[A 56-year-old woman complaining of faintness].
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Biomedical subjects
Publications and source records attributed to T Oka.
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Multivariate analyses were performed by logistic regression procedure to identify the significant risk factors for postoperative arrhythmias. The 29 variables included in the analyses were as follows: age, sex, hemodynamic variability, preoperative complication (hypertension, myocardial ischemia, and diabetes mellitus et al), surgical staging for lung cancer, anesthetic method, surgical procedure, intraoperative complications (hypoxemia, arrhythmia and myocardial ischemia), and so on. We evaluated intraoperative hemodynamic variability using mean value and coefficient of variation (CV) of heart rate and blood pressure computed from anesthetic records. Supraventricular tachyarrhythmias occurred in 27 (22.3%) of 121 consecutive patients undergoing pulmonary resection. Increases in mean heart rate and CV of heart rate, older patients, intraoperative blood transfusion, and left thoracotomy were associated with arrhythmias (P < 0.05). There was no correlation of arrhythmia with preoperative complications, surgical staging for lung cancer, anesthetic method, or surgical procedure. It is suggested that impairment of cardiac autonomic nervous system function associated with possible injury to the cardiac autonomic nerves during pulmonary resection is one of the risk factors for arrhythmias after thoracotomy.
The present study was carried out to clarify the effects of chest deformation by upper abdominal retractor on respiratory system impedance during abdominal surgery. We measured the impedances of respiratory system (RS), lung, and chest wall (CW) in nine anesthetized paralyzed subjects employing a pseudorandom noise forced volume oscillation technique. These measurements were performed before and after the lifting chest wall by upper abdominal retractor. The effects of chest deformation was significant on the impedances of RS, lung, while no discernible effect was found in CW impedance. Lifting chest wall decreased RS resistance which was totally accounted for by the decrease in lung resistance, whereas the lifting did not affect reactance in either RS or lung. The mathematical modeling showed the significant lifting effect on the resistance of the parenchyma. In conclusion, change in RS mechanics produced by chest deformation by upper abdominal retractor is dominated in lung but not in CW. Among the lung mechanical components, parenchyma is the primary site of the lifting effect.
Plasma phospholipid transfer protein (PLTP) is a factor that plays an important role in HDL metabolism. In this study we present data suggesting that PLTP has an inherent protease activity. After incubation of HDL3 in the presence of purified plasma PLTP, the d < 1.25 g/ml particles (fusion particles) contained intact 28.2 kDa apoA-I while the d > 1.25 g/ml fraction (apoA-I-PL complexes) contained, in addition to intact apoA-I, a cleaved 23 kDa form of apoA-I. Purified apoA-I was also cleaved by PLTP and produced a similar 23 kDa apoA-I fragment. The cleavage of apoA-I increased as a function of incubation time and the amount of PLTP added. The process displayed typically an 8-10 h lag or induction period, after which the cleavage proceeded in a time-dependent manner. This lag-phase was necessary for the development of the cleavage activity during incubation at 37 degrees C. The specific apoA-I cleavage activity of different PLTP preparations varied between 0.4-0.8 microg apoA-I degraded/h per 1000 nmol per h of PLTP activity. The 23 kDa apoA-I fragment reacted with monoclonal antibodies specific for the N-terminal part of apoA-I, indicating that the apoA-I cleavage occurred in the C-terminal portion. The apoA-I cleavage products were further characterized by mass spectrometry. The 23 kDa fragment yielded a mass of 22.924 kDa, demonstrating that the cleavage occurs in the C-terminal portion of apoA-I between amino acid residues 196 (alanine) and 197 (threonine). The intact apoA-I and the 23 kDa fragment revealed identical N-terminal amino acid sequences. The cleavage of apoA-I could be inhibited with APMSF and chymostatin, suggesting that it is due to a serine esterase-type of proteolytic activity. Recombinant PLTP produced in CHO cells or using the baculovirus-insect cell system caused an apoA-I cleavage pattern identical to that obtained with plasma PLTP. The present results raise the question of whether PLTP-mediated proteolytic cleavage of apoA-I might affect plasma HDL metabolism by generating a novel kinetic compartment of apoA-I with an increased turnover rate.
The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.
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Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1997 to May 1998, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis The MIC90s of quinolones for E. faecalis isolated from uncomplicated UTIs have changed better state during the latest period. Among E. faecalis strains, those with high susceptibilities to ampicillin (ABPC) and minocycline (MINO) appeared to had decreased during period of 1995-1997, which recovered during the latest period. 2. S. aureus The sensitive strains of S. aureus to imipenem (IPM) and clindamycin (CLDM) had increased during the period of 1996-1997, but those have decreased again during the latest period. 3. E. coli The susceptibilities of E. coli to MINO have been better in the latest period with the MIC90 was ranged from 2 to 4 micrograms/ml. The susceptibilities to quinolones of E. coli isolated from complicated UTIs had decreased during the period of 1995-1997, but those have recovered during the latest period. 4. Klebsiella spp. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems have increased in the latest period. To other antimicrobial agents, the susceptibilities of Klebsiella spp. did not show any changes during the latest period. 5. P. aeruginosa The susceptibilities to most agents of P. aeruginosa did not show any changes, the decreased susceptibilities to cefozopran (CZOP), carbapenems and monobactams of P. aeruginosa observed in 1996 appeared to have been retrieved in 1997. These susceptibility changes should be utilized in determining clinical treatments.
The mechanism of Adenovirus (Ad) and Adeno-associated virus (AAV) vector-mediated gene transduction in murine tracheae has not been fully understood. Excised tracheae from mice were exposed to either Ad vector (Ad-CMV-LacZ) or AAV vector (AAV-CMV-LacZ) for 1 hour. LacZ gene expression in tracheal epithelial cells was detected by X-gal staining. Only patch distributions of LacZ expressing cells were observed. The percentage of LacZ expressing cells to total cells was less than 1% with either vector. Ad-mediated LacZ transduction was increased by mechanical damage using forceps. AAV-mediated gene transduction in tracheal epithelial cells was also increased by mechanical damage. Furthermore, this increased expression of vector LacZ by damaged epithelial cells was not affected by pretreatment with anti-ICAM-1 mAb or platelet-activating factor receptor antagonist. Although the Ad and AAV vectors were inefficient in transferring genetic material to murine trachea ex vivo, our results suggest that mechanical damage can enhance their transduction efficiency.
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Malignant lymphoma (ML) induction in rabbits by Epstein-Barr virus (EBV)-related herpesvirus of cynomolgus (Cyno-EBV) is reported. Twenty-seven of 30 (90%) rabbits inoculated intravenously with Cyno-EBV-producing simian (cynomolgus) lymphocyte cell line (Ts-B6) cells developed ML between 45 and 115 days after inoculation. The peroral inoculation of Ts-B6 cells induced ML in only 2 of 10 (20%) rabbits (75 to 85 days). Five of 6 (83%) rabbits injected with cell-free pellets from Ts-B6 cultures also developed ML (27 to 122 days). Antibody response to the viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Ts-B6. ML of the large cell or mixed type infiltrated diffusely in many organs, frequently involving the spleen, liver, kidneys, heart, and less frequently the lungs, lymph nodes, brain, eyes, gastrointestinal tract, thymus, and bone marrow. A chromosomal analysis of five lymphoma cell lines established from tumor-bearing rabbits revealed the rabbit karyotype. Three of these cell lines showed the chromosomal abnormalities with 12q- or t (7p+:12q-). EBV-encoded small RNA-1 and EBV-associated nuclear antigen 1 were expressed in Ts-B6 cells, the tumor tissues, and all rabbit cell lines by in situ hybridization and by immunofluorescence tests, respectively. EBV DNA was also detected in Ts-B6 cells and rabbit lymphoma cell lines by polymerase chain reaction and Southern blot analysis. The Southern blots of EBV termini revealed oligoclonal bands in the Cyno-EBV-induced rabbit lymphomas. No lymphoma was induced by the inoculation of B95-8 (EBV-producing cells) or peripheral leukocytes from normal cynomolgus (controls). These data suggest that the high rate of lymphoma induction in rabbits may be caused not by human EBV (B95-8) but by Cyno-EBV from Ts-B6 cells. A sequence analysis of the IR1 (BamHIW) region of Cyno-EBV revealed that this region is quite similar to that of herpesvirus Macaca fascicularis 1, which is a causative agent for a monkey model of AIDS-related lymphomas. The present rabbit model of lymphoma with specific chromosomal abnormalities is very useful to clarify the role of EBV in human EBV-associated lymphoma and provides a means for studying prophylactic and therapeutic regimens.
BACKGROUND/AIMS: We investigated the clinical efficacy of systemic and locoregional adoptive immunotherapy (AIT) with or without interleukin-2 (IL-2) against solid metastatic lesions from digestive tract cancer, which are refractory to conventional chemotherapy or radiotherapy. METHODOLOGY: Seven of 18 patients received hepatic arterial infusion (HAI) of lymphokine-activated killer (LAK) cells with or without IL-2 against metastatic liver tumors (local therapy group). The remaining 11 patients received systemic transfer of LAK cells with IL-2 against metastatic lesions located in organs other than the liver (systemic therapy group). RESULTS: Three of the 7 local therapy group patients showed clinically significant tumor regressions and this was evaluated as being equivalent to partial response (PR) (response rate: 43%). Two of the 11 systemic therapy group patients showed tumor regression which was evaluated as being equivalent to either complete response (CR) or PR (response rate: 18%). These 2 effective cases in the systemic therapy group were esophageal cancer patients. CONCLUSIONS: Locoregional AIT with or without IL-2 against liver metastases of digestive tract cancer could be an effective therapeutic modality in some patients who are refractory to conventional therapies. However, clinical efficacy of systemic AIT with IL-2 against metastases of digestive tract cancer would not be an effective modality except for the metastases of esophageal cancer.
1934, vitamin B6 was discovered by P. György. Vitamin B6 consists of 3 closely related pyrimidine derivatives: pyridoxine, pyridoxal and pyridoxamine and their phosphate esters. The tumor-specific compound has been recently found to be as a new B6 derivatives. The active form of vitamin B6 is pyridoxal phosphate (PLP) which is produced by multi-metabolizing enzymes including pyridoxine kinase and PNP/PMP oxidase. PLP functions as the coenzymes of many enzymes which catalyze biochemical reactions such as transamination and decarboxylation. A novel physiological function of PLP which is the negative modulator of the steroid-dependent gene expression and the albumin gene expression has been also revealed.
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cDNA encoding N(G),N(G)-dimethylarginine dimethylaminohydrolase from rat kidney had been cloned [Kimoto, M., Sasakawa, T., Tsuji, H., Miyatake, S., Oka, T., Nio, N. & Ogawa, T. (1997) Biochim. Biophys. Acta 1337, 6-10]. The enzyme hydrolyzes N(G),N(G)-dimethyl-L-arginine and N(G)-monomethyl-L-arginine, which are known as endogenous inhibitors for the nitric oxide-generating system. In the present study, human N(G),N(G)-dimethylarginine dimethylaminohydrolase has been purified to homogeneity from liver and characterized. The cDNA clone encoding human N(G),N(G)-dimethylarginine dimethylaminohydrolase was isolated from a human kidney lambda gt10 library using a probe prepared from a plasmid containing the entire coding region of rat N(G),N(G)-dimethylarginine dimethylaminohydrolase. Its open reading frame encoded a protein of 285 amino acids with a molecular mass of 31,121 Da. The deduced amino acid sequence exhibits 93% identity with that of rat. The cDNA was expressed as a fusion protein in Escherichia coli and the recombinant protein exhibited enzyme activity which is the same as that of natural enzyme.
A cDNA encoding a putative copper chaperone protein, CUC-1, was cloned from Caenorhabditis elegans. CUC-1 had the characteristic motifs of MTCXXC and KKTGK, and showed 49.3 and 39.1% sequence identity with yeast Atx1p and human HAH1, respectively. Expression of CUC-1 cDNA complemented a null atx1 mutant, the yeast copper chaperone gene, thus demonstrating that CUC-1 is a functional copper chaperone. Studies with transgenic worms indicated that cuc-1 and cua-1, which encodes the copper transporting ATPase, are expressed together in intestinal cells of adult and hypodermal cells in the larvae. cua-1 was also expressed in pharyngeal muscle but cuc-1 was not. These results suggest that CUC-1 and CUA-1 constitute a copper trafficking pathway similar to the yeast counterparts in intestinal and hypodermal cells, and CUA-1 may have a different function in pharyngeal muscle.
Four monoclonal antibodies (mAbs) against 4-aminobenzoate hydroxylase (EC 1.14.13.27) have been produced (H. Tsuji et al., J. Biol. Chem. 265 (1990) 16064; T. Ogawa et al., Biochim. Biophys. Acta 1115 (1992) 220). Of the mAbs, three mAbs (mAb-A, -B1 and -B2) recognize the FAD-binding domain of the enzyme. In the present study, the epitopes of the mAbs on the enzyme have been examined using pGEX-2T expression systems for DNA fragments encoding various partial amino acid sequences of 4-aminobenzoate hydroxylase. The epitopes for mAb-A, -B1 and -B2 were shown to be on sequences 413-434, 435-460 and 380-413, respectively. These findings suggest that these epitopes for mAb-A, -B1 and -B2 may be close to the isoalloxazine moiety of FAD, which plays a central role in the catalysis of the enzyme.
Basic fibroblast growth factor (bFGF) stimulated [3H]thymidine incorporation at all stages of development, although the magnitude of this effect was the greatest in cells derived from pregnant mice. Cells primed with insulin and bFGF synthesized more casein than cells not exposed to either hormone. bFGF inhibited casein synthesis and decreased the amounts of beta-casein and alpha-lactalbumin transcripts in cells from pregnant animals simultaneously incubated with insulin, hydrocortisone and prolactin. bFGF content in mammary gland increased with puberty and pregnancy, but decreased markedly in lactation; the number of bFGF receptors in epithelial cells changed in parallel. These data suggest that bFGF may have a physiological role both in stimulating growth and in inhibiting functional differentiation of normal mouse mammary epithelial cells.