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Biomedical subjects

I Nishimura

Publications and source records attributed to I Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed1996

Uptake and intracellular activity of NM394, a new quinolone, in human polymorphonuclear leukocytes.

The uptake of NM394, a new quinolone, by and its subsequent elution from human polymorphonuclear leukocytes were studied and compared with those of ofloxacin and ciprofloxacin. The kinetics of the uptake of NM394 was similar to that of ciprofloxacin. The maximum intracellular-to-extracellular concentration ratio was 12.3, compared with 8.6 for ciprofloxacin and 4.9 for ofloxacin at the extracellular concentration of 20 micrograms/ml. The elution of NM394 from human polymorphonuclear leukocytes occurs relatively slowly; 5 min after the removal of extracellular NM394, nearly 100% still remained in polymorphonuclear leukocytes, compared with ofloxacin, which was so rapidly eluted that only 12% remained. The uptake of NM394 was significantly decreased at 4 degrees C and by the presence of NaCN but was not affected by the presence of L-glycine, L-leucine, L-serine, adenosine, or NaF. NM394 showed intracellular activity at a concentration of 0.1 microgram/ml that significantly reduced the number of phagocytosed Pseudomonas aeruginosa cells with 2 h of incubation. These results suggest that uptake of NM394 by human polymorphonuclear leukocytes occurs via an active transport system differing from that of ofloxacin, whose uptake is affected by the presence of L-glycine and L-leucine, and that once accumulated, NM394 remains intracellularly active and participates in protection against bacterial infection.

Amino Acids↗
PubMed1996

Therapeutic effect of the quinolone prodrug prulifloxacin against experimental urinary tract infections in mice.

The in vitro antibacterial activity of prulifloxacin (CAS 123447-62-1, NM441), a new quinoline prodrug, against clinical isolates from urinary tract infections was investigated. In addition, it was compared with ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4), ciprofloxacin urinary tract infections in mice, as well as its pharmacokinetics. 1. The antibacterial activity of NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]quinoline-3-carboxylic acid), an active metabolite of prulifloxacin, against gram-positive clinical isolates was inferior to that of levofloxacin and tosufloxacin, and equal to that of ofloxacin and ciprofloxacin. Against gram-negative clinical isolates, the activity of NM394 was superior to that of the reference drugs. 2. The therapeutic effect of prulifloxacin on experimental urinary tract infection with Escherichia coli in mice was equal to that of tosufloxacin and ciprofloxacin and superior to that of ofloxacin and levofloxacin. Its therapeutic effect on Pseudomonas aeruginosa infection was equal to that of tosufloxacin and ciprofloxacin, and superior to that of ofloxacin. Against urinary tract infection with olfloxacin-resistant Enterobacter cloacae, prulifloxacin was the most effective of all the drugs tested. 3. The maximal serum concentration of prulifloxacin was slightly higher than that of ciprofloxacin, and the area under the curve (AUC) for prulifloxacin was 1/4 that of ofloxacin, levofloxacin and tosufloxacin. The maximal concentration and AUC of prulifloxacin in lung and kidney were slightly higher than the corresponding values for ciprofloxacin but only 1/2 to 1/4 of the values for ofloxacin, levofloxacin and tosufloxacin. In conclusion, prulifloxacin (NM394) showed potent antibacterial activity against clinical isolates and potent therapeutic efficacy against experimental infection in spite of its lower AUCs compared with the reference drugs. These findings suggest that prulifloxacin may be a useful drug in the treatment of urinary tract infections.

Animals↗
PubMed1995

Modulated expression of type X collagen in Meckel's cartilage with different developmental fates.

Mammalian Meckel's cartilage undergoes regionally diverse histodifferentiation: the caudal end of Meckel's cartilage extends to the developing ear and gives rise to malleus and incus through endochondral ossification while its major distal region differentiates into sphenomandibular ligament and the anterior ligament of the malleus tympanic plate through fibrous transformation. Since the entire Meckel's cartilage develops up to chondrocyte hypertrophy, the regional extracellular matrix components in the hypertrophic Meckel's cartilage may differ in association with the diverse developmental fates. In this project, the expressions of cartilage collagens were investigated in developing rat Meckel's cartilage and particular interest was given to type X collagen. A cDNA, HP114, encoding the NC1 domain of rat alpha 1(X) collagen was cloned, and a synthetic peptide based on the sequence deduced from HP114 was used to generate a monospecific antibody. In situ hybridization of newborn rat condylar and angular cartilages undergoing endochondral ossification showed restricted labeling with the alpha 1(X) collagen probe in the hypertrophic chondrocyte layer. In contrast, the alpha 1(X) collagen probe totally failed to label the major distal portion of Meckel's cartilage even in the hypertrophic cartilage zone. Immunohistochemistry using the anti-type X collagen monospecific antibody consistently failed to recognize the epitope in the corresponding portion of Meckel's cartilage throughout the experimental periods of gestational Day 17, newborn, and Postnatal Day 7, while the strictly localized positive staining was found in the posterior part of Meckel's cartilage which gave rise to malleus and incus. Since major cartilage collagens type II and type IX were found to be present throughout Meckel's cartilage, we postulate that the regulatory molecular mechanism of type X collagen expression may be closely associated with the developmental fates of fibrous transformation and endochondral ossification in mammalian Meckel's cartilage.

Amino Acid Sequence↗
PubMed1995

Chronic inhalation exposure and phospholipids in lung surfactant and tissue.

Golden hamsters were exposed to 2 mg/m3 coal fly ash for 180 days. The exposure raised the phospholipid level in the tissue, whereas no such elevation was observed in the surfactant. Increased phospholipid in the tissue is thought to reflect the accumulated surfactant in type II cells. Fatty acid composition analysis indicated an increase of arachidonic acid in the surfactant and increases of palmitic acid and arachidonic acid in the tissue. In conclusion, the pulmonary surfactant high in fluidity was stored in the lung tissue more than control, and the surfactant was secreted into the alveoli normally.

Administration, Inhalation↗
PubMed1995

Animal model for evaluating the effect of systemic estrogen deficiency on residual ridge resorption.

The rate of resorption of residual ridges after tooth extraction varies among subjects. Despite many human studies, the etiologic factors of severe forms of resorption of residual ridges are unknown and probably multifactorial. To facilitate investigations of resorption of residual ridges, it is preferable to use an animal model with a dentoalveolar component similar to that of human beings. This study developed a rapid, nonhuman primate model in which one could measure resorption of residual ridges at the most critical period, with the least amount of time, minimal operation, and the least interference with normal nutrition. Three female Macaca fascicularis monkeys, 7 to 9 years old, were selected for simple extraction of four maxillary incisors, four mandibular incisors, and two mandibular canines. Lateral cephalographs were taken at weeks 0, 1, 2 to 3, 5 to 6, 8 to 9, 11 to 12, and 26 to 28 after extraction with a newly constructed cephalostat that allowed easy reproducibility of animal placement in the prone position. Height and area measurements were made of maxillary and mandibular anterior residual ridges in the superimposed cephalographs. Sequential mean bone loss data produced bone loss curves similar to those observed in humans. One animal underwent ovariectomy. The plasma levels of both estrogen and progesterone decreased over 25 days and stayed below the detection limits thereafter. Tooth extraction was done 4 weeks after the ovariectomy and the bone resorption pattern was able to be observed longitudinally with the newly established monkey cephalostat. The results indicated that Macaca fascicularis need not be sacrificed when used in longitudinal studies of resorption of residual ridges in a relatively short period of experimental time. This model can provide an excellent opportunity to investigate a causal relationship between the rate of resorption of residual ridges and predisposing systemic factors such as estrogen deficiency.

Alveolar Bone Loss↗
PubMed1995

Pilot study of the heterogeneous patterns of masticatory muscle coordination in nonpatient population.

This pilot study characterized coordination patterns of the muscles of mastication during voluntary chewing in a nonclinical population. Dental students (n = 177) who did not exhibit symptoms of temporomandibular disorder were screened by a comprehensive muscle and temporomandibular joint palpation examination. A group of 44 students was identified on the basis of the presence of four or more tender points indicated during palpation. This group was further subgrouped by the absence (group A-1) and presence (group A-2) of temporomandibular joint clicking. Five volunteers from groups A-1 and A-2 and five volunteers without any palpation tenderness and joint clicking (control group) were examined by simultaneous recordings of electromyography of bilateral masseter and posterior one third of the temporalis muscles and by mandibular kinesiography. The electromyographic coordination pattern for the control group demonstrated predominantly working masseter muscle activity. This "predominant working masseter" pattern was not observed in groups A-1 or A-2. Additional analyses of the recordings indicated that a hypoactive tendency of the working side masseter muscle particularly outlasting the tooth contact was present in group A-1, whereas significant hyperactivity of the posterior one third of the temporalis was present in group A-2. The data suggested that an asymptomatic nonpatient population may be functionally diverse.

Adult↗
PubMed1995

Temporal and spatial expressions of type XII collagen in the remodeling periodontal ligament during experimental tooth movement.

This study tested the hypothesis that the remodeling processes of adult periodontal ligament (PDL) reiterate the cellular and molecular events that occur sequentially during development. Type XII collagen has been implicated in the three-dimensional organization of the PDL extracellular matrix, and its expression has been restricted to the terminally differentiated stages. This study focused on the examination of the temporal and spatial expression of type XII collagen during experimental PDL remodeling in the rat. The temporal expressions of types I and XII collagen mRNAs were examined by RNA transfer blot and RNase protection assays, respectively, and were found to be relatively stable in the control group throughout the experimental period. In the tooth movement group, the expression of type I collagen increased at 72 hours and sustained the high level of expression at one week, while an increase in the expression of type XII collagen was first noted at the one-week period. The temporal activation of types I and XII collagen expression in the remodeling occurred in a pattern similar to that found during the development of the PDL. The spatial expression of type XII collagen mRNA was examined by in situ hybridization in the one-week-tooth-movement specimens. Labeled cells, which were more evident in the tension side, typically exhibited a spindle shape and were surrounded by the mature PDL matrix. Our data suggest that the type XII collagen expression may be closely associated with the functional regeneration of the PDL.

Animals↗
PubMed1995

A new animal model for molecular biological analysis of the implant-tissue interface: spatial expression of type XII collagen mRNA around a titanium oral implant.

The objective of this study was to develop an animal model to investigate the molecular biological healing events at the tissue-implant surface occurring in the alveolar bone. Newly designed mini-titanium implants (2mm in length and 1 mm in diameter) were placed in the maxilla of retired-breeder male Sprague-Dawley rats. The implants were placed in freshly drilled holes in the maxillary bone, or in an area close to the roots of the maxillary first molar. The healing phase in each group was studied histologically at 28 days and at 56 days by means of non-decalcified polymethylmethacrylate-embedded sections and decalcified paraffin-embedded sections. Initial osseointegration was observed at 28 days, with mature osseointegration seen at 56 days. Specimens with implants placed immediately adjacent to the root showed fibrous healing at the implant-tissue surface. As a pilot study, the expression of type XII collagen, a molecular marker specific to the mature periodontal ligament (PDL), was studied by in situ hybridization. There was an absence of type XII expression close to the implant surface, whereas there was a zone of type XII collagen expression closest to the bony wall. Our preliminary results indicated a significant molecular variation in the fibrous-implant interface. This model will be useful in studies of the wound-healing patterns of the extracellular matrix around oral implants specifically relevant to alveolar bone osseointegration and potential formation of PDL.

Alveolar Process↗
PubMed1994

Blood compatibility of sputter-deposited alumina films.

The surface modification of metals by the application of blood compatible ceramics is one approach to developing durable and blood-compatible materials. The blood compatibility of sputter-deposited alumina films was investigated in vitro. The alumina films were prepared by reactive sputtering and conventional sputtering. Diffractometer studies of the alumina films indicate that the sputter-deposited alumina films have amorphous structures. Electron spectroscopy chemical analysis studies of the alumina films indicate that the sputter-deposited alumina films are nonstoichiometric (O/A1 ratio of 1.15-1.66). We examined the platelet reaction to the alumina films and the intrinsic coagulation factor XII activation by the alumina films. Medical grade segmented polyurethane was also tested. The alumina films experienced an adhesion of about 50% fewer platelets than the segmented polyurethane. Also, fewer platelet morphologic changes were observed on the alumina films than on the segmented polyurethane. Factor XII activation was less on the alumina films than on the segmented polyurethane. Surface modification by the sputter-deposited alumina films is promising for developing blood-compatible and durable materials.

Aluminum Oxide↗
PubMed1994

Altered bone remodeling pattern of the residual ridge in ovariectomized rats.

This study investigated the effect of estrogen deficiency on residual ridge remodeling after tooth extraction. Ovariectomy was performed on female Sprague-Dawley rats, and the plasma levels of estrogen and progesterone were monitored. The maxillary molars of the ovariectomized and control rats were extracted and the remodeling residual ridge tissues were harvested at 2, 4, and 8 weeks postextraction. The specimens were examined at the mesiodistal center point of the residual ridge by use of light and scanning electron microscopy. The surface of the residual ridge of the control animals showed a number of osteoclastic lacunae indicating bone resorption activity. In the ovariectomized animals, the surface of the residual alveolar bone was partially covered by a distinct calcified tissue. This tissue contained large cells and a mesh-like structure of thin calcified extracellular matrix consistent with the tissue characteristics of chondroid bone. The chondroid bone-like calcified tissue was found only in the ovariectomized animals throughout the experiment period. This study's data suggest that a systemic condition such as estrogen deficiency due to ovariectomy may alter the phenotypic expression of cells associated with the residual ridge and result in less osteoclastic activity and a different type of calcified tissue.

Alveolar Process↗
PubMed1993

Altered cartilage phenotype expressed during intramembranous bone formation.

The sequential phenotypic expression occurring during intramembranous bone formation was investigated using the tooth extraction socket created in rat alveolar bone in vivo. The differential expression of bone extracellular matrix genes, such as collagen I and osteocalcin, was confirmed by RNA transfer blot analysis and in situ hybridization during the active healing period of the bony socket. To clarify the possible involvement of the chondrogenic phenotype during the process of intramembranous bone formation, the expression of cartilage collagen II and IX was further examined in this model. It was found that both alpha 1(II) and alpha 1(IX) mRNAs were present, but the alpha 1(IX) mRNA was a transcript from the downstream start site/promoter, which is a different site in the alpha 1(IX) gene from that used in hyaline cartilage. In situ hybridization indicated that the alpha 1(IX) message was expressed by cells associated with bone matrix in the early formation stage. This finding led to the investigation of type IX collagen expression by osteogenic cells isolated from newborn rat calvariae, in which only the truncated form of alpha 1(IX) mRNA was indicated by RNA transfer analysis. The expression of collagen II and a truncated form of collagen IX may represent an early phenotypic feature of osteoblast differentiation.

Animals↗
PubMed1993

Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria.

Osteogenetic protein-1 (OP-1), a member of the TGF-beta superfamily, induces endochondrial bone formation at subcutaneous sites in vivo and stimulates osteoblastic phenotypic expression in vitro. Primary cultures of newborn rat calvarial cells contain a spectrum of osteogenic phenotypes ranging from undifferentiated mesenchymal osteoprogenitor cells to parathyroid hormone (PTH)-responsive osteoblasts. We examined whether treatment of this cell population with recombinant human osteogenic protein-1 could induce chondrogenesis in vitro. Markers of chondroblastic versus osteoblastic differentiation included alcian blue staining at pH 1, alkaline phosphatase-specific activity, osteocalcin radioimmunoassay, and expression of collagen mRNAs. 6 d of treatment (culture days 1-7) with 4-100 ng OP-1/ml caused dose-dependent increases in alcian blue staining intensity and alkaline phosphatase activity (4.7- and 3.4-fold, respectively, at 40 ng/ml), while osteocalcin production decreased twofold. Clusters of round, refractile, alcian blue-stained cells appeared by day 3, increased in number until day 7, and then became hypertrophic and gradually became less distinct. Histochemically, the day 7 clusters were associated with high alkaline phosphatase activity and became mineralized. mRNA transcripts for collagen types II and IX were increased by OP-1, peaking at day 4, while type X collagen mRNA was detectable only on day 7 in OP-1-treated cultures. Delay of OP-1 exposure until confluence (day 7) amplifies expression of the normal osteoblastic phenotype and accelerates its developmental maturation. In contrast, early OP-1 treatment commencing on day 1 strongly amplifies chondroblastic differentiation. In the same protocol, TGF-beta 1 alone at 0.01-40 ng/ml fails to induce any hypertrophic chondrocytes, and in combination with OP-1, TGF-beta 1 blocks OP-1-dependent chondroinduction. OP-1 is believed to act on a subpopulation of primitive osteoprogenitor cells to induce endochondrial ossification, but does not appear to reverse committed osteoblasts to the chondrocyte phenotype.

Alkaline Phosphatase↗
PubMed1993

Lung free cells following short-term inhalation of coal fly ash particles in golden hamsters.

Male golden hamsters were exposed to coal fly ash (FA) at the concentration of 2 or 5 mg/m3 for 10 days (20 hr/day, Experiment 1) or 5 mg/m3 for 4 weeks (10 hr/day, 7 days/week) and maintained in clean air condition for subsequent 4 weeks (Experiment 2) to investigate the effect on the induced changes of lung free cells. Free cells were collected by lung lavage in Exp. 1 and histologically examined in lung sections in Exp.2. In Exp. 1 the number of alveolar macrophages (AMs) increased in a dose-dependent manner. In Exp. 2 AMs increased till at 2 weeks of exposure, while the subsequent increase did not occur. The ratio of particle-laden AMs increased in a dose- and time-dependent manner in each exposed group. Particle number ingested in AMs tended to increase with exposure time. In the recovery period in Exp. 2 the ratio of particle-laden AMs reduced from about 80 to 20% at the 1st week after the cessation of exposure and remained at the similar level to the termination of the experiment. On the other hand decrease in the number of total AMs was slight in the recovery period. These results suggest that the pool size of AMs is mainly dependent on the inhaled dust concentrations and some of particle-laden AMs remain in alveoli for a long time. The number of polymorphonuclear leukocytes (PMNs) also increased after inhalation of FA particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1993

Dust inhalation system for small laboratory animals.

In order to stabilize the dust concentration for animal inhalation studies, two feedback systems were introduced. Dusts generated were passed through two cyclone separators and stored first in a storage chamber. Then they were aspirated into an ejector by compressed carrier air, mixed with filtered room air in a mixing box, and introduced into an exposure chamber. The first feedback system was for dust generation. Dusts were reaerosolized by on-off control using the output signals from a light-scattering dust detector connected to a storage chamber. The second system was for the control of compressed carrier air flow into an ejector. Compressed air flow was automatically regulated by a PID-controller in combination with a mass flow controller. The PID-controller processed continuous signals from another dust detector connected to an exposure chamber and fed control signals to a mass flow controller for regulation of the compressed air flow. This automatic control system could not only reduce hunchings of dust concentration following on-off control of a dust generator but also reduce overshooting of dust concentration in the exposure chamber following the detachment and dispersion of dusts adhering to the inner walls of the dust-supplying route. The system could also maintain a desired dust concentration in the exposure chamber for up to 180 days (20 hr/day, 7 days/week). In addition, this system could simultaneously introduce different doses of dust to other exposure chambers stably while maintaining similar size distribution of the dusts if additional identical exposure units were used. These results indicate that this dust inhalation system is suitable both for long-term studies and for investigating a dose-response relationship.

Animals↗
PubMed1992

The knife-edge tendency in mandibular residual ridges in women.

To investigate the bone resorption pattern of the residual alveolar bone, the morphologic change that occurred in mandibles was analyzed with standardized lateral cephalographs of 30 edentulous patients (15 women and 15 men). The longitudinal morphologic changes were measured at the sagittal sections of the mandibular bony contour at the symphysis area on superimposed cephalographic tracings. To quantify the morphologic change, a knife-edge index (KEI) was developed as the area change divided by the height change. Geometrically, the higher value of KEI represents the greater tendency to become a narrow residual ridge. The KEI values were statistically higher in the women than in the men (p less than 0.002). In addition, the value of KEI seems to correlate with osteopenic change at the center point of the body of the second vertebra (p less than 0.01). The continuous bone resorption activity in the edentulous mandible of women seems to be emphasized at the labial and lingual surfaces of the residual alveolar bone, resulting in a knife-edge type of residual ridge.

Absorptiometry, Photon↗
PubMed1992

Effect of the substitutions in the alpha helix and the beta sheet of HLA class I molecule on allorecognition of T cells specific for HLA-B51 and HLA-Bw53.

HLA-B51 and HLA-Bw53 differ by eight amino acids on the alpha 2 domain. Of these eight amino acid substitutions, two are in the alpha helix and six are in the beta sheet. The effect of these substitutions on allorecognition of HLA-B51-specific cytotoxic T lymphocyte (CTL) clones and HLA-Bw53-specific CTL clones was investigated using chimeric antigen (Ag) between HLA-B51 and HLA-Bw53. Of 12 HLA-B51-specific CTL clones, recognition of one clone was abolished by the substitutions on the beta sheet alone, that of two clones by the substitutions on the alpha helix alone, and that of nine clones not only by the substitutions on the alpha helix but also by those on the beta sheets. On the other hand, of 17 HLA-Bw53-specific CTL clones, recognition of 10 clones was affected by the substitutions on the alpha helix alone and that of 7 clones not only by the substitutions on the alpha helix but also by those on the beta sheet. The present study demonstrated that the substitutions (residues 152 and 171) on the alpha helix critically affect recognition of HLA-B51-specific CTL clones and HLA-Bw53-specific CTL clones and that the substitutions on the beta sheet affect also recognition of the majority of HLA-B51-specific CTL clones and 40% of HLA-Bw53-specific CTL clones. These results indicate that the substitutions at the floor of the peptide binding groove affect recognition of allogeneic CTL.

Amino Acid Sequence↗