[Physicochemical studies on the binding of chemicals with proteins IV. Hydrogen ion equilibria of lens proteins].
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Biomedical subjects
Publications and source records attributed to N Koga.
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Renal ultrasonographic studies were done in 26 patients with acute tubular necrosis. Prominent findings were an increase in renal size, especially the anteroposterior diameter, and sharp delineation of swollen pyramids. The ratio of anteroposterior to longitudinal diameter (H/L) was correlated with serum creatinine levels and inversely correlated with urine osmolalities. It was well correlated with the recovery time of acute renal failure. The patient group having an increased H/L had a mean recovery time of 32.4 days and 11 of the 12 patients required hemodialysis (mean of 10 times). The patient group having a normal H/L had a mean recovery time of 15.5 days and 9 of the 14 required hemodialysis (mean of 3 times).
COX-2 is a key factor in the progression of inflammation, the effects of a specific COX-2 inhibitor in cardiac transplantation have not yet been elucidated. To test the hypothesis that a COX-2 inhibitor can alter cardiac rejection, we analyzed graft survival using totally allomismatched grafts. Although the COX-2 inhibitor attenuated myocardial cell infiltration, the inhibitor did not prolong survival. We conclude that the COX-2 inhibition may have potential for the suppression of inflammation in cardiac allografts.
The metabolism of 2,3',4',5-tetrachlorobiphenyl (TCB) was compared using liver microsomes and six isoforms of cytochrome P450 purified from rats, guinea pigs and hamsters. In microsomal study, the following species differences were observed: 1) Untreated guinea pigs and hamsters but not rats can metabolize this TCB to 3-hydroxy- or 4-hydroxy-2,3',4',5-TCB, 2) Guinea pig microsomes showed only 3-hydroxylating activity, whereas hamster microsomes showed higher activity of 4-hydroxylation than that of 3-hydroxylation. In common with three species, the 3-hydroxylation was accelerated by phenobarbital. The 4-hydroxylation in rats and hamsters was increased by pretreatment with 3-methylcholanthrene and 3,3',4,4',5-pentachlorobiphenyl. The hydroxylation activities of liver microsomes from the three species could be explained by an involvement of different isoforms of cytochrome P450. In addition, it is apparent that hamster CYP1A2 as well as hamster CYP2A8 is involved in the 4-hydroxylation of 2,3',4',5-TCB although it has no activity for 2,2',5,5'-TCB.
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In chronic hemodialysis patients, there is the major problem of occlusion in the arteriovenous fistulae. To investigate this problem, the authors have developed angioscopy for examination and detection of occlusion developing to allow early use of transluminal balloon angioplasty (PTA) or laser angioplasty and prevent occlusions. The authors have examined 27 patients using a 2.7 mm diameter Olympus flexible angioscope and 9F sheath, following-up with a 4 mm balloon catheter (BARD) or SLT Nd-YAG laser. PTA was performed for 25 cases, with 19 demonstrating after one session patency lasting 9 months to date. Three cases revealed restenosis and have each received three PTA sessions. Laser angioplasty was performed in one case of 15 cm chronic occlusion, with subsequent PTA successfully enabling hemodialysis. Angioscopically, the authors were able to observe the various rest-forms within the shunt and detected the mural thrombus attached to the punctured pore. Both circumferential and valvular stenoses were observed. Initially after laser angioplasty, rough irregularity and a mural thrombus in the vessel was observed, but 2 months later, the vessel lumen had become smooth, probably due to intimal growth. Thrombus is acute stenosed cases were clearly observed. Angioplasty enabled new observations in the A-V fistulae, which allows investigation of the mechanism of stenosis or occlusion and enables an extended use of the hemodialysis blood access.
PURPOSE: Intensive chemoradiotherapy followed by peripheral blood stem cell transplantation has been introduced to treat children with advanced neuroblastoma (NBL). Detection of NBL cells in peripheral blood (PB) is important to prevent reinfusion of NBL cells. Several immunologic methods have been proposed for detecting NBL cells in hematologic samples. The development of a sensitive and specific combination of monoclonal antibodies (MoAbs) for detecting small numbers of NBL cells in PB using flow cytometry remains an important challenge. METHODS: Twenty-one clinical samples from NBL tissues or smears containing NBL cells were examined for reactivity against CD81, CD56, and CD9 using an immunocytochemical technique. The expressions of CD81, CD56, CD9, and antihuman disialoganglioside GD2 MoAb (GD2) in five NBL cell lines were assayed by flow cytometry. For the evaluation of sensitivity, five NBL cell lines were added to normal PB and the detection level of the combination of CD81/CD56/CD45 MoAbs was compared with that of CD9/CD56/CD45 MoAbs (reported previously). One hundred thirty-three normal PB samples were examined to determine the sensitivity and specificity of this method. RESULTS: All NBL cell lines showed strong positivity with CD81 and CD56 MoAb. However, CD9 MoAb was weakly positive against the five NBL cell lines. GD2 MoAb reacted strongly with four NBL cell lines, although almost the entire cell population of the SK-N-SH NBL line failed to bind the GD2 MoAb. In vitro experiments using NBL cell lines demonstrated that tumor cells added to normal PB cells could be detected by flow cytometry using CD81/CD56/CD45 MoAbs even at a concentration of 0.005%. Through comparative studies, the combination of CD81/CD56/CD45 MoAbs was found to be more sensitive and specific than that of CD9/CD56/CD45 MoAbs for detecting small numbers of NBL cells using the above cell lines. CONCLUSIONS: Triple-color flow cytometric analysis using CD81/CD56/CD45 MoAbs is useful for detecting NBL cells in PB. Further studies testing this approach using samples of PB with NBL contamination are needed to test this approach in patients.
We investigated a nonradioisotope method for the evaluation of glucose uptake activity using enzymatic measurement of 2-deoxyglucose 6-phosphate (2DG6P) content in isolated rat soleus muscle in vitro and in vivo. The 2DG6P content in isolated rat soleus muscle after incubation with 2-deoxyglucose (2DG) was increased in a dose-dependent manner by insulin (ED(50) = 0.6 mU/ml), the maximum response being about 5 times that of the basal content in vitro. This increment was completely abolished by wortmannin (100 nM), with no effect on basal 2DG6P content. An insulin-mimetic compound, vanadium, also increased 2DG6P content in a dose-dependent manner. In isolated soleus muscle of Zucker fa/fa rats, well known as an insulin-resistant model, insulin did not increase 2DG6P content. The 2DG6P content in rat soleus muscle increased after 2DG (3 mmol/kg) injection in vivo, and conversely, the 2DG concentration in plasma was decreased in a dose-dependent manner by insulin (ED(50) = 0.11 U/kg). The maximum response of the accumulation of 2DG6P in soleus muscle was about 4 times that of the basal content. This method could be useful for evaluating glucose uptake (transport plus phosphorylation) activity in soleus muscle in vitro and in vivo without using radioactive materials.
The pathogenesis of the increased number of megakaryocytes and thrombocytosis in essential thrombocythemia (ET) is still unknown. We examined the expression of c-mpl, a receptor of thrombopoietin (TPO), and its signaling molecules in a patient with ET. An 8-year-old girl showed a high platelet count and an increased number of bone marrow megakaryocytes. Neither chromosomal abnormalities nor myelofibrosis was observed. Following the diagnosis of ET, aspirin therapy was begun for the patient, with only modest improvement of symptoms. Her platelet count ranged from 1,200,000/microL to 2,200,000/microL for more than 2 years. In the analyses, the serum TPO level in the patient was 420 attomoles/mL (normal, 760 +/- 320). The level of c-mpl expression in bone marrow mononuclear cells was higher in the patient than in healthy children, while there was no difference in the level of c-mpl expression in CD34+ cells, indicating an expanded pool of megakaryocytic lineage cells. The level of Janus kinase 2 (Jak2) expression was lower in the patient than in a healthy child. These findings indicate that the signal pathway mediated by c-Mpl after binding to TPO may be impaired in ET. Further analysis is needed to clarify the mechanism underlying the development of thrombocytosis in ET patients.
An anaphylactoid reaction was observed in a patient treated with low density lipoprotein (LDL) apheresis using a dextran sulfate cellulose (DSC) column and administration of an angiotensin converting enzyme (ACE) inhibitor. The authors have investigated to determine the causes and countermeasures. When using heparin as the anticoagulant, large increases in bradykinin levels in plasma were observed after its passage through the column during the procedure. Increase in bradykinin levels in blood were observed, to a lesser but still significant degree, after terminating the procedure. When withholding the ACE inhibitor for a few days before LDL-apheresis, the increase in bradykinin levels was much weakened and the anaphylactoid reactions became mild. Such anaphylactoid reactions were not observed when the ACE inhibitor was withheld for a few weeks, or when using Futhan instead of heparin as the anticoagulant. Although the critical level of bradykinin needed to cause the anaphylactoid reaction and the other possible causal factors remained unclear, the bradykinin levels are thought to be related to the reactions.