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Biomedical subjects

S Wood

Publications and source records attributed to S Wood.

At least 19 recordsLinked to original sources

T cell receptor V beta complementarity-determining region 1 peptide administration moderates immune dysfunction and cytokine dysregulation induced by murine retrovirus infection.

Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we reported that autoantibodies were elevated during the initiation phases of this murine retrovirus infection and bound peptide determinants corresponding to CDR1 of several TCR V beta-chains. Therefore, we designed studies to determine whether administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation of T cell function. Administration of the TCR V beta CDR1 peptide before murine retrovirus infection significantly prevented its suppression of splenic NK cell activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk postinfection. However, delaying peptide immunization until severe suppression of T and B cell mitogenesis had occurred did not restore their functions. Immunization with TCR V beta peptide prevents development of retrovirus-induced immune dysfunction, which suggests a possible pathogenic role of autoreactive T cells as regulatory elements.

Amino Acid Sequence

Escherichia coli DNA polymerase III holoenzyme subunits alpha, beta, and gamma directly contact the primer-template.

Escherichia coli DNA polymerase III holoenzyme forms a stable initiation complex with RNA-primed template in the presence of ATP. To determine the linear arrangement of the holoenzyme subunits along the primer-template duplex region, we cross-linked holoenzyme to a series of photo-reactive primers. Site-specific photo-cross-linking revealed that the alpha, beta, and gamma subunits formed ATP-dependent contacts with the primer-template. The alpha-polymerase catalytic subunit covalently attached to nucleotide positions -3, -9, and -13 upstream of the primer terminus, with the most efficient adduct formation occurring at position -9. The gamma subunit contacted the primer at positions -13, -18, and -22, with the strongest gamma-primer interactions occurring at position -18. The beta subunit predominated in cross-linking at position -22. Thus, within the initiation complex, alpha contacts roughly the first 13 nucleotides upstream of the 3'-primer terminus followed by gamma at -18 and beta at -22, and the gamma subunit remains a part of the initiation complex, bridging the alpha and beta subunits. Analyses of the interaction of photo-activatible primer-templates with the preinitiation complex proteins (gamma-complex (gamma-delta-delta'-chi-psi) and beta subunit) revealed the gamma subunit within the preinitiation complex covalently attached to primer at position -3. However, addition of core DNA polymerase III to preinitiation complex, fully reconstituting holoenzyme resulted in replacement of gamma by alpha at the primer terminus. These data indicate that assembly of holoenzyme onto a primer-template can occur in distinct stages and results in a structural rearrangement during initiation complex formation.

Adenosine Triphosphate

Identification of the human neuronal nicotinic cholinergic alpha 2 receptor locus, (CHRNA2), within an 8p21 mapped locus, by sequence homology with rat DNA.

We have identified a cosmid, at the D8S131 locus, that shows sequence homology with exon 2 of the rat gene for the neuronal nicotinic acetylcholine receptor alpha 2 subunit. A 357-bp sequence surrounding a rare cutter AscI site contains a 152-bp region of homology. The human CHRNA2 gene is therefore positioned at the D8S131 locus, which has been mapped to 8p21.

Amino Acid Sequence

Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in a liquid diet, significantly restored levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which were suppressed by retrovirus infection. Retrovirus infection elevated levels of IL-6 and IL-10 produced by splenocytes, which were significantly normalized by all levels of vitamin E supplementation, respectively. Increased levels of IL-6 and tumor necrosis factor-alpha, produced by splenocytes during progression to murine AIDS, were also significantly normalized by all levels of vitamin E supplementation. Vitamin E supplementation restored retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E supplementation also alleviated the AIDS symptoms: splenomegaly and hypergammaglobulinemia. These data indicate that dietary vitamin E supplementation at extremely high levels was not immunotoxic, and can modulate cytokine release and normalize immune dysfunctions during progression to murine AIDS. It should favorably affect host resistance and thereby retard the development of AIDS.

Animals

Pulmonary nodules: improved detection with vascular segmentation and extraction with spiral CT. Work in progress.

PURPOSE: To determine whether extraction of pulmonary vessels from computed tomographic (CT) images with automated segmentation improves the detection of pulmonary nodules. MATERIALS AND METHODS: Simulated nodules were superimposed on normal spiral CT images. Eight patients referred for CT assessment of pulmonary nodules were selected for clinical evaluation. Vessels were extracted from both the simulation and clinical study with a three dimensional seeded region-growing algorithm. Three experienced radiologists were asked to locate the nodules and assign a level of confidence to their findings. Sensitivity and proportion of false-positive results per case (FPC) were calculated. Observer performance was evaluated by alternate free-response receiver operating characteristic analysis. RESULTS: Extraction of vascular structures from CT scans improved sensitivity from 63% to 84% in the simulation study and from 58% to 78% in the clinical study. The proportion of FPC decreased from 52% to 24% and from 55% to 12%, respectively. Radiologists performed consistently better with the segmented images than with the original images in both the simulation (P = .006) and the clinical (P = .0013) study. CONCLUSION: Automated vessel subtraction and extraction improves detection of pulmonary nodules.

Adult

Sequence identity locates CEBPD and FGFR1 to mapped human loci within proximal 8p.

The gene loci for human CEBPD (CCAAT enhancer binding protein, delta chain) and FGFR1 (fibroblast growth factor receptor) have been identified within two genetically mapped cosmids by sequence homology between rare cutter site regions and data base sequences for these loci. Cell hybrid and fluorescence in situ hybridization mapping places both of these loci within the chromosome region 8p11.2-->p11.1.

Animals

Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition.

Exposing the rat fetus to maternal low-protein diets during gestation has been shown to programme a number of metabolic and physiological changes. The present study examines the effects of maternal dietary manipulation upon glutathione cycle enzymes in the rat. Pregnant rats were fed either a non-purified chow diet or purified diets containing 18, 9 or 6% casein. Enzyme activities in the resulting offspring were determined at 4 weeks of age. Weanling pups exposed to the chow diet in utero had significantly lower activities of the glutathione synthetic enzyme gamma-glutamylcysteine synthetase in liver and lung than rats exposed to purified diets. Glutathione peroxidase activity in the liver also tended to be lower in these animals. Glutathione reductase activity in liver was negatively correlated with maternal protein intake, with rats exposed to 6% casein in utero having a significantly raised activity of this recycling enzyme, relative to controls exposed to 18% casein. These data are consistent with the hypothesis that components of maternal diet, including the level of protein intake, programme glutathione cycle enzymes, or production of their regulatory elements, in utero.

Animal Nutritional Physiological Phenomena

Case study: abscess of the labia.

A 68 year old female with no history of perianal abscess was examined in the Emergency Department of the hospital verbalizing complaints of swelling and tenderness in the left inguinal area. Physical examination revealed redness and swelling of the left labial area. The patient was admitted to the hospital and, following surgical incision and drainage by the physician, wound exploration revealed tunneling extending into the perirectal and vaginal areas. ET Nurse consultation was requested to establish a wound treatment regimen. The system of dressing used were a sterile, rayon/polyester dressing impregnated with 15 percent crystalline sodium chloride to cleanse the wound of slough and debris, in a ribbon form to facilitate packing of tunneling; a sterile 0.9 percent sodium chloride solution in gel form to protect the wound bed and keep it moist during granulation and reepithelialization; and an absorbent pad to collect drainage. This system of dressings addressed the patient's specific needs, was easy to use and proved easy to teach to a family member managing the patient's wound care at home. During the 10 1/2 weeks of treatment, wound healing progressed steadily, odor diminished rapidly and granulation of the wound bed progressed to healing with no maceration of the surrounding skin.

Abscess

The Wisconsin Diabetes Control Program: a health systems and community-based approach.

The Wisconsin Diabetes Control Program will address the health needs of people with diabetes by working closely with the Wisconsin Affiliate of the American Diabetes Association and other diabetes health professionals in the state. The 5-year program will use both health systems and community-based approaches to coordinate prevention, detection, and control activities required to reduce the burden of this chronic condition. This program represents a major shift in focus from previous diabetes control programs supported by the CDC, and is designed to establish the program as a key component of an evolving health care environment.

Community Health Services

Integrated mapping analysis of the Werner syndrome region of chromosome 8.

The Werner syndrome locus (WRN) is located at 8p11-p12. To facilitate eventual cloning of the WRN gene, a 10,000-rad radiation-reduced hybrid (RH) cell panel was generated to map genetic markers, sequence-tagged sites (STSs), and genes in this region. A hamster cell line carrying an intact human chromosome 8 was fused with another hamster cell line. Two sets of hybrid cell panels from 2 separate fusions were generated; each panel consisted of 50 independent clones; 33 and 34 cell lines from the 2 fusions retained human chromsome material as determined by inter-Alu PCR. The combined panel was genotyped for 52 markers spanning the entire chromosome, including 10 genes, 29 anonymous polymorphic loci, and 13 STSs. Seventeen of these markers have not been previously described. Markers near the centromere were retained at a higher frequency than more distal markers. Fluorescence in situ hybridization was also used to localize and order a subset of the markers. A RH map of the WRN region was constructed using a maximum likelihood method, giving the following most likely order: D8S131-D8S339 (GSR)-D8S124-D8S278-D8S259-(D8S71)-D8S283- D8S87-D8S105-D8S135 (FGFR1)-D8S135PB-D8S255-ANK1. A genetic map of 15 short tandem repeat polymorphic loci in the WRN region was also constructed. The marker orders from the genetic and RH maps were consistent. In addition, an integrated map of 24 loci in the WRN region was generated using information from both genetic and RH mapping methods. A 1000:1 framework map for 6 loci (LPL-D8S136-D8S137-D8S87-FGFR1-ANK1) was determined by genetic mapping, and the resulting locus order was fixed during analysis of the RH genotype data. The resulting integrated map contained more markers than could confidently be ordered by either genetic or RH mapping alone.

Base Sequence

Mesenchymal chondrosarcoma of the maxilla.

We report, to our knowledge, the 10th recorded case of mesenchymal chondrosarcoma (MC) occurring in the maxilla. Our case is the youngest person reported with a tumour in this location. The prognosis for cure is poor with a high incidence of local recurrence as well as metastases. Treatment is based on radical surgery. Radiotherapy and chemotherapy have a adjuvant role but additional experience with this tumour is required to define the most efficacious treatment.

Adolescent

Cervical pregnancy following in vitro fertilization: evacuation after uterine artery embolization with subsequent successful intrauterine pregnancy.

A case is described in which a cervical pregnancy followed in vitro fertilization. Treatment was delayed at the request of the patient until the second trimester, and was successfully managed by preoperative bilateral angiographic uterine artery occlusion, surgical evacuation, and postoperative balloon tamponade. Subsequent embryo transfer of previously cryopreserved embryos resulted in a normal intrauterine pregnancy and delivery without complications. This case highlights the need for awareness of cervical pregnancy following in vitro fertilization and the success of management which preserves fertility.

Adult

Ethanol consumption and early murine retrovirus infection influence liver, heart, and muscle levels of iron, zinc, and copper in C57BL/6 mice.

The relative and combined roles of ethanol and murine acquired immunodeficiency syndrome (MAIDS) on the mineral status (Fe, Zn, and Cu) of liver (storage site), heart, muscle (nutrient mobile sites) were investigated. C57BL/6 mice were randomly assigned to four groups: (a) uninfected mice fed isocaloric, adequate nutrient diet (NRC), (b) uninfected mice fed the NRC diet with 25% of energy derived from ethanol, (c) LP-BM5 retrovirus-infected mice fed the isocaloric NRC diet, and (d) retrovirus-infected mice fed the NRC diet with 25% of its energy derived from ethanol. The levels of Cu and Zn levels in the liver did not significantly change as a result of ethanol consumption. However hepatic Zn concentration was increased significantly in retrovirus-infected mice. This may be correlated to the increase in their liver weight. Ethanol administration significantly increased Fe concentration in the liver, yet significantly decreased concentration of Cu in the heart. Retrovirus infection alone, which had not proceeded to murine AIDS, resulted in a significant increase in heart Cu and Zn concentration as compared with uninfected mice. Retrovirus infection in C57BL/6 mice significantly increased Fe and Zn level/g of muscle. Early retrovirus infection alters tissue micronutrient levels, and may thus contribute to immunological changes.

Alcoholism