[Treatment of patients with chronic kidney failure].
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Biomedical subjects
Publications and source records attributed to N Mimura.
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Intervertebral discs of 41 chronic renal failure autopsy cases were examined histologically and immunohistochemically to assess the distribution of beta 2-microglobulin-associated (beta 2m) amyloid in the vertebral column. The results demonstrated beta 2m amyloid to appear first in the cervical discs, then in the lumbar and upper thoracic discs, and finally in the middle and lower thoracic discs as the dialysis period is prolonged. The shortest dialysis period for which beta 2m amyloid was detected was one year and seven months. Deposition of beta 2m amyloid was most remarkable in the C4-5, 5-6, and 6-7 levels, which are known to sustain severe mechanical stress in daily life. Thus it is suggested that local mechanical stress accelerates beta 2m amyloidosis. A marked macrophage reaction was observed around the amyloid in cases of severe amyloidosis, the macrophages themselves being immunohistochemically positive for IL-1 beta and TNF-alpha. Amyloid deposition and reactive inflammation mediated by cytokines appear to be closely related to the pathogenesis of destructive spondyloarthropathy.
Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.
In a phase II clinical trial to test the ability of recombinant human erythropoietin (r-HuEPO) to reverse the anemia of patients undergoing hemodialysis, the changes of enzyme activity in red blood cells were evaluated in 5 hemodialysis anemic patients who were treated with r-HuEPO. Concerning the activity levels measured, the following conclusions are drawn. 1) HK, ALD, TPI, G6PD and 6PGD were statistically significantly increased at the time when the hematocrit has risen by 8% with the use of r-HuEPO. 2) The enzyme activity levels of PFK, GA3PD, MPGM, ENOL, PK, GR and ADA were higher than normal already before the r-HuEPO treatment. 3) The increases of HK and G6PD by r-HuEPO, as age dependent enzymes, may reflect the generation of young red blood cells. 4) In view of the fact that they are related to ATP production in the glycolysis cycle, we infer that increases of red blood cell enzymes by r-HuEPO may play at least some part in bringing a sensation of "well-being" to severely anemic patients undergoing hemodialysis.
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Two protein factors which bind to, and induce gelation of, actin filaments were purified from Ehrlich tumour cells. Filamin induced Ca2+-insensitive gelation, whereas a new protein factor ('actinogelin') was found to induce Ca2+-sensitive gelation.
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To study the carbohydrate metabolism in uremic patients, the intravenous glucose tolerance test (iv GTT) and insulin sensitivity test were investigated on 69 patients with chronic renal failure, 27 of whom were under the dialysis treatment. 1) Abnormal K-values averaging 1.05 were obtained in uremic patients (creatinine clearance less than 20 ml/min). 2) Carbohydrate intolerance in uremic patients was corrected with regular dialysis and the improvement was correlated with the duration of dialyses. 3) The mechanisms of improvement in carbohydrate metabolism were different between the short-term dialysis group (less than 12 months of dialysis) and the long-term group (more than 12 months). Enhanced secretion of insulin seemed to be the main cause of this improvement in the former, while the correction of impaired sensitivity to insulin in peripheral tissues in the latter.
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Changes in the in vivo luminescence, respiratory activities, contents of cytochromes, extractable luciferase and NAD(P)H-FMN reductase during growth of the wild (bright) strain of Photobacterium phosphoreum and its dim mutant were determined. The intensity of the in vivo luminescence per cell increased 10 times in the wild strain and 750 times in the dim strain during logarithmic growth, while the contents of luciferase and NAD(P)H-FMN reductase remained almost constant. It is suggested that a characteristic change in the mode of competition of the luminescence reaction system with another electron transfer chain involving cytochromes for NAD(P)H take place during the growth of this bacterium.