Systemic lupus erythematosus mimicking retinal migraine: a case report.

BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

Characterization of Collagen from Sakhalin Taimen Skin as Useful Biomass.

RESEARCH BACKGROUND: Animal collagen has been widely utilized in foods, cosmetics and biomedical fields. The non-edible portion, such as fish skin and bones, are obtained during cooking. Most of them are currently discarded as wastes, although the nutritional value of the skin and bones is high. The non-edible portion needs to be reused in order to reduce environmental impact, as it is one of the sources of environmental pollution. EXPERIMENTAL APPROACH: Collagen was prepared by cold acetone treatment from Sakhalin taimen skin as a waste produced during cooking. Next, the colour, SDS-polyacrylamide gel electrophoresis, ultraviolet absorption, subunit composition, amino acid composition, denaturation temperature and attenuated total reflectance-Fourier transform infrared spectroscopy analyses were conducted to explore the properties of the collagen. Lastly, we attempted to improve the functional properties of the collagen for future applications using chemical modification technique (succinylation). RESULTS AND CONCLUSIONS: Cold acetone treatment easily removed the fats and pigments from the skin. The odourless and pure white collagen was obtained with high yield. The α3 chain did not exist in the collagen. Sakhalin taimen skin collagen had rich α-helix and low ß-sheet structures. Succinylation caused the secondary structural changes of the collagen molecule. Moreover, it made it possible not only to increase the viscosity of the collagen solution but also to improve the solubility of the collagen under the physiological conditions around pH=6. NOVELTY AND SCIENTIFIC CONTRIBUTION: This finding is the first report on the absence of the α3 chain from salmonid fish skin collagens. The succinylated collagen from Sakhalin taimen skins as useful biomass has potential to utilize in foods, cosmetics and related industries.

Revolving Vernier Mechanism Controls Size of Linear Homomultimer.

A new kind of the Vernier mechanism that is able to control the size of linear assembly of DNA origami nanostructures is proposed. The mechanism is realized by mechanical design of DNA origami, which consists of a hollow cylinder and a rotatable shaft in it connected through the same scaffold. This nanostructure stacks with each other by the shape complementarity at its top and bottom surfaces of the cylinder, while the number of stacking is limited by twisting angle of the shaft. Experiments have shown that the size distribution of multimeric assembly of the origami depends on the twisting angle of the shaft; the average lengths of the multimer are decamer, hexamer, and tetramer for 0°, 10°, and 20° twist, respectively. In summary, it is possible to affect the number of polymerization by adjusting the precise shape and movability of a molecular structure.

Flow Type Bio-Chemical Calorimeter with Micro Differential Thermopile Sensor.

Bio-chemical calorimeters with a MEMS (Micro-Electro-Mechanical Systems) thermopile sensor have been studied for monitoring detailed processes of the biochemical reactions of a minute sample with a high temporal resolution. The bio-calorimeters are generally divided into a batch-type and a flow-type. We developed a highly sensitive batch-type calorimeter which can detect a 100 nW level thermal reaction. However it shows a long settling time of 2 hours because of the heat capacity of a whole calorimeter. Thus, the flow-type calorimeters in passive and active mode have been studied for measuring the thermal reactions in an early stage after starting an analysis. The flow-type calorimeter consists of the MEMS differential thermopile sensor, a pair of micro channel reactor in a PDMS (polydimethylsiloxane) sheet in a three-fold thermostat chamber. The calorimeter in the passive mode was tested with dilution reactions of ethanol to water and NaCl aqueous solution to water. It was shown that the calorimeter detects exo- and endothermic reaction over 250 nW at solution flow rate of 0.05 ~ 1 µl/min with a settling time of about 4 minutes. In the active mode, a response test was conducted by using heat removal by water flow from the reactor channel. The active calorimetry enhances the response time about three to four times faster.

Improvements in pincer nail deformity occur earlier and last longer when acetylcysteine gel is added to an overcurvature-correcting device: Results of a phase 3, multicenter, randomized, vehicle-controlled, investigator-blinded study.

Acetylcysteine (AC) destabilizes keratin and softens nails, reducing the time needed to correct pincer nail deformity with an overcurvature-correcting device. The objective of this phase 3, multicenter, randomized, investigator-blinded study was to evaluate the early and sustained therapeutic effectiveness and safety of 10% AC gel plus an overcurvature-correcting device to treat pincer nails. Patients aged 12 years and older with hallux pincer nail were fitted with an overcurvature-correcting device for 7 days, with a 24-h application of AC gel (n = 40) or vehicle (n = 39) on day 1. The primary end point (achievement of a distal narrowed nail width ratio ≥70% on day 8) was met by 47.5% in the 10% AC group and 25.6% in the vehicle group (difference 21.9%; p = 0.0439). Secondary end points showed a greater tendency towards improvement with 10% AC. The nail correction effect was maintained for at least 12 weeks in the majority of AC-treated patients, although the study duration was insufficient to assess the long-term probability of recurrence. No AC-related adverse events were reported. In conclusion, a single application of 10% AC gel combined with short-term device use facilitated earlier correction of pincer nails compared with the device alone, with improvements maintained after device removal.

Successful treatment of onychomatricoma with minimally invasive surgical procedures based on its pathogenesis: A case report.

Onychomatricoma is a rare, fibroepithelial tumor of the nail. Although it is benign, unnecessary and excessive treatment, such as extensive or total removal of the nail matrix, has been reported in the past. Recently, it was speculated that onychomatricoma is derived from onychomatricodermis, the dermal stroma of the nail matrix. Excision of the stromal rather than the epithelial component of the tumor is important. However, since the boundary between the normal and diseased stroma is usually unclear, minimal excision at the base of the tumor projection should be sufficient. We report a case of onychomatricoma and suggest a method of surgical treatment that would minimize postoperative deformity of the nail plate.

Efficacy and safety of topical acetylcysteine combined with the use of an overcurvature-correcting device in patients with pincer nail deformity: a randomized, vehicle-controlled, investigator-blinded study.

BACKGROUND: While pincer nails may be treated using overcurvature-correcting devices, it takes several months to achieve successful outcomes. Nail-softening drugs may reduce the treatment duration required. OBJECTIVE: To evaluate the efficacy and safety of treatment with acetylcysteine (AC) gel added to an overcurvature-correcting device, and define the optimal AC concentration. METHODS: In this investigator-blinded study, 70 patients with hallux pincer nail were fitted with an overcurvature-correcting device for 7 days and were randomly assigned to receive a single 24-h administration of a gel containing 10%, 20% or 30% AC or vehicle. Nail improvement was objectively evaluated by calculating the distal narrowed nail width (dNNW) ratio. RESULTS: All three AC concentrations plus device showed earlier sustained improvement of pincer nails versus vehicle plus device. There was no observable correlation between AC concentration and effectiveness. No clinically problematic adverse events were observed at any AC concentration, and we recommended AC gel at a concentration of 10%. CONCLUSIONS: By adding AC gel application to an overcurvature-correcting device, early and sustained reductions in transverse curvature were produced compared with using a device alone (vehicle control). The dNNW ratio used in this study was an appropriate objective index for evaluating therapeutic effects.

Pathogenic relevance of IgG and IgM antibodies against desmoglein 3 in blister formation in pemphigus vulgaris.

Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23 IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister formation. In the present study, we generated a transgenic mouse expressing AK23 IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3 AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did not develop an obvious pemphigus vulgaris phenotype, however, even though an excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering was observed. Immunoelectron microscopy revealed IgM binding at the edges of desmosomes or interdesmosomal cell membranes, but not in the desmosome core, where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab')(2) fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together, these observations indicate that antibodies must gain access to Dsg3 integrated within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These findings provide an important framework for improved understanding of B-cell tolerance and the pathophysiology of blister formation in pemphigus.

Congenital curved nail of the fourth toe: Report of three cases and review of the literature.

Congenital curved nail of the fourth toe (CNFT) is a rare disorder in which the nail plate of the fourth toe is deformed as it curves toward the sole of the foot. The cause is still unknown, but the congenital deformity of the nail plate is thought to be due to shortening of the terminal phalanx and hypoplasia of soft tissue of the fourth toe. Here, we report three typical cases who presented congenital curving nail on both their fourth toes. Their X-ray showed that the distal phalanges of the fourth toes were short. Thus far, 19 cases of CNFT were reported in English literature. Interestingly, almost all cases have been from Asia (18 out of 19). The majority of the cases were bilateral and asymptomatic. Tenderness was seen in eight cases, which was caused by the pressure of the nail plate on the skin or ingrown nail. Treatment is basically unnecessary for the deformity, but it is important to teach safe and appropriate nail clipping methods to avoid pain. We can easily diagnose CNFT because of the characteristic clinical presentation and should provide appropriate advice on the nail care from early stage.

Lemierre's syndrome followed by acute respiratory distress syndrome successfully rescued by antibiotics and hemoperfusion with polymyxin B-immobilized fiber.

Lemierre's syndrome is characterized by a primary oropharyngeal infection in a young healthy person who subsequently develops septic thrombophlebitis of the internal jugular vein and metastatic abscesses. We here report an uncommonly severe case of Lemierre's syndrome with acute respiratory distress syndrome (ARDS), in which polymyxin B-immobilized fiber (PMX) was used as supportive therapy. A 30-year-old, previously healthy man presented with sore throat, fever, rigor, and dyspnea. Chest computed tomography scan revealed multiple bilateral peripheral pulmonary nodules with small bilateral pleural effusions. The patient's condition rapidly deteriorated into ARDS after admission. Intubation followed by mechanical ventilation was required, and hemoperfusion with PMX was useful in alleviating the patient's condition. Isolation of Fusobacterium necrophorum from the blood culture and the contrast-enhanced scan revealed thrombosis and thrombophlebitis in the left internal jugular vein. The patient was diagnosed with Lemierre's syndrome, and an alternative treatment regimen with prolonged administration of ampicillin, clindamycin, and metronidazole resulted in improvement of the patient's respiratory function and general condition. Our case indicated that PMX might be an effective supportive therapy in severe cases of Lemierre's syndrome with ARDS that possessed no indication of surgical interventions.

Genotype-phenotype correlations in six Japanese patients with recessive dystrophic epidermolysis bullosa with the recurrent p.Glu2857X mutation.

BACKGROUND: General genotype-phenotype correlations have been delineated in recessive dystrophic epidermolysis bullosa (RDEB), but these remain complicated and it is still difficult to assess the clinical consequences of individual COL7A1 mutations. OBJECTIVE: To characterize recurrent p.Glu2857X mutations and show how other COL7A1 mutations influence the phenotype in RDEB patients harboring p.Glu2857X. METHODS: Genotype-phenotype correlations were studied in six Japanese RDEB patients with the p.Glu2857X mutation. RESULTS: Besides the common p.Glu2857X mutation, premature termination codon (PTC) mutations were found in three patients, glycine substitution missense mutations in two patients, and a non-glycine substitution missense mutation in one patient. PTC mutations in both alleles generally cause the most severe, mutilating Hallopeau-Siemens (HS) variant of RDEB, whereas none of the PTC mutations resulted in severe phenotypes consistent with the HS subtype when coupled with p.Glu2857X. Missense glycine and non-glycine mutations caused phenotypes of differing severity, suggesting that the extent of destabilization of anchoring fibrils depends on the type of mutation. CONCLUSION: A p.Glu2857X mutation exhibits mild pathogenic effects compared to other PTC mutations in COL7A1, and its uniqueness enables detailed analysis and comparison of the destabilizing effects of missense mutations in RDEB patients.

Levels of plasma insulin, leptin and adiponectin, and activities of key enzymes in carbohydrate metabolism in skeletal muscle and liver in fasted ICR mice fed dietary n-3 polyunsaturated fatty acids.

The aim of this study was to clarify the mechanisms related to plasma glucose concentration in mice fed a diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs). Male Crlj:CD-1 (ICR) mice were fed experimental diets containing 6% lard (LD), 6% fish oil (FO) or 4.1% lard plus 1.5% docosahexaenoic acid ethyl ester and 0.4% eicosapentaenoic acid ethyl ester (DE) for 12 weeks. There were no marked differences in plasma glucose and insulin concentration changes on glucose tolerance test between the three dietary groups. At the end of the feeding trial, plasma glucose concentration was significantly lower in fasted mice in the FO group than in those in the LD group (P<.005). Plasma adiponectin concentration was significantly higher in the FO group than in the LD group (P<.05). Hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and glycerophosphate dehydrogenase activities in skeletal muscle tended to be lower in the FO group than in the LD group, while there were no differences in glucokinase and phosphofructokinase activities in liver between the three dietary groups. However, hepatic glycerophosphate dehydrogenase activity was 53-fold and 4.2-fold higher in the FO group than in the LD and DE groups, respectively (P<.0005 and P<.05, respectively). These results suggest that the reduction in plasma glucose concentration in mice fed n-3 PUFAs is mainly caused by acceleration of glucose uptake and glycerol synthesis in the liver rather than in the skeletal muscle.

Differential modulation of lipopolysaccharide- and zymosan-induced hypophagia by dexamethasone treatment.

The treatment of experimental animals with lipopolysaccharide (LPS) induces behavioral depression, in which the central and peripheral inductions of proinflammatory cytokines are proposed to play an important role. We have shown that the intraperitoneal injection of zymosan, composed of insoluble particles prepared from yeast cell walls, can induce behavioral depression assessed as hypophagia in mice, although the role of proinflammatory cytokines in this response has not yet been investigated. We have also shown that the subcutaneous injection of the corticoid, dexamethasone (Dex), a potent inhibitor of cytokine production, is effective in attenuating hypophagia in LPS-treated mice. The attenuated response was associated with the suppression of the gene induction of proinflammatory cytokines (i.e., IL-1beta, IL-6 and TNFalpha) in the brain and liver. In contrast, no significant induction of proinflammatory cytokine genes was observed in the brain or liver during zymosan-induced hypophagia; the subcutaneous injection of Dex did not attenuate zymosan-induced hypophagia but its intraperitoneal injection did. Thus, zymosan-induced hypophagia was less responsive to a subcutaneous injection of dexamethasone than LPS-induced hypophagia, which may be due to the limited role of systemic inflammation in this response. An important role of localized, rather than systemic, inflammation in zymosan-induced hypophagia was suggested, although the role of local proinflammatory cytokines remains to be clarified.

Rapid growth of malignant melanoma in pregnancy.

Malignant melanoma during pregnancy is a difficult problem as a variety of risks to both the mother and fetus must be weighed. We describe a rapidly progressive malignant melanoma diagnosed during pregnancy. There are no standarized guidelines for treatment; each case requires an individualized approach. We review the literature and present an algorithm to aid in approaching such patients.

Purification and characterization of calpain and calpastatin from rainbow trout, Oncorhynchus mykiss.

Although the calpain system has been studied extensively in mammalian animals, much less is known about the properties of mu-calpain, m-calpain, and calpastatin in lower vertebrates such as fish. These three proteins were isolated and partly characterized from rainbow trout, Oncorhynchus mykiss, muscle. Trout m-calpain contains an 80-kDa large subunit, but the approximately 26-kDa small subunit from trout m-calpain is smaller than the 28-kDa small subunit from mammalian calpains. Trout mu-calpain and calpastatin were only partly purified; identity of trout mu-calpain was confirmed by labeling with antibodies to bovine skeletal muscle mu-calpain, and identity of trout calpastatin was confirmed by specific inhibition of bovine skeletal muscle mu- and m-calpain. Trout mu-calpain requires 4.4+/-2.8 microM and trout m-calpain requires 585+/-51 microM Ca(2+) for half-maximal activity, similar to the Ca(2+) requirements of mu- and m-calpain from mammalian tissues. Sequencing tryptic peptides indicated that the amino acid sequence of trout calpastatin shares little homology with the amino acid sequences of mammalian calpastatins. Screening a rainbow trout cDNA library identified three cDNAs encoding for the large subunit of a putative m-calpain. The amino acid sequence predicted by trout m-calpain cDNA was 65% identical to the human 80-kDa m-calpain sequence. Gene duplication and polyploidy occur in fish, and the amino acid sequence of the trout m-calpain 80-kDa subunit identified in this study was 83% identical to the sequence of a trout m-calpain 80-kDa subunit described earlier. This is the first report of two isoforms of m-calpain in a single species.

Additive contribution of multiple factors in the development of pneumatosis intestinalis: a case report and review of the literature.

We describe a 53-year-old patient with dermatomyositis, who developed pneumatosis intestinalis (PI) accompanied by pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema of the neck. The development of PI in our patient was possibly attributed to the effect of factors such as dermatomyositis, corticosteroids, methotrexate, and alpha-glucosidase inhibitor (AGI). The coexistence of multiple factors associated with PI might enhance the risk of developing PI, even though each of them alone is not sufficient to induce it. In particular, the use of AGIs for patients treated with immunosuppressive agents such as corticosteroids requires evaluation.

Quantitative assessment of tumour extraction from dermoscopy images and evaluation of computer-based extraction methods for an automatic melanoma diagnostic system.

The aims of this study were to provide a quantitative assessment of the tumour area extracted by dermatologists and to evaluate computer-based methods from dermoscopy images for refining a computer-based melanoma diagnostic system. Dermoscopic images of 188 Clark naevi, 56 Reed naevi and 75 melanomas were examined. Five dermatologists manually drew the border of each lesion with a tablet computer. The inter-observer variability was evaluated and the standard tumour area (STA) for each dermoscopy image was defined. Manual extractions by 10 non-medical individuals and by two computer-based methods were evaluated with STA-based assessment criteria: precision and recall. Our new computer-based method introduced the region-growing approach in order to yield results close to those obtained by dermatologists. The effectiveness of our extraction method with regard to diagnostic accuracy was evaluated. Two linear classifiers were built using the results of conventional and new computer-based tumour area extraction methods. The final diagnostic accuracy was evaluated by drawing the receiver operating curve (ROC) of each classifier, and the area under each ROC was evaluated. The standard deviations of the tumour area extracted by five dermatologists and 10 non-medical individuals were 8.9% and 10.7%, respectively. After assessment of the extraction results by dermatologists, the STA was defined as the area that was selected by more than two dermatologists. Dermatologists selected the melanoma area with statistically smaller divergence than that of Clark naevus or Reed naevus (P = 0.05). By contrast, non-medical individuals did not show this difference. Our new computer-based extraction algorithm showed superior performance (precision, 94.1%; recall, 95.3%) to the conventional thresholding method (precision, 99.5%; recall, 87.6%). These results indicate that our new algorithm extracted a tumour area close to that obtained by dermatologists and, in particular, the border part of the tumour was adequately extracted. With this refinement, the area under the ROC increased from 0.795 to 0.875 and the diagnostic accuracy showed an increase of approximately 20% in specificity when the sensitivity was 80%. It can be concluded that our computer-based tumour extraction algorithm extracted almost the same area as that obtained by dermatologists and provided improved computer-based diagnostic accuracy.

Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.

We performed this study to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of the rat trachea. In vitro measurements of isometric tension and [3H] inositol monophosphate (IP1) that was formed were conducted by using rat tracheal rings or slices. Neostigmine- and pyridostigmine-induced contractions were almost completely inhibited by Y-27632 and fasudil at 30 microM each, whereas acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 microM for each, respectively. The inhibitory effects of fasudil on neostigmine- and acetylcholine-induced contractions were completely reversed by calyculin-A, a myosin phosphatase inhibitor. Neostigmine-induced IP1 accumulation was attenuated by fasudil at 100 microM. The results suggest that anti-ChEs cause airway smooth muscle contraction, in part, through activation of the Rho-kinase pathway.