Stereologic characterization and spatial distribution patterns of Betz cells in the human primary motor cortex

Betz cells are giant motoneurons located in layer Vb of the primate primary motor cortex. We conducted stereological analyses of Betz cells and neighboring pyramidal cells from the brains of six neurologically normal elderly humans to determine their volume, total number, and spatial distribution, and to relate these data to functional localization. The distribution of cellular volumes exhibits a bimodal pattern, delineating two different subpopulations. Betz cell volumes follow a mediolateral gradient, the largest Betz cells being located on the most medial part of the motor cortex. Additionally, the shape of Betz cells varies between the rostral and caudal parts of the primary motor cortex, supporting the notion that there are anatomically distinct zones in primary motor cortex. The total number of Betz cells per hemisphere accounts for about one-tenth of the total number of pyramidal cells in layer Vb. Analysis of spatial distribution using Voronoi tessellation revealed maximal clustering of Betz cells in a zone situated two-thirds from the midline along the mediolateral axis of the primary motor cortex. These data suggest that Betz cells have a discrete subregional distribution that may correspond to certain aspects of the functional parcellation of area 4. These results may offer a histological correlate of functional imaging studies and are relevant in the context of neurodegenerative diseases such as amyotrophic lateral sclerosis, progressive supranuclear palsy, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia, and in studies of normal brain aging.     

Influence of food on the absorption of albuterol Repetabs

A study was conducted in 12 healthy, nonsmoking male volunteers to examine the effect of food intake on the absorption profile of albuterol repeat-action tablets. This randomized crossover study consisted of two phases separated by a 1-week washout period. All subjects fasted 10 hours preceding drug administration. Each subject received two 4 mg albuterol repeat-action tablets with and without a high fat content breakfast. Plasma albuterol concentrations were determined by a gas chromatographic/mass spectrophotometric assay. Relative bioavailability was assessed by comparing areas under the plasma-albuterol concentration time curves as well as peak concentrations and time to peak concentration. No significant differences were noted between the two treatment phases in the area under the curve or peak plasma concentrations. The areas under the curve were 100 and 105 hr.ng/ml when the drug was administered with and without food, respectively. The corresponding peak plasma concentration values were 9.4 and 10.4 ng/ml, respectively. The only significant difference observed was in the maximum time to reach peak plasma concentrations, which was delayed by about 1 hour when the drug was administered with food. Therefore, food has minimal effect on the absorption of albuterol from repeat-action tablets.     

Minicircular DNA having sequence homologies with chloroplast DNA in a bleached mutant of Euglena gracilis

Summary Chloroplast DNA was isolated from total cellular DNA of a bleached mutant of Euglena gracilis (Y₃BUD) by enrichment of the light component (p = 1.686) by repeated CsCl equilibrium centrifugations. Electron microscope visualization of this DNA showed minicircular DNA molecules in addition to large circular molecules (42 pm) identical to wild type chloroplast DNA. They were heterogenous in size and their contour lengths ranged from 0.8 to 8.5 m. Fractionnation by agarose gel electrophoresis gave several discrete bands. Some of them hybridized with pure chloroplast DNA and with several cloned chloroplast DNA fragments, particularly to ribosomal fragments, while others did not show homology with chloroplast DNA being probably of extrachloroplatic origin.     

Three new families with arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition.     

Test of the dual‐belief system in women with and without phobic fear of spiders: a pilot study

This study tests the so‐called dual‐belief systems. According to this concept, patients with phobia foster two conflicting peripheral beliefs (situational dependent) about the fear‐inducing stimulus. The existence of such conflicting beliefs can only be explained by so‐called bridging core beliefs. These bridging core beliefs are situation independent and integrate the contradictions of the peripheral beliefs. To test the existence of bridging core beliefs, 60 women with and without spider phobia were interviewed during exposition to phobic and neutral stimuli. Women with phobic anxiety reported more phobic emotions, thoughts, and peripheral beliefs during exposure to a phobic stimulus than during exposure to a neutral stimulus. In core beliefs no differences between the two conditions were found. In the non‐phobic control group, no differences were found for the conditions in any of the dependent variables. All together, these data provide support for the existence of dual‐belief systems as well as bridging core beliefs. Copyright © 2006 John Wiley & Sons, Ltd.     

The incorporation of iodine in thyroid hormone may stem from its role as a prehistoric signal of ecologic opportunity: an evolutionary perspective and implications for modern diseases

To optimize fitness under conditions of varying Darwinian opportunity, organisms demonstrate tremendous plasticity in their life-history strategies based on their perception of available resources. Higher-energy environments generally promote more aggressive life-history strategies, such as faster growth, larger adult size, greater genetic variation, shorter lifespan, larger brood sizes, and offspring ratio skewed towards the larger-sized gender. While numerous mechanisms regulate life-history plasticity including genetic imprinting, methylation, and growth factors, evidence suggests that thyroid hormone plays a central role. Given the pivotal adaptive role of thyroid hormone, the teleology of its dependence on dietary iodine for production remains unexplained. We hypothesize that iodine may have emerged as a substrate for production of thyroid hormone in prehistoric ecosystems because the former represented a reliable proxy for ecologic potential that enabled the latter to modulate growth, reproduction, metabolic rate, and lifespan. Such a scenario may have existed in early marine ecosystems where ocean-surface vegetation, which concentrates iodine for its antimicrobial and antioxidant properties, formed the basis of the food chain. Teleologic parallels can be drawn to the food-chain accumulation of antimicrobials that also exhibit antioxidant properties and promote adult size, brood size, and offspring quality by modulating central hormonal axes. As each higher species in the food chain tunes its life-history strategy based on iodine intake, the coupling of this functional role of iodine with its value as a resource signal to the next member of the food-chain may promote runaway evolution. Whereas predators in prehistoric ecosystems successfully tuned their life-history strategy using iodine as a major input, the strategy may prove maladaptive in modern humans for whom the pattern of iodine intake is decoupled from resource availability. Iodine acquired through sodium iodide supplementation may independently contribute to some biologic dysfunctions currently attributed to sodium.     

SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis

Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms.     

Quantification of Human Immunodeficiency Virus Type 1 RNA Levels in Plasma by Using Small-Volume-Format Branched-DNA Assays

We have developed small-volume (50 or 250 μl)-format branched-DNA assays for human immunodeficiency virus type 1 (HIV-1) RNA for use with specimens in which the volume is limited and/or a high viral load is anticipated. These formats exhibited good correlation with the standard 1-ml format; high specificity, reproducibility, and linearity; and no significant difference in the quantification of HIV-1 subtypes.