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.     

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.     

Highly Methylated 6-Hydroxyflavones and Other Flavonoids from Thymus piperella

From the aerial parts of THYMUS PIPERELLA, the free flavone aglycones 5,6-dihydroxy-7,8,4'-trimethoxyflavone ( 1), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone ( 2), 5,6-dihydroxy-7,3',4'-trimethoxyflavone ( 3), ladanein ( 4) (5,6-dihydroxy-7,4'-dimethoxy-flavone), 5-hydroxy-7,4'-dimethoxyflavone ( 5) and apigenin ( 6), the flavanones naringenin ( 7) and eriodictyol ( 8), and the flavone glycosides vicenin-2 ( 9), apigenin-7- O-beta- D-glucoside (10) and luteolin-7- O-beta- D-glucoside ( 11), have been isolated and identified. This is the first time that 5,6-dihydroxy-7,8,4'-trimethoxyflavone has been found as a natural product.     

Development and Measurement of the Treatment Perceptions Survey (TPS) for Clients with Substance Use Disorders

The Journal of Behavioral Health Services & Research - Statistical reliability of the Treatment Perceptions Survey (TPS) questionnaire was examined using data from 19 California counties. The...     

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.     

The Effect of Functional Pelvic Tilt on the Three-Dimensional Acetabular Cup Orientation in Total Hip Arthroplasty Dislocations

BackgroundAnterior and posterior pelvic tilt appears to play a role in total hip arthroplasty (THA) stability. When changing from the standing to the sitting position, the pelvis typically rotates posteriorly while the hips flex and this affects the femoro-acetabular positions. This case-control study compares changes in 3-D acetabular cup orientation during functional pelvic tilt between posterior THA dislocations vs stable THAs.MethodsStanding and sitting 3-D cup orientation was compared between fifteen posterior dislocations vs 233 prospectively followed stable THAs. 3-D cup orientation was calculated using previously validated trigonometric algorithms on biplanar radiographs. Those algorithms combine the angles in the three anatomical planes (coronal inclination, transverse version, and sagittal ante-inclination) in the standing position with the change in sagittal pelvic tilt from standing to sitting to calculate the 3-D orientation in the sitting position.ResultsThe standing cup orientation of the dislocated THAs was only characterized by a lower coronal inclination (P = .039). Compared with the controls, from standing to sitting, they showed less posterior pelvic tilt (P < .001). This led to a significant lower coronal inclination (P < .001) and sagittal ante-inclination (P < .001) in the sitting position but similar transverse version (P = .366).ConclusionsComparing posterior THA dislocations to stable THAs, there is a lower increase of all three orientation angles from standing to sitting. This leads to a decreased sitting coronal inclination and sagittal ante-inclination which may lead to an increased risk of impingement ensued by THA instability. By contrast, the transverse version was not significantly different in both positions. This confirms the importance of biplanar data on functional cup orientation.Level of EvidenceDiagnostic, Level III.