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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 145 records · Page 8Linked to original sources

Effective suppression of HIV-1 gene expression by a mammalian tRNA 3' processing endoribonuclease and external guide sequence oligozymes.

We examined the suppression of virus expression by cleavage of the HIV-1 RNA gene using a mammalian tRNA 3' processing endoribonuclease and an External Guide Sequence Oligozyme (EGS) in vivo. We constructed an EGS expression vector that used the tRNA(met) promoter as an expression cassette for EGS. The EGS expression vector was targeted to the upstream region of gag, region. The EGS expression vector was co-transfected into COS cells with the HIV-1 gene plasmid vector. As compared with the EGS non-expressing cells and the EGS expressing cells, the EGS expressing cells with the targeted gag start codon had a clearly decreased amount of the HIV-1 gag p24 protein. The EGS expressing cells with the targeted gag start codon showed effective suppression of HIV-1 gene expression. Thus, these studies describe novel gene targeting agents for the inhibition of gene expression and antiviral activity.

Animals↗

Serum immunosuppressive acidic protein and natural killer cell activity in patients with metastatic renal cell carcinoma before and after nephrectomy.

PURPOSE: To our knowledge the impact of nephrectomy on stage M1 renal cell carcinoma remains to be determined. We previously reported that nephrectomy is beneficial in patients with elevated serum C-reactive protein before treatment, and those in whom nadir C-reactive protein decreases postoperatively to within the normal range may expect longer survival when surgery is combined with postoperative immunotherapy. In this study we determine the effect of nephrectomy on the immune response in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 40 patients with metastatic renal cell carcinoma diagnosed at our institution between 1986 and 1999. These patients underwent nephrectomy before cytokine therapy with interferon. Before and after nephrectomy we measured serum C-reactive protein, serum immunosuppressive acidic protein and peripheral blood natural killer cell activity. RESULTS: In 15 patients with pretreatment serum C-reactive protein within the normal range (less than 1 ng./ml.) there was no significant difference before and after nephrectomy in the serum immunosuppressive acidic protein level or natural killer cell activity (p = 0.4587 and 0.3892, respectively). On the other hand, in 25 patients with serum C-reactive protein elevated before treatment to 1 ng./ml. or greater serum immunosuppressive acidic protein decreased significantly and natural killer cell activity increased significantly after cytoreductive surgery (p = 0.0002 and 0.0286, respectively). CONCLUSIONS: Our study implies that nephrectomy may be beneficial in patients with elevated serum C-reactive protein before treatment. Further evaluation by a prospective study is needed to make a definitive conclusion.

Adult↗

Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%, 0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.

Animals↗

A prospective randomized study comparing endocrinological and clinical effects of two types of GnRH agonists in cases of uterine leiomyomas or endometriosis.

OBJECTIVE: In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis. METHODS: A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups. RESULTS: The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups. CONCLUSION: Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Adult↗

Prostate-specific antigen levels and clinical response to flutamide as the second hormone therapy for hormone-refractory prostate carcinoma.

BACKGROUND: Some authors have recently reported that maximum androgen block (MAB), in which the nonsteroidal anti-androgen, flutamide, is used together with conventional hormone therapy such as castration or luteinizing hormone-releasing hormone analogue, is more effective for prostate cancer than conventional methods. However, others have reported that the effect of MAB on survival is minimal, and definite conclusions concerning MAB remain unclear. Conversely, using flutamide as a second-line hormone therapy after recurrence is also considered, but few authors have reported whether this therapeutic option is effective or for which patients it is effective. MATERIALS AND METHODS: 124 patients with prostate cancer were diagnosed and followed at Kobe City General Hospital between 1995 and 1997. Twenty-two of these cases developed recurrence during first-line hormone therapy, and flutamide was prescribed in these cases. The prognostic value and effectiveness of flutamide were evaluated by measurement of serum prostate-specific antigen (PSA) at diagnosis, posttreatment nadir PSA level, PSA at the time of flutamide use, histological grade, recurrence-free time after firstline hormone therapy and age at the time of diagnosis. RESULTS: Six of 9 cases whose post-treatment nadir PSA levels after initial hormone therapy were within the normal limit (<4 ng/ml) achieved complete remission (CR) with flutamide use, but no patient whose post-treatment nadir PSA level remained elevated achieved CR. PSA at diagnosis and PSA at the start of flutamide use were significantly lower for patients with CR. However, the results of multivariate logistic regression analysis demonstrated that only the post-treatment nadir PSA level was significantly correlated with prognosis of flutamide use. CONCLUSIONS: Flutamide use as second-line hormone therapy should be limited to cases in which first-line hormone therapy has been highly effective and for whom the post-treatment nadir PSA level was within normal limits, and other patients should undergo other therapies. By limiting flutamide use to patients in whom the effect of flutamide is considered to be maximal, the incidence of complications and medication costs can be decreased.

Aged↗

Temperature-induced crystallization and compactibility of spray dried composite particles composed of amorphous lactose and various types of water-soluble polymer.

The purpose of this study was to investigate the temperature-induced crystallization and the compactibility of the composite particles containing amorphous lactose and various types of polymers. The composite particles were prepared by spray-drying an aqueous solution of lactose and various types of gel forming water-soluble polymers at various formulating ratios. The stabilizing effect of hydroxypropylcellulose (HPC) and polyvinyl pyrrolidone (PVP) on amorphous lactose in the composite particles was smaller than that of sodium alginate in comparing at the same formulating ratios. The difference in the stability of amorphous lactose in the composite particles was attributed to the difference in the glass transition temperature (Tg) of the composite particles caused by the polymers formulated. The tensile strength of compacted spray-dried composite particles containing the polymers was higher than commercial lactose for direct tabletting (DCL21). The tensile strength of the composite particles was increased with an increase in water content in the particles. The difference in compactibility of the composite particles containing the different amount of polymer and water could be explained by the difference in Tg of the particles.

Alginates↗

Modification of the physicochemical properties of minocycline hydrochloride ointment with cyclodextrines for optimum treatment of bedsore.

Modification to find the best physicochemical properties of minocycline hydrochloride ointment for optimum treatment of bedsore was investigated by coformulating various types of cyclodextrins (CyD) in the ointment base. It was found that the drug release rate from the ointment base was modified according to the preparation method of ointment base and the type of CyD admixed. The physicochemical properties, such as viscosity, elution volume, water absorption of ointment base were also modified by those factors. The mechanism of physicochemical modification with CyD was explained by the structural change of ointment base and the change of surface tension of emulsifying agent solution with the CyD. The stability of ointment was investigated by confirming the reproducibility of drug release rate after storage at ambient and cooled temperature conditions. In conclusion, a fused mixed ointment with beta-CyD was found to be preferable for treatment of bedsore, because of the improved drug release rate, lowered viscosity and increased elution volume of the resultant ointment.

Absorption↗

Quinochalcones and flavonoids from fresh florets in different cultivars of Carthamus tinctorius L.

The flavonoid constituents in fresh florets of the three distinctive cultivars of Carthamus tinctorius L. were purified and identified to investigate flavonoid biosynthesis in the petals. From the orange flower of cv. Kenba (K.), four new compounds, anhydrosafflor yellow B (1), two kaempferols, 9 and 13, and a quercetin, 17, were isolated, as well as the twelve known compounds, and their structures were determined by spectral data, chemical reactions, and molecular mechanics calculations. From the yellow flower of cv. Ogon-hanagasa (O.), two flavonols and two quinochalcones, and from the white flower of cv. Shiro-bana (S.), three flavonois were isolated. These compounds were the same as those contained in cv. K. To compare the flavonoid constituents among the three cultivars, crude extracts were analyzed by a LC/PDA/MS system. In cv. K., six quinochalcones and eleven flavonols were identified. In cv. O., three quinochalcones and nine flavonols were identified, but the red pigment, carthamin (4), and its precursor, precarthamin (3), were not detected. In cv. S., four flavonols without a 6-hydroxyl group were identified. On the basis of a comparative study on the constituents among these three cultivars, a possible biosynthetic pathway to form quinochalcones via the intermediate, pentahydroxychalcone (19), is proposed.

Asteraceae↗

[A new decision tree method for statistical analysis of quantitative data obtained in toxicity studies on rodents].

Regarding the statistical analysis of the quantitative data obtained in control and dosage groups in toxicity studies, we tried to simplify the decision tree method. In a new decision tree presented in this article, one-way analysis of variance and Kruskal-Wallis nonparametric analysis of variance are excluded from the traditional decision tree: (1) Bartlett's test is used as a test for the equality of k variances: (2) Then, if the k sampled populations have equal variances (p > 0.05 by the Bartlett's test), Dunnett's multiple comparison test is performed: otherwise, Steel's test is used. This new method, which increases the power in some conditions, may serve as an alternative to the traditional decision tree method.

Analysis of Variance↗

Low-energy diet in atopic dermatitis patients: clinical findings and DNA damage.

Undernutrition without malnutrition (low-energy diet) increases maximum longevity, reduces the incidence of several cancers and delays their onset, in animal studies. It has also been demonstrated by experimental study that caloric restriction provides a beneficial effect on various inflammatory diseases. In this study, we offered a low-energy diet to patients with atopic dermatitis (AD). Nineteen adult patients (5 males and 14 females aged 15 to 36 years) were enrolled in the study which lasted 8 weeks. The energy intake was 55% of nutritional requirements; protein was 75%, calcium 180%, iron 130%, vitamin A 105%, vitamin C 250% and vitamin E 110% of the daily requirement. No patient experienced adverse reaction, and none dropped out of the trial. Body weight, body mass index (BMI), and systolic blood pressure had decreased significantly by the end of study. The SCORAD (scoring atopic dermatitis) index, which combines objective (extent and intensity of lesions) and subjective (daytime pruritus and sleep loss) criteria, was reduced significantly. In 11 patients with severe AD, there was a significant reduction in oxidative DNA damage. The change in the inflammatory intensity score and the change in BMI caused by energy restriction showed a significant positive correlation. The change in oxidative DNA damage levels and the change in BMI showed a positive correlation. These results clarify the relationship between weight loss and the improvement of AD. It may be hypothesized that this low-energy diet which included several additional nutrients has a possibility to reduce inflammatory symptoms of patients with AD.

Adolescent↗

Accelerative effect of olive oil on adrenal corticosterone secretion in rats loaded with single or repetitive immersion-restraint stress.

The present study was performed to clarify the effects of dietary oils on physiological and metabolic changes induced by a stress, using one-time or repetitive water-immersion of restrained rats (single or repetitive stress) as an experimental stress load. In rats fed any test diets containing 20%) of the mixture of tripalmitin, tristearin, and corn oil (PSC), olive oil (OLI). safflower oil (SAF), and linseed oil (LIS) with repetitive stress loading, body weight gains and food intakes were generally reduced. The weights of the thymus and spleen also declined, but the adrenal weights were enhanced. Particularly, the increase in the adrenal weight of rats given the OLI diet was greater than of rats supplied with other diets. When the rats were loaded with the single or repetitive stress, the concentrations of urea, lipid peroxide, and corticosterone in the plasma were increased in rats fed any of dietary oils. The rise of plasma corticosterone level was especially great in rats fed the OLI diet. The concentrations of total cholesterol (T-CHOL) and triglyceride (TG) in the plasma and liver generally tended to be higher in rats fed the OLI diet than in rats given the other diets with and without stress exposure. Plasma corticosterone concentration was correlated to the adrenal weight (r=0.87, p<0.05). This study showed that OLI especially enhanced the adrenal weight in rats exposed to the repetitive stress and further raised the increased secretion of adrenal corticosterone in rats loaded with the single or repetitive stress compared with the other oils. The mechanism explaining these actions of OLI was inferred to be related to the levels of T-CHOL and TG in the plasma and liver generally enhanced by stress.

Adrenal Cortex↗

Effects of graded levels of dietary casein and corn oil on total cholesterol and triacylglycerol in plasma and liver of rats.

With the intention of examining the effects of dietary protein and oil levels on total cholesterol (T-CHOL) and triacylglycerol (TG) concentrations in the plasma and liver, male Wistar rats, weighing about 170 g, were fed diets containing graded levels of casein and corn oil for 2 wk. At the 5, 20, and 30% levels of dietary corn oil, plasma T-CHOL concentrations were generally enhanced in proportion to the rise of dietary casein level, but plasma TG contents were scarcely influenced by the level. At the 8 to 35% casein levels, plasma T-CHOL and TG concentrations were the highest at the 5% corn oil level, followed in order by the 20 and 30% levels of oil. At the 5 and 20% oil levels, hepatic T-CHOL contents were hardly changed at the 8 to 30% casein levels, but enhanced at the 35% casein level. At the 30% oil level, the T-CHOL contents tended to be changed proportionally to casein levels. At all levels of casein, hepatic T-CHOL contents tended to be relatively high at the 30% corn oil, middle at the 20% oil, and low at the 5% one. At each corn oil level, TG contents in the liver tended to be elevated at the 8 to 15% casein levels and highly preserved at the 15 to 25% ones. Then, the raised TG contents declined at the 5 and 20% levels of corn oil and remained constant at the 30% oil. At each casein level, the contents of hepatic TG were generally high at the 30% oil level, followed in order by the 20 and 5% oil levels. These results indicated that plasma and liver T-CHOL concentrations were proportionately enhnaced by the increase in casein level, and plasma TG contents were hardly affected by the level and hepatic TG ones were lowered by relatively lower or higher casein level, and the rise in corn oil level generally reduced plasma T-CHOL and TG concentrations, but raised hepatic ones.

Animals↗

[Distribution of intraglandular metastatic foci in the contralateral lobe of papillary thyroid carcinoma].

The distribution of metastatic foci in the opposite lobe has not been studied in detail despite of several reports on the high incidence of contralateral metastasis. Whether foci spread to the upper one-third of the contralateral lobe influences the choice of total or subtotal thyroidectomy. Metastasis was studied in 66 patients 11 men and 55 women aged 24-73 years (mean; 51.3), undergoing primary total thyroidectomy from 1988 to 1996. Serial blocks of the opposite lobe, approximately 5 mm thick were sliced and stained by hematoxylin-eosin. Metastases were found in 44 patients (67%). Based on the size of the primary focus, these patients were divided into group A (smaller than one-third of the lobe) and group B (greater than that of group A). The average size of the primary focus was 21 mm in group A and 36 mm in group B. The contralateral metastatic rate was 64% (14/22) in group A and 68% (30/44) in group B. The distribution of metastatic foci in the opposite lobe was studied in 44 positive patients. The spread to the upper one third occurred in 61% (27/44); 29% (4/14) in group A and 76% (23/30) in group B a significant difference (p < .003). We thus concluded that the larger the primary focus, the wider the spread of metastatic foci to the opposite lobe.

Adult↗

[Chemotherapy based on EBM in the field of hematological malignancies].

In the field of hematology/oncology, there are reasonable number of chemotherapy-related reports with level 1 evidences based on the analysis of the evidence based medicine (EBM). Following reasons may be pointed out; the first is that the history of chemotherapy has been initiated in the field of in hematology/oncology so it has more than 50 years' experience. The second is that leukemia and lymphoma are very chemosensitive diseases to compare with solid tumor, so the ultimate goal of their therapy is increase of the cure rate. The third is hematologists with high specialty only can manage such serious patients. Thus they have proposed plenty well-designed and well-organized clinical protocols and have performed some of them in this field. We have learned several recommended therapy of some hematological malignancies with level 1 evidences. It is not so easy, however, to treat all patients according to the best recommended therapy for Japanese patients, because of some limitations of using Japanese health insurance. This is very crucial problem for the patients. We should settle the issue from the scientific and social aspects as soon as possible.

Clinical Trials as Topic↗

[A case of unilateral and metachronous occurrence of renal tubulopapillary adenoma and renal cell carcinoma].

A 50-year-old male underwent a nephron-sparing surgery for a small renal incidentaloma, which was atypical for renal cell carcinoma in diagnostic images. The tumor was pathologically diagnosed as renal tubulopapillary adenoma. Three years later, another tumor was pointed out in the ipsilateral kidney, and he underwent a radical nephrectomy. The latter was diagnosed as clear cell carcinoma. We report this very rare case of unilateral and metachronous occurrence of renal tubulopapillary adenoma and renal cell carcinoma.

Adenoma↗