Search PubMed⌕ Search

Biomedical subjects

J Wortman

Publications and source records attributed to J Wortman.

At least 19 recordsLinked to original sources

A preliminary analysis of the process of protein secretion and the diversity of putative secreted hydrolases encoded in Aspergillus fumigatus: insights from the genome.

The genome sequence of Aspergillus fumigatus has enabled the annotation of genes likely to encode secreted enzymes that may be important in underpinning the natural lifestyle of the fungus and its pathogenicity. We summarize the data from the genome sequence relevant to both the process of protein secretion and the predicted hydrolase enzymes secreted by A. fumigatus.

Animals↗

The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus.

The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. The azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site that alter drug-target interactions and those that decrease net azole accumulation. The reduced intracellular accumulation has also been correlated with overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About 20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There are several duplicated genes in this pathway. Interestingly, erg3 and erg11 showed two copies in A. fumigatus. In general, Aspergillus spp. have proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae, S. pombe, and Neurospora crassa. The drug H+ (12 and 14 spanners) sub-families are also proportionally greater than in the other species. Although the numbers of ABC transporter encoding genes are comparable, again the Aspergillus spp. have more ABC transporters related to multidrug permease than the other fungal species.

ATP-Binding Cassette Transporters↗

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Animals↗

The Genome Sequence DataBase: towards an integrated functional genomics resource.

During 1998 the primary focus of the Genome Sequence DataBase (GSDB; http://www.ncgr.org/gsdb ) located at the National Center for Genome Resources (NCGR) has been to improve data quality, improve data collections, and provide new methods and tools to access and analyze data. Data quality has been improved by extensive curation of certain data fields necessary for maintaining data collections and for using certain tools. Data quality has also been increased by improvements to the suite of programs that import data from the International Nucleotide Sequence Database Collaboration (IC). The Sequence Tag Alignment and Consensus Knowledgebase (STACK), a database of human expressed gene sequences developed by the South African National Bioinformatics Institute (SANBI), became available within the last year, allowing public access to this valuable resource of expressed sequences. Data access was improved by the addition of the Sequence Viewer, a platform-independent graphical viewer for GSDB sequence data. This tool has also been integrated with other searching and data retrieval tools. A BLAST homology search service was also made available, allowing researchers to search all of the data, including the unique data, that are available from GSDB. These improvements are designed to make GSDB more accessible to users, extend the rich searching capability already present in GSDB, and to facilitate the transition to an integrated system containing many different types of biological data.

Animals↗

Contrast enhancement of spontaneous animal CNS tumors with gadolinium DTPA: a correlation of MRI with x-ray CT.

A visual comparison was made between both pre-contrast and post-contrast x-ray computerized tomographic images (X-CT) and magnetic resonance tomographic images (MRI) of spontaneous CNS tumors in three animals. The contrast agents, HypaqueR-76 (X-CT) and Gadolinium DTPA (MRI), were administered as an intravenous bolus injection. The parameters for comparison of pre- and post-contrast features included: lesion discrimination, demarcation, and intensity and pattern of enhancement. Necropsy specimens were included to correlate the anatomic fidelity of scan appearances for each modality and to establish a final diagnosis. There was good visual correlation of the lesion site with both X-CT and MRI. The intensity of lesion enhancement with the contrast reagents was similar for each modality but there were subtle differences in the pattern of enhancement. Overall, MRI in conjunction with the contrast agent Gadolinium DTPA, was as good or better at delineating the presence and extent of CNS tumors than contrast enhanced X-CT. Contrast agents may be necessary to provide increased lesion detectability and delineation when imaging with magnetic resonance.

Adenoma↗

Sex steroid receptor analysis in human melanoma.

Melanomas from 20 patients were evaluated for estrogen and progesterone receptors. No restriction as to patient's age, sex, race, or menstrual status was made. Fifteen of the tumors were melanin producing. Of the 20 tumors examined, seven contained more than 3 fm/mg protein of specifically inhibitable estrogen binding. None of the tumors reported here demonstrated either a 4S or 8S binding protein as shown by sucrose density gradient analysis. All tumors in which estradiol binding was observed were melanin producing, whereas none of the amelanotic melanomas (five tumors) bound this steroid. Purified tyrosinase appeared to mimic the estrogen binding detected in melanoma cytosols, as demonstrated with the dextran-coated charcoal technique. Although the binding of estradiol to tyrosinase was inhibited by DOPA, the binding of estradiol to estrogen receptor preparations was not. These studies represent an extensive of previous studies of sex steroid binding in melanomas and suggest that gradient analysis and DOPA inhibition studies should be included in the evaluation of the estrogen binding phenomenon in human melanoma.

Adult↗

Malignant effusions in recurrent breast cancer: steroid hormone receptor analysis of effusion fluid derived cells.

Estrogen and progesterone receptor determination in breast cancer is of significance in determining a patient's potential response to hormonal manipulation. One practical limitation to this procedure has been availability of material for receptor assay. We describe 12 patients in whom quantitative estrogen and/or progesterone receptor analysis was accomplished utilizing tumor cells obtained from malignant effusions. The ability to obtain quantitative steroid receptor data on material derived from malignant effusions provides an effective source for this important biochemical parameter in patients in whom no other tumor tissue is available for study.

Adult↗

A scleral buckle pressure gauge for continuous monitoring of intraocular pressure.

An implantable variable resistance pressure gauge has been constructed from a conductive elastomere in the form of a scleral buckle which is suitable for recording intraocular pressure in vivo continuously over an indefinite period of time. The similarity of the pressure transducer to the standard scleral buckles used to reduce retinal detachments suggests that it will be tolerated over a period of years without significant effect on intraocular pressure. The electrical output from these pressure gauges appears to be both well defined and of sufficient magnitude to operate a valve to control intraocular pressure.

Animals↗

Chloroma (granulocytic sarcoma) without evidence of leukemia: facilitated light microscopic diagnosis.

Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lacks the characteristic green color. The diagnostic difficulty may be further compounded when the granulocytic sarcoma develops before there is peripheral blood or bone marrow evidence of leukemia. Previous criteria for the diagnosis of chloroma have been ambiguous because of the capricious nature of the hydroperoxidase activity and the lack of definitive histochemical criteria. In this case, a combination of Sudan black B and myeloperoxidase histochemical staining and ultrastructural evaluation was applied. The light microscopic histochemical studies suggested the presence of Phi bodies and rods both in the formalin-fixed tumor and in the cells derived from the subsequent pleural effusion; this was confirmed by electron microscopy, which demonstrated the peridicity of the crystalline rod substructure. These observations show that light microscopic histochemical studies can facilitate the diagnosis of granulocytic sarcoma or chloroma in the absence of peripheral blood or bone marrow manifestations of leukemia.

Adult↗

Cold agglutinin autoimmune hemolytic anemia in nonhematologic malignancies.

Four patients with nonhematologic malignancies had the simultaneous finding of hemolytic anemia due to high-titer cold agglutinins. In each patient, the cold agglutinin had "anti-I" specificity and was of the IgM kappa immunoglobulin class. Although patients with hematologic malignancies not uncommonly have cold agglutinins, the association between these antibodies and nonhematologic malignancies is unusual.

Adolescent↗