Destructive effects of chlorotetracycline on DNA structure by combined fluorometry with ethidium bromide.
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Biomedical subjects
Publications and source records attributed to M Takasugi.
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Serum concentrations of dibekacin (DKB), sisomicin (SISO) and gentamicin (GM) were measured in 3 rabbits after intratracheal administration through the transtracheal teflon tube. The peak serum levels (average) were 106 micrograms/ml (administrated 100 mg DKB for injection), 148 micrograms/ml (administrated 100 mg DKB solution), 166 micrograms/ml (administrated 100 mg SISO solution) and 80 micrograms/ml (administrated 80 mg GM solution). Serum concentrations and urine excretions of DKB were measured in 3 volunteers after aerosol administration using ultrasonic nebulizer. The peak serum levels (average) were 4.6 micrograms/ml (administrated 100 mg DKB for injection) and 3.1 micrograms/ml (administrated 100 mg DKB solution). The urine excretions (average) were 3.7 mg and 4.3 mg respectively during 6 hours. Before and after administration of DKB aerosol the spirogram and flow-volume curve were examined in the volunteers. But the examinations showed no changes. Sputum concentrations were measured in 1 patient with chronic bronchobronchiolitis after administration of DKB aerosols using the ultrasonic nebulizer. The highest sputum concentration was acquired immediately after nebulization and the sputum levels decreased gradually while time passed. Six patients with the lower respiratory tract infections were treated with DKB aerosol therapy and the utility rate was 80%.
A patient with markedly elevated diaphragm due to massive ascites secondary to nephrotic syndrome demonstrated an intense early diastolic sound with low- and medium-pitch. This abnormal sound coincided closely with the "D" point of the anterior mitral valve echogram. This sound remarkably diminished in intensity during inspiration with lowering of diaphragm, and after removing ascites it completely disappeared. Noninvasive study with phonoechocardiograms showed neither constrictive pericarditis nor large pericardial effusion. These findings lead us to believe that the sound may be related to an abnormal ventricular recoil striking the extracardiac structures at the end of the isovolumetric relaxation time. To our knowledge, the fact that the elevated diaphragm itself can produce an early diastolic sound ("pseudo-knock sound") has not been previously reported.
The relationship between natural cell-mediated cytotoxicity (NCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in an Epstein-Barr virus-infected target cell system. The total ADCC reactivity to Epstein-Barr virus-infected target cells varied considerably with different effector cells, indicating contributions to specificity by the effector cells as well as by antibodies in the sera. To investigate the role of each reactant, the effector cells, sera, and target cells were tested according to a three-dimensional experimental design and examined for selectivity with the two- and three-way interaction analysis. The two-way analysis was applied to different planes from the experiment to examine special interactions involving two of the three reactants. Selective ADCC was examined through the results from sera versus target cells, selective NCMC was examined by effector cells versus target cells, and the relationship between NCMC and ADCC was examined through the final plane of effector cells versus sera. A three-way interaction analysis applied to the same results supported the conclusions from the two-way analysis and allowed further inquiry into the concurrent role of three reactants. The design and analysis used in the study allowed detection of selective ADCC and NCMC for Epstein-Barr virus-infected target cells and variations in the efficiency of ADCC by different effector cells and in the modulation of NCMC by different sera.
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The case of a 42-year-old woman with Sjögren's syndrome accompanied by severe gastric infiltration and interstitial nephritis is reported. Presentation was with finger stiffness, Raynaud's phenomenon and abdominal discomfort. There were endoscopic and radiological features of early cancer, type IIc (depressed type). Resected stomach showed atrophic gastritis with erosion. Histology showed focal to relatively diffuse destruction of the gastric glands with minimal intestinal metaplasia and dense collections of lymphoid cells with occasional germinal centers in the interstitium of the gastric mucosa. Renal biopsy revealed similar severe diffuse interstitial infiltration of lymphoid cells. Distal renal tubular acidosis was confirmed by sodium bicarbonate and ammonium chloride loading test. Satisfactory improvement in xerostomia, keratoconjunctivitis sicca and other laboratory data occurred on prolonged administration of adrenal steroids and cyclophosphamide.
The possibility of an association between HLA profile and the probability of having esophageal cancer was explored among patients from different ethnic groups residing in the Caspian Littoral of Iran. A total of 151 esophageal cancer patients and 214 normal controls with ethnic affiliations similar to those of the patients were typed for HLA antigens. No statistically significant differences were found between patients and controls with regard to HLA antigens.
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Freshly isolated effector cells expressing natural cell-mediated cytotoxicity (NCMC) against cultured target cells possessed antibodies attached to Fc receptors on their cell surfaces. A wide variety of natural antibodies in the circulation combined with the receptors on effector cells to allow recognition of the many specificities on cultured target cells and resulted in reactions with an overall appearance of nonselectiveness. The role of antibodies in the specificity of NCMC was demonstrated by recovery of NCMC by trypsinized effector cells when incubated in serum. With absorbed serum, activity was selectively weaker against the absorbing target cell. When effector cells were reconstituted with antibodies eluted from the absorbing cells, selective cytotoxicity for that cell was detected. The specificity of effector cells reconstituted with eluted antibodies confirmed the results from previous studies on specificity by direct cytotoxicity and by competitive inhibition of cytotoxicity and supported the role of antibodies in NCMC.
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Differences in antigenicity between the human osteosarcoma cell line TE 85/B and its feline sarcoma virus-infected subline NIH E1041 were detected by competitive inhibition of natural cell-mediated cytotoxicity (NCMC). Whether the differences could be attributed to the viral infection was investigated by absorption and elution studies of antibodies that determine the specificity of NCMC against the cell lines. Antibodies from the serum of healthy individuals were first absorbed onto target cells against which they were to be tested and then eluted to provide antibodies putatively specific for the target cells. Trypsin-treated effector cells were restored with the absorbed serum or eluted antibodies and tested against TE 85/B and its intentionally infected sublines. The differences observed previously between TE 85/B and NIH E1041 were extended to the detection of small differences in antigenicity among all sublines. Separately maintained sublines from the same culture became antigenically different with continuous passage. The causes for these specific changes were unknown, but a role for the control of these antigens by NCMC was suggested. Differences in antigenicity between virus-infected sublines cultured separately need not be related to the virus infection.
IgG antibodies bound to effector cells through Fc receptors were observed to determine the specificity of natural cell-mediated cytotoxicity (NCMC) against cultured target cells. When effector lymphocytes were isolated from the peripheral blood of most individuals, they already possessed natural antibodies specific for antigens on cultured cells. Since they lacked IgG antibodies specific for antigens on sheep red blood cell (SRBC) targets, natural cytotoxicity against SRBC was almost non-existent. Effector cells incubated in IgG anti-SRBC became specifically cytotoxic to SRBC. In the process, NCMC and antibody-dependent cell-mediated cytotoxicity was diminished, indicating that arming with anti-SRBC replaced natural antibodies and occupied Fc receptors on effector cells. Thus, treating effector cells with serum may result in increased or decreased cytotoxicity depending upon the specificity of antibodies within the serum. This type of modulation of NCMC occurs at the interaction between antibody Fc and Fc receptors and can explain blocking and unblocking.
The apparent nonselective effects of natural cell-mediated cytotoxicity tested directly on different lymphoblastoid cell targets were found to be quite specific in the cross-competition assay. The specificity was detected through inhibition of cytotoxicity by competitor cells sharing common specificities with the target cells. Cross-competition tests were performed employing eight lymphoblastoid lines including four T and four B cells. Selective inhibition observed between lymphoblastoid cell lines indicated that T and B cell lines were more antigenically similar within each group than between them. The target antigens that distinguish T cell from B cell lines have been tentatively called TA-T and TA-B.
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Natural cell-mediated cytotoxicity (NCMC) like immune T cell-mediated cytotoxicity and antibody production is regulated by a soluble factor released during co-culture of lymphocytes with mitomycin C-treated lymphoblastoid cell lines. This N-cell-activating factor (NAF) enhances the activity of effector N cells and increases natural cytotoxicity. There appears to be no restriction for compatibility at the A and B locus of the major human histocompatibility complex in the production or activity of the factor. NAF was observed in the supernatant as soon as 2 days after initiation of mixed culture with a peak of production at 5 days. A soluble factor produced and released by T cells in response to stimulation by other cells acts by enhancing cytotoxicity of effector cells in NCMC, demonstrating a T-N cell cooperation.
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