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Biomedical subjects

Toshiaki Kobayashi

Publications and source records attributed to Toshiaki Kobayashi.

17 recordsLinked to original sources

Studies on the role of HtpG in the tetrapyrrole biosynthesis pathway of the cyanobacterium Synechococcus elongatus PCC 7942.

In cyanobacterium Synechococcus elongatus PCC 7942, we observed that htpG-overexpression caused remarkable growth inhibition. In addition, subcellular fractionation experiments showed that HtpG was localized in the membrane fraction. To understand its function in cyanobacteria, we carried out yeast two-hybrid screening to identify specific proteins interacting with HtpG, and found out, HemE, uroporphyrinogen decarboxylase. When compared to the wild-type strain, the htpG-null mutant and -overexpressing strains exhibited higher and lower cytosolic HemE activity, based on the coproporphyrin production, respectively. These results strongly suggest that HtpG is involved in the regulation of tetrapyrrole biosynthesis through interacting with HemE protein.

Bacterial Proteins↗

Stable top-up operation at SPring-8.

Top-up operation allows SPring-8 to provide highly stable X-ray beams with arbitrary filling patterns. The implementation of top-up operation is described, with a focus on the simultaneous achievement of stability of stored current, beam orbit, purity of an isolated single bunch, and beam injection efficiency. Stored-current fluctuations have been routinely reduced to a level of 10(-3). Stored-beam oscillation on frequent beam injection, which was originally regarded as the most serious problem, has been successfully suppressed to a sufficiently low level that it never perturbs imaging experiments. Current impurities in nominally empty buckets have been reduced to a level of 10(-9) over more than one week of operation, making possible the measurement of time-resolved spectra using high-current bunches. Finally, excellent injection efficiency, higher than 80%, is routinely obtained, even for small undulator gaps, which is critical for preventing radiation damage to insertion-device magnets and to reduce leakage radiation. The process of achieving highly stabilized top-up operation at SPring-8 and its utility for user experiments are described.

Electrons↗

[F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas.

OBJECTIVE: To predict a malignant grade of lung cancer by fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, we investigated the correlation between FDG uptake and pathological tumor stage, proliferative activities determined by Ki-67 and cyclin D1, and an alteration of p53, in clinical stage (c-stage) IA lung adenocarcinomas. METHODS: FDG-PET was performed for 71 patients with c-stage IA lung adenocarcinomas. FDG uptake was measured by a contrast ratio (CR) between the tumor and contralateral lung. Ki-67, cyclin D1 and p53 staining scores were examined by immunohistochemistry. RESULTS: The lesions with ground-glass opacity were found in 26 patients, and solid lesions in 45 by computed tomography. The pathological tumor stages (p-stage) were stage IA in 59 and more advanced stages in 12. The latter had significantly higher CR value than the former (P < 0.001). Patients with CR > or = 0.55 could be predicted to be at advanced tumor stages, with a sensitivity of 0.83 and a specificity of 0.82. The CR and staining scores of Ki-67 were significantly correlated with each other (P < 0.0001), and both the values were significantly higher in advanced tumor stages than in p-stage IA, and were also significantly higher in tumors with intratumoral lymphatic, vascular and pleural involvements than in those without such features (P < 0.05-0.0001). CONCLUSIONS: In c-stage IA lung adenocarcinomas, the FDG uptake can predict p-stage and tumor proliferative activity determined by Ki-67. For c-stage IA lung adenocarcinomas showing CR > or = 0.55, mediastinoscopy or neoadjuvant chemotherapy is indicated.

Adenocarcinoma↗

[The development of magnetically operated microforceps and microendoscopes].

In minimally-invasive intraluminal diagnosis or treatment, catheters or endoscopes need a high degree of operator ability for guidance to appropriate routes, especially in small peripheral regions. Movable microstructures and assistant guiding technolgies should be developed to make these procedures easier. The use of magnetism, which can give force to simple internal objects safely with no contact, is a possible option. To facilitate the realization of magnetic operation in clinical medicine, magnetically operated microforceps which assist endoscopic submucosal dissections in the stomach have been developed, and are being tested in clinical trials. As a next step, flexible microendoscopes which can be guided by magnetic force are being developed. Automated magnetic guidance is also being developed for future assistance in intraluminal procedures.

Animals↗

A flexible endoscopic surgical system: first report on a conceptual design of the system validated by experiments.

BACKGROUND: Surgery is a standard diagnostic and therapeutic procedure. However, its technical difficulty and invasiveness pose problems that are yet to be solved even by current surgical robots. Flexible endoscopes can access regions deep inside the body with less invasiveness than surgical approaches. Conceptually, this ability can be a solution to some of the surgical problems. METHODS: A flexible (surgical) endoscopic surgical system was developed consisting of an outer and two inner endoscopes introduced through two larger working channels of the outer endoscope. The concept of the system as a surgical instrument was assessed by animal experiments. RESULTS: Gastric mucosa of the swine could be successfully resected using the flexible endoscopic surgical system, thereby showing us the prospect and directions for further development of the system. CONCLUSION: The concept of a flexible endoscopic surgical system is considered to offer some solutions for problems in surgery.

Animals↗

11C-acetate positron emission tomography imaging for lung adenocarcinoma 1 to 3 cm in size with ground-glass opacity images on computed tomography.

BACKGROUND: Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for well-differentiated adenocarcinomas of the lung, especially, those with ground-glass opacity images. Recently, PET with 11C-acetate (AC) has been reported to detect slow-growing tumors that have failed to be identified by FDG-PET, such as well-differentiated hepatocellular carcinomas and prostate cancers. To determine the usefulness of AC-PET in detecting well-differentiated adenocarcinomas of the lung, we performed both AC-PET and FDG-PET on pulmonary nodules with ground-glass opacity images on computed tomography (CT). METHODS: Fifty-four pulmonary nodules 1 to 3 cm in size, which showed ground-glass opacity images over their whole or peripheral area on CT, were examined by both AC-PET and FDG-PET. RESULTS: Thirty-seven nodules were adenocarcinoma of the lung, while 17 were inflammatory. Of the 37 adenocarcinomas, 19 (51%) were positively identified by AC-PET and 14 (38%) by FDG-PET. Of the 23 adenocarcinomas which were not identified by FDG-PET, 8 (35%) were positively identified by AC-PET; all were well-differentiated adenocarcinomas. Of the 17 inflammatory nodules, 8 were chronic and 9 were acute ones. While none of the 8 chronic inflammatory nodules were identified by either technique, 9 acute ones showed a variety of the results with AC- and FDG-PET. CONCLUSIONS: AC-PET detected approximately one third of well-differentiated adenocarcinomas of the lung which were not identified by FDG-PET. AC-PET could be useful to diagnose pulmonary nodules with ground-glass opacity images which were not identified by FDG-PET.

Acetates↗

Radiofrequency ablation of pulmonary tumors and normal lung tissue in swine and rabbits.

OBJECTIVE: The purpose of the present study was to examine the following during radiofrequency ablation (RFA): (1) the risk of hemorrhage from intrapulmonary large vessels; (2) the risk of incomplete ablation of pulmonary tumors; and (3) the late effect on lung tissue. MATERIALS AND METHODS: A 17-gauge, cool-tip-type radiofrequency electrode was used. The damage to the vessels and bronchi was examined by the injection of a colored silicone rubber, a liquid compound that hardens after injection. To examine the risk of hemorrhage from intrapulmonary large vessels, RFA was conducted at eight sites near the central pulmonary vessels in two swine. To examine the risk of an incomplete ablation for pulmonary tumors, 10 pulmonary nodules were made from a gelatin mixture in another two swine and were treated by RFA. To examine the late effect on lung tissue, RFA was conducted on the peripheral lung in 10 rabbits, and then the ablated regions were examined on days 1, 7, 14, 21, and 28 after RFA. RESULTS: The use of colored silicone rubber enabled us to examine the intrapulmonary vessels and bronchi for opening and leakage. RFA did not damage the large intrapulmonary vessels, even when they were located within the ablated regions. Lung tissue surrounding the gelatin nodules was hardly ablated over its entire circumference. Six of 10 gelatin nodules (60%) showed nonablated areas on the peripheral edges of the nodules. From 21 days after RFA, the ablated rabbit lung formed noninfectious cavities by communicating with the surrounding bronchi. CONCLUSION: It was improbable for hemorrhage to occur even when RFA was conducted near the large intrapulmonary large vessels. Because an incomplete ablation that left tumor cells at the site of ablation could occur during surgery due to the difficulty of ablating the entire tumor circumference, CT scan-guided RFA would be preferable to a surgical approach for making a safe margin. Cavity formation can occur beginning 21 days after RFA, which should be carefully followed up in a clinical setting to identify infection, especially in immunocompromised patients.

Animals↗

Vascular virtual endoluminal visualization of invasive colorectal cancer on MDCT colonography.

OBJECTIVE: The purpose of this study was to assess the utility of vascular views for visualization of invasive colorectal cancers on contrast-enhanced MDCT colonography. CONCLUSION: By means of Hounsfield-transparency settings, we obtained virtual endoluminal images that show vascular structures and delineate invasive cancers of the colorectal wall, and we call these images "vascular views." Using this technique for contrast-enhanced MDCT colonography, we found that the increase in flow and pooling of blood related to angiogenesis of cancerous lesions is easy to identify and that this finding is useful in the detection of invasive colorectal cancers.

Adult↗

Comparison in fractal dimension between those obtained from structure factor and viscoelasticity of gel networks of 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol in polystyrene melt at gel point.

We investigated time evolution of shear moduli in the physical gelation process of 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol in polystyrene melt. At the gel point, storage and loss shear moduli, G' and G", were described by the power law of frequency omega, G' approximately G" approximately omegan, with the critical exponent n being nearly equal to 2/3, in agreement with the value predicted by the percolation theory. We also investigated the structure factor over two decades in length scale at gel point by using ultra-small-angle X-ray scattering, and small-angle X-ray scattering. We found the power-law behavior in low-q region, indicating that the gel network forms the self-similar structure with mass-fractal dimension. Comparison between the exponent of mass-fractal dimension from structure factor and that from viscoelasticity indicates that hydrodynamic interactions are completely screened out and the excluded volume effects are dominant in the gel. The gel strength was found to increase with the decrease in the lower limit length scale of fractality.

Benzylidene Compounds↗

Fluorine 18-tagged fluorodeoxyglucose positron emission tomographic scanning to predict lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0 lung adenocarcinoma.

OBJECTIVE: We sought to predict lymph node metastasis and tumor invasiveness in clinical T1 N0 M0 lung adenocarcinomas, and we measured fluorodeoxyglucose uptake on positron emission tomography. METHODS: Fluorodeoxyglucose positron emission tomography was performed on 44 patients with adenocarcinomas of 1 to 3 cm in size clinically staged as T1 N0 M0 before major lung resection with lymph node dissection. Fluorodeoxyglucose uptake was evaluated by using the contrast ratio between the tumor and contralateral healthy lung tissue. Lymphatic and vascular invasion within tumors, pleural involvement, and grade of histologic differentiation were examined. RESULTS: The pathologic tumor stage was T1 N0 M0 in 36 patients, and a more advanced stage was found in 8 patients. Although all 22 adenocarcinomas with a contrast ratio of less than 0.5 in fluorodeoxyglucose uptake were pathologic T1 N0 M0 tumors, 8 (36%) of 22 with a contrast ratio of 0.5 or greater were of a more advanced stage than T1 N0 M0, with the difference being significant (P =.002). Adenocarcinomas with a contrast ratio of less than 0.5 showed less lymphatic and vascular invasion and less pleural involvement than those with a contrast ratio of 0.5 or greater (P =.006, P =.004, and P =.02, respectively). The grade of histologic differentiation was well differentiated in 19 of 22 adenocarcinomas with a contrast ratio of less than 0.5 (86%), which was a greater frequency than the 4 (18%) of 22 adenocarcinomas with a contrast ratio of 0.5 or greater (P <.001). CONCLUSION: Clinical T1 N0 M0 lung adenocarcinomas with a contrast ratio of less than 0.5 usually did not have lymph node metastasis, had less tumor involvement of vessels or pleura, and were more frequently well differentiated than those with a contrast ratio of 0.5 or greater. Limited lung resection could be indicated, lymph node dissection or mediastinoscopy could be reduced, or both in this type of adenocarcinoma.

Adenocarcinoma↗

Magnetic anchor for more effective endoscopic mucosal resection.

BACKGROUND: Technical difficulties are involved in endoscopic mucosal resection (EMR) of gastric cancer since it is a "one handed surgery". These difficulties prevent this technique from being indicated for larger lesions, even when it can possibly be performed for patients with such lesions. If microforceps could assist EMR, this procedure would become easier and safer. Since magnetic force can control objects without direct contact, it can be applied to control microforceps internally in assistance with EMR. METHODS: We developed a magnetic anchor consisting of three parts: a magnetic weight with dimensions of 1.0 x 1.0 x 1.5 cm, microforceps and a connecting thread. Endoscopic clips used in hemostasis were used as the microforceps of the magnetic anchor in this study. The magnetic control system consisted of a 0.68 kOe/10 cm/100 A electromagnet, 350 mm in diameter and a circumventing positional frame. The microforceps were inserted into a sheath within the endoscope, and the magnetic weight was secured to the tip of the sheath protruding from the endoscope. The magnetic anchor, along with the endoscope, was inserted through an overtube into the gastric cavity of a swine under general anesthesia. The magnetic anchor was used in a manner similar to that in standard surgery, and EMR was thereby performed. RESULTS: The mucosa to be resected was satisfactorily dragged and stabilized. The magnetic anchor facilitated EMR, regardless of the technical skills of the endoscopist and region of the stomach at which the technique was performed. CONCLUSION: The magnetic anchor is considered to have alleviated some technical problems involved in EMR. It has the potential for making EMR a safer and quicker procedure for the treatment of early gastric cancer, when appropriately indicated.

Animals↗

Self-assembly and morphology of gel networks in l,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol/n-dibutylphthalate.

We investigated the self-assembling structure of the 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol (PDTS)/n-dibutylphthalate (DBP) system in the parameter space of temperature T and solute concentration Phi(PDTS). Optical microscopic studies revealed that the phase diagram can be divided into four regions. In region I at high T the system is a homogeneous solution. In region II at lower T and low Phi(PDTS), the system still has fluidity but has microgels having spherulitic texture of PDTS crystallites. Regions III and IV at even lower T but higher Phi(PDTS) are in a gel state. In region III, the PDTS forms volume-filling spherulites due to the solid-liquid phase transition of the saturated PDTS solutions. In region IV at the lowest T, both the liquid-liquid phase-separation process and the solid-liquid transition of the PDTS are involved in the self-assembling processes. In this region a bicontinuous phase-separated structure is first formed by liquid-liquid phase separation via spinodal decomposition (SD). The subsequent solid-liquid transition of the PDTS in the PDTS-rich region forms percolating crystalline fibrils rather than spherulites. The formation of the crystalline fibrils pins further growth of the bicontinuous structure via SD.

Dibutyl Phthalate↗

Time evolution of dynamic shear moduli in a physical gelation process of 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol in polystyrene melt: critical exponent and gel strength.

We investigated time evolution of shear moduli in the physical gelation process of 1,3:2,4-bis-O-(p-methylbenzylidene)-D-sorbitol (PDTS) in the polystyrene melt system containing 2.5 wt % of PDTS. At the gel point, storage and loss shear moduli, G' and G", were described by the power law of frequency omega, G' approximately G" approximately omega(n), with the critical exponent n equal to 2 / 3, in agreement with the value predicted by the percolation theory. The exponent n and the gel strength S at the gel point measured as a function of quench depth DeltaT indicated that the fractal network structure of PDTS does not change with DeltaT but that the mechanical strength of the network increases with DeltaT. Before reaching the gel point, G'(omega) and G"(omega) obtained at various times can be well superposed onto the master curves, indicating that the mechanical as well as structural self-similarity hold in this gelation process.

Journal Article↗

Screening for lung cancer with low-dose helical computed tomography: anti-lung cancer association project.

PURPOSE: Because efficacy of lung cancer screening using chest x-ray is controversial and insufficient, other screening modalities need to be developed. To provide data on screening performance of low-dose helical computed tomography (CT) scanning and its efficacy in terms of survival, a one-arm longitudinal screening project was conducted. PATIENTS AND METHODS: A total of 1,611 asymptomatic patients aged 40 to 79 years, 86% with smoking history, were screened by low-dose helical CT scan, chest x-ray, and 3-day pooled sputum cytology with a 6-month interval. RESULTS: At initial screening, the proportions of positive tests were 11.5%, 3.4%, and 0.8% with low-dose helical CT scan, chest x-ray, and sputum cytology, respectively. In 1,611 participants, 14 (0.87%) cases of lung cancer were detected, with 71% being stage IA disease and a mean tumor diameter of 19.8 mm. At repeated screening, the proportions of positive tests were 9.1%, 2.6%, and 0.7% with low-dose helical CT, chest x-ray, and sputum cytology, respectively. In 7,891 examinations, 22 (0.28%) cases of lung cancer were detected, with 82% being stage IA disease and a mean tumor diameter of 14.6 mm. The 5-year survival rate for screen-detected lung cancer was 76.2% and 64.9% for initial and repeated screening, respectively. CONCLUSION: Screening with low-dose helical CT has potential to improve screening efficacy in terms of reducing lung cancer mortality. An evaluation of efficacy using appropriate methods is urgently required.

Adult↗

Progression of focal pure ground-glass opacity detected by low-dose helical computed tomography screening for lung cancer.

OBJECTIVE: To clarify the progression of focal pure ground-glass opacity (pGGO) detected by low-dose helical computed tomography (CT) screening for lung cancer. METHODS: A total of 15,938 low-dose helical CT examinations were performed in 2052 participants in the screening project, and 1566 of them were judged to have yielded abnormal findings requiring further examination. Patients with peripheral nodules exhibiting pGGO at the time of the first thin-section CT examination and confirmed histologically by thin-section CT after follow-up of more than 6 months were enrolled in the current study. Progression was classified based on the follow-up thin-section CT findings. RESULTS: The progression of the 8 cases was classified into 3 types: increasing size (n = 5: bronchioloalveolar carcinoma [BAC]), decreasing size and the appearance of a solid component (n = 2: BAC, n = 1; adenocarcinoma with mixed subtype [Ad], n = 1), and stable size and increasing density (n = 1: BAC). In addition, the decreasing size group was further divided into 2 subtypes: a rapid-decreasing type (Ad: n = 1) and a slow-decreasing type (BAC: n = 1). The mean period between the first thin-section CT and surgery was 18 months (range: 7-38 months). All but one of the follow-up cases of lung cancer were noninvasive whereas the remaining GGO with a solid component was minimally invasive. CONCLUSIONS: The pGGOs of lung cancer nodules do not only increase in size or density, but may also decrease rapidly or slowly with the appearance of solid components. Close follow-up until the appearance of a solid component may be a valid option for the management of pGGO.

Adenocarcinoma, Bronchiolo-Alveolar↗

Local delivery of doxorubicin for malignant glioma by a biodegradable PLGA polymer sheet.

Implantable, biocompatible and biodegradable devices bearing an anticancer drug can provide promising local therapy to patients with malignant disorders. With the aim of treating brain tumors, especially gliomas, a membranous sheet containing doxorubicin was produced by co-polymerization to poly(D,L-lactide-co-glycolide) (PLGA). When release of the drug from the sheet was measured, sustained release continued until day 34. The data contrasted with the burst release from material containing a higher proportion of the drug. In terms of biodegradability, a subcutaneous 3 x 3-mm tetragonal sheet was almost completely absorbed by day 80. When a glioma was implanted subcutaneously and the tumor nodule exposed to the sheet, the device inhibited tumor growth significantly. The sheet consisted of an amorphous structure with cavities estimated to have a diameter of 0.5 - 3 microm by electron microscopic observation. Since the sheet is implantable, biodegradable and has a sustained-drug release property, the device may play a role in the local therapy of brain tumors.

Animals↗