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Biomedical subjects

K Otsuka

Publications and source records attributed to K Otsuka.

At least 307 records · Page 17Linked to original sources

Effects of adrenoceptor agonists and antagonists on the firing of neurons in the rat A1 noradrenergic region.

Noradrenaline (NA), but not clonidine applied microiontophoretically, inhibited the firing of neurons in the rat A1 noradrenergic region, whereas intravenous clonidine dose-dependently inhibited their firing (ED50 = 18.3 micrograms/kg). The NA-induced inhibition was blocked by the beta-antagonist timolol, but not by the alpha-antagonists phentolamine or piperoxane. These results suggest that neurons in the A1 region possess beta-adrenoceptors rather than alpha-adrenoceptors near their cell bodies, and that systemically administered clonidine acts indirectly on these cells.

Adrenergic Agonists↗

Changes in isoenzyme profiles during induction of differentiation in human myelomonocytic leukemia cell lines.

The human leukemia cell lines HL-60, KG-1, KLM-2, ML-3, THP-1, and U-937 were treated with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA partially or completely inhibited the proliferative activity of the cell cultures. The number of cells with the ability to reduce nitroblue tetrazolium increased in the TPA-treated cell lines HL-60, ML-3, THP-1, and U-937, whereas the cell lines KG-1 and KLM-2 remained nitroblue tetrazolium negative. Except for KG-1 and KLM-2, all TPA-treated cell lines showed varying degrees of strong adherence to plastic surface. The carboxylic esterase, acid phosphatase, hexosaminidase, and lactate dehydrogenase isoenzyme profiles from these cell lines were analyzed by isoelectric focusing on horizontal polyacrylamide gels. The new or stronger expression of an esterase isoenzyme which is specific for monocytes-macrophages was induced in HL-60, ML-3, THP-1, and U-937 but not in KG-1 or KLM-2. The new expression of the tartrate-resistant acid phosphatase isoenzyme was induced in ML-3, THP-1, and U-937. The number of esterase and acid phosphatase isoenzymes and the staining intensity of isoenzymes characteristic for myeloid cells were increased by TPA in all cell lines. The loss of the hexosaminidase I isoenzyme which is a marker of immature hematopoietic cells was noted in KG-1, ML-3, THP-1, and U-937. TPA triggered an increase in number and staining intensity of the lactate dehydrogenase isoenzymes in all cell lines. Some isoenzymatic changes (e.g., monocyte-specific esterase, tartrate-resistant acid phosphatase, hexosaminidase I) appear to correlate with TPA-induced differentiation while other alterations in the isoenzyme patterns do not (e.g., lactate dehydrogenase, other esterase and acid phosphatase isoenzymes). Differentiation of nonmonocytoid cells appears, at the isoenzyme level, to be quite different from that of the monocytoid cell lines.

Acid Phosphatase↗

Localization of the spinal accessory motoneurons in the cervical cord in connection with the phrenic nucleus: an HRP study in cats.

The localization of the spinal accessory motoneurons (SAMNs) that innervate the accessory respiratory muscles, the sternocleidomastoid (SCM) and trapezius (TP) muscles, was identified in the cat using the horseradish peroxidase (HRP) method. In the cases of HRP bathing of the transected spinal accessory nerve (SAN), HRP-labeled motoneurons were observed ipsilaterally from the C1 to the rostral C6 segments of the spinal cord. Labeled neurons were located principally in the medial and central regions of the dorsomedial cell column of the ventral horn in the C1 segment, in the lateral region of the ventrolateral cell column in the C2-C4 segments, between the ventrolateral and ventromedial cell columns in the C5 segment and in the lateral region of the ventromedial cell column in the C6 segment. In the cases of HRP injection into either SCM or TP muscles, labeled SCM motoneurons were found in the C1-C3 segments of the spinal cord and labeled TP motoneurons were chiefly localized more caudally within the spinal accessory nucleus. The present study revealed that, in the C5 and C6 segments, the SAMNs have a very similar topographic localization to the phrenic nucleus in the ventral horn. This finding implicated the functional linkage of the SAMNs with the phrenic motoneurons in particular types of respiration.

Accessory Nerve↗

Noninvasive recording of His bundle electrograms using vectorial leads system.

His bundle electrograms were recorded in 8 rats by a signal averaging technique using the Takayasu vectorial lead system. Animals were anesthetized and placed in the prone position. The polarity of three orthogonal leads were: the X axis, from right to left; the Y axis, from top to bottom; the Z axis, from back to front. Potentials from the X, Y, and Z leads were amplified by 20,000 with high-pass 12 dB/octave filtering at 80 Hz, and signal averaging of 2000 beats was performed at a sampling interval of 100 microseconds. The His bundle potential could be clearly defined in all 8 rats. The mean amplitude of the His potential was larger in the X-axis (23.6 +/- 9.2 mu V) or the Y-axis (28.4 +/- 14.5 mu V) than the Z-axis lead (11.5 +/- 8.6 mu V). Directions of the His potential vectors were to the left in 5 of 8 rats (62.5%), to the caudal in 4 of 6 rats (66.7%), and to the dorsal site in 6 of 8 rats (75.0%). This vectorial lead system, devised in accordance with McFee and Johnston's theory on lead field, was useful for recording His bundle electrograms.

Animals↗

Influence of lesions in the limbic-hypothalamic system on metabolic response of pyruvate to daily repeated cold exposure in rabbits.

The effects of lesions of the limbic-hypothalamic structures on the pyruvate metabolic responses to daily repeated cold exposures in the liver of rabbits have been investigated. The experimental results were as follows: The metabolic pattern of pyruvate and the pyruvate metabolic responses to the 1st cold exposure (cold exposure on the 1st day) were altered by lesions of periventricular arcuate nucleus (ARC), ventromedial hypothalamus (VMH), stria terminalis (ST) and dorsal fornix (FX). The pyruvate metabolic responses to cold exposure were completely abolished by seven times repetition of daily cold exposures in rabbits with lesions of ARC, VMH and FX, as well as in each sham-operated group. In rabbits with ST lesions, the pyruvate metabolic responses to cold exposure remained even after the seven times repetition of daily cold exposures. From these results, it might be suggested that the ARC, VMH, amygdala (AMYG)-ST system and dorsal hippocampus (HPC)-FX system played a certain role in the metabolic regulation of pyruvate and in the mechanisms of pyruvate metabolic responses to the 1st cold exposure, but that only the AMYG-ST system participated in the process of pyruvate metabolic adaptation to daily repeated cold exposures.

Animals↗

Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant.

A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, exhibited full endotoxic activities identical to or sometimes stronger than those of a reference lipid A from an Escherichia coli Re-mutant (strain F515). Endotoxic activities tested include pyrogenicity and leukopenia-inducing activity in rabbits, body weight-decreasing toxicity in normal mice, lethal toxicity in galactosamine-sensitized mice and chicken embryos, and the preparation and provocation of the local Shwartzman reaction in rabbits. Compound 406, a synthetic counterpart of a biosynthetic precursor of lipid A molecule, showed by contrast only weak activities in all of the above assay systems except for the lethality in galactosamine-loaded mice. This finding strongly suggests that the presence of acyloxyacyl groups at the C-2' and C-3' positions of the disaccharide backbone is one of the most important determinant structures of the lipid A molecule for exhibition of strong biological activities characteristic of lipopolysaccharide and its lipid A moiety. The activities of the corresponding 4'-monophosphate (compound 504) and 1-monophosphate (505) analogs were considerably less than those of the parent molecule 506 and the reference F515 lipid A. Regarding other biological activities, not only compound 506 but also compounds 504, 505, and 406 showed definite activities, sometimes comparable to those of F515 lipid A and other reference natural products. These are the activation of Tachypleus tridentatus amoebocyte clotting enzyme cascade and human complement via the classical pathway, mitogenic and polyclonal B-cell activation of murine splenocytes, stimulation of peritoneal macrophages in a guinea pig, enhancement of migration of human blood polymorphonuclear leukocytes, and induction of a serum factor that is cytostatic and cytocidal to L-929 cells in Mycobacterium bovis BCG-primed mice. Relative potencies of test synthetic compounds depended on the assay systems and varied from one system to another. Dephospho-compound 503 lacked most of the biological activities that were definitely observed with phosphorylated compounds, probably because of its insolubility. This study demonstrates the successful chemical synthesis of an E. coli-type lipid A.

Adjuvants, Immunologic↗

Synthesis of collagenase and collagenase inhibitors by osteoblast-like cells in culture.

A rat osteosarcoma cell clone (ROS 17/2), and osteoblast-enriched populations from rat calvaria cultured in the presence of concanavalin A, have been shown to produce latent collagenase and collagenase inhibitors. The enzymes and inhibitor activities from the ROS 17/2 cells were concentrated by ammonium sulphate precipitation and separated by gel filtration on AcA 54 resin. The size of the latent collagenase (Mr approximately equal to 58000) was reduced on conversion to active enzyme (Mr approximately equal to 48000) by p-aminophenylmercuric acetate. Latent and active forms of gelatinase activity, similar in size to the corresponding forms of collagenase, were also resolved. The collagenase inhibitor activity, which was sensitive to organomercurials, was recovered in two peaks (Mr approximately equal to 68000 and 30000). The active collagenase cleaved interstitial collagens (type I = III greater than II) producing typical 3/4 and 1/4 fragments. This activity was inhibited by the metal ion chelators ethylenediaminetetraacetic acid and o-phenanthroline. Additional specific cleavages of native collagen were also observed which, from the susceptibility of this activity to phenylmethylsulphonyl fluoride, leupeptin and antipain, suggested the presence of a second collagenolytic enzyme. This synthesis of collagenolytic enzymes by these osteoblast-like cells suggests that individual osteoblasts, like fibroblasts, are capable of both synthesizing and degrading their respective organic matrices in vivo.

Ammonium Sulfate↗