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Biomedical subjects

S Ichikawa

Publications and source records attributed to S Ichikawa.

At least 55 records · Page 3Linked to original sources

Small-angle X-ray scattering analysis of stearic acid modified lipase.

Stearic acid modified lipase (from Rhizopus japonicus) exhibited remarkable interesterification activity in n-hexane, but crude native lipase did not. The structure of the fatty acid modified lipase had not been analyzed until now. We analyzed the modified lipase by small-angle X-ray scattering (SAXS) measurements in order to clarify the structure. SAXS measurements showed that the modified lipase consisted of a lipid lamellar structure and implied that the lipase was incorporated into the lamellar structure of stearic acid. The long spacings in the lamellar structures of the modified lipase and stearic acid were measured.

Algorithms↗

Effects of double mutation at two distant IgE-binding sites in the three-dimensional structure of the major house dust mite allergen Der f 2 on IgE-binding and histamine-releasing activity.

Recently, we reported that introduction of mutations that induced conformational changes of the major mite allergen Der f 2 was an efficient strategy to reduce the allergenicity for safer allergen-specific immunotherapy. In this study, we evaluated another strategy, disruption of two independent IgE epitopes without inducing conformational change. We analyzed allergenicities of the wild-type Der f 2, two single mutants with a mutation at either of the two IgE-binding sites (K15A and K77A), and a double mutant with mutations at both of the sites (K15/77A). Purified recombinant forms of Der f 2 expressed in Escherichia coli had correct disulfide bonds, equivalent apparent molecular masses of approximately 15 kDa, and similar secondary structures. The mutants of Der f 2 had less IgE reactivities than the wild-type Der f 2 and reduced inhibitory activities for IgE-binding to the wild-type Der f 2. However, the mutations did not significantly reduce histamine-releasing activity.

Allergens↗

Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients.

The object of this study is to evaluate the long-term effects of olmesartan on hypertension and the renin-angiotensin-aldosterone system in hypertensive patients. This study evaluated 26 hypertensive male and female outpatients, 38-69 years of age, with a systolic blood pressure > or = 160 mmHg and/or a diastolic blood pressure > or = 95 mmHg. Oral doses of 5 to 40 mg olmesartan were administered once daily. Blood pressure and renin-angiotensin-aldosterone parameters (plasma renin activity and plasma angiotensin I, II, and aldosterone concentrations) were evaluated at 12-16 weeks, 6 months, and 1 year after the start of olmesartan administration. Systolic and diastolic blood pressures were significantly decreased following the administration of olmesartan. The observed decreases in systolic and diastolic blood pressures after 1 year of treatment were 28.8+/-2.1 mmHg and 15.8+/-1.3 mmHg, respectively. No change was observed in the pulse rate. The plasma renin activity increased significantly from a baseline premedication mean of 1.26+/-0.31 ng/ml/h to a mean of 2.58+/-0.74 ng/ml/h and 2.87+/-0.72 ng/ml/h after 6 months and 1 year of treatment, respectively. Angiotensin II levels decreased significantly from a baseline of 20.4+/-3.2 pg/ml to a mean of 8.6+/-2.1 pg/ml and 6.8+/-1.8 pg/ml after 6 months and 1 year of treatment, respectively. The plasma aldosterone level also decreased significantly after 6 months of treatment. In hypertensive patients, the long-term administration of olmesartan, a novel AT1 receptor antagonist, decreased both blood pressure and plasma angiotensin II levels.

Adult↗

[Inferior mini-sternotomy for off-pump CABG using bilateral internal thoracic arteries].

Case 1: A 72-year-old woman with effort angina underwent coronary artery bypass grafting. A preoperative coronary angiogram showed 90% stenosis in the proximal main RCA, and total occlusion in the proximal LAD, distal of which was an area well supplied by collaterals from the RCA. This patient had previously undergone right upper lobectomy due to lung cancer. With a skin incision of 8 cm, the LITA was inserted into the LAD and the RITA was inserted into the mid RCA through an inferior mini-sternotomy while the heart was beating. Case 2: A 69-year-old man with effort angina underwent CABG. A preoperative coronary angiogram showed 90% stenosis in the proximal main RCA, 75% stenosis in the PDA and total occlusion in the proximal LAD, distal of which was an area well supplied by collaterals from the RCA. With a skin incision of 11 cm, the LITA was inserted into the LAD, the RITA into the mid-RCA and the radial artery graft attached to the RITA was grafted to the PDA through an inferior mini-sternotomy while the heart was beating. In both cases, the sternum was not cut transversely in order to prevent injury to the ITAs and pseudo-joint formation. With the use of this technique, exposure of the LAD and RCA was excellent. Postoperative recovery in both patients was uneventful and postoperative angiograms revealed widely patent grafts. This technique was very useful when performing off-pump CABG using bilateral ITAs.

Aged↗

Asymptomatic case of congenital absence of the gallbladder.

Congenital absence of the gallbladder is rare among biliary abnormalities, and its preoperative diagnosis has been considered very difficult. We encountered a patient with congenital absence of the gallbladder and suggest a possible preoperative diagnosis of the abnormality, as well as reviewing the literature.

Adult↗

[Characteristics of heterosexually acquired AIDS in Japan. An inter-country comparison using AIDS Surveillance data].

OBJECTIVES: To identify epidemiological characteristics of heterosexually acquired AIDS in Japan, with emphasis on potential influence on future trends. METHODS: National AIDS Surveillance data in Japan were compared with those in the UK and US, where detailed information is available from well-established surveillance procedures. Data on AIDS cases diagnosed until the end of 1996, particularly those acquired heterosexually, were analyzed by year of diagnosis, gender and age group. RESULTS: The number of heterosexually acquired AIDS cases in Japan has continued to increase, while those in the UK and US leveled out or decreased recently. The increase during a two-year period after reaching a certain number of cases per year was found to be 2.3-fold in Japanese, 2.4-fold in UK whites and 5-fold in US whites. The male to female ratio (M/F) for heterosexually acquired AIDS was 6.3 among Japanese, while the ratio was 1.1 and 0.5 in the UK and US, respectively. The age distribution at AIDS diagnosis demonstrated a peak from 35 to 54 years of age among Japanese males, as compared to 30 to 34 among males in the UK and the US. No significant difference was apparent in the age distribution among females in the three countries. CONCLUSIONS: The relatively small number of AIDS cases in Japan is attributable to the late introduction of HIV and the limited chance of heterosexual transmission from homosexual/bisexual men and injecting drug users. In addition, transmission has probably most often occurred between middle-aged Japanese males and non-Japanese females. As there is a growing risk of HIV infection among Japanese females and young Japanese males, new prevention strategies targeting these groups are urgently required.

Acquired Immunodeficiency Syndrome↗

[Coronary artery bypass-grafting using interrupted anastomosis with the U-clip].

For coronary artery anastomosis, the continuous suture technique is generally used because it is easy to perform, there is less anastomotic leakage, and a shorter anastomotic time compared with the interrupted suture technique. However, with this technique there is a potential risk of anastomotic stenosis caused by the purse-string effect, which does not occur with the interrupted suture technique. The U-Clip device was designed to facilitate the interrupted suture technique in coronary anastomosis by eliminating the need for suture management, knot tying, and surgical assistance. The device employs the superelastic properties of nitinol and two components: 1. a needle/suture delivery system, and 2. a detachable nitinol self-closing wire. We used this device successfully for LITA-LAD anastomosis in MIDCAB. When this device is applied to small caliber conduits, such as the internal thoracic arteries and the gastroepiploic artery, the side-to-side anastomosis can reduce the anastomotic leakage more efficiently, since the coronary incision and graft incision can be perfectly matched. The U-Clip facilitates coronary anastomosis by simplifying and decreasing the amount of manipulation and complexity required in minimally invasive CABG procedures. Nitinol technology also has potential in robotic and endoscopic surgical applications.

Aged↗

[Hormone replacement therapy and vascular function].

Hormone replacement therapy (HRT) by estrogen has a cardioprotective effect in postmenopausal women. This effect results partly from the direct actions of estrogen on vascular receptors. These are mainly endothelium-dependent or endothelium-independent vascular relaxing effects. Increases in prostacyclin and bradykinin, and a decrease in endothelin-1 by estrogen are involved.

English Abstract↗

Synthesis of pyrimidine 2'-deoxy ribonucleosides branched at the 2'-position via radical atom-transfer cyclization reaction with a vinylsilyl group as a radical-acceptor tether.

Recently, we developed a regio- and stereoselective method for introducing a vinyl group at the position beta to a hydroxyl group in halohydrins or alpha-phenylselenoalkanols via a radical atom-transfer cyclization reaction with a vinylsilyl group as a temporary connecting radical-acceptor tether. The synthesis of 2'-deoxy-2'-C-vinyl- and 2'-deoxy-2'-C-hydroxymethyluridines (7 and 8, respectively) and the corresponding 2'-deoxycytidine congeners (10 and 11, respectively), which were designed as potential antitumor and/or antiviral agents, was achieved using this radical atom-transfer cyclization as the key step. When the 2'-deoxy-2'-iodo-5'-O-monomethoxytrityl (MMTr) uridine derivative 19a, bearing a vinylsilyl group at the 3'-hydroxyl group, was heated with (Me(3)Sn)(2) and AIBN in benzene, the corresponding radical atom-transfer product was generated, which in turn was successively treated with tetrabutylammonium fluoride and TBSCl/imidazole to give the desired 2'-deoxy-5'-O-MMTr-3'-O-TBS-2'-C-vinyluridine (25). Compound 25 was successfully converted into the target 2'-deoxy-2'-branched pyrimidine ribonucleosides 7, 8, 10, and 11.

Antineoplastic Agents↗

Analyses of spontaneous pink mutant events in the stamen hairs of Tradescantia clone BNL 4430 cultivated in a nutrient solution circulating growth chamber.

In order to obtain more fundamental data on Tradescantia clone BNL 4430, one of the most suitable testers for environmental mutagens, the occurrences of spontaneous somatic pink mutations in the stamen hairs were scored for 52 weeks from 12 December 1998 to 10 December 1999, cultivating the young inflorescence-bearing shoots with roots in a nutrient solution circulating (NSC) growth chamber. The environmental conditions in the chamber were 22.0+/-0.5 degrees C during the 16h day with the light intensity of 7.5klx from white fluorescent tubes, and 20.0+/-0.5 degrees C at night. During the scoring period, 697,443 stamen hairs with an average cell number of 25.36 were observed and 2642 pink mutant events (PMEs) were detected. The overall spontaneous mutation frequency was 1.56+/-0.03 PMEs per 10(4) hair-cell divisions, and the frequency was significantly lower in May, July and August and significantly higher in November and December. By analyzing the sectoring patterns of 1856 PMEs (70.25% of PMEs detected), the most of 172 cases of multiple (two to five) pink sectors observed in the same hairs (scored as 232 PMEs for calculating mutation frequency) were found to be the results of events involving somatic recombinations occurred in single cells or cell lineages, rather than those of two or more independent somatic mutations occurred in different cells. This finding clearly shows the significance of somatic recombinations in producing such multiple sectors (382 sectors in total) which occupied 19.0% of the 2006 pink sectors in total analyzed. Somatic recombinations were considered to be playing a significant role also in producing single PMEs in the stamen hairs.

Environmental Monitoring↗

Formation of biocompatible reversed micellar systems using phospholipids.

Formation of reversed micellar systems using biocompatible components was revealed by a significant increase of water content in the organic phase. Soybean lecithin (SL), which is a mixture of different phospholipids, and phosphatidylcholine (PC) purified from soybean were used as the amphiphilic molecule. Fatty acid and fatty acid ethyl esters were used as the organic solvent. Reversed micelles were formed in the following combinations of (amphiphilic molecule)/(organic solvent): SL/ethyl caproate, SL/ethyl oleate, SL/ethyl linoleate, PC/ethyl caproate, and PC/oleic acid. Characterization of the micelles using small angle X-ray scattering analysis was presented. Reversed micelles formed in SL/ethyl caproate, SL/ethyl oleate, and PC/ethyl caproate systems were spherical. Their radius of gyration was about 40Å when the water concentration in the organic phase was maximal. Maximal water concentrations in SL/ethyl caproate and PC/ethyl caproate reversed micellar systems decreased with increasing salt concentration in the aqueous phase. Micelle sizes also decreased with increased salt concentration. The extraction of protein cytochrome c using the reversed micellar system was demonstrated. Application of these reversed micellar systems will expand to pharmaceutical and food industries.

Journal Article↗

Unlocking the allergenic structure of the major house dust mite allergen der f 2 by elimination of key intramolecular interactions.

We report on the structural background of the remarkable reduction of allergenicity in engineering of the major house dust mite allergen Der f 2. Disruption of intramolecular disulfide bonds in Der f 2 caused extensive conformational change that was monitored by circular dichroism and gel-filtration analysis. The degree of conformational change correlated well with the degree of reductions in the capacity to bind IgE and to induce histamine release from basophils in mite-allergic patients. Loosening the rigid tertiary structure by elimination of key intramolecular interactions is an effective strategy to reduce the number of high affinity IgE epitopes of allergen vaccine.

Animals↗

Synthesis of 3,7-anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate as an IP(3) receptor ligand using a radical cyclization reaction with a vinylsilyl tether as the key step. Conformational restriction strategy using steric repulsion between adjacent bulky protecting groups on a pyranose ring

3,7-Anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate (5) was designed as a novel IP(3)-receptor ligand having a C-glycosidic structure and was synthesized via a radical cyclization reaction with a temporary connecting vinylsilyl tether as the key step. The phenyl 2-O-dimethylvinylsilyl-3,4, 6-tri-O-benzyl-1-seleno-beta-D-glucopyranoside (7), in the usual (4)C(1)-conformation, was successively treated with Bu(3)SnH/AIBN and under Tamao oxidation conditions to give a mixture of five C-glycosidic products. On the other hand, similar successive treatment of the corresponding 3,4-di-O-TBS-protected substrates 13 and 24, which were in an unusual (1)C(4)-conformaion due to the steric repulsion between the bulky silyl protecting groups, gave the desired 1alpha-C-glycosides 18 and 25, respectively, as the major products. Thus, the course of the radical cyclization was effectively controlled by a change in the conformation of the pyranose ring into a (1)C(4)-form due to steric repulsion between the adjacent bulky TBS-protecting groups at the 3- and 4-hydroxyl groups. From 25, the target 5 was synthesized via phosphorylation of the hydroxyls by the phosphoramidite method. The C-glycoside trisphosphate 5 has significant binding affinity for IP(3) receptor of calf cerebella.

Journal Article↗

Regulation of UDP-glucose:ceramide glucosyltransferase-1 by ceramide.

We report that the expression of mRNA and the activity of UDP-glucose:ceramide (Cer) glucosyltransferase-1 (GlcT-1) of human hepatoma Huh7 and mouse melanoma B16 cells increases after treatment with bacterial sphingomyelinase or upon addition of short-chain Cer. Interestingly, however, GlcT-1 gene transcription was not increased by Cer when GlcT-1 cDNA was introduced with the CMV promoter in GlcT-1-deficient GM95 cells, suggesting that the normal promoter region of GlcT-1 gene is essential for the response. The conversion of C6-Cer to C6-GlcCer occurred much more rapidly in GlcT-1-overexpressing Huh7 cells than in mock transfectants. As a result, GlcT-1-overexpressing cells acquired a greater resistance to C6-Cer-mediated cell death.

Animals↗

Genomic structure and promoter analysis of putative mouse acetyl-CoA transporter gene.

The acetyl-CoA transporter gene (Acatn) encodes a hydrophobic, multitransmembrane protein that is involved in the process of O-acetylation of sialic acid residues on gangliosides. O-Acetylated gangliosides have been found to play important roles in tissue development and organization during early embryonic stages. We have cloned the gene for mouse acetyl-CoA transporter. The gene spans approximately 20 kb and is composed of seven exons and six introns. A single transcription initiation site, 371 bp upstream of the ATG start codon, was identified. The promoter region was found to lack a TATA box. However, several potential transcription factor binding motifs such as AP1, AP2, C/EBPalpha, C/EBPbeta, HSF, GATA2 and MZF1 were identified in the promoter region.

Animals↗

Small angle X-ray scattering studies on local structure of tobacco mosaic virus RNA in solution.

Effects of temperature and ionic strength (S) on the local structure of tobacco mosaic virus RNA in phosphate buffer solution are studied by analyzing the small-angle X-ray scattering (SAXS) curves. The root-mean-square radius of a cross-section of RNA chain was kept at 0.845+/-0.005 nm over a wide range of S from 0.2 to 0.003 at 20 degrees C, whereas it gradually diminished from 0.85 to 0.61 nm when the temperature is raised from 20 to 50 degrees C at S = 0.2. Nevertheless, all of SAXS curves reflecting the backbone structures were equally mimicked by theoretical ones of freely hinged rod (FHR) models, i.e. several straight rods joined with freely hinged joints in the form of a combination of the letter Y, if the constituent rod lengths in the models are adjusted. From these facts, it is suggested that the local structure of the RNA chain in aqueous solution is characterized by an essential feature that unpaired bases in the partially double-stranded helix are constantly far isolated from each other along the helix and the rod-like structure of the helix is preserved over a range of helical contents. Such a characteristic local structure of the chain is entirely collapsed in the formamide solution at 50 degrees C.

Buffers↗

Core-excited states in the doubly magic 68Ni and its neighbor 69Cu

In deep-inelastic collisions of 8 MeV/nucleon 70Zn projectiles with 198Pt, we have found an 8(+) isomer with T(1/2) = 23(1) ns at 4208 keV in 68Ni; the nug(9/2) E2 effective charge was determined to be 1. 5(1)e. In 69Cu, a 19/2(-) isomer with T(1/2) = 22(1) ns at 3691 keV was identified and its decay data were calculated quite accurately by a parameter-free shell model calculation using empirical input parameters. Proton 2p- 1h excitation, fed by another T(1/2) = 39(6) ns isomer at 3827 keV, induces large collectivity in 69Cu.

Journal Article↗

Continuous estimation of systolic blood pressure using the pulse arrival time and intermittent calibration.

A continuous noninvasive method of systolic blood pressure estimation is described. Systolic blood pressure is estimated by combining two separately obtained components: a higher frequency component obtained by extracting a specific frequency band of pulse arrival time and a lower frequency component obtained from the intermittently acquired systolic blood pressure measurements with an auscultatory or oscillometric system. The pulse arrival time was determined by the time interval from QRS apex in electrocardiogram to the onset of photoplethysmogram in a fingertip beat-by-beat via an oximetric sensor. The method was examined in 20 patients during cardiovascular surgery. The estimated values of systolic blood pressure were compared with those measured invasively using a radial arterial catheter. The results showed that the correlation coefficients between estimated values and invasively obtained systolic blood pressure reached 0.97 +/- 0.02 (mean +/- SD), and the error remained within +/- 10% in 97.8% of the monitoring period. By using a system with automatic cuff inflation and deflation to acquire intermittent systolic blood pressure values, this method can be applicable for the continuous noninvasive monitoring of systolic blood pressure.

Adolescent↗