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T Nishimura

Publications and source records attributed to T Nishimura.

At least 127 records · Page 7Linked to original sources
PubMed1991

A slow calcium-dependent chloride current in rhythmic hyperpolarization in neurones of the rabbit vesical pelvic ganglia.

1. Voltage-clamp recordings were made from neurones of vesical pelvic ganglia isolated from the rabbit urinary bladder. A rhythmic outward current, ISH, which corresponds to the spontaneous hyperpolarization, occurred at fairly constant intervals in fifty-eight of eighty-four neurones superfused with Krebs solution. The peak amplitude of the ISH was 0.5 +/- 0.2 nA (n = 48; mean +/- S.E.M.). 2. The ISH was eliminated in a Krebs solution containing nominally zero calcium and 12 mM-magnesium. Lowering the temperature of the superfusing solution from 36 to 22 degrees C also inhibited the occurrence of the ISH. 3. Bath application of caffeine increased the frequency of ISH. In contrast, ryanodine and procaine reversibly blocked ISH. 4. In thirty-four of fifty-eight neurones, the ISH was composed of two current components, an initial fast ISH with duration of 1-10 s and a slow ISH lasting 15-60 s. In the remaining twenty-four neurones, ISH showed only the fast component. 5. The fast ISH was associated with an increased membrane conductance and the slow ISH was associated with a decreased membrane conductance. The reversal potentials of the fast and the slow ISH were -88 +/- 7 mV (n = 4) and -30 +/- 6 mV (n = 4), respectively. 6. Tetraethylammonium (5 mM) and barium (1 mM) blocked the fast ISH but not the slow ISH. Intracellular caesium injected by ionophoresis through a Cs(+)-filled microelectrode blocked the fast ISH, without affecting the slow ISH. Apamin and (+)-tubocurarine selectively suppressed the fast component of the ISH. 7. Substitution of isethionate (67 mM) for chloride increased the amplitude of the slow ISH and shifted the reversal potential of the slow ISH to +1 +/- 8 mV (n = 5). A slow ISH with amplitude of 0.1-1 nA and was still observed in a low-sodium (26.2 mM) solution. The stilbene derivative, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), a chloride channel blocker, suppressed the slow ISH. 8. These results suggest that ISH is composed of two distinct calcium-dependent currents, a fast ISH produced by activation of potassium conductance and a slow ISH produced by inactivation of chloride conductance. 9. The after-hyperpolarization (AHP) following the action potential was also composed of apamin-sensitive and insensitive spontaneous hyperpolarizing oscillations. The apamin-insensitive component of IAHP was increased by lowering external chloride activity, while it was depressed by SITS.

Animals↗
PubMed1991

Endothelin causes prolonged inhibition of nicotinic transmission in feline colonic parasympathetic ganglia.

The action of endothelin (0.03-1 microM) on neurons in colonic parasympathetic ganglia of cats was studied in vitro, using intracellular microelectrode recording techniques. Electrical stimulation of the pelvic nerve evoked excitatory postsynaptic potentials (EPSPs) and orthodromic action potentials that were reversibly blocked by (+)-tubocurarine, hexamethonium, or external solutions containing nominal zero calcium and elevated magnesium. Endothelin blocked orthodromic action potentials and caused a concentration-dependent prolonged reversible depression of fast EPSPs. Endothelin had minimal effects on nicotinic depolarizations evoked by pressure application of acetylcholine. Endothelin also caused membrane depolarization (2-12 mV) followed by membrane hyperpolarization (1-8 mV). The depolarization and hyperpolarization were associated with a decrease and increase in membrane input resistance, respectively. The actions of endothelin were not altered by superfusion of the ganglia with external solutions containing atropine (300 nM), yohimbine (300 nM), naloxone (1 microM), or substance P (3 microM). We conclude that endothelin modulates synaptic transmission by slow membrane depolarization, membrane hyperpolarization, and prolonged depression of fast EPSPs. We suggest that the blockade of orthodromic action potentials and the depression of fast EPSPs is primarily due to inhibition of release of acetylcholine from presynaptic terminals.

Acetylcholine↗
PubMed1991

Characterization of intracytoplasmic neurofilament accumulation in hamster brain caused by Alzheimer buffy coat inoculation: comparison with experimental neurofibrillary changes produced by aluminum intoxication.

Neurofilament accumulation was produced in neuronal perikarya of the lower brain stem nuclei in the hamster brain by inoculating buffy coat from a patient with Alzheimer's disease. The abnormally proliferated neurofilament was characterized by immunostaining and electron microscopy. The intracytoplasmic neurofilament accumulation was positively stained with anti-tau and anti-ubiquitin, but not with antibody against paired helical filaments. Experimental neurofibrillary changes were produced in the rabbit brain by aluminum injection, and the proliferated neurofilaments in the rabbit brain were compared with those in the hamster brain inoculated with Alzheimer buffy coat. The results indicate that the long pathological process in the hamster brain is triggered by Alzheimer's buffy coat inoculation which results in intracytoplasmic accumulation of modified neurofilaments.

Aluminum↗
PubMed1991

Study of macrophages in prostatic fluid from nonbacterial prostatitis patients. V. Relation between activation of macrophages and stage of prostatitis.

Relationship between activation of macrophages in prostatic fluid and stage of nonbacterial prostatitis was studied by observing the rate of adherence of leukocytes, percentage of macrophages among adherent leukocytes and presence of spreading of macrophages. As a result, it was found that macrophages in the early stage of NBP were more activated than macrophages in the chronic stage.

Adult↗
PubMed1991

Recombinant interleukin-2-expanded tumor infiltrating lymphocytes from human renal cell cancer do not exhibit autologous tumor cell-specific cytotoxicity.

We studied subsets and cytotoxicity of recombinant interleukin-2 (rIL-2)-expanded tumor-infiltrating lymphocytes (TIL) from renal cell cancer (RCC) patients. TIL were successfully expanded in 13 of 14 RCC cases using anti-CD3 during the initial 48 h of culture. Percentages of CD8-positive cells among rIL-2-expanded TIL at 1-4 week(s) of culture were 56.2 +/- 15.1% (range 26.2-79.8%, n = 13) and not necessarily predominant over CD4-positive cells. Natural killer and lymphokine-activated killer (LAK) activities of TIL at 3-6 weeks of culture were 31.6 +/- 15.8% (range 1.4-57.4%, n = 9) and 16.6 +/- 11.6% (range 3.8-35.6%, n = 6), respectively. Autologous and allogeneic RCC cytotoxicity of TIL at 3-4 weeks of culture were 17.9 +/- 19.7% (range 0-47.6%, n = 4) and 18.9 +/- 14.8% (range 0-47.3%, n = 12), respectively. Since there was no statistical difference between them, autologous specific cytotoxicity was not demonstrated. From these result of the present study, it is unlikely that most of effector cells of rIL-2-expanded TIL in autologous RCC lysis are major histocompatibility complex-restricted cytotoxic T cells. We concluded that it is doubtful whether TIL is significantly superior over LAK cells in immunotherapy of human RCC.

Carcinoma, Renal Cell↗
PubMed1991

Interaction of endocytotic vacuoles with the inner nuclear membrane in simian virus 40 entry into CV-1 cell nucleus.

The transfer of endocytosed simian virus 40 (SV40) to the nuclear position was investigated ultrastructurally using cationized ferritin (CF), ferritin labelled concanavalin A (Fer-Con A) and Con A as cell membrane markers. In the cells incubated with these markers and SV40 at 4 degrees C, and then chased for 2 h at 37 degrees C in serum-free medium, ferritin particles representing CF and/or Fer-Con A binding sites were found in vacuoles with SV40. The membrane of some vacuoles seemed to be in contact with the outer nuclear membrane. Several ferritin particles were located in the perinuclear cisterna and within the nucleoplasm, but not within the nuclear pores. In addition, there were vacuoles with ferritin particles and SV40 near the nuclear membrane, which looked like a single diaphragm with heterochromatins inside it. The outer nuclear and vacuole membranes were often obscure in the areas where the vacuole was very close to the diaphragm. In the case of cells incubated with CF, SV40 and Con A at 4 degrees C, chased for 2 h at 37 degrees C, and then reacted with horseradish peroxidase (HRP), HRP activity showing Con A-binding sites was also observed along the nuclear side of the inner nuclear membrane as well as in the perinuclear cisterna along the outer membrane. These results confirm that SV40-induced endocytotic vacuoles fuse with the outer nuclear membrane, and further indicate that some endocytotic vacuoles may well interact directly with the diaphragm, suggesting another path for migration of SV40 into CV-1 cell nuclei besides the path going through the process of fusion of the vacuole membrane with the outer nuclear membrane.

Animals↗
PubMed1991

Evaluation with Fourier analysis on radionuclide angiography of viable but stunned myocardium in patients with right ventricular myocardial infarction.

Stunned myocardium of right ventricle was studied by radionuclide angiography (RNA) and Thallium myocardial scintigraphy (TL) in 39 patients with inferior myocardial infarction with and without right ventricular myocardial infarction (RVMI). RNA was performed within 1 week of the onset (acute phase) and after 1 month, when exercise cardiac scintigraphy (EX-TL) was also performed. The ejection fraction (EF) of each ventricle calculated from RNA and the phase and amplitude evaluated visually and quantitatively by Fourier analysis were compared between the acute phase and 1 month after the onset of myocardial infarction. The degree of visualization of right ventricle was examined in EX-TL 1 month after the onset. (1) In RNA obtained in the acute myocardial infarction, abnormalities in the right ventricle (delayed phase or low amplitude image) were observed in 18 (46%) but not in 21 (54%) of the 39 patients (N group). Of those 18 patients, the abnormalities in the right ventricle alleviated in 11 (RVMI-A group) but persisted in 7 (RVMI-B group) in RNA obtained 1 month after the onset. (2) In the acute phase, the right ventricular ejection fraction (RVEF) was 39.4 +/- 10.4% in N group, 30.8 +/- 5.3% in RVMI-A group, and 29.6 +/- 8.9% in RVMI-B group, with significant differences between N group and the other two groups (P less than 0.05) but no significant difference between RVMI-A and RVMI-B groups. (3) After 1 month, RVEF was 40.1 +/- 10.1% in N group, 42.2 +/- 8.4% in RVMI-A group, and 32.2 +/- 9.8% in RVMI-B group, being improved in RVMI-A group and showing a significant difference as compared with RVMI-B group (p less than 0.05). (4) In EX-TL of RVMI-A group, the right ventricle was visible although the uptake of TL was reduced in the entire right ventricle. In RVMI-B group, only part of the right ventricular free wall was visible with defects in the other areas of right ventricle. The sign of RVMI showed improvements in many of the patients after the acute phase, and their condition was considered to have been so-called stunned myocardium, which is a complex of symptoms of reversible myocardial ischemia, rather than RVMI.

Aged↗
PubMed1991

Radionuclide assessment of stunned myocardium by alterations in perfusion, metabolism and function.

A method for the diagnosis of stunned myocardium has not yet been established, although it has been retrospectively demonstrated in patients after intracoronary thrombolysis, unstable angina, and coronary revascularization. In this study, radionuclide cardiac imaging was carried out to evaluate the existence of stunned myocardium. 1) Gated blood pool scanning was performed in patients undergoing intracoronary thrombolysis both at the time of reperfusion (Rp) and 10 days later. In the Rp less than 4 h group, about half of the initially abnormal segments showed complete improvement on quantitative wall motion analysis, which was more than in the Rp greater than 4 h and control groups. 2) In patients with acute myocardial ischemia, the correlation between thallium perfusion and regional wall motion was assessed semiquantitatively. In unstable angina, 5.8% of the ventricular wall segments showed dissociation between perfusion and wall motion (well-perfused asynergy). These segments had abnormal wall motion although perfusion was maintained, and were thought to be areas of stunned myocardium. 3) Fourteen dogs were studied using thallium and 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) fatty acid imaging to evaluate the relationship of perfusion to metabolism. In the reperfusion model, mismatching of the pattern of thallium and BMIPP uptake was observed. Reperfused myocardium probably has an increased triglyceride content, which is related to the degree of myocardial viability. In conclusion, stunned myocardium may be correctly diagnosed acutely on the basis of alterations in its perfusion, metabolism, and function by using radionuclide cardiac imaging.

Coronary Thrombosis↗
PubMed1991

Comparative study of computerized trapezoid rotation test and sinusoidal harmonic acceleration test.

By using the Contraves computerized rotary chair system, trapezoid rotation (TR) test and sinusoidal harmonic acceleration (SHA) test were performed on each subject on the same day. The results in 25 normal volunteers and 145 patients with peripheral vestibular disorders were as follows: 1) As regards directional preponderance, the results of two rotation tests agreed in 75.9% of all patients, but a discrepancy was found in the rest. Abnormality was detected by TR test in 57.2% of all patients, and, less frequently, in 45.5% by SHA test. 2) In normal subjects, the maximum slow phase velocity of nystagmus provoked by TR test was greater than that of nystagmus provoked by SHA test using angular acceleration of a magnitude comparable to that in TR test. 3) As to the detection of abnormal VOR gain, the results of two rotation tests agreed in 100% of patients with bilateral vestibular disorders. However, in patients with unilateral vestibular disorders, the detection rate was higher for SHA test than that for TR test.

Acceleration↗
PubMed1991

Studies on condensed-heterocyclic azolium cephalosporins. I. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- alkoxyiminoacetamido]-3-(imidazo[1,2-a]pyridinium-1-yl)methyl-3- cephem-4-carboxylates.

In our study of the structure-activity relationships of cephalosporins bearing quaternary ammonium groups at the 3 position, we postulated that delocalization of the azolium positive charge would lead to an expanded antibacterial spectrum and increased activity. Since quaternization of condensed-heterocyclic compounds such as imidazo[1,2-a]pyridine gives positive charge delocalization, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporin derivatives (1-53) bearing various (imidazo[1,2-a]pyridinium-1-yl)methyl moieties at the 3 position were prepared and their antibacterial activity was determined. As expected, these cephalosporins exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. These results imply that imidazo[1,2-a]pyridine is a quite useful substituent for improving antibacterial activity and spectrum. The structure-activity studies revealed that a favorable substituent on the imidazo[1,2-a]pyridine is the cyano radical at the 6 position of the ring, and ethoxyimino or 1-carboxy-1-methylethoxyimino groups are suitable for the alkoxyimino substituent. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- ethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2-a]pyridinium -1-yl)methyl-3-cephem-4-carboxylate (45) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-(1- carboxy-1-methylethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2- a] pyridinium-1-yl)methyl-3-cephem-4-carboxylate (49) showed good antibacterial activity.

Cephalosporins↗
PubMed1991

Studies on condensed-heterocyclic azolium cephalosporins. II. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3-(condensed- heterocyclic azolium)methyl-3-cephem-4-carboxylates.

From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]ceph alosporins containing imidazo[1,5-a]pyridinium, imidazo[1,2-b]pyridazinium, imidazo[1,2-a]pyrimidinium, imidazo[1,2-c]pyrimidinium, and pyrazolo[1,5-a]pyridinium methyl groups at the 3 position. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3- (imidazo[1,5-a]pyridinium-2-yl) (1), (imidazo[1,2-b]pyridazinium-1-yl) (2), and (pyrazolo[1,5-a]-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum. The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ). These results imply that the delocalization of the positive charge of the imidazo[1,5-a]pyridinium, pyrazolo[1,5-a]pyridinium and imidazo[1,2-b]pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo[1,2-a]pyridine are effective moieties for improving antibacterial activity and spectrum.

Cephalosporins↗
PubMed1991

Structure-activity relationships of cadeguomycin analogs.

The relationship between the activity and the chemical structure of cadeguomycin (CDM, 7-carboxy-7-deazaguanosine) was studied with six analogs of CDM. Both activities of CDM, enhancing the incorporation of [3H]thymidine in K562 cells and potentiating the cytotoxicity of cytosine arabinoside for K562 cells, were significantly augmented by the replacement of the 7-carboxyl group with cyano (CDM-CN) or formyl (CDM-CHO), but they were not changed by the replacement with methyl. The activities were almost completely diminished by the replacement of ribose with arabinose, but the simultaneous replacement of carboxyl and ribose with formyl and arabinose showed higher activities than those of CDM. The replacement of 7-carboxy-7-deazaguanine with 7-carboxy-7-deazainosine markedly weakened the activity. CDM-CN and CDM-CHO at 0.2 micrograms/ml significantly potentiated the activity of cytosine arabinoside against MOLT-3 cells but CDM at 1 micrograms/ml did not. These results indicate that the ribose and guanine moieties in the CDM molecule are very important for its activity. Also replacing the carboxyl group at the C-7 position with cyano or formyl group is a useful way to strengthen the CDM activity. These compounds would effectively potentiate cytosine arabinoside against various kinds of tumor cells which CDM could not do.

Anti-Bacterial Agents↗
PubMed1991

Purification and properties of aminopeptidase C from chicken skeletal muscle.

Aminopeptidase C was purified from fresh chicken skeletal muscle by ammonium sulfate fractionation, and by successive chromatography on DEAE-cellulose, Ultrogel AcA 34, DEAE-cellulose again, and an alanine AH-Sepharose 4B affinity column twice. The purified enzyme migrated as a single band by SDS-PAGE. Aminopeptidase C was purified about 300-fold over the crude extract with a yield of 0.6%. The molecular weight of this enzyme was found to be 185,000 by gel filtration in a Sepharose 6B column and 92,000 by SDS-PAGE. The optimum pH for the hydrolysis of L-leucine beta-naphthylamide was 6.0-7.0, the enzyme being stable in the range of pH 6.5-8.0. The activity of this enzyme was strongly inhibited by EDTA and puromycin, and was high against the beta-naphthylamide derivatives of Lys, Leu, Ala and Met. The enzyme was more active towards tri- and tetrapeptides than towards dipeptides.

Amino Acid Sequence↗
PubMed1991

Pharmacological properties of the new non-steroidal anti-inflammatory agent etodolac.

The anti-inflammatory, analgesic, antipyretic and ulcerogenic activities of etodolac (CAS 41340-25-4), a new nonsteroidal anti-inflammatory agent, were compared with those of indometacin and other anti-inflammatory drugs in experimental animals. Etodolac had a remarkable anti-inflammatory effect in various experimental models: ultraviolet erythema, carrageenin-induced edema and swelling of adjuvant arthritis. In these models, the effective dose of etodolac was several fold that of indometacin. Etodolac inhibited prostaglandin E2 formation in a concentration-dependent manner, and its inhibitory potency was about 1/5 of that of indometacin. Etodolac also caused marked inhibition of granuloma formation and leucocyte functions such as chemotaxis, lysosomal enzyme release and active oxygen generation. These effects of etodolac were observed at similar doses of indometacin. Etodolac suppressed inflammatory pain but not non-inflammatory pain, and had an antipyretic effect but did not lower normal rectal temperature. Etodolac had no effect on delayed hypersensitivity reactions and was much less ulcerogenic than indometacin. These results indicate that etodolac is a low ulcerogenic anti-inflammatory agent with suppressing activities on leucocyte functions to the same extent as indometacin and prostaglandin biosynthesis.

Animals↗
PubMed1991

[Primary cardiac tumor with singular findings on cardiac radionuclide scintigraphy].

We encountered a primary cardiac tumor originated from the right atrium or pericardium with singular findings on cardiac radionuclide scintigraphy. The patient was 43-year-old female who showed asymptomatic cardiomegaly and abnormal cardiac silhouette by chest X-ray. First pass radionuclide angiography using Tc-99m pertechnetate revealed the abnormal stain filled from the stem of ascending aorta inner and outer portion of the right atrium. Selective angiography showed that the main feeding artery of the tumor was right coronary artery and right internal mammary artery. The pathological diagnosis of the surgically resected specimen was angiosarcoma. It was suggested that detail evaluation of first pass radionuclide angiography give us a useful clinical information linked the feeding artery of cardiac tumor in this case.

Adult↗
PubMed1991

Enhancement of activities of anti-tumor drugs by dipyridamole against multidrug-resistant human hepatoma PLC/PRF/5 cells.

Dipyridamole (DPM) at 10 microM enhanced the cytotoxicity of anti-tumor drugs, which were associated with multidrug resistance, more in multidrug-resistant human hepatoma PLC/PRF/5 cells (PLC/COL) than in its parental cells (PLC/S). DPM increased, dose-dependently, the intracellular accumulation of [3H]vinblastine in PLC/COL. However, the effect was immediately diminished by its removal from the medium, indicating that DPM needed to be present together with the anti-tumor drugs to enhance the intracellular accumulation of the drugs. DPM inhibited the efflux of [3H]vinblastine from the PLC/COL cells, the binding of [3H]vinblastine to membrane vesicles of PLC/COL, and the binding of [3H]azidopine to P-glycoprotein in the plasma membrane of PLC/COL. Apparently DPM binds to P-glycoprotein and inhibits active efflux. [14C]labeled DPM was quickly incorporated into the cells and the cellular level of [14C]DPM reached a plateau after 5 min. It was slightly higher in PLC/S than in PLC/COL. The cellular [14C]DPM quickly disappeared after its removal from the medium. These results indicate that DPM binds quickly but reversibly to various kinds of cellular proteins including P-glycoprotein and inhibits active efflux of some anti-tumor drugs in multi-drug-resistant tumor cells, resulting in the enhancement of the activities of these drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗