Two-Dimensional Laser Diagnostics and Modeling of Counterflow Diffusion Flames

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86756/1/Sick51.pd

Spectroscopy of free radicals and radical containing entrance-channel complexes in superfluid helium nano-droplets

The spectroscopy of free radicals and radical containing entrance-channel complexes embedded in superfluid helium nano-droplets is reviewed. The collection of dopants inside individual droplets in the beam represents a micro-canonical ensemble, and as such each droplet may be considered an isolated cryo-reactor. The unique properties of the droplets, namely their low temperature (0.4 K) and fast cooling rates ($\sim10^{16}$ K s$^{-1}$) provides novel opportunities for the formation and high-resolution studies of molecular complexes containing one or more free radicals. The production methods of radicals are discussed in light of their applicability for embedding the radicals in helium droplets. The spectroscopic studies performed to date on molecular radicals and on entrance / exit-channel complexes of radicals with stable molecules are detailed. The observed complexes provide new information on the potential energy surfaces of several fundamental chemical reactions and on the intermolecular interactions present in open-shell systems. Prospects of further experiments of radicals embedded in helium droplets are discussed, especially the possibilities to prepare and study high-energy structures and their controlled manipulation, as well as the possibility of fundamental physics experiments.Comment: 25 pages, 12 figures, 4 tables (RevTeX

Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

<div><p>Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.</p></div

CVID-Associated B Cell Activating Factor Receptor Variants Change Receptor Oligomerization, Ligand Binding, and Signaling Responses.

Binding of the B cell activating factor (BAFF) to its receptor (BAFFR) activates in mature B cells many essential pro-survival functions. Null mutations in the BAFFR gene result in complete BAFFR deficiency and cause a block in B cell development at the transition from immature to mature B cells leading therefore to B lymphopenia and hypogammaglobulinemia. In addition to complete BAFFR deficiency, single nucleotide variants encoding BAFFR missense mutations were found in patients suffering from common variable immunodeficiency (CVID), autoimmunity, or B cell lymphomas. As it remained unclear to which extent such variants disturb the activity of BAFFR, we performed genetic association studies and developed a cellular system that allows the unbiased analysis of BAFFR variants regarding oligomerization, signaling, and ectodomain shedding. In addition to genetic association studies, the BAFFR variants P21R, A52T, G64V, DUP92-95, P146S, and H159Y were expressed by lentiviral gene transfer in DG-75 Burkitt's lymphoma cells and analyzed for their impacts on BAFFR function. Binding of BAFF to BAFFR was affected by P21R and A52T. Spontaneous oligomerization of BAFFR was disturbed by P21R, A52T, G64V, and P146S. BAFF-dependent activation of NF-κB2 was reduced by P21R and P146S, while interactions between BAFFR and the B cell antigen receptor component CD79B and AKT phosphorylation were impaired by P21R, A52T, G64V, and DUP92-95. P21R, G64V, and DUP92-95 interfered with phosphorylation of ERK1/2, while BAFF-induced shedding of the BAFFR ectodomain was only impaired by P21R. Although all variants change BAFFR function and have the potential to contribute as modifiers to the development of primary antibody deficiencies, autoimmunity, and lymphoma, P21R is the only variant that was found to correlate positively with CVID

Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group

Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1–12 months for adult patients and every 3–6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients

Case series: convalescent plasma therapy for patients with COVID-19 and primary antibody deficiency

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding

Cerebral involvement in a patient with Goodpasture's disease due to shortened induction therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Goodpasture's disease is a rare immunological disease with formation of pathognomonic antibodies against renal and pulmonary basement membranes. Cerebral involvement has been reported in several cases in the literature, yet the pathogenetic mechanism is not entirely clear.</p> <p>Case presentation</p> <p>A 21-year-old Caucasian man with Goodpasture's disease and end-stage renal disease presented with two generalized seizures after a period of mild cognitive disturbance. Blood pressure and routine laboratory tests did not exceed the patient's usual values, and examination of cerebrospinal fluid was unremarkable. Cerebral magnetic resonance imaging (MRI) revealed multiple cortical and subcortical lesions on fluid-attenuated inversion recovery sequences. Since antiglomerular basement membrane antibodies were found to be positive with high titers, plasmapheresis was started. In addition, cyclophosphamide pulse therapy was given on day 13. Encephalopathy and MRI lesions disappeared during this therapy, and antiglomerular basement membrane antibodies were significantly reduced. Previous immunosuppressive therapy was performed without corticosteroids and terminated early after 3 months.</p> <p>The differential diagnostic considerations were cerebral vasculitis and posterior reversible encephalopathy syndrome. Vasculitis could be seen as an extrarenal manifestation of the underlying disease. Posterior reversible encephalopathy syndrome, on the other hand, can be triggered by immunosuppressive therapy and may appear without a hypertensive crisis.</p> <p>Conclusion</p> <p>A combination of central nervous system symptoms with a positive antiglomerular basement membrane test in a patient with Goodpasture's disease should immediately be treated as an acute exacerbation of the disease with likely cross-reactivity of antibodies with the choroid plexus. In our patient, a discontinuous strategy of immunosuppressive therapy may have favored recurrence of Goodpasture's disease.</p