The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Stephen E Straus - One of the best experts on this subject based on the ideXlab platform.
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Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs
Vaccine, 2008Co-Authors: Y Hoshino, Stephen E Straus, Lesley Pesnicak, David M. Knipe, Kennichi C. Dowdell, Juan C. Lacayo, Timothy Dudek, Jeffrey I CohenAbstract:Abstract A replication-defective herpes simplex virus (HSV)-2 vaccine, dl 5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl 5-29 termed dl 5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wild-type HSV-2 in mice when compared with dl 5-29. To determine if deletion of UL41 improves the efficacy of dl 5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl 5-29, dl 5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl 5-29 and dl 5-29-41L recipients were comparable (10 1.97 and 10 2.19 , respectively, p = 0.15). After intravaginal challenge with wild-type HSV-2, the dl 5-29-41L and dl 5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in Sacral Ganglia were similar for dl 5-29 and dl 5-29-41L (all p values >0.05). dl 5-29 and dl 5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8 + T cells in the spleens of the animals. Thus, dl 5-29 was as immunogenic and protective as dl 5-29-41L under these conditions. dl 5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl 5-29-41L and dl 5-29 are equally effective and immunogenic in guinea pigs, and dl 5-29 is very safe in immunocompromised animals.
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Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs
Journal of Virology, 2005Co-Authors: Y Hoshino, Kening Wang, Jeffrey I Cohen, Sarat K. Dalai, Lesley Pesnicak, David M. Knipe, Stephen E StrausAbstract:Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in Sacral Ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal Ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8+-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.
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characterization of herpes simplex virus type 2 latency associated transcription in human Sacral Ganglia and in cell culture
The Journal of Infectious Diseases, 1991Co-Authors: Kenneth D Croen, Jeffrey M Ostrove, L Dragovic, Stephen E StrausAbstract:: The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from Sacral dorsal root sensory Ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human Sacral Ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in Sacral Ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal Ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory Ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.
Christoph Rischpler - One of the best experts on this subject based on the ideXlab platform.
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68ga psma hbed cc uptake in cervical celiac and Sacral Ganglia as an important pitfall in prostate cancer pet imaging
The Journal of Nuclear Medicine, 2018Co-Authors: Christoph Rischpler, Teresa Beck, Shozo Okamoto, Anna Melissa Schlitter, K Knorr, Markus Schwaiger, J E Gschwend, Tobias MaurerAbstract:: The study aims to investigate the presence of physiologic prostate-specific membrane antigen (68Ga-PSMA)-ligand uptake on PET in cervical, celiac, and Sacral Ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Methods: Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled with 68Ga-gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid (68Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of 68Ga-PSMA PET-positive cervical, celiac, and Sacral Ganglia was determined, and the configuration and SUVmax of each ganglion were measured. In addition, the configuration and SUVmax of adjacent lymph node metastases in the respective region (cervical, celiac, or Sacral) were determined. Results:68Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral Ganglia, in 369 (92%) patients in cervical Ganglia, in 363 (89%) patients in celiac Ganglia, and in 183 (46%) patients in Sacral Ganglia. The 68Ga-PSMA-ligand uptake was highest in celiac (mean SUVmax, 2.9 ± 0.8 vs. cervical mean SUVmax, 2.4 ± 0.6) and Sacral (mean SUVmax 1.7 ± 0.5; both P < 0.0001) Ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the 68Ga-PSMA-ligand uptake in cervical versus celiac Ganglia (R = 0.34, P < 0.0001), cervical versus Sacral (R = 0.52, P < 0.0001), and celiac versus Sacral (R = 0.16, P < 0.05). The 68Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective Ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, P < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, P < 0.0001; Sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, P < 0.0001). Furthermore, Ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) (P < 0.00001). Conclusion:68Ga-PSMA-ligand uptake in Ganglia along the sympathetic trunk as assessed by 68Ga-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The 68Ga-PSMA-ligand uptake is higher in celiac Ganglia than cervical or Sacral Ganglia, and the level of 68Ga-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic Ganglia, both intensity of 68Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.
Christine Johnston - One of the best experts on this subject based on the ideXlab platform.
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virologic and immunologic evidence of multifocal genital herpes simplex virus 2 infection
Journal of Virology, 2014Co-Authors: Christine Johnston, Lichen Jing, Kerry J Laing, Christopher M Mcclurkan, Alexis Klock, Kurt Diem, Jeffrey D Stanaway, Elizabeth Tronstein, William W KwokAbstract:UNLABELLED: Genital herpes simplex virus (HSV) reactivation is thought to be anatomically and temporally localized, coincident with limited ganglionic infection. Short, subclinical shedding episodes are the most common form of HSV-2 reactivation, with host clearance mechanisms leading to rapid containment. The anatomic distribution of shedding episodes has not been characterized. To precisely define patterns of anatomic reactivation, we divided the genital tract into a 22-region grid and obtained daily swabs for 20 days from each region in 28 immunocompetent, HSV-2-seropositive persons. HSV was detected via PCR, and sites of asymptomatic HSV shedding were subjected to a biopsy procedure within 24 h. CD4(+) and CD8(+) T cells were quantified by immunofluorescence, and HSV-specific CD4(+) T cells were identified by intracellular cytokine cytometry. HSV was detected in 868 (7%) of 11,603 genital swabs at a median of 12 sites per person (range, 0 to 22). Bilateral HSV detection occurred on 83 (67%) days with shedding, and the median quantity of virus detected/day was associated with the number of sites positive (P < 0.001). In biopsy specimens of asymptomatic shedding sites, we found increased numbers of CD8(+) T cells compared to control tissue (27 versus 13 cells/mm(2), P = 0.03) and identified HSV-specific CD4(+) T cells. HSV reactivations emanate from widely separated anatomic regions of the genital tract and are associated with a localized cellular infiltrate that was demonstrated to be HSV specific in 3 cases. These data provide evidence that asymptomatic HSV-2 shedding contributes to chronic inflammation throughout the genital tract. IMPORTANCE: This detailed report of the anatomic patterns of genital HSV-2 shedding demonstrates that HSV-2 reactivation can be detected at multiple bilateral sites in the genital tract, suggesting that HSV establishes latency throughout the Sacral Ganglia. In addition, genital biopsy specimens from sites of asymptomatic HSV shedding have increased numbers of CD8(+) T cells compared to control tissue, and HSV-specific CD4(+) T cells are found at sites of asymptomatic shedding. These findings suggest that widespread asymptomatic genital HSV-2 shedding is associated with a targeted host immune response and contributes to chronic inflammation throughout the genital tract.
Kenneth D Croen - One of the best experts on this subject based on the ideXlab platform.
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characterization of herpes simplex virus type 2 latency associated transcription in human Sacral Ganglia and in cell culture
The Journal of Infectious Diseases, 1991Co-Authors: Kenneth D Croen, Jeffrey M Ostrove, L Dragovic, Stephen E StrausAbstract:: The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from Sacral dorsal root sensory Ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human Sacral Ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in Sacral Ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal Ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory Ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.
Tobias Maurer - One of the best experts on this subject based on the ideXlab platform.
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68ga psma hbed cc uptake in cervical celiac and Sacral Ganglia as an important pitfall in prostate cancer pet imaging
The Journal of Nuclear Medicine, 2018Co-Authors: Christoph Rischpler, Teresa Beck, Shozo Okamoto, Anna Melissa Schlitter, K Knorr, Markus Schwaiger, J E Gschwend, Tobias MaurerAbstract:: The study aims to investigate the presence of physiologic prostate-specific membrane antigen (68Ga-PSMA)-ligand uptake on PET in cervical, celiac, and Sacral Ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Methods: Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled with 68Ga-gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid (68Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of 68Ga-PSMA PET-positive cervical, celiac, and Sacral Ganglia was determined, and the configuration and SUVmax of each ganglion were measured. In addition, the configuration and SUVmax of adjacent lymph node metastases in the respective region (cervical, celiac, or Sacral) were determined. Results:68Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral Ganglia, in 369 (92%) patients in cervical Ganglia, in 363 (89%) patients in celiac Ganglia, and in 183 (46%) patients in Sacral Ganglia. The 68Ga-PSMA-ligand uptake was highest in celiac (mean SUVmax, 2.9 ± 0.8 vs. cervical mean SUVmax, 2.4 ± 0.6) and Sacral (mean SUVmax 1.7 ± 0.5; both P < 0.0001) Ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the 68Ga-PSMA-ligand uptake in cervical versus celiac Ganglia (R = 0.34, P < 0.0001), cervical versus Sacral (R = 0.52, P < 0.0001), and celiac versus Sacral (R = 0.16, P < 0.05). The 68Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective Ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, P < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, P < 0.0001; Sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, P < 0.0001). Furthermore, Ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) (P < 0.00001). Conclusion:68Ga-PSMA-ligand uptake in Ganglia along the sympathetic trunk as assessed by 68Ga-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The 68Ga-PSMA-ligand uptake is higher in celiac Ganglia than cervical or Sacral Ganglia, and the level of 68Ga-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic Ganglia, both intensity of 68Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.
