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Biomedical subjects

Y Saitoh

Publications and source records attributed to Y Saitoh.

At least 163 records · Page 9Linked to original sources

[Diagnosis of inflammatory myopathy; usefulness of 99mTc MDP scintigraphy and muscle MRI for determination of affected sites].

We studied the effectiveness of 99mTc-MDP (methylendiphosphate) scintigraphy in imaging inflammatory myopathy. The three subjects including 1 male and 2 female patients had high creatine kinase (CK) levels and proximal dominant muscle weakness. In whole body muscle surveillance by 99mTc-MDP scintigraphy, abnormal 99mTc-MDP accumulation was found in the extremities of all patients. The sites with high 99mTc-MDP accumulation showed high intensity on T2 weighted MR imaging, suggesting an inflammatory process. Muscle biopsy was performed on two patients from the muscles with the abnormal MRI findings, which showed the diagnostic finding of inflammatory changes. Because muscle involvement in inflammatory myopathy differs from muscle to muscle, it is sometimes difficult to choose appropriate muscle biopsy sites for diagnostic purposes. Affected muscles are more easily identified by using 99mTc-MDP muscle scintigraphy and muscle MRI, therefore, a correct diagnosis and choice of biopsy site can be made. 99mTc-PYP scintigraphy is permitted for use in myocardial infarction alone and 111In-antimyosin scintigraphy is not available in Japan. Therefore, we recommend 99mTc-MDP scintigraphy for diagnosis of inflammatory myopathy and for determination of muscle biopsy sites.

Adolescent↗

Human megasatellite DNA RS447: copy-number polymorphisms and interspecies conservation.

We previously isolated a novel 4.7-kb RS447 sequence, which tandemly repeated approximately 50-70 copies and resided on human chromosome 4p15 (M. Kogi et al., 1997, Genomics 42: 278-283). Another tandem array (or arrays) of several RS447 copies was hereby identified on the distal part of chromosome 8p. To analyze copy-number polymorphisms of the RS447 repeats, genomic DNA samples of eight nonkindred Japanese were subjected to pulsed-field gel electrophoresis. The copy numbers of the RS447 tandem arrays on 4p15 varied drastically from allele to allele and ranged from approximately 34 to 94 copies. All eight Japanese subjects were apparently heterozygous for the RS447 copy number, and 12 copy-number-different alleles have been at least clearly distinguished. The RS447 tandem repeats were thus found to be hypervariable and highly polymorphic in a human population. The RS447 sequences, however, do not appear to be either "selfish" or "junk" DNA. The unit size and sequence of RS447 were found to be very similar between members in the human genome. The unit size of 4746 bp comprises a putative open reading frame of 1590 bp. The RS447 sequence was well conserved in all the tested mammalian species. The head-to-tail tandem repetitive structure in the RS447 homologs was also confirmed in those species. The RS447 sequence is, therefore, considered to consist of a new class of tandemly repeated satellite DNA elements in the mammalian genome, which may thus be called "megasatellite DNA."

Animals↗

Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors.

Vesl-1S (186 amino acids, also called Homer) is a protein containing EVH1- and PDZ-like domains whose expression in the hippocampus is regulated during long term potentiation (LTP), one form of synaptic plasticity thought to underlie memory formation (Kato, A., Ozawa, F., Saitoh, Y., Hirai, K., and Inokuchi, K. (1997) FEBS Lett. 412, 183-189; Brakeman, P. R., Lanahan, A. A., O'Brien, R., Roche, K., Barnes, C. A., Huganir, R. L., and Worley, P. F. (1997) Nature 386, 284-288). Here we report additional members of the Vesl/Homer family of proteins, Vesl-1L and Vesl-2. Vesl-1L (366 amino acids), a splicing variant of Vesl-1S, shares N-terminal 175 amino acids with Vesl-1S and contains additional amino acids at the C terminus. Vesl-2 (354 amino acids) was highly related to Vesl-1L in that both contain EVH1- and PDZ-like domains at the N terminus (86% conservation) and an MCC (mutated in colorectal cancer)-like domain and a leucine zipper at the C terminus. In contrast to vesl-1S, we observed no changes in the levels of vesl-1L and vesl-2 mRNAs during dentate gyrus LTP. All these proteins interacted with metabotropic glutamate receptors (mGluR1 and mGluR5) as well as several hippocampal proteins in vitro. Vesl-1L and Vesl-2, but not Vesl-1S, interacted with each other through the C-terminal portion that was absent in Vesl-1S. Vesl-1L and Vesl-2 may mediate clustering of mGluRs at synaptic junctions. We propose that Vesl-1S may be involved in the structural changes that occur at metabotropic glutamatergic synapses during the maintenance phase of LTP by modulating the redistribution of synaptic components.

Amino Acid Sequence↗

Dose-dependent doxycycline-mediated adrenocorticotropic hormone secretion from encapsulated Tet-on proopiomelanocortin Neuro2A cells in the subarachnoid space.

We previously reported that polymer-encapsulated mouse neuroblastoma cells that are capable of secreting beta-endorphin may reduce pain sensitivity in rats after capsule implantation into the cerebrospinal fluid (CSF)-filled subarachnoid space of the spinal cord. The neuroblastoma cells carry the proopiomelanocortin (POMC) gene that encodes the precursor of adrenocorticotropic hormone (ACTH) and beta-endorphin. To control the expression of these hormones in the present study, a promoter that is inducible by administration of tetracycline derivatives such as doxycycline (Dox) was linked to the POMC gene. Encapsulated cells in the CSF space of rats stimulated by four intraperitoneal doses of Dox responded with ACTH expression as determined in a subsequence 36-hr in vitro incubation. The amount of ACTH released was dependent on the in vivo Dox dose. These findings indicate that gene expression in xenogeneic cells in the CSF space can be manipulated by injection of a relatively innocuous drug, and suggest that this system may be applicable to cell transplantation therapy in patients with central nervous system diseases that require temporary control of ligand delivery.

Adrenocorticotropic Hormone↗

Twin helical undulator beamline for soft X-ray spectroscopy at SPring-8.

A very high resolution soft X-ray beamline, BL25SU, has been designed and is under construction at SPring-8. Completely right or left circularly polarized light is supplied on a common axis of a newly designed twin helical undulator. A helicity modulation up to 10 Hz can be performed using five kicker magnets. The fundamental radiation covers the region 0.5-3 keV. Higher-order radiation is rather weak on the axis. A monochromator with varied-line-spacing plane gratings is installed to cover the region below 1.5 keV. A very high resolution beyond 10(4) is expected for the whole energy region.

Journal Article↗

Characterization and interpretation of the quantum efficiencies of multilayer semiconductor detectors using a new theory.

On the basis of a new theory of semiconductor X-ray detector response, a new type of multilayer semiconductor detector was designed and developed for convenient energy analyses of intense incident X-ray flux in a cumulative-current mode. Another anticipated useful property of the developed detector is a drastic improvement in high-energy X-ray response ranging over several hundred eV. The formula for the quantum efficiency of multilayer semiconductor detectors and its physical interpretations are proposed and have been successfully verified by synchrotron radiation experiments at the Photon Factory. These detectors are useful for data analyses under strong radiation-field conditions, including fusion-plasma-emitting X-rays and energetic heavy-particle beams, without the use of high-bias applications.

Journal Article↗

Construction of the JAERI soft X-ray beamline for actinide material sciences.

An undulator beamline for spectroscopy studies focusing on the electronic structure of actinide materials is under construction. Linearly or circularly polarized soft X-rays are provided by employing a variably polarizing undulator. Varied-line-spacing plane gratings and a sagittal-focusing system are used to monochromatize the undulator beam, whose energy ranges from 0.3 to 1.5 keV. A resolving power of 10(4) is expected in the whole energy region. These components are methodically operated by the SPring-8 beamline control system. There are three experimental stations in the beamline. In one of the stations the photoemission spectroscopy experiments are carried out at a radioisotope-controlled area where actinide compounds as well as unsealed radioactive materials are usable. Other experimental stations are planned in the beamline for surface photochemical reactions and biological applications.

Journal Article↗

Soft X-ray beamline specialized for actinides and radioactive materials equipped with a variably polarizing undulator.

This report presents the design of an undulator beamline at SPring-8 to be used for soft X-ray spectroscopy focused on radioactive materials. Photoemission spectroscopy experiments are carried out in a radioisotope (RI)-controlled area where actinide compounds as well as unsealed radioactive materials are usable. Intrusion of the radioactive materials into the electron storage ring or to the outside of the evacuated beamline components can be avoided by a specially devised RI protection/inspection mechanism. The combination of a variably polarizing undulator and a varied-line-spacing plane-grating monochromator provides linearly or circularly polarized soft X-rays with a high resolving power in the energy range 0.28-1.5 keV. The beamline will become operational in December 1997.

Journal Article↗

Identification of allelic loss on chromosome arm 6p in human astrocytomas by arbitrarily primed polymerase chain reaction.

We employed the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting technique, to detect novel genetic alterations in human astrocytomas. DNA fingerprints generated by arbitrary primers were compared in normal lymphocytes and tumor tissues from the same individuals. We cloned and sequenced an AP-PCR band showing a greatly decreased intensity in tumor tissue DNA, relative to normal. Southern blot showed that this sequence was homozygously deleted in the tumor cell genome. Semiquantitative PCR analysis further showed significant decreases of signals in seven of 24 tumors, consistent with homozygous deletion of this sequence. The deleted sequence was localized to chromosome region 6p21.1 by the fluorescence in situ hybridization method. Microsatellite analysis also showed frequent allelic loss of this locus compared to neighboring loci in astrocytoma tissues. These results suggest the presence of a novel tumor suppressor gene at the 6p21.1 locus.

Alleles↗

Percutaneous isolated liver chemoperfusion for treatment of unresectable malignant liver tumors: technique, pharmacokinetics, clinical results.

We have developed a single-catheter technique for percutaneous isolated liver chemoperfusion (PILP) with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) for the treatment of malignant liver tumors. We report here the surgical technique, pharmacokinetics, and effectiveness of PILP in multiple advanced liver tumors. Twenty-eight patients with hepatocellular carcinoma (HCC) and 18 with metastatic liver tumors underwent a total of 61 PILPs with HVI-CHP. HVI-CHP was accomplished mainly by the single-catheter technique using a novel four-lumen, two-balloon catheter; it was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. Under HVI-CHP, either doxorubicin 960-150 mg/m2) or cisplatin (150-200 mg/m2) was infused via the hepatic artery. The PILP was completed successfully in all 61 trials. Two of forty-six patients died early; one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Excluding these two deaths, the treatments were well tolerated. The major side effects were mild to moderate chemical hepatitis and reversible myelosuppression. Of the 27 evaluable HCC patients, 17 (63%) had an objective tumor response (5 complete and 12 partial responses). In 15 patients with colorectal hepatic metastases (CHM), 7 had a sharp decrease in serum carcinoembryonic antigen (CEA) levels (to < 50% of their pretreatment levels) after treatment. However, a single PILP had limited efficacy in terms of the durability of remission (< or = 6 months in most CHM patients, as assessed by CEA levels). These results indicate that PILP with HVI-CHP has high efficacy in most patients with multiple advanced liver tumors. In addition, the results suggest a role of multiple treatment courses of PILP in the induction of long-term remission, especially for patients responsive to the first treatment.

Antineoplastic Agents↗

Diltiazem-lidocaine combination for the attenuation of cardiovascular responses to tracheal intubation in hypertensive patients.

PURPOSE: Hypertensive patients are prone to haemodynamic changes after laryngoscopy and tracheal intubation. This study was undertaken to compare the efficacy of a combination of diltiazem and lidocaine with that of each drug alone for suppressing the cardiovascular responses to tracheal intubation. METHODS: Sixty hypertensive patients (ASA II), defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg (World Health Organization), undergoing elective surgery received, in a randomized, double-blind manner, 0.3 mg.kg-1 diltiazem, 1.5 mg.kg-1 lidocaine, or 0.3 mg.kg-1 diltiazem plus 1.5 mg.kg-1 lidocaine i.v. (n = 20 of each) before the initiation of laryngoscopy. Anaesthesia was induced with 5 mg.kg-1 thiopentone i.v., and tracheal intubation was facilitated with 2 mg.kg-1 succinylcholine i.v. after precurarization with 0.02 mg.kg-1 vecuronium i.v. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and at immediate, 1, 2, 3, 5 and 10 min after tracheal intubation. RESULTS: The inhibitory effects of diltiazem-lidocaine combination on cardiovascular responses to tracheal intubation was greater than those of diltiazem or lidocaine as a sole medicine (RPP; 10,602 +/- 1448 (combination) vs 11,787 +/- 1345 (diltiazem), 15,428 +/- 1756 (lidocaine), mean +/- SD, P < 0.05). CONCLUSION: Prophylactic therapy with diltiazem-lidocaine combination is more effective than diltiazem or lidocaine alone for attenuating the cardiovascular changes associated with tracheal intubation in hypertensive patients.

Aged↗

Prophylactic antiemetic therapy with granisetron-droperidol combination in patients undergoing laparoscopic cholecystectomy.

PURPOSE: A relatively high incidence of postoperative nausea and vomiting (PONV) occurs in patients undergoing laparoscopic cholecystectomy. This study was undertaken to compare the efficacy of granisetron-droperidol combination with each drug alone for the prevention of PONV after laparoscopic cholecystectomy. METHODS: In a randomized, double-blind manner, 150 female inpatients received 3 mg granisetron (Group G), 1.25 mg droperidol (Group D) or 3 mg granisetron plus 1.25 mg droperidol (Group GD)(n = 50 for each) i.v. immediately before the induction of anaesthesia. The same standard general anaesthetic technique, which consisted of isoflurane and nitrous oxide in oxygen, was used. Nausea, vomiting and safety assessments were performed continuously during the first 24 hr after anaesthesia. RESULTS: Complete response, defined as no PONV and no administration of rescue antiemetic medication, was 86% in Group G, 64% in Group D and 98% in Group GD (P = 0.03 vs Group G, P = 0.001 vs Group D). No clinically adverse events were observed in any group. CONCLUSION: Granisetron-droperidol combination is more effective than each antiemetic alone in the prevention of PONV after laparoscopic cholecystectomy.

Adult↗

Prevention of PONV with granisetron, droperidol or metoclopramide in patients with postoperative emesis.

PURPOSE: A high incidence of postoperative nausea and vomiting (PONV) has been noted in patients with a history of postoperative emesis. This study was undertaken to compare the efficacy of granisetron, droperidol and metoclopramide, in the prevention of PONV in such patients undergoing general anaesthesia for major gynaecological surgery. METHODS: In a randomised, double-blind study, 90 female patients received 2.5 mg granisetron, 1.25 mg droperidol or 10 mg metoclopramide (n = 30 of each) i.v. immediately before induction of anaesthesia. The same standard general anaesthetic technique, which consisted of isoflurane in nitrous oxide and oxygen, was used. Nausea, vomiting and safety assessments were performed continuously during the first 24 hr after anaesthesia. RESULTS: The incidence of PONV was 20% with granisetron, 57% with droperidol and 60% with metoclopramide (P < 0.05; overall Fisher's exact probability test). No clinically adverse events were observed in any group. CONCLUSION: Granisetron is more effective than droperidol or metoclopramide in preventing PONV in female patients with a history of postoperative emesis.

Adult↗

Cardiovascular responses to tracheal extubation or LMA removal in children.

PURPOSE: This study was designed to investigate the cardiovascular effects related to tracheal extubation or laryngeal mask airway (LMA) removal in children. METHODS: Sixty children, ASA physical status 1, 4-10 yr of age, undergoing minor elective surgery (inguinal hernia and phimosis) were allocated randomly to have their surgery performed with endotracheal intubation (Group ET, n = 30) or LMA (Group LMA, n = 30) and were studied for cardiovascular responses related to extubation or LMA removal. Changes in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before and 1, 2, 3, 5, and 10 min after tracheal extubation or LMA removal when the patients were awake. RESULTS: The maximal changes in HR, SBP and DBP were less in Group LMA than in Group ET during the observation period (HR; 12 vs 26, SBP; 14 vs 28, DBP; 9 vs 13, median, P < 0.05). CONCLUSION: Laryngeal mask airway removal elicited less haemodynamic change than tracheal extubation in paediatric patients.

Blood Pressure↗