Biomedical subjects
Publications and source records attributed to H Morii.
This is a report of a case of acute renal failure associated with McArdle's disease. A 45-year-old man had acute renal failure that required dialysis. His case was subsequently diagnosed as rhabdomyolysis secondary to McArdle's disease, a primary myopathy due to myophosphorylase deficiency. History-taking revealed nothing suspected to be responsible for precipitating the renal failure.
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.
Plasma levels of atrial natriuretic peptide (ANP) were measured in 57 patients with chronic renal failure (CRF) using a specific and sensitive RIA. The mean plasma ANP level in CRF patients [173 +/- 17.0 pg/ml (+/- SEM); n = 57] was significantly higher than that in normal subjects (37.6 +/- 1.9 pg/ml; n = 40). No significant correlation was found between plasma ANP and serum creatinine concentrations. CRF patients treated by maintenance hemodialysis had significantly higher plasma ANP levels than did nondialysis patients. Hemodialysis significantly decreased plasma ANP, and changes in plasma ANP levels after hemodialysis differed from those in serum creatinine concentrations. The mean serum creatinine concentration rose significantly 24 h after hemodialysis. In contrast, plasma ANP levels did not change in the first 24 h, but then rapidly increased. When ANP in predialysis plasma from patients with CRF was analyzed by reverse phase high performance liquid chromatography, the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results suggest that expanded extracellular volume stimulates the secretion of ANP in CRF patients and that this increase in ANP release reflects a mechanism of compensation in volume homeostasis in man.
The immunoregulatory effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3), a precursor form of active vitamin D3, was examined in hemodialyzed patients. Four weeks of oral administration of 0.5 micrograms/day 1 alpha OHD3 markedly enhanced the lymphoproliferative responses to mitogens without influencing lymphocyte counts or the ratios of lymphocyte subpopulations. In fact, these responses were nearly normal after treatment. These results suggest that deficiency of 1,25-dihydroxyvitamin D3 may play a role in the impairment of cellular immunity in hemodialyzed patients, and that administration of 1 alpha OHD3 may have therapeutic immunological benefit.
A 59 year-old patient had lumbago and pain in hip joints, knees, and ribs of long duration. Severe hypophosphatemia and high serum ionized calcium were found in spite of normal level of total serum calcium. The serum parathyroid hormone and alkaline phosphatase levels were elevated, and diffuse demineralization of the bones and renal stones were found by x-ray examination. Parathyroid adenoma was diagnosed from the subtraction image of the 99mTc O-4 and 201Tl-Cl2 scintigrams. Osteomalacia was demonstrated by bone biopsy at the right iliac crest. A right lower parathyroid adenoma of 2.0 X 1.8 cm, weighing 4.0 g was removed. The long standing phosphate depletion and hypophosphatemia, due to hyperparathyroidism causing renal damage with nephrocalcinosis and reduced synthesis of active vitamin D, and milk tolerance due to gastroduodenostomy were probably responsible for producing the clinical picture of normocalcemic hyperparathyroidism complicated with osteomalacia.
Nephrotic range proteinuria occurred in a 42-year-old woman with renal arterial occlusion and hyperreninemia. The administration of captopril, an angiotensin converting enzyme inhibitor, led to an amelioration of the proteinuria and the decrease of blood pressure, without surgical treatment. From the present observation, it is highly probably that the increased activity of the renin-angiotensin system plays an important role in massive proteinuria. Conservative treatment for renovascular hypertension with nephrotic syndrome was effective in this patient.
We wished to investigate the pathophysiology of hypertriglyceridemia in chronic renal failure. Our subjects were 30 patients under hemodialysis for at least five years who had never taken vitamin D analogues or calcitonin preparations. During those five years, triglycerides were high, with no significant changes, although the cholesterol level decreased significantly 10 to 12 months after the first hemodialysis treatment. There was a significant correlation between alkaline phosphatase and triglycerides (p less than 0.025) in these patients in the same assay. In the two patients with hypertriglyceridemia, serum triglycerides decreased to within the normal range by six months after parathyroidectomy, and remained there 30 months after surgery. These results suggested that secondary hyperparathyroidism may be involved in the pathophysiological mechanism of hypertriglyceridemia seen in chronic renal failure.
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Several ninhydrin-positive lipids were found in methanogenic bacteria and the structure of one of them, designated as PNL2 from Methanobrevibacter arboriphilus, was identified as a diphytanyl ether analog of phosphatidylserine. The chromatographic behavior of the lipid on thin-layer plates and on a DEAE-cellulose column was identical to the ester form of phosphatidylserine. The infrared spectra showed the presence of amino, carboxyl, ether, and phosphate groups, and the absence of an ester linkage. The hydrophobic portion of the lipid was identified as diphytanyl glycerol diether on the basis of the mass spectrum of the acetolysis product and gas-liquid chromatography of the iodinated alkyl chain prepared by hydroiodic acid cleavage of PNL2. The fast atom bombardment-ionization and field desorption mass spectrum provided a molecular weight of 819 and several fragment ions consistent with the proposed structure. Hydrofluoric acid hydrolysis resulted in water-soluble products including serine, phosphoserine, and ammonia, which accounted for 95% of hydrolyzed PNL2. The lipid product of the hydrolysis was mainly the diether form of phosphatidic acid. This is the first report on the structural characterization of an amino-containing phospholipid in archaebacteria. Amino lipids have been found in many other methanogenic bacteria.
ATP-dependent Ca2+ uptake by subfractions of skeletal muscle sarcoplasmic reticulum (SR) was studied with the Ca2+ indicator dye, antipyrylazo III. Ca2+ uptake by heavy SR showed two phases, a slow uptake phase and a fast uptake phase. By contrast, Ca2+ uptake by light SR exhibited a monophasic time course. In both fractions a steady state of Ca2+ uptake was observed when the concentration of free Ca2+ outside the vesicles was reduced to less than 0.1 microM. In the steady state, the addition of 5 microM Ca2+ to the external medium triggered rapid Ca2+ release from heavy SR but not from light SR, indicating that the heavy fraction contains a Ca2+-induced Ca2+ release channel. During Ca2+ uptake, heavy SR showed a constant Ca2+-dependent ATPase activity (1 mumol/mg protein X min) which was about 150 times higher than the rate of Ca2+ uptake in the slow uptake phase. Ruthenium red, an inhibitor of Ca2+-induced Ca2+ release, enhanced the rate of Ca2+ uptake during the slow phase without affecting Ca2+-dependent ATPase activity. Adenine nucleotides, activators of Ca2+ release, reduced the Ca2+ uptake rate. These results suggest that the rate of Ca2+ accumulation by heavy SR is not proportional to ATPase activity during the slow uptake phase due to the activation of the channel for Ca2+-induced Ca2+ release. In addition, they suggest that the release channel is inactivated during the fast Ca2+ uptake phase.
In a 19-year-old Japanese male (case 1) with thyrotoxic periodic paralysis (TPP), an increase of plasma glucose concentration together with abnormally high levels of serum immunoreactive insulin (IRI) was observed preceding a spontaneous attack of paralysis. Therefore, the plasma glucose, glucagon, epinephrine, norepinephrine, serum IRI, growth hormone and cortisol levels, and the erythrocyte insulin receptors were measured in case 1 and a 40-year-old Japanese male (case 2) with TPP during attacks of paralysis induced by prolonged glucose loading. In case 1, the serum IRI concentration was elevated to the extraordinarily high level of 655.0 microU/ml at the beginning of paralysis, and at that time, the plasma glucose concentration was 147 mg/dl. However, when paralysis was not induced by a similar glucose loading during methimazole treatment, the serum IRI and plasma glucose levels at the corresponding time after glucose loading were 20.9 microU/ml and 87 mg/dl, respectively. Furthermore, the affinity of the erythrocyte insulin receptors was decreased during the attack. In case 2, plasma glucose and serum IRI concentrations were increased in accordance with the initiation of paralysis although the blood levels of hormones counteracting insulin were not significantly changed. These findings suggest that there is something interacting with the normal action of the insulin in the early phase of paralysis.
Nutritional factors, especially calcium, calorie and fat intakes may be important in the treatment with active vitamin D, so that the effect appears more efficient. Incidence of bone changes, due to hyperparathyroidism in diabetic nephropathy, was less than that in non-diabetic patients under hemodialysis. No effect of control status of diabetes mellitus was demonstrated, regarding incidence of subperiosteal resorption of finger bones. Bone mass was decreased in diabetic patients in whom the control of blood glucose was inadequate.
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Cyclic nucleotide-independent protein kinases that preferentially phosphorylated casein and phosvitin as substrate were detected in the nuclei of human and porcine thyroid tissues, and compared with those from rat liver. Enzymes were extracted from the isolated nuclei with a buffer solution containing 0.4 M NaCl, and analyzed by DEAE-Sephadex and phosphocellulose column chromatographies. The chromatographies, together with the characterization of the enzymes, demonstrated that human and porcine thyroid tissues contained two major casein kinases in the cell nuclei, the properties of which revealed that they are to be identified as protein kinases NI and NII.
In order to understand the phosphatidylglycerol turnover mechanism, especially the differential turnover of diacylated and unacylated glycerol moieties of the lipid, products of phosphatidylglycerol metabolism were surveyed in vivo in Bacillus subtilis W23 and an alkalophile, Bacillus sp. strain A007. When cells of B. subtilis W23 labeled with radioactive glycerol were chased, lipoteichoic acid accumulated 90% of the radioactivity lost from the unacylated glycerol moiety of phosphatidylglycerol. Also, lipids other that phosphatidylglycerol, except diacylglycerol, and glycerol and glycerophosphate incorporated much less radioactivity. The [32P]phosphoryl group was also transferred from phosphatidylglycerol to lipoteichoic acid almost quantitatively in B. subtilis W23. A unique metabolism of phosphatidylglycerol was found in Bacillus sp. strain A007 which lacked phosphoglycolipid and lipoteichoic acid, that is, the turnover of phosphatidylglycerol of this organism was less extensive compared with that of B. subtilis W23, and both glycerol moieties of the lipid were metabolized at an identical rate. These results suggested that the major reaction involved in the turnover of phosphatidylglycerol was the transfer of glycerophosphate residue to lipoteichoic acid in a bacterium which possessed lipoteichoic acid and that several minor reactions also were involved in phosphatidylglycerol turnover.