Search

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children's Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104-1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Objectives The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HR-pQCT parameters in the tibia than in the radius, the magnitude of association is modest.

Fruit shape of cultivated strawberry (Fragaria × ananassa Duch.) is an important breeding target. To detect genomic regions associated with this trait, its quantitative evaluation is needed. Previously we created a multi-parent advanced-generation inter-cross (MAGIC) strawberry population derived from six founder parents. In this study, we used this population to quantify fruit shape. Elliptic Fourier descriptors (EFDs) were generated from 2 969 two-dimensional binarized fruit images, and principal component (PC) scores were calculated on the basis of the EFD coefficients. PC1–PC3 explained 96% of variation in shape and thus adequately quantified it. In genome-wide association study, the PC scores were used as phenotypes. Genome wide association study using mixed linear models revealed 2 quantitative trait loci (QTLs) for fruit shape. Our results provide a novel and effective method to analyze strawberry fruit morphology; the detected QTLs and presented method can support marker-assisted selection in practical breeding programs to improve fruit shape.

To identify factors, including mental health, associated with smoking relapse among women in Japan from pregnancy to early parenthood.Secondary analysis of data from an ongoing cross-sectional study conducted between 2013 and 2016.We mailed questionnaires to all women who received a maternal and child health handbook from a municipality in Fukushima Prefecture or who underwent a maternal health checkup and gave birth in Fukushima Prefecture.Of the 28,562 women who responded to the questionnaire, 6,747 who previously smoked and quit around the time they registered their pregnancies were included in the analysis.Participants were divided into groups according to smoking relapse status: a nonrelapse group, which included those who maintained smoking cessation, and a relapse group, which included those who quit smoking but later relapsed. We further classified the latter group into those who quit smoking before or after pregnancy registration. We used a logistic regression model with forced entry to calculate adjusted odds ratios.Of the 6,747 participants who previously smoked, 881 (13.1%) relapsed. Regardless of the timing of smoking cessation, younger age and living in a specific region of Fukushima Prefecture were associated with smoking relapse. Relapse was associated with symptoms of depression in participants who quit smoking before registration and with multiparity in participants who quit smoking after registration of their pregnancies.Support for women at risk of smoking relapse after pregnancy requires consideration of regional characteristics and incorporation of family and mental health support with a focus on younger women.

Gene expression vectors are useful and important tools that are commonly used in a variety of experiments, including expression of foreign genes, functional analysis of genes of interest and complementation experiments. In this study, a hybrid promoter, combining the adh1+ upstream activating sequence (UAS) of fission yeast and the GAL10 core promoter of budding yeast, was constructed to enable high level expression depending on the presence of zinc in culture medium for fission yeast. When the hybrid promoter was cloned on the multicopy plasmid, it was fully induced and repressed within 10 h in the presence and absence of zinc, respectively. The kinetics of induction and reduction were similar to those of the endogenous adh1+ mRNA. In contrast, native adh1+ promoter lost its tight repression in zinc-depleted condition when it was cloned on the plasmid. Because adh1+ UAS-specific transcription factors have not yet been identified, we identified UAS elements involved in zinc sensing by characterizing this hybrid promoter. We also found that the expression level increased by the TATA box mutation, GATAA, in the presence of zinc.

The abnormal spindle-like, microcephaly-associated (ASPM) gene is a causative gene of autosomal recessive primary microcephaly (MCPH) 5 in humans, which is characterized by a reduction in brain volume. It was previously reported that truncated Aspm proteins in transgenic mice caused major defects in the germline, a severe reduction in ovary weight and the number of follicles accompanied by reduced fertility. However; it remains unknown whether a loss of Aspm induces abnormal ovarian function, resulting in female infertility. In order to assess the ovary function, we examined vaginal smear cytology from the age of 7 weeks to 100 weeks in CAG-mediated Cre-loxP conditional Aspm

We evaluated the association between maternal prenatal folic acid supplementation/dietary folate intake and motor and cognitive development in 2-year-old offspring using data from the Japan Environment and Children’s Study database. Neurodevelopment of 2-year-old offspring were evaluated using the Kyoto Scale of Psychological Development 2001. In total, data of 3839 offspring were analysed. For folic acid supplementation, a multiple regression analysis showed that offspring of mothers who started using folic acid supplements before conception had a significantly lower developmental quotient (DQ) in the postural-motor DQ area than offspring of mothers who did not use them at any time throughout their pregnancy (partial regression coefficient (B) −2·596, 95 % CI −4·738, −0·455). Regarding daily dietary folate intake from preconception to early pregnancy, a multiple regression analysis showed that the group with ≥ 200 µg had a significantly higher DQ in the language-social area than the group with

Background Although mental health disorders of health care workers in the coronavirus disease 2019 (COVID-19) pandemic have been focused, little is known about the psychological impact on nurses and the influence on their behavior and awareness, such as professionalism and views on life and death, in Japan where there are fewer cases of infection and deaths than in other countries. Moreover, the influence of the pandemic on nursing students is still unclear. Methods An online questionnaire survey was conducted among nurses and nursing students. Feelings during the state of emergency (at the peak of the pandemic) in Japan, changes in behavior and awareness after the rise of COVID-19, and the associated factors influencing these changes were analyzed, comparing nurses with nursing students. Results Significantly increased scores of anxiety/fear (p p p p p p p p p p p = .008), increased preventive behavior (p = .021) and decreased motivation (p = .005) were more marked in nurses than in students, while change in views on life and death was greater in students than in nurses (p = .002). Conclusion The COVID-19 pandemic has had a psychological impact on nurses and nursing students, associated with changes in behavior and awareness even in Japan. Of note, the COVID-19 pandemic has affected nurses’ professionalism and views on life and death. This study demonstrates the importance of having a coping strategy for anxiety and damaged professionalism in nurses, and education on life and death in nursing students.

This study was conducted with the aim of presenting cases in which high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate changes in the bone microstructure due to once-weekly/twice-weekly administration of teriparatide (TPTD). Of osteoporosis patients who participated in a non-inferiority trial (TWICE study: once-weekly vs twice-weekly TPTD) with lumbar bone mineral density as the primary endpoint, five cases scanned by HR-pQCT before TPTD administration were analysed. Two cases were given once-weekly TPTD, three were given twice-weekly TPD, and HR-pQCT was repeated after 48 weeks. A sufficient anabolic effect of once-weekly/twice-weekly TPTD on the trabecular and cortical bone at the tibia was obtained. In addition, the average change in cortical porosity (Ct.Po) was only 0.3% in the tibia and 0.2% in the radius. These findings indicate that once-weekly and twice-weekly TPTD can be expected to improve the bone microstructure, and the increase in Ct.Po may be suppressed.

Background: The abnormal spindle-like, microcephaly-associated (ASPM) gene is a causative gene of autosomal recessive primary microcephaly (MCPH) 5 in humans, which is characterized by a reduction in brain volume. It was previously reported that truncated ASPM proteins in transgenic mice caused major defects in the germline, a severe reduction in ovary weight and the number of follicles accompanied by reduced fertility. However; it remains unknown whether a loss of ASPM induces abnormal ovarian function, resulting in female infertility. Methods: In order to assess the ovary function, we examined vaginal smear cytology from the age of 7 weeks to 100 weeks in CAG-mediated Cre-loxP conditional Aspm-/- knockout mice and control female mice. In addition, we evaluated the ovarian size, fibrosis ratio and the number of follicles (primordial, primary, secondary, antral and atretic follicles) in mice from 15 weeks to 100 weeks old by image analyses. Mann-Whitney U-test was used for statistical analysis. Results: The size of the ovary was significantly reduced in Aspm knockout mice at 15-20 weeks, 40-50 weeks and 70-80 weeks old. compared with the control mice. Furthermore, at all stages, we found a severe decrease in the number of developing follicles at 10-15 weeks, 40-50 weeks and 70-80 weeks old, accompanied by disrupted cyclic changes of vaginal cytology. Conclusion: The results showing that folliculogenesis was significantly decreased and associated with abnormal vaginal cytology in Aspm knockout female ovaries suggested that ASPM might play an important role in the folliculogenesis and estrous cyclicity of the postnatal ovary.

To examine the effect of moxibustion on the wound healing process and its mechanism using a rat wound model. Sixty male Sprague-Dawley rats were randomly divided into a sham-treated group (n=30, wound surgery only) and a moxibustion group (n=30, wound treated with moxibustion). Circular full-thickness skin wounds were produced in rats. Moxibustion was applied to the edge of wound and was continued on alternating days till 14 days after surgery, followed by measurement of wound size. Expression of collagens, prolyl-4-hydroxylase (P4H) and transforming growth factor-β (TGF-β) were evaluated by histochemical study and real-time polymerase chain reaction. The size of the wound lesion was significantly reduced in rats treated with moxibustion as compared to that in sham-treated rats at 4–10 days after wounding (P

A strawberry Multi-parent Advanced Generation Intercrosses (MAGIC) population, derived from crosses using six strawberry cultivars was successfully developed. The population was composed of 338 individuals; genome conformation was evaluated by expressed sequence tag-derived simple short repeat (EST-SSR) markers. Cluster analysis and principal component analysis (PCA) based on EST-SSR marker polymorphisms revealed that the MAGIC population was a mosaic of the six founder cultivars and covered the genomic regions of the six founders evenly. Fruit quality related traits, including days to flowering (DTF), fruit weight (FW), fruit firmness (FF), fruit color (FC), soluble solid content (SC), and titratable acidity (TA), of the MAGIC population were evaluated over two years. All traits showed normal transgressive segregation beyond the founder cultivars and most traits, except for DTF, distributed normally. FC exhibited the highest correlation coefficient overall and was distributed normally regardless of differences in DTF, FW, FF, SC, and TA. These facts were supported by PCA using fruit quality related values as explanatory variables, suggesting that major genetic factors, which are not influenced by fluctuations in other fruit traits, could control the distribution of FC. This MAGIC population is a promising resource for genome-wide association studies and genomic selection for efficient strawberry breeding.

Inappropriate use of essential oils may entail risks to human health due to mutational events, carcinogenic effects, genetic damages and sensitizing effect caused by generation of reactive oxygen species. In order to detect radicals that are expected to form during their oxidation, we measured the electron spin resonance (ESR) spectra of a standard reaction mixture (I) containing 25 μM flavin mononucleotide, 0.018% several essential oils (or 0.015% geraniol), 1.9 M acetonitrile, 20 mM phosphate buffer (pH 7.4), 0.1 M α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) and 1.0 mM FeSO4(NH4)2SO4 irradiated with 436 nm visible light (7.8 J/cm(2)). The ESR peak heights of the standard reaction mixture (I) of the essential oils increased in the following order: tea tree palmarosa geranium clary sage petitgrain lavender bergamot frankincense ravintsara ylang ylang lemongrass niaouli eucalyptus globulus peppermint. The ESR peak height of the standard reaction mixture (I) of geraniol, a main component of palmarosa, was comparable to the one of palmarosa (97 ± 19% of palmarosa). Furthermore, high performance liquid chromatography (HPLC)-ESR analyses of the standard reaction mixture (I) of palmarosa and geraniol gave the same peaks. The results suggest that the radicals formed in the standard reaction mixture (I) of palmarosa are derived from geraniol. HPLC-ESR-mass spectrometry analyses detected m/z 294 ions, 4-POBN/5-hydroxy-3-methyl-3-pentenyl radical adducts and m/z 320 ions, 4-POBN/C7O2H9 radical adducts in the standard reaction (I) of geraniol. The 5-hydroxy-3-methyl-3-pentenyl and C7O2H9 radicals may be implicated in the sensitizing effect of palmarosa.

Photocurable adhesives based on polymers and resins are an integral part of different production processes because of their fast curing and local area bonding ability. Recently, dismantlable adhesives have attracted a lot of attention for recycling adherends or replacement of adhesion defects. However, adhesives that allow repeatable bonding and debonding solely by light irradiation, i.e., without heat activation, are lacking. Here, ABA-type triblock copolymers consisting of poly(meth)acrylates bearing an azobenzene moiety (A block) and 2-ethylhexyl (B block) side chains were synthesized and utilized as photocurable adhesives. In contrast to the azo homopolymers, the block copolymer structure and incorporation of the soft middle block actualized a low concentration of the azobenzene moiety and consequently, higher flexibility of the resultant copolymers. This enabled film formation of the azobenzene-based adhesives and light-induced bonding for the first time. On the basis of the photoisomerization of the azobenzene moiety, changes in their viscoelastic property, i.e., softening and hardening, were induced by UV irradiation at 365 nm (50-100 mW cm

It has been reported that bisphenol A (BPA), a widespread xenoestrogen employed in the production of polycarbonate plastics, affects brain development in both humans and rodents. In the present study employing mice, we examined the effects of exposure to BPA (500 μg/kg/day) during fetal and lactational periods on the development of the locus coeruleus (LC) at the age of embryonic day 18 (E18), postnatal 3 weeks (P3W), P8W and P16W. The number of tyrosine hydroxylase-immunoreactive cells (TH-IR cells) in females exposed to BPA was decreased, compared with the control females at P3W. At P8W, the number of TH-IR cells in females exposed to BPA was significantly decreased, compared with the control females, whereas the number of TH-IR cells in males exposed to BPA was significantly increased, compared with the control males, which resulted in reversed transient sexual differences in the numbers of TH-IR cells observed in the controls at P8W. However, no significant changes were demonstrated at E18 or P16W. Next, we examined the density of the fibers containing norepinephrine transporter (NET) in the anterior cingulate cortex (ACC) and prefrontal cortex, at P3W, P8W and P16W, because NET would be beneficial in identifying the targets of the LC noradrenergic neurons. There were no significant differences shown in the density of the NET-positive fibers, between the control and the groups exposed to BPA. These results suggested that BPA might disrupt the development of physiological sexual differences in the LC-noradrenergic system in mice, although further studies are necessary to clarify the underlying mechanisms.

The ATP-binding cassette subfamily B member 1 (ABCB1) is an efflux transporter that excretes xenobiotics and waste matter. High expression of ABCB1 induced by forskolin (FSK) and rifampicin (RIF) in the bovine blastocysts reportedly improves the cellular quality. In the present study, interferon-α, similar to FSK and RIF, was highly potent in inducing the expression of ABCB1 in the bovine blastocysts but did not exhibit an additive effect with FSK and RIF. Bovine blastocysts stimulated by the combined treatment with FSK, RIF, and interferon-α to express high levels of ABCB1 displayed better freezing resistance as indicated by higher cell numbers in post thawing cultures. On transfer to recipients, such embryos established pregnancies with significantly higher frequencies in repeat breeder cows rather than normal ones.

Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ. To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS-R, from SAS cells. SAS-R cells continue to proliferate when exposed to fractionated radiation (FR) of 2 Gy/day for more than 30 days in vitro. A xenograft tumor model of SAS-R was also resistant to 2 Gy/day of X-rays for 30 days. The density of blood vessels in SAS-R tumors was higher than in SAS tumors. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, sensitized microvascular endothelial cells to radiation, but failed to radiosensitize SAS and SAS-R cells in vitro. Everolimus with FR markedly reduced SAS and SAS-R tumor volumes. Additionally, the apoptosis of endothelial cells (ECs) increased in SAS-R tumor tissues when both Everolimus and radiation were administered. Both CD34-positive and tomato lectin-positive blood vessel densities in SAS-R tumor tissues decreased remarkably after the Everolimus and radiation treatment. Everolimus-induced apoptosis of vascular ECs in response to radiation was also followed by thrombus formation that leads to tumor necrosis. We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs.

The ATP-binding cassette sub-family B member 1 (ABCB1) plays a critical role in maintaining the metabolic capability of cells as an efflux transporter that pumps xenobiotics out of cells. We investigated the effects of highly expressed ABCB1 on the development and viability of cryopreserved bovine embryos. The ABCB1 level in cultured bovine embryos was decreased during development to blastocyst-stage compared to germinal vesicle- and second metaphase-stage oocytes. When bovine embryos were cultured with forskolin and/or rifampicin, the ABCB1 level was significantly increased in blastocysts but embryo development was not significantly improved. After embryo cryopreservation, highly ABCB1-expressed blastocysts exhibited significant increases in viability and hatching rates. The high viability of the cryopreserved blastocysts was accompanied by a significant increase in cell proliferation during culture for 48 h. Thus, ABCB1 is expressed in bovine oocytes and embryos, and the cellular quality of bovine blastocysts is improved by the enhancement of ABCB1 expression.

To improve the development of singly cultured bovine embryos, we developed a co-culture method with trophoblastic vesicles. The growth of trophoblastic cells was markedly increased in vitamin-supplemented medium 199 compared with medium 199. Upon co-culture of a single embryo with trophoblastic vesicles in vitamin-supplemented medium 199, embryo development to the blastocyst stage was significantly higher than in embryos co-cultured with trophoblastic vesicles in RPMI 1640 or with cumulus cells in medium 199 (control). In the absence of the vitamin cocktail, co-culture with trophoblastic vesicles in medium 199 did not improve embryo development compared with that of the control. The vitamin cocktail was effective in embryo development when co-cultured with trophoblastic vesicles, but not with cumulus cells. Embryo development was not improved in the absence of co-cultured trophoblastic vesicles, even in the presence of vitamin cocktail. In conclusion, the co-culture system with trophoblastic vesicles in vitamin-supplemented medium 199 efficiently enhances the development of singly cultured embryos.

Lipid-membrane-incorporating C(60) and C(70) (LMIC(60) and LMIC(70)) were prepared by the fullerene-exchange reaction from the γ-cyclodextrin cavity to vesicles (we call this method the "exchange method"). An advantage of this method is that the ratios of [C(60)]/[lipids] and [C(70)]/[lipids] can be arbitrarily controlled by adjusting the ratios of the fullerenes and liposome. The maximum ratio (30 mol%) obtained was approximately 14 and 100 times higher than those achieved for LMIC(60) and LMIC(70) , respectively, that were prepared by the classical method, which we call the "premixing method" (dissolving lipids and C(60) or C(70) in chloroform, followed by concentration and extraction with water). Furthermore, the stabilities and photodynamic activities of the LMIC(60) and LMIC(70) solutions prepared by the exchange method were shown to be much higher than those prepared by the premixing method. That is, the exchange method was found to be superior to the premixing method as a preparative method of LMIC(60) and LMIC(70) for applications in photomedical and photomaterials chemistry.

Statins are known to lessen the severity of renal ischemia-reperfusion injury. The present study was undertaken to define the mechanism of renoprotective actions of statins using a mouse kidney injury model. Treatment of mice with pravastatin, a widely used statin, improved renal function after renal ischemia-reperfusion without lowering the plasma cholesterol level. Administration of pravastatin with mevalonate, a product of HMG-CoA reductase, eliminated renal protection suggesting an effect of pravastatin on mevalonate or its metabolism. In hypercholestrolemic apolipoprotein E knockout mice with reduced HMG-CoA reductase activity; the degree of injury was less severe than in control mice, however, there was no protective action of pravastatin on renal injury in the knockout mice. Treatment with a farnesyltransferase inhibitor (L-744832) mimicked pravastatin's protective effect but co-administration with the statin provided no additional protection. Both pravastatin and L-744832 inhibited the injury-induced increase in plasma IL-6 concentration to a similar extent. Our results suggest the protective effect of pravastatin on renal ischemia-reperfusion injury is mediated by inhibition of the mevalonate-isoprenoid pathway independent of its lipid lowering action.

Glucosyltransferases (GTFs) secreted by mutans streptococci and some other lactic acid bacteria catalyze glucan synthesis from sucrose, and possess a C-terminal glucan-binding domain (GBD) containing homologous, directly repeating units. We prepared a series of C-terminal truncated forms of the GBD of Streptococcus sobrinus GTF-I and studied their binding to dextran by isothermal titration calorimetry. The binding of all truncates was strongly exothermic. Their titration curves were analyzed assuming that the GBD recognizes and binds to a stretch of dextran chain, not to a whole dextran molecule. Both the number of glucose units constituting the dextran stretch (n) and the accompanying enthalpy change (DeltaH degrees ) are proportional to the molecular mass of the GBD truncate, with which the Gibbs energy change calculated by the relation DeltaG degrees = -RT ln K (R, the gas constant; T, the absolute temperature; K, the binding constant of a truncate for a dextran stretch of n glucose units) also increases linearly. For the full-length GBD (508 amino acid residues), n = 33.9, K = 4.88 x 10(7) M-1, and DeltaH degrees = -289 kJ mol-1 at 25 degrees C. These results suggest that identical, independent glucose-binding subsites, each comprising 14 amino acid residues on average, are arranged consecutively from the GBD N-terminus. Thus, the GBD binds tightly to a stretch of dextran chain through the adding up of individually weak subsite/glucose interactions. Furthermore, the entropy change accompanying the GBD/dextran interaction as given by the relation DeltaS degrees = (DeltaG degrees - DeltaH degrees)/T has a very large negative value, probably because of a loss of the conformational freedom of dextran and GBD after binding.

Background Although previous studies have suggested that lavender oil promote wound healing, no study has examined the molecular mechanisms of its effect. In this study, we investigated the effect of lavender oil on various steps of wound healing and its molecular mechanism, focusing on transforming growth factor-β (TGF-β). Methods Circular full-thickness skin wounds were produced on rats. Control solution or lavender oil was topically applied to the wounds on alternating days for 14 days. Results The area of wounds topically treated with lavender oil was significantly decreased as compared to that of wounds of control rats at 4, 6, 8, and 10 days after wounding. Topical application of lavender oil induced expression of type I and III collagen at 4 days after wounding, accompanied by an increased number of fibroblasts, which synthesize collagen. Induced expression of type III collagen by topical application of lavender oil was reduced to control level at 7 days after wounding although increased expression of type I collagen still continued even at 7 days, suggesting rapid collagen replacement from type III to type I in wounds treated with lavender oil. Importantly, expression of TGF-β in wounds treated with lavender oil was significantly increased as compared to control. Moreover, an increased number of myofibroblasts was observed in wounds treated with lavender oil at 4 days after wounding, suggesting promotion of differentiation of fibroblasts through induction of TGF-β, which is needed for wound contraction. Conclusion This study demonstrated that topical application of lavender oil promoted collagen synthesis and differentiation of fibroblasts, accompanied by up-regulation of TGF-β. These data suggest that lavender oil has the potential to promote wound healing in the early phase by acceleration of formation of granulation tissue, tissue remodeling by collagen replacement and wound contraction through up-regulation of TGF-β. The beneficial effect of lavender oil on wound healing may raise the possibility of new approaches as complementary treatment besides conventional therapy.

本論文では、まずはじめにErstes Klavierspielを旧版、Europaische Klavierschuleを新版とよび、ピアノ学習の初期段階における教授法を比較していきたいと思う。次に、1990年代以降に出版されたピアノ学習初期段階のための様々な指導書を中心にして、現代ドイツにおけるピアノ学習初期段階の教授法を考察していきたい。

We described two patients with chronic sensory neuronopathy who had anti-HTLV-I antibody in serum and cerebrospinal fluid but no signs of myelopathy, A sural nerve specimen revealed severe degeneration of myelinated and unmyelinated axons. The second patient had subclinical Sjogren's syndrome suggestive of a possible link among human T-cell lymphotropic virus type I (HTLV-I), Sjogren's syndrome and sensory neuronopathy, respectively. The broad spectrum of neurologic disorders associated with HTLV-T infection now would include chronic sensory neuronopathy.

It has been reported that bisphenol A (BPA), a widespread xenoestrogen employed in the production of polycarbonate plastics, affects brain development in both humans and rodents. In the present study employing mice, we examined the effects of exposure to BPA (500 μg/kg/day) during fetal and lactational periods on the development of the locus coeruleus (LC) at the age of embryonic day 18 (E18), postnatal 3 weeks (P3W), P8W and P16W. The number of tyrosine hydroxylase-immunoreactive cells (TH-IR cells) in females exposed to BPA was decreased, compared with the control females at P3W. At P8W, the number of TH-IR cells in females exposed to BPA was significantly decreased, compared with the control females, whereas the number of TH-IR cells in males exposed to BPA was significantly increased, compared with the control males, which resulted in reversed transient sexual differences in the numbers of TH-IR cells observed in the controls at P8W. However, no significant changes were demonstrated at E18 or P16W. Next, we examined the density of the fibers containing norepinephrine transporter (NET) in the anterior cingulate cortex (ACC) and prefrontal cortex, at P3W, P8W and P16W, because NET would be beneficial in identifying the targets of the LC noradrenergic neurons. There were no significant differences shown in the density of the NET-positive fibers, between the control and the groups exposed to BPA. These results suggested that BPA might disrupt the development of physiological sexual differences in the LC-noradrenergic system in mice, although further studies are necessary to clarify the underlying mechanisms.

We have previously reported that an adenosine deaminase (ADA)-deficient patient treated with T cell-directed gene therapy had an increase in serum IgE levels, despite a marked inversion of the CD4/CD8 ratio. In the present report, we have analyzed the phenotypic and functional profiles of the patient's lymphocytes obtained during the clinical trial. In peripheral blood mononuclear cells (PBMC) that were freshly prepared from the patient, both CD4 + and CD8 + T cell subsets were negative for CD40 ligand (CD40L; CD154) and Fas ligand (FasL; CD95L), while CD20 + B cells constitutively expressed CD40 and HLA-DR and were negative for CD80, CD86 and Fas (CD95). The expression of CD23 was detected on the majority of CD20 + B cells and expression was upregulated by interleukin (IL)-4. Furthermore, the patient's PBMC, which already expressed both germline and mature Ce transcripts in vivo, spontaneously secreted IgE and responded to IL-4 with increased IgE production during in vitro culture. When stimulated with anti-CD3e monoclonal antibody (mAb), CD8 + T cells from gene-transduced T cells displayed high production of interferon (IFN)-γ, low production of IL-4 and IL-13 and comparable levels of CD40L and FasL expression; however, lined CD8 + T cells from circulating T cells expressing the transgene produced IL-4 and IL-13 together with smaller amounts of IFN-γ and preferably expressed CD40L rather than FasL. Two such CD8 + T cells, in conjunction with the presence of IL-4, supported CD40L-mediated B cell proliferation and IgE production after stimulation and fixation. These results indicate that ADA-deficient B cells are functionally mature and that gene-transduced CD8 + T cells and lined CD8 + T cells containing the transgene exhibit T helper 0- and T cytotoxic (c) 2-like phenotypes, respectively. Our data also suggest that immuno-logic reconstitution with genetically modified CD8 + T cells may promote IgE production.

DNA from Papanicolaou-stained smears was successfully amplified using the polymerase chain reaction (PCR) to investigate if it could be used for retrospective genome studies, such as for the detection of Trichomonas vaginalis. DNA was isolated from 20 archival Papanicolaou-stained smears (19 cervical and 1 seminal fluid samples) and purified by treatment with proteinase K, phenol/chloroform, and ethanol. The method of recovering DNA from the Papanicolaou-stained smear is very important in the successful amplification of Trichomonas DNA in archival cytological smears. We used a specific sequence and successfully amplified DNA in cytological smears of T. vaginalis using PCR. We conclude that the diagnostic accuracy of the detection of T. vaginalis in cervical smears is enhanced by using a combination of a Papanicolaou-stained smear and PCR.