Variability analysis of SAR from 20 MHz to 2.4 GHz for different adult and child models using finite-difference time-domain

This paper deals with the variability of body models used in numerical dosimetry studies. Six adult anthropomorphic voxel models have been collected and used to build 5-, 8- and 12-year-old children using a morphing method respecting anatomical parameters. Finite-difference time-domain calculations of a specific absorption rate (SAR) have been performed for a range of frequencies from 20 MHz to 2.4 GHz for isolated models illuminated by plane waves. A whole-body-averaged SAR is presented as well as the average on specific tissues such as skin, muscles, fat or bones and the average on specific parts of the body such as head, legs, arms or torso. Results point out the variability of adult models. The standard deviation of whole-body-averaged SAR of adult models can reach 40%. All phantoms are exposed to the ICNIRP reference levels. Results show that for adults, compliance with reference levels ensures compliance with basic restrictions, but concerning children models involved in this study, the whole-body-averaged SAR goes over the fundamental safety limits up to 40%.     

B-cell maturation defects in common variable immunodeficiency and association with clinical features

AIMS: Patients with common variable immunodeficiency (CVID) often have defects in post-antigenic B-cell differentiation with fewer memory B cells and impaired isotype switching. We aimed to classify CVID patients according to these defects and determine whether this predicted clinical manifestations. METHODS: We analysed the memory marker CD27, maturation marker CD21, and IgD on peripheral blood B cells from 31 CVID patients and 23 controls using a whole-blood lysis technique, allocated patients according to two classifications ('Freiburg' and 'Paris') and correlated results with clinical manifestations. RESULTS: CVID patients had fewer memory (CD27(+)) B cells and isotype-switched (IgD(-)) memory B cells in absolute number and proportion. Many CVID patients had increased immature (CD21(-)) B cells. Lymphoproliferation and autoimmune cytopenias were found almost exclusively in these patients, including Freiburg group Ia (decreased switched memory and increased immature B cells), but also those with normal switched memory and increased immature B cells. The Paris classification was less useful in predicting clinical manifestations. CONCLUSIONS: CVID is associated with defects in memory B-cell differentiation. Subclassification helps identify patients with clinical manifestations, particularly lymphoproliferation and autoimmune cytopenias in those with impaired B-cell maturation and isotype switching. Routine B-cell phenotyping may assist clinicians in predicting these clinical features.     

Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P<0.001), caudate putamen (122%, P=0.002) and nucleus accumbens (170%, P<0.001) compared with controls; while lower but still significant increases of [(3)H]pirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.     

Common effects of touch and vision on postural parameters

Subjects stood upright with the index finger of the right hand either touching a nearby surface gently or not touching it at all and with the eyes either open or closed. Trajectories of the center of pressure (COP) were analyzed as fractional Brownian motion. The extracted parameters were the effective diffusion (D) coefficients and Hurst (H) exponents for short-term time intervals (corresponding to positively correlated random walks) and long-term time intervals (corresponding to negatively correlated random walks). Gentle tactile contact reduced the effective stochastic activity measured by D to the same extent as the availability of vision. Further, touch interacted with time interval in the same way as vision, with the correlated activity closer to H = 0.5 at both time scales when the finger contacted the nearby surface. The results corroborate and extend major features of recent investigations of haptic influences on posture and recent analyses of vision’s influence on the fractional Brownian motions of the COP. Discussion focused on (a) the equivalence of expropriospecific information (about the body’s orientation to the environment) registered haptically and visually and (b) the possibility that postural sway may reflect exploratory motions in the short term (obtaining information about the postural system) and performatory motions in the long term (using this information). Received: 17 February 1997 / Accepted: 18 June 1997     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception

The aim of this study was to compare 70 couples who had conceived by in- vitro fertilization (IVF) with 63 matched controls for the prevalence of anxiety and quality of attachment to the baby during pregnancy. Results for mothers showed no group differences using a global measure of anxiety, the Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific measures revealed significantly higher levels of anxiety in IVF mothers about the survival and normality of their unborn babies, about damage to their babies during childbirth and about separating from their babies after birth. When IVF mothers were differentiated according to the number of treatment cycles, more differences in anxiety level were revealed, with most increases occurring in mothers who had experienced two or more treatment cycles. IVF fathers did not differ from controls on the global anxiety measure. No data on pregnancy-specific anxiety were available for fathers. Neither IVF mothers nor IVF fathers differed from controls on measures of attachment to the baby during pregnancy. Results are discussed in the context of the need for researchers to employ differentiated and issue-specific measures to identify concerns that may be unique to IVF couples. Clinical implications regarding the need for psychological support during pregnancy are also discussed.      

Minimal progesterone support required for the maintenance of pregnancy in mice

A study of the degree of progesterone support required for the maintenance of various stages of pregnancy was undertaken in mice. Mated females were ovariectomized at various stages of pregnancy and progesterone and oestradiol support provided by s.c. Silastic implants with known release characteristics. In the earliest stages of pregnancy (days 1-5), very low concentrations of progesterone (<25% of normal physiological values) were sufficient to maintain pre-implantation stages and allow implantation. In the immediate post-implantation period (days 5-9), the development of implantation sites and decidualization required considerably higher progesterone support. In mid-pregnancy (days 11-14), progesterone alone could not maintain pregnancy unless present in very high amounts; however, the presence of oestradiol during this period lowered the progesterone requirements to well within the physiological range. This effect of oestradiol started on day 11 but required the level of oestradiol support to be kept within strictly defined limits, with high concentrations inducing abortion. Progesterone alone was able to maintain pregnancy from day 15. These results indicate that the minimal progesterone support required for pregnancy in mice varies considerably at different stages of pregnancy and is at least partly modulated by oestradiol.      

Patent applications for using DNA technologies to authenticate medicinal herbal material

Herbal medicines are used in many countries for maintaining health and treating diseases. Their efficacy depends on the use of the correct materials, and life-threatening poisoning may occur if toxic adulterants or substitutes are administered instead. Identification of a medicinal material at the DNA level provides an objective and powerful tool for quality control. Extraction of high-quality DNA is the first crucial step in DNA authentication, followed by a battery of DNA techniques including whole genome fingerprinting, DNA sequencing and DNA microarray to establish the identity of the material. New or improved technologies have been developed and valuable data have been collected and compiled for DNA authentication. Some of these technologies and data are patentable. This article provides an overview of some recent patents that cover the extraction of DNA from medicinal materials, the amplification of DNA using improved reaction conditions, the generation of DNA sequences and fingerprints, and the development of high-throughput authentication methods. It also briefly explains why these patents have been granted.     

Synergistic effects of dehydroepiandrosterone and fluoxetine on proliferation of progenitor cells in the dentate gyrus of the adult male rat

The 5-HT re-uptake inhibitor (SSRI) fluoxetine and the adrenal hormone dehydroepiandrosterone (DHEA) both increase the proliferation of progenitor cells in the adult hippocampus and also have antidepressant activity. This paper explores the combined ability of fluoxetine and DHEA to affect this process in the dentate gyrus of adult rats. We show that DHEA can render an otherwise ineffective dose of fluoxetine (2.5 mg/kg) able to increase progenitor cell proliferation to the same extent as doses four times higher (10 mg/kg). This synergistic action does not appear to be mediated by alterations in brain-derived neurotrophic factor (BDNF) gene expression; or by TrkB, mineralocorticoid, glucocorticoid, or 5-HT (5HT1A) receptor expression in the dentate gyrus; or by altered levels of plasma corticosterone. In a second experiment, the synergism between DHEA and fluoxetine was replicated. Furthermore, flattening the diurnal rhythm of plasma corticosterone by implanting additional corticosterone pellets s.c. prevented the effect of fluoxetine on progenitor cell division. This was not overcome by simultaneous treatment with DHEA, despite the latter's reported anti-glucocorticoid actions. The cellular mechanism for the potentiating action of DHEA on the pro- proliferative effects of fluoxetine in the adult hippocampus remains to be revealed. Since altered neurogenesis has been linked to the onset or recovery from depression, one consequence of these results is to suggest DHEA as a useful adjunct therapy for depression.     

Cloning and characterization of the mitochondrial heat-shock protein 60 gene of<Emphasis Type="Italic"> Trichinella spiralis</Emphasis>

The full-length cDNA of mitochondrial heat-shock protein (hsp) 60 of the infective-stage larva of Trichinella spiralis was cloned by degenerative PCR and rapid amplification of cDNA end reactions. The 1,945 bp full-length cDNA sequence contained an open reading frame of 576 amino acids. A mitochondrial signal peptide was located at the N-terminal and a GGM motif at the C-terminal. The gene contained ten exons and nine introns. RT-PCR analysis indicated that thermal, cold, acidic and oxidative treatment did not elicit significant changes in the expression of mitochondrial hsp 60 in the larvae. Cluster analysis showed that the sequence of the hsp 60 gene of T. spiralis is closely related to that of Drosophila melanogaster.