Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara

Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals.     

Extrapulmonary effects of maintenance therapy with theophylline and inhaled albuterol in patients with chronic asthma

The extrapulmonary effects of slow-release theophylline and an inhaled beta 2-agonist (albuterol) were examined separately and in combination among 18 adults and adolescents with asthma during a 3-month randomized, double-blind, crossover trial. Although neither global impressions nor daily diaries revealed differences in adverse effects, a structured questionnaire completed at the end of each regimen suggested a small but statistically significant increase in nausea and depressive and caffeine-like symptoms during the theophylline-containing regimens. Theophylline was also associated with improved verbal learning but decreased motor steadiness. Metabolic effects associated with theophylline included lower serum bicarbonate, greater urinary calcium excretion, and higher serum calcium, uric acid, and creatinine. Albuterol was associated with lower neutrophil counts and lower serum theophylline concentrations. There were no drug-induced effects on cardiac rhythm.     

One-way positive cellular reactions between two HLA-A, B, C, D/DR genotypically identical brothers following active allogeneic immunization

The HLA-D/DR region in man encodes major determinants which stimulate T lymphocytes to proliferation. The genetic organization of this region is apparently complex and is at present largely unknown. One obstacle is the scarcity and quality of available typing reagents. In an attempt to obtain high quality anti-DR sera, a series of active immunizations was performed between highly selected, healthy unrelated donors and recipients.
One recipient (AR8) was immunized using cells incompatible for HLA-A2, B40 (w60), Cw3 and DIDRw6 and readily developed anti-A2 and B40 antibodies but no anti-C, DR, or other antibodies. When tested against his HLA genotypically fully identical brother using the cellular MLC, PLT, or CML techniques before immunization, results were mutually negative as expected. Following immunization, however, AR8 was able to mount MLC, PLT, and possibly CML responses against lymphocytes from the brother while the reverse combinations remained negative. When tested in the family the trait(s) thus identified seems to be maternally inherited.
These results suggest the existence of minor histocompatibility determinants encoded from regions not closely linked to HLA. The brother of AR8 and the immunizing donor thus seem to share one or more determinants not possessed by AR8.     

Laminar distribution and morphology of NADPH-diaphorase containing neurons in the superior colliculus and underlying periaqueductal gray of the rat

Summary We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d-negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d-positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme.     

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease)

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30–20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG light-rise potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of non-invasive diagnosis.     

Epidemiologische Ansätze zur Klärung wichtiger Forschungsfragen zu COVID-19 – eine Übersicht

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Die Epidemiologie als wissenschaftliche Disziplin ist prädestiniert dafür, Kernfragen der COVID-19-Pandemie zu...     

Distal rectus femoris surgery in children with cerebral palsy: results of a Delphi consensus project

PurposeThe purpose of this study was for an international panel of experts to establish consensus indications for distal rectus femoris surgery in children with cerebral palsy (CP) using a modified Delphi method.MethodsThe panel used a five-level Likert scale to record agreement or disagreement with 33 statements regarding distal rectus femoris surgery. The panel responded to statements regarding general characteristics, clinical indications, computerized gait data, intraoperative techniques and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert ratings, and general agreement as 60% to 79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached.ResultsConsensus or general agreement was reached for 17 of 33 statements (52%). There was general consensus that distal rectus femoris surgery is better for stiff knee gait than is proximal rectus femoris release. There was no consensus about whether the results of distal rectus femoris release were comparable to those following distal rectus femoris transfer. Gross Motor Function Classification System (GMFCS) level was an important factor for the panel, with the best outcomes expected in children functioning at GMFCS levels I and II. The panel also reached consensus that they do distal rectus femoris surgery less frequently than earlier in their careers, in large part reflecting the narrowing of indications for this surgery over the last decade.ConclusionThis study can help paediatric orthopaedic surgeons optimize decision-making for, and outcomes of, distal rectus femoris surgery in children with CP.Level of evidenceV