Search PubMed⌕ Search

Biomedical subjects

Y Sakaguchi

Publications and source records attributed to Y Sakaguchi.

At least 37 records · Page 2Linked to original sources

[Neuraxial blockade using image intensifier in patients after spinal instrumentation].

There is scant information in the literature regarding central neuraxial blockade in patients with previous back surgery or severe kyphoscoliosis. This report describes a 58-year-old female and an 84-year-old female with spinal instrumentation who presented for orthopedic surgery under neuraxial blockade. In both cases, multiple attempts of needle insertion using standard technique were unsuccessful, whereas spinal combined with epidural anesthesia was performed successfully using image intensifier. The anatomical considerations and difficulties in achieving reliable neuraxial blockade after spinal instrumentation are reviewed. Neuraxial blockade using image intensifier may provide less technical difficulty and a more reliable result in such patients.

Aged↗

Crystallization and preliminary X-ray studies of the Ia component of Clostridium perfringens iota toxin complexed with NADPH.

A recombinant Ia component of Clostridium perfringens iota toxin, which ADP-ribosylates actin, was crystallized by the hanging drop vapor diffusion method using PEG4000 as a precipitating agent. The crystals were obtained in the presence of NADPH, which is similar to a real substrate, NADH, and belongs to the space group P1 (a = 47.9 A, b = 54.5 A, c = 103.1 A, alpha = 99.0 degrees, beta = 93.3 degrees, and gamma = 107.2 degrees ). The Matthews coefficient of native crystal was 2.7, assuming 2 mol/asymmetric unit. Native data were collected at 2.4-A resolution. The results from a heavy-atom search showed that lanthanide ions (samarium, holmium) altered the molecular packing, judging from the unit-cell difference. The crystals also belonged to the space group P1 (a = 47.7 A, b = 53.9 A, c = 54.6 A, alpha = 68.9 degrees, beta = 78.3 degrees, and gamma = 73.7 degrees ), which is consistent with only one molecule per asymmetric unit.

ADP Ribose Transferases↗

Clostridium perfringens beta-toxin is sensitive to thiol-group modification but does not require a thiol group for lethal activity.

The beta-toxin gene isolated from Clostridium perfringens type B was expressed as a glutathione S-transferase (GST) fusion gene in Escherichia coli. The purified GST-beta-toxin fusion protein from the E. coli transformant cells was not lethal. The N-terminal amino acid sequence of the recombinant beta-toxin (r toxin) isolated by thrombin cleavage of the fusion protein was G-S-N-D-I-G-K-T-T-T. Biological activities and molecular mass of r toxin were indistinguishable from those of native beta-toxin (n toxin) purified from C. perfringens type C. Replacement of Cys-265 with alanine or serine by site-directed mutagenesis resulted in little loss of the activity. Treatment of C265A with N-ethylmaleimide (NEM), which inactivated lethal activity of r toxin and n toxin, led to no loss of the activity. The substitution of tyrosine or histidine for Cys-265 significantly diminished lethal activity. In addition, treatment of C265H with ethoxyformic anhydride which specifically modifies histidyl residue resulted in significant decrease in lethal activity, but that of r toxin with the agent did not. These results showed that replacement of the cysteine residue at position 265 with amino acids with large size of side chain or introduction of functional groups in the position resulted in loss of lethal activity of the toxin. Replacement of Tyr-266, Leu-268 or Trp-275 resulted in complete loss of lethal activity. Simultaneous administration of r toxin and W275A led to a decrease in lethal activity of beta-toxin. These observations suggest that the site essential for the activity is close to the cysteine residue.

Amino Acid Sequence↗

Structural analysis of human SCC antigen 2 promoter.

The squamous cell carcinoma antigen (SCCA) has been used as a circulating tumor marker for the management of squamous cell carcinoma. SCCA consists of a small gene family of at least two in human genome (SCCA1 and SCCA2), which are tandemly arrayed on chromosome 18q21.3 and share 92% identical residues. SCCA expressions are tightly controlled in a tissue-specific manner. To investigate the role of SCCA2 in the cancer cells, we first isolated the human genomic clones, containing the promoter region of SCCA2 gene, and determined the nucleotide sequence surrounding the exon 1. The transcription start site was mapped by primer extension analysis, and a putative TATA box element was found in the 5'-flanking region. Other putative regulatory sequences, which include Ets binding sequence, NF-IL6 binding sequence and IRE consensus sequence, were also found in the region. Analysis of luciferase reporter gene expression in transient transfection showed that the promoter region of SCCA2 gene was located within the region from -424 to +47.

Antigens, Neoplasm↗

Sequence analysis of a cryptic plasmid from Flavobacterium sp. KP1, a psychrophilic bacterium.

A cryptic plasmid found at high copy number was isolated from Flavobacterium sp. KP1, a psychrophilic Gram-negative bacterium, cloned, and sequenced. The sequence will appear in the DDBJ/EMBL/GenBank databases under the accession number AB007196. The pFL1 plasmid is 2311 nucleotides in length with 32.7% GC content, and shows a distinctive nucleotide sequence without homology to other plasmids of similar length. The plasmid contains two open reading frames of significant length, ORFI and ORFII. ORFI encodes a protein similar to the replication proteins found in Gram-negative bacterial plasmids, Bacteroides fragilis plasmid pBI143 and Zymomonas mobilis plasmid pZM2. The putative translation product of ORFII shows homologies with plasmid recombination proteins found mainly in Gram-positive bacterial plasmids such as Staphylococcus aureus plasmid pT181.

Amino Acid Sequence↗

Identification of squamous cell carcinoma antigen-2 in tumor tissue by two-dimensional electrophoresis.

The aim of this study was to identify two homologous serine proteinase inhibitor (serpin) molecules, squamous cell carcinoma (SCC) antigen-1 and -2, by two-dimensional electrophoresis (2-DE), combined with immunoblotting, and examine their expression in tumor tissue. The recombinant SCC (rSCC) antigen-1 showed four spots with p/ 6.5, 6.4, 6.3 and 6.0, whereas rSCC antigen-2 showed a more acidic spot with p/5.95. SCC antigen in tumor tissue appeared in three new acidic spots (p/5.7-5.5, M(r) 44 500), numbered 5, 6 and 7, besides the previously reported four spots numbered 1 to 4. These new acidic spots of SCC antigen apparently increased in SCC tissue. Treatment of tissue extract by carboxymethyl (CM)-papain agarose matrix extinguished spots 1 to 4 encoded on the SCCA1 gene, but not 5 to 7 on the SCCA2 gene. Overexpression of the SCCA2 gene may play an important role in the malignant behavior of tumor cells.

Antigens, Neoplasm↗

A case of eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma.

This report describes a patient with eosinophilic myocarditis complicated by Kimura's disease (eosinophilic hyperplastic lymphogranuloma) and erythroderma. A 50-year-old man presented with a complaint of precordial pain. However, the only abnormal finding on examinatioin was eosinophilia (1617 eosinophils/microl). Three years later, the patient developed chronic eczema, and was diagnosed with erythroderma posteczematosa. One year later, a tumor was detected in the right auricule, and a diagnosis of Kimura's disease was made, based on the biopsy findings. The patient developed progressive dyspnea 6 months later and was found to have cardiomegaly and a depressed left ventricular ejection fraction (17%). A diagnosis of eosinophilic myocarditis was made based on the results of a right ventricular endomyocardial biopsy. The eosinophilic myocarditis and erythrodrema were treated with steroids with improvement of both the eosinophilia and left ventricular function.

Angiolymphoid Hyperplasia with Eosinophilia↗

Assessment of long-distance running performance in elite male runners using onset of blood lactate accumulation.

The purpose of this study was to evaluate the relationship between onset of blood lactate accumulation (OBLA) and long-distance running performance in order to examine whether OBLA can be a good predictor of long-distance running performance even in elite male runners with similar performance levels. Eleven highly-trained male long-distance runners participated in this study. The average running velocities of the individuals' running performance were 5.918 +/- 0.084 m.s-1 and 5.672 +/- 0.095 m.s-1 for 5000 m (V5000) and 10,000 m (V10000), respectively. The blood lactate concentrations and heart rate responses were measured immediately after field running, and the average value of running velocity corresponding to OBLA (VOBLA) was 5.447 +/- 0.132 m.s-1. Variations of these three velocities expressed as a coefficient of variance (CV) ranged from 1.4 to 2.4%. A strong inverse relationship between heart rate corresponding to OBLA (HROBLA) and performance was observed (r = -0.709, p < 0.02 for V5000 and r = -0.830, p < 0.01 for V10000), while there was a lack of significant relationship between VOBLA and performance (r = 0.293, NS for V5000 and r = 0.130, NS for V10000). Furthermore, the average value of HROBLA obtained in this study (174.5 +/- 8.2 b.min-1) was quite similar to that of the heart rate threshold reported by some previous researchers. In conclusion, VOBLA alone could not explain the small variation of long-distance running performance, and HROBLA should be used in place of VOBLA for evaluating long-distance running performance in elite runners with quite similar performance levels.

Adult↗

[An elderly case of triple-vessel coronary artery disease with alternating bundle branch blocks in serial electrocardiograms].

An 82-year-old woman was admitted with severe chest pain and orthopnea on January 17, 1997. Physical examination revealed bilateral leg edema and cyanosis at the periphery of the extremities. The serum CK level was 488 IU/l on admission and increased to a maximum value of 4,866 IU/l 8 hours after admission. An echocardiogram demonstrated diffuse severe hypokinesis in the left ventricle. Serial electrocardiograms showed transient right bundle branch block, left bundle branch block, and normal sinus rhythm. The patient was diagnosed as having congestive heart failure. Artificial ventilation was performed, and furosemide, isosorbide dinitrate and dopamine were administered. A right ventricular endomyocardial biopsy performed on the 13th hospital day demonstrated moderate hypertrophy and disparity of cardiac myocytes and fibrosis around the myocytes, and few inflammatory cells in the specimens. This biopsy finding was not compatible with acute myocarditis but with the chronic stage of myocarditis. The patient was discharged on the 45th hospital day, but returned because of a recurrence of congestive heart failure. After an improvement of the heart failure, a coronary angiography was performed on the 20th hospital day. The coronary angiography revealed significant stenosis in three vessels. This elderly patient had congestive heart failure and triple-vessel coronary artery disease with transient alternating bundle branch blocks on serial electrocardiograms. Alternating bundle branch blocks and diffuse left ventricular dysfunction was considered to be induced by the aging process, postmyocarditic change of myocytes, and triple-vessel coronary artery disease in this case.

Aged↗

Serum levels of VEGF and basic FGF in the subacute phase of myocardial infarction.

We examined serial changes in serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) measured by ELISAs in 45 patients with acute myocardial infarction (AMI) who received heparin intravenously for 3 to 5 days after the onset and in 30 control subjects with an old myocardial infarction. To evaluate the effect of heparin on these serum levels, heparin was administered intravenously in 10 patients with AMI on day 21. Blood samples were obtained from all AMI patients on days 1, 2, 3, 7, 14, 21, and 28 and from 10 AMI patients before and 1 h after heparin administration. Serum VEGF level was significantly reduced after heparin administration (P<0.001). Serum samples from day 1 to 3 were therefore excluded from the subsequent analysis. Serum VEGF level in AMI patients was significantly higher on day 7 than in the control subjects (P<0.0001), and then decreased over time (P<0.0001). The serum VEGF level on day 7 was independently associated with the peak serum CK level (P<0.05). The serum bFGF level did not differ significantly between the AMI patients and the control subjects. In conclusion, the serum VEGF level may be selectively elevated during the healing process after AMI.

Anticoagulants↗

Vertebral osteomyelitis: an analysis of 38 surgically treated cases.

The purpose of the study was to evaluate the characteristics of patients with vertebral osteomyelitis who were treated by anterior debridement and interbody fusion. Thirty-eight patients with vertebral osteomyelitis, who were treated between 1980 and 1993, were analyzed in terms of age at the occurrence of disease, duration of disease, type of onset symptoms, radiological type of vertebral destruction, species of pathogen, and surgical result. Thirty-one out of 38 patients (82%) were more than 40 years of age. The patients with severe vertebral destruction were significantly older than those with mild vertebral destruction. Vertebral destruction in the thoracic spine was significantly more severe than that in the lumbar spine. Staphylococcus aureus was identified in only six patients (32% of organism-determined cases). In the present patients who required anterior debridement and bone grafting for this disease, the prognosis was quite good after anterior interbody fusion in conjunction with antibiotics therapy.

Adolescent↗

Induction of apoptosis in human tumour xenografts after oral administration of uracil and tegafur to nude mice bearing tumours.

Various types of anti-neoplastic agents induce apoptosis in vitro, but less is known of the role of this mode of cell death in tumours treated in vivo. We examined the induction of apoptosis by oral anti-neoplastic agents, tegafur and uracil (UFT, a combined preparation of 1 mol tegafur and 4 mol uracil), and the relationship of effects on tumour growth. Seven different human gastrointestinal tumour xenografts were transplanted into nude mice, including two colon adenocarcinomas (KM20C and Col-1), three gastric carcinomas (SC-6, St-40 and 4-1ST) and two pancreatic carcinomas (PAN-4 and PAN-12), followed by oral administration of UFT (24 mg kg(-1) day(-1)) for 9 days. The percentage of apoptotic cells in each tumour was scored in histological sections, chronologically, using a molecular biological-histochemical system and growth inhibition was examined in each tumour. A significant growth inhibition by UFT was observed for all tumours, except PAN-12. In KM20C and SC-6, growth inhibition rates were 61.7% and 60.6% respectively. Quantitative assay for apoptosis showed a remarkable induction of apoptosis in KM20C (4.2%) and SC-6 (3.5%), which were relatively sensitive to UFT. In addition, KM20C and SC-6 showed a higher incidence of spontaneous apoptosis. In five other tumours, which responded to a lesser extent than KM20C and SC-6, UFT altered little the changes in apoptosis (less than 2%) and spontaneous apoptosis was relatively low. Thus, tumours with a higher apoptosis induced by UFT had a higher response to UFT. Apoptosis observed in tumours might serve as a predictor of a preferable response to UFT.

Animals↗

A possible increase in plasma norepinephrine by removal of the liver.

BACKGROUND: It has recently been suggested that the human liver plays an important role in clearing plasma norepinephrine, especially in restricting most of the norepinephrine to reach the systemic circulation from the gut. METHODS: We examined the changes in plasma catecholamine levels in a patient undergoing extracorporeal hepatic resection and 4 patients undergoing living-related orthotopic liver transplantation. RESULTS: While the changes in plasma epinephrine levels were not necessarily consistent with the proposal that plasma catecholamine levels increase during the anhepatic period, plasma norepinephrine did show a transient increase in accordance with the anhepatic period in all cases. Although we could not rule out the increase in the inflow rate of norepinephrine into plasma, the interrupted hepatic elimination of norepinephrine, especially released from the gut, seemed to be partly responsible for the anhepatic period-associated increase in plasma norepinephrine. CONCLUSION: The present finding might have the potential to improve perioperative management of patients undergoing extracorporeal hepatic resection and orthotopic liver transplantation.

Adrenergic Agonists↗

Apical hypertrophy with massive myocardial fibrosis: comparison with electrocardiographic changes.

We report the case of a 48-year-old woman with apical hypertrophy with massive myocardial fibrosis. She was admitted to our hospital because of general malaise. Echocardiographic examination showed asymmetrical apical hypertrophy, and an electrocardiogram showed a giant negative T wave on V3-V6. Right ventricular endomyocardial biopsy revealed massive myocardial fibrosis. Apical hypertrophy can lead to disorders that vary in severity, including rare massive myocardial fibrosis.

Biopsy↗

Electrophysiological effects of MS-551, a new class III agent: comparison with dl-sotalol in dogs.

MS-551 is a newly synthesized, nonspecific K+ channel blocker. To elucidate its electrophysiological and potential proarrhythmic effects relative to those of dl-sotalol in vivo, serial changes in ECGs, endocardial and epicardial monophasic action potential durations, and left and right ventricular pressures were measured simultaneously in pentobarbital-anesthetized open-chest dogs. Complete heart block was produced by the injection of 37% formaldehyde into the atrioventricular node. Intravenous administration of MS-551 produced prolongation of action potential duration at 90% repolarization time (APD90) immediately after the beginning of infusion and reached plateau at 10 min. MS-551 (1 mg/kg) caused 73 +/- 8% increase in APD90 and 28 +/- 5% increase in QTc at basic cycle length of 700 msec. The maximal prolongation of APD90 induced by 1 mg/kg MS-551 was 39% greater than that by the same dose of sotalol (P < .01). The dose-response curve of prolongation of ventricular effective refractory period produced by MS-551 was shifted significantly to the left compared with that induced by sotalol. The EC50 was 0.5 +/- 0.1 mg/kg and 1.2 +/- 0.2 mg/kg for MS-551 and sotalol, respectively (P < .05). When 0.5 mg/kg MS-551 doses were used, no ventricular arrhythmia was induced by stimulation at 200-msec basic cycle length. When 1.5 mg/kg sotalol was administered, 5 of 15 developed torsade de pointes, 2 of 15 developed ventricular fibrillation and 5 of 15 developed sustained ventricular tachycardia. The idioventricular rates and left ventricular pressures were reduced significantly by sotalol, not by MS-551. In conclusion, MS-551 is a potent class III antiarrhythmic agent that selectively prolongs repolarization in the ventricular myocardium and appears to be devoid of autonomic effects. Dose for dose, it is more potent in prolonging the APD90 and the right ventricular effective refractory period possibly with a lower tendency for the development of proarrhythmia in a canine heart-block model.

Action Potentials↗

Mechanism of cardiac involvement in the WBN/Kob rat.

The cardiac characteristics of the WBN/Kob rat resemble those of rats with catecholamine-induced myocarditis. To determine the etiology of these WBN cardiac characteristics, we assessed the number and affinity of beta-adrenergic receptors, and investigated adenylate cyclase activity, the cardiac myocyte cyclic adenosine monophosphate (cAMP) concentration and the activity of guanosine triphosphate (GTP)-binding protein in 3-month-old WBN/Kob rats. Age-matched Wistar rats served as controls. The mean number of beta-adrenergic receptors was similar in WBN/Kob and Wistar rats (28.0+/-9.1 v 28.3+/-8.9 fmol/mg protein), and there was no significant difference in beta-adrenergic receptor affinity between groups (1.09+/-0.54 v 1.26+/-0.60 nM). The mean cAMP concentration in cardiac myocytes was significantly higher in WBN/Kob rats than in Wistar rats 1975.6+/-247.8 v 344.9+/-83.6 pmol/g wet tissue), (P=0.0112) as was adenylate cyclase activity (33.61+/-8.32 v 24.3+/-12.78 pmol/mg/min), (P=0.0174). The activity of GTP-binding protein was significantly higher in WBN/Kob rats than in Wistar rats. After a beta-agonist binds to a beta-adrenergic receptor, activated adenylate cyclase produces cAMP in myocytes, which in turn opens the Ca2+ channel, leading to an influx of Ca2+ into myocytes. Our results suggest that the increase in adenylate cyclase activity in WBN/Kob rats have led to an increase in the cAMP concentration in myocytes. This process may have resulted in excessive beta-adrenergic activity due to high activity of GTP binding protein in WBN/Kob rats, which may explain the hypersensitivity of WBN/Kob rats to isoproterenol and the development of catecholamine-induced myocarditis.

Adenylyl Cyclases↗