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Biomedical subjects

T Akizawa

Publications and source records attributed to T Akizawa.

At least 73 records · Page 4Linked to original sources

Levels of serum 1,25(OH)2D in patients with pre-dialysis chronic renal failure.

One hundred and ninety-five outpatients in pre-dialysis period served as subjects. The mean age of subjects was 58.0 +/- 11.2 (range: 29-82) years. The subjects were divided into 8 groups according to their serum creatinine (Cr) levels (Cr < or = 1.0, 1.0 < Cr < or = 2.0, 2.0 < Cr < or = 3.0, 3.0 < Cr < or = 4.0, 4.0 < Cr < or = 5.0, 5.0 < Cr < or = 6.0, 6.0 < Cr < or = 8.0, and Cr > 8.0 mg/100 ml). The level of 1,25-dihydroxyvitamin D (1,25(OH)2D) decreased in accordance with the progression of chronic renal failure (CRF). Even in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, the levels of 1,25(OH)2D were significantly lower than those in subjects with Cr < or = 1.0 mg/100 ml. The levels of calcium adjusted by serum albumin levels (adjusted Ca) were relatively maintained within the normal range until Cr > 8.0 mg/100 ml. The levels of inorganic phosphate (IP) were significantly lower in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, but significantly higher in subjects with Cr > 4.0 mg/100 ml than those in subjects with Cr < or = 1.0 mg/100 ml. The levels of immunoreactive high-sensitive parathyroid hormone (HS-PTH) were greatly increased and the levels of intact PTH were significantly increased even in subjects with 1.0 < Cr < or = 2.0 mg/100 ml, in association with a decrease in levels of 1,25(OH)2D suggesting that a decline in 1,25(OH)2D production due to a decrease in renal mass contributes to the acceleration of secondary hyperparathyroidism. When the levels of adjusted Ca, intact PTH and 1,25(OH)2D of subjects with hypophosphatemia (IP < 2.8 mg/100 ml), normophosphatemia and hyperphosphatemia (IP > 4.4 mg/100 ml) were compared, there were not any significant differences in the levels of adjusted Ca among these subjects in each group. But, the levels of 1,25(OH)2D in subjects with hypophosphatemia were significantly higher than those with normophosphatemia in groups with Cr < or = 2.0 mg/100 ml, and those with hyperphosphatemia were significantly lower than those with normophosphatemia in groups with 3.0 < Cr < or = 4.0, 5.0 < Cr < or = 6.0 and Cr > 8.0 mg/100 ml. These results suggest that increased secretion of PTH might compensate the decreased production of 1,25(OH)2D3 by lowering phosphate in the early phase of CRF, and phosphate retention inhibits the activity of 1 alpha-hydroxylase and contributes to the decrease in 1,25(OH)2D3 in the advanced stage of CRF. Monitoring of 1,25(OH)2D is considered to be vitally important for diagnosing the 1,25(OH)2D3 deficiency in CRF.

Adult↗

[The study of the relationship between serum eosinophil cationic protein and bronchial responsiveness in the patients with bronchial asthma].

Eosinophil cationic protein (ECP) has been expected as an index of eosinophilic inflammation in bronchial asthma. However, there are many questions about the clinical meaning of the serum ECP, yet. To examine that problem, we measured serum ECP levels in healthy subjects and the asthmatics patients, with and without attack. We also studied the relationship between bronchial responsiveness and serum ECP levels in the asthmatics patients without attack. Patients taking any steroids (including inhaled steroid), anti-allergic agents or cigarettes were excluded. The highest levels of ECP were found in serum sampled from the patients with asthma attack. The levels of the patients without attack were lower, and the levels of the healthy subjects were the lowest of all. To study the relationship between serum ECP and bronchial responsiveness in the asthmatics patients, who had not an asthma attack for at least one week, serum was sampled and simultaneously bronchial responsiveness (Dmin) was measured by Astograph. The serum ECP levels correlated negatively with Dmin, a threshold-type index of bronchial responsiveness (r = -0.569, p < 0.01). These data indicate that between attacks of bronchial asthma, bronchial responsiveness is related to the levels of serum ECP, and that during attacks the level of serum ECP increases further. They also suggest that abnormally high levels of serum ECP are associated with a preattack state in patients with bronchial asthma.

Adolescent↗

Effects of membrane characteristics on cytokine production by mononuclear cells in regular haemodialysis patients.

To determine the relationship between haemodialysis and cytokine production, the effects of solute permeability and biocompatibility of dialysis membranes on cytokine production by mononuclear cells were evaluated. Eighteen stable haemodialysis patients were divided into three groups and underwent haemodialysis under the same conditions except for the dialysis membrane used. Endotoxin in dialysate remained at concentrations of 10 pg/ml or less throughout the study. Haemodialysis was performed for a total of 6 weeks. Group A used a regenerated cellulose low-flux membrane during the first 2 weeks, a regenerated cellulose high-flux membrane during the next 2 weeks and a polymethylmethacrylate (PMMA) high-flux membrane during the last 2-week period, while Group B used the regenerated low-flux cellulose membrane first, followed by the PMMA low-flux membrane and PMMA high-flux membrane. Group C used the same membrane throughout the 6-week study period. Peripheral mononuclear cells were sampled before, 30 min after the start and upon completion of the final dialysis session and incubated for 18 h in the presence and absence of lipopolysaccharide (LPS) stimulation. Tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6 concentrations in the supernatant and cell lysate were determined. In all groups, cytokine production just before the final dialysis using each membrane was comparable regardless of the presence or absence of LPS stimulation. LPS-stimulated TNF-alpha production decreased significantly 30 min after the start of dialysis compared to the predialysis baseline. This change was not affected by the type of membrane used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects and pharmacokinetics of rhG-CSF in patients with chronic renal failure.

The pharmacokinetics and effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophils and immunological function were studied in 10 patients with end-stage renal failure. A single dose and 2-week consecutive dosing of 50 micrograms/m2 of rhG-CSF were drip infused intravenously, and plasma rhG-CSF levels, peripheral blood cell counts, coagulation, and neutrophil and immunological functions were determined during treatment. The mean half-life of rhG-CSF in patients (2.47 +/- 0.64 h) was prolonged to about twice that of healthy subjects, and hemodialysis did not affect the pharmacokinetics. A marked increase in neutrophils and a slight increase in lymphocytes were observed with the single and consecutive administration of rhG-CSF, but no significant changes were noted in other leukocyte fractions and erythrocyte and platelet counts. The neutrophil alkaline phosphatase value increased significantly following rhG-CSF administration, and other neutrophil functions were also ameliorated in several patients with neutrophil dysfunction. In consecutive administration, however, mild bone pain and increased serum alkaline phosphatase were observed in about half the patients, but neither accumulation of rhG-CSF nor antibody production was detected. From these results, it is concluded that rhG-CSF is safe and effective for the treatment of neutropenia and neutrophil dysfunction in patients with renal failure.

Adult↗

Relative hypoparathyroidism in hemodialysis patients.

To clarify the incidence and contributing factors of hypoparathyroidism in a hemodialysis (HD) population, 224 patients undergoing maintenance HD were investigated. They were divided into 4 groups according to their high-sensitive parathyroid hormone levels: extra-high (EH) group > 420,000 pg/ml; high (H) group 20,000-420,000 pg/ml; moderate (M) group 4,500-20,000 pg/ml; low (L) group, < 4,500 pg/ml. In group L, a 25-mg/kg deferoxamine (DFO) infusion test was undertaken to estimate aluminum (Al) accumulation. The distribution in each group was 42, 35, 12, and 11% for groups L, M, H and EH, respectively. Group-L patients were relatively older than those of the other groups. Diabetes was seen in 20% of group-L patients, as opposed to no diabetes in groups H and EH. Among the 22 diabetics, 82% were in group L. 70% of group-L patients showed a less than 50-micrograms/l Al increment after the DFO infusion test. Bone mineral density (BMD) did not differ between the groups with relative hypoparathyroidism (RHP=L) and background-matched non-RHP, either at the initiation of HD or the recent period, and the changes in BMD were comparable between the 2 groups. These results suggest that a considerable number of HD patients show RHP. Diabetes, but not Al accumulation, was considered to be one of the predisposing factors of RHP. Though the outcome of RHP will be aplastic bone disease (ABD) in HD patients, the clinical significance of ABD has not been fully evaluated. Further studies are required to clarify the precise mechanisms of RHP and the significance of ABD.

Adult↗

Effects of rHuEpo on cellular proliferation and endothelin-1 production in cultured endothelial cells.

BACKGROUND: Although elevation of blood pressure is considered to be the main adverse effect under rHuEpo therapy in haemodialysis patients, the precise mechanism remains obscure. The direct effect of rHuEpo on endothelial cells (EC) has been suggested as one of contributing factors of rHuEpo-induced hypertension. METHODS: EC were incubated with various concentrations of rHuEpo (0, 1000, 5000, 10,000 mU/ml) for up to 7 days, and cell numbers, DNA and protein synthesis by EC and supernatant concentrations of immunoreactive endothelin-1 (ET) were determined by haemocytometer, 3H-thymidine and 3H-leucine incorporation, and RIA, respectively. The effect of rHuEpo on EC proliferation was confirmed by anti-rHuEpo rabbit antiserum. The effect of cycloheximide or acinomycin D was also examined on the increase in ET production by rHuEpo. RESULTS: rHuEpo dose-dependently stimulated the proliferation of cultured EC, and this proliferative effect was inhibited by anti-rHuEpo rabbit antiserum. DNA and protein syntheses by EC were also increased by rHuEpo. The supernatant concentrations of ET cultured with rHuEpo at 5000 mU/ml or more showed significantly greater values than those without rHuEpo and the increase in ET in the supernatants of media containing 5000 mU/ml rHuEpo was inhibited by incubation with 0.2 microgram/ml actinomycin D or 10 micrograms/ml cycloheximide. Further, rHuEpo increased DNA synthesis by EC which had been cultured in E-BM medium containing 0.5 or 2% FBS for 3 h and which were recultured in E-BM medium containing 5% FBS for 15 h. CONCLUSIONS: rHuEpo directly stimulates EC proliferation as a competence factor, and it also accelerates endothelin-1 production in association with stimulation of DNA and protein syntheses by EC.

Animals↗

Plasma bradykinin levels during hemodialysis with PAN DX and polysulfone membranes with and without concurrent ACE inhibitor.

The effects of dialyzer membrane material and concurrent angiotensin converting enzyme (ACE) inhibitor on plasma bradykinin levels during hemodialysis were investigated by administration of 3 successive hemodialyses using a PAN DX membrane dialyzer and another 3 using a polysulfone membrane dialyzer with the order of the 2 sequences randomized, for 6 patients receiving concurrent treatment with ACE inhibitor and 6 others receiving no ACE inhibitor. With the PAN DX membrane dialyzer the plasma bradykinin concentration obtained from the dialyzer outlet was significantly higher than that from the inlet at 10 min, but not at 5 min after initiation of dialysis, whereas no significant difference between inlet and outlet bradykinin concentrations was observed at either time with the polysulfone membrane dialyzer. No significant difference was observed between the changes in plasma bradykinin concentration in cases involving concurrent ACE inhibitor and that in cases receiving no ACE inhibitor. The results suggest that the PAN DX membrane dialyzer stimulates bradykinin production, but also that its release of bradykinin is delayed, possibly because of adsorption and modified release of bradykinin by the PAN DX membrane, and that ACE inhibitor may have no significant effect on the change in plasma bradykinin levels.

Anaphylaxis↗

Finding of primitive polyamine toxins in the venom of a joro spider, Nephila clavata.

A series of joro spider toxins, novel polyamines sharing a common moiety of 2,4-dihydroxyphenylacetyl cadaverine, have been identified using various bioassays, such as inhibition of a glutamatergic transmission and insecticidal activity. In this paper, we tried to chemically find still unknown polyamine toxins in the venom of a joro spider, N. clavata, by several analytical methods based on the characteristics of the common moiety. An aqueous extract from 3000 venoms was separated by preparative high performance liquid chromatography (HPLC). The polyamine toxins were detected by monitoring the fluorescence produced in an on-line reaction of o-phthalaldehyde with amino groups and UV absorption of the phenol group. Two compounds in minute quantity were purified and analyzed by gas-liquid chromatography (GC) and HPLC, which we specifically developed for the simultaneous determination of amino acids and polyamines of the toxins. Judging from the constituents of the hydrolysate by GC and HPLC and the molecular weights determined by fast atom bombardment mass spectrometry, the two compounds were estimated to be N-(2,4-dihydroxyphenylacetyl-L-asparaginyl)-N'- (3-aminopropyl-beta-alanyl) cadaverine and N-(4-hydroxyphenylacetyl-L-asparaginyl)-N'-(3-aminopropyl-beta-ala nyl) cadaverine. These compounds were small in content and molecular weight compared with hitherto known toxins. Both were presumed to be biochemically primitive toxins and were named spidamine and joramine, respectively.

Animals↗

Structures of novel bufadienolides in the eggs of a toad, Bufo marinus.

In this paper, we report chemical structures of five compounds including four novel polyhydroxylated cardiac steroids in the eggs of a toad, Bufo marinus. These cardiac steroids were purified by high-performance liquid chromatography, and their structures were determined to be 11 alpha,19-dihydroxy-telocinobufagin (I), 11 alpha-hydroxytelocinobufagin (II), 11 alpha,19-dihydroxymarinobufagin (III), 11 alpha-hydroxymarinobufagin (IV) and 19-hydroxytelocinobufagin (V) on the basis of spectral data of nuclear magnetic resonance and mass spectroscopy. All the five compounds showed biological activity, as tested by inhibition of Na+,K(+)-ATPase activity and of [3H]ouabain binding to the receptor on Na+,K(+)-ATPase. This is the first finding of bufadienolides as cardiac steroids in animal eggs.

Animals↗

[Anticoagulant effect of a single bolus injection of parnaparin sodium (LHG) on a hemodialysis model in dogs].

Hemodialysis was performed on dogs, following intravenous bolus injections of LHG at dosage levels of 50, 100 and 200 IU/kg and heparin at the levels of 100 and 200 IU/kg. LHG exerted dose-dependent anticoagulant effects and prolonged the hemodialysis time, compared to heparin with similar anti-Xa activity. When LHG was administered, the half-life of plasma anti-Xa activity was longer than that of heparin at similar anti-Xa activity. LHG prolonged the activated partial thromboplastin time (APTT) linearly and dose-dependently. However, the prolongation was much less than that of heparin, and the anticoagulant activity of LHG continued even after the APTT returned to the value before LHG administration. When LHG was administered, whole blood Xa activated coagulation time (XCT) and plasma Xa activated coagulation time (PXCT) were prolonged in a significantly greater degree compared to APTT. Therefore, XCT and PXCT were considered to be appropriate parameters for monitoring LHG. In the groups administered with LHG at 100 and 200 IU/kg, where hemodialysis could be continued for 8 hr, the tissue factor pathway inhibitor (TFPI) activity in the plasma tended to show a sustained increase. These findings suggested the possibility that not only the antithrombin III dependency mechanism but also the TFPI mechanism contributed to a longer LHG hemodialysis duration compared to heparin administration.

Animals↗

Bile salts of the toad, Bufo marinus: characterization of a new unsaturated higher bile acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid.

The bile salts present in gallbladder bile of the toad, Bufo marinus, were found to consist of a mixture of bile alcohol sulfates and unconjugated bile acids. The major bile alcohol was 5 beta-bufol; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 26-tetrols occurred as the minor bile alcohols. Bile acids of Bufo marinus were cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholestan-26-oic acids, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholest-23-en-26-oic acids, 3 alpha,7 alpha,12 alpha, 26-tetrahydroxy-5 beta-cholestan-27-oic acid, and a C27 bile acid which has not been previously described. By chromatographic behavior, mass spectral data, and identification of the products of catalytic hydrogenation and ozonolysis, the structure of the new higher bile acid was elucidated as 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid. The bile salt pattern of Bufo marinus closely resembles that of Bufo vulgaris formosus, except for the absence of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-22-ene-24-carboxylic acid, the major bile acid of the latter toad.

Animals↗

Effect of dialysis membranes and ACE inhibitor on bradykinin levels during hemodialysis.

The effects of dialyzer membrane material and concurrent angiotensin converting enzyme (ACE) inhibitor on plasma bradykinin levels during hemodialysis were investigated. Six patients treated with an ACE inhibitor and 6 other patients not receiving an ACE inhibitor underwent three consecutive hemodialysis sessions with an AN-69 dialyzer and three sessions with a polysulfone dialyzer. The sequence of dialyzers (AN-69 followed by polysulfone or the reverse) was determined randomly. With the AN-69 membrane dialyzer, the plasma bradykinin level at the dialyzer outlet was significantly greater than that at the dialyzer inlet at 5 min but not at 10 min after initiation of dialysis, whereas no significant difference between inlet and outlet bradykinin concentrations was observed at either time with the polysulfone membrane dialyzer. The changes in plasma bradykinin level in patients with concurrent ACE inhibitor did not differ from those found in patients without ACE inhibitor. These results indicate that the AN-69 membrane stimulates bradykinin production at the initial stage of hemodialysis in patients with as well as without concurrent ACE inhibitor. Further study is necessary to clarify the exact role of ACE inhibitor in elevation of bradykinin levels during hemodialysis.

Anaphylaxis↗

[Clinical usefulness of visual analog scale for assessment of dyspnea at rest in patients with chronic respiratory diseases].

To evaluate the validity and clinical usefulness of the visual analog scale (VAS) for the measurement of dyspnea at rest, we employed the 150 mm VAS in 29 chronic respiratory disease patients who were clinically stable, and repeated the measurement 4 weeks and 8 weeks later for the evaluation of reproducibility. For the 8-week period, the individual medical treatments remained generally unchanged in all patients. Two patients were excluded from the study due to infection and pneumothorax. Dyspnea at rest was detected on VAS in 23 patients at the first measurement. The VAS measurement was 23.9 +/- 28.4 (mean +/- SD) mm at the first time, 22.0 +/- 23.1 mm at the 4th week, and 22.4 +/- 26.0 mm at the 8th week. There was no significant change among the three measurements. Twenty among the 23 patients with VAS indicative of dyspnea at rest were categorized into grades 4 and 5 of the Fletcher dyspnea category. However, the intensity of dyspnea was distributed widely within each Fletcher category. These results lead to the conclusion that VAS shows good reproducibility over a period of as long as 8 weeks and that VAS measurements can reveal patient-to-patient individual differences in dyspnea intensity which cannot be detected by the Fletcher dyspnea category. We propose that measuring dyspnea at rest using VAS is a useful method to obtain a valid clinical parameter.

Adult↗

Recent progress in management of secondary hyperparathyroidism of chronic renal failure.

Recent progress in cellular and molecular biology has had a great impact on our understanding of parathyroid hormone-vitamin D physiology and of the pathogenesis of secondary hyperparathyroidism in chronic renal failure and made possible the development of new therapeutic approaches for management of bone disease in dialysis patients. Management of parathyroid hyperplasia by calcitriol pulse therapy is one example. Suppression of parathyroid hyperfunction by other vitamin D analogues was also proposed, and some of these analogues are now under clinical trial. Further, percutaneous ethanol injection into hyperplastic parathyroid glands under ultrasonographic guidance has become the choice practical procedure under certain clinical settings and can be an effective alternate to surgical parathyroidectomy. In this article, we review selected and pertinent progress in the pathogenesis and management of secondary hyperparathyroidism and parathyroid hyperplasia, major causes of morbidity in chronic dialysis patients, emphasizing the important contributions made by laboratory research and critical clinical observations.

Animals↗