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Biomedical subjects

Y Machida

Publications and source records attributed to Y Machida.

At least 19 recordsLinked to original sources

Biodegradation and distribution of water-soluble chitosan in mice.

Randomly 50% deacetylated chitin, called Chi, was examined on the biodegradability, body distribution and urinary excretion after the intraperitoneal (ip) administration to mice. These characteristics were investigated using fluorescein isothiocyanate (FITC)-labeled Chi (FTC-Chi). The in vitro biodegradability was investigated by incubation with lysozyme and murine plasma and urine. The degradation of Chi or FTC-Chi was accelerated by lysozyme, plasma and urine. The molecular weight was checked by gel-chromatography. The degradation product showed a fairly small molecular weight and contained no FTC-Chi of a large one. The body distribution and urinary excretion of FTC-Chi were investigated at 1, 14 and 24 h after the ip injection to mice. FTC-Chi moved fast to the kidney and urine, and was scarcely distributed to the liver, spleen, abdominal dropsy and plasma. Most of FTC-Chi was excreted into urine after 14 h, and the molecular weight of the excreted FTC-Chi was as small as that of the product obtained by the long in vitro incubation. Therefore, Chi is considered to be highly biodegradable and easily excreted in urine, and further it is suggested to have no problem on accumulation in the body; however, at the same time, Chi is found not to operate as a polymer support showing long retention in the body.

Acetylation

Biodisposition characteristics of N-succinyl-chitosan and glycol-chitosan in normal and tumor-bearing mice.

Two water-soluble chitosan derivatives, N-succinyl-chitosan (Suc-chi; average MW 3x10(5)) and glycol-chitosan (Gly-chi; average MW 1.5x10(5)), were examined concerning their biodisposition characteristics in order to evaluate their possible use as water-soluble drug carriers. Their body distribution and urinary excretion were investigated by i.v. administration of FITC-labeled Suc-chi (FTC-Suc-chi) and FITC-labeled Gly-chi (FTC-Gly-chi) to normal and Sarcoma 180 solid tumor-bearing mice. In normal mice, both polymers showed good retention in blood circulation; especially, FTC-Suc-chi exhibited a long half-life of 51 h, and its distribution to other tissues was very small. FTC-Gly-chi was distributed into the kidney to a relatively high extent. In tumor-bearing mice, FTC-Suc-chi and FTC-Gly-chi were eliminated faster from the blood circulation than in normal mice, that is, with half-lives of 11 and 7 h, respectively. FTC-Suc-chi was less partitioned to the tumor tissue but accumulated more easily into it compared with FTC-Gly-chi. This suggested the enhanced permeability and retention (EPR) effect of Suc-chi and explained the previous result that a water-soluble Suc-chi-mitomycin C conjugate injected intravenously exhibited a good effect against Sarcoma 180 solid tumor. FTC-Gly-chi showed greater distribution to the kidney than in normal mice. Urinary excretion studies indicated the faster excretion of both polymers in tumor-bearing mice. The molecular weight of the products excreted into urine indicated that both polymers should be pretty resistant to the hydrolytic enzyme, lysozyme. Taking toxicities into account, Suc-chi is considered to be available as a drug carrier showing long systemic retention and tumor accumulation.

Animals

[Effect of temperature on drug release and drug absorption in mixed type diclofenac sodium suppositories].

New types of diclofenac sodium suppositories known to control a drug release function for hospital preparations were developed based on a concept of the drug delivery system. Hard fat (Witepsol) used as a base of the suppository consists of a mixture of triglycerides, diglycerides and monoglycerides, and each Witepsol is characterized by its physicochemical properties. Authors disclosed that the amount of drug release measured in the commercially available diclofenac sodium suppositories decreased at a low temperature (36 degrees C). Mixed types of diclofenac sodium suppositories consisting of Witepsol W35 and Witepsol E85 as a base were also prepared and their drug release functions investigated in vitro and in vivo. The in vitro drug release properties changed with the mixing ratios of the two bases and with the temperature of the fluid tested. The amount of released diclofenac sodium increased with increases of both the ratio of Witepsol W35 in the suppository and the temperature of the test fluid. Moreover, several processes causing these phenomena were evidenced by the image analysis. The in vivo absorption of diclofenac sodium was found to be also influenced by these factors. Consequently, it is predicted that such factors as the ratio of Witepsol W35 in the suppository and the temperature will influence the drug absorption and the pharmacological effect of diclofenac sodium suppositories.

Administration, Rectal

Local dynamic changes of the cervix associated with incompetent cervix before and after Shirodkar's operation.

A 31-year-old woman, gravida 2 para 1, visited our clinic for routine follow-up at 20 weeks' gestation. Although she had no abdominal pain or pressure, digital vaginal examination revealed dilatation of the internal cervical os of 1.5 cm, and transvaginal sonography demonstrated dynamic changes in the shape of the cervical canal. The patient underwent Shirodkar's operation. Routine postoperative assessment of the cervix with transvaginal sonography showed dynamic dilatation of the upper cervix (above the cerclage), which was accompanied by a sensation of pelvic pressure but no apparent uterine contractions. A healthy male infant weighing 2,980 g was delivered at 38 weeks' gestation.

Adult

The expression pattern of the gene for NPK1 protein kinase related to mitogen-activated protein kinase kinase kinase (MAPKKK) in a tobacco plant: correlation with cell proliferation.

Mitogen-activated protein kinase (MAPK) cascades consist of members of three families of protein kinases: the MAPK family, the MAPK kinase family, and the MAPK kinase kinase (MAPKKK) family. Some of these cascades have been shown to play central roles in the transmission of signals that control various cellular processes including cell proliferation. Protein kinase NPK1 is a structural and functional tobacco homologue of MAPKKK, but its physiological function is yet unknown. In the present study, we have investigated sites of expression of the NPK1 gene in a tobacco plant and developmental and physiological controls of this expression. After germination, expression of NPK1 was first detected in tips of a radicle and cotyledons, then in shoot and root apical meristems, surrounding tissues of the apical meristems, primordia of lateral roots, and young developing organs. No expression was, however, observed in mature organs. Incubation of discs from mature leaves of tobacco with both auxin and cytokinin induced NPK1 expression before the division of cells. It was also induced at early stages of the development of primordia of lateral roots and adventitious roots. Thus, NPK1 expression appears to be tightly correlated with cell division or division competence. Even when an inhibitor of DNA synthesis was added during the germination or the induction of lateral roots by auxin, NPK1 expression was detected. These results showed that the NPK1 expression precedes DNA replication. We propose that NPK1 participates in a process involving the division of plant cells.

Base Sequence

A novel cis-acting element in promoters of plant B-type cyclin genes activates M phase-specific transcription.

Plant B-type cyclin genes are expressed late in the G2 and M phases of the cell cycle. Previously, we showed that the promoter of a Catharanthus roseus B-type cyclin, CYM, could direct M phase-specific transcription of a beta-glucuronidase reporter gene in synchronously dividing BY2 tobacco cells. In this study, we determined the regulatory elements contained within the CYM promoter by using a luciferase reporter gene. Mutational analysis showed that a 9-bp element is essential for M phase-specific promoter activity in synchronized BY2 cells. The CYM promoter contains three other sequences similar to this element. A gain-of-function assay demonstrated that when fused to a heterologous promoter, these elements are sufficient for M phase-specific expression; therefore, we named these elements M-specific activators (MSAs). We found MSA-like sequences in B-type cyclin promoters from tobacco, soybean, and Arabidopsis as well as in the promoters of two M phase-specific genes, NACK1 and NACK2, which encode tobacco kinesin-like proteins. Thus, MSA may be a common cis-acting promoter element that controls M phase-specific expression of cell cycle-related genes in plants.

Base Sequence

Periodic discharge of adrenocorticotropin and vasopressin associated with focal glomerulosclerosis.

We report the first case of the syndrome of periodic adrenocorticotropin (ACTH) and vasopressin (ADH) discharge associated with focal glomerulosclerosis. Approximately 30 cases of this syndrome have so far been reported in Japan, but no cases associated with renal dysfunction have yet been reported. The patient, a 10-year-old Japanese boy, was referred to our hospital because of recurrent attacks of vomiting. He was diagnosed as having this syndrome from clinical and laboratory findings. While various drugs were tried to manage his vomiting attacks, only valproic acid appeared to be effective in reducing the frequency of the attacks. Chronic nephritis was manifested when the patient was 12 years old, which required treatment with continuous ambulatory peritoneal dialysis. Valproic acid was proved to be effective in reducing the number of attacks over 4 months.

Adrenocorticotropic Hormone

In vivo properties of the conjugates of mitomycin C with estradiol benzoate and estradiol: pharmacokinetics and antitumor characteristics against P388 leukemia and sarcoma 180.

Conjugates of mitomycin C (MMC) with estradiol benzoate and estradiol via glutaric acid, abbreviated to EB-glu-MMC and E-glu-MMC, respectively, as previously reported, were examined concerning their pharmacokinetic behaviors and antitumor effects against two kinds of general and popular tumors, P388 leukemia and Sarcoma 180. EB-glu-MMC and E-glu-MMC were dissolved in propylene glycol. Their solution was administered intraperitoneally to rats and mice in order to examine their plasma concentration-time profiles and antitumor characteristics, respectively. After the administration of EB-glu-MMC, EB-glu-MMC was detected slightly in blood only in the initial stage, while E-glu-MMC and MMC were observed there for a prolonged period. In the administration of E-glu-MMC, a similar phenomenon was observed but the drug retention effect seemed lower than that in EB-glu-MMC. In the antitumor test against P388 leukemia, E-glu-MMC exhibited a better effect than EB-glu-MMC; however, neither conjugate surpassed the effect of MMC. The toxic side effect was improved in each conjugate. As to the growth inhibition against Sarcoma 180, EB-glu-MMC and E-glu-MMC produced good effect and improved the toxic side effect. Especially, in the administration of EB-glu-MMC at the dose of 30 mg eq MMC/kg, a decrease in tumor volume was observed in the latter stage. EB-glu-MMC and E-glu-MMC were demonstrated to produce prolonged retention, to enter the systemic circulation to a fair extent, and to exhibit a good effect against the general solid tumor, Sarcoma 180, in vivo.

Animals

[Preparation and utility of glibenclamide suppository for hospital use].

Glibenclamide (GC) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). Since GC is usually taken for a long period, side effects and noncompliance are among the problems. In order to solve those problems, we prepared GC suppositories and examined their usefulness. Suppositories containing 4, 20, and 40 mg of GC were prepared and examined for drug release, drug absorption and blood glucose levels after the rectal administration of suppositories in rabbits. In the release test, GC suppositories released the drug continuously for 6 hours. The areas under the drug release time curve (ADT) of 20 and 40 mg GC suppositories were 3.5 and 6.2 times of 4 mg GC suppositories respectively. The plasma concentrations after administration of 4 and 20 mg GC suppositories showed about the same profiles for 6 hours. After administration of 40 mg GC suppositories, the maximum plasma concentration (Cmax) was observed at 2 hours. All the GC suppositories showed lower blood glucose levels compared with the control. The remainder of the area under the blood glucose concentration time curve between the control (RAUC) in the case of 40 mg GC suppository was 1.3 times larger than that of the 4 mg GC suppository. The GC suppositories sufficiently lowered the blood glucose levels. These results suggest that the GC suppositories should be useful in the hospital preparation for the treatment of NIDDM patients.

Animals

Doppler echocardiographic method to determine early and late diastolic filling volume separately. Validation and relationship between filling velocity and volume.

We devised a pulsed Doppler echocardiographic method of separately calculating early diastolic filling volume (EDFV) and late diastolic filling volume during atrial contraction (LDFV) and observed a relationship between diastolic filling volume and velocity in thirty patients with coronary artery disease. By analysing the transmitral flow velocity curve and mitral valve motion, EDFV and LDFV were measured on the basis of the equality of left ventricular inflow and outflow volumes. The Doppler-determined EDFV and LDFV correlated well with those obtained from the left ventricular filling curve produced by left ventriculography. Angiographic EDFV and LDFV were measured from the time (t)-volume (V) curve, using the t-dV/dt curve to define early and late diastolic phases. A good correlation was found between Doppler and angiographic EDFV (y = -3.0 + 1.0 x, r = 0.98, p = 0.0001, n = 20), Doppler and angiographic LDFV (y = 1.6 + 1.0 x, r = 0.86, p = 0.0001), and also between Doppler and angiographic EDFV/LDFV (y = 0.05 + 0.9 x, r = 0.93, p = 0.0001). EDFV and the peak early diastolic filling velocity were significantly correlated (E velocity; y = 25 + 0.51 x, r = 0.48, p = 0.0068), while LDFV and the peak late diastolic filling velocity during atrial contraction (A velocity) were not. Our results validate the method of calculating EDFV and LDFV separately and suggest that early diastole in the left ventricle has flow volume dependency, but that the late diastole filling velocity during atrial contraction may be regulated by other factors such as increased left atrial contraction.

Adult

Caries development in children from 1.5 to 3 years of age: a longitudinal study.

This study was designed as a prospective clinical caries prevalence study starting with children at 1.5 years of age. The subjects were 374 children who were born between 1989 and 1991. All subjects visited a public health center in Kunitachi-city, Tokyo, at 1.5 years, 2 years, and 3 years of age. All the children and parents have followed preventive dental care guidance. Dental caries were always examined by one of the authors. The caries prevalences at 1.5 years, 2 years, and 3 years of age were 6.1%, 14.7%, and 31.8%, respectively. The mean dft at 3 years of age in children who developed caries before 2 years of age was significantly greater than that in children caries free at 2 years of age. The findings from the current study showed that children who develop caries before 2 years of age are at greater risk for dental caries.

Chi-Square Distribution

Dentin bridge formation following direct pulp capping in dog's.

The effectiveness of two different calcium hydroxide pastes; "Calvital and "Dycal", for the direct pulp capping in dog's permanent teeth with incompletely formed roots were evaluated in this study. Forty-eight vital permanent premolar teeth with incompletely formed apices were obtained from 6 dog's (6 months of age). Exposure sites on contralateral pairs of teeth were capped with either "Calvital" or "Dycal". Then intravenous injections of tetracycline were administered to the dogs at various intervals. Animals were sacrificed at 56 days. The teeth were fixed, undecalcified ground sectioned, observed by microradiography, and evaluated by ultraviolet light. In cases treated with "Calvital", a fluorescent line resulting from tetracycline administration 7 days after experimental procedures was seen in the newly formed dentin bridge. In cases treated with "Dycal", a fluorescent line resulting from tetracycline administration 14 days after experimental procedures was seen in the newly formed dentin bridge. Continued physiological root formation was observed well in all teeth. This experiment may explain why some "Dycal" failures occur in the earlier postoperative periods; serves as a stimulus potential for a hardening reaction.

Animals

A longitudinal study of the development of crowded dental arch.

It is important to determine both where and when in the process of dental arch development crowding occurs. The authors investigated 81 children (boys/37, girls/44). These children were developing permanent dentition without early loss of deciduous or permanent teeth, which is considered to be one of the causes of malocclusion. Impressions were taken from subjects who had normal, spaced, or crowded permanent dental arch, and longitudinal casts made every two months from three years of age. In both the maxilla and the mandible, the transition to the crowded condition most often occurred (maxillary: 84.6%, mandibular: 64.5%) at the time of eruption. Crowding condition was also caused by the eruption of other teeth; however, this was rare. The maxillary and mandibular crowding mostly occurred (maxillary: 69.2%, mandibular: 77.4%) in the anterior teeth. It was seldom observed in the premolar and first molar regions.

Child

A longitudinal study of the growth and development of the dental arch width from childhood to adolescence in Japanese.

The purpose of this study was to evaluate the longitudinal changes in arch width from childhood to adolescence. The subjects were 28 persons (13 males and 15 females) with untreated normal occlusion. Dental casts were taken at bimonthly intervals from childhood to adolescence. These materials were measured; the changes in the dental arch were compared on the basis of the status of the tooth emergence of certain permanent teeth and also on the chronological age from 3 years to 20 years of age. In the maxilla and mandibula, the width between the deciduous canines, the width between the first deciduous molars, and the width between the second deciduous molars were nearly stable or slightly increased until 6 years of age. After that, all of the deciduous tooth widths gradually increased, especially in the width between the deciduous canine at the emergence of the permanent incisors. The width between the canines decreased until 13 years of age in the maxilla and until 15 years of age in the mandibula. After that, the width between the canines were nearly stable. Until 1 year after emergence, the width between the canines decreased, in particular during the transition to the canines, based on dental age observation. The maxillary first premolar width decreased until 6 months after emergence, based on dental age observation. Thereafter, the width between the maxillary first premolars showed no clear change. The width between the mandibular first premolars, the width between the maxillary second premolars, and the width between the mandibular second premolars increased until about 2-3 years after emergence, but they showed no clear changes thereafter. The width between the maxillary first molars gradually increased until 15 years of age; there was no clear change thereafter. The width between the mandibular first molars was nearly stable throughout the observation period. The width between the maxillary second molars decreased until 2 years after emergence; no clear change was observed thereafter. The width between the mandibular second molars was unstable until after about 2-3 years after emergence and then became nearly stable.

Adolescent

Rapid and sensitive determination of amprolium in chicken plasma by high-performance liquid chromatography with post-column reaction.

A rapid, sensitive and reproducible reversed-phase HPLC assay was developed for the determination of amprolium (APL) in chicken plasma. Protein in plasma sample was precipitated with 0.33 M perchloric acid and supernatant solution was injected into the HPLC system. Following the chromatographic separation of APL and the beclotiamine (I.S.) on a C18 column, the derivatives of APL and I.S. were formed by post-column reaction and detected by fluorescence detection (excitation at 400 nm, emission at 460 nm). The method showed excellent precision, accuracy and speed with a detection limit of 2 ng/ml. The intra- and inter-assay variance of this method were less than 11.2%. This method has been successfully applied to plasma determinations after oral administration of APL to chicken.

Amprolium

Chromatography of crotamiton and its application to the determination of active ingredients in ointments.

Crotamiton, which is a mixture of cis and trans isomers, was investigated by several separation techniques. One of the HPLC modes, in which crotamiton eluted as a single peak, was selected for the determination of five active ingredients (crotamiton, prednisolone, glycyrrhetinic acid, dibucaine and chlorhexidine hydrochloride) in an ointment. The simultaneous determination was performed using isocratic reversed-phase mode within 20 min by employing an octyl (C8) column and a mobile phase containing sodium dodecyl sulfate (SDS) and 2-propanol. The method was successfully applied to quality control and stability testing of the ointment.

Antipruritics

Possible involvement of differential splicing in regulation of the activity of Arabidopsis ANP1 that is related to mitogen-activated protein kinase kinase kinases (MAPKKKs).

Three types of Arabidopsis cDNA (cANP1, cANP2 and cANP3) have been isolated that encode putative protein kinases, designated ANP1, ANP2 and ANP3. These kinases exhibit a high degree of homology to NPK1, a tobacco protein that is a member of the family of mitogen-activated protein kinase kinase kinases (MAPKKKs), which appears to function in the proliferation of tobacco cells. The predicted amino acid sequences of the kinase domains in the amino-terminal halves of the ANPs were more than 80% identical to that of NPK1, while the kinase-unrelated regions in the carboxy-terminal halves exhibited relatively low homology. Two species of cANP1 were identified, ANP1L cDNA (cANP1L) and ANP1S cDNA (cANP1S), which were derived from a single ANP1 gene: the former had an intron-like sequence in the coding region for the kinase-unrelated region, while the latter did not include such an intron-like sequence. cANP1L encoded a putative protein with both kinase and kinase-unrelated domains, resembling NPK1, whereas cANP1S encoded only the amino-terminal kinase domain because the intron-like sequence was absent, with resulting elimination of most of the kinase-unrelated region. Genetic analysis with mutant yeast cells showed that over-expression of cANP1L or of cANP1S activated the mating pheromone-responsive signal pathway which is mediated by a MAP kinase cascade. Moreover, the extent of such activation by cANP1S was greater than that by cANP1L. These results predict that differential splicing of the intron-like sequence in the ANP1 transcript might be at least one of the molecular mechanisms involved in the generation of active ANP1 protein kinase.

Alternative Splicing

[Characteristic situation on prevention of nosocomial infection in the hospital for the severely multi-disabled--experiences in care and treatment of 4 kinds of viral hepatitis].

We experienced Hepatitis A, B, C and fulminant hepatitis due to Herpes simplex virus type 1 (HSV-1) in our hospital for the severely multi-disabled (SMD) who had both severe motor and intellectual disabilities, and some of whom might be further complicated by blindness and/or deafness. In this hospital, 100 SMDs are hospitalized. Case 1: The disabled, 25 year old male, was transmitted Hepatitis A from a nurse. Case 2: The disabled, 60 year old female carrier of Hepatitis B virus (HBV) who has been cared for more than 10 years. Case 3: The disabled, 46 year old male carrier of Hepatitis C virus (HCV) (RNA type 3), has been cared for more than 4 years. Case 4: The disabled, 39 year old male, had a fever of 39 degrees C for 9 days and suddenly died. He was diagnosed as fulminant hepatitis due to HSV-1 by necropsy. The hospitals for SMD are characteristic in prevention of nosocomial infections; 1) The disabled infected is not aware of the fact that he or she is the source of infection and that the other disabled living with him or her are in risk of infection, because of their severe mental condition. 2) All of the disabled need complete or incomplete helps for activities of daily life (ADL), so that the disabled who is the carrier of some pathogen constantly gives risk of infection to staffs, including medical staffs (doctor, nurse and therapist), psychologist and helpers by bloody secretion from wounds, saliva, urine, feces as well as menstrual blood. 3) If a carrier of some pathogen is hospitalized, the staffs should serve under risk of infection involving blood-mediated infectious disease for many years, because SMDs are permitted lifelong stay in the hospitals for SMD, which also play a role of care house or institution, by public expense in Japan. In case of an outbreak of Hepatitis A, nosocomial infection ended in the original case (a nurse), another nurse and a case of the disabled by general treatment and care against communicable diseases of the digestive organs. In care of HBV and HCV carriers, an ordinary program to prevent nosocomial infection has been practiced in our hospital more strictly than in conventional hospital. HBV vaccine is injected to staffs caring the HB carriers who are negative on HBs antibody. Thus, during more than 10 years of care of HBV carrier and more than 4 years of care of HCV carrier, nosocomial infection has never been experienced clinically as well as serologically in our hospital. However, we have often been faced by difficulty to guarantee QOL (quality of life) of the carriers, because carrier states of HBV or HCV have been long-lasting and they have been occasionally and inevitably separated physically and/or psychologically in order to prevent nosocomial infection. In case 4, it was suspected that previously latently infected HSV-1 would be activated by another viral infection which had elicited fever for 9 days before death. The patient had neither history nor sign or symptom of immunodeficiency and had never been given drugs known as to be immunosuppressive as side effect.

Adult