Roles of vaccinia virus in the development of new vaccines

Vaccinia virus is an efficient expression vector with broad host range infectivity and large DNA capacity. This vector has been particularly useful for identifying target antigens for humoral and cell-mediated immunity. With increased levels of gene expression, obtained either with stronger vaccinia promoters or through incorporation of the bacteriophage T7 RNA polymerase gene into the vaccinia genome, proteins may be synthesized in mammalian cells for use as subunit vaccines. For use as a live recombinant vaccine, efforts are being made to attenuate vaccinia virus further, either by inactivating genes contributing to virulence or by introducing human lymphokine genes into the vaccinia genome.     

A methodological approach to the classification of dermoscopy images.

In this paper a methodological approach to the classification of pigmented skin lesions in dermoscopy images is presented. First, automatic border detection is performed to separate the lesion from the background skin. Shape features are then extracted from this border. For the extraction of color and texture related features, the image is divided into various clinically significant regions using the Euclidean distance transform. This feature data is fed into an optimization framework, which ranks the features using various feature selection algorithms and determines the optimal feature subset size according to the area under the ROC curve measure obtained from support vector machine classification. The issue of class imbalance is addressed using various sampling strategies, and the classifier generalization error is estimated using Monte Carlo cross validation. Experiments on a set of 564 images yielded a specificity of 92.34% and a sensitivity of 93.33%.     

Metastasizing meningioma

A very unusual case of metastatic spread of a meningioma is described. The clinical presentation was of extradural spinal cord compression, without evidence of a primary tumor. Computed tomography did not reveal any intracranial meningioma; the histopathology of the extradural spinal tumor was identical with that of two intracranial meningiomas previously excised.     

Survival Strategies for Nurse-Midwifery Students

Nurse-midwifery students face multiple stressors in their educational experience. Strategies to resolve stress and promote adaptation to the new role are examined and measures used to promote students' adaptation to the educational experience are described.     

Selective polysaccharide antibody deficiency in familial DiGeorge syndrome.

A family including three children with DiGeorge syndrome is described. One child died in the neonatal period from cardiac anomalies accompanying complete DiGeorge syndrome. The two surviving siblings shared a common set of pharyngeal pouch anomalies and immunodeficiency consistent with partial DiGeorge syndrome, and other morphologic anomalies characteristic of the velocardiofacial syndrome with which familial DiGeorge syndrome is associated (reviewed in reference 1). Both had normal karyotypes. Both presented with recurrent otitis media and sinopulmonary infections, CD4+ T cell lymphopenia, and defective DCH skin test responses to recall T cell antigens. Both had low serum IgM levels and IgG4 levels at the lower limits of normal. Immunization with bacterial polysaccharides resulted in impaired IgG antibody responses to the same set of antigens (H. influenzae polyribophosphate and S. pneumoniae capsular serotypes 9N and 14), while responses to protein antigens were intact. Both siblings were treated successfully with intravenous gamma globulin. The pattern of selective antibody deficiency in these patients with familial DiGeorge syndrome suggests a heritable lesion in certain regulatory antipolysaccharide CD4+ T cell subpopulations.     

Small Conductance Ca2+-Activated K+ Channels Formed by the Expression of Rat SK1 and SK2 Genes in HEK 293 Cells

The rat SK1 gene ( rSK1 ) does not form functional Ca²⁺-activated potassium channels when expressed alone in mammalian cell lines. Using a selective antibody to the rSK1 subunit and a yellow fluorescent protein (YFP) tag we have discovered that rSK1 expression produces protein that remains largely at intracellular locations. We tested the idea that rSK1 may need an expression partner, rSK2, in order to form functional channels. When rSK1 was co-expressed with rSK2 in HEK 293 cells it increased the current magnitude by 77 ± 34 % (as compared with cells expressing rSK2 alone). Co-expression of rSK1 with rSK2 also changed the channel pharmacology. The sensitivity of SK current to block by apamin was reduced ~16-fold from an IC₅₀ of 94 p m (for SK2 alone) to 1.4 n m (for SK2 and SK1 together). The sensitivity to block by UCL 1848 (a potent small molecule blocker of SK channels) was similarly reduced, ~26-fold, from an IC₅₀ of 110 p m to 2.9 n m . These data clearly demonstrate that rSK1 and rSK2 subunits interact. The most likely explanation for this is that the subunits are able to form heteromeric assemblies.     

Susceptibility and amplification of sensitivity in contact dermatitis.

We have examined the hypothesis that people who develop contact allergies to environmental substances do so because they have heightened susceptibility. Analysis of data from 2200 consecutive patients tested with the 20 commonest antigens in a patch-test clinic showed that more people developed multiple contact allergies than would be predicted from the frequency of single allergies; the excess was too great to be explained by chance and increased with number and rarity of the combinations of sensitizers. The possibility that this was due to enhanced individual susceptibility to sensitization rather than concomitant exposure to several sensitizers was confirmed by showing that patients with multiple allergies are more readily sensitized experimentally, and to a greater degree than normal, by dinitrochlorobenzene (DNCB), an unrelated antigen. The defect involves induction rather than expression of sensitivity. Amplification of the response to DNCB is proportional to susceptibility (calculated from the ratio of observed prevalence of multiple allergies to that predicted from the prevalence of single allergies) throughout the range from normal subjects, through those with a single sensitivity, to those with rare, multiple allergies. Therefore, we conclude that individual susceptibility is an important factor in the development of contact dermatitis, and occurs by a non-antigen-specific amplification of immune sensitization.     

Loratadine-pseudoephedrine combination versus placebo in patients with seasonal allergic rhinitis

Two hundred sixty-four patients with moderate to severe seasonal allergic rhinitis were treated with loratadine 5 mg plus pseudoephedrine 120 mg twice a day or placebo in a 28-day multicenter study. Four nasal and four non-nasal symptoms were evaluated for efficacy. At the last evaluable visit, the active treatment group had significantly lower (P = .05) mean combined nasal and non-nasal symptom scores than the placebo group. Also, the physician's rating of overall therapeutic response was significantly better in the active-treatment group (P = .03). Dry mouth, insomnia, and nervousness were reported by a significantly greater proportion (P less than or equal to .04) in the active-treatment group. Sedation occurred in 7% of patients in each treatment group and 6% of patients in each group discontinued the study because of adverse experiences. Loratadine plus pseudoephedrine was safe and significantly more effective than placebo in relieving the symptoms of allergic rhinitis.     

Do semantic categories activate distinct cortical regions? Evidence for a distributed neural semantic system

A key issue in cognitive neuroscience concerns the neural representation of conceptual knowledge. Currently, debate focuses around the issue of whether there are neural regions specialised for the processing of specific semantic attributes or categories, or whether concepts are represented in an undifferentiated neural system. Neuropsychological studies of patients with selective semantic deficits and previous neuroimaging studies do not unequivocally support either account. We carried out a PET study to determine whether there is any regional specialisation for the processing of concepts from different semantic categories using picture stimuli and a semantic categorisation task. We found robust activation of a large semantic network extending from left inferior frontal cortex into the inferior temporal lobe and including occipital cortex and the fusiform gyrus. The only category effect that we found was additional activation for animals in the right occipital cortex, which we interpret as being due to the extra visual processing demands required in order to differentiate one animal from another. We also carried out analyses in specific cortical regions that have been claimed to be preferentially activated for various categories, but found no evidence of any differential activation as a function of category. We interpret these data within the framework of cognitive accounts in which conceptual knowledge is represented within a nondifferentiated distributed system.