E-Cell 2: multi-platform E-Cell simulation system.
A new version of the E-Cell simulation system,which runs on Windows as well as Linux, has been released as free software under the terms of the GNU General Public License.
Biomedical subjects
Publications and source records attributed to N Ishikawa.
A new version of the E-Cell simulation system,which runs on Windows as well as Linux, has been released as free software under the terms of the GNU General Public License.
The authors studied the association between incidence of primary cardiac arrest and daily measures of fine particulate matter (</=2.5 micro m) using a case-crossover study of 1,206 Washington State out-of-hospital cardiac arrests (1985-1994) among persons with (n = 774) and without (n = 432) clinically recognized heart disease. The authors compared particulate matter levels on the day of the cardiac event and the 2 days preceding the event with levels from matched reference days. The estimated relative risk for a 13.8- micro g/m(3) increase in fine particulate matter (nephelometry: 0.54 x 10(-1) km(-1 )bsp) on the day prior to cardiac arrest was 0.94 (95% confidence interval: 0.88, 1.02). Pollutant levels measured on the same day as the event and on the 2 days preceding the event demonstrated similar results. No increased risk was found among all cases with preexisting cardiac disease (odds ratio = 0.97, 95% confidence interval: 0.89, 1.07); however, an unexpected association appeared between current smokers with preexisting heart disease and increased particulate matter levels 2 days prior to the event (odds ratio = 1.29, 95% confidence interval: 1.06, 1.55). This association was not present in the 0- or 1-day lag analyses or in persons with other diseases. There was no consistent association between increased levels of fine particulate matter and risk of primary cardiac arrest.
Hashimoto's thyroiditis (HT) is an autoimmune disease of the thyroid gland, and like many other autoimmune diseases, it is associated with the HLA and CTLA-4 gene. We have examined the distribution of the HLA DRB4*0101 allele and a CTLA-4 exon 1 A/G polymorphism in Japanese HT patients and controls and investigated possible interactions of these genes with thyroid function. Seventy Japanese HT patients and 105 controls were included in this study. HT was diagnosed on the basis of positivity for thyroid peroxidase (TPO) autoantibodies and the presence of a palpable diffuse goiter. Genotyping was performed by polymerase chain reaction (PCR)-based methods. CTLA-4-GG or -AG was more prevalent in the patients, and the odds ratio for the G allele was 4.95. The frequency of DRB4*0101-positive individuals was significantly higher in HT (odds ratio=2.17). The TSH values of HT patients at the time of diagnosis were compared to CTLA-4 genotype and HLA-DRB4*0101 positivity. They were slightly higher in the CTLA-4-AG group than in the -GG group and significantly higher in the HLA-DRB4*0101-positive group than in the -negative group (p<0.01). When the TSH values were compared in 4 groups based on positivity or negativity for HLA-DRB4*0101 and CTLA-4 GG or AG, they were found to be significantly higher in the CTLA-4-AG and HLA-DRB4*0101-positive group than in the 3 other groups (F=5.75, 3 degrees of freedom, p<0.01). These findings suggest that the interaction between the HLA-DRB4 and CTLA-4 genes determines the thyroid function of TPO-positive goitrous Japanese HT patients.
We studied the signal pathways for regulation of serine/threonine protein kinase Akt in Jurkat cells that had been treated with 4-hydroxynonenal (HNE) for caspase-dependent apoptosis induction. Treatment of cells with HNE led to a decrease in the level of Akt activity due to the dephosphorylation at Ser473, a major regulatory phosphorylation site. HNE-mediated dephosphorylation of Akt was prevented by a protein phosphatase 2A (PP2A) inhibitor, okadaic acid, and by a caspase-3 inhibitor, DEVD-CHO. HNE treatment resulted in an increase in the total level of PP2A activity, release of active tyrosine-dephosphorylated PP2A from the cytoskeleton and PP2A-Akt association, which were all dependent on caspase-3 activation. These results suggest that the level of PP2A activity is at least in part determined by its tyrosine phosphorylation, which is dually controlled by okadaic acid-sensitive phosphatases and protein-tyrosine kinases. Possibly underlying the mechanism of caspase-mediated activation of PP2A, HNE treatment resulted in downregulation of the activity of Src kinase, as a representative caspase-sensitive kinase to phosphorylate PP2A at tyrosine. In addition, activated caspase-3 partially cleaved Akt at a late stage of the apoptosis. These results indicate the existence of two distinct caspase-dependent signal pathways for downregulation of Akt that works as a mechanism of positive feedback regulation for HNE-triggered apoptotic signals.
A 16-year-old woman presented with chest pain on 2 days before the onset of menstruation and was referred to our hospital because of a pneumothorax. She was diagnosed as spontaneous penumothorax and surgical treatment was performed. Thoracoscopy revealed the presence of multiple blueberry spots near central tendon of the diaphragm and little pleural effusion. No other abnormal lesions were found in the left pleural cavity and left lung. Thoracoscopic biopsy and coagulation of the lesions were successfully performed. Histological findings of biopsied specimen did not contradict as an endometoriosis and catamenial pneumothorax was diagnosed. CA 125 level of the pleural effusion had increased to 99.2 U/ml. Because she was young, she did not receive a systemic hormonal therapy.
We performed off-pump coronary artery bypass grafting (CABG) in all cases without reoperation case from July, 2002. Advantage of off-pump CABG versus on-pump CABG which is reduced a number of perioperative complication and early patients recovery was previously demonstrated. In our institute, the mean number of grafts per patients was 4.7 +/- 1.3, and the rate of using arterial grafts was 99.5% in all cases without minimally invasive direct coronary artery bypass (MIDCAB). The mean hospital stay after operation was 10.8 +/- 2.8. It was shorted remarkably in comparison with on-pump CABG; 19.4 +/- 6. Furthermore, sever complication was not occurred in any cases after operation though high risk cases were increased. In the early cases, atrial fibrillation complicated frequently (32%), but using after magnesium sulfate it was remarkably decreased (8.4%). On the other-hand, attention is necessary for the infection caused by the increase of high risk patients. Therefore, we used vancomycin (VCM) at these cases from the viewpoint of prevention. Recently, we performed remnant omental transfer for the sever diabetes mellitus case which was used bilateral internal thoracic artery on CABG. It learned to get the early recovery which was necessary for the off-pump CABG by the above additional treatment.
A 59-year-old woman was admitted to our hospital complaining of a productive cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no marked abnormalities, her level of serum KL-6 was extremely high. We therefore suspected the presence of interstitial pneumonia. High-resolution computed tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1) antibodies. From the clinical symptoms, radiographic findings, and histological findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP). After high-dose corticosteroid therapy, the level of serum KL-6 decreased rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating the activity of pulmonary manifestations in HTLV-1 carriers and that it is especially useful in monitoring the effectiveness of treatments.
The length polymorphism in the waxy gene, which encodes a granule-bound ADP-glucose-glucosyl transferase [granule-bound starch synthase I (GBSS I), E.C. 2.4.1.11] in barley ( Hordeum vulgare), was found. The 5' leader sequence of the waxy gene of barley germplasm from Japan and Korea was analyzed by the polymerase chain reaction (PCR). The waxy gene of these genetic stocks had three types of length polymorphisms, suggesting that there are insertion/deletion mutations at the 5' leader sequence of the waxy gene. DNA sequence analysis of the polymorphic PCR products showed that: (1) a 403-bp deletion mutation, which included a complete exon I, was found in the wax allele and a 193-bp insertion sequence was located in the intron I, and (2) the insertion sequence was also located in intron I of the Wax allele. The identity of the insertion sequence was completely conserved between the wax allele and the novel Wax allele. These finding s implying that the wax allele, which was found in indigenous waxy barley, originated in non-waxy barley with the novel Wax allele.
OBJECTIVES: The purpose of the study was to assess quantitative measurements of the manipulative dexterity of patients suffering from hand-transmitted vibration disorder, and to investigate a possible link with impaired tactile perception in their hands. SUBJECTS AND METHODS: The subjects were 30 patients with hand-arm vibration syndrome, 30 office workers and 20 manual laborers of similar ages. Manipulative dexterity was assessed by measuring the performance time of buttoning-unbuttoning a work jacket with five buttons and of picking up and transferring 30 red beans, one by one, with the fingers from one plate to another. Patients were also examined on vibrotactile thresholds at 125 Hz as well as pain thresholds. RESULTS: The buttoning-unbuttoning time and the bean transfer time were significantly prolonged in the patients compared with the worker groups. The patients showed a close correlation between the buttoning-unbuttoning time and the bean transfer time. Performance times did not differ between patients with vibration-induced white finger and those without it. Those times also correlated with the vibrotactile and pain thresholds in the patients. When a cut-off value was set at 2 SDs from the mean performance times of the manual laborers, exceeding the cut-off value was found in 70% of the patients for the button-unbutton test and in 80% of those for the bean transfer test. All patients with moderately or severely increased vibrotactile and pain thresholds exceeded that value in performing the two tasks. CONCLUSION: The present measurements quantitatively showed impaired manipulation in patients with hand-arm vibration syndrome. Such difficulty with manipulation seems to be associated with the impaired tactile sensation in their hands.
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OBJECTIVE: To evaluate the efficacy and safety of self-expanding metallic stents after insertion into the canine ureter. MATERIALS AND METHODS: Actively expanding metallic (Nitinol) stents (diameter 8-10 mm, length 4-6 cm) were placed in eight mongrel dogs (18-34 kg). Under general anaesthesia, a midline abdominal incision was made and a stent inserted directly into the ureter through a small incision; each animal was stented on one side. The dogs were assessed after 6 or 19 days or 2, 5 (two), 6 (two) and 7 months. Ureteric specimens were evaluated both macroscopically and microscopically. RESULTS: Macroscopically there was no leakage of urine in any of the animals. On day 6 the inserted stent was patent despite blood clots in the mesh. The lumen was smooth and shiny in three dogs examined at 5, 6 and 7 months. One of the two dogs assessed at both 5 and 6 months had hydronephrosis associated with papillary hyper-epithelialization inside the stent, while the other animals had no dilatation of the renal pelvis. Microscopically there was loss of epithelium and bleeding of the ureteric wall at 6 days. Epithelial regeneration started after 19 days and was complete in the lumen at 2 months, with the stent incorporated into the wall of the ureter. Epithelialization was maintained up to 7 months, after which the problem of urothelial hyperplasia persisted, but an adequate lumen was maintained by epithelial regeneration. This epithelium was smooth and shiny, and composed of thin layers of cells. CONCLUSION: Self-expanding metallic stents may be effective if hyperplastic epithelialization does not occur, as the stent was epithelialized within 2 months and the regenerated epithelium maintained for up to 7 months. Metallic stents may be useful for treating patients with renal failure caused by ureteric stenosis from malignant tumours.
OBJECTIVE: The aim of this study was to investigate the impact of Helicobacter pylori infection on clinical features in patients with rheumatoid arthritis (RA) under medication with non-steroidal anti-inflammatory drugs. METHODS: One hundred and eighty-four patients with RA were tested for the presence of H. pylori infection. Clinical features and gastroduodenal lesions were compared between H. pylori-positive and -negative patients. RESULTS: One hundred and thirteen patients were positive and 71 patients were negative for H. pylori. The age, severity of RA, prevalence of gastrointestinal symptoms and gastroduodenal lesions and the class of gastroprotective drugs were not different between the two groups. Reflux oesophagitis was less frequent and sulphasalazine was less frequently administered in the H. pylori-positive group. CONCLUSIONS: The severity of RA, prevalence of gastroduodenal lesions other than reflux oesophagitis and the application of gastroprotective drugs do not seem to depend upon H. pylori infection in RA patients. Sulphasalazine may be protective against H. pylori infection.
OBJECTIVE: To observe the recent epidemiological trend of tuberculosis and to determine the factors related to the deteriorating trend in incidence and mortality rates in Japan. DESIGN: Descriptive analyses of tuberculosis notification rates and mortality rates by age, sex, year and birth-cohort. RESULTS: The decline in the tuberculosis notification rate has started slowing down since around 1980. Among the cohorts born before 1950, the trend of notification rate by age has levelled off since around 1980. The reduction in the tuberculosis mortality rate has also recently begun to slow down, but later and to a lesser extent than that of the notification rate. Although deaths due to tuberculosis occur mostly among the elderly, the rate of decline in mortality among middle-aged males has slowed down recently. The trend in the mortality rate of birth-cohorts has recently shown an upward trend with age. CONCLUSION: A major cause of the current stagnation of the decline in notification rates is the increase in the elderly population with a high prevalence of tuberculosis infection in the past, who are more likely to develop the disease as they approach biological senescence. Other possible causes are a gradual shift of the tuberculosis problem to socio-economically deprived segments of the urban population, and behavioural changes causing delay in case-finding.
Nine cases of thymic carcinoma (mean age 53.9 years old, 8 males and 1 female) were treated in our hospital from 1973 to 1998. The histological subtypes of thymic carcinoma were squamous cell in six, adenosquamous cell in one, Lymphoepithelioma-like carcinoma in one, mixed type of small cell and squamous cell in one. We applied Yamakawa clinical staging, 9 cases consisted of 2 stage II cases, 2 stage III cases, and 5 stage IV b cases. Adjuvant radiotheraphy was administered in one case, registering remarkable reduction of tumor size. All of the four cases which had been performed complete resection are alive without recurrence for 17 to 136 months after operation. The mean survival time was 47 months in stage III, and 18 months in stage IV b. By the review of the Japanese literature, most of the patient who revealed long-term survival fulfill the conditions as follow, squamous cell carcinoma in histologically, earlier stage than III at his operation, performed complete resection, performed postoperative radiotherapy. Our cases covering all these condition are alive without carcinoma for 136 months after operation.
The mutable flaked or a (flaked) (a(f)) line of the common morning glory (Ipomoea purpurea) displays white flowers with colored flakes, and the a(f) mutation is caused by the insertion of a transposable element named Tip100 into the CHS-D gene for anthocyanin biosynthesis. The 3.9-kb Tip100 element belongs to the Ac/Ds family and contains an ORF encoding a polypeptide of 808 amino acids. The frequency and timing of flower variegation vary in different a(f) lines, and a genetic element termed Modulator has been postulated to affect the variegation pattern. Since the pattern of flower variegation is determined by the frequency and timing of excision of Tip100 from the CHS-D gene, we wished to determine whether Tip100 is an autonomous element that is itself capable of transposition in a heterologous host. To do this, we introduced the element into the genome of tobacco plants by Agrobacterium-mediated transformation. The intact Tip100 element was able to excise from its original position in the chromosome and reinsert into new sites in the tobacco genome, whereas an internal deletion derivative was not. Based on these results, we conclude that Tip100 is an autonomous element. We also discuss the nature of the putative Modulator element affecting flower and leaf variegation in various mutable lines of the morning glory.
To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure. MRP3 and MRP4 gene expression levels were monitored in the PMN of 10 previously untreated lung cancer patients within 24 hr after carboplatin (CBDCA) administration. Expression levels for both genes were also examined in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients with lung cancer. MRP3 and MRP4 gene expression levels were assessed by quantitative reverse transcription-polymerase chain reaction. MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same. Furthermore, MRP3 expression levels in normal lung and tumor tissues from autopsy samples that had been exposed to platinum drugs while the patients were alive were significantly higher than those in unexposed tissues, but again MRP4 expression levels remained the same. These results suggest that platinum drugs and/or the physiological stress response to xenobiotics induce expression of the MRP3 gene.
Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is caused by multiple genetic and environmental factors. The clinical and immunological features of GD and HT are distinct; however, there are multiplex families with both GD and HT, and cases in which GD evolves into HT. Thus, there may be specific susceptibility loci for GD or HT, and common loci controlling the susceptibility to both GD and HT may exist. A genome-wide analysis of data on 123 Japanese sib-pairs affected with AITD was made in which GD- or HT-affected sib-pairs (ASPs) were studied to detect GD- or HT-specific susceptibility loci, and all AITD-ASPs were used to detect AITD-common susceptibility loci. Our study revealed 19 regions on 14 chromosomes (1, 2, 3, 5, 6, 8, 9, 10, 11, 12, 13, 15, 18 and 22) where the multipoint maximum LOD score (MLS) was >1. Especially, chromosome 5q31-q33 yielded suggestive evidence for linkage to AITD as a whole, with an MLS of 3.14 at D5S436, and chromosome 8q23-q24 yielded suggestive evidence for linkage to HT, with an MLS of 3.77 at D8S272. These observations suggest the presence of an AITD susceptibility locus at 5q31-q33 and a HT susceptibility locus at 8q23-q24.
A novel heat shock gene, orf7.5, which encodes a putative acidic polypeptide of 63 amino acids, was cloned from the cyanobacterium Synechococcus sp. PCC 7942. Northern blot analysis revealed the presence of 400- and 330-base orf7.5 mRNAs, which were barely detectable in the cells grown at 30 degrees C but increased transiently in response to heat shock at 40 or 45 degrees C. Primer extension analysis showed that the two mRNAs have different 5'-ends. Chloramphenicol enhanced the accumulation of the orf7.5 mRNA, whereas it inhibited the increase in the amount of the groESL mRNA. To reveal the role of the orf7.5 gene in thermal stress management, we constructed a stable mutant in which a gene conferring resistance to an antibiotic was inserted into the coding region of the orf7.5 gene. The interruption led to a marked inhibition of growth at 45 degrees C and a decrease in the basal and acquired thermo-tolerances at 50 degrees C in the transformants, indicating that the gene plays a role in thermal stress management. The orf7.5 mutant could be complemented with a return to the wild type phenotype by a DNA fragment containing orf7.5 but not by mutated orf7.5s, in which a nonsense mutation was generated by introducing a frameshift or a point mutation within the orf7.5-coding region. Thus, thermo-tolerance requires an appropriate translation product, not simply a transcript. Accumulation of the groESL transcript in the orf7.5 mutant was strongly reduced, suggesting that the orf7.5 gene product controls the expression of the groESL operon.