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The inhibitory activity of peripheral blood lymphocytes on autologous bone marrow was studied in 27 patients with aplastic anaemia after treatment with androgen. Inhibitory activity was hard to assess in 10 patients studied during the first year of treatment. The colony count was too low to be certain of differences between the samples incubated with or without lymphocytes. Among the 17 patients who had more than 10 colonies per 2 x 10(5) mononuclear bone marrow cells, nine showed inhibitory activity by peripheral blood lymphocytes. After 12 months of androgen therapy each of these patients showing inhibitory activity of bone marrow colony forming cells by peripheral lymphocytes responded to antithymocyte globulin. None of nine patients with few colony forming cells or no inhibitory activity of lymphocytes responded to immunosuppression. [ABSTRACT FROM PUBLISHER]

The cytological and electron-microscopic appearance of aneutrophil phagocytosis by macrophages in normal human bone marrow is described. This feature can be observed in every normal bone marrow and is especially frequent in autoimmune disease. Bone marrrow phagocytosis of polymorphonuclear neutrophils seems to be a physiological process resulting from the random egress of neutrophils from bone marrow to blood. [ABSTRACT FROM PUBLISHER]

The cellular composition of the granulocytic series in normal human bone marrow was studied in aspirates of different volume. An increase in the proportion of polymorphonuclears was observed in samples of more than 1 ml, thus indicating a dilution of bone marrow by peripheral blood. Certain data from the literature, referring to the differential count in the bone marrow granulocytic series, are discussed. The differences between these data can be explained by the dilution of bone marrow cells by mature granulocytes in blood. [ABSTRACT FROM PUBLISHER]

Background: Allergic diseases are among the most common chronic diseases in childhood. Early childhood allergy prevention (ECAP) behaviors of those caring for the infant during pregnancy and the first months of life may influence the risk of allergy development over the life course. Motivation and intention to use appropriate primary ECAP measures are thus of critical importance., Aims: To characterize parental ECAP motivation, (a) valid indicators will be developed and (b) typical parental characteristics will be identified. (c) According to socio-cognitive models, the predictive value of parental risk perception, control belief and self-efficacy for parental ECAP motivation shall be determined., Method: A sample of N = 343 (expectant) mothers of infants completed a questionnaire on self-reported ECAP motivation, risk perception, control belief, and self-efficacy. The cross-sectional data were analyzed using latent class analysis and structural equation modelling including nominal regression models., Results: Four typical maternal response profiles (motivated to a customary degree, 70%; motivated to use primary preventive measures, 17.8%; reluctant towards new prevention measures, 6.4%; highly motivated to apply preventive measures in case of an existing allergy, 5.8%) could be identified for the items on ECAP motivation. After splitting the model variables "risk perception" (allergy vs. allergy-associated general health problems) and "self-efficacy" (trust vs. insecurity) a satisfactory model-fit was achieved (CFI = .939; RMSEA = .064). Particularly, increased "risk perception-allergy" (OR = 1.655) and "self-efficacy-insecurity" (OR = 2.013) as well as lower "risk perception-general health" (OR = 0.555) and "control belief" (OR = 0.217), respectively, are associated with higher ECAP motivation., Conclusion: The use of ECAP-measures by parents to protect their newborns from allergies is important, but there are deficiencies in their implementation. Based on a social cognitive model approach, predictive characteristics could be identified, which are associated with increased motivation to implement ECAP-measures. For public health our findings provide a promising basis for conception of behavioral and environmental ECAP prevention measures and their motivated implementation by parents., (© 2024. The Author(s).)

Background: Mobile health (mHealth) tools were developed during the past decades and are increasingly used by patients in cancer care too. Scientific research in the development of mHealth services is required in order to meet the various needs of patients and test usability., Objective: The aim of this study is to assess patients' needs, preferences, and usability of an app (My University Clinic [MUC] app) developed by the Comprehensive Cancer Center Freiburg (CCCF) Germany., Methods: Based on a qualitative cross-sectional approach, we conducted semistructured interviews with patients with cancer, addressing their needs, preferences, and usability of the designed MUC app. Patients treated by the CCCF were recruited based on a purposive sampling technique focusing on age, sex, cancer diagnoses, and treatment setting (inpatient, outpatient). Data analysis followed the qualitative content analysis according to Kuckartz and was performed using computer-assisted software (MAXQDA)., Results: For the interviews, 17 patients with cancer were selected, covering a broad range of sampling parameters. The results showed that patients expect benefits in terms of improved information about the disease and communication with the clinic staff. Demands for additional features were identified (eg, a list of contact persons and medication management). The most important concerns referred to data security and the potential restriction of personal contacts with health care professionals of the clinical departments of the CCCF. In addition, some features for improving the design of the MUC app with respect to usability or for inclusion of interacting tools were suggested by the patients., Conclusions: The results of this qualitative study were discussed within the multidisciplinary team and the MUC app providers. Patients' perspectives and needs will be included in further development of the MUC app. There will be a second study phase in which patients will receive a test version of the MUC app and will be asked about their experiences with it., Trial Registration: Deutsches Register Klinischer Studien DRKS00022162; https://drks.de/search/de/trial/DRKS00022162., (©Joachim Weis, Lucy Raphaela Wolf, Melanie Boerries, Daniela Kassahn, Martin Boeker, Carolin Dresch. Originally published in JMIR Cancer (https://cancer.jmir.org), 27.07.2023.)

Background: Ensuring motivated and successful study participation is a key challenge in the design and conduct of health research studies. Previously, recruitment barriers and facilitators have been identified mainly from experience, and rarely based on theoretical approaches. We developed a framework of intentional and actional components of engaged participation in public health research studies (INTACT-RS), informed by psychological behavioral models. We aimed a) to identify precise indicators for each framework component and b) to better understand which components and decision processes are essential for study participants., Methods: Within a multicenter research network, we applied various approaches to recruit parents of newborns, pediatricians, and midwives. All recruitment processes were documented from the perspective of both participants and researchers. We used different qualitative and quantitative data material, which we applied in a multistage process according to the basic principles of qualitative content analysis., Results: INTACT-RS encompasses pre-intentional, intentional and actional phases with a total of n = 15 components covering all aspects of an individual's involvement with a research study. During intention formation, an understanding of efforts and benefits, why participation is valuable beyond contributing to research, and how others perceive the study, were particularly important to (potential) participants. Subsequently (intentional phase), participants consider how and when participation is compatible with their own resources, ability and availability, and hence seek for close communication with, and flexibility and support from the research team. During and after (initial) participation (actional phase), participants' assessment of whether expectations and interests have been met impact crucial further steps, especially the willingness to continue and to recommend participation to others. A strong topic-wise and or supportive participation interest as well as active, continuous exchange with the researchers appeared to be central determinants of study completion and data validity., Conclusions: A theoretical framework is now available to plan and conduct recruitment of different target groups, which accounts for essential motivational and volitional decision-making processes. Based on empirically specified constructs, possible barriers can be addressed even before the initial recruitment process. Therefore, recommendations for scientific practice have been formulated., (© 2023. The Author(s).)

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals.

Delivering antigens in vivo by coupling them to mAbs specific for unique receptors on antigen-presenting cells (APCs) is a promising approach for modulating immune responses. Antigen delivery to receptors found on myeloid dendritic cell (DC) subsets, plasmacytoid DCs and B cells has shown them all to be viable targets to stimulate either the cellular or humoral arms of the immune system. It is now evident that antigen-targeting approaches can also be used to invoke antigen-specific inhibition of immune responses. The outcome of activation versus inhibition is determined by a combination of factors that include the choice of APC, the receptor that is targeted, whether to include an adjuvant and, if so, which adjuvant to employ. In addition to their use as a means to modulate immune responses, antigen-targeting systems are also a useful method to investigate the function of DC subsets and the early mechanistic events that underlie the initiation of both cellular and humoral immune responses. In this review, we focus on the literature surrounding the control of B-cell responses when antigen is delivered to various APC subsets.

Virus-like particles (VLPs) are promising vaccine candidates because they represent viral antigens in the authentic conformation of the virion and are therefore readily recognized by the immune system. As VLPs do not contain genetic material they are safer than attenuated virus vaccines. In this study, herpes simplex virus type 1 (HSV-1) amplicon vectors were constructed to coexpress the rotavirus (RV) structural genes VP2, VP6, and VP7 and were used as platforms to launch the production of RV-like particles (RVLPs) in vector-infected mammalian cells. Despite the observed splicing of VP6 RNA, full-length VP6 protein and RVLPs were efficiently produced. Intramuscular injection of mice with the amplicon vectors as a two-dose regimen without adjuvants resulted in RV-specific humoral immune responses and, most importantly, immunized mice were partially protected at the mucosal level from challenge with live wild-type (wt) RV. This work provides proof of principle for the application of HSV-1 amplicon vectors that mediate the efficient production of heterologous VLPs as genetic vaccines.

Adeno-associated virus (AAV) has previously been shown to inhibit the replication of its helper virus herpes simplex virus type 1 (HSV-1), and the inhibitory activity has been attributed to the expression of the AAV Rep proteins. In the present study, we assessed the Rep activities required for inhibition of HSV-1 replication using a panel of wild-type and mutant Rep proteins lacking defined domains and activities. We found that the inhibition of HSV-1 replication required Rep DNA-binding and ATPase/helicase activities but not endonuclease activity. The Rep activities required for inhibition of HSV-1 replication precisely coincided with the activities that were responsible for induction of cellular DNA damage and apoptosis, suggesting that these three processes are closely linked. Notably, the presence of Rep induced the hyperphosphorylation of a DNA damage marker, replication protein A (RPA), which has been reported not to be normally hyperphosphorylated during HSV-1 infection and to be sequestered away from HSV-1 replication compartments during infection. Finally, we demonstrate that the execution of apoptosis is not required for inhibition of HSV-1 replication and that the hyperphosphorylation of RPA per se is not inhibitory for HSV-1 replication, suggesting that these two processes are not directly responsible for the inhibition of HSV-1 replication by Rep.

Butoxamine, a beta 2-adrenergic blocking agent, which temporarily blocks the G1-S transition of human bone marrow granulocyte precursors in vitro, was used in vivo together with 1-beta-D-arabinofuranosylcytosine (ara-C) in mice. Butoxamine alone depressed the granulocyte labeling index and granulocyte-monocyte colony-forming Cell (GM-CFC) suicide rate at a dose of 3 micrograms/g body weight. A maximum effect was produced 6 to 12 hr after injection. Butoxamine administered 8 hr before an injection of ara-C modified the proportion of GM-CFC in S phase as compared with the number found after ara-C alone. After a series of five ara-C injections, administered at intervals of 16 hr, 70% of the treated mice died within 2 weeks, whereas only 42% of mice pretreated with butoxamine 7 to 9 hr before each ara-C injection died. This difference was due to the more rapid return to normal of GM-CFC numbers and an increase in the proportion of GM-CFC and granulocyte precursors in S phase in the butoxamine-pretreated animals. These findings suggest that butoxamine may have a potential use in protecting hematopoiesis during intensive chemotherapy for cancer.