Imaging of elasticity distribution in arterial wall by transcutaneous ultrasound and electronic staining

Knowledge of the physical properties of atherosclerotic plaque is essential when evaluating its vulnerability in a clinical setting. Such knowledge, however, is still difficult to obtain with the various approaches developed to date. This paper describes a novel noninvasive method (phased tracking method) for measuring minute change in thickness of each of the multiple layers of the arterial wall during one cardiac cycle. Such minute change in thickness less than 100 microns of the arterial wall cannot be measured by conventional ultrasound B-mode or M-mode images. A method for evaluation of the regional elastic modulus in the circumference direction, E theta, from the resultant change in wall thickness is also described. This method was applied to in vivo experiments in subjects with hyperlipemia and normal subjects. The spatial distribution of the regional elastic moduli, E theta, was evaluated for the carotid atherosclerotic plaques. By comparing the pathological findings with the distribution of elasticity, average elasticity of lipid and that of a mixture of smooth muscle and collagen fiber could be determined. Based on these reference parameters, each point was statistically categorized as lipid, mixture, or other. Thus, the plaque was electronically stained using transcutaneous ultrasound. By applying this method to the common carotid arteries, the presence of thin collagen fiber was clarified along the arterial axis for normal subjects, while soft inclusion of lipid was found for every plaque in subjects with hyperlipidemia. This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution.     

The kinesin superfamily protein Rab6KIFL is not involved in the pathophysiology of Charcot-Marie-Tooth disease type 4C

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive peripheral neuropathy reported in several Algerian families. The gene locus of this disease has been narrowed to 5q31-33. Recently, a missense mutation in the gene for the kinesin superfamily KIF1B was reported as the cause of Charcot Marie Tooth disease type 2A (CMT2A). We suspected that Rab6KIFL, one of the kinesin superfamily proteins, might be involved in the pathophysiology of CMT4C, because Rab6KIFL gene is located in 5q31. The coding regions of the Rab6KIFL gene of genomic DNA derived from one Algerian family with CMT4C were analyzed by direct sequencing. No mutation in Rab6KIFL gene was found in this family. Further investigation is necessary to identify the causative gene for CMT4C.     

High-resolution nuclear magnetic resonance spectroscopic study of metabolites in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

There have been few reports describing substances related to oxidative and intermediary metabolism in the cerebrospinal fluid (CSF) in patients with spinal degenerative disorders. This study investigated whether the concentrations of metabolites in the CSF differed between patients with spinal degenerative disorders and controls, and whether the concentrations of these metabolites correlated with the severity of symptoms. CSF samples were obtained from 30 patients with cervical myelopathy (Group M), 30 patients with lumbar radiculopathy (Group R), and 10 volunteers (control). Metabolites in these CSF samples were measured by nuclear magnetic resonance spectroscopy. There were no differences in the concentrations of lactate, alanine, acetate, glutamate, pyruvate, or citrate between Groups M and R, between Group M and the control, or between Group R and the control. In Group M, neither symptom duration nor the Japanese Orthopaedic Association score correlated with the concentration of any metabolite. In Group R, the symptom duration positively correlated with the concentration of lactate, glutamate, and citrate in CSF. The duration of nerve root block showed a negative correlation with the concentrations of acetate in CSF of the patients in Group R. In patients with lumbar radiculopathy, there is a possibility of increased aerobic metabolic activity or decreased gluconeogenic activity in patients with shorter symptom duration, and increased aerobic metabolic activity in patients with severe inflammation around a nerve root.     

Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro

The substantia gelatinosa (SG) of the spinal dorsal horn shows significant morphological heterogeneity and receives primary afferent input predominantly from Aδ- and C-fibres. Despite numerous anatomical and physiological studies, correlation between morphology and functional connectivity, particularly in terms of inhibitory inputs, remains elusive. To compare excitatory and inhibitory synaptic inputs on individual SG neurones with morphology, we performed whole-cell recordings with Neurobiotin-filled-pipettes in horizontal slices from adult rat spinal cord with attached dorsal roots. Based on dendritic arborization patterns, four major cell types were confirmed: islet, central, radial and vertical cells. Dorsal root stimulation revealed that each class was associated with characteristic synaptic inputs. Islet and central cells had monosynaptic excitatory inputs exclusively from C-afferents. Islet cells received primary-afferent-evoked inhibitory inputs only from Aδ-fibres, while those of central cells were mediated by both Aδ- and C-fibres. In contrast, radial and vertical cells had monosynaptic excitatory inputs from both Aδ- and C-fibres and inhibitory inputs mediated by both fibre types. We further characterized the neurochemical nature of these inhibitory synaptic inputs. The majority of islet, central and vertical cells exhibited GABAergic inhibitory inputs, while almost all radial cells also possessed glycinergic inputs. The present study demonstrates that SG neurones have distinct patterns of excitatory and inhibitory inputs that are related to their morphology. The neurotransmitters responsible for inhibitory inputs to individual SG neurones are also characteristic for different morphological classes. These results make it possible to identify primary afferent circuits associated with particular types of SG neurone.     

PMMA-based bioactive cement: effect of glass bead filler content and histological change with time.

A new bioactive bone cement (designated GBC), which is a polymethyl methacrylate (PMMA)-based composite consisting of bioactive glass beads as an inorganic filler and high molecular-weight PMMA as an organic matrix, has been developed. The purpose of the present study was to evaluate the effect of the filler content on the mechanical properties and osteoconductivity of GBC, to decide the most suitable filler proportion, and to evaluate the degree of cement degradation with time. The bioactive beads, consisting of MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass, were added to the cement in various proportions (40-70 wt %). The bending strength of GBC did not differ among the proportions (approximately 136 MPa), but the elastic modulus of bending of GBC increased as the glass bead filler content increased (approximately 4.1-7.2 GPa). The all types of GBC were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index calculated as the length of bone in direct contact with the cement surface expressed as a percentage of the total length of the cement surface. Rats were sacrificed at 4, 8, 25, and 39 weeks after implantation, and the affinity index was calculated for each type of GBC at each time point. Histologically, new bone had formed along the surface of all types of GBC within 4 weeks, even in GBC containing only 40 wt % of glass beads. The affinity indices of GBC tended to increase as the proportion of glass bead filler increased and as the implantation period increased. In GBC containing 60 or 70 wt % of glass beads, significant rapid increases in the affinity indices were found from 4 to 8 weeks, and the high values (approximately 70%) were maintained up to 39 weeks. A sign of glass bead degradation was observed at the bone-cement interface in the rat tibiae at 39 weeks. We conclude that, when mechanical properties and osteoconductivity are both taken into consideration, GBC containing 60 or 70 wt % of glass beads is the most suitable formulation, but that further studies are needed to investigate and overcome the degradation.     

Mutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence

Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1 (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide and CA repeat polymorphisms in the 5' region and 3' untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22-q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence.     

A unique localization of mechanoreceptors in the periodontal tissue of guinea pig teeth

This study describes the unique distribution of Ruffini endings (RE) in the periodontal tissues of the guinea pig teeth with special references to their presence in the enamel-related aspects of the continuously growing incisors and molars. In guinea pig incisors, immunohistochemistry for PGP 9.5 and glia specific S-100 protein revealed a condensed distribution of well-developed RE in the bone-related part of the lingual periodontal ligament as has been reported in many other rodents. In most cases, some RE-like nerve elements characterized by dendritic ramification and rounded terminal Schwann cells were found to be located in the labial, enamel-related regions, where no periodontal ligament-like fiber arrangement was established. In the molar periodontal ligament, well-developed RE-like nerve elements were also distributed in the enamel-related part, but in intimate relation to thick periodontal fiber bundles inserted in the cementum pearls grown on the enamel surface. In some cases, few RE were located in the apical region of the alveolar socket, where no periodontal fiber bundles could be identified. Our data provide the first morphological evidence of the presence of RE-like nerve elements in the enamel-related, fibrous connective tissue of continuously erupting rodent incisors. These data indicate that RE in guinea pig periodontal tissues have variable spatial correlation to the surrounding fibers, implicating their diverse mechanoreceptive properties depending on the anatomical location.     

Mutation analysis of the retinoid X receptor beta,nuclear‐related receptor 1, and peroxisome proliferator‐activated receptor alpha genes in schizophrenia and alcohol dependence: Possible haplotype association of nuclear‐related receptor 1 gene to alcohol dependence

Because retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear‐related receptor 1 (NURR1) or with peroxisome proliferator‐activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22–q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2–13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single‐nucleotide and CA repeat polymorphisms in the 5′ region and 3′ untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22–q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence. © 2001 Wiley‐Liss, Inc.