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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 1,063 records · Page 59Linked to original sources

Effects of adrenergic agonists and antagonists on immediate cutaneous reactions in bronchial asthma.

Asthmatic patients who showed an allergic skin reaction to house-dust antigen (HD) were injected intradermally with a mixture of HD and a various dose of isoproterenol (Isopr) or propranolol (Propr). In some cases Isopr clearly suppressed the formation of the wheal, but in some others Isopr did not much affect the allergic skin reaction. Also Propr increased markedly the skin reaction of some patients, or had little effect on it. The sensitivity of the skin of asthmatic patients to these drugs was closely correlated with the general response of the patients to adrenaline, such as changes in heart rate, diastolic blood pressure, blood glucose level, and blood triglyceride level.

Adrenergic Agonists↗

Metabolism of 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil in mice.

1,3-Bis(tetrahydro-2-furanyl)-5-fluorouracil (FD-1) is a new masked compound of fluorinated pyrimidine and a derivative of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207). The pharmacokinetics of FD-1 and FT-207 were compared in the livers and kidneys of control mice and in mice (DD males) pretreated with phenobarbital. The half-time in the liver of FD-1 orally administered was about 40 minutes, whereas that of FT-207 in the liver was about 3 hours. Hepatic concentrations of 5-fluorouracil (FUra) originating from FD-1 were three to five times as much as those originating from FT-207. FD-1 formed 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-T-F-FU) and FT-207 by a ratio of about 3 to 10, respectively. Although FD-1 had a short period of half reduction, FT-207 and 3-T-F-FU had a half-time lasting for 3--4 hours. In contrast, the renal concentration of FD-1 was one-third that of FT-207. Oral administration of FD-1 to the mice pretreated with phenobarbital elevated the FT-207 and 3-T-F-FU levels in the livers to twice the levels in the control mice and further elevated the FUra levels in the livers to twice the levels in the controls. These results indicate that FD-1 is catabolized in the liver by microsomal enzymes (including cytochrome P450) faster than is FT-207, which consequently enlarges the hepatic pool of the intermediates on the way to FUra formation.

Animals↗

The relationship between the arterial level of angiotensin-converting enzymes and arterial gas tension in bronchial asthma.

To study the mechanism which causes a lowered serum level of angiotensin-converting enzyme (ACE) in asthma patients, the changes in serum ACE in arterial blood gas tension was measured. Serum ACE was also determined in patients with chronic obstructive lung disease (COLD) and fibrosing lung disease (FLD). A reduced level of serum ACE was found in some patients with COLD, similar to that in patients with asthma. A significant relationship existed between the lowered serum ACE level and the degree of arterial hypoxia, especially in asthmatic patients and some patients with COLD. The significance of lowered serum ACE is discussed in relation to the pathogenesis and the mechanism of hypoxemia in patients with asthma, COLD and FLD.

Asthma↗

Microiontophoretic studies on noradrenergic inhibition from locus coeruleus of spinal trigeminal nucleus neurons.

Microiontophoretic studies using cats anesthetized with alpha-chloralose and local anaesthetic were undertaken in an attempt to determine whether or not norepinephrine (NE) derived from the locus coeruleus (LC) acts on neurons of the spinal trigeminal nucleus (STN) as an inhibitory transmitter. Both conditioning stimulation of the LC and iontophoretic application of NE inhibited orthodromic spike generation by interior alveolar nerve stimulation in 9 out of 14 STN relay neurons, without affecting antidromic spikes elicited by stimulation of the contralateral medial lemniscus. Glutamate-induced spike firing of the STN relay neurons, however, remained unaltered with iontophoretic application of NE up to 200 nA. The LC conditioning stimulation inhibited orthodromic spikes in 22 out of 25 type-B interneurons in the STN, while iontophoretic NE application seldom had an effect on orthodromic spikes and spontaneous firing of the interneurons. Only 5 out of the 25 interneurons exhibited an inhibition of orthodromic spike generation and spontaneous firing with iontophoretic NE. These neurons fired spikes upon orthodromic stimulation with a relatively short latency, compared with the spike latency of neurons unaffected by iontophoretic NE. The present results strongly suggest that NE released from the terminals of the LC neurons inhibits transmission of STN relay neurons, probably by acting on primary afferent terminals to produce presynaptic inhibition.

Action Potentials↗

The effect of sympathomimetic drugs on immediate skin reactions and metabolic responses in asthmatic patients.

The varied effects of intradermal injection of isoproterenol and propranolol on the immediate skin reaction were studied in relation to the metabolic responses to the intravenous injection of epinephrine. In asthmatic patients whose skin reaction was not suppressed with 10(-7) M isoproterenol, the hyperglycemic response after the injection of epinephrine was significantly reduced.

Adolescent↗

Differential activation of cytotoxic and suppressor T cells against syngeneic tumors in the mouse.

The cytotoxic T cell against a methylcholanthrene-induced sarcoma, S1509a, was induced in syngeneic mice by deliberate immunization with mitomycin C (MMC)-treated live tumor cells. The soluble tumor antigen (STA) extracted from the same tumor by 3 M KCl was, however, unable to induce the cytotoxic T cell upon immunization, although it was able to activate predominantly the suppressor T cell that then specifically suppressed the effect of the cytotoxic T cell against the homologous tumor. The suppressor T cell generated by STA had the same characteristics as those found in tumor-bearing animals: 1) The suppressor T cell has a very strict specificity against individual tumors; 2) The cell expresses cell surface determinants controlled by genes in the I-J subregion of the mouse H-2 complex. The activity of the cytotoxic T cell was completely inhibited by live tumor cells but not by STA, whereas that of the suppressor T cell was neutralized by STA. The results that cytotoxic and suppressor T cells are activated under different conditions, and that the antigenic determinants recognizable by these two cell types are not the same. The soluble extract contains only the determinants recognizable by the suppressor T cell, and the cytotoxic T cell can be activated only by the determinants associated with self antigen present on the surface of live tumor cells.

Animals↗

Combination chemotherapy with a new anthracycline glycoside, aclacinomycin-A, and active drugs for malignant lymphomas in P388 mouse leukemia system.

Aclacinomycin-A is a new anthracycline glycoside and has less cardiotoxicity than adriamycin. In an attempt to provide an experimental model of a phase III study of aclacinomycin-A, particularly for the treatment of malignant lymphomas, various therapeutic designs of combinations of this drug with other conventional agents were investigated using a P388 mouse leukemia system. Aclacinomycin-A showed no treatment schedule dependency in this tumor system and the optimal dosage of this drug was twice higher than that of adriamycin on each treatment schedule; i.e., single treatment on day 1, three treatments on days 1, 5, and 9, or 10 treatments on every other day from days 1 to 19 after an inoculation of 10(6) leukemic cells on day 0. This antibiotic was ineffective against an adriamycin-resistant subline of P388 leukemia. Among combinations of aclacinomycin-A with cyclophosphamide, vincristine, procarbazine, or bleomycin, the combinations of aclacinomycin-A with cyclophosphamide or vincristine showed a therapeutic synergism in P388 leukemia system.

Animals↗

Selective effect of cinnarizine on the vestibular nucleus neurons.

Effects of cinnarizine were studied on the lateral vestibular nucleus (LVN) and spinal trigeminal nucleus (STN) of cats anesthetized with alpha-chloralose. Cinnarizine did not produce any obvious alterations of the field potential and spike generation of type B interneurons in STN elicited by trigeminal nerve stimulation as well as the field potential in LVN by vestibular nerve stimulation. Spike generation of monosynaptic LVN neurons elicited by the suprathreshold stimulus to the vestibular nerve was unaffected by cinnarizine up to 4 mg/kg. When the subthreshold stimulus was applied to the vestibular nerve, however, the spike number of LVN monosynaptic neurons was significantly increased after cinnarizine treatment. The enhancement of spike firing by cinnarizine upon both supra- and subthreshold stimuli to the vestibular nerve was found to be more pronounced in LVN polysynaptic neurons than monosynaptic ones. Since the effect of cinnarizine on LVN neurons was not dose-dependent, it is suggested that the enhanced responsiveness of the neurons by the drug might be due to an increase of blood flow, but not to a direct excitation of the neurons themselves.

Animals↗

Serum alkaline phosphatase (Al-Pase) isozyme in gastric and colonic cancer (using a simple thin layer polyacrylamide gel electrophoresis).

Using the simple thin layer polyacrylamide gel electrophoresis, serum alkaline phosphatase could be separated 5 isozyme bands in various digestive diseases, consisting of 54 cases of gastric cancer, 11 of colonic cancer, 12 of hepatoma, 4 of cholangioma, 14 of pancreatic cancer, 81 of benign hepatobilliary diseases, 13 of cancers of other organs and 61 of control. The obtained results were as follows: 1) The electrophoretic analysis of serum alkaline phosphatase showed the specific band remaining at the origin, already reported as "alkaline phosphatase O", in primary and metastatic cancer of the liver and cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cancerous metastasis to the liver, and it was also inclined to be positive with the progress of liver metastasis among them. 2) Intestinal alkaline phosphatase was usually found in higher frequency in blood group B and O than in the others, and it was apt to disappear in gastric or colonic cancer with an exacerbation of its cancerous lesions. 3) Heat-stable alkaline phosphatase was found in 10% of gastric or colonic cancer, all of which were histologically proved to be well differentiated adenocarcinoma.

Adenocarcinoma↗

Mutagenicity of benzotrichloride and related compounds.

Benzotrichloride (BTC), benzal chloride (BDC), benzyl chloride (BC) and benzoyl chloride (BOC) were surveyed for their mutagenicity in microbial systems such as rec-assay using Bacillus subtilis and reversion assays using E. coli WP2 and Ames Salmonella TA strains with or without metabolic activation in vitro. BTC and BDC required metabolic activation for their mutagenic activities in several strains of E. coli and Salmonella. The mutagenic metabolites of these compounds may not have been produced by hydrolysis. BC was weakly mutagenic without metabolic activation. Only BOC exhibited no mutagenic activity in the detection procedures used. The mutagenic metabolite of BTC might be very unstable under our experimental conditions. The strain E. coli WP2 try hcr was more sensitive than E. coli B/r WP2 try (hcr+) with regard to the mutagenicity of BTC.

Bacillus subtilis↗