Psychiatric disorders in adolescents and adults with autism and intellectual disability: A representative study in one county in Norway

Few studies assess psychiatric disorders in representative samples of individuals with autism and ID. Symptoms of autism and psychiatric disorders have been confounded. PAC, a conceptually analysed and validated screening instrument, was used.AimsAssess prevalence of psychiatric disorders in individuals with intellectual disability only (ID-only) and with combination of autism and ID (autism). Sixty-two (autism) and 132 (ID-only) participants were screened for psychiatric disorders with the Psychopathology in Autism Checklist (PAC); included general adjustment problems (GAP), and severe adjustment problems (SGAP) in one county in Norway. Psychosis, depression, anxiety, and OCD were addressed. Both SGAP and a high psychiatric disorder score were required to screen a psychiatric disorder. “Diagnostic overlap” was defined as more than one psychiatric disorder concurrent with autism.Psychiatric disorders and SGAP were found to be high both in the autism (53.2%) and ID-only group (17.4%). More than 50% of the autism and approximately 20% of ID-only group had SGAP. The differences were significant. The autism–psychiatric disorder interaction was significant. The largest differences between the prevalence in the autism and the ID-only group were shown in individuals with anxiety. The majority of the individuals in both study groups were afflicted with more than one psychiatric disorder. About 60% were found to have more than one disorder. The individuals with more severe psychiatric symptoms had higher degrees of diagnostic overlap. Having an intellectual disability seem to imply high risk for developing adjustment problems, and it seems especially difficult for individuals with autism to master every-day challenges.     

Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ

E7 is the major oncoprotein of high-risk human papillomaviruses (HPV) which causes cervical cancer. To date E7 oncoproteins have not been investigated in cervical adenocarcinoma. In this study we generated a rabbit monoclonal anti-HPV-16 E7 antibody, RabMab42-3, which recognizes a conformational epitope in the E7 carboxy-terminal zinc-finger resulting in a strong increase in the sensitivity for the detection of cell-associated HPV-16 E7 protein relative to conventional polyclonal anti-HPV-16 E7 antibodies. Using RabMab42-3, we show that the subcellular localization of endogenous HPV-16 E7 oncoprotein varies during the cell cycle in cervical cancer cells. Moreover, we demonstrate for the first time that the HPV-16 E7 oncoprotein is abundantly expressed in cervical adenocarcinoma in situ and adenocarcinoma, suggesting an important role of HPV-16 E7 for the development of these tumors. Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors.     

Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy

Light and heat distributions are measured in a rat glioma model used in photodynamic therapy. A fiber delivering 632-nm light is fixed in the brain of anesthetized BDIX rats. Fluence rates are measured using calibrated isotropic probes that are positioned stereotactically. Mathematical models are then used to derive tissue optical properties, enabling calculation of fluence rate distributions for general tumor and light application geometries. The fluence rates in tumor-free brains agree well with the models based on diffusion theory and Monte Carlo simulation. In both cases, the best fit is found for absorption and reduced scattering coefficients of 0.57 and 28 cm(-1), respectively. In brains with implanted BT(4)C tumors, a discrepancy between diffusion and Monte Carlo-derived two-layer models is noted. Both models suggest that tumor tissue has higher absorption and less scattering than normal brain. Temperatures are measured by inserting thermocouples directly into tumor-free brains. A model based on diffusion theory and the bioheat equation is found to be in good agreement with the experimental data and predict a thermal penetration depth of 0.60 cm in normal rat brain. The predicted parameters can be used to estimate the fluences, fluence rates, and temperatures achieved during photodynamic therapy.     

CD95 ligand expression as a mechanism of immune escape in breast cancer

Interaction of CD95 (Apo-1/Fas) and its ligand (CD95L) plays an important role in the regulation of the immune response, since CD95+ lymphocytes may be killed after engagement of the CD95 receptor. Studying the CD95/CD95L system in 40 cases of breast cancer, the malignant cells expressed CD95L, but lost CD95 expression, when compared with non-malignant mammary tissue. Jurkat T cells incubated on breast cancer sections underwent CD95L-specific apoptosis. The rate of apoptosis correlated with the CD95L mRNA levels of the tissue samples. In four breast cancer cell lines, CD95L expression was increased by interferon-gamma (IFN-gamma), which resulted in higher levels of CD95L-specific apoptosis in co-cultured Jurkat T cells. Since IFN-gamma is mainly secreted by activated T cells, up-regulation of CD95L in breast cancer cells in response to IFN-gamma may thus counterselect activated tumour-infiltrating T cells and favour the immune escape of breast cancer. As demonstrated by inhibition of matrix metalloproteinases, CD95L expressed on breast cancer cells can also be shed from the cell membrane into the culture supernatant. Supernatants derived from cultured breast cancer cells induced apoptosis in Jurkat T cells via CD95L. In breast cancer patients, depletion of CD4+ and CD8+ peripheral blood lymphocytes was significantly correlated with CD95L expression in the tumours. This might be suggestive for a relationship between CD95L expression by breast cancer and systemic immunosuppression.     

Polyclonal B cell activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes

Concentrations of IgM and IgG isotypes were determined by capture ELISA in plasma of Swiss, BALB/c and C58/M mice. Plasma IgG isotype concentrations, especially of IgM, IgG1 and IgG2a, varied considerably between mouse strains, batches of mice of the same strain and individual mice and as a function of age. Infection of the mice with LDV, which is known to replicate primarily in a subpopulation of macrophages, consistently resulted in a rapid elevation of plasma IgG2a (or of IgG2b in some Swiss nu/+ mice), but no plasma IgG increases were observed in mice immunized with inactivated LDV. Plasma IgG2a elevation after LDV infection was greatly delayed and reduced by depletion of the mice of CD4+, but not of CD8+, T cells by administration of protein-G-purified anti-CD4 or anti-CD8 mAbs, and completely inhibited by repeated treatment of the mice with cyclophosphamide. Treatment with anti-CD4 mAbs, or cyclophosphamide also greatly reduced the production of anti-LDV antibodies, while not significantly affecting the replication of LDV in these mice. Nude Swiss mice also failed to produce anti-LDV antibodies, though supporting normal LDV replication. Plasma IgM, IgG1, IgG2a and IgG2b levels increased in LDV-infected nu/nu mice, but similar changes were observed in uninfected mice. The results indicate that the LDV-induced polyclonal activation of B cells requires productive LDV infection of mice and is, at least partly, dependent on functioning CD4+ cells. They suggest that productive infection of the LDV-permissive subpopulation of macrophages leads to the activation of CD4+ T lymphocytes of subset 1 and their Spleen cells from 5-day LDV-infected BALB/c mice incorporated [3H]thymidine 2-3 times more rapidly in vitro than spleen cells from companion uninfected mice, whereas their responses to concanavalin A and lipopolysaccharide were reduced 60-70%.     

The final version of the Patient Perspective Survey (PPS): a new tool to improve consultation outcome and patient participation in general practice patients with complex health problems. Doctors' and patients' evaluation and guidelines for clinical use

BACKGROUND: The Patient Perspective Survey (PPS) is a new clinical communication tool designed to stimulate patient involvement in the management of complex health problems in general practice and to improve patient and doctor satisfaction with the consultation. The development of this final 38-item version of the PPS has been described elsewhere. OBJECTIVE: The aims of this article are to present recommendations for clinical use and how GPs and patients have evaluated this new tool. METHODS: The study material included 159 patients (78% females) with a mean age of 45 years, mainly presenting with longstanding musculoskeletal and psychosocial disorders, selected by 32 GPs. After the PPS-based consultation, both doctor and patient were asked to fill in evaluation forms. RESULTS: In as many as 55-85% of the consultations' various aspects, it was perceived by the GPs that the use of the survey helped (to some extent, much or very much) in achieving improved clinical communication and a constructive consultation. The most important elements appeared to be stimulation of positive interaction/processes and obtaining new and relevant information. Similar results were found regarding patient evaluation. There was significantly more positive doctor evaluation if the doctor-patient relationship had lasted less than 1 year, and if the patient agreed to prepare a 'plan of action' for a follow-up consultation. Guidelines for clinical use are presented. CONCLUSION: We now regard the PPS to be completed for daily clinical use and believe that it has been shown to be a potent tool to improve consultation outcome in the large and challenging group of patients with complex health problems in general practice.     

The second laminin G-type domain of protein S is indispensable for expression of full cofactor activity in activated protein C-catalysed inactivation of factor Va and factor VIIIa

Vitamin K-dependent protein S is a cofactor to the anticoagulant serine protease activated protein C (APC) in the proteolytic inactivation of the procoagulant, activated factor V (FVa) and factor VIII (FVIIIa). In the FVa degradation, protein S selectively accelerates the cleavage at Arg306, having no effect on the Arg506 cleavage. In the FVIIIa inactivation, the APC-cofactor activity of protein S is synergistically potentiated by FV, which thus has the capacity to function both as a pro- and an anticoagulant protein. The SHBG-like region of protein S, containing two laminin G-type domains, is required for the combined action of protein S and FV. To elucidate whether both G domains in protein S are needed for expression of APC-cofactor activities, chimeras of human protein S were created in which the individual G domains were replaced by the corresponding domain of the homologous Gas6, which in itself has no anticoagulant activity. In a plasma-based assay, chimera I (G1 from Gas6) was as efficient as wild-type recombinant protein S, whereas chimera II (G2 from Gas6) was less effective. The synergistic cofactor activity with FV in the inactivation of FVIIIa was lost by the replacement of the G2 domain in protein S (chimera II). However, chimera I did not exert full APC-cofactor activity in the FVIIa degradation, indicating involvement of both G domains or the entire SHBG-like region in this reaction. Chimera I was fully active in the degradation of FVa in contrast to chimera II, which exhibited reduced cofactor activity compared to protein S. In conclusion, by using protein S-Gas6 chimeric proteins, we have identified the G2 domain of protein S to be indispensable for an efficient inactivation of both FVIIa and FVa, whereas the G1 domain was found not to be of direct importance in the FVa-inactivation experiments.