Dyslipoproteinemia (a remnant lipoprotein disease) in uremic patients on hemodialysis.
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Biomedical subjects
Publications and source records attributed to J Mise.
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An unusual serum lipoprotein (Lp) profile was detected in a Japanese family. A double beta-Lp was observed when serum was subjected to polyacrylamide gel electrophoresis. The slower migrating beta-Lp was identified as a subfraction of high density lipoprotein (HDL). It was present in the d 1.063--1.21 fraction, migrated to the position designated as the midband L.1 (sinking pre-beta-lipoprotein) by Mead, M.G. and Dangerfield, W.G. (1974) (Clin. Chim. Acta 51, 173--182) [1], and reacted against human anti-beta-Lp antiserum. This lipoprotein contained greater amounts of triglyceride than the usual beta-lipoprotein and could not be clearly detected by paper electrophoresis. Individuals exhibiting this high density midband lipoprotein appeared to be heterozygous for an autosomal dominant gene. Although other reports have indicated the possibility of a positive association between the occurrence of serum lipoproteins with unusual eletrophoretic mobility and premature ischemic heart disease, no such correlation was demonstrable in these subjects.
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The present study has indicated the presence of 3 heart specific antigens, using homologous and heterologous antibodies produced in immunized rabbits. Two of these antigenic proteins exhibit restricted organ specificity for heart and the other one shares by heart and kidney. One of these 2 heart specific antigens reacts to both homologous and heterologous anti-heart sera absorbed with kidney, while the other reacts to only heterologous anti-heart sera. The former has an electrophoretic mobility corresponding to that of serum beta-globulin, and is found to have a molecular weight of about 175,000. The latter has the same electrophoretic mobility as that of alpha2-globulin and is found to have a molecular weight of about 50,000.
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In patients with chronic obstructive pulmonary disease, quantitative analysis of serum IgG, IgA and IgM were carried out by use of the radial immunodiffusion method. The concentration of IgE in sera was also determined by the radioactive radial immunodiffusion method. The mean value of serum IgG level in the group of cor pulmonale was higher than that in groups of emphysema, asthma and normal subjects. The mean value of serum IgA level was higher in two groups of cor pulmonale and emphysema than in the group of asthma and of normal subjects. There was no difference of serum IgM levels between these four groups. The mean value of serum IgE in the group of allergic asthma was higher than that in the group of non-allergic asthma or normal subjects and an elevated serum IgE level was also found in patients with cor pulmonale. Findings of this study suggested that the raised level of serum IgG in patients with chronic cor pulmonale might reflect production of antiheart antibodies against cardiac tissue.
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The relation between K2 and PHLA was studied in human subjects with special reference to clinical data determined by routine laboratory and physical examinations. The results obtained by Multiple Regression Analysis indicated that those factors which may contribute to K2 variation were fasting triglyceride level and age. There was an inverse partial correlation between K2 and fasting triglyceride level and between K2 and age. The first and second principal components calculated by Principal Component Analysis indicated that K2 is closely related to obesity and hyperlipidemia, especially hypertriglyceridemia, while PHLA related to albumin. These two components also suggested that K2 fibes different clinical information from that obtained by PHLA measurement. There was no partial correlation between K2 and PHLA. The various lipoprotein paper electrophoretic patterns, type IIa, type IIb, type IV and normal patterns, were clearly characterized by such factors as K2, plasma triglyceride and degree of obesity which has high coefficients in the first principal component.
Studies on lipid and lipoprotein abnormalities which are associable with ischemic heart disease were presented. None of the subjects studied for this report had clinical signs or symptoms characteristic to "familial or sporadic" hyperlipoproteinemia. Only few showed gross abnormalities in lipid chemistries which are compatible with these clinical entities. Lipid abnormalities characteristic to the majority of ischemic heart patients were modest to moderate increase of serum total and free cholesterol and triglyceride; either independent increase or combined increase of these lipid fractions. Determination of free cholesterol may favor to detect such minute abnormality in modest hyperlipidemia as seen in ischemic heart patients. As expressed by our lipoprotein PAG electrophoresis pattern, B and Bp pattern (Fig. 1) seemed to be important lipoprotein abnormalities because of high incidence of ischemic heart disease (60 to 65%). Another feature of these hyperbeta lipoproteinemic state without (B pattern) or with (Bp pattern) moderate prebeta lipoprotein is highly suggestive of premature onset of ischemic heart suggestive premature onset of ischemic heart disease in the subjects with these lipoprotein patterns. Pb battern (hyperpre-beta lipoproteinemic state) was the next, because of frequent occurrence of this pattern (approx. 30%) among the cardiovascular patients and relatively high incidence (approx. 40%) of ischemic heart disease. PB pattern (combine hyperpre-beta and hyperbeta lipoproteinemic state) occurred rarely but incidence of ischemic heart disease in the subject with this pattern was high (approx. 40%). Midband lipoprotein which is one of the unique lipoprotein species detected by PAG electrophoresis may possibly reflect disordered lipoprotein metabolism. However, its association with ischemic heart disease seemed highly unlikely. However, further studies on this and other unusual lipoproteins detectable with PAG electrophoresis seems productive. Extensive studies on cine coronary angiographically established subjects (well characterized study subjects) with this new method in addition to the others would be highly productive to obtain more reliable conclusion on this subject, and hence, to obtain more effective guide line for early identification or for prevention of coronary atherosclerosis.
In patients with chronic cor pulmonale caused by pulmonary emphysema, circulating autoantibodies against the heart tissue were investigated by the HA and HI techniques using the myocardium as antigen. Quantitative analysis of serum IgG, IgA and IgM were carried out by use of the radial immunodiffusion method. These results were compared with clinical findings, especially cardiopulmonary hemodynamics and pulmonary function tests and with the prognosis. Circulating anti-heart antibodies were found in 15 of 29 (51.7 per cent) patients with chronic cor pulmonale. The titers of circulating anti-heart antibodies indicated a good correlation with pulmonary hypertension, hypoxia and respiratory impairment. Furthermore, a good correlation was noted between anti-heart antibody titers and the serum IgG level. Five of 15 (33.3 per cent) patients with positive results for anti-heart antibodies died, while one of 13 (7.7 per cent) with negative results died. In this investigation, circulating anti-lung antibodies were also searched in sera from patients with chronic cor pulmonale, but they showed no cross reaction with anti-heart antibodies, of which the specificity was found in the patients. These data could be utilized in evaluation and discussion of the pathophysiological findings of the patients with chronic cor pulmonale.