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Biomedical subjects

C Ikeda

Publications and source records attributed to C Ikeda.

At least 19 recordsLinked to original sources

Self-assembly of a porphyrin array via the molecular recognition approach: synthesis and properties of a cyclic zinc(II) porphyrin trimer based on coordination and hydrogen bonding.

Self-assembly of [5-(pyrazol-4-yl)-10,20-bis(p-tolyl)-15- (2-ethoxycarbonylphenyl)porphyrinato]-zinc(II) (1), designed to have both a coordination site and a hydrogen bonding site, leads to a stable cyclic trimer array where coordination of the pyrazole nitrogen to the zinc(II) ion as well as hydrogen bonding between carbonyl oxygen and pyrazole NH holds each zinc(II) porphyrin. The recognition event for pyrazole has been confirmed preliminarily in the model studies using [5-(2-ethoxycarbonylphenyl)tris(p-tolyl)porphyrinato]-zinc(II) (3). The zinc(II) porphyrin 3 has large affinity for pyrazole due to the hydrogen bond between pyrazole and the 2-ethoxycarbonyl group in addition to the coordination bonding accompanied by the conformational change of the ethoxycarbonyl group in the coordination process. The (1)H NMR, IR, and UV-vis spectra of 1 and its ESI-MS and VPO measurements have revealed the cyclic trimer structure with an overall association constant of 6.0 x 10(13) M(-2) at 22 degrees C. The contribution of the hydrogen bond to the total free energy change in trimer formation is estimated to be 7.5 kcal/mol based on a reference trimer system without a hydrogen bonding site. The trimer geometry causes characteristic exitonic interaction between porphyrin units to yield a broad Soret band which is deconvoluted into four components by UV-vis and MCD spectral analyses. Electrochemical measurements have shown that only the first ring-oxidation process proceeds stepwise in the trimer.

Electrochemistry↗

Efficiency of rice bran for removal of organochlorine compounds and benzene from industrial wastewater.

Rice bran was found to effectively adsorb several organic compounds, such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, tetrachloroethylene, and benzene. Equilibrium adsorption isotherms conformed to the Freundlich type (log-log linear). The adsorption of dichloromethane and chloroform by rice bran was observed over the range of pH 1-11. Therefore, rice bran is applicable for treatment of wastewater over a wide pH range. Dichloromethane was successfully removed from water samples with an average removal efficiency of 70% after 60 min when rice bran was added to water samples containing from 0.006 to 100 mg/L dichloromethane. The removal of these organochlorine compounds and benzene by rice bran was attributed to the uptake by intracellular particles called spherosomes. Here, we report the results of a fundamental study of the efficiency of rice bran for removal of organochlorine compounds and benzene using a batch system on the laboratory scale, and describe elucidation of the mechanism of removal of these compounds by rice bran.

Adsorption↗

Pressure effect on the conformational fluctuation of apomyoglobin in the native state.

We have investigated the effect of pressure on fluctuations of the native state of sperm whale apomyoglobin (apoMb) by H/D exchange, fluorescence, and limited proteolysis. The results from intrinsic fluorescence showed that a large fraction of apoMb molecules is in the native conformation in the pressure range from 0.1 to 150 MPa at 293 K and pH 6.0. The H/D exchange of protons of the individual backbone amino acids in this pressure range was monitored by NMR. The rate of H/D exchange was enhanced at high pressure, with the protection factors for some residues decreasing by factors of more than 100 compared to the values at 0.1 MPa. The amplitude of the decrease of the protection factor varied among the individual amino acids on the same secondary structure unit. This result suggests that H/D exchange in apoMb is explained best by the penetration model, in which solvent penetrates into the protein matrix via small motions. The result from limited proteolysis under high pressure showed that a pressure increase does not induce local unfolding of the secondary structure units of apoMb. Conformational fluctuations much smaller than local unfolding evidently provide pathways for water to diffuse into the protein interior, and are enhanced by an increase of pressure.

Animals↗

Molecular analysis and diagnosis in Japanese patients with Wilson's disease.

BACKGROUND: Wilson's disease is characterized by the toxic accumulation of copper in the liver, brain, cornea and other organs. It is caused by both impaired excretion via the bile and impaired incorporation of copper into ceruloplasmin in the liver. The Wilson's disease gene (ATP7B) has been cloned as a putative copper-transporting P-type ATPase gene. We therefore analysed mutations of ATP7B in Japanese patients with Wilson's disease. METHODS: Twenty-three Japanese patients with Wilson's disease were investigated. In all patients, the ATP7B coding sequence, including exon-intron junctions, was analysed by restriction endonuclease digestion, mutation detected enhancement gel electrophoresis and/or direct sequencing analysis of amplified fragments. RESULTS: Thirteen mutations were identified, including seven missense mutations, four detections, one insertion and one exon skipping in the coding region. The most common mutations were 2874deletion(del)C in exon 13 and arginine (Arg)778 leucine (Leu) in exon 8. DISCUSSION: None of the observed mutations, except for 2302insertion(ins)C, have been previously detected in either European or North American patients. We conclude that the mutation spectrum of Wilson's disease may thus indicate a population-dependent pattern. Based on the population-dependent manner of the occurrence of ATP7B gene mutations, it may be possible to establish a molecular diagnosis system. A molecular diagnosis system is considered to be very effective for making a definitive diagnosis in very young patients and for also detecting carriers.

Adenosine Triphosphatases↗

Trends in HIV and AIDS based on HIV/AIDS surveillance data in Japan.

BACKGROUND: In recent years a decline in the number of new AIDS cases has been observed in several industrialized countries. It is important to know whether these recent trends observed in North America and Europe are also occurring in Japan. METHODS: The number of people reported with HIV and AIDS by nationality, route of infection, and sex was calculated based on the HIV/AIDS surveillance data available in Japan through December 1997. The effect of reporting delay, which was defined as those HIV and AIDS cases reported in the calendar year following diagnosis, on the trends was examined. The coverage rate in reporting HIV cases was estimated as the ratio of the reported AIDS cases with prior report as an HIV-positive to the total number of reported AIDS cases. RESULTS: The cumulative number of reported cases of HIV among Japanese and non-Japanese residents of Japan up to the end of 1997 were 1,300 and 1,190, respectively. The cumulative number of reported cases of AIDS among Japanese and non-Japanese up to the end of 1997 were 758 and 298, respectively. The number of reported cases of HIV among Japanese was found to be still increasing, with the major contribution from male cases. The increasing trend in the number of reported AIDS cases among Japanese began to slow in 1996 and 1997. The number of reported cases of HIV among non-Japanese residents of Japan peaked in 1992, and has decreased since then, and remained constant after 1994. In contrast, the number of reported AIDS cases among these non-Japanese tended to increase gradually. There was a slight reporting delay for people with HIV and AIDS. The estimated coverage rate in reporting HIV cases tended to decrease in 1996 and 1997 (1/7.2, 1/10.2, respectively). We point out several reasons for this recent decline and suggest the possibility of an ostensible decline in the estimates. CONCLUSIONS: We suggest that the number of people with HIV among Japanese has continued to increase, and that the increase in the number of AIDS cases among Japanese is now slowing.

Acquired Immunodeficiency Syndrome↗

Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988-991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 microg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 +/- 132 versus 995 +/- 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% +/- 22.1%) and high at neutrophilia with rhG-CSF therapy (73. 0% +/- 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.

Adjuvants, Immunologic↗

Studies on removal efficiency of chloroform from tap water by rice bran.

Removal efficiency of chloroform from tap water by rice bran was investigated. The adsorption rate by rice bran was similar to activated carbon. The amount of chloroform adsorbed was plotted against the equilibrium concentration of chloroform in solution on a logarithmic scale. A linear relationship was obtained, indicating that the adsorption reaction was a Freundlich type. The adsorption of chloroform by rice bran was observed in the range of pH 1-11. Chloroform was successfully removed from tap water with average removal efficiency of 70% after 60 min when rice bran was applied to tap water that contained 0.0064 mg/L chloroform.

Adsorption↗

Drinking habit as a base for blood pressure elevation--difference in epidemiological significance by beverage type.

To investigate whether blood pressure differs by taking preferred alcoholic beverage among habitual drinkers, systolic and diastolic blood pressure (SBP, DBP) were compared among groups with different beverage types in 563 middle-aged Japanese males using data from a cross-sectional health survey conducted from February, 1989 through March, 1991 in five areas of Japan. Mean values of SBP and DBP, adjusted for residence, age and body mass index (BMI), were significantly greater in 'exclusively sake' drinkers (adjusted SBP: 127.2 mmHg, adjusted DBP: 83.0 mmHg) and in 'exclusively shochu' drinkers (adjusted SBP: 127.5 mmHg, adjusted DBP: 84.2 mmHg) than in non-drinkers (adjusted SBP: 120.9 mmHg, adjusted DBP: 77.3 mmHg). Adjusted SBP and DBP of 'exclusively beer' drinkers (adjusted SBP: 121.9 mmHg, adjusted DBP: 79.1 mmHg) were significantly (for SBP: p = 0.016, for DBP: p = 0.008) lower than those of 'exclusively sake' drinkers. Similar patterns of blood pressure differences between five beverage types of habitual drinkers were found especially in the group with less than 150 g of weekly ethyl-alcohol consumption. Even after adding ethyl-alcohol consumption as a covariate among 479 habitual drinkers, the significant differences in adjusted SBP and DBP between 'exclusively beer' drinkers and 'exclusively sake' drinkers (for SBP: p = 0.032, for DBP: p = 0.044) were noted. These results may suggest that the effects of drinking on blood pressure differ by beverage type in middle-aged Japanese males.

Adult↗

Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs.

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.

Animals↗

Phorbol ester stimulates acetylcholine synthesis in cultured endothelial cells isolated from porcine cerebral microvessels.

Acetylcholine (ACh) is one of the factor which induces vasodilation through the release of endothelium-derived relaxing factor. The aim of this study was to clarify whether endothelial cells can synthesize ACh and the types of substance which regulate the synthesis of ACh in endothelial cells. We determined the ACh content of endothelial cells isolated from porcine cerebral microvessels and of the culture medium. ACh was detected in the medium after 12 h incubation in the presence of diisopropylfluorophosphate, a non-specific cholinesterase inhibitor, and increased linearly up to 24 h. Phorbol 12-myristate 13-acetate (PMA, 10(-7) M) increased the ACh content of the medium in a dose-dependent manner. The effect of PMA was most apparent between 12 and 24 h after treatment, and was inhibited by cycloheximide. Calphostin C, a specific inhibitor of protein kinase C (PKC), did not inhibit the effect of PMA. Dioctanoyl glycerol, a specific activator of PKC, did not increase the intracellular ACh content or the amount released into the culture medium. ACh synthesis was not inhibited by bromoacetylcholine, a specific inhibitor of choline acetyltransferase (ChAT). PMA treatment did not affect the specific activity of ACh synthesis in endothelial cells. These data show that endothelial cells are able to synthesize ACh, and that ACh synthesis is up-regulated by PMA through the PKC independent mechanism via protein induction. The enzyme which synthesizes ACh in endothelial cells is not ChAT. The increase in ACh synthesis induced by PMA may not be due to induction of the ACh synthetic enzyme.

Acetylcholine↗

Different effect of 5,6-trans-prostaglandin E2 on plasminogen activation by urokinase and streptokinase.

We examined the effects of 5,6-trans-prostaglandin E2 (trans-PG E2) on fibrinolysis and plasminogen activation by either urokinase or streptokinase. trans-PG E2 was found to enhance fibrinolysis induced by urokinase and inhibit the one by streptokinase. These effects were also appeared in the method using synthetic chromogenic substrate S-2251, which suggested that the effects of trans-PG E2 were induced in the circumstances without coagulation factors such as fibrinogen, thrombin or fibrin. Moreover, the enhancement effect of trans-PG E2 on fibrinolysis by urokinase was investigated. The result of SDS-PAGE indicated that plasmin formation rate from plasminogen by urokinase was accelerated in the presence of trans-PG E2. As trans-PG E2 increased the hydrolyzing rate of S-2288 by urokinase, trans-PG E2 directly interacted with urokinase. Therefore, the enhancement effect of trans-PG E2 on plasminogen activation by urokinase could be explained, at least in part, as follows: at first trans-PG E2 directly exerts its effect on urokinase, then it causes the increase of generation rate of plasmin from plasminogen.

Amino Acid Sequence↗

BMS-181184, a new pradimicin derivative. Screening, taxonomy, directed biosynthesis, isolation and characterization.

BMS-181184 is a new semisynthetic pradimicin derivative with a broad-spectrum antifungal activity. In a search for actinomycetes producing BMS-181184, 4 strains of Actinomadura sp. isolated from soil samples were found to produce the antibiotic under conditions of directed biosynthesis. Among them, Actinomadura sp. AB1236 proved most useful in the production of BMS-181184 when fermented in a medium containing D-serine and D-cycloserine. A minor product isolated from the broth of strain AB1236 was identified as the dexylosyl analog of BMS-181184, which was also obtained by acid hydrolysis of BMS-181184.

Actinomycetales↗

Changes in oxygen uptake-work rate relationship as a compensatory mechanism in patients with heart failure.

To assess the compensatory change in oxygen uptake (VO2) kinetics during exercise in patients with heart failure, we performed cardiopulmonary exercise testing using a cycle ergometer in 29 cardiac patients and 18 normal subjects. The work rate increased linearly (1w/6sec) after a 4 min, 20w warm-up. The ratio of increase in VO2 to increase in work rate (delta VO2/delta WR) was determined by linear regression of VO2 plots. Cardiac output by dye dilution method and plasma norepinephrine concentration (NE) were measured at rest and 20w warm-up. VO2 at rest and at 20w warm-up and delta VO2/delta WR decreased significantly with increasing severity in NYHA functional classification. delta VO2/delta WR showed significant negative correlation to the difference in NE levels at rest and at 20w (r = -0.69, p less than 0.001). The delta values of arteriovenous O2 content difference, calculated using Fick's principle, and cardiac index from rest to 20w warm-up failed to show significant relationship to delta VO2/delta WR. These results suggest that the decrease in VO2 requirement in heart failure patients is due probably to blood redistribution during exercise as a compensatory mechanism for exercise intolerance.

Adolescent↗

The efficacy of aerobic exercise therapy on hypertensive patients with mild cardiac complications.

To investigate the antihypertensive efficacy of aerobic exercise therapy in essential hypertensives, 20 patients underwent eight weeks of cycle ergometer training at anaerobic threshold (AT) point. Cardiopulmonary exercise testings with ramp protocol were performed before and at two/four/eight weeks during the training period in order to determine AT and to evaluate the changes in blood pressure (BP), heart rate (HR), oxygen uptake (VO2; ml/min/kg), and O2 pulse (ml/min/beat) during exercise. 75g glucose tolerance test (OGTT) was measured before and after exercise therapy. The mean values of systolic blood pressure, oxygen uptake, O2 pulse, before and after exercise therapy were as follows: systolic blood pressure at rest = 160 +/- 19 mmHg and 135 +/- 11 mmHg, systolic blood pressure at AT = 195 +/- 13 mmHg and 180 +/- 10 mmHg, oxygen uptake AT = 12.0 +/- 0.9 ml/min/kg and 14.4 +/- 1.0 ml/min/kg, O2 pulse at AT = 6.8 +/- 1.5 ml/min/beat and 7.6 +/- 1.88 ml/min/beat. After exercise therapy, systolic blood pressure decreased (p less than 0.01), while O2 pulse and VO2 increased (p less than 0.01). Hyperresponse of serum insulin to glucose also improved. These results show that aerobic exercise therapy at AT level has beneficial effects on high blood pressure and improves exercise tolerance and hyperresponse of serum insulin to glucose without any complications.

Adult↗

[Incidence of renal diseases in the general population].

The purpose of this study was to determine the incidence of the urological diseases of the kidney. Among 4,094 persons (3,146 men and 948 women) studied, 86 cases of renal cyst, 7 cases of urolithiasis, 3 cases of cystic kidney, and one case of renal cell carcinoma were discovered. The rate of renal cyst was two times higher in men than in women. One sixth of renal cyst patients showed microscopic hematuria. Renal cysts tended to progress in number and size with age. The size of the renal cyst did not correlate with the appearance rate of microscopic hematuria.

Carcinoma, Renal Cell↗