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Biomedical subjects

A Katoh

Publications and source records attributed to A Katoh.

At least 91 records · Page 5Linked to original sources
PubMed1990

Behavioral changes induced by stressful situations: effects of enkephalins, dynorphin, and their interactions.

Effects of opioid peptides on behavioral changes induced by stressful situations were investigated. [D-Ala2,Met5]-enkephalinamide and [D-Ala2,D-Leu5]-enkephalin, degrading-enzyme-resistant derivatives of methionine-enkephalin and leucine-enkephalin, respectively, significantly attenuated both environment-induced conditioned suppression of motility and forced swimming-induced immobility in a dose-dependent manner. The [D-Ala2,Met5]-enkephalinamide- and [D-Ala2,D-Leu5]-enkephalin-induced attenuations were antagonized by naloxone at different doses. In contrast, dynorphin A(1-17) and [N-methyl-Tyr1,N-methyl-Arg7,D-Leu8]-dynorphin A(1-8) ethylamide (E 2078), a degrading-enzyme-resistant derivative of dynorphin, significantly potentiated both behavioral changes. The dynorphin- and E 2078-induced potentiations were inhibited by Mr 2266. [D-Ala2,Met5]-enkephalinamide-induced attenuation of environment-induced conditioned suppression of motility and forced swimming-induced immobility was prevented by treatment with dynorphin and E 2078 at the doses that did not affect the behavioral changes. This antagonism by both dynorphin and E 2078 was inhibited by Mr 2266. However, [D-Ala2,D-Leu5]-enkephalin-induced attenuation of both behavioral changes was not affected by either dynorphin or E 2078. These results indicated that activation of the methionine- or leucine-enkephalinergic system attenuates behavioral changes induced by stress, whereas activation of the dynorphinergic system potentiates those changes. Furthermore, the dynorphinergic system may interact with the methionine-enkephalinergic system, but not with the leucine-enkephalinergic system.

Animals↗
PubMed1990

[Acute myeloblastic leukemia and hepatocellular carcinoma following Waldenström's macroglobulinemia].

A 54-year-old man was admitted to our hospital for precise examination of pancytopenia in October 1988. He had been cut off his left femur and irradiated because of osteosarcoma in 1954. After 30 years, he was diagnosed as Waldenström's macroglobulinemia. Melphalan had been given 2 mg daily for 19 months until August 1988, when it was discontinued due to pancytopenia. Peripheral blood showed Hb 6.6 g/dl, platelet 40 x 10(3)/microliters, and WBC 2000/microliters with 33% blasts. Bone marrow showed normocellularity with 36% blasts. Although blasts were negative for peroxidase staining, surface marker analysis revealed myeloid (CD 13, CD 33) phenotypes. Chromosome analysis showed 45, XY, -7, inv (3). A CT scan of the liver showed a mass, 10 by 10 cm, compatible with hepatocellular carcinoma. He was treated with very low dose Ara-C without noticeable effect. Hepatic tumor gradually enlarged, and he died of hepatic failure. This is a rare case of quadruplicate malignancies. The chromosomal abnormality suggests that AML was secondary leukemia which might be associated with immunosuppression due to macroglobulinemia and/or melphalan therapy.

Carcinoma, Hepatocellular↗
PubMed1990

Novel fatty acyl substrates for myristoyl-CoA:protein N-myristoyl-transferase.

Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the covalent attachment of myristic acid to the NH2-terminal Gly residues of a number of viral and cellular proteins. The remarkable specificity of this enzyme for myristoyl CoA observed in vivo appears to arise in large part from a cooperativity between NMT's acylCoA and peptide binding sites: the length of the acylCoA bound to NMT influences the interactions of peptide substrates with NMT. We have previously synthesized analogs of myristic acid with single oxygen or sulfur for methylene substitutions. These heteroatom substitutions produce significant reductions in acyl chain hydrophobicity without accompanying alterations in chain length or stereochemical restrictions. In vitro studies have shown that the CoA thioesters of these analogs are substrates for S. cerevisiae NMT and that the efficiency of their transfer to octapeptide substrates is peptide sequence-dependent. In vivo studies with cultured mammalian cells have confirmed that these fatty acid analogs are selectively incorporated into a subset of cellular N-myristoylproteins, that only a subset of analog-substituted proteins undergo redistribution from membrane to cytosolic fractions, and that these analogs can inhibit the replication of human immunodeficiency virus I and Moloney murine leukemia viruses--two retroviruses that depend upon N-myristoylation of their gag polyprotein precursors for assembly. We have now extended our analysis of NMT-acylCoA interactions by synthesizing additional analogs of myristic acid and testing them in a coupled in vitro assay system. Myristic acid analogs with two oxygen or two sulfur substitutions have hydrophobicities comparable to that of hexanoic acid and decanoic acid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl Coenzyme A↗
PubMed1989

Intracytoplasmic eosinophilic inclusions in the neurons of the central nervous system.

This study reports the histological, ultrastructural, and immunocytochemical characteristics of intracytoplasmic eosinophilic inclusion bodies occurring in various types of neurons of the human central nervous system. By light microscopy, the inclusions were brightly eosinophilic, slightly birefringent, and sharply demarcated; they were found in the thalamus in 92% of the cases, in the substantia nigra in 88%, in the locus coeruleus in 45%, and rarely in the spinal cord. Ultrastructurally, the inclusions were composed of assemblies of parallel, alternating dark and light rectilinear profiles. The dark profiles corresponded to thin filaments (microfilaments) that measured 5.5-6.0 nm in diameter. A second set of dense lines crisscrossed the first at right angles. In sections perpendicular to their long axis, the filaments were distributed in a tetragonal lattice pattern in which individual elements occupied the angles of a square. Immunocytochemical preparations for actin were negative. Due to their high rate of occurrence in nonpathological brains, it is thought that the inclusions represent a normal but as yet unidentified cytoplasmic organelle.

Adult↗
PubMed1989

The combined effect of interferon and 5-FU on tumor-cell metastasis in the nude mouse.

In searching for a suitable animal model system to study colorectal tumor-cell metastasis, the method of injecting tumor cells directly into the spleen of athymic nude mice was explored. The cells used in this study consisted of the Colo 205 cell line, isolated and established from the ascitic fluid of a patient with adenocarcinoma of the colon. In spite of showing tumorigenicity in nude mice after subcutaneous injections, anchorage-independent clonal growth in soft agar, and invasion in the chick embryo skin, the Colo 205 cells failed to metastasize to the lung or liver after intrasplenic injections. The effects of interferon, and interferon in combination with 5-fluorouracil (5-FU), on tumor formation in the spleen, were studied. The combined interferon- and 5-FU-treated animals displayed a significant difference from the controls in the generation of spleen tumors. This combination may possess potentially useful applications in the treatment of solid tumors such as those in the colon and rectum.

Adenocarcinoma↗
PubMed1989

Bilateral vertebral arteriovenous fistulas and atlantoaxial dislocation associated with neurofibromatosis--case report.

The authors report a rare case involving neurofibromatosis associated with bilateral vertebral arteriovenous fistulas and atlantoaxial dislocation. Multiple neurofibromas in the craniocervical junction appeared to be the cause of the atlantoaxial dislocation in this patient, and the dislocation might have contributed to the formation of the bilateral vertebral arteriovenous fistulas. The fistulas were successfully treated by a combination of balloon embolization and surgery followed by occipitocervical fusion.

Arteriovenous Fistula↗
PubMed1989

[Case report of a patient with advanced pelvic and ureteral cancer whose primary lesion could be enucleated after cytoreduction by modified CAP regimen].

A 52-year-old man got right renal pelvic and ureteral carcinoma involving metastases in lung, and para-aortic and supraclavicular nodes, he underwent courses of combination chemotherapy consisting of cyclophosphamide, adriamycin and cisplatinum, including bleomycin. The initial response was encouraging with some regression of the primary tumor and pulmonary metastases. Accordingly, the patient then underwent extirpation of the primary cancer. Two weeks after the surgery, relapse of the lung metastatic lesion was observed, and the lesion was refractory to the chemotherapy. This investigation reports a case and discusses the pre-and-postoperative chemotherapy for upper urothelial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Effects of prenatal administration of phencyclidine on the learning and memory processes of rat offspring.

The effects of prenatal administration of phencyclidine (PCP) on the learning and memory processes of rat offspring were investigated at doses below the level for producing malformations. The offspring prenatally treated with PCP (10 or 20 mg/kg) on days 7 to 17, as well as on days 7 to 21 of gestation, showed disruption of the acquisition of passive avoidance response and pole-climbing avoidance response at the ages of 4 and 7 weeks, respectively. The brain weight of the offspring prenatally treated with PCP was significantly decreased. These results suggest that prenatal PCP administration impairs learning and memory processes of passive and active avoidance tasks and that more attention should be given to the developmental toxicity of PCP.

Animals↗
PubMed1988

[Effect of naftidrofuryl oxalate (LS-121) on experimental amnesia model in rats].

Effects of naftidrofuryl oxalate (LS-121) on experimental amnesia models, which were induced by cycloheximide (CXM), scopolamine (SCOP) and basal-forebrain (BF) lesion, were investigated using the step-through passive avoidance response in rats. In the retention test, a cut-off time of 600 sec was employed for the measurement of step-through latency (STL). The animals, that showed over 300 sec of STL was regarded as having the criterion of memory retention (% of retention). Increase in both parameters of STL and % of retention was regarded to indicate that the drug was able to improve the amnesia. If only one of the two parameters was increased, we considered that the drug had a tendency to improve the amnesia. Pretraining, post-training and pre-retention treatment of LS-121 (25 mg/kg) improved CXM- and SCOP-induced amnesia. Post-training treatment of LS-121 (25 mg/kg) showed a tendency to improve the BF lesion-induced amnesia. These results suggest that the antiamnesic action of LS-121 may be produced through an activation of the acetylcholinergic neuronal system. Since it improved the amnesia when administered in the pre-retention test, there is a possibility that LS-121 has not only a protective effect, but also a therapeutic effect. Furthermore, it is suggested that LS-121 may also have a therapeutic effect on Alzheimer's disease, since it showed a tendency to improve the BF lesion-induced amnesia.

Amnesia↗
PubMed1988

Inhibition of enkephalin degradation attenuated stress-induced motor suppression (conditioned suppression of motility).

Mice exhibit a marked suppression of motility when they are placed in the same cage in which they had previously received an electric shock. This suppression of motility is believed to be stress-induced and is a conditioned response. A decrease in the Met-enkephalin levels and a decrease in the dopamine (DA) turnover in the striatum of these "conditioned suppression" groups have been exhibited. The present study investigates whether inhibition of enkephalin degradation induced by an enkephalinase A and/or an aminopeptidase inhibitor attenuates a conditioned suppression of motility. The effects of thiorphan and bestatin, both alone and in combination, were investigated. Thiorphan alone (25, 50 and 100 micrograms i.c.v.) significantly attenuated the conditioned suppression of motility in a dose-dependent manner, but not bestatin (25, 50 and 100 micrograms i.c.v.) alone. The combination of these drugs (25 and 50 micrograms, each, i.c.v.) also significantly reduced the conditioned suppression of motility in a dose-dependent manner. The attenuation of conditioned suppression of motility induced by thiorphan and bestatin was antagonized by naloxone (5 mg/kg s.c.) and pimozide (100 micrograms/kg i.p.). In addition, the combination of thiorphan and bestatin reversed the decreases of Met-enkephalin levels and the decreases of DA turnover in the striatum in conditioned suppression group. These results suggest that attenuation of the conditioned suppression of motility induced by thiorphan and bestatin may be directly proportional to the increases of endogenous opioid peptide contents, and that the effect of these drugs may be related to the striatal DAergic system.

Amino Acids, Sulfur↗
PubMed1987

[Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on congestive heart failure in dogs].

Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on a model of congestive heart failure (CHF), we established in dogs, were investigated. The model was made by protease injection into the left ventricular free wall, saline loading, and dextran and methoxamine infusion. By this maneuver, left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular end-diastolic pressure (LVEDP) were markedly increased, aortic blood flow (AoBF) was decreased and systemic blood pressure (SBP) was unchanged. Following intravenous application of 0.50 microgram/kg alpha-hANP, LAP was reduced from 18.9 to 14.0 mmHg (N = 7, mean); SBP, from 114.4 to 105.1 mmHg; SVR, from 21603 to 15602 dyne sec/cm5; and LVEDP, from 22.2 to 17.6 mmHg; while AoBF was increased from 0.46 to 0.54 l/min. Vmax and T were little influenced. The results indicate that alpha-hANP improved canine CHF mainly through its vasodilating action.

Animals↗
PubMed1987

Selective calmodulin inhibition toward myosin light chain kinase by a new cerebral circulation improver, Ro 22-4839.

Ro 22-4839, a new cerebral circulation improver, has shown to be a potent calmodulin antagonist toward myosin light chain kinase (MLCK). It inhibited in vitro activity of calmodulin-activated cyclic AMP phosphodiesterase isolated from either bovine heart or brain and ATP-induced superprecipitation of chicken gizzard actomyosin with respective IC50 values of 20 microM, 17 microM, and 2.0 microM. The inhibitory action of Ro 22-4839 on the contractile system of the smooth muscle was demonstrated directly by its inhibition of chicken gizzard MLCK. Ro 22-4839 was found to potently inhibit MLCK with an IC50 value of 3.1 microM but was unable to inhibit the activity of MLCK rendered Ca2+/calmodulin independent by limited tryptic digestion. The inhibition of MLCK induced by Ro 22-4839 was completely overcome by addition of excess calmodulin. In contrast, Ro 22-4839 hardly inhibited calmodulin-activated Ca2+, Mg2+-ATPase from rat erythrocyte membrane or adenylate cyclase from rat brain. Use of hydrophobic fluorescence probes showed that Ro 22-4839 binds to the hydrophobic region of calmodulin like other calmodulin antagonists, trifluoperazine and W-7. However, the precise binding site of Ro 22-4839 to calmodulin is different from those of trifluoperazine and W-7, as suggested from differing IC50 values of these compounds against the probes. We conclude that Ro 22-4839 inhibits calmodulin-activated enzymes, most significantly of MLCK, highly specific to smooth muscle contractile systems by binding to the hydrophobic domain of the calmodulin and inducing its conformational change in the presence of calcium.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

A role played by dopamine and opioid neuronal systems in stress-induced motor suppression (conditioned suppression of motility) in mice.

Mice exhibited a marked suppression of motility (conditioned suppression of motility, which is one of stress-induced motor suppressions) when placed in the same chamber where they had previously received an electric footshock. In the present study the role played by dopamine and opioid neuronal systems in the conditioned suppression of motility has been investigated. In conditioned suppression group, the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methionine-enkephalin (Met-enk) did not change in the hypothalamus, cerebral cortex and medulla oblongata/pons, while a decrease in the contents of striatal DOPAC were induced compared to that in the control group, which was accompanied by reduction in the contents of Met-enk. In addition, the contents of DA were increased in the midbrain. The ratio of DA metabolites/DA contents in the striatum of the conditioned suppression group was decreased. In the striatum, moreover, the depletion of DA induced by alpha-methyl-p-tyrosine (alpha-MT) in the conditioned suppression group was significantly lower than that in the control group but not in the midbrain. These results suggest that the DA turnover rate and Met-enkergic activity decrease in the striatum of conditioned suppression group.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

[A method for evaluating visual impairments using operant behavior in mice].

A behavioral method, using a shuttle box (one of the conditioned behaviors) for assessing visual function in mice, was investigated. Normal ICR mice were trained to avoid the unconditioned stimulus (electric footshock) during the presentation of conditioned stimuli (tone and light). After acquisition of avoidance response, normal ICR mice were presented randomly tone or light as the conditioned stimulus. The percent of avoidance in the presentation of light was decreased suddenly, but that of tone was not. However, the decrease of avoidance response to light stimulus was recovered by following trainings. The mice, which had acquired the condition response to tone and light stimulus alone, were treated in their cornea with 4N NaOH. The decrease of percent of avoidance in the mice with alkali-treated cornea after differentiation of conditioned stimuli did not recover following training. These results suggested that visual impairment of mice can be detected by this method. Therefore, we attempted to detect the visual impairments of dominant (Cts) and recessive (cac) hereditary cataract mice, hereditary retina degenerated mice (C3H) and first filial generation mice of C3H, F1 [(ICR X C3H) F1]. The acquisition curves of both Cts and cac cataract mice were similar to that of normal ICR mice, but those of C3H and F1 were similar to that of ICR mice treated with alkali. Moreover, changes in recovery %, which was calculated from avoidance response in the presentation of light alone after differentiation of conditioned stimuli, corresponded to the above results. These findings demonstrated that the visual impairment of Cts and cac cataract mice is weak, while that of C3H and F1 mice is strong.

Animals↗