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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 325 records · Page 18Linked to original sources

Changes in the latency of the maximum positive peak of visual evoked potential during anesthesia.

The relationship between the latency of visual evoked potential (VEP) and the anesthetic concentration was investigated in surgical patients in order to examine the applicability of VEP in monitoring of the depth of anesthesia. The VEP was recorded with a standard EEG electrode from the midline parietal region in reference to both earlobes linked to the ground. An array of light-emitting-diodes mounted in opaque goggles was used to stimulate both eyes simultaneously and photic stimuli were delivered at random inter-pulse intervals with uniform distribution ranging from 2 to 5 seconds. Fifty trials of data were averaged to estimate that Pmax latency, i.e., the latent period from the photic stimulus to the maximum positive peak arising after 170 msec. Increases in the Pmax latency following the administration of anesthetics and restorations to preanesthetic values after recovery from anesthesia were found. A significant correlation was demonstrated between the Pmax latency and the inspiratory concentration of enflurane. The latency of the Pmax showed a drastic and a sensitive prolongation from about 200 msec in the awake state up to about 600 msec at the stage where the EEG exhibits large-voltage slow waves. Thus the measurement of the Pmax latency of VEPs was found to be useful for monitoring the depth of anesthesia.

Anesthesia↗

Two-dimensional flow cytometric analysis of intrahepatic lymphocyte subsets from patients with chronic hepatitis.

Peripheral and intrahepatic lymphocyte subsets were analyzed in 22 patients with chronic hepatitis by two-dimensional flow cytometry. Activated T cells in the liver significantly increased compared with those in the peripheral blood. Helper T cells increased, but the CD4+ cells decreased due to a marked decrease of suppressor inducer T cells. CD8+ cells increased due to a increase of both cytotoxic T and suppressor T cells. Fc-receptor-positive cells, which increased significantly, were not NK cells but Fc-receptor-bearing T cells. In comparison with immunohistochemical methods, flow cytometric analysis enables more objective quantitation and simpler two-color staining of intrahepatic lymphocytes. Our findings using this method suggest that activated T cells and helper T cells have important roles in hepatitis and that hepatocellular injury may be generated not only by cytotoxic T cells but also by Fc-receptor-bearing T cells.

Adult↗

Collagenase production in the exudate of a novel adjuvant-induced air pouch inflammation model in rats.

To elucidate the role of collagenase in tissue destruction in chronic inflammation (e.g., in rheumatoid arthritis), we established a novel air pouch model in rats. Ten ml of air was injected subcutaneously on the dorsa of F344 rats, and 24 hours thereafter, Freund's complete adjuvant was injected into the air pouch. A remarkably high activity of trypsin-activated collagenase was detected dose-dependently in the pouch fluid at 8 days after the challenge injection. Concomitantly with the increase of collagenase activity, the weight of granuloma formed in the pouch decreased, suggesting that collagenase participates in the resorption of granuloma tissues.

Air↗

Determination of plasma leukotrienes in antigen-induced bronchoconstrictive guinea pigs.

Convenient extraction and radioimmunoassay methods for measurement of leukotrienes C4 and D4 (LTC4 and LTD4) in biological fluids are described. LTC4 or LTD4 in plasma was extracted with acetonitrile, and the extract was washed with dichloromethane then adjusted to pH 3.5 or 6.0, respectively. Each leukotriene was partially purified by using a C18-bonded silica cartridge and quantitated by radioimmunoassay. Amounts of LTC4 and LTD4 in the range of 0.025-1.6 ng could be assayed in plasma. This procedure was employed to examine the increase in plasma LTC4 (0.249 +/- 0.036 ng/ml) and LTD4 (1.399 +/- 0.235 ng/ml) of guinea pigs during intravenous challenge-induced anaphylactic bronchoconstriction, and the suppression of the increase of bronchoconstriction and leukotrienes by the administration of 5-lipoxygenase inhibitors such as E6080 (6-hydroxy-2-(4-sulfamoylbenzyl-amino)- 4,5,7-trimethylbenzothiazole hydrochloride), AA861 (2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone ) and phenidone. On the other hand, LTC4 and LTD4 were not detected in plasma after an inhaled challenge, though significant bronchoconstriction was provoked. It was concluded that the present study validates a new technique for quantitating plasma leukotrienes on the basis of pH and a suitable method for evaluating the pharmacological efficacy of 5-lipoxygenase inhibitors.

Administration, Inhalation↗

Inhibitory effects of a novel PAF antagonist E6123 on anaphylactic responses in passively and actively sensitized guinea pigs and passively sensitized mice.

The effects of the platelet-activating factor (PAF) antagonist, E6123, on anaphylactic responses in guinea pigs and mice were investigated. E6123 inhibited i.v. antigen (Ag)- or inhaled Ag-induced bronchoconstriction in passively and actively sensitized guinea pigs after oral administration at 3 and 10 micrograms/kg, respectively. E6123 inhibited Ag inhalation-induced airway hyperreactivity in guinea pigs after oral administration at 30 micrograms/kg. E6123 protected mice from anaphylactic death with an ED50 value (p.o.) of 7 micrograms/kg. The inhibitory effects of E6123 described above were very potent compared to those of the PAF-antagonists WEB2347 and Y-24180. The present results suggest that E6123 may be beneficial for the treatment of asthma, a condition in which PAF is assumed to be involved.

Administration, Inhalation↗

Pharmacological effects of oral E6123, a novel PAF antagonist, on biological changes induced by PAF inhalation in guinea pigs.

The effects of a newly synthesized PAF antagonist E6123, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2, 3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine, on in vivo inhaled PAF-induced pulmonary changes were investigated. E6123 inhibited PAF inhalation-induced bronchoconstriction in guinea pigs with an ED50 value (p.o.) of 1.3 micrograms/kg which was lower than those of other PAF-antagonists such as WEB2347 (ED50 = 26 micrograms/kg) and Y-24180 (ED50 = 12 micrograms/kg). E6123 significantly inhibited PAF inhalation-induced eosinophil infiltration into the bronchiole and trachea, and bronchial hyperreactivity in guinea pigs after oral administration at 1 and 10 micrograms/kg, respectively. E6123 inhibited the PAF-induced increase in intracellular free calcium ion concentration ([Ca2+]i) in guinea pig eosinophils with an IC50 value of 14 nM. The present results suggest that E6123 may be beneficial for the treatment of asthma, in which PAF is assumed to be involved.

Administration, Oral↗

Effects of competitive and noncompetitive NMDA receptor antagonists on kindling and LTP.

In the present study, comparative studies of the effects of competitive and noncompetitive antagonists of NMDA receptors (CPP, CGS19755 and MK-801) on two models of neuronal plasticity, kindling and long-term potentiation (LTP), were performed in rats. Systemic administration of CPP (5, 10 mg/kg), CGS19755 (5, 10 mg/kg) or MK-801 (1, 2 mg/kg) strongly retarded kindling development from the amygdala (AM), in which the early stage of kindled seizures and the growth of afterdischarges (ADs) recorded from the AM were significantly suppressed. After establishment of kindling, however, these compounds only reduced the previously AM-kindled seizure stage without shortening the AD duration. These NMDA receptor antagonists with the same dose sufficient for suppressing AM kindling almost completely blocked LTP of the synaptic component in the hippocampal dentate gyrus following high-frequency trains of the perforant path in urethane-anesthetized rats. These results further support the hypothesis that neuronal plasticity is induced by activation of the NMDA receptor complex and one of the basic neuronal mechanisms underlying kindling may be a long-lasting increase in synaptic transmission.

Animals↗

Effect of a novel 5-lipoxygenase inhibitor, E6080 on bronchospasm, airway cellular infiltration and leukotriene production in guinea pigs.

6-Hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (E6080), an orally active and selective 5-lipoxygenase inhibitor, dose-dependently inhibited the bronchospasm induced by antigen (ovalbumin) inhalation in sensitized conscious guinea pigs. The inhibitory effect of E6080 was more potent than that of a typical 5-lipoxygenase inhibitor, AA861, but less than that of a leukotriene (LT) antagonist, LY171883. When airway infiltration of neutrophils and eosinophils was measured in bronchoalveolar lavage fluid (BALF) at 6 h after antigen inhalation by passively sensitized guinea pigs, the inhibitory effect of E6080 on neutrophil infiltration was more marked than that on eosinophil infiltration. The inhibitory effect of E6080 on bronchoalveolar cellular infiltration and bronchoepithelial damage was confirmed by examination of photomicrographs of the lung. In addition to the above pharmacological effects, E6080 inhibited the increase in BALF levels of both i-LTC4 and i-LTB4. These results suggest that E6080 may prove to be effective for the treatment of asthma, in which large amounts of leukotrienes (LTs) are elaborated.

Acetophenones↗

A new anti-platelet drug, E5510, has multiple suppressive sites during receptor-mediated signal transduction in human platelets.

The mode of action of E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, which has very potent anti-platelet activities, was investigated by examining its effects on the biochemical responses in the process of human platelet activation. In a whole-cell system, E5510 inhibited the increased turnover of inositol phospholipids arising from phospholipase C activation, arachidonic acid release from phospholipids by phospholipase A2, mobilization of intracellular free Ca2+, protein kinase C activation, and thromboxane A2 production. In a cell-free system, E5510 inhibited cyclooxygenase activity and cyclic AMP-dependent phosphodiesterase activity in a dose-dependent manner. An elevation of cyclic AMP in platelets was also observed at a relatively high concentration of E5510. It was suggested that receptor-mediated turnover of inositol phospholipids, intracellular Ca2+ increase, arachidonic acid release from phospholipids and protein kinase C activation might be indirectly inhibited by the increased cyclic AMP level in platelets. Thromboxane A2 production in the whole-cell system was very strongly inhibited by E5510, and the IC50 for this effect was 100 times lower than that of direct inhibition of cyclooxygenase in the cell-free system. It was concluded that although the primary mode of action of E5510 is the inhibition of the cyclooxygenase pathway of positive signal transduction in platelets, E5510 has another mode of action by increasing platelet cyclic AMP, which can act as a negative messenger in platelet signal transduction, and these multiple sites of action synergistically antagonize platelet cellular activation.

Arachidonic Acid↗

Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice.

The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.

Animals↗

[Striatal involvement on MRI in adrenomyeloneuropathy].

Adrenomyeloneuropathy (AMN), a clinical variant of child adrenoleukodystrophy (ALD), is an adult-onset progressive disorder which presents spastic paraparesis with peripheral nerve involvement and affects mainly the pyramidal tracts from the brainstem to the spinal cord. We report a case of AMN in which serial MRI showed unusual development of areas of high signal in the right striatum. The patient was in good health until the age of 12, when he began to lose his hair. At age 25 he started to have progressive gait disturbance and erectile impotence. In his first admission to our hospital at age 33, he showed diffuse baldness. He was intelligent but childish. His cranial nerves were normal. Muscle strength was weak (3-4/5) in the lower extremities. Deep tendon reflexes were hyperactive in the lower extremities while normal in the upper extremities. Babinski signs were elicited bilaterally. Pinprick and vibratory sensation was impaired in the lower legs. Proprioceptive sensations were normal. Co-ordination was intact. There were urinary incontinence and impairment of erection with preserved libido and ejaculation. Routine laboratory data including hematological studies, serum chemistry and urinalysis were all normal except for mild hyperlipidemia. Serum cortisol response to ACTH was low and serum levels of very long chain fatty acids were increased. Nerve conduction studies were abnormal and consistent with peripheral polyneuropathy. A biopsy specimen of left sural nerve revealed a mild loss of myelinated fibers with thinning of the myelin. These findings and the clinical features confirmed the diagnosis of AMN. MRI in SE2000/40 scans at age 34 disclosed areas of high signal in the bilateral internal capsules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenoleukodystrophy↗

[Detection of hepatitis C virus RNA in serum during treatment of chronic hepatitis C with interferon alpha].

We estimated HCV RNA in serum of 20 patients with chronic hepatitis C during interferon therapy using a combination assay of reverse transcription and polymerase chain reaction (RT-PCR). RNA was extracted from 200 microliters of serum. The primers were chosen from the NS3 region of prototype HCV RNA sequence. After 40 cycles of PCR, the products were analyzed by Southern hybridization. HCV RNA was detected in 18 of 20 (90%) patients before therapy. In cases with improvement of serum GPT level, HCV RNA became undetectable at 4 weeks of the therapy. However, HCV RNA reappeared within 4 weeks after the therapy in cases with relapse. In the no response group, HCV RNA did not disappear during the therapy. Interferon therapy is beneficial in improvement of viremia of HCV, and the detection of HCV RNA in serum is useful to evaluate the antiviral effect of interferon.

Adult↗

Inhibitory effects of the novel platelet activating factor receptor antagonist, 1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2R)-2-methoxy-3-(4- octadecylcarbamoyloxy) piperidinocarbonyloxypropyloxy]carbonyl] aminomethyl-pyridinium chloride, in several experimentally induced shock models.

E5880 (1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2R)-2-methoxy-3-(4- octadecylcarbamoyloxy) piperidinocarbonyloxypropyloxy] carbonyl]aminomethylpyridinium chloride, CAS 128420-61-1) is a novel analog-type antagonist of platelet activating factor (PAF). This paper describes the in vitro PAF antagonistic activity of E5880 and its in vivo effect in various experimentally induced shock models. Inhibition by E5880 of [3H]platelet activating factor (PAF) binding to human platelet PAF receptor was extremely potent; its IC50 value was 0.27 nmol/l, so that it was about 5 times more potent than PAF itself. Its IC50 value in inhibition of washed human platelet aggregation induced by PAF was 0.66 nmol/l. Intravenous treatment with E5880 dose-dependently reversed PAF-induced hypotension in rats and protected mice from lethality caused by PAF. Lipopolysaccharide (LPS)-induced hypotension in rats was inhibited by both pre- and post-treatment with E5880. It was also confirmed that blood PAF level, measured by the GC-NICI-MS method, was increased after LPS challenge in this model. Furthermore, E5880 was extremely effective in preventing passive anaphylactic lethality in mice. Blood PAF level in this model was also increased immediately after antigen challenge, and this was coincident with the time at which signs of shock became apparent. These findings support the concept that PAF is an important mediator in the development of LPS-induced shock and anaphylactic shock, and suggest that E5880, a novel and potent PAF antagonist, may be effective in clinical treatment for shock states.

Animals↗

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis.

The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.

Animals↗

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

Aerosols↗

[Complete response provided by new antitumor agent, MST-16 (sobuzoxane), in a breast cancer with multiple cutaneous metastases].

A case of recurrent breast carcinoma was successfully treated with MST-16 in an early phase II study. A 60-year-old woman developed skin metastases on the forehead, neck, abdomen and back 8 months after receiving standard radical mastectomy for right breast carcinoma. MST-16 was given p.o. at the dose of 1,200 mg/body/day initially, and the dosage was modified thereafter depending on the grade of leukopenia. All metastatic lesions disappeared completely 38 weeks after the initiation of the treatment. The CR thus obtained has continued for 8 months up to the present. Although leukopenia was observed during the administration of MST-16, it could be well managed by dose modification. Further trials with this drug for breast carcinoma should be conducted, since complete responses are expected with few adverse effects as in the case under study.

Adenocarcinoma, Papillary↗

[Experimental studies on prevention of liver metastases by continuous intraportal chemotherapy].

Our experiment was designed to elucidate the efficacy of continuous intraportal chemotherapy (CIPC) for the prevention of liver metastases. Catheter was introduced into ileocecal vein of white rabbit for administration of adriamycin (ADM). VX2 cells were inoculated into portal vein to form liver metastases. Three experiments were designed as follows: 1) Immediately after inoculation of tumor cells, ADM was administered continuously for 7 days. 2) Continuous administration of ADM started on the 3rd day after inoculation of tumor cells. 3) Immediately after inoculation of tumor cells, ADM was administered by CIPC or systemically for 7 days. The same number of tumor cells were inoculated into portal vein and no treatment was given in control group. The rabbits were sacrificed on the 14th day. Number and size of liver metastases were calculated. Results were as follows: In 1) and 2), the metastases in CIPC group were significantly decreased in number and size compared with those in control group. In 3), no metastasis was observed in CIPC group, but a third of the rabbits developed metastases in systemic group. These results suggest that CIPC is effective for prevention of liver metastases and its efficacy is greater than for systemic chemotherapy.

Animals↗

[Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin].

Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.

Antineoplastic Combined Chemotherapy Protocols↗