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Biomedical subjects

T Kuno

Publications and source records attributed to T Kuno.

At least 55 records · Page 3Linked to original sources

Plasma beta-carotene, retinol, and alpha-tocopherol levels in relation to glycemic control of children with insulin-dependent diabetes mellitus.

Plasma beta-carotene, alpha-tocopherol and retinol were measured in 15 female and 5 male children with insulin-dependent diabetes mellitus (IDDM), and the correlations with plasma hemoglobin A1c (HbA1c) and fructosamine were analyzed. Twelve female and 8 male children served as age-matched controls. The plasma beta-carotene and alpha-tocopherol levels of the IDDM children were significantly higher than those of the control children, but there were no differences in plasma retinol or total lipid levels. The plasma beta-carotene level, beta-carotene/retinol ratio and beta-carotene/total lipids ratio each showed significant correlations with serum HbA1c and fructosamine in all subjects studied. Similarly, the plasma alpha-tocopherol level and alpha-tocopherol/total lipids ratio were correlated with these indexes of glycemic control. These findings suggest certain mechanisms may exist to prevent lipid peroxidation and vascular complications in IDDM patients.

Adolescent↗

Possible involvement of calcineurin in retinoic acid-induced inhibition of leukemic HL-60 cell proliferation.

Differentiation of leukemic HL-60 cells by all transretinoic acid (ATRA) resulted in a reduced rate of growth. Cyclosporin A and FK506, at concentrations that inhibited calcineurin activity, abrogated the ATRA-induced inhibition of HL-60 cell growth but these immunosuppressants had no effect on the ATRA-induced granulocytic differentiation. Treatment with 1 microM ATRA led to a progressive increase in calcineurin phosphatase activity of HL-60 cells; the increase in this activity appeared to parallel the functional change of HL-60 cells during granulocytic differentiation. Increase in calcineurin activity was concordant with the increased expressions of calcineurin A and calcineurin B subunit proteins. The FKBP12 expression increased during ATRA-induced differentiation and expression of cyclophilin A remained unchanged. We propose that the increased expression of calcineurin is involved in the ATRA-induced inhibition of HL-60 cell proliferation, as in the case with 1,25alpha-dihydroxy-vitamin D3.

Calcineurin↗

[The influence of correction of acidosis on plasma level of branched-chain amino acids in chronic hemodialysis patients].

Seven patients undergoing chronic hemodialysis three times a week and whose plasma bicarbonate concentration on predialysis was consistently under 18 mmol/l due to bicarbonate dialysis (BCD), were treated with BCD for 2 weeks, then switched to acetate-free biofiltration (AFB) for 8 weeks. In both periods, the same high flux dialyzer (AN69HF) was used. The treatment time, dialysate flow rate and blood flow rate were kept constant in each patient during both periods. Plasma bicarbonate concentration (HCO3-), serum urea nitrogen (SUN), serum creatinine (Cr) and plasma amino acids concentrations (AA) were measured before dialysis and KT/V was calculated on the 2nd days of the last week in both periods. HCO3- on AFB was significantly higher than that on BCD (16.4 +/- 0.9 vs 19.9 +/- 1.8 mmol/l; p < 0.05). SUN on AFB was significantly lower than that on BCD even though the dialysis schedule and dietary content were not changed (84.7 +/- 3.7 vs 76.6 +/- 3.8 mg/dl; p < 0.05). TP, Cr and KT/V were not significantly different. Plasma total amino acid concentration (TAA) and plasma essential amino acid concentration (EAA) were not significantly different in both periods. In contrast, plasma branched-chain amino acid concentrations (BCAA) on AFB were significantly higher than that on BCD (313.5 +/- 44.3 vs 390.3 +/- 50.7 mumol/l; p < 0.05). Plasma BCAA concentrations, valine (VAL), leucine (LEU) and isoleucine (ILE), were significantly higher on AFB than that on BCD, respectively (p < 0.05). These findings suggest that optimal correction of the metabolic acidosis in chronic hemodialysis patients by AFB leads to a significant increase in plasma BCAA concentration.

Acidosis, Lactic↗

Insulin-Dependent Diabetic Mastopathy: A Case Report.

We report a case of insulin-dependent diabetic fibrous mastopathy, which clinically simulated breast cancer. The patient is a 55-year-old woman with stony-hard breast lumps, who had been treated with insulin for diabetes mellitus. Mammmography revealed a highly-dense mass shadow in the left breast and ultrasonography detected hypoechoic lesions with acoustic shadows in both breasts, suggestive of malignancy. Excisional biopsy was performed for the left breast lump. On histopathological examination, this was fibrosis with dense lymphocytic infiltration around lobules, which is a characteristic feature of diabetic fibrous mastopathy

Journal Article↗

CT and MRI of sellar spine with upward extension of the pituitary gland: case report.

This is a report of CT and MRI findings in a patient with a sellar spine which caused deformity of the pituitary gland. The sellar spine is an infrequent anatomical variant characterized by an osseous spine which arises in the midline from the anterior aspect of the dorsum sellae and extends into the pituitary fossa. The CT and MRI findings of sellar spine have been described in previous reports; however, only one investigator reported deformity of the pituitary gland as revealed by CT. This is the first report of the MRI finding of the sellar spine associated with a deformity and superior extension of the pituitary gland, mimicking pituitary hypertrophy.

Adolescent↗

The R40H mutation in a late onset type of human ornithine transcarbamylase deficiency in male patients.

Ornithine transcarbamylase (OTC) deficiency is an X-linked trait and is one of the most frequent of the inherited urea cycle enzyme deficiencies. Most male patients with OTC deficiency develop a hyperammonemic crisis and die in the neonatal period or in early infancy. In contrast to those patients, in some male patients the disease first becomes overt in adolescence or during the reproductive age period. In the present report, we describe six such male patients who first developed clinical signs at ages ranging from 6 to 58 years, all of whom came from a limited area of the northern part of Kyushu Island in southern Japan. The mutation analysis disclosed a R40H mutation in exon 2 of the OTC gene in each of these patients. Transmission of this mutant gene through paternal lineage as well as through maternal lineage was documented in one family. The levels of mRNA of the mutant OTC gene expressed in transfected Cos 1 cells and in the liver tissue obtained by biopsy in one patient were both similar to those of the wild-type gene. The activity of the mutant OTC was, however, decreased to a level of 28% of the wild-type OTC, and the levels of the mutant OTC protein expressed in Cos 1 cells were decreased, as assessed by western blot analysis. Apparent Km values of the mutant enzyme for ornithine (1.1 mM) and carbamylophosphate (2.0 mM) were similar to those of the wild-type enzyme. Both enzymes gave similar pH-dependency profiles, giving a maximal activity at pH 7.8-7.9. Activity of wild-type OTC expressed in Cos 1 cells did not change after five cycles of freezing and thawing, whereas that of the mutant OTC decreased to 17% by this treatment. These results suggest that deficiency is due to inactivation of the mutant OTC under certain conditions.

Adolescent↗

Rapid decrease of urinary pyridinoline excretion in growth hormone deficient children following discontinuation of growth hormone therapy.

In order to examine the effect of growth hormone on urinary pyridinoline excretion, 32 patients with complete or partial growth hormone deficiency had their urinary pyridinoline excretion measured while receiving growth hormone and for 14 days after it was discontinued. There was a significant positive correlation between increases in growth velocities during the first year of growth hormone administration compared to before it, and the ratio of the urinary pyridinoline excretion levels while receiving growth hormone to those after discontinuation. Therefore, urinary pyridinoline excretion rapidly decreased in patients with growth hormone deficiency when the administration of growth hormone was stopped. Exogenous growth hormone appears to stimulate bone resorption in these patients.

Adolescent↗

A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer.

A 5-year-old male patient with X-linked alpha-thalassemia/mental retardation syndrome is reported. He showed multiple minor anomalies including characteristic facial abnormalities, alpha-thalassemia, severe mental retardation, and hypogonadism. Analysis of his hemoglobin by high performance liquid chromatography using an automated glycated hemoglobin analyzer revealed an abnormal peak. Identification of an abnormal peak by an automated glycated hemoglobin analyzer will aid in the diagnosis of patients with X-linked alpha-thalassemia/mental retardation syndrome.

Abnormalities, Multiple↗

Influence of dialysis membranes on interleukin-1 beta and interleukin-1 receptor antagonist production by peripheral blood mononuclear cells.

We investigated the production of interleukin (IL)-1 beta and IL-1 receptor antagonist (Ra) by peripheral blood mononuclear cell (PBMC) in vitro during hemodialysis of 7 dialysis patients using 4 differential dialysis membranes (regenerated cellulose [RC], polyamide [PA], polysulfone [PS] and AN-69). Blood sampling was performed before dialysis (0 min), 15 min after starting dialysis, and after dialysis (240 min) during the last session of each treatment. The cellular content of fresh cells and the production of IL-1 beta and IL-1Ra with and without lipopolysaccharide (LPS) stimulation of the cells were evaluated and measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-1 beta with LPS stimulation using RC, PA, and PS membranes was significantly reduced at 15 min and was not changed at 240 min as compared with the level at 0 min. On the other hand, the level of IL-1 beta with LPS stimulation using an AN-69 membrane at 15 and 240 min was not significantly different from that at 0 min. Neither initial cellular content nor spontaneous production of IL-1 beta were detected at 0, 15, or 240 min in any of the membranes. The spontaneous production of IL-1Ra at 15 and 240 min was not significantly different from that at 0 min in any of the membranes. The cellular content of IL-1Ra using the RC membrane was significantly lower at 15 min and did not differ at 240 min from the level at 0 min. The cellular content of IL-1Ra using PA, PS, and AN-69 membranes was not significantly different at 15 and 240 min from that at 0 min. However, the IL-1Ra level with LPS stimulation using RC and PA membranes was significantly reduced from that at 0 min, but the level using PS and AN-69 membranes was not different from that at 0 min. Because IL-1 beta and IL-1Ra levels 15 min after starting dialysis using bioincompatible dialysis membranes were reduced from the levels at 0 min, the findings suggest that measurement of cytokines' during dialysis treatment at an early stage is a useful marker for evaluating the biocompatibility of a dialysis membrane.

Acrylic Resins↗

Chronic effects of long-term acetate-free biofiltration on the production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells.

The production of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) was examined in patients on long-term acetate-free biofiltration (AFB). Five stable patients on AFB were switched to bicarbonate hemodialysis (BCD) for a 2-week period using the same AN69 membrane dialyzer. IL-1beta and IL-1Ra production was measured by ELISA before and after dialysis in the last session of both treatments. Cytokine production by unstimulated PBMC did not differ significantly before and after both AFB and BCD. However, the spontaneous IL-1Ra/IL-1beta production ratio in AFB was significantly higher than that in BCD. These findings indicate that AFB may have more beneficial effects on cytokine production by PBMC compared to BCD.

Acetates↗

Increased production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells in undialyzed chronic renal failure.

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.

Adult↗

Cloning and characterization of hsc1+, a heat shock cognate gene of the fission yeast Schizosaccharomyces pombe.

A heat shock cognate gene from the fission yeast Schizosaccharomyces pombe (Sp), designated hsc1+, was cloned. The putative translation product of hsc1+ contains 613 aa, with an estimated molecular mass of 67,205 Da, and is more similar to the Saccharomyces cerevisiae (Sc) heat shock cognate protein SSB1 (69% identity) than the Sp heat-inducible ssp1+ gene product (41% identity). The hsc1+ mRNA was abundant during steady-state growth at 23 degrees C and decreased upon heat shock. Immunoblot analysis showed that the hsc1 protein is also abundant and constitutively expressed, however, we could not observe significant change in the protein level upon heat shock. DNA blot analyses indicated that hsc1+ is localized in Sp chromosome II, and suggested that the Sp genome contains a relatively smaller number of HSP70 genes compared with the Sc genome.

Amino Acid Sequence↗

A facilitatory effect on the induction of long-term potentiation in vivo by chronic administration of antisense oligodeoxynucleotides against catalytic subunits of calcineurin.

A rise in Ca2+ concentration at postsynaptic sites provides an initial step in inducing both the long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus. LTP induction requires the activation of Ca(2+)-sensitive protein kinases following the rise in Ca2+. By contrast, the activity of protein phosphatase(s) appears to be critical to induce LTD. Here we demonstrate that inhibition of the synthesis of calcineurin A alpha and A beta, catalytic subunits of Ca2+/calmodulin- (CaM) dependent protein phosphatase, reduces the threshold of induction for commissural-CA1 LTP in anesthetized rats. In rats administered antisense oligodeoxynucleotides (ODNs) against calcineurin A alpha and A beta intraventricularly for 7 days, a brief tetanic stimulation to the CA3 region, which in the control case was below threshold for the induction of LTP, now produced a long-lasting increase in both the EPSP slope and the amplitude of population spike recorded from the commissural-CA1 pathway. Western blot analysis of calcineurin showed that the threshold reduction was accompanied by a selective decrease in the protein levels in the hippocampus. Thus our study provides direct evidence that calcineurin per se has an antagonizing role in LTP induction. Complementary experiments with the selective calcineurin inhibitor, FK506, also showed the reduction of LTP threshold in a dose-dependent manner. These results, together with previous studies, support the hypothesis that the quantitative phosphorylation level of critical intracellular proteins determines whether the synaptic efficacy will increase or decrease after the activity-dependent rise in postsynaptic Ca2+.

Animals↗

1 alpha,25-dihydroxyvitamin D3-induced upregulation of calcineurin during leukemic HL-60 cell differentiation.

Cyclosporin A and FK506, at concentrations that inhibited phosphatase activity of calcineurin in HL-60 cellular lysates, augmented the proliferation of leukemic HL-60 cells. These immunosuppressants did not affect 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced monocytic differentiation of HL-60 cells, but did abrogate the 1,25(OH)2D3-induced inhibition of HL-60 cell growth. Treatment with 20 nmol/L 1,25(OH)2D3 led to a progressive increase in calcineurin phosphatase activity in subcellular fractions from HL-60 cell extracts, the increase in this activity appeared to parallel the phenotypic and functional changes of HL-60 cells during monocytic differentiation induced by 1,25(OH)2D3. Immunoblot analysis indicated that increase in calcineurin activity was concordant with the increased expressions of calcineurin catalytic subunit isozymes, calcineurin A alpha (CNA alpha), and calcineurin A beta(CNA beta), and a regulatory calcineurin B subunit (CNB) proteins, which were preceded by a coordinate increase in the levels of CNA alpha, CNA beta and CNB mRNAs. The expression of calmodulin remained unaltered throughout 1,25(OH)2D3-induced monocytic differentiation. These results suggest that calcineurin activation has a net negative effect on HL-60 cell proliferation, and that the increased expression of calcineurin may be involved in 1,25(OH)2D3-induced inhibition of HL-60 cell proliferation.

Calcineurin↗