Hemoglobin Machida [beta 6 (A3) Glu replaced by Gln], a new abnormal hemoglobin discovered in a Japanese family: structure, function and biosynthesis.
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Biomedical subjects
Publications and source records attributed to K Imai.
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The mouse immunoglobulin G2 monoclonal antibody (MoAb) 465.12S reacts with a cytoplasmic antigen present in human melanoma cells but not detectable in melanocytes. Indirect immunofluorescent staining of a large number of surgically removed normal adult and fetal tissues with the MoAb 465.12S detected the cytoplasmic antigen in epithelial cells from several organs. The intensity of staining was greater in adult tissues than in the corresponding fetal tissues. Furthermore, the MoAb 465.12S stained nearly all of the surgically removed tumors tested but did not stain many of the normal tissues from which they originated. In almost all cases, the intensity and frequency of staining wa greater for tumor cells than for corresponding normal tissues. From cultured carcinoma and melanoma cells, the MoAb 465.12S immunoprecipitated four glycopolypeptides with molecular weights of 94,000, 75,000, 70,000, and 25,000. Incorporation of 3H-labeled sugars into the various components of the cytoplasmic antigen revealed that the M.W. 75,000 component was unusual in that it contained only glucosamine and mannose. The antigenic determinant defined by the MoAb 465.12S appears to be protein rather than carbohydrate in nature since it is heat sensitive and is expressed on the antigens synthesized by cells in presence of tunicamycin. Analysis of the spent culture medium of carcinoma and melanoma cell lines revealed that the cytoplasmic antigen is readily shed by these cells and consists of a major M.W. 94,000 and a minor M.W. 72,000 component. Treatment of cultured melanoma cells with the antibiotic tunicamycin showed that glycosylation of the cytoplasmic antigen is required for its shedding and/or stability in the spent culture medium.
Combination chemotherapy of cis-diammine dichloro platinum (II) (CDDP) and bleomycin was given to 10 patients with advanced squamous cell carcinoma of the head and neck. Nine patients had received prior radical radiotherapy, 2 had major ablative surgical procedures, and one had been previously treated with chemotherapy. Responses were as follows (duration in months): 2 CRs (4,6+), 2 PRs (1.5,1.5), and 2 minors. Vomiting related to CDDP was observed in 5 patients, nephrotoxicity and hypocalcemia in one patient were also observed.
Combination chemotherapy of cis-diammine dichloro platinum (II) (CDDP) and bleomycin was given to 10 patients with advanced squamous cell carcinoma of the esophagus. Nine patients had had major ablative surgical procedures, 8 had received prior radiotherapy, and 4 had been previously treated with chemotherapy. Responses were as follows (duration in months): 3 complete (1, 1.5, 7), 1 partial (1.5), and 3 minor. Vomiting related to CDDP was observed in 6 patients, and nephrotoxicity in 2 patients.
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The effects of tetanus toxin on neuromuscular transmission of mice in acute intoxication produced by intravenous injection of a large amount of the toxin were examined by (1) recording the phrenic nerve impulses, the electromyograms (EMGs) of the diaphragm and the electrocardiograms, and (2) the evoked EMGs of the gastrocnemius muscle in response to electrical stimulation of the sciatic nerve. The evoked EMGs of the gastrocnemius muscle were analyzed in terms of kinetic and tonic components by their different latencies. Just before death of animals, the EMGs of the diaphragm appeared with some delay relative to the corresponding phrenic discharges. Finally, the EMG of the diaphragm disappeared even in the presence of phrenic discharge, but cardiac electrical activities continued. The amplitudes of the evoked EMGs of the gastrocnemius muscle invariably became low before death, but the muscle action potential could be recorded by direct muscle stimulation for several minutes after death. The latencies of the evoked EMGs were constant until about the middle of the survival time when the latencies suddenly became prolonged. The longer latency was the same as that of the tonic action potentials. Thus, in acutely tetanus-intoxicated mice, neuromuscular transmission was blocked rapidly and the kinetic component of the muscle was blocked earlier than the tonic component.
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The IgG2a monoclonal antibody (MoAb) 376.96S, secreted by a hybridoma derived from a mouse immunized with cultured human melanoma cells COLO 38, reacts with a single 94,000-dalton glycoprotein that is peripherally associated with the plasma cell membrane of cultured melanoma cells. Indirect immunofluorescence analysis with cryostat thin sections of human tissues showed that this antigen is absent from a large variety of normal tissues but is readily detectable on melanomas, nevi, and several different carcinomas. The MoAb 376.96S binds with cultured melanoma and carcinoma cell lines to a similar extent and can mediate both complement-dependent and cell-dependent lysis of these cells. The 94,000-dalton glycoprotein detected by MoAb 376.96S is distinct in its tissue distribution, antigenicity, and molecular profile from several structures previously identified with monoclonal antibodies that have similar molecular weights.
External photoscanning with display of radioactivity data as a color-scaled image detected xenografts of human melanoma in male nude inbred mice of BALB/c background 48 hours after injection of 131I-labeled monoclonal IgG 225.28S that is specific for human melanoma. A 131I-labeled polyclonal goat IgG against human melanoma-associated antigens could also image the tumor, but with this preparation there was considerable localization of radioactivity in normal tissues, resulting in less satisfactory tumor definition. Labeled normal mouse IgG did not image the melanoma grafts. Assay of radioactivity in tissues of melanoma-grafted mice confirmed tumor-specific localization of the antimelanoma antibodies. The tumor:blood ratio of radioactivity was 6.55 with the monoclonal antimelanoma IgG and 0.45 with the polyclonal IgG.
With the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry, human melanoma cell lines (Colo 38, M-16, and M-21) were examined for the quantitative level of expression of HLA-A,B antigens, Ia-like antigens, and two human melanoma-associated antigens (MAA) referred to as 280K and 94K MAAs. Each of the melanoma cell lines examined showed tremendous heterogeneity with regard to antigen expression. A detailed study of the heterogeneity of the four antigens listed revealed that variation in cell size could, in part, account for the large differences in antigen expression observed. Cell surface density of HLA-A,B antigens, Ia-like antigens, and the 280K and 94K MAAs remained relatively constant over a wide range of cell sizes that were examined, with the exception that small melanoma cells showed a slightly lower mean surface density of MAA expression than did large cells. A novel method was used to detect the expression of the two MAAs as a function of the Colo 38 cell cycle using dual-laser beam flow cytometry. The results of these experiments show that both the 280K MAA and the 94K MAA are differentially expressed during various stages of the cell cycle, with each antigen being maximally detected during G2 + M.
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NK activity of patients with cancer against gastric carcinoma cell line KATO-III, lung carcinoma cell line A-549 as well as K-562 was significantly lower than that in the control group. We investigated in vitro effects of immunopotentiator, OK-432, on the effector cells of both healthy donors and cancer patients. NK activity of healthy donors was clearly augmented after treatment of effector cells with OK-432. NK activity of some patients with cancer, however, showed no augmentation after OK-432 treatment. These results might be helpful for monitoring cancer patients from immunological view point.
The effects of temperature on food intake were observed on activities of 54 ventromedial hypothalamic neurons in rats in response to iontophoretically applied glucose and to preoptic thermal stimulation. The major response was that 16 neurons out of 22 facilitated by glucose in the satiety center were facilitated by a rise in preoptic temperature.
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