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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 847 records · Page 47Linked to original sources

Prevalence and risk factors of allergic rhinitis and cedar pollinosis among Japanese men.

BACKGROUND: Although recent reports show a worldwide increase in allergic diseases during the past 10-20 years, few epidemiological studies on secular trend and the age-specific prevalence of allergic rhinitis have been carried out in Japan. We conducted a study to clarify the age-specific prevalence of allergic rhinitis and cedar pollinosis to provide baseline data for a prospective study and to investigate the association of rhinitis with both environmental and personal factors among 2,307 Japanese men. METHODS: Allergic rhinitis was determined from self-reported allergic rhinitis or from the seasonal symptoms of the nose. Seasonal rhinitis was defined as symptoms evoked in the subjects from February to May. Cedar pollinosis was defined as the presence of cedar-specific IgE positivity among subjects with seasonal rhinitis. RESULTS: The prevalences of allergic rhinitis, seasonal rhinitis, and cedar pollinosis were 35.5, 28.8, and 11.0%, respectively. Age was a negative risk factor for all allergic conditions. Allergic family history and residence along a main street were strong risk factors for all allergic rhinitis. CONCLUSIONS: The current prevalence of each rhinitis was higher than previously reported. The risk factors were similar for each allergic rhinitis except for a past history of atopy.

Adult↗

Quantitative estimation of tumor metastasis by measurement of DNA polymerase activity.

Metastatic tumor burden in the lung of C57BL/6 or BDF1 mice was quantitated by measuring DNA polymerase alpha activity in the lung of tumor-bearing animals. DNA polymerase activity in the lung increased time-dependently following the inoculation of Lewis lung carcinoma (s.c.) or B16 melanoma variant B16-B2 (i.v.). In the Lewis lung carcinoma system, the number of metastatic modules and the weight of lung also increased time-dependently. Results from the B16 melanoma showed that the increase in lung nodules occurred 10 to 20 days after i.v. inoculation of tumor cells. DNA polymerase activity increased significantly during this period. Because the lung nodules were very small there was no obvious concomitant increase in lung weight. Since no significant infiltration of host cells was observed in the lung in response to metastatic foci, the rise in DNA polymerase activity should be due to tumor cells and not to infiltrating host cells. When the metastasis of Lewis lung carcinoma was inhibited by adriamycin and cyclophosphamide, decrease in DNA polymerase activity in the lung occurred. These results indicate that the degree of tumor metastasis can be quantitated by measuring DNA polymerase activity.

Animals↗

Preparation of micelle-forming polymer-drug conjugates.

Adriamycin, a hydrophobic anticancer drug, was conjugated with poly(ethylene oxide)-poly(aspartic acid) block copolymers composed of various lengths of each block copolymer segment ranging from 1000 to 12,000 in molecular weight and from 10 to 80 units, respectively. Conjugation was achieved without precipitation by adjusting the ratio of adriamycin to aspartic acid residues of the block copolymer and the quantity of DMF used for the reaction. Thus obtained conjugates showed high water solubility irrespective of a large amount of the conjugated adriamycin. Furthermore, these conjugates were found to form micellar structures with a hydrophobic inner core and a hydrophilic outer shell. This micellar architecture may be utilized for effective drug targeting.

Chromatography, Gel↗

Temperature-responsive bioconjugates. 1. Synthesis of temperature-responsive oligomers with reactive end groups and their coupling to biomolecules.

Using 3-mercaptopropionic acid (MPA) as a chain-transfer agent, the radical oligomerization of N-isopropylacrylamie (IPAAm) was carried out with varying molar ratios of MPA to IPAAm and DMF. The molecular weight of oligo-IPAAm (OIPAAm) could be controlled by the ratio of MPA to IPAAm. The OIPAAm was confirmed to average one carboxyl end group per chain. All OIPAAms samples were highly water-soluble at lower temperatures and exhibited phase separation near 32 degrees C. The optical transmittance of the OIPAAms aqueous solutions changed drastically at 32 degrees C which was independent of OIPAAms molecular weight. In aqueous solutions of OIPAAm having concentrations higher than 1 wt% and molecular weight of 6100, the oligomers were precipitated and recovered in 85 wt% yield of their original content. Further, OIPAAm was grafted to atelo collagen by activated ester-amine coupling. The OIPAAm-collagen conjugates were able to dissolved in cold water and precipitated at 34 degrees C. Temperature-responsive OIPAAm-collagen conjugates are expected to maintain native collagen functionality in the solution state, react at lower temperatures, and be easily removed from the system with small temperature increases.

3-Mercaptopropionic Acid↗

Temperature-responsive bioconjugates. 2. Molecular design for temperature-modulated bioseparations.

We have synthesized carboxyl semitelechelic oligo(N-isopropylacrylamide) (OIPAAm) using radical telomerization with 3-mercaptopropionic acid. This telomerization is also effective for the synthesis of carboxyl semitelechelic co-oligomers of IPAAm with butyl methacrylate (BMA) as hydrophobic or N,N-dimethylacrylamide (DMAAm) as hydrophilic comonomers. All co-oligomers are highly water-soluble at lower temperatures and exhibit phase separation with increasing temperature. Pure OIPAAm exhibits a lower critical solution temperature (LCST) at 32 degrees C, and the LCST for co-oligomers can be controlled to increase over 32 degrees C with increasing DMAAm composition and to decrease below 32 degrees C with increasing BMA composition. OIPAAm was grafted to bovine serum albumin (BSA) and bovine plasma fibrinogen (BPF) by activated ester-amine coupling. These OIPAAm-biomolecule conjugates maintain their temperature responses, are soluble in cold water, and precipitate over a range of temperatures related to oligomer content. Conjugates could be selectively precipitated and independently separated from conjugate solution mixtures with increasing temperature. In this case, the number of OIPAAm molecules attached to a conjugate affects the aggregate sizes of precipitated conjugates in mixtures. Both conjugate mixture ratios and solution concentrations influence the contamination of oligo(IPAAm-co-DMAAm)-BSA conjugates in precipitated oligo(IPAAm-co-BMA)-BPF conjugates. Furthermore, precipitated conjugates separated using centrifugation and filtration redissolve in water and maintain their biofunctionality, indicating the potential of strategy in reversible bioreactors and protein separations.

3-Mercaptopropionic Acid↗

Temperature-responsive bioconjugates. 3. Antibody-poly (N-isopropylacrylamide) conjugates for temperature-modulated precipitations and affinity bioseparations.

Immunoglobulin G (IgG) has been modified by poly(N-isopropylacrylamide) (PIPAAm) to create a novel bioconjugate which exhibits reversible phase transition behavior at 32 degrees C in aqueous media. A terminal carboxyl group introduced into PIPAAm molecule by polymerization of IPAAm with 3-mercaptopropionic acid was used for conjugation to IgG via coupling reaction of activated ester with protein amino group. These conjugates exhibited rapid response to changes in solution temperature and significant phase separation above a critical solution temperature corresponding to that for the original PIPAAm. These conjugates bound to antigen quantitatively in aqueous system, and antigen-bound complex also demonstrated phase separation and precipitation above a critical temperature. Precipitate was reversibly redissolved in cold buffer. Though particular conjugate which includes 12 molecules of PIPAAm with 6,100 molecular weight suppressed more than 95% of Fc-dependent binding with protein A, it retained approximately 60% of original specific antigen binding activity. It was manifested that polymer content of conjugate was 20-30 wt% for the case of 6,100 molecular weight of PIPAAm to demonstrate specific antigen binding activity most effectively and to reduce Fc-dependent binding with protein A. IgG-PIPAAm conjugates were soluble in water and formed antigen-bound complex in homogeneous solution system below a critical temperature. These conjugates were separated from solution and other solutes corresponding to PIPAAm nature and scarcely bound to antigen above a critical temperature. It is revealed that temperature-responsive PIPAAm conjugated to biomolecule operated as a switching molecule. These phenomena are attractive for not only reversible bioreactors and protein separations but also carrier substrate to localize biomolecules such as drugs, peptides and hormones in a living body.

3-Mercaptopropionic Acid↗

Effect of molecular architecture of poly(N-isopropylacrylamide)-trypsin conjugates on their solution and enzymatic properties.

Polymer-enzyme hybrid conjugates modified by a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm), have been synthesized. We have investigated the molecular architecture of PIPAAm-enzyme conjugates by preparing two types of PIPAAm-trypsin conjugates, wherein PIPAAm chains are attached by either single-end or multipoint chemistry. A semitelechelic co-oligomer (IDc) was attached to trypsin by single-point conjugation (IDc-trypsin). A copolymer (PIDAAc) consisting of acrylic acid and IPAAm randomly linked in polymer chains was attached to trypsin using multipoint conjugation (PIDAAc-trypsin). Both conjugates exhibited reversible temperature-responsive phase separation. The IDc-trypsin conjugate exhibited phase separation at the same temperature as pure IDc, due to the highly mobile free polymer end group which remains sensitive to small temperature changes. The PIDAAc-trypsin conjugate precipitated at higher temperatures than pure PIDAAc, whose movement was restricted by multiple binding points. Enzyme stability in solution was improved after introduction of PIPAAm chains, which prevented autolysis attributed to conjugate steric hindrance. Stability under repeated temperature cycling was also dependent on the architecture of conjugates; the IDc-trypsin conjugate was more stable than the PIDAAc-trypsin. As a consequence, single-end conjugation of polymer to enzyme provides novel bioconjugate with novel functionality attributed to attached polymer while retaining native biological function with high stability.

Acrylic Resins↗

Platelet adhesion and activation on polyethylene glycol modified polyurethane surfaces. Measurement of cytoplasmic calcium.

Polyurethane (PU) surfaces were modified by coupling polyethylene glycol (PEG; molecular weight, 1,000) chains carrying different terminal groups (PU-PEG1K-OH, PU-PEG1K-NH2, PU-PEG1K-SO3) and longer PEG chains (MW, 3,350; PU-PEG3.4K-OH). The modified PU surfaces have the same PEG (1K) chain density. Surface induced platelet activation was evaluated by measuring cytoplasmic free calcium concentration in platelets contacting modified surfaces, and platelet adhesion onto modified surfaces was investigated in vitro. Cytoplasmic free calcium levels in platelets contacting PU-PEG-SO3 remained relatively constant, in contrast to the significant increase observed for PU-PEG-NH2, PU-PEG-OH, and control PU surfaces. The degree of platelet adhesion clearly demonstrates that all PEG graft surfaces prevented platelet adhesion. Among PEG1K surfaces, PU-PEG-SO3 shows the lowest platelet adhesion. In the case of relatively longer PEG grafted surfaces (PU-PEG3.4K-OH and PU-PEG3.4K-Hep), both surfaces were found to prevent the increase in both cytoplasmic free calcium and platelet adhesion. These results suggest that longer PEG chain grafting is more effective than shorter grafting in preventing platelet activation and adhesion because of the highly dynamic movement of hydrated PEG chains at the interface. In addition, in vitro platelet interaction is dependent upon terminal groups of PEG chains on PEG1K series surfaces.

Biocompatible Materials↗

A new blood compatible and permselective hollow fiber membrane for hemodialysis.

The authors have prepared a blood compatible and highly permselective hemodialysis membrane composed of polyether segmented nylon. This block copolymer was synthesized by polycondensation of bis-3-aminopropyl-poly(tetramethylene oxide) (PTMO) and poly(imino-1,3-bismethyl-cyclohexyl-iminoisophtharoyl) (NyBl) prepolymer obtained by polycondensation of 1,3-bis(aminomethyl)cyclohexane (B) and isophthalic acid (I). The molecular weight (MW) calculated from the number of end-groups was 16,000-21,000. In vitro blood compatibility was evaluated in terms of platelet adhesion onto the surface. PTMO-NyBl surfaces showed excellent platelet adhesion preventing properties. The PTMO-NyBl hollow fiber membrane was obtained by a dry-wet spinning process. The membranes had higher permeability coefficients for macromolecules ranging from MW 10,000 to 20,000 than polysulfone hollow fiber membrane (PS membrane), and had acceptably low albumin permeability for use as a dialysis membrane. The ex vivo blood compatibilities of PTMO-NyBl membrane and PS membrane were investigated by extracorporeal circulation in a pig model. The PTMO-NyBl membrane gave excellent results when assessing hemodialysis leukopenia, oxidative burst, and free platelet count decrease.

Biocompatible Materials↗

Working memory for temporal and nontemporal events in monkeys.

This is the first report that introduces appropriate behavioral tasks for monkeys for investigations of working memory for temporal and nontemporal events. Using several behavioral tests, the study also shows how temporal information is coded during retention intervals in the tasks. Each of three monkeys was trained with two working memory tasks: delayed matching-to-sample of stimulus duration (DMS-D) and delayed matching-to-sample of stimulus color (DMS-C). The two tasks employed an identical apparatus and responses and differed only in the temporal and nontemporal attribute of the stimuli to be retained for correct performance. When a retention interval between the sample and comparison stimuli was prolonged, the monkeys made more incorrect responses to short samples in the DMS-C task, suggesting "trace decay" of memory for short stimuli. However, the same monkeys showed no such increase in incorrect responses to short samples in the DMS-D task, suggesting active coding of temporal information, that is, the length of stimulus duration, during the retention interval. When variable lengths of samples were presented with a fixed retention interval, the monkeys made more incorrect responses when length differences between short and long samples were small in the DMS-D task, but not in the DMS-C task. This suggests that the codes of working memory retained in the DMS-D task were not absolute (analogical) but rather were relative (categorical) and related to differences in the duration of the samples.

Animals↗

Low-dosage intravenous immunoglobulin in the management of a patient with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance.

We report herein the case of a 69-year-old Japanese man with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance who developed IgG1-kappa antibodies against von Willebrand factor (VWF). The patient was urged to undergo tooth extractions because of alveolar pyorrhea, and a low-dosage intravenous immunoglobulin (IV-Ig) therapy (0.3 g of IgG/kg/day for 3 days) was chosen for him. On the 4th day after the infusion, VWF antigen and VWF ristocetin cofactor increased to 40 and 78% of the control, respectively, and dental extractions were performed successfully. On the 7th day, these values reached a maximum, i.e. 95 and 160% of the control, respectively. Then, they quickly decreased to 35 and 75% on the 10th day, and 6 months later, they became 16 and <3% of the control, respectively. Upon analysis of plasma VWF multimers (VWFMs) in this patient, those with large to medium molecular masses more selectively disappeared before the IV-Ig infusion than did those with small molecular masses. On the 4th day, the pattern of VWFMs was completely normalized and appeared to persist until the 10th day. Six months later, a small amount of large to medium-sized VWFMs was still present, but at 7-8 months, the pattern of VWFMs became almost the same as that before infusion. Throughout the patient's clinical course, the activity of plasma VWF-cleaving protease, which specifically cleaves the Tyr842-Met843 bond of the subunit and reduces its multimeric sizes, was quite normal (95-119%). These results provided consistent evidence that the selective absence of VWFMs with large to medium molecular masses in this patient is caused by the heightened clearance of a complex of IgG inhibitor and VWFMs from the circulation, presumably through IgG binding to the Fc receptor of macrophages. Furthermore, these results also indicated that a low-dosage IV-Ig therapy is effective enough for hemostatic management for programmed surgery.

ADAM Proteins↗

Continuous measurement of regional cerebral blood flow using krypton-81m.

We have developed a new method for taking continuous measurements of rCBF by means of continuous infusion of 81mKr. Using this method, it is possible to follow the sequential changes in blood flow of various brain regions continuously. The method makes it possible to observe the sequential changes in CBF following drug administration, motor activation and various kinds of stimulation, and, furthermore, to observe the CO2 reactivity and autoregulation of cerebral vessels. It will undoubtedly prove useful in the investigation of various pathological states.

Adult↗

Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound.

Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to be an efficient radiosensitizer. We have investigated the radiosensitizing effect of wortmannin on cell killing against thermal neutrons produced by the Kyoto University Research (KUR) reactor. Wortmannin was added to cells 2 hours before irradiation and removed 16 hours after irradiation. Cells were irradiated by thermal neutrons with or without boron at 0, 10, and 20 ppm. The biological end point of cell survival was measured by colony formation assay. The D0 values of thermal neutrons in different boron concentrations, 0, 10, and 20 ppm were 1.2, 1.1, and 1.0 Gy, respectively. When cells were treated with wortmannin, the D0 values decreased to 0.5, 0.6, and 0.8 Gy at boron concentrations of 0, 10, and 20 ppm, respectively. Wortmannin enhanced cell death against thermal neutron irradiation especially in the absence of boron. Thus, our results suggest that wortmannin may be useful to combine with boron neutron capture therapy (BNCT) treatment when boron uptake by cells is limited.

Androstadienes↗

Contrast-enhanced MR angiography of the carotid artery using 3D time-resolved imaging of contrast kinetics: comparison with real-time fluoroscopic triggered 3D-elliptical centric view ordering.

PURPOSE: To evaluate contrast-enhanced MR angiography using the 3D time-resolved imaging of contrast kinetics technique (3D-TRICKS) by direct comparison with the fluoroscopic triggered 3D-elliptical centric view ordering (3D-ELLIP) technique. METHODS: 3D-TRICKS and 3D-ELLIP were directly compared on a 1.5-Tesla MR unit using the same spatial resolution and matrix. In 3D-TRICKS, the central part of the k-space is updated more frequently than the peripheral part of the k-space, which is divided in the slice-encoding direction. The carotid arteries were imaged using 3D-TRICKS and 3D-ELLIP sequentially in 14 patients. Temporal resolution was 12 sec for 3D-ELLIP and 6 sec for 3D-TRICKS. The signal-to-noise ratio (S/N) of the common carotid artery was measured, and the quality of MIP images was then scored in terms of venous overlap and blurring of vessel contours. RESULTS: No significant difference in mean S/N was seen between the two methods. Significant venous overlap was not seen in any of the patients examined. Moderate blurring of vessel contours was noted on 3D-TRICKS in five patients and on 3D-ELLIP in four patients. Blurring in the slice-encoding direction was slightly more pronounced in 3D-TRICKS. However, qualitative analysis scores showed no significant differences. CONCLUSION: When the spatial resolution of the two methods was identical, the performance of 3D-TRICKS was found to be comparable in static visualization of the carotid arteries with 3D-ELLIP, although blurring in the slice-encoding direction was slightly more pronounced in 3D-TRICKS. 3D-TRICKS is a more robust technique than 3D-ELLIP, because 3D-ELLIP requires operator-dependent fluoroscopic triggering. Furthermore, 3D-TRICKS can achieve higher temporal resolution. For the spatial resolution employed in this study, 3D-TRICKS may be the method of choice.

Adult↗

Extramedullary plasmacytoma extensively affecting the sella turcica and paranasal sinuses.

We report a 62-year-old Japanese male who complained of double vision and showed clear boundary mass extending to the clivus, intrasella, suprasella, ethmoidal sinus and sphenoid sinus on neuroimaging. The tumor mass was partially resected via transsphenoidal approach and was diagnosed as the extramedullary plasmacytoma by IgA immunostaining and electron microscopy. Making diagnosis from the imaging findings was difficult in this rare case, but immunohistological and electron microscopic examinations were useful for pathological diagnosis.

Adenoma↗