Microassay of cyclic nucleotides in vessel wall. V. Simultaneous assay of cyclic AMP and cyclic GMP.
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Biomedical subjects
Publications and source records attributed to H Maezawa.
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Plasma renin activity (PRA) and plasma aldosterone (PA) were measured under conditions of bed rest and after administration of furosemide and/or angiotensin II to adult-onset diabetics and age-matched controls. Seventeen of the diabetics had no proteinuria (non-proteinuria group) while in the other ten subjects, there was a persistent proteinuria, but no hypertension and renal dysfunction (proteinuria group). In the non-proteinuria group, changes in PRA and PA levels during both bed rest time and after the stimulation with furosemide did not significantly differ from findings in the control group. In the proteinuria group, PRA and PA levels were significantly lower than in the other two groups. PA and diastolic pressure responses to angiotensin II were slightly increased in diabetics (N.S.). PA responses to furosemide had significant positive correlation with those to angiotensin II. These findings suggest that the renin-aldosterone system responds normally in adult onset diabetics without proteinuria, but shows lower response in diabetics with persistent proteinuria, even without complications of hypertension and a decreased renal function.
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In our ongoing studies of the interrelationship between platelets and the vascular wall we found that an accurate estimate could be made of the clinical condition and more effective therapy prescribed when we monitored alterations in the plasma levels of TXB2. For this purpose we devised a radioimmunoassay with I125-TXB2-Tyramide. Patients with ischemic heart disorders, cerebral apoplexy, diabetes mellitus, Buerger's disease, Takayasu disease etc., all had statistically high levels of TXB2 as compared with healthy controls. In particular, patients with myocardial infarction, cerebral thrombosis and/or hemorrhage all revealed increases in levels of TXB2 and these levels increased in parallel with a worsening of the clinical condition, and there was always a re-increase in TXB2 level before a recurrence of an attack. As plasma TXB2 levels clearly reflect thrombogenic disorders, the assessment of these levels on a routine basis, enables a more accurate diagnosis, an indication of possible recurrences, and more effective chemotherapy and rehabilitation.
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The cytotoxic and radiosensitizing effects of low concentrations of misonidazole were examined by measurement of the colony-forming ability and growth of HeLa S3 cells. Under hypoxic conditions, cytotoxicity depended on the misonidazole concentration and the exposure time. After 24 hr exposure, the surviving fraction of cells treated with 0.1 mM misonidazole decreased to 0.2. The ability of cells to adhere to the growth surface of plastic dishes was reduced by 0.1 mM misonidazole upon 24 hr hypoxia and this effect persisted even during subsequent euoxia, irrespective of whether the drug was removed from the original growth medium. The growth of aerobic cells was not affected when 0.1 mM misonidazole containing medium, obtained from the hypoxia-treated dishes, was applied, nor when those cells were exposed for 72 hr to freshly prepared 1.0 mM misonidazole. Upon 24 hr exposure, 0.1 mM misonidazole exerted no obvious radiosensitizing effect on hypoxic cells. Based on these results, it is suggested that continuous administration of low doses of misonidazole may be efficacious as a specific chemotherapeutic in the treatment of hypoxic cells in tumor tissue.
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Circulating immune complexes in Takayasu disease were investigated to assess the involvement of autoimmune mechanisms. Antibody dependent cell-mediated cytotoxicity (ADCC) and Raji cell assay revealed: The 10 percent inhibition of ADCC in 37 patients was 35.6 +/- 5.2, this being a non-statistically significant value as compared with the values of 25.6 +/- 3.0 in 33 apparently healthy controls. Raji cell assay values were 30.4 +/- 11.5 and 3.5 +/- 2.3 for patients and controls, respectively. As 54% of all these patients had a negative reaction and there was no correlation between immune complex levels and BSR, CRP, or ASO, immune complexes, while accelerating or modifying the pathophysiological state, probably are not primary causative factors.
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Takayasu's disease is characterized by a "pulseless" condition which most often occurs in young females from Asian or South American areas. The cause of this disease remains obscure. Recently, we encountered monozygotic, Japanese, identical twin sisters, both of whom were diagnosed as having Takayasu's disease. The parents, two sisters, and one brother are healthy. HL-A typing analyses revealed that one haplotype found in the father had passed only to these twins. Such observations led us to search HL-A typing in Takayasu's disease to determine the possible participation of genetic factors in the pathogenesis of this morbid condition. Ten families, including that of our own patient, have been reported in the literature in Japan, as family cases of Takayasu's disease. HL-A typings in A and B locus analyzed in all family members of six families in attempts to find a common haplotype composed of A9, A10, B5, or BW40 in patients with Takayasu's disease, were confirmed statistically (chi 2 = 7.8, 0.01 less than p less than 0.05). In a population study, HL-A typing analyses of 65 patients with Takayasu's disease also revealed a high frequency of HL-A A10 and HL-A B5 with the level of 15.3 and 17.0 in the chi 2-test (p less than 10(-4)), as compared with the frequency in 128 healthy Japanese. These data strongly suggest that a genetic-related factor has to be given serious consideration.
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Although 99mTc and 51Cr have been used for lymphocyte labeling, these radionuclides have several disadvantages for study on immunological behaviour of lymphocyte; very high rate elution and low labeling efficiency for both radionuclides, and short half life for 99mTc. Indium-111 has quite suitable physical properties for clinical nuclear medicine, i.e. desirable photon energy (247,173 keV) and 2.8 day half life. 111In-oxine is lipid soluble and is known to pass through the cell membrane and attaches firmly to cytoplasmic component of the cell. On the other hand, 3H-thymidine is well known substance which incorporated to nucleic acid in the cell. In this study, distribution patterns of 111In-oxine and/or 3H-thymidine labeled lymphocyte in C3H/He mice were examined and the suitability of 111In-oxine labeled lymphocyte for radionuclide imaging in vivo was discussed. Thirty minutes after intravenous injection of 3H and/or 111In labeled lymphocyte, about 12% of lymphocyte were found in the lungs and rest of them were distributed mainly in the blood, kidneys and liver. After 24 hours the activity in the lung decreased markedly and the activity in the liver and kidneys increased with time. Between lymphocyte labeled with 111In-oxine and 3H-thymidine, there is not so much differences in terms of distribution patterns. From this study, it is concluded that the 111In-oxine labeled lymphocyte distributes in the same way as 3H labeled one, in spite of different labeling sites. This 111In-oxine labeling method can be used as a useful tool of radionuclide imaging in kinetic studies of lymphocyte in vivo.