Prevalence of obstructive sleep apnea syndrome in a population of patients with transient global amnesia.

OBJECTIVE: The etiology of transient global amnesia (TGA) is largely undetermined. The aim of this study was to investigate whether the prevalence of obstructive sleep apnea syndrome (OSAS), a condition associated with subtle changes in brain structures involved in memory processes, increases in subjects who have previously experienced a TGA episode. METHODS: Twenty-nine patients who had had a TGA episode were included. A case-control model was used, matching cases with controls by sex, age, and body mass index category. Diagnosis of OSAS was based on the results of the Berlin Questionnaire, which was later confirmed by means of an all-night polysomnography recording. RESULTS: The prevalence of OSAS among TGA patients was significantly higher with respect to that in controls (44.8% vs 13.8%, p = 0.020, χ2 test). At logistic regression model, subjects with TGA had an odds ratio of 8.409 (95% confidence interval = 1.674-42.243; p = 0.010) of having OSAS when compared with controls. CONCLUSIONS: According to our findings, an accurate investigation of sleep disturbances could be considered for a complete assessment of patients with TGA. The subtle cerebral anatomo-functional damage induced by the repeated nocturnal apneic episodes may be a pathophysiologic link between OSAS and TGA.

The role of specific early trauma in adult depression: A meta-analysis of published literature. Childhood trauma and adult depression.

BACKGROUND: A large literature has long focused on the role of trauma in childhood and risk for psychological disorders in adulthood. Despite several studies performed, to date, it is not clear which weight have different childhood stressors specifically on the risk for depression in adult life. In the present study, we performed a meta-analysis of the literature in order to assess the effective role of childhood traumas as risk factor in the onset of depressive disorders in adults. METHODS: Previously published papers investigating the exposure to childhood trauma and their association with depression in adult subjects were retrieved in literature through common databases. Meta-analysis was conducted by the RevMan software. The quality of studies was evaluated by an adapted version of the New-Ottawa Quality Assessment Scale; bias publication was evaluated by the Egger's test. Meta-regression analysis was employed to detect potential confounders and/or moderating variables. Finally, a sensitivity analysis was post-hoc performed to control for potential confounders. RESULTS: Emotional abuse showed the strongest association with depression (OR=2.78) followed by neglect (OR=2.75) and sexual abuse (OR=2.42). Significant associations were also found for domestic violence (OR=2.06) and physical abuse (OR=1.98). Nevertheless, in post-hoc analysis, emotional abuse and neglect showed the strongest associations with depression as compared to other kinds of child trauma. CONCLUSIONS: These findings support the role of neglect and emotional abuse as significantly associated to depression. Sexual/physical abuse or violence in family may be unspecific risk factors for mental disturbance. Other kind of trauma may play a less relevant role in risk of adult depression, though they should be not underestimated.

Emergency room access for recurring seizures: when and why.

BACKGROUND AND PURPOSE: To develop a hypothetical model identifying potentially modifiable predictive factors of Emergency Room (ER) visits by patients suffering from drug resistant epilepsy. METHODS: During a 1-year period, all adult drug resistant patients followed by the same epileptologist were recruited after the occurrence of one or more epileptic attacks. They were divided into two groups based on whether they went to the ER after seizures. A prospective comparative analysis of the clinical and social characteristics of the two groups was performed in order to identify independent predictors of ER visits. Logistic regression analysis was used to confirm the potential predictive role of the evaluated variables. RESULTS: Logistic regression analysis confirmed the potential role in predicting ER visits for these variables: foreign nationality, current psychiatric therapy, current antiepileptic drug polytherapy, comorbidities, more than one episode in the same day and changes in usual seizure pattern. A relevant association was also found between the frequency of ER neuroimaging use and the following variables: occurrence of episodes on holidays or weekends, current antiepileptic drug monotherapy, multiple comorbidities and brain injury after seizure. CONCLUSIONS: The present study evaluated factors, some potentially amenable to change, related to drug resistant epileptic patients' ER visits following a seizure. This information may serve to improve the clinical and therapeutic management of patients, decrease the need for urgent care and reduce subsequent patient stress and related costs.

Substance P downregulates basal and gonadotropin-releasing hormone-induced gonadotropin in vitro secretion by pituitary gland of crested newt, Triturus carnifex.

The possible role of Substance P (SP) was studied in the modulation of basal and gonadotopin-releasing hormone (GnRH)-induced gonadotropin secretion in the urodele crested newt, Triturus carnifex. During prereproduction, reproduction (noncourtship and courtship), refractory, recovery and aestivation, male and female pituitaries were incubated with medium-alone, GnRH, SP, GnRH receptor antagonist (antide), and SP receptor antagonist (L-703606). Since antisera raised against gonadotropins are not available for this species, we measured these hormones indirectly through their effects on the secretion of testicular androgens and ovarian progesterone from gonads superfused with the preincubated pituitaries. Pituitaries of both sexes preincubated with medium-alone, GnRH, GnRH plus L-703606, and GnRH plus SP plus L-703606 increased steroid secretion during prereproduction, noncourtship, courtship, and recovery; the increase induced by the pituitaries incubated with medium-alone was lower during prereproduction, noncourtship, and recovery. Pituitaries preincubated with SP, GnRH plus SP, GnRH plus SP plus antide, and SP plus antide did not change basal steroid secretion in any of the reproductive phases considered. Antide, L-703606, GnRH plus antide, GnRH plus SP plus antide plus L-703606, SP plus L-703606, and antide plus L-703606 experimental groups showed the same results as those with medium-alone. These results suggest that SP downregulates gonadotropin release in both Triturus carnifex sexes. In addition, an antagonist role, through receptor-independent mechanisms, exists between GnRH (upregulation) and SP (downregulation) in the modulation of pituitary.

DNA vaccination with full-length or truncated neu induces protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice.

Genetic immunization against tumor antigens is an effective way to induce an immune response able to oppose cancer progression. Overexpression of HER-2/neu can lead to neoplastic transformation and has been found in many human primary breast cancers. We constructed DNA expression vectors encoding the full-length neu oncogene of rat cDNA (pCMV-NeuNT), the neu extracellular domain (pCMV-ECD), or the neu extracellular and transmembrane domains (pCMV-ECD-TM). We evaluated whether i.m. injection of these plasmids induces protection against the development of mammary tumors occurring spontaneously in FVB/N neu-transgenic mice. We found that pCMV-ECD-TM induced the best protection, whereas both pCMV-ECD and pCMV-NeuNT were less effective. The coinjection with a bicistronic vector for murine IL-12 increased the efficacy of pCMV-ECD and pCMV-NeuNT plasmids, and led to the same protection obtained with pCMV-ECD-TM alone. Anti-neuECD antibodies were detected in pCMV-ECD-TM vaccinated mice and, after coinjection with pCMV-IL12 plasmids, they appeared also in animals immunized with pCMV-ECD. Our data demonstrate the effectiveness of DNA vaccination using truncated Neu plasmids in inducing antitumor protection in a spontaneous mammary tumor model.

Rapid desensitization of PC12 cells stimulated with high concentrations of extracellular S100.

Undifferentiated PC12 cells undergo apoptosis, via a calcium-induced calcium release mechanism, when the calcium-binding protein purified from bovine brain (native S100) is present in micromolar concentration in the medium. This process begins when S100 binds to specific membrane binding sites and involves up to 50% of the cell population. In the experiments reported here, we demonstrate that, by utilizing [3H]S100, the S100 protein can be displaced from its binding sites only during the first 10 min of incubation. This fact is due to an internalization mechanism, having a time-course with a plateau after 10-20 min of incubation. The native form of S100 is a mixture of two different S100 isoforms: S100A1 (20%) and S100B (80%). Using confocal microscopy and monoclonal antibodies, we demonstrated that only one of these isoforms, S100A1, was autoexpressed in more than 50% of the PC12 cells analysed. After cell incubation with 2 microM native S100, S100B also appears in PC12 cells, with a maximum presence after 10 min of incubation. This fact seems to indicate that this isoform, at least, is effectively translocated when stimulated with external native S100. From the data reported, it is possible to hypothesize that, in PC12 cells, a possible homeostatic mechanism is present that can counteract the effect of a continuously applied lethal stimulus (stimuli) on cell viability.

Autoantibody to p185erbB2/neu oncoprotein by vaccination with xenogenic DNA.

The passive transfer of antibodies and vaccination procedures against p185, the erbB2/neu oncoprotein, are approaches being explored for treatment of human breast cancer. We now report the possibility of using the erbB2/neu gene as an immunogen. This study demonstrates that intramuscular or intradermal injections of rat neuNT full-length DNA into mice generate anti-p185 autoantibodies. Anti-p185 polyclonals were also shown to bind the homologous human receptor ErbB2 and to stain specimens of breast adenocarcinoma from both neu-transgenic mice and humans. Further, in vitro assays demonstrated that anti-p185 IgG (probably dependent on CD4+ Th1) were able to inhibit human SKBR3 tumour cell growth and to mediate their lysis by natural killer cells. The continuous presence of circulating neu autoantibodies in mice did not cause any discernible toxic effects on normal tissues expressing low levels of self-antigen, even after 1 year. The experiments reported here raise the possibility that boosting anti-ErbB2 immunity by DNA vaccination will not induce harmful autoimmunity in humans.

Protein kinase NII from calf thymus chromatin. Isolation, characterization and some functional properties.

1. A protein kinase type II was purified from calf thymus chromatin using ammonium sulphate fractionation, ion exchange chromatography on DEAE and phosphocellulose and affinity chromatography on phosvitin- and casein-sepharose columns. 2. The enzyme moves as a single band in non-denaturing gel electrophoresis at pH 8.3, which coincides with the enzyme activity assayed on gel slices. 3. Sodium dodecyl sulphate gel electrophoresis shows three separate polypeptide chains having M(r) of 40,000, 38,000 and 25,000, respectively. The native M(r) was about 130,000, as measured by HPLC on Superose 12 column, suggesting a subunit structure of alpha, alpha', beta 2 type. The enzyme incubated with [gamma 32P]ATP or [gamma 32P]GTP as phosphoryl donors undergoes autophosphorylation in the M(r) = 25,000 subunit. 4. The enzyme phosphorylates casein (Km = 7 microM) and phosvitin (Km = 5 microM) but not histones and was strongly deactivated by Zn2+ ions (I50 = 0.05 mM) and heparin (I50 = 0.1 micrograms/ml). 5. The enzyme seems to be the major phosphorylating system present in the 0.35 M NaCl chromatin extract of calf thymus. The RNA polymerase II from calf thymus and RNA polymerase from E. coli are both phosphorylated by protein kinase NII. The effect of phosphorylation, which causes a remarkable increase of DNA transcription rate, was studied in vitro and extensively discussed.

A low molecular weight calf pineal peptide with an inhibiting effect on the growth of L1210 and HL60 cells.

The peptide isolated by us from calf pineal gland causes a reduction of RNA synthesis in vitro in L1210 and HL60 tumoral cells. This peptide also causes inhibition of cell proliferation; the cell viability is not modified. The effects are dose-dependent and reversible.

Purification of a low molecular weight calf pineal peptide controlling DNA transcription in vitro.

A low molecular factor showing high specific activity in the control DNA of transcription in vitro was isolated from aqueous ultrafiltered calf pineal gland extracts. The active factor was purified by means of Gel filtration on Sephadex G-25 and G-10, thin layer chromatography on aluminum sheet cellulose and high performance liquid chromatography using a Supelcosil LC 318 reverse phase column. The purified pineal factor was characterized as a peptide of low molecular weight (of about 1200 Dalton) containing glutamic acid, leucine, glycine, threonine and alanine in their approximate molar ratio, referred to glycine taken as 1: glycine 1, threonine 1, leucine 1, alanine 6, glutamic acid 2. Studies of the aminoacid sequence by N-terminal analysis using the automated Edman degradation procedure, were unsuccessful, suggesting the presence of a blocked NH2 group. The purified peptide appears to be different from peptide factors till now isolated from pineal gland.

Relationships between biotin and thymus morphology, and thymic and plasma peptides controlling DNA transcription.

Biotin-deficient rats show a slower growth rate and thymus involution. The amount of the thymic peptides controlling DNA template, based on thymus weight, is higher in deficient than control rats. No significant difference was noticed in the content of active peptides when evaluated for the rat. This observation suggests that involution of the thymus does not involve those cells which produce active peptides. Inhibition of RNA synthesis is the same for peptides extracted from normal and from biotin-deficient rat thymus. The amount of plasma peptides controlling DNA template per milliliter of plasma is higher and inhibition of activity on RNA synthesis is lower in deficient as compared to control rats. These effects are reversible following biotin administration.