Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 289 records · Page 16Linked to original sources

PubMed1996

Radioimmunoassay method for DX-9065a, an anticoagulant agent. Development, evaluation and application to human plasma.

A simple and sensitive radioimmunoassay (RIA) method was developed for determination of DX-9065a, (+)-(2S)-2[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl] oxy]phenyl]-3-[7-amidino-2-naphthyl]propanoic acid hydrochloride pentahydrate, a newly synthesized anticoagulant agent. Immunogens were prepared by condensation of a hapten with bovine serum albumin via a carboxyl group. Antisera was obtained by immunization of five rabbits with immunogen. High-titer antisera was obtained from 2 rabbits immunized with immunogen. The sensitivity of this newly developed RIA method was 100-fold greater than that of a previously used conventional HPLC method. This method was validated for determination of human plasma samples in clinical trials. The cross-reactivities of employed antisera with three steroisomers (2R3R-, 2R3S- and 2S3R forms) were 0.7, 20.2 and 43.9% respectively. The effect of cross-reactivity of postulated stereoisomers in clinical samples was evaluated by a parallelism study using human plasma samples obtained after oral administration of the drug to healthy Japanese volunteers. Results showed no effect on measured concentration. From these data, this method showed suitable accuracy and precision for the pharmacokinetic evaluation of DX-9065a in clinical study. The method was applied to plasma samples obtained from a healthy Japanese volunteer who had orally received 12.85 mg (10 mg as DX-9065) of the drug. The maximum plasma concentration measured was 6.2 ng ml-1 1 h after administration.

Animals↗

PubMed1996

Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis.

The effects of high molecular weight hyaluronan (HA) on cartilage degeneration were investigated in a partial menisectomy model of osteoarthritis (OA) in the rabbit knee. This study compared HA80 (0.8 x 10(6) Da, 1%), HA190 (1.9 x 10(6) Da, 0.01-1%) and saline. HA (0.1 ml/kg) or saline were injected intra-articularly twice a week immediately after surgery. Degenerative changes in femoral and tibial cartilages were graded histopathologically 2 and 4 weeks after surgery. Two weeks after surgery, HA190, only when used at a 1% concentration, resulted in a dramatic inhibition of cartilage degeneration in both the femoral condyle and the tibial plateau (P < 0.01). Two weeks after surgery, the protection against cartilage degeneration was significantly (P < 0.05) greater with HA190 than with HA80. Four weeks after surgery, only the femoral cartilage degeneration was significantly and similarly inhibited with HA190 (P < 0.01) and HA80 (P < 0.05). Scanning electron micrographs of femoral cartilage showed that cartilage degeneration was less severe with HA190 than with saline. These results might suggest that, in the rabbit model, intra-articular administration of higher molecular weight HA is more effective than lower molecular weight HA in inhibiting cartilage degeneration in early OA.

Animals↗

PubMed1996

Detection of Kanji words in a rapid serial visual presentation task.

In 3 experiments, lists of 12 Kanji words were rapidly presented in the same position, and participants reported a red target word embedded in green distractor words. Two lists were used: same and different category. A tendency toward category priming was found at longer durations. Frequency of target localization indicated that participants familiar with Kanji had a greater tendency to report the word immediately preceding the target. These pretarget intrusion errors dominated the posttarget intrusion errors, when the luminance of red and green stimuli were equated (Experiment 2), and when the response was recall (Experiments 1 and 2) or recognition (Experiment 3). In contrast, participants unfamiliar with Kanji made posttarget intrusion errors as frequently as pretarget intrusion errors (Experiment 3), suggesting that knowledge of Kanji influences the integration of color and form codes in visual information processing.

Adult↗

PubMed1996

Cancer cell progression and chemoimmunotherapy--dual effects in the induction of resistance to therapy.

To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-bearing mice. Nearly all the mice that were treated with cyclophosphamide (CY) and lentinan achieved complete tumour regression. Only a few of the mice that achieved complete regression of the primary tumours showed a recurrence of the tumour in regional lymph nodes. S908.D2-vp.1 was established from metastatic tumours that developed in the regional lymph nodes of parental S908.D2-bearing mice during therapy. S908.D2-vp.2-or vp.3 cells were sequentially derived in a similar way from S908.D2-vp.1-or-vp.2-bearing mice respectively, in which complete tumour regression at each primary site was achieved during therapy. These lines acquired resistance to CY and lentinan and also to 5-fluorouracil (5-FU)/5'-deoxy-5-fluorouracil and lentinan. No significant difference in either the sensitivity to 5-FU or 4-deoxycyclophosphamide in vitro or in the susceptibility to immune effector cells was observed between the parental and progressed lines (S908.D2-vp1 -vp3). There was an increase in the level of prostaglandin E2 (PGE2) in the progressed lines during repeated therapy (parental, 1171 pg ml(-1); vp.1, 2199 pg ml(-1); vp.2, 5500pg ml(-1); vp3, 16187 pg ml(-1)). There was no significant increase in the production of transforming growth factor beta (TGF-beta). The amount of interleukin-2 (IL-2) produced by spleen cells isolated from the S908.D2-vp.2-bearing mice was decreased compared with the amount produced by the parental S908.D2- bearing mice. Furthermore, combination therapy with lentinan and IL-2 achieved complete tumour regression in all the mice transplanted with S908.D2 progressed tumour lines, although IL-2 alone did not show any anti-tumour effects in either the S908.D2 parental or progressed lines. The findings suggest that the reduced production of IL-2 induced an increase in the production of the PGE2 by progressed tumour lines is involved in the acquisition of resistance.

Animals↗

PubMed1996

New furostanol glycosides, chinenoside IV and V, from Allium chinense.

Further studies on water-soluble components in the bulbs of Allium chinense G. Don have led to the isolation of two new furostanol saponins, chinenoside IV (1) and V (2). On the basis of chemical evidence and spectral analyses [1H-, 13C-NMR (DEPT), 1H-1H COSY (COSY45 and p-type), 1H-1H relay-COSY, 1H-13C COSY, HMBC, and FAB-MS], the structure of 1 was established as 26-O-beta-glucopyranosyl-3 beta,26-dihydroxy-23-hydroxymethyl-25(R)- 5 alpha-furost-20(22)-en-6-one 3-O-beta-xylopyranosyl(1-->4)-[alpha- arabinopyranosyl(1-->6)]-beta-glucopyranoside and that of 2 to be 26-O-beta-glucopyranosyl-3 beta, 26-dihydroxy-23-hydroxymethyl-25-(R)-5 alpha-furost-20(22)-en-6-one 3-O-alpha-arabinopyranosyl (1-->6)-beta- glucopyranoside, respectively.

Allium↗

PubMed1996

Differential effects of ketamine and pentobarbitone on acetylcholine release from the rat hippocampus and striatum.

Using microdialysis, we examined the effects of ketamine and pentobarbitone on acetylcholine (ACh) release from the rat hippocampus and striatum. Ketamine 25 and 50 mg kg-1 increased ACh release from the hippocampus to 295% and 353% of basal release, respectively, but not from the striatum. SCH 23390 1 mumol litre-1, a D1 antagonist, significantly inhibited the facilitatory effect of ketamine 50 mg kg-1 on hippocampal ACh release (to 241% of basal level). In contrast, pentobarbitone 20 and 40 mumg kg-1 decreased basal ACh release from both the hippocampus by 41% and 69%, respectively, and the striatum by 37% and 58%, respectively. The results suggest that ketamine and pentobarbitone exert opposite effects on ACh release from the rat hippocampus and that the stimulating effect of ketamine may involve dopamine D1 receptors.

Acetylcholine↗

PubMed1996

Nucleotide sequence of the uricase gene from Bacillus sp. TB-90.

The nucleotide sequence of the uricase gene from the thermophilic bacterium Bacillus sp. TB-90 was determined. The primary structure of the uricase deduced from the nucleotide sequence comprised 332 amino acids, with a total molecular mass of 37,994 Da. The molecular mass of the subunit of the uricase produced by the transformant of Escherichia coli agreed well with this value. However, the molecular mass of a subunit of the uricase produced by Bacillus sp. TB-90 was found to be 34,000 Da by SDS-PAGE. The difference between these molecular masses was attributed to processing of the C-terminal 13 amino acid residue in Bacillus sp. TB-90. Comparison of the enzymatic properties of both uricases showed that the thermostability of the uricase produced by the transformant was enhanced by about 10 degrees C in comparison to that produced by Bacillus sp. TB-90.

Amino Acid Sequence↗

PubMed1996

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children.

A recent study reported a significant relationship between a T704-->C (Met235-->Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.

Angiotensinogen↗

PubMed1996

Effect of clonidine on the height of a child with glycogen storage disease type VI: a 13 year follow-up study.

A 9-month-old male was found to have hepatomegaly when he was treated by his doctor for bronchitis. At the age of 2 years and 3 months, glycogen storage disease (GSD) of type VI (GSD VI) was diagnosed in this patient. Despite the recommended diet therapy, his growth was not good, changing under or along the line of -2.0 SD. At the age of 6 years, oral clonidine therapy (0.15 mg/day, 0.2 mg/m2 body surface per day) was started. Six to 10 months after the initiation of clonidine therapy, his height began to increase more than the values for -2.0 SD and once reached the value for -1.0 SD at the age of 10 years. His growth rate and bone age increased. Clonidine therapy was continued regularly for 7 years until the age of 13 years, 11 months. At that time his development was normal and his height reached 150.8 cm (-1.34 SD). However, cessation of the treatment at the patient's free will resulted in a reduction of the growth rate at age 15 years 6 months. These observations suggest the effect of clonidine therapy on height. Side effects were not noted during the clonidine therapy. Other clinical and laboratory findings of GSD VI also completely improved during treatment. In conclusion, administration of clonidine could be another treatment modality in children with GSD, not only of type VI but also I and III.

Administration, Oral↗

PubMed1996

The usefulness of measuring body fat deposition for detecting obesity and atherogenesity in Japanese school children.

Body fat deposition was measured in overweight and non-overweight children using a bioelectrical impedance method, and its relationship with serum lipids and apolipoproteins was investigated in 90 overweight children (over 120% of their ideal weight) and 241 non-overweight children aged 10-15 years in Niigata Prefecture. The results were as follows. Overweight boys had significantly higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), atherogenic index (AI), RLP-cholesterol (RLP-C), apoA1, apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non-overweight boys. Overweight girls had significantly higher levels of TC, LDL-C, AI, remnant-like lopoprotein cholesterol (RLP-C), apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non-overweight girls. It has been reported that of all children studied 2.1% had higher levels of RLP-C than its upper limit known for adults (12 mg/dL). Of the overweight children in the present study, 4.4% had a high level of RLP-C whereas only 1.2% of non-overweight children had a high RLP-C level. No difference in the lipoprotein levels was found between overweight and non-overweight children. In both boys and girls, relative weight, body fat, skinfold thickness and body mass index (BMI) were correlated with the lipoprotein levels. Non-overweight boys whose body fat was over 20% had significantly higher levels of TC, LDL-C, apoA2, apoB, apoC2, apoE and apoB/A1 than those whose body fat was less than 20%. It was concluded that the measurement of body fat deposition, together with relative weight, was useful for detecting obesity and atherogenesity in Japanese school children.

Adolescent↗

PubMed1996

The relationship between the intrauterine environment and blood pressure in 3-year-old Japanese children.

In 195 Japanese children the systolic pressure at 3 years of age was inversely correlated to the body weight at birth and positively correlated to the mothers' systolic pressure during pregnancy: the average systolic pressure in children whose body weight at birth exceeded 3510 g was 3.0 mmHg, which was lower than that of children whose body weight at birth was 2990 g or less. There was an increase of 0.12 mmHg in the children's systolic pressure with each increment of 1 mmHg in the systolic pressure of their mothers. The systolic pressure at 3 years in children of mothers who had had pretibial oedema during pregnancy (101.0 +/- 8.8 mmHg) was significantly higher compared with children whose mothers did not have oedema (96.6 +/- 9.6 mmHg).

Anthropometry↗

PubMed1996

Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise.

To investigate the cause of disagreement within the large body of literature concerning the effect of exercise on the capacity of circulating neutrophils to produce reactive oxygen species (ROS), 10 male endurance-trained athletes underwent maximal exercise. The generation of superoxide radical (O2-.) by neutrophils was first detected on a cell-by-cell basis by using histochemical nitro blue tetrazolium tests performed directly on fresh unseparated blood, which showed that responsive neutrophils under several stimulatory conditions relatively decreased after exercise. Similarly, O2-. detected with bis-N-methylacridinium nitrate (lucigenin)-dependent chemiluminescence (CL) of a fixed number of purified neutrophils on stimulation with opsonized zymosan was decreased slightly after exercise. In contrast, the 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-dependent CL response of the neutrophils indicative of the myeloperoxidase (MPO)-mediated formation of highly reactive oxidants was significantly enhanced after exercise. It therefore suggests that the pathway of neutrophil ROS metabolism might be forwarded from the precursor O2-. production to the stages of more reactive oxidant formation due to the facilitation of MPO degranulation. In addition, these phenomena were closely associated with the exercise-induced mobilization of neutrophils from the marginated pool into the circulation, which was mediated by the overshooting of catecholamines during exercise. These findings indicate that the use of different techniques for detecting ROS or the different stages of neutrophil ROS metabolism could explain some of the disparate findings of the previous studies.

Adult↗

PubMed1996

Michael-type addition of illudin S, a toxic substance from Lampteromyces japonicus, with cysteine and cysteine-containing peptides in vitro.

Reactions of illudin S with cysteine derivatives (cysteine methyl ester, glutathione and a peptide, Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg) were investigated. In the reaction with cysteine methyl ester, four products (P1, P2, P3, P4) were obtained and their structures were determined, on the basis of MS and NMR data, to be adducts of the mercapto group of cysteine methyl ester with the alpha,beta-unsaturated carbonyl group of illudin S. In the reactions with glutathione and the peptide, two addition products in each case were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and NMR analyses. The structures of these adducts also indicated that the alpha,beta-unsaturated carbonyl group in illudin S behaves as a Michael acceptor for the mercapto group in cysteine.

Amino Acid Sequence↗

PubMed1996

Studies on metabolites of mycoparasitic fungi. V. Ion-spray ionization mass spectrometric analysis of trichokonin-II, a peptaibol mixture obtained from the culture broth of Trichoderma koningii.

The sequence of a peptide, trichokonin-II (TK-II), obtained from the culture broth of Trichoderma koningii OUDEMANS, was examined by ion-spray ionization mass spectrometry (ISI-MS), including the collision-induced dissociation (CID) technique. TK-II was concluded to be a mixture of three peptaibols, TK-IIa, TK-IIb, and TK-IIc.

Alamethicin↗

PubMed1996

[Changes in the production of reactive oxygen species from neutrophils following a 100-km marathon].

Recently, the numbers of city marathon runners and joggers have increased. They believe that exercise can enhance their fitness level and health maintenance. However, many researchers have suggested that exhausting exercise may increase the risk of infection and free radical generation. In this study, eight male and ten female city marathon runners who participated in the Akita Nairiku Resort Cup 100-km Challenge Marathon Race were studied using luminol-dependent chemiluminescence (LDCL) to examine the ability of their neutrophils to produce reactive oxygen species. Furthermore, serum opsonic activity using LDCL, serum concentrations of the third and fourth components of the complement (C3, C4), the total number of leukocytes, and proportion of leukocytes were also determined. Evaluation of LDCL was undertaken using the maximum light emission (peak height) and the time to reach the maximum light emission (peak time) in the response curve of LDCL. Following the race, the peak time was prolonged by 11% in males and 15% in females, and the peak height increased by 68% in males and 48% in females. These results suggest that exhausting exercise stimulates neutrophils to produce reactive oxygen species. The total number of leukocytes increased about twofold, whereas the number of neutrophils increased about threefold after the race as compared to before. The rate of the increase in leukocytes was closely associated with that of neutrophils (r = 0.96, P < 0.01). Therefore, the leukocytosis observed in this study was dependent on neutrophilia. Serum opsonic activity and serum concentrations of C3 and C4 were not changed following the race. The increase in the ability of neutrophils to produce reactive oxygen species and neutrophilia after the race, suggests that a large quantity of reactive oxygen species may be produced in vivo following exhausting exercise.

Adult↗

PubMed1996

Human T-cell lymphotropic virus type I (HTLV-I) carrier with clinical manifestations characteristic of diffuse panbronchiolitis.

A 45-year-old male was referred due to prolonged productive cough. Despite the fact that bronchoalveolar lavage fluid suggested lymphocytic and neutrophilic alveolitis, the histologic diagnosis of his biopsied lung was diffuse panbronchiolitis-like lesion with infiltration of lymphocytes and plasma cells into respiratory bronchioles but few foamy cells. Serologic examination revealed that he was a carrier of human T-cell lymphotropic virus type I (HTLV-I). Together with uveitis and ulcerative colitis in his past history, the persistent respiratory symptoms of this patient can be attributed to non-neoplastic inflammation due to the chronic HTLV-I infection.

Bronchiolitis↗

PubMed1996

Chronobiometric assessment of autogenic training effects upon blood pressure and heart rate.

Autogenic training, a method of self-hypnosis, lowers the extent of within-day variation of systolic blood pressure assessed by the circadian double amplitude. The blood pressure and heart rate of ten patients, conventionally diagnosed as having hypertension or white-coat hypertension, were automatically monitored at 30-min intervals for 7 days before autogenic training and again for 7 days, at 1 or 2 months after the start of autogenic training (practiced three times daily). The circadian double amplitude of systolic blood pressure of the patients investigated was 3 to 17 mm Hg lower on autogenic training. In 5 patients, reductions by 7 to 17 mm Hg were statistically significant. These results are regarded as provisional statistics, the utility of which depends on replication. By contrast, the over-all group reduction of the circadian double amplitude of systolic blood pressure by 8 mm Hg on the average can be taken at face value. Autogenic training also lowered the circadian double amplitude of diastolic blood pressure, but the effect was small as was the effect of autogenic training upon the MESOR (a rhythm adjusted mean) and acrophase (a measure of the timing of over-all high values recurring each day). The effect of autogenic training upon the circadian double amplitude of systolic blood pressure suggests its trial as first-line treatment of patients with an excessive circadian blood pressure amplitude, a condition which, even in the absence of an elevated 24-hr, average of blood pressure, is associated with a large increase in the risk of developing ischemic stroke or nephropathy.

Aged↗

PubMed1996

Metabolism of illudin S, a toxic substance of Lampteromyces japonicus: urinary excretion of mercapturic acids in rat.

1. The urinary excretion of the mercapturic acids of illudin S after oral administration to rat has been studied. 2. From lc-ms/ms analysis of methanolic extracts of lyophilized rat urine, stereo-isomeric mercapturic acids were detected. 3. The mercapturic acids excreted 3 days following administration amounted to approximately 0.39-0.73% of the administered dose. 4. In vitro glutathione conjugation of illudin S by subcellular fractions was also examined. 5. No significant increases in the formation of glutathione adducts were observed in any subcellular fractions examined.

Acetylcysteine↗