The Influence of Maternal Schizotypy on the perception of Facial Emotional Expressions during Infancy: an Event-Related Potential Study.

Parenting directly affects the developmental and clinical outcomes of children. How parental personality relates to perceptual and cognitive mechanisms during early development is not clear. For parents with traits of the personality dimension schizotypy, would their infant display brain responses similar to those on the schizophrenia-spectrum? This study investigates whether maternal personality influences early social-cognitive awareness during the first 6 postnatal months. Schizotypy is a dimension of personality within the general population. If deficits contribute to the development of schizophrenia-spectrum disorders by influencing the development of symptom-like characteristics, they may be observable in neurotypical individuals with schizotypal characteristics. Parents and their infants were shown standardised positive and negative faces and event-related potential responses were assessed. It was hypothesised that the infants of schizotypic mothers would display differential Negative-central event-related potentials for the happy and fearful expressions when compared to infants of non-schizotypic mothers. Results support prior literature; indicating 6-month-old infants allocate more attentional resources to fearful when contrasted to happy faces. The adult cohort displays this same ability. In addition, schizotypic mothers displayed comparable amplitudes for both expressions in comparison to the control mothers who exhibited larger amplitudes towards the fearful compared to the happy expression. Infants of schizotypic mothers did not show a greater sensitivity to facial expressions at 6-months, but schizotypic mothers showed a generalised response towards facial expressions compared to the typical P600 response illustrated by the control mothers. The present study suggests that development in the higher cognitive domains, such as the allocation of attention to novel stimuli, are not affected at 6 months of age by maternal personality related to schizotypy when examined at the group level. Implications for personality development, maternal-infant interactions and cognitive neuroscience methodologies are discussed.

Can probiotics enhance vaccine-specific immunity in children and adults?

The growing use of probiotics by the general public has heightened the interest in understanding the role of probiotics in promoting health and preventing disease. General practitioners and specialists often receive inquiries from their patients regarding probiotic products and their use to ward off systemic infection or intestinal maladies. Enhanced immune function is among the touted health benefits conferred by probiotics but has not yet been fully established. Results from recent clinical trials in adults suggest a potential role for probiotics in enhancing vaccine-specific immunity. Although almost all vaccinations are given during infancy and childhood, the numbers of and results from studies using probiotics in pediatric subjects are limited. This review evaluates recent clinical trials of probiotics used to enhance vaccine-specific immune responses in adults and infants. We highlight meaningful results and the implications of these findings for designing translational and clinical studies that will evaluate the potential clinical role for probiotics. We conclude that the touted health claims of probiotics for use in children to augment immunity warrant further investigation. In order to achieve this goal, a consensus should be reached on common study designs that apply similar treatment timelines, compare well-characterised probiotic strains and monitor effective responses against different classes of vaccines.

A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk.

BACKGROUND: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown. METHODS: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro. RESULTS: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35. CONCLUSION: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not always provide sufficient pain relief in dogs with osteoarthritis (OA). HYPOTHESIS: The use of amantadine in addition to NSAID therapy will provide improved pain relief when compared with the use of nonsteroidal analgesics alone in naturally occurring OA in dogs. ANIMALS: Thirty-one client-owned dogs with pelvic limb lameness despite the administration of an NSAID. METHODS: The study was randomized, blinded, and placebo controlled with parallel groups (days 21-42). On day 0, analgesic medications were discontinued. On day 7, all dogs received meloxicam for 5 weeks. On day 21, all dogs received amantadine (3-5 mg/kg once daily per os) or placebo for 21 days, in addition to receiving meloxicam. Assessments were performed before the study and on days 7, 21, and 42. Primary outcome measures were blinded owner assessments of activity using client-specific outcome measures (CSOM) on days 0, 7, 21, and 42. Data were analyzed by a mixed model approach. RESULTS: For CSOM activity, there was a significant time by treatment effect (P=.009). On the basis of the planned post hoc t-tests of postrandomization means, there was a significant difference between treatment groups on day 42 (P=.030), with the amantadine group being more active. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with osteoarthritic pain refractory to an NSAID, physical activity is improved by the addition of amantadine. Amantadine might be a useful adjunct therapy for the clinical management of canine osteoarthritic pain.

Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action.

Acid-sensing ion channels (ASICs) are activated by a decrease in extracellular pH. ASICs are expressed in nociceptive sensory neurons, and several lines of evidence suggest that they are responsible for signaling the pain caused by extracellular acidification, but little is understood of the modulation of ASICs by pro-inflammatory factors. Using whole-cell patch clamp we demonstrate that low pH evokes three distinct inward currents in rat dorsal root ganglion neurons: a slowly inactivating transient current, a rapidly inactivating transient current, and a sustained current. All three currents were potentiated by arachidonic acid (AA), to 123%, 171%, and 264% of peak current, respectively. Membrane stretch had no effect on proton-gated currents, implying that AA is unlikely to act via local membrane deformation. The current carried by heterologously expressed ASIC1a and ASIC3 was also potentiated by AA. AA potentiates ASIC activation by a direct mechanism, because inhibition of AA metabolism had no effect on potentiation, and potentiation of single ASIC2a channels could be observed in cell-free patches. Potentiation by lipids with the same chain length as AA increased as the number of double bonds was increased. AA is known to be released in inflammation and the results suggest that AA may be an important pro-inflammatory agent responsible for enhancing acid-mediated pain.

Observation of an exotic S = +1 baryon in exclusive photoproduction from the deuteron.

In an exclusive measurement of the reaction gammad-->K(+)K(-)pn, a narrow peak that can be attributed to an exotic baryon with strangeness S=+1 is seen in the K(+)n invariant mass spectrum. The peak is at 1.542+/-0.005 GeV/c(2) with a measured width of 0.021 GeV/c(2) FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is (5.2+/-0.6)sigma. The mass and width of the observed peak are consistent with recent reports of a narrow S=+1 baryon by other experimental groups.

Demographics of aging and skin disease.

What are the dermatologic needs of aging and skin disease in the elderly in the new millennium? This question may be impossible to answer, but predictions may be derived from current sources of data. Data from the US Census Bureau and the National Ambulatory Medical Care Survey are used to characterize current use of dermatologic care in the aging population of the United States and to estimate possible future trends in dermatologic care as the elderly population continues to grow. Dermatologic accompaniments of aging are briefly reviewed, as are issues in health care financing.

Lethality-based selection of recombinant genes in mammalian cells: application to identifying tumor antigens.

Many biological processes result in either cell death or cessation of cell growth. However, plasmid- and retrovirus-based mammalian expression vectors in which it has been possible to construct representative cDNA libraries cannot be readily recovered from cells that are not actively dividing. This has limited the efficiency of selection of recombinant genes that mediate either lytic events or growth arrest. Examples include genes that encode the target antigens of cytotoxic T cells, genes that promote stem-cell differentiation and pro-apoptotic genes. We have successfully constructed representative cDNA libraries in a poxvirus-based vector that can be recovered from cells that have undergone lethality-based selection. This strategy has been applied to selection of a gene that encodes a cytotoxic T-cell target antigen common to several independently derived tumors.

Generation and regeneration of a novel anti-CD8-resistant cytolytic T lymphocyte population.

We recently reported that the in vivo development of a novel CD8(+), but anti-CD8 mAb-resistant, CTL population is complex and distinct from that of conventional anti-CD8 mAb-sensitive CD8(+) CTL. In this study, we explored the role of the thymus in the generation of anti-CD8-resistant pCTL and in their maintenance once they are generated. We also investigated the capacities of the adult periphery and thymus to support the regeneration of anti-CD8-resistant pCTL after peripheral lymphocyte and/or thymocyte depletion. These studies indicate that the thymus is necessary for the generation but not the maintenance of peripheral anti-CD8-resistant pCTL. These studies also indicate that the adult thymus can produce these pCTL and the adult periphery can support their regeneration, if a new wave of thymic maturation is experimentally induced. These results may have implications for immune reconstitution after treatment for cancer or HIV infection.

Polarization of Porphyromonas gingivalis-specific helper T-cell subsets by prior immunization with Fusobacterium nucleatum.

Antigen-specific T-cell clones were obtained from mice immunized with Fusobacterium nucleatum ATCC 10953 and/or Porphyromonas gingivalis 381. 10 BALB/c mice per group were immunized with F. nucleatum followed by P. gingivalis, or with P. gingivalis alone by intraperitoneal injection of viable microorganisms. Spleen T cells were isolated and stimulated in vitro with viable P. gingivalis cells to establish P. gingivalis-specific T-cell clones. T-cell phenotypes and cytokine profiles were determined along with T-cell responsiveness to F. nucleatum or P. gingivalis. Serum immunoglobulin G antibody titers to F. nucleatum or P. gingivalis were also determined by enzyme-linked immunosorbent assay. All the T-cell clones derived from mice immunized with F. nucleatum followed by P. gingivalis demonstrated Th2 subsets, while those from mice immunized with P. gingivalis alone demonstrated Th1 subsets based on the flow cytometric analysis and cytokine profiles. All T-cell clones from both groups were cross-reactive to both P. gingivalis and F. nucleatum antigens. Phenotypes of T-cell clones were all positive for CD4. Mean post-immune serum IgG antibody levels to F. nucleatum or P. gingivalis were significantly higher than the pre-immune levels (P < 0.05, P < 0.01, respectively). There were no significant differences in the antibody titers between the two groups. It was concluded that P. gingivalis-specific T cells initially primed by cross-reactive F. nucleatum antigens were polarized to Th2 subset, while T cells stimulated with P. gingivalis alone maintained the profile of Th1 subset.

Cytokine requirements for production of a novel anti-CD8-resistant CTL population.

A population of CD8+ CTL can be generated in vitro in the presence of anti-CD8 mAb. Due to their apparent high avidity characteristic, these anti-CD8-resistant CD8+ CTL may have important functional in vivo roles in graft rejection, and may be important in antiviral and antitumor responses. We have previously reported that this anti-CD8-resistant subset of CD8+ CTL demonstrates functional differences from anti-CD8-sensitive CD8+ CTL. One important difference between the subsets is the markedly greater dependence of anti-CD8-resistant CTL upon exogenous cytokines for their generation in vitro. In this study, we have investigated in detail the cytokine requirements for the generation of allospecific CD8+ CTL in vitro and have found that IL-4 can augment the generation of anti-CD8-sensitive but not anti-CD8-resistant CTL, whereas IL-2 or IL-12 can augment the generation of both anti-CD8-sensitive and anti-CD8-resistant CTL. However, anti-CD8-resistant CTL require at least 10-fold higher concentrations of IL-2 than do anti-CD8-sensitive CTL. This more stringent IL-2 requirement precludes the efficient generation of anti-CD8-resistant CTL in vitro in the absence of exogenous IL-2 because they cannot produce sufficient IL-2 to meet their needs, in contrast to anti-CD8-sensitive CTL. By providing exogenous cytokines to allospecific CTL generation cultures, we further demonstrate that anti-CD8-resistant CTL can be functionally skewed to the Tc1 subset, but differ from anti-CD8-sensitive conventional CTL in that they cannot be skewed to the Tc2 subset.

Characteristics of office-based visits for skin cancer. Dermatologists have more experience than other physicians in managing malignant and premalignant skin conditions.

BACKGROUND: Actinic keratoses and skin cancer constitute a major public health problem for predisposed individuals. OBJECTIVE: The purpose of this paper is to determine the characteristics of office-based visits for actinic keratoses and skin cancer in the United States. METHODS: The National Ambulatory Medical Care Survey provided data on office-based physician visits for actinic keratoses and skin cancer in 1993 and 1994. RESULTS: There were 3.7 million visits per year for actinic keratoses, 3.1 million visits per year for nonmelanoma skin cancer (NMSC), and 430,000 visits per year for melanoma. Excisions and destructions of lesions accounted for 90%, 67%, and 62% of procedures for actinic keratoses, NMSC, and melanoma, respectively. Dermatologists (683), plastic surgeons (37), and general and family physicians (11) managed more visits per physician per year than other specialists. CONCLUSION: Dermatologists have significantly more experience managing skin cancer than do other physicians.

Nondermatologists are more likely than dermatologists to prescribe antifungal/corticosteroid products: an analysis of office visits for cutaneous fungal infections, 1990-1994.

BACKGROUND: Dermatologists have greater accuracy than nondermatologists for diagnosis of skin disease. However, it is not clear whether this affects medical outcome. OBJECTIVE: We tested the hypothesis that nondermatologists would be more likely than dermatologists to prescribe combination products for the treatment of common fungal skin infections. METHODS: We analyzed office-based physician visits for fungal skin infections recorded in the 1990-1994 National Ambulatory Medical Care Survey. RESULTS: There were 4.1 million visits for cutaneous fungal disease of which 82% were to nondermatologists. Nondermatologists were more likely to prescribe combination agents (34.1%) than dermatologists (4.8%, p=0.001). If the percentage of combination agents used by nondermatologists was reduced to that of dermatologists, an estimated $24.9 million or $10.3 million would be saved if clotrimazole or ketoconazole, respectively, were the substituted drug for the combination agent clotrimazole/betamethasone dipropionate. CONCLUSION: Nondermatologists are more likely to use a more expensive, less effective regimen than are dermatologists, suggesting that dermatologists are more cost-effective than nondermatologists in the treatment of common fungal skin disorders.

Activation requirements, lytic mechanism, and development of a novel anti-CD8-resistant CTL population.

Almost all conventional CD8+ CTL and their CD8+ precursors are inhibited by anti-CD8 mAb. This requirement for CD8 function reflects both an avidity-augmentation role and a signal-transduction role for CD8 on T cells. We have, however, previously identified and partially characterized a novel functional population of CD8+, but anti-CD8-resistant, MHC class I-allospecific CTL. These CTL have unusual activation requirements in that their efficient generation in vitro requires inhibition of the CD8 avidity contribution (but not the CD8 signaling contribution), by anti-CD8 mAb. In this study, we have investigated the relationship of anti-CD8-sensitive and anti-CD8-resistant CTL by several criteria. These CTL populations share the phenotypic markers we have tested to date, they have similar but not identical Ag-specific repertoires, and they both appear to be generated from naive unprimed T cells. However, anti-CD8-sensitive and anti-CD8-resistant CTL populations exhibit important functional differences. They differ in their kinetics of activation in vitro, their dependence on exogenous cytokines, their use of lytic effector mechanisms, and their tissue distribution during ontogeny. Based on these results, we favor the hypothesis that these CTL populations represent distinct T cell lineages or subsets, and not merely different TCR avidity ranges within a single T cell lineage or subset.

Comparative evaluation of six rapid serological tests for HIV-1 antibody.

Six commercial rapid test kits for HIV-1 antibody were evaluated. Four laboratory technologists tested sera from four groups of U.S. military personnel or dependents: 202 subjects positive for HIV-1 antibody by Western blot, 200 seronegative voluntary blood donors, 199 seronegative obstetrics/gynecology patients, and 99 subjects with sera reactive by ELISA but negative by recombinant protein EIA and indeterminate by Western blot. The three tests using solid-phase immunoassay technology demonstrated the highest mean sensitivity (> 99%) and specificity (> 91%) for all groups tested, including sera indeterminate by Western blot. Two dot-immunoblot assays were less specific, possibly due to indistinct reaction end points, and a latex agglutination assay was also less specific because of difficulty distinguishing reactive results from the granular background. In an "ease-of-use" assessment, solid-phase capture immunoassays required less time and equipment and were easier to interpret than other testing methods. Solid-phase capture immunoassays for HIV-1 antibody may be suitable for use in emergency situations and in developing countries because they are highly sensitive and specific and are rapidly performed with minimal laboratory equipment.