Bullous pemphigoid with neurofibroma-like histopathological change in two patients without neurofibromatosis type 1: Coincidence or association?

The author reports two cases of Bullous pemphigoid (BP) with neurofibroma (NF)-like histopathological change. The two patients without neurofibromatosis type 1 (NF1) presented with several bullae on their trunk. Based on the results of positivity for anti-BP180 antibody, direct immunofluorescence, and histopathological findings, they were diagnosed with BP. Histologically, another lesion in the dermis, which was composed of spindle cells with wavy nuclei, collagen fibers, and mast cells, was located close to the bulla. Immunohistochemically, the spindle cells were diffusely positive for S-100 protein and CD34, and weakly positive for epithelial membrane antigen in certain foci. These findings were considered to be "NF-like" histopathological change. This is the first two cases of BP with NF-like histopathological change in patients without NF1.

Antioxidant treatment ameliorates diabetes-induced dysfunction of the vas deferens in a rat model.

Diabetes mellitus (DM) affects the male ejaculatory function. This study was designed to evaluate the role of oxidative stress in the development of diabetes-induced dysfunction of vas deferens (VD) in the rat. DM was induced by streptozotocin in 40 male Wistar rats. Subsequently, the diabetic animals were divided into three groups: DM group, DM + Eda group and DM + Tau group. These groups were administered saline, edaravone and taurine, respectively, daily for 4 weeks. Another group of ten rats served as a control group. DM was diagnosed in the 40 streptozotocin-injected rats. DM significantly reduced the VD weight. Additionally, DM induced in vitro VD hypercontractility, VD histological abnormalities and increased the serum and VD tissue concentration of malondialdehyde. VD immunohistochemistry revealed overexpression of three markers of oxidative stress. DM significantly reduced serum testosterone levels. No live birth was documented in all DM rats in mating experiments. Antioxidants significantly improved all the aforementioned parameters, except the testosterone levels. This study indicates a deleterious impact of DM-induced oxidative stress on VD histological and functional features. Antioxidant treatment may provide an adjunct tool to alleviate ejaculatory disorders for male patients with type 1 diabetes.

Effective three-dimensional evaluation analysis of upper airway form during oral appliance therapy in patients with obstructive sleep apnoea.

The oral appliance (OA) is considered to be an effective treatment modality for obstructive sleep apnoea (OSA). Upper airway enlargement during OA therapy is critical, and lateral cephalometry has been used for the two-dimensional evaluation of upper airway form during this therapy. However, this method cannot provide an accurate three-dimensional (3D) view of upper airway form. To confirm the effects of OA on the upper airway in patients with OSAS, we performed CT in the presence and absence of OA in 15 Japanese patients (12 males, 3 females) who responded to OA therapy. CT in the presence and absence of OA was consecutively performed for each patient, and upper airway cross-sectional area in six arbitrary planes parallel to the palatal plane was measured. Next, 3D image reconstruction was performed; morphological changes in upper airway form were evaluated, and upper airway volume at three levels from the palatal plane to the deepest point of the epiglottis was measured. The cross-sectional area of two planes in the posterior soft palate region significantly increased in the presence of OA compared with that in the absence of OA. In the presence of OA, upper airway cross-sectional area and volume significantly increased in the posterior soft palate region compared with those in the posterior tongue region. 3D CT image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. Continued use of this 3D evaluation is expected to improve the results of OA therapy in the future.

Clinicopathological study of invasive extramammary Paget's disease: subgroup comparison according to invasion depth.

BACKGROUND: Extramammary Paget's disease (EMPD) is a distinct form of malignant skin neoplasm. Invasive EMPD is relatively rare and its detailed histopathological features have not been investigated to date. METHODS: Surgical specimens were obtained from 51 patients with primary invasive EMPD. Clinical data including lymph node status were retrieved from the patients' medical records. Cases were divided into subgroups according to invasion depth: dermal invasion ≤ 1 mm (minimal invasion) and dermal invasion > 1 mm in depth. Histological patterns (nodular/glandular pattern or micronodular pattern), lymphatic/venous invasion, mitosis and lymph node status were compared between the two groups. RESULTS: The invasive EMPDs included 26 cases (51.0%) with dermal invasion ≤ 1 mm (minimal invasion) and 25 cases (49.0%) with dermal invasion > 1 mm in depth. Lymph node metastasis was detected in 2/26 (7.7%) patients with minimally invasive EMPD. Nodular/glandular pattern (72.0%), lymphatic/venous invasion (52.0%), mitosis (88.0%) and nodal metastasis (88.0%) were all significantly more frequent in cases with dermal invasion > 1 mm, compared to EMPDs with dermal invasion ≤ 1 mm (minimal invasion) (P < 0.001). CONCLUSION: These results suggest that invasive EMPD can be divided according to invasion depth, with a cut-off depth of 1 mm. This might represent the basis for a useful, EMPD-specific staging system.

Influence of medial meniscectomy on stress distribution of the femoral cartilage in porcine knees: a 3D reconstructed T2 mapping study.

OBJECTIVE: Previous studies have shown that meniscectomy results in an increase of local load transmission and may cause degeneration of the knee cartilage. Using 3D reconstructed T2 mapping, we examined the influence on the femoral cartilage under loading after medial meniscectomy. DESIGN: Ten porcine knees were imaged using a pressure device and a 3.0-T magnetic resonance imaging (MRI) system. Consecutive sagittal T2 maps were obtained in neutral alignment with and without compression, and under compression at 10° varus alignment. After medial meniscectomy, the aforementioned MRI was repeated. Cartilage T2 before and after meniscectomy under each condition were compared at the 12 regions of interest (ROIs) defined on the 3D weight-bearing area of the femoral cartilage. RESULTS: Before meniscectomy, large decreases in T2 under neutral compression were mainly seen at the anterior and central ROIs of the medial cartilage, which shifted to the posterior ROIs after meniscectomy. There were significant differences in decrease in T2 ratio with loading before and after meniscectomy (9.8%/4.3% at the anterior zone, 4.0%/11.4% at the posterior zone, P < 0.05). By applying varus compression, a more remarkable decrease in the cartilage T2 in posterior ROIs after meniscectomy was achieved. (Before/after meniscectomy: 8.7%/2.5% at the anterior zone, 7.2%/18.7% at the posterior zone, P < 0.05). CONCLUSIONS: Assuming a decrease in T2 with loading correlated with the applied pressure, a deficiency of the medial meniscus resulted in a shift of the primary area with a maximal decrease of cartilage T2 with loading posteriorly in the porcine knee joint, presumably reflecting the intraarticular environment of load transmission.

Three-dimensional patterns of early acetabular cartilage damage in hip dysplasia; a high-resolutional CT arthrography study.

OBJECTIVE: The purpose of this study was to examine the three-dimensional (3D) progression patterns of early acetabular cartilage damage in hip dysplasia using high-resolutional computed tomography (CT) arthrography. DESIGN: Thirty-two dysplastic hips of 26 Japanese symptomatic females including 21 hips in pre-stage of osteoarthritis (Kellgren-Lawrence (K-L) grade 0; mean patient age, 32.0 years) and 11 hips in early stage of osteoarthritis (K-L grade 1 or 2; mean patient age, 32.8 years) were examined. Isotropic high-resolutional CT arthrography with an image resolution of 0.5 mm in any orthogonal direction was performed. A 3D acetabular cartilage model was generated and we evaluated distribution of cartilage thickness in 12 zones after dividing the weight-bearing area of the hip joint in radial and lateral/medial directions. RESULTS: In pre-stage of osteoarthritis, significant differences in cartilage thickness were observed between the lateral and medial zones in all radial regions, most prominently in the antero-superior region. In early stage of osteoarthritis, no significant differences in cartilage thickness were observed, except in the most posterior region. The lateral-medial (LM) ratio was defined as cartilage thickness in the lateral zone divided by that in the medial zone, and hips with the LM ratio in the antero-superior region of <1.4 had significantly more extensive involvement of labral tears than hips with the LM ratio of ≥1.4. CONCLUSIONS: In hip dysplasia, acetabular cartilage damage was probably occurred in the antero-superior lateral area. The LM ratio may be a sensitive index to quantify early cartilage damage associated with extent of labral disorders.

Non-linear analysis of stabilograms with alcoholic intake.

Equilibrium function in the cerebellum (vestibulo-cerebellar system) can deteriorate under the influence of alcohol. In the Romberg posture, the center of gravity, which was measured every 50 ms by stabilometry, appeared to shift with alcohol ingestion. In the previous study, a locus in the center of gravity (stabilogram) was converted to values of statistical indices such as area of sway, total locus length, and locus length per unit area, although these indices could not always distinguish between the statokinesigrams sampled from seven healthy young males in sober and intoxicated states. This measurement was made with an AMTI force plate. In this study, "translation error" was estimated in a d-dimensional embedding space in order to compare statokinesigrams recorded before and after the ingestion of doubly diluted brandy in 30 s (1 ≤ d ≤ 10). We succeeded in validating a stochastic differential equation as a mathematical model of the body sway. The randomness in the model was preserved after alcohol intake and significantly increased in the medial/lateral direction. Visual information referred by the postural control system when standing might be interfered by the effects of intoxication, which was regarded as disturbance. This method is considered to be useful to diagnose the disorders of the vestibulocerebellar system.

Loading and knee alignment have significant influence on cartilage MRI T2 in porcine knee joints.

OBJECTIVE: Physiological magnetic resonance imaging (MRI) under loading or knee malalignment conditions has not been thoroughly investigated. We assessed the influence of static loading and knee alignment on T2 (transverse relaxation time) mapping of the knee femoral cartilage of porcine knee joints using a non-metallic pressure device. METHODS: Ten porcine knee joints were harvested en bloc with intact capsules and surrounding muscles and imaged using a custom-made pressure device and 3.0-T MRI system. Sagittal T2 maps were obtained (1) at knee neutral alignment without external loading (no loading), (2) under mechanical compression of 140 N (neutral loading), and (3) under the same loading conditions as in (2) with the knee at 10 degrees varus alignment (varus loading). T2 values of deep, intermediate, and superficial zones of the medial and lateral femoral cartilages at the weight-bearing area were compared among these conditions using custom-made software. Cartilage contact pressure between the femoral and tibial cartilages, measured by a pressure-sensitive film, was correlated with cartilage T2 measurements. RESULTS: In the medial cartilage, mean T2 values of the deep, intermediate, and superficial zones decreased by 1.4%, 13.0%, and 6.0% under neutral loading. They further decreased by 4.3%, 19.3%, and 17.2% under varus loading compared to no loading. In the lateral cartilage, these mean T2 values decreased by 3.9%, 7.7%, and 4.2% under neutral loading, but increased by 1.6%, 9.6%, and 7.2% under varus loading. There was a significant decrease in T2 values in the intermediate zone of the medial cartilage under both neutral and varus loading, and in the superficial zone of the medial cartilage under varus loading (P<0.05). Total contact pressure values under neutral loading and varus loading conditions significantly correlated with T2 values in the superficial and intermediate zones of the medial cartilages. CONCLUSIONS: The response of T2 to change in static loading or alignment varied between the medial and lateral cartilages, and among the deep, intermediate, and superficial zones. These T2 changes were significantly related to the contact pressure measurements. Our results indicate that T2 mapping under loading allows non-invasive, biomechanical assessment of site-specific stress distribution in the cartilage.

Development of a gamma ray monitor using a CdZnTe semiconductor detector.

The aim of this study was to develop a new X ray and gamma ray monitor using the CdZnTe semiconductor detector, which has high sensitivity at room temperature. The pulse height spectra and the detection efficiencies of a 10 mm x 10 mm by 2 mm thick CdZnTe detector were measured in the energy range of 10 keV to 1.8 MeV by using monoenergetic X ray and gamma ray sources. The measured results showed very good agreement with the results calculated using the EGS4 Monte Carlo code taking into account the charge collection efficiency in the detector. By using two CZT detectors of 10 mm x 10 mm x 2 mm and 3 mm x 3 mm x 2 mm coupled with a filter, the weighted sum of a few energy channels with different cut-off energies was finally found to achieve a flat energy response with an equivalent dose (counts per microSv) within +/-30% or +/- 10% deviation.

8-oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts.

BACKGROUND: Reactive oxygen species (ROS) can cause an oxidative modification of nucleotides, such as 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), which can lead to defects in DNA replication. The misincorporation of 8-oxo-dGTP into DNA is prevented by 8-oxo-dGTPase, which hydrolyzes 8-oxo-dGTP into 8-oxo-dGMP. The changes in this defensive system have not yet been examined in failing hearts, in which the generation of ROS increases. METHODS AND RESULTS: Myocardial infarction (MI) was created in mice by ligating the left coronary artery. Four weeks later, the left ventricle was dilated and contractility was diminished on echocardiography. The generation of ROS, as measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, increased in the noninfarcted left ventricle from MI mice. The formation of thiobarbituric acid-reactive substances also increased in the mitochondria from MI mice. 8-Oxo-dGTPase was detected in the mitochondrial fractions isolated from MI mice using a Western blot analysis with an antibody to its human homologue (hMTH1). Immunohistochemistry showed positive staining for hMTH1 was localized in the cardiac myocytes. CONCLUSIONS: The level of 8-oxo-dGTPase increased in the mitochondria isolated from post-MI hearts as oxidative stress increased, thus suggesting that a preventive mechanism is activated against ROS-induced DNA damage. As a result, 8-oxo-dGTPase is considered a useful marker of mitochondrial oxidative stress in heart failure.

Disruption of Xpg increases spontaneous mutation frequency, particularly A:T to C:G transversion.

Cells isolated from Xpg (the mouse counterpart of XPG)-disrupted mice underwent premature senescence and showed early onset of immortalization, suggesting that Xpg might be involved in genetic stability. Recent studies showed that human XPG, in addition to its function in the nucleotide excision repair (NER), was involved in the repair of oxidative base damages such as thymine glycol (Tg) and 8-oxo-guanine (8-oxoG), and this may explain the genetic instability observed in Xpg-deficient cells. To clarify this point, we determined spontaneous mutation frequencies and the type of spontaneous base substitution mutations in cells obtained from normal and Xpg-deficient mice using the supF shuttle vector (pNY200) for mutation assay. The spontaneous mutation frequency of the supF gene in pNY200 propagated in the Xpg-deficient cells was about three times higher than that in normal cells, indicating the importance of Xpg in reducing the frequency of spontaneous mutations. The frequency of spontaneous base substitution mutations at A:T sites, particularly that of the A:T to C:G transversion, increased markedly in the Xpg-deficient cells.

Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation.

Various proinflammatory and vasoactive actions of platelet-activating factor (PAF) are mediated through a specific G-protein-coupled PAF receptor (PAFR). We identified a novel DNA variant in the human PAFR gene, which substitutes an aspartic acid for an alanine residue at position 224 (A224D) in the putative third cytoplasmic loop. This mutation was observed in a Japanese population at an allele frequency of 7.8%. To delineate the functional consequences of this structural alteration, Chinese hamster ovary cells were stably transfected with constructs encoding either wild-type or A224D mutated PAFR. No significant difference was observed in the expression level of the receptor or the affinity to PAF or to an antagonist, WEB2086, between the cells transfected with wild-type and mutant PAFR. Chinese hamster ovary cells expressing A224D mutant PAFR displayed partial but significant reduction of PAF-induced intracellular signals such as calcium mobilization, inositol phosphate production, inhibition of adenylyl cyclase, and chemotaxis. These findings suggest that this variant receptor produced by a naturally occurring mutation exhibits impaired coupling to G-proteins and may be a basis for interindividual variation in PAF-related physiological responses, disease predisposition or phenotypes, and drug responsiveness.

Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure.

BACKGROUND: The generation of reactive oxygen species (ROS) is enhanced in the failing myocardium. We hypothesized that ROS were also increased in the limb skeletal muscles in heart failure. Methods and Results-- Myocardial infarction (MI) was created in mice by ligating the left coronary artery. After 4 weeks, the left ventricle was dilated and contractility was diminished by echocardiography. Left ventricular end-diastolic pressure was elevated after MI in association with an increase in lung weight/body weight and the presence of pleural effusion. The generation of ROS in the limb muscles, including the soleus and gastrocnemius muscles, which were excised after MI, was measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO). Overall, generation was increased, but it was attenuated in the presence of dimethylthiourea or 4,5-dihydroxy-1,2-benzenedisulfonic disodium salt in the reaction mixture, indicating increased generation of hydroxyl radicals originating from superoxide anion. Thiobarbituric acid-reactive substance formation was also increased in muscles after MI. Mitochondrial complex I and III activities were both decreased after MI, which may have caused the functional uncoupling of the respiratory chain and ROS production. Antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, were comparable between groups. CONCLUSIONS: Skeletal muscle in post-MI heart failure expressed an increased amount of ROS in association with ROS-mediated lipid peroxidation. This supports the hypothesis that oxidative stress may cause (at least in part) skeletal muscle dysfunction in heart failure.

[Le Duc-Camey procedure as a method of ureteroileal implantation on augmentation cystoplasty in patients with myelodysplasia].

PURPOSE: We investigated the results of Le Duc-Camey procedure as a method of ureteroileal implantation on augmentation cystoplasty in patients with myelodysplasia. MATERIALS AND METHODS: A total of 14 patients (25 renal units) underwent ureteroileal implantation with Le Duc-Camey procedure on augmentation cystoplasty. The possible causes of complications concerning ureteroileal implantation that developed during the postoperative observation were classified as preoperative factors and postoperative factors.: The preoperative factors were the causative disease required ureteroneostomy, the grade of preoperative VUR, and the ureteral diameter at the anastomosis with the ileum.: The postoperative factors were the volume, and the compliance of the urinary bladder, and the maximum intravesical pressureled by the peristalsis of the utilized intestine. RESULTS: With the mean observation period of 31.6 months, no complications developed but VUR observed in 4 renal units of 4 patients. The patients with VUR had a larger ureteral diameter at the anastomosis site to the ileum among the preoperative factors and a significantly larger maximum intravesical pressure led by the intestinal peristalsis among the postoperative factors when compared with the patients without VUR. CONCLUSION: Regarding ureteroileal implantation with Le Duc-Camey procedure on augmentation cystoplasty in patients with myelodysplasia. It seems necessary to consider some countermeasures for the dilated ureters and for the unexpected 2 elevation of intravesical pressure due to the peristalsis of the utilized intestine.