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Biomedical subjects

Shinichi Suzuki

Publications and source records attributed to Shinichi Suzuki.

At least 19 recordsLinked to original sources

New safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes.

INTRODUCTION: A non-toxic and stable sarin analogue, isopropyl p-nitrophenyl methylphosphonate (INMP), was synthesized for safe preparation of sarin-exposed acetylcholinesterase (AChE). RESULTS AND DISCUSSION: This agent was stable for years, able to be handled in an ordinary laboratory without special care, and its 50% inhibitory concentration (IC50) on 0.04 U/ml human erythrocytes AChE was 15 nM. This reagent was thought to be especially useful since it enables experiments that require sarin-inhibited AChE, such as the development of antidotes for sarin, in a usual laboratory. To demonstrate the usefulness of this method, 40 known and novel pyridinealdoxime methiodide (PAM)-type oxime antidotes were synthesized, and their reactivation activities to INMP-exposed AChE and structure-activities correlation were studied. CONCLUSION: Among the antidotes tested in this experiment except for 2-PAM, the compound found to have the highest reactivation activity, was the novel hydrophobic 2-PAM-type compound, 2-[(hydroxyimino)methyl]-1-[4-(tert-butyl)benzyl] pyridinium bromide.

Acetylcholinesterase↗

Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome.

BACKGROUND: A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism-jaw tumour syndrome (HPT-JT). AIM/PATIENTS AND METHODS: We investigated the involvement of the HRPT2, MEN1 and CASR genes in 11 provisional FIHP families and two HPT-JT families. RESULTS: Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in two of five parathyroid tumours in a family with a 518-521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected. CONCLUSION: Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.

Adenoma↗

Porcine enamel protein fractions contain transforming growth factor-beta1.

BACKGROUND: Enamel extracts are biologically active and capable of inducing osteogenesis and cementogenesis, but the specific molecules carrying these activities have not been ascertained. The purpose of this study was to identify osteogenic factors in porcine enamel extracts. METHODS: Enamel proteins were separated by size-exclusion chromatography into four fractions, which were tested for their osteogenic activity on osteoblast-like cells (ST2) and human periodontal ligament (HPDL) cells. RESULTS: Fraction 3 (Fr.3) and a transforming growth factor-beta 1 (TGF-beta1) control reduced alkaline phosphatase (ALP) activity in ST2 but enhanced ALP activity in HPDL cells. The enhanced ALP activity was blocked by anti-TGF-beta antibodies. Furthermore, using a dual-luciferase reporter assay, we demonstrated that Fr.3 can induce the promoter activity of the plasminogen activator inhibitor type 1 (PAI-1) gene. CONCLUSION: These results show that the osteoinductive activity of enamel extracts on HPDL cells is mediated by TGF-beta1.

Alkaline Phosphatase↗

Midterm results of transluminal endovascular grafting in patients with DeBakey type III dissecting aortic aneurysms.

OBJECTIVE: Transluminal endovascular grafting (TEG) is less invasive than conventional operative procedures for the treatment of DeBakey type III dissecting aortic aneurysms (DAA). We have used two different kinds of stent grafts covered with woven Dacron grafts, a Gianturco Z-stent graft (G-SG) and a Spiral Z-stent graft (S-SG). Because the G-SG lacks adequate flexibility, the end of the graft may injure the intima after long-term deployment in the proximal descending aorta. We have used S-SGs, which are more flexible than G-SG, to improve outcome. We report our late midterm results and discuss treatment policy. SUBJECTS AND METHODS: We studied 45 patients with DeBakey type III DAA. Thirty-two G-SGs and 13 S-SGs were used. Follow-up ranged from 1 year 6 months to 8 years 5 months (mean, 5 years 2 months). RESULTS: 1) Surgical outcome: (a) TEG was technically successful in all patients. There was no operative mortality. (b) One week after surgery, 36 patients had no endoleaks, 5 had minor endoleaks, and 4 had major endoleaks. 2) Late midterm results: (a) Four patients with residual major endoleaks, underwent replacement of the descending thoracic aorta. (b) Intimal injury occurred at the distal end of the stent graft 4 to 18 months (mean, 10.5 months) after surgery in 12 patients with G-SG and 1 with S-SG. One of these patients had recurrent dissection, and 12 had ulcer like projections (ULP). Two patients underwent additional stent implantation to block blood flow. (c) Four patients with S-SG had major endoleaks 3 to 6 months after surgery. In 3 of these patients, the Spiral Z-stents were compressed and occluded, and thrombus had formed in the lumen. Three patients underwent replacement of the descending thoracic aorta. (d) Additional replacement of the descending thoracic aorta was done in 9 of the 45 patients (20%) 4 to 24 months after TEG. All patients responded to treatment and were discharged from the hospital. CONCLUSION: Intimal injury was caused by Gianturco Z-stents because of inadequate flexibility, and endoleaks and stent-graft occlusion were caused by Spiral Z-stents because of insufficient radial force against the aortic wall. The development of stents with these improved properties is expected to further improve outcome.

Adult↗

[Current topics of endoscopic surgery for thyroid cancer].

Endoscopic surgery has been introduced in the field of thyroid disease. Endoscopic thyroid surgery is divided into complete endoscopic surgery using CO2 gas, which is approached from the axilla, mammary areola, and anterior chest; and video-assisted thyroid surgery without CO2 gas, approached from the neck or anterior chest under the clavicula through a small incision. Many thyroid tumors are benign, and cases of thyroid cancer are few. Only 7.9% of patients who underwent endoscopic thyroid surgery in the English and Japanese literature had papillary thyroid cancer. Most of these underwent video-assisted thyroidectomy without gas. The indications for endoscopic surgery in papillary thyroid cancer is microcancer or small tumor without lympnode metastasis before surgery. In follicular thyroid cancer, minimally invasive thyroid cancer of less than 5cm is recommended for endoscopic thyroid surgery. Furthermore, in medullary carcinoma with multiple endocrine neoplasia, prophylactic thyroidectomy can be performed using these endoscopic techniques. At present, it is still controversial whether endoscopic surgery should be performed to treat thyroid cancer.

Carbon Dioxide↗

Aortic root necrosis after surgical treatment using gelatin-resorcinol-formaldehyde (GRF) glue in patients with acute type A aortic dissection.

BACKGROUND: Although gelatin-resorcinol-formaldehyde (GRF) glue is used for surgical repair of acute type A aortic dissections, late complications possibly ascribed to toxic effects of GRF glue have been reported. We analyzed the benefits and risks of using GRF glue. PATIENTS AND METHODS: Between January 1990 and August 2003, 269 consecutive patients underwent emergency operations for acute type A aortic dissection. GRF glue was not used in 47 patients (non-GRF group) who were operated on until May 1995 and was used in the 222 (GRF group) who underwent operation subsequently. RESULTS: The rate of in-hospital mortality was significantly higher in the non-GRF group (31.9%) than in the GRF group (12.6%) (p<0.0001). In the GRF group, false aneurysms were found in 31 patients (31/194 survivors, 16.0%) 1-65 (mean, 30+/-18) months after initial operation. Reoperation was done in 24 of these patients. At reoperation, the site to which GRF glue was applied had degenerated, and the anastomosis between the aortic root and prosthesis had opened widely, creating a false aneurysm and resulting in aortic regurgitation with prolapse of the coronary cusps. The mortality rate of reoperation was 4.2% (1/24). CONCLUSION: The use of GRF glue improved the short-term outcome of surgery for acute type A aortic dissection, but was associated with a high incidence of false aneurysms forming at the site of proximal anastomosis, where GRF glue had been applied. Patients in whom GRF glue has been used should be carefully followed up after surgery.

Acute Disease↗

Type-3 ryanodine receptor involved in Ca2+-induced Ca2+ release and transmitter exocytosis at frog motor nerve terminals.

Ca(2+)-induced Ca2+ release (CICR) occurs in frog motor nerve terminals after ryanodine receptors (RyRs) are primed for activation by conditioning large Ca2+ entry. We studied which type of RyR exists, whether CICR occurs without conditioning Ca2+ entry and how RyRs are primed. Immunohistochemistry revealed the existence of RyR3 in motor nerve terminals and axons and both RyR1 and RyR3 in muscle fibers. A blocker of RyR, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) slightly decreased rises in intracellular Ca2+ ([Ca2+]i) induced by a short tetanus (50 Hz, 1-2s), but not after treatment with ryanodine. Repetitive tetani (50 Hz for 15s every 20s) produced repetitive rises in [Ca2+]i, whose amplitude overall waxed and waned. TMB-8 blocked the waxing and waning components. Ryanodine suppressed a slow increase in end-plate potentials (EPPs) induced by stimuli (33.3 Hz, 15s) in a low Ca2+, high Mg2+ solution. KN-62, a blocker of Ca(2+)/calmoduline-activated protein kinase II (CaMKII), slightly reduced short tetanus-induced rises in [Ca2+]i, but markedly the slow waxing and waning rises produced by repetitive tetani in both normal and low Ca2+, high Mg2+ solutions. Likewise, KN-62, but not KN-04, an inactive analog, suppressed slow increases in EPP amplitude and miniature EPP frequency during long tetanus. Thus, CICR normally occurs weakly via RyR3 activation by single impulse-induced Ca2+ entry in frog motor nerve terminals and greatly after the priming of RyR via CaMKII activation by conditioning Ca2+ entry, thus, facilitating transmitter exocytosis and its plasticity.

Animals↗

5-(4-Nitrophenyl)-2,4-pentadien-1-al (NPPD) used as a tracer by nonscientists at a simulated crime scene.

5-(4-Nitrophenyl)-2,4-pentadien-1-al (NPPD) was used as a tracer by nonscientists at a simulated crime scene. A card with both a plastic-coated smooth surface and a porous cellulose matrix paper surface was coated with a methanol solution containing 0.5mg/mL of NPPD. The card was touched with bare fingers and fingers covered by a cotton glove. A color-change protocol was then used to detect the presence of NPPD. The bare fingers or the fingers of gloves were swabbed with a cotton swab, or the parts of the glove that had touched the card were cut out. The swabs or the cloth pieces were dipped in methanol, a 0.1% methanol solution of naphthoresorcinol was added, and then concentrated hydrochloric acid was added. The observation of a red color at this point indicated a positive test. NPPD was easily observed in the experiments involving bare fingers, but no color change was observed from the swabbing of the cotton glove. However, when the cloth pieces cut from the fingers of the glove were subjected to the test, the red color was observed. In an attempt to enhance the sensitivity of the test, the volumes of the reagent solutions were reduced, but no improvement in sensitivity was obtained.

Journal Article↗

Discrimination of arsenous acids with comparison of trace elements contained by using synchrotron X-ray fluorescence spectrometry.

In the poisonous incident case occurred in Japan, clarification of the identity between seized poisons and retrieved from crime scene is strictly required from the court. In this case, arsenous acid was used as a poisonous material and, seized one from suspect's house was only twenty particles. The synchrotron X-ray fluorescence spectrometry by comparing the intensity ratios of L(alpha) line of four heavy metal, such as Bi, Sn, Sb, Se to K(beta) line of As was performed to overcome this problem. In this paper, the evaluation of this new method using 13 authentic arsenous acid samples, 4 of 13 were refined by Chinese method, 7 of 13 were refined by Japanese method (Sumitomo mining Co. Ltd. method), 2 of 13 were refined by German and Swiss method. As a result, by the comparison of the ratios of these four elements to As, these 13 samples were clearly classified to three products classes produced by different refining methods.

Journal Article↗

Mucinous cystic neoplasm in a young male patient.

A 25-year-old Japanese man was admitted to our hospital with a history of recurrent pancreatitis and a pseudocyst of the pancreas. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an encapsulated multilocular cystic mass 5 cm in diameter in the pancreatic tail. Endoscopic ultrasonography demonstrated a mural nodule, and endoscopic retrograde pancreatography showed a communication of the lesion with the main pancreatic duct. A neoplastic cystic tumor was suspected, and a resection of the body tail of the pancreas was performed. The lesion was a multilocular cyst having a common fibrous capsule and viscous content. Histologically, the cystic lesion was lined with a single layer of columnar cells with low-grade atypia. Ovarian-type stroma (OS) was confirmed, and it showed positive for antiestrogen receptor and antiprogesteron receptor staining. Based on these findings, the lesion was diagnosed as mucinous cystic neoplasm (MCN), an adenoma that shows extraordinarily high prevalence in women. Further study on the pathogenesis of MCN in male patients should be undertaken to elucidate the process of development.

Adult↗

Stenting of a left main coronary artery dissection and stent-graft implantation for acute type a aortic dissection.

PURPOSE: To report successful endovascular repair of Stanford type A acute aortic dissection associated with a proximally extended dissection of the left main coronary artery. CASE REPORT: A 71-year-old man presented with acute type A aortic dissection. One day after admission, dissection of the left main coronary artery accompanied by severe myocardial ischemia prompted Palmaz stent placement. Three days later, a customized stent-graft was placed across the entry site of the dissection in the descending aorta. The false lumen in the ascending aorta, transverse arch, and the descending thoracic aorta thrombosed, and the left coronary artery remained patent. At 14 months after the procedures, the patient is doing well and has had no cardiac event. CONCLUSIONS: This staged procedure may be one option for the management of acute type A aortic dissection complicated by coronary artery dissection.

Acute Disease↗

Evaluation of a quantitative method for trace impurities in arsenous acids by synchrotron radiation X-ray fluorescence spectrometry and inductively coupled plasma-atomic emission spectrometry.

Thirteen arsenous acid samples of known origins and refining methods were collected. Each sample was subjected to quantitative analysis of any impurity elements present using synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) and inductively coupled plasma-atomic emission spectrometry (ICP-AES). The trace elements selected were Sn, Sb and Bi for the reasons that they were considered not to be changed by their circumstances and that they showed high sensitivity to SR-XRF. These results obtained by both methods were compared and the correlation between these two methods was determined. The quantification of trace impurities obtained by SR-XRF using As as an internal standard showed good agreement with the results obtained by ICP-AES. The discrimination of refining method became possible by the comparison of these impurities' contents measured with non-destructive SR-XRF using several arsenous acid particles.

Journal Article↗

Nondestructive analysis of silver in gold foil using synchrotron radiation X-ray fluorescence spectrometry.

Small particles of gold foil detached from an indoor decoration might be important evidence to associate a suspect with a crime scene. We have investigated the application of elemental analysis using synchrotron radiation X-ray fluorescence spectrometry to discriminate small particles of gold foil. Eight kinds of gold foil samples collected in Japan were used in the experiments. As a result of synchrotron radiation X-ray fluorescence spectrometry, only two elements, gold and silver, were detected from all gold foil samples. The intensity ratios of AgKalpha/AuLalpha showed good correlation with the content ratios of Ag/Au. The variation of intensity ratio within a same sample was sufficiently small compared with those of different samples. Therefore the comparison of this intensity ratio can be an effective method to discriminate small particles originating from different types of gold foil.

Journal Article↗

Forensic discrimination of sheet glass by a refractive-index measurement and elemental analysis with synchrotron radiation X-ray fluorescence spectrometry.

Measurements of the refractive index (RI) and elemental analysis using synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) were applied to the forensic discrimination of sheet-glass samples from different origins. The refractive index was calculated from the matching temperature at which the glass fragments became invisible in silicone oil. Fragments smaller than 1 mm in maximum diameter were taken from each of 11 sheet glasses and subjected to analysis by SR-XRF. The XRF spectrum of these samples indicated that a comparison of 6 elements (Ca, Fe, Sr, Zr, Ba and Ce) was useful for the discrimination of sheet glasses. Cluster analysis was performed using 33 sets of SR-XRF data obtained by triplicate measurements for the 11 glasses. Comparing 528 pairs among 33 samples, 515 pairs could be correctly discriminated. The number of indistinguishable pairs could be reduced from 36 to 4 by comparing the SR-XRF data. Elemental analysis by SR-XRF could provide small glass fragments with a more evidential value than the solely measurement of only RI, through a significant improvement of the discrimination capability.

Journal Article↗