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Souvent, les traitements topiques ne permettent pas de contrôler suffisamment une dermatite atopique (DA) modérée à sévère. Nous avons évalué l’efficacité et la sécurité à long terme du dupilumab jusqu’à 5 ans chez des patients adultes avec DA modérée à sévère.

The international society has steadily become integrated in a borderless economy towards the 21st century. The accessibility to a common market in such an economy will promote a new era of mega-competition. Some of the new high-technology industries that are forecast to succeed in the 21st century include computer, electronics, superconductivity technology, biotechnology, and information technology industries.

This article presents a theoretical model of the kinetic friction characteristics for sliding velocity under mild wear condition, assuming a simple effective hardness at asperity contacts. The proposed model depends on the surface temperature distribution obtained by using Jaeger's estimation for a moving homogeneous heat source with an infinitely long band on a semi-infinite solid and a relation between steel hardness and temperature measured by Tominaga. Further, the model takes into consideration the stochastic model of a rough surface contact that was proposed by Greenwood and Williamson. The calculation results show that the surface temperature increases and the surface hardness and the friction coefficient decrease as the sliding velocity increases. However, the variation in the friction coefficient is less than that in the surface hardness. The initial value of the friction coefficient and the contact pressure has a great influence on the relation between the friction coefficient and the sliding velocity. In contrast, the standard deviation of the asperity summit heights has little influence on the relation.

Alcohol consumption induces a dose‐dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high‐dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult.

A comparison between electrospray ionization (ESI) and the recent introduced atmospheric pressure photo-ionization (APPI) technique is described for the liquid chromatography/mass spectrometric (LC/MS) determination of aflatoxin B1, B2, G1 and G2 in food. For the optimization of APPI, several APPI ion source parameters were examined. Furthermore, the chemical noise and signal suppression of ESI and APPI by sample matrix interference were investigated. The results indicated that APPI has the low chemical noise and the little signal suppression in comparison with ESI. The mean recovery of each aflatoxin from peanuts, corn, nutmeg and red pepper sample spiked at 1 ng g-1 ranged from 89 to 105% with relative standard deviations of 3.3-5.1%. The limit of detection (S/N = 3) in all food was in the range 0.11-0.5 ng g-1. From these studies, it is suggested that APPI can be used as an additional tool in food residue analysis.

We report the histological findings in two patients treated using Guglielmi detachable coils with almost complete occlusion of the aneurysms. Autopsies of these patients were performed one week and one year after GDC embolization respectively. In one aneurysm that was obtained at autopsy one week after embolization, the histological findings revealed coils and an unorganized thrombus-filled aneurysm sac; an incomplete cell-lining on the luminal side of fibrin thrombi in the region of the neck of the aneurysm was recognized. In the other aneurysm in which autopsy was performed one year after embolization, an organized fibrous tissue at the margin of the aneurysmal wall and vascular granulation tissue at the center of the aneurysm were observed. There is a single layer of endothelium covering fibrous tissue in the neck of the aneurysm. We discuss the healing process after GDC treatment.

Introduction: Alveolar bone resorption and atrophy of the mandible are a major challenge for regeneration medicine. In the present investigation, a collagen sponge that contained TGF-ß1 was placed at a mandibular defect and the osteogenic effects of collagen-TGF-ß1complex were evaluated.Material and Methods: The Pm2, Pm3, and Pm4 teeth on both sides of the mandibles of 12 adult beagle dogs (9.0–12.0 kg) were extracted. After the extraction-site wounds healed, a bone defect (10.0 × 15.0 mm-wide, 10.0mm-deep or 10.0 × 10.0mm-wide,10.0mm-deep) was created on the mandible. A collagen sponge (10.0 × 10.0 × 10.0 mm) that contained TGF-ß1(1.0 µg, 5.0 µg, or 10.0 µg, in physiological saline) was placed at the bottom of the defect and the overlying mucous membrane was sutured with 4–0 prolene. As a control, a collagen sponge that contained physiological saline only was placed in a defect on the opposite side. Two weeks after the surgery the wounds above the bone defects on both the control and TGF-ß1-treated sides had healed completely.Results: At four, six, or eight weeks post-operatively animals were killed. Soft X-ray and bone-salt measurement analyses confirmed clearly that there was greater calcified bone formation in the defects into which TGF-ß1had been incorporated than with the control defects. The implanted collagen sponges were fully resorbed and the bone tissue had regenerated from the bottom of the defects on the TGF-ß1side by four weeks. On the control side, no such regeneration was observed.Conclusions: These results indicate that TGF-ß1released slowly from a collagen sponge was effective in promoting bone remodeling when applied to mandibular defects in adult dogs.

The object of this paper is to provide an enzymatic means to attain faster swelling or shrinking kinetics of polyelectrolyte gels that undergo volume phase transition as an immobilized enzyme reaction sets in. For this, we studied the coimmobilization of gluconolactonase (GL) with glucose oxidase (GOD). A gel used was in the shape of a small cylinder (several hundred micrometers in diameter) and composed of a lightly cross-linked copolymer of N-isopropylacrylamide and acrylic acid. GL was isolated from Aspergillus niger and purified about 100-fold. It was found that in a substrate solution containing glucose, the gel with the coimmobilized GL and GOD shrinks very rapidly. The shrinking rate was identical to that of the enzyme-free gel that undergoes a shrinking transition in response to a sudden pH change of the outer medium from 7 to 5. This indicates the rate-limiting step in the shrinking process to be diffusion of the networks, but not the enzyme reaction. In the gel with singly immobilized GOD, a very slow shrinking was observed because the process is governed by the enzyme reaction. These results were discussed in full in connection with an enzymatically induced decrease in pH within and in the vicinity of the gel phase. As a result, it has become apparent that the faster shrinking kinetics in the coimmobilized enzyme system is attained by the GL-catalyzed hydrolysis of d-glucono-δ-lactone resulting from the oxidation of glucose with GOD.

Microbial transformation of betulin (1), a lupane-type triterpene obtained from the bark extract of white birch (Betula platyphylla Sukatshev var. japonica), and its chemical oxidation product, betulonic acid (2), by the fungus Chaetomium longirostre yielded 4,28-dihydroxy-3,4-seco-lup-20(29)-en-3-oic acid (3) and 4-hydroxy-3,4-seco-lup-20(29)-ene-3,28-dioic acid (4) from 1, and 4,7β,17-trihydroxy-3,4-seco-28-norlup-20(29)-en-3-oic acid (5) and 7β,15α-dihydoxy-3-oxolup-20(29)-en-28-oic acid (6) from 2. The four metabolites, 3−6, along with 1 and 2, were evaluated for their inhibitory effects on Epstein−Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promotion. All of the triterpenes tested showed potent inhibitory effects, with the four metabolites 3−6 exhibiting the more potent effects.

The purpose of this study was to evaluate the correlation between fluorine-18 fluorodeoxyglucose (FDG) thymic uptake and a normal appearing thymus on CT. Non-attenuation corrected FDG positron emission tomography (PET) data from 94 young persons (mean age 25.4 years, range 18–29 years) with a normal thymus diagnosed on CT were retrospectively evaluated. No subject had clinical symptoms suggestive of thymus-related disease or mediastinal tumour (follow-up period 6–69 months). PET images were visually assessed and the count ratio between the thymus and the lung (T/L ratio) was calculated. Increased FDG uptake occurred in 32 (34%) subjects. In these 32 cases, the T/L ratio was 2.86±0.49 (range 2.02–3.99). In 86 subjects whose CT images were available to calculate the CT attenuation of the thymus (CAT), the CAT value was −17.5±45.7 HU (range –103.6 HU to 79.9 HU). The T/L ratio correlated with the CAT value (r=0.58). CAT values in subjects with positive PET findings were significantly higher than CAT values in subjects with negative PET findings (p<0.001, unpaired t-test). These results suggest that even in young adults, if the thymus has a relatively high CT attenuation value, the presence of physiological thymic uptake in FDG-PET is a normal variant. In this study, the diagnosis of normal thymus was based on CT appearance and clinical course. Further studies are needed to clarify the relationship between histopathology and FDG uptake in the thymus.

The authors have developed a new artificial dental implant and evaluated it in a dog model in terms of its potential to produce: I) regeneration of junctional epithelium; II) regeneration and attachment of connective tissue. The implants were constructed from allo-teeth. We removed the cell components from the periodontal ligaments of these teeth with a detergent (1% TritonX-100); the remaining acellular periodontal ligament acted as an extracellular matrix upon which regeneration and attachment could proceed. We placed 10 of these implants in the just-extracted sites of three beagle dogs. We observed regeneration of both junctional epithelium and connective tissue at all implant sites after 3 months. The connective tissue was attached in all cases. Use of the acellular periodontal ligament as an extracellular matrix may facilitate regeneration of host periodontal ligament tissue, thus contributing to recovery of host immunological defense and long-term oral function.

We reported the results of the endovascular treatment using Guglielmi detachable coil (GDC) for wide-necked aneurysms. Fourteen aneurysms were treated with remodeling technique. One aneurysm was performed endovascular treatment followed by partial neck clipping. The other was treated with scaffolding technique. All aneurysms could not be performed by conventional GDC treatment initially because of coil protrusion into the parent artery due to wide neck of these aneurysms.These aneurysms sited at anterior circulation system in 10 cases, and at posterior circulation system in 6 cases. Immediately after the procedure, the obliteration rate could be obtained complete occlusion in 3 cases, > 95% occlusion in 7 cases, > 90% occlusion in 3 cases and < 90% occlusion in 3 cases. In 14 patients follow-up angiography or magnetic resonance image (MRI) was carried out. The angiographic follow-up period is range from 2 to 19 months (mean: 10 months).The results of angiographical follow-up indicated increasing obliteration rate with all aneurysms except for 2 cases. In these 2 cases, the reembolization was needed for recanalization of the aneurysm. The clinical follow-up period is range form one to 26 months (mean: 15 months). There is no evidence of aneurysmal rupture and all cases have been survival without any permanent neurological deficits. The GDC treatment with additional technique (remodeling technique, combined neck-clipping and coiling therapy, scaffolding technique) provides safety and effectiveness, even if there are wide-necked aneurysms.

The pathways leading to G:C-->C:G transversions and their repair mechanisms remain uncertain. C/C and G/G mismatches arising during DNA replication are a potential source of G:C-->C:G transversions. The Escherichia coli mutHLS mismatch repair pathway efficiently corrects G/G mismatches, whereas C/C mismatches are a poor substrate. Escherichia coli must have a more specific repair pathway to correct C/C mismatches. In this study, we performed gel-shift assays to identify C/C mismatch-binding proteins in cell extracts of E. COLI: By testing heteroduplex DNA (34mers) containing C/C mismatches, two specific band shifts were generated in the gels. The band shifts were due to mismatch-specific binding of proteins present in the extracts. Cell extracts of a mutant strain defective in MutM protein did not produce a low-mobility complex. Purified MutM protein bound efficiently to the C/C mismatch-containing heteroduplex to produce the low-mobility complex. The second protein, which produced a high-mobility complex with the C/C mismatches, was purified to homogeneity, and the amino acid sequence revealed that this protein was the FabA protein of E.COLI: The high-mobility complex was not formed in cell extracts of a fabA mutant. From these results it is possible that MutM and FabA proteins are components of repair pathways for C/C mismatches in E.COLI: Furthermore, we found that Saccharomyces cerevisiae OGG1 protein, a functional homolog of E.COLI: MutM protein, could specifically bind to the C/C mismatches in DNA.

Abstract Background:: The renin-angiotensin system (RAS) plays a key role in the pathophysiology of chronic heart failure (CHF). In rats, we reported that CHF enhances dipsogenic responses to centrally administered angiotensin I, and central inhibition of the angiotensin-converting enzyme (ACE) prevents cardiac hypertrophy in CHF. This suggests that the brain RAS is activated in CHF. To clarify the mechanism of the central RAS activation in CHF, we examined brain ACE and the angiotensin receptor (AT) among rats with CHF. Methods and Results:: We created high-output heart failure in 22 male Sprague-Dawley rats by aortocaval shunt. Four weeks after surgery, we examined ACE mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and AT by binding autoradiography. ACE mRNA levels were not significantly increased in the subfornical organ (SFO), the hypothalamus, or in the lower brainstem of CHF rats (n=5) compared with sham-operated rats (SHM) (n=6). Binding densities for type 1 AT (AT"1) in the SFO (P<.05), paraventricular hypothalamic nuclei (P<.05), and solitary tract nuclei (P<.05) were higher in rats with CHF (n=5) than in SHM rats (n=6). Thus, in rats with CHF, AT"1 expression is increased in brain regions that are closely related to water intake, vasopressin release, and hemodynamic regulation. Conclusions:: The fact that AT"1 expression was upregulated in important brain regions related to body fluid control in CHF rats indicates that the brain is a major site of RAS action in CHF rats and, therefore, a possible target site of ACE-inhibitors in the treatment of CHF.

We report our initial results of stent placement for extra-cranial carotid stenosis. Fifteen patients aged 54 to 83 years (10 men) with >60% extra-cranial carotid stenosis were treated with percutaneous stent implantation. Four patients were asymptomatic.The rate of stenosis ranged from 60% to 93% (mean: 74%). Balloon-expandable stents (Palmaz stent 11, Cordis stent: 1, GFX stent:2) were placed for fourteen patients and for one patient a self-expandable stent was used (Memotherm biliary stent). The proximal protective balloon technique was used in the most possible cases during predilatation or stent placement. Angiography or ultrasonography was performed as the evaluation of restenosis after stent placement. The definition of restenosis was > 50% stenosis. The mean period of follow-up was 8.5 months (from 1 to 20 months). In all patients, carotid stents were successfully placed.The mean rate of stenosis immediately after the procedure decreased to 0%. The protective balloon technique could be used in ten patients during pre-dilatation, in six during stent placement. One patient suffered a transient ischemic attack immediately after predilatation. The symptoms disappeared completely 15 minutes after onset. There was no patient with relapse or deterioration of neurological deficits after the procedure. There was no restenosis and stent deformation in the follow-up period.In our small series, stent placement for extra-cranial carotid stenosis was performed with a low rate of morbidity and mortality. However, it is necessary to develop more flexible, more controllable stents with increased mesh densities for exclusive neurointervention. In addition, the development of a more reliable protective balloon technique to decrease procedure-related complications is needed.

A 63 year old man developed dysaesthesia in the legs followed by a subacute ascending flaccid paraparesis with sacral sensory and autonomic involvement. Intravascular lymphomatosis (IVL) was favoured by the presence of low grade fever and raised serum C reactive protein, CSF pleocytosis, raised lymphoma markers (serum LDH, soluble IL-2 receptor), and steroid responsiveness. Only muscle, among several organ biopsies, confirmed IVL. A cytogenetic study of the bone marrow showed chromosome 6 monosomy, as previously reported. The monosomy of chromosome 19, which bears the intercellular cell adhesion molecule-1, newly found in this case, may be related to the unique tumour embolisation of IVL. The CHOP regimen (six courses in 12 weeks) using granulocyte colony stimulating factor (G-CSF) led to gradual resolution of myeloradiculopathy and laboratory supported remission lasting for more than 13 months. The biweekly CHOP with G-CSF support may be a choice of chemotherapy in averting rapidly fatal IVL.

Abstract: Spontaneous basilar dissecting aneurysms secondary to subarachnoid hemorrhage are rare, usually presenting with ischemia rather than a subarachnoid hemorrhage (SAH). A 63-year-old man who had SAH repeatedly from a ruptured basilar dissecting aneurysm was treated with endovascular occlusion of the unilateral vertebral artery. Postoperative angiograms 1 month after the procedure showed complete obliteration of the aneurysm. The clinical follow-up at 20 months showed no evidence of recurrent hemorrhage.

Abstract: Polyurethane (PUR) is a polymer derived from the condensation of polyisocyanate and polyol and it is widely used as a base material in various industries. PUR, in particular, polyester PUR, is known to be vulnerable to microbial attack. Recently, environmental pollution by plastic wastes has become a serious issue and polyester PUR had attracted attention because of its biodegradability. There are many reports on the degradation of polyester PUR by microorganisms, especially by fungi. Microbial degradation of polyester PUR is thought to be mainly due to the hydrolysis of ester bonds by esterases. Recently, polyester-PUR-degrading enzymes have been purified and their characteristics reported. Among them, a solid-polyester-PUR-degrading enzyme (PUR esterase) derived from Comamonas acidovorans TB-35 had unique characteristics. This enzyme has a hydrophobic PUR-surface-binding domain and a catalytic domain, and the surface-binding domain was considered as being essential for PUR degradation. This hydrophobic surface-binding domain is also observed in other solid-polyester-degrading enzymes such as poly(hydroxyalkanoate) (PHA) depolymerases. There was no significant homology between the amino acid sequence of PUR esterase and that of PHA depolymerases, except in the hydrophobic surface-binding region. Thus, PUR esterase and PHA depolymerase are probably different in terms of their evolutionary origin and it is possible that PUR esterases come to be classified as a new solid-polyester-degrading enzyme family.

A marine microbe (strain SR21) from the coral reef area of the Yap Islands was isolated by a screening test for polyunsaturated fatty acids and was found to accumulate lipid that contained 22:5n-6 docosapentaenoic acid (DPA) as well as 22:6n-3 docosahexaenoic acid (DHA). Strain SR21 was identified as genusSchizochytriumin Labyrinthulomycota, owing to its ultrastructural character and life cycle, which is composed of vegetative cell, zoosporangium, and zoospore stages. After cultural optimization, both in flask and fermenter, the highest DHA and DPA productivities of 2.0 and 0.44 g/L per day, respectively, were obtained in a medium of 60 g/L glucose and corn steep liquor/ammonium sulfate in a half salt concentration of seawater in fermenter culture at 28°C and pH 4. This productivity was almost twice that obtained with flask culture, indicating its high resistance to mechanical stirring. The lipid extracted from the cell was about 50% of the dry cell weight and was composed of 93% triacylglycerol (TG). DHA content of the lipid was 34% of total fatty acids. The TG profile was simple, and the content of the most dominant TG, 1,3-dipalmitoyl-2-DHA-TG, was 27%. TG that contained DHA and n-6-DPA amounted to 57 and 17%, respectively, of total TG molecules. Strain SR21 was revealed to be an excellent source of microbial DHA and n-6 DPA.

Jelly-filled optical fiber cables have been investigated. The waterproof characteristics and transmission and mechanical properties of the fabricated jelly-filled cables, including temperature and aging characteristics, were sufficient to apply them for practical use.

Abstract: The fungal oil extracted fromMortierella ramanniana var.angulispora (IFO 8187) was solvent winterized in order to raise the content of γ-linolenic acid (GLA). Effects of winterization conditions (solvent, oil concentration in the solvent and temperature) and changes of glyceride compositions were discussed. The fungal oil was separated into four diglycerides and 17 triglycerides (TG) with high performance liquid chromatography. The predominant species were POO, POP and LOP, whose contents were 24.4, 22.9 and 9.4% of the total TG, respectively. Ethanol at 4C gave the highest GLA content of 10.5% in spite of lower yield than with acetone at −20C. The highest separation efficiency for GLA (ηGLA) was 0.27 with acetone at −20C and 10% oil concentration, resulting in 8.3% of GLA from the fungal oil at 5.7% LGA. In case of lower oil concentration at 5–20%, ηGLA showed higher in the following order: acetone (−20C)>n-hexane (−20C)>acetone (4C)>petroleum ether (−20C). The winterization process also proved to be effective for the separation of TG type, Sa2U (Sa; saturated fatty acid; U, unsaturated fatty acid) into the crystallized fraction and SaU2 into the liquid fraction. Acetone at −20C showed higher separation efficiency for triunsaturated TG than the other solvents.

This paper describes the recent progress in research and development of fiber optics in Japan. A review is presented of recent developments in fiber manufacturing, cabling, and fiber splicing. Experimental results are given for an optical communication system with optoelectronic components. Theoretical analysis and fundamental experiments are not included, nor are research activities in such devices as lasers or in such applications as those in medical fields. Transmission characteristics of optical fibers - in particular loss and pulse spreading - are assessed from the viewpoint of their structures. Various methods of fiber strengthening and structuring cables are described from the viewpoint of mechanical strength. Coupling efficiencies of detachable connectors and methods of permanent fiber splicing are described. Experimental results on optical fiber communication systems are presented and coupling techniques between a light source and an optical fiber are described.

Streptococcus pyogenes T1 was previously found to produce an acidic mitogenic exotoxin, designated A beta, antigenically distinct from erythrogenic toxin type A (ETA) of strains T1 and NY5. Following chemical analysis and biological characterization, we have renamed this toxin streptococcal mitogenic exotoxin Z (SMEZ). Physicochemical separation of SMEZ from ETA was successfully performed on a hydrophobic chromatograph. The isoelectric point was pH 5.3, and the molecular size was estimated to be 28 kDa. These values were similar to those of ETA, but the amino acid composition and the NH2-terminal sequence of SMEZ were distinct from those of any mitogenic exotoxins hitherto described. Its mitogenic activity was found to be more potent than that of ETA in rabbit lymphocyte cultures. A specific antiserum raised against SMEZ did not cross-react with ETA, ETB, or ETC in the neutralization tests of mitogenic and erythrogenic activities. Its superantigenic nature was evident from the reverse transcriptase PCR findings of the T-cell receptor Vbeta profiles of rabbit lymphocytes stimulated in vitro. The Vbeta 8 subfamily was unique to SMEZ, while the Vbeta 2 and 6 subfamilies were found to be common among lymphocytes stimulated with ETA, ETB, ETC, or SMEZ. The results from this study provide an additional example of the diversity that exists among mitogenic or superantigenic exotoxins of streptococcal origin.

Injection of pregnant rats with cytosine arabinoside (ara-C) (280 mg/kg) on day 15 of gestation caused a significant rise (about two times the control value) in monoamine concentrations (norepinephrine, dopamine, and serotonin) accompanied by a decrease (about 60% of the control) in the brain weight and DNA content in the cerebrum of the offspring at 60 days of age. When neonatal rats were injected with ara-C (30 mg/kg/day) for four consecutive days from the fourth to seventh days after birth, a decrease of DNA content per cerebellum and an elevation of monoamine concentrations in the cerebellum were found. However, the total content of each monoamine per cerebrum or cerebellum showed no difference from the control. These results suggest that monoaminergic neurons may remain intact, with normal monoaminergic synapses compressed into a small brain volume. The neonatal administration of ara-C caused an elevation of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) (EC 3.1.4.37) activity and myelin protein content in the cerebellum, suggesting a relative increase in myelin concentration as a result of hypoplasia of granule cells.