Peritoneal flap for lymphocele prophylaxis following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection: study protocol and trial update for the randomized controlled PELYCAN study.

BACKGROUND: Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. METHODS/DESIGN: PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups-either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. DISCUSSION: The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016794 . Registered on 14 May 2019.

[Results of preoperative SARS-CoV-2 testing in the coronavirus pandemic]. / Ergebnisse der präoperativen SARS-CoV-2-Testung ("severe acute respiratory syndrome coronavirus 2") in der Coronaviruspandemie.

BACKGROUND: Surgery is challenging during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in elective and emergency surgery and to calculate the patient contacts during hospital stay. MATERIALS AND METHODS: All surgeries defined by the German procedural classification (starting with a 5) from 1 June until 29 November 2020 were retrospectively evaluated regarding the preoperative SARS-CoV­2 nasopharyngeal swab test. The results were then divided in emergency and elective surgeries. To show the personal contacts of the patients in a university hospital, we calculated the patient pathway within the department of urology and urosurgery for April 2020. Therefor we used the electronic patient records. RESULTS: Altogether 7745 surgical procedures in 5985 patients were performed, whereby 39 (0.5%) SARS-CoV­2 tests were positive. 2833 (37%) surgical procedures were emergency cases and 4912 (63%) were elective procedures. 25 (0.9%) of the emergency group and 14 (0.3%) of the elective surgeries had a positive SARS-CoV­2 test. The average number of contacts in the patient room was 12.83 (0-50) and 84.22 (0-249) at the ward level, not counting contacts with the clinic staff. CONCLUSIONS: Nearly 1% of the preoperative SARS-CoV­2 tests of either emergency or elective surgeries tested positive in the 6 months prior to November 2020. Although the risk of undetected SARS-CoV­2 infection appears to be low in terms of costs and personnel, preoperative screening is useful in high-risk areas to ensure further necessary surgeries, especially concerning cancer patients and to prevent virus spread in a hospital.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

Precision of MRI/ultrasound-fusion biopsy in prostate cancer diagnosis: an ex vivo comparison of alternative biopsy techniques on prostate phantoms.

PURPOSE: Comparing the accuracy of MRI/ultrasound-guided target-biopsy by transrectal biopsy (TRB) with elastic versus rigid image fusion versus transperineal biopsy (TPB) with rigid image fusion in a standardized setting. METHODS: Target-biopsy of six differently sized and located lesions was performed on customized CIRS 070L prostate phantoms. Lesions were only MRI-visible. After prior MRI for lesion location, one targeted biopsy per lesion was obtained by TRB with elastic image fusion with Artemis™ (Eigen, USA), TRB with rigid image fusion with real-time virtual sonography (Hitachi, Japan) and TPB with rigid image fusion with a brachytherapy approach (Elekta, Sweden), each on a phantom of 50, 100 and 150 ml prostate volume. The needle trajectories were marked by contrast agent and detected in a postinterventional MRI. RESULTS: Overall target detection rate was 79.6% with a slight superiority for the TPB (83.3 vs. 77.8 vs. 77.8%). TRB with elastic image fusion showed the highest overall precision [median distance to lesion center 2.37 mm (0.14-4.18 mm)], independent of prostate volume. Anterior lesions were significantly more precisely hit than transitional and basal lesions (p = 0.034; p = 0.015) with comparable accuracy for TRB with elastic image fusion and TPB. In general, TRB with rigid image fusion was inferior [median 3.15 mm (0.37-10.62 mm)], particularly in small lesions. CONCLUSION: All biopsy techniques allow detection of clinically significant tumors with a median error of 2-3 mm. Elastic image fusion appears to be the most precise technique, independent of prostate volume, target size or location.

[Antibiotic stewardship (ABS). Definition, contents, necessity and practice on examples of current clinical-urological controversies]. / Antibiotic Stewardship (ABS). Definition, Inhalte, Notwendigkeit und Umsetzung an Beispielen aktueller klinisch-urologischer Kontroversen.

BACKGROUND: Infectious diseases caused by multi-resistant pathogens are increasing worldwide and are posing a challenge to German urology as well. Furthermore, there is a limited perspective of new antibiotic developments. One way out of this dilemma is a differentiated handling and use of antibiotics (antibiotic stewardship, ABS). AIM: The aim of this review is to identify key issues in modern urological antibiotic therapy, which can be considered as exemplary for the whole topic of ABS. This includes a review of the current data of the individual topics, including thought-provoking impulse for future clinical application and research. MATERIAL AND METHODS: The research group "infectious diseases" of GeSRU Academics identified the following central topics: excessive use of fluoroquinolones, diagnosis and treatment of urethritis and perioperative antibiotic prophylaxis. Subsequently, we performed a literature research in MEDLINE to uncover controversies and open questions of the individual topics within the meaning of ABS. RESULTS: The analysis of modern antibiotic therapy in urology shows numerous open questions in all quality dimensions of ABS: structural quality (e.g. through improved training of medical staff in the differentiated use of antibiotics), process quality (e.g. by improved adherence to existing infectiological guidelines, here in particular the perioperative prophylaxis and therapy of urethritis) and outcome (e.g. by detection of resistance rates and infection rates). DISCUSSION: The overarching and common goal is to avoid a post-antibiotic era. ABS programmes and a 10-point plan of the federal government are considered positive political developments in this area but do not release the individual urologist from a personal responsibility as part of his daily routine. A critical analysis of the topic "antibiotic treatment" is essential.

Comparison of the roll-plate and sonication techniques in the diagnosis of microbial ureteral stent colonisation: results of the first prospective randomised study.

BACKGROUND: Microbial ureteral stent colonisation (MUSC) is one leading risk factor for complications associated with ureteral stent placement. As MUSC remains frequently undetected by standard urine cultures, its definitive diagnosis depends on microbiological investigation of the stent. However, a standard reference laboratory technique for studying MUSC is still lacking. MATERIALS AND METHODS: A total of 271 ureteral stents removed from 199 consecutive patients were investigated. Urine samples were obtained prior to device removal. Stents were divided into four parts. Each part was separately processed by the microbiology laboratory within 6 h. Ureteral stents were randomly allocated to roll-plate or sonication, respectively, and analysed using standard microbiological techniques. Demographic and clinical data were prospectively collected using a standard case-report form. RESULTS: Overall, roll-plate showed a higher detection rate of MUSC compared with sonication (35 vs. 28 %, p < 0.05) and urine culture (35 vs. 8 %, p < 0.05). No inferiority of Maki's technique was observed even when stents were stratified according to indwelling time below or above 30 days. Compared with roll-plate, sonication commonly failed to detect Enterococcus spp., coagulase-negative staphylococci (CoNS) and Enterobacteriaceae. In addition, sonication required more hands-on time, more equipment and higher training than roll-plate in the laboratory. CONCLUSIONS: This prospective randomised study demonstrates the superiority of Maki's roll-plate technique over sonication in the diagnosis of MUSC and that urine culture is less sensitive than both methods. The higher detection rate, simplicity and cost-effectiveness render roll-plate the methodology of choice for routine clinical investigation as well as basic laboratory research.

Influence of surgeon's experience on fluoroscopy time during endourological interventions.

INTRODUCTION AND OBJECTIVE: Fluoroscopy time influences radiation exposure of both surgeons and patients during endourological interventions. Changes in fluoroscopy habits of endourological surgeons after being informed about their fluoroscopy times were evaluated depending on their endourological experience. MATERIALS AND METHODS: From April 2010 to April 2011, 402 endourological interventions in 337 Patients were assessed. Evaluated interventions were ureter stent placement (USP), ureter stent change (USC) nephrostomy change (NC), ureterorenoscopy (URS) and percutaneous nephrolithotomy (PCNL). Fluoroscopy time (FT) and operation time (OT) were recorded. For USP, USC and NC, the surgeons were divided into two groups: group I with >2 years of endourological experience and group II with <2 years experience. URS and PCNL only were performed by experienced surgeons. After 6 months, all surgeons were informed about their mean detected results. Both groups were compared, and changes in FT and OT in the second part of the study were analysed. RESULTS: Surgeons reduced their median fluoroscopy times up to 55 % after being informed about their fluoroscopy manners. Experienced surgeons reduced both operation and fluoroscopy times significantly for USP, USC and NC. For URS and PCNL, and OT and FT, the differences were not statistically significant. Inexperienced surgeons were not able to reduce both OT and FT significantly. CONCLUSION: If experienced surgeons are informed about their fluoroscopy time during endourological interventions, fluoroscopy times can be reduced significantly in easy procedures, which leads to less radiation exposure of surgeons and patients. Inexperienced surgeons have less possibility to influence their fluoroscopy manners.

Impact of mutant ß-catenin on ABCB1 expression and therapy response in colon cancer cells.

BACKGROUND: Colorectal cancers are often chemoresistant toward antitumour drugs that are substrates for ABCB1-mediated multidrug resistance (MDR). Activation of the Wnt/ß-catenin pathway is frequently observed in colorectal cancers. This study investigates the impact of activated, gain-of-function ß-catenin on the chemoresistant phenotype. METHODS: The effect of mutant (mut) ß-catenin on ABCB1 expression and promoter activity was examined using HCT116 human colon cancer cells and isogenic sublines harbouring gain-of-function or wild-type ß-catenin, and patients' tumours. Chemosensitivity towards 24 anticancer drugs was determined by high throughput screening. RESULTS: Cell lines with mut ß-catenin showed high ABCB1 promoter activity and expression. Transfection and siRNA studies demonstrated a dominant role for the mutant allele in activating ABCB1 expression. Patients' primary colon cancer tumours shown to express the same mut ß-catenin allele also expressed high ABCB1 levels. However, cell line chemosensitivities towards 24 MDR-related and non-related antitumour drugs did not differ despite different ß-catenin genotypes. CONCLUSION: Although ABCB1 is dominantly regulated by mut ß-catenin, this did not lead to drug resistance in the isogenic cell line model studied. In patient samples, the same ß-catenin mutation was detected. The functional significance of the mutation for predicting patients' therapy response or for individualisation of chemotherapy regimens remains to be established.

Microbial ureteral stent colonization in renal transplant recipients: frequency and influence on the short-time functional outcome.

Ureteral stent insertion at the time of renal transplantation significantly decreases complications of urine leakage and obstruction, but bears an intrinsic risk of microbial colonization. Associated urinary tract infection (UTI) may pose a significant risk for graft infection and subsequent graft failure, in particular, during high-level immunosuppression in the early phase after transplantation. The aims of this prospective study were (i) to assess the frequency of microbial ureteral stent colonization (MUSC) in renal transplant recipients by sonication, (ii) to compare the diagnostic value of sonication with that of conventional urine culture (CUC), (iii) to determine biofilm forming organisms, and (iv) to investigate the influence of MUSC on the short-time functional outcome. A total of 80 ureteral stents from 78 renal transplant recipients (deceased donors n = 50, living donors n = 28) were prospectively included in the study. CUC was obtained prior to renal transplantation and at ureteral stent removal. In addition, a new stent sonication technique was performed to dislodge adherent microorganisms. CUCs were positive in 4% of patients. Sonicate-fluid culture significantly increased the yield of microbial growth to 27% (P < 0.001). Most commonly isolated microorganisms by sonication were Enterococcus species (31%), coagulase-negative staphylococci (19%), and Lactobacillus species (19%), microorganisms not commonly observed in UTIs after renal transplantation. The median glomerular filtraton rate (GFR) of the study population increases from 39 mL/min immediately after transplantation (time point A) to 50 mL/min 6 month post transplantation (time point B). In patients without MUSC, the GFR improves from 39 mL/min (A) to 48 mL/min (B) and in patients with MUSC from 39 mL/min (A) to 50 mL/min (B), respectively. In summary, MUSC in renal transplant recipients is common and remains frequently undetected by routine CUC, but colonization had no measurable effect on renal function.

Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution.

AIM: To establish the most common vacA alleles in Helicobacter pylori (H pylori) strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers. METHODS: Two hundred and forty five H pylori clinical isolates were obtained from 79 biopsies from Chilean infected patients suffering from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vacA genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing. RESULTS: The most prevalent vacA genotype in Chilean patients was s1b m1 (76%), followed by s1a m1 (21%). In contrast, the s2 m2 genotype was scarcely represented (3%). The s1b m1 genotype was found most frequently linked to gastropathies (P<0.05) rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patients living in cities located North and far South of Santiago, the capital and largest Chilean city, carried almost exclusively strains with the s1b m1 genotype. In contrast, patients from Santiago and cities located South of Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes. Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India. CONCLUSION: Differences in geographic distribution of the s and m vacA alleles in Chile and a relationship of s1b m1 genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype. Asymmetric distribution of genotypes s1b m1 and s2 m2 recedes H Pylori strain distribution in Spain and Portugal.

Protection against tetanus by needle-free inoculation of adenovirus-vectored nasal and epicutaneous vaccines.

The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against live Clostridium tetani infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.

Increased glutamate, GABA and glutamine in lateral geniculate nucleus but not in medial geniculate nucleus caused by visual attention to novelty.

This study is concerned with cortico-thalamic neural mechanisms underlying attentional phenomena. Previous results from this laboratory demonstrated that the visual sector of the GABAergic thalamic reticular nucleus is selectively c-fos activated in rats that are naturally paying attention to features of a novel-complex environment, and that this activation is dependent on top-down glutamatergic inputs from the primary visual cortex. By contrast, the acoustic sector of the thalamic reticular nucleus is not activated despite noise generated by exploration and c-fos activation of brainstem acoustic centers (e.g. dorsal cochlear nucleus, inferior colliculus). A prediction of these results is that the levels of the neurotransmitters glutamate and GABA, and the glutamate-related amino acid glutamine, will be increased in the lateral geniculate nucleus (LGN), but not in the medial geniculate nucleus (MGN) of rats that explore a novel-complex environment in comparison to levels of these amino acids in control rats. By means of neurochemical analysis of these amino acids (HPLC) the results of this study confirmed this prediction. The results are consistent with the previously proposed 'focal attention' hypothesis postulating that a focus of attention in the primary visual cortex generates top-down center-surround facilitatory-inhibitory effects on geniculocortical transmission via corticoreticulogeniculate pathways. The results also supports the notion that a main function of corticothalamic pathways to relay thalamic nuclei is attention-dependent modulation of thalamocortical transmission.

A novel inhibitor of beta-glucuronidase: L-aspartic acid.

Infants who consume casein hydrolysate formula have been shown to have lower neonatal jaundice levels than infants who consume routine formula or breast milk. Because casein hydrolysate has been shown to contain a beta-glucuronidase inhibitor, one possible mechanism to explain this finding is blockage of the enterohepatic circulation of bilirubin by a component of the formula. The aim of this research was to identify the source of the beta-glucuronidase inhibition in hydrolyzed casein. A beta-glucuronidase inhibition assay and measurements of physical and kinetic parameters were used to analyze the components of hydrolyzed casein and infant formulas. Kinetic studies used purified beta-glucuronidase. The L-aspartic acid in hydrolyzed casein accounts for the majority of the beta-glucuronidase inhibition present. Kinetic studies indicate a competitive inhibition mechanism. L-aspartic acid is a newly identified competitive inhibitor of beta-glucuronidase.

Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA vaccine.

We investigated the DNA immunization approach in order to induce a protective immune response against hepatitis delta virus (HDV) superinfection of chronically woodchuck hepatitis virus (WHV) infected woodchucks. The animals were immunized with an expression vector encoding HDAg by gene gun. T cell and humoral immune responses induced by this protocol were determined and compared with those induced by HDAg immunization using a CpG oligonucleotide as an adjuvant. After immunization the woodchucks were challenged with 10(6) genome equivalents of HDV. The protein immunization with HDAg induced good humoral and T helper cell responses in the woodchucks, but did not protect them from HDV superinfection. The DNA immunized woodchucks were also not protected from HDV superinfection, however, the course of infection was modified: HDV viremia occurred later, the typical fluctuation of the HDV RNA titer with several peaks was absent, and antibodies to HDV were not detectable.

[Acute hepatitis caused by virus A, E and non A-E in Chilean adults]. / Hepatitis aguda por virus A, E y no A-E en adultos chilenos a fines de los años 90.

BACKGROUND: Sanitary and socioeconomic changes and the identification of new causative virus, have changed the epidemiology of hepatitis in Chile. AIM: To study the natural history of acute hepatitis caused by virus A, E and non A-E in Chilean adults. PATIENTS AND METHODS: A special study protocol was followed for patients with a clinical picture of acute hepatitis. Anti HAV IgM, anti HBc IgM, anti HEV IgG and IgM and Anti HCV antibodies were determined by ELISA. RESULTS: Fifty nine patients (30 male), aged 15 to 58 years old were studied. Eighty nine percent had jaundice and 50 to 70% had malaise and abdominal pain. Virus A was positive in 80%, virus E in 7%. In 14% of patients, all viral markers were negative. The evolution was typical in 78%, biphasic in 14% and cholestatic in 5%. One patient had a prolonged and one a fulminant course. Mean ALT was 1148 U/l and mean total bilirubin was 5.5 mg/dl. Seventy three percent of cases occurred during early winter and spring and 27% during summer and early autumn. CONCLUSIONS: The main etiology of acute viral hepatitis in Chile is virus A and most cases occur during the rainy season. Clinical features of hepatitis non A-E are similar to enteral transmission forms.

Coadministration of gamma interferon with DNA vaccine expressing woodchuck hepatitis virus (WHV) core antigen enhances the specific immune response and protects against WHV infection.

DNA vaccinations are able to induce strong cellular immune responses in mice and confer protection against infectious agents. However, DNA vaccination of large animals appears to be less effective and requires repeated injections of large amounts of plasmid DNA. Enhancement of the efficiency of DNA vaccines may be achieved by coapplication of cytokine-expressing plasmids. Here we investigated, with woodchucks, whether coadministration of an expression plasmid for woodchuck gamma interferon (IFN-gamma), pWIFN-gamma, can improve DNA vaccination with woodchuck hepatitis virus core antigen (WHcAg). Animals were immunized with pWHcIm (a plasmid expressing WHcAg) alone or with a combination of pWHcIm and pWIFN-gamma using a gene gun. Six weeks postimmunization, all animals were challenged with 10(5) genome equivalents of woodchuck hepatitis virus (WHV). The antibody and lymphoproliferative immune responses to WHV proteins were determined after immunization and after challenge. Vaccination with pWHcIm and pWIFN-gamma led to a pronounced lymphoproliferative response to WHcAg and protected woodchucks against subsequent virus challenge. Two of three animals vaccinated with pWHcIm alone did not show a detectable lymphoproliferative response to WHcAg. A low-level WHV infection occurred in these woodchucks after challenge, as WHV DNA was detectable in the serum by PCR. None of the pWHcIm-vaccinated animals showed an anti-WHcAg antibody response after DNA vaccination or an anamnestic response after virus challenge. Our results indicate that coadministration of the WIFN-gamma gene with pWHcIm enhanced the specific cellular immune response and improved the protective efficacy of WHV-specific DNA vaccines.

Induction of a cellular and humoral immune response against preprocalcitonin by genetic i: a potential new treatment for medullary thyroid carcinoma.

Currently, no effective therapy exists for patients suffering from progressive medullary thyroid carcinoma (MTC), a calcitonin (CT)-secreting C cell tumor. As CT, which arises from the precursor protein preprocalcitonin (PPCT), is expressed by almost all MTC cases, these molecules may represent target antigens for immunotherapy against MTC. In our study we investigated whether DNA immunization is able to induce cellular and humoral immune responses against human PPCT (hPPCT) in mice. Antigen-encoding expression plasmids were delivered intradermally by gene gun. One group of mice received DNA encoding hPPCT only. Two groups were coinjected with mouse cytokine genes. We observed in lymphocyte proliferative assays substantial proliferation against hPPCT in mice coinjected with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, in contrast to mice vaccinated with hPPCT expression plasmid only. In addition, codelivery of the GM-CSF gene augmented the frequency of anti-hPPCT antibody seroconversions in sera of immunized animals, as shown by enzyme-linked immunosorbent assay. These results illustrate that cellular and humoral immune responses against hPPCT can be generated by DNA immunization and increased by coinjection of the GM-CSF gene. Our findings may have implications for the use of DNA immunization as a potential novel immunotherapeutic treatment for patients suffering from progressive MTC.

Increased immunoreactivity of glutathione-S-transferase in the retina of Swiss Webster mice following inhalation of JP8 + 100 aerosol.

The current study was designed to determine whether exposure of mice to aerosolized jet fuel (JP8 + 100) resulted in changes in the cellular distribution or immunoreactivity of the enzyme glutathione S-transferase (GST), a biomarker of toxicant exposure. Male mice were exposed to JP8 + 100 at 1000 mg/m3 or 2500 mg/m3 in aerosol for 1 h per day for 7 days and then sacrificed. The retinas were studied by immunohistochemical methods. The JP8 + 100 exposure caused a marked increase in the immunoreactivity of anti-GSTM antibodies with the radial glial cells of the retina, the Müller cells. These results are consistent with the hypothesis that JP8 + 100 acts as a toxicant to mouse retina by permitting the flux of materials across the blood-retina barrier. The findings are relevant to humans because recent studies indicate that Air Force personnel assigned to clean and maintain fuel pods may be exposed to concentrations of JP8 + 100 exceeding 1000 mg/m3.