Hypoxia inducible factor one alpha and human viral pathogens.

If the oxygen tension level is 21% in ambient air, it is only between 14% and 1% in vivo. Consequently, viral pathogens are exposed and must adapt to these fluctuating oxygen levels to colonize the host and cause diseases. The problem is that for many years, the virological studies have been performed at 21% oxygen levels and consequently this is a real handicap to have a correct view of the mechanistic aspects of human viral infections. In this brief review, we describe for some selected examples the interactions of human viruses with this relative hypoxia observed in vivo.

The importance of EN ISO 15189 accreditation of allergen-specific IgE determination for reliable in vitro allergy diagnosis.

BACKGROUND: Allergen-specific serum immunoglobulin E detection and quantification have become an important step in allergy diagnosis and follow-up. In line with the current trend of laboratory test accreditation to international standards, we set out to design and assess an accreditation procedure for allergen-specific serum IgE. METHODS: Method validation according to the accreditation procedure under the EN ISO 15189 standard was carried out for allergen-specific immunoglobulin E determination using the fluoroimmunoenzymatic method ImmunoCAP(®) (ThermoFisher). Data were produced by 25 hospital laboratories in France. A total of 29 allergen specificities including mixes, extracts, and molecular allergens were assayed. Allergen-specific serum immunoglobulin E concentrations ranged from 0.1 to 100 kUA /l. RESULTS: Repeatability, reproducibility, and accuracy results fulfilled method validation criteria for automated laboratory tests and proved similar irrespective of the allergen specificity, allergen-specific serum immunoglobulin E concentration, or individual laboratory. CONCLUSION: Allergen-specific serum immunoglobulin E determination with the fluoroimmunoenzymatic method ImmunoCAP(®) is a highly repeatable, reproducible, and accurate method which may be considered as a single analyte assay in view of the EN ISO 15189 accreditation procedure.

Viability and stress protection of chronic lymphoid leukemia cells involves overactivation of mitochondrial phosphoSTAT3Ser727.

Chronic lymphoid leukemia (CLL) is characterized by the accumulation of functionally defective CD5-positive B lymphocytes. The clinical course of CLL is highly variable, ranging from a long-lasting indolent disease to an unpredictable and rapidly progressing leukemia requiring treatment. It is thus important to identify novel factors that reflect disease progression or contribute to its assessment. Here, we report on a novel STAT3-mediated pathway that characterizes CLL B cells-extended viability and oxidative stress control. We observed that leukemic but not normal B cells from CLL patients exhibit constitutive activation of an atypical form of the STAT3 signaling factor, phosphorylated on serine 727 (Ser(727)) in the absence of detectable canonical tyrosine 705 (Tyr705)-dependent activation in vivo. The Ser(727)-phosphorylated STAT3 molecule (pSTAT3Ser(727)) is localized to the mitochondria and associates with complex I of the respiratory chain. This pSer(727) modification is further controlled by glutathione-dependent antioxidant pathway(s) that mediate stromal protection of the leukemic B cells and regulate their viability. Importantly, pSTAT3Ser(727), but neither Tyr705-phosphorylated STAT3 nor total STAT3, levels correlate with prolonged in vivo CLL B cells survival. Furthermore, STAT3 activity contributes to the resistance to apoptosis of CLL, but not normal B cells, in vitro. These data reveal that mitochondrial (Mt) pSTAT3Ser(727) overactivity is part of the antioxidant defense pathway of CLL B cells that regulates their viability. Mt pSTAT3Ser(727) appears to be a newly identified cell-protective signal involved in CLL cells survival. Targeting pSTAT3Ser(727) could be a promising new therapeutic approach.

Neurodevelopmental outcome following prenatal diagnosis of an isolated anomaly of the corpus callosum.

OBJECTIVES: To assess the ability of prenatal ultrasound and magnetic resonance imaging (MRI) to diagnose isolated anomalies of the corpus callosum (ACC) and to further document the long-term prognosis following diagnosis. METHODS: This was a prospective case-control study carried out between 1999 and 2004. Diagnosis was made by a combination of ultrasound and MRI. All infants were examined by a neuropediatrician and parents consented to answer questionnaires (CDI, Ireton's Child Developmental Inventory) in 22 cases, which were matched with 44 control infants. The CDI was used to assess neurodevelopmental outcome in cases and controls. Mean DQ-CDI (development quotient calculated from CDI) values and frequencies of abnormal results were compared between groups, and a meta-analysis of previous studies was performed. RESULTS: The diagnosis of ACC was made prenatally and confirmed postnatally in 175 cases. The diagnosis was thought to be isolated ACC in 88/175 (50%) cases. Sixty of these 88 cases (68%) underwent termination of pregnancy and one died in utero. Twenty-seven were liveborn, of which 26 were followed up for a median of 50 (range, 30-74) months. Additional anomalies were diagnosed postnatally in four (15%) of these 26 neonates. The control group was significantly better (P < 0.05) compared with the cases diagnosed prenatally with isolated ACC with respect to gross motor, fine motor, language comprehension, numbers and general development, and it was marginally better for letters (P = 0.066). Seven of 26 (27%) (95% CI, 13-46%) infants with ACC over the age of 30 months had neurodevelopmental delay, compared with only one case with borderline developmental delay among the 44 controls (P = 0.006). CONCLUSION: Prenatal diagnosis of ACC by a combination of ultrasound and MRI is reliable. However, the isolated nature of the anomaly could only be assessed in 85% of our cases. Since counseling is provided at the time of prenatal diagnosis, our population of isolated ACC included the cases that were missed prenatally as being ACC with associated anomalies. A meta-analysis of nine studies suggests that the development of children diagnosed prenatally with isolated ACC is normal in up to 70% (CI 95%, 56-83%) of cases. This means that the prospective risk of neurodevelopmental delay for a fetus with ACC described as isolated prenatally is 27%, compared with 15% for an infant whose diagnosis of isolated ACC is confirmed postnatally.

Measurement of the corpus callosum using magnetic resonance imaging: analyses of methods and techniques.

Since the first postmortem report of sex-related differences in the size of the human corpus callosum, a number of studies on sex differences have been published, but results conflicted. The aim of this review was not to assess the possible existence and magnitude of sex variations in the size of the corpus callosum but to analyze methodological differences in several studies using Magnetic Resonance Imaging to investigate the sexual dimorphism in the size of the corpus callosum. Methodological problems arise at several steps of the method: sampling, imagery techniques, and measurements. Moreover, the means of callosal areas obtained by the nine reported studies are significantly different. The hypothesis that methodoiogical differences could explain these differences is supported by statistical results. A common method for investigating sex-related differences in callosal morphology appears necessary to resolve the question of a real sexual dimorphism of the corpus callosum and its subregions.

Magnetic resonance imaging and cerebral volumic evaluation: comparison of four post-processing techniques.

Four different MRI techniques of volumetric evaluation were applied in 10 healthy females and compared. The results have shown that not all techniques were interchangeable, but that the results of two groups of methods are not statistically different.

Hemispheric asymmetry and corpus callosum morphometry: a magnetic resonance imaging study.

Previous post-mortem studies (Aboitiz, F., Scheibel, A.B., Fisher, R.S., Zaidel, E., 1992. Brain Res. 598, 154-161 and Aboitiz, F., Scheibel, A.B., Zaidel, E., 1992. Brain 115, 1521-1541) have shown an inverse association between asymmetry in perisylvian areas and the size of a specific segment, the isthmus, of the corpus callosum (CC) in males. The purpose of this work was to study in vivo the association between hemispheric asymmetry and the total size of the CC in 35 right-handed subjects (16 males, 19 females; mean age 24.9 +/- 3.9). An MRI scan was performed for each subject. The area of the right (RH) and left (LH) hemispheres were measured from images in the sagittal plane and the area of the CC from images in the mid-sagittal plane. The index of hemispheric asymmetry was absolute value((LH - RH)/[(LH + RH)/2]). There was a negative correlation between the absolute value of hemispheric asymmetry and the size of the CC in males (r = -0.55, P = 0.03) but not in females (r = -0.20, P = 0.42). These findings, like those of Aboitiz et al. (Aboitiz, F., Scheibel, A.B., Zaidel, E., 1992. Brain 115, 1521-1541), suggest a sex-dependent decrease in interhemispheric connectivity with increasing hemispheric asymmetry.

Procedure to extract a weekly pattern of performance of human reaction time.

A study of reaction time in six tests (speed of simple identification, simultaneous and sequential letter identification, simultaneous and sequential stimulus word matching, and semantic verification) was carried out on 130 children aged 7 to 12 years. Subjects were tested Monday, Tuesday, Thursday, and Friday, using a cross-sectional design. The answers to each of the tests are binary in nature (Yes/No) measured by the recording of a click one of the two buttons of a microcomputer. Controlled variables were age, failure, sex, and day of test. The greatest percentage of the variance produced by the data was due to the age (typically 25%). The percentage attributable to the "day of test" (typically 5%) is hence masked by the variance due to the other factors. The method proposed herein makes it possible to isolate the percentage of the variance for the variable "day of test" alone and to provide evidence for a circaseptan effect on reaction time. It used a regressive correction on predominant variables. This effect shows performance is best on Thursday and weakest on Monday, the amplitude of the weekly rhythm being related to the task.

Is a dot-filling group test a good tool for assessing manual performance in children?

A dot-filling test was used to assess hand performance in two populations of French children. In the first experiment, the effect of sex, age and handedness on hand performance was examined (1742 children). Age was related to the degree of laterality, but girls were less lateralized than boys. The second experiment (200 children) showed that the surprising sex differences cannot be explained by the group testing procedure. Underlying processes leading to performance in the dot-filling task are probably different from those involved in other tests generally used for children.

[Continuous-flow determination of delta-aminolevulinic acid in urine (author's transl)]. / Dosage de l'acide delta-aminolévulinique urinaire. Automatisation en flux continu.

The automatic determination of urinary ALA using a continuous flow methodology, is described. The amplification of the measured signal, with an adjusted range expander, allows to reduce the sample volume and to decrease drastically the effects of interfering substances. The results are compared with the reference method of Davis and Andelman [11].

[Properties of histones on hydrophobic chromatography]. / Le comportement des histones en chromatographie hydrophobe

The hydrophobic chromatography on alkylated Sepharose allows to separate the histones into three groups which exhibit an increasing affinity for the support HI less than H2A-H2B less than H3-H4. In this fractionation procedure, the behaviour of the histones taken separately or pair-associated, is discussed in relation with the ability of these proteins to complex each other in vitro and in vivo.