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Differentiated cell nuclei can be reprogrammed after nuclear transfer (NT) to oocytes and the produced NT embryos can give rise to cloned animals. However, development of NT embryos is often hampered by recurrent reprogramming failures, including the incomplete activation of developmental genes, yet specific genes responsible for the arrest of NT embryos are not well understood. Here, we searched for developmentally important genes among the reprogramming-resistant H3K9me3-repressed genes and identified Alyref and Gabpb1 by siRNA screening. Gene knockout of Alyref and Gabpb1 by the CRISPR/Cas9 system resulted in early developmental arrest in mice. Alyref was needed for the proper formation of inner cell mass by regulating Nanog , whereas Gabpb1 deficiency led to apoptosis. The supplement of Alyref and Gabpb1 mRNA supported efficient preimplantation development of cloned embryos. Alyref and Gabpb1 were silenced in NT embryos partially because of the repressed expression of Klf16 by H3K9me3. Thus, our study shows that the H3K9me3-repressed genes contain developmentally required genes, and the incomplete activation of such genes results in preimplantation arrest of cloned embryos., (© 2023 Ihashi et al.)

Background: Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF., Methods: Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge., Results: Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002)., Conclusions: Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The utilisation and fermentation of highly cross-linked phosphate starches made from two different origins, potato (HXL-P) and tapioca (HXL-T) were investigated in rats and humans. HXL-P and HXL-T were highly resistant to digestion by carbohydrate enzymes and were also resistant to fermentation by gut microbiota in rats. The postprandial blood glucose scarcely increased after administration of HXL-P or HXL-T in healthy humans. Incremental AUC of both HXL-P and HXL-T for 180 min was significantly lower than that of glucose ( p  < .05). Breath hydrogen excretion was very low after oral administration of HXL-P or HXL-T, and AUCs of breath hydrogen excretion for 13 h after administration were significantly lower than that of fructooligosaccharide as a reference of fermentation ( p  < .05). These results show that HXL-P and HXL-T were hardly digested and were highly resistant to fermentation. In conclusion, HXL-P and HXL-T could be good low-energy bulking ingredients to replace wheat flour.

Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar relaxation is achieved through dynein-mediated removal of myosin II from the polar cortexes. Mutants that position centrosomes closer to the polar cortex accelerated furrow induction, whereas suppression of dynein activity delayed furrowing. We show that dynein-mediated removal of myosin II from the polar cortexes triggers a bidirectional cortical flow toward the cell equator, which induces the assembly of the actomyosin contractile ring. These results provide a molecular mechanism for the aster-dependent polar relaxation, which works in parallel with equatorial stimulation to promote robust cytokinesis., (© 2020 Chapa-y-Lazo et al.)

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an OTC drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action. Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to the 5-hydroxytryptamine (5HT) 2B receptor in concentration-dependent manner with modest inhibitory effects on monoamine oxidase-A and transient potential vanilloid 1 channel. The 5HT 2B receptor antagonist activity of ETZ was also confirmed in a cellular functional assay. Furthermore, the drug exerted no inhibitory effects on cycrooxygenase-1 and -2. In the rat formalin test, oral administration of ETZ significantly reduced the nociceptive responses of the second phase and also the number of c-Fos-expressing cells in the spinal dorsal horn, in a dose-dependent manner. Moreover, intrathecal administration of ETZ significantly reduced the nociceptive responses. These results suggest that the analgesic effect of ETZ is exerted at least in the spinal cord, and the effect would be attributed to multiple mechanisms of action including 5HT 2B receptor blockade.

The purpose of the present study was to assess the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan against locally advanced lower rectal cancer according to UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms. Between 2009 and 2016, 46 patients with resectable rectal cancer (T3-T4, N0-N2, M0) received preoperative chemoradiotherapy consisting of 80 mg/m 2 per day tegafur/gimeracil/oteracil (S-1; days 1-5, 8-12, 22-26, and 29-33), 60 mg/m 2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Six to eight weeks after completing chemoradiotherapy, total mesorectal excision was carried out. Patients with UGT1A1 polymorphisms were divided into WT (n = 26), heterozygous (n = 15), and homozygous (n = 5) groups, the latter including double heterozygosities. We evaluated associations between clinical characteristics, including UGT1A1 polymorphisms, and chemoradiotherapy efficacy and toxicity. Incidence rates of grade 3+ neutropenia and diarrhea were 17.0% and 30.4%, respectively. Relative dose intensity was 89.3%. Pathological complete response rate (grade 3) was 26.1%, and the good response (grade 2/3) rate was 84.8%. UGT1A1 polymorphisms were significantly associated with neutropenia and pathological good responses, but not with diarrhea. UGT1A1 polymorphism was the only predictive factor for pathological good responses. Our results indicate that UGT1A1 polymorphism is a predictive factor to determine the clinical efficacy of preoperative chemoradiotherapy and hematological toxicity induced by chemoradiotherapy using irinotecan in locally advanced rectal cancer patients., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Introduction: The follow-up schedule for colorectal cancer patients after curative surgery is inconsistent among the guidelines. Evaluation of time to recurrence (TTR) and survival after recurrence (SAR) may provide evidence for appropriate follow-up., Methods: We assessed 3039 colon cancer (CC) and 1953 rectal cancer (RC) patients who underwent curative surgery between 2007 and 2008. We evaluated the pre- and post-recurrent clinicopathological factors associated with TTR and SAR in each stage of CC and RC., Results: The recurrence rates of stages I, II, and III were 1.2%, 13.1%, and 26.3%, respectively, for CC, and 8.4%, 20.0%, and 30.4%, respectively, for RC. In CC patients, high carcinoembryonic antigen (CEA) level and lymphovascular invasion were independent predictors of short TTR. In RC patients, metastatic factors (liver metastasis in stage III) and venous invasion (stage III) were independent predictors of short TTR. The prognostic factors of SAR were age (stage II CC and stage III RC), female gender (stage III RC), high CEA level (stage II RC), histological type (stage III CRC), nodal status (stage III CC), recurrence within 1 year (stage III RC), M1b recurrence (stage II CRC), local recurrence (stage II CC), and no surgical resection after recurrence (stage II and III CRC)., Conclusions: The follow-up schedule for stage I should be different from that for the other stages. We recommend that intensive follow-up is appropriate in stage III CC patients with undifferentiated adenocarcinoma or N2 nodal status, stage II RC patients with high preoperative CEA level, and stage III RC patients., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

Background: Adjuvant therapy for colorectal cancer (CRC) in patients aged ≥75 years is supported by inadequate evidence, although such patients are increasing in number worldwide., Patients and Methods: We assessed the influence of age and comorbidities on the prognosis of CRC in elderly patients using pooled data by the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. In total, 4598 patients (3304 with colon cancer and 1294 with rectal cancer) who underwent curative surgery from 2004 to 2006 were analysed with respect to age, Charlson comorbidity score (CS), tumour marker positivity, adjuvant therapy and prognosis., Results: The number of patients aged <64, 65-74 and >75 years was 2007 (44%), 1614 (35%) and 977 (21%), respectively. Tumour location, tumour marker positivity, clinical stage, performance of adjuvant therapy, CS and overall survival (OS) were significantly different among these age groups (P < 0.0001). Among patients aged ≥75 years with stage III CRC, 35% with colon cancer and 21% with rectal cancer received adjuvant therapy; these proportions were much lower than those in younger patients. Application of adjuvant therapy was dependent on the CS in patients aged ≤74 years, but not in older patients. Sex, the carcinoembryonic antigen concentration and adjuvant therapy were significantly associated with OS in elderly patients with stage III CRC., Conclusion: Age and comorbidities worsened the OS of patients with CRC who underwent curative surgery. However, patients aged ≥75 years were undertreated regardless of their CS despite the possibility of OS improvement by adjuvant therapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and are associated with other malignancies. There is some heterogeneity in management strategies in Japan. We undertook a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research. One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. The DCCHs performed better with regard to usage of Japan Society of Colorectal Cancer Research guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011-2015, which is fewer than the number expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was carried out in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more surgery than non-DCCH departments, although most of the management, including surgical procedures and use of non-steroidal anti-inflammatory drugs, was similar. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Computational prediction of compound-protein interactions (CPIs) is of great importance for drug design as the first step in in-silico screening. We previously proposed chemical genomics-based virtual screening (CGBVS), which predicts CPIs by using a support vector machine (SVM). However, the CGBVS has problems when training using more than a million datasets of CPIs since SVMs require an exponential increase in the calculation time and computer memory. To solve this problem, we propose the CGBVS-DNN, in which we use deep neural networks, a kind of deep learning technique, instead of the SVM. Deep learning does not require learning all input data at once because the network can be trained with small mini-batches. Experimental results show that the CGBVS-DNN outperformed the original CGBVS with a quarter million CPIs. Results of cross-validation show that the accuracy of the CGBVS-DNN reaches up to 98.2 % (σ<0.01) with 4 million CPIs., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes., Methods: Between January 2008 and December 2014, 54 consecutive patients with T3-4, N0-2, M0-1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6-8 weeks after CRT. We assessed malnutrition after completion of CRT (5-6 weeks after CRT start date) and at surgery (11-14 weeks after CRT start date), defining weight loss as ≥5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone., Results: Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1-3 patients., Conclusion: Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT., Competing Interests: Compliance with ethical standards Informed consent was obtained from all included patients and the Medical Ethics Committee of the hospital approved this study.

Background: Extramural tumor deposits (TDs) and extracapsular lymph node involvement (ECLNI) are considered to be poor prognostic factors in patients with T3-4, N0-2, M0 colorectal cancer (CRC). Although TDs are known to have multiple origins and pleomorphic features, the prognostic significances of the different type of TDs have not yet been established., Methods: We performed a retrospective review of 385 consecutive patients with T3-4, N0-2, M0 CRC who received curative resection at our institution between 2006 and 2012. We classified the TDs into two groups: invasive-type TD (iTD), which is characterized by the presence of lymphatic invasion, vascular invasion, perineural invasion, or undefined cancer cell clusters and nodular-type TD (nTD), which is characterized by a smooth or irregular-shaped tumor nodule other than an iTD. ECLNI was defined as invasion of cancer cells into capsular collagen tissues or adipose tissues beyond the capsular collagen. Multivariate analyses were used to assess the prognostic significance of iTD, ND, and ECLNI for relapse-free survival (RFS), disease-specific survival (DSS), and sites of recurrence., Results: In patients without lymph node (LN) metastasis, the incidences of iTD and nTD were both in the range of 2-3 %. Conversely, in patients with LN metastasis, the incidences of iTD, nTD, and ECLNI were 31, 22, and 34 %, respectively. iTD, nTD, and ECLNI were all significant independent adverse factors for RFS in rectal cancer, and were all associated with pT, pN, and LN ratio. iTD was a significant independent adverse prognostic factor for DSS in rectal cancer, metastasis to the liver in colorectal cancer, and distant LN metastasis in colon cancer. ECLNI was a significant independent prognostic factor for RFS in colon cancer., Conclusions: Classifying TDs and assessing ECLNI may help establish significant prognostic factors for patients with T3-4, N0-2, M0 CRC.

An 85-year-old woman with rectal carcinoma was referred to our hospital for surgical treatment. She had a history of constipation treated with oral magnesium oxide. She received 34 g of magnesium citrate (Magcolol P(®)) orally for 2 days as a mechanical bowel preparation prior to the operation. Just before the operation, she suddenly developed nausea, vomiting, and cyanosis and went into cardiac arrest. Despite support by mechanical ventilation, dopamine, dobutamine, and norepinephrine, she exhibited repeated bradycardia that was nearly fatal and required temporary pacing. The following day, her laboratory tests revealed marked hypermagnesemia (14.3 mg/dL). After a hemodialysis session, she recovered dramatically and all vasopressors were withdrawn. We conclude that preoperative mechanical bowel preparation with magnesium-containing cathartics can cause fatal hypermagnesemia in elderly patients even if their renal function is normal.

Objective: In order to identify the factors that influence the swallowing function in patients who develop Wallenberg syndrome (WS) following lateral medullary infarction (LMI), we examined various patient characteristics, including the passage pattern abnormality (PPA) of a bolus through the upper esophageal sphincter (UES)., Methods: Fifty-four pure LMI patients with dysphagia participated in this study. PPA, defined as the failure of bolus passage through the UES corresponding to the intact side of the medulla, was identified during videofluorographic swallowing evaluations of each patient. On brain magnetic resonance imaging, the subjects' lesions were classified vertically into three levels and horizontally into seven levels in relation to the involvement of the ambiguous and/or solitary nuclei. Logistic regression analyses were performed for age, sex, PPA and the vertical and horizontal sites of the lesions., Results: In terms of severity, 15 subjects were categorized as having mild dysphagia, 26 subjects were categorized as having moderate dysphagia and 13 were categorized as having severe dysphagia. Subjects with cephalic lesions, greater vertical spread of the lesion and PPA were more likely to have severe dysphagia. PPA and a greater vertical spread of the lesion were related to the severity of the functional outcome (p<0.01). The horizontal extent of the lesion was not strongly related to the prognosis., Conclusion: The presence of PPA in LMI patients is suggestive of abnormalities in the swallowing pattern and, in turn, damage to the medullary central pattern generator. The presence of PPA and a greater vertical spread of the lesion can be useful predictors of severe dysphagia.

The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23-71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3-25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.

Background: Colorectal metastasis of lobular carcinoma of the breast is a diagnostic challenge. It may macroscopically simulate primary colon cancer or inflammatory bowel disease. In some cases, the interval between the primary breast cancer and metastatic colorectal lesions is so long that the critical records for diagnosis including history might be lost or missed., Case Presentation: Reported herein is a case of metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer developed in a 62-year-old Japanese woman. The case initially presented as a circumferential rectal lesion, and information on the patient's history of breast cancer was not noted. As the result of endoscopic biopsy, diagnosis of poorly differentiated rectal adenocarcinoma was made. The lesion was surgically resected after chemo-radiotherapy. Histopathological examination of the resected specimen with hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical analysis revealed an immunophenotype consistent with lobular carcinoma of the breast. Because further review of the patient's history revealed an occurrence of 'poorly differentiated adenocarcinoma of the breast', which she had experienced 24 years earlier, the final diagnosis of the lesion was made as rectal metastasis from lobular breast carcinoma., Conclusions: Poorly differentiated adenocarcinoma of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer of the colorectum is also rarer than that of the stomach. A lesson from the present case is that before we conclude a linitis plastica-type cancer of poorly differentiated type as a primary colorectal cancer, it is critical to exclude a possibility of metastatic colorectal cancer.

The base excision repair gene MUTYH encodes glycosylase which removes adenine residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic germline mutations of the MUTYH gene are known to cause multiple colorectal adenomas including polyposis and cancer, mostly due to G:C➝T:A transversions in proto-oncogenes or tumor suppressor genes. The risk of colorectal cancer (CRC) in monoallelic mutation carriers of MUTYH is estimated to be higher in comparison with non-carriers. To investigate the possible role in sporadic CRC, we examined alterations of the MUTYH gene including somatic mutations and allelic loss in 101 cases of sporadic CRC, together with the KRAS mutation in some cases. MUTYH mutations in cancer DNA were detected in 3 cases, while mutations were also found in DNA samples from normal tissues, indicating that all were germline mutations. Allelic loss at the MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS mutations were found in 33 of the 101 (32.7%) samples. There was no significant difference in the rate of G:C➝T:A transversion in KRAS between cases with allelic loss (1 of 10, 10.0%) and without allelic loss (9 of 41, 22.0%). Investigation of quantitative allelic imbalance at SNP rs3219489 of MUTYH showed that CRC cases with C allele dominance (minor type corresponding to His) were more frequently detected with G:C➝T:A transversions than in those with G allele dominance (major type corresponding to Gln). In conclusion, somatic alterations of MUTYH in sporadic CRC were rare, similar to other DNA repair genes. However, it is possible that unknown mutations of regions not analyzed in this study and epigenetic changes of the promoter region of MUTYH may contribute to the disease.

Background: Small deep brain infarcts are often caused by two different vascular pathologies: 1. atheromatous occlusion at the orifice of large caliber penetrating arteries termed branch atheromatous disease (BAD) and 2. lipohyalinotic degenerative changes termed lipohyalinotic degeneration (LD). We herein analyze and describe the characteristics of these 2 different pathologies., Methods: We studied 394 patients with penetrating artery territory infarcts in the territories of the lenticulostriate arteries and anterior pontine arteries. Radiologically defined BAD of the lenticulostriate arteries was defined as infarcts with size more than 10mm in diameter on axial slice and visible for 3 or more axial slices, and that of the anterior pontine arteries was defined as unilateral infarcts extending to the basal surface of the pons. Within each of the 2 territory groups, differences between BAD and LD were compared., Results: Ninety five patients in the lenticulostriate arteries group (36.1%) and 78 patients in anterior pontine arteries group (59.5%) were classified as BAD. Initial NIHSS, incidence of progressive motor deficits and poor functional outcome were significantly higher and incidence of concomitant silent lacunar infarcts tended to be lower in BAD than LD. In logistic regression analysis, BAD compared with LD was independently associated with PMD, in lenticulostriate arteries group (OR: 4.21, p=0.0001) and in anterior pontine arteries group (OR: 5.32, p=0.0018)., Conclusions: Radiologically defined BAD and LD had different characteristics. BAD was significantly associated with progressive motor deficits and considered as a major vascular mechanism of progressive motor deficits in penetrating artery infarcts., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Progressive motor deficits (PMD) are common in cerebral penetrating artery disease (PAD) during the acute stage and leads to severe disability. Reliable predictors and stroke mechanism for PMD in PAD have been yet to be elucidated. Moreover, difference of predictors between topographically classified PAD has not ever been systematically studied., Methods: Three hundred ninety two consecutive patients with acute PAD (<20 mm) who showed lacunar motor syndrome and admitted within 24 h after onset were selected for this study. Patients were divided into 2 groups whose infarcts were topographically located within the territories of lenticulostriate arteries (LSA), and anterior pontine arteries (APA). Within each of the 2 groups, factors associated with PMD were analyzed., Results: Progressive motor deficits were found in 55 patients (21.0%) in LSA group and 38 patients (29.0%) in APA group. In multivariate analysis, female sex and severity of motor deficit on admission (NIHSS 5 or more) were common independent predictors for PMD in both groups. The specific predictors were single infarcts without concomitant silent lacunar infarcts and preceding TIAs in LSA group and diabetes mellitus in APA group., Conclusions: Predictive factors for PMD were different in the 2 different territory groups. Diabetes mellitus was particularly associated with PMD in APA group.

We evaluated the effectiveness of bakumijiogan (BJG), an herbal formula in traditional Chinese medicine used to treat atopic dermatitis (AD), using a NC/Jic mouse model of AD. AD symptoms were induced by repeated injections of Dermatophagoides farinae antigen (Df-antigen) into the ear auricle at 2- to 3-d intervals for 16 d. Ear thickness dramatically increased up to 16 d after the first injection of Df-antigen. Daily oral administration of BJG from 7 d before to 16 d after the first injection significantly reduced ear swelling. Serum concentrations of total immunoglobulin (Ig)E and Df-antigen-specific IgG1 were augmented when assayed 17 d after the first injection of Df-antigen, and these increases were slightly suppressed by BJG administration. Serum interferon (IFN)-gamma and lesional IFN-gamma mRNA levels were significantly higher, whereas lesional IL-1alpha and tumor necrosis factor-alpha mRNA levels were lower in BJG-treated mice than those in control mice. These results suggest that BJG suppressed AD-like symptoms by correcting the Th1/Th2 imbalance skewed toward Th2. Evaluation of herbal constituents in BJG revealed that the combination of two herbal ingredients, ophiopogon tuber and schisandra fruit, mainly contributed to the effects of BJG.

A saponin-enriched fraction prepared from the MeOH extract of the roots of Clematis chinensis showed cytotoxic activity against HL-60 promyelocytic leukemia cells, from which five new triterpene saponins based on oleanolic acid, along with three known saponins, were isolated. The structures of the new saponins were determined on the basis of spectroscopic analysis, including extensive 1D and 2D NMR data and hydrolysis followed by chromatographic and spectroscopic analysis. Among the isolated saponins, monodesmosidic saponins exhibited cytotoxic activities against cultured tumor cells.

Objectives: This study aimed to establish a reliable method for detecting the threshold for perception of force applied to tooth and to report the basic properties of force threshold in the normal dentition subjects., Background: The perception of mechanical stimulation exerted to tooth is formed by input from periodontal ligament mechanoreceptors and intradental mechanoreceptors. Periodontal ligament mechanoreceptors respond to a wide range speed of stimulus, whereas intradental mechanoreceptors are activated only by a rapid stimulation. Reliable properties of perception have not been reported because of the difficulties to regulate velocity and degree of the stimulus., Methods: Eighteen healthy subjects were observed in this study (mean age: 27.2 +/- 5.7 years). A loading device to generate slow speed loading was fabricated and measured as follows: (i) the fluctuation of the force threshold within a day, (ii) day-to-day fluctuation, (iii) changes in the force threshold by a transient mechanical loading., Results: In the normal dentition, it was observed that the fluctuation within a day and day to day of the pressure sense showed no significant differences; however, a transient mechanical loading caused the sensitivity of the periodontal ligament to decrease significantly., Conclusions: The device examining the force threshold resulted from periodontal ligament mechanoreceptors was useful in evaluating the sensitivity of the periodontal ligament.

A 44 year old right handed woman complained of difficulty in moving. She and her relatives had skin telangiectasia or recurrent epistaxis. On neurological examination, she had a mask-like facies and bradykinesia in both extremities. Laboratory examinations showed iron deficiency anaemia and mild liver dysfunction with raised serum manganese. On T1 weighted cranial magnetic resonance imaging there were hyperintense areas in the globus pallidus bilaterally, suggesting manganese deposition. Abdominal angiography confirmed multiple portal-systemic shunts in the liver, and a needle biopsy of the liver showed diffuse dilatation of the sinusoids with fatty change. Levodopa did not improve the bradykinesia. This appears to be a case of hereditary haemorrhagic telangiectasia with manganese induced parkinsonism, which may be a new type of neurological disorder in such patients.

Further phytochemical analysis aimed at the triterpene saponin constituents of the roots of Pulsatilla chinensis has resulted in the isolation of four new bisdesmosidic triterpene saponins whose aglycons are based on the lupane skeleton (1-4), together with three known saponins (5-7). The structures of the new compounds were determined by spectroscopic analysis and acid-catalyzed hydrolysis.