Biomedical subjects

Junko Kawakami

Publications and source records attributed to Junko Kawakami.

7 recordsLinked to original sources

PubMed2006

Comparison between properties of 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) phosphorothioate oligonucleotides and N3'-P5' thiophosphoramidate oligonucleotides.

Synthesis and properties of an oligonucleotide uniformly modified with 2'-O,4-C-ethylene-bridged nucleic acid (ENA) units were compared with those of GRN163, which is modified with N3'-P5' thiophosphoramidates, with the sequence targeting human telomerase RNA subunit. Although an ENA phosphorothioate oligonucleotide, ENA-13, could be synthesized using ENA phosphoramidites on a 100-mg scale, synthesis of GRN163 was very hard even on a 1-micomol scale. In view of both stability of the duplex formation with complementary RNA and the efficiency of cellular uptake by endocytosis, ENA-13 was superior to GRN163. These findings suggest that ENA-13 has useful properties for antisense therapeutic application.

Chromatography, High Pressure Liquid↗

PubMed2006

Assisting the diagnosis of thyroid diseases with Bayesian-type and SOM-type neural networks making use of routine test data.

Patients with hyperthyroidism sometimes take much time to receive the final diagnosis. To improve patient QOL, simple screening for hyperthyroidism by thyroid non-specialists at the physical check-up is highly expected. Therefore, we applied both Bayesian-type and SOM-type neural networks since we assured the approach useful in analysing thyroid function diagnosis in the previous work. Routine test (14 parameters) data from 66 subjects with a known diagnosis (18 patients with hyperthyroidism and 48 healthy volunteers) were adopted as learning data, and then 142 individuals who also received the same routine tests at the Tohoku University Hospital were screened to predict patients with hyperthyroidism. Both neural networks using 14 parameters predicted several patients as having hyperthyroidism with high probability, including all three hyperthyroid patients diagnosed later by the physician. Further detailed analysis of the routine test parameters that were important for classification found that screening with a set of three parameters (alkaline phosphatase, serum creatinine and total cholesterol) or plus aspartate aminotransferase allowed for quite accurate screening. These results showed that the same neural networks as previous work allows simple screening of patients for hyperthyroidism on the basis of routine test data, and that physicians not specializing in the thyroid can rapidly identify individuals suspected of having hyperthyroidism, to permit a rapid referral for examination and treatment by thyroid specialists.

Bayes Theorem↗

PubMed2005

Synthesis and properties of ENA oligonucleotides targeted to human telomerase RNA subunit.

Oligonucleotides uniformly modified with 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) units were synthesized using the phosphoramidite method on a hundred-milligram scale for the evaluation of thermodynamic and chemical properties. The properties of these ENA oligonucleotides with the sequences targeted to human telomerase RNA subunit (hTR) were compared with those of GRN163, which is an oligonucleotide modified with N3'-P5' thiophosphoramidates. The melting temperatures of the duplexes of ENA oligonucleotides with complementary RNA were higher than that of the duplex of GRN163. Moreover, ENA oligonucleotide ENA-13 was more highly stable than GRN163 under acidic conditions (pH 5.0). ENA-13, which contained contiguous guanine sequences, could not form a G-quadruplex, which formation is not feasible for binding to hTR as an antisense molecule. The above findings suggest that ENA oligonucleotides may be useful for antisense therapeutic applications.

Humans↗

PubMed2005

An analysis of thyroid function diagnosis using Bayesian-type and SOM-type neural networks.

Thyroid function diagnosis is an important classification problem, and we made reanalysis of the human thyroid data, which had been analyzed by the multivariate analysis, by the two notable neural networks. One is the self-organizing map approach which clusters the patients and displays visually a characteristic of the distribution according to laboratory tests. We found that self-organizing map (SOM) consists of three well separated clusters corresponding to hyperthyroid, hypothyroid and normal, and more detailed information for patients is obtained from the position in the map. Besides, the missing value SOM which we had introduced to investigate QSAR problem turned out to be also useful in treating such classification problem. We estimated the classification rates of thyroid disease using Bayesian regularized neural network (BRNN) and found that its prediction accuracy is better than multivariate analysis. Automatic relevance determination (ARD) method of BRNN was surely verified to be effective by the direct calculation of classification rates using BRNN without ARD for all possible combinations of laboratory tests.

Bayes Theorem↗

PubMed2004

An example of social activities by registered dietitians: development of recipes for cook-chilled meals to be delivered to kidney disease patients in the conservative treatment and maintenance dialysis stages.

BACKGROUND: Many studies have indicated the effectiveness of medical nutrition therapy for kidney diseases in various stages. However, compliance with dietary therapy over a long period is not easy for patients living alone, elderly patients, and disabled patients, and the concern of registered dietitians working at medical facilities has become increased. Our activities started in the form of social services, developing recipes for cook-chilled foods, collaborating with a firm that had been providing a meal-delivery service, for patients with kidney diseases. METHODS: Our subjects were outpatients with renal failure at the conservative treatment stage, patients at the dialysis stage, and those with diabetic nephropathy. To develop recipes, the nutritional amounts of energy, protein, potassium, phosphorus, salt, and water content in the diet were determined on the basis of the guidelines of the Japanese Society of Nephrology. In 2000, a survey was conducted of 140 regular users of the cook-chilled and delivered foods. The items surveyed were: age, sex, duration of the use of the service, degree of satisfaction with the meals, palatability of menu items, opinions and requests, and reasons for the use of the service. RESULTS: Between February 1996 and August 2000, recipes for cook-chilled foods for patients with kidney diseases at the conservative-treatment stage, those at the dialysis stage, and those with diabetic nephropathy were gradually developed. As of July 2003, the total number of recipes was 946. Of the 140 users surveyed, we obtained valid responses from 91 (65.0%). Regarding duration of usage of the service (n = 91): it was 1 year or more in 38.6%, 6-12 months in 15.7%, 3-6 months in 22.9%. 1-3 months in 12.3%, and 1 month or less in 10.8%. Regarding degree of satisfaction with the meals (n = 91), it was very good or good in 58%, fair in 30%, and no good in 12% of respondents. CONCLUSIONS: As the results of the survey indicated, the home-delivered, cook-chilled foods were generally, favorably accepted by users (rate of satisfaction, 58% [very good and good], duration of usage, 54.3% [6 months or longer]), for them to continue their dietary therapy at their homes. It is suggested that the service of delivering cook-chilled meals can be used as one of the choices enabling continued dietary therapy for patients with chronic renal failure who have difficulty in self-management of the diet at home for diverse reasons.

Adult↗

PubMed2004

Application of a self-organizing map to quantitative structure-activity relationship analysis of carboquinone and benzodiazepine.

Self-organizing map (SOM) of Kohonen seems to be a promising approach beyond the standard one to regression for some classification problems encountered in the field of pharmacy. We apply them, therefore, to the quantitative structure-activity relationship (QSAR) in carboquinones and benzodiazepines, and show their usefulness. Most QSAR analysis using neural networks has been made by adopting neural networks with supervised learning. On the contrary, SOM obeys unsupervised learning and originally does not involve the use of desired target data. If we note that an appreciable fraction of data may be missing without making the similarity comparison impossible in SOM if the number of attributes considered is appreciable, QSAR analysis using SOM is found to be possible as if supervised learning. Similar to target data in supervised learning, we can take into account target data (=observed activity) as one of attributes in addition to other attributes (=structural descriptors). Choice of optimal descriptors as input parameters was found to be essential to generate valuable SOM.

Benzodiazepines↗

PubMed2003

Evaluation of amino acid patterns in recipes for kidney disease patients.

OBJECTIVE: To examine first-limiting amino acids in EAA patterns of a low-protein diet from card-style printed recipes on the market in Japan. In addition, this research explored practical knowledge about which combination of foods could cause an imbalance, if any, of amino acids, and seek to further improve diets for patients with kidney disease. METHODS: Thirty-nine card-style printed recipes for patients with diabetic nephropathy or chronic renal disease or those already on dialysis were chosen for this study. These recipes are available at major book stores in Japan. From each recipe, the first-limiting amino acid, if any, and corresponding amino acid score were investigated and identified. To determine them, the reference amino acid scoring pattern in Report of a Joint FAO/WHO Ad Hoc Expert Committee, 1973, was used as a reference. RESULTS: Among the 39 cards (recipes) examined, we found threonine to be the first-limiting amino acid in 59% of those samples, followed by valine in 8%, methionine + cystine in 3%, lysine in 3%, and leucine in 3%. In the remaining 26%, we did not find any limiting amino acids. Amino acid scores ranged from > or = 100 (26%) to 90-99 (54%), 80-89 (18%), and 70-79 (3%). QUALITY: In 26% of the samples, no deficits in regard to amino acid patterns were found in our analysis of these recipes. Valine, which is an index of malnutrition, was found to be among the first-limiting amino acids. However, because amino acid scores of less than 79 represented only 3% of all recipes chosen, EAAs in protein-controlled diets might not necessarily be deficient. CONCLUSION: The majority of the tested sample recipes were not balanced in EAA pattern, especially for threonine as the first-limiting amino acid of a meal. To prevent malnutrition in chronic renal disease, especially for those following low-protein diets, well-balanced meals on a daily basis as well as adequate energy intake are considered to be necessary.

Amino Acids↗