Hypothalamic-pituitary-adrenal axis activity in depressive illness. Its relationship to classification

Serum cortisol response to the 1-mg overnight dexamethasone suppression test was studied in 221 depressed patients and 109 nondepressed psychiatric controls. Nonsuppression distinguished patients with primary unipolar depression (65/146) from patients with secondary unipolar depression (0/42) and nondepressed controls (0/109). Furthermore, nonsuppression distinguished the three familial subtypes of primary unipolar depressive illness: familial pure depressive disease (FPDD; 38/50 patients), sporadic depressive disease (SDD; 24/55 patients), and depression spectrum disease (3/41 patients). Moderate elevations in baseline serum cortisol levels were found in FPDD, SDD, and bipolar depression. Medication did not affect the results. The data suggest that the depressive syndrome is composed of separate illnesses, each of which has a distinctive pattern of hypothalamic-pituitary-adrenal axis activity during the depressed state as well as a specific clinical and familial psychiatric history.     

Comparison of the influence of spermicidal and non-spermicidal contraception on bacterial vaginosis, candidal infection and inflammation of the vagina--a preliminary study

This preliminary study compared the signs, symptoms and prevalence of bacterial vaginosis (BV) and candidal infections in women using spermicides, with those using other forms of contraception, to establish whether nonoxynol-9 had any therapeutic value against BV or gave rise to vaginal candidiasis and inflammation. Overall results showed that the prevalence of BV in non-spermicide users was 35/113 (31%) but was significantly less in spermicide users, 10/66 (15%), P < 0.05. Nonoxynol-9 was not associated with increased isolation of Candida albicans, which was found in 16/113 (14%) of non-spermicide users, and in 8/66 (12%) of those using spermicides, P > 0.1. Vaginal inflammation and discharge were significantly less in spermicide users, 19/66 (29%) than in the non-spermicide group, 50/113 (44%), P < 0.05. Nonoxynol-9 contraception was associated with a significantly reduced prevalence of BV, but not with increased candidiasis or vaginal inflammation.     

The distribution of omega-conotoxin MVIICnle-binding sites in rat brain measured by autoradiography

An analogue of omega-conotoxin MVIIC, [125I]omega-MVIICnle, has been employed in an autoradiographic assay to define the distribution of binding sites in rat brain of this neuronal calcium channel antagonist. In comparison with N-type channels (labeled by [125I]omega conotoxin GVIA), omega-MVIICnle sites are much denser in cerebellum (molecular layer) than in forebrain. Binding in thalamus is also comparatively high for omega-MVIICnle. Under these conditions, [125I]omega-MVIICnle binding to rat brain sections is not displaceable by the N-channel antagonist, omega-conotoxin GVIA. The calcium channel blocker [125I]omega-conotoxin MVIICnle labels a unique set of binding sites in mammalian brain.     

Erythropoietic changes effected by foreign serum in the mouse

Injection of foreign serum into mice increases erythrocyte formation as evaluated by ferrokinetics studies. When erythropoiesis is depressed either by fasting or plethora, the wave of erythropoiesis that follows a transient increase of endogenous erythropoietin is clearly enhanced by pretreatment of the recipients with foreign serum. The response includes a restoration of the responsiveness of the spleen of fasted mice to endogenous erythropoietin stimulation. These changes seem related to an effect of foreign serum on the transition of primitive hematopoietic progenitors into erythroid-committed progenitors.     

Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis

We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE synthesis in a culture system where IgE synthesis was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells. Similar effects on IgE synthesis were observed by adding ACTH-related peptides, e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha-melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not act directly on either B or T cells as there was no influence on IgE synthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings suggest that ACTH and the related peptides CRF and alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40 monoclonal antibody driven class switching to IgE via accessory cells.     

Characterisation of Australian ovine adenovirus isolates

The influenza virus haemagglutinin has an important role in the infectious cycle of the virus and carries multiple B and T cell epitopes. It is synthesized as a single polypeptide chain but viral infectivity depends on its post-translational enzymatic cleavage. The cleavage site of a trypsin-like enzyme responsible for this modification is found in the most conserved intersubunit region of the molecule. In this study the role of this region in antibody recognition was investigated. Synthetic peptides comprising the intact and cleaved forms of the intersubunit segment were used to examine the specificity of virus- or peptide-induced antibodies. The immune response elicited by viral infection resulted in the appearance of antibodies capable of neutralizing the virus without interfering with its binding to the receptor. A monoclonal antibody (MoAb) of such functional properties was shown to recognize the intact intersubunit region both in the uncleaved haemagglutinin molecule and in a 25-mer synthetic peptide comprising the intact intersubunit region. Specificity and functional studies revealed the conformation-dependent recognition of the C-terminal segment of the haemagglutinin 1 subunit by this MoAb. The binding of the antibody was shown to inhibit the trypsin-mediated cleavage of the haemagglutinin molecule and the membrane fusion event. The enzymatic cleavage of the haemagglutinin was demonstrated to abolish antibody recognition of the infective virus suggesting an escape mechanism mediated by the functional destruction of this highly conserved region. The synthetic peptide corresponding to the intact intersubunit region is characterized by an ordered structure and is able to elicit an antibody response in BALB/c mice while its subfragments are nonimmunogenic. Furthermore, this peptide elicited a protective immune response demonstrated by in vivo experiments.     

Characteristics of children selecting low-fat foods in an elementary school lunch program

OBJECTIVE: To describe the demographic characteristics of children that were associated with the selection of low-fat entrees available in a school lunch program. DESIGN: For 5 consecutive months, we recorded student entree selections on the 46 days in which one of the two available lunch entrees was low fat (< or = 30% of calories from fat). Entree selections were tracked using a computerized meal-card system. The lunch menus did not indicate that one of the two entrees was low fat. Demographic and family characteristics were obtained from the school district's registration database and, in one school, from a household telephone survey. SETTING: A school lunch program in two public elementary schools in Bellevue, Wash. PARTICIPANTS: Students who regularly eat school lunches (N = 471). Sixty-five percent were from families with incomes less than 185% of the federal poverty level, and 49% were nonwhite. INTERVENTION: None. MAIN OUTCOME MEASURE: The proportion of days that each student selected the low-fat entree. RESULTS: Girls selected the low-fat entree more often than boys (33% of days vs 27% of days; P < .001), and the proportion of students selecting the low-fat entree increased with grade level (P = .003). Children were more likely to select low-fat entrees if a household member was known to have an elevated blood cholesterol level (P = .004). The proportion of students selecting the low-fat entree increased with maternal education level (P = .007), but children receiving free or reduced-price lunches (< 185% of the federal poverty level) chose the low-fat entree as often as those receiving full-price lunches (30% of days vs 29% of days; P = .14). There were no significant differences in entree selection among races. CONCLUSIONS: Given a choice of low-fat school lunch entrees, girls, older children, and those who had family members with elevated cholesterol levels were most likely to select these entrees. While parental education level was directly related to the selection of low-fat entrees, race and family income had little association with entree selection.     

The phosphorylation state of phosducin determines its ability to block transducin subunit interactions and inhibit transducin binding to activated rhodopsin

Heterotrimeric GTP-binding proteins (G-proteins) serve many different signal transduction pathways. Phosducin, a 28-kDa phosphoprotein, is expressed in a variety of mammalian cell types and blocks activation of several classes of G-proteins. Phosphorylation of phosducin by cyclic AMP-dependent protein kinase prevents phosducin-mediated inhibition of G-protein GTPase activity (Bauer, P. H., Müller, S., Puzicha, M., Pippig, S., Obermaier, B., Helmreich, E. J. M., and Lohse, M. J. (1992) Nature 358, 73-76). In retinal rods, phosducin inhibits transducin (Gt) activation by binding its beta gamma subunits. While rod phosducin is phosphorylated in the dark and dephosphorylated after illumination (Lee, R.-H., Brown, B. M., and Lolley, R. N. (1984) Biochemistry 23, 1972-1977), the significance of these reactions is still unclear. The data presented here permit a more precise characterization of phosducin function and the consequences of its phosphorylation. Dephosphophosducin blocked binding of the Gt alpha 1 subunit to activated rhodopsin in the presence of stoichiometric amounts of Gt beta gamma, whereas phosphophosducin did not. Surprisingly, the binding affinity of phosphophosducin for Gt beta gamma was not significantly reduced compared with the binding affinity of dephosphophosducin. However, the association of phosducin with Gt beta gamma in a size exclusion column matrix was dependent on the phosphorylation state of phosducin. Moreover, the ability of phosducin to compete with Gt alpha for binding to Gt beta gamma was also dependent on the phosphorylation state of phosducin. No interaction was found between phosducin and Gt alpha. These data indicate that phosducin decreases rod responsiveness by binding to the beta gamma subunits of Gt and preventing their interaction with Gt alpha, thereby inhibiting Gt alpha activation by the activated receptor. Moreover, phosphorylation of phosducin blocks its ability to compete with Gt alpha for binding to Gt beta gamma.     

Fluorescein angiographic characteristics of macular holes before and after vitrectomy with transforming growth factor beta-2

We evaluated the fluorescein angiographic features of full-thickness macular holes before and after vitrectomy, fluid-gas exchange, and instillation of transforming growth factor beta-2 in 43 eyes in a masked fashion to evaluate the angiographic characteristics of macular holes preoperatively and the changes that occur with successful and unsuccessful closure of the macular hole. Hyperfluorescence was present in the base of the macular hole preoperatively in 34 of 43 eyes (79.1%), was questionable in eight of 43 eyes (18.6%), and was definitely absent in only one of 43 eyes (2.3%). The hyperfluorescence in the base of the macular hole disappeared in 19 of 20 eyes (95%) with successful closure of the macular hole (P < .00001) and appeared to be caused by blocked fluorescence at the site of the macular hole. The photographic features of eyes with unsuccessful closure of the macular hole changed little, except that the size of the cuff of neurosensory detachment around the hole increased and was associated with decreased postoperative visual acuity. These angiographic changes support the presence of a glial tissue plug bridging a small defect in the fovea of eyes with successful closure of a macular hole.