Search PubMed⌕ Search

Biomedical subjects

T Saga

Publications and source records attributed to T Saga.

At least 163 records · Page 9Linked to original sources

Fascicular parasystole associated with tachycardia-dependent right bundle branch block.

A 43-year-old female with a chief complaint of palpitation was subjected to clinical electrophysiological studies. Initial standard 12-lead ECG revealed that her palpitation was caused by fascicular parasystole firing at the basic cycle length of 1.25-1.40 seconds, and that both sinus and parasystolic beats were associated with left anterior fascicular block and tachycardia-dependent RBBB. His-bundle electrocardiogram suggested that the parasystolic focus was located in the proximal portion of the anterior fascicle of the left bundle branch and that the site of tachycardia-dependent conduction block was located in the main right bundle branch. These findings suggest that diffuse pathological changes in the intraventricular conducting system were responsible for both the conduction block and automatic impulse formation in the present case.

Adult↗

[Distribution of C3b receptors on polymorphonuclear leukocytes from normal healthy adults by scanning immunoelectron microscopy].

The distribution of C3b receptors on polymorphonuclear leukocytes cultured from normal healthy volunteers was examined by scanning immunoelectron microscopy with mouse anti-CR1 monoclonal antibody and 40 nm-goat anti-mouse IgG antibody. The distribution was categorized into three types; first, Au-particles clustered in numbers of several to ten or more on polymorphonuclear leukocytes (mean +/- S.D. = 59.5 +/- 36.8, n = 146), second, tens of the particles mostly on two or three ruffles of the cells (121.7 +/- 63.8, n = 45), and third, particles assembled at one part of the cells (74.1 +/- 47.4, n = 59). The distribution of Au-particles on all polymorphonuclear leukocytes showed a normal distribution curve (74.1 +/- 50.6, n = 250, p less than 0.02). These results show that polymorphonuclear leukocytes had some tendencies but no uniformity of distribution of C3b receptors on their plasma membrane when they were cultured.

Cells, Cultured↗

[Clinical evaluation of surgical treatment of children with Kawasaki disease].

Clinical problems in the surgical treatment for the vascular lesion after Kawasaki disease were evaluated in five patients who underwent myocardial revascularization. Each patient had significant stenosis or complete occlusion with aneurysmal formation. Four patients received single aortocoronary bypass and one patient received double bypass. Three saphenous veins and three internal mammary arteries were used for bypass grafting. There were no operative or late deaths. Three saphenous vein grafts and two internal mammary artery grafts were patent both in the early postoperative and in the late postoperative studies. Progression of the obstructive lesions at other coronary arteries which were not bypassed at the operation were found in two patients. One patient revealed bilateral common iliac aneurysms associated with progressive obstruction of urinary tract followed by renal dysfunction. It appears that even the patient who had satisfactory surgical results in late studies are required to be followed up with utmost care to other coronary lesions or other vascular lesions in addition to the lesions bypassed.

Child↗

67Ga-labeled antibodies for immunoscintigraphy and evaluation of tumor targeting of drug-antibody conjugates in mice.

To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with 67Ga, was conjugated with monoclonal antibodies using three different methods. One method used a homocoupling reagent, glutaraldehyde, whereas two other methods used heterocoupling reagents, N-succinimidyl-3-(2-pyridyldithio)propionate and succinimidyl-6-maleimidohexanoate, linking deferoxamine to antibodies through alkylamine, disulfide, and thioether bonds, respectively. Antibodies were efficiently labeled with 67Ga through chelation with deferoxamine without losing antigen-binding capability. 67Ga-labeled antibodies clearly visualized transplanted tumors in nude mice. However, the biodistribution of radioactivity was markedly different with the coupling methods used for the conjugation of deferoxamine and antibodies. High nonspecific uptake in the liver and spleen was observed with 67Ga-labeled antibodies prepared by the glutaraldehyde method. 67Ga-labeled antibodies linked by thioether bonds demonstrated in vivo stability and the highest tumor:liver ratio, whereas 67Ga-labeled antibodies conjugated with disulfide bonds were rapidly cleared from the circulation. These results indicate that antibody conjugates linked by thioether bonds are a better choice for drug targeting and that 67Ga-labeled antitumor monoclonal antibodies are useful not only for the immunoscintigraphy but also for the quantitative assessment and visualization of the biodistribution of drug-antibody conjugates.

Animals↗

Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells.

CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen.

Adenocarcinoma↗

Immunoscintigraphy and pharmacokinetics of indium-111-labeled ZME-018 monoclonal antibody in patients with malignant melanoma.

Immunoscintigraphic and pharmacokinetic characteristics of 111In-labeled ZME-018 monoclonal antibody were examined in 8 patients with malignant melanoma. Each patient received a single intravenous infusion of 20 mg of ZME-018, coupled to 3 mCi of 111In without any acute toxicity. Scintigrams were taken 1, 3, and 6 days after the administration, and blood and urine samples were also taken frequently. Rapid clearance of some radioactivity was seen in early urine samples in the form of 111In DTPA, but after 1 day, urinary excretion of radioactivity was slow and steady, with an average of 2.5% of the injected dose excreted per day. The scans demonstrated that there was blood retention of radioactivity in the heart and great vessels 1 day after infusion and considerable clearance from the blood pool occurred by 3 days. However, 111In was deposited in the liver, spleen and bone for up to 6 days. The optimal time for imaging appeared to be at 3 days. Nineteen out of 26 known lesions or 6 out of 8 patients were positive. There were 21 lesions detected that were not suspected during the work-up the patient. Five patients developed human anti-mouse antibody in the serum by 3 weeks. These results suggest that immunoscintigraphy with 111In-labeled ZME-018 antibody is safe and useful for the detection of metastatic lesions in a selected group of patients with malignant melanoma.

Adult↗

Autonomic innervation of pulmonary artery: evidence for a nonadrenergic noncholinergic inhibitory system.

We have investigated the presence and significance of the nonadrenergic noncholinergic relaxant system in isolated strips of guinea pig and cat pulmonary artery (PA), using transmural electrical field stimulation (EFS). Changes in PA strip tension were measured isometrically, in response to EFS with 50-70 V at 20 Hz and pulse durations of 1 or 2 ms. We examined the influence on these responses of alpha- and beta-adrenergic and cholinergic muscarinic receptor blockade, the neurotoxin tetrodotoxin, and the local anesthetic lidocaine. EFS induced an initial brief contraction followed by a slow prolonged relaxation. Phenoxybenzamine, 1.5 X 10(-5) M, greatly reduced the contraction (74.1-87.6% in guinea pig, 65.7-67.4% in cat) and enhanced the subsequent relaxation (23.9-35.5% in guinea pig, 66.8-67.8% in cat). The relaxation was moderately reduced by propranolol, 7.7 X 10(-6) M (30.5-35.0% in guinea pigs, 6.0-21.2% in cat), and by atropine, 1.4 X 10(-6) M (23.7-32.1% in guinea pig, 24.9-40.6% in cat). The major portion of the relaxation, however, persisted in the presence of these blockers. The neurogenic origin of this relaxation was confirmed by its loss with either tetrodotoxin or lidocaine. We conclude that in guinea pig and cat lungs (1) neurogenic pulmonary vascular contraction is principally mediated by the alpha-adrenergic system, (2) the beta-adrenergic and cholinergic components have a moderate relaxant influence, but (3) the dominant part of neurogenic relaxation is mediated by a nonadrenergic noncholinergic mechanism.

Animals↗

Semiquantitative in vitro binding assay of indium-111-labeled monoclonal antibodies to human cancer and normal tissues.

We have developed a simple in vitro method for the semiquantitative assessment of the radiolabeled antibody binding to cancer and normal tissues. Indium-111-labeled F(ab')2 fragments of 17-1A and 19-9 monoclonal antibodies with well-characterized specificity for gastrointestinal cancer demonstrated similar binding properties between cultured cancer cells and membrane fractions of homogenates prepared from tumor tissues. All of the 17 colon cancer specimens and seven (64%) of 11 gastric cancer specimens obtained by surgery showed positive binding with 17-1A. Specific binding of 19-9 was observed in 9 (53%) colon cancers and 4 (36%) gastric cancers. However, some normal colon tissues were also positive with 111In-labeled 17-1A. Relative levels of CA 19-9 antigen expression, determined by the binding with radiolabeled antibodies, correlated with percent positive cells determined by the immunohistochemical assays. Furthermore, membrane fractions could be cryopreserved without losing antibody-binding activity. These results indicate that this assay can be used for testing the immunoreactivity of radiolabeled anti-tumor antibodies and in vitro binding properties to cancer and normal tissues.

Antibodies, Monoclonal↗