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Biomedical subjects

S Kondo

Publications and source records attributed to S Kondo.

At least 505 records · Page 28Linked to original sources

A new drug delivery system using plasma-irradiated pharmaceutical aids. VII. Control release of theophylline from plasma-irradiated polymer-coated granules.

With a view to expanding the application of a drug delivery system (DDS) preparation using plasma-irradiated pharmaceutical aids for various dosage forms, we studied the theophylline release property from plasma-irradiate polymer-coated granules, the polymers of which differ in the plasma irradiation effect. We used a new type of rotational plasma-irradiation reactor to perform plasma-irradiation uniformly on the surface of polymer-coated granules based on scanning electron microscope (SEM) observation. It was shown that an increase in theophylline release rate with an increase in plasma duration was observed in all polymer-coated granules, although the factors of such release properties vary with the polymers, as evidenced by the SEM observations. Such results provided the criteria for selecting polymer structures for granule coating. Thus, the present method for the control of drug release is considered principally applicable not only to polymer-coated granules but also to various drug forms under consideration of the above criteria.

Delayed-Action Preparations↗

A new drug delivery system using plasma-irradiated pharmaceutical aids. VI. Controlled release of theophylline from plasma-irradiated double-compressed tablet composed of water-soluble polymers as a wall material.

The rapid drug release from a double-compressed tablet containing theophylline with the water-soluble polymer polymethacrylic acid (PMAA) or polyacrylamide (PAAm) used as a wall material can be suppressed by argon plasma irradiation and changed into the slow release due to a decrease in the solubility of water-soluble polymers used as the outer layer. This report is the first to deal with an attempt to control the release of drugs by controlling polymer solubility, and to fabricate a completely soluble controlled release type of drug delivery system (DDS) making use of plasma processing.

Acrylic Resins↗

Protein sequences of two keto ester reductases: possible identity as hypothetical proteins.

We determined the amino acid sequences of two keto ester reductases (YKER-V and -VI) purified from a cell-free extract of Saccharomyces cerevisiae. The N-terminal and internal amino acid sequences of YKER-VI (AcKR) were in agreement with the sequence of hypothetical 36.4-kDa protein (S. cerevisiae chromosome X reading frame ORF YJR105w) in yeast. The N-terminal amino acid sequence of YKER-V was also identical with that of the hypothetical protein coded by yeast chromosome XIV or II. These results suggested that two hypothetical proteins were expressed as keto ester reductases in yeast cells.

Alcohol Oxidoreductases↗

Estimation of pH and the number of lytic granules in a CD8+ CTL clone treated with an inhibitor of vacuolar type H(+)-ATPase concanamycin A.

A vacuolar type H(+)-ATPase inhibitor, concanamycin A (CMA), raised the pH and induced morphologic changes such as vacuolation in lytic granules in the CD8+ cytotoxic T lymphocyte clone OE4. Here we measured the pH in lytic granules present in OE4 by immunoelectron microscopic observation using (3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) as a pH probe. In control OE4, only the peripheral region, but not cores, were heavily stained with DAMP. Exposure to 100 nM CMA for 60 min raised the pH in the lytic granules from 5.7 +/- 0.2 to 6.8 +/- 0.2. Furthermore, the number of lytic granules in OE4 was estimated under phase contrast microscopy after Wright staining. About 20 lytic granules in average were detected in control cells, while CMA induced vacuolation and decreased their number by 20 to 30%.

Animals↗

A novel endogenous mediator of cutaneous inflammation: leukemia inhibitory factor.

Keratinocytes produce a variety of cytokines, including leukemia inhibitory factor. We hypothesised that this cytokine may play a pro-inflammatory role in the skin and tested this hypothesis by injecting recombinant leukemia inhibitory factor (1-100 ng) into the ear pinnae of C3H/HeJ mice. To other groups of animals, we injected boiled leukemia inhibitory factor or phosphate-buffered saline (negative control) or 0.4 ng human interleukin-1 alpha as a positive control. Following injection of 100 ng leukemia inhibitory factor, ear thickness, measured by micrometer, increased 66% over controls at 12 h and 100% at 24 h (overall p = 0.041 by analysis of variance). Injection of 0.4 ng interleukin-1 alpha caused greater ear swelling. Compared with controls, swelling increased by 67% at 6 h, 100% at 12 h and 340% after 24 h (overall p < or = 0.00001). Leukemia inhibitory factor (100 ng only) stimulated a 3.5-fold increase in leukocytes after 6 h. After 12 h, a 14-fold increase was seen in ears injected with 10 ng leukemia inhibitory factor and a 12-fold increase with 100 ng leukemia inhibitory factor, which remained elevated (17-fold) at 24 h (overall p = 0.0001). Injection of interleukin-1 alpha led to a 3.4-fold increase in leukocytes (mean per 20 high-power fields) after 6 h, a 14-fold increase at 12 h and a 25-fold increase at 24 h (overall p < or = 0.00001). These results demonstrate that leukemia inhibitory factor appears to be a mediator of cutaneous inflammation.

Analysis of Variance↗

Studies on the reduction indices of the deciduous teeth of Chinese living in Taiwan.

The reduction index of deciduous teeth was investigated statistically. Materials used were plaster casts of the deciduous dentition taken from Chinese children living in Taiwan. The reduction indices showed no sexual differences. In the maxillary teeth, reduction indices of the bucco-lingual diameters (BL) had the largest values, followed by those of the mesio-distal diameters (MD), and those of the crown area (AREA) which were the least. In contrast to the maxillary teeth, in the mandibular teeth, the reduction indices of MD and those of BL had nearly the same values although the reduction indices of MD were slightly larger than those of BL in females (p < 0.05). With respect to the difference between the maxilla and the mandible, in deciduous incisors the reduction index of MD in the mandible was larger than that in the maxilla (p < 0.01). While in BL the reverse relation was noted. In the deciduous molars the reduction indices of BL and AREA in the maxilla were larger than those in the mandible (p < 0.01). The reduction indices showed no significant difference among the Mongoloid populations sampled. This result may be explained by the primitiveness of deciduous teeth.

Asian People↗

Comparison of the crown dimensions between the maxillary second deciduous molar and the first permanent molar.

The morphologic relationship of the crown structures of the maxillary second deciduous molar (m2) and the first permanent molar (M1) was investigated with odontometric methods. Materials used were 124 male dental casts taken from Chinese living in Kaohsiung (Taiwan). The mesiodistal and buccolingual diameters, cusp sizes, and intercusp distances were measured. The mean crown diameters were larger in M1 than in m2. The tooth crown proportions were similar in m2 and M1. The intercusp distance was compressed buccolingually in m2. With respect to the relative cusp size, the paracone was not significantly different between m2 and M1. The metacone was relatively larger in m2 than M1, while lingual cusps (protocone and hypocone) were relatively smaller in m2 than in M1. Principal component analysis was performed to investigate factors influencing the variation in crown dimensions of the two teeth. Four components were extracted: (1) buccolingual intercusp distances, (2) crown proportion (mesiodistal and buccolingual diameters), (3) mesiobuccal and distolingual compression, and (4) protocone and mesiodistal intercusp distance. Analysis of principal component scores indicated that the crown proportions of m2 and M1 were similar. The m2 had a smaller protocone and more buccolingually compressed intercusp distances than did M1. The morphologic characteristics of the crown of m2 indicate that it is more primitive and has developed less than M1.

Humans↗

Seasonal variation in the circadian rhythm of pulmonary function in stable asthmatic children who have nearly outgrown their asthma.

To study whether nocturnal bronchial obstruction changes during the year, we assessed the circadian FEV1 variation during four consecutive seasons in 20 children (12 boys; aged 9-12 years) with episodic asthma who were outgrowing their asthma. FEV1 was determined every 4 h between 10:00 and 10:00 during two consecutive days. The last six FEV1 values were submitted to cosinor and coefficient of variation (CV) analyses. The seasonal means (SD) in the group 24 h percent predicted FEV1 was 85.5 (11.4), 81.2 (10.6), 86.0 (11.6), and 82.2 (14.0)% during spring, summer, autumn, and winter, respectively. The difference between the summer and autumn FEV1 values was statistically significant (p < 0.05). The mean (SD) of the circadian amplitude values was 4.1 (4.3), 6.0 (3.8), 4.9 (3.4), and 7.2 (4.1)% during spring, summer, autumn, and winter, respectively. The difference in amplitude between the spring and winter and between the autumn and winter values was statistically significant (p < 0.05). CV values of 48 of the 80 (60%) circadian FEV1 time series exceeded the average CV of 5% observed in nonasthmatic children studied in our laboratory. There was an unequal distribution during the year in elevated CV values; 6, 17, 10, and 15 of the high CV values occurred, respectively, in the spring, summer, autumn, and winter. These results suggest that nocturnal bronchial obstruction may change seasonally in terms of severity and amplitude in children who have nearly outgrown their asthma.

Asthma↗

Antifungal antibiotic benanomicin A increases susceptibility of Candida albicans to phagocytosis by murine macrophages.

Benanomicin A is an antifungal antibiotic produced by Actinomadura spadix. In the present study, we investigated the effect of benanomicin A on the phagocytosis of Candida albicans by murine peritoneal macrophages and on the cell-surface hydrophobicity (CSH) of C. albicans. Although pretreatment of macrophages with benanomicin A had no effect on the phagocytosis, addition of benanomicin A to the culture of macrophages and Candida cells increased the susceptibility of Candida cells to the phagocytosis by the macrophages. Pretreatment of Candida cells with benanomicin A also increased the susceptibility of Candida cells to the phagocytosis. When Candida cells were mixed with benanomicin A, the antibiotic bound irreversibly to Candida cells. These data suggest the possibility that the increased susceptibility of Candida cells to the phagocytosis is mediated by the binding of benanomicin A to Candida cells. Examination of physicochemical property of Candida cell surface showed that the CSH of Candida cells significantly decreased by the treatment with benanomicin A. Thus, binding of benanomicin A to Candida cells may induce biochemical/physicochemical alternation of the surfaces, so that they become more susceptible to phagocytosis by murine macrophages. These properties of benanomicin A, along with its antifungal activity, seem to be beneficial in the treatment of fungal infections.

Animals↗

Binding of benanomicin A to fungal cells in reference to its fungicidal action.

An antifungal antibiotic, benanomicin A, binds in the presence of Ca2+ to susceptible fungi and some bacteria, but not to antibiotic-resistant bacteria and mammalian cells. With the susceptible yeast Saccharomyces cerevisiae, benanomicin A binds similarly to whole cells and to protoplasts. Studies using benanomicin A and three structurally related derivatives suggested that a carboxylic acid in the D-alanine moiety and a sugar moiety in the benanomicin A molecule are essential for both binding and antifungal activities against growing S. cerevisiae. An amino substituent on the sugar moiety can be replaced with a hydroxyl group without the loss of activities. Benanomicin A binds to various yeast mannans which differ in glycosidic linkages. These results indicate that binding of benanomicin A to the mannan portion of fungal cells is essential for exertion of the antifungal activity.

Anthracyclines↗

Enzymatic 2'-N-acetylation of arbekacin and antibiotic activity of its product.

Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.

Acetylation↗

[Measurement of serum tissue polypeptide antigen (TPA) in patients with malignant tumor using prolifigen TPA-M "Daiichi" kit].

Serum tissue polypeptide antigen (TPA) was measured using a newly developed Prolifigen TPA-M "Daiichi" kit in 1,236 healthy subjects, 2,867 patients with malignant tumors, and 901 with benign diseases. Because 94.0% of healthy subjects had serum TPA under 70 U/l, the cut-off value was set at 70 U/l. Serum TPA was elevated in more than 50% of patients with head and neck cancer, lung cancer, liver cancer, gallbladder or bile duct cancer, pancreatic cancer, colorectal cancer, ovarian cancer, and prostate cancer. The overall positive rate in malignant tumors was 55.5%. Serum TPA was higher in advanced cancer than in earlier stage cancer, and decreased after the resection of the tumor. The false positive rate in benign diseases was 31.3%. ROC analysis revealed the usefulness of TPA as a tumor marker in many cancers. The correlation coefficient between TPA and CYFRA 21-1, and between TPA and TPSA, was 0.747 and 0.694, respectively. In conclusion, measurement of serum TPA using the new kit is useful in the management of patients with various malignant tumors.

Antigens, Neoplasm↗

[Clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis in Japanese].

In order to examine the clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis, we analyzed clinical features and HLA typing of 85 patients in a multicenter study. Eighty-five patients with secondary amyloidosis associated RA were studied. The diagnosis of secondary amyloidosis were made on histological findings by biopsy or autopsy. The most common biopsy site was gastrointestinal tract (79.5%). Clinical symptom and the frequency at the time of diagnosis were; diarrhea (35 cases), abdominal pain (22 cases) and vomiting and nausea (16 cases). Abnormalities and the frequency in a laboratory test included proteinuria (49 cases), increased serum creatinine (32 cases), anemia (30 cases) and hematuria (15 cases). Twenty-eight patients were dead and 57 patients were alive at the time of the study. The average duration between diagnosis of amyloidosis and death was 19.4 +/- 18.5 (SD) months among the dead patients. The average duration after diagnosis of amyloidosis was 24.2 +/- 19.5 (SD) months in surviving patients. The causes of death were renal failure complicated with heart failure (6 patients), heart failure alone (3 patients) and renal failure alone (2 patients). Fifty-nine patients in the control group who were negative to amyloid deposition on biopsies at more than one site in the gastrointestinal tract, were clinically compared with patients in the amyloidosis group. No difference were noted in the age of RA occurrence and the stage between the two groups. As to the class, however, the number of patients with severe functional disorder (class 3 or severe) was larger in the amyloidosis group. There were no significant difference between the two groups in Lansbury's activity index. On hematology, biochemistry and urinalysis, the incidences of increased white blood cell count, anemia, increased platelet count, increased serum creatinine, hypoproteinemia, hypoalbuminemia, increased IgA, and increased urine and blood BMG were statistically significantly higher in the amyloidosis group than in the control group. HLA-A, -B, -C, and DR-locus antigens were compared in the 53 patients in the amyloidosis group and in the 59 subjects in the control group. There were no significant differences in frequency of HLA-A, and -B antigens between two groups. Frequency of CW7 antigen was significantly decreased in the amyloidosis group (13.2%) than in the control group (39.0%). Frequency of DR1 antigen was decreased in the amyloidosis group (3.8%) than in the control group (22.0%), although the difference was not significant. These findings suggest the possible involvement of genetic factors in the occurrence of amyloidosis. It is suggested that the occurrence of amyloidosis is suppressed by some genes which are linked with CW7 antigen.

Adolescent↗

[A high concentration of itraconazole in an aspergilloma].

A 66-year-old woman was given 100 mg/day of itraconazole for eight months to treat pulmonary aspergillosis with an aspergilloma. The amount of purulent sputum decreased, but open drainage was done because the fever continued and because no improvement was seen on the chest X-ray film. No aspergillus was cultured from the surgical specimen, but fungi were observed microscopically. The concentration of itraconazole in plasma was 249 ng/ml. The concentrations in specimens of the lung and of the aspergilloma obtained by thoracotomy were 81 ng/g and 837 ng/g, respectively. The high concentration in the aspergilloma had made the fungus inactive. The itraconazole concentration may have been very high for three reasons: (1) the concentration increased in purulent fluid, (2) itraconazole easily entered the aspergilloma through the root at the cavity wall, and (3) itraconazole dissolved in lipid derived from destroyed fungus.

Administration, Oral↗

Chilblain lupus erythematosus of Hutchinson responding to surgical treatment: a report of two patients with anti-Ro/SS-A antibodies.

We report two patients with chilblain lupus erythematosus of Hutchinson (CL) who responded to surgical treatment. One of them was a 72-year-old woman (case 1), and the other a 62-year-old man (case 2). We attempted to treat these patients by excising the lesions and subsequently performing full-thickness free skin grafting, using skin from the abdominal region. No recurrence was seen in the operated area 7 years (case 1) and 3 years (case 2) after surgery. However, lesions persisted in the areas not operated upon, and in the areas where lesions had not been adequately excised. These results suggest that surgical removal of local factors reduces the rash in these cases. In addition, both patients were serologically positive for the anti-Ro/SS-A antibody suggesting that local expression of the Ro/SS-A antigen may be involved in the pathogenesis of the skin lesions. To our knowledge, full thickness free skin grafting has not been used previously to treat CL-associated skin lesions, and is promising as a treatment for patients who do not respond to conventional means.

Aged↗

Leukaemia inhibitory factor is expressed by normal human keratinocytes in vitro and in vivo.

Leukaemia inhibitory factor (LIF) is a pleotropic cytokine, regulating differentiation, cell growth, cachexia and inflammation. Using the reverse transcription-polymerase chain reaction (RT-PCR) we found that, in culture, normal human keratinocytes (KC) expressed mRNA transcripts for both LIF and the LIF receptor. In the conditioned medium (CM), constitutive LIF protein production was barely detectable but stimulation of KC with 10 ng/ml of either interleukin (IL)-1 alpha, or IL-8, for 24 h, resulted in small but significant increases (P < 0.05) in LIF protein, as measured by enzyme-linked immunosorbent assay. After culture in media containing 1.5 mmol/l calcium, a time-dependent increase in LIF mRNA was seen up to 72 h (an 8.5-fold increase), over levels in cells cultured in 0.05 mmol/l calcium. A large increase in LIF protein in the CM (from 1.15 +/- 0.15 pg/ml to 178.7 +/- 75.7 pg/ml) was seen 72 h after a switch to media containing 1.5 mmol/l calcium (P = 0.05). Twenty-four hours after stimulation of human KC in culture with 10 ng/ml recombinant LIF, a twofold increase in both IL-1 alpha and IL-8 protein in the CM (P < 0.05) was observed. In normal human scalp and foreskin, the epidermis was shown to contain LIF protein by immunostaining. LIF staining was found throughout the epidermis, and in the cells of the outer layer of the root sheath. Thus, KC synthesize LIF in vitro and in vivo.

Base Sequence↗