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T Nishimura

Publications and source records attributed to T Nishimura.

At least 109 records · Page 6Linked to original sources
PubMed1991

Bispecific antibody-directed antitumor activity of human CD4+ helper/killer T cells induced by anti-CD3 monoclonal antibody plus interleukin 2.

Freshly isolated human CD4+ T cells can not respond to recombinant interleukin 2 (rIL-2) because of their lack of p75 IL-2 receptor expression. However, we succeeded in inducing a marked proliferation of purified CD4+ T cells by activation with rIL-2 plus anti-CD3 monoclonal antibody (mAb) cross-linked to a plastic plate. The proliferated CD4+ T cells produced a significant amount of IL-2 upon stimulation with phorbol ester plus A23187. Interestingly, CD4+ T cells activated with anti-CD3 mAb plus rIL-2 revealed a strong cytotoxic activity against Fc receptor (FcR)-positive tumor cells in the presence of anti-CD3 mAb. Moreover, the CD4+ T cells could lyse FcR-negative glioma cells by targeting with bispecific mAb containing anti-CD3 mAb and anti-glioma mAb. Thus, we demonstrated that rIL-2 and immobilized anti-CD3 mAb allowed the rapid generation of human CD4+ helper/killer T cells, which may be useful for the development of a new adoptive tumor immunotherapy.

Antibodies, Monoclonal↗
PubMed1991

Macrophage-T cell interaction is essential for the induction of p75 interleukin 2 (IL-2) receptor and IL-2 responsiveness in human CD4+ T cells.

Fresh human CD8+ T cells showed a strong proliferative response to a high concentration of interleukin 2 (IL-2) in the absence of macrophages. In contrast, CD4+ T cells revealed no significant IL-2 responsiveness in the absence of macrophages. However, if CD4+ T cells were cocultured with macrophages, they showed higher proliferative response to IL-2 than CD8+ T cells. In accordance with the magnitude of IL-2 responsiveness, freshly isolated CD8+ T cells expressed significant amounts of p75 IL-2 receptor, while fresh CD4+ T cells did not express p75 IL-2 receptor. The expression of p75 IL-2 receptor on CD4+ T cells was induced by coculture with macrophages. The macrophage-induced p75 IL-2 receptor acquisition was blocked by monoclonal antibody (mAb) against class II antigen. Moreover, the addition of anti-CD4 mAb or anti-class II mAb to the culture caused a great inhibition of IL-2 responsiveness of CD4+ T cells. These results strongly suggest that macrophage-T cell interaction through CD4 and/or class II molecules is essential for the expression of p75 IL-2 receptor and IL-2 responsiveness in human CD4+, but not CD8+ T cells.

Antibodies, Monoclonal↗
PubMed1991

T cell receptor-independent cell-mediated cytotoxicity by nude mouse lymphokine-activated killer cells.

Lymphokine-activated killer (LAK) cells, which can lyse a variety of tumor cells, can be induced from both normal and athymic nude mouse spleen cells by culture with high doses of recombinant interleukin 2 (rIL-2). LAK cells generated from nude mouse spleen cells (Nude-LAK cells) express just Thy 1.2 antigen, but not CD4 and CD8 antigens. Nude-LAK cells express neither T3 molecule, T cell receptor (TCR) alpha beta nor TCR gamma delta on their cell surface. The lack of TCR expression on Nude-LAK cells was confirmed by the results of northern blot analysis. LAK cells generated from normal mouse spleen cells (Nor-LAK) express TCR alpha, beta transcripts, while Nude-LAK cells express only sterile TCR beta transcript, but not TCR alpha transcript. TCR gamma delta transcripts were scarcely detected in both Nor-LAK cells and Nude-LAK cells. Thus, it is strongly suggested that Nude-LAK cells can recognize and lyse tumor cells by TCR-independent mechanisms. Monoclonal antibody against lymphocyte function-associated antigen (LFA-1) molecule can block the cytotoxicity of Nude-LAK cells, indicating an important role of such accessory molecules in Nude-LAK cell-mediated cytotoxicity.

Animals↗
PubMed1991

Endothelin modulates calcium channel current in neurones of rabbit pelvic parasympathetic ganglia.

1. The effects of endothelin were studied, in vitro, on neurones contained in the rabbit vesical pelvic ganglion by use of intracellular and single-electrode voltage clamp techniques under conditions where sodium and potassium channels were blocked. 2. In the current-clamp experiments, endothelin (1 microM) caused a depolarization followed by a hyperpolarization of the membrane potential. In the voltage-clamp experiments, endothelin (0.01-1 microM) caused an inward current followed by an outward current in a concentration-dependent manner. 3. Membrane conductance was increased during the endothelin-induced depolarization and inward current. Membrane conductance was decreased during the endothelin-induced hyperpolarization and outward current. 4. The endothelin-induced inward and outward currents were not altered by lowering external sodium concentration or raising external potassium concentration. 5. The endothelin-induced inward current was depressed (mean 72%) in a Krebs solution containing nominally zero calcium and high magnesium. These results suggest that a predominent component of the endothelin-induced inward current is mediated by calcium ions. 6. The calcium-insensitive component of the inward current was abolished by a chloride channel blocker, 4-acetamide-4'-isothiocyanostilbene-2,2'-disulphonic acid. The mean reversal potential for the calcium-insensitive component of the inward current was -18 mV. This value is near the equilibrium potential for chloride. Thus, it is presumed that the calcium-insensitive component of the inward current is carried by chloride ions. 7. Endothelin caused an initial depression followed by a long lasting facilitation of both rapidly and slowly decaying components of high-threshold calcium channel currents (N- and L-type). 8. In summary, the data show that for neurones in the vesical pelvic ganglia, endothelin causes membrane depolarization and activates an inward current. The ionic mechanisms involve receptor-operated calcium and chloride currents. Also, endothelin causes an initial depression followed by a long-lasting facilitation of the voltage-dependent calcium current.

Animals↗
PubMed1991

Memory loss due to transient hypoperfusion in the medial temporal lobes including hippocampus.

A typical case of transient global amnesia (TGA) was investigated with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) with 1.5-tesler scans. During the amnesic episode, a marked decrease of cerebral blood flow was observed in the areas confined to the territory of the bilateral posterior cerebral arteries including the hippocampus. After the episode, cerebral blood flow returned to normal and a circumscribed lesion was detected in the middle portion of CA 1 field of the left hippocampus. The SPECT findings prove direct evidence that the medial temporal structures are involved in the establishment of new memories, as well as in process of recalling only recently acquired memories, but not in retrieval of memories acquired long ago. The MRI findings indicate that a unilateral partial damage to CA 1 sector of the hippocampus does not develop a definite memory impairment and that high-resolution MRI study on the hippocampus is necessary in TGA patients.

Amnesia↗
PubMed1991

Study of cytoskeletal proteins in fibroblasts cultured from familial Alzheimer's disease.

Cytoskeletal proteins of the cultured fibroblasts obtained from Alzheimer's disease patients were studied. Western blotting studies of tubulin, actin, and vimentin showed no difference between Alzheimer and the control fibroblasts. Western blotting studies of vimentin revealed five partial degradation products in 50 K-57 K Da. molecular size region, but no difference in the degradation pattern was noticed between Alzheimer and the control fibroblasts. The size of fodrin molecule, however, was quite different between Alzheimer and the control fibroblasts. Comparing the molecular size of fodrin purified from the bovine brain, it is concluded that fodrin in Alzheimer fibroblasts is not degraded, while significant amount of fodrin in the control fibroblasts is partially degraded resulting in the smaller size of the 160 K and 200 K Da. molecular weight products.

Actins↗
PubMed1991

Therapeutic effects of combined treatment using tetracycline-immobilized collagen film and root planing in periodontal furcation pockets.

46 upper and lower molars with furcation grade II involvement were selected from 16 patients with periodontal disease. The teeth were randomly allocated to the following groups according to treatment; (1) 4 consecutive administrations of tetracycline-immobilized cross-linked collagen film (TC film) at intervals of 1 week (TC group); (2) 1 root planing treatment (RP group); (3) combination treatment (TC + RP group); (4) no treatment (control group). The therapeutic effects of each treatment were compared both clinically and microbiologically. Records of plaque index, gingival index, bleeding on probing, probing depth, probing attachment level and microscopic counts were obtained at 0, 4, 6 and 8 weeks. The results showed marked decreases in probing depth and density of micro-organisms in both the RP and TC + RP groups. In particular, the TC + RP group was characterized by a decreased rate of bleeding on pocket probing and an increased probing attachment gain. The above findings demonstrated that root planning is effective in the treatment of furcation involvement and that the effects are enhanced by the local administration of TC films.

Collagen↗
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↗