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Biomedical subjects

Y Machida

Publications and source records attributed to Y Machida.

At least 37 records · Page 2Linked to original sources
PubMed1993

Site-dependent effect of aprotinin, sodium caprate, Na2EDTA and sodium glycocholate on intestinal absorption of insulin.

In order to determine an advantageous site for intestinal insulin absorption, the hypoglycemic effects of insulin after administration to the duodenum, the jejunum, the ileum and the colon were investigated using an in situ loop method. Insulin solution was administered to the various loops of fasted rats with or without aprotinin (AP) as a protease inhibitor, or absorption enhancers such as sodium caprate, Na2EDTA or sodium glycocholate. An obvious hypoglycemic effect of insulin alone was seen only in the ileum loop washed with phosphate buffered saline. When coadministered with AP, the most remarkably amplified effect was again observed in the ileum. In the ileum, the area under the serum insulin levels vs. time curve from 0 to 4 h was linearly related to the logarithm of the AP dose. Both sodium caprate and Na2EDTA significantly promoted the hypoglycemic effect of insulin at all sites, and their intensity increased towards the distal regions of the intestine. On the other hand, sodium glycocholate improved only colonic insulin efficacy. These results suggest that the ileum seems to be the most useful region in the small intestine for insulin absorption; however, insulin must be protected from proteolysis to enhance its absorption. In addition, the insulin efficacy could be increased by absorption promoters more effectively in the colon than in the small intestine.

Animals↗
PubMed1993

[Development of topical drug delivery systems utilizing polymeric materials].

Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

Administration, Topical↗
PubMed1993

Evaluation of the conjugate between N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine and chitosan as a macromolecular prodrug of 1-beta-D-arabinofuranosylcytosine.

The conjugate of N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C) with chitosan, named chi-glu-ara-C, was prepared and evaluated on its utility as a macromolecular prodrug. 1-beta-D-Arabinofuranosylcytosine (ara-C) was predominantly regenerated gradually from chi-glu-ara-C in 1/15 M phosphate buffer, pH 7.4, at 37 degrees C, and its amount after 7 d incubation was 56% (w/w). The antitumor effect was evaluated by an increase in the lifespan (ILS) of the mice bearing P388 leukemia at the single administration at 24 h after inoculation. Ara-C exhibited an ILS of 3.4% at a dose of 100 mg/kg, and the survival time was not significantly different from that of the control. However, chi-glu-ara-C showed an ILS of 60.7% at a dose of 88 mg eq ara-C/kg, and the survival time was significantly different from that of the control. Chitosan and chi-glu-ara-C were observed to cause the side effects judged from the body weight loss to a certain extent. However, chi-glu-ara-C was recognized to be useful because of its effectiveness.

Animals↗
PubMed1993

[Severely mentally and physically disabled in Gunma Prefecture].

We studied severity, causes of the disabilities, complications due to disabilities, and past histories of the severely mentally and physically disabled whose guardians or parents were residents in Gunma prefecture on September 1, 1991. This survey was made on severely disabled schoolboys and girls aged 6 to 15 years with IQ of 35 or less who could not stand or walk, even if they were supported. The number of them was 133 at the moment of this survey. Asphyxia at birth and congenital but unknown etiology were the major causes in the institutionalized cases, but cerebral palsy of unknown etiology and "no information" were frequent in the cases cared at home. The institutionalized patients showed severer mental retardations, palsies and disabilities on activities of daily lives, though not with statistically significant difference, and contained significantly larger number of cases fed by gastric tube or having meals as blended foods and significantly smaller number of cases having conventional meals than cases cared at home. Furthermore, epilepsies or constipations as complications were found more frequently in institutionalized cases than in cases cared at home with significant difference. On past history, relatively large numbers of the disabled suffered from various infectious diseases, especially from measles, varicella, mumps and pneumonia. Histories of measles, varicella and mumps showed higher frequency in institutionalized cases than in cases cared at home, though not with significant difference. On the cases cared at home, some of them did not have their home doctors, though in small numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Prevalence rate of the severely mentally and physically disabled children in Gunma Prefecture].

Children were studied on distribution of the severely mentally and physically disabled aged 6 to 15 years in Gunma Prefecture as of September 1, 1991. They were all bedridden or able to sit, but could not stand or walk, even with support. Today, all the Japanese should attend elementary school as well as junior high school. Even though they are severely disabled, they are all registered by the regional Board of Education, where we could get exact data on the disabled children throughout Gunma Prefecture. We collaborated with the regional Board of Education, the Child Consultation Center of Gunma Prefecture and 6 hospitals for the disabled. A total of 129 cases were found. The population of schoolboys and schoolgirls aged 6 to 15 years of age was 236,000, most of whose guardians were residents of this prefecture, and the prevalence rate was 0.55/1000. Among 129 cases, 53 cases (41.1%) were institutionalized and 76 cases (58.9%) were cared for at home. Fifty-nine cases (45.7%) were males and 70 cases (54.3%) were females. Thirty-four cases were aged 6 to 7 years (26.4%) and older cases declined probably due to premature deaths. Ninety-four of the 129 cases (72.9%) were bedridden and mentally retarded with IQs 20 or less.

Adolescent↗
PubMed1992

Prospective study on maternal, intrauterine, and perinatal infections with cytomegalovirus in Japan during 1976-1990.

Since 1976, sera obtained serially from 10,218 pregnant women during the first, second, and third trimesters of gestation and cord sera were tested for CMV complement-fixing (CF) and immunofluorescent (IF) antibodies. CMV IgG-IF antibody was positive in 9,735/10,218 (95%) in the first trimester, and a significant rise of CF antibodies during pregnancy was found in 70/9,206 (0.76%) of the seropositive group and in 5/438 (1.14%) of the seronegative group. IgM antibody was found in 6/9,206 (0.06%) of seropositive women during the first trimester and in 7/70 (10.0%) of seropositive mothers with CF antibody rise and in 4/5 of seroconverted mothers of the seronegative group, suggesting that the incidence of primary infection with CMV during pregnancy was approximately 1% of susceptible women. All the mothers with immune response had infants with neither viruria nor IgM antibody in the cord blood, whereas seropositive mothers without an immune response had infants with viruria (7/1,826; 0.4%) or with IgM antibody in the cord blood (6/9,136; 0.06%). None of these 13 babies, shedding CMV or with IgM IF antibody, had physical or mental retardation. CMV IgG-IF antibody was present in almost 80% of infants between 7 and 12 months of age in 1988, suggesting that perinatal or postnatal CMV infection may occur in infants born to seropositive mothers in 70-80% of pregnancies.

Antibodies, Viral↗
PubMed1992

Factors affecting prednisolone release from hydrogels prepared with water-soluble dietary fibers, xanthan and locust bean gums.

The release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums was investigated. Newly developed equipment was employed in order to increase the gum concentration in the hydrogels. The apparent release rate of prednisolone from the hydrogels decreased with increasing gum concentration, suggesting that the diffusion of drug molecules was mainly controlled by the density of the three-dimensional network structure in the matrix. The effect of additives such as glycerin and sucrose on the release behavior of prednisolone was also investigated in detail. Drug release was significantly lowered by the addition of these compounds to these hydrogels. A linear relation was observed between the apparent release rate of prednisolone and microscopic viscosity of the hydrogels. These results indicated that the drug release could be controlled not only by the density of the network structure but also by the microscopic viscosity of the hydrogels.

Delayed-Action Preparations↗
PubMed1992

Hapten synthesis for (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tet rahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] triazolo[4,3-a][1,4]diazepine (E6123).

(+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4, 5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f]triazolo[4,3-a] [1,4]diazepine (E6123) is a very potent platelet-activating factor (PAF) receptor antagonist and shows potent anti-PAF activities at the microgram level in a variety of animal models. In order to examine the pharmacokinetics of E6123 at low doses, establishment of a radioimmunoassay is required. On the basis of the metabolic pattern of E6123, we synthesized 6-[2-chloro-4-(3-carboxypropyl) phenyl]-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H -pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 22 as a potential hapten. In the synthesis of 22, we developed butynyl carbamate as a piperidine ring N-protecting group to prevent possible side reaction, namely oxidation of the methylene at position 2. This protecting group is stable under usual basic and acidic conditions.

Azepines↗
PubMed1991

Operation of an efficient site-specific recombination system of Zygosaccharomyces rouxii in tobacco cells.

Recombinase encoded by the R gene of pSR1 of Zygosaccharomyces rouxii mediates reciprocal recombination between two specific recombination sites (RSs) to induce excision or inversion of the DNA segment that is flanked by the RSs. We report here that site-specific recombination mediated by this system takes place effeciently in tobacco cells. To monitor the recombination events in tobacco cells, we have constructed two types of cryptic beta-glucuronidase reporter gene in such a way that recombination such as inversion of the construct or excision of the intervening sequence results in their expression. When these cryptic reporter constructs were transiently introduced together with the R gene by electroporation into protoplasts of tobacco cells, beta-glucuronidase activity was detected. The cryptic reporter genes, when stably resident in the chromosome of tobacco cells, were also activated by the R gene. Structural analyses of the genomic DNA isolated from these tobacco cells showed that the R protein did in fact catalyze precise recombination between two copies of RSs in tobacco cells, with resultant activation of the cryptic reporter genes. This observation provides the basis for development of a DNA technology whereby large regions of DNA can be manipulated in plant chromosomes. Potential uses of this recombination system are discussed.

Base Sequence↗
PubMed1991

Localization and orientation of the VirD4 protein of Agrobacterium tumefaciens in the cell membrane.

The virD4 gene of Agrobacterium tumefaciens is essential for the formation of crown galls. Analysis of the nucleotide sequence of virD4 has suggested that the N-terminal region of the encoded protein acts as a signal peptide for the transport of the VirD4 protein to the cell membrane of Agrobacterium. We have examined the localization and orientation of this protein in the cell membrane. When the nucleotides encoding the first 30 to 41 amino acids from the N-terminus of the VirD4 protein were fused to the gene for alkaline phosphatase from which the signal sequence had been removed, alkaline phosphatase activity was detectable under appropriate conditions. Immunoblotting with VirD4-specific antiserum indicated that the VirD4 protein could be recovered exclusively from the membrane fraction of Agrobacterium cells. Moreover, when the membrane fraction was separated into inner and outer membrane fractions by sucrose density-gradient centrifugation, VirD4 protein was detected in the inner-membrane fraction and in fractions that sedimented between the inner and outer membrane fractions. By contrast, the VirD4'/alkaline phosphatase fusion protein with the N-terminal sequence from VirD4 was detected only in the inner membrane fraction. Treatment of spheroplasts of Agrobacterium cells with proteinase K resulted in digestion of the VirD4 protein. These results indicate that the VirD4 protein is transported to the bacterial membrane and anchored on the inner membrane by its N-terminal region. In addition, the C-terminal portion of the VirD4 protein probably protrudes into the periplasmic space, perhaps in association with some unidentified cellular factor(s).

Alkaline Phosphatase↗
PubMed1991

[Subgingival microflora in children of early childhood, school age and circumpuberty. The proportion and frequency of gram-negative bacteria in periodontally healthy and gingivitis groups].

The present study characterized the microbial profiles of the gingival sulci in children. Subgingival samples from 36 gingivitis lesions of 18 patients and 36 sites in 18 healthy persons were examined. The tested individuals were divided into three stages according to physiological maturation i.e. early childhood, school age, circumpuberty. Puberty was confirmed through examination of wrist radiographs. Using continuous anaerobic techniques, samples were dispersed, diluted and then inoculated on selective and nonselective media and cultured under the condition appropriate gaseous phase respectively. Isolates were identified microbiologically and counted. All values were evaluated statistically. The samples were simultaneously examined by dark-field microscopy. Changes in the proportions and the frequency of periodontophathic bacteria were distinct in different stages of physiological maturation. Black-pigmented Bacteroides species were commonly found in gingivitis lesions. Bacteroides intermedius was frequently detected in the subgingival samples from children with gingivitis. In all stages, the proportion of black-pigmented Bacteroides and B. intermedius in the gingivitis groups were found to be significantly higher than that of the healthy groups. Statistical analysis revealed that levels of B. intermedius increased in circumpuberty stage compared with the 2 younger stages. Black-pigmented Bacteroides and B. intermedius were closely related to GI, PlI in 3 stages. Bacteroides gingivalis was found only in two gingivitis sites of a circumpubertal child with gingivitis. Actinobacillus actinomycetemcomitans was detected in 4 out of 12 sites in the school age group, and in 6 out of 12 sites in the circumpuberty group with gingivitis respectively. In the circumpuberty group, the proportion of A. actinomycetemcomitans in the gingivitis group was significantly higher than that of the healthy group, and A. actinomycetemcomitans was closely related to GI, PlI, CI, PPD. Eikenella corrodens was found to be associated with gingivitis in the school age and circumpuberty groups. No correlation was found in the detection of Fusobacterium nucleatum in 3 stages. Microscopic examination showed that the proportion of rods, fusiforms, filaments, motile rods, spirochetes in the gingivitis groups was significantly higher than that of the healthy groups, while the proportion of cocci in gingivitis groups was significantly lower than that of the healthy groups in 3 stages. Spirochetes were closely related to GI, PlI, PPD in all stages.

Adolescent↗
PubMed1991

Combined effect of cyclic monoterpenes and ethanol on percutaneous absorption of diclofenac sodium.

The combined effect of cyclic monoterpenes and ethanol on the percutaneous absorption of diclofenac sodium (DFS) from gel ointments was investigated in vivo in rats. The enhancing activity of terpenes was significantly affected by the concentration of ethanol formulated in the gel ointments. At a lower concentration of ethanol (20%), 1,8-cineole was observed to be the most effective. On the other hand, d-limonene showed strong activity when the large amount of ethanol was formulated (40%). A synergistic effect between terpenes and ethanol on the percutaneous absorption of DFS was significantly observed in cases of 1,8-cineole and l-menthol using an analysis of variance (ANOVA). When the diclofenac (DF) free form was formulated in gel ointment, the percutaneous absorption was significantly reduced. The reduction of the percutaneous absorption was closely related to the decrease in pH of the gel ointment owing to the free form of DF which was formulated.

Analysis of Variance↗
PubMed1991

Histological study of therapy for infected nonvital permanent teeth with incompletely formed apices.

The histological response of periapical tissues to root canal fillings with calcium hydroxide (Ca(OH)2)-iodoform paste, Vitapex (Neo Dental Chemical Products Co., Ltd., Tokyo, Japan), and Ca(OH)2-camphorated paramonochlorophenol (CMCP) paste in nonvital permanent teeth with incompletely formed apices was investigated in 160 root canals from 90 dog premolar and incisor teeth. Periapical inflammatory lesions were initially induced in the experimental teeth. After debridement and cleaning, root canals were filled with one of the two materials. The animals were sacrificed after 30, 60, 120, or 180 days, and histological sections of each specimen were prepared with hematoxylin and eosin staining. Histological findings showed periapical repair and apical closure in both experimental groups. However, the differences in the level of inflammation, apical closure, and reparative process among the two groups were significant (p less than 0.05). It was concluded that the Ca(OH)2-iodoform paste, Vitapex, produced better results than Ca(OH)2-CMCP paste in treatment of infected nonvital permanent teeth with incompletely formed apices.

Animals↗
PubMed1991

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

Aerosols↗
PubMed1991

Controlled release microspheres based on Eudragit L100 for the oral administration of erythromycin.

The use of Eudragit L100, a copolymer based on methacrylic acid and methacrylic acid methyl ester, in preparing erythromycin microspheres is described. The microspheres were simply prepared in liquid paraffin by solidifying an Eudragit L100 in ethanol solution. When gelatin was incorporated in the solidifying solution, the resultant microspheres were more spherical and had a smooth surface. The size of the microspheres could be controlled by varying the Eudragit L100 concentration in ethanol, and erythromycin was incorporated with 60-70% efficiency. The degradation of erythromycin by acid was markedly protected when the erythromycin microspheres were coated with the polymer. The in vitro release rate of erythromycin from the microspheres was also modified by the coating process. The feasibility of preparing formulations of erythromycin for oral administration, which release the drug at a controlled rate, and protect the drug from gastric acid, is thus demonstrated.

Acrylic Resins↗
PubMed1990

Vacuolar targeting and posttranslational processing of the precursor to the sweet potato tuberous root storage protein in heterologous plant cells.

Sporamin, the tuberous root storage protein of the sweet potato, which is localized in vacuoles, is synthesized as a prepro-precursor with an N-terminal sequence of amino acids that includes a signal peptide and an additional pro-segment of 16 amino acids. A full-length cDNA for sporamin was placed downstream of the 35 S promoter of cauliflower mosaic virus and introduced into tobacco and sunflower genomes by Ti plasmid-mediated transformation. A polypeptide of nearly the same size as mature sporamin from the sweet potato was detected in transformed calli of tobacco and sunflower, as well as in the leaves, stems, and roots of regenerated, transgenic tobacco plants. Amino acid sequence analysis of the nearly mature-sized form of sporamin from the transformed tobacco cells revealed that it is actually longer by three amino acids at its N terminus than authentic sporamin purified from the sweet potato. By pulse labeling of suspension-cultured tobacco cells with [35S]methionine, the pro-form of the precursor to sporamin, but not the prepro-precursor, was detected. The 35S-labeled proform was chased to the nearly mature-sized form via an intermediate form which is slightly larger than the nearly mature-sized form. Analysis by Edman degradation of the intermediate form that was labeled in vivo with [3H]histidine suggested that it is longer by two amino acids at its N terminus than the nearly mature-sized form of sporamin. These results suggest that at least two steps of posttranslational processing of the pro-form occurs sequentially in tobacco cells. The posttranslational processing of the pro-form of the precursor to sporamin was inhibited by monensin, suggesting that this step takes place in the acidic compartment, probably in the vacuole. All of the sporamin polypeptides synthesized in transformed tobacco cells were retained inside the cell and sporamin was localized in the vacuole, as judged from results of subcellular fractionation. These results indicate that sporamin is appropriately targeted to the vacuole in tobacco cells.

Amino Acid Sequence↗