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Biomedical subjects

T Oda

Publications and source records attributed to T Oda.

At least 109 records · Page 6Linked to original sources

Application of a newly developed photoluminescence glass dosimeter for measuring the absorbed dose in individual mice exposed to low-dose rate 137Cs gamma-rays.

A photoluminescence glass dosimeter, GD-301, was applied to the measurement of low absorbed doses in mice exposed to low-dose rate 137Cs gamma-rays. The dosimeter system consists of small rod-shaped glass chip detectors capable of embedded in the body of a mouse and an automatic readout device equipped with a standard detector irradiated with 137Cs gamma-source. The measured absorbed doses were compared with the "exposure" estimated by an ionization chamber and with the doses measured by a BeO:Na thermoluminescence system. The results clearly demonstrate the superiority of the glass dosimetry regarding simplicity of operation, stability of long-term dose accumulation and good detector uniformity, which allow accurate tissue dosimetry.

Animals↗

Isolated ricin B-chain-mediated apoptosis in U937 cells.

We have previously reported that ricin, a toxic lectin that inhibits protein synthesis induced apoptotic cell death. In this study, we have found that isolated ricin CM-B-chain, which has no effect on cellular protein synthesis, induced DNA fragmentation in U937 cells in a dose- and time-dependent manner, albeit it required a longer incubation time and higher concentration than those of holotoxin ricin. Z-Asp-CH2-DCB, a caspase family inhibitor and serine protease inhibitor, 3,4-dichloroisocoumarine (DCI) effectively inhibited the CM-B-chain-mediated DNA fragmentation as well as in ricin. Thus, like ricin, multiple proteases with different substrate specificity may also be involved in the CM-B-chain-mediated apoptotic pathway. Furthermore, BFA inhibited both ricin- and CM-B-chain-mediated DNA fragmentation, suggesting an intracellular vesicle transport system through the Golgi complex may be involved in the apoptotic induction by these proteins as a common feature. On the other hand, cycloheximide (CHA) strongly increased the CM-B-chain-mediated DNA fragmentation, but inhibited ricin-mediated DNA fragmentation. The opposite effects of CHA may reflect the difference in the apoptotic mechanism between ricin and CM-B-chain. In conclusion, our results suggest that ricin-B-chain can induce apoptosis through its lectin activity, but the underlying mechanism may be distinct from that of ricin in which the A-chain contributes profoundly to the apoptotic induction.

Apoptosis↗

Concanavalin A-induced discharge of glycocalyx of raphidophycean flagellates, Chattonella marina and Heterosigma akashiwo.

Chattonella marina and Heterosigma akashiwo, known as red tide phytoplankton, are naturally wall-less and have quite fragile cell structures. In this study, we found that an equilibrium dialysis technique allowed the study of lectin binding to these flagellates. The results suggested that concanavalin A (Con A) binds to these flagellate cells through the specific carbohydrate moieties on the cell surface. Interestingly, the binding of an excess of Con A on the cell surface caused morphological changes concomitant with discharge of glycocalyx, a polysaccharide-containing common structure on the external cell surface of these flagellates. Fluorescent microscopic observation using FITC-labeled Con A (F-Con A) confirmed that F-Con A molecules are localized on the discharged glycocalyx.

Animals↗

Effects of glutathione-related compounds on increased caspase-3 and caspase-6-like activities in ricin-treated U937 cells.

Both caspase-3 and -6-like activities increased in the cytosolic extract from ricin-treated U937 cells that were inhibited by glutathione disulfide (GSSG) in a dose-dependent manner, but reduced glutathione (GSH) had no effect. Interestingly, caspase-6 like activity was more sensitive to GSSG than caspase-3 like activity. The IC50 of GSSG against caspase-3 and caspase-6 like activities were estimated to be 2.8 mM and 0.8 mM, respectively. Cystine but not cysteine also showed similar inhibitory effect on caspase-3-like activity. The inhibitory effect of GSSG on these caspase-like activities was prevented by the addition of DTT to the assay mixture. These results suggest that an intact disulfide portion of GSSG is required for the effective inhibition of caspase activity.

Apoptosis↗

Some molecular and inhibitory specifications of a dipeptidyl carboxypeptidase from the polychaete Neanthes virens resembling angiotensin I converting enzyme.

Dipeptidyl carboxypeptidase (DCP) from the polychaete Neanthes virens, resembling mammalian angiotensin I converting enzyme (ACE), was studied to discover some of its molecular and inhibitory properties, as the first evidence of these in a marine invertebrate. Amino acid and carbohydrate contents were analyzed. The N-terminal amino acid sequence of N. virens DCP was (NH2)D-E-E-A-G-R-Q-W-L-A-E-Y-D-L-R-N-Q-T-V-L-. Peptide maps of N. virens DCP from lysyl endopeptidase digestion were different from rabbit p-ACE. The far-ultraviolet circular dichroic spectra of N. virens DCP indicated that the secondary structure of this enzyme seemed to be an alpha-helical structure and was similar to that of rabbit p-ACE, but the near-ultraviolet circular dichroic spectra of N. virens DCP indicated that the aromatic amino acid residue circumambience of this enzyme was different from rabbit p-ACE. The effects of several reagents for chemical modification of amino acids on the activity of N. virens DCP were tested. Arg, Tyr, Glu, and/or Asp, His, Trp, and Met caused loss of the activity. In addition, the IC50 and Ki values for a well-known ACE inhibitor, Val-Tyr, which was a competitive inhibitor of N. virens DCP, were 263 and 20 microM, respectively. These results suggested that N. virens DCP is different from mammalian ACE in the molecular and inhibitory properties, although the same substrate specificity was demonstrated in a previous paper.

Amino Acid Sequence↗

Specific toxic effect of dinoflagellate Heterocapsa circularisquama on the rotifer Brachionus plicatilis.

Heterocapsa circularisquama (Dinophyceae), a noxious red tide dinoflagellate, is known to have a specifically lethal effect on shellfish, especially bivalves such as pearl oyster (Pinctada fucata), but no detrimental effects of this alga on fishes have not been observed so far. In this study, we found that H. circularisquama was toxic to a microzooplankton, a rotifer (Brachionus plicatilis) in a cell concentration-dependent manner, while the cultured supernatant or ultrasonic ruptured H. circularisquama had no significant toxic effect on the rotifer. Since no such toxic effects on the rotifer were observed in Chattonella marina, Heterosigma akashiwo, or Cochlodinium polykrikoides, other species of harmful red tide plankton, H. circularisquama may have a strictly specific toxic mechanism against the rotifer as well as bivalves.

Animals↗

Galacturonic-acid-induced increase of superoxide production in red tide phytoplankton Chattonella marina and Heterosigma akashiwo.

Red tide phytoplankton, Chattonella marina and Heterosigma akashiwo, are known to generate superoxide anion (O2-). We found that galacturonic acid (GaLUA) stimulated C. marina and H. akashiwo to generate increased amounts of O2-. Since such effect was not observed in any other monosaccharides tested, our results suggest that the binding of GalUA to specific sites on the flagellate cell surface may induce the increase of 02- production.

Culture Media↗

Primary hyperoxaluria type 1 in Japan.

Glyoxylate is an immediate precursor of oxalate, but in its metabolism the conversion into glycine catalyzed by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) appears to be the main route. When SPT/AGT is missing as in the case of primary hyperoxaluria type 1 (PH1) more glyoxylate is used for the oxalate production, resulting in calcium oxalate urolithiasis and finally systemic oxalosis. SPT/AGT is a unique enzyme of species-specific dual organelle localization; it is located largely in mitochondria in carnivores and entirely in peroxisomes in herbivores and man. For herbivores, the peroxisomal localization of SPT/AGT is indispensable to avoid massive production of oxalate, probably because liver peroxisomes are the main site of glyoxylate production from glycolate, and plants contain glycolate much more than animal tissues. Recently, we took charge of laboratory examination for 8 cases of primary hyperoxaluria in Japan, and felt that symptoms of some of the Japanese PH1 patients are apparently milder than those of Western patients. The reason of this is not clear, but from the above mentioned seemingly indispensable association of grass-eating with the peroxisomal localization of SPT/AGT it may be related, at least in part, to the food habit of Japanese, especially that of old generation, that they prefer boiled greens rather than frying or raw vegetables.

Diet↗

Peroxisomal and mitochondrial targeting of serine:pyruvate/alanine:glyoxylate aminotransferase in rat liver.

Serine:pyruvate/alanine:glyoxylate aminotransferase (SPT or SPT/AGT) of rat liver is a unique enzyme of dual subcellular localization, and exists in both mitochondria and peroxisomes. To characterize a peroxisomal targeting signal of rat liver SPT, a number of C-terminal mutants were constructed and their subcellular localization in transfected COS-1 cells was examined. Deletion of C-terminal NKL, and point mutation of K2 (the second Lys from the C-terminus), K4 and E15 caused accumulation of translated products in the cytoplasm. This suggests that the PTS of SPT is not identical to PTS1 (the C-terminal SKL motif) in that it is not restricted to the C-terminal tripeptide. In vitro synthesized precursor for mitochondrial SPT was highly sensitive to the proteinase K digestion, whereas peroxisomal SPT (SPTp) was fairly resistant to the protease. In in vitro import experiment with purified peroxisomes, however, SPTp recovered in the peroxisomal fraction was very sensitive to the protease. These results suggest that the mitochondrial precursor is synthesized as an unfolded form and is translocated into the mitochondrial matrix, whereas SPTp is synthesized as a folded form and its conformation changes to an unfolded form just before translocation into peroxisomes.

Animals↗

Successful removal of an infected pacemaker electrode by open heart surgery under extracorporeal circulation.

A 33-year-old male with sick sinus syndrome, who had received a pacemaker implant 18 years earlier, was complicated with a generator infection. Although the infected generator was removed, he was suffered from the recurrent local infection associated with a retained pacemaker lead. After a new pacemaker system implantation from the other side of the subclavian vein, we attempted to remove the lead utilizing a pacemaker removal kit. However, this intervention procedure was unsuccessful, because fibrous adhesions had developed around the lead, accompanied by calcification along its course. As a last resort, we opened the heart under extracorporeal circulation and removed the lead under direct vision. The post-operative course was uneventful. In order to remove a long-term implanted pacemaker lead, the direct surgical procedure with extracorporeal circulation is a favorable mean alternative to conventional intervention techniques.

Adult↗

Effects of supplemental L-arginine during warm blood cardioplegia.

OBJECTIVES: Effects of supplemental L-arginine, nitric oxide precursor, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. METHODS: The isolated hearts were perfused with blood at 37 degrees C from a support rat. After 20 minutes of aerobic perfusion, the hearts were arrested for 60 minutes with warm blood cardioplegia given at 20-minute intervals. This was followed by 60 minutes of reperfusion. The hearts were divided into the following three groups according to the supplemental drugs added to the cardioplegic solution. The control group (n = 10) received standard warm blood cardioplegia. The L-ARG group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l). The L-NAME group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l) and L-nitro-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (1 mmol/l). After 60 minutes of cardioplegic arrest, cardiac function, myocardial metabolism and myocardial release of circulating adhesion molecules were measured during reperfusion. RESULTS: Left ventricular end-diastolic pressure was significantly lower (p<0.05) in the L-ARG group than in the control group and the L-NAME group during reperfusion. Isovolumic left ventricular developed pressure, dp/dt and coronary blood flow were significantly greater (p< 0.05) in the L-ARG group during reperfusion. The L-ARG group resulted in early recovery of lactate metabolism during reperfusion. Myocardial release of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin were significantly less (p<0.05) in the L-ARG group at 15 minutes of reperfusion. CONCLUSIONS: The results suggest that augmented nitric oxide by adding L-arginine to warm blood cardioplegia can preserve left ventricular function and ameliorate endothelial inflammation. The technique can be a novel cardioprotective strategy in patients undergoing cardiac surgery.

Animals↗

[Hemodynamic assessment of the Carpentier-Edwards pericardial valve compared with the St. Jude Medical valve in the aortic position using dobutamine-stress echocardiography].

To assess the hemodynamic performance of the prosthetic valve in the aortic position, we examined dobutamine-stress echocardiography (DSE) to the patients underwent AVR with CEP valve or SJM valve. In 23 mm size, there were no significant differences between CEP group and SJM group in Peak velocity of the aortic jet (PV), peak pressure gradient (PPG) and effective orifice area (EOA). On the other hand, in 21 mm size, PV and PPG of the CEP group were significantly lower than those of the SJM group after DSE. The EOA of the CEP group was significantly larger than that of the SJM group after DSE. Our results suggest that the hemodynamic function of the CEP valve is superior to that of the SJM valve especially in small aortic annuli.

Aged↗

ATS prosthetic valve motion: an in vitro analysis.

BACKGROUND AND AIM OF THE STUDY: We have reported clinical findings that normally functioning open pivot ATS valves did not open completely. In order to analyze features of the ATS valve motion more precisely, in vitro tests were conducted. METHODS: Opening angles and pressure gradients of the ATS valve were measured and compared with those of the St. Jude Medical (SJM) valve under steady flow, but with various outlet configurations. Second, opening angles of the two valves were measured under pulsatile conditions in two different outflow configurations: (i) a 'straight outlet' where the leaflets did not extend into the tapering outflow chamber, and (ii) an 'abrupt enlargement outlet' where the leaflets extended directly into the enlarged outflow space. Third, flow visualization studies were made under steady flow conditions in the straight and abrupt enlargement outlet conduits, respectively. RESULTS: Under steady flow conditions, opening of the ATS valve was restricted in most outflow configurations; only when the outlet angle was 0 degrees did the valve open fully. The SJM valve opened completely in all downstream configurations. Despite restricted opening in the ATS valve, the pressure gradient was similar in both valves. Under pulsatile conditions, both valves opened fully in the straight outlet; however, in the abrupt enlargement outlet the ATS valve opened incompletely and the SJM valve completely. Substantial turbulent flow was observed at the outside of the leaflet and corners of the conduit, notably with the ATS valve. CONCLUSION: This study showed that the ATS valve did not open fully except when the outflow was straight, and the leaflet did not extend into an enlarged downstream chamber. Structural features of the ATS, such as its axis being located close to the straight edge and its leaflets extending further downstream from the ring orifice, may cause this unique valve behavior.

Heart Valve Prosthesis↗

Role of magnetic resonance imaging (MRI) in early cervical cancer.

The aim of this study was to prospectively determine if invasive carcinoma of the cervix can be ruled out by negative magnetic resonance image (MRI) findings. Eligible patients were those who were scheduled to undergo either hysterectomy or conization because of invasive or non-invasive lesions of the cervix. T2-weighted and T1-dynamic enhancement images were reviewed by two radiologists who had no information on these patients except for the preoperative diagnosis. Clinical information regarding location of the disease was not given. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist who was not provided with MRI information. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and 0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647, respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist 1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and specificities were calculated for prediction of non-invasive plus microinvasive lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The dynamic technique provided only limited additional value in the detection of early invasive cervical carcinoma.

Adult↗

Oxalate synthesis in mammals: properties and subcellular distribution of serine:pyruvate/alanine:glyoxylate aminotransferase in the liver.

Primary hyperoxaluria Type 1 (PH1) is caused by a functional deficiency of a liver enzyme, serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), which catalyzes transamination between L-serine or l-alanine as an amino acid substrate and glyoxylate or pyruvate as an alpha-keto acid substrate. A high affinity for glyoxylate is a notable feature of this enzyme, suggesting a role in glyoxylate metabolism in vivo. Another conspicuous feature of SPT/AGT is its species-specific and food habit-dependent subcellular distribution. Thus, the enzyme is located in peroxisomes in herbivores and man, largely in mitochondria in carnivores, and in both the organelles in rodents. The mechanism of the species-specific dual organelle localization of SPT/AGT is either transcription of the gene from two different start sites or loss of the upstream translation initiation ATG codon by mutations. It appears that the mitochondrial versus peroxisomal distribution of SPT/AGT in different animal species is indispensable in meeting the metabolic needs caused by their respective food habits. As for the peroxisomal localization, glycolate is contained in plants much more than in animal tissues, and when ingested, it is converted to glyoxylate, an immediate precursor of oxalate, in liver peroxisomes. Therefore, peroxisomal localization of SPT/AGT may be indispensable for herbivores to convert the glyoxylate formed in peroxisomes into glycine in situ rather than forming oxalate. On the other hand, our recent studies showed that SPT/AGT contributed substantially to serine metabolism in rabbit, human, and dog livers; i.e., irrespective of its mitochondrial or peroxisomal localization. Thus, the mitochondrial localization of SPT/AGT was not a prerequisite for the metabolism of L-serine. Another source of glyoxylate is the metabolism of L-hydroxyproline, and in this case, the enzyme responsible for the glyoxylate formation has been reported to be a mitochondrial matrix enzyme. Collagen accounts for about 30% of total animal proteins and contains about 13% (w/w) hydroxyproline. It is therefore possible that both mitochondrial and peroxisomal SPT/AGT contribute to the metabolism of glyoxylate and serine, but the subcellular site for glyoxylate metabolism is different in herbivores and carnivores.

Animals↗

Effects of aging on EMG variables during fatiguing isometric contractions.

The purpose of this study was to evaluate the neuromuscular adaptation that occurred with aging, by comparing young and aged subjects with respect to changes in surface EMG from the tibialis anterior muscle during fatiguing contractions. EMG variables such as the averaged rectified value (ARV), median frequency (MDF), and muscle fiber conduction velocity (MFCV) were calculated during maximal (MVC, 3 sec) and submaximal (60% MVC, 60 sec) isometric contractions. Muscular force, ARV, MDF, and MFCV during MVC were significantly greater in the young than in the elderly (p < 0.05). EMG amplitude increased and the waveform slowed in all subjects during submaximal contractions, indicating the development of local muscle fatigue. As fatigue progressed, the ARV increased and the MDF and MFCV decreased significantly (p < 0.01). The fatigue-induced changes in the MDF and MFCV were significantly smaller in aged than in young subjects (p < 0.05), a trend also seen in the ARV change, which means that the elderly cannot be fatigued as much as the young with contractions of the same relative intensity. These results as a whole suggest that the aged subjects hold an adaptive motor strategy to cope with age-related neuromuscular deteriorations, due to the decline of motor unit activation and selective atrophy of fast twitch muscle fibers.

Adult↗