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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 865 records · Page 48Linked to original sources

Central action of endogenous sugar acid (2-buten-4-olide): comparison with local anesthesia in hypothalamus.

Rats were trained to discriminate cue tone stimuli (CTS) predicting reward (CTS+) [juice or intracranial self-stimulation (ICSS)], or aversion (CTS-) (mild electric shock or tail pinch). Unit activity in the lateal hypothalamus (LHA) and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during CTS learning. The effects of local anesthesia of the amygdala (AM), ventral tegmental area (VTA) or LHA by procaine hydrochloride, and the effects of intraperitoneal or intravenous 2-buten-4-olide (2-B4O) on LHA neural activity and licking behavior were compared. LHA neurons differentiated between rewarding and aversive stimuli, and acquired corresponding discrimination of CTS+ and CTS-. In the lPOA-AHA, neurons responded similarly to CTS+, rewarding stimuli, CTS- and aversive stimuli. Procainization of the AM suppressed LHA neural responses to CTS1+ predicting juice, and stopped licking for juice. Procainization of the VTA suppressed LHA neural responses to CTS2+ predicting ICSS, and stopped licking for ICSS. LHA procainization suppressed both licking for juice and ICSS. Both intraperitoneal and intravenous 2-B4O stopped licking for juice and ICSS, but did not influence LHA responses to CTS1+ or CTS2+. The results suggest that dynamic interaction of AM-LHA-VTA are important for CTS+ learning, and 2-B4O acts directly on LHA neurons while maintaining afferent sensory inputs to the LHA.

4-Butyrolactone↗

Action of neurotropin on rat hypothalamic neurons in tissue slices.

To clarify some of the actions of Neurotropin (NSP), intra- and extracellular measurements were made of 140 paraventricular (PVN) and 48 ventromedial nucleus (VMH) neurons in rat hypothalamic tissue slices in vitro while perfusing NSP, an extract from the inflamed skin of rabbits inoculated with vaccinia virus, through the recording chamber. NSP mostly decreased activity in PVN neurons (inhibition, 46; excitation, 27; excitation-inhibition, 5; no response, 62), and mostly increased it in VMH neurons (excitation, 12; inhibition, 3; no response, 33). Inhibition of PVN neurons by NSP was due to hyperpolarization with no change in membrane conductance. Since ouabain antagonized the NSP-induced inhibition of PVN neurons, the effect was probably due to activation of the sodium pump. Activity of some NSP-responsive PVN neurons was increased by increase of extracellular osmolarity, and activity of some NSP-responsive VMH neurons was increased by glucose application. The results suggest central modulation of autonomic or neuroendocrinological function by distinct NSP influence on PVN and VMH neural activity.

Action Potentials↗

Dopamine and ACh involvement in plastic learning by hypothalamic neurons in rats.

Unit activity in the rat lateral hypothalamus (LHA) was recorded during discrimination learning of cue tone stimuli (CTS). CTS+ predicted reward (glucose or intracranial self-stimulation); CTS- predicted aversion (electric shock or tail pinch); and all behavior responses were by the same act, licking. Roles of the LHA dopaminergic and cholinergic systems in CTS learning were investigated by electrophoretic application of dopamine (DA) and acetylcholine (ACh), and their antagonists. The CTS+, the predicted reward and DA, all had similar effects (inhibition) on many LHA neurons; and these were all opposite to the effects (excitation) of CTS-, the predicted aversion, and ACh. Neural responses to CTS+ were blocked by spiperone, and responses to CTS- were blocked by atropine. Sensitivity of LHA neurons to DA was reduced by extinction of CTS+ learning for reward, and sensitivity to ACh was reduced by CTS- learning for aversion. The data suggest that afferent DA and ACh inputs to LHA neurons are essential for plastic CTS+ and CTS- learning.

Acetylcholine↗

Activity and distribution of learning-related neurons in monkey (Macaca fuscata) prefrontal cortex.

The involvement of monkey (Macaca fuscata) prefrontal cortex (PFC) neurons in motor output decisions was studied by recording single neuron activity during 3 tasks: (a) go-left, go-right, or no-go decisions, (b) operant bar press feeding based on discrimination of food and nonfood, and (c) either delayed matching-to-sample (DMS) or DMS with response delay. Combinations of single neuron responses during the 3 tasks suggested 7 types of PFC neurons that were related to attention, choice, task-unique memory, reward anticipation, laterality, initiation of movement, and suppression of movement. The authors suggest that responses of PFC neurons do not depend on physical properties of the stimuli, but on their behavioral significance. PFC neurons might be important for appropriate behavior in response to external stimuli and internal or motivational factors.

Animals↗

Percutaneous fiberoptic spinal laser endoscopy.

For percutaneous observation of lesions near the spinal cord and percutaneous spinal laser surgery under the visual field, we studied a method and approach to the spinal cord and intraspinal surgical procedures with laser using a newly developed, small-diameter laser endoscope. The subarachnoid and epidural spaces of a goat were punctured using a 17-gauge epidural needle, and the endoscope (diameter 0.7 mm) was inserted through the needle. The spinal cord and surrounding tissue were observed. Next, an endoscope (diameter 1.5 mm) was inserted into the subarachnoid space, and the quality of the picture and manageability of the endoscope were examined. The Xe:Cl excimer laser was irradiated to a nerve root through a 0.4 mm optical fiber for laser transmission through this endoscope. The spinal cord, nerve roots, and arachnoid were clearly observed through this endoscope. The pulsation of the artery accompanying a root was seen clearly, and the quality of the picture of the endoscope was thought to be sufficient for diagnosis. The nerve root was cut within 30 seconds by excimer laser, and the possibility of laser surgery was demonstrated. Although it was shown that this endoscope could be a useful diagnostic and therapeutic tool, improvement in the manageability of the tip of the endoscope was considered to be important for a clinically usable endoscope.

Animals↗

Mn K-edge XANES spectroscopy of a photosynthetic O2-evolving complex. High-quality pre-edge features and distinct fine structures in the S1- and S2-states.

High-resolution XANES (X-ray Absorption Near Edge Structure) spectroscopy for Mn in the S1 and S2 states of the spinach photosynthetic O2-evolving complex revealed distinct features in K-edge spectra, when a high signal-to-noise (S/N) ratio of ca. 80 with a low and constant background-to-signal (B/S) ratio of 0.15 to 0.18 was attained. Six features resolved in each S-state spectrum involve a pre-edge feature due to 1s----3d transitions, a main-edge feature possibly due to 1s----4s transitions and four fine structures superimposed on the principal absorption bands due to 1s----4p* transitions. The high-quality pre-edge features were analyzed according to a parametric ligand-field theory in comparison with those of some typical authentic Mn complexes. It was deduced that i) all of the four Mn ions in the S1-state are octahedrally coordinated and two of them constitute a di-mu-oxo bridged Mn(III, III) dimeric subunit; ii) the bridged Mn(III) ions are further bridged by a deprotonated water dimer, (HOHOH)-, and coordinated by imidazole-N and carboxylate-O- on the opposite side of the Mn atom from the di-mu-oxo bridge; iii) the other two Mn ions exist in the form of Mn(III) monomeric subunits; and iv) upon the S1----S2 transition, only the bridged Mn(III,III) is oxidized to Mn(III,IV). The distinct change in the principal absorption band shape upon the S1----S2 transition is briefly discussed to obtain the XANES evidence for a tetrameric Mn-cluster.

Cell Membrane↗

Basal cell carcinoma originating from an epidermoid cyst.

Basal cell carcinoma (BCC) originating from an epidermoid cyst which existed for about 50 years was seen in a 78-year-old Japanese male. Nests of basal cell carcinoma were connected with the epidermoid cyst, partially replacing the cyst wall.

Aged↗

Anticonvulsant syndrome with multiple symptoms, including porphyria, IgA deficiency, and liver dysfunction.

A 19-year-old Japanese female who had been treated for epilepsy with a combined phenytoin-phenobarbital preparation for the past three years presented with increasing skin pigmentation and hirsutism. She had suffered two attacks of loss of consciousness after bilateral partial oophorectomy at the age of 16. Investigations revealed a marked increase in coproporphyrin levels in the urine and feces, a marked decrease in her serum IgA level, and liver dysfunction. All these manifestations gradually improved upon the withdrawal of her antiepileptic treatment. In vitro studies revealed B cell dysfunction producing IgA deficiency, which normalized within one year after discontinuation of the antiepileptic therapy. It was assumed that her treatment had worsened preexisting porphyria, which was misdiagnosed as epilepsy because of abnormal EEG findings. The type of porphyria appeared to be hereditary coproporphyria, despite the lack of a family history.

Adult↗

Effects of growth factors and hormones on growth and morphological differentiation of human breast epithelial cells within collagen gel in serum-free medium.

When human epithelial cells that had grown out from either carcinoma or histologically non-malignant breast tissues were seeded within type I collagen gels in serum-free medium, they successively grew and protruded many radial duct-like extensions with lumina. Separate deletion of each of the supplements from the medium showed that growth as well as morphological differentiation of carcinoma-derived cells were prevented in the absence of epidermal growth factor (EGF) or hydrocortisone. Removal of insulin or ethanolamine plus phosphoethanolamine caused a significant inhibition of cell growth without interfering with the morphological differentiation. Contrary to the case with carcinoma-derived cells, both growth and morphological differentiation of epithelial cells derived from non-malignant breast tissues were prevented when EGF, hydrocortisone or insulin was absent. Removal of each of the other supplements (except for transferrin), including ethanolamine plus phosphoethanolamine, prolactin, or prostaglandin, caused a significant inhibition of cell growth with no apparent inhibition of morphological differentiation. The present results suggest that human epithelial cells derived from either carcinoma or histologically non-malignant breast tissues strongly depend on the presence of EGF and hydrocortisone and there is a decreased dependence on insulin in carcinoma-derived cells with respect to their growth and morphological differentiation during culture within collagen gels.

Alprostadil↗

Changes of DNA methylation level during pre- and postnatal periods in mice.

DNA methylation in an adult mammalian body shows tissue-specificity. But when and how the specificity is established in the process of development has not yet been elucidated. Here we have investigated age-dependent changes in the amount of 5-methyldeoxycytidine (5mdC) that DNA of various mouse tissues contains during the late-fetal and postnatal periods, using high-performance liquid chromatography. The tissue-specificity in the 5mdC level was observed in the late-fetal stage, and the level continued to change during the subsequent periods. The most pronounced alterations were observed in brain and liver, where similar biphasic changes were seen, but at different ages. At maturation, the 5mdC levels were high in thymus, spleen and brain, intermediate in lung, and low in liver and sperm. The data demonstrate the importance of the peri- and postnatal periods in establishment of tissue-specificity in 5mdC content.

Aging↗

[HTLV-I associated interstitial pneumonia--a case report and bronchoalveolar lavage study].

A 70-year-old male was admitted to our hospital because of fever and dyspnea. The patient was seropositive for HTLV-I and ATL cells were seen in the peripheral blood in the percentage of 2-5. The proviral DNA was positive and the diagnosis of smoldering ATL was made. His chest X-ray film showed diffuse reticulo-nodular infiltrates in both lung fields. The lung tissue obtained by transbronchial lung biopsy showed the lymphocytic infiltrations in the alveolar septa and the submucosa of the bronchioles. Bronchoalveolar lavage (BAL) fluid showed an increased proportion of lymphocytes that consisted mainly of CD3+ DR+ cells and the CD4+/CD8+ ratio was 2.1 during exacerbation and 0.8 after steroid therapy. Anti-HTLV-I IgG and IgA antibodies were positive in both serum and BAL fluid by Western blotting method. It is suggested that T-lymphocyte alveolitis may occur in patients who are seropositive for HTLV-I and the immunological mechanism seems to be responsible.

Aged↗

Two cases of parathyroid carcinoma in patients on long-term hemodialysis.

Two cases of parathyroid carcinoma, in a 46-year-old male on maintenance hemodialysis for 135 months and a 55-year-old female on maintenance hemodialysis for 64 months were reported. In both cases, the parathyroid carcinoma showed local invasion and the other glands were hyperplasia and/or adenoma, which would support the concept of malignant transformation occurring in parathyroid hyperplasia. The concurrence of parathyroid carcinoma with hyperplasia and/or adenoma is a pertinent feature in patients on maintenance dialysis, although it is rare in primary parathyroid carcinoma.

Female↗

Cytoskeleton in human mammary carcinoma cells forming three-dimensional cellular structures within collagen gels.

Human mammary carcinoma cell line MCF-7 cells grown on type I collagen gels floating in a medium occasionally invaginated into the gels as a cell mass and formed cylindrical or domed structures within it. The 0.05% Triton-insoluble cytoskeleton of such cellular structures sedimented as a white flocculent layer at the boundary between 60 and 70% sucrose layers by ultracentrifugation, and consisted of 4 basal components: 54-kD (beta-tubulin), 45-kD, 42-kD (actin), and 39-kD polypeptides. By contrast, the isolated cytoskeleton of MCF-7 cells grown as monolayers on plastic substratum formed a finer cytoskeletal network with a smaller buoyant density and consisted of two distinct polypeptides with apparent molecular sizes of 80-kD and 65-kD in addition to the 4 basal components found in the morphologically developing cells. The present results indicate that the cytoskeleton of MCF-7 cells forming the three-dimensional cellular structures within collagen gels is lacking in these two polypeptides, and that it has a coarser cytoskeletal network with a greater buoyant density than that of the monolayered cells on plastic.

Actins↗

Regulation of cytoskeletal structure in human mammary carcinoma cells MCF-7 by culture substrata.

Three-dimensional cellular structures formed by MCF-7 human mammary carcinoma cells within collagen gels were isolated with collagenase and cultivated on plastic substratum to examine whether the cytoskeleton specific for cells forming cellular structures (S-type) changes to that specific for cells grown as monolayers (M-type). The cytoskeleton isolated as 0.05% Triton-insoluble fraction from the cellular structures after culture for 1 day on plastic was exclusively S-type. However, both types of cytoskeletons were observed in the cellular structures cultivated for 7 days on plastic as well as in the cells grown as monolayers for 2 days after dissociation of the cellular structures with trypsin. By use of an antibody raised against a 65-kD polypeptide that was specific for the M-type cytoskeleton, the presence of the polypeptide was found to be restricted to the cells grown out as monolayers from the edge of the cellular structures. In the cells grown for 2 days as monolayers, a mixture of cells both having and lacking the polypeptide was observed. After a 7-day culture of the dissociated cells as monolayers on plastic, however, most of the cells had M-type cytoskeletons. The present results show that the apparent change in the cytoskeleton of MCF-7 cells from S-type to M-type does not occur in cells involved in the three-dimensional cellular structures even in the absence of collagen gels, but that it occurs in cells which are grown as monolayers for at least 7 days on plastic substratum.

Adenocarcinoma↗

A model to account for the blood-to-plasma distribution of cyclosporin A in human blood.

A mathematical model to account for the blood-to-plasma distribution of cyclosporin A (CyA) in human blood was derived, and alterations in the blood-to-plasma distribution of CyA under several influencing conditions were examined using this model. The model was derived on the assumption that there are two CyA binding sites in human blood, which exist in plasma and cellular fractions. In the plasma fraction, the CyA binding sites are mainly lipoproteins (LPs), in which CyA exhibits nonsaturable, low affinity binding with LPs independent of drug concentration. In the cellular fraction, the binding site of CyA is the CyA binding protein (CBP), in which CyA shows a specific binding in a temperature dependent, saturable process. The results obtained from simulative studies agreed with previous reports on the blood-to-plasma distribution of CyA, indicating the usefulness of this approach. And also, this model may be used to predetermine individual variations in the blood-to-plasma distribution of the drug in renal transplant patients.

Blood↗

Inhibition of testosterone biosynthesis in testicular microsomes by various imidazole drugs. Comparative study with ketoconazole.

Ketoconazole (KCZ), an imidazole-containing antimycotic, has been demonstrated to inhibit testosterone biosynthesis in man. In this study, the inhibitory activities of various imidazole drugs such as miconazole (MCZ), cimetidine (CIM), ozagrel (OZA) and its metabolites (M-1 and M-2) on the pathway of testosterone biosynthesis in testicular microsomes were compared with that of KCZ in vitro. Additionally, the changes in serum testosterone level in the patients by the treatments with MCZ were followed. KCZ inhibited 17 alpha-hydroxylase and C17,20-lyase activities in a dose-dependent manner, while it did not affect 17 beta-hydroxysteroid dehydrogenase activity. Although the patterns of the inhibitory actions and the interaction of either imidazole drugs with cytochrome P-450 as 17 alpha-hydroxylase and C17,20-lyase were similar to those of KCZ, the inhibitory potencies and affinities for the cytochrome P-450 system decreased in the order of KCZ greater than MCZ greater than OZA greater than M-2 greater than M-1 greater than CIM. At the end of the intravenous injection of 200 mg MCZ to the patients, the serum testosterone levels decreased by about 16% of the original level and then returned to the original level 5 h after the end of injection. These results indicate that either imidazole drugs tested could inhibit a cytochrome P-450 enzyme C17,20-lyase mainly in testicular microsomes, and suggest that MCZ, a potent inhibitor subsequent to KCZ, induces a slight alteration in the testosterone biosynthesis in its clinical use.

Animals↗