Biomedical subjects
Publications and source records attributed to T Irie.
A new method was developed to implant a microcatheter-port system for repeat intraarterial chemotherapy of liver metastases. The microcatheter-port system was successfully implanted in all 20 patients reported in this study, and the only complications were one early occlusion of the hepatic artery and one dislocation of the implanted catheter.
PURPOSE: To estimate the effects of a lead plate, three types of needle holders, tube current, and slice thickness on decreasing the radiation dose to the physician's hand during interventional procedures with computed tomographic (CT) fluoroscopic guidance. The needle holders (I-I devices), which were developed by the authors, maintained the distance between the physician's hand and the CT plane at 7 cm, 10 cm, and 15 cm, respectively. MATERIALS AND METHODS: The dose rate (mSv/tube current/CT fluoroscopy time) was measured in 55 cases, which were divided into six groups. In group A (n = 14), the current was 135 kV, there was a 5-mm slice thickness, and a 7-cm I-I device was used without the lead plate. Group B (n = 11) entailed a 120-kV current, a 5-mm slice thickness, and a 7-cm I-I device without the lead plate. Group C (n = 8) entailed a 120-kV current, 5-mm slice thickness, and 7-cm I-I device with the lead plate. Group D (n = 9) entailed a 120-kV current, 5-mm slice thickness, and 10-cm I-I device with the lead plate. Group E (n = 7) entailed a 120-kV current, 5-mm slice thickness, and 15-cm I-I device with the lead plate. Group F (n = 6) entailed a 120-kV current, 1-mm slice thickness and 10-cm I-I device with the lead plate. To compare the effects of tube voltage, lead plate use, slice collimation, and I-I devices, differences were compared between groups A and B, B and C, D and F, and among groups C, D, and E. RESULTS: The dose rates of groups A, B, C, D, E, and F were 126.3, 75.2, 17.8, 13.9, 2.8, and 4.1 mSv/mA/sec x 100,000, respectively. There were significant differences in dose rates between groups A and B (t-test, P =.037), B and C (Student t-test, P =.002), D and F (Mann-Whitney test, P =.011), and among groups C, D, and E (Kruskal-Wallis test, P =.016). CONCLUSION: The lead plate, the improved I-I devices, use of a 120 kV (vs 135 kV) current, and 1-mm (vs 5 mm) collimation were all useful in decreasing the dose rate.
PURPOSE: To investigate the efficacy of computed tomography (CT) fluoroscopy and a new needle holder (the I-I device) in lung nodule biopsy. MATERIALS AND METHODS: The I-I device is made of acrylate resin and was used to keep the entire needle in the tomographic plane. This study consisted of biopsies of 79 lung nodules in 77 patients. The final diagnoses were malignant in 54 patients, benign in 23, and unconfirmed in two. The biopsy procedure time from the beginning of the CT fluoroscopy procedure to the removal of the needle was measured for 24 needle passes. The radiation dose on the physician's hand was measured in five cases with use of a thermoluminescence ring. RESULTS: Fifty-one malignant and 20 benign lesions were correctly diagnosed with histologic specimens (90%). In 58 of 77 patients (75%), the biopsy procedures were completed within a single breath-hold. Pneumothorax occurred in 20 of 77 patients (26%) and chest tube insertion was required in five. The incidence of pneumothorax was significantly lower in patients who held their breath during biopsy procedures compared with those who did not (P < .0001; chi2 test). The biopsy procedure time ranged from 15 to 39 seconds (mean: 28.2 sec). The mean radiation dose on the physician's hand was 2 mSv/case. CONCLUSION: The diagnostic accuracy of biopsy with use of the I-I device under CT fluoroscopic guidance is comparable with that of the conventional method; however, a combination of CT fluoroscopy and the I-I device enables rapid biopsy procedures.
Thirteen patients with invasive bladder cancer who had residual tumor after transurethral resections, were treated with consecutive intraarterial (IA) cisplatin (15 mg/d; total, 150 mg) and concurrent radiation (1.8 Gy/d; total, 30.6 Gy). All patients received unilateral or bilateral placement of vascular access devices (VAD) to perform daily cisplatin infusion after alteration of intrapelvic blood flow by coil embolizations. Tumor response was evaluated by transurethral biopsy 2 weeks after treatment. Complete response, defined as no viable tumor cell in the biopsy specimen, was achieved in seven patients (54%). After a median follow-up of 30 months (range, 12-48 months), 10 patients (77%) were alive, five (38%) of whom had no recurrence. Two cancer-related deaths were observed. All complete response cases survived with a median follow-up of 35 months (range, 25-48 months). Cause-specific and disease-free survival rates at 4 years were 85% and 28%, respectively. The regimen was well-tolerated, with no dose-limiting toxic events. There were no VAD-related complications. Consecutive IA low-dose cisplatin and concurrent radiation may be an acceptable alternative treatment for patients with bladder cancer who are not suitable for systemic chemotherapy. The use of a VAD contributed to successful consecutive IA infusions.
Cl(-)-ATPase in the CNS is a candidate for an outwardly directed neuronal Cl(-) transporter requiring phosphatidylinositol-4-phosphate (PI4P) for its optimal activity. To test its pathophysiological changes in a phosphatidylinositol (PI) metabolism disorder, the effects of neurotoxic factors in Alzheimer's disease (AD), amyloid beta proteins (Abetas), on the Cl(-)-ATPase activity were examined using primary cultured rat hippocampal neurons. Amyloid beta proteins (1-40, 1-42 and 25-35) concentration-dependently (1-100 nM) and time-dependently (from 1 h to 6 day) decreased Cl(-)-ATPase activity and elevated intracellular Cl(-) concentrations ([Cl(-)]i), Abeta25-35 being the most potent. Addition of inositol or 8-Br-cyclic GMP completely reversed these Abeta-induced changes. The recoveries in enzyme activity were attenuated by an inhibitor of PI 4-kinase, 10 microM wortmannin or 20 microM quercetin, but not by a PI 3-kinase inhibitor, 50 nM wortmannin or 10 microM LY294002. The PI, PIP and PIP2 levels of the plasma membrane-rich fraction were lower in the Abeta-treated cells as compared with each control. In the Abeta-exposed culture, but not in control, stimulation by 10 microM glutamate for 10 min significantly increased fragmentation of DNA and decreased cell viability. Addition of inositol or 8-Br-cyclic GMP prevented the effect of Abeta-treatment on the neurotoxicity of glutamate. Thus, Abetas reduce neuronal Cl(-)-ATPase activity, resulting in an increase in [Cl(-)]i probably by lowering PI4P levels, and this may reflect a pre-apoptotic condition in early pathophysiological profiles of AD.
Activators of peroxisome proliferator-activated receptor gamma (PPAR gamma), which forms a heterodimer with retinoic X receptor (RXR), inhibit the production of certain inflammatory mediators. To clarify the role of the PPAR gamma:RXR signaling pathway in Kupffer cells, we studied the effect of an RXR agonist and PPARgamma agonist on LPS-induced nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production. An RXR-specific agonist, Ro47-5944, and a PPAR gamma-specific agonist, AD4833 (pioglitazone hydrochloride), each inhibited LPS-induced NO and TNF-alpha production. The combined treatment of Ro47-5944 and AD4833 resulted in enhanced inhibition, and suppressed the mRNA levels of NO and TNF-alpha. PPAR gamma:RXR activation did not affect the level of LPS-induced phosphorylation of c-jun N-terminal kinase and p38 mitogen-activated protein kinase. PPAR gamma:RXR activation also did not affect nuclear factor kappa B (NF-kappa B) nuclear translocation nor NF-kappa B and activator protein 1 (AP-1) activation in the electrophoretic mobility-shift assay. Finally, PPAR gamma:RXR activation suppressed the LPS-induced promoter activity of the NF-kappa B-luciferase reporter gene in RAW 264.7 cells. These data imply that PPARgamma:RXR activation suppresses LPS-induced NO and TNF-alpha production in Kupffer cells, and that this inhibition occurred at the transcriptional level. Although no consensus PPAR gamma:RXR-responsive element in the promoter regions of the inducible isoform of nitric oxide synthase (iNOS) and TNF-alpha genes was found, PPAR gamma:RXR may interfere with NF-kappa B and AP-1 transcriptional activity. Our data also suggest a potential therapeutic approach for moderating hepatic injury such as endotoxin shock in which Kupffer cell activation has been implicated.
Thirty-seven patients with dorsal wrist ganglia underwent arthroscopic resection. The mean follow-up was 20 months, and no complications were encountered. The ganglia were classified into three types according to their arthroscopic appearance. This classification helps to determine the amount of dorsal capsular resection required.
N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolite-corrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis. First, the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacent scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and bias in brain regions with low k3 values such as neocortex. Estimates in regions with higher k3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer's disease (AD). There was a highly significant linear correlation in regional k3 estimates between shape and compartment analyses (300 neocortical regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant reductions in k3 estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P < 0.013, two-tailed t-test), although these reductions (17% to 20%) were somewhat less than those obtained by compartment analysis (22% to 27%). The sensitivity of shape analysis for detecting neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of 200 regions, 46%) also was somewhat less than compartment analysis (136 out of 200 regions, 68%). However, taking its simplicity and noninvasiveness into account, the authors conclude that quantitative measurement of neocortical AChE activity with shape analysis and [11C]MP4A PET is practical and useful for clinical diagnosis of AD.
N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies.
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Stimulation of monocytes/macrophages with lipopolysaccharide (LPS) results in activation of nuclear factor-kappaB (NF-kappaB), which plays crucial roles in regulating expression of many genes involved in the subsequent inflammatory responses. Here, we investigated roles of transforming growth factor-beta activated kinase 1 (TGF-TAK1), a mitogen-activated protein kinase kinase kinase (MAPKKK), in the LPS-induced signaling cascade. A kinase-negative mutant of TAK1 inhibited the LPS-induced NF-kappaB activation both in a macrophage-like cell line, RAW 264.7, and in human embryonic kidney 293 cells expressing toll-like receptor 2 or 4. Furthermore, we demonstrated that endogenous TAK1 is phosphorylated upon simulation of RAW 264.7 cells with LPS. These results indicate that TAK1 functions as a critical mediator in the LPS-induced signaling pathway.
An automatic DNA fragment collector using capillary array gel electrophoresis has been developed. A sheath flow technique is used for not only detection but also collection of DNA fragments. In a sheath flow cell, the DNA fragments separated by 16 capillaries flow independently into corresponding sampling capillaries. The fraction collector consists of 16 sampling trays and each sampling tray is set beneath each end of the sampling capillaries to collect the flow-through DNA fragments. Certain DNA fragments are automatically sorted by controlling the movement of the sampling trays according to the signals from the system. The collector experimentally separated two mixtures of polymerase chain reaction (PCR) products: one prepared by using eight different sizes (base lengths from 161 to 562) of DNAs; and the other prepared by a differential display (DD) method with cDNA fragments. Collected DNA fragments are amplified by PCR and measured by electrophoresis. DNA fragments with base length differences of one (base lengths 363 and 364) were successfully separated. A separated DNA fragment from the DD sample was also successfully sequenced. In addition, differentially expressed DNA fragments were automatically sorted by comparative analysis, in which two similar cDNA fragment groups, labeled by two different fluorophores, respectively, were analyzed in the same gel-filled capillary. These results show that the automatic DNA fragment collector is useful for gene hunting in research fields such as drug discovery and DNA diagnostics.
A novel selection marker gene for transformation of the white-rot basidiomycete Pleurotus ostreatus was developed by introducing a point mutation in a gene which encodes the iron-sulfur protein (Ip) subunit of succinate dehydrogenase. The mutant gene, CbxR, encodes a modified Ip subunit with an amino-acid substitution (His239 to Leu) and confers resistance to the systemic fungicide, carboxin. The DNA sequence was integrated ectopically in the chromosome of the transformants. This is the first report of a homologous marker gene which is available for the molecular breeding of an edible mushroom.
The purpose of the study was to obtain useful information for diagnosing internal abnormalities of bones by ultrasound. We fabricated a transmitting and receiving system mainly targeting the bone and an image processing system using a computer, and studied the attenuation of ultrasound in animal bone (in vitro). The average value was about 37 dB. The examination was able to determine successfully the proper dynamic range for detection, and a B-mode image of the inside of the bone could be displayed. Here we describe a new transmitting and receiving system developed to improve the detection of echo signals from inside bones. In this method, two kinds of high sensitivity transducer were made as follows: (1) 5 HMz frequency, 6.5 mm diameter; (2) 10 HMz frequency, 13 mm diameter. By using this method, detectability of the echo signals can be increased more than with the former system. The results showed that the structure of the bones could be clearly seen in the B-mode images.
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AIMS: The aim of the present study was to evaluate the outcome of patients with stage lb-IIb cervical adenocarcinoma treated with radical hysterectomy, and to determine the clinicopathological characteristics of those patients. METHODS: A total of 255 patients with cervical carcinoma stage Ib-IIb (57 adenocarcinoma and 198 squamous cell carcinoma) who had undergone radical hysterectomy were included in this study. Patient survival distribution was calculated using the Kaplan-Meier method. RESULTS: The estimated 5-year survival rate for patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma (77.9% vs 91.7%). The survival rate in stage Ib patients did not differ between two groups (95.8% vs 94.4% respectively). The incidence of lymph node involvement was significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma (31.6% vs 14.8%). Among patients receiving post-operative radiotherapy, the survival rate for adenocarcinoma (71.1%) was significantly poorer than that for squamous cell carcinoma (90.0%). When patients underwent radical hysterectomy, the survival rate for stage II patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma. CONCLUSIONS: The higher incidence of lymph node involvement and lower response to post-operative radiotherapy are considered to be factors of poorer prognosis in cervical adenocarcinoma.
Brain acetylcholinesterase activity was measured in 14 patients with Alzheimer disease and 14 age-matched control subjects by positron emission tomography with a radioactive acetylcholine analogue. Kinetic analysis was performed to calculate k3, an index of acetylcholinesterase activity. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala of all patients with Alzheimer disease, suggesting a loss of cholinergic innervation from the basal forebrain. Most profound reductions of k3 values were observed in the temporal (-30%) and parietal cortices (-31%), although reductions of k3 values were relatively uniform in the cerebral neocortex. This technique may be a powerful tool for early diagnosis of Alzheimer disease and also for therapeutic monitoring of acetylcholinesterase inhibitors in Alzheimer disease.