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Biomedical subjects

Tohru Ogihara

Publications and source records attributed to Tohru Ogihara.

9 recordsLinked to original sources

Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia.

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants <32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants <28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD <28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.

Antigens, Neoplasm↗

Plasma cell leukemia presenting with diplopia due to unilateral abducens paralysis and complex chromosomal abnormalities.

Involvement of cranial nerves is rare in plasma cell leukemia (PCL). Here, we report a case of PCL presenting with unilateral abducens paralysis. Cranial magnetic resonance imaging (MRI) disclosed a mass in the sphenoid sinus. Although the patient showed an initial response to chemotherapy, he died of disease progression 5 months later. Cytogenetic analysis showed translocation of chromosomes 11 and 14, t(11;14) (q13;q32), with additional complex abnormalities. This case implies an association between clinical manifestations and chromosomal abnormalities.

Abducens Nerve Diseases↗

Regulation of apoptosis by glutathione redox state in PC12 cells exposed simultaneously to iron and ascorbic acid.

We previously reported that the levels of non-protein-bound iron (NPBI) and ascorbic acid (AA) are markedly increased in the cerebrospinal fluid of infants with perinatal asphyxia. The present study showed that FeSO4 and AA synergistically induced apoptosis of PC12 cells, which was prevented by alpha-tocopherol and glutathione (GSH) ethyl ester. Markers of free radical damage, such as ortho-tyrosine, meta-tyrosine, and F(2alpha)-isoprostane, showed a gradual increase. AA and ferrous NPBI disappeared rapidly from the culture medium, but exposure for only a few hours was sufficient to trigger apoptosis. Intracellular GSH decreased progressively along with a concomitant increase of glutathione disulfide (GSSG). The baseline half-cell reduction potential (Ehc) for GSSG, 2H+/2GSH couple was -246 mV and an Ehc of -200 mV was the critical level to switch on apoptosis, although some cells escaped this fate by transient increase of intracellular GSH. Once Ehc reached around -165 mV (81 mV oxidation from the baseline), all cells lost the ability to maintain an adequate intracellular GSH level and subsequently underwent apoptosis. These findings at least partly explain the mechanism of Fe-AA cytotoxicity, in that ferrous iron catalyzes hydroxyl radical generation and induces lipid peroxidation, after which subsequent depletion of GSH raises Ehc to the critical level for triggering or potentiating the apoptotic cascade.

Animals↗

Identification of apo- and holo-forms of ceruloplasmin in patients with Wilson's disease using native polyacrylamide gel electrophoresis.

OBJECTIVES: To determine the serum ratio of holo-ceruloplasmin to total ceruloplasmin in patients with Wilson's disease (WD), we identified apo- and holo-forms of serum ceruloplasmin with native-PAGE electrophoresis. DESIGN AND METHODS: Serum obtained from nine patients with Wilson's disease was subjected to native-PAGE analysis. We also determined the ceruloplasmin level and ferroxidase activity in all of the samples. RESULTS: Among the nine patients, three had both forms of ceruloplasmin and six had only apo-ceruloplasmin. In the patients who had only apo-ceruloplasmin, the serum ceruloplasmin level was significantly lower than in the patients with both forms. CONCLUSIONS: Differences in the ability to incorporate copper into ceruloplasmin may have a role in ceruloplasmin concentrations in patients with Wilson's disease.

Adolescent↗

[Allantoin].

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Allantoin↗

Non-protein-bound transition metals and hydroxyl radical generation in cerebrospinal fluid of newborn infants with hypoxic ischemic encephalopathy.

Among various hypothetical mechanisms for the in vivo production of reactive oxygen species, transition metal-catalyzed reactions in cooperation with a biologic reducing agent like ascorbic acid or superoxide may be some of the most important. In the present study, we retrospectively examined the existence of non-protein-bound metal ions, an essentially hazardous pro-oxidant form of various transition metals, and the occurrence of metal-catalyzed reactive oxygen species production in cerebrospinal fluid (CSF) of 10 infants with hypoxic ischemic encephalopathy (HIE) subsequent to perinatal asphyxia and 12 control infants within 72 h of birth. Non-protein-bound iron was detected in eight out of 10 CSF samples from the HIE infants and its level was significantly correlated with Sarnat's clinical stage, whereas none of the control infants had detectable non-protein-bound iron levels. Non-protein-bound copper was below the detection limit in all CSF samples from both groups. Ascorbic acid was significantly increased in the CSF of HIE infants when compared with that of controls (means, 664.9 versus 449.4 microM, p = 0.008). ortho-Tyrosine and meta-tyrosine, which are highly specific and sensitive markers of protein oxidation induced by hydroxyl radicals, were significantly higher in HIE infants than in controls when evaluated by the ratio relative to their source amino acid, phenylalanine [means, 110.5 versus 75.4, p = 0.018 for ortho-tyrosine/phenylalanine; 104.6 versus 67.7 (nM/microM x 10(2)), p = 0.048 for meta-tyrosine/phenylalanine]. Both ratios were significantly correlated with non-protein-bound iron, but not with ascorbic acid. Our preliminary observations provide direct evidence that hydroxyl radicals are generated in the CNS during asphyxiation. Iron chelation therapy could be worth developing as a neuroprotective strategy for perinatal asphyxia.

Allantoin↗

Two cases in which an abnormal hemoglobin (Hb Kamakura) was identified on the basis of an abnormally low glycohemoglobin levels.

We encountered two patients with abnormally low glycohemoglobin levels in spite of normal plasma glucose levels. Since the presence of an abnormal hemoglobin was suggested by high-performance liquid chromatography (HPLC), gene analysis of these two patients was conducted by single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing, and Hb Kamakura with one base substitution (beta3 Leu --> Val) in the beta globin gene was detected in both patients. There was been only one report of Hb Kamakura in Kanagawa Prefecture, and our patients represent the second and third cases, respectively.

Adult↗

Alpha-tocopherol content and alpha-tocopherol transfer protein expression in leukocytes of children with acute leukemia.

Alpha-tocopherol (a form of vitamin E) is a fat-soluble vitamin that can prevent lipid peroxidation of cell membranes. This antioxidant activity of alpha-tocopherol can help to prevent cardiovascular disease, atherosclerosis and cancer. We investigated the alpha-tocopherol level and the expression of alpha-tocopherol transfer protein (alpha-TTP) in the leukocytes of children with leukemia. The plasma and erythrocyte alpha-tocopherol levels did not differ between children with leukemia and the control group. However, lymphocytes from children with leukemia had significantly lower alpha-tocopherol levels than lymphocytes from the controls (58.4 +/- 39.0 ng/mg protein versus 188.9 +/- 133.6, respectively; p < 0.05), despite the higher plasma alpha-tocopherol/cholesterol ratio in the leukemia group (5.83 +/- 1.64 micromol/mmol versus 4.34 +/- 0.96, respectively; p < 0.05). No significant differences in the plasma and leukocyte levels of isoprostanes (the oxidative metabolites of arachidonic acid) were seen between the leukemia patients and controls. The plasma level of acrolein, a marker of oxidative stress, was also similar in the two groups. Investigation of alpha-TTP expression by leukocytes using real-time PCR showed no difference between the two groups. These findings suggest that there may be comparable levels of lipid peroxidation in children with untreated leukemia and controls, despite the reduced alpha-tocopherol level in leukemic leukocytes.

Acrolein↗

alpha-Tocopherol transfer protein expression in rat liver exposed to hyperoxia.

alpha-Tochopherol transfer protein (alpha TTP), a 32 kDa protein exclusively expressed in liver cytosol, has a high binding affinity for alpha-tochopherol. The factors that regulate the expression of hepatic alpha TTP are not clearly understood. In this study, we investigated whether or not exposure to hyperoxia (> 95% O2 for 48 h) could alter the expression of hepatic alpha TTP. We also examined the association between the expression of antioxidant enzymes (hepatic glutathione peroxidase (GPX) and Mn-superoxide dismutase (Mn-SOD)) and the expression of hepatic alpha TTP. The levels of thiobarbituric acid-reactive substances (TBARS) in both plasma and liver were significantly higher after rats were exposed to hyperoxia for 48 h when compared with the levels in control rats. Northern blotting showed a decrease in the expression of alpha TTP messenger RNA (mRNA) after hyperoxia, although the alpha TTP protein level remained constant. Expression of Mn-SOD mRNA and protein, as well as the expression of GPX mRNA, were stable after hyperoxia. These findings indicate that mRNA for hepatic alpha TTP, rather than Mn-SOD or GPX, may be highly responsive to oxidative stress.

Alanine Transaminase↗