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Biomedical subjects

S Ikeda

Publications and source records attributed to S Ikeda.

At least 415 records · Page 23Linked to original sources

[A case of post-radiation constrictive pericarditis developing 12 years after radiation therapy].

A 70-year-old woman underwent radical mastectomy for carcinoma of the left breast in 1982. Postoperative radiation therapy was given in a total dose of 50 Gy for parasternal and left subclavian nodes. Symptoms of heart failure such as exertional dyspnea, facial edema, and hepatomegaly manifested in 1992. Cardiac catheterization revealed marked elevation of mean right atrial pressure and right ventricular end-diastolic pressure. The pressure wave form of the right ventricle showed the so called "dip and plateau" feature. Pericardiectomy without using extracorporeal circulation was performed in 1994. Operative findings and pathological study results were compatible with radiation-induced constrictive pericarditis. She rapidly recovered from heart failure after this operation, and has done very well to date.

Aged↗

Efficacy of intraoperative blood salvage during coronary artery bypass grafting.

OBJECTIVE: To analyze the usefulness of autologous blood salvage and intraoperative isovolemic hemodilution in conjunction with autologous blood salvage in cardiac surgery, and also to compare two different autologous blood salvage methods. EXPERIMENTAL DESIGN: Retrospective analysis of transfusion practice in cardiac surgery. SETTING: University hospital. PATIENTS: One hundred and sixty two consecutive patients who had coronary artery bypass grafting (CABG) from January to September, 1993. INTERVENTIONS: A review of transfusion records of patients who underwent intraoperative autologous blood salvage and isovolemic hemodilution. MEASURES: Perioperative transfusion requirements were analyzed in patients undergoing CABG using a cell saver system whereby blood was collected, processed and reinfused to the patients in the operating room. RESULTS: Nineteen percent of patients did not receive perioperative homologous blood transfusion when a cell saver was used intraoperatively. When autologous isovolemic hemodilution was used in conjunction with a cell saver, fifty-four percent of the patients did not receive homologous blood transfusion. The results of this study were compared to matched patients undergoing CABG using a different type of cell saver system whereby blood was collected in the operating room, processed in the blood bank and reinfused in the intra- and/or postoperative period. We found that the former system provided a more timely and greater yield of blood salvaged and as a consequence, less homologous blood transfusion. CONCLUSIONS: Intraoperative blood salvaging provides an immediate source of red blood cells and decreases the utilization of homologous blood. In addition, isovolemic hemodilution in conjunction with blood salvage further decreases homologous blood transfusion needs.

Aged↗

[Correlation of cardiac muscle involvement and the dystrophin gene abnormality in Becker muscular dystrophy].

Cardiomyopathy is one of the most important clinical manifestations in Becker muscular dystrophy (BMD), but the severity of cardiac involvement is not usually related to that of skeletal muscle disability in this disease. In general, BMD patients who carry the mutations in the 5' end of the dystrophin gene tend to show severe cardiac dysfunction compared with skeletal myopathy, and these mutations may be responsible for more selective involvement of dystrophin appearance in the myocardium. In this article, we review the causative relationship of the variable clinical pictures and the dystrophin gene abnormalities in BMD patients, focusing on the severity of cardiac disorder.

Cardiomyopathy, Dilated↗

Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation.

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.

Adult↗

Change in ascorbate radical production in an irradiated experimental tumor with increased tumor size.

We have reported that ascorbate radical (Asc.-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc.- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc.- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc.- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc.- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc.- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

Amifostine↗

Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene.

Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Escherichia coli. Sequencing peptides spanning 63% of the native dCK subunit revealed a sequence identical to that deduced from dgk (beginning MTVIVL...), except that dCK lacks residues 2 and 3 (dCK is M..IVL; dGK is .TVIVL). Also, mass spectrometry indicates that native dCK and dGK subunits are identical in mass adjusted for the first three residues. Furthermore, the native enzymes have identical isoelectric pH values, indicating an equal number of charged residues. To enable E. coli to express peptide having the native dCK sequence, codons 2 and 3 were deleted from the dgk portion of the tandem genes, resulting in expression of protein having the specificities and regulatory properties of native dAK/dCK, including heterotropic stimulation of dAK activity by deoxycytidine or dCTP (not deoxyguanosine or dGTP) and end-product inhibition of the respective activities by dATP and dCTP. Subcloning normal and mutant dgk yielded homodimeric dGK and dCK, respectively. The dCK homodimer strongly resembles human dCK, with a low K(m) for deoxycytidine, the ability to phosphorylate deoxyadenosine and deoxyguanosine at much higher K(m) values, and end-product inhibition by dCTP. Thus two distinct and specific enzymes evidently are derived from a single Lactobacillus gene. The mechanism by which this occurs in vivo has yet to be elucidated.

Amino Acid Sequence↗

Fluorescence-based polymerase chain reaction-single-strand conformation polymorphism analysis of p53 gene by capillary electrophoresis.

Mutation of the p53 gene plays an important role in neoplastic progression in human tumorigenesis. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques are now available for the detection of point mutations. The original method using polyacrylamide gel electrophoresis is disadvantageous, particularly for clinical tests and for analysis of large numbers of samples. Therefore, using an automated capillary electrophoresis (CE) technique with a molecular-sieving polymer solution, we have devised a completely automatic fluorescence-based PCR-SSCP system (CE-FSSCP) for the differential detection of point mutations that dose not require SSCP with radioisotopes and polyacrylamide gels. The automatic CE-FSSCP system was developed for reproducible operations in the denaturation of double-stranded DNA and electrophoresis of single-stranded DNA. The detection system consists of a 100 W I2 lamp and photomultiplier. We performed CE-FSSCP with a 2% linear polyacrylamide polymer solution containing 5% glycerol. Four tissue specimens of lung tumors with mutations in exon 7 of the p53 gene were found to have mutant alleles; six-base-pair deletion at codons 247-248, a one-base-pair deletion at codon 260, a one-base-pair deletion at codon 244 and a GGC to CGC substitution at codon 244. We expect this technique to prove useful for the clinical DNA diagnosis of human cancers, determination of the therapeutic effect of anticancer agents and for the study of the molecular aspects of the mechanisms involved in the pathogenesis of human cancers.

Alleles↗

Amyloid beta protein and its 3-kDa fragment are present in the axoplasm fraction of the white matter in human brain.

Production of the soluble amyloid beta-protein (A beta) precedes abnormal accumulation of A beta amyloid in the brains of subjects with Alzheimer's disease. To determine the cellular source and generating mechanisms of soluble A beta in the human brain, we separated an axoplasm fraction from the cerebral white matter and analyzed it. The axoplasm fraction contained secretory isoforms of beta-amyloid precursor protein (APP) and 11.5 kDa A beta-bearing carboxyl-terminal fragments (CTFs) of APP. Furthermore, soluble 4 kDa A beta and 3 kDa fragments of A beta (p3) were obtained from the axoplasm fraction. These results suggest that amyloidogenic 4 kDa A beta is intracellularly produced in cerebral neurons and carried through the axons in human brain.

Aged↗

Effects of a new endothelin receptor antagonist, TAK-044, on myocardial stunning in dogs.

The effects of a new endothelin receptor antagonist, TAK-044, (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]L-alan yl-L-alpha aspartyl-D-2-(2-thienyl)glycyl-L-leucyl-D-tryptophyl]disodium salt, on ischemic and post-ischemic myocardial dysfunction (stunned myocardium) were studied in anesthetized open-chest dogs. A short (15 min) occlusion of the left anterior descending coronary artery followed by 5-h reperfusion significantly reduced myocardial segment shortening during and after the ischemic period in the ischemic region. Regional myocardial blood flow was also decreased significantly 10 min after the occlusion, whereas it returned almost completely to its pre-ischemic value 5 h after reperfusion TAK-044 (3 mg/kg,i.v.) administered 10 min before occlusion significantly improved the reduced myocardial segment shortening in the ischemic region during and after occlusion. Cardiovascular hemodynamics and regional myocardial blood flow in a TAK-044-treated group were identical to those in the control group. These results indicate that endogenous endothelin contributes to the cause of ischemic and post-ischemic myocardial dysfunction without changing either hemodynamics or regional myocardial blood flow.

Animals↗

An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.

SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.

Adult↗

Polyanion inhibitors of human immunodeficiency virus and other viruses. Part 2. Polymerized anionic surfactants derived from amino acids and dipeptides.

A series of new polyanions was synthesized via gamma-polymerization, in aqueous micellar solution, of omega-unsaturated anionic surfactants whose polar head was derived from amino acids or dipeptides. The obtained polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1, HIV-2) and various other RNA and DNA viruses. All the test compounds proved active against HIV-1 and HIV-2, their 50% inhibitory concentration (IC50) being in the range of 0.04-7.5 micrograms/mL, while they were not toxic to the host cells (CEM-4 or MT-4) at concentrations up to 100 micrograms/mL or higher. The HIV-inhibitory effect increased with the hydrophilic character of the amino acid moiety. The compounds were found to interact with both the viral envelope glycoprotein gp120 and the cellular CD4 receptor, thus blocking virus-cell binding and virus-induced syncytium formation. These polyanions also proved active against human cytomegalovirus at about the same IC50 as for HIV. In addition, they were also active, albeit at somewhat higher IC50 values (0.8-20 micrograms/mL), against other enveloped viruses such as respiratory syncytial virus and arenaviruses (Junin and Tacaribe). At yet higher IC50 values ( > or = 20 micrograms/mL), some of the compounds showed activity against influenza A virus. No activity was observed with any of the compounds against vesicular stomatitis virus, Sindbis virus, Semliki forest virus, influenza B, parainfluenza type 3, and the nonenveloped viruses Coxsackie type B4, polio type 1, and reovirus type 1.

Animals↗

No association between apolipoprotein E epsilon4 allele and the age of onset in type I familial amyloid polyneuropathy.

It has been shown that the Apolipoprotein E (ApoE) epsilon4 allele increases the risk of developing Alzheimer's disease (AD) and lowers the age of its onset. ApoE has also been suggested to be a common facilitating factor in the different types of amyloidoses. However, the association of ApoE epsilon4 with the onset of disease in various types of amyloidoses has not been extensively investigated. Type I familial amyloid polyneuropathy (FAP) is one form of systemic amyloidosis in which ApoE co-localizes with amyloid deposits. We examined 54 patients with type I FAP and found that there was no significant effect of either ApoE epsilon2 or epsilon4 allele on the age at onset. Our results suggest that ApoE4 is not a facilitating factor in the development of FAP, transthyretin amyloidosis.

Age of Onset↗

Pharmacological characterization of cardiovascular responses induced by endothelin-1 in the perfused rat heart.

The effects of the endothelin receptor antagonist TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-ala nyl-L-alpha-aspartyl-D-2-(2-thienyl)glycyl-L-leucyl-D-tryptophyl]+ ++disodiu m salt) and BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) were studied in the rat heart to characterize the receptor subtypes responsible for the cardiovascular actions of endothelin-1. Endothelin-1 induced a transient decrease and subsequent increase in perfusion pressure in perfused rat hearts, and increased left ventricular developed pressure. TAK-044 diminished these endothelin-1-induced responses (100 pmol/heart) with IC50 values of 140, 57 and 1.3 nM, respectively. BQ-123 (1-30 mu M) partially inhibited the endothelin-1-induced hypertension (30-40%) in the rat heart, and failed to inhibit the hypotension. The positive inotropic effect of endothelin-1 was abolished by BQ-123. Neither indomethacin (10 mu M) nor Nomega-nitro-L-arginine methyl ester (100 mu M) attenuated the endothelin-1-induced hypotension. TAK-044 and BQ-123 attenuated the positive inotropic effect of endothelin-1 in rat papillary muscles. In rat cardiac membrane fractions, TAK-044 and BQ-123 inhibited [125I]endothelin-1 binding to endothelin ET(A) receptors with IC50 values of 0.39 +/- 0.6 and 36 +/- 9 nM, respectively, whereas only TAK-044 potently blocked the endothelin ET(B) receptor subtype (IC50 value: 370 +/- 180 nM). These results suggest that endothelin-1 modulates cardiovascular functions in the rat heart by activating both endothelin ET(A) and endothelin ET(B) receptors, all of which are sensitive to TAK-044.

Analysis of Variance↗

Hypertrophic neuritis due to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): a postmortem pathological study.

A postmortem pathological study of a 65-year-old woman with hypertrophic neuritis associated with hand tremor and limb ataxia is described. There were many onion bulbs and loss of myelinated nerve fibers in the peripheral nerves, including the facial and subserosal visceral nerves. The hypertrophic neuritis was caused by chronic inflammatory demyelinating neuropathy (CIDP), in which interstitial amorphous substances in the endoneurium and onion bulb formation might contribute to nerve swelling. We speculate that visceral autonomic nerves as well as somatic peripheral nerves are involved in patients with a long clinical CIDP course and that peripheral nerve pathology in this disorder shows more heterogeneous changes than previously recognized.

Aged↗

Resolution of cirrhosis-related pulmonary shunting in two children with a transplanted liver.

We treated two children with hypoxemia caused by intrapulmonary shunting associated with cirrhosis secondary to extrahepatic biliary atresia. Following orthotopic liver transplantation, digital clubbing and intrapulmonary shunting were resolved, as demonstrated by normalization of room air arterial blood gases, reduction in shunt fraction, and perfusion lung scanning with 99mTc-labeled macroaggregates of albumin. We recommend that early liver transplantation be considered for young subjects with a severe hepatopulmonary syndrome.

Biliary Atresia↗