Brown and Eccles'' Depiction of Vagal Effects: An Old and Widely Used Method Reexamined

It can be shown that the procedure for representing the effect of the vagal innervation of the heart introduced by Brown and Eccles in 1934 distorts the actual course of the inhibitory effect. A corrected procedure is proposed. It is stressed that cycle phase specificity of the stimulation can be studied only by drawing different curves representing the course of the vagal effect for different times of stimulation within the cardiac cycle.     

Perceptual Performance as a Function of Intra-Cycle Cardiac Activity

The purpose of the experiment was to test the hypothesis of a systematic change in perceptual performance within a single cardiac cycle due to the activity of the baroreceptors in carotid sinus. As an index of perceptual performance the d_s-parameter from signal detection theory (TSD) was used. A 1000 Hz sine tone had to be detected in a background of white noise. Each of 4 subjects received on the average 4605 noise or noise plus tone stimuli distributed over 10 experimental sessions. When comparing performance during time intervals before and after baroreceptor activity onset no significant difference was found. Also, when tracing perceptual performance over the whole cardiac cycle in steps of 66,100, and 200 msec, no systematic variation could be detected. For steps of 33 msec a rhythmic pulsation of perceptual performance of about 8 Hz appeared. An influence of electrical activity of the brain on perceptual performance was postulated. This activity would have to be time-locked to carotid sinus baroreceptor activity.     

Improvements in Gene Therapy

Gene therapy is an interesting approach for the correction of defective genes, the treatment of cancer and the introduction of immunomodulatory genes. Various techniques for gene transfer into cells or tissues have been developed within the last decade; these can be divided generally into viral and nonviral gene transfer systems. Nonviral techniques include the liposome- or gene gun-mediated introduction of therapeutic genes; however, the efficiency of gene transfer by these applications is still very low. In contrast, viruses have optimised their strategies for efficient infection of virtually any cell type in a mammalian organism. The genetic modification of genomes from different virus families (Adenoviridae, Retroviridae, Herpesviridae) led to the development of gene therapy vectors with a similar capacity to infect cells or tissues as that of wild type viruses. In contrast to wild type viruses, gene therapy vectors are engineered to transfer therapeutic genes into the target cells or tissues. In addition, they have lost their capacity for replication in target cells, because of the removal of essential genes, which allows replication only in specialised packaging cell lines engineered for the production of recombinant viruses. Despite considerable progress over the past decade in the generation of gene transfer systems with reduced immunogenic properties, the remaining immunogenicity of many gene therapy vectors is still the major hurdle, preventing their frequent application in clinical trials. Recombinant adenoviruses have been shown to be promising vectors for gene therapy, since they are able to transduce both quiescent and proliferating cells very efficiently. However, a major disadvantage of adenoviral vectors lies in the activation of both the innate and adaptive parts of the recipient's immune system when applied in vivo. The inflammatory responses induced by adenovirus particles can be very strong and can be fatal in patients treated with these adenoviral constructs. Therefore, many experiments have been performed in the effort to prevent these inflammatory responses mediated by adenoviral particles. The depletion of cell populations responsible for these inflammatory responses as well as the application of immunosuppressive drugs have been investigated. Moreover, the generation of less immunogenic adenoviral vectors by further genetic modification within the adenoviral genome has led to vectors with reduced immunogenic properties. Both strategies to reduce inflammatory responses against adenoviral particles are discussed in this review.     

Detection and identification of fungi from fungus balls of the maxillary sinus by molecular techniques

The aim of this study was to find a reliable method for the detection and identification of fungi in fungus balls of the maxillary sinus and to evaluate the spectrum of fungi in these samples. One hundred twelve samples were obtained from patients with histologically proven fungal infections; 81 samples were paraffin-embedded tissue sections of the maxillary sinus. In 31 cases, sinus contents without paraffin embedding were sent for investigation. PCR amplification with universal fungal primers for 28S ribosomal DNA and amplicon identification by hybridization with species-specific probes for Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus glaucus, Pseudallescheria boydii, Candida albicans, and Candida glabrata were performed for all samples. Furthermore, PCR products were sequenced. Fresh samples were also cultivated. Fungal DNA was detected in all of the fresh samples but only in 71 paraffin-embedded tissue samples (87.7%). Sequence analysis was the most sensitive technique, as results could be obtained for 28 (90.3%) fresh samples by this method in comparison to 24 (77.4%) samples by hybridization and 16 (51.6%) samples by culture. However, sequence analysis delivered a result for only 36 (50.7%) of the paraffin-embedded specimens. Hybridization showed reliable results for A. fumigatus, which proved to be the most common agent in fungus balls of the maxillary sinus. Other Aspergillus species and other genera were rarely found.     

Depressive symptoms and disability in acute and chronic back pain patients

Depression and level of disability are evaluated in acute and chronic low back pain (LBP) patients. To assess the possibility that some somatic symptoms are confounded with pain, the items of the Beck Depression Inventory arc divided into a cognitive-affective and somatic subscale. The sample consisted of 37 chronic LBP patients. 41 acute LBP patients, and 28 healthy participants. The level of disability was assessed by the Oswestry Low Back Pain Disability Questionnaire. Chronic LBP patients, but not acute LBP patients, have more depressive symptoms than controls. Additionally, chronic LBP patients report more somatic symptoms of depression (e.g.. emo ltional and self disturbance complaints) than cognitive-affective symptoms. Finally, correlation statistics reveal significant relations between the level of disability and depression scores. Whereas chronic patients show a significant correlation between the somatic subscale and level of disability, in acute patients the cognitive-affective subscale is significantly related to the level of disability. The findings suggest careful consideration of whether somatic symptoms of depression are related to pain when using self-report measurements of depression in pain patients. The separation of cognitive-affective and somatic symptoms of depression to evaluate pain problems seems appropriate.     

Studies with a pathogenic and an attenuated strain of Venezuelan equine encephalitis virus and aedes aegypti (L.) mosquitoes

Summary Venezuelan equine encephalitis virus was passaged in KB cell cultures. The virus lost its mouse pathogenicity following subcutaneous inoculation during KB cell passage; the attenuated strain also produced smaller plaques than the pathogenic strain. Both strains grew to the same extent inAedes aegypti (L.) mosquitoes after intrathoracic inoculation. If any reversions to pathogenicity occur during development of the attenuated virus in mosquitoes, then the mutation frequency per duplication per particle must be smaller than 3.5×10^–6.     

Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella Enteritidis

Induction of the interleukin-12 (IL-12) cytokine family comprising IL-12, IL-23, IL-27, and IL-12p40 by intracellular pathogens is required for orchestration of cell-mediated immune responses. Macrophages (MΦ) have been shown to be a source of IL-12 following TLR4-dependent activation by Salmonella (S.). In this study another antigen-presenting cell type, the conventional dendritic cell (cDC), was analyzed and its cytokine responses compared with those of MΦ. We generated bone marrow-derived conventional dendritic cells (BMDC) and macrophages (BMMΦ) by incubating murine bone marrow cells with supernatants containing granulocyte/macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. Stimulation of BMDC and BMMΦ with S. enterica serovar Enteritidis (SE) or LPS resulted in the release of IL-12 and IL-23 by BMDC but not by BMMΦ. Furthermore, BMDC secreted approx. 20-fold more IL-12p40 and IL-27p28 than BMMΦ. However, BMDC and BMMΦ produced similar levels of IL-10. Using BMDC originating from wild-type (wt), TLR2^def and TLR4^def mice, we show that in BMDC the induction of IL-12, IL-23, and IL-27p28 by SE is dependent on TLR4, whereas low-level production of p40 is also mediated by pattern recognition receptors (PRR) other than TLR4. Interestingly, LPS- and SE-provoked responses of BMDC were remarkably similar indicating that LPS is the primary danger molecule of SE. Taken together, our results point to cDC rather than MΦ as the major producers of the IL-12 family members during in vitro infection with SE. The mechanisms of recognition of SE, however, appear to be the same for cDC and MΦ     

Radiopharmacokinetics and radiation dose from 99mTc-HM-PAO (Preliminary report)

Whole body retention measurements were performed in volunteers after i.v. injection of ^99mTc-HM-PAO (Ceretec^®). The organ accumulation was measured in mice and data were transferred to standard man according to ICRP. Absorbed dose calculations were made with these data by using the concept of absorbed fractions (MIRD method). In man, the whole body retention and the retention in the brain could be calculated by direct measurement, absorbed doses to the other organs could only be derived from animal data. The absorbed dose to the brain derived from human data (10.3 Gy/MBq) is greater by a factor of 2 than that derived from animal data. The highest absorbed dose was received by the thyroid (24.4 Gy/MBq), the absorbed dose to the ovaries, testes and whole body ranged from 2.8 to 4.2 Gy/MBq.Dedicated to Professor Dr. Guenter Liess on the occasion of his 65th anniversary     

Liver transplantation in a patient after COVID-19 – Rapid loss of antibodies and prolonged viral RNA shedding

To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA.