Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin- releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.      

Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro

Candida albicans must penetrate the endothelial cell lining of the vasculature to invade the deep tissues during a hematogenously disseminated infection. We compared 27 C. albicans mutants with their wild-type parent for their capacity to damage endothelial cells in vitro and cause a lethal infection in mice following tail vein inoculation. Of 10 mutants with significantly impaired capacity to damage endothelial cells, all had attenuated virulence. Therefore, the endothelial cell damage assay can be used as a screen to identify some virulence factors relevant to hematogenously disseminated candidiasis.     

In vivo Junin virus-mouse macrophages interaction

The role of mononuclear phagocytic cells in extraneural infection of the mouse with Junin virus (JV) was studied. Endpoint susceptibility (4 days of life) was evaluated by intraperitoneal (i.p.) inoculation of suckling mice. By means of immunofluorescence (IF) and C3 receptor assays, it was found that macrophages were permissive to viral replication in vivo and fostered the recruitment of inflammatory cells as evidenced by the absence of C3 marker. In support, in vitro infection failed to induce alterations of this receptor. Throughout, both in vivo and in vitro, there were no signs of C3-mediated phagocytosis. Silica treatment had no effect on either resistance or susceptibility, suggesting that the "macrophage-barrier" failed to hinder or favour the course of disease. Differences with other JV models are discussed.     

The Electron Microsopic Features of Sinus Histiocytosis with Massive Lymphadenopathy: A Study of 11 Cases

Eleven cases of sinus histiocytosis with massive lymphadenopathy (SHML) involving lymph nodes were studied electron microscopically. Histiocytes were the most conspicuous element of the infiltrate. They could be divided into small and large forms, although transitions were apparent among them. Most of the small histiocytes were located in the medullary cords. The large histiocytes were predominantly seen within sinuses and were subdivided into two types on the basis of their appearance. The most distinctive feature of these histiocytes was the presence of lymphocytes, plasma cells, and neutrophils within their cytoplasm. Other cells present in the infiltrate were lymphocytes, plasma cells, and occasional neutrophils and mast cells. Blood vessels were prominent throughout. Virus particles, bacteria, and Langerhans granules were consistently absent. No morphologic clues were provided by this study as to the etiology of this disorder.     

S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by acute imipramine in the frontal cortex of the rat

S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the antidepressant effect of imipramine in depressed patients. This effect may be related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/- 8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did not show antidepressant effect. Acute SAM and imipramine+SAM did not modify frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the chronic treatments showed antidepressant effects and up-regulated the hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation induced by acute imipramine in the frontal cortex. This mechanism may contribute to imipramine's antidepressant effect.     

Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Diet restriction plays an important role in the alterations of heart mitochondrial function following exposure of young rats to chronic hypoxia

Male Wistar rats aged 4 weeks, were subjected to hypobaric hypoxia (barometric pressure 505 hPa, PI,O2 106 hPa) or to diet restriction (reproducing the effect of hypoxia-induced anorexia) for 4 weeks. Each group (control, hypoxic, pair-fed, n = 16), was divided into two sub-groups housed individually in either normal cages or cages with running wheels allowing evaluation of voluntary activity (n = 8 each). The skinned-fibre technique was used to evaluate the functional properties of myofibrillar mitochondria from right and left ventricles in situ. The oxidative fibres from the soleus and diaphragm muscles were also investigated for comparison. Analysis of variance did not detect any significant effect of voluntary running activity. With calorie restriction, the maximal respiratory rate (Vmax) in the presence of 1 mM adenosine 5'-diphosphate (ADP) in myocardial fibres fell significantly (by about 25%) but was unchanged in skeletal myocytes. Following hypoxia, Vmax in myocardial fibres increased by 25% compared with the calorie restricted group and in soleus and diaphragm muscle fibres by about 30% compared with control. In myocardial fibres of control rats, creatine (20 mM) increased the sub-maximal respiratory rate by 80% in the presence of 0.1 mM ADP. Under calorie restriction or hypoxia the stimulatory effect was significantly reduced to 34-56%. This alteration was due to a decrease in the apparent Michaelis-Menten constant (Km) of mitochondrial respiration for ADP evaluated in the absence of creatine, while the Km in presence of creatine 20 mM was unchanged. In conclusion, reduced food intake decreased the oxidative capacity (Vmax) and the apparent Km for ADP of mitochondria in both left and right ventricles. Chronic hypoxia per se was responsible for an increase in the oxidative capacity of all oxidative muscles but did not exert significant effects on the control of respiration by ADP and creatine in myocardium.     

Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes

Using an 'oligoclonal' model, we have previously shown that mice transgenic for a mu chain (H3) and deficient for kappa chain expression display a mature B cell repertoire largely dominated by the H3/lambda1 pair, while the four H3/lambda available combinations can be observed in the immature B cell compartment. This led us to propose the existence of a positive selection process. To test this hypothesis, we have introduced the SJL lambda locus coding for a defective lambda1 chain (lambda1(s)) that creates a dysfunctional Ig receptor complex during B cell differentiation. Our results show that the lambda1(s) defect impairs the development of mature B cells when the H3-mu transgene insert is present in the hemizygous state. This suggests that the Gly --> Val substitution present in the C(lambda)1(s) chain at position 155 is sufficient to abrogate the selection of the H3/lambda1 pair. Unexpectedly, when the H3-mu transgene array is present in a homozygous state in lambda1(s) mice but not in 'wild-type' lambda1 mice (lambda1(+)), a significant number of mature B cells expressing all H3/lambda combinations can be developed. These results indicate that the overriding H3/lambda1 dominance observed in lambda1(+) mice is due to a positive selection process and not to a negative selection of other H3/lambda combinations. They also show that the export of B cells to the periphery can be controlled by the expression of the mu chain.