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Biomedical subjects

A Nitta

Publications and source records attributed to A Nitta.

At least 73 records · Page 4Linked to original sources
PubMed1994

Nicotine reverses scopolamine-induced impairment of performance in passive avoidance task in rats through its action on the dopaminergic neuronal system.

Interest has recently focused on tobacco and/or nicotine in relation to senile dementia of the Alzheimer type because the population of patients with this disease among tobacco smokers is significantly smaller than in nonsmokers. We investigated whether, in relation to the dopaminergic neuronal system, nicotine was effective in ameliorating the impairment of performance in passive avoidance tasks in rats induced by scopolamine, an inhibitor of muscarinic acetylcholine receptors. Scopolamine and nicotine were coadministered to rats 30 min before the acquisition trial. Some rats received scopolamine alone; they showed much shorter step-through latency (STL) than the control group in the retention test. Nicotine significantly prolonged the decreased STL induced by scopolamine. The effects of nicotine were inhibited by the preadministration of mecamylamine, SCH 23390, and (-)sulpiride, which are nicotinic acetylcholine, D1, and D2 receptor antagonists, respectively. These results suggest that nicotine, by activating the nicotinic acetylcholinergic and dopaminergic neuronal systems, ameliorates the impairment of performance in the passive avoidance task induced by a muscarinic acetylcholine receptor blocker.

Animals↗
PubMed1994

Oral administration of NGF synthesis stimulators recovers reduced brain NGF content in aged rats and cognitive dysfunction in basal-forebrain-lesioned rats.

Nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. Since this 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 report here that repeated oral administration of the stimulators for the NGF synthesis, idebenone and propentofylline, produced a significant recovery of the reduced NGF content in the frontal and parietal cortices of aged rats. These compounds also improved deficits of performance in water maze, passive avoidance and habituation tasks in basal-forebrain-lesioned rats. These results suggest that the use of the stimulators for the NGF synthesis may provide a therapeutic approach to cholinergic dysfunction.

Administration, Oral↗
PubMed1994

Nerve growth factor content of rat brain increases following basal-forebrain lesions induced by ibotenic acid but not by electrolysis.

We attempted to measure the change in the nerve growth factor (NGF) content in the hippocampus and parietal cortex following basal-forebrain lesions induced by ibotenic acid and electrolysis. The NGF content of the parietal cortex and hippocampus increased transiently on days 3 to 7, and then returned to the control level on day 14 after the lesion of the basal forebrain induced by ibotenic acid. Ibotenic acid decreased both the choline acetyltransferase (ChAT) activity in the parietal cortex and the dopamine content in the striatum. Electrolytic lesions of the basal forebrain decreased the dopamine content in the striatum, but did not affect the NGF content and ChAT activity in any of the brain regions examined. These results suggest that the mechanism of NGF synthesis is related to cholinergic, but not to dopaminergic, neurons in the basal forebrain.

Analysis of Variance↗
PubMed1994

Memory impairment and neuronal dysfunction induced by beta-amyloid protein in rats.

Alzheimer's disease (AD) is characterized by the presence of senile plaques. The core of the plaque consists of beta-amyloid protein. In AD patients, learning and memory are impaired with a concomitant loss of the cholinergic marker enzyme, choline acetyltransferase (ChAT). However, direct evidence that beta-amyloid protein is related to the impairment of learning and memory has not been demonstrated. In this study, we investigated whether memory impairment and neuronal dysfunction were produced after 2 weeks continuous infusion of beta-amyloid protein (3, 30 and 300 pmol/day) into the cerebral ventricles in adult rats. To investigate the ability of learning and memory in beta-amyloid protein-treated rats, water maze and passive avoidance tasks were carried out. The performance of both tasks in beta-amyloid protein-treated rats was impaired. ChAT activity in the frontal cortex (3 and 30 pmol/day) and hippocampus (300 pmol/day) significantly decreased. These results suggest that beta-amyloid protein is related to the impairment of learning and memory, and neurodegeneration, and that beta-amyloid protein-treated rats could be used as an animal model for AD.

Acetylcholinesterase↗
PubMed1994

[Clinical study of ambulatory cancer chemotherapy for recurrent breast cancer].

To evaluate ambulatory cancer chemotherapy, the clinical response, toxicities and survival time were analysed among 12 outpatients with recurrent breast cancer who were treated by sequential methotrexate (MTX)/5-FU therapy for the past 2 years. In this study, MTX (70 mg/m2, i.v.) and 5-FU (370 mg/m2, d.i.v.) were given on days 1 and 15 every 4 weeks, the 5-FU being given one hour after the MTX. Partial response (PR) was observed in 3 patients (25%), no change (NC) in 9. One-year survival ratio was 59%, and 7 out of 12 patients survived at the end of this study. The median disease free interval was 7.3 months, and 3 cases survived for more than one year without disease. Although nausea/vomiting, stomatitis, leukopenia and alopecia were noted, no severe side effects were observed. These results suggested that sequential MTX/5-FU therapy might be a useful ambulatory cancer chemotherapy for patients with recurrent breast cancer.

Adult↗
PubMed1994

[Nuclear DNA ploidy pattern and proliferating cell nuclear antigen labeling index in gastric cancer with mucosal involvement].

The DNA ploidy pattern and the expression of proliferating cell nuclear antigen (PCNA) were investigated in 72 gastric carcinoma patients to determine the possible correlation between proliferation kinetics and biological behavior. The diploid pattern was more often observed in cases with mucosal invasion (m cancer) than other cases (sm or advanced cancer). The PCNA labelling index in cases with mucosal invasion was significantly lower than in other cases. The sm cancer was more often observed in patients with high PCNA labelling index (> or = 30%) and aneuploid pattern, while m cancer was more common in patients with low PCNA labelling (< 20%) index and diploid pattern. As a result of this study, we conclude that proliferating kinetics of m cancer may differ from that for sm or advanced cancer. Furthermore, DNA ploidy pattern and PCNA labelling index may be useful as a parameter of depth of invasion.

Adult↗
PubMed1993

Oral administration of idebenone, a stimulator of NGF synthesis, recovers reduced NGF content in aged rat brain.

The relationship between nerve growth factor (NGF) and senile dementia of the Alzheimer type is of interest. We demonstrate here that the oral administration of idebenone, a stimulator of NGF synthesis in vitro, produced recovery of reduced NGF content in aged rat brain. Twenty-one-day successive administration of idebenone produced significant recovery of reduced NGF content in the frontal cortex and parietal cortex of aged rats. These results suggest that NGF content in the brain is low in aged rats and that oral administration of idebenone leads to a recovery of this reduction.

Administration, Oral↗
PubMed1993

Effects of oral administration of a stimulator for nerve growth factor synthesis 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 senile dementia of the Alzheimer type. We now found that 6-(4-hydroxybutyl)-2,3,5-trimethyl-1,4- benzoquinone (TMQ) stimulates nerve growth factor synthesis in mouse astroglial cells and that the compound has improving effects on memory and choline acetyltransferase activity in basal forebrain-lesioned rats, an amnesia animal model. TMQ ameliorated amnesia in the water maze and passive avoidance tasks. The compound not only restored the reduced choline acetyltransferase activity in the parietal cerebral cortex, but also increased nerve growth factor content and choline acetyltransferase activity in the hippocampus, although it did not change either of these parameters in any brain region in intact rats. These results suggest that the compound activates cholinergic neurons only in the damaged brain and, further, indicate that nerve growth factor stimulators could be used in clinical trials for the treatment of senile dementia of the Alzheimer type.

Administration, Oral↗
PubMed1993

Development of plasticity of brain function with repeated trainings and passage of time after basal forebrain lesions in rats.

Basal forebrain (BF) lesion-induced amnesia in rats is widely used as an animal model of Alzheimer's disease (AD). To study the plasticity of brain function in BF-lesioned rats, we examined the effects of repeated trainings and the passage of time after the lesion on learning ability 3 weeks and 3 months after BF-lesions with ibotenic acid, using an eight-arm radial maze and passive avoidance tasks, and measured choline acetyltransferase (ChAT) activity. Both time and re-training played important roles in the recovery of the ability to learn, as measured with the eight-arm radial maze task, but not the passive avoidance task. In contrast, ChAT activity in the frontal cortex, which was low 3 weeks after the lesion, still low 3 months after lesion, even though the ability to learn had recovered. Recovery of the ability to learn can be attributed to undamaged cholinergic neurons, or to other neuronal systems, or to both. This animal model can be used to demonstrate the plasticity of brain function.

Animals↗
PubMed1993

Memory impairment and neural dysfunction after continuous infusion of anti-nerve growth factor antibody into the septum in adult rats.

Nerve growth factor is required for the survival and maintenance of cholinergic neurons in the central nervous system. The direct infusion into the rat's septum of an anti-nerve growth factor monoclonal antibody, which inhibits nerve growth factor bioactivity seven times more strongly than a polyclonal antibody, caused very severe damage to the hippocampal cholinergic system. Anti-nerve growth factor polyclonal antibody also neutralized endogenously occurring nerve growth factor. The infusion of anti-nerve growth factor polyclonal antibody produced a dysfunction of memory and decreased choline acetyltransferase activity and acetylcholinesterase staining in the hippocampus. The cholinergic dysfunction and impairment of memory recovered to the normal level two weeks after cessation of the infusion of the anti-nerve growth factor polyclonal antibody. These results suggest that a deficit of nerve growth factor in the adult brain causes neuronal dysfunction.

Acetylcholinesterase↗
PubMed1993

Carcinoma of the papilla of Vater accompanied by non-invasive adenomatous component (NAC).

Surgical specimens from 40 patients with carcinoma of the papilla of Vater were submitted to histopathological analysis of tumor. The lesions were divided into two groups: non-invasive adenomatous component (NAC)-positive carcinoma and NAC-negative carcinoma. NAC was observed in 44% of our series. The incidence of the NAC-positive carcinoma declined with advancing cancer stage, but there was no significant relationship between the tumor size and the presence of NAC. NAC was shown to co-exist in 65% of tumor-forming type carcinomas, 0% of ulcerating type and 38% of the mixed type. The NAC-negative carcinoma invaded or metastasized to the pancreas, duodenum, lymph nodes or veins more frequently than NAC-positive carcinoma. Five year survival rates of patients with NAC-positive and NAC-negative carcinomas were 78% and 21%, respectively (p < 0.01). Patients with NAC-positive carcinoma, most of which were detected preoperatively by endoscopic biopsy, underwent a standard pancreatoduodenectomy with Level 1 lymph node (peripancreatic) dissection. It is considered that pylorus and duodenal bulb-preserving pancreatoduodenectomy is an alternative for patients with localized lesion, while patients with NAC-negative carcinoma should be treated by performing pancreatoduodenectomy together with extended lymph node dissection.

Adenoma↗
PubMed1993

Different distribution of CA19-9 in carcinomas arising in the papilla of Vater. An immunohistochemical study.

The origin and pathogenesis of the carcinoma of the Vater's papilla were estimated by immunohistochemically analysing the distribution of CA19-9 in the tumor tissue. The material comprised surgical specimens from 29 patients with carcinoma of the Vater's papilla, 15 with carcinoma of the pancreas, 24 with carcinoma of the bile duct and two with carcinoma of the duodenum. A non-invasive adenomatous component (NAC) was shown to coexist with carcinoma of the Vater's papilla in 14 patients. Besides, normal papilla of Vater from ten autopsy cases were added as control. The presence of CA19-9 in the tissue was demonstrated by ABC method using a monoclonal antibody. The epithelia of normal pancreatic and bile ducts showed diffuse distribution of CA19-9, while at the common channel and the orifice of the papilla it was partially distributed. CA19-9 was not demonstrated in the duodenum. The NAC-positive carcinoma of the papilla of Vater showed partially distributed CA19-9. In contrast, NAC-negative carcinoma of the Vater's papilla and carcinomas of the pancreas and bile duct showed diffuse distribution of CA19-9. Moreover, the level of serum CA19-9 in most of the patients with NAC-positive carcinoma of Vater's papilla remained within the normal limit, while in patients with NAC-negative carcinoma, or with carcinoma of the pancreas or bile duct, the level was higher. Thus it was speculated that NAC-positive carcinoma of Vater's papilla may arise from the common channel, the orifice of the papilla, or the duodenum acquiring antigenicity against CA19-9 during the cancer development. On the other hand, NAC-negative carcinoma of the Vater's papilla may originate from the pancreatic or bile ducts.

Ampulla of Vater↗
PubMed1993

Impairment of learning and memory and the accessory symptom in aged rat as senile dementia model (3): Oral administration of propentofylline produces recovery of reduced NGF content in the brain of aged rats.

The relationship between nerve growth factor (NGF) and senile dementia of the Alzheimer type is of interest. The administration of NGF in clinical trials has been expected; however, NGF cannot cross the blood brain barrier, since it is a polypeptide. We demonstrate here that oral administration of propentofylline, a stimulator of NGF synthesis in vitro, produced recovery of reduced NGF content. In aged rats (24-months-old), NGF content in the frontal cortex, parietal cortex, and hippocampus was lower than in young rats (8-weeks-old). Twenty-one-day successive administration of propentofylline (10 and 25 mg/kg, p.o.) produced recovery of reduced NGF content in the frontal cortex and parietal cortex of aged rats to a significant extent. There were no differences among aged, young, and propentofylline-treated groups in choline acetyltransferase activity in any brain regions. These results suggest that NGF content in the brain is reduced in aged rats and that oral administration of propentofylline leads to a recovery of this reduction.

Administration, Oral↗
PubMed1992

Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain.

Denervation of dopaminergic neurons by intra nigral injection of 6-hydroxydopamine (6-OHDA) increased nerve growth factor (NGF) content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. The decreased dopamine content produced in the striatum by 6-OHDA injection was not recovered during the observation period. These results suggest that dopaminergic neuron damage may affect NGF synthesis.

Animals↗