Changes in TRPV1 Receptor, CGRP, and BDNF Expression in Rat Dorsal Root Ganglion with Resiniferatoxin-Induced Neuropathic Pain: Modulation by Pulsed Radiofrequency Applied to the Sciatic Nerve.

Pulsed radiofrequency (PRF) is a safe method of treating neuropathic pain by generating intermittent electric fields at the needle tip. Resiniferatoxin (RTX) is an ultrapotent agonist of transient receptor potential vanilloid subtype-1 (TRPV1) receptors. We investigated the mechanism of PRF using a rat model of RTX-induced neuropathic pain. After administering RTX intraperitoneally, PRF was applied to the right sciatic nerve. We observed the changes in TRPV1, calcitonin gene-related peptide (CGRP), and brain-derived neurotrophic factor (BDNF) in the dorsal root ganglia by western blotting. Expressions of TRPV1 and CGRP were significantly lower in the contralateral (RTX-treated, PRF-untreated) tissue than in control rats (p<0.0001 and p<0.0001, respectively) and the ipsilateral tissues (p<0.0001 and p<0.0001, respectively). BDNF levels were significantly higher in the contralateral tissues than in the control rats (p<0.0001) and the ipsilateral tissues (p<0.0001). These results suggest that, while TRPV1 and CGRP are decreased by RTX-induced neuronal damage, increased BDNF levels result in pain development. PRF may promote recovery from neuronal damage with concomitant restoration of TRPV1 and CGRP, and exert its analgesic effect by reversing BDNF increase. Further research is required to understand the role of TRPV1 and CGRP restoration in improving mechanical allodynia.

Comprehensive ECG reference intervals in C57BL/6N substrains provide a generalizable guide for cardiac electrophysiology studies in mice.

Reference ranges provide a powerful tool for diagnostic decision-making in clinical medicine and are enormously valuable for understanding normality in pre-clinical scientific research that uses in vivo models. As yet, there are no published reference ranges for electrocardiography (ECG) in the laboratory mouse. The first mouse-specific reference ranges for the assessment of electrical conduction are reported herein generated from an ECG dataset of unprecedented scale. International Mouse Phenotyping Consortium data from over 26,000 conscious or anesthetized C57BL/6N wildtype control mice were stratified by sex and age to develop robust ECG reference ranges. Interesting findings include that heart rate and key elements from the ECG waveform (RR-, PR-, ST-, QT-interval, QT corrected, and QRS complex) demonstrate minimal sexual dimorphism. As expected, anesthesia induces a decrease in heart rate and was shown for both inhalation (isoflurane) and injectable (tribromoethanol) anesthesia. In the absence of pharmacological, environmental, or genetic challenges, we did not observe major age-related ECG changes in C57BL/6N-inbred mice as the differences in the reference ranges of 12-week-old compared to 62-week-old mice were negligible. The generalizability of the C57BL/6N substrain reference ranges was demonstrated by comparison with ECG data from a wide range of non-IMPC studies. The close overlap in data from a wide range of mouse strains suggests that the C57BL/6N-based reference ranges can be used as a robust and comprehensive indicator of normality. We report a unique ECG reference resource of fundamental importance for any experimental study of cardiac function in mice.

Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center ( https://brc.riken.jp ) and the Experimental Animal Division ( https://mus.brc.riken.jp/ ) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG+ ( https://molossinus.brc.riken.jp/mogplus/ ), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

An atlas of evidence-based phenotypic associations across the mouse phenome.

To date, reliable relationships between mammalian phenotypes, based on diagnostic test measurements, have not been reported on a large scale. The purpose of this study was to present a large mouse phenotype-phenotype relationships dataset as a reference resource, alongside detailed evaluation of the resource. We used bias-minimized comprehensive mouse phenotype data and applied association rule mining to a dataset consisting of only binary (normal and abnormal phenotypes) data to determine relationships among phenotypes. We present 3,686 evidence-based significant associations, comprising 345 phenotypes covering 60 biological systems (functions), and evaluate their characteristics in detail. To evaluate the relationships, we defined a set of phenotype-phenotype association pairs (PPAPs) as a module of phenotypic expression for each of the 345 phenotypes. By analyzing each PPAP, we identified phenotype sub-networks consisting of the largest numbers of phenotypes and distinct biological systems. Furthermore, using hierarchical clustering based on phenotype similarities among the 345 PPAPs, we identified seven community types within a putative phenome-wide association network. Moreover, to promote leverage of these data, we developed and published web-application tools. These mouse phenome-wide phenotype-phenotype association data reveal general principles of relationships among mammalian phenotypes and provide a reference resource for biomedical analyses.

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.

Soft windowing application to improve analysis of high-throughput phenotyping data.

MOTIVATION: High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. RESULTS: Here we introduce 'soft windowing', a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. AVAILABILITY AND IMPLEMENTATION: The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

Principles and application of LIMS in mouse clinics.

Large-scale systemic mouse phenotyping, as performed by mouse clinics for more than a decade, requires thousands of mice from a multitude of different mutant lines to be bred, individually tracked and subjected to phenotyping procedures according to a standardised schedule. All these efforts are typically organised in overlapping projects, running in parallel. In terms of logistics, data capture, data analysis, result visualisation and reporting, new challenges have emerged from such projects. These challenges could hardly be met with traditional methods such as pen & paper colony management, spreadsheet-based data management and manual data analysis. Hence, different Laboratory Information Management Systems (LIMS) have been developed in mouse clinics to facilitate or even enable mouse and data management in the described order of magnitude. This review shows that general principles of LIMS can be empirically deduced from LIMS used by different mouse clinics, although these have evolved differently. Supported by LIMS descriptions and lessons learned from seven mouse clinics, this review also shows that the unique LIMS environment in a particular facility strongly influences strategic LIMS decisions and LIMS development. As a major conclusion, this review states that there is no universal LIMS for the mouse research domain that fits all requirements. Still, empirically deduced general LIMS principles can serve as a master decision support template, which is provided as a hands-on tool for mouse research facilities looking for a LIMS.

Is the canal flare index a reliable means of estimation of canal shape? Measurement of proximal femoral geometry by use of 3D models of the femur.

BACKGROUND: The canal flare index (CFI; the ratio of the diameter of the femoral canal at the isthmus in the anteroposterior (A-P) view to the diameter of the medullary canal 20 mm above the lesser trochanter) is often used as a canal characteristic. Clinically, however, CFI measurements are sometimes untrustworthy because of femoral rotation and, especially, greater anteversion among Japanese patients. Our objectives were to analyze femoral geometry, by use of 3D CAD models, to evaluate the effects of rotational error, and to seek an index less affected by rotation. METHODS: Computed axial tomography (CAT) scan data from 60 femurs were used. By use of CAD software, 3D femoral models were created. The outside of the femur and the inside canal width 20 mm (P20) and 10 mm proximal (P10), and 10 mm (D10), 20 mm (D20), 30 mm (D30), and 40 mm (D40) distal from the center of the lesser trochanter, and at the isthmus were measured for different angles of femoral rotation. CFI, FFI (femoral flare index; the ratio of the extra-cortical diameters at the same levels as for the CFI), and other canal ratios (P20/D10, P20/D20, P20/D30, and P20/D40) were then calculated and the effect of rotational errors was investigated. RESULTS: Mean CFI, FFI, P20/D10, P20/D20, P20/D30, and P20/D40 were 4.29, 2.08, 2.05, 2.49, 2.85, and 3.09 in the position without rotational error. CFI was not related to anteversion but had a negative correlation with isthmus canal width (only). In contrast FFI was almost constant at approximately 2.1 for different anteversion and age. With regard to the effect of rotational error, CFI changed by 1.31, FFI by 0.40, P20/D10 by 0.41, P20/D20 by 0.40, P20/D30 by 0.59, and P20/D40 by 0.80 for a variety of rotational angles. CONCLUSIONS: Outside femoral shape was little different for any person; as a result, FFI was almost constant. In contrast, CFI was revealed to be affected by canal width at the isthmus only. With regard to the effect of rotation, P20/D20 was much less affected by rotation than CFI; it could, therefore, be an appropriate index for expressing proximal canal shape.

The RIKEN integrated database of mammals.

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN's original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies. Our integrated database has been implemented on the infrastructure of publication medium for databases, termed SciNetS/SciNeS, or the Scientists' Networking System, where the data and metadata are structured as a semantic web and are downloadable in various standardized formats. The top-level ontology-based implementation of mammal-related data directly integrates the representative knowledge and individual data records in existing databases to ensure advanced cross-database searches and reduced unevenness of the data management operations. Through the development of this database, we propose a novel methodology for the development of standardized comprehensive management of heterogeneous data sets in multiple databases to improve the sustainability, accessibility, utility and publicity of the data of biomedical information.

The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats.

BACKGROUND: Pulsed radiofrequency (PRF) is a popular pain treatment modality. The effect of PRF current on neuropathic pain has not been examined in detail. We investigated the effect of PRF current on mechanical allodynia induced with resiniferatoxin (RTX) in rats, especially regarding the influence of the duration of allodynia before PRF procedures and that of exposure time to PRF. METHODS: Adult male Sprague-Dawley rats (weighing 250-400 g) received a single intraperitoneal injection of RTX (200 microg/kg) under 2 to 3% sevoflurane anesthesia. Rats in group S(2) (n = 5) were assigned to receive PRF current to the right sciatic nerve for 2 minutes 1 week after RTX treatment; rats in group M(2) (n = 6), PRF current for 2 minutes 3 weeks after RTX treatment; rats in group L(2) (n = 7), PRF current for 2 minutes 5 weeks after RTX treatment; rats in group S(4) (n = 5), PRF current for 4 minutes 1 week after RTX treatment; rats in group S(6) (n = 5), PRF current for 6 minutes 1 week after RTX treatment; and rats in group S(0) (n = 3), no PRF current was delivered. Instead, the needle and electrode were inserted at proper points for 6 minutes 1 week after RTX treatment. All rats were evaluated for sensitivity to mechanical stimulation with von Frey filaments and to thermal stimulation with a thermal testing apparatus and for motor function using placing and grasping reflexes before injection of RTX, every week after injection of RTX, and 1, 2, 3, 4, and 5 weeks after PRF treatment. RESULTS: The paw withdrawal thresholds of both hindpaws 1 week after RTX treatment were significantly lower than the pre-RTX baseline in all groups. In groups S(2), S(4), S(6), and M(2), after PRF procedures, the ipsilateral paw withdrawal thresholds significantly increased. A statistically significant difference was detected between the PRF-treated and PRF-untreated hindpaws. The ipsilateral-contralateral paw withdrawal thresholds after PRF procedures in group S(2) were significantly higher than those in groups M(2) and L(2). Between groups M(2) and L(2), significant differences were found 1, 2, 4, and 5 weeks after PRF procedures. The ipsilateral-contralateral paw withdrawal thresholds in group S(6) were significantly higher than those in groups S(2) and S(4) 5 weeks after PRF procedures. No significant difference was found between groups S(2) and S(4) at any time. After PRF procedures, no difference in the withdrawal latency after heat stimulation and no motor disturbance were observed at any time in all groups. CONCLUSIONS: PRF treatment was more effective when applied in the early stages of mechanical allodynia (1 week) in rats. Increased exposure time to PRF current from 2 to 6 minutes showed a significant antiallodynic effect without motor impairment. We propose the application of PRF current for 6 minutes adjacent to the nerve as soon as possible when allodynia appears.

SDOP-DB: a comparative standardized-protocol database for mouse phenotypic analyses.

UNLABELLED: This article reports the development of SDOP-DB, which can provide definite, detailed and easy comparison of experimental protocols used in mouse phenotypic analyses among institutes or laboratories. Because SDOP-DB is fully compliant with international standards, it can act as a practical foundation for international sharing and integration of mouse phenotypic information. AVAILABILITY: SDOP-DB (http://www.brc.riken.jp/lab/bpmp/SDOP/).

Introduction to the Japan Mouse Clinic at the RIKEN BioResource Center.

A systematic and comprehensive phenotyping platform has been developed by the RIKEN ENU-mutagenesis project between 1999 and 2007. As a result of phenotype screening on this platform, we have discovered about 400 mutants as animal models for human diseases. All information regarding these mouse mutants is now available to the public through our home page (http://www.brc.riken.jp/lab/gsc/mouse/indexJ.html). In 2008, we reconstructed the existing phenotyping platform and built a new platform. The new system has a hierarchical structure, consisting of a fundamental pipeline that utilizes the existing platform and an additional pipeline, which is optimized for more in-depth phenotyping assays. Using this system, we have started to perform more comprehensive phenotyping of mouse mutants. We have opened this system to Japanese scientists as the Japanese Mouse Clinic. It is anticipated that existing mouse mutants will be reevaluated as disease models by identifying novel phenotypes on the new platform. We will share detailed information about the standard operating procedures (SOPs) of our phenotyping analyses with other related large-scale projects, such as the European Mouse Disease Clinic (EUMODIC) and the German Mouse Clinic (GMC). Moreover, we will contribute to international efforts to standardize mouse phenotype data by sharing annotation of mutant phenotypes, which are made by internationally standardized methods, with other related projects.

Application of full-scale three-dimensional models in patients with rheumatoid cervical spine.

Full-scale three-dimensional (3D) models offer a useful tool in preoperative planning, allowing full-scale stereoscopic recognition from any direction and distance with tactile feedback. Although skills and implants have progressed with various innovations, rheumatoid cervical spine surgery remains challenging. No previous studies have documented the usefulness of full-scale 3D models in this complicated situation. The present study assessed the utility of full-scale 3D models in rheumatoid cervical spine surgery. Polyurethane or plaster 3D models of 15 full-sized occipitocervical or upper cervical spines were fabricated using rapid prototyping (stereolithography) techniques from 1-mm slices of individual CT data. A comfortable alignment for patients was reproduced from CT data obtained with the patient in a comfortable occipitocervical position. Usefulness of these models was analyzed. Using models as a template, appropriate shape of the plate-rod construct could be created in advance. No troublesome Halo-vests were needed for preoperative adjustment of occipitocervical angle. No patients complained of dysphasia following surgery. Screw entry points and trajectories were simultaneously determined with full-scale dimensions and perspective, proving particularly valuable in cases involving high-riding vertebral artery. Full-scale stereoscopic recognition has never been achieved with any existing imaging modalities. Full-scale 3D models thus appear useful and applicable to all complicated spinal surgeries. The combination of computer-assisted navigation systems and full-scale 3D models appears likely to provide much better surgical results.

Effects of U0126 and fibroblast growth factor on gene expression profile in Ciona intestinalis embryos as revealed by microarray analysis.

Fibroblast growth factor (FGF) induces the notochord and mesenchyme in ascidian embryos, via extracellular signal-regulated kinase (ERK) that belongs to the mitogen-activated protein kinase (MAPK) family. A cDNA microarray analysis was carried out to identify genes affected by an inhibitor of MAPK/ERK kinase (MEK), U0126, in embryos of the ascidian Ciona intestinalis. Data obtained from the microarray and in situ hybridization suggest that the majority of genes are downregulated by U0126 treatment. Genes that were downregulated in U0126-treated embryos included Ci-Bra and Ci-Twist-like1 that are master regulatory genes of notochord and mesenchyme differentiation, respectively. The plasminogen mRNA was downregulated by U0126 in presumptive endoderm cells. This suggests that a MEK-mediated extracellular signal is necessary for gene expression in tissues whose specification does not depend on cell-to-cell interaction. Among 85 cDNA clusters that were not affected by U0126, 30 showed mitochondria-like mRNA localization in the nerve cord/muscle lineage blastomeres in the equatorial region. The expression level and asymmetric distribution of these mRNA were independent of MEK signaling.

[Anesthetic management for removal of a giant ovarian tumor by monitoring transesophageal Doppler cardiac output].

Transesophageal Doppler cardiac output was monitored in two cases for removal of a giant ovarian tumor. In case 1, cardiac output (CO) increased following the drainage of the tumor, and CO decreased following blood loss. In case 2, CO increased following the removal of the tumor, and remained stable because of small blood loss. Cardiovascular parameters changed remarkably with the drainage of tumors and blood loss. Therefore, noninvasive Doppler cardiac output monitor was useful for rapid estimation of cardiovascular changes.

[Evaluation of a lockable combined spinal-epidural device for use with needle-through-needle technique].

BACKGROUND: Recently, a new combined spinal-epidural (CSE) device has been introduced which allows the spinal needle to be extended a maximum of 15 mm beyond the Tuohy needle and locked onto the epidural needle after dural puncture. The aim of this study was to compare this lockable CSE device with the conventional CSE device, which allows the spinal needle to be extended 9 mm beyond the Tuohy needle, and to measure the length of the protrusion of the spinal needle beyond the Tuohy needle (top-to-top distance: TTD). METHODS: We studied sixty patients scheduled to undergo elective gynecological surgery and cesarean section. Patients were divided into three groups: patients in Group I (n = 20) using the conventional CSE device in gynecological surgery; patients in Group II (n = 20) using the lockable CSE device in gynecological surgery; and patients in Group III (n = 20) using the lockable CSE device in cesarean section. RESULTS: The success rate of spinal anesthesia with needle-through-needle technique was higher with the lockable CSE device (100%) than with the conventional CSE device (75%). The TTD was 7.9 +/- 1.8 (SD) cm in non-pregnant group (Group II) and 8.7 +/- 1.5 cm in pregnant group (Group III). This difference was not statistically significant. In the lockable CSE device groups (Group II and III), 10 patients (25%) had a TTD of 10 mm or more. CONCLUSIONS: The lockable CSE device improves the success rate of spinal anesthesia in needle-through-needle CSE anesthesia.

Detachment analysis of the translocated W chromosome shows that the female-specific randomly amplified polymorphic DNA (RAPD) marker, female-218, is derived from the second chromosome fragment region of the translocated W chromosome of the sex-limited p(B) silkworm (Bombyx mori ) strain.

The sex chromosomes of the silkworm, Bombyx mori, are designated ZW for the female and ZZ for the male. We previously characterized a female-specific randomly amplified polymorphic DNA (RAPD) marker, designated Female-218, from the translocation-bearing W chromosomes. These W chromosomes contain a region of the second chromosome, which carries visible larval markers of the p loci. We used strain TWPB in which female larvae have black skin due to the p(B) gene (T(W;2)p(B), +p/+p) while male larvae have whitish skin (+p/+p). To determine whether the Female-218 RAPD marker is derived from the "W region" or a "second chromosome fragment", we induced a detachment of the translocated W chromosome, T(W;2)p(B), by treating the eggs with hot water at an early developmental stage. After hot water treatment, we obtained 27 white female larvae out of 4850 female larvae. The Female-218 RAPD marker was not amplified in 26 out of 27 white female larvae, and was amplified from one white female larva. Moreover, we obtained 11 black male larvae out of 5377 male larvae. Eight out of 11 black male larvae became adult moths, and the Female-218 RAPD marker was amplified from all eight male moths. Examination of the genetic relationship between the Female-218 RAPD marker and the second chromosome fragment of the translocated W chromosome strongly indicates that the Female-218 RAPD marker is amplified from the region of second chromosome fragment of the T(W;2)p(B) chromosome.

The presence of D-beta-aspartic acid-containing peptides in elastic fibers of sun-damaged skin: a potent marker for ultraviolet-induced skin aging.

Biologically uncommon d-aspartyl residues have been reported in proteins of various elderly tissues. We prepared a polyclonal antibody against d-beta-Asp-containing peptide and examined its immunoreactivity in the skin. The antibody recognized integrated or disintegrated elastic fibers in the sun-exposed skin but not in the sun-protected skin of the elderly donors. Western blot analysis of the proteins isolated from sun-damaged skin demonstrated that the 50 kDa protein was immunoreactive with both antibodies for d-beta-Asp-containing peptide and elastin. Ultraviolet (UV) irradiation on normal skin caused the appearance of d-beta-Asp-containing peptide-immunoreactive fibers in the dermis. These results suggest that UV irradiation is closely related to the formation of d-beta-Asp in the elastic fibers of skin. We propose that the antibody could be a useful indicator for sun damage of the skin.

A variant of acrokeratoelastoidosis in systemic scleroderma: report of 7 cases.

We describe acrokeratoelastoidosis-like lesions on the palms of the patients with systemic scleroderma. Histology showed a focal hyperkeratosis with or without epidermal concavity, regular acanthosis, and hyalinization of collagen fibers and, in some cases, fragmentation and diminution of elastic fibers in the deep dermis. A slight degree of fibrotic change of collagen in the uninvolved neighboring skin was found in one case. The lesions were found in 7 of 26 patients with systemic scleroderma who were analyzed here, and were not found in the unrelated connective tissue disorders (n = 32) and normal controls (n = 27). The cause of the unique skin lesions may be related to the altered connective tissue metabolism similar to that of systemic scleroderma.