSH secretion.

The protein information resource (PIR).

The Protein Information Resource (PIR) produces the largest, most comprehensive, annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Sequence Database (JIPID). The expanded PIR WWW site allows sequence similarity and text searching of the Protein Sequence Database and auxiliary databases. Several new web-based search engines combine searches of sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. New capabilities for searching the PIR sequence databases include annotation-sorted search, domain search, combined global and domain search, and interactive text searches. The PIR-International databases and search tools are accessible on the PIR WWW site at http://pir.georgetown.edu and at the MIPS WWW site at http://www. mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.

PIR-ALN: a database of protein sequence alignments.

MOTIVATION: The Protein Information Resource (PIR) maintains a database of annotated and curated alignments in order to visually represent interrelationships among sequences in the PIR-International Protein Sequence Database, to spread and standardize protein names, features and keywords among members of a family or superfamily, and to aid us in classifying sequences, in identifying conserved regions, and in defining new homology domains. RESULTS: Release 22.0, (December 1998), of the PIR-ALN database contains a total of 3806 alignments, including 1303 superfamily, 2131 family and 372 homology domain alignments. This is an appropriate dataset to develop and extract patterns, test profiles, train neural networks or build Hidden Markov Models (HMMs). These alignments can be used to standardize and spread annotation to newer members by homology, as well as to understand the modular architecture of multidomain proteins. PIR-ALN includes 529 alignments that can be used to develop patterns not represented in PROSITE, Blocks, PRINTS and Pfam databases. The ATLAS information retrieval system can be used to browse and query the PIR-ALN alignments. AVAILABILITY: PIR-ALN is currently being distributed as a single ASCII text file along with the title, member, species, superfamily and keyword indexes. The quarterly and weekly updates can be accessed via the WWW at pir.georgetown.edu. The quarterly updates can also be obtained by anonymous FTP from the PIR FTP site at NBRF.Georgetown.edu, directory [ANONYMOUS.PIR.ALIGNMENT].

The PIR-International Protein Sequence Database.

The Protein Information Resource (PIR; http://www-nbrf.georgetown. edu/pir/) supports research on molecular evolution, functional genomics, and computational biology by maintaining a comprehensive, non-redundant, well-organized and freely available protein sequence database. Since 1988 the database has been maintained collaboratively by PIR-International, an international association of data collection centers cooperating to develop this resource during a period of explosive growth in new sequence data and new computer technologies. The PIR Protein Sequence Database entries are classified into superfamilies, families and homology domains, for which sequence alignments are available. Full-scale family classification supports comparative genomics research, aids sequence annotation, assists database organization and improves database integrity. The PIR WWW server supports direct on-line sequence similarity searches, information retrieval, and knowledge discovery by providing the Protein Sequence Database and other supplementary databases. Sequence entries are extensively cross-referenced and hypertext-linked to major nucleic acid, literature, genome, structure, sequence alignment and family databases. The weekly release of the Protein Sequence Database can be accessed through the PIR Web site. The quarterly release of the database is freely available from our anonymous FTP server and is also available on CD-ROM with the accompanying ATLAS database search program.

Database of protein sequence alignments: PIR-ALN.

The Protein Information Resource (PIR) has been maintaining a database of curated protein sequence alignments since 1991. The collection includes superfamily, family and homology domain alignments. CLUSTAL V/W is used to generate multiple sequence alignments and ALNED, an interactive alignment editor, is used to check and correct them. The database has helped in classifying sequences, in defining new homology domains, and in spreading and standardizing protein names, features and keywords among members of a family or superfamily. The ATLAS information retrieval system can be used to browse and query the PIR-ALN alignments. The quarterly and weekly updates can be accessed via the WWW at http://www-nbrf. georgetown.edu/pir/

The PIR-International Protein Sequence Database.

From its origin the Protein Information Resource (http://www-nbrf. georgetown.edu/pir/) has supported research on evolution and computational biology by designing and compiling a comprehensive, quality controlled, and well-organized protein sequence database. The database has been produced and updated on a regular schedule since 1984. Since 1988 it has been maintained collaboratively by the PIR-International, an association of data collection centers engaged in international cooperation for the development of this research resource during a period of explosive acquisition of new data. As of June 1997, essentially all sequence entries have been classified into families, allowing the efficient application of methods to propagate and standardize annotation among related sequences. The databases are available through the Internet by the World-Wide Web and FTP, or on CD-ROM and magnetic media.

Analysis and organization of protein sequence data: a retrospective spanning four decades.

Protein sequence data are as useful and valuable today as was envisioned by pioneering sequencers and by the organizers of the first sequence database. Sequence analysis was first the province of specialists who developed search, comparison, and tree-building methods. Microcomputers, communication satellites, and the Internet have made these methods accessible to any scientist. The rapid increase in the data has driven a succession of changes in how databases are compiled, distributed, and accessed. Large public databases have become international collaborations. Although they need to develop still more efficient ways to accumulate, organize, annotate, and standardize huge amounts of data, inadequate support is available for such efforts. Thus there will be greater reliance on direct input from the scientific community. The World Wide Web is essential but not sufficient for integrated access to related databases.

Glycophorin A as a biological dosimeter for radiation dose to the bone marrow from iodine-131.

The frequency of peripheral blood erythrocyte variants exhibiting allelic loss of glycophorin A (N/M antigen) has been used previously as a biological dosimeter to assess somatic mutations in bone marrow cells from external whole-body irradiation. The aim of the present study was to determine whether this marker could be used as a measure of bone marrow genotoxicity induced by 131I in the treatment of thyroid cancer. Flow cytometry of immunolabeled erythrocytes was performed to enumerate glycophorin A variants before and after eight therapy doses of 131I administered to five patients with differentiated thyroid carcinoma. Bone marrow radiation exposure from each dose was calculated from the integrated retention of 131I in the whole body and in the blood. In addition, the accumulated dose to the bone marrow received from earlier 131I therapy was calculated for each patient. Regression analysis was performed on the frequency of two glycophorin A variant cell types (N/O and N/N) as a function of accumulated dose to the bone marrow. Frequency of N/O variant cells showed a significant dose-related increase with a slope of 10.9 x 10(-6) per sievert. This dose effect is about one-half that previously observed after whole-body external irradiation at high dose rate. This decreased response could be explained by the low dose rate of the radiation to the bone marrow from 131I.

The Protein Information Resource (PIR) and the PIR-International Protein Sequence Database.

From its origin, the PIR has aspired to support research in computational biology and genomics through the compilation of a comprehensive, quality controlled and well-organized protein sequence information resource. The resource originated with the pioneering work of the late Margaret O. Dayhoff in the early 1960s. Since 1988, the Protein Sequence Database has been maintained collaboratively by PIR-International, an association of macromolecular sequence data collection centers dedicated to fostering international cooperation as an essential element in the development of scientific databases. The work of the resource is widely distributed and is available on the World Wide Web, via FTP, E-mail server, CD-ROM and magnetic media. It is widely redistributed and incorporated into many other protein sequence data compilations including SWISS-PROT and theEntrezsystem of the NCBI.

Implications of dual-energy-window (DEW) scatter correction inaccuracies for 111In quantitative geometric mean imaging.

There is increasing clinical interest in the use of quantitative imaging for radiopharmaceuticals labelled with 111In. Dual-energy-window (DEW) scatter correction is a frequently used component of planar geometric mean quantitative imaging, but it is known that the scatter multiplier k suffers from significant dependence on the characteristics of the scatter medium. Phantom studies with a variety of source geometries were carried out to determine the clinical impact of this dependence on the quantitative accuracy of tumour imaging carried out in conjunction with attenuation correction. Spheres of various sizes (5-20 ml volumes) containing approximately 3.7 MBq (100 microCi) 111In were imaged at a variety of depths (4.8-10.5 cm) within an elliptical water-filled phantom, as well as in air. Geometric mean emission images were acquired using a 20% photopeak window at 247 keV and a 10% scatter window at 205 keV. These emission images were corrected for attenuation using measured 99Tcm transmission data that were scaled to 111In photon energies. Scatter correction was performed in two ways: (1) using the standard DEW method and (2) using a modified DEW method that takes into account benign scatter in the detector crystal. Errors in the activity estimates ranged from -4% to +3% for method 1 in water, and -5% to +3% for method 2 in water. In air, method 1 ranged from -13% to -5%, and method 2 ranged from -10% to -1%. Method 1 was found to yield an accuracy equivalent to that of method 2, except in conditions of very low patient scatter, when the modified method behaved significantly better. We conclude that in a variety of realistic geometries, variations in scatter fraction as determined by the DEW scatter correction method combined with appropriate attenuation correction need not inhibit accurate absolute quantitation of spherical 'tumours' labelled with 111In when using planar imaging.

Left ventricular ejection fraction: comparison of results from planar and SPECT gated blood-pool studies.

UNLABELLED: Global ejection fraction (EF) from planar gated blood-pool (GBP) imaging is a widely accepted measure of cardiac function. It has been suggested that planar GBP could be replaced by SPECT. In this article, we compare counts-based global EF measured from SPECT and planar images and investigate reasons for discrepancies between the two. METHODS: Twenty-three subjects were imaged with both planar and SPECT GBP. SPECT short-axis slices were projected to create reprojected images. Reprojected SPECT (rSPECT) images were created in both the true long-axis view and also in a view typical of planar studies (found to be 60 degrees from the true long-axis). Thus, angle of view effects on global EF could be investigated. In addition, we studied the effects of background and attenuation. RESULTS: Long-axis rSPECT EF correlated well with planar EF (r = 0.89) but EF values were significantly higher for rSPECT than for planar (slope = 1.4, intercept = -8 EF units; p < 0.001). We found that background correction may not be necessary with rSPECT, but neither background nor attenuation explained the observed discrepancy between rSPECT and planar EFs. This discrepancy was found to be caused by atrial overlap in the planar image and disappeared when the SPECT slices were reprojected at the same angle of view as the planar images. CONCLUSION: Global EF can be easily measured from rSPECT GBP images. Long-axis rSPECT EFs are, however, greater than planar EFs by a factor of 1.4 because atrial overlap causes a significant drop in planar EF in planar images. These results suggest that (long-axis) rSPECT EFs may be more accurate than planar EFs.

The PIR-International Protein Sequence Database.

From its origin the Protein Sequence Database has been designed to support research and has focused on comprehensive coverage, quality control and organization of the data in accordance with biological principles. Since 1988 the database has been maintained collaboratively within the framework of PIR-International, an association of macromolecular sequence data collection centers dedicated to fostering international cooperation as an essential element in the development of scientific databases. The database is widely distributed and is available on the World Wide Web, via ftp, email server, on CD-ROM and magnetic media. It is widely redistributed and incorporated into many other protein sequence data compilations, including SWISS-PROT and the Entrez system of the NCBI.

Continuous intraoperative external monitoring of perfusate leak using iodine-131 human serum albumin during isolated perfusion of the liver and limbs.

Regional isolated perfusion using tumor necrosis factor (TNF) shows significant promise for treatment of cancer which is limited to limbs or organs. The high toxicity of TNF requires very sensitive real time monitoring of leakage in order to avoid serious patient complications. Human serum albumin labeled with iodine-131 is used with an externally mounted and collimated NaI(Tl) detector to track the leakage of blood from the isolated perfusion blood circuit into the general systemic vascular space. Blood activity levels measured using the monitor demonstrated a very good correlation with blood serum samples taken concurrently with external monitoring. External monitoring can reduce the risks of perfusion leakage intraoperatively with the precision necessary to safely perform isolated perfusion using TNF.