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Biomedical subjects

H Hatanaka

Publications and source records attributed to H Hatanaka.

At least 253 records · Page 14Linked to original sources

[Transplant-induced recovery from 6-OHDA lesions of the nigro-striatal dopamine neurons in mice].

Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. Our study established that unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal-dopamine (DA) neurons produced a well-characterized functional asymmetry in the behavior of C57BL/6 (H-2b) mice. The intraperitoneal administration of methamphetamine induced ipsilateral rotation at 7-20 turns/min. 11 x 10(6) syngenic DA-rich cells of embryonic ventral mesencephalon were stereotaxically transplanted in the caudate-putamen. A complete recovery of methamphetamine-induced rotational response was produced around the 60-th day after the syngenic cell suspension graft. And a complete compensation of the rotational response was also brought about with the DA-rich cells from embryonic ventral mesencephalon (crown-rump length; 10-13 mm) of allogenic C 3 H/HeN (H-2k) mice. The FACS IV analysis revealed no H-2 (Kk and Iak) antigens before transplantation of these embryonic cells. Immunohistochemistry showed that the dopaminergic fibers had grown predominantly into the ipsilateral caudate-putamen. These results provide evidence of integration of syngenic and allogenic grafts and host tissue. And the immunological response in the transplanted brain are under investigation.

Animals↗

[Boron-neutron capture therapy in brain tumors and other cancers--a radiosurgery].

If a certain means enables a selective loading of tumor cells with a stable isotope of boron-10, the tumor tissue can be selectively destroyed when the tumor-containing organ is exposed to slow neutron beams as the result of intracellular heavy particle radiations which arise from boron-10 atoms in the neutron capture reactions. An early clinical trial in the U.S.A. was discontinued after the 1953-1961 series, but the clinical trial resumed in Japan in 1968 has so far treated almost 90 patients with malignant brain tumors. The longest surviving patient has lived 16 years, and two others have lived 10 years. A median survival of 2 years was obtained with 12 patients with grade III - IV gliomas which had been within 6 cm from the cortical surface. This success has caused a reassessment of this therapy throughout the world, and there is an internationally concerted effort is going on in most countries with advanced technology. Application of this therapy to other incurable cancers, such as those of the liver, pancreas, skin and even of the bone-marrow is being sought.

Animals↗

Septal cholinergic neurons from postnatal rat can survive in the dissociate culture conditions in the presence of nerve growth factor.

The survival effect by nerve growth factor (NGF) on the cholinergic neurons of postnatal rat septal neurons in culture was examined. When the septal neurons from 10 to 12-day-old rats were cultured without NGF, the activities of choline acetyltransferase gradually decreased during the period of cultivation. The addition of NGF to the culture prevented the decline of activities. And, the number of acetylcholinesterase-positive neurons in culture with NGF was found to be more than that without NGF, after 5 days in culture. These results suggest that NGF promotes the survival of septal cholinergic neurons from postnatal rats in culture.

Acetylcholinesterase↗

[The effects of carbamylation of hormones on their biological activities--with reference to 3,5,3'-L-triiodothyronine and insulin].

It has been demonstrated that the binding of cyanic acid, formed from urea which is increased in renal failure, to hemoglobin (Hb) results in the formation of HbA1. The combination of Hb and cyanic acid is called carbamylation, a nonspecific reaction between protein and cyanic acid. It is theoretically considered that like glycation, carbamylation may occur between cyanic acid and not only Hb but also various peptides and proteins. In the present study, hormones were subjected to carbamylation, and the effects of carbamylation on the biological activity of the hormones, i.e. 3,5,3'-L-triiodothyronine (T3) and insulin, were investigated. Carbamylated T3 and carbamylated insulin were synthesized in vitro, using KCNO. The carbamylated hormones were isolated by high-performance liquid chromatography (HPLC). The biological activities of carbamylated T3 and carbamylated insulin were assayed by employing the metamorphosis of tadpoles (Rana nigromaculata) and the glucose oxidation of fat cells or the receptor binding capacity of rat hepatocytes, respectively. The biological activity of carbamylated T3 was less than about 1/13 of that of T3, and the binding activity of carbamylated insulin was 1/5 of that of insulin. Therefore, carbamylation of hormones may be an important factor in the analysis of clinical conditions, especially the endocrine condition in renal failure.

Animals↗

Binding characteristics of [3H]opioid ligands to active opioid binding sites solubilized from rat brain membranes by glycodeoxycholate and NaCl: the recovery of binding activity by dilution.

This paper describes the binding properties of [3H]peptidergic opioid ligands to binding sites solubilized from rat brain membranes by the treatment with 0.125% sodium glycodeoxycholate and 1 M NaCl. The highest amount of the specific binding of [3H]-[D-Ala2-, Met5]enkephalinamide was obtainable when 10-fold diluted solubilized preparations were incubated in the presence of 0.1 mM MnCl2 and 100 mM NaCl at 0 degree C (on ice) for 3 h. With this assay condition, the significant binding of following [3H]opioid ligands, which have been thought to be selective for receptor types, was also observed: [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin (mu-type), [3H]-[D-Ala2, D-Leu5]enkephalin (delta-type) and [3H]dynorphin1-9 (kappa-type). The number of binding sites in solubilized preparations for each [3H]ligand corresponded to 40-50% recovery of original membrane-bound binding sites. The Scatchard plot of the concentration-saturation binding curve showed only one class of binding sites, with a high affinity for each [3H]ligand. Apparent dissociation constants between solubilized receptors and [3H]ligands were the same as membrane-bound ones, but the ligand specificity for each receptor-type, which was examined by binding inhibition tests with unlabeled ligands, decreased. Present results indicate that heterogeneous opioid receptors in rat brain membranes seem to be transformed into less heterogeneous forms through the treatment with glycodeoxycholate and NaCl and the dilution process.

Animals↗

Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics.

There is increasing agreement about the atherogenicity of intermediate density lipoprotein (IDL). In order to determine whether normocholesterolemic diabetics are at a higher risk of atherosclerosis, cholesterol concentrations in three subclasses of triglyceride-rich lipoprotein fraction (Sf 12-400) were examined. Their plasma triglyceride and cholesterol levels were limited to below 150 and 250 mg/dl, respectively. They were divided into 3 groups according to their treatment: insulin injection (group I), sulphonylurea (group S) and diet alone (group D). Age-matched healthy normolipidemic non-obese subjects served as controls (group C). Triglyceride-rich lipoproteins were separated by ultracentrifugation: very low density lipoprotein (VLDL), Sf 60-400; intermediate density lipoprotein (IDL1), Sf 20-60; IDL2; Sf 12-20. Cholesterol concentrations in total plasma, VLDL, IDL2 and high density lipoprotein (HDL) were all identical in every group. A significant increase in cholesterol concentration was found in IDL1 of groups S and D. Low density lipoprotein-cholesterol of group I was also increased. These findings indicate an increased risk factor in normolipidemic diabetics.

Adult↗

Accelerated glycation of the aorta in diabetic rats.

Glycation of the aorta in rats with streptozotocin-induced diabetes was estimated by determining the early-stage product and the advanced product of the Maillard reaction. The early-stage product of the Maillard reaction was determined using furosine, which is derived from glycated lysine residues by acid hydrolysis. The advanced product was determined by fluorescence high-performance liquid chromatography. The levels of both early-stage and advanced products in diabetic rats were significantly higher than those in non-diabetic rats at the age of both 20 and 50 weeks. The levels of both early-stage and advanced products at 50 weeks in rats tended to be higher than those at 20 weeks. However, the level of glycated hemoglobin in both non-diabetic and diabetic rats showed no significant change between 20 and 50 weeks of age. These results suggest that tissue glycation may be involved in the development of diabetic complications and may be related to the aging mechanism.

Animals↗

Carbamylation of insulin and its biological activity.

A nonspecific binding reaction between cyanic acid formed from urea and protein or peptide is called carbamylation. In the present study, insulin, a peptide hormone, was subjected to carbamylation and the activity of carbamylated insulin was determined. Both immunological and biological activities of insulin changed on carbamylation. The decrease in biological activity in respect to glucose oxidation of fat cells or receptor-binding capacity of rat hepatocytes was greater than that in immunological activity.

Adipose Tissue↗

FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.

FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin.

Animals↗

FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.

Animals↗

The formation of new neuronal circuit between transplanted nigral dopamine neurons and non-immunoreactive axon terminals in the host rat caudate nucleus.

Using immunoelectron microscopic techniques, whether or not host neuronal elements newly form synaptic contact with the grafted dopamine (DA) neurons in the caudate nucleus of the rat with unilateral lesion in the nigrostriatal DA pathway was examined. Tyrosine hydroxylase (TH) was used as a marker for DA-containing structures. Motor imbalances after the lesion and before or after the transplantation were assessed by the amount of circlings after the injection of Met-amphetamine. In animals which recovered well from motor imbalance, non-immunoreactive axon terminals made synaptic contact with grafted TH-positive cell bodies and their dendrites. Since the incidence of these synapses was quite low in poorly recovered animals, the formation of a new neuronal circuit may be one of the important bases for behavior recovery.

Animals↗

Estrogen treatment enhances survival of cultured fetal rat amygdala neurons in a defined medium.

Effects of estradiol on the survival of cultured fetal rat amygdala neurons were estimated to assess a possible organizational action of the sex steroid on the developing amygdala tissue. Dissociated 17-day fetal amygdala cells were cultivated initially in a serum-containing and then in a serum-free defined medium. The survival of the cells in the serum-free medium was highly enhanced when supplemented with estradiol at the concentration of 10 ng/ml. Predominant cell populations of the culture were identified as neuronal cells by the tetanus toxin labeling method. The results support the idea that sex steroids play a role in the brain sexual differentiation by enhancing the neuronal survival in the developing amygdala tissue.

Amygdala↗