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Our previous study indicated that the acinar cells regenerated actively in the rat pancreatic remnant after partial (90%) pancreatectomy. On that occasion, a twofold higher mitotic activity was observed in the cells of paraduodenal than those of the medial and stump regions (regional difference). Since cholecystokinin (CCK) has been known to have various physiological functions in the digestive system, especially in the pancreas, through the CCK-A receptor, we determined the effect of a CCK-A receptor competitive antagonist (CCK-RA) (SR27897B) on pancreatic regeneration after pancreatectomy. A group of Wistar rats was administered 1 mg/kg CCK-RA twice daily for 5 days. On the 2nd day of administration, partial pancreatectomy was performed. Proliferation activity of both exocrine and endocrine cells was found to be enhanced uniformly 5 days after the pancreatectomy, and the effect was inhibited by CCK-RA. Plasma CCK level was increased by 90% pancreatectomy and decreased by CCK-RA. CCK was hypothesized to be an important factor of pancreatic exocrine and endocrine regeneration. Administration with CCK-RA suppressed mitotic activity uniformly in the three regions of paraduodenal, medial and stump. From the evidence, it was presumed that regional difference in regeneration was produced not by paracrine factor from the duodenum but by some other unknown mechanism including anatomical difference in vascular and autonomic nervous system.

Summary. T-cell granular lymphocyte-proliferative disorder (T-GLPD) is characterized by the proliferation of cytotoxic T lymphocytes, and is often associated with pure red cell aplasia (PRCA). The mechanism involved in the development of PRCA in T-GLPD is unknown. Peripheral blood mononuclear cells were isolated from 20 patients with T-GLPD. Ten patients had associated PRCA. Granular lymphocytes (GLs) of T-GLPD are positive for CD94, but not NKG2A. To clarify the functional role of CD94 in T-GLPD, we performed a cytotoxicity assay against the trophoblast cell line, BeWo, which is known to express human leucocyte antigen (HLA)-E, a natural ligand of CD94, and is deficient in other HLA class I and class II antigens. GLs isolated from T-GLPD with PRCA patients killed BeWo cells more significantly than GLs from T-GLPD without PRCA patients. Furthermore, GLs from T-GLPD with PRCA were significantly stimulated by a monoclonal antibody against CD94, whereas those of T-GLPD without PRCA were not. Taken together, HLA-E, a ligand of CD94, was suggested to stimulate CD94+ cells to kill HLA-E+ cells in T-GLPD with PRCA. GLs of T-GLPD with PRCA have a potential positive activity against HLA-E+ cells, whereas GLs from T-GLPD without PRCA do not. CD94 may play a key role in the pathogenesis of PRCA in T-GLPD.

We treated rapidly growing Jurkat cells with 40 nmol/l of doxorubicin for 72 h. After 36 h, the G2-arrested cells became larger and some of them started endoreplication. Nuclear staining with Hoechst 33342 combined with propidium iodide (PI) exclusion revealed that about 90% of the cells were necrotic at 72 h, although apoptotic cells accounted for only 8%. Incubation with 40 nmol/l of aclarubicin or cytosine beta-d-arabinofuranoside for 60 h induced necrosis both in Jurkat and ml-1 cells. Pre-necrotic Jurkat cells incubated with 40 nmol/l of doxorubicin had much higher intracellular reactive oxygen species (ROS) levels than pre-apoptotic ones. Addition of Tempol or Desferal accelerated doxorubicin-induced necrosis and partially converted it into apoptosis. Both antioxidants reduced surviving colony numbers of prenecrotic Jurkat cells. n-acetyl-l-cysteine had little effect on the apoptotic conversion but profoundly accelerated necrosis. Because an apoptosis-resistant Jurkat subclone was also refractory to doxorubicin-induced necrosis, apoptosis and necrosis might share some common pathways. Low-dose doxorubicin increased micronuclei-positive cell percentages and also suppressed high-dose doxorubicin-induced apoptosis in Jurkat and ml-1 cells. Some of the prenecrotic cells, therefore, might survive and obtain genomic instability. Antioxidants may be useful to suppress, at least to some extent, this vicious consequence.

Sterols have important functions in membranes and signaling. Plant sterols are synthesized via the isoprenoid pathway by cyclization of 2,3-oxidosqualene to cycloartenol. Plants also convert 2,3-oxidosqualene to other sterol-like cyclization products, including the simple triterpene β-amyrin. The function of β-amyrin per se is unknown, but this molecule can serve as an intermediate in the synthesis of more complex triterpene glycosides associated with plant defense. β-Amyrin is present at low levels in the roots of diploid oat (Avena strigosa). Oat roots also synthesize the β-amyrin–derived triterpene glycoside avenacin A-1, which provides protection against soil-borne diseases. The genes for the early steps in avenacin A-1 synthesis [saponin-deficient 1 and 2 (Sad1 and Sad2)] have been recruited from the sterol pathway by gene duplication and neofunctionalization. Here we show that Sad1 and Sad2 are regulated by an ancient root developmental process that is conserved across diverse species. Sad1 promoter activity is dependent on an L1 box motif, implicating sterol/lipid-binding class IV homeodomain leucine zipper transcription factors as potential regulators. The metabolism of β-amyrin is blocked in sad2 mutants, which therefore accumulate abnormally high levels of this triterpene. The accumulation of elevated levels of β-amyrin in these mutants triggers a “superhairy” root phenotype. Importantly, this effect is manifested very early in the establishment of the root epidermis, causing a greater proportion of epidermal cells to be specified as root hair cells rather than nonhair cells. Together these findings suggest that simple triterpenes may have widespread and as yet largely unrecognized functions in plant growth and development.

Background Rice blast is a destructive disease caused by Magnaporthe oryzae, and it has a large impact on rice production worldwide. Compared with leaf blast resistance, our understanding of panicle blast resistance is limited, with only one panicle blast resistance gene, Pb1, isolated so far. The japonica cultivar Miyazakimochi shows resistance to panicle blast, yet the genetic components accounting for this resistance remain to be determined. Results In this study, we evaluated the panicle blast resistance of populations derived from a cross between Miyazakimochi and the Bikei 22 cultivar, which is susceptible to both leaf and panicle blast. The phenotypic analyses revealed no correlation between panicle blast resistance and leaf blast resistance. Quantitative trait locus (QTL) analysis of 158 recombinant inbred lines using 112 developed genome-wide and 35 previously reported polymerase chain reaction (PCR) markers revealed the presence of two QTLs conferring panicle blast resistance in Miyazakimochi: a major QTL, qPbm11, on chromosome 11; and a minor QTL, qPbm9, on chromosome 9. To clarify the contribution of these QTLs to panicle blast resistance, 24 lines homozygous for each QTL were selected from 2,818 progeny of a BC2F7 backcrossed population, and characterized for disease phenotypes. The panicle blast resistance of the lines harboring qPbm11 was very similar to the resistant donor parental cultivar Miyazakimochi, whereas the contribution of qPbm9 to the resistance was small. Genotyping of the BC2F7 individuals highlighted the overlap between the qPbm11 region and a locus of the panicle blast resistance gene, Pb1. Reverse transcriptase PCR analysis revealed that the Pb1 transcript was absent in the panicles of Miyazakimochi, demonstrating that qPbm11 is a novel genetic component of panicle blast resistance. Conclusions This study revealed that Miyazakimochi harbors a novel panicle blast resistance controlled mainly by the major QTL qPbm11. qPbm11 is distinct from Pb1 and could be a genetic source for breeding panicle blast resistance, and will improve understanding of the molecular basis of host resistance to panicle blast.

Background/aims Because little has been known about the morphological and functional consequences of liver transplantation on hepatic autonomic nerves, we examined the time-course of extrinsic hepatic innervation at the level of the porta hepatis of liver allografts. Methods Orthotopic liver transplantation was performed using male Lewis rats. Crosscut tissue specimens were obtained postoperatively for up to 6 months from the porta hepatis of transplanted livers, and processed for immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and growth-associated protein 43 (GAP-43), and for transmission electron microscopy (TEM). Results Extrinsic nerve fibers at the porta hepatis stained positively for PGP 9.5 throughout the entire study period. In contrast, the immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP-43-positive nerves were first observed to appear in the porta hepatis at POD 3. The immunoreactivity of GAP-43 remained positive thereafter until 3 months post-OLT, and became negative in all the specimens at 4 months post-OLT. Transmission electron microscopy demonstrated a small number of regenerating axons existing among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating axons had been fully ensheathed by the cytoplasm of Schwann cells, although their density remained at a lower level compared with normal. Conclusion The results of this study suggest that liver allografts become extrinsically reinnervated, with the regenerating axons reaching the hepatic hilus 3 days after transplantation. The process of extrinsic hepatic reinnervation is considered to almost terminate 4 months after transplantation in rats.

A fusion between the plastid psbA promoter and the green fluorescent protein gene (gfp) was introduced into the tobacco chloroplast genome by stable plastid transformation. GFP was synthesized actively and exclusively in the chloroplasts. Tubular projections filled with GFP but containing no chlorophyll were visualized for the first time in chloroplasts of these transplastomic plants. Occasionally, the tubules connect chloroplasts with each other, suggesting the possibility of the exchange of endogenous proteins. However, the fusion of protoplasts between the transplastomic and wild-type plants showed that such chloroplast connections might be rare in mesophyll protoplasts.

The relationship between the index of general trust and decision making process of civil engineers is examined by using analysis of answers to question sheet. From the analysis, it appears that there is a close relationships between them. As the score of general trust increases, the decision of engineers becomes more positive. It is also found out that socialization process of civil engineers is completed at around 30 years old. It is necessary to do ethics education before this age.

The results of the investigation on reading strategies and extensive reading of EFL students indicate that reading a lot in both L1 and L2/FL becomes basically the most important factor for improving reading skills rather than just teaching reading strategies. Extensive reading gives learners a rich background knowledge, vocabulary recognition, a high motivation for more reading, and becomes the basic skill of rapid reading, discovery of reading strategies by learners themselves, and increases guessing ability in context.

We have cloned the gene encoding RNase HII (RNase HII Pk ) from the hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1 by screening of a library for clones that suppressed the temperature-sensitive growth phenotype of an rnh mutant strain of Escherichia coli . This gene was expressed in an rnh mutant strain of E. coli , the recombinant enzyme was purified, and its biochemical properties were compared with those of E. coli RNases HI and HII. RNase HII Pk is composed of 228 amino acid residues (molecular weight, 25,799) and acts as a monomer. Its amino acid sequence showed little similarity to those of enzymes that are members of the RNase HI family of proteins but showed 40, 31, and 25% identities to those of Methanococcus jannaschii , Saccharomyces cerevisiae , and E. coli RNase HII proteins, respectively. The enzymatic activity was determined at 30°C and pH 8.0 by use of an M13 DNA-RNA hybrid as a substrate. Under these conditions, the most preferred metal ions were Co 2+ for RNase HII Pk , Mn 2+ for E. coli RNase HII, and Mg 2+ for E. coli RNase HI. The specific activity of RNase HII Pk determined in the presence of the most preferred metal ion was 6.8-fold higher than that of E. coli RNase HII and 4.5-fold lower than that of E. coli RNase HI. Like E. coli RNase HI, RNase HII Pk and E. coli RNase HII cleave the RNA strand of an RNA-DNA hybrid endonucleolytically at the P-O3′ bond. In addition, these enzymes cleave oligomeric substrates in a similar manner. These results suggest that RNase HII Pk and E. coli RNases HI and HII are structurally and functionally related to one another.

Lampreys are eel-like jawless fishes evolutionarily positioned between invertebrates and vertebrates, and have been used as model organisms to explore vertebrate evolution. In this study we determined the complete genome sequence of the mitochondrial DNA of the Japanese river lamprey, Lethenteron japonicum, using next-generation sequencers. The sequence was 16,272 bp in length. The gene content and order were identical to those of the sea lamprey, Petromyzon marinus, which has been the reference among lamprey species. However, the sequence similarity was less than 90%, suggesting the need for the whole-genome sequencing of L. japonicum.

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

The patient was a 66-year-old woman with left breast cancer who underwent left segmental mastectomy with sentinel lymph node biopsy. The histopathological diagnosis was estrogen receptor-positive (ER+), progesterone receptor-positive( PgR+), human epidermal growth factor receptor-2-equivocal( HER2()2+)( with no HER2 gene amplification by fluorescence in-situ hybridization analysis) invasive ductal carcinoma (scirrhous carcinoma) with Ki-67 expression of less than 10% (pathological T1c, N0, M0, stage I). The patient requested chemotherapy, and 4 cycles of docetaxel plus cyclophosphamide (TC) were scheduled. Fever and epigastric pain developed on day 13 of cycle 2. On day 22, the patient was examined before the third cycle of TC, and right lower abdominal pain was reported. Computed tomography revealed appendicitis and an intraperitoneal abscess. She was admitted to the hospital and underwent partial ileocecal resection. The patient was discharged on the 12th postoperative day with no further complications. Acute abdomen during chemotherapy for malignant tumors has been reported sporadically in patients with leukemia. A diagnosis of acute abdomen in patients undergoing cancer treatment requires careful assessment of gastrointestinal symptoms such as nausea and vomiting during chemotherapy, fever associated with granulocytopenia, and findings indicative of local inflammation. The patient in this case recovered uneventfully because imaging studies and surgery were performed promptly after presentation.

Purpose To report a case of optic neuropathy associated with prolonged use of a new antibiotic, linezolid. Design Interventional case report. Methods Optic and peripheral neuropathy occurred in a 27-year-old woman who was undergoing prolonged linezolid therapy for osteomyelitis. The use of corticosteroid exacerbated visual loss. Discontinuation of the linezolid therapy resulted in marked improvement of optic neuropathy. Results Linezolid-induced optic neuropathy was diagnosed in this case, because prolonged linezolid therapy was performed at a higher dose than usual and because the patient recovered after linezolid therapy was discontinued. Conclusions With prolonged linezolid therapy, ophthalmologists should be aware that bilateral optic neuropathy can occur and that corticosteroids are not indicated for this neuropathy.

UDP-glucuronosyltransferase 1A9 (UGT1A9) contributes to the glucuronidation of numerous drugs. Cynomolgus monkeys are regarded as experimental animals similar to humans in studies on safety evaluation and biotransformation for drug development. In this study, the similarities and differences in the enzymatic properties of UGT1A9 between humans and cynomolgus monkeys were precisely identified. UGT1A9 cDNAs of humans (humUGT1A9) and cynomolgus monkeys (monUGT1A9) were cloned, and the corresponding proteins were heterologously expressed in Sf9 cells. The enzymatic properties of UGT1A9s were characterized by kinetic analysis of propofol glucuronidation. The amino acid homology between humUGT1A9 and monUGT1A9 was 93.2 %. Propofol glucuronidation by recombinant humUGT1A9 and monUGT1A9 exhibited substrate inhibition and monophasic Michaelis-Menten kinetics, respectively. The K m, V max and CL int values of humUGT1A9 were 15.0 μM, 1.56 nmon/min/mg protein and 107 μL/min/mg protein, respectively. The K m value of monUGT1A9 was 8.8-fold higher than humUGT1A9, and the V max and CL int values of monUGT1A9 were 15 and 2 % of humUGT1A9, respectively. These findings suggest that the enzymatic properties of UGT1A9 are considerably different between humans and cynomolgus monkeys, although humUGT1A9 and monUGT1A9 were highly conserved at the amino acid level. The information on species differences in UGT1A9 function gained in this study should help with the in vivo extrapolation of drug metabolism.

Background/Aims: Missense, nonsense, and splice mutations in the Fibroblast Growth Factor 8(FGF8) have recently been identified in patients with hypothalamo-pituitary dysfunction and craniofacial anomalies. Here, we report a male patient with a frameshift mutation in FGF8. Case Report: The patient exhibited micropenis, craniofacial anomalies, and ventricular septal defect at birth. Clinical evaluation at 16 years and 8 months of age revealed delayed puberty, hyposmia, borderline mental retardation, and mild hearing difficulty. Endocrine findings included gonadotropin deficiency and primary hypothyroidism. Results: Molecular analysis identified a de novo heterozygous p.S192fsX204 mutation in the last exon of FGF8. RT-PCR analysis of normal human tissues detected FGF8 expression in the genital skin, and whole-mount in situ hybridization analysis of mouse embryos revealed Fgf8 expression in the anlage of the penis. Conclusion: The results indicate that frameshift mutations in FGF8 account for a part of the etiology of hypothalamo-pituitary dysfunction. Micropenis in patients with FGF8 abnormalities appears to be caused by gonadotropin deficiency and defective outgrowth of the anlage of the penis.

The western flower thrips (WFT), Frankliniella occidentalis, was first discovered in a southern area of Fukuoka Prefecture in April, 1994. Our census surveys revealed that the distribution of WFT has been limited to the southern part and a few restricted areas in Fukuoka Prefecture even one and a half years after its' initial discovery. In strawberry greenhouses, the number of WFT adults captured on blue sticky traps remained low during winter. However, the number increased rapidly in late March and early April. In a rose greenhouse, a similar tendency in the number of WFT was observed. Judging from the abundance pattern in greenhouses and the low temperature conditions outside the greenhouses, the WFT populations overwintering in greenhouses appeared to be a major source of the spring populations. From the control perspective, applications of insecticides immediately after planting and in early spring were thought to be crucial. The number of WFT adults captured in traps placed around a strawberry greenhouse and its surrounding vegetation showed that WFT adults dispersed from the greenhouse during late April and early May, and then colonized the surrounding vegetation. Thus, WFT appeared to utilize greenhouse crops and their surrounding vegetation successively as temporal habitats.

The patient was a 73-year-old woman with diabetes mellitus who was receiving insulin therapy. A poorly demarcated mass of 2 cm in diameter was palpated in the C region of the left breast. Mammography showed a dense locally asymmetric shadow. Ultrasonography revealed an irregular, poorly demarcated, hypoechoic mass measuring 14×21×10 mm accompanied by an attenuated posterior echo. Needle biopsy showed no evidence of malignancy, and the patient was kept under observation. An ultrasonographic examination performed 6 months later showed no change, but the possibility of cancer could not be ruled out on contrast-enhanced computed tomography and magnetic resonance imaging. Tumor resection at the patient's request was therefore performed. Histopathological examination of the breast revealed interstitial fibrosis with superimposed ground-glass opacities and lymphocyte infiltration around the ducts, leading to a diagnosis of diabetic mastopathy. Diabetic mastopathy occurs primarily in patients with a prolonged history of diabetes mellitus. It is difficult to distinguish diabetic mastopathy from breast cancer by palpation and imaging studies. Most cases are conclusively diagnosed by needle biopsy. Clinicians should be aware of diabetic mastopathy to avoid overdiagnosis and overtreatment. In our patient, diabetic mastopathy could be diagnosed on the basis of clinical characteristics and needle biopsy.

Patient 1 was a 63-year-old woman whose chief complaint was a mass in the left breast. Physical examination revealed an inverted left nipple, a very large mass on the anterior aspect of the sternum, and erythema. Because the tumor had directly invaded the sternum, T4cN3M0, stage IIIC breast cancer was diagnosed. The patient preoperatively received chemotherapy with 6 courses of FEC100 (5-fluorouracil, epirubicin, and cyclophosphamide) and 5 courses of nanoparticle albumin -bound paclitaxel (260 mg/m2), which enabled a partial response. Patient 2 was an 83-year-old woman whose chief complaint was a mass in the upper internal and external quadrants of the right breast measuring 20×15 cm and erythema. The mass was accompanied by enlarged right axillary lymph nodes(T4bN1M0, stage IIIB breast cancer). Both patients underwent core needle biopsy of the skin and breast masses. They were both diagnosed with invasive, lobular, triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 negative). The surgical resection line was drawn to include the extensive skin invasion, and mastectomy and axillary dissection were performed. Skin grafting was scheduled but the retromammary space on the healthy side was dissected to the anterior border of the latissimus dorsi muscle, and the skin of the healthy side was used to cover the defect on the affected side. Consequently, the pendulous breast on the healthy side was elevated. This surgical technique provided an excellent aesthetic outcome without any skin problems, because autologous skin was used to fill the defect. Radiotherapy could subsequently be administered as scheduled. This procedure may be useful for elderly patients.

A 38-year-old premenopausal woman with a right axillary mass was told that she had an atheroma. The mass enlarged. An infectious atheroma was suspected, and incision and drainage were performed. A mass 4 cm in diameter was palpated in the right axillary region. Ultrasonography showed a mass 6 cm in diameter, and magnetic resonance imaging revealed a hypervascular mass at the same site. Stage IIIB triple-negative of accessory breast cancer (T4bN1M0) was diagnosed. The patient received four courses of FEC 100 (5-fluorouracil, epirubicin, and cyclophosphamide) as preoperative chemotherapy, but progressive disease was diagnosed, and the regimen was switched to weekly paclitaxel. The tumor became ulcerated and friable, and the hemoglobin level fell to 6 g/dL. Emergency surgery was thus performed. Postoperatively, the patient received six courses of chemotherapy with paclitaxel plus gemcitabine. Accessory breast cancer is extremely rare, but should be borne in mind when an axillary mass is encountered. In our patient, progressive disease had developed during the preoperative chemotherapy for accessory breast cancer. Although treatment was switched to a different regimen, bleeding was detected, and the patient underwent a semi-emergency surgery.

A case was a 40-year-old woman. Her right breast was presented with massive bleeding ulcer and fixed with a pectoral muscle. Diagnosis of Stage IIIb breast cancer( T4b, N1, M0) showed a high inflammatory response and severe anemia. Palliative surgery was difficult because of hemostasis, and her general health also was in poor condition. The pathological diagnosis was squamous cell cancer. We underwent a total of 30 Gy radiation emergency hemostasisose. After radiation and chemotherapy, the lesion was undergone a radical surgery, and was reduced in size significantly. It was diagnosed as squamous cell cancer, which was more sensitive to general radiation so neoadjuvant chemoradiation therapy was effective.

To characterise the optic nerve head (ONH) configurations of superior segmental optic hypoplasia (SSOH) using a spectral-domain optical coherence tomography (SD-OCT).Horizontal cross-sectional images of the ONH were obtained by a SD-OCT in 20 eyes of 14 patients with clinically typical SSOH and 20 age- and refraction-matched normal eyes.Extension of retinal pigment epithelium (RPE) over the disc margin was observed in 20 eyes (100%) with SSOH and eight (40%) control eyes (p0.001). The maximum length of the overhanging RPE measured at the nasal disc margin was significantly longer in eyes with SSOH than in controls (295.9+/-112.6 vs 24.3+/-33.9 microm; p0.0001). In eyes with SSOH, the retinal nerve fibre layer (RNFL) was significantly thinner in the temporal-superior to nasal sectors (p0.01).The extension of RPE over the nasal disc margin was more common and longer in eyes with SSOH than in normal eyes, suggesting that the SD-OCT findings might facilitate the diagnosis of SSOH. Substantial thinning of the RNFL was present in wider areas than previously expected in SSOH.

An 83-year-old postmenopausal woman was referred to our hospital in order to get the treatment for ER positive advanced breast cancer (T4aN2M0, stage III b). The patient was diagnosed as the dissected aortic aneurysm and the hypertension. It was decided that an operation and chemotherapy would be too difficult with high existing risks. As a result, she was treated with anastrozole of PST, a 3rd-generation aromatase inhibitor, which led to the marked regression of the left breast cancer within a month. The cancer wasn't visualized after eighteen months. With the ongoing breast-hormone Therapy, no remote metastasis has been found after thirty months to this day. The patient hasn't experienced any adverse effects with the above-mentioned therapy. We concluded that the hormone (anastrozole) therapy as PST is a useful treatment for elderly postmenopausal woman with ER positive advanced breast cancer.

PURPOSE: To evaluate the cross-sectional configurations of peripapillary atrophy (PPA)-alpha and -beta in ophthalmologically normal subjects using spectral domain-optical coherence tomography (SD-OCT). METHODS: One hundred twenty normal subjects had a complete ophthalmic examination including axial length measurement, standard automated perimetry, fundus imaging with photography, and SD-OCT (3D OCT-1000; Topcon Inc., Tokyo, Japan). PPA-alpha and -beta were identified in color photographs of the optic disc. Cross-sectional B-mode images of the peripapillary retina and sclera, including PPA-alpha and -beta obtained with SD-OCT, were analyzed. RESULTS: Of 120 normal eyes, 120 (100%) had PPA-alpha and 90 (75%) had PPA-beta. In OCT images of the peripapillary retina, the ganglion cell layer and the inner and outer plexiform layers were observed to end in a tapering fashion at the edge of the optic disc, whereas the retinal nerve fiber layer continued into the optic cup. The external limiting membrane (ELM), inner-outer segments (IS-OS), and retinal pigment epithelium(RPE)/Bruch's membrane complex were significantly more commonly absent before the optic disc edge within the PPA-beta compared with areas outside the PPA-beta (P < 0.0001). Specific findings in the peripapillary area including slope and step configurations of the scleral bed and hump- and wedge-shaped appearances of the RPE-Bruch's membrane complex were identified in 63 (52.5%), 6 (5.0%), 19 (15.8%), and 6 (5.0%) of 120 eyes, respectively. The presence of the step configuration was associated with myopia and longer axial length (P = 0.0014 and 0.0105, respectively). CONCLUSIONS: The cross-sectional anatomic configurations of the peripapillary atrophy were evaluated by using SD-OCT. The termination of the retinal layers and configurations of the scleral bed in the peripapillary area varied among normal subjects.

The 14-epimer of MART-10, namely 14-epi-MART-10 (14-epi-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D3) and its 2-epimeric analog (14-epi-MART-11) were efficiently synthesized using the Julia coupling reaction to connect between the C5 and C6 positions (steroid numbering). An A-ring precursor was prepared from (-)-quinic acid as shown in the previous MART-10 synthesis. The novel 14-epi-CD-ring coupling partner with an elongated two carbon unit as a sulfone was synthesized from 14-epi-25-hydroxy Grundmann's ketone in good yield. The subsequent coupling reaction followed by a deprotection step afforded a mixture of 14-epi-MART-10 and 14-epi-MART-11 in 40% yield. To separate 14-epi-MART-10 and 14-epi-MART-11, each primary hydroxyl group was esterified with a pivaloyl group and the resulting pivalates 2alpha and 2beta were separated by high performance liquid chromatography. After the separation, the C2-stereochemistry of each (2alpha or 2beta) was determined by 1H NMR (nuclear magnetic resonance) studies including NOE (nuclear Overhauser effect) experiments. The pivaloyl group was removed under basic conditions to obtain the target molecules of 14-epi-MART-10 and 14-epi-MART-11, respectively. The VDR (vitamin D receptor)-binding affinity, HL-60 (human promyelocytic leukemia) cell differentiation activity, antiproliferative activity in PZ-HPV-7 (immortalized normal prostate) cells and transactivation activity of the osteocalcin promoter in HOS (human osteoblast cell line) cells (serum-free conditions) were investigated. In addition, the effects on bone mineral density (BMD) and the blood and urine calcium concentrations of ovariectomized (OVX) rats were examined. 14-epi-MART-10 has much greater antiproliferative and cell differentiation activities compared to 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3).

We here describe a case of advanced breast cancer (Stage IV) in which an oral S-1+TAM therapy following a primary systemic chemo-radiotherapy has been effective in maintaining the patient's QOL. A 40-year-old woman visited our hospital because of her left breast tumor. On physical examination, the tumor had invaded to the skin adjacent to the nipple forming a skin ulcer and marked deformity of the entire breast. Also noted were swollen lymph nodes in the left armpit. Subsequently, radiographic imaging tests revealed that the tumor had metastasized to the liver and lungs, as well as the skull. Accordingly, a primary systemic chemotherapy (4 series of AC/T) was started and followed by local radiation therapy (60 Gys) immediately after completing the chemotherapy. The metastasizing lesions in the liver, lungs, and skull had markedly reduced in the size and number, and the skin ulceration had healed up by these treatments. Afterwards, she has been given TAM daily and S-1 for 4 weeks with a 2-week interval. She has been quite well without any adverse effects by S-1 and TAM, and the primary as well as metastasizing lesions remain stable with normalized tumor marker levels (NC) for nearly 3 years.

CYP105A1 from Streptomyces griseolus has the capability of converting vitamin D 3 (VD 3) to its active form, 1alpha,25-dihydroxyvitamin D 3 (1alpha,25(OH) 2D 3) by a two-step hydroxylation reaction. Our previous structural study has suggested that Arg73 and Arg84 are key residues for the activities of CYP105A1. In this study, we prepared a series of single and double mutants by site-directed mutagenesis focusing on these two residues of CYP105A1 to obtain the hyperactive vitamin D 3 hydroxylase. R84F mutation altered the substrate specificity that gives preference to the 1alpha-hydroxylation of 25-hydroxyvitamin D 3 over the 25-hydroxylation of 1alpha-hydroxyvitamin D 3, opposite to the wild type and other mutants. The double mutant R73V/R84A exhibited 435- and 110-fold higher k cat/ K m values for the 25-hydroxylation of 1alpha-hydroxyvitamin D 3 and 1alpha-hydroxylation of 25-hydroxyvitamin D 3, respectively, compared with the wild-type enzyme. These values notably exceed those of CYP27A1, which is the physiologically essential VD 3 hydroxylase. Thus, we successfully generated useful enzymes of altered substrate preference and hyperactivity. Structural and kinetic analyses of single and double mutants suggest that the amino acid residues at positions 73 and 84 affect the location and conformation of the bound compound in the reaction site and those in the transient binding site, respectively.

The stereoselective glucuronidation of propranolol (PL) in human and cynomolgus monkey liver microsomes, and the roles of human hepatic UDP-glucuronosyltransferase (UGT) isofoms involved in the enantiomeric glucuronidation of PL using recombinant UGT enzymes were investigated. In Michaelis-Menten plots, R- and S-PL glucuronidation by human liver microsomes showed sigmoidal kinetics whereas the kinetics of enantiomeric PL glucuronidation by cynomolgus monkey liver microsomes was monophasic. The Km, Vmax and CLint values of cynomolgus monkey liver microsomes were generally higher than the S50, Vmax and CLmax values of human liver microsomes in R- and S-PL glucuronidation. The glucuronidation of R- and S-PL was catalyzed by at least 3 UGT isoforms: UGT1A9, UGT2B4 and UGT2B7. Michaelis-Menten plots for R- and S-PL glucuronidation by UGT1A9 were monophasic, whereas the kinetics of UGT2B7 showed sigmoidal curves. Enantiomeric R-PL glucuronidation by UGT2B4 showed sigmoidal kinetics, whereas S-PL glucuronidation displayed monophasic kinetics. UGT1A9 showed remarkable stereoselectivity in Vmax and CLint values of R-PL < S-PL. These findings demonstrate that the profiles of enantiomeric PL glucuronidation in human and cynomolgus monkey liver microsomes are largely different and suggest that the human hepatic UGT isofoms UGT1A9, UGT2B4 and UGT2B7 play distinctive roles in enantiomeric PL glucuronidation.

持続性低血圧透析患者の臨床的特徴と看護について検討するために, 透析前収縮期血圧100mmHg以下の低血圧者10名A群と正常血圧者11名B群とについて比較した.両群の透析歴はA群11.3±6年, B群10.4±4年であり, 透析前平均血圧はA群69±7mmHg, B群では99.6±8mmHgであった.A群は合併症に2次性副甲状腺機能亢進症および手根管症候群を多数認めたが, 両群において副甲状腺ホルモン, β2-マイクログロブリン値には有意差を認めなかった, また貧血との相関関係も認められなかった. 心胸比, 体重増加率, 摂取栄養量においても両群間に差を認めなかった. A群の10例中8例においては, 循環血液量減少予防または低血圧の治療が必要であった. 血圧下降症状出現時の血圧値は各々の症例でほぼ一定であり, 透析中の血圧維持レベルを決めることにより下降防止が可能であった. また水分, 塩分摂取量の管理により適正体重を維持することが重要と考えられた.

Rice is a dietary staple worldwide, especially pre-germinated brown rice has recently been widely served in Japan because of its abundant nutrition. Relationship between lactation and pre-germinated brown rice has attracted interest in terms of mental health and immunity. To demonstrate that Japanese foods are beneficial for psychosomatic health, the effects of pre-germinated brown rice on the mental status and immunological features during lactation were investigated. Forty-one breast-feeding mothers were recruited, and randomly divided into two groups. One group took pre-germinated brown rice and the other white rice (control) as their staple diet for 2 weeks. The Profile of Mood States (POMS) and salivary amylase activity as psychological indices and secretory IgA (s-IgA) and lactoferrin (LTF) in breast milk as immunological indices were determined before and after dietary intervention, and changes were investigated. In the psychological assessment, the scores of depression, anger-hostility, and fatigue were decreased on POMS analysis in the pre-germinated brown rice diet group, resulting in a significant decrease in total mood disturbance (TMD). The salivary amylase activity measurement suggested that resistance to stress was increased in the pre-germinated brown rice diet group. On the immunological assessment, the s-IgA level was significantly increased in the pre-germinated brown rice diet group. We have shown that pre-germinated brown rice may have beneficial effects on psychosomatic health.

Aims Reduction of left atrial appendage (LAA) flow velocity (FV) is a risk factor for thrombus formation and increases the risk of stroke in patients with atrial fibrillation (AF). Furthermore, LAA morphology is correlated with stroke in patients with AF. The aim of this study was to correlate LAAFV with LAA morphology in patients with AF. Methods and results We studied 96 patients (age 59.0 ± 10.2 years, 75% male) referred for radiofrequency catheter ablation for paroxysmal AF. All patients underwent computed tomography (CT) and transthoracic and transoesophageal echocardiography during sinus rhythm. LAA morphology was classified as one of the four types (chicken wing, windsock, cactus, and cauliflower) on CT images. There were significant differences in LAAFV among LAA morphologies (chicken wing 73.7 ± 21.9 cm/s, windsock 61.9 ± 19.6 cm/s, cactus 55.3 ± 14.1 cm/s, cauliflower 52.7 ± 18.1 cm/s, P = 0.008). Post hoc multiple comparisons showed that LAAFV was higher in patients with chicken wing than in those with cactus ( P = 0.006, vs . chicken wing) and cauliflower ( P = 0.006, vs . chicken wing), but not with windsock ( P = 0.102). After adjustment for clinical and LAA anatomical covariates (orifice area, volume, and trabeculation), multiple linear regression analyses revealed that LAA morphology was an independent determinant of LAAFV [chickens wing: standardized partial regression coefficients ( β ) = 0.317, P = 0.0014; windsock: β = 0.303, P = 0.038]. Conclusion LAA morphology is a significant determinant of LAAFV, suggesting an underlying mechanism for the association between LAA morphology and embolic events.

Background Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy. Methods and Results TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart. Conclusions These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.

Background: Positive emotions influence endocrinological and immunological response. This study examined the effect of laughter,as an expression of positive emotion, in terms of gene expression changes. Methods: Using a microarray technique, we analyzed the changes in expression of 18,716 genes from peripheral blood leukocytes in patients with type 2 diabetes, which were induced by laughter. Results: Of the 18,716 genes, 23 genes showed significantly different expression changes after listening to the comic story compared to the lecture. Eight were relatively upregulated and 15 were downregulated 1.5 h after the laughing episode. However, these genes did not include genes that are directly involved in blood glucose metabolism. Among the 23 genes discriminated, all 4 genes encoding proteins involved in the immune response and all 4 signal transduction genes were downregulated. Moreover, it is noteworthy that 5 of the 8 relatively upregulated genes were related to the cell cycle, apoptosis, and cell adhesion. Conclusions: We demonstrated that laughter, which is an expression of positive emotion, is linked to gene expression. However, the finding of this study does not allow reasonable interpretation for the regulation of gene expression by laughter. A more focused study is needed that may identify the candidate genes for the association between physical condition and positive emotion.

The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584. The cluster contains a structural gene, godA, and nine god (goadsporin) genes involved in post-translational modification, immunity and transcriptional regulation. Although the gene organization is similar to typical bacteriocin biosynthetic gene clusters, each goadsporin biosynthetic gene shows low homology to these genes. Goadsporin biosynthesis is initiated by the translation of godA, and the subsequent cyclization, dehydration and acetylation are probably catalysed by godD, godE, godF, godG and godH gene products. godI shows high similarity to the 54 kDa subunit of the signal recognition particle and plays an important role in goadsporin immunity. Furthermore, four goadsporin analogues were produced by site-directed mutagenesis of godA, suggesting that this biosynthesis machinery is used for the heterocyclization of peptides.

The effect of laughter therapy on the plasma levels of renin, angiotensinogen, and prorenin was investigated in patients with type 2 diabetes. In the diabetic patients, the mean plasma renin concentrations were 24.6+/-12.1 ng/ml/h in the first observation (at the beginning of laughter therapy), 8.2+/-3.4 ng/ml/h in the second observation (three months after the beginning of laughter therapy) and 7.7+/-1.7 ng/ml/h in the third observation (six months after the beginning of laughter therapy). The mean plasma angiotensinogen concentrations in the 1st, 2nd and 3rd observations were 0.19+/-0.08, 0.47+/-0.12, 0.42+/-0.14 microg/ml, respectively. The mean plasma prorenin concentrations in the 1st, 2nd and 3rd observations during the laughter therapy were 195.1+/-66.2, 193.4+/-88.2 and 170.7+/-52.5 pg/ml, respectively. Plasma renin concentrations were significantly decreased (p

T-cell granular lymphocyte-proliferative disorder (T-GLPD) is characterized by the proliferation of cytotoxic T lymphocytes, and is often associated with pure red cell aplasia (PRCA). The mechanism involved in the development of PRCA in T-GLPD is unknown. Peripheral blood mononuclear cells were isolated from 20 patients with T-GLPD. Ten patients had associated PRCA. Granular lymphocytes (GLs) of T-GLPD are positive for CD94, but not NKG2A. To clarify the functional role of CD94 in T-GLPD, we performed a cytotoxicity assay against the trophoblast cell line, BeWo, which is known to express human leucocyte antigen (HLA)-E, a natural ligand of CD94, and is deficient in other HLA class I and class II antigens. GLs isolated from T-GLPD with PRCA patients killed BeWo cells more significantly than GLs from T-GLPD without PRCA patients. Furthermore, GLs from T-GLPD with PRCA were significantly stimulated by a monoclonal antibody against CD94, whereas those of T-GLPD without PRCA were not. Taken together, HLA-E, a ligand of CD94, was suggested to stimulate CD94+ cells to kill HLA-E+ cells in T-GLPD with PRCA. GLs of T-GLPD with PRCA have a potential positive activity against HLA-E+ cells, whereas GLs from T-GLPD without PRCA do not. CD94 may play a key role in the pathogenesis of PRCA in T-GLPD.