Studies on vaccination against bacillary dysentery. 2. Safety tests and reactogenicity studies on a live dysentery vaccine intended for use in field trials

In view of the encouraging results obtained in active mouse protection experiments, several batches of live oral vaccine prepared from streptomycin-dependent Shigella flexneri were tested in vitro for any indication of reversion to streptomycin-independence and in man for their reactogenicity.     

Selective kinase inhibition with daily imatinib intensifies toxicity of chemotherapy in patients with solid tumours

The aim of this study was to determine the safety and maximum-tolerated doses of imatinib combined with cytotoxic chemotherapy (either gemcitabine or doxorubicin). Patients with advanced solid tumours were enrolled separately in two different combinations of imatinib with chemotherapy (imatinib + gemcitabine or imatinib + doxorubicin). A standard modified Fibonacci inter-cohort dose escalation was planned for each combination. Sixteen patients were accrued. Seven patients received gemcitabine and imatinib. A separate cohort of nine patients received imatinib and doxorubicin. In both groups, dose-limiting toxicity (DLT) was observed at the initial dose level requiring dose reductions for subsequent cohorts. Further DLTs were observed necessitating closure of the protocol. Daily dosing of imatinib with concurrent administration of cytotoxic chemotherapy (either gemcitabine or doxorubicin) at standard doses was associated with toxicity that was clinically unacceptable. It remains unclear whether addition of growth factors might improve tolerability for imatininb in combination with cytotoxic chemotherapy.     

Von einer importierten Katze übertragene, durch M. canis hervorgerufene Mikrosporie bei Menschen und Hund

Es wurden die häufigsten Kulturanlagen der Dermatophyten des Einzugsgebietes der Belgrader Dermatologischen Klinik ausgewertet. Am häufigsten wurden bei Landbewoh-nern die klassischen anthropophilen Dermatophyten und animale "microides"- und "megasporon"-Pilzarten isoliert. Bei Stadtbewohnern dominierten in den positiven Kulturanlagen Tr. mentagrophytes var. interdigitale, Ep. floccosum und Tr. rubrum. Ver-einzelte Isolate von M. Audouini und Tr. ferrugineum gehören den migrierenden Dermatophyten, die aus dem Norden bzw. Süden des Landes in diesem Gebiet zeitweilig importiert werden.
M. canis als importierter Dermatophyt hat einstweilen für unser Gebiet keine epidemiologische Bedeutung. Die Isolierung desselben verbreitert jedoch das Spektrum der Dermatophyten und weist auf die Möglichkeit des Erscheinens dieses animalen Mikrosporums auch bei uns hin.     

Application of correlation techniques in the analysis of corpus cavernosum electromyographic signals

Aim： To establish an objective, easy-to-use and comprehensive method to analyze corpus cavernosum electromyo- graphic signals （CC-potentials）. Methods： CC-potentials were recorded during flaccidity in 23 young healthy volunteers, with surface electrodes placed on the penile shaft bilaterally. Based on the correlation function of Matlab software, an application program for the analysis of CC-potentials was developed. Individual CC-potentials and their autocorrelation function were evaluated, yielding parameters amplitude （A）, duration （D）, and dominant frequency （DF）. The crosscorrelation function of both longitudinal and bilateral pairs of adjacent electrodes was calculated to assess the similar- ity and mutual delay of CC-potentials recorded simultaneously from different parts of the CC. The parameters derived were squared maximum cross-correlation coefficient （Rmax） and delay （τ）. Based on the absolute value of τ and the corresponding inter-electrode distance, propagation velocity （PV） was calculated. Results. The values of the parameters were determined automatically. No significant difference related to the locations of the electrodes for parameters A, D, and DF was detected. The cross-correlation showed that both longitudinal and bilateral CC-potential pairs had highly similar waveforms （the absolute values of Rmax were 0.80 ± 0.05 and 0.87 ± 0.06, respectively）. PV of longitudinal pairs was estimated as 6.15 ± 3.98 cm/s. Conclusion： The application program for correlation analysis of CC-potentials is a comprehensive and versatile method to analyze corpus cavernosum electromyographic recordings. Its objectiveness makes multi-center application possible.     

Investigating the development of temperament and character in school-aged children using a self-report measure

BackgroundDevelopmental studies of temperament and character dimensions are crucial for a better understanding of how genetic and environmental factors interact in shaping individual personality. However, although several studies have been conducted in adults, a few studies have addressed the evaluation of temperament and character in children. Here, we tested the suitability of self-report evaluation and the developmental trend of temperament and character dimensions among school-aged children using an Italian version of the junior Temperament and Character Inventory (jTCI).MethodsThe jTCI was completed by 572 Italian children (292 girls and 280 boys) aged 8 to 12 years. We evaluated the internal consistency of the 7 jTCI scales at each age, the intercorrelations between the scales, and the factorial model of the questionnaires. Furthermore, we tested the differences between the development of the temperament and character dimensions in girls and boys.ResultsAlthough the data from 8-year children showed unacceptably low internal consistency, better reliability was observed for older children. Intercorrelations and factor analysis partially confirmed the hypothesized structure of the jTCI items, with problems observed for some items of the Novelty Seeking, Harm Avoidance, Reward Dependence (RD), and Self-Directedness scales. Furthermore, in keeping with previous studies, girls presented lower scores in Novelty Seeking and higher RD, Self-Directedness, and Cooperativeness scales than did boys, with the between-sex difference in RD becoming larger at older ages.ConclusionsAlthough the use of the self-administered jTCI in clinical settings should be cautious, it may serve as a useful complementary instrument to describe the development of personality in childhood.     

C–C Chemokines Released by Lipopolysaccharide (LPS)-stimulated Human Macrophages Suppress HIV-1 Infection in Both Macrophages and T Cells

Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C–C chemokines (RANTES, MIP-1α, and MIP-1β) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C–C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C–C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.     

Mu opioid receptor mRNA expression, binding, and functional coupling to G-proteins in human epileptic hippocampus

Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.     

Specific protein profile in cerebrospinal fluid from HIV-1-positive cART-treated patients affected by neurological disorders

Cytokines/chemokines are involved in the immune response of infections, including HIV-1. We defined the profile of 48 cytokines/chemokines in cerebrospinal fluid from 18 cART patients with chronic HIV-1 infection by Luminex technology. Nine patients were affected with leukoencephalopathies: five with John Cunningham virus (JCV) + progressive multifocal leukoencephalopathy (PML) and four with JCV-not determined leukoencephalopathy (NDLE). In addition, nine HIV-1-positive patients with no neurological signs (NND) and five HIV-1-negative patients affected with acute disseminated encephalomyelitis (ADEM) were enrolled. Ten cytokines (IL-15, IL-3, IL-16, IL-18, CTACK, GRO1, SCF, MCP-1, MIF, SDF) were highly expressed in HIV-1-positive patients while IL-1Ra and IL-17 were present at a lower level. In addition, the levels of IL-17, IL-9, FGF-basic, MIP-1??, and MCP-1 were significantly higher (p?<?0.05) in patients with neurological diseases (PML, NDLE, ADEM) with respect to NND. Focusing the attention to the cytokine profile in JCV + PML patients with respect to JCV-NDLE patients, only TNF-?? was significantly downregulated (p?<?0.05) in JCV + PML patients. This pilot study emphasized the role of immunoregulation in HIV-1-related neurological disorders during cART treatment.