Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro.

The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown. Folate shortage results in homocysteine accumulation. Elevated levels of homocysteine have been related to neural tube defects. We studied the behavior of neuroepithelial cells and cranial and cardiac neural crest cells in vitro. Neural tube explants were cultured for 24 and 48 hr in medium after addition of folic acid and/or homocysteine. Folic acid addition increased neuroepithelial cell outgrowth and increased neural crest cell differentiation into nerve and smooth muscle cells. Addition of homocysteine increased neural crest cell outgrowth and migration from the neural tube and inhibited neural crest cell differentiation. Our findings suggest that neural tube defects caused by folate deficiency and hyperhomocysteinemia develop due to increased neuroepithelial to neural crest cell transformation. This increased transformation leads to a shortage of neuroepithelial cells in the neural tube. Defects in orofacial and conotruncal development are explained by abnormal differentiation of neural crest cells in the presence of high homocysteine concentrations. Our findings supports a critical role for folic acid and homocysteine in the development of neural tube defects and neural crest related heart malformations.     

Common genetic variants do not associate with CAD in familial hypercholesterolemia

In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49–0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD.     

Energy expenditure at rest and during activities: A comparison between young and elderly women

Energy expenditure at rest (resting metabolic rate, RMR) and during several activities was measured in 20 young (age 19–27 years) and 19 elderly (age 65–78 years) females. Fat-free mass (FFM) was estimated by means of a four compartment model which accounted for variability in water and bone mineral in the FFM. RMR was lower (P < 0.05) in the elderly (mean ± SE 3.55 ± 0.05 kJ/min) compared to the younger females (3.92 ± 0.09 kJ/min). However, after correction for differences in FFM between the groups, RMR was 3.71 ± 0.07 kJ/min and 3.77 ± 0.06 kJ/min for the elderly and young, respectively, and the difference was not significant. Energy expenditure (EE) during several activities, standing with arm movement, bicycling at 25 Watts, and walking at 3 km/h, were not different between the two groups. However, the physical activity ratios (PAR) for the activities were higher (P < 0.05) in the elderly (1.61 ± 0.03, 3.29 ± 0.07, 4.11 ± 0.16, respectively) than in the young (1.47 ± 0.03, 2.93 ± 0.05, 3.58 ± 0.14, respectively). EE due to physical activity alone (total EE minus RMR) was significantly higher for all activities in the elderly, except for walking at fixed speed of 3 km/h. After correction for the lower relative FFM in the elderly, differences between age groups disappeared. EE for walking 500 m at an individually selected speed was higher in the elderly, although they selected a lower walking speed. Differences between young and elderly decreased when step frequency was taken into account. It is concluded that EE due to physical activity in elderly women is higher than in younger females, but that the differences in EE due to physical activity are largely attributable to differences in body composition. © 1996 Wiley-Liss, Inc.     

Pulmonary problems associated with lymphoplasmacytic lymphoma (Waldenström's macroglobulinemia)

A 62-year-old man, known for some years due to lymphoplasmacytic lymphoma, was admitted with progressive dyspnoea. Multiple lung infiltrates were found upon X-ray examination. Because of the suspicion of an infection, a bronchoscopy with bronchoalveolar lavage was performed. No infectious cause could be established. Upon cytological examination, a highly increased level of kappa-positive B-lymphoid cells was found, as is seen in cases of lymphoplasmacytic lymphoma (Waldenstr?m's macroglobulinaemia). Following chemotherapy, the dyspnoea lessened and the pulmonary infiltrates disappeared. In patients with a lymphoproliferative disorder, pulmonary infiltrates due to infection are found relatively frequently. This case report highlights a rare complication of the disease, namely pulmonary infiltrates caused by infiltration of lymphoplasmacytic cells, emphasising the importance of cytological examination of broncho-alveolar lavage fluid.     

Gait in children with cerebral palsy: observer reliability of Physician Rating Scale and Edinburgh Visual Gait Analysis Interval Testing scale

The aim of this study was to test the inter- and intraobserver reliability of the Physician Rating Scale (PRS) and the Edinburgh Visual Gait Analysis Interval Testing (GAIT) scale for use in children with cerebral palsy (CP). Both assessment scales are quantitative observational scales, evaluating gait. The study involved 24 patients ages 3 to 10 years (mean age 6.7 years) with an abnormal gait caused by CP. They were all able to walk independently with or without walking aids. Of the children 15 had spastic diplegia and 9 had spastic hemiplegia. With a minimum time interval of 6 weeks, video recordings of the gait of these 24 patients were scored twice by three independent observers using the PRS and the GAIT scale. The study showed that both the GAIT scale and the PRS had excellent intraobserver reliability but poor interobserver reliability for children with CP. In the total scores of the GAIT scale and the PRS, the three observers showed systematic differences. Consequently, the authors recommend that longitudinal assessments of a patient should be done by one observer only.     

ITS barcodes for Trichophyton tonsurans and T. equinum.

Early molecular biosystematic studies of dermatophytes created considerable confusion about the taxonomic status of the horse-associated Trichophyton equinum vis-à-vis the anthropophilic T. tonsurans. Though this matter has recently been clarified, routine identification of these species based on the commonly used ribosomal internal transcribed spacer (ITS) sequence has been impractical. This is because, in the available sequences attributed to the species in GenBank, a clear species-level distinction does not appear to exist. In the present study, resequencing the ITS regions of several anomalous isolates is shown to eliminate this problem, which was mainly based on read errors in older sequences. Newly generated sequences and recent GenBank additions are analysed to show that T. equinum appears to be uniform in ITS sequence worldwide, while T. tonsurans is also uniform, excepting a single-base change found in one otherwise typical strain. Analysis also reveals a distinct, as yet incompletely classified Asian genotype that may belong to one or the other of these species. Standard ITS 'barcode sequences' are proposed for T. tonsurans and T. equinum, and a taxonomic neotype is designated to anchor the latter species. T. equinum var. autotrophicum is further evidenced as very closely related to T. equinum var. equinum, and the anomaly of its plesiomorphous phenotype is discussed in a population genetics context.