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Biomedical subjects

Jennifer Wilson

Publications and source records attributed to Jennifer Wilson.

7 recordsLinked to original sources

Overwintering of West Nile virus in Southern California.

West Nile virus (family Flaviviridae, genus Flavivirus, WNV) invaded southern California during 2003, successfully overwintered, amplified to epidemic levels, and then dispersed to every county in the state. Although surveillance programs successfully tracked and measured these events, mechanisms that allowed the efficient overwintering and subsequent amplification of WNV have not been elucidated. Our current research provided evidence for three mechanisms whereby WNV may have persisted in southern California during the winters of 2003-2004 and 2004-2005: 1) continued enzootic transmission, 2) vertical transmission by Culex mosquitoes, and 3) chronic infection in birds. WNV was detected in 140 dead birds comprising 32 species, including 60 dead American crows, thereby verifying transmission during the November-March winter period. Dead American crows provide evidence of recent transmission because this species always succumbs rapidly after infection. However, WNV RNA was not detected concurrently in 43,043 reproductively active female mosquitoes comprising 11 species and tested in 1,258 pools or antibody in sera from 190 sentinel chickens maintained in 19 flocks. Although efficient vertical transmission by WNV was demonstrated experimentally for Culex tarsalis Coquillett infected per os, 369 females collected diapausing in Kern County and tested in 32 pools were negative for WNV. Vertical transmission was detected in Culex pipiens quinquefasciatus Say adults reared from field-collected immatures collected from Kern County and Los Angeles during the summer transmission period. Chronic infection was detected by finding WNV RNA in 34 of 82 birds that were inoculated with WNV experimentally, held for >6 wk after infection, and then necropsied. Frequent detection of WNV RNA in kidney tissue in experimentally infected birds >6 wk postinfection may explain, in part, the repeated detection of WNV RNA in dead birds recovered during winter, especially in species such as mourning doves that typically do not die after experimental infection. In summary, our study provides limited evidence to support multiple modes of WNV persistence i n southern California. Continued transmission andvertical transmission by Culex p. quinquefasciatus Say seem likely candidates for further study.

Animals↗

Neutron versus photon radiotherapy for local control in inoperable breast cancer.

BACKGROUND AND PURPOSE: By virtue of their high linear energy transfer (LET) characteristics the biologic effectiveness of neutrons is less dependent on tissue oxygenation tension and cell cycle phase as compared to that with photons. Hence, an improved clinical benefit is to be expected predominantly in large, hypoxic and slowly growing tumors. Since a short course of radiotherapy is required for clinical reasons, it prompted the authors to initiate a randomly controlled trial on locally advanced breast cancer. PATIENTS AND METHODS: Between 1996 and 1999, 27 patients with locally advanced breast cancer were irradiated with photons (60 Gy, 30 fractions; 8 MV, (60)Co) or neutrons (18 Gy, twelve fractions; 66 MeV(p-->Be)). The mean tumor diameters were 699 +/- 399 ml for the photon group and 1,097 +/- 831 ml in the neutron group. RESULTS: After a mean follow-up period of 21.5 months tumor involution was evaluated in 22 patients. Partial and complete remissions were registered in 6/10 patients of the photon group and 5/12 patients of the neutron group. Late grade 3-4 morbidity according to RTOG definition was scored in 5/10 patients in the photon group and in 6/12 patients in the neutron group. With regard to tumor control and late radiation morbidity no differences between the two treatment arms were observed. CONCLUSION: The underlying data indicate that no benefit is to be expected from neutron therapy in breast cancer.

Adult↗

Hard metal lung disease: high resolution CT and histologic correlation of the initial findings and demonstration of interval improvement.

Hard metal lung disease (HMLD) is a rare form of interstitial lung disease caused by sensitization to cobalt. It occurs in patients exposed to hard metal (tungsten carbide) and in diamond workers who use cobalt-containing polishes. The chest radiograph may be normal or show a nodular, reticulonodular, or reticular pattern. The high-resolution CT findings have been described in a small number of patients. Reported abnormalities include patchy lobular ground glass opacities, consolidation, reticulation, centrilobular nodularity, and, occasionally, honeycombing.We describe the high-resolution CT findings in a patient with pathologically proven HMLD who demonstrated interval improvement in the ground glass opacities and persistence of the centrilobular nodules following cessation of exposure to hard metal and treatment with corticosteroids. To our knowledge, this is the first described case of HMLD with follow-up CT examination.

Adult↗

CD4+ T-cell responses and distribution at the colonic mucosa during Brachyspira hyodysenteriae-induced colitis in pigs.

The spirochaete Brachyspira hyodysenteriae causes swine dysentery, a severe colitis characterized by mucosal enlargement as a result of crypt elongation and epithelial necrosis. Most efforts to understand the pathogenesis of this disease have focused on the aetiological agent and its virulence factors. However, the host immune response has been considered an important factor in disease development. Previous research has shown that B. hyodysenteriae induces systemic CD4(+) and gammadelta T-cell responses after intramuscular immunization. Here, we have evaluated changes in the CD4(+) and gammadelta T-cell composition and distribution the different compartments of the colonic mucosa of pigs challenged with B. hyodysenteriae. We report that, in infected pigs, gammadelta T cells were significantly depleted from the epithelial layer, although their numbers were maintained in the lamina propria. In addition, CD4(+) T cells aggregated in clusters located in the lamina propria and submucosa. Ex vivo analyses of CD4(+) T-cell responses to B. hyodysenteriae antigens correlated with the changes in the mucosal CD4(+) T-cell distribution observed in infected pigs; CD4(+) T cells recovered from peripheral blood and colonic lymph nodes of infected pigs proliferated to B. hyodysenteriae antigens, whereas no differences were found in the gammadelta T-cell responses between challenged and control groups. In addition, colonic lymph node CD4(+) T cells had a predominant memory/activated phenotype. These results indicate that infection with B. hyodysenteriae induces a mucosal CD4(+) T-cell response and points to CD4(+) T cells being important contributors to the immunopathogenesis of swine dysentery.

Animals↗

High throughput screening for cyanovirin-N mimetics binding to HIV-1 gp41.

The human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp41 is an important mediator of viral entry into host cells. Previous studies showed that the virucidal protein cyanovirin-N (CV-N) bound to both gp120 and gp41, and that this binding was associated with its antiviral activity. We constructed an HTS assay based on the interaction of europium-labeled CV-N with recombinant glycosylated gp41 ectodomain to support identification of small-molecule mimetics of CV-N that might be developed as antiviral drug leads. Primary screening of over 107,000 natural product extracts in the assay yielded 347 confirmed hits. Secondary assays eliminated extracts that bound directly to labeled CV-N or for which the simple sugars mannose and N-acetylglucosamine blocked the interaction with gp41 (lectin activity). Extracts were further prioritized based on anti-HIV activity and other biological, biochemical, and chemical criteria. The distribution of source organism taxonomy of active extracts was analyzed, as was the cross-correlation of activity between the CV-N-gp41 binding competition assay and the previously reported CV-N-gp120 binding competition assay. A limited set of extracts was selected for bioassay-guided fractionation.

Acetylglucosamine↗

Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101.

High-grade dysplasia induced by high-risk types of human papillomavirus (HPV) precedes invasive cancer in anal squamous epithelium just as it does in the cervix. A therapeutic HPV vaccine strategy as a potential treatment for anal dysplasia was tested in a standard Phase I dose escalation trial. The primary objective was to evaluate the safety of the agent; additional study aims were to evaluate the histological response, immune response, and effect on anal HPV-16 infection. Each subject was treated with four i.m. injections of 50-400 microg of ZYC101 at 3-week intervals. ZYC101 is composed of plasmid DNA encapsulated in biodegradable polymer microparticles. The plasmid DNA encodes for multiple HLA-A2-restricted epitopes derived from the HPV-16 E7 protein, one of two HPV oncoproteins consistently expressed in neoplastic cells. Fifty-six potential anal dysplasia subjects were screened to identify 12 eligible subjects with HPV-16 anal infection and a HLA-A2 haplotype. The investigational agent was well tolerated in all subjects at all dose levels tested. Three subjects experienced partial histological responses, including one of three subjects receiving the 200-microg dose and two subjects at the 400-microg dose level. Using a direct Elispot, 10 of 12 subjects demonstrated increased immune response to the peptide epitopes encoded within ZYC101; each continued to show elevated immune responses 6 months after the initiation of therapy. These results support the continued investigation of a therapeutic vaccination strategy for anal dysplasia.

Adult↗