A sex difference in the response to fasting

We determined whether women and men would alter their pattern of food intake after they had deprived themselves of food. We found that women consumed 12% less food after fasting and that men ate 28% more food after fasting. Serving more food on the test day did not increase food intake of women. Women, who ate at a nearly constant rate (linear eaters), consumed less food than those eating at an initially high speed which decreased over the course of the meal (decelerated eaters). Women decreased their food intake after fasting as their eating pattern became more linear. After fasting, men increased their food intake, and the rate at which they ate became more decelerated. Food intake of both women and men was normalized after fasting by providing feedback that encouraged them to eat according to the pattern they showed in the non-fasted condition. The results support the hypothesis that linear eating, and the dieting that elicits linear eating, are risk factors for the development of the abnormal linear eating pattern that characterizes patients with anorexia nervosa. The data also provide additional support for the use of behavioral feedback to normalize the pattern of eating for individuals who have difficulty maintaining their body weight.     

A sex difference in the leucocyte count

In a study of a group of 325 blood donors between the ages of 18 and 65 years, the total leucocyte and polymorph counts of the females aged 50 to 65 years were found to be significantly lower than those of the corresponding group of male donors. In the whole series of female donors, there were significantly lower total leucocyte and lymphocyte counts with increasing age and a less significant (P [unk] 0.1) fall in the polymorph count. No age variation in the male counts was found.Analysis of large numbers of leucocyte counts performed on hospital patients has confirmed the sex difference in the total leucocyte count found in the blood donors.The factors responsible for the differences are discussed.     

Localization of brucella antigens that elicit a humoral immune response in Brucella abortus-infected cells.

Localization of brucella antigens, to which brucella-infected cattle make antibodies, and the surface characteristics of Brucella abortus smooth strain 19 and rough strain 45/20 were studied by the use of monospecific antisera in absorption tests, electron microscopy, and electrophoretic mobility of organisms in microelectrophoresis. Antigenic determinants of electrophoretically defined antigen A5 were present on the surface of B. abortus rough strain 45/20 organisms, and protein moieties were most probably exposed on the surface of this strain in contrast with smooth strain 19 organisms. Several antigens distinct from the smooth lipopolysaccharide complex, to which brucella-infected cattle make antibodies, were not detected on the surface of smooth organisms. Agglutinating antibodies present in anti-B. abortus strain 19 serum did not bind to all areas on the surface of the smooth cells, suggesting the presence of different antigenic moieties on their surface. It is also postulated that the surface of B. abortus rough strain 45/20 displays receptors able to strongly bind immunoglobulin molecules, as well as other serum components.     

Protective immunity to genital herpes simplex virus type 1 and type 2 provided by self-adjuvanting lipopeptides that drive dendritic cell maturation and elicit a polarized Th1 immune response

Genital herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections are a significant health problem worldwide. While it is believed that CD4+ Th1 cells are among the effectors to herpes immunity, developing an epitope-based clinical vaccine capable of inducing an effective anti-herpes CD4+ Th1-mediated protection is still under investigation. Few molecules achieve this target without the aid of external immuno-adjuvant. The present study was undertaken to examine the immunogenicity in mice of five CD4+ T cell epitope peptides (gD1-29, gD49-82, gD146-179, gD228-257, and gD332-358), recently identified from the HSV-1 glycoprotein D (gD), covalently linked to a palmitic acid moiety (lipopeptides) using the high-yielding chemoselective ligation method and delivered subcutaneously in free-adjuvant saline. Their protective efficacy was evaluated in a progestin-induced susceptibility mouse model of genital herpes following intravaginal challenge with either HSV-1 or HSV-2. Four out of five gD lipopeptides effectively induced virus-specific CD4+ Th1 responses associated with a reduction of virus replication in the genital tract and protection from overt signs of genital disease. A cocktail of three highly immunogenic lipopeptides provoked maturation of dendritic cells, induced interferon gamma (IFN-gamma)-producing CD4+ T cells, and protected against both HSV- 1 and HSV-2 infections. Depletion of specific T cell subsets from lipopeptideimmunized mice before intravaginal HSV challenges demonstrated that CD4+ T cells were primarily responsible for this protection. The strength of induced T cell immunity, together with the ease of construction and safety of these totally synthetic self-adjuvanting lipopeptides, provide a molecularly defined formulation that could combat genital herpes and other human viral infections for which induction of Th1 immunity is crucial.     

IAPS includes photographs that elicit low-arousal physiological responses in healthy volunteers

This article describes pleasant IAPS pictures that elicit low-arousal rather than the high-arousal physiological responses previously reported in the literature. Thirty-two International Affective Picture System (IAPS) photographs were grouped into 4 sets of 8 photographs: highly pleasant-arousing (sexual content and adventures), highly pleasant-relaxing pictures (landscapes, flowers or babies), neutral on both valence/arousal, and highly unpleasant-arousing ones. These stimuli were shown to 24 healthy Brazilian University students (12 males) who had their physiological responses recorded [corrugator and zygomatic facial electromyography activity, skin conductance, heart rate, and peripheral temperature]. Zygomatic EMG differentiated low-arousal pleasant photographs from high-arousal pleasant stimuli of the same valence.     

A possible mechanism in arterial wall for mediation of sex difference in atherosclerosis

Female rabbits on an atherogenic diet were treated with cottonseed oil (control), tamoxifen, testosterone, or progesterone. After 10 weeks the rabbits were killed, the aortas quickly removed, graded for atherosclerosis, and incubated with [14C]proline to determine collagen and elastin synthesis. Rabbits treated with testosterone and progesterone had the greatest degree of atherosclerosis, the highest DPM in hydroxyproline of collagen and elastin, and the greatest accumulation of collagen and elastin in the aorta. Tamoxifen-treated rabbits had less incorporation of radioactivity. In separate experiments aortas of similarly treated rabbits were analyzed for estradiol and progesterone receptor density. These receptors were found to be present, and progesterone and testosterone administration caused a translocation of progesterone receptors from cytosol to nucleus. Results are consistent with the hypothesis that sex hormones can affect the development of atherosclerosis through a direct effect of the hormones on arterial wall to alter collagen and elastin synthesis, the effect being mediated through hormone receptors in the wall.     

Hazelnut Allergy: evidence that hazelnut can directly elicit specific IgE antibody response via activating type 2 cytokines in mice

BACKGROUND: Hazelnut is one of the major tree nuts that causes potentially fatal food allergy, with underlying mechanisms that are unclear at present. One suggestion is that hazelnut allergy results from immune crossreactivity of IgE antibodies produced against certain aeroallergens. We tested the hypothesis that hazelnut is intrinsically capable of eliciting an allergic response using a mouse model. METHODS: Groups of mice were injected intraperitoneally with hazelnut/filbert protein extract with or without alum as an adjuvant, and hazelnut-specific antibody (IgE, IgG1) responses were examined using optimized enzyme-linked immunosorbent assay. Hazelnut-specific type 2 and type 1 cytokine responses were evaluated by ex vivo antigen-mediated activation of spleen cells. RESULTS: Hazelnut elicited robust IgE and IgG1 antibody responses. Timecourse and dose-response analyses further provided evidence for memory type 2-dependent antibody responses to hazelnuts. Hazelnut-specific IgE response in two strains of mice with different MHC haplotypes and IgE response to hazelnut without the use of alum adjuvant asserted that hazelnut is intrinsically an allergenic food. The type 2 cytokine analyses revealed that hazelnut sensitization results from activation of IL-4 and IL-5, thus providing a mechanistic basis for hazelnut-specific IgE response. CONCLUSION: Our data argue that hazelnut - a widely consumed food - is intrinsically an allergenic food capable of directly eliciting hazelnut-binding specific IgE antibodies viaactivation of type 2 cytokines in mice.     

Replicon-based Japanese encephalitis virus vaccines elicit immune response in mice

In this study, a replicon vaccine vector system for Japanese encephalitis virus (JEV) was established. The system included a trans-complementing cell line, a series of JEV DNA-based subgenomic replicons, and several encapsidated JEV propagation-deficient pseudoinfectious particles (PIPs). The DNA-based JEV replicon vectors, which deleted the structural coding region, could be able to self-replicate and express the reporter gene. A stable BHK packaging cell line named BHK-CME, which constitutively expressed the capsid protein C, the precursor membrane and envelope proteins (C-prM-E) of JEV, was generated. BHK-CME cells were used to trans-complement the JEV replicons and proved to package the JEV replicons into single-round infectious PIPs efficiently. The PIPs were produced in titers of up to 1.6 × 10⁵ IU/ml. To investigate the efficacy of JEV replicon-based vaccines, four groups of female BALB/c mice were inoculated three times at 3-week intervals with the JEV PIPs and others. The JEV-specific antibody titers reached to 1:6400 and the neutralizing antibody titers reached 1:256 after three rounds of immunization with JEV PIPs. And the antisera collected from immunized mice were shown to be protective partially against lethal infection when passively transferred to susceptible weanling mice. These results demonstrated the value of the JEV replicon vector system for the development of new vaccine candidates.     

Identification of an epitope on the recombinant bovine PrP that is able to elicit a prominent immune response in wild-type mice

The main cause for the development of transmissible spongiform encephalopathies (TSE) is the conformational change of prion protein from the normal cellular isoform (PrP(C)) into the abnormal isoform, named prion (PrP(Sc)). The two isoforms have the same primary structure, and with PrP being highly conserved among different species, no immune response to PrP(Sc) has been observed in infected humans or other mammals so far. The problem of inducing immune response was encountered when producing monoclonal antibodies against PrP, therefore mice lacking a functional Prnp gene were predominantly used for the immunization. In the present paper we report that by immunizing wild-type BALB/c mice with chemically unmodified recombinant bovine PrP a potent humoral immune response was achieved. Furthermore, we were able to isolate the monoclonal antibody (mAb) E12/2 and few other mAbs, all reacting specifically with bovine and human PrP, but not with PrP from several other mammals. The epitope of mAb E12/2 is located at the C-terminal end of helix 1, with His155 being crucial for binding. It has been proven that mAb E12/2 is useful for human and bovine TSE research as well as for diagnostics. Our results show that there are sufficient structural differences between mouse and bovine PrP to provoke a prominent humoral immune response.     

A novel sex difference in Drosophila contact chemosensory neurons unveiled using single cell labeling

Among the sensory modalities involved in controlling mating behavior in Drosophila melanogaster, contact sex pheromones play a primary role. The key receptor neurons for contact sex pheromones are located on the forelegs, which are activated in males upon touching the female abdomen during tapping events in courtship actions. A fruitless (fru)-positive (fru [+]) male-pheromone sensing cell (M-cell) and a fru [+] female-pheromone sensing cell (F-cell) are paired in a sensory bristle on the legs, and some fru [+] chemoreceptor axons project across the midline in the thoracic neuromere in males but not in females. However, the receptor cells that form sexually dimorphic axon terminals in the thoracic ganglia remain unknown. By generating labeled single-cell clones, we show that only a specific subset of fru [+] chemosensory neurons have axons that cross the midline in males. We further demonstrate that there exist two male-specific bristles, each harboring two chemosensory neurons; neither of which exhibits midline crossing, a masculine characteristic. This study reveals hitherto unrecognized sex differences in chemosensory neurons, imposing us to reinvestigate the pheromone input pathways that impinge on the central courtship circuit.     

Identification ofSchistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained fromS. haematobium-infected patients and sex- and agematched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples from 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84 000, 63 000, 57 000, 55 000, 40 000, 30 000, and 28 000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evok in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.     

Interhemispheric difference in emotional response without awareness

To investigate interhemispheric differences concerning unconscious human emotional responses processed, we measured human skin conductance responses (SCRs) to masked (unseen) emotional stimuli presented to left or right visual fields. Backward masking was used to preclude conscious processing of emotional stimuli. Masked negative or neutral emotional pictures from the International Affective Picture System (IAPS) were presented to 11 right-handed male volunteers. Mean SCR for negative emotional stimuli presented to the left visual field was significantly greater than mean SCRs for negative emotional stimuli to the right visual field and for neutral stimuli to the left or right visual fields. Thus, the right rather than the left hemisphere appears to respond to preattentive negative emotional stimuli.     

Molecular biological features of ectopic and eutopic endometrium in genital endometriosis

The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group. Both the glandular and stromal components of the ectopic and eutopic endometrium in different forms of endometriosis were shown to differ from the intact endometrium in their molecular biological features (the expression of Ki-67, Bcl-2, Bax, vascular endothelial growth factor, transforming growth factor-beta1, matrix metalloproteinases 2 and 10, matrix metalloproteinase-2 inhibitor, the enzyme cytochrome P450 aromatase.     

Dengue virus premembrane and membrane proteins elicit a protective immune response

We have constructed recombinant vaccinia viruses that express the premembrane (pre-M), membrane (M), or the cleaved, residual portion of pre-M (non-M) proteins of dengue 4 virus, or the pre-M, non-M, or envelope (E) proteins of dengue 2 virus, to evaluate their ability to induce protective immunity in mice. Cells infected with these recombinants make proteins of expected size. Mice immunized with recombinants expressing dengue 4 pre-M or M were protected against subsequent dengue 4 encephalitis challenge, but non-M was not protective. However, a recombinant that expressed both pre-M and E as a polyprotein gave solid protection, while the simultaneous administration of the two recombinants expressing pre-M and E gave a significant level of protection. Pre-M and M function as antigens eliciting a protective immune response, and the combination of pre-M plus E is more protective than E alone.