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Biomedical subjects

K Ijiri

Publications and source records attributed to K Ijiri.

At least 55 records · Page 3Linked to original sources

Primordial germ cells in the embryos of Medaka fish.

In the second International Microgravity Laboratory (IML-2) mission in 1994, four small Japanese killifish (Medaka, Oryzias latipes) made a space travel of 15 days aboard a space shuttle. These four adult Medaka fish successfully mated in space for the first time among vertebrate animals. Moreover, the eggs they laid developed normally, at least in their external appearance, hatching as fry (baby fish) in space. Fish mated and laid eggs every day during the first week. Near the end of the mission most of the eggs had a well-developed body with two pigmented eyes. In total, 43 eggs were laid (detected), out of which 8 fry hatched in space, as truly 'space-originated' babies. A further 30 fry hatched within 3 days after landing. This is the normal hatching rate, compared with the ground-based data. Among the 8 space-originated fry, four were killed for histological sections, and germ cells at the gonadal region were counted for each fry. Their numbers were in the range of the germ cells of the normal control fry (ground-kept samples). Thus, as embryos developed normally in their external appearance, inside the embryos the formation of primordial germ cells took place normally in space, and their migration to the genital ridges was not hindered by microgravity. The two of the remaining space-originated fry have grown up and been creating their offspring in the laboratory. This proved that the primordial germ cells formed in space were also normal from a functional point of view. The four space-travelled adult fish re-started mating and laying eggs on the 7th day after landing and continued to do so every day afterward. Fertilization rate and hatchability of these eggs were as high as the eggs laid by the laboratory-kept fish. This fact implies that in gametogenesis of adult fish, there are no specific stages of germ cells extremely susceptible to microgravity.

Animals↗

Indomethacin inhibition of ossification induced by direct current stimulation.

In this study, we sought to clarify the mechanism of ossification induced by direct current stimulation by analyzing changes in local blood flow and vascular permeability and by examining the involvement of chemical mediators. Changes in blood flow were studied with laser Doppler flowmetry, and vascular permeability was determined by microquantification. To examine the involvement of chemical mediators, we determined the effect on vascular permeability of histamine H1 and H2-receptor blockers and indomethacin. In addition, direct current stimulation was performed during administration of indomethacin to determine whether indomethacin inhibits electrically induced callus formation. Local blood flow remained unchanged in the control group and in the group receiving 5 microA of stimulation, but it increased in the groups receiving 10 and 50 microA. Vascular permeability increased in the 5 and 10 microA stimulation groups. This increase was not suppressed by histamine-receptor blockers, but it was suppressed by indomethacin. Two weeks of electrical stimulation without concomitant indomethacin treatment resulted in active callus formation around the needle electrode and in the vicinity of the endosteum; however, direct current stimulation during administration of indomethacin inhibited callus formation. The results suggest that these changes serve as microenvironmental factors that play an important role in the promotion of ossification and that a prostaglandin-mediated mechanism is involved in the promotion of ossification by direct current stimulation.

Animals↗

Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to aging and immobilization in rat.

No data exit for distal tibia (DT), a bone site with growth plate closure at 3 months of age and with very low trabecular bone turnover rate. The purpose of this study was to characterize the response of DT to aging and immobilization (IM) in 6 to 16.5 month-old female rats. One hundred and forty six 6 month-old Sprague-Dawley rats were divided into aging controls and right hindlimb immobilization (RHLI) groups. The right hindlimb was immobilized against the abdomen with elastic bandages. Rats were sacrificed serially from 6 to 16.5 months old at intervals of 2 to 8 weeks. The histomorphometric study was performed on areas of former epiphyseal and metaphyseal trabecular bone of DT. No changes on bone mass or architecture were found in aging controls throughout the study. There was a decrease in bone mass of the former epiphysis after 3.5 months of IM due to resorption exceeding formation. Then it reverted to the aging control level at 4 months post IM. At the former metaphyseal site, significant bone loss (-19%) was observed as early as two weeks after IM. The peak bone loss (-54%) was reached at 1.5 months after IM and plateaued thereafter. The bone loss was mainly due to the reduction of trabecular thickness although trabecular number decreased significantly after 3.5 months IM. These results suggest that both former epiphysis and metaphyseal trabecular bones in DT can quickly adapt by losing bone to immobilization.

Adaptation, Physiological↗

Remobilization partially restored the bone mass in a non-growing cancellous bone site following long term immobilization.

There is no report in the rat of the effects of remobilization (RM) in an adult bone site. The aim of this study was to determine whether complete recovery from IM-induced bone loss will occur in a non-growing bone site, the distal tibia. Seventy-five 6-month-old virgin Sprague-Dawley female rats were used in this study. Their hindlimbs were immobilized against the abdomen with bandages for 18 weeks, then remobilized for 2, 10 or 20 weeks. Distal tibial sections were analyzed in the former epiphysis, 0.3 mm proximal from the calcified cartilage, and in trabecular bone of the former metaphysis between 0.3 mm and 1.92 mm proximal to the former epiphysis. A significant bone loss occurred in both former epiphyseal and metaphyseal trabeculae at 18 weeks after IM. The lost bone was partially recovered at 10 weeks of RM, but the bone mass was still lower than in aging controls by the end of the study. The partial recovery was characterized by decreasing former epiphyseal bone porosity and thickening of former metaphyseal trabeculae with no effect on trabecular number. We concluded that both distal tibia regions only partially recovered, during 20 weeks of RM from the long time IM.

Animals↗

Parathyroid hormone therapy accelerates recovery from immobilization-induced osteopenia.

Previous reports have shown that bone mass and architecture will partially recover by remobilization (RM) in immobilization (IM)-induced osteopenia. The aim of this study was to test whether PTH can accelerate the recovery during RM from the IM-induced osteopenia. Six-month-old Sprague-Dawley female rats were divided into aging and IM groups. The right hindlimb of rats was immobilized against the abdomen by elastic bandages for 18 weeks, then groups of rats were further IM or RM for 2, 10 and 20 weeks and given 30 or 80 micrograms hPTH (1-38)/kg/d s.c. Secondary spongiosa of proximal tibial metaphyses (PTM) were studied. Immobilization reduced the trabecular area, number and thickness at the first 18 weeks post IM, then plateaued. Ten weeks of RM restored 40% trabecular bone from IM controls due to thickening of the trabeculae. However, the trabecular area was still -14% and -13% lower than that of aging controls at 10 and 20 weeks. Two weeks of 30 micrograms PTH/kg/d in IM rats restored the bone to aging control levels, two weeks of 30 micrograms PTH/kg/d in RM rats and of 80 micrograms PTH/kg/d in both RM and IM rats added extra bone. Extending the treatment to 10 and 20 weeks, the same amount of total bone was added to both IM and RM rats. These findings indicate PTH is a powerful agent that can accelerate the recovery and add extra bone to osteopenic cancellous bone in both IM and RM rats.

Analysis of Variance↗

Co-treatment of PGE2 and risedronate is better than PGE2 alone in the long-term treatment of ovariectomized-induced osteopenic rats.

We studied the effects of prostaglandin (PGE2) and risedronate (Ris) alone or in combination in 3.5-month-old intact and ovx-induced osteopenic rat skeletons to determine whether PGE2 plus Ris was more anabolic than PGE2 alone. Six mg PGE2/kg/d and 5 micrograms Ris/kg/2x/wk alone or in combination were given to sham-ovx and ovx rats for 30 or 90 days beginning 60 days post operation. Secondary spongiosa of proximal tibial metaphyses (PTM) was studied. Ovariectomy (ovx) induced dramatic bone loss. Ris increased bone mass in sham-ovx rats and prevented further bone loss in ovx rats. PGE2 treatment for 30 days added extra bone in sham-ovx rats and no further increase after 90 days treatment. Thirty days of PGE2 alone treatment restored the bone mass in ovx rats to the level of sham-ovx rats, but the restored bone was partially lost by 90 days of treatment. Co-treatment for 30 days produced the same amount of bone mass in both sham-ovx and ovx rats as PGE2 alone did. However, unlike the PGE2 alone treated, co-treatment animals continued to form more bone for 90 days. The difference in tissue-level histomorphometry between co-treatment and PGE2 alone was that the former depressed the bone resorption and turnover. These findings indicated that the long-term administration of PGE2 alone cannot maintain or continue to add bone mass in ovx rats but that co-treatment of a PGE2 with an anti-resorptive or activation agent can resist the influence of the mechanostat induced bone loss as well as continue to add bone.

Aging↗

Fish mating experiment in space--what it aimed at and how it was prepared.

The code name 'MEDAKA' was given to the fish experiment in the IML-2 (the second International Microgravity Laboratory), a Space-shuttle mission (STS-65) carried out in July 1994. Medaka is the Japanese name for a small fresh-water fish, Oryzias latipes. This experiment titled 'Mating behavior of the fish Medaka and development of their eggs in space' aimed to present data for designing the future fish-culture in space. The Medaka experiment accomplished its objectives to the point of 100%. The fish mated, laid eggs in space, and these eggs developed normally to hatching (coming out as a baby fish) under microgravity. Its success totally depended on selection of the four fish sent to space. This paper describes the aims of the IML-2 Medaka fish experiment and how it was prepared, together with a brief report on what were achieved in space.

Animals↗

Comparison of operative results of lumbar disc herniation in manual laborers and athletes.

The results of various surgical treatments for lumbar disc herniation in laborers and athletes were compared on the basis of the relative success of return to work and athletic activity. The rate of successful return to manual labor was the highest at 89% after spinal fusion, but no difference was observed between simple disc excision and percutaneous discectomy. Return to competitive sports was achieved at rate of 81% after percutaneous discectomy, and the time until return to sports activity was significantly shorter than after other procedures. In individuals whose lumbar region is expected to be subjected to great mechanical stress, it is important to take work needs and the special needs of athletes into consideration when selecting the surgical procedure.

Adult↗

Preoperative and postoperative magnetic resonance image evaluations of the spinal cord in cervical myelopathy.

To evaluate the morphologic changes of the spinal cord in patients with cervical myelopathy due to cervical spondylosis and ossification of the posterior longitudinal ligament, the authors measured the thickness and signal intensity of the cervical cord with magnetic resonance imaging in healthy adults and patients with cervical myelopathy, and compared these findings. In patients with cervical myelopathy, the preoperative and postoperative magnetic resonance imaging findings were compared with the severity of myelopathy and postoperative results. In healthy adults, the anteroposterior diameter of the cervical cord was 7.8 mm at the C3 level and decreased at lower levels. In the patients with cervical myelopathy, the preoperative spinal anteroposterior diameter was significantly reduced at various levels corresponding to the stenosis site within the vertebral canal. In the group with ossification of the posterior longitudinal ligament, the minimal anteroposterior diameter of the cervical cord tended to decrease with increasing severity of myelopathy. However no relationship was observed between the two parameters in the cervical spondylotic myelopathy group. In the group with ossification of the posterior longitudinal ligament, surgical results were good when the postoperative anteroposterior diameter was increased, whereas in the cervical spondylotic myelopathy group there was no relationship between the two parameters. In the patients with myelopathy, a high intensity area was observed in about 40% of all patients before operation and about 30% after operation. However, the presence or absence of a high intensity area did not correlate with the severity of myelopathy or with surgical results in the group with ossification of the posterior longitudinal ligament and the cervical spondylotic myelopathy groups.

Cervical Vertebrae↗

The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine.

Apoptosis is a mode of cell death involving nuclear pycnosis, cytoplasmic condensation and karyorrhexis. Changes in the number of apoptotic cells at various times (3-12 h) after a single dose of either 0.5 or 9.0 Gy given at 09.00, 21.00 or 03.00 h were studied in histological sections of small intestinal crypts of mice. The incidences of apoptosis were examined 3 or 6 h after irradiation at different times of day with different doses of gamma-rays ranging from 0.15 to 9.0 Gy. Survival curves were constructed from the dose-incidence curves for apoptosis, using the number of apoptotic cells after high doses (NM) as the maximum cell population size. The mean lethal doses (Do) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both Do and NM values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. A possible explanation based on the cell-cycle states of the target cell population for apoptosis (presumably functional stem cells) was drawn. Most of the target cells were assumed to be in an extended G1 phase. Around 21.00 h a transition from G1 to S phase takes place in some of these cells (approximately seven or eight cells per whole crypt). The S phase then lasts till around 06.00 h. They may be at G2 and M around 06.00-09.00 h, and then they re-enter G1. The circadian rhythm for the number and sensitivity of the cells susceptible to apoptosis obtained in the present report agrees well with this pattern of cell-cycle phases of target cells.

Animals↗

[Solid scintillator "Ready Cap" for measurement with a liquid scintillation counter--spectra and counting efficiencies for 15 different radionuclides].

"Ready Cap", a small plastic container coated with solid scintillator has recently been introduced (Beckman Instruments, Inc.). Pulse height spectra and counting efficiencies obtained with a liquid scintillator and Ready Cap using a liquid scintillator counter were compared for 15 different radionuclides. For radionuclides emitting low-energy beta-rays or characteristic X-rays, the spectra for Ready Cap shifted toward the higher energy side compared with the spectra for the liquid scintillator. This tendency was reversed for the nuclides emitting higher-energy beta-radiations (36Cl and 32P). Generally, counting efficiencies both in Ready Cap and in liquid scintillator increased with increase in the energy of beta- or X-rays. For some nuclides, Ready Cap gave higher counting efficiencies and for others it gave lower values than in the liquid scintillator. However, the differences were not large within each nuclide. The use of Ready Cap is recommended for measurements of radionuclides when liquid scintillation cocktails have no means of waste disposal under the present Japanese radioisotope regulation.

Evaluation Studies as Topic↗

Apoptosis (cell death) induced in mouse bowel by 1,2-dimethylhydrazine, methylazoxymethanol acetate, and gamma-rays.

Apoptosis is a pattern of cell death involving nuclear pyknosis, cytoplasmic condensation, and karyorrhexis. The frequency of apoptosis after treatment with two colon carcinogens and radiation was studied in the crypts of five different portions of mouse bowel. When 1,2-dimethylhydrazine (DMH) was injected s.c., the earliest rise in apoptotic incidence after a high dose (200 mg/kg) was noted at 3 h in small intestine and at 6 h in large bowel. After i.p. administration of methylazoxymethanol (MAM) acetate, apoptotic cells were seen in large bowel after 3 h. When the plateau values attained after high doses of DMH were compared, many apoptotic cells were found in the lower part of the large bowel, whereas few such cells were observed in the small intestine and the upper part of the large bowel. This finding was reversed in the case of radiation-induced apoptosis. In the descending colon, a definite circadian rhythm in the apoptotic incidence was observed 6 h after injection of DMH or MAM acetate. Apoptosis showed a high incidence when these drugs were given between 2400 h and 0900 h, but a low incidence after administration between 1200 h and 2100 h. In the small intestine a rhythm was also noted for MAM acetate, but not significantly for DMH.

1,2-Dimethylhydrazine↗

Cell death (apoptosis) in mouse intestine after continuous irradiation with gamma rays and with beta rays from tritiated water.

Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed dose from HTO, the water content both of the mouse body and of the cells was assumed to be 70%. One megabecquerel of HTO per mouse (i.e., 40 MBq/kg body wt) gave a dose rate of 0.131 mGy/h. The mean lethal doses (D0) were calculated for gamma rays and HTO, and relative biological effectiveness values of HTO relative to gamma rays were obtained. The D0 values for continuous irradiation with gamma rays were 210 mGy for small intestine and 380 mGy for descending colon, and the respective values for HTO were 130 and 280 mGy, indicating the high radiosensitivity of target cells for apoptotic death. The relative biological effectiveness of HTO relative to 137Cs gamma rays for cell killing in both the small intestine and the descending colon in the mouse was 1.4-2.1.

Animals↗

Circadian rhythms in the incidence of apoptotic cells and number of clonogenic cells in intestinal crypts after radiation using normal and reversed light conditions.

Variations in the number of radiation-induced morphologically dead or dying cells (apoptotic cells) in the crypts in the small intestine of the mouse have been studied throughout a 24-h period under a normal light regimen (light on, 07.00-19.00 h; light off, 19.00-07.00 h). A clear circadian rhythm was displayed in the apoptotic incidence 3 or 6 h after irradiation for each gamma-ray dose studied (range 0.14-9.0 Gy). The most prominent circadian rhythm was obtained after 0.5 Gy. The peak time of day for inducing apoptosis was 06.00-09.00 h, and the trough occurred at 18.00-21.00 h. Some mice were also transferred to a room with the light cycle reversed, and were irradiated on different days after the transfer. The apoptosis induced by 0.5 Gy or 9.0 Gy, or the number of surviving crypts (microcolonies) after 11.0 Gy or 13.0 Gy was examined. The transition point for reversal (i.e. the switch time from the normal-light pattern to the reversed-light pattern) of the circadian rhythm in apoptosis (after 0.5 Gy) occurred 7 days after the transfer and the rhythm was reversed by 14 days. The rhythm for crypt survival (i.e. for clonogenic cell radiosensitivity) was disturbed on 1 day and the transition point for reversal occurred 3 days after the transfer. The rhythm became reversed by 7 days. These observations are discussed in relation to the identity of clonogenic cells, (functional) stem cells, proliferating transit cells and the cells sensitive to small doses of radiation (i.e. hypersensitive cells) in the crypt.

Animals↗

Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents.

Adult male mice were treated with one or two different doses of each of 18 different cytotoxic agents. They were sampled at various times (3-12h) thereafter, and the spatial distributions of cell death in the small intestinal crypts were studied. Dead or dying cells or cells carrying dead cell fragments were examined histologically, and all of these were recorded (for convenience as apoptotic fragments), relative to the cell position in the crypt. Thus, distributions of apoptotic fragments against cell position were determined. A regression analysis of the data obtained at different times after administration of each agent was undertaken and the position of the median of the spatial distribution of presumptive target cells was deduced for each cytotoxic agent. The accuracy of this median value was determined to be +/- 0.5 cell positions. From these median values, the different cytotoxic agents could be divided roughly into three groups: [3H]thymidine, isopropyl-methane-sulphonate, gamma-rays, bleomycin and adriamycin all have their median values (susceptible cells) at cell positions 4 to 6; bischlorethylnitrosourea, actinomycin D, cyclophosphamide and cycloheximide at cell positions 6-8; mechlorethamine, triethylenethiophosphoramide, vincristine, 5-fluorouracil, hydroxyurea and methotrexate at cell positions 8-11. The position of these medians was considered in relation to the killing of clonogenic cells. Preliminary studies on the distributions of dead cells after myleran, cis-platinum and heat (hyperthermia) were also reported. There is a general tendency for antibiotics and radiation to attack the lower cell positions in the crypt. Alkylating agents on the other hand have a somewhat broad spectrum of action. Antimetabolites and a microtubule dissociating agent act on higher cell positions. No difference could be detected between two different forms (sources) of actinomycin D. The changes in the yields of apoptotic and mitotic cells with time and the migration velocities of cells in the crypts carrying apoptotic fragments after exposure to cytotoxics are also presented.

Animals↗

Effect of corticosteroids on the thymus of the fish Oryzias latipes.

Morphology and development of the thymus in fish Oryzias latipes was studied in response to corticosteroids. Adult fish were subjected to different concentrations of two corticosteroids, deoxycorticosterone acetate (DOCA) and cortisone acetate (CA). Histology of the thymus and thymocyte counts in treated fish were compared to normal ones. There was no change in histology of thymus due to CA treatment even those subjected to 10 mg/l water which is a lethal dose of DOCA. In contrast, the effect of DOCA at low doses (0.01 and 0.1 mg/l water) was examined and resulted in reduction of thymus volume due to depopulation of thymocytes from the entire gland. Thymus subjected to DOCA at a high dose (1 mg/l water) caused destruction of all thymocytes and reticular cells resulting in complete disappearance of the thymus. There was dose dependent mortality associated with DOCA. The maximum lethal dose was 10 mg/l causing death of all treated fish within a few hours. This information is relevant to the use of CS in fish therapy in response to stress.

Aging↗