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Objective: Platinum-free interval (PFI) is the period from the end of platinum-based chemotherapy to the date of recurrence. If the PFI is > 6 months, a platinum-based chemotherapy rechallenge is considered; however, its efficacy after poly adenosine 5'-diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy is unknown. This study aimed to examine the efficacy of a platinum-based chemotherapy rechallenge after PARP inhibitor therapy., Methods: We retrospectively evaluated patients with ovarian cancer with a PFI≥6 months with PARP inhibitor maintenance therapy, receiving platinum-based chemotherapy. Duration of PARP inhibitor therapy, best response to subsequent platinum chemotherapy rechallenge, and clinical characteristics were collected from medical records. Tumor response was assessed according to RECIST 1.1. Correlations were calculated using Spearman's correlation coefficients., Results: Among the 10 included patients, seven (70 %) received PARP inhibitors after primary chemotherapy, and three (30 %) received chemotherapy for platinum-sensitive relapse. One and five patients harbored a germline BRCA1 and BRCA wild-type mutations, respectively, and two had homologous recombination proficiency. The median PFI was 303.5 (182-602) days, and PARP inhibitor therapy duration was 249 (147-570) days. Platinum chemotherapy rechallenge efficacy was complete and partial response and stable disease in one (10 %), six (60 %), and three (30 %) patients, respectively. The longer the duration of PARP inhibitor treatment, better the response to platinum agents (Spearman correlation coefficient 0.284, p = 0.0288)., Conclusion: Platinum-based chemotherapy rechallenge is reasonable for patients with platinum-sensitive disease, using the traditional PFI cutoff of 6 months, even when the PFI is obtained with a maintenance PARP inhibitor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: The objective of this study was to verify that spine surgery for late-stage elderly (LSE) (age 65-74 years) is as safe as that for early-stage elderly (ESE) (age 65-74 years)., Methods: This retrospective multicenter study included elderly patients aged ≥65 years who underwent spine surgery between 2018 and 2021. The medical information for individual patients was obtained from medical records. Activities of daily living (ADL) were estimated using a 5-grade scale based on the Eastern Cooperative Oncology Group performance status. Good outcome was defined as ADL grade 0 or 1 at discharge; poor outcome was defined as ADL grade 2 to 4 at discharge. The postoperative complications were listed with reference to the Common Terminology Criteria for Adverse Events v5.0., Results: There were 311 patients in the ESE group and 395 patients in the LSE group. Reoperation during hospitalization was significantly higher in the LSE group (4.6%) than in the ESE group (1.6%). The total number of days of hospitalization was significantly longer in the LSE group than in the ESE group. However, there was no significant difference in the postoperative complications or ADL at discharge between the 2 groups. In the statistical analysis, preoperative American Society of Anesthesiologists physical status class 3-6, underlying heart or renal disease, and cervical or thoracic spine level of surgical procedures were significantly associated with poor ADL outcomes at discharge., Conclusions: Spine surgery even for LSE can be safely done, if perioperative risk factors are appropriately managed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Lumbar traction is a treatment method traditionally used for chronic low back pain (CLBP) in many countries. However, its clinical effectiveness has not been proven in medical practice. The purpose is to conduct a multi-center, crossover, randomized controlled trial (RCT) to prove the efficacy and safety of traction on CLBP patients, using equipment capable of precise traction force control and of reproducibility of the condition based on the previous biomechanical and pre-clinical studies., Methods: Ninety-five patients with non-specific CLBP from 28 clinics and hospitals were randomly assigned to either the intermittent traction with vibration (ITV) first group (A: sequence ITV to ITO) or the intermittent traction only (ITO) first group (B: sequence ITO to ITV); the former was treated with repeated traction and vibration force added to preload. All patients were followed up weekly for 2 periods after study-initiation. The primary outcome measures were disability level including pain and quality of life (based on Japan Low back pain Evaluation Questionnaire; JLEQ), and JLEQ was measured repeatedly. Statistical analysis was performed using linear mixed model., Results: Comparing to pre-traction data, both traction modes significant improvement except the first intervention of ITO treatment. The differences in JLEQ scores over time showed significant improvements in the treatment to which vibrational force was added in contrast to the conventional traction treatment; Mean difference was significant to compare ITV treatment and ITO treatment (-1.75 (p = 0.001), 95% CI; -2.69 to -0.80). However, neither difference between the two sequences (p = 0.884) nor carryover effect (p = 0.527) was observed., Conclusions: Altogether, the results indicate that lumbar traction was able to improve the pain and functional status immediately in patients with CLBP. This study contributes to add some evidence of the efficacy of lumbar traction., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest. The device providers had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The use of plasters is a well-accepted treatment with high adherence. However, the characteristics such as its cool feeling or extensibility favored by elderly have a possibility to contribute to clinical utility. The purpose is to examine the effect of anti-inflammatory drug plasters for knee osteoarthritis and the clinical preference of the patients for using plasters. We conducted a crossover, double-blind, randomized controlled trial (RCT) recruited 168 patients with knee osteoarthritis., Methods: We included a "run-in-period" to evaluate the patients' preference among A (first-generation; methyl salicylate), B (second-generation; indomethacin), and N (base substrate for B) before the crossover sequence of two treatment periods with A and B plasters; four arms (N-A-B, A-A-B, N-B-A, and B-B-A) were made to compare the assessment of A, B, and N plasters. We used two measures: The Japanese Knee Osteoarthritis Measure (JKOM), for clinical functions, and the usability questionnaire to evaluate the clinical value of plasters., Results: At baseline, there were no significant differences in characteristics. The subjects in groups A and B showed improved overall JKOM scores at the end of each intervention. Comparison of the change of the mean difference showed that A and B were statistically significant improvement over N (-2.40, (95%CI = -3.58 to -1.21), -2.52, (-3.65 to -1.40)) but no significant difference between A and B - 0.13, (-1.14 to 0.89)). In network analysis for usability, twelve items were independent of JKOM's network structure and consisted of two domains. The analysis of usability showed that N and B were preferred over A significantly., Conclusion: Both the first- and second-generation plasters were statistically superior to the base only, but no significant difference between two generations. The patient is surely aware of the effect of the drug itself, but the two feelings are important in the preference., Competing Interests: Declaration of Competing Interest All authors declare that they have no competing interests. (Please see COI Disclosure Form)., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Current guidelines recommend early termination of triple therapy and the use of direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) patients who undergo percutaneous coronary intervention (PCI), due to safety concerns. However, to date, real-world medication usage and safety outcomes (specifically bleeding) in NVAF patients with stent implantation have not been well assessed., Methods: This was a retrospective, observational, medical database cohort study in Japanese ischemic heart disease (IHD) patients with NVAF who underwent PCI between 2012 and 2017. The primary outcome was clinically relevant bleeding; secondary outcomes included individual bleeding events. A multivariate analysis was conducted to identify risk factors affecting the occurrence of clinically relevant bleeding events., Results: The analysis population comprised 5695 patients [3530 received DOACs and 2165 received vitamin K antagonists (VKAs)]. The incidence of primary outcome events (clinically relevant bleeding/100 patient-years) was 6.05 in the DOAC group and 8.42 in the VKA group, resulting in a nonsignificant 21% lower risk in the DOAC group. The DOAC group also had a nonsignificant 24%, 24%, and 34% lower risk of bleeding requiring transfusion, intracranial bleeding, and lower gastrointestinal bleeding, respectively, compared with the VKA group. A multivariate analysis of the primary outcome showed a significantly higher risk of bleeding among older patients and those with lower body weight and abnormal renal function., Conclusions: In this retrospective real-world evaluation of IHD patients with NVAF and PCI, DOAC-treated patients had a lower risk of developing clinically relevant bleeding compared with the VKA group., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs., Methods: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions., Results: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations., Conclusions: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tearing maturates rapidly after birth, and external environmental challenges play a key role in promoting lacrimal functional maturation. However, little is known about the facilitative factors underlying this developmental process or the potential of application of these factors to treat hypofunction of the lacrimal gland. In this study, eye opening and the subsequent ocular surface sensory experience, which is thought to be involved in postnatal maturation of lacrimal function, were investigated. Our results demonstrated that eye opening after birth is essential for the maturation of neonatal tearing. The maturation process of lacrimal function is dependent on the ocular surface sensory experience via transient receptor potential cation channel subfamily member 1 after birth. This study provides, for the first time, important evidence of the sensory experience of the ocular surface in relation to the maturation of functional tear secretion during the postnatal period., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial-mesenchymal transition in the atrium of patients with atrial fibrillation., Methods and Results: The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery (n=38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial-mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31 + cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen., Conclusions: In this study, we showed that the endothelial-mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high-grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P < 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P < 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P < 0.001, respectively), findings reproduced in 89 validation cases (P < 0.05, respectively). The CLOVAR&#95;MES&#95;UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane-containing regimens improved survival of cases with high MES&#95;UP scores compared with nontaxane regimens (P < 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Duodenal obstruction caused by aneurysmal dilatation of the abdominal aorta is a rare clinical entity that is traditionally treated by open aneurysm repair, aneurysmorrhaphy, and duodenal release. We present here the case of aortoduodenal syndrome treated by endovascular therapy., Case Report: A 73-year-old man diagnosed simultaneously with sigmoidovesical fistula and an abdominal aortic aneurysm (AAA) underwent resection of the sigmoid colon followed by colostomy. On postoperative day 34, the patient experienced nausea and vomiting. Computed tomography revealed the AAA causing duodenal obstruction by direct compression. We chose endovascular therapy for treating the AAA rather than graft replacement because of the risk of infection by the colostomy orifice. Postoperatively, the patient reacquired the ability to eat. However, postoperative computed tomography revealed that the diameter of the AAA had not changed., Conclusions: We considered that the decreased intra-aneurysmal pressure caused a release of duodenal obstruction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

While the progress of chemotherapy and molecular targeted therapy has improved the outcome of colorectal cancer patients, the mortality of colon cancer remains high, indicating the need to develop novel therapeutic targets for improving the outcome of colon cancer. Heterogeneous ribonucleoprotein A1 (hnRNP A1) is highly expressed in colorectal cancer and its expression correlates with malignant transformation. In this study, we performed a microarray analysis with the RNA immunoprecipitation (RNA-IP) method and identified hnRNP A1-interacting miRs, including miR-26a and -584, in a colorectal cancer cell line, SW620. A SRB assay revealed the tumor suppressive effect of miR-26a and -584, and the tumor suppressive effect of these miRs was diminished by the downregulation of hnRNP A1. The combined method of a transcriptome analysis and RNA-IP revealed hnRNP A1-interacting mRNAs, including cyclin dependent kinase 6 (CDK6). A Western blot analysis revealed the downregulation of CDK6 in miR-26a and -584 overexpression cells, as well as hnRNP A1 knockdown cells. The binding assay indicated that the binding of hnRNP A1-CDK6 mRNA was reduced by transfection of miR-26a and -584. The expression of cleaved caspase-3 was induced in miR-26a and -584 overexpression cells. These data indicate that miR-26a and -584 inhibit the binding of hnRNP A1-CDK6 mRNA and induce colorectal cancer cell apoptosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Probiotics exhibit beneficial functions for host homeostasis maintenance. We herein investigated the mechanism by which Lactobacillus brevis-derived poly P exhibited a beneficial function. Immunostaining indicated that poly P was captured in the plasma membrane via integrin β1 in Caco2/bbe cells. The uptake of poly P was reduced by the inhibition of integrin β1 as well as caveolin-1, a major component of lipid rafts. The function of poly P, including the induction of HSP27 and enhancement of the intestinal barrier function, was suppressed by the inhibition of caveolin-1, illustrating that the function of poly P was mediated by the endocytic pathway. High-throughput sequencing revealed that poly P induced tumor necrosis factor alpha-induced protein 3, which contributes to cytoprotection, including upregulation of the intestinal barrier function. The present study demonstrates a novel host-probiotic interaction through the uptake of bacterial substance into host cells, which is distinct from pattern recognition receptor pathways., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis. To clarify the mechanism responsible for the observed effects, Caco-2/brush border epithelial (BBE) and naive T helper lymphocyte (THP)-1 cells were treated with lipopolysaccharide (LPS) to induce inflammation. Non-cancer human colon fibroblast (CCD-18) cells were treated with transforming growth factor beta 1 (TGF-β1) to induce fibrosis. The expression levels of fibrosis- and inflammation-associated molecules were evaluated by both a Western blotting analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). The histologic inflammation and fibrosis were significantly improved in the group administered poly P in both the DSS and TNBS colitis models. The levels of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly decreased by poly P treatment. The expression levels of TGF-β1 and collagens in the colitis mice were decreased by poly P. The LPS-induced expressions of IL-1β and TGF-β1 in Caco-2/BBE cells and of TNF-α in THP-1 cells were reduced by poly P treatment. Poly P did not affect the expression of collagens and connective tissue growth factor in the CCD-18 cells. In conclusion, poly P suppresses intestinal inflammation and fibrosis by downregulating the expression of inflammation- and fibrosis-associated molecules in the intestinal epithelium. The administration of poly P is therefore a novel option to treat fibrosis because of chronic intestinal inflammation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hydrogen (H2) protects against inflammation-induced oxidative stress. Nondigestible saccharides (NDSs) enhance colonic H2 production. We examined whether colonic H2 transfers to tissues in the abdominal cavity and whether it affects expression of proinflammatory cytokines. In Expts. 1 and 2, rats were fed diets containing fructooligosaccharides [FOSs; 25 (Expt. 1) and 50 g/kg (Expts. 1 and 2)] for 7 and 14 d, respectively. The no-FOS diet was used as the control diet. At the end of the experiment, H2 excretion and the portal H2 concentration were significantly greater in the FOS group than in the control group. In the FOS group, the arterial H2 concentration was no more than 1.5% of the portal H2 concentration (P = 0.03). The H2 concentration in abdominal cavity tissues, especially adipose tissue, in the FOS group was 5.6- to 43-fold of that in the control group (P < 0.05). The H2 content in the abdominal cavity in the FOS group was 11-fold of that in the control group (P < 0.05). In Expt. 3, rats were fed a high-fat diet containing FOS and inulin (50 g/kg) for 28 d. The area under the curve for H2 excretion between 0 and 28 d and portal and adipose H2 concentrations were significantly higher in the FOS and inulin groups than in the high-fat control group. Adipose mRNA abundance of nuclear factor kappa-light-chain-enhancer of activated B cells 1 was lower in the FOS group than in the control group (P = 0.02) and those of interleukin-6 and chemokine (C-C motif) ligand 2 tended to be lower (P < 0.11). Colonic H2 generated from NDS diffuses to the abdominal cavity before transferring to abdominal tissues. Reduced cytokine expression by FOS feeding might be dependent on increased colonic H2. Colonic H2 may have important implications in the suppressive effect on metabolic syndrome via oxidative stress.

Background: A blue letter (safety advisory) for dabigatran was issued by the Japanese Ministry of Health, Labour and Welfare in August 2011. Changes in physicians' attitudes toward dabigatran use before and after the blue letter have not been previously reported., Methods and Results: Between March 2011 and July 2012, dabigatran was prescribed to 404 Japanese patients with nonvalvular atrial fibrillation at The Cardiovascular Institute (Tokyo, Japan). Patients were divided into three groups according to the first prescription date: phase I (before the blue letter, n=135); phase II (after the blue letter and before permission for longer-term prescriptions, n=112); and phase III (after permission for longer-term prescriptions, n=157). In phase II, dabigatran use tended to be avoided for patients with older age, renal dysfunction, receiving antiplatelet medication, or p-glycoprotein inhibitors. Measurement of activated partial thromboplastin time significantly increased from phase I to III. In phase III, the tendencies seen in phase II were reversed: dabigatran use in patients with older age and renal dysfunction tended to increase, but decreased or remained the same in patients receiving antiplatelet medications or p-glycoprotein inhibitors., Conclusions: We described the changes in the attitudes of attending physicians toward dabigatran prescription after the blue letter in a specialized hospital for cardiovascular care in Japan, which, we believe, involve useful information for safe use of dabigatran in a real-world clinical setting. However, a true impact or effect of the blue letter should be ascertained in a nationwide, multicenter study., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the incidence of complications of intrathecal baclofen (ITB) therapy for spasticity in Japan, where a unique training course and nationwide registration are required., Materials and Methods: An analysis of complications was performed in all patients who underwent ITB in Japan from 2005 to 2011. Prior to surgery, all the doctors involved took a one-day training course, which included hands-on training. Surgical techniques that avoided complications were emphasized., Results: A total of 406 pumps were implanted in 400 patients (277 men, 123 women) having severe spasticity. Because this study is currently in progress, among the 400 patients, 78.3% (313/400) had finished a one-year observation follow-up. There were 369 adult and 31 juvenile (under 17 years old) patients, including 12 patients under nine years old. All-cause adverse events were seen in 148 patients (37%), and 93 (23.3%) of these were regarded as severe. Catheter problems were observed in 34 (8.5%) patients: catheter migration in 25 (6.3%), breakage in 6 (1.5%), obstruction in 2 (0.5%), kinking in 1 (0.3%), and dislodgement in 1 (0.3%). Pump trouble was observed in seven (1.8%) patients: alarm abnormality in one (0.3%), memory error in one (0.3%), delayed recovery in one (0.3%), rotation in one (0.3%), malfunction in one (0.3%), and abnormal infusion rate in two (0.6%). Device-related and surgical wound infection occurred in 12 patients (3%), and nine were regarded as severe. Leakage or subcutaneous accumulation of the cerebrospinal fluid was seen in 13 patients (3.3%)., Conclusion: The requirement of taking of a training course before starting ITB seemed to reduce complications. Although there were surgery-related complications, the rate of complications in Japan appeared to be lower than those reported in larger series of ITB. However, whether the reported rates can be primarily ascribed to a mandatory training course requires further investigations., (© 2012 International Neuromodulation Society.)

The purpose of this study was to detect the characteristics of center of pressure (COP) movement during tiptoe standing (TS) compared to quiet standing (QS). Eight healthy subjects were asked to perform QS and TS on a force platform. During standing, surface electromyograms (EMGs) were recorded from the soleus (SOL), flexor hallucis brevis (FHB), medial gastrocnemius (MG), lateral gastrocnemius (LG), and tibialis anterior (TA) muscles. The path length and rectangular area of the COP trajectory were significantly larger during TS than during QS. In contrast, irrespective of standing condition, the scaling coefficients in the short and long regions were above and below 0.5, respectively. The coherence spectrum between the COP and EMG from the SOL and FHB muscles was statistically significant during TS at frequencies up to 17 Hz, while that for the QS was only significant below 1 Hz. In conclusion, the control of COP movement during TS was similar to that during QS despite large COP fluctuations during TS. Our results suggest that unstable posture during TS is compensated for by the activities of the SOL and FHB muscles, which enhance postural control., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We hypothesized that movement fluctuations in the index finger reflect the integrated result of the coordination of multiple muscles because index finger movements are determined by the cooperation of multiple muscles spanning the metacarpophalangeal (MCP) joint. To evaluate this hypothesis, the aim of the present study was to examine the fluctuations of the index finger in abduction-adduction and extension-flexion directions during a position-holding task using two laser displacement sensors. Eleven healthy men maintained their index finger position while supporting a load at 5% of the maximal voluntary contraction force. To maintain the position of the index finger, displacement of the index finger in the abduction-adduction and extension-flexion directions was measured from a distance with two laser displacement sensors that were positioned to the lateral side of and above the index finger. The index finger movements fluctuated around the target position in not only the abduction-adduction direction but also the extension-flexion direction. The path length of finger displacement and the standard deviation of finger acceleration were significantly greater in the extension-flexion direction than in the abduction-adduction direction. These results suggest that the index finger movements quantified by two laser displacement sensors reflect the coordination of multiple muscles spanning the MCP joint., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: We developed a novel method of methylation-specific PCR (MSP) using immunoprecipitation with anti-histone antibody (IP-MSP) to efficiently detect serum methylated DNA tightly bound to de-acetylated histones., Materials and Methods: The detection limit of IP-MSP for p16 methylation was determined with a standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was detected with conventional MSP or IP-MSP., Results: IP-MSP detected p16 methylation from 0.5pg/mul of the cell lysate. The sensitivity of IP-MSP for detecting serum p16 methylation in 27 patients with tumors characterized by p16 methylation was significantly higher than that with conventional method (81% versus 59%), particularly in Stage II patients (91% versus 45%). IP-MSP detected no p16 hypermethylation in sera of adenoma patients and volunteers., Conclusions: IP-MSP is thus considered to be a promising procedure to detect serum methylated DNA in colorectal cancer patients.

Each chromosome occupies its own-specific space called a 'territory' within the interphase nucleus, and the arrangement of chromosome territories (CTs) is important in epigenetic mechanisms. The molecular mechanism to determine the positioning of CTs, however, remains unknown. On the other hand, dioxin is known to be the typical environmental pollutant that affects a wide variety of biological events in many species. Here, we show that dioxin enlarges the minimum distance between chromosome 12 and chromosome 16 territories in human preadipocyte cells, and the alteration of chromosome positioning is canceled by an aryl hydrocarbon receptor (AhR) antagonist alpha-naphthoflavone. Thus, AhR may be a key molecule to regulate chromosome positioning. Our results suggest a novel effect of dioxin toxicity, and demonstrate a clue to reveal the novel molecular mechanism for the arrangement of CTs.

To identify the novel inhibitor of de novo lipogenesis in hepatocytes, we screened for inhibitory activity of triglyceride (TG) synthesis using [14C]acetate in the human hepatoma cell line, HepG2. Using this assay system we discovered the novel compound, benzofuranyl alpha-pyrone (TEI-B00422). TEI-B00422 also inhibited the incorporation of acetate into the triglyceride (TG) fraction in rat primary hepatocytes. In HepG2 cells, the incorporation of oleate into TG was unaffected. TEI-B00422 inhibited rat hepatic acetyl-CoA carboxylase (ACC), K(i)=3.3 microM, in a competitive manner with respect to acety-CoA but not fatty acid synthase and acyl-CoA transferase/diacylglycerol. Thus, these results suggest that the inhibition of TG synthesis by TEI-B00422 is based on the inhibitory action of ACC. The structure of TEI-B00422 is totally different from the known inhibitors of ACC and may be useful in the development of therapeutic agents to combat a number of metabolic disorders.

alpha-Defensin is an antimicrobial peptide which plays an important role in innate immunity. Human defensin (HD)-5 is stored in the Paneth cells of the small intestine as a pro-form and is cleaved by trypsin, which is co-secreted from the Paneth cell granules. The mature HD-5 is protected from further digestion by the proteolysis enzyme. We generated both recombinant HD-5 and proHD-5, and the reduced form of each peptide in order to determine their physiological roles of the disulfide bonds. The reduced proHD-5 attenuated the bactericidal activity and the stability against the trypsin digestion. Human defensin was protected from the enzymatic degradation by disulfide bridges. We further purified the HD-5 with a disulfide variation in the small intestine of Crohn's disease patients. The HD-5 was sensitive to the trypsin treatment. These observations evidently predict that a defensin deficiency may be caused by a disulfide disorder in the disease.

Purpose: The purpose of this study was to use near-infrared spectrometry (NIR) with chemoinformetrics to predict the change of dissolution properties in indomethacin (IMC) tablets during the manufacturing process. A comparative evaluation of the dissolution properties of the tablets was performed by the diffused reflectance (DRNIR) and transmittance (TNIR) NIR spectroscopic methods., Methods: Various kinds of IMC tablets (200 mg) were obtained from a powder (20 mg of IMC, 18 mg of microcrystalline cellulose, 160 mg of lactose, and 2 mg of magnesium stearate) under various compression pressures (60-398 MPa). Dissolution tests were performed in phosphate buffer, and the time required for 75% dissolution (T75) and mean dissolution time (MDT) were calculated. DRNIR and TNIR spectra were recorded, and the both NIR spectra used to establish a calibration model for predicting the dissolution properties by principal component regression analysis (PCR)., Results: The T75 and MDT increased as the compression pressure increased, since tablet porosity decreased with increasing pressure. Intensity of the DRNIR spectra of the compressed tablets decreased as the compression pressure increased. However, the intensity of TNIR spectra increased along with the pressure. The calibration models used to evaluate the dissolution properties of tablets were established by using PCR based on both DRNIR and TNIR spectra of the tablets. The multiple correlation coefficients of the relationship between the actual and predictive T75 by the DRNIR and TNIR methods were 0.831 and 0.962, respectively., Conclusion: It is possible to predict the dissolution properties of pharmaceutical preparations using both DRNIR and TNIR chemoinformetric methods. The TNIR method was more accurate for predictions of the dissolution behavior of tablets than the DRNIR method., ((c) 2007 Wiley-Liss, Inc.)

We tested whether increased mucin secretion due to ingestion of insoluble dietary fiber (IDF) affects small intestinal nutrient absorption in rats. Polystyrene foam (PSF) with a true expansion ratio of 54.9 was used as a model for IDF with high bulk-forming properties. In Expt. 1, rats were fed a control diet or diet containing 50 g PSF/kg for 1, 3, 5, or 7 d. Small intestinal mucin fractions were isolated, and O-linked oligosaccharide chains were measured. The luminal mucin content reached a maximum within 5 d after PSF ingestion. In Expt. 2, rats were fed a control diet or diet containing 50 g PSF/kg for 7 d, and then all rats were switched to the control diet for 1, 3, or 5 d. The increased capacity for luminal mucin secretion disappeared within 5 d after ceasing PSF ingestion. In Expt. 3, rats were fed a control diet or diet containing 70 g PSF/kg for 7 d. Glucose (1g/kg) was administered orally after 12 h of food deprivation. The blood glucose concentrations did not differ between the groups. In Expt. 4, rats were fed a control diet or diet containing 90 g PSF/kg for 14 d. At d 7, portal cannulae were installed. A mixed solution of glucose (1g/kg) and ovalbumin (OVA, 250 mg/kg) was orally administered after 12 h of food deprivation, and responses of portal glucose and OVA concentrations were monitored for 120 min. Although luminal mucin contents were almost doubled in the 9% PSF group compared with the control group, neither portal glucose nor OVA concentration differed at any time point. The results suggest that the short-term ingestion of IDF significantly increases the luminal mucin content, but that this does not disturb nutrient absorption.

The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.

The aim of this study was to clarify the effect of dietary indigestible components on small intestinal mucin secretion. We prepared polystyrene foam (PSF) with different expansion ratios (PSF-30, -60 and -90) in which powders had different settling volumes in water (SV). Rats were fed a purified diet containing 0, 10, 30, or 90 g of PSF-60/kg for 10 d. After 8 h of food deprivation, rats were refed 3 g of their respective diets within 90 min. Small intestinal mucin fractions were prepared, and periodic acid/Schiff-reactive substances and O-linked oligosaccharide chains were determined as mucin markers. Feeding of PSF-60 increased the small intestinal mucin secretion dose dependently (control vs. 30 or 60 g of PSF-60/kg, P < 0.05). When rats were fed either purified diet or diets containing PSF-30, 60, or 90 at 10 g/kg for 7 d, small intestinal mucins were greatly affected by the SV of the respective PSF tested. Rats fed the diet containing PSF-90 with the highest SV had the highest amount of mucins (vs. control, P < 0.05). In some natural dietary fibers, the small intestinal mucins and SV were correlated (r = 0.967, P = 0.002). Finally, rats were fed a purified diet or that diet containing 50 g of PSF-60/kg for 7 d. Then, each dietary group was further divided into 2 groups. After 8 h of food deprivation, rats were refed 3 g of purified or PSF diet. Greater mucins in the small intestine were manifest only in rats previously fed the PSF diet whether they were refed purified or PSF diet (control vs. PSF, P < 0.05). These results suggest that the small intestinal mucins are secreted in proportion to the SV of dietary indigestible components, and chronic ingestion of indigestible components is required for the appearance of enhanced mucin secretion.

A 35-year-old diabetic man presented with a left ventricular aneurysm very close to the mitral valve annulus. He had been conservatively treated for suppurative pericarditis and sepsis due to Staphylococcus aureus during the previous 3 weeks. The left ventricular aneurysm rapidly enlarged (6 cm in diameter) and the patient underwent emergent surgery. Cardiopulmonary bypass and cardioplegic arrest were induced, and the left ventricular aneurysm orifice was closed with a double layer of autologous pericardium. Mitral valve function was not impaired. He has been doing well for 4 years. Surgery is indicated as soon as possible after the diagnosis of infective left ventricular aneurysm.

Background: Culture morphology of Trichophyton (T.) tonsurans, an emerging pathogen of dermatophytosis in Japan, varies widely and species level identification is sometimes very difficult. Reliable molecular markers are expected to be introduced for their identification., Objective: The present study was conducted to evaluate the efficacy of restriction fragment length polymorphism (RFLP) analysis of PCR amplified ribosomal (r) DNA including internal transcribed spacers (ITS), as an identification tool., Methods: Total cellular DNA was extracted from 26 Japanese isolates of T. tonsurans, along with several taxa of the members in the T. mentagrophytes complex, T. rubrum, T. violaceum and Epidermophyton floccosum, using a mini-preparation method. PCR amplicons were digested with restriction enzymes Mva I or Hinf I, then electrophoresed on 5% polyacrylamide gel., Results: The banding profiles were observed about 8 h from initiating DNA extraction. Intraspecies polymorphism was not detected among T. tonsurans isolates, and their profiles obtained using Mva I digestion were clearly different from those of the other dermatophyte species. The restriction profiles evaluated from nucleotide sequence of the regions by a computer analysis were compatible with the electrophoresed profiles on gel., Conclusion: PCR-RFLP analysis is a rapid and reliable tool for the identification of T. tonsurans.

Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal genetic diseases that predispose to cancer and are associated with genomic instability. To characterize the genomic instability of WS and BS, we analyzed and compared the cytogenetics of B-lymphoblastoid cell lines (LCLs) from WS and BS patients and healthy donors. Although, similar spontaneous frequencies of micronuclei (MN) and sister chromatid exchanges (SCE) were observed in LCLs from WS patients and healthy donors, they were much higher in BS-LCLs. We also examined the cells' cytotoxic and cytogenetic formation (MN) response to camptothecin (CAM), etoposide (ETO), 4-nitroquinoline 1-oxide (4NQO), and mitomycin C (MMC). Compared to healthy donor LCLs, BS-LCLs but not WS-LCLs tended to be resistant to cytotoxicity and sensitive to MN induction by 4NQO and MMC. Spectrum karyotyping analysis revealed that most WS- and BS-LCLs generated "variegated translocation mosaicism" at high frequencies during cell culture. These findings support the idea that the basis of genomic instability in WS is different from that in BS.

In the nucleus of animal and plant cells individual chromosomes maintain a compartmentalized structure. Chromosome territories (CTs), as these structures were named by Theodor Boveri, are essential components of the higher-order chromatin architecture. Recent studies in mammals and non-mammalian vertebrates indicate that the radial position of a given CT (or segments thereof) is correlated with its size, its gene-density and its replication timing. As a representative case, chicken cell nuclei show highly consistent radial chromatin arrangements: gene-rich, early replicating microchromosomes are clustered within the nuclear interior, while gene-poor, later replicating macrochromosomes are preferentially located at the nuclear periphery. In humans, chromosomes 18 and 19 (HSA18 and 19) territories that are of similar size show a distinctly different position in the cell nuclei of lymphocytes and lymphoblastoid cells: the gene-rich and early replicating HSA19 CTs are typically found close to the nuclear center, while the gene-poor and later replicating HSA18 CTs are preferentially located at the nuclear periphery. Recent comparative maps between human and chicken chromosomes revealed that the chicken macrochromosomes 2 and Z contain the genes homologous to HSA18, while the genes on HSA19 are located onto the chicken microchromosomes. These data lend tentative support to the hypothesis that differences in the radial nuclear positions of gene-rich, early replicating and gene-poor, later replicating chromatin have been evolutionarily conserved during a period of more than 300 million years irrespective of the evolution of highly divergent karyotypes between humans and chicken.

Skull base surgery was performed on 18 patients with anterior skull base injuries. The operative technique consisted of opening the operative field in the anterior skull base via a coronal incision and a frontal craniotomy, debridement of the anterior skull base including the injured dura mater, performing drainage from the anterior skull base to the nasal cavity by ethmoidectomy, and reconstructing the resulting dural and anterior skull base defect using bilateral temporal musculo-pericranial flaps and a bone graft. Seventeen of the 18 patients recovered without any complications, although epidural abscesses in the anterior skull base had been present in four patients at the time of the operation. Only one patient developed an epidural abscess in the anterior skull base after the operation. None of the patients developed any other complications including meningitis, recurrent liquorrhoea or cerebral herniation. Satisfactory aesthetic results were achieved in 16 of the 18 patients. In one patient, uneven deformity of the forehead, which was caused by the partial sequestration of the frontal bone due to postoperative infection, was observed. In another patient, a depressed deformity of the forehead, which was caused by the partial loss of the frontalis muscle following the use of the frontal musculo-pericranial flap instead of a temporal musculo-pericranial flap, was observed. Anterior skull base reconstruction using bilateral temporal musculo-pericranial flaps provides excellent results in terms of patient recovery and aesthetics.

This paper reports the use of cranioplasty using segments of split lateral skull plate to correct large skull defects (larger than 8 x 8 cm). The subjects consisted of 10 patients with head trauma who had undergone decompression surgery, and two patients who had undergone tumour resection. Bone grafts were obtained by cutting approximately 2 cm wide strips from the lateral skull plate using a bone saw that was inserted from a free margin of the bone defects. By cutting strips laterally from the bone defect, the necessary amount of split lateral skull plate can be obtained without performing craniotomy. The pieces of split lateral skull plate are then fixed to the defect using wire or titanium mini-plates. At this point, the selection of bone grafts that match the curvature of the dura mater is important, so that no dead spaces are created between the dura mater and the bone grafts. Infection was not detected in any of the 12 patients, and all bone grafts took completely. One of the 12 patients suffered from a pathological fracture and bone resorption 6 months after surgery. The fracture occurred because the use of basket-shaped reconstruction plates resulted in large spaces between the plate segments, and in addition the intracranial pressure was kept low by a V-P shunt, thus rendering the patient more vulnerable to atmospheric pressure.

To clarify the relationship between the temporal component of the temporomandibular joint and facial bone structure, we measured anthropologic craniometric points and the structure of the mandibular fossa, including the eminence in 33 Japanese male dry skulls, with a three-dimensional apparatus. The length from the articular tubercle to the medial glenoid tubercle is correlated with skeletal variables such as the length of the fossae, the width of the masseter origin, and the mandibular length. Therefore it appears that the frontal dimension is related to the facial development, which is attributable to bite force. Goniometrically, the angle between the line deepest point of the fossa--the midpoint of the eminence and the Frankfort horizontal plane (middle angle)--was negatively correlated only with the ANB angle, suggesting that a steeper middle angle of the eminence is related to a retrusive maxilla or protrusive mandible.

We investigated the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the C1 and A2 regions of the medulla, the sites of the baroreflex arc, in 7 patients with multiple system atrophy (MSA), 8 with Parkinson's disease (PD), 9 with amyotrophic lateral sclerosis (ALS), and 12 age-matched normal subjects to analyze the relationship between cardiovascular dysfunction and medullary catecholaminergic neurons. Orthostatic hypotension (OH) was marked in all the MSA patients and moderate in three PD patients. Three of the five ALS patients who had been on respirators showed lability of blood pressure; paroxysmal hypertension and nocturnal hypotension without compensatory tachycardia. All the MSA patients showed extremely marked decrease of TH-immunoreactive neurons in both the C1 and A2 regions. In the patients with Parkinson's disease, numerous TH-immunoreactive neurons contained Lewy bodies that were immunostained by antibody to TH. TH-immunoreactive neurons were decreased very markedly in the A2 regions of two patients with OH, and three patients without OH showed fairly marked decreases in the C1 or A2 region. In contrast, the number of TH-immunoreactive neurons in ALS was the same as in normal subjects. In MSA and some PD patients, orthostatic hypotension may partly be due to the involvement of the medullary catecholaminergic neurons. The lability of blood pressure in ALS probably is not related to the medullary catecholaminergic neurons.

Vocal cord abductor paralysis (VCAP) is rare in Parkinson's disease (PD), while it is frequent in multiple system atrophy (MSA). Although VCAP is a life-threatening complication it has not yet been clarified whether there is any difference in the mechanism of VCAP between PD and MSA. Examining 3 autopsy-proven PD patients who developed severe VCAP requiring tracheostomy, we found the following differences in the mechanism of VCAP between MSA and PD: (1) clinical and laryngofiberscopic examination showed that VCAP in PD was not exacerbated during sleep, unlike in MSA; (2) On histological examination of the intrinsic laryngeal muscles, the posterior cricoarytenoid muscle demonstrated no abnormalities in PD, while the muscle showed characteristic neurogenic atrophy in MSA. There seemed to be two types of VCAP, namely the nonparalytic type observed in PD, and the paralytic type observed in MSA. Severe dysphagia requiring tube-feeding was common among PD patients who presented with VCAP. Although the relationship between VCAP and dysphagia is unknown, one should be aware of the possibility of fatal VCAP in PD patients with severe dysphagia.

Three cases of histologically-proven Machado-Joseph disease (MJD) (clinically, types II and III) are described with special reference to the peripheral nervous system. We systematically and quantitatively analyzed the myelinated fiber densities in various nerves of three MJD patients and compared the results with the patients' clinical features and the pathological findings for the central nervous system (CNS). The results obtained were (1) motor system: The number of intermediate gammamotoneuron fibers was decreased prominently in all three MJD patients. In the type III MJD cases, the number of large alpha-motoneuron fibers also were decreased. (2) Sensory system: it generally was less involved than the motor system at the root level; but the large fibers of the distal portion were vulnerable. (3) Oculomotor system: the number of large oculomotor fibers was decreased markedly in all three cases, but there was relative preservation of parasympathetic fibers. (4) Autonomic system: the preganglionic sympathetic fibers from the intermediate lateral nucleus generally were preserved. These results suggest that in MJD the vulnerability of the peripheral nerves reflects the degree of loss of their original neuronal cells and varies according to the clinical phenotype. The characteristic peripheral neuropathy of MJD may be the result of axonal degeneration due to perikaryal neuronal damage in the central nervous system.

A 27-year-old man with Behçet's disease presented with dyskinesia of the right hand and leg, but without paresis. MRI showed a discrete lesion in the internal segment of the left globus pallidus. SPECT (single photon emission tomography) disclosed increased perfusion in the hand and leg area of the left motor cortex and ipsilateral thalamus compared to that of the corresponding regions on the right. The dyskinesia was considered to be produced by disinhibition of the motor cortex due to loss of inhibitory inputs from the ipsilateral pallidum via the thalamus. Double transcranial magnetic stimulation revealed loss of suppression (loss of intracortical inhibition) of the left motor cortex while it showed normal suppression on the right, even though conventional techniques of magnetic stimulation failed to show any changes in excitability of the left motor cortex. We conclude that it is possible to detect changes of motor cortical excitability caused by dysfunction of some inputs from the basal ganglia by using the double cortical stimulation technique here described.

A right-handed Japanese crossed Wernicke's aphasic showed complete neologistic jargonagraphia in kanji and kana with anosognosia of his writing deficits. Prominent jargonagraphia in kanji is quite rare and has not been previously described in the literature. Marked dissociation between speaking and writing during the course suggested that his jargonagraphia might be unique to crossed aphasia. His condition was interpreted for the main part by Yokoyama, Okubo, Doseki, and Yamadori's hypothesis (1981) that free-running on of motor engrams of characters stored in the left hemisphere caused jargonagraphia in crossed aphasia. This case of jargonagraphia in kanji suggests that this hypothesis should be supplemented by the following points: (1) in kanji, not necessarily a character as a whole, but radicals or parts of radicals, function as motor units, which may be released to produce jargonagraphia in kanji; (2) free-running on of visual images as well as of kinesthetic images should be considered especially in written jargon in kanji.

Circulatory collapse and sudden death was defined retrospectively as one of the major critical problems among 23 respirator-dependent patients with amyotrophic lateral sclerosis (ALS). Six cases died from sudden cardiac arrest or anoxic encephalopathy following the circulatory collapse. In five among the six cases, sudden death or cardiac arrest occurred during sleep at night. Eight cases had had episodes of marked fluctuation of blood pressure before death, including paroxysmal elevation of blood pressure and heart rate, and successive sudden pressure fall without compensatory tachycardia. The spells of hypotension often occurred during sleep. In addition, the prospective study of diurnal variation of blood pressure, heart rate, plasma norepinephrine and plasma renin activity in nine respirator-dependent ALS patients showed continuous tachycardia and more remarkable nocturnal decrease of blood pressure compared with the control subjects. Plasma norepinephrine levels were constantly higher in the ALS patients particularly in a daytime. These indicate the continuous sympathetic hyperactivity in ALS. We discuss the cause of the circulatory collapse and sudden death in the respirator-dependent ALS patients in terms of the autonomic dysregulatory mechanism or the sympathetic hyperactivity.

Spontaneously existing and chemically induced micronuclei were isolated from mouse blood. 50 microliters of cardiac blood was diluted with PBS and centrifuged. After this, the cell pellet was subjected to hypotonic treatment, fixed with acetic acid-methanol (1:3), and the lysate was filtrated through a 2-microns polycarbonate nucleopore membrane. Isolated micronuclei were air-dried on a glass slide and subjected to fluorescence in situ hybridization (FISH) using a mouse centromeric gamma satellite probe. Approximately half of the micronuclei isolated from vehicle control mice showed centromere signal(s). In these preliminary studies, the proportion of centromere-positive micronuclei was increased by treatment with spindle poisons (colchicine and vinblastine sulfate), decreased only slightly by 1-beta-D-arabinofuranosylcytosine, and was generally unaffected by mitomycin C.

Dystrophin is a muscle cytoskeletal protein with a molecular mass (MM) of approximately 420 kDa and an isoelectric point (pI) of approximately 5.5, which is abnormal in size and/or abundance in Becker muscular dystrophy (BMD). We investigated the abnormality of dystrophin molecule in muscles biopsied from 23 BMD patients using the two-dimensional gel electrophoresis (TDGE). We found 7 protein spots which reacted specifically with the monoclonal anti-dystrophin antibody (mAb) A1C raised against N-terminal domain of the normal dystrophin. These spots were focused on the two-dimensional gel at the same position as the normal dystrophin (#1), at the position with MM approximately 480 kDa/pI approximately 5.35 (#2), the position with MM approximately 400-330 kDa/pI approximately 5.51-5.47 (#3), the position with MM approximately 300 kDa/pI approximately 5.4 (#4), the position with MM approximately 235-250 kDa/pI approximately 5.53-5.5 (#5), the position with MM approximately 165 kDa/pI approximately 6.0 (#6), and the position with MM approximately 160 kDa/pI approximately 5.75 (#7). These spots were classified into five patterns in individuals, that is, #1 alone in 3 patients, #3 alone in 1, the combination of #3 and 5 in 17, the combination of #1, 3 and 5 in 1 and the combination of #1, 2, 4, 6 and 7 in 1. The combination of #3 and 5 was observed in 17 of 23 patients (75%).(ABSTRACT TRUNCATED AT 250 WORDS)

Two cases of melorheostosis of the hand are reported. Histopathologic examination confirmed the characteristic x-ray findings and excluded other skeletal dysplasias, such as osteopoikilosis and osteopathia striata.