Biomedical subjects

Y Kimoto

Publications and source records attributed to Y Kimoto.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1987

Monoclonal antibody-defined correlations in melanoma between levels of GD2 and GD3 antigens and antibody-mediated cytotoxicity.

A monoclonal antibody is described that specifically detects the ganglioside antigens GD2 and GD3, binding preferentially to GD2, in melanoma. Antibody specificity was demonstrated with solid-phase radioimmunoassay and enzyme-linked immunosorbent assay as well as by immunostaining on thin-layer chromatography plates using structurally characterized gangliosides. Binding of both the IgG3 antibody and its IgG2a switch variant were assayed on live cells by cytofluorography and by immunoperoxidase staining on frozen tissue sections. The binding patterns correlated with antitumor activity in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays with human effector cells and complement in an 111In-release assay using cell lines derived from the same individual. The significant level of killing in all tumor cells tested that express GD2, GD3, or both, suggests the importance of multiple specificity towards tumor antigens, i.e., binding of a monoclonal antibody to two or more tumor-associated antigens.

Animals↗

PubMed1987

Interferon treatment of human stomach and breast carcinoma xenografts in nude mice.

Comparative effects of natural and recombinant interferons (IFNs)-alpha and -beta on xenografted human gastric and breast carcinoma lines in nude mice were studied. The lines were sensitive to IFNs. The breast carcinoma lines were more sensitive than the gastric carcinoma lines to IFNs. Natural IFN-beta was more effective than the other three IFNs on the gastric carcinoma lines. One breast carcinoma line was more sensitive to IFN-alpha whereas the other was more sensitive to IFN-beta. Large doses and frequent injections of IFNs were necessary for optimal effectiveness.

Animals↗

PubMed1987

Autonomic innervation of the canine penile artery and vein in relation to neural mechanisms involved in erection.

Neural control of the penile artery and vein of dogs was investigated using isometric tension recording and microelectrode methods. Field stimulation evoked twitch-like contractions of these two vessels and these contractions were blocked by guanethidine. In the artery, twitch-like contractions were more effectively blocked by yohimbine than by prazosin. During high tone of arterial and venous tissues evoked by noradrenaline (NA) in the presence of guanethidine, field stimulation evoked muscle relaxation that was not affected by atropine but was abolished by tetrodotoxin. In parallel to the mechanical responses, field stimulation evoked excitatory junction potentials (EJPs) in both arterial and venous smooth muscle cells. In the case of the artery, an action potential was superimposed on the EJP. The NA-induced contraction was suppressed by vasoactive intestinal polypeptide (VIP), dose-dependently. On the other hand, alpha, beta-methylene-ATP did not affect the muscle relaxation induced by field stimulation. These results indicate that the penile artery and vein of the dog are innervated by adrenergic excitatory nerves and non-adrenergic, non-cholinergic inhibitory nerves. The transmitter possibly involved in the latter is discussed.

Adenosine Diphosphate↗

PubMed1987

Actions of prostaglandin I2 and thromboxane A2 on vascular smooth muscle tissues.

Actions of prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) on vascular smooth muscles were investigated in relation to the function of the endothelium. In intact vascular smooth muscle tissues of the thoracic aorta, PGI2-Na, used as a substitute substrate of PGI2, relaxed the precontracted tissue, in a dose dependent manner, in intact tissues and also after mechanical ablation of the endothelium. Acetylcholine (ACh) relaxed the tissue precontracted by noradrenaline, in the presence or absence of indomethacin; however, the relaxation required the presence of an intact endothelium. On the other hand, increased amounts of PGI2 with the application of acetylcholine, as estimated from the amount of 6-keto-PGF1 alpha, were markedly attenuated by indomethacin. In smooth muscles of this tissue without the endothelium, ACh synthesized lesser amounts of PGI2, while PGI2-Na increased the amount of cyclic AMP. Thus, PGI2 was synthesized in both the endothelium and smooth muscles. The former produces a larger amount of PGI2 than the latter, but the PGI2 synthesized in smooth muscles may act more potently on the smooth muscle than does that synthesized in the endothelium. In the canine coronary artery, mechanical responses induced by TXA2, as estimated from actions of 9, 11,-epithio-11, 12-methano-thromboxane A2 (STA2) were enhanced after ablation of the endothelium. The minimum concentration of STA2 required to produce the contraction was above 1 nM and the maximum amplitude was evoked with 30 nM. The amplitude of the STA2-induced contraction was reduced in Ca-free solution or with the application of nifedipine. However, prazosin, propranolol or atropine had no effect on the STA2-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Actions of the alpha-1 adrenoceptor blocker bunazosin on the norepinephrine-induced contraction of smooth muscles in the rabbit proximal urethra.

Effects of bunazosin on the norepinephrine-induced electrical and mechanical activities of smooth muscles of the rabbit proximal urethra were investigated using microelectrode and tension recording methods. Responses to norepinephrine were mediated by activation of both alpha-1 and beta adrenoceptors. In the presence of propranolol, the norepinephrine-induced contraction increased and, with yohimbine, the phasic but not tonic contraction was only inhibited slightly. Contributions of the alpha-2 adrenoceptor to the norepinephrine-induced contraction were negligible. Bunazosin inhibited in a concentration-dependent manner both the phasic and tonic responses of the norepinephrine-induced contraction, and the concentration-response relationship for norepinephrine shifted to the right. The Schild plot obtained from measurements of tonic responses in this antagonism yielded a straight line with a slope of 0.96. The pA2 value for bunazosin was 8.39 and the KB value was 4.1 nM. Prazosin had similar effects (the corresponding values being 0.96, 8.21 and 6.2 nM, respectively). The mechanical response evoked by field stimulation was composed of cholinergic, noradrenergic alpha-1 and noncholinergic-nonadrenergic contractions and of a subsequent nonadrenergic-noncholinergic relaxation. Bunazosin inhibited the twitch contraction evoked by field stimulation more than did prazosin, albeit not completely. These results indicate that although the smooth muscle tone in the urethra is regulated by multiple neural factors, the elevation of the tone is regulated predominantly by activation of the alpha-1 adrenoceptors. Bunazosin has an antagonistic action on this receptor. The actions of bunazosin are discussed in relation to the clinical application in cases of inadequate micturition.

Acetylcholine↗

PubMed1987

Augmentation of cytotoxic activity of recombinant human tumor necrosis factor (rHu-TNF) by recombinant human interferon-gamma (rHu-IFN-gamma).

The present study was undertaken to examine the effect of recombinant human interferon-gamma (rHu-IFN-gamma) on the in vitro antitumor activity of recombinant human tumor necrosis factor (rHu-TNF) against rHu-TNF-sensitive and resistant tumor cells. rHu-IFN-gamma augmented both cytostatic and cytocidal activity of rHu-TNF. When 14 tumor cells were tested, augmentation by rHu-IFN-gamma was observed in most of rHu-TNF-sensitive tumor cells and in few cases in rHu-TNF-resistant tumor cells. Among rHu-TNF-sensitive tumor cells, there was no relationship between the degree of augmentation and the susceptibility to rHu-TNF. Augmentation was marked when tumor cells were treated with rHu-IFN-gamma either before the exposure to rHu-TNF or during the early period of the exposure to rHu-TNF. On the other hand, augmentation was not observed when tumor cells were treated with rHu-IFN-gamma during a late period of the exposure to rHu-TNF. From these results, a combined treatment with both agents can be expected to provide an approach to get better results in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

[Adoptive immunotherapy of malignant diseases with LAK cells].

Peripheral blood lymphocytes obtained from patients by leukapheresis were cultured in RPMI 1640 containing human plasma and interleukin 2. The morphology, phenotypes and cytotoxicity of induced LAK cells were studied. Lymphoblastoid cells mainly proliferated were OKIa1+ cells and were thought to be LAK cells. Maximal cytotoxicity was obtained after two weeks of incubation. IL-2 enhanced the cytotoxicity of LAK cells. Autologous LAK cells induced by two weeks of incubation were injected into patients. One case of pulmonary metastases of breast cancer showed reduction and two lesions showed partial regression. Also, no new lesions appeared in the lungs of a patient with alveolar soft-part sarcoma.

Adult↗

PubMed1987

[Interleukin 2].

Effectiveness of IL-2 and LAK cells induced by IL-2 on malignant diseases was discussed. IL-2 alone administered systemically showed a poor effect, and combination of IL-2 are necessary for LAK cells to kill the target malignant cells. Adoptive immunotherapy using IL-2 and LAK cells should be applied for pulmonary and hepatic metastases. Postoperative adjuvant therapy and combination with chemotherapy will become important in the future.

Humans↗

PubMed1987

[Adoptive immunotherapy of malignant diseases using normal allogeneic LAK cells].

Allogeneic LAK cells induced from PBL of normal donors were used for adoptive immunotherapy of malignant diseases. The possibility of an antibody against allogeneic LAK cells was suggested. However, no immune reaction was observed and LAK activity was maintained in vitro in the presence of patient's plasma sampled during the course of therapy.

Graft vs Host Reaction↗

PubMed1987

Adoptive immunotherapy of malignant diseases with IL-2-activated lymphocytes.

Lymphokine activated killer cells (LAK cells) or interleukin 2 (IL-2)-activated killer cells were induced by recombinant IL-2 (TGP-3) for clinical adoptive immunotherapy of malignant diseases. After incubation of peripheral blood lymphocytes (PBL) with IL-2 and normal human plasma for 1-2 weeks LAK cells were obtained that showed a maximum cytotoxicity against target cells, and did not need a toxic dose of IL-2 to enhance or maintain their cytotoxicity. Both autologous and allogeneic LAK cells were used in five clinical cases without any immune side effects, and were effective in three cases.

Adult↗