Sensory functions of institutionalized Romanian infants: A pilot study

Infants living in an orphanage (n = 22) in Romania were assessed on the Test of Sensory Functions in Infants (TSFI). Testing of the institutionalized infants was done before and 6 months after an enriched caregiver intervention program. Results showed significant changes in areas of reactivity to tactile deep pressure, visual-tactile integration, oculomotor control, reactivity to vestibular stimulation and total test responses. No significant changes occurred in the area of adaptive motor functions. Effects of sensory deprivation resulting from institutional settings and changes that can occur from enriched caregiver environments are discussed.     

The Sesto Fiorentino study: point and one-year prevalences of psychiatric disorders in an Italian community sample using clinical interviewers

BACKGROUND: It has been argued that lay interviewers' use of fully-structured interviews could lead to a diagnostic pattern different to that by treating physicians. Clinical interviewers in community samples should probably identify cases that are closer to those seen in clinical settings. The greatest advantage of using clinical interviewers consists of the immediate assessment of a possible psychopathology, i.e. the evaluation of current disorders. METHODS: Two thousand three hundred and sixty-three citizens from the community of Sesto Fiorentino, Italy, were interviewed by their own general practitioners using the Mini International Neuropsychiatric Interview (MINI). Positive cases for any lifetime psychiatric disorder as well as a random sample of the negative cases were re-interviewed by psychiatrists or trained residents in psychiatry using the Florence Psychiatric Interview (FPI). RESULTS: The point prevalence for any current disorder was 8.7%; the two disorders with the highest prevalence were generalised anxiety disorder (2.9%) and major depressive episode (2.7%). The figures increase about 50% when the sub-threshold sequelae of previous disorders are considered. Current comorbidity was generally high. The one-year prevalence of any disorder was 10.6%. Ninety-two percent of the cases sought help, 82% were being treated at the moment of interview. Social impairment was considerable. CONCLUSIONS: The period prevalence rates for most of the disorders considered were generally comparable with the range defined by previous studies conducted in other Western countries, despite using different methodologies. Conversely, the use of health facilities, the treatment received and the social impairment were much higher than those reported by the other studies, suggesting a greater similarity with the clinical samples.     

Magnitude of serum and intestinal antibody responses induced by sequential replicating and nonreplicating rotavirus vaccines in gnotobiotic pigs and correlation with protection

A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05) intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers postchallenge compared to those in the other groups. Statistical analyses of the correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers and protection demonstrated that each of these was an indicator of protective immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA and not IgM or IgG antibody titers in serum were highly correlated (R2 = 0.89; P < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines among all the vaccinated groups, indicating that the IgA antibody titer is probably the most reliable indicator of protection.     

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.     

Identification and Subcellular Localization of Neuronal Calcium Sensor-1 (NCS-1) in Human Neutrophils and HL-60 Cells

Secretion in neutrophils is thought to be regulated in different ways for the different granule types. Specific granules are endowed with proteins which are related to docking and fusion events and are absent on azurophilic granules. Furthermore, even if secretion of content from all neutrophil granules is a Ca(2+)-dependent process, a higher concentration of cytosolic calcium is required for azurophilic than for specific granule secretion. In this paper we show that human neutrophils and promyelocitic cells express neuronal calcium sensor-1 (NCS-1), a calcium binding protein involved in exocytosis in various cell types. Both mRNA and protein were found in mature cells and precursors. NCS-1 is shown to be mainly associated with azurophilic granules and, therefore could play an instrumental role in the calcium-dependent secretion of azurophilic granules.     

CDK9/CYCLIN T1 expression during normal lymphoid differentiation and malignant transformation

CDK9 is a member of the CDC2-like family of kinases. Its cyclin partners are members of the CYCLIN T family (T1, T2a, and T2b) and CYCLIN K. The CDK9/CYCLIN T1 complex is very important in the differentiation programme of several cell types, controlling specific differentiation pathways. Limited data are available regarding the expression of CDK9/CYCLIN T1 in haematopoietic and lymphoid tissues. The aim of this study was to analyse the expression of the CDK9/CYCLIN T1 complex in lymphoid tissue, in order to assess its role in B- and T-cell differentiation and lymphomagenesis. CDK9/CYCLIN T1 expression was found by immunohistochemistry in precursor B and T cells. In peripheral lymphoid tissues, germinal centre cells and scattered B- and T-cell blasts in interfollicular areas expressed CDK9/CYCLIN T1, while mantle cells, plasma cells, and small resting T-lymphocytes displayed no expression of either molecule. CDK9/CYCLIN T1 expression therefore appears to be related to particular stages of lymphoid differentiation/activation. CDK9 and CYCLIN T1 were highly expressed in lymphomas derived from precursor B and T cells, from germinal centre cells, such as follicular lymphomas, and from activated T cells (ie anaplastic large cell lymphomas). Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma also showed strong nuclear staining. Diffuse large B-cell, Burkitt's lymphomas, and peripheral T-cell lymphomas, among T-cell lymphoproliferative disorders, showed a wide range of values. No expression of CDK9 or CYCLIN T1 was detected in mantle cell and marginal zone lymphomas. However, at the mRNA level, an imbalance in the CDK9/CYCLIN T1 ratio was found in follicular lymphoma and diffuse large B-cell lymphomas with germinal centre phenotype, and in the cell lines of classical Hodgkin's lymphomas, Burkitt's lymphomas, and anaplastic large cell lymphoma, in comparison with reactive lymph nodes. These results suggest that the CDK9/CYCLIN T1 complex may affect the activation and differentiation programme of lymphoid cells. The molecular mechanism through which the CDK9/CYCLIN T1 complex is altered in malignant transformation needs to be elucidated.     

F2-isoprostanes stimulate collagen synthesis in activated hepatic stellate cells: a link with liver fibrosis?

Carbon tetrachloride (CCl4)-induced hepatic fibrosis has been considered to be linked to oxidative stress and mediated by aldehydic lipid peroxidation products. In the present study, we investigated whether collagen synthesis is induced by F2-isoprostanes, the most proximal products of lipid peroxidation and known mediators of important biological effects. By contrast with aldehydes, F2-isoprostanes act through receptors able to elicit definite signal transduction pathways. In a rat model of CCl4-induced hepatic fibrosis, plasma F2-isoprostanes were markedly elevated for the entire experimental period; hepatic collagen content also increased. When hepatic stellate cells (HSCs) from normal liver were cultured with F2-isoprostanes in the concentration range found in the in vivo studies (10(-9)-10(-8) M), a striking increase in DNA synthesis (reversed by the thromboxane A2 antagonist SQ 29 548), in cell proliferation and in collagen synthesis was observed. Total collagen content was similarly increased. Moreover, F2-isoprostanes markedly increased the production of transforming growth factor-beta1 by U937 cells, considered a model of liver macrophages. The data provide evidence for the possibility that F2-isoprostanes generated by lipid peroxidation in hepatocytes mediate HSC proliferation and collagen production seen in hepatic fibrosis.