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Biomedical subjects

Y Kimoto

Publications and source records attributed to Y Kimoto.

At least 19 recordsLinked to original sources
PubMed1992

Enhancing effect of pokeweed mitogen on the proliferation and the cytotoxicity of lymphokine-activated killer cells.

In order to obtain more potent lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy, pokeweed mitogen (PWM) was added to the culture medium for the initial 24-48 h of culturing. The proliferation rate of PWM-stimulated LAK cells reached about 1000-fold after 3-week culture. This rate was nearly the same as that of LAK cells stimulated by 10 ng/ml of OKT3, the mouse anti-CD3 monoclonal antibody. However, the cytotoxicity of PWM-stimulated LAK cells was significantly more potent than that of OKT3-stimulated LAK cells. Phenotypic analysis revealed that PWM-stimulated LAK cells were CD3+CD56(+)-dominant while OKT3-stimulated LAK cells were CD3+CD56(-)-dominant. About half of CD3+CD56+ PWM-stimulated LAK cells was CD8+. These results suggest that more efficient adoptive immunotherapy is possible by using high-dose PWM-stimulated LAK cells with more potent cytotoxicity. Interleukin-1 beta and tumor necrosis factor alpha were significantly increased in the culture media after 24-h incubation with 1 micrograms/ml of PWM. Secretion of interferon-gamma was not enhanced by this concentration of PWM within 24 h. Therefore, PWM is considered to activate monocytes or macrophages to produce these cytokines in advance, influencing the proliferation and the cytotoxicity of LAK cells.

Antigens, CD↗
PubMed1992

Topological localization of the frequency and amplitude characteristics of the whole and segmented renal pelvis.

The contractile characteristics of pacemaker regions in the unicalyceal renal pelvis of the rabbit were examined in vitro. The amplitude and frequency spectra of spontaneous contractions of whole and separated circular and longitudinal renal pelvic strips were identified. The effect of stretch on these parameters were examined in order to establish whether the pacemaker region that generates contractions in the renal pelvis was sensitive to distention. The results show that the frequency of spontaneous contractions in the whole pelvis (65 +/- 18 mHz) was significantly higher than any part of the circularly (41 x 8 mHz) or longitudinally cut (43 +/- 8 mHz) pelvis. The amplitude of longitudinal strips, 52 +/- 11 mg, was significantly smaller than that of the circular strips, 267 +/- 52 mg. In the circularly separated pelvis the frequency of spontaneous contractions was highest in the proximal part (41 +/- 8 mHz) and lowest in the pelviureteral junction (8 +/- 1 mHz). No significant increase in frequency was seen upon stretch in the whole or separated pelvis although there was a decrease in the amplitude of both the whole and separated pelvis. These results show that the frequency of contraction of the whole or the segmented renal pelvis is not sensitive to stretch.

Animals↗
PubMed1992

Pokeweed mitogen induces p55 interleukin-2 receptor expression on human monocytes and its effect on interleukin-2 activated monocyte cytotoxicity.

Activation of human peripheral blood monocytes by pokeweed mitogen (PWM) results in the expression of interleukin 2 receptor(IL-2R) p55 chains, which are absent on resting monocytes. By dual-fluorescence flow cytometry, we found PWM induced detectable numbers of IL-2R+ cell which were further identified as LeuM3+ monocytes (22.91% of the LeuM3+ cells were IL-2R+ within 24h, and 32.17% in 48h). In addition, LPS can also induce IL-2R on 15.39% of LeuM3+ cells. On the contrary, other mitogens such as PHA or Con A, and cytokines as IFN-gamma, IL-2, M-CSF, TNF-alpha and IL-1 beta showed no influence on the IL-2R expression on monocytes. It was also noticed that PWM itself had no direct effect on HLA-DR antigen expression on LeuM3+ cells. The addition of IL-2 to PWM-pretreated IL-2R positive monocytes significantly augmented their tumoricidal activity. Thus monocytes when activated underwent a series of phenotypic and functional changes including the expression of IL-2R which may provide an important immunoregulatory pathway.

Cytotoxicity, Immunologic↗
PubMed1992

Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies.

Clinical effects and side effects were investigated in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of healthy donors with the same blood types as those of patients. Recently we succeeded in increasing the proliferation rate and enhancing the cytotoxic activity of LAK cells by means of initial stimulation with pokeweed mitogen (PWM, PWM-LAK cells). Five of 12 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastases and pleural effusion. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies existed in the patients; this phenomenon suggests the safety of the adoptive immunotherapy using allogeneic LAK cells. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells. Recently, LAK cells, particularly PWM-LAK cells were found to obtain significantly potent and prompt lectin-dependent cell-mediated cytotoxicity (LDCC). All tumor cells confluent in microtest plate well could be annihilated by PWM-LAK cells plus PWM less than 8 hours. New immunotherapy using PWM-LAK cells or lectin-stimulated LAK cells with PWM or other lectins is discussed.

Adult↗
PubMed1991

Biological activity in the human system of isotype variants of oligosaccharide-Y-specific murine monoclonal antibodies.

The capacity of isotype variants of BR55-2, an anti-tumor monoclonal antibody directed against Y oligosaccharide, to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in the human system was evaluated using freshly isolated peripheral blood mononuclear cells, lymphocytes, monocytes and complement. The ADCC activities of the BR55-2 IgG3 isotype and its switch variants (IgG1, IgG2b, and IgG2a) with human monocytes were high for all isotypes, whereas the activity of all isotypes was lower with freshly isolated lymphocytes, IgG1 being the least effective. The CDC on the other hand was strong with IgG3, IgG2b and IgG2a and negative with the IgG1 variant. The IgG3 and IgG2a isotypes were selected for further development. Their strong ADCC and CDC activity against mammary carcinoma, colon carcinoma and small-cell lung tumor cell lines was confirmed quantitatively using proteins highly purified from tissue-culture supernatants. Significant variations in ADCC and CDC competence was observed among human donors.

Antibodies, Monoclonal↗
PubMed1991

Regional effects of indomethacin, acetylsalicylic acid and SC-19220 on the contractility of rabbit renal pelvis (pacemaker regions and pelviureteric junction).

The effects of the cyclooxygenase inhibitors indomethacin and acetylsalicylic acid (ASA) and the prostaglandin (PG) antagonist 1-acetyl-2-[8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl]hydrazine (SC-19220) on smooth muscle strips from the rabbit renal pelvis were examined. Circularly oriented tissues were taken from within the renal pelvis and subdivided into the four adjoining regions, from fornix to pelviureteric junction (PUJ). They were set in a tissue bath and isometric tension changes were recorded. Spontaneous contractions were observed and electrical field stimulations evoked twitch-like contractions. The frequency of spontaneous contractions was dependent on the region within the renal pelvis from which they were dissected, gradually decreasing from fornix (3.92/min.) to PUJ (0.43/min.). Indomethacin (10(-5)M) or ASA (10(-4)M) significantly increased the frequencies of spontaneous contractions in all four regions. In the upper three regions (pacemaker regions), both agents significantly decreased the amplitudes of spontaneous and stimulation-induced contractions. In the PUJ region, both agents significantly increased the amplitudes of spontaneous and stimulation-induced contractions. SC-19220 (3 x 10(-5)M) significantly increased the frequencies and decreased amplitudes of spontaneous contractions in all four regions. These results suggest that the PUJ has different contractile characteristics from those of pacemaker regions and that decrease of amplitude by indomethacin or ASA is based on their cyclooxygenase inhibitor property.

Animals↗
PubMed1991

Purification and characterization of aseanostatins: actinomycete-derived fatty acid inhibitors to myeloperoxidase release from human polymorphonuclear leukocytes.

We found inhibitors, designated aseanostatins P1 and P5, against myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). Aseanostatins were extracted from an actinomycete isolated in Thailand and purified by a series of column chromatography of charcoal and silica gel, and HPLC. Physico-chemical characterization by gas liquid chromatography and GC-MS indicated that aseanostatins were fatty acids. The active forms of aseanostatins were recovered by hydrolyzing their methyl esters after HPLC. Two components P1 and P5 with the IC50 of 0.96 and 0.54 microgram/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin P1. The component P1 was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1 microgram/ml) did not inhibit beta-glucuronidase release, but O2- production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10(-8)M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.

Actinomycetales↗
PubMed1990

Effects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvis.

The effects of [1-desamino-8-D-arginine]vasopressin (DDAVP) (V2 receptor agonist) and papaverine on four continuous circular smooth muscle strips in rabbit renal pelvis were studied by an isometric tension recording methods. DDAVP suppressed spontaneous contractions in a dose-dependent and region-dependent way. Papaverine suppressed these contractions in a dose-dependent way simultaneously in all four portions. These results suggest that there may be distribution differences of V2 receptors in the renal pelvis. Together with its anti-diuretic action, DDAVP may merit consideration for the treatment of renal colic.

Animals↗
PubMed1990

Endothelium dependent relaxation of human corpus cavernosum by bradykinin.

The release of endothelium-derived relaxing factor (EDRF) from human corpus cavernosum (CC) tissue was confirmed by demonstrating that bradykinin produces endothelium dependent relaxation of human CC tissue. Human CC strips were set in a tissue bath and isometric tension changes were recorded. All strips showed spontaneous contractions and produced tonic contractions by both high potassium solution and noradrenaline (NA) (10(-9) to 10(-4) M) in a dose dependent manner. In preparations precontracted with NA, relaxation was produced by bradykinin (10(-7) to 2 x 10(-6) M). Strips lacking endothelium were contracted by NA but no relaxation was observed with the addition of bradykinin. More direct evidence of the release of EDRF from human CC was demonstrated by a "sandwich" mount. We conclude that bradykinin relaxes human CC by releasing EDRF and that this EDRF may be a factor in erectile function.

Bradykinin↗
PubMed1990

Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum.

The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.

Calcium↗
PubMed1989

Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice.

The results of single-agent chemotherapy, with 11 anticancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3-4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.

Animals↗
PubMed1989

[Mass culture of LAK cells by a hollow-fiber bioreactor system].

We attempted to culture LAK cells by the use of the hollow-fiber bioreactor system, "Acusyst-P". The number of LAK cells increased by 30-40 times. The majority of LAK cells cultured by this hollow fiber system originated in T cell. LAK cells cultured by hollow-fiber system were different from LAK cells statically cultured in their cytotoxicity and change of phenotype. We obtained LAK cells more efficiently and safely which have higher viability and cytotoxicity by the use of hollow-fiber bioreactor system than by static culture.

Cytological Techniques↗
PubMed1989

[Mycotic liver and spleen abscesses successfully treated by intraportal and intrahepatosplenic arterial administration of antimycotic drugs in two cases with acute leukemia].

Case 1. A 34-year-old male was admitted in July, 1986 with a diagnosis of AML (M2). Two courses of BHAC-DMP regimen induced complete remission in October, while marked pyrexia resistant to antibiotics remained. An ultrasonography (US) and computed tomography (CT) revealed multiple liver and spleen abscesses suspected of mycotic etiology. Administration of amphotericin B (AMPH-B) by intravenous injection was difficult owing to its severe side effect. Multiple abscesses increased in the size and number despite treatment with Miconazole (MCZ) and Ketoconazole. Exploratory laparotomy was performed with splenectomy, and splenic specimens were found to contain Candida organisms. Soon AMPH-B was administered through a catheter inserted into the portal vein at the same time. A side effect by AMPH-B was tolerable and his fever resolved to normal in 2 weeks after institution of this therapy, and the sizes of abscesses were markedly reduced. The patient remained in remission through 23 months, free of fungal infection. Case 2. A 23-year-old female was admitted for relapse of ALL (L2), in April, 1987. Reinduction therapy with BHAC-L-AVP achieved again in May but fever unresponsive to antibiotics occurred. Since multiple liver-spleen abscesses were showed by US and CT suspected mycotic etiology, antimycotic therapy with Miconazole and AMPH-B was performed but clinical findings were deteriorated. AMPH-B was administered through a catheter inserted into the hepatic artery for two weeks, following into the splenic artery for a week. Splenic abscesses were resolved in a week and liver abscesses were markedly reduced at three weeks after initiation of intra-arterial antifungal treatment. Through the analysis of these case studies we confirmed the usefulness of intraportal and intrahepatosplenic arterial administration of AMPH-B.

Abscess↗
PubMed1988

Killing of human tumor cell lines by human monocytes and murine monoclonal antibodies.

We evaluated the capacity of freshly isolated blood monocytes to mediate antibody-dependent cellular-mediated cytotoxicity (ADCC) in cooperation with murine anti-tumor monoclonal antibodies (MAbs). Blood monocytes isolated from most donors by adherence selection to fibronectin-coated plastic surfaces and subsequently depleted of natural killer/killer (NK/K) cells exhibited significant ADCC activity against tumor cell lines in combination with an IgG3 antitumor MAb (BR55-2). However, significant variation in ADCC competence was observed among donors. Culture parameters influencing monocyte ADCC activity were evaluated and optimized. The influence of MAb isotype on ADCC capacity of anti-tumor MAbs was also evaluated using anti-tumor class-switch variant hybridoma proteins and a panel of anti-tumor MAbs. MAbs of the IgG2a and IgG3 subclasses exhibited high ADCC potential, whereas MAbs of the IgG2b subclass exhibited no ADCC activity. One of two IgG1 MAbs tested exhibited high ADCC activity with monocyte effectors. The role of monocytes or macrophages in tumor remission of cancer patients undergoing MAb immunotherapy is not known. However, correlative studies of monocyte ADCC capacity and responsiveness of cancer patients to MAb immunotherapy may help to establish the role of these effectors in MAb-mediated tumor remissions.

Animals↗
PubMed1988

Functional innervation patterns in the corpus spongiosum and glans in the dog.

The neural control of smooth muscle cells in the corpus spongiosum, helicine artery and bulbus glandis of the dog was investigated in relation to the mechanism involved in erection, using isometric tension recording and micro-electrode methods. In the corpus spongiosum, field stimulation evoked twitch-like contractions followed by relaxations. These relaxations were enhanced and prolonged by neostigmine and partly suppressed by atropine. Guanethidine abolished the twitch-like contractions and increased muscle tone. The relaxations observed after pre-treatment with guanethidine were abolished by tetrodotoxin (TTX), thereby indicating that these muscles are innervated by adrenergic excitatory, cholinergic and non-adrenergic non-cholinergic inhibitory nerves. In the helicine artery and bulbus glandis, field stimulation evoked contractions and these contractions were abolished by guanethidine or TTX, indicating that these muscles are innervated by adrenergic excitatory nerve fibres. After pre-treatment with guanethidine and atropine, muscle relaxation appeared in response to field stimulation in the helicine artery but not in the bulbus glandis, indicating that the helicine artery in the corpus spongiosum is also innervated by non-adrenergic non-cholinergic inhibitory nerves in addition to the excitatory adrenergic nerves. In the smooth muscle cells of the corpus spongiosum, slow potential changes were correlated with spontaneous contractions and field stimulation evoked excitatory or inhibitory junction potentials. The neural mechanism involved in erection is discussed in relation to the topical difference in the autonomic innervation patterns in the corpus spongiosum, helicine artery and bulbus glandis.

Animals↗
PubMed1988

[Adoptive immunotherapy of malignant disease using LAK cells].

Adoptive immunotherapy of malignant diseases was tried using LAK cells induced from peripheral blood lymphocytes with recombinant IL-2 (TGP-3) and fresh human plasma. The cytotoxicity of autologous and mixed cultured allogeneic LAK cells reached maximum after two weeks, and after 7 to 10 days of incubation, respectively. The necessary dose of IL-2 combined with LAK cells was 1000 or 2000 units for maintenance and enhancement of LAK activity, which did not cause any lethal side effect, i.e., capillary permeability leak syndrome. A clinical effect was observed in cases of carcinomatous pleural effusion of colon cancer, pulmonary metastases from breast cancer and rhabdomyosarcoma, and pulmonary, hepatic and abdominal wall metastases from squamous cell carcinoma of the epipharynx. The only side effect observed was fever. No pathological reaction occurred after frequent injection of allogeneic LAK cells. The most important problem to be solved is how to induce a large amount of LAK cells.

Adult↗