Intermittent preventive sulfadoxine-pyrimethamine treatment of primigravidae reduces levels of plasma immunoglobulin G, which protects against pregnancy-associated Plasmodium falciparum malaria

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A. Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA(PAM)-that specifically mediate protection against PAM than did women receiving a placebo. VSA(PAM)-specific IgG levels depended on the number of IPTp doses received and were sufficiently low to be of clinical concern among multidose recipients. Our data suggest that IPTp should be extended to women of all parities, in line with current World Health Organization recommendations.     

Improvement of Accuracy in a High-Capacity, Six Degree-of-freedom Load Cell: Application to Robotic Testing of Musculoskeletal Joints

This study investigated a previously unaccounted for source of error in a high-capacity, six degree-of-freedom load cell used in multi-degree-of-freedom robotic testing of musculoskeletal joints, an application requiring a load cell with high accuracy in addition to high load capacity. A method of calibration is presented for reducing the error caused by changes in universal force-moment sensor (UFS) orientation within a gravitational field. Uncorrected, this error can exceed a magnitude of 1% of the full-scale load capacity—the manufacturer-stated accuracy of the UFS. Implementation of the calibration protocol reduced this error by approximately 75% for a variety of loading conditions. This improvement in load cell accuracy (while maintaining full load capacity) should improve both the measurement and control of specimen kinetics by robotic/UFS and other biomechanical testing systems. © 1999 Biomedical Engineering Society. PAC99: 8719Rr, 8780Vt, 0620Fn, 0620Dk, 8719Ff     

Analogue simulator of e.e.g. signals based on spectral components

A model describing the spectral properties of e.e.g signals by a set of parameters has previously been introduced. It leads to a decomposition of the spectrum into one or more spectral components. The described e.e.g.-signal simulator is based on such a decomposition into one delta, and three rhythmic components called theta, alpha and beta denoting the location of the resonance peaks. Each component is generated separately with a noise generator and a spectral shaping filter. Care is taken to make the noise generator have a flat spectrum down to zero frequency. The spectral shaping filters are of an active type with a configuration that allows easy adjustment of poles and zeros. The use of the equipment is demonstrated by simulating five different e.e.g. signals first by analysing the e.e.g., and then by setting the simulator to produce an identical spectrum.     

Glucose-6-phosphate dehydrogenase activity in monolayer cultures of thyroid epithelial cells: TSH and inhibition of nitrogen oxide synthase affect the enzyme activity and the oxygen sensitivity of the histochemical assay

The objective was to investigate glucose-6-phosphate dehydrogenase (G6PD) activity in monolayer cultures of thyroid epithelial cells and to examine whether inhibition of nitric oxide synthase affects activity of G6PD or oxygen sensitivity of the assay. Primary cultures without TSH addition prior to experiments demonstrated a TSH-dependent increase in G6PD activity. G6PD activity was higher in F12 medium than in a serum-free physiological medium. Secondary cultures grown in F12 medium demonstrated a diminished activity of G6PD and a lack of response to TSH. In the serum-free physiological medium, G6PD activity was comparable to that found in primary cultures and a response to high concentrations of TSH was maintained. In primary cultures grown in F12 medium devoid of TSH, G6PD activity decreased dose-dependently when nitric oxide synthase activity was inhibited. The oxygen sensitivity of the assay was comparable to that reported previously in malignant cells and correlated with the activity of G6PD in primary cultures. We suggest that thyroid epithelial cells may be an appropriate system to investigate oxygen sensitivity of the G6PD assay as the cells demonstrate a reduced oxygen sensitivity which can be influenced by culture conditions.     

Contact heat evoked potentials to painful and non-painful stimuli: effect of attention towards stimulus properties

The study aim was to evaluate the effect of different attentional tasks on the amplitudes and latencies of painful and non-painful contact heat evoked potentials (CHEPs). CHEPs were recorded in 12 healthy subjects during two experimental conditions, in which attention was oriented towards the intensity and the distress caused by the stimuli and were compared with CHEPs recorded during a neutral condition. The painful heat stimulation produced a negative potential at Cz vertex with a latency around 540 ms (Cz/N540), a positive peak at Cz electrode around 730 ms (Cz/P730) and, lastly, a positive peak around 1000 ms (Pz/P1000) in the Pz traces. The Cz/P730 wave was significantly higher in amplitude only during the painful stimulation and is probably related to coding the nociceptive activity. Varying the attentional target towards different properties of the stimulus did not cause any significant change in CHEP responses amplitude and latencies compared with the neutral condition. Our results suggest that CHEPs represent a reliable functional measure of the nociceptive pathways and that they are generated by the activation of different cerebral areas involved in pain processing. The high activation level of each of these area or their spatial neighbouring might explain the strong similarity of CHEP components recorded during different attentional manipulations.     

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.     

Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP)

The D allozyme of placental alkaline phosphatase (PLAP) displays enzymatic properties at variance with those of the common PLAP allozymes. We have deduced the amino acid sequence of the PLAP D allele by PCR cloning of its gene, ALPP. Two coding substitutions were found in comparison with the cDNA of the common PLAP F allele, i.e., 692C>G and 1352A>G, which translate into a P209R and E429G substitution. A single nucleotide primer extension (SNuPE) assay was developed using PCR primers that enable the amplification of a 1.9 kb PLAP fragment. Extension primers were then used on this PCR fragment to detect the 692C>G and 1352A>G substitution. The SNuPE assay on these two nucleotide substitutions enabled us to distinguish the PLAP F and D alleles from the PLAP S/I alleles. Functional studies on the D allozyme were made possible by constructing and expressing a PLAP D cDNA, i.e., [Arg209, Gly429]PLAP, into wild-type Chinese hamster ovary cells. We determined the k(cat) and K(m), of the PLAP S, F, and D allozymes using the non-physiological substrate p-nitrophenylphosphate at an optimal pH (9.8) as well as two physiological substrates, i.e., pyridoxal-5-phosphate and inorganic pyrophosphate at physiological pH (7.5). We found that the biochemical properties of the D allozyme of PLAP are significantly different from those of the common PLAP allozymes. These biochemical findings suggest that a suboptimal enzymatic function by the PLAP D allozyme may be the basis for the apparent negative selective pressure of the PLAP D allele. The development of the SNuPE assay will enable us to test the hypothesis that the PLAP D allele is subjected to intrauterine selection by examining genomic DNA from statistically informative population samples.     

Does a torn anterior cruciate ligament lead to change in the central nervous drive of the knee extensors?

Summary Integrated surface electromyograms of the three superficial parts of the quadriceps and isokinetic knee extensor maximum torque and power production were recorded simultaneously and at different angular velocities in both legs in 11 male subjects with unilateral tear of the anterior cruciate ligament. The cross-sectional area (CSA) of the thigh and its muscular components were measured by computerized tomography. The principal findings were a small but significant decrease in quadriceps CSA on the affected side; a decreased active, but not passive, range of movement; decreased mechanical output, whether or not corrected for differences in CSA; and decreased electrornyographic activity — particularly in rectus femoris. These findings suggest that the reason for the decreased maximum and total knee extensor performance seen in these patients is a change in knee joint receptor afferent inflow.