3-Methylglutaconic aciduria type I causes leukoencephalopathy of adult onset.
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Amino Acid Metabolism, Inborn Errors↗
Biomedical subjects
S Yamaguchi
Publications and source records attributed to S Yamaguchi.
SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress.
We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein. We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5'untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis.
Cell Line, Tumor↗
Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China.
We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.
Animals↗
Dwarfism and cytochrome P450-mediated C-6 oxidation of plant steroid hormones.
BRs (brassinosteroids) are plant steroid hormones that are essential for normal plant development. The dramatic dwarfism exhibited by mutants in the CYP (cytochrome P450) enzymes involved in BR biosynthesis indicates a role for these hormones in plant growth and development. Since the mid-1990s, collaborative research has been geared towards developing a better understanding of the CYP85 class of CYPs involved in BR biosynthesis in both Arabidopsis and tomato. Some of the most recent observations include the fact that certain CYP85 CYPs catalyse the synthesis of the most bioactive BR, BL (brassinolide). Current evidence suggests that evolution of this function may have occurred independently in different dicotyledonous species. Interestingly, BL accumulates in tomato fruits, highlighting a key role for this hormone in fruit development. At the same time as developing a better understanding of the enzymatic function of these CYPs, we have also carried out experiments towards characterizing where and when these genes are expressed and mechanisms of their regulation. As expected for a hormone involved in growth and development, biosynthetic gene promoter activity is associated with young rapidly growing cells and with fruit development.
Arabidopsis↗
Development and assessment of morphologic criteria for diagnosing gastric cancer using confocal endomicroscopy: an ex vivo and in vivo study.
BACKGROUND AND STUDY AIMS: The Confocal Endomicroscopy System (Optiscan Pty Ltd. and Pentax Corp.) is a newly developed imaging tool that uses laser light and optical technology to visualize living tissue at the cellular level. Digital images of cells magnified 1000-fold appear in real time on a computer screen, which enables immediate detection of changes in cellular structure without the need for a biopsy. The aim of this study was to assess the features of the cellular architecture of cancerous tissue that can be used in the differential diagnosis of cancerous tissue and normal mucosa using this system's image-processing software. PATIENTS AND METHODS: A total of 27 gastric cancers were examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent, acriflavine, was applied topically to normal and to cancerous mucosa. In vivo imaging of the gastric mucosa after intravenous injection of fluorescein sodium was also performed in nine patients with gastritis or gastric cancer. RESULTS: The nuclear area in the ex vivo specimens was calculated using Scion Image software. The mean nuclear area of cancer cells was found to be significantly larger than that of normal cells in 18/27 gastric cancers (67 %). The mean nuclear area of the cancers tended to be larger than that of normal mucosa, especially in cases of differentiated adenocarcinoma. In more than half the cases, it was possible to diagnose malignancy automatically using confocal endomicroscopy and image-processing software without the need for biopsy and pathological examination. In vivo imaging of cancerous lesions showed irregularity in cellularity and vascularity. CONCLUSION: The ability of this imaging device to differentiate between normal tissue and cancerous tissues gives it potential value as a new screening tool for early detection of malignancy.
Adenocarcinoma↗
Comparison between intraperitoneal CO2 insufflation and abdominal wall lift on QT dispersion and rate-corrected QT dispersion during laparoscopic cholecystectomy.
This study compared the effect of intraperitoneal CO2 insufflation with abdominal wall lift on RR interval, QT interval, the rate-corrected QT (QTc) interval, QT dispersion (QTD), and the rate-corrected QTD (QTcD) using computerized measurement during laparoscopic cholecystectomy. Thirty patients scheduled for laparoscopic cholecystectomy were randomly assigned to 2 groups: intraperitoneal CO2 insufflation (CO2 group) or abdominal wall lift (lift group). A 12-lead electrocardiogram was monitored to measure parameters. The RR interval, QT interval, and QTc interval did not change significantly during the study in both groups. The QTD and QTcD in the CO2 group increased significantly during CO2 insufflation, and were significantly higher than those of the lift group. Statistically significant increases of QTD and QTcD, which are associated with an increased risk of arrhythmias and cardiac events, occur during CO2 insufflation, and QTD and QTcD in the CO2 group were significantly higher than those of the lift group.
Abdominal Wall↗
Overall activity of all masticatory muscles during lateral excursion.
Quantification of the overall activity of every masticatory muscle is requisite for the analysis of stomatognathic function, which has not been accomplished by conventional electromyography. We used positron emission tomography and 18F-fluoro-deoxy-glucose to quantify the overall activity of every masticatory muscle during lateral excursion, and to evaluate the relative contribution of each masticatory muscle to lateral excursion. The present study suggested that lateral and medial pterygoid muscles are more responsible for lateral excursion than are masseter and temporal muscles. In particular, the contralateral lateral pterygoid muscle plays a major role, followed by the contralateral medial pterygoid muscle.
Adult↗
Pathology of fatal highly pathogenic H5N1 avian influenza virus infection in large-billed crows (Corvus macrorhynchos) during the 2004 outbreak in Japan.
Highly pathogenic H5N1 avian influenza viruses were isolated in 9 large-billed crows that died in Kyoto and Osaka prefectures in Japan from March to April in 2004. We studied 3 of the 9 crows using standard histologic methods, immunohistochemistry, and virus isolation. The most prominent lesions were gross patchy areas of reddish discoloration in the pancreas. The consistent histologic lesions included severe multifocal necrotizing pancreatitis, focal degeneration and necrosis of neuron and glial cells in the central nervous system, and focal degeneration of cardiac myocytes. All of these tissues contained immunohistochemically positive influenza viral antigens. The virus was isolated from the brain, lung, heart, liver, spleen, and kidney of the crows examined. Thus we concluded that highly pathogenic avian influenza virus was associated with clinical disease, severe pathologic changes, and death in the 3 crows.
Animals↗
Effect of different dialyzer membranes on cutaneous microcirculation during hemodialysis.
AIM: Biocompatibility profiles of synthetic membranes may vary. In this prospective crossover study, we examined the effect of various membranes on cutaneous microcirculation during HD. SUBJECTS AND METHODS: 11 HD patients without cardiovascular complications were enrolled in this study. They were dialyzed using three types of membrane in a randomized order: ethylene-vinyl alcohol copolymer (EVAL), vitamin E-bonded cellulose (VE-C) and polysulfone (PS). The transcutaneous oxygen tension (TcPO2) was examined on the dorsum of foot to assess the cutaneous microcirculation. Serum biochemical parameters were also measured. RESULTS: The TcPO2 as a percentage of the predialysis level decreased from the beginning of HD, and significant differences were observed after 15 min of HD between EVAL and the other 2 membranes (98 +/- 6% (mean +/- SD) for EVAL versus 89 +/- 7% for VE-C (p < 0.01) and 88 +/- 10% for PS (p < 0.01)). Furthermore, there were significant differences at 30 and 60 min between EVAL and PS (30 min: 93 +/- 9% for EVAL versus 85 +/- 7% for PS (p < 0.05); 60 min: 92 +/- 10% for EVAL versus 79 +/- 10% for PS (p < 0.01)). The serum level of thiobarbituric acid reactants (TBARs), a marker of lipid peroxidation, increased significantly at the end of HD relative to that at the beginning of HD when using a PS membrane (from 1.9 +/- 0.5 to 2.1 +/- 0.5 nmol/ml, p < 0.05). CONCLUSION: Our results indicate that an EVAL membrane is superior to PS and VE-C membranes in terms of its smaller influence on cutaneous microcirculation. The repeated occurrence of microcirculatory disturbance during HD sessions may cause chronic endothelial dysfunction and even cardiovascular complications in HD patients.
Adult↗
Laparoscopic cholecystectomy using a newly developed laparoscope manipulator for 10 patients with cholelithiasis.
BACKGROUND: Laparoscopic surgery has continued to gain popularity in almost all fields of abdominal surgery, and robotic systems have been introduced in general surgery. Naviot is a new remote-controlled laparoscope manipulator system controlled by the operator's hand. This study assessed its introduction into clinical practice. METHODS: A group of 10 consecutive patients with cholelithiasis underwent laparoscopic cholecystectomy assisted by the Naviot system (Naviot group). Another group of 41 patients who underwent laparoscopic cholecystectomy with a conventional human camera holder (human camera group) were selected for a comparison of their operative results with those of the Naviot group. RESULTS: The operative time of 89.3 +/- 27.1 min for the Naviot group was significantly longer than that of 74.8 +/- 28.1 min for the human camera group (p < 0.05). However, when the setup time for the Naviot system was excluded, the operative time was not significantly different from that for the human camera group. Other operative results showed no significant difference between the two groups. CONCLUSIONS: The authors believe that the new Naviot system is feasible for clinical use, and that it enables surgeons to perform solo gastrointestinal surgery.
Aged↗
Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.
The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status </=2 entered the study. Docetaxel 70 mg m(-2) was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39-74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1-50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3-4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.
Adenocarcinoma↗
Intraarterial injection of colforsin daropate hydrochloride for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage: preliminary report of two cases.
We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.
Cerebral Angiography↗
Thermolabile phenotype of carnitine palmitoyltransferase II variations as a predisposing factor for influenza-associated encephalopathy.
To assess the etiology of influenza-associated encephalopathy (IAE), a surveillance effort was conducted during 2000-2003 in South-West Japan. All fatal and handicapped patients except one (4/34 patients) exhibited a disorder of mitochondrial beta-oxidation evoked by the inactivated carnitine palmitoyltransferase II (CPT II) with transiently elevated serum acylcarnitine ratios (C(16:0) + C(18:1))/C(2) > 0.09 during high-grade fever. Analyses of genotypes and allele compositions of CPT II revealed a thermolabile phenotype of compound heterozygotes for [1055T > G/F352C] and [1102G > A/V368I], which shows a higher frequency in IAE patients than healthy volunteers (P < 0.025). The thermolabile phenotype of CPT II variations may be a principal genetic background of IAE in Japanese.
Adolescent↗
Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.
Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.
Adolescent↗
Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses.
The mucopolysaccharidoses (MPS) is characterized by accumulation of glycosaminoglycans (GAGs), and mucolipidosis (ML) by accumulation of GAGs and sphingolipids. Each type of MPS accumulates specific GAGs. The lysosomal enzymes N-acetylgalactosamine-6-sulphate sulphatase and beta-galactosidase involve the stepwise degradation of keratan sulphate (KS). Deficiency of these enzymes results in elevation of KS levels in the body fluids and in tissues, leading to MPS IV disease. In this study, we evaluated blood and urine KS levels in types of MPS and ML other than MPS IV. Eighty-five plasma samples came from MPS I (n = 18), MPS II (n = 28), MPS III (n = 20), MPS VI (n = 3), MPS VII (n = 5) and ML (n = 11) patients while 127 urine samples came from MPS I (n = 34), MPS II (n = 34), MPS III (n = 32), MPS VI (n = 7), MPS VII (n = 9) and ML (n = 11) patients. KS levels were determined using the ELISA method. Plasma KS levels varied with age in both control and patient populations. In all age groups, the mean values of plasma KS in MPS and ML patients were significantly higher than those in the age-matched controls. Plasma KS values in four newborn patients were above the mean + 2SD of the age-matched controls (mean, 41 ng/ml). Overall, 85.9% of individual values in non-type IV MPS and ML patients were above the mean + 2SD of the age-matched controls. For urine KS levels, 24.4% of individual values in patients were above the mean + 2SD of the age-matched controls. In conclusion, KS in blood is elevated in each type of non-type IV MPS examined, in contrast to the conventional understanding. This finding suggests that measurement of KS level provides a new diagnostic biomarker in a wide variety of mucopolysaccharidoses and mucolipidoses in addition to MPS IV.
Adolescent↗
Changes in histology and expression of cytokines and chemokines in the rat lung following exposure to ovalbumin.
Brown Norway (BN) and Fischer 344 (F344) rats were exposed to aerosol of 1% ovalbumin (OVA) solution for 30 min at 1 week after the second sensitization with 1 mg of OVA at 2-week intervals. Changes in the histology and expression of cytokines and chemokines in the lung were examined for up to 96 h after the exposure. The lung weight significantly increased in BN rats but not in F344 rats. Histologically, in the lung of BN rats, multiple foci of hemorrhage in the alveolar space with infiltration of eosinophils and macrophages in the surrounding alveolar septa were first observed. Thereafter, granulomatous lesions developed in the preexisting hemorrhagic foci, finally resulting in formation of multiple eosinophilic granulomas. On the other hand, in F344 rats, infiltration of eosinophils and macrophages was observed around the vessels and bronchi. Thereafter it progressed gradually, resulting in mild thickening of alveolar septa. The levels of Th1- (interferon-gamma and interleukin 2 (IL-2)) and Th2-related cytokines (IL-4 and IL-5) and chemokines (eotaxin and monocyte chemoattractant protein-1) mRNAs measured by reverse transcription-polymerase chain reaction method were elevated in the lung of both strains, and the levels were higher in BN rats than in F344 rats. These results suggest that BN rats are more sensitive to OVA-sensitization/inhalation than F344 rats and that the difference in the severity of lung lesions between BN and F344 rats may reflect the difference in the expression levels of cytokines and chemokines between these two strains.
Animals↗
RASSF1A gene promoter methylation in esophageal cancer specimens.
SUMMARY. RASSF1A is frequently inactivated by promoter methylation in human cancers. To understand the involvement of the RASSF1A gene in esophageal squamous cell cancer (ESCC), we investigated the methylation of the RASSF1A gene in primary ESCC to define the frequency of this epigenetic aberration and its clinicopathological significance. Methylation-specific polymerase chain reaction (MSP) was used to detect RASSF1A gene methylation in DNA from 55 cases of ESCC. Methylation of the RASSF1A gene was found in 13 of 55 (24%) cases of primary ESCC. No association was found between the promoter methylation of the RASSF1A gene in primary ESCC and age, gender, localization, invasion depth, or tumor stage. Association was found with tumor differentiation. There was no correlation with its prognosis. In conclusion, it was suggested that an inactivation of the RASSF1A gene due to promoter methylation was associated with de-differentiation of the tumor in ESCC.
Age Factors↗
Evaluation of skin perfusion after nipple-sparing mastectomy by indocyanine green dye. Preliminary results.
The aim of the study was to investigate the blood supply of the normal nipple areola complex (NAC) and the spared areola complex after a nipple-sparing mastectomy using the analysis of the fluorescence from the indocianine green dye (ICG) injection. Between December 2002 and July 2003 we performed the ICG analysis in 10 cases of healthy breasts and in 9 patients after a nipple-sparing mastectomy and one patient after subcutaneous mastectomy. In all cases, the resulting fluorescence was measured in three different zones: nipple, areola, surrounding mammary skin. Three parameters of the fluorescence curve (slope, maximum intensity, time to achieve a maximum level) were recorded. On the healthy breast, the nipple showed a very high perfusion as compared to the other zones. On the contrary, after the mastectomy the fluorescent pattern was completely altered, being the perfusion of the nipple very low. In conclusion, these preliminary results confirm the applicability and the importance of the ICG technique for evaluating the perfusion of the healthy and spared areola after surgery. Because of the small number of patients further studies are needed.
Female↗