[A case of atrial fibrillation induced by interferon treatment for chronic hepatitis C].
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Biomedical subjects
Publications and source records attributed to T Tamai.
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Epidemiological studies have demonstrated that high density lipoprotein cholesterol (HDL-C) is inversely related to the incidence of coronary heart disease morbidity and mortality. In the present paper, we summarized the recently published data on HDL receptor, reverse cholesterol transport, and antiatherogenic effect of HDL particle. Several investigators have reported the apparent molecular weight of HDL binding protein using ligand blotting by radiolabeled HDL and immunoblotting by antibody against the purified binding protein. These results, however, were not consistent among the data reported from several laboratories. In 1992 a cDNA of HDL binding protein (HBP) was isolated from a human fibroblast and a human erythroleukemia cell cDNA library but it does not contain a classical hydrophobic membranes spanning domain. At present, it is reasonable to assume that HBP is different structurally and functionally from a classical plasma membrane receptor. We hope putative HDL receptor will be isolated, characterized and its cDNA will be cloned in the near future. It has been postulated that there are four functional steps in the pathway of reverse cholesterol transport. The main step is CETP-mediated transfer of cholesteryl esters from HDL to the VLDL/LDL fraction. Recent development of molecular biological techniques enable us to make a animal model over expressing apolipoprotein A-I or A-II, namely a transgenic mouse. These models indicated that apolipoprotein A-I has an antiatherogenic effect in vivo but apolipoprotein A-II does not.
Fish interferon (IFN) cDNA was first cloned from the cDNA library of immortalized flatfish leukocytes. The clone contains an open reading frame that encodes a 138 amino acid polypeptide including a glycosylation site and a signal peptide containing 30 amino acids. BHK-21 cells transfected with the INF-expression plasmid produced active recombinant IFN (about 16 kDa) which was then purified by WGA agarose affinity chromatography. This recombinant IFN inhibited infection of fish cells with the Hirame (flatfish) rhabdovirus.
Flatfish leukocytes were transfected with the expression plasmids of the v-myc, c-myc, c-fos, v-myb and c-Ha-ras oncogenes. Only cotransfection of c-Ha-ras with c-myc or c-fos resulted in complete immortalization of the cells. Interferon-like anti-viral protein was found in the cultured medium of the immortalized lymphocytes. The protein was purified by DEAE-Toyopearl 650 M ion exchange chromatography and WGA agarose affinity chromatography. The protein was a glycoprotein of about 16 kDa. The antiviral activity of the protein was trypsin-sensitive and was fairly stable at pH values from 4 to 8. The protein retained about 60% of the activity even at 60 degrees C and showed a broad antiviral activity for various fish cells and viruses.
Ca2+ regulates a variety of cellular mechanisms in vascular cells as well as in platelets. Nicorandil interacts with the intracellular Ca(2+)-activated processes in vascular smooth muscle cells, while Ca2+ channel blockers such as verapamil and diltiazem block voltage-dependent Ca2+ channels. The effects of nicorandil are due to the hyperpolarization of the membrane, interference with mobilization of Ca2+ from the intracellular storage sites, and blockade of receptor-operated Ca2+ channels. In the present study, the effects of nicorandil on cell proliferation and cholesteryl ester accumulation in rat arterial smooth muscle cells in culture were compared to Ca2+ channel blockers. Smooth muscle cells were prepared from rat thoracic aorta, and the rate of proliferation was determined by measuring the cell number and by [3H]-thymidine incorporation into cellular DNA. The effect of nicorandil on cholesteryl ester content in smooth muscle cells was determined by thin-layer chromatography of the cell extracts. Nicorandil at concentrations of 10(-6) to 10(-4) M, as well as Ca2+ channel blockers (verapamil and diltiazem) inhibited the proliferation and DNA synthesis of cultured smooth muscle cells. The acute inhibitory effects on cell proliferation were observed significantly 16 hours after the addition of the three agents in serum-stimulated cells. These effects were dose dependent, both in acute and in chronic treatment with the three agents. Addition of 10(-5) M nicorandil to medium supplemented with 10% serum resulted in a decrease of the net cholesteryl ester content by 18 +/- 1%, while cellular free cholesterol content was the same as control. Similar results were also obtained in the presence of verapamil and diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)
Cine magnetic resonance imaging (MRI) was used to assess aortic regurgitation (AR) in 13 patients with valvular disease and 3 normal subjects, and the results were compared to color Doppler flow mapping findings. AR produced a signal void in the left ventricle during the diastolic phase in all patients by MRI. There were no false positive or negative results compared with echocardiographic findings. Visual grading of cine MRI gave results similar to color flow Doppler echocardiography (88%). The distance and the area of aortic regurgitation using MRI correlated well with color Doppler flow mapping (r = 0.82 and 0.88). However, measurements of distance and area by color flow Doppler tended to be larger than those by cine MRI. With current techniques echocardiography may overestimate the severity of AR as compared with cine MRI. In addition, MRI gives clinically useful information in patients in whom transthoracic Doppler echocardiography is not adequate.
Two new derivatives, 3''-epi-erythromycin A (2) and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11-oxoerythromycin A (3), have been synthesized by using glycosylation with glycal (Ferrier rearrangement), bromomethoxylation and bis(tributyltin) oxide-bromine oxidation as the key steps. Their antimicrobial activities were compared with those of erythromycin A (1).
Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.
A case of lung cancer associated with eosinophilia in the peripheral blood and pleural fluid is reported. A 55-year-old man with a tumor in the right lower lung lobe and right pleural effusion was admitted to Ehime University Hospital. Histology of specimens biopsied under a bronchoscope revealed that he had poorly differentiated squamous cell carcinoma. On admission, his peripheral blood leukocyte count was 11,500/microliters with 7.8% eosinophils and the pleural fluid showed a high eosinophil count (60.5%). After chemotherapy, blood eosinophilia disappeared and the pleural effusion was decreased with the reduction of the tumor. The patient's serum had the activity to stimulate eosinophil proliferation in human bone marrow cell culture, suggesting that the tumor may have produced an eosinophil proliferating factor.
To analyze the characteristics of Leptospira strains HY-1, HY-2, and HY-10, which were isolated from patients with leptospirosis in Korea in 1985, 12 monoclonal antibodies (MAbs) against strain HY-1 and six MAbs against serovar lai strain 017 were produced, and their properties were determined by the microscopic agglutination test. Genetic relationships among the leptospires were determined by restriction endonuclease DNA analysis. Three MAbs reacted with all strains of serogroup Icterohaemorrhagiae, but did not react with any strains of the other 10 serogroups. All MAbs reacted with strains 017, HY-1, HY-2, and HY-10 at nearly identical titers. Two MAbs reacted only with these four strains. These four strains also had the same restriction endonuclease cleavage patterns. Based on these results, strains HY-1, HY-2, and HY-10 were identified as serovar lai, which is one of the common serovars in China. It is suggested that serovar lai is one of the prevalent serovars in Korea, and that the Mabs produced in this study are useful for the accurate and rapid identification of this serovar.
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To investigate the relation between renal function and concentrations of lipoprotein(a) [Lp(a)] in serum, we measured Lp(a) in samples of serum and urine from patients with diabetes mellitus and in samples sent to a laboratory center for measurements of creatinine clearance. Serum Lp(a) concentrations were significantly increased in subjects with obvious renal dysfunction (serum creatinine > or = 176.8 mumol/L) compared with normal control subjects. Urinary Lp(a) excretion was decreased in subjects with obvious renal dysfunction compared with subjects without obvious renal dysfunction (serum creatinine < or = 88.4 mumol/L) and was negatively and positively correlated with serum creatinine and creatinine clearance, respectively. More than 80% of urinary Lp(a) was recovered in the d > 1.21 kg/L fraction. At least six bands for apolipoprotein(a) [apo(a)] fragments, which were smaller than native apo(a) in serum, were observed in urine by immunoblotting, and some of these were also detected in serum. Degraded apo(a) fragments are probably present in urine, and their excretion decreases in parallel with decreases in the glomerular filtration rate.
1) In Mg-deficient rats, kynureninase activity is decreased. 2) p-Hydroxyphenylpyruvate inhibits kynureninase activity. 3) -SH groups in the apoenzyme of kynureninase play a very important role in the enzymatic reaction. 4) 3-Hydroxykynurenine may be a very important regulative metabolite in the 3-hydroxykynurenine----xanthurenic acid pathway.
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In order to elucidate the full serological characteristics of strain Ictero No. I, the first strain of Leptospira isolated by Inada and Ido in 1914, 17 monoclonal antibodies against the strain were produced by cell fusion technology. The antibody-producing hybridomas were designated IMAs 1 to 17. The reactivities of the monoclonal antibodies produced by the hybridomas were determined by the microscopic agglutination test. One of the 17 monoclonal antibodies, IMA 1, reacted with strains Ictero No. I, LT 1131 and Naam, but not with other strains of the serogroup Icterohaemorrhagiae including strain RGA used in the present study. Moreover, the reactivity of the antigenic determinant of IMA 1 was inactivated by treatment at 56 C for 30 min. The 16 other monoclonal antibodies, IMAs 2 to 17, showed different reaction patterns against Leptospira strains of the serogroup Icterohaemorrhagiae. All of the 16 antibodies reacted with both Ictero No. I and RGA strains. The antigens against antibodies IMAs 2 to 17 were thermostable. The present study thus clarified the presence of a thermolabile antigen in strain Ictero No. I, and allowed correct distinction between the serotype of strain Ictero No. I and that of strain RGA using IMA 1. Therefore, we propose that strain Ictero No. I represents serovar icterohaemorrhagiae, as originally designated by Inada and Ido. Moreover, strain Ictero No. I should be designated as the type strain of Leptospira interrogans.
Plasma lipid and lipoprotein profiles were compared in elderly female runners (RU: n = 15, aged 66 +/- 5 years, body fat 20 +/- 4%, training distance 35 +/- 15 km week-1, VO2max 36 +/- 4 ml kg-1 min-1, mean +/- SD) and age-matched untrained women (UT: n = 28, 66 +/- 4 years, body fat 26 +/- 6%, VO2max 26 +/- 3 ml kg-1 min-1). There were insignificant differences in total cholesterol (RU: 5.04 +/- 0.60 vs. UT: 5.48 +/- 0.85 mmol l-1), HDL-cholesterol (RU: 1.97 +/- 0.41 vs. UT: 1.91 +/- 0.36 mmol l-1) and LDL-cholesterol (RU: 2.72 +/- 0.59 vs. UT: 3.03 +/- 0.80 mmol l-1) between the two groups. Plasma triglyceride concentration of the runners was significantly lower than that of the untrained women (RU: 0.80 +/- 0.27 vs UT: 1.14 +/- 0.36 mmol l-1, P less than 0.01). No difference was observed in the LDL-cholesterol/HDL-cholesterol ratio between the two groups (RU: 1.45 +/- 0.51 vs UT: 1.64 +/- 0.53 units). These results suggest that regularly performed running of 35 km week-1 in elderly women does not further elevate their HDL-cholesterol level which is already high compared to the levels found in elderly men. However, elderly female runners appear to be protected against age-related increases in the levels of triglyceride and LDL-cholesterol.
We evaluated total and split renal functions from the pattern for renal arterial blood flow detected by ultrasound Doppler in healthy subjects and patients with varying degrees of renal function and disorders other than renovascular hypertension or severe aortic valvular disease. A renal-time pulsed ultrasonic echo-Doppler device at 2.5 MHz was used with a translumbar approach. The ratio of peak diastolic (D) to systolic (S) velocity correlated well with both p-aminohippurate clearance and creatinine clearance. Acceleration time was correlated with the clearance of neither compound. To evaluate the clinical usefulness of ultrasound Doppler in the assessment of split renal function, we compared the D/S ratio with the renal function obtained by radionuclide methods for individuals. The split renal glomerular filtration rate, calculated by a method which makes use of the early renal uptake of 99mTc-diethylenetriam-inepentaacetic acid, correlated well with the D/S ratio. These results indicate that the ultrasonic measurement of renal arterial blood flow by the pulsed Doppler method should be useful for assessment of total and split renal functions.
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