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Biomedical subjects

J Peterson

Publications and source records attributed to J Peterson.

At least 73 records · Page 4Linked to original sources

The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.

Tcf/Lef transcription factors mediate signalling from Wingless/Wnt proteins by recruiting Armadillo/beta-catenin as a transcriptional co-activator. However, studies of Drosophila, Xenopus and Caenorhabditis elegans have indicated that Tcf factors may also be transcriptional repressors. Here we show that Tcf factors physically interact with members of the Groucho family of transcriptional repressors. In transient transfection assays, the Xenopus Groucho homologue XGrg-4 inhibited activation of transcription of synthetic Tcf reporter genes. In contrast, the naturally truncated Groucho-family member XGrg-5 enhanced transcriptional activation. Injection of XGrg-4 into Xenopus embryos repressed transcription of Siamois and Xnr-3, endogenous targets of beta-catenin-Tcf. Dorsal injection of XGrg-4 had a ventralizing effect on Xenopus embryos. Secondary-axis formation induced by a dominant-positive Armadillo-Tcf fusion protein was inhibited by XGrg-4 and enhanced by XGrg-5. These data indicate that expression of Tcf target genes is regulated by a balance between Armadillo and Groucho.

Animals↗

Complete genome sequence of Treponema pallidum, the syphilis spirochete.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Bacterial Proteins↗

Spectral and cyanide binding properties of the cytochrome aa3 (600 nm) complex from Bacillus subtilis.

The cytochrome aa3 (600 nm) complex, or menaquinol oxidase, from Bacillus subtilis is a member of the cytochrome oxidase superfamily of respiratory membrane protein complexes. We have characterized some spectral properties of this enzyme and its reaction with cyanide. The magnetic circular dichroism (MCD) spectrum of the oxidized enzyme has a single band at 1560 nm in the near-infrared region assigned to bis-histidine-ligated, low-spin ferricytochrome a. The other heme, cytochrome a3, is presumably high-spin in the oxidized enzyme, as isolated. The absence of a trough in the MCD spectrum at 790 nm, observed previously with mammalian cytochrome c oxidase and assigned to CuA (Greenwood et al., Biochem. J. 215, 303-316, 1983), is consistent with the absence of this center from the menaquinol oxidase. When the heme ligand cyanide is added to oxidized menaquinol oxidase, a new MCD band appears at 2010 nm, while the band at 1560 nm is unperturbed. The new band is assigned to low-spin ferricytochrome a3 bound with cyanide. The long-wavelength position of this cyanide-induced band is proposed to arise from the close interaction of cytochrome a3 with the copper atom, CuB. The kinetics of cyanide binding to oxidized cytochrome aa3(600 nm) reveal a spectrally simple, yet kinetically complex process. The reaction is biphasic with second-order rate constants of 45 and 0.61 M-1s-1 at 1 mM KCN, with each phase constituting about 50% of the overall reaction. When the enzyme is subjected to a cycle of anaerobic reduction and air oxidation, the subsequent reaction with cyanide occurs in a single phase at the faster rate. This behavior is ascribed to different conformations of the binuclear center exhibiting different reactivities with cyanide, and is in keeping with that previously established for the structurally more complex mitochondrial cytochrome c oxidase. However, the electronic spectral characteristics of some of the species involved in these reactions are different in the present bacterial case from those of reported eukaryotic systems.

Bacillus subtilis↗

Axonal transection in the lesions of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis. METHODS: Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions. RESULTS: Transected axons were a consistent feature of the lesions of multiple sclerosis, and their frequency was related to the degree of inflammation within the lesion. The number of transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains. CONCLUSIONS: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.

Adolescent↗

Clearance of murine leukaemia virus from monoclonal antibody solution by a hydrophilic PVDF microporous membrane filter.

Continuous cell lines (used in the manufacture of monoclonal antibodies and other therapeutic proteins) may harbour retroviral particles; nevertheless, they are deemed acceptable if the production system is validated for clearance of these contaminants. As part of a campaign to evaluate and validate appropriate virus removal methodologies for monoclonal immunoglobulin G (IgG) products, studies were undertaken with a hydrophilic polyvinylidene fluoride (PVDF) microporous membrane-the Ultipor(R) VF grade DV50 virus removal membrane. Testing conducted with murine leukaemia virus, a specific model virus used in viral validation studies to document removal of retroviruses, demonstrated a greater that 7 log clearance by the Ultipor(R) VR grade DV50 membrane. Filterability testing established the feasibility of positioning the filter at either of two different stages during manufacture. The results presented in this study demonstrate that membrane filtration through the Ultipor VF grade DV50 virus removal filter can constitute part of the purification regimen to effect removal of endogenous retrovirus-like contaminants from monoclonal IgG products.

Animals↗

Taxonomic classification helps identify flavonoid-containing foods on a semiquantitative food frequency questionnaire.

We describe foods on the National Cancer Institute (NCI) semiquantitative food frequency questionnaire with respect to their botanical taxonomic classification and the likely presence of flavonoids. Foods listed in the NCI questionnaire were classified for potential flavonoid content using information from Linnaean taxonomic classification and processing techniques known to modify flavonoid content. The outcome measure was flavonoid presence in foods as evidenced in the food composition analytical literature. We then verified the presence of 6 classes of flavonoids in these foods by searching the chemical analytical literature (represented by Food Science and Technology Abstracts Service from January 1969 to June 1996). One hundred ninety foods were mentioned on the NCI questionnaire; after duplications were removed, 153 foods remained. Data obtained from literature searches indicated that 54 foods (35%) contained flavonoids. An additional 19 recipe foods (12%) had flavonoid-containing components or ingredients. Thirty-nine foods (25%) had flavonoids that had been reduced or removed during milling and other processing. Seven foods (5%) were stripped and judged to have no flavonoids. Thirty-four foods (22%), for example, dairy, meat, and sugar, were completely devoid of flavonoids. When food composition data are unavailable, botanical taxonomic classifications may be helpful in ascertaining the likely presence of flavonoids in foods. However, quantitative estimates are likely to be imprecise.

Databases, Factual↗

Differential expression of the HMG box transcription factors XTcf-3 and XLef-1 during early xenopus development.

The recent discovery that the HMG box transcription factor XTCF-3 is involved in early axis specification in Xenopus laevis (Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J. Godsave, S., Korinek, V., Roose, J., Destree, O., Clevers, H., 1996. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell 86, 391-399) led us to search for other members of the TCF/LEF family in this species. A newly identified HMG box factor was cloned with highest homology to human LEF-1, called XLEF-1. Unlike XTcf-3, XLef-1 is not expressed maternally, but its transcripts become detectable directly after the mid blastula transition (MBT). At later stages, both genes are expressed in the central nervous system (CNS), eyes, otic vesicles, head mesenchyme, neural crest and derivatives, branchial arches, developing heart, tailbud and limb buds. The expression pattern of Lef-1 during later stages of development is evolutionarily conserved.

Amino Acid Sequence↗

The Bridge to Health Project: a collaborative model for assessing the health of a community.

The Bridge to Health Project, a collaborative effort of 70 health related organizations, was designed to collect population-based health status data about approximately a half million residents in a primarily rural region in northeast Minnesota and northwest Wisconsin. Funding and staff support were provided by a regional medical center. The importance of sound survey methodology, role clarification, adequate staff support, and a well organized process to foster collaboration have applicability to other regions considering a collaborative process of health status assessment.

Academic Medical Centers↗

Systematisation of anthropometric data of 17-year-old schoolgirls from Tartu, Estonia.

An anthropometric study of 358 healthy schoolgirls at the age from 17 to 18 years from all secondary schools of Tartu was carried out. 42 single body measurements and 11 skinfolds were measured, and 45 indices and body composition characteristics were derived from them. The data were systematised into 5 height-weight SD-classes according to the correspondence between height and weight. There were 3 classes with relative correspondence between height and weight: 1. short and light girls, 2. medium-height and medium-weight girls, 3. tall and heavy girls and 2 classes with the largest relative non-correspondence between height and weight: 4. pycnics, 5. leptosomes. In addition to the well-known differences between pycnics and leptosomes it was also shown that in the classes small--medium--big statistically significant gradual changes take place. The increase in the fullness of the body and in the amount of soft tissue was in positive correlation with total body fat and subcutaneous body fat and with bone-muscle rate in the cross-sectional area of the arm and the thigh. The increase in height was connected with proportional changes in the whole skeleton. As the proportions of fat, muscles and bones are in mutual correlation, for establishing of norms for these proportions it is necessary to take the body size into consideration.

Anthropometry↗

Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.

The genome of the bacterium Borrelia burgdorferi B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like Mycoplasma genitalium, it contains no genes for cellular biosynthetic reactions. Because B. burgdorferi and M. genitalium are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.

Biological Transport↗

CNP overexpression induces aberrant oligodendrocyte membranes and inhibits MBP accumulation and myelin compaction.

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) is highly enriched in myelin-forming cells where it is concentrated at the cytoplasmic side of all surface membranes except those of compact myelin. Previous studies have provided evidence that CNP is functionally involved in migration or expansion of membranes during myelination. This hypothesis is supported, in part, by the production of aberrant myelin membranes in transgenic mice that have a 6-fold increase in CNP expression. In addition, many myelin lamellae in these CNP-overexpressing mice lacked major dense lines (MDLs). The purpose of the present study was to determine if CNP overexpression altered: (1) oligodendrocyte and myelin membrane production during early stages of myelination, and (2) the ultrastructural distribution of CNP and myelin basic protein (MBP) in myelin membranes. We identified aberrant membrane expanses that extended from premyelinating oligodendrocyte processes, the periaxonal membrane, and the contact point between oligodendrocyte processes and myelin internodes. Myelin membranes without MDLs were deficient in MBP and enriched in CNP. These data support a functional role for CNP during oligodendrocyte membrane expansion and indicate, for the first time, that CNP may help target MBP to compact myelin.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Growth and Structure of Zirconium Hydrous Polymers in Aqueous Solutions

Zirconium oxychloride solutions prepared at different pH were heated at elevated temperatures for various aging periods to gain an understanding of the growth mechanism and structure of zirconium hydrous polymers. Small angle X-ray scattering (SAXS) measurements were made on these solutions. It was observed that shape of clusters at the earlier stages of growth is close to a rod rather than a sheet as suggested earlier. The scattering data indicate that a rod-shaped primary particle is formed at pH 1.2, and on an increase in the pH, the primary particles become more branched. On aging more than 1250 min at 92°C, these primary particles form large aggregates while retaining the primary particle structure. These aggregates, which are mass fractal in nature, restructure while growing in size and eventually transform into dense particles. Scattering data in this study were not enough to determine a specific kinetic growth model of the aggregates because the scattering intensity at low q constantly changes with time during the restructuring process. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗