Concordant and discordant effects on cardiovascular risks exerted by oestrogen and progestogen in women using oral contraception and hormone replacement therapy. ESHRE Capri Workshop Group

The major indications for the clinical use of oestrogen and progestogen are oral contraception (OC) in young women, and hormonal replacement therapy (HRT) in menopause. Over the past few years, epidemiological data have associated the use of these hormones to different cardiovascular conditions such as myocardial infarction, cerebrovascular disease and venous thromboembolism. This review summarizes the data discussed and the conclusions achieved by the ESHRE Capri Workshop Group, recently published in Human Reproduction.     

Control of pulmonary vascular smooth muscle tone by sarcoplasmic reticulum ca2+ pump blockers: thapsigargin and cyclopiazonic acid

The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (-escin)-skinned arterial strips, application of TG (0.1–1 M) or CPA (0.5–10 M) prior and throughout the loading procedure of the internal Ca²⁺ stores (0.3 M free Ca²⁺ ions for 8–10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 M) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca²⁺-containing solution (2.5 mM for 10 min), followed by incubation in a Ca²⁺-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca²⁺. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca²⁺ ions was not antagonized by verapamil (10 M) or nifedipine (1 M) but was blocked by La³⁺ (50 M) and Co²⁺ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca²⁺] [0.1–10 mM, concentration for half maximal effect (EC₅₀) =0.85 mM], not modified by the reduction of the external [Na⁺] (from 130 to 10 mM) and decreased by depolarization of the strip using K⁺-rich (30–120 mM) solutions. Under the latter condition, 38±9 and 83±4% reduction (n=5) was observed in the presence of 60 and 120 mM K⁺ respectively. This contraction was also concentration dependently inhibited by the tyrosine kinase inhibitors genistein (0.5–50 M) and tyrphostin (2–50 M). Sr²⁺ ions, which contracted both depolarized intact and skinned strips, failed to replace Ca²⁺ ions in the verapamil-insensitive contraction induced by TG or CPA (n=4). Finally, TG (1 M) and CPA (10 M) did not modify the pCa tension relationship in skinned strips (n=5). These results show that the main action of TG and CPA in rat pulmonary artery is to prevent the refilling of the internal Ca²⁺ store. TG and CPA also seem to facilitate a Ca²⁺ influx through a specific verapamil-insensitive pathway. The biophysical and molecular characteristics of this pathway remain to be elucitated, although it appears to involve a tyrosine kinase activity.     

Reciprocal stimulation of gammadelta T cells and dendritic cells during the anti-mycobacterial immune response

Gammadelta T cells and dendritic cells (DC) are two distinct cell types of innate immunity that participate in early phases of immune response against Mycobacterium tuberculosis infection. Here we show that a close functional relationship exists between these cell populations. Using an in vitro coculture system, Vgamma1 T cells from Tcrb(-/- )mice were found to be activated by DC infected in vitro with BCG, as indicated by the elevated CD69 expression, IFN-gamma secretion and cytotoxic activity. This activation process was due to a non-cognate mechanism since it required neither cell to cell contact nor interaction between the TCR and a specific antigen, but was mediated by DC-derived IL-12. Reciprocally, Vgamma1 T cells provided a key cytokine, IFN-gamma, which increased IL-12 production by BCG-infected DC. Moreover, exposure of BCG-infected DC to Vgamma1 T cells conditioned the former to prime a significantly stronger anti-mycobacterial CD8 T cell response. Consequently, stimulation of gammadelta T cells and their non-cognate interaction with DC could be applied as an immune adjuvant strategy to optimize vaccine-induced CD8 T cell immunity.     

Genotypic characteristics of two serotypes of Bartonella henselae

The study of 16S rRNA gene sequences of all isolates of Bartonella henselae obtained in our laboratory and others from human patients or cats has revealed two genotypes according to the sequence of the 16S rRNA gene. Two isolates of these genotypes have previously been related to two different serotypes, and lack of cross-protection of the two serotypes has been demonstrated in cats. We investigated the grouping of eight strains of B. henselae on the basis of 16S ribosomal DNA, 35-kDa protein, Pap 31 protein, and internal transcribed spacer (ITS) gene sequencing; sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles; and monoclonal antibody reactivity studies. Houston-1, 90-615, and SA2 strains showed the same patterns in SDS-PAGE, but they differed from the patterns of B. henselae isolates URBHLLY8, URBHLIE9, Cat6, Fizz, and CAL-1. Nine monoclonal antibodies derived from BALB/c mice immunized with B. henselae Houston-1 strain reacted only with strains Houston-1, 90-615, and SA2, and not with any other Bartonella strains. The two serogroups corresponded with two genotypes based on differences in the sequences of the genes encoding 16S rRNA, 35-kDa protein, and Pap 31 protein. Sequences of ITS genes were highly divergent among strains, as each had a unique sequence and the subdivision was not supported by DNA-DNA relatedness study. Study of 22 additional strains of B. henselae isolated from French bacteremic cats demonstrated that they all belong to one or the other of the proposed serotype or genotype.     

Childhood peer rejection and aggression as predictors of adolescent girls' externalizing and health risk behaviors: a 6-year longitudinal study

This 6-year longitudinal study examined girls' peer-nominated social preference and aggression in childhood as predictors of self- and parent-reported externalizing symptoms, substance use (i.e. cigarette, alcohol, and marijuana use), and sexual risk behavior in adolescence. Participants were 148 girls from diverse ethnic backgrounds, who were initially assessed in Grades 4-6 and again in Grades 10-12. Results supported a moderator model, indicating that social preference changed the nature of the association between childhood aggression and adolescent outcomes. When accompanied by peer rejection, aggressive behavior was moderately stable over time and significantly associated with adolescent girls' substance use and sexual risk behavior. However, under conditions of peer acceptance, no significant association between childhood aggression and adolescent outcomes emerged.     

Erratum: Neurofibromatosis type 1 (NF1): Identification of eight unreported mutations in NF1 gene in Italian patients

In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180     

Impact of in utero exposure to EtOH on corpus callosum development and paw preference in rats: protective effects of silymarin

Background  

Using a rat model we have found that the bioflavonoid silymarin (SY) ameliorates some of the negative consequences of in utero exposure to ethanol (EtOH). In the current study our aim was to determine if laterality preference and corpus callosum development were altered in rat offspring whose mothers were provided with a concomitant administration of SY with EtOH throughout gestation.     

Activation of protein kinase C-α isoform in murine melanoma cells with high metastatic potential

Metastasis is a multistep process in which protein kinase C (PKC) appears to be significantly involved. We analysed the activity and expression of classical (, , ) and novel PKC isoforms in B16-F1 and B16-BL6 melanoma cells maintained under different culture conditions in vitro. We used high and low concentrations of tyrosine and phenylalanine in different media (DMEM or RPMI 1640 respectively) that affect the metastatic potential and also the proliferative capacity of the cells. We also tested a weakly metastatic amelanotic B78-H1 melanoma cell line which is unaffected by the different culture conditions. In both B16 melanoma cell lines activation of PKC (without increased expression) occurred under growth conditions permissive of metastasis (DMEM). In contrast, the weakly metastatic amelanotic B78-H1 cell line showed a substantial inactivation of this isoform in the two different culture media, suggesting a specific involvement of PKC in the metastatic process. Moreover, in B16 melanoma cells, novel PKC was activated under culture conditions which stimulated growth but not metastasis (RPMI 1640). In order to define the relationship between PKC activation and the metastatic process we also determined the release of cathepsin B. No correlation between PKC activity and cathepsin B release in either B16 melanoma cell lines could be demonstrated.     

Capillary electrophoretic profiling and pattern recognition analysis of urinary nucleosides from uterine myoma and cervical cancer patients

Capillary electrophoretic (CE) profiling analysis combined with pattern recognition methods is described for the correlation between urinary nucleoside profiles and uterine cervical cancer. Nucleosides were extracted from urine specimens by solid-phase extraction in affinity mode using phenylboronic acid gel. CE separation was carried out with an uncoated fused-silica capillary (570 mm x 50 microm I.D.) maintained at 20 degrees C, using 25 mM borate-42.5 mM phosphate buffer (pH 6.7) containing 200 mM sodium dodecyl sulfate as the run buffer under the applied voltage of 20 kV. A total of 15 nucleosides were positively identified in urine samples (2 ml) from eight uterine myoma (benign tumor group), 10 uterine cervical cancer (malignant tumor group) patients and 10 healthy females (normal group) studied. The star symbol plots drawn based on each mean concentration of nucleosides normalized to that in normal group enabled one to discriminate malignant and benign groups from normal group. In addition, canonical discriminant analysis performed on the nucleoside data of 28 individual urine specimens correctly classified into three separate clusters according to groups in the canonical plot.