Biomedical subjects

Koji Uetsuka

Publications and source records attributed to Koji Uetsuka.

8 recordsLinked to original sources

PubMed2003

Distribution of N-methyl-D-aspartate receptors (NMDARs) in the developing rat brain.

The N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, is considered to have a close relationship to synaptic plasticity in the developing brain. In addition, it is known that the excessive stimulation of NMDARs can trigger neuronal apoptosis. In this study, we examined the distribution of NMDAR subunits [anti-NR1, NR2(A-C)] in the developing rat brain immunohistochemically. As a result, NR1, an essential subunit for the formation of a functional NMDAR complex, was mildly expressed in the restricted areas such as the temporal region of the cerebral cortex and the hippocampus in the fetal brain at Embryonal Days 18 and 20. On the other hand, in neonates, NR1 was expressed widely throughout the whole brain. The distributions of NR2A and NR2C showed temporal and spatial similarities to that of NR1, while the expression of NR2B showed differences in the intensity and distribution. A progressive change in subunit expression seen prenatally and postnatally could contribute to variation of NMDARs and synaptic plasticity during the developing period.

Animals↗

PubMed2003

Impaired liver regeneration after partial hepatectomy in db/db mice.

Fatty liver is the most common hepatic disorder in humans and supposed to be a cause of poor prognosis after liver transplantation and hepatic resection which could be resulted from impaired liver regeneration. This study was carried out to analyze the process of liver regeneration in db/db mice which show severe steatosis because of abnormal leptin receptor. We performed 70% partial hepatectomy (PH) on db/db mice and normal +m/+m mice, and then sacrificed the animals 1, 2, 3, 5, 7 and 10 days later. The liver samples were weighed and examined histologically or immunohistochemically. As a result, the liver mass restitution was significantly inhibited in db/db mice compared with +m/+m mice. The BrdU labelling index peaked at 2 days after PH in both strains, although the value was lower in db/db mice. After that, interestingly, it decreased to the control level at 5 days in +m/+m mice while the recovery was delayed in db/db mice. Similar sequence was also observed in the PCNA labelling index. In addition, the peak time of the mitosis index was 2 days and 5 days after PH in +m/+m mice and in db/db mice, respectively. Thus, although not significant, the proliferative response of hepatocytes to PH occurred somewhat more transient and sharply in +m/+m mice while it lasted somewhat longer in db/db mice. This suggests that db/db mice may be valuable as one of the animal models for the investigation of the effects of steatosis on the liver regeneration.

Animals↗

PubMed2003

NMDA-induced apoptosis in the developing rat brain.

The N-methyl-D-aspartate receptor (NMDAR), which is one of the glutamate receptors, is considered to have a close relation to synaptic plasticity in the developing brain. In addition, it is also known that the excessive stimulation of NMDARs can trigger neuronal apoptosis. In this study, we examined the expression of neuronal apoptosis in the developing rat brain after the administration of NMDA to pregnant dams or neonates (embryonal days 18 to postnatal days 14). In the NMDA-treated group, the significant increase in nuclei of apoptotic neuronal cells occurred in the dose-dependent manner in the lateral-ventral regions of the fetal cerebral cortex, reaching maximum values at 24 hours after treatment. On the other hand, the induction of apoptosis did not occur in the neonatal brain.

Animals↗

PubMed2003

Effects of granulocyte colony-stimulating factor on the kinetics of inflammatory cells in the peripheral blood and pulmonary lesions during the development of bleomycin-induced lung injury in rats.

We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on the kinetics of inflammatory cells during the development of inflammation in bleomycin (BLM)-induced lung injury. G-CSF (100 microg/kg/day, s.c.) was administered to rats treated with or without BLM (2 mg/200 microl, intratracheally) for up to 14 days (Day 14) immediately after BLM treatment. In the BLM + G-CSF group, the lung injury score increased on Days 1 and 14, and the score of lung fibrosis on Day 14, respectively. Except for neutrophils, there were no effects of G-CSF on the number of inflammatory cells both in the peripheral blood and in the lung in both BLM-treated and -untreated rats at the acute inflammatory phase. In the G-CSF-treated groups, the number of neutrophil counts in the peripheral blood drastically increased on Day 1, temporally decreased on Day 3, and increased again on Days 7 and 14. The number of neutrophils in the lung markedly increased on Day 1 and then remained at a plateau level until Day 14. The neutrophil alkaline phosphatase score in the lung commenced to increase on Day 1, reached the maximal level on Day 7, and then remained at a plateau level until Day 14. Correlations between the numbers of neutrophils in the lung and the peripheral blood or the lung lesion score were only observed on Day 14. These findings suggest that the exacerbating effect of G-CSF on the lung injury coincided with the increase in the number of alkaline phosphatase-positive neutrophils infiltrating in the pulmonary lesion at the acute inflammatory phase and it lasted to the fibrogenic phase. The exacerbating effect of G-CSF on the severe BLM-induced lung injury seems to be related not only to the pulmonary accumulation of activated neutrophils but also to the severity of lung injury caused by the direct effects of BLM.

Alkaline Phosphatase↗

PubMed2002

Granulocyte colony-stimulating factor exacerbates the acute lung injury and pulmonary fibrosis induced by intratracheal administration of bleomycin in rats.

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.

Acute Disease↗

PubMed2002

Dorsal skin responses to topical application with hydrogen peroxide in Mini and Wistar rats.

Mini rats (Jcl: WistarTGN(ARGHGEN) 1Nts) (MRs) are Wistar rat (WR)-derived transgenic rats in which the expression of growth hormone (GH) gene is suppressed under the presence of antisense RNA transgene. In order to evaluate the effects of GH-deficiency on the acute injury by external stimuli, the dorsal skin responses to a single topical application with 20% hydrogen peroxide (HPO), one of the environmental oxidative stressors, were histologically compared between male MRs and WRs of 8 weeks old, whose hair cycle was under the telogen phase. As a result, formation of granulation tissues, reepithelialization and regrowth of hair follicles were delayed in MRs compared with WRs. While hair follicles of MRs of this age are under a long-lasting telogen phase after their 2nd cycle, a new hair cycle started not only in the HPO-applied area but also in the solvent-applied area with a little time lag. These findings suggest that GH-deficiency may influence the skin responses to the external chemical stimuli.

Administration, Topical↗

PubMed2002

Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta.

Ethylnitrosourea (ENU), a well known alkylating agent, induces congenital anomalies in fetuses when it is administered to pregnant animals. In previous studies, we reported that ENU induced apoptosis and growth arrest in fetal tissues and organs immediately after its administration to pregnant rats. In the present study, we investigated the histopathological changes of the placenta after ENU administration to pregnant rats on Day 13 of gestation (GD13) to obtain a clue for clarifying the role of the placenta in the process of fetal developmental disability induced by genotoxic stress. Apoptotic cells increased and DNA-replicating cells decreased in the trophoblastic cells in the placental labyrinth zone of the ENU-treated group by 3 h after treatment. The number of apoptotic cells peaked at 6 h after treatment and returned to control levels at 48 h after treatment. The number of DNA-replicating cells reached minimum levels at 6 h after treatment and returned to control levels at 48 h after treatment. By immunohistochemistry, p53-positive signals were observed in trophoblastic cells in the labyrinth zone of the ENU-treated group from 3 to 6 h after treatment. Significant decreases in fetal and placental weights were observed in the ENU-treated group at 2 days (GD15) and 8 days (GD21) after treatment. A reduction in the thickness of the labyrinth zone was histopathologically significant in the ENU-treated group. These results indicate that ENU induces apoptosis and growth arrest not only in fetal tissues, but also in trophoblastic cells in the rat placental labyrinth zone, and these placental changes may have roles in the induction of fetotoxicity and teratogenicity of ENU. Moreover, a possible involvement of p53 in the induction of apoptosis and growth arrest is suggested.

Alkylating Agents↗

PubMed2002

Cerebellar myxoid type meningioma in a Shih Tzu dog.

A 6-year and 9 month-old, male, Shih Tzu dog showed ataxia and trembling. By MRI examination, a mass (1 cm) was found in the right cerebellum. As the dog did not respond to radiation therapy, and showed a rise of intracranial pressure, he was euthanized. The cerebellar mass was soft and hemorrhagic. Histologically, the mass contained vimentin-positive spindle- or polyhedral-shaped cells arranged in a cord-like pattern. Mucinous materials were observed in the intercellular spaces. Ultrastructural examination revealed cell processes, microtubule-like structures and desmosomes. The case was diagnosed as myxoid type meningioma.

Animals↗