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Biomedical subjects

K Yamamoto

Publications and source records attributed to K Yamamoto.

At least 37 records · Page 2Linked to original sources

Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice.

Listeriolysin O (LLO) derived from Listeria monocytogenes is highly capable of inducing interleukin (IL)-12, IL-18 and interferon (IFN)-gamma, and facilitates the generation of Th1 cells. We have recently shown that recombinant LLO (rLLO) inhibits generation of ovalbumin (OVA)-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells. In the present study, we investigated the effect of rLLO on the effector phase of Th2-dependent allergic rhinitis in BALB/c mice sensitized with OVA. In mice sensitized intraperitoneally and challenged intranasally with OVA, nasal allergic symptoms such as sneezing and nose-scratching were observed at a high frequency. A high titre of anti-OVA IgE antibody was detected in sera and a large number of eosinophils migrated into the nasal tissue. However, rLLO treatment during the intranasal challenge inhibited the allergic symptoms, production of anti-OVA IgE antibody and eosinophil infiltration. Though rLLO did not affect antigen-specific cytokine production from splenic CD4(+) T cells, rLLO significantly suppressed OVA-specific IL-4 and IL-5 production from nasal mononuclear cells. We further found that rLLO inhibited the recruitment of CD4(+) T cells in nasal mucosa, and diminished the transcription and cell surface expression of CCR4 on splenic CD4(+) T cells. Moreover, rLLO was able to inhibit the passive cutaneous anaphylaxis reaction mediated by anaphylactic antibodies (IgE and IgG(1)) and mast cells. Taken together, these data showed that rLLO suppresses the effector phase of allergic rhinitis by inhibition of Th2 cell recruitment to nasal mucosa and type I allergic reaction.

Animals↗

A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene.

We investigated the molecular basis of a severe factor V (FV) deficiency in a Japanese female, and identified two distinct mutations in the FV gene, a novel cytosine insertion (1943insC) and a previously reported point mutation (A5279G). We expected the patient to be a compound heterozygote for those mutations, as a 1943insC, but not an A5279G, was found in the mother and a sibling. The 1943insC will cause a frame-shift after 590Gln, resulting in amino acid substitutions with two abnormal residues followed by a stop codon in the FV A2 domain (FS592X). The A5279G will cause an amino acid alteration in the FV A3 domain (Y1702C), which has been observed in several ethnic groups. We found that both mutant mRNAs were detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the patient's platelets, whereas no FV antigen and activity were detected in plasma. On the one hand, the RT-PCR signal from the FS592X-FV mutant mRNA was markedly reduced, suggesting that the RNA surveillance system would eliminate most of the abnormal FS592X-FV transcripts with a premature termination. On the other hand, expression analyses revealed that only small amounts of Y1702C-FV with a low specific activity were secreted, and that the FS592X-FV was not detected in cultured media. These data indicated that both mutant FV molecules would be impaired, at least in part, during the post-transcriptional process of protein synthesis and/or in secretion. Taken together, it seems to suggest that each gene mutation could be separately responsible for severe FV deficiency, while this phenotype is due to the in-trans combination of the two defects.

Adult↗

Fatal thrombosis of antithrombin-deficient mice is rescued differently in the heart and liver by intercrossing with low tissue factor mice.

BACKGROUND: We previously reported that the targeted disruption of murine antithrombin (AT) gene resulted in embryonic lethality before 16.5 gestational days (gd) because of severe cardiac and hepatic thrombosis. OBJECTIVE AND METHODS: To investigate the influences of lowered tissue factor (TF) activity upon hypercoagulation of AT-/- embryos, we crossed AT+/- with low TF (mTF-/- hTF+) mice to yield homozygous AT-deficient mice with the extremely low TF activity, that is expressed from the inserted human TF mini gene. RESULTS: AT-/- embryos either with 50% TF (AT-/- mTF+/- hTF+) or with low (approximately 1% TF, AT-/- mTF-/- hTF+) were not born, although the survival was prolonged until 18.5 gd. In both genotypes, histological examination showed disseminated thrombosis in hepatic sinusoidal space or in the portal veins, suggesting that the thrombogenesis caused loss of hepatic blood flow. As in original AT-/-, AT-/- mTF+/- hTF+ showed subcutaneous (s.c.) bleeding and also suffered from the myocardial degeneration apparently because of coronary thrombus formation. However, AT-/- mTF-/- hTF+ had no skin hemorrhage and the thrombosis and degeneration were completely abolished in the heart. Myocardium of adult low TF mice had exhibited fibrosis secondary to hemorrhage; however, it was significantly decreased in low TF mice with AT+/-. CONCLUSIONS: Our current model suggests that, in the heart, TF plays an important role in the thrombogenesis and it counterbalances AT-dependent anticoagulation. AT may be a potent anticoagulant during mice development and the activation and subsequent regulation of TF-procoagulant activity take place differently between the liver and the heart. These differences appear to point to local regulatory mechanisms in murine hemostasis.

Animals↗

In vitro characterization of missense mutations associated with quantitative protein S deficiency.

OBJECTIVE: To elucidate the molecular consequences of hereditary protein S (PS) deficiency, we investigated the in vitro synthesis of the PS missense mutants in COS-1 cells and their activated protein C (APC) cofactor activities. PATIENTS: Four patients with quantitative PS deficiency suffering from venous thrombosis were examined. RESULTS: We identified three distinct novel missense mutations, R275C, P375Q and D455Y, and two previously reported missense mutations, C80Y and R314H. The P375Q and D455Y mutations were found in one patient and observed to be in linkage on the same allele. The R314H mutant showed the lowest level of expression (32.7%), and the C80Y, P375Q + D455Y, and R275C mutants exhibited a moderate impairment of expression, that is, 43.8%, 49.5%, and 72.3% of the wild type, respectively. Furthermore, pulse-chase experiments demonstrated that all mutants showed impaired secretion and longer half-lives in the cells than the wild type PS. In the APC cofactor assays, the C80Y mutant showed no cofactor activity, and the R275C mutant showed reduced activity, 62.3% of the wild type PS, whereas the R314H and P375Q + D455Y mutants exhibited normal cofactor activity. CONCLUSION: These data indicate that the C80Y and R275C mutations affect the secretion and function of the PS molecule, and that the R314H and P375Q + D455Y mutations are responsible for only secretion defects, causing the phenotype of quantitative PS deficiency observed in the patients.

Adult↗

Morphological differences in the temporomandibular joints in asymmetrical prognathism patients.

OBJECTIVE: To investigate the morphology of the temporomandibular joints (TMJ) in skeletal asymmetry with prognathism. DESIGN: Three-group observational clinical study. SETTING AND SAMPLE POPULATION: University setting. Thirty-five patients undergoing orthognathic surgery without signs and symptoms of TMJ disorder were assigned to three groups (right deviation, n = 11; left deviation, n = 14; and non-deviation; n = 10) based on anteroposterior cephalometric analysis. OUTCOME MEASURE: Positional and morphological differences of the TMJs were evaluated using a total of 70 bilateral sagittal TMJ magnetic resonance images. RESULTS: In both the right and left deviation groups, the TMJ on the deviated side showed a significantly steeper eminence than that on the non-deviated side (p < 0.05). The anterior joint space was narrower on the deviated side than on the non-deviated side whereas the posterior joint space did not differ markedly, indicating an anterior position of the condyle in the glenoid fossa of the TMJ on the deviated side. Disk displacement comparisons revealed no significant differences between left and right sides in the symmetry or asymmetry group. CONCLUSION: Asymmetrical prognathism patients exhibit significant morphological differences between the right and left TMJs concerning the slope of the articular eminence, which correspond to facial asymmetry.

Adolescent↗

Chronic posterior dislocation of the glenohumeral joint complicated by a fractured proximal humerus: a case report.

A 41-year-old right-handed woman was involved in a traffic accident and landed on the right arm while the right shoulder was in flexion. She experienced pain and severe impairment of right shoulder motion immediately following the accident. She was misdiagnosed with a fractured proximal humerus with no displacement and was treated conservatively by immobilisation. There was inadequate recovery in range of motion and gradual development of severe pain. Two years and 4 months after the injury, the patient presented to our hospital where a diagnosis of chronic posterior fracture dislocation of the shoulder with split articular surface of the humeral head was made. A humeral head replacement without resection of the greater tuberosity or the coracoid process was performed. Postoperative recovery was uneventful. The patient returned to work as a cook one year later. At 20-month follow-up, the patient had no pain, and her shoulder range of motion was forward flexion 160 degrees, abduction 140 degrees, external rotation 40 degrees, and internal rotation L3.

Adult↗

Estimation of particulate nutrient load using turbidity meter.

The "Nutrient Load Hysteresis Coefficient" was proposed to evaluate the hysteresis of the nutrient loads to flow rate quantitatively. This could classify the runoff patterns of nutrient load into 15 patterns. Linear relationships between the turbidity and the concentrations of particulate nutrients were observed. It was clarified that the linearity was caused by the influence of the particle size on turbidity output and accumulation of nutrients on smaller particles (diameter < 23 microm). The L-Q-Turb method, which is a new method for the estimation of runoff loads of nutrients using a regression curve between the turbidity and the concentrations of particulate nutrients, was developed. This method could raise the precision of the estimation of nutrient loads even if they had strong hysteresis to flow rate. For example, as for the runoff load of total phosphorus load on flood events in a total of eight cases, the averaged error of estimation of total phosphorus load by the L-Q-Turb method was 11%, whereas the averaged estimation error by the regression curve between flow rate and nutrient load was 28%.

Agriculture↗

Total cost minimization control scheme for biological wastewater treatment process and its evaluation based on the COST benchmark process.

This paper proposes a new cost minimisation control scheme for a predenitrification type of biological wastewater treatment process and evaluates the validity of the control scheme based on the benchmark process presented by Copp. The control scheme adopting a hierarchical control structure incorporates lower-level controllers that consist of a set of local dynamic controllers and a higher-level static optimiser that provides the set points of the lower-level controllers based on the total cost index of Vanrolleghem and Gillot. Prior to benchmarking, this paper derives a simplified process model used for the optimiser, which is able to approximate the benchmark process model effectively as well as is simplified sufficiently for faster set point optimisation for on-line purposes. Numerical experiments evaluate the effectiveness of the proposed control scheme from various viewpoints including process operational and optimisation viewpoints.

Benchmarking↗

Evaluation of a long-term operation of a submerged nanofiltration membrane bioreactor (NF MBR) for advanced wastewater treatment.

Nanofiltration (NF) is considered as one of the most promising separation technologies to obtain a very good-quality permeate in water and wastewater treatment. A submerged NF membrane bioreactor (NF MBR) using polyamide membranes was tested for a long-term operation and the performance of the NF MBR was compared with that of a microfiltration MBR (MF MBR). Total organic carbon (TOC) concentration in the permeate of the NF MBR ranged from 0.5 to 2.0 mg/L, whereas that of the MF MBR showed an average of 5 mg/L. This could be explained by the tightness of the NF membrane. Although the concentration of organic matter in the supernatant of the NF MBR was higher than that in the permeate due to high rejection by the NF membrane, the NF MBR showed excellent treatment efficiency and satisfactory operational stability for a long-term operation.

Bioreactors↗

Demonstration of inter- and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission (Micro-PIXE).

Micro-proton-induced X-ray emission (Micro-PIXE) was applied to determine inter- and intracellular distribution of boron (10B) and gadolinium (157Gd), the capture atoms used to kill tumor cells in neutron capture therapy (NCT). Cultured 9L gliosarcoma cells on Mylar film were exposed to sodium borocaptate (BSH) and gadobenate dimeglumine (Gd-BOPTA). To analyze the inter- and intracellular distribution of 10B and 157Gd in 9L gliosarcoma cells, the cells were irradiated using a proton beam of 1.7 or 3 MeV energy collimated to 1 microm diameter and emission X-ray was detected. The distribution of 10B and 157Gd in 9L gliosarcoma cells was then examined. In this study, we could directly analyze the inter- and intracellular distribution of 10B and 157Gd elements in 9L gliosarcoma cells directly using Micro-PIXE. This is the first report on the distribution of 10B employing a method to detect gamma-rays resulting from the nuclear reaction of 10B using particle-induced gamma-ray emission (PIGE). These results show that the distribution of 157Gd elements was correctly measured using micro-PIXE. 157Gd should have the same tendency as 10B in cultured 9L gliosarcoma cells and agree with the distribution in 9L gliosarcoma cells. Further investigation is necessary for a higher spatial resolution and optimization of the measurement time or improvement of the sampling method. In the future, it will be possible to employ this method to analyze the intracellular microdistribution of the capture element and in the development of new drugs for NCT.

Boron↗

Carotid endarterectomy may reduce the high stroke rate for patients with the disease of abdominal aorta and peripheral arteries.

AIM: The prevalence of carotid stenosis is reported to be high among patients with arteriosclerosis, but the hazards of carotid stenosis and the benefits of carotid endarterectomy (CEA) on long-term event-free survival are still unknown. The aim of this prospective study was to screen preoperative patients with arterial disease for carotid stenosis, and to determine whether CEA had any effect on stroke during the postoperative follow-up period. METHODS: From 1999 to 2003, 406 consecutive preoperative patients with arterial disease underwent routine carotid duplex scan. Patients with known carotid stenosis and those due to undergo operation in emergency were excluded from the study. CEA was performed before or simultaneously with vascular surgery if necessary. The prevalence and risk factors for carotid stenosis were studied, and the patients were followed up for stroke or death. RESULTS: Among the 406 patients examined, 19.4% had greater than 50% stenosis and 11.3% had greater than 70% stenosis. The risk factors for carotid stenosis were having occlusive arterial disease (P=0.0001), and history of stroke (P=0.0038). Long-term follow-up study revealed that patients with greater than 70% carotid stenosis without CEA had a higher tendency for stroke or death, but the stroke rate in patients with severe stenosis who underwent CEA remained low, as in patients with less than 70% stenosis. CONCLUSIONS: Patients with greater than 70% carotid stenosis, diagnosed before arterial operation who did not undergo CEA, had a higher risk for stroke during the postoperative follow-up period. However, their risk could be reduced by performing CEA before or simultaneously with scheduled vascular surgery.

Aged↗

Drug nanoparticle formation from drug/HPMC/SDS ternary ground mixtures.

Drug nanoparticle formation from a ternary ground mixture consisting of a poorly water-soluble drug, hydroxypropylmethylcellulose (HPMC), and sodium dodecyl sulfate (SDS) was investigated. Flurbiprofen, which did not show nanoparticle formation by co-grinding with polyvinylpyrrolidone (PVP) and SDS, was used as a model drug. Flurbiprofen, HPMC and SDS were mixed at the weight ratio of 1:3:1 and ground for 30 min in a vibrational rod mill. The drug nanoparticle formation was observed after the ternary ground mixture (GM) was dispersed into distilled water. Molecular interactions both between flurbiprofen and HPMC and between polymer and surfactant were found to be important factors for the nanoparticle formation. The GM was stable for 2 months at the storage condition of 40 degrees C and RH 22%. Mean particle size of the dispersed particles was still less than 350 nm after storage at 25 degrees C for 1 month. It was found that the drug/HPMC/SDS ternary grinding method was applicable not only for flurbiprofen but also for other hydrophobic drugs, such as tolbutamide, probucol, phenytoin and griseofulvin. The drug nanoparticles were also obtained using other cellulose derivatives, indicating that these pharmaceutical excipients were alternative to PVP for the grinding-induced drug nanoparticle formation.

Anti-Inflammatory Agents, Non-Steroidal↗

[Drug-eluting stents restenosis 2 months after the procedure and necessitating semi-emergency off-pump coronary artery bypass].

Drug-eluting stents (sirolimus-eluting stent: Cypher stent) have showed a reducing the frequency of in-stent restenosis and a good safety profile. One case involving edge dissection with Cypher stent restenosis for 2 lesions was diagnosed in 2 months after the procedure. This case occurred in a hypertensive 63-year-old woman with complex coronary lesions. The coronary angiography showed uncovered proximal dissection with 90% restenosis in left anterior descending coronary artery to left main trunk and 75% restenosis in right coronary artery. We were able to perform semi-emergency off-pump coronary artery bypass (OPCAB). There is the relationship between coronary dissection and restenosis. Cypher stent delayed dissected arterial healing and promote some inflammation at the lesion. Patients implanted Cypher stent with uncovered coronary dissection need more frequent follow-up.

Angina, Unstable↗

[Extracardiac rupture of aneurysm of the noncoronary sinus of valsalva: report of a case].

A 78-year-old female was admitted to our hospital because of sudden onset of chest pain and general fatigue. A chest X-ray showed marked cardiomegaly and computed tomography (CT) revealed pericardial effusion with left pleural effusion. Upon admission to CCU, she suddenly lost consciousness and was intubated. Echocardiography confirmed increase in the amount of the pericardial effusion, which was drained at CCU. By an emergent operation, ruptured aneurysm of the noncoronary sinus of Valsalva to the pericardial space was confirmed upon opening the chest and patch plasty of the sinus of Valsalva was performed. The postoperative course was uneventful, and she was discharged on the 24th postoperative day. Extracardiac rupture of aneurysm of the sinus of Valsalva is extremely rare, and the emergent operation is indispensable.

Aged↗

[Early results of new style aortosaphenous vein graft connector in coronary artery bypass grafting].

We retrospectively studied early clinical results of PAS-Port (PP) system. Fifty patients who underwent coronary artery bypass surgery with saphenous vein graft (SVG) from April 2004 to May 2005 were enrolled in this study. PP was tried for 36 SVGs in 32 patients. In 2 patients, SVG 4.0 mm in diameter could not be loaded into the device. In other 2 patients, anastomosis with PP was failed and followed by hand-sewing under aortic clamp or with Heartstring. Anastomosis with PP was successfully completed for 34 SVGs in 30 patients (group P) and conventional hand-sewing was performed for 23 SVGs in 20 patients (group C). The target vessels for SVG were similar between the 2 groups. No complication occurred in the use of PP. Postoperative angiography before discharge was performed for 31 SVGs in 27 patients (90.0%) in group P and 20 SVGs in 17 patients (85.0%) in group C. The patency rate of SVG was 96.8% in group P and 100% in group C. In conclusion, early results of PP were satisfactory compared with those of conventional hand-sewing. Severely sclerotic aorta and oversized SVG should be excluded because of possibility for incomplete deployment of the inner flange in PP.

Aged↗