Biomedical subjects
Publications and source records attributed to T Doi.
The highest specific activity of thiamin pyrophosphokinase was found in the cerebellum, and lower activity in cerebral cortex and midbrain. The regional difference in the enzyme activity was similar to that in thiamin content and the influx rate in rat brain, suggesting that the enzyme is involved in the thiamin transport.
Insertion of the four major nucleotides at the 5'-side of the anticodon triplet of E. coli tRNAMetf was performed by joining of the half molecules obtained by limited digestion with RNase A and the chemically synthesized tetranucleotide pN-C-A-U using RNA ligase. Insertion of U-U at the 5'-side or A and A-A at the 3'-side of the anticodon were also performed using U-U-C-A-U, C-A-U-A and C-A-U-A-A. The constant U next to the 5'-side of the anticodon was replaced with A and C by ligation of A-C-A-U and C-C-A-U to the 5'-half molecule which had been treated with periodate plus lysine, followed by joining to the 3'-half. These modified tRNAs were tested for their ability to accept methionine with the methionyl-tRNA synthetase of E. coli. The affinity of these analogs for the synthetase decreased more extensively when the insertion was at the 3'-side of the anticodon triplet. Insertion of mononucleotides at the 5'-side or replacement of the constant U next to the 5'-side of the anticodon did not affect aminoacylation drastically. This may mean that the 3'-side of the anticodon loop of tRNA is one of the major recognition sites for the methionyl-tRNA synthetase.
Thiamine metabolism in vivo was studied by intracerebroventricular injection of labeled thiamine in rat brain. Labeled thiamine was found to be rapidly converted to the phosphorylated thiamine esters. The distribution of the radioactive thiamine compounds was reached to steady state at 3 hr after injection: thiamine, thiamine monophosphate, thiamine pyrophosphate, and thiamine triphosphate were 8-12%, 12-14%, 72-74%, and 2-3%, respectively, in cerebral cortex. The presence of labeled thiamine triphosphate in the brain was further confirmed by the treatment with thiamine triphosphatase which had an absolute substrate specificity for thiamine triphosphate. These results suggest that thiamine triphosphate is synthesized in vivo in rat brain.
Cutaneous basophil hypersensitivity factor (CBH-F) from the sera of 1-fluoro-2,4-dinitrobenzene contact-sensitized guinea pigs promoted histamine release from bone marrow basophils in the presence of the antigen, dinitrophenylated epidermal microsomes as well as in vivo activity to induce CBH reaction in naive recipients and in vitro activity to mediate antigen-dependent basophil chemotaxis. The amount of histamine released was around 20% of the total release when compared to that of concanavalin A-induced basophil degranulation (50-60%). Divalent cations were required in this reaction because addition of EDTA completely suppressed histamine release from passively sensitized basophils with CBH-F. Though it is not known at present whether the same molecule is involved in basophil chemotaxis and histamine release, this histamine-releasing activity was recovered in the same preparations with basophil chemotactic activity after several purification steps.
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Metabolic studies of ipriflavone (TC-80) in rats by gas-liquid chromatography-mass spectrometry led to the characterization of the following metabolites: the parent compound, 7-hydroxy-3-phenyl-4H-1-benzopyran-4-one, 7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, 3-(4-hydroxyphenyl)-7-isopropoxy-4H-1-benzopyran-4-one, 2-(3-phenyl-4-oxo-4H-1-benzopyran-7-yl)oxypropionic acid, 2-[3-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl]oxypropionic acid and 2-[3-(3-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl]oxypropionic acid. From the metabolites identified, TC-80 was shown to be metabolized primarily by oxidation. In vitro study using tissue slices of rats indicated that the above metabolic changes occurred exclusively in the liver. It was also demonstrated that the compound did not undergo metabolic conversion by gut flora of rats.
Oral 14C-ipriflavone was absorbed by rats to give a maximum plasma 14C level at 1.5 h and a half-life of 5.8 h. In dogs, after po dosing, the plasma 14C peaked at 0.5 h, followed by gradual decline. The plasma of both animals contained mostly metabolites, with small amounts of unchanged ipriflavone. In rats, 14C was distributed widely in tissues, with relatively high concns. in the liver, kidney and gut. Distribution in rat thigh bone of unmetabolized ipriflavone was also demonstrated. 14C-Ipriflavone was eliminated mostly as metabolites within 48 and 72 h, respectively, in rats and dogs. Rats excreted more 14C in urine than in feces, whereas the reverse was noted in dogs. Biliary excretion and reabsorption of 14C were also obvious in both animals.
Sixteen patients with benign prostatic hypertrophy (BPH, 5 cases) and neurogenic bladder (NB, 11 cases) were treated with Robaveron tablets (KN-7) containing an extract of swine prostate gland 20 mg/T. at the dose of 2 tablets t.i.d. for a long term of 6-33 months. Evaluation of drug efficacy and safety were based on decrease of residual urine, improvement of subjective symptoms, complaints of side effects and clinical laboratory tests recorded every three months. Significant decrease of residual urine rate and good improvement of various subjective symptoms such as difficulty in urination, pollakisuria, urinary incontinence, etc. were obtained and maintained. The overall effectiveness, rated as slightly improved or better on the final evaluation of these cases was 68.8%. No cases of side effects or abnormal changes in the laboratory tests directly due to the test drug were observed. Robaveron tablet is both safe and effective for the long-term therapy of urinary disturbance.
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IgA class circulating immune complexes (CIC) were detected by solid-phase fluorescent enzyme immunoassay of F(ab')2 anti-C3d antibody in the serum of 52 patients with IgA nephropathy. Conglutinin (Kg) binding IgA class CIC were also measured, and results by these assays were compared. Kg binding IgA class CIC and anti-C3d binding IgA class CIC were detected in 27% and 44%, respectively, of the patients with IgA nephropathy. Either or both of the two were found in 65% of the patients. There was no significant correlation between IgA class CIC detected by these methods and serum IgA. Although all samples with a very high level of anti-C3d binding IgA class CIC did not also have a very high level of Kg binding IgA class CIC, there was a slight quantitative correlation between the 2 assays. Ultracentrifugation analysis showed that anti-C3d binding IgA class CIC were of various sizes between polymeric (21 S) and monomeric IgA (7 S), whereas Kg binding IgA class CIC were mostly monomeric IgA (8 S) with a minor component of heavy fractions (14 S). Both IgA class CIC fixed iC3b and IgA class CIC fixed C3d are present in IgA nephropathy. These observations suggest that the different types of complement bound to IgA class CIC have different roles in IgA nephropathy.
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A successful reconstruction of a large tibial defect with a free vascularized fibular graft is presented. The fibular graft demonstrated a significant hypertrophy 2 years postoperatively.
By a direct immunofluorescent technique, glomerular C3d deposition was examined in a total of 50 renal biopsy specimens from patients with lupus nephritis. C3d deposition was then compared with disease activity, glomerular IgG and C3c deposition, and the levels of circulating immune complexes (CIC) measured by a solid-phase anti-C3d assay. There was a good correlation between disease activity and the positivity of glomerular C3d deposits (P less than 0.001), as well as C3c deposits (P less than 0.001). Even in clinically inactive patients, a relatively high percentage (59%) of C3d deposits were positive compared with C3c deposits (17%). Mesangial C3d deposition correlated with clinical disease activity more significantly (P less than 0.005) than capillary wall C3d deposition (P less than 0.025). C3d deposits were detected in all of the 30 cases with positive C3c deposits, and moreover, in 15 of the 20 (75%) cases with negative C3c deposits. Glomerular IgG deposits were almost always associated with C3d deposits, both in mesangial areas and along capillary walls, with statistical significance (P less than 0.005, P less than 0.001, respectively). The serum levels of C3d-fixing immune complexes (IC) were significantly correlated with the positivity and intensity of mesangial C3d deposits. This study demonstrates glomerular deposition of C3d in patients with lupus nephritis and reveals a significant correlation between mesangial C3d deposition and disease activity.
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Immunoelectron microscopy was used in this study of IgA nephropathy to examine the relationship between immune deposits and electron-dense deposits seen by electron microscopy, and these findings were correlated with the severity of mesangial proliferation. Immunoelectron microscopic studies for antihuman gamma-chain, alpha-chain, mu-chain, C3, and C3d were performed by the method of Nakane in 16 patients with IgA nephropathy. The patients with minimal glomerular involvement and focal proliferative glomerulonephritis showed electron-dense reaction products of IgA in the paramesangial area, while the patients with diffuse proliferative glomerulonephritis showed electron-dense reaction products of IgA throughout the enlarged mesangial matrix. Immunoelectron microscopy showed electron-dense reaction products of IgA at the same locations as the electron-dense deposits seen on electron microscopy. C3 deposits were identified in 15 out of the 16 patients, but were less dense than IgA deposits. Electron-dense reaction products of C3 contained both positive and negative sites in 7 patients. Extensive C3d deposits were found in all cases in association with IgA deposits. The locations of these deposits were the same as those of the IgA deposits. These findings suggest that C3 deposits dissociate from the immune deposits and that the locations of the immune deposits correlate well with the severity of mesangial proliferation.
An immunoperoxidase technique for light microscopy was carried out in 16 patients with idiopathic membranous nephropathy in order to determine the role of the complement system in glomeruli. Although C3 deposits are found in 50% of the cases, C3d deposits are identified in all cases in association with IgG deposits. This suggests that C3 deposits are degraded and dissociated from immune complexes. Patients with glomerular C3 deposits showed more proteinuria than those without glomerular C3 deposits. The presence of C3 deposits indicates the importance of proteinuria in human membranous nephropathy.