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Biomedical subjects

S Oikawa

Publications and source records attributed to S Oikawa.

At least 55 records · Page 3Linked to original sources

[Off-pump coronary artery bypass grafting: comparison between standard CABG and off-pump CABG].

UNLABELLED: We have performed 321 cases of coronary artery bypass grafting (CABG), between October 15 1995 and November 20 2000. We have evaluated the operative results of 142 cases (44.2%) of conventional CABG and 179 cases (55.8%) of off-pump CABG performed during this period. The average numbers of bypassed grafts was 3.53 for conventional CABG, and 1.62 for off-pump CABG. The total number of 369 grafts were anastomosed to 501 coronary arteries for conventional CABG, and 283 grafts were anastomosed to 290 coronary arteries for off-pump CABG. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using RITA, LITA, GEA and RA. Three site of stenosis in 18 LITAs and 2 in 16 RITAs were recognized in off-pump CABG without the use of stabilizers. One site of stenosis in 130 LITAs and 3 string signs in 44 GEA were recognized in off-pump CABG with the use of stabilizers. Postoperative angiography in 52 off-pump CABG cases at one year later showed no new lesion. CONCLUSION: The use of stabilizers and LIMA suture enables adaptation of the MIDCAB procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.

Adult↗

[Minimally invasive direct coronary artery bypass performed via diaphragmatic approach].

From October 1996 until August 2000, coronary artery bypass grafting (CABG) for right coronary artery was performed via diaphragmatic approach. This procedure was done in 18 patients consist of 13 male and 5 female ranging in age from 47 to 81 years old. Ten of 18 cases were performed coronary bypass reoperation. Right gastroepiploic artery was used in 16 cases, and branched radial artery or saphenous vein graft from gastroduodenal artery was used in one case. Bypassed region in right coronary artery was segment 3 in 9 cases, right posterior descending artery in 8 and right atrio-ventricular branch in one. All grafts were patent in postoperative cardiac catheterization. This approach was desirable for the case, which bypass grafting to right coronary artery is necessary, on account of avoiding injury of patent bypassed graft by median sternotomy in re-do CABG. For the patient whose stomach had been resected, bypass grafting from gastroduodenal artery with radial artery or saphenous vein graft to right coronary artery is useful procedure.

Aged↗

Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8.

CEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins on neutrophils that belong to the human carcinoembryonic antigen (CEA) family. CEACAM6 reveals homophilic adhesion and heterophilic adhesion to other CEACAM family antigens including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic adhesion to CEACAM6. Here, we investigated and compared structural requirements for the homophilic adhesion of CEACAM6 and heterophilic adhesion between CEACAM6 and CEACAM8 at the amino acid level by using CHO transfectants expressing their mutant and chimeric proteins. The NH(2)-terminal domain (N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell. By homologue-scanning mutagenesis, we found that the locations of the sequences critical for the adhesion of CEACAM6 to itself and to CEACAM8 are overlapped and that they are highly similar but not identical to the locations of the residues previously shown to be essential for the binding of CEACAM antigens to Opa proteins of pathogenic NEISSERIAE: Our findings imply that subtle differences in the N-domain sequences determine the specificity of the CEACAM antigens on neutrophils for interaction with the same or different CEACAM antigens and the bacterial proteins.

Amino Acid Sequence↗

Extracellular N-domain alone can mediate specific heterophilic adhesion between members of the carcinoembryonic antigen family, CEACAM6 and CEACAM8.

The domain(s) responsible for the specific heterophilic adhesion between two members of the carcinoembryonic antigen (CEA) family, CEACAM6 and CEACAM8, both of which with three extracellular domains, were investigated using Chinese hamster ovary (CHO) transfectants expressing chimeric antigens. Using a chimeric antigen in which the N-domain, a sole extracellular domain, of CEACAM3 was substituted with that of CEACAM6, it was shown that the N-domain of CEACAM6 alone was able to mediate specific adhesion to CEACAM8. Furthermore, the chimeric antigen was shown to bind significantly to chimeric CEA whose N-domain was substituted with that of CEACAM8, but not to unsubstituted CEA. These results demonstrate that the N-domain alone is sufficient and other domains of CEACAM6 or CEACAM8 are not required for this specific binding. We therefore propose a model of heterophilic interaction between the N-domains, which is distinct from that of CEA-CEA homophilic binding.

Animals↗

Amplification of pepleomycin-mediated DNA cleavage and apoptosis by unfused aromatic cations.

An important approach to improve chemotherapy of members of the bleomycin (BLM) family of antibiotics is to find compounds (amplifiers) that enhance the activity of BLM-mediated DNA cleavage and apoptosis. Using a DNA-sequencing technique and pulsed field gel electrophoresis, we have investigated whether BLM-mediated cleavage of isolated and cellular DNA is amplifed by three compounds (RW-12, LS-20, 1S-5Me) which have a conformationally flexible, unfused polyaromatic system and cationic side chain in the molecules. RW-12 enhanced most effectively both pepleomycin (PEM)-induced cytotoxicity and apoptosis. The order of the maximum enhancing effect of amplifiers on PEM-mediated DNA damage is RW-12 > LS-20 > 1S-5Me. RW-12 amplified PEM-mediated DNA cleavage most effectively not only in vitro but also in cultured cells. We have reported that the order of the DNA binding constants of these compounds is RW-12 > LS-20 > 1S-5Me. In this study, we found a good correlation between PEM-mediated cleavage of isolated DNA and cellular DNA. These results suggest that BLM amplifiers bind to DNA and by doing so enhance drug-mediated DNA degradation, ultimately leading to apoptosis. The present study on amplifiers of anticancer agents shows a novel approach to the potentially effective anticancer therapy.

Apoptosis↗

Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by thrombus-like substances in markedly dilated glomerular capillaries, dysbetalipoproteinemia, and elevated plasma concentrations of apoE. Recent studies identified several apoE mutations in patients with LPG, including apoE2(R145P) Sendai (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in apoE-deficient hypercholesterolemic mice resulted in insufficient correction of hypercholesterolemia and a marked and temporal induction of plasma triglyceride levels. In vitro binding studies showed that apoE-Sendai has a reduced affinity for the low density lipoprotein receptor, suggesting that dysbetalipoproteinemia in LPG is caused by the apoE mutation. Furthermore, histological examination revealed marked intraglomerular depositions of apoE-containing lipoproteins in mice injected with apoE-Sendai virus. These LPG-like depositions were detected 6 days after virus injection and were sustained for at least 60 days. Our results demonstrated that apoE-Sendai is an etiological cause of LPG.

Adenoviridae↗

Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.

Bone morphogenetic protein (BMP)-2, a member of the BMP family, plays an important role in osteoblast differentiation and bone formation. To discover small molecules that induce BMP-2, a luciferase reporter vector containing the 5'-flanking promoter region of the human BMP-2 gene was constructed and transfected into human osteosarcoma (HOS) cells. By the screening of an in-house natural product library with stably transfected HOS cells, a fungal metabolite, compactin, known as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was isolated. The stimulation of the promoter activity by compactin seemed to be specific for BMP-2 gene in HOS cells, since it had little effect on BMP-4 or SV40 promoter activity and the stimulation was not observed in Chinese hamster ovary (CHO) cells. RT-PCR analysis and alkaline phosphatase assay revealed that compactin induced an increase in the expression of BMP-2 mRNA and protein. Like compactin, simvastatin also activated the BMP-2 promoter, whereas pravastatin did not. The statin-mediated activation of BMP-2 promoter was completely inhibited by the downstream metabolite of HMG-CoA reductase, mevalonate, indicating that the activation was a result of the inhibition of the enzyme. These results suggest that statins, if they are selectively targeted to bone, have beneficial effects in the treatment of osteoporosis or bone fracture.

Anti-Bacterial Agents↗

Measurement of serum low density lipoprotein-cholesterol in patients with hypertriglycemia.

Low density lipoprotein-cholesterol (LDL-c) concentration measured by a homogeneous enzymatic assay was reported to correlate well with the modified beta-quantification assay, especially in samples with high triglyceride (TG) concentration. In this study, we evaluated a homogeneous enzymatic assay, Cholestest-LDL assay system, in hypertriglycemic patient samples, and found that 56% (9/16) of serum samples with intermediate TG concentrations (2.27-4.52 mmol/L) showed more than 10% discrepancy with concentration by the modified beta-quantification assay. Such serum samples originated from patients with hyperglycemia of type II a (three cases), type II b (two cases), type III (one case), and type IV (six cases). Differential staining of cholesterol and triglyceride after agarose gel electrophoresis revealed that these serum samples contained significant amounts of intermediate fractions between pre-beta- and beta-lipoproteins. Since lipoprotein (a), which migrates between pre-beta- and beta-lipoproteins, is not correlated with the discrepancy, we believe the intermediate fraction consists of intermediate density lipoprotein (IDL) and a chylomicron remnant. A part of IDL and chylomicron remnant, which contain a significant amount of triglyceride, might be measured as LDL-c by the homogeneous enzymatic assay, but not by the modified beta-quantification assay.

Cholesterol, LDL↗

Standard coronary artery bypass grafting and beating heart bypass. Indications and long-term results.

OBJECTIVES AND METHOD: We have performed 225 cases of coronary artery bypass grafting (CABG), between October 15 1995 and September 8 1999. We have evaluated the operative results of 121 cases (53.8%) of conventional CABG and 104 cases (46.2%) of minimally invasive coronary artery bypass grafting performed during this period. The average numbers of bypassed grafts was 3.45 for conventional CABG, and 1.41 for minimally invasive coronary artery bypass grafting. Sixty-seven right internal thoracic arteries, 145 left internal thoracic arteries, 71 gastroepiploic arteries, 38 radial arteries and 12 saphenous veins were used for conventional CABG, and 29 right internal thoracic arteries, 81 left internal thoracic arteries, 18 gastroepiploic arteries, 3 radial arteries, 10 saphenous veins and 2 inferior epigastric arteries were used for minimally invasive coronary artery bypass grafting. The total number of 303 grafts were anastomosed to 417 coronary arteries for conventional CABG, and 143 grafts were anastomosed to 147 coronary arteries for minimally invasive coronary artery bypass grafting. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using right internal thoracic arteries, left internal thoracic arteries, gastroepiploic arteries and radial arteries. Three site of stenosis in 18 left internal thoracic arteries and 2 in 16 right internal thoracic arteries were recognized in minimally invasive coronary artery bypass grafting without the use of stabilizers. One site of stenosis in 63 left internal thoracic arteries was recognized in minimally invasive coronary artery bypass grafting with the use of stabilizers. CONCLUSION: The use of stabilizers enables adaptation of the minimally invasive coronary artery bypass grafting procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.

Coronary Artery Bypass↗

DNA damage by dimethylformamide: role of hydrogen peroxide generated during degradation.

Dimethylformamide (DMF) has been suspected to associate with cancers in exposed workers, whereas there has been inadequate evidence for carcinogenicity in experimental animals. We demonstrated that H(2)O(2) was generated during the degradation of DMF under aerobic conditions, and that the amount of H(2)O(2) was enhanced by exposure to solar light or by the contamination of trace metal. Experiments using (32)P-5'-end-labeled DNA fragments revealed that the degraded DMF induced DNA damage in the presence of Cu(II). However, purified DMF did not induce DNA damage even in the presence of Cu(II). Addition of purified DMF enhanced DNA damage induced by H(2)O(2) in the presence of Cu(II). The degraded DMF caused Cu(II)-mediated DNA cleavage frequently at thymine and cytosine residues. The similar pattern of site-specific DNA damage was observed with purified DMF and H(2)O(2). Bathocuproine and catalase inhibited the DNA damage, indicating the involvement of Cu(I) and H(2)O(2). A typical free hydroxy radical scavenger showed no inhibitory effect on the DNA damage. Addition of purified DMF enhanced about 3-4-fold 8-oxo-7, 8-dihydro-2'-deoxyguanosine formation induced by H(2)O(2) and Cu(II). ESR spectroscopic study demonstrated that carbon-centered radicals and nitrogen-centered radicals were generated in the reaction mixture of DMF, H(2)O(2), and Cu(II). Inhibitory effects of scavengers on radical formation and DNA damage suggest that carbon-centered radicals and/or nitrogen-centered radicals may contribute to the DNA damage. These results suggest that H(2)O(2) generation during DMF degradation is related to the possible carcinogenic activity of DMF.

Copper↗

Participation of mitogen-activated protein kinase in thapsigargin- and TPA-induced histamine production in murine macrophage RAW 264.7 cells.

1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha-Fluoromethylhistidine, a suicide substrate of L-histidine decarboxylase (HDC), suppressed the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production. 4. Both thapsigargin (30 nM) and TPA (30 nM) induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. 5. PD98059, a specific inhibitor of MEK-1 which phosphorylates p44/p42 MAP kinase, strongly suppressed both the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production, whereas SB203580, a specific inhibitor of p38 MAP kinase, inhibited them only partially. 6. The other MEK-1 inhibitor, U-0126, also inhibited both the thapsigargin- and TPA-induced histamine production in a concentration-dependent manner. 7. Thapsigargin (30 nM) and TPA (30 nM) increased the levels of HDC mRNA at 4 h, but PD98059 suppressed both the thapsigargin- and TPA-induced increases in the HDC mRNA level. 8. These findings indicate that thapsigargin and TPA induce histamine production in RAW 264.7 cells by increasing the level of HDC mRNA, and that both the thapsigargin- and TPA-induced histamine production are regulated largely by p44/p42 MAP kinase and partially by p38 MAP kinase.

Animals↗