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Biomedical subjects

A Nitta

Publications and source records attributed to A Nitta.

At least 55 records · Page 3Linked to original sources
PubMed1997

Oral administration of propentofylline, a stimulator of nerve growth factor (NGF) synthesis, recovers cholinergic neuronal dysfunction induced by the infusion of anti-NGF antibody into the rat septum.

We have reported that the continuous infusion of anti-nerve growth factor (NGF) monoclonal antibody into the septum of rats produces an impairment of memory and a decrease in choline acetyltransferase (ChAT) and cholinesterase (ChE) activities in the hippocampus. Propentofylline, a xanthine derivative, has potent stimulatory effects on NGF synthesis/secretion in mouse astrocytes in vitro. To investigate the pharmacological effects of propentofylline in vivo, we induced amnesia in rats by infusing anti-NGF antibody into the septum for 16 days. One group of rats was given no further treatment, while the other group was treated with propentofylline orally once a day for 19 days, commencing 3 days before the implantation of the mini-osmotic pump, and continuing throughout the period during which the animals performed the behavioral tasks. In the treated amnesic rats, learning and memory in the 3 tasks and ChAT and ChE activity were reduced compared to values in control rats. The administration of propentofylline recovered the decreased learning capacity and the deficit in cholinergic marker enzyme activity. These results suggest that the use of NGF stimulators may provide a new approach to the treatment of dementia.

Amnesia↗
PubMed1997

Continuous infusion of beta-amyloid protein into the rat cerebral ventricle induces learning impairment and neuronal and morphological degeneration.

To investigate the toxicity of beta-amyloid protein, a component of the senile plaques in Alzheimer's disease, it was infused into the cerebral ventricle of rats for 14 days by a mini-osmotic pump. Performances in the water maze and passive avoidance tasks in beta-amyloid protein-treated rats were impaired. Choline acetyltransferase activity significantly decreased in the hippocampus both immediately and 2 weeks after the cessation of the infusion. However, the learning impairment was recoverable 2 weeks after cessation of the infusion. Both immediately and 2 weeks after the cessation of the infusion, glial fibrillary acidic protein immunoreactivity increased. Furthermore, beta-amyloid protein altered the staining in the nuclei of hippocampal cells for only 2 weeks after the cessation. These results suggest that beta-amyloid protein produces some damage in the central nervous system in vivo.

Amyloid beta-Peptides↗
PubMed1996

Propentofylline prevents neuronal dysfunction induced by infusion of anti-nerve growth factor antibody into the rat septum.

We have reported that the continuous infusion of anti-nerve growth factor (NGF) monoclonal antibody into the septum of rats produces neuronal dysfunction in the cholinergic system. Propentofylline has potent stimulatory effects on NGF synthesis/secretion in mouse astrocytes in vitro. To investigate the pharmacological effects of propentofylline, we used an animal model of dementia in which anti-NGF antibody was infused into the septum for 16 days via a mini-osmotic pump. The rats were treated with propentofylline orally once a day throughout the period during which performance in learning and memory tasks was observed. In the vehicle-treated dementia rats, learning and memory ability and choline acetyltransferase and cholinesterase activity were reduced compared to values in the control rats. The administration of propentofylline prevented the decreased learning capacity and the deficit in cholinergic marker enzyme activities. These results suggest that the use of NGF stimulators may provide a new approach to the treatment of dementia.

Administration, Intranasal↗
PubMed1996

Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein--infused rats.

Accumulations of beta-amyloid protein are characteristic and diagnostic features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previously reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acetyltransferase activity, a marker enzyme of cholinergic neuron. In this study, the effects of beta-amyloid protein infusion on the release of neurotransmitters in cholinergic and dopaminergic neuronal systems were investigated by using an in vivo brain microdialysis method. Nicotine-stimulated release of acetylcholine and dopamine in these animals was significantly lower than that in vehicle-infused rats. Further, dopamine release induced by high-K stimulation was decreased in beta-amyloid protein-infused rats compared with vehicle-infused rats. These results suggest that the release of the two transmitters, acetylcholine and dopamine, was decreased by beta-amyloid protein and that learning deficits observed in the beta-amyloid protein-infused rats are partly due to the impairment of neurotransmitter release. Furthermore, continuous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.

Acetylcholine↗
PubMed1996

[Experimental techniques for developing new drugs acting on dementia (10)--Alzheimer's disease animal model induced by beta-amyloid protein].

To develop an animal model of Alzheimer's disease, beta-amyloid protein was infused into the rat cerebral ventricle for 14 days using a mini-osmotic pump. The performance of some memory tasks in the beta-amyloid protein-treated rats was impaired. Long-term potentiation in the hippocampus was impaired in beta-amyloid-infused rats. The impairment of memory under the infusion could be recovered by two cognitive enhancer drugs. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus but glial fibrillary acidic protein immunoreactivity increased in the cortex both immediately and 2 weeks after cessation of the infusion. Ciliary neurotrophic factor contents in several brain areas in beta-amyloid-infused rat significantly increased. Substance P and microtubule-associated protein, which play an important role in neuronal transmission and construction of neuronal cells, respectively, decreased. Moreover, the release of acetylcholine and dopamine from the cortex/hippocampus and striatum, respectively, in the beta-amyloid-infused rats after depolarization was smaller than that from the control rats. These results suggest that beta-amyloid protein induced dysfunction of the central nervous system in vivo, and that the animal could be used as a model of Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

Age-related changes in learning and memory and cholinergic neuronal function in senescence accelerated mice (SAM).

The senescence-accelerated mouse (SAM) has been established as a murine model of accelerated aging. We investigated learning ability and memory in various tasks in a SAM strain, SAMP1TA, and in a control strain of SAMR1TA at the ages of 20, 30 and 40 weeks. We also measured choline acetyltransferase (ChAT) and cholinesterase (ChE) activity in the brains of these mice at the same ages. In a Y-maze task, in which short-term memory can be examined, there was no difference in learning ability between SAMP1TA and SAMR1TA at any age. Ability in latent learning and passive-avoidance tasks was less in SAMP1TA at 30 weeks of age than in age-matched SAMR1TA. The level of ChAT activity in the striatum of SAMP1TA was lower, than that of SAMR1TA at the ages of 20 and 30 weeks. At the ages of 40 and 50 weeks, ChE activity in the striatum of SAMP1TA was lower than that of SAMR1TA. These results suggest that SAMP1TA has a deficit, with cholinergic neuronal dysfunction, in learning ability and memory, as shown by impairment of performance in latent learning and long-term memory, but not in short-term memory.

Aging↗
PubMed1995

Changes in ciliary neurotrophic factor content in the rat brain after continuous intracerebroventricular infusion of beta-amyloid(1-40) protein.

We have previously shown that the continuous intracerebroventricular infusion of beta-amyloid(1-40) protein results in memory impairments in rats, associated with a reduction of choline acetyltransferase activity in the frontal cortex and hippocampus. In the present study, we examined whether the infusion of beta-amyloid(1-40) protein affected the content of ciliary neurotrophic factor (CNTF) in the rat brain. The beta-amyloid(1-40) infusion increased CNTF content in the frontal cortex, hippocampus, and the cerebellum, but decreased its content in the brain stem. These results suggest that accumulation of beta-amyloid(1-40) in the brain may affect CNTF production in vivo.

Amyloid beta-Peptides↗
PubMed1995

Tumour angiogenesis and tumour cell proliferation as prognostic indicators in gastric carcinoma.

Tumour growth depends on neovascularisation and tumour cell proliferation. Factor VIII-related antigen (F-VIII RA) localises to vascular endothelium. Expression of proliferating cell nuclear antigen (PCNA) is correlated with cell proliferation. We investigated the correlation between the expression of these antigens and prognosis in gastric carcinoma. A total of 108 specimens resected from patients with gastric carcinoma were investigated by staining with monoclonal antibodies against F-VIII RA and PCNA. Microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200 x magnification) and PCNA labelling index (PCNA LI; percentage of positive cells in more than 500 tumour cells) were determined. The results showed that prognosis was significantly worse in patients who had a tumour with a high MVC (16 or greater) or a high PCNA LI (42% or greater) than in those patients who had a tumour with a low MVC (less than 16) or a low PCNA LI (less than 42%). Furthermore, MVC was significantly associated with the risk of hepatic recurrence. In conclusion, both MVC and PCNA LI may be good prognostic indicators in patients with gastric carcinoma.

Adult↗
PubMed1995

Tumor angiogenesis as a predictor of recurrence in gastric carcinoma.

PURPOSE: We investigated the correlation between tumor angiogenic activity and progression of gastric carcinoma using immunohistochemical staining with antifactor VIII-related antigen (F-VIII RAg) antibody. MATERIALS AND METHODS: One hundred twenty-four specimens resected from patients with gastric carcinoma were investigated by staining with a monoclonal antibody against F-VIII RAg. Correlations between the microvessel count (the mean number of microvessels in the five areas of highest vascular density at 200 times magnification), various clinicopathologic factors, and prognosis were studied. RESULTS: The microvessel count increased with histologic stage. The microvessel count was significantly higher in patients with lymph node metastases than in those without such metastases. Moreover, in patients with a high microvessel count (> or = 16), prognosis was significantly poorer than in those with low count (< 16). Multivariate analysis indicated that the microvessel count is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased in patients with a high count. CONCLUSION: Microvessel count may be a good prognostic indicator and may be useful as a predictor for the mode of recurrence in patients with gastric carcinoma.

Adenocarcinoma↗
PubMed1995

[Correlation between malignancy of gastric cancer and c-myc DNA amplification or overexpression of c-myc protein].

The amplification of c-myc DNA for fresh frozen tissue of 31 gastric adenocarcinomas was examined with dot blot hybridization method. Using the avidin-biotin peroxidase complex method, the expression of c-myc protein was examined immunohistochemically for formalin-fixed paraffin embedded tissue of 51 gastric adenocarcinomas including the same cases for c-myc DNA analysis. c-myc DNA amplification was detected in only 4 cases (12.9%). However, c-myc protein overexpression was recognized in 21 cases (41.2%). Only one of 4 cases showing c-myc DNA amplification indicated overexpression of c-myc protein. There was no statistically significant relation of c-myc protein overexpression with clinicopathological factors (histology, depth of invasion, invasion of the vessels, metastasis, intraabdominal dissemination and histological staging). These results suggest overexpression of c-myc protein could be recognized even in early gastric cancer indicating the relation of this gene product with proliferation of gastric cancer cells, although its role in the progression and metastasis of gastric adenocarcinoma might be minimal.

Adenocarcinoma↗
PubMed1995

[Malignancy of gastric cancer analyzed by the expression of thymidine phosphorylase].

In this study, the expression of thymidine phophorylase (dThdPase) was investigated immunohistochemically in 73 patients with gastric cancer. dThd Pase was mainly distributed at the apical portion, or cytoplasm of cancer cells and its expression was detected in 52 tumors (71.2%). There were no significant association among the expression of dThdPase, histologic type, depth of invasion, and lymph node metastasis. However, a significant difference was noted with respect to liver metastases. Among 73 patients, liver metastases were observed in 11 patients. dThdPase expression was detected in all of these cases with liver metastases, which was significantly more common than those without such metastases. In relation to the prognosis, patients with dThdPase-positive tumors had a significantly worse prognosis than those with dThdPase-negative tumors. In conclusion, the expression of dThdPase may be useful as a predictor of malignant potential in gastric cancer.

Adult↗
PubMed1994

beta-Amyloid protein-induced Alzheimer's disease animal model.

To investigate the toxicity of beta-amyloid protein which consisted of senile plaques of Alzheimer's disease (AD), this was infused into cerebral ventricle for 14 days by using mini-osmotic pump. The performance of the water maze task in beta-amyloid protein-treated rats was impaired. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus. These results suggest that the deposition of beta-amyloid protein in the brain is related to the impairment of learning and cholinergic neuronal degeneration, and that beta-amyloid protein-treated rats could be used as an animal model for AD.

Alzheimer Disease↗
PubMed1994

Proliferating cell nuclear antigen labeling index of preoperative biopsy specimens in gastric carcinoma with special reference to prognosis.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to correlate with the cell's proliferative state. Immunohistochemical methods with a anti-PCNA antibody (PC10) have particular advantages compared with other techniques because of the maintenance of the tissue architecture and simplicity of the methodology. The authors investigated the correlation between the tumor's proliferative activity and progression of gastric carcinoma using immunohistochemical staining with PC10. METHODS: One hundred eighty-nine endoscopic biopsy specimens from patients with gastric carcinoma before operation were investigated by immunohistochemical study, using anti-PCNA monoclonal antibody (PC10). The correlation of PCNA labeling index (percentage of positive cells in more than 500 tumor cells) with various clinicopathologic factors and prognosis was studied. RESULTS: The PCNA labeling index became higher as the histologic stage increased. In patients with lymph node metastasis, vascular invasion, liver metastasis, and peritoneal metastasis, the labeling index was significantly higher. In patients with high PCNA labeling index (50% or greater), prognosis was significantly poorer than in those with a low index (less than 50%). The rate of disease recurrence after curative resection was significantly higher in patients with high PCNA grade group. CONCLUSION: As a result of this study, PCNA labeling index is suggested to be correlated with the depth of invasion, organ metastasis, vascular invasion, and tumor stage and to be effective as a prognostic factor.

Adult↗
PubMed1994

Oral administration of idebenone induces nerve growth factor in the brain and improves learning and memory in basal forebrain-lesioned rats.

Nerve growth factor plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. In senile dementia of the Alzheimer type, learning and memory are impaired by the loss of neurons in the magnocellular cholinergic neuronal system. It is therefore, of interest to investigate the role of nerve growth factor in this degenerative disorder. Since nerve growth factor does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We demonstrate here that the oral administration of idebenone, a potent in vitro nerve growth factors synthesis stimulator, induced an increase in nerve growth factor protein and mRNA, and in choline acetyltransferase activity, in basal forebrain lesioned rats, but not in intact rats. Idebenone also ameliorated the behavioral deficits in habituation, water maze, and passive avoidance tasks in these animals. These results suggest that idebenone stimulated nerve growth factor synthesis in vivo and ameliorates the behavioral deficits which were accompanied with the recovery of the reduced choline acetyltransferase activity in the basal forebrain-lesioned rats.

Animals↗
PubMed1994

Effects of subacute administration of methamphetamine and nicotine on locomotor activity in transgenic mice expressing the human tyrosine hydroxylase gene.

We produced transgenic (Tg) mice carrying the human tyrosine hydroxylase (TH) gene. To investigate differences in the dopaminergic (DAergic) neuronal activity between the Tg and nTg mice, we examined changes in the locomotor activity induced by methamphetamine (MAP) and nicotine (NIC), which enhances DA release and induces TH enzyme activation, respectively. Surprisingly, however, the intensity of MAP (2.5 mg/kg, once a day for 14 days)-induced hyperlocomotion in the nTg mice was greater than that in the Tg mice, and, furthermore, the Tg mice were less sensitive to subacute administration of NIC (0.5 mg/kg, once a day for 14 days) than the nTg mice. These results suggest that DAergic neuronal function is suppressed in Tg mice to compensate for the overexpression of TH.

Animals↗