Interferon-γ signal transduction during parasite infection: modulation of MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii

We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii . In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii . The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-γ. However, IFN-γ treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-γ altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-γ directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-γ may be involved in mediating their protective signals .     

Lupus anticoagulant: a clinical and laboratory study of 100 cases

Summary The clinical and laboratory features of 100 patients with lupus anticoagulant (LA) are reviewed. Subjects were divided into three groups according to their age (1–5, 15–35, 45–89 years). Female prevalence was observed in each group and overall F/M ratio was 3/1. An underlying autoimmune disease (principally lupus erythematosus) was found in 47 cases (10% of the children, 80% of the 15–35-year-old patients and 37% of the elderly patients). Biological criteria for the LA diagnosis were prolonged activated partial thromboplastin time and diluted thromboplastin time (1.3 × control), not corrected after addition of control to patient's plasma. Thromboplastin time was normal in 77 patients. Other types of coagulation inhibitors were eliminated by specific factor assays (with a 10-fold increase of cephalin concentration when necessary). Twenty-three thrombotic episodes were observed. No significant difference was found in the incidence of thrombosis between the autoimmune and non-autoimmune disease group, but the age when first thrombosis occurred was clearly lower in the former. Fourteen obstetrical accidents were noted in eight women but 13 pregnancies terminated without accident. Four patients experienced haemorrhagic complications; they all presented with a severe thrombocytopenia associated with the LA. In our experience, LA is a frequent coagulation abnormality, associated in about half of the cases with a clearly defined autoimmune disease. Clinical presentation appears as notably different according to the patient's age; it is particularly noteworthy that in nine out of 10 children, LA disappeared spontaneously within 6 months.     

Anaphylactic reactions during paediatric anaesthesia; results of the survey of the French Society of Paediatric Anaesthetists (ADARPEF) 1991–1992

A prospective survey was conducted among the anaesthetists of the French Society of Paediatric Anaesthetists (Association des Anesthésistes-Réanimateurs Pédiatriques d'Expression Française, ADARPEF) between January 1991 and June 1992 in order to evaluate the frequency of peroperative anaphylactic reactions in children. Data were collected from 38 Belgian and French institutions. During the study period, 162 551 children were anaesthetized, and 21 anaphylactic reactions were observed. Sixteen reactions were due to exposure to natural rubber, four were drug-related (vecuronium, suxamethonium, contrast medium and penicillin) and one occurred during removal of a hydatid cyst. The overall incidence (1/7741 anaesthetics) was close to that reported in adults (1/6000 to 1/6500), but anaphylaxis to latex was the main cause of anaphylactic reactions in children while it accounted for only 10% of reactions in adults. The incidence of reactions to muscle relaxants, the main aetiology reported in adults, appears to be ten times less frequent in children (1/81 275 anaesthetics) compared with adults (1/8000). All children were successfully resuscitated. Risk factors, clinical signs and treatment are described.     

Cardioversion of Atrial Fibrillation and Subsequent Maintenance of Sinus Rbythm

This article gives an overview of electrical cardioversion of AF and includes the discussion of newer strategies. DC external cardioversion is highly effective and carries a low risk of complications. Other approaches, like transesophageal cardioversion and high energy internal cardioversion, may improve the acute success rate but do not enhance long-term maintenance of sinus rhythm compared to external cardioversion. An atrial defibrillator may have important advantages which relate to the fact that the duration and possibly also the number of AF episodes become reduced. Supposedly, shortening the attacks of AF may exert an antiarrhythmic effect by limiting electrical, anatomical, and neurohumoral remodeling. So far. low energy biatrial defibrillation using an atrial defibrillator seems to be effective and safe (i.e., does not induce ventricular arrhythmias). However, discomfort limits its tolerability in clinical practice. Future improvement of leads and light sedation that is easy to administer may overcome this problem. In the second part of this overview, the probability of AF recurrence using a serial cardioversion approach is discussed. In middle-aged patients with a fair exercise tolerance and an arrhythmia duration < than 36 months this approach may be worthwhile. Young patients (age < 57 years) with an arrhythmia duration < 3 months and without hypertension may be cured from the arrhythmia with a single shock and without the institution of antiarrhythmic drugs. However, the serial electrical cardioversion approach is unlikely to succeed in elderly patients with a duration of AF exceeding 36 months and a poor exercise tolerance (NYHA Functional Class III or IV).     

Dental agenesis in Kallmann syndrome individuals with FGFR1 mutations

International Journal of Paediatric Dentistry 2010; 20: 305–312 Background. Kallmann syndrome (KS) is a rare genetic disorder characterised by central hypogonadism with a lack of sense of smell and in some cases renal aplasia, deafness, syndactyly, cleft lip/palate, and dental agenesis. To date, five genes for KS have been identified: KAL1, located on the X chromosome, and FGFR1, PROKR2, PROK2 and FGF8, which are involved in autosomally transmitted forms of KS. Aim. The study characterised the dental ageneses of individuals with KS associated with mutations in the FGFR1 gene. Design. Six individuals displaying dental agenesis were included. Clinical and radiological dental evaluations as well as medical anamneses were carried out. Results. Microdontia, screwdriver‐shaped mandibular incisors, thin molar roots, and patterns of dental agenesis in both dentitions were observed. One to nine teeth were missing, most frequently, in descending order, lateral mandibular incisors, second premolars of upper and lower jaws, and lateral maxillary incisors. The pattern of dental agenesis is associated with four new mutations in the FGFR1 gene. Conclusion: Dental agenesis may be a clinical feature of Kallmann syndrome caused by a mutation in the FGFR1 gene. These findings highlight the role that odontologists can play in the early diagnosis and treatment of gonadotropic deficiency.     

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h⁻¹ was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI ( r  =   0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5–30 h⁻¹) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.     

Solid phase synthesis of the retro viral nucleocapsid protein NCp10 of Moloney Murine Leukaemia virus and related “zinc-fingers” in free SH forms

The core of retroviruses contains a highly conserved, low molecular weight, basic protein that binds nucleic acids and is essential for genomic RNA packaging. The 56 amino acid protein, NCp10, of Moloney Murine Leukaemia virus (MoMuLV) has the CysX₂CysX⁴HisX⁴Cys zinc finger-like motif shared by all retrovirus nucleocapsid proteins. The native protein and five modified peptides containing the zinc binding domain were synthesized by solid phase in order to investigate the structural and biochemical role of Zn²⁺ chelation in MoMuLV NCp10 activity. The purity of the synthetic molecules was verified by HPLC and their sequences were confirmed by amino acid analysis and sequencing in the case of NCp10. Thiol dosage agreed with the theoretical value of free cysteine for all these molecules. Fluorescence measurements performed on synthetic NCp10 and zinc finger fragments showed that the tryptophan quantum yield was Zn²⁺ -dependent allowing a 1:1 stoichiometry for the complex to be determined. The apparent affinity constant of NCp10 for the metal was estimated to be superior to 10⁶ M^-1. The synthetic protein, in the presence of Zn²⁺ ions, possesses all the biological properties of NCp10 isolated from virions. It catalyzes both the MoMuLV RNA dimerization and the annealing of the replication primer tRNA^Pro onto MoMuLV RNA.     

Measurement of factor Xa-antithrombin III in plasma: relationship to prothrombin activation in vivo

Summary. The M_r of the complexes formed when factor Xa reacts with antithrombin III (ATIII) in plasma were estimated by gel filtration and SDS-polyacrylamide electrophoresis. The predominant species of factor Xa-ATIII detected after plasma and plasma to which factor Xa had been added were gel filtered on Sephadex G-200 and Sepharose 4B had apparent M_r >200 000, in which factor Xa-ATIII was associated with vitronectin. Addition of factor Xa-ATIII to ATIII-depleted plasma also resulted in the formation of factor Xa-ATIII-vitronectin complexes with M_r > 200 000. Using polyclonal antibodies to human factor Xa-ATIII and ATIII as the capture and detector antibodies, respectively, a sensitive and specific enzyme-linked immunosorbent assay was developed to quantify factor Xa-ATIII in plasma. The relationship between factor Xa-ATIII production and prothrombinase activity in vivo was investigated by quantifying factor Xa-ATIII and prothrombin fragment 1 + 2 endogenous to the plasmas of blood donors and patients with Hodgkin's and non-Hodgkin's lymphoma. Whereas the concentrations of prothrombin fragment 1+2 in the 84 normal plasmas increased with age, those of factor Xa-ATIII (mean ±SD of 34.7 ± 13.8 PM) did not, and no correlation existed between the concentrations of the two parameters in normal plasmas. In contrast, a highly significant correlation between the concentrations of these two parameters was found in the plasmas of the cancer patients which coincidentally also had higher concentrations of both factor Xa-ATIII and prothrombin fragment 1 + 2 than the normal plasmas. Thus, ATIII may differentially influence prothrombinase formation and activity in normal individuals and cancer patients.     

The oro-dental phenotype in Prader–Willi syndrome: a survey of 15 patients

Background.  Prader–Willi syndrome (PWS) is a rare disorder caused by genetic defects in certain regions of chromosome 15q11–13. It is characterized by severe neonatal hypotonia and feeding problems, childhood-onset hyperphagia and obesity, short stature, facial dysmorphy, hypogonadism, learning and behavioural difficulties, and dental abnormalities.
Aim.  To describe the oro-dental phenotypic spectrum of patients with PWS.
Design.  Fifteen PWS patients (3–35 years of age) being followed at the Centre for Human Genetics of the University Hospital of Leuven were examined at the dental clinic of the same institution. Medical information collected included age at diagnosis, body mass index (BMI) and level of cognitive functioning. Oral, clinical and radiological evaluations were performed. Caries experience (cavitation level), dental erosion and salivary flow rates were assessed.
Results.  The 15 patients had dmft/DMFT scores ranging from 0 to 28, while nine were cavity-free. Those with severe caries experience also presented advanced dental erosion. BMI ranged from 16 to 42.6. There was no association between BMI and caries experience or erosive tooth wear. The PWS patients in our survey presented with a more favourable oral health status than those in previous studies. This might be due to early diet management or better oral hygiene during childhood or both.     

Catheter Ablation of Atrial Tachycardia Following Atrial Fibrillation Ablation

Atrial tachycardias represent the second front of atrial fibrillation (AF) ablation. They are frequently encountered during the index ablation for patients with persistent AF and are common following ablation of persistent AF, occurring in half of all patients who have had AF successfully terminated. An atrial tachycardia is rightly seen as a failure of AF ablation, as these tachycardias are poorly tolerated by patients. This article describes a simple, practical approach to diagnosis and ablation of these atrial tachycardias.