Sexually transmitted diseases and infertility

In the past decade, involuntary childlessness has become a major problem in many areas of the world. At the same time evidence confirms a link between sexually transmitted diseases (STDs) and the burgeoning infertility problem. STDs can adversely affect fertility by three primary mechanisms: (1) pregnancy wastage; (2) neonatal deaths; and (3) obstruction of either male or female reporductive ducts. STD control programs have been effective in preventing sequelae of disease, including infertility. The first step in developing such a program is to identify the magnitude and distribution of the problem, and to identify the specific agents most commonly involved. Subsequently, an STD control program emphasizing the prevention of infertility, can be incorporated into the existing health care system whenever STDs are an important cause of infertility.     

A rapid and reliable in vivo method for anti-GPLA (class I and class II antigens) antibody titration and GPLA typing

A reverse Arthus reaction (RAR) may be successfully used in guinea pigs to detect histocompatibility alloantigens of the GPLA type. Epidermal cells carry class I GPLA antigens, and Langerhans cells also bear class II alloantigens. It is therefore possible to elicit an RAR by intradermal injection of relevant alloimmune sera in the skin of guinea pigs of known GPLA haplotype. RAR is detected by increased vascular permeability due to IgG1 antibody and hemorrhage due to IgG2 antibody. Compared with an in vitro protein A-rosetting method RAR is easier and quicker. It proved more sensitive for class II antigens in which Langerhans cells are the target for anti-class II antibody and rather less sensitive for class I antigens. RAR is a convenient method for following the course of GPLA alloimmunization, allowing titration of antibodies against both classes of antigen. It may also be used to type guinea pigs of unknown GPLA haplotype.     

Molecular alterations during development of esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma has risen significantly over the last decades. During esophageal carcinogenesis many molecular alterations occur that disrupt essential cellular processes, directing the cell to a rapidly proliferating, immortal state. The chronic inflammation that is present in Barrett's esophagus creates an environment in which such molecular alterations are both induced and tolerated. Here, the novel insights in the molecular mechanisms that underlie the development of esophageal adenocarcinoma are reviewed, focusing on the role of inflammation, angiogenesis, apoptosis inhibition, loss of cell cycle control, and loss of cell-cell adhesion. These novel developments will open new perspectives for diagnosis, treatment, and prevention of esophageal adenocarcinoma.     

Iron homeostasis in mother and child during placental malaria infection

In malaria-endemic areas, iron deficiency and placental Plasmodium falciparum infection commonly coexist. In primigravidae and their newborns, hepcidin and other iron parameters were evaluated in groups and classified according to placental P. falciparum and maternal anemia status. Mothers had relatively high hepcidin levels considering their low iron status. In cord blood, levels of hepcidin, hemoglobin, and other iron parameters were also similar for groups. We conclude that maternal hepcidin is not significantly altered as a function of placental infection and/or anemia. Importantly, fetal hemoglobin and iron status were also unaffected, regardless of the presence of placental infection or maternal anemia.     

Mild increases in serum hepcidin and interleukin-6 concentrations impair iron incorporation in haemoglobin during an experimental human malaria infection

The correct selection of individuals who will benefit from iron supplements in malaria-endemic regions requires improved insight in the effects of malaria on host iron homeostasis and innovative biomarkers. We assessed sequential changes in serum hepcidin and in traditional biochemical iron status indicators during an experimental Plasmodium falciparum malaria infection with five adult volunteers. The haemoglobin content of reticulocytes (Ret-H_e) and of mature red blood cells (RBC-H_e) represented iron incorporation into haemoglobin. Low-density parasitaemia and its treatment induced a mild increase in interleukin (IL)-6 and serum hepcidin concentrations. Despite this only mild increase, a marked hypoferraemia with a strong increase in serum ferritin concentrations developed, which was associated with a sharp fall in Ret-H_e, while RBC-H_e remained unchanged. The ratio of soluble transferrin receptor (sTfR) to log ferritin concentrations decreased to an average nadir of 63% of the baseline value. We concluded that even mild increases in serum hepcidin and IL-6 concentrations result in a disturbed host iron homeostasis. Serum hepcidin, Ret-H_e and Delta-H_e (Ret-H_e minus RBC-H_e) are promising biomarkers to select those individuals who will benefit from iron supplements in malaria endemic regions, while the sTfR/log ferritin ratio should be used with caution to assess iron status during malaria.     

Impact of CD8-MHC class I interaction in detection and sorting efficiencies of antigen-specific T cells using MHC class I/peptide multimers: contribution of pMHC valency

Recombinant soluble multimeric forms of MHC class I molecules loaded with antigenic peptides (pMHC) have turned out to be particularly useful to detect and isolate specific T cells. These applications both rely on the oligomerization of pMHC monomers in order to compensate for their inherent low affinity for the TCR. In this study, we have evaluated the precise contribution of CD8-pMHC interaction on the specificity and sorting efficiency of pMHC multimers according to their degree of oligomerization. To this end several wild-type versus mutated pMHC complexes (A*0201, B*0701, B*0801, B*3501) carrying point mutations known to reduce (245V mutants) or to abrogate (227,8KA mutants) CD8-pMHC interaction and showing various degrees of valency have been used. We show that irrespective of the HLA allele tested, 245V mutation strongly improves the binding specificity and immunomagnetic sorting efficiency of pMHC multimers. Our results also indicate that the contribution of CD8 to the binding of pMHC multimers to specific CD8+ T cells is inversely correlated to the degree of pMHC oligomerization. Consequently, efficient staining or specific sorting of high-affinity T cells (i.e. CD8 independent) can only be achieved using 227,8KA pMHC complexes with low-order oligomerization.     

The use of recurrent signals about adaptation for subsequent saccade programming depends on object structure

Executing sequences of accurate saccadic eye movements supposes the use of signals carrying information about the first saccade for updating the predetermined motor plan of the subsequent saccades. The present study examines the signals used in planning a second saccade when subjects made two successive saccades towards one long or two short peripheral objects displayed before the first saccade execution. Different first eye movement signals could be used: desired eye movement signals, representing the movement necessary for attaining the intended target, or actual eye movement signals, representing the movement actually executed. Experimental dissociation of desired and actual eye movement signals is made possible by adaptive modifications of the first saccade, obtained by transfer of single saccade adaptation, during which the motor vector was progressively modified in response to the systematic intra-saccadic step of a single target. Whether the second saccade used the actual eye movement signal to compensate or not for the adaptive changes in the first saccade depended on which object properties were relevant for saccade planning. Compensation was observed for saccades that aimed for a new object (between-object saccades) because adaptation modifies relative object location. No compensation was observed for saccades that explored an extended object (within-object saccades). Implications for the on-line control of subsequent eye movements are discussed.     

Visual versus motor vector inversions in the antisaccade task: a behavioral investigation with saccadic adaptation

In the antisaccade task, subjects must execute an eye movement away from a visual target. Correctly executing an antisaccade requires inhibiting a prosaccade toward the visual target and programming a movement to the opposite side. This movement could be based on the inversion of the visual vector, corresponding to the distance between the fixation point and the visual target, or the motor vector of the unwanted prosaccade. We dissociated the two vectors by means of saccadic adaptation. Adaptation can be observed when systematic targeting errors are caused by the displacement of the visual target during the saccade. Adaptation progressively modifies saccade amplitude (defined by the motor vector) such that it becomes appropriate to the postsaccadic stimulus position and thus different from the visual vector of the target. If antisaccade preparation depended on visual vector inversion, rightward prosaccade adaptation should not transfer to leftward antisaccades (which are based on the same visual vector) but should transfer to rightward antisaccades (which are based on a visual vector inside the adaptation field). If antisaccade preparation depended on motor vector inversion, rightward prosaccade adaptation should transfer to leftward antisaccades (which are based on the same, adapted motor vector) but should not transfer to rightward antisaccades (which are based on a nonadapted motor vector). The results are in line with the first hypothesis, showing that vector inversion precedes saccadic adaptation and suggesting that antisaccade preparation depends on the inversion of the visual target vector.