Novel ultrasonic bone densitometry based on two longitudinal waves: significant correlation with pQCT measurement values and age-related changes in trabecular bone density, cortical thickness, and elastic modulus of trabecular bone in a normal Japanese population.

UNLABELLED: A reference database for trabecular bone density, cortical thickness, and elastic modulus of trabecular bone for a novel ultrasonic bone densitometry system (LD-100) based on two longitudinal waves (fast and slow) was determined over a wide age range in a normal Japanese population. INTRODUCTION: A novel ultrasonic bone densitometry system (LD-100 system) was applied to create a reference database for trabecular bone density (TBD), cortical thickness (CoTh), and elastic modulus of trabecular bone (EMTb) for this device over a wide age range in a normal Japanese population. METHODS: In a comparative study between LD-100 and peripheral quantitative computed tomography (pQCT) systems, 52 individuals were examined by both systems at the same radius simultaneously. To create a reference database, a total of 2,380 healthy subjects (1,179 men, 1,201 women), ages 18-99 years, were examined using the LD-100 system. RESULTS: Highly significant correlations between the LD-100 and pQCT systems were found in TBD (r = 0.877, p < 0.001) and CoTh (r = 0.723, p < 0.001). For the reference database, peak values of TBD, CoTh, and EMTb were observed at 30-34 years (255.09 mg/cm(3)), 20-24 years (5.23 mm), and 20-24 years (4.09 GPa) in men, and at 25-29 years (209.24 mg/cm(3)), 25-29 years (3.98 mm), and 20-24 years (3.33 GPa) in women, respectively. The TBD fell significantly (p < 0.05) beginning at 55-59 years in both sexes, with a relatively rapid decrease in women. The CoTh showed a significant decrease beginning at 40-44 years in men and 50-54 years in women. The EMTb showed a significant decrease beginning at 40-44 years in men and 55-59 years in women. CONCLUSIONS: The LD-100 system is a useful bone densitometry device and the database of age-related changes in TBD, CoTh, and EMTb established in this study will provide fundamental data for future studies related to bone status.

Measurement of human trabecular bone by novel ultrasonic bone densitometry based on fast and slow waves.

SUMMARY: Two longitudinal transmitted waves, fast and slow waves, were observed by employing a new quantitative ultrasound (QUS) method. The trabecular bone measurements generated by this method reflect three-dimensional structural information, and the new QUS parameters were able to identify vertebral fractures. INTRODUCTION: The aims were to identify new quantitative ultrasound (QUS) parameters that based on new QUS method reflecting not only bone volume but also the microstructures of trabecular bone ex vivo and to observe how much they predict fracture risk in vivo. METHODS: Ex vivo measurement: Three human femoral heads were used for the experiment. Attenuation of the slow wave, attenuation of the fast wave, speed of the slow wave, speed of the fast wave (SOFW), bone mass density of trabecular bone, and elastic modulus of the trabecular bone (EMTb) of each specimen were obtained using a new QUS method and compared with three-dimensional structural parameters measured by micro-computed tomography. In vivo measurement: Eighty-nine volunteers were enrolled, and the bone status in the distal radius was measured using a new QUS method. These parameters were compared with data evaluated by peripheral quantitative computed tomography and dual X-ray absorptiometry. RESULTS: Ex vivo measurement: SOFW and EMTb showed correlations with the parameter of trabecular anisotropy. In vivo measurement: The new QUS parameters were able to identify vertebral fractures. CONCLUSION: The newly developed QUS technique reflects the three-dimensional structure and is a promising method to evaluate fracture risk.

In vivo structure-function analyses of Caenorhabditis elegans MEC-4, a candidate mechanosensory ion channel subunit.

Mechanosensory signaling mediated by mechanically gated ion channels constitutes the basis for the senses of touch and hearing and contributes fundamentally to the development and homeostasis of all organisms. Despite this profound importance in biology, little is known of the molecular identities or functional requirements of mechanically gated ion channels. We report a genetically based structure-function analysis of the candidate mechanotransducing channel subunit MEC-4, a core component of a touch-sensing complex in Caenorhabditis elegans and a member of the DEG/ENaC superfamily. We identify molecular lesions in 40 EMS-induced mec-4 alleles and further probe residue and domain function using site-directed approaches. Our analysis highlights residues and subdomains critical for MEC-4 activity and suggests possible roles of these in channel assembly and/or function. We describe a class of substitutions that disrupt normal channel activity in touch transduction but remain permissive for neurotoxic channel hyperactivation, and we show that expression of an N-terminal MEC-4 fragment interferes with in vivo channel function. These data advance working models for the MEC-4 mechanotransducing channel and identify residues, unique to MEC-4 or the MEC-4 degenerin subfamily, that might be specifically required for mechanotransducing function. Because many other substitutions identified by our study affect residues conserved within the DEG/ENaC channel superfamily, this work also provides a broad view of structure-function relations in the superfamily as a whole. Because the C. elegans genome encodes representatives of a large number of eukaryotic channel classes, we suggest that similar genetic-based structure-activity studies might be generally applied to generate insight into the in vivo function of diverse channel types.

Organization and expression of the gene encoding chick kainate binding protein, a member of the glutamate receptor family.

The gene encoding chick cerebellar Bergmann glia-specific kainate binding protein (chKBP), has been isolated, characterized and expressed in heterologous systems. The structural gene spans 11.2 kb and contains 11 exons and 10 introns. Several of the exons encode specific receptor domains, including each of the predicted transmembrane regions. Exon/intron boundaries flanking the second, putative channel-forming transmembrane domain are conserved between chKBP and other glutamate/kainate receptor subunits. The putative promoter region 5' to the first exon displays high GC content and TATA, CAAT and AP1 consensus sequences. Transcription of the chKBP gene is evident prior to full cerebellar cortical maturation. Transcripts are abundant in cells consistent with Bergmann glia, as revealed by in situ hybridization. Transfection of 293 kidney cell cultures with chKBP cDNA or chKBP gene expression constructs confers CNQX-sensitive kainate binding with the pharmacological specificity displayed by both chKBP and kainate receptors. However, expression of the same constructs in Xenopus oocytes fails to yield detectable agonist-activated currents.

Proton nuclear magnetic resonance imaging of acute experimental cerebral ischemia.

To determine the efficacy of proton nuclear magnetic resonance (NMR) imaging in documenting acute ischemic infarction and to characterize the changes in these images during the first 24 hours following the ischemic insult, serial NMR imaging was performed in gerbils that had undergone unilateral carotid artery ligation. No significant changes in the signal intensity, T1 or T2 relaxation times were noted for either asymptomatic animals or the control hemisphere of symptomatic gerbils. There was a significant increase in T1 and especially T2 relaxation times and in both the relative signal intensity and Hf(v) for the ischemic hemisphere of symptomatic gerbils. These parameters appeared to increase linearly over 24 hours. The ischemic lesion first could be detected by NMR as early as 3 hours after carotid artery ligation, our earliest time point. The physiologic significance of these changes is discussed. These data suggest that NMR imaging may have significant diagnostic importance for acute cerebral ischemia and infarction in man.

A tetrameric subunit stoichiometry for a glutamate receptor-channel complex.

The structure of glutamate receptor-channel (GluR) subunits has recently been shown to differ from that of other ligand-gated channels and to contain a voltage-gated channel-like pore-forming motif. The view that the structure of GluR complexes is similar to the pentameric structure of other ligand-gated channels was questioned here. Studies of the response properties of the GluR1 subunit of the AMPA subtype of GluRs, co-expressed in Xenopus oocytes with its L646A mutant, which differs only by a greatly reduced sensitivity to quisqualate, provide new evidence suggesting that the GluR1 homomeric receptor channel has a tetrameric structure.

NMR imaging of acute experimental cerebral ischemia: time course and pharmacologic manipulations.

Nuclear magnetic resonance (NMR) imaging was used to evaluate the intracerebral changes over time in gerbils after unilateral carotid artery ligation. Each animal was imaged during one of three stated periods 3-28 hr after surgery and again after administration of dexamethasone, morphine, or naloxone, agents reported to affect the clinical outcome of ischemic cerebral lesions. Asymptomatic animals exhibited no differences between the occluded and control hemispheres in relative signal intensity or in T1 or T2 relaxation times, but symptomatic animals demonstrated significant differences in these parameters between hemispheres. The ischemic lesion was detected at the earliest imaging time, 3 hr after surgery. A linear increase was observed in the relative interhemispheric signal intensity in three of four intensity images and in T1 and T2 relaxation times over the 24 hr experiment. No effect was noted on any image parameter as a result of pharmacologic manipulations. The results suggest that NMR may be of significant diagnostic importance for acute cerebral ischemia and infarction in man.

A research method for MRI tissue characterization studies using small coils for excised organs.

The main purpose of this report is to describe our method of MRI tissue characterization studies, which consists of MR imaging of the patient, precision MR imaging of the excised organ, and pathological examination of the organ. We first made small coils to be used with conventional MRI scanners to examine the excised organs. In order to make it easier to understand the effectiveness of our method, three illustrative case reports of abdominal or pelvic tumors were presented as examples of the tissue characterization studies. In conclusion, this method seemed very useful and, in addition, it was found that this small coil technique has several advantages in other applications.

MRI of brain infarction.

MRI of twenty patients with cerebral infarction were reported with their X-CT. MRI with long SE mode clearly showed the ischemic lesion at 18 hours after insult, whereas X-CT performed immediately after MRI scanning showed no abnormality. The signal contrast of the lesion with long SE mode seemed to increase slightly during the patient's course, for a period of several months. The MRI images with long SE at the chronic stage were varied: small lesions appeared as hot areas, whereas large lesions appeared as cold areas and were accompanied with signal enhancement in the surrounding areas. A phantom study was also performed and it was determined that MRI was superior to X-CT in its ability to detect tissue water. One of the reasons for the high diagnostic capability of MRI for acute stroke was, therefore, attributed to this experimental result.

Computerized three-dimensional normal atlas.

This paper presents our ongoing project in which normal human anatomy and its quantitative data are systematically arranged in a computer. The final product, the Computerized Three-Dimensional Normal Atlas, will be able to supply tomographic images in any direction, 3-D images, and coded information on organs, e.g., anatomical names, CT numbers, and T1 and T2 values.

[Magnetic resonance imaging in 38 cases of acoustic tumors].

The value of magnetic resonance imaging (MRI) in the diagnosis of acoustic tumors was retrospectively assessed in 38 cases. A 0.15 Tesla permanent magnet and a 1.5 Tesla superconducting magnet were employed in 24 and 14 cases, respectively. Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), a paramagnetic contrast agent, was used in 10 cases. Acoustic tumors were identified in all cases. Small, medium, and large tumors were depicted with equal clarity by MRI and computed tomography (CT). However, tumor contour and extension, accompanying cysts, and brainstem displacement were more clearly visualized on MRI. The use of Gd-DTPA improved the quality of the MR images by markedly enhancing the acoustic tumors in all cases. In particular, detection of small acoustic tumors and intra- or paratumoral cysts was facilitated by the use of Gd-DTPA. The possibility of a correlation between acoustic tumor histology and MRI features was studied by calculation of the contrast to noise (C/N) ratio in 10 cases of acoustic tumor and 7 cases of meningioma. No definite correlation was demonstrated, but there appeared to be some difference in the C/N ratio between acoustic tumors and meningiomas. In three volunteers, MRI demonstrated intracanalicular nerves, separately. Because of its higher resolution, MRI can be expected to replace CT and air CT in the diagnosis of acoustic tumors.

Informed consent: myth or reality.

The rapidly growing awareness and respect of the social needs and legal rights of the patient in many countries is a sign of cultural maturity of society at large. However, the implementation of these achievements is especially arduous in the field of psychiatry because often mental patients have cognitive restrictions and/or emotional distress both of which may interfere with the exercise of their civil rights. One focus of this paper is the challenging process of obtaining legally valid consent from a severely ill psychiatric patient for diagnostic procedures and for treatment and also for participation in research projects. This paper also analyzes and discusses the new developments in the health legislation in Israel and focuses on the questions that arise in its application to the field of psychiatry. A recommendation for practical assessment of competence is presented. Systematic studies ofthe application of legal regulation and appropriate modifications are needed.

[Super conductive MR imaging of small acoustic tumor].

Eight patients with acoustic tumor were studied with a superconductive MR imaging. T1-weighted images with Gd-DTPA most accurately showed the margin of the seventh and eighth nerves in the internal auditory canal and were most sensitive in detecting small tumors. T2-weighted images were inferior to T1-weighted images, that could fail to detect small tumors. High resolution, thin slice, MR imaging using surface coil is particularly useful for small acoustic tumor because of its higher specificity compared with air-CT, cisternography.

Trabecular and cortical bone separately assessed at radius with a new ultrasound device, in a young adult population with various physical activities.

The aim was to evaluate a new ultrasound device in a young adult population and to assess its reproducibility via comparison to DXA measurements and geometrical measurements from high-resolution radiographs. Ninety-three subjects aged between 20 and 51 years were recruited and divided into four groups according to their gender and physical activity status: 22 male athletes, 19 male controls, 21 female athletes, and 31 female controls. Ultrasonic measurements were assessed by the prototype LD-100 (Oyo Electric Co., Kyoto, Japan) on the dominant distal radius. Attenuation in the radius (dB), cortical bone thickness (mm), radius thickness (mm), mass density of cancellous bone (mg/cm(3)), and elasticity (GPa) of cancellous bone were obtained. BMD was measured by DXA at the dominant distal radius. Radius images were obtained with a direct high-resolution digital X-ray device (BMA, D(3)A Medical Systems), and radius and cortical thicknesses were estimated using a specific software (ImageJ, Bethesda, USA), in an area site-matched with LD-100. There was a significant positive correlation between site-matched BMD measurement and LD-100 parameters (p<0.004), X-ray radius thickness, and LD-100 parameters except elasticity (p<0.05, r>0.32), X-ray cortical thickness and LD-100 attenuation and cortical thickness (p<0.01). A significantly higher attenuation, cortical and radius thicknesses were found in athletes compared to controls (p<0.05). The radius thickness measured on radiographs was significantly higher in athletes versus controls in both sexes, and cortical thickness was significantly higher in male athletes versus controls. These data suggest a positive influence of physical activity on bone cortical measurements. This study also confirmed the particular interest of bone assessment by ultrasound.