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Biomedical subjects

M Taki

Publications and source records attributed to M Taki.

At least 55 records · Page 3Linked to original sources

Three novel integrin beta3 subunit missense mutations (H280P, C560F, and G579S) in thrombasthenia, including one (H280P) prevalent in Japanese patients.

We analyzed three unrelated Japanese patients with type II Glanzmann thrombasthenia (GT) for associated mutations. Polymerase chain reaction and subsequent direct sequencing of platelet RNA and genomic DNA revealed three single nucleotide substitutions of the integrin beta3 subunit gene (His (CAT)-280 to Pro (CCT), Cys (TGT)-560 to Phe (TTT), and Gly(GGC)-579 to Ser(AGC)). Interestingly, the three unrelated patients all had the H280P mutation; one was homozygous and the other two heterozygous for this mutation. Ectopic expression of wild type and mutant complexes in Chinese hamster ovary cells revealed decreased surface expression of the mutated alphaIIbbeta3 complexes, thus demonstrating that these mutations may result in the mild GT phenotypes. The identification of three unrelated patients having the same mutation (H280P) suggests that this mutation might be prevalent in the Japanese thrombasthenic population.

Aged↗

Preadministration of incadronate disodium can prevent bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage.

The purpose of this study is to determine whether short-term preadministration of bisphosphonates prevents bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage. Six-month-old female Sprague Dawley rats were injected with incadronate disodium (YM-175, 10 micrograms/kg) or vehicle, three times per week for 2 weeks (YM or V groups). Then, the left hindlimb was fixed to the abdomen with a bandage (V-B, YM-B groups), or only the abdomen was bandaged as control (V-SHM, YM-SHM groups), for 4 weeks. The animals were subsequently killed and left proximal tibiae were processed undecalcified for quantitative histomorphometric evaluation. Immobilization-induced cancellous bone loss resulted not only from increased percent eroded surface area but also from decreased percent labeling surface and bone formation rate in V-B compared with V-SHM animals. In contrast, preadministration of YM-175 decreased percent eroded surface significantly and prevented the loss of cancellous bone mass in YM-B compared with V-B animals. Cancellous bone mass was neither increased nor decreased by preadministration of YM-175 in YM-SHM animals. Our results suggest that preadministration of bisphosphonates is effective in prevention of bone loss at the tibial metaphysis when induced by hindlimb immobilization in rats.

Animals↗

Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship.

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with a activity of about an order of magnitude greater than genistein. Various flavonoids possessing isopentenyl side chains in the A-ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated that the presence of an 8-isopentenyl group is an important factor for binding. Flavones, flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl substituent at C-8 did not show this activity. Movement of the isopentenyl group from position 8 to 6 resulted in loss of the activity. No significant difference was observed between 2(S)- and 2(R)-enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities; however, estrogenic activity has not been described.

Breast Neoplasms↗

Lack of promoting effects of the electromagnetic near-field used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay.

The possible cancer promotion potential of local exposure to a pulse modulated 929.2 MHz electromagnetic near-field on chemically-initiated rat liver carcinogenesis was investigated employing a medium-term bioassay. A 929.2-MHz electromagnetic near-field of time division multiple access (TDMA) signal for PDC (Personal Digital Cellular, Japanese cellular telephone standard) system was directed to rats through a quarter-wavelength monopole antenna. Maximum local specific absorption rates (SARs) on temporal average were 7.2-6.6 W/kg within the whole body and 2.0-1.7 W/kg within the liver, which was the target organ. The whole-body average SARs on temporal average were 0.80-0.58 W/kg. Temporal peak SARs had three times these values due to the duty ratio of the PDC signal. Exposure was for 90 min a day, 5 days a week, over 6 weeks. The exposure apparatus was specially designed for this experiment, to allow exposure of the lateral mid-section of the rat body to the electromagnetic near-field. Male F344 rats, 6 week-old, were initially (at week 0) given a single dose of diethylnitrosamine (DEN, 200 mg/kg body wt, i.p.). At 2 weeks later, exposure (48 rats) or sham-exposure (48 rats) was started. The exposure of electromagnetic near-fields was performed using the exposure apparatus mentioned above. At week 3, all rats were subjected to a 2/3 partial hepatectomy. At week 8 (i.e. after 6 weeks exposure or sham-exposure), the experiment was terminated and all rats were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P) positive foci in the livers of the exposed and sham-exposed rats. A further group of 24 animals, given only DEN and partial hepatectomy, served as the controls. The numbers (no./cm2) of GST-P positive foci were 4.61 +/- 1.77, 5.21 +/- 1.92 (P < 0.05, versus control) and 4.09 +/- 1.47 and the areas (mm2/cm2) were 0.30 +/- 0.16, 0.36 +/- 0.21 and 0.28 +/- 0.15, for the exposed, sham-exposed and control groups, respectively. There were no significant differences between the exposed and sham-exposed groups. These findings clearly indicated that local body exposure to a 929.2-MHz field, modulated in a PDC waveform, has no significant effect on rat liver carcinogenesis under the experimental conditions employed.

Adrenocorticotropic Hormone↗

The 1.5 GHz electromagnetic near-field used for cellular phones does not promote rat liver carcinogenesis in a medium-term liver bioassay.

We have recently established that local exposure to a 929.2 MHz electromagnetic near-field, used for cellular phones, does not promote rat liver carcinogenesis in a medium-term bioassay system. In the present study, a 1.439 GHz electromagnetic near-field (EMF), another microwave band employed for cellular phones in Japan, was similarly investigated. Time division multiple access (TDMA) signals for the Personal Digital Cellular (PDC) Japanese cellular telephone standard system were directed to rats through a quarter-wavelength monopole antenna. Numerical dosimetry showed that the peak SARs within the liver were 1.91-0.937 W/kg, while the whole-body average specific absorption rates (SARs) were 0.680-0.453 W/kg, when the time-averaged antenna radiation power was 0.33 W. Exposure was for 90 min a day, 5 days a week, over 6 weeks, to male F344 rats given a single dose of diethylnitrosamine (200 mg/kg, i.p.) 2 weeks previously. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At week 8, the experiment was terminated and the animals were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P)-positive foci in the livers of exposed (48) and sham-exposed rats (48). Despite increased serum levels of corticosterone, adrenocorticotropic hormone (ACTH) and melatonin, the numbers and the areas of GST-P-positive foci were not significantly altered by the exposure. These findings clearly indicated that local body exposure to a 1.439 GHz EMF, as in the case of a 929.2 MHz field, has no promoting effect on rat liver carcinogenesis in the present model.

Adrenocorticotropic Hormone↗

[Prospective matched control study concerning the treatment and quality of life of hemophiliacs with inhibitors].

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

Adult↗

Retrodihydrochalcones and homoisoflavones isolated from Thai medicinal plant Dracaena loureiri and their estrogen agonist activity.

Biological evaluation of the extract prepared from the stem wood of Dracaena loureiri, a Thai folkloric medicine called "Chan-daeng", revealed a significant capacity to inhibit [3H]-estradiol binding to the estrogen receptor. During the course of separation, two novel (1 and 2) and two known retrodihydrochalcones (3 and 4), in addition to three known homoisoflavones (5, 6, and 7), were isolated. The structures of compounds 1 and 2 were established by NMR and MS studies by correlating their spectroscopic properties with those of 3 and 4. Each isolate was assessed for its estrogenic activity. Compounds 1 and 6 exhibited activity comparable to that of genistein and daidzein.

Chalcone↗

A simple computer-assisted method to identify schistosome cercariae.

Several methods have been suggested to identify schistosome cercariae. In the present work, a new method is proposed, based on the analysis of the distribution of sensory endings (sensillae) on the body of the cercariae, revealed by an impregnation with silver nitrate. We determined the mutual distances between the sensillae and calculated the mean values, standard deviations, coefficients of asymmetry, and of kurtosis of the distribution of these mutual distances. Applied to two species, Schistosoma mansoni from Brazil and S. intercalatum from Cameroon, these mutual distances had the same mean value and the same standard deviation but quite different coefficients of symmetry (0.34 +/- 0.11 versus 0.73 +/- 0.08; P < 0.0001) and of kurtosis (-0.82 +/- 0.27 versus -0.58 +/- 0.31; P < 0.0001). The latter two indices were therefore very effective for discriminating the two species. The present method can be applied to other species and to hybrids in the field.

Animals↗

[Evaluation of sensitivity and specificity of confirmatory assays for lupus anticoagulant (LA) detection].

To evaluate the sensitivity and specificity of confirmatory assays for LA detection, we performed the platelet neutralization procedure (PNP), diluted Russell's viper venom time (dRVVT) confirmatory assay (the ratio of LA-screen and LA-confirm:S/C), and specific hexagonal phase neutralization test (StaLA) on, plasma samples 43 LA-positive in either the ratio of dilute APTT and APTT(dAPTT/APTT) or dRVVT(LA-screen). The sensitivity and the specificity were evaluated by 4 different analyses based on, 1) maximal plasma dilution, 2) correlation between the screening assays and these confirmatory assays, 3) ratio of LA-positive in the confirmatory assays, and 4) receiver operation characteristic (ROC) method. All 4 analyses showed that sensitivity was in the order of PNP > S/C > Staclot-LA. However, the order of the specificity evaluated by the ROC method was Staclot-LA > S/C > PNP. The APTT-based confirmatory assay, PNP can detect LA of the plasma samples that were all positive in the dAPTT/APTT ratio, while the LA-positive plasma samples in dRVVT-confirm were all positive in the dRVVT-screen assay. Our findings suggest that confirmatory assays should be based on the method giving an abnormal screening assay. Accordingly, we recommend the following combinations of screening and confirmatory assays in terms of specificity; 1) dAPTT/APTT ratio and Staclot-LA as the APTT-based assay, and 2) LA-screen and LA-confirm as the dRVVT-based assay.

Blood Coagulation Tests↗

[Age-related changes and sex differences on the serum chemistry values in Sprague-Dawley rats--I. 6-30 weeks of age].

Age-related changes of 27 items in serum chemistry were investigated in Sprague-Dawley rats of both sexes from 6 to 30 weeks of age. The following 12 items were shown as an increase in those values during growth and maturity, i.e., total protein, albumin (female only), glucose, total cholesterol, triglyceride, phospholipid (female only), beta-lipoprotein, cholinesterase (female only), asparate aminotransferase (female only), creatinine, direct-bilirubin and total-bilirubin. However, the following 4 items decreased with aging, i.e., asparate aminotransferase, alkaline phosphatase, creatine phosphokinase and inorganic phosphorus. No age-related changes were found in the values for calcium, sodium and chloride in both sexes and for alanine aminotransferase, cholinesterase and albumin in males. The sex differences were shown in the following 12 items: higher values in males were alkaline phosphatase, creatinephosphokinase, glucose and inorganic phosphorus, and higher values in females were cholinesterase, albumin, phospholipid, non-esterified fatty acid, urea nitrogen, direct-bilirubin, total-bilirubin and serum iron. No sex-related differences were found in the values for calcium, sodium, chloride and total cholesterol.

Aging↗