Search PubMed⌕ Search

Biomedical subjects

H Hatanaka

Publications and source records attributed to H Hatanaka.

At least 235 records · Page 13Linked to original sources

Neuropeptide Y-immunoreactive neurons receive synaptic inputs from dopaminergic axon terminals in the rat neostriatum.

Double immunocytochemistry using peroxidase-antiperoxidase and protein A-gold was performed to determine whether neuropeptide Y (NPY) immunoreactive neurons receive synaptic inputs from catecholaminergic axon terminals in the rat neostriatum. Tyrosine hydroxylase-immunoreactive axons were found to be in synaptic contact with the somas and proximal dendrites of NPY-immunoreactive neostriatal neurons. These latter neurons were medium-sized and had indented nuclei, and thus were thought to be medium aspiny interneurons. Thus nigrostriatal dopaminergic neurons may monosynaptically influence striatal NPY neurons.

Animals↗

Nerve growth factor promotes survival of cultured magnocellular cholinergic neurons from nucleus basalis of Meynert in postnatal rats.

One of the possible causes of Alzheimer's disease is thought to be a lack of nerve growth factor (NGF), which plays an important role in the neuronal differentiation and cell survival of basal forebrain cholinergic neurons. In the present study, we report for the first time a direct in vitro effect of NGF on the survival of magnocellular cholinergic neurons of the nucleus basalis of Meynert. A dissociated culture of cholinergic neurons was prepared after dissecting out the nucleus from vibratome slices of postnatal rat forebrain. After culturing the neurons of this nucleus from 2-week-old rats for 6 days, the cell number of viable acetylcholinesterase-positive cholinergic neurons in the presence of NGF was found to be greater than that in the absence of NGF. Also, more extensive and denser acetylcholinesterase-positive neurites were observed in the NGF-treated culture. Higher activities of choline acetyltransferase were also observed in the NGF-treated culture. Cellular choline acetyltransferase activity, which was calculated by dividing the enzyme activity by the viable number of acetylcholinesterase-positive neurons for each well, was almost the same with or without NGF. These results mean that NGF enhanced cholinergic neuronal survival and cholinergic neurite regeneration, but did not induce cellular choline acetyltransferase activities.

Acetylcholinesterase↗

Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats.

Nerve growth factor (NGF), a well-characterized target-derived growth factor, has been postulated to promote neuronal differentiation and survival of the basal forebrain cholinergic neurons. In the present paper, we demonstrate that a developmental change in NGF action occurs in postnatal rat basal forebrain cholinergic neurons in culture. Firstly, NGF acts as maturation factor by increasing choline acetyltransferase (ChAT) activity and acts later as a survival factor. In dissociated cell cultures of septal neurons from early postnatal (P1-4) rats, ChAT activities were increased by the addition of NGF. That is, ChAT activities in P1 septal cells cultured for 7 days was increased 4-fold in the presence of NGF at a concentration of 100 ng/ml. However, the number of the acetylcholinesterase (AChE)-positive neurons was not significantly different between these groups. In contrast, septal neurons from P8 to P14 rats showed different responses to NGF. Although the P14 septal neurons in culture for 7 days without NGF lost about half of the ChAT activity during a 7-day cultivation, cells cultured with NGF retained the activity at the initial level. The number of AChE-positive neurons counted in cultures with NGF was much greater than the number without NGF. These results suggest that, during the early postnatal days, the action of NGF on the septal cholinergic neurons in culture changes from induction of ChAT activity to the promotion of cholinergic neuronal cell survival. During this developmental period in vivo, septal neurons are terminating their projections to the hippocampal formation. Similar NGF-regulated changes in cholinergic neurons were observed in cultured postnatal neurons from vertical limb of diagonal band. An analogy has been pointed out between the neuronal death of the basal forebrain cholinergic neurons and a similar neuronal death in senile dementia, especially Alzheimer's type. The work reported here might present a possibility that NGF could play a role in preventing the loss of the basal forebrain cholinergic neurons in this disease.

Acetylcholinesterase↗

Experience of boron-neutron capture therapy for malignant brain tumours--with special reference to the problems of postoperative CT follow-ups.

Boron-neutron capture therapy (BNCT) is theoretically a highly selective treatment of infiltrating tumours, in that the tumoricidal heavy particle radiation is limited to a sphere of 10 microns around a tumour cell which is loaded with non-radioactive boron-10 atoms. There were 73 gliomas among the 83 cases treated by boron-neutron capture therapy. For grade III-IV cerebral gliomas, 5 and 10 year survival rates were an unimpressive 19 and 10% respectively. This was the result of technical problems such as unsatisfactory reactors and inadequate craniotomies for the majority of the patients. If the analysis was limited to those whose tumours had been irradiated with more than 2.5 x 10(12) neutrons/cm2 (yielding more than 3,000 rem or more), the 5 and 10 year survival were almost 100 and 50%. The longest surviving glioblastoma (grade IV) patient has lived in a satisfactory manner for the past 15 years. For the cases who had been treated with borderline doses (lethal or sublethal), interpretation of the postoperative CTs was frequently intriguing. Several cases had to undergo re-opening and occasionally even another BNCT, only to find no viable tumour tissue. Death occurred in some, either due to discontinuation of supportive treatments by local physicians, or due to excessive therapies by the author directly involved in the patient's care, both of whom had erroneously believed in recurrence. At autopsy, residual tumour cells were recognized only in the areas where the above-mentioned neutron fluence had not been delivered at the time of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A study of the age-related acceleration of glycation of tissue proteins in rats.

The relationship between age-related glycation and a fluorescent product attributable to the advanced Maillard reaction was investigated in the aortas of rats between 4 and 120 weeks of age. The early-stage product of the Maillard reaction was measured using furosine (epsilon-N-(2-furoylmethyl)-L-lysine) as a marker. The advanced product was measured by fluorescence high-performance liquid chromatography. The level of furosine in the aorta increased with aging to reach a maximum value in rats of 50 to 70 weeks of age, and decreased in rats from 90 to 120 weeks of age. By contrast, the level of the putative advanced product reached a maximum in 90-week-old rats and remained at the maximum level in 120-week-old rats. The level of glycated hemoglobin showed no significant change in rats of more than 14 weeks of age. The advanced Maillard products may play an important role in the pathophysiology of aging arteries.

Aging↗

The appearance of a highly digitalis-sensitive isoform of Na+,K+-ATPase during maturation in vitro of primary cultured rat cerebral neurons.

Immature neurons from the cerebra of 17-day rat fetuses were cultured, and changes in Na+, K+-ATPase activity of the cells were investigated during maturation in culture. The Na+, K+-ATPase activity of the particulate fraction from the cells increased during the course of culture, up to 0.38 +/- 0.01 (mumol/min/mg protein) (= 8.25 +/- 0.85 (mumol/min/mg DNA] by day 13 in culture. The values were more than 3 and 19 times those of the 17-day fetal cerebrum on the bases of protein and DNA, respectively. The enzyme in the immature neurons was mainly a weakly digitalis-sensitive form in terms of the inhibition pattern of the Na+,K+-ATPase activity by strophanthidin. Along with the maturation in vitro of the neurons, a highly digitalis-sensitive form of the enzyme was shown to appear and increase by the biphasic inhibition patterns of Na+,K+-ATPase activity by strophanthidin and of K+ uptake activity by ouabain. The enzyme activity of the highly sensitive form overwhelmed that of the weakly sensitive form by day 13 in culture. In cultured rat cerebral astrocytes, the enzyme was judged to be only the weakly digitalis-sensitive form from the simple inhibition patterns of the Na+,K+-ATPase and K+ uptake activities by digitalis.

Brain↗

Nerve growth factor increases the intracellular content of acetylcholine in cultured septal neurons from developing rats.

The effects of nerve growth factor (NGF) on the intracellular content of acetylcholine (ACh) in cultured septal neurons from developing rats have been examined. The content of ACh could be measured by using HPLC and electrochemical detection (HPLC-ECD), coupled with an immobilized enzyme column. This method of determination is very simple and rapid, and is highly sensitive. The content of ACh and the activity of choline acetyltransferase (ChAT) in cultured postnatal day 1 (P1) septal neurons grown on an astroglial "feeder" layer was increased during the period of cultivation by the addition of NGF. The activities of ChAT and the content of ACh increased in a dose-dependent manner in direct relationship to the different amounts of NGF employed. These effects of NGF, i.e., elevating the intracellular content of ACh, accompanied by an increase in activity of ChAT, also were confirmed in the P1 septal organotypic cultures. Additionally, embryonic day 17 (E17) septal neurons in a serum-free medium displayed a similar responsiveness to NGF with respect to the elevation in the content of ACh and the increase in activity of ChAT. These results suggest that intracellular levels of ACh are likely to be regulated by NGF in a fashion similar to that of the activity levels of the biosynthetic enzyme.

Acetylcholine↗

Nerve growth factor induces Na+,K+-ATPase in a nerve cell line.

The effects of nerve growth factor (NGF) on induction of Na+,K+-ATPase were examined in a rat pheochromocytoma cell line, PC12h. Na+,K+-ATPase activity in a crude particulate fraction from the cells increased from 0.37 +/- 0.02 (n = 19) to 0.55 +/- 0.02 (n = 20) (means +/- SEM, mumol Pi/min/mg of protein) when cultured with NGF for 5-11 days. The increase caused by NGF was prevented by addition of specific anti-NGF antibodies. Epidermal growth factor and insulin had only a small effect on induction of Na+,K+-ATPase. A concentration of basic fibroblast growth factor three times higher than that of NGF showed a similar potency to NGF. The molecular form of the enzyme was judged as only the alpha form in both the untreated and the NGF-treated cells by a simple pattern of low-affinity interaction with cardiotonic steroids: inhibition of enzyme activity by strophanthidin (Ki approximately 1 mM) and inhibition of Rb+ uptake by ouabain (Ki approximately 100 microM). As a consequence, during differentiation of PC12h cells to neuron-like cells, NGF increases the alpha form of Na+,K+-ATPase, but does not induce the alpha(+) form of the enzyme, which has a high sensitivity for cardiotonic steroid and is a characteristic form in neurons.

Adrenal Gland Neoplasms↗

Capillary permeability and boron distribution in ethylnitrosourea-induced rat glioma.

The vasculature and capillary permeability of gliomas induced by ethylnitrosourea in Sprague-Dawley rats were studied with horseradish peroxidase and Evans blue dye. The distribution of the boron-10 compound, Na2(10)B12H11SH, which is now in clinical use for boron neutron capture therapy (BNCT) for brain tumors, was investigated quantitatively using neutron-induced alpha-autoradiography. The vasculature and the degree of capillary permeability varied widely, depending mainly on the size of the glioma, and were often heterogeneous even in the same tumor. The distribution of boron-10 also varied, correlating to capillary permeability. The boron-10 concentration and the tumor:blood concentration ratio in large and medium-sized gliomas were adequate for successful BNCT. This study suggests that the vasculature and capillary permeability of the target brain tumor exert an important influence on the therapeutic efficacy of BNCT.

Animals↗

FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. I. Taxonomy of the producing strain.

A new subspecies of the genus Streptomyces, the proposed name of which is Streptomyces hygroscopicus subsp. yakushimaensis subsp. nov., is described. Soil isolate, strain No. 7238, produces the novel immunosuppressants, FR-900520 and FR-900523. The organism is characterized by its gray aerial mycelium color, hygroscopic spore mass and spiral spore chains with warty or spiny spore surfaces. It is nonchromogenic. Strain No. 7238 shows characteristics most closely related to Streptomyces antimycoticus and S. hygroscopicus, although there are differences in physiological characteristics and carbohydrate utilization. In terms of morphological characteristics, strain No. 7238 is different from S. antimycoticus, but resembles S. hygroscopicus. The differences are not sufficient to establish a new species. It would be most suitable to designate strain No. 7238 as a new subspecies within the species of S. hygroscopicus.

Immunosuppressive Agents↗

FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics.

FR-900520 and FR-900523, novel neutral macrolide immunosuppressants, were isolated from the cultured broth of Streptomyces hygroscopicus subsp. yakushimaensis No. 7238. Their molecular formulae were determined as C43H69NO12 and C42H67NO12, respectively. The compounds suppressed immune response in vitro. IC50 values of FR-900520 and FR-900523 for mouse mixed lymphocyte reaction were 0.55 nM and 1.6 nM, respectively. FR-900520, the major component, clearly prolonged skin allograft survival in rats.

Animals↗

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

FR65814, a novel immunosuppressant, was isolated from the cultured broth of Penicillium jensenii F-2883. The structure was assigned to be 5,6-dihydroxy-4-(1,2-epoxy-1,5-dimethyl-4-hexenyl)-1-oxaspiro++ +[2,5]octane by spectroscopic analyses. The compound suppressed the immune response at low concentration. In addition, a structually related component fumagillol, a known carcinolytic agent, was also isolated and found to show immunosuppressive activity.

Animals↗