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A rhizomatous Dioscorea crop “Edo-dokoro” was described in old records of Japan, but its botanical identify has not been characterized. We found that Edo-dokoro is still produced by four farmers in Tohoku-machi of Aomori Prefecture, Japan. Rhizomes of Edo-dokoro are a delicacy to the local people and are sold in the markets. Morphological characters of Edo-dokoro suggest its hybrid origin between the two species, D. tokoro and D. tenuipes. Genome analysis revealed that Edo-dokoro is likely originated by hybridization of a male D. tokoro to a female D. tenuipes, followed by a backcross with a male plant of D. tokoro. Edo-dokoro is a typical minor crop possibly maintained for more than 300 years but now almost forgotten from the public. We hypothesize that there are many such uncharacterized genetic heritages passed over generations by small scale farmers that await serious scientific investigation for future use and improvement by using modern genomics information., 忘れられた作物「えどどころ」の起原 --ゲノム解析が明らかにする青森県三八上北地域に残る栽培イモの歴史--. 京都大学プレスリリース. 2022-08-10.

Because ceramide-like lipo-amino acid cholesteryl derivatives can exert a bound water-holding function due to their lamellae-forming properties, in this study, we determined if topical application of those derivatives to atopic dry skin would elicit an ameliorative effect on skin symptoms, at least on its water-holding function. In this clinical study, daily treatment with a nano-emulsion containing 10% phytosteryl/octyldodecyl lauroyl glutamate (POLG) significantly (p < 0.0001) improved skin symptoms, including dryness/scaling, itchiness and stimulus sensations, in the non-lesional skin of patients with atopic dermatitis (AD) at 3 and at 6 weeks compared with week 0. Those significant improvements in skin symptoms were accompanied by a significantly enhanced water content (conductance) and a significant improvement of roughness (SESC) and smoothness (SESM) values measured using a Visioscan at 3 and 6 weeks. Those effects appeared concomitant with a significantly increased corneocyte size, a significantly down-regulated degree of thick abrasions, and a significant impairment of the corneocyte lipid envelope at 6 weeks. Thus, our clinical study suggests, for the first time, that topical application of the POLG nano-emulsion has the distinct potential to ameliorate atopic dry skin symptoms, particularly scaling and itchiness, in the skin of patients with AD. Those effects result from alleviation of the disrupted water-holding function probably due to the increased supply of lamellae structures into the stratum corneum despite the failure to improve barrier function.

Preliminary studies have shown that a lithogenic diet (LG), which contains cholesterol and cholic acid, induces gallstones and hepatic lipid accumulation (HLA), and reduction of blood triglyceride in mice. We hypothesized that an LG induces HLA by diminishing hepatic triglyceride excretion; however, there is no clear understanding of the mechanism of LG-induced HLA. This study aimed to investigate transcript expression related to the synthesis, expenditure, and efflux of hepatic triglyceride, in mice fed an LG for 4 weeks. Results showed lower plasma concentrations of triglyceride in the LG group than in the control group, but no symptoms of hepatic injury were observed. Hepatic mRNA expressions of patatin-like phospholipase domain containing 3 (Pnpla3), microsomal triglyceride transfer protein (Mttp), and acyl-CoA oxidase 1 (Acox1) were also reduced in the LG group. Deoxycholic acid and lithocholic acid promoted intracellular lipid accumulation, reduced triglyceride concentration in media, and suppressed expression of PNPLA3 and MTTP in HepG2 human hepatoma cells. These findings suggest that deoxycholic acid and lithocholic acid promote HLA by inhibiting the expression of PNPLA3, ACOX1, and MTTP that are involved in lipid metabolism.

Background Clinical evidence is required about the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions. Methods We conducted a 26-week, multicenter, collaborative, uncontrolled, open-label, phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems. The study consisted of the 2-week screening phase, the 26-week medication phases I and II, and the 2-week follow-up phase. Children received 1, 2, or 4 mg melatonin granules orally in the medication phases. Variables of sleep status including sleep onset latency (SOL), aberrant behaviors listed on the Aberrant Behavior Check List-Japanese version (ABC-J), and safety were examined. The primary endpoint was SOL in the medication phase I. Results Between June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan—74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximal dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly (mean ± standard deviation [SD], − 36.7 ± 46.1 min; 95% confidence interval [CI], − 45.9 to − 27.5; P P P = 0.0322) in the medication phase I; and irritability, hyperactivity, and inappropriate speech (P Conclusions Long-term melatonin treatment in combination with adequate sleep hygiene interventions may afford clinical benefits to children with NDDs and potentially elevates their well-being. Trial registration ClinicalTrils.gov, NCT02757066. Registered April 27, 2016.

The lycopene content of tomatoes is important because of its effects on vital physiological functions such as improvement of glucose tolerance and non-alcoholic fatty liver disease. To investigate the influence of the lycopene content of tomatoes on glucose tolerance and hepatic lipid content, homogenates of lycopene-rich (LR) or lycopene-free negative control (NC) tomato varieties were administrated to normal rats for 4 weeks. At the end of the experiment, an oral glucose tolerance test (OGTT) was performed. Rats were fed once and then dissected. According to the OGTT results, plasma glucose levels in the LR group were 10% and 9% lower at 15 min and 30 min, respectively, than those in the NC group, whereas plasma insulin levels did not differ between the groups at either time point. Upon dissection, plasma leptin levels in the LR group were higher than those in the NC group, while plasma adiponectin levels did not differ between groups. With the exception of retinol palmitate, no carotenoids were detected in the liver by HPLC analysis. Hepatic retinol palmitate levels and hepatic triacyl glyceride levels did not differ between the groups. We concluded that in normal rats, a lycopene-rich tomato variety improved glucose tolerance via an increase in plasma leptin levels that enhanced insulin sensitivity but did not affect carotenoid accumulation or lipid metabolism.

Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (− 22.0, − 28.0, and − 5.0 min, respectively; p

This study aimed to elucidate the role of the Sonic hedgehog (Shh)–Patched (Ptch)–Gli signaling pathway in maintaining dental epithelial and pulp stem/progenitor cells and regulating the function of odontoblasts. Doxycycline (dox)-inducible histone 2B (H2B)–green fluorescent protein (GFP) transgenic mice ingested dox at prenatal embryonic days 14.5 or 15.5 and their offspring were collected from postnatal day 1 (P1) to week 3 (P3W). Immunohistochemistry for Gli1, Ptch1, and Ptch2 andin situhybridization forShhandPtch1were conducted. Mandibular incisors of postnatal day 2 H2B-GFP transgenic and wild-type mice were cultivated in a nutrient medium with Shh antibody for 4 days and subsequently processed for immunohistochemistry for Sox2. In molars, dense H2B-GFP-label-retaining cells (H2B-GFP-LRCs) were densely distributed throughout the dental pulp during P1 to postnatal week 2 (P2W) and decreased in number by postnatal P3W, whereas the number of dense H2B-GFP-LRCs in the subodontoblastic layer increased in number at P2W. Gli1+and Pthc1+cells were distributed throughout the enamel organ and dental pulp, including the odontoblast and subodontoblastic layers.ShhmRNA was expressed in the inner enamel epithelium and shifted into odontoblasts after dentin deposition.Ptch1mRNA was expressed in the inner enamel epithelium and cuspal pulpal tissue on P1 and decreased in intensity from postnatal week 1 to P3W. In incisors, the apical bud contained H2B-GFP-LRCs, Gli1+cells, and Ptch1+cells. The addition of Shh antibody to explants induced a decrease in the number of Sox2+cells due to the increase in apoptotic cells in the apical bud. Thus, the Shh–Ptch–Gli signaling pathway plays a role in maintaining quiescent adult stem cells and regulating the function of odontoblasts.

Objectives Limited biological evidence exists regarding donor–host interaction in the periodontal tissue during allogenic tooth germ transplantation. This study aimed to clarify donor–host tissue interactions during periodontal tissue healing following tooth germ transplantation. Methods This study compared the localization of putative stem cells in the periodontal ligament (PDL) by 5-bromo-2′-deoxyuridine (BrdU), Gli1, and periostin immunoreactions using pulse-chase paradigm (BrdU prenatal labeling: peritoneal pulse injections at embryonic days [E] 15–17) in TetOP–H2B–GFP mice (doxycycline administration at E14.5). The current study characterized periodontal tissue healing following allogenic tooth grafts in GFP-labeled donor or host and wild-type mice by pulse-chase paradigm and GFP, BrdU, Gli1, and periostin immunohistochemistry. Results BrdU prenatal labeling demonstrated that dense label-retaining cells (BrdU–LRCs) disappeared from the PDL by postnatal week 2 (P2W). However, H2B–GFP–LRCs were localized in the PDL of TetOP–H2B–GFP mice during P3–8W, and Gli1-positive cells in the PDL increased at P2–3W, showing that H2B–GFP–LRCs in the PDL are derived from non-proliferating cells during E15–17. Transplanted molars formed cusps and roots and erupted into occlusion by two weeks postoperatively. The junctional epithelium and tooth-related zone of PDL were exclusively composed of donor cells, whereas the PDL alveolar-related zone was a hybrid structure of donor and host cells. Conclusions The current tooth germ transplantation suggests that the PDL contains putative stem cells, which never proliferate during E15–17, and is composed of resident dental follicle-derived cells and other cell population.

This study aimed to characterize the inactivation kinetics of cytochrome P450 3A4 (CYP3A4) by erythromycin, which involves mechanism-based inhibition (MBI), in detail. In addition to an MBI assay based on the conventional method in which erythromycin and recombinant CYP3A4 were pre-incubated for 15 min, the study also evaluated the long-term MBI kinetics of this reaction by pre-incubation for 120 min. Mechanism-based inhibition profiles were obtained using three typical substrates, testosterone, midazolam and nifedipine. In the long-term assay, erythromycin evoked a time-dependent biphasic reduction in enzyme activity, but some residual activity (α) was detected in the terminal phase. The inactivation rate constant obtained in the presence of 30 μm erythromycin using nifedipine as a substrate was 1.44-fold higher than that acquired using testosterone, while there was no difference among the α values obtained with the three substrates. In the short-term assay, time-dependent monophasic inactivation was observed. To extrapolate these data to in vivo, the extent of the increase in the area under the curve (AUC ratio) induced by erythromycin was estimated from the results of the conventional short-term experiment and the long-term experiment examining residual activity. The AUC ratio estimated from the long-term kinetics (2.92) was closer to the clinically reported values (3.3-4.42). In conclusion, the relatively long-term evaluation of the kinetics of CYP3A4 inactivation revealed that the enzyme was not fully inactivated by erythromycin. To improve the estimation of the extent of the drug-drug interactions induced by MBI from in vitro data, longer-term investigations of the target enzyme's inactivation profile might be necessary.

The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors. In developing molars, dense LRCs were numerous at P1 but then decreased in number over the course of odontogenesis and were maintained in the center of pulp tissue. Gli1-(+) cells were maintained in the pulp horn during the examined stages, while they increased in number and were maintained in the center of pulp tissue during P2-5W. Ptch1-(+) cells were localized in the pulp horn at P1 and increased in number in the center of the pulp after P3W. Shh mRNA was first expressed in the enamel epithelium and then shifted to odontoblasts and other pulp cells. Shh protein was distributed in the epithelial and mesenchymal tissues of incisors and molars. These findings suggest that quiescent dental stem cells are regulated by Shh signaling, and that Shh signaling plays a crucial role in the differentiation and integrity of odontoblasts during epithelial-mesenchymal interactions and dentinogenesis.

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Objectives. Although deuterium oxide (D2O) has preservative property on the extracted organ, whether D2O also protects the in situ myocardial injury remains unknown. Using cardiac microdialysis, lo...

Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels &ge, 120 to &lt, 160 mg/dL. The subjects were randomly assigned to either the high-lycopene tomato or placebo (lycopene-free tomato) group. Each subject in the high-lycopene group ingested 50 g of semidried PR-7 (lycopene, 22.0&ndash, 27.8 mg/day) each day for 12 weeks, while subjects in the placebo group ingested placebo semidried tomato. Medical interviews were conducted, vital signs were monitored, body composition was determined, and blood and saliva samples were taken at weeks 0 (baseline), 4, 8, and 12. The primary outcome assessed was LDL-C. The intake of high-lycopene tomato increased lycopene levels in this group compared to levels in the placebo group (p &lt, 0.001). In addition, high-lycopene tomato intake improved LDL-C (p = 0.027). The intake of high-lycopene tomato, PR-7, reduced LDL-C and was confirmed to be safe.

Tomato (Solanum lycopersicum) is a rich source of lycopene, a carotenoid that confers various positive biological effects such as improved lipid metabolism. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study to investigate the effects of regular and continuous intake of a new high-lycopene tomato, a variety named PR-7, for 12 weeks, based on 74 healthy Japanese subjects with low-density lipoprotein cholesterol (LDL-C) levels ≥120 to

Little is known about the anti-pigmenting effects of whitening agents on solar lentigos (SLs), which comprise ~ 60% of hyperpigmented facial lesions of Asian subjects. Lotions with or without 6% l-ascorbate-2-phosphate trisodium salt (APS) [test lotion (TL) and placebo lotion (PL), respectively] were applied twice daily for 24 weeks in a double-blind half-face study of 27 Japanese females with SLs on both sides of their faces. Pigmentation scores were evaluated using a photo-scale and the skin colors were assessed using a color difference meter and a mexameter for SLs and the non-lesional surrounding skin (NLS). Although the pigmentation scores were not significantly different between the TL and PL-treated SLs after 24 weeks, the L values of TL-treated SLs and NLS increased significantly with a significantly higher △L value in SLs than in NLS. In contrast, the L values of PL-treated SLs and NLS remained unchanged after the treatment. The number of subjects with > 2.0 △L was 7 of 27 (TL) and 0 of 27 (PL) in SLs and 3 of 27 (TL) and 0 of 27 (PS) in NLS. In contrast, the melanin index in TL-treated SLs and NLS significantly decreased with a significantly higher △melanin index in SLs than in NLS. Similarly, the melanin index of PL-treated SLs and NLS were significantly decreased with a significantly higher △melanin index in SLs than in NLS. These findings strongly indicate that APS has a weak but significant anti-pigmenting effect on SLs and a significant whitening effect even on normally pigmented healthy skin.

Preferential attention to living creatures is believed to be an intrinsic capacity of the visual system of several species, with perception of biological motion often studied and, in humans, it correlates with social cognitive performance. Although domestic dogs are exceptionally attentive to human social cues, it is unknown whether their sociability is associated with sensitivity to conspecific and heterospecific biological motion cues of different social relevance. We recorded video clips of point-light displays depicting a human or dog walking in either frontal or lateral view. In a preferential looking paradigm, dogs spontaneously viewed 16 paired point-light displays showing combinations of normal/inverted (control condition), human/dog and frontal/lateral views. Overall, dogs looked significantly longer at frontal human point-light display versus the inverted control, probably due to its clearer social/biological relevance. Dogs’ sociability, assessed through owner-completed questionnaires, further revealed that low-sociability dogs preferred the lateral point-light display view, whereas high-sociability dogs preferred the frontal view. Clearly, dogs can recognize biological motion, but their preference is influenced by their sociability and the stimulus salience, implying biological motion perception may reflect aspects of dogs’ social cognition.

Although triple-negative breast cancer (TNBC) with epidermal growth factor receptor (EGFR) expression has been extensively studied, few studies have simultaneously examined EGFR expression and EGFR gene amplification. Here, we examined the correlations of EGFR expression with EGFR gene amplification, EGFR-activating mutations, and the expression of components of the Akt pathway.Tumor tissues were obtained from 84 patients with TNBC. We analyzed the expression of EGFR, phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and other relevant proteins using immunohistochemistry. We also analyzed EGFR gene and chromosome 7 copy numbers by dual-color in situ hybridization. DNA was extracted from formalin-fixed paraffin-embedded samples. Analysis of EGFR gene-activating mutations was performed using the smart amplification process version 2 assay.Most TNBCs expressing EGFR are non-specialized invasive ductal carcinomas, whereas others are likely to be rare specialized carcinomas, such as typical medullary carcinoma, apocrine carcinoma, metaplastic carcinoma, and adenoid cystic carcinoma. EGFR was expressed in samples from 28 of 84 (33.3%) patients, but the EGFR gene was not amplified in any of the 84 samples. There were significant correlations between EGFR expression and the number of polysomic cells and the presence of high polysomy of chromosome 7. However, EGFR expression was not correlated with p-Akt or p-mTOR expression, nor with the other clinicopathological factors recorded in this study. We found no evidence of EGFR gene-activating mutations.EGFR gene amplification and EGFR-activating mutations might not be the mechanisms leading to the constitutive activation of EGFR in TNBC. Further investigation is needed to clarify the other molecular mechanisms for oncogenic activation of EGFR in TNBC.

Human dental pulp contains adult stem cells. Our recent study demonstrated the localization of putative dental pulp stem/progenitor cells in the rat developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no available data on the localization of putative dental pulp stem/progenitor cells in the mouse molar. This study focuses on the mapping of putative dental pulp stem/progenitor cells in addition to the relationship between cell proliferation and differentiation in the developing molar using BrdU-labeling. Numerous proliferating cells appeared in the tooth germ and the most active cell proliferation in the mesenchymal cells occurred in the prenatal stages, especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive odontoblasts were arranged in the cusped areas and disappeared after postnatal Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5 to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in number and reached a plateau after P1W when they mainly resided in the center of the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells harboring in the perivascular niche surrounding the endothelium.

A starch ingredient with antioxidative activity, as measured by the DPPH method, was produced by baking corn starch with an organic acid; it has been named ANOX sugar (antioxidative sugar). The baking temperature and time were fixed at 170 °C and 60 min, and the organic acid used was selected from preliminary trials of various kinds of acid. The phytic acid ANOX sugar preparation showed the highest antioxidative activity, but the color of the preparation was almost black; we therefore selected L-tartaric acid which had the second highest antioxidative activity. The antioxidative activity of the L-tartaric acid ANOX sugar preparation was stable against temperature, light, and enzyme treatments (α-amylase and glucoamylase). However, the activity was not stable against variations in water content and pH value. The antioxidative activity of ANOX sugar was stabilized by treating with boiled water or nitrogen gas, or by pH adjustment.

To reveal heterogeneous properties of triple-negative (TN) breast cancers (estrogen receptor negative, progesterone receptor negative and HER2 negative) and to clarify whether the developmental pathways to TN breast cancer are single or multiple, we conducted clinicopathological and immunohistochemical studies on TN breast cancers, with special reference to comparison of the invasive component (iIC) and the ductal component (dcIC) of invasive TN breast cancer and pure TN ductal carcinoma in situ (TNDCIS). Tumor tissues were obtained from 97 patients with TN invasive carcinoma and 10 patients with TNDCIS. Two histological subclassifications, "atypical" medullary carcinoma (type A, n=16) and carcinoma with a central acellular zone (type B, n=11), were distinguished from conventional ductal carcinoma. Other invasive ductal carcinomas were classified as type C (n=64) and special types were classified as type D (n=5). The follow-up period for the 96 patients ranged from 5 to 147.8 months (mean, 47.6 months). Out of 97 cases, dcIC was present in 29 (30%) cases and type A and B had significantly few ductal components, 0% and 18%, respectively. There were only six (6%) cases with non-TN cells in dcIC and TN cells in iIC and five of them were type C. In 13 (13%) cases, epidermal growth factor receptor (EGFR) expression existed only in iIC. Therefore, most of the TN carcinoma develops originally and rapidly invades at the early stage, especially in types A and B. The relapse rate of type B was the highest (36.4%) and the overall survival of patients with type B was the shortest (P=0.02), which indicates that the prognosis of type B is significantly worse than the other types.

e18093Background: Anaplastic thyroid carcinoma (ATC) has a poor prognosis despite multimodal treatment approaches. Innovative strategies are required for treatment. Our primary aim was to determine...

It is currently unclear which patients with breast cancer with sentinel lymph node (SLN) metastases do not need axillary lymph node dissection (ALND). A cohort of 1,132 women who had unilateral invasive breast cancer with clinically negative nodes or nodes suspicious for metastasis, were intraoperatively diagnosed as having negative SLNs, and did not undergo an immediate ALND. Our intraoperative histological investigation uses H&E staining of a frozen section from a maximum cut surface of each SLN. Of these 1,132 women, 132 (11.7%) were postoperatively diagnosed as having positive SLNs, which classifies them as having an intraoperative, false-negative SLN biopsy (SLNB). Patient and tumor characteristics, treatment methods, and the prognoses of these patients were investigated and compared with the remaining 1,000 patients who were negative for SLNB. Of the 132 patients with intraoperative, false-negative SLNB, none underwent a further ALND. With a median follow-up period of 58.1 months, none of these patients exhibited recurrence in the axillary nodes. Their recurrence-free survival rates were not statistically different from those of patients with negative SLNB. ALND can be avoided in most patients with breast cancer with intraoperative, false-negative SLNB.

Ipsilateral breast tumor relapse (IBTR) is a potentially a significant problem after breast conserving surgery (BCS). With a median follow-up period of 64.7 months, IBTR occurred as a first relapse in 67 (3.0%) of a total of 2243 patients and distant recurrence occurred in 167 (7.4%). A positive surgical margin and the omission of radiotherapy (RT) were independently associated with IBTR. The five-year cumulative IBTR rates were 5.1% in patients with positive margins and 2.0% in the patients with negative margins. The five-year cumulative IBTR rates were 1.8% in patients with RT and 8.1% in patients without RT. IBTR was independently associated with distant-recurrence-free survival rates as well as age, nodal metastasis, lymphovascular invasion and progesterone receptor status. The five-year distant-recurrence-free survival rates were 81.9% in patients with IBTR and 93.2% in patients without IBTR. In order to prevent IBTR, a negative margin and the administration of RT are therefore considered to be important in patients who undergo BCS.

Aim To evaluate the feasibility and safety of vacuum-assisted resection of benign breast tumours using an 8 G handheld device. Materials and Methods Over a 2-year period, 22 patients with 26 breast tumours diagnosed as benign using aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500 ultrasonography device with a linear-type 7.5 MHz transducer was inserted into the posterior aspect of the tumour with the patient under local anaesthesia, and the tumour was resected under ultrasonographic guidance. Results This method was employed successfully in all patients, and the mean operation time was 33 min. Post-procedure complications included subcutaneous bleeding in 12 cases and haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases, mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia in two cases each, respectively. Follow-up ultrasonography revealed residual tumours in four cases (15.4%). Conclusions Although this method is feasible and safe without severe complications, it is necessary to select appropriate patients, and to obtain informed consent regarding the possibility of recurrence or residual tumour.

A task force of the Japanese Breast Cancer Society has proposed a recommendation for adequate evaluation of hormone receptors in routine practice, in order to standardize handling of tissues, staining techniques and scoring systems. As a part of the study, several examinations were conducted to detect the effect of technical problems, including the influence of fixation time and other fixation and processing conditions, on the immunoreactivity for ERalpha. There is little influence of prolonged fixation on the immunoreactivity for ERalpha, except for cases in which particularly over-fixed blocks are used. A delay in the onset of fixation could decrease the immunohistochemical findings of steroid receptors, compared with shorter or longer fixation, and the situation is similar to the fixation of a whole large surgical specimen in formalin in a big bucket. Incomplete fixation might be an important cause of heterogeneiety of immunoreactivity for ERalpha. Manual and automated immunohistochemical (IHC) staining by DAKO (Glostrup, Denmark) and Biogenex (San Ramon, CA) and automated IHC staining by Ventana Medical Systems (Tucson, AZ) each employ different methods. Using a scoring system, in which the proportion of cells stained in each specimen was recorded as 0, less than 1%, 1% or more and less than 10%, and 10% or more, the intermethod variability of those IHC staining methods exhibited substantial multi-rater kappa values concerning the ER and PgR (kappa for ER according to the percentage of positive cells=0.67; PgR=0.72). Concerning intermethod consistency, the scoring system based on the percentage of positive cells was advantageous over other scoring systems, based on the intensity of nuclear staining. Using double staining, patients with ER-positive and HER2-positive tumors can be classified as those with co-expressed tumors and those with differently expressed tumors. As such, the co-expressed tumor might be resistant to antiestrogen therapy in ERalpha-positive and HER2-positive breast cancer and double staining might lead to the development of new therapeutic strategies for hormone and HER2-positive breast cancer.

症例は49才女性．右背部痛にて当院受診し，腹部超音波，単純CTにて，多発する肝嚢胞を認め，そのうち肝前上区域（S8）の嚢胞内に充実性部分が見られたが，造影効果なく，出血を伴った肝嚢胞と診断され経過観察となった．4カ月後に変化を認めなかったが，10カ月後に嚢胞径ならびに充実性部分の増大と内部性状の変化がみられた．各種造影検査で充実性部分に造影効果を認めたため，肝嚢胞腺癌を疑い肝前区域切除を施行した．組織学的に充実性部分は内部出血を伴った凝血塊と壊死組織で，血管腫様の不規則に拡張した血管腔の増生を伴っていた．

Background& Aims: True local recurrences(TR)and new primary tumors(NP)in the conserved breast\nafter breast-conserving surgery with radiation therapy are determined by the initial surgical margin, the\nlocation of recurrent tumors and the histological consistency between initial tumors and recurrent tumors.\nMethods: A total of 15 patients with breast recurrence out of a group of 389 women with breast cancer\nwho underwent breast-conserving therapy between 1991 and 2003 were included in this study. The\nbiological differences between TR and NP were examined. Results: Eight patients had TR, and seven\nhad NP. The disease-free interval was 34.6 months in the TR group and 94.1 in the NP group.\nBreast-free survival was significantly better in the NP group than the TR group. The accumulated\n10-year overall survival after salvage surgery in patients with TR or NP tumors was 85.1％. The\naccumulated overall survival after salvage surgery was better in the NP group than the TR group.\nConclusions: Patients with NP tumors have a favorable prognosis compared to those with TR tumors.\nIt is important to determine the type of breast recurrence in order to accurately predict the prognosis of\npatients with breast recurrence.

鹿児島県産のカンキツの炎症性サイトカイン産生抑制効果を検討した.今回供試したカンキツはすべての品種でアルコール抽出,水抽出画分共に産生抑制効果を示した.タンカンでは未熟果皮で抑制活性が高かった.このタンカンから抑制成分の同定を行った結果,主要成分がノビレチンであることを高速液体クロマトグラフィーによる単離後,質量分析で同定した.またノビレチン関連物質であると想定される,さらに強い抑制活性の分画の存在も確認した.

The "thrifty" genotype and phenotype that save energy are detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms (SNPs), some of which promote the development of obesity/type 2 diabetes mellitus. In this review, four major questions are addressed: (1) Why did regional differences in energy metabolism develop during evolution? (2) How do genes respond to starvation and affluence? (3) Which SNPs correspond to the hypothetical "thrifty genes"? (4) How can we cope with disease susceptibility caused by the "thrifty" SNPs? We examined mtDNA and genes for energy metabolism in people who live in several parts of Asia and the Pacific islands. We included 14 genes, and the SNP frequencies of PPAR gamma 2, LEPR, and UCP3-p and some other genes differ significantly between Mongoloids and Caucasoids. These differences in SNPs may have been caused by natural selection depending on the types of agriculture practiced in different regions. Interventions to counteract the adverse effects of "thrifty" SNPs have been partially effective.