A Very Strong Enhancer Is Located Upstream of an Immediate Early Gene of Human Cytomegalovirus

A strong transcription enhancer was identified in the genomic DNA (235 kb) of human cytomegalovirus (HCMV), a ubiquitous and severe pathogen of the herpesvirus group. Cotransfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-HCMV recombinant viruses that had incorporated overlapping segments of HCMV DNA to substitute for the missing SV40 enhancer. Within HCMV, these enhancer sequences are located upstream of the transcription initiation site of the major immediate-early gene, between nucleotides -118 and −524. Deletion studies with the HCMV enhancer, which harbors a variety of repeated sequence motifs, show that different subsets of this enhancer can substitute for the SV40 enhancer. The HCMV enhancer, which seems to have little cell type or species preference, is severalfold more active than the SV40 enhancer. It is the strongest enhancer we have analyzed so far, a property that makes it a useful component of eukaryotic expression vectors

Cell Surface Markers in HTLV-1 Pathogenesis

The phenotype of HTLV-1-transformed CD4+ T lymphocytes largely depends on defined viral effector molecules such as the viral oncoprotein Tax. In this review, we exemplify the expression pattern of characteristic lineage markers, costimulatory receptors and ligands of the tumor necrosis factor superfamily, cytokine receptors, and adhesion molecules on HTLV-1-transformed cells. These molecules may provide survival signals for the transformed cells. Expression of characteristic surface markers might therefore contribute to persistence of HTLV-1-transformed lymphocytes and to the development of HTLV-1-associated disease

The strong enhancer element in the immediate early region of the human cytomegalovirus genome

The human cytomegalovirus (HCMV), a member of the herpesvirus group, was found to possess a strong transcription enhancer in the immediate early gene region. Co-transfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-like recombinant viruses , each containing HCMV DNA fragments that were substituting for the missing SV40 enhancer. The two inserts , 341 and 262 bp in length , are overlapping segments of genuine viral DNA representing part of the 5'flanking region of the major immedistte early gene i n HCMV. Studies with deletion mutants showed that different nonoverlapping subsets of the HCMV enhancer region can substitute for the 72 bp repeats of SV40. Transient expression assays indicated that the HCMV enhancer is significantly stronger than the SV40 element, activating cis-linked heterologous promoters in a wide spectrum of cultured cells. It appears that the HCMV enhancer is positively regulated by viral immediate early genes

Hepatocellular carcinoma tumor thrombus entering the right atrium treated with combining percutaneous and intravenous high-dose-rate brachytherapy: a case report

The presented report describes a case of a Hepatocellular carcinoma (HCC) tumor thrombus (TT) infiltrating the inferior vena cava (IVC) and the right atrium (RA) in a 66-year old male patient who initially presented with TT related symptoms. CT-guided high-dose-rate brachytherapy (HDRBT) was performed for both, the intraparenchymal primary and the TT. A marked improvement of the tumor-related symptoms and shrinkage of the tumor mass were achieved six months after treatment initiation. The combination of intravascular and percutaneous HDRBT demonstrating a promising approach to palliate tumor-related symptoms in advanced HCC with macrovascular invasion

Changes of radiological examination volumes over the course of the COVID-19 pandemic: a comprehensive analysis of the different waves of infection

Objectives: Data from radiological departments provide important information on overall quantities of medical care provided. With this study we used a comprehensive analysis of radiological examinations as a surrogate marker to quantify the effect of the different COVID-19 waves on medical care provided. Methods: Radiological examination volumes during the different waves of infection were compared among each other as well as to time-matched control periods from pre-pandemic years using a locally weighted scatterplot smoothing as well as negative binominal regression models. Results: A total of 1,321,119 radiological examinations were analyzed. Examination volumes were reduced by about 10% over the whole study period (IRR = 0.90; 95% CI 0.89-0.92), with a focus on acute medical care (0.84; 0.83-0.85) and outpatients (0.93: 0.90-0.97). When compared to wave 1, examination volumes were about 17% higher during wave 2 (1.17; 1.10-1.25), and 33% higher in wave 3 of the pandemic (1.33; 1.24-1.42). Conclusions: This study shows the severe effect of COVID-19 pandemic and related shutdown measures on overall provided medical care as measured by radiological examinations. When compared, the decrease of medical care was more pronounced in the earlier waves of the pandemic

Combining Transarterial Radioembolization (TARE) and CT-Guided High-Dose-Rate Interstitial Brachytherapy (CT-HDRBT): A Retrospective Analysis of Advanced Primary and Secondary Liver Tumor Treatment

Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and Methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with Purpose: Treatment of patients with primary and secondary liver tumors remains challenging. This study analyzes the efficacy and safety of transarterial radioembolization (TARE) combined with CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT) for the treatment of primary and secondary liver tumors. Patients and methods: A total of 77 patients (30 female) with various liver malignancies were treated. Primary endpoints were median overall survival (OS) and time to untreatable progression (TTUP). Additionally, subgroup analyses were performed in consideration of diagnosis and procedure sequence. Median OS and TTUP prediction were estimated using Kaplan-Meier analysis and hazard ratios (HR) were calculated using a multivariate Cox proportional hazard model. Results: A total of 115 CT-HDRBT and 96 TARE procedures were performed with no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival.no significant complications recorded. Median OS and TTUP were 29.8 (95% CI 18.1-41.4) and 23.8 (95% CI 9.6-37.9) months. Median OS for hepatocellular carcinoma (HCC)-, cholangiocarcinoma carcinoma (CCA) and colorectal cancer (CRC) patients was 29.8, 29.6 and 34.4 months. Patients starting with TARE had a median OS of 26.0 (95% CI 14.5-37.5) compared to 33.7 (95% CI 21.6-45.8) months for patients starting with CT-HDRBT. Hazard ratio of 1.094 per month was shown for patients starting with CT-HDRBT. Conclusion: Combining TARE and CT-HDRBT is effective and safe for the treatment of advanced stage primary and secondary liver tumors. Our data indicate that early TARE during the disease progression may have a positive effect on survival

Splenic artery steal syndrome in patients with orthotopic liver transplant: Where to embolize the splenic artery?

Purpose: This study compared proximal and distal embolization of the splenic artery (SA) in patients with splenic artery steal syndrome (SAS) after orthotopic liver transplantation (OLT) regarding post interventional changes of liver function to identify an ideal location of embolization. Methods and materials: 85 patients with SAS after OLT treated with embolization of the SA between 2007 and 2017 were retrospectively reviewed. Periinterventional DSA was used to assess treatment success and to stratify patients according to the site of embolization. Liver function was assessed using following laboratory values: bilirubin, albumin, gamma-glutamyl transferase, glutamat-pyruvat-transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), Alkaline Phosphatase (ALP), aPTT, prothrombin time and thrombocyte count. Descriptive statistics were used to summarize the data. Median laboratory values of pre, 1- and 3-days, as well as 1-week and 1-month post-embolization were compared between the respective embolization sites using linear mixed model regression analysis. Results: All procedures were technically successful and showed an improved blood flow in the hepatic artery post-embolization. Ten Patients were excluded due to re -intervention or inconsistent image documentation. Pairwise comparison using linear mixed model regression analysis showed a significant difference between proximal and distal embolization for GPT (57.0 (IQR 107.5) vs. 118.0 (IQR 254.0) U/l, p = 0.002) and GOT (48.0 (IQR 48.0) vs. 81.0 (IQR 115.0) U/l, p = 0.008) 3-days after embolization as well as median thrombocyte counts 7-days after embolization (122 (IQR 108) vs. 83 (IQR 74) in thousands, p = 0.014). For all other laboratory values, no statistically significant difference could be shown with respect to the embolization site. Conclusion: We conclude that long-term outcomes after embolization of the SA in the scenario of SAS after OLT are irrespective of the site of embolization of the SA, whereas a proximal embolization potentially facilitates earlier normalization of liver function. Choice of technique should therefore be informed by anatomical conditions, safety considerations and preferences of the interventionalist

Short- and long-term evaluation of disease-specific symptoms and quality of life following uterine artery embolization of fibroids

Background: The purpose of this study is to evaluate uterine artery embolization (UAE) for the management of symptomatic uterine leiomyomas regarding changes in quality of life after treatment in a large patient collective. This study retrospectively analyzed prospectively acquired standardized questionnaires of patients treated with UAE. Clinical success was evaluated before and after embolization. Patients were stratified into short- (7 months) follow-up groups depending on the time of completion of the post-interventional questionnaire. Uterine leiomyomas were furthermore divided into small (= 10 cm) tumors based on the diameter of the dominant fibroid. Results: A total of 245 patients were included into the final data analysis. The Kaplan-Meier analysis showed a cumulative clinical success rate of 75.8% after 70 months until the end of follow-up (9.9 years). All questionnaire subscales showed a highly significant clinical improvement from baseline to short- and long-term follow-up (p = 10 cm who had a twofold higher probability of re-intervention in the Cox-regression model. Conclusions: UAE is an effective treatment method for symptomatic fibroids that leads to quick relief of fibroid-related symptoms with marked improvement of quality of life and is associated with a low risk for re-interventions. Patients with small fibroids tend to show a better response to UAE compared to patients with large fibroids